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Preview: Nephrology Dialysis Transplantation - recent issues

Nephrology Dialysis Transplantation - recent issues



Nephrology Dialysis Transplantation - RSS feed of recent issues (covers the latest 3 issues, including the current issue)



 















Can there be science without philosophy?

2016-12-08T23:49:54-08:00

Over the last few decades, philosophy has gained an increasingly bad reputation among working scientists. Prominent researchers have suggested, in various forms and degrees of mockery, that philosophy has little or nothing positive to contribute to science. This essay provides a response to these allegations. We begin by examining, and ultimately questioning, an influential argument purporting to undermine the significance of a philosophical approach to science. Next, we offer some biomedical examples where philosophical speculation plays a prominent role. We conclude by arguing that, when understood in the appropriate context, philosophical reflection is an important—indeed, integral—ingredient of healthy scientific inquiry.




Efficacy of a remote web-based lung ultrasound training for nephrologists and cardiologists: a LUST trial sub-project

2016-12-08T23:49:54-08:00

Within the framework of the LUST trial (LUng water by Ultra-Sound guided Treatment to prevent death and cardiovascular events in high-risk end-stage renal disease patients), the European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association–European Dialysis Transplant Association established a central core lab aimed at training and certifying nephrologists and cardiologists participating in this trial. All participants were trained by an expert trainer with an entirely web-based programme. Thirty nephrologists and 14 cardiologists successfully completed the training. At the end of training, a set of 47 lung ultrasound (US) videos was provided to trainees who were asked to estimate the number of B-lines in each video. The intraclass correlation coefficient (ICC) for the whole series of 47 videos between each trainee and the expert trainer was high (average 0.81 ± 0.21) and >0.70 in all but five cases. After further training, the five underperforming trainees achieved satisfactory agreement with the expert trainer (average post-retraining ICC 0.74 ± 0.14). The Bland–Altman plot showed virtually no bias (difference between the mean 0.03) and strict 95% limits of agreement lines (–1.52 and 1.45 US B-lines). Only four cases overlapped but did not exceed the same limits. Likewise, the Spearman correlation coefficient applied to the same data series was very high (r = 0.979, P < 0.0001). Nephrologists and cardiologists can be effectively trained to measure lung congestion by an entirely web-based programme. This web-based training programme ensures high-quality standardization of US B-line measurements and represents a simple, costless and effective preparatory step for clinical trials targeting lung congestion.




Hedgehog Gli signalling in kidney fibrosis

2016-12-08T23:49:54-08:00

Kidney fibrosis is the common final pathway of virtually all progressive injury to the kidney and a promising therapeutic target in chronic kidney disease (CKD). The Hedgehog pathway has been reported to be critical in kidney development, and recent evidence suggests a role in kidney injury and fibrosis. This review provides an overview of recent data suggesting an important role of Gli transcriptional activators in kidney injury and repair. We have reported that the hedgehog transcriptional activator Gli1 specifically marks perivascular mesenchymal stem cells, which are an important source of kidney myofibroblasts. Genetic ablation of these cells ameliorated kidney and heart fibrosis and stabilized organ function after injury. Recent data suggest that Gli2 is an important driver of myofibroblast cell cycle progression and a promising therapeutic target in kidney fibrosis progression and CKD. However, the non-canonical mechanism of Gli activation in kidney fibrosis remains an open question, and further studies are needed to elucidate the role of Hedgehog Gli and Gli1+ perivascular cells in human kidney fibrosis.




Should belatacept be the centrepiece of renal transplantation?

2016-12-08T23:49:54-08:00

Belatacept was developed to minimize cardiovascular risk and nephrotoxicity associated with calcineurin inhibitor (CNI)–based immunosuppression. Recently, 7-year data from the Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial (BENEFIT), a phase III study comparing belatacept with cyclosporine, have been published. While during the first year of belatacept the risk of acute rejection episodes was elevated, this seemingly had marginal consequences for long-term graft survival and function as well as patient survival.

For patients at a low-immunological risk, this drug seems to be a safe and effective alternative to CNI-based immunosuppression. Whether the higher rates of acute rejection episodes in the first year outweigh the gain in long-term graft function is still debated. In particular, the lower incidence of donor-specific antibodies indicates that belatacept should not be considered as lower intensity immunosuppression over the long term.

Therefore, should belatacept be the centrepiece of immunosuppression for renal patients?

All randomized trials so far have focussed on patients at a low immunological risk. Furthermore, cyclosporine A (CsA), the comparator of belatacept in BENEFIT and the Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial-EXTended criteria donors (BENEFIT-EXT), is not the CNI of choice in modern transplantation. Furthermore, while at Year 7 the rate of cancer and infections was comparable with the CsA group, long-term data are missing on safety issues for a large number of patients. Thus, currently belatacept may be the drug of choice for a select group of patients, but not for everyone.

This review highlights the benefits and uncertainties of the use of belatacept in kidney transplantation.




The application of multi-omics and systems biology to identify therapeutic targets in chronic kidney disease

2016-12-08T23:49:54-08:00

The quest for the ideal therapeutic target in chronic kidney disease (CKD) has been riddled with many obstacles stemming from the molecular complexity of the disease and its co-morbidities. Recent advances in omics technologies and the resulting amount of available data encompassing genomics, proteomics, peptidomics, transcriptomics and metabolomics has created an opportunity for integrating omics datasets to build a comprehensive and dynamic model of the molecular changes in CKD for the purpose of biomarker and drug discovery. This article reviews relevant concepts in omics data integration using systems biology, a mathematical modelling method that globally describes a biological system on the basis of its modules and the functional connections that govern their behaviour. The review describes key databases and bioinformatics tools, as well as the challenges and limitations of the current state of the art, along with practical application to CKD therapeutic target discovery. Moreover, it describes how systems biology and visualization tools can be used to generate clinically relevant molecular models with the capability to identify specific disease pathways, recognize key events in disease development and track disease progression.




Sustained remission in lupus nephritis: still a hard road ahead

2016-12-08T23:49:54-08:00

End-stage renal disease caused by lupus nephritis (LN) is an avoidable outcome yet there is considerable uncertainty and variability among nephrologists in their approaches to this disorder. This review discusses recent evidence relevant to the management of LN including recent consensus statements. Long-term results are encouraging compared with 30 years ago, but despite the use of the best available current therapies and achieving high levels of early clinical responses, the kidney often sustains long-term damage and nephritis relapses affect over 50%. Major hurdles to management include the complexity of the clinical presentation, histological features and serological tests, and the absence of reliable outcome predictors or markers of treatment response. The key serological and histopathological characteristics relevant to the practising nephrologist are reviewed, and the limitations of current disease activity markers discussed. There are many potential biomarkers under evaluation, and a framework for their validation is presented. Clinical trials of existing or newer agents for LN have typically been inconclusive and have raised problems of trial design and interpretation that are a barrier to new drug development. The major issues affecting clinical trial design and their potential solutions are summarized.




Four seasons for reflecting: Winter. Touch

2016-12-08T23:49:54-08:00




Urinary soluble CD163 level reflects glomerular inflammation in human lupus nephritis

2016-12-08T23:49:54-08:00

Background

In addition to classically activated macrophages that have effector roles in tissue injury, alternatively activated M2 macrophages are involved in the resolution of inflammation in animal models of kidney disease. To clarify the clinical relevance of macrophage phenotypes in human glomerular diseases, we evaluated the renal accumulation of macrophages and plasma and urine levels of CD163, an M2 marker, in lupus nephritis (LN) patients.

Methods

Kidney biopsies and plasma and urine samples were obtained from LN patients who underwent renal biopsy between 2008 and 2012. CD163+, CD68+ and CD204+ cells were counted in paraffin-embedded and frozen sections. LN histological activity was evaluated semiquantitatively using the biopsy activity index. Plasma and urinary soluble CD163 (sCD163) concentrations were also measured and evaluated for their significance as potential LN biomarkers.

Results

Immunohistological analysis of glomeruli from LN patients revealed that >60% of CD68+ macrophages had merged with CD163+ cells. The increased number of glomerular CD163+ macrophages was correlated with LN severity, as determined by the biopsy active index (r = 0.635). Urinary (u-) sCD163 level was strongly correlated with glomerular CD163+ cell counts and histological disease score as well as urinary monocyte chemoattractant protein 1 levels (r = 0.638 and 0.592, respectively). Furthermore, the u-sCD163 level was higher in patients with active LN than in those with other diseases.

Conclusions

Glomerular CD163+ macrophages are the predominant phenotype in the kidneys of lupus patients. These findings indicate that the u-sCD163 level can serve as a biomarker for macrophage-dependent glomerular inflammation in human LN.




Genotypic and phenotypic predictors of inflammation in patients with chronic kidney disease

2016-12-08T23:49:54-08:00

Background

In complex diseases such as chronic kidney disease (CKD), the risk of clinical complications is determined by interactions between phenotypic and genotypic factors. However, clinical epidemiological studies rarely attempt to analyse the combined effect of large numbers of phenotype and genotype features. We have recently shown that the relaxed linear separability (RLS) model of feature selection can address such complex issues. Here, it is applied to identify risk factors for inflammation in CKD.

Methods

The RLS model was applied in 225 CKD stage 5 patients sampled in conjunction with dialysis initiation. Fifty-seven anthropometric or biochemical measurements and 79 genetic polymorphisms were entered into the model. The model was asked to identify phenotypes and genotypes that, when combined, could separate inflamed from non-inflamed patients. Inflammation was defined as a high-sensitivity C-reactive protein concentration above the median (5 mg/L).

Results

Among the 60 genotypic and phenotypic features predicting inflammation, 31 were genetic. Among the 10 strongest predictors of inflammation, 8 were single nucleotide polymorphisms located in the NAMPT, CIITA, BMP2 and PIK3CB genes, whereas fibrinogen and bone mineral density were the only phenotypic biomarkers.

Conclusion

These results indicate a larger involvement of hereditary factors in inflammation than might have been expected and suggest that inclusion of genotype features in risk assessment studies is critical. The RLS model demonstrates that inflammation in CKD is determined by an extensive panel of factors and may prove to be a suitable tool that could enable a much-needed multifactorial approach as opposed to the commonly utilized single-factor analysis.




Factors influencing withdrawal from dialysis: a national registry study

2016-12-08T23:49:54-08:00

Background

Dialysis withdrawal is the third most common cause of death in patients receiving dialysis for established renal failure (ERF) in Scotland. We describe incidence, risk factors and themes influencing decision-making in a national renal registry.

Methods

Details of deaths in those receiving renal replacement therapy (RRT) for ERF in Scotland are reported to the Scottish Renal Registry via a unique mortality report. We extracted patient demographics and comorbidity, cause and location of death, duration of RRT and pertinent free text comments from 1 January 2008 to 31 December 2014. Withdrawal incidence was calculated and logistic regression used to identify significantly influential variables. Themes emerging from clinician comments were tabulated for descriptive purposes.

Results

There were 2596 deaths; median age at death was 68 [interquartile range (IQR) 58, 76] years, 41.5% were female. Median duration on RRT was 1110 (IQR 417, 2151) days. Dialysis withdrawal was the primary cause of death in 497 (19.1%) patients and withdrawal contributed to death in a further 442 cases (17.0%). The incidence was 41 episodes per 1000 patient-years. Regression analysis revealed increasing age, female sex and prior cerebrovascular disease were associated with dialysis withdrawal as a primary cause of death. Conversely, interstitial renal disease, angiographically proven ischaemic heart disease, valvular heart disease and malignancy were negatively associated. Analysis of free text comments revealed common themes, portraying an image of physical and psychological decline accelerated by acute illnesses.

Conclusions

Death following dialysis withdrawal is common. Factors important to physical independence—prior cerebrovascular disease and increasing age—are associated with withdrawal. When combined with clinician comments this study provides an insight into the clinical decline affecting patients and the complexity of this decision. Early recognition of those likely to withdraw may improve end of life care.




Prognostic implications of adding urine output to serum creatinine measurements for staging of acute kidney injury after major surgery: a cohort study

2016-12-08T23:49:54-08:00

Background

Current guidelines recommend staging acute kidney injury (AKI) according to the serum creatinine (SCr) or urine output (UO) criteria that achieve the highest stage. There is little information about the implications of adding UO to SCr measurements for staging AKI outside intensive care units and after cardiac surgery.

Methods

We performed a cohort study of all adults without end-stage renal disease who underwent major noncardiac surgery between January 2005 and March 2011 in Calgary, AB, Canada. Participants required at least two SCr and UO measurements to be included. We examined the implications of adding UO to SCr to stage AKI based on Kidney Disease: Improving Global Outcomes criteria. Logistic and linear regression models were used to examine the associations between AKI stage and 30-day mortality or hospital length of stay (LOS), respectively.

Results

A total of 4229 (17%) surgical patients had sufficient SCr and UO measurements for inclusion in the cohort. The apparent incidence of postoperative AKI substantially increased with the addition of UO to SCr criteria (8.1% with SCr alone versus 64.0% with SCr and UO). Mortality for a given stage of AKI was lower when UO was added to SCr criteria (0.3, 3.2, 1.9 and 3.0% for no AKI and Stages 1, 2 and 3, respectively) versus with SCr alone (1.2, 4.2, 15.4 and 12.8%). However, among participants without AKI based on the SCr criterion, the odds of mortality and mean LOS both significantly increased with lower UO. Models that reclassified AKI stage based on UO in addition SCr criteria had the best discrimination for mortality and LOS.

Conclusions

Adding UO to SCr criteria substantially increases the apparent incidence of AKI on hospital wards and significantly changes the prognostic implications of AKI identification and staging. These measures should not be considered equivalent criteria in AKI staging.




Markers of kidney disease and risk of subclinical and clinical heart failure in African Americans: the Jackson Heart Study

2016-12-08T23:49:54-08:00

Background

African Americans and patients with chronic kidney disease (CKD) are at high risk for clinical heart failure (HF). In this study, we aimed to determine the association of markers of kidney disease with subclinical HF (by echocardiogram) and risk of clinical HF among a large, well-characterized community-based cohort of African American patients. We also examined whether the association of markers of kidney disease with HF was attenuated with adjustment for echocardiographic measures.

Methods

We studied participants in the Jackson Heart Study, a large community-based cohort of African Americans. Estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (ACR) were measured at baseline. We tested the association of eGFR and urine ACR with left ventricular mass (LVM), left ventricular ejection fraction (LVEF) and physician-adjudicated incident HF.

Results

Among the 3332 participants in the study, 166 (5%) had eGFR <60 mL/min/1.73 m2 and 405 (12%) had urine ACR ≥30 mg/g. In models adjusted for demographics, comorbidity and the alternative measure of kidney disease, lower eGFR and higher urine ACR were associated with higher LVM {β-coefficient 1.54 [95% confidence interval (CI) 0.78–2.31] per 10 mL/min/1.73 m2 decrease in eGFR and 2.87 (95% CI 1.85–3.88) per doubling of urine ACR}. There was no association of eGFR and urine ACR with LVEF [β-coefficient –0.12 (95% CI –0.28–0.04) and –0.11 (95% CI –0.35–0.12), respectively]. There was no association of eGFR with the risk of incident HF [HR 1.02 (95% CI 0.91–1.14) per 10 mL/min/1.73 m2 decrease], while there was a significant association of urine ACR [HR 2.22 (95% CI 1.29–3.84) per doubling of urine ACR]. This association was only modestly attenuated with adjustment for LVM [HR 1.95 (95% CI 1.09–3.49)].

Conclusions

Among a community-based cohort of African Americans, lower eGFR and higher ACR were associated with higher LVM. Furthermore, higher urine ACR was associated with incident HF, which was not entirely explained by the presence of left ventricular disease.




Impaired vascular function contributes to exercise intolerance in chronic kidney disease

2016-12-08T23:49:54-08:00

Background

Exercise intolerance is an important feature in patients with chronic kidney disease (CKD) and is prognostic for both increased morbidity and mortality. Little is known about the underlying mechanisms in predialysis CKD. This study aimed to gain more insight into the role of vascular dysfunction in the exercise intolerance of predialysis CKD. In addition, vascular-related microRNAs (miRNAs)—as epigenetic regulators of exercise capacity—were analysed.

Methods

Sixty-three patients with CKD stages 1–5 and 18 healthy controls were included. Peak oxygen consumption (VO2peak) was determined by cardiopulmonary exercise testing, endothelial function by flow-mediated dilation (FMD) and arterial stiffness by carotid-femoral pulse wave velocity (PWV). Plasma miRNA levels (miR-21, miR-126, miR-146a, miR-150 and miR-210) were quantified by quantitative RT-PCR.

Results

VO2peak was already impaired in mild CKD (stages 1–3A) and significantly correlated with estimated glomerular filtration rate (eGFR; r = 0.525, P < 0.001). Likewise, both FMD and PWV were significantly correlated with eGFR (r = 0.319, P = 0.007 and r = –0.365, P = 0.001, respectively). In multiple regression analysis, PWV remained one of the strongest independent determinants of VO2peak (β = –0.301, P = 0.01). Of the studied miRNA, circulating levels of miR-146a and miR-150 correlated with eGFR, PWV and VO2peak, but the association with the latter was lost when correcting for PWV.

Conclusions

Arterial stiffness contributes to the observed reduced aerobic capacity in predialysis CKD, independent of age, haemoglobin levels and endothelial function and represents a promising therapeutic target for improving exercise capacity in this population. Future work is required to elucidate why higher circulating levels of miR-146a and miR-150 are associated with impaired renal function and increased arterial stiffness.




Outcomes in patients with chronic kidney disease not on dialysis receiving extended dosing regimens of darbepoetin alfa: long-term results of the EXTEND observational cohort study

2016-12-08T23:49:54-08:00

Background

Extended dosing of the erythropoiesis-stimulating agent (ESA) darbepoetin alfa (DA) once biweekly or monthly reduces anaemia treatment burden. This observational study assessed outcomes and dosing patterns in patients with chronic kidney disease not on dialysis (CKD-NoD) commencing extended dosing of DA.

Methods

Adult CKD-NoD patients starting extended dosing of DA in Europe or Australia in June 2006 or later were followed up until December 2012. Outcomes included haemoglobin (Hb) concentration, ESA dosing, mortality rates and receipt of dialysis and renal transplantation. Subgroup analyses were conducted for selected outcomes.

Results

Of 6035 enrolled subjects, 5723 (94.8%) met analysis criteria; 1795 (29.7%) received dialysis and 238 (3.9%) underwent renal transplantation. Mean (standard deviation) Hb concentration at commencement of extended dosing was 11.0 (1.5) g/dL. Mean [95% confidence interval (CI)] Hb 12 months after commencement of extended dosing (primary outcome) was 11.6 g/dL (11.5, 11.6) overall and was similar across countries, with no differences between subjects previously treated with an ESA versus ESA-naïve subjects, subjects with versus without prior renal transplant or diabetics versus non-diabetics. Weekly ESA dose gradually decreased following commencement of extended DA dosing and was similar across subgroups. The decrease in weekly DA dose was accompanied by an increase in the proportion of patients receiving iron therapy. Hb concentrations declined following changes in ESA labels and treatment guidelines. The mortality rate (95% CI) was 7.06 (6.68, 7.46) deaths per 100 years of follow-up. Subjects alive at study end had stable Hb concentrations in the preceding year, while those who died had lower and declining Hb concentrations in their last year.

Conclusions

Long-term, extended dosing of DA maintained Hb concentrations in patients already treated with an ESA and corrected and maintained Hb in ESA-naïve patients.




Prevalence and recognition of chronic kidney disease in Stockholm healthcare

2016-12-08T23:49:54-08:00

Background

Chronic kidney disease (CKD) is common, but the frequency of albuminuria testing and referral to nephrology care has been difficult to measure. We here characterize CKD prevalence and recognition in a complete healthcare utilization cohort of the Stockholm region, in Sweden.

Methods

We included all adult individuals (n = 1 128 058) with at least one outpatient measurement of IDMS-calibrated serum creatinine during 2006–11. Estimated glomerular filtration rate (eGFR) was calculated via the CKD-EPI equation and CKD was solely defined as eGFR <60 mL/min/1.73 m2. We also assessed the performance of diagnostic testing (albuminuria), nephrology consultations, and utilization of ICD-10 diagnoses.

Results

A total of 68 894 individuals had CKD, with a crude CKD prevalence of 6.11% [95% confidence interval (CI): 6.07–6.16%] and a prevalence standardized to the European population of 5.38% (5.33–5.42%). CKD was more prevalent among the elderly (28% prevalence >75 years old), women (6.85 versus 5.24% in men), and individuals with diabetes (17%), hypertension (17%) or cardiovascular disease (31%). The frequency of albuminuria monitoring was low, with 38% of diabetics and 27% of CKD individuals undergoing albuminuria testing over 2 years. Twenty-three per cent of the 16 383 individuals satisfying selected KDIGO criteria for nephrology referral visited a nephrologist. Twelve per cent of CKD patients carried an ICD-10 diagnostic code of CKD.

Conclusions

An estimated 6% of the adult Stockholm population accessing healthcare has CKD, but the frequency of albuminuria testing, nephrology consultations and registration of CKD diagnoses was suboptimal despite universal care. Improving provider awareness and treatment of CKD could have a significant public health impact.




Zoster vaccination is associated with a reduction of zoster in elderly patients with chronic kidney disease

2016-12-08T23:49:54-08:00

Background

Growing epidemiological evidence demonstrates increased zoster risks in people with chronic kidney disease (CKD). Study objectives were to determine zoster vaccine effectiveness in individuals with CKD in pragmatic use.

Methods

A population-based cohort study was undertaken in a 5% random sample of US Medicare from 2007 to 2009 involving 766 330 eligible individuals aged ≥65 years who were (29 785) and were not (736 545) exposed to the zoster vaccine. Incidence rates for zoster in vaccinated and unvaccinated individuals and hazard ratios for zoster comparing vaccinated with unvaccinated were determined for individuals with CKD. Time-updated Cox proportional hazards models were used, adjusting for relevant confounders.

Results

CKD was present in 183 762 (24%) of individuals (15% of vaccinees). Adjusted vaccine effectiveness [95% confidence intervals (CIs)] in individuals with CKD was 0.49 (0.36–0.65). The adjusted vaccine effectiveness in participants with both CKD and diabetes mellitus was 0.46 (95% CI 0.09–0.68). Vaccine effectiveness estimates were similar to those previously reported for the general population [vaccine effectiveness 0.48 (95% CI 0.39–0.56)].

Conclusions

Zoster vaccine is effective against incident zoster in older individuals with CKD. Extra efforts are warranted to increase vaccine uptake in individuals with CKD given the known low uptake in these higher risk individuals.




Clinical characteristics and outcomes of HIV-associated immune complex kidney disease

2016-12-08T23:49:54-08:00

Background

The pathogenesis and natural history of HIV-associated immune complex kidney disease (HIVICK) is not well understood. Key questions remain unanswered, including the role of HIV infection and replication in disease development and the efficacy of antiretroviral therapy (ART) in the prevention and treatment of disease.

Methods

In this multicentre study, we describe the renal pathology of HIVICK and compare the clinical characteristics of patients with HIVICK with those with IgA nephropathy and HIV-associated nephropathy (HIVAN). Poisson regression models were used to identify risk factors for each of these pathologies.

Results

Between 1998 and 2012, 65 patients were diagnosed with HIVICK, 27 with IgA nephropathy and 70 with HIVAN. Black ethnicity and HIV RNA were associated with HIVICK, receipt of ART with IgA nephropathy and black ethnicity and CD4 cell count with HIVAN. HIVICK was associated with lower rates of progression to end-stage kidney disease compared with HIVAN and IgA nephropathy (P < 0.0001). Patients with HIVICK who initiated ART and achieved suppression of HIV RNA experienced improvements in estimated glomerular filtration rate and proteinuria.

Conclusions

These findings suggest a pathogenic role for HIV replication in the development of HIVICK and that ART may improve kidney function in patients who have detectable HIV RNA at the time of HIVICK diagnosis. Our data also suggest that IgA nephropathy should be viewed as a separate entity and not included in the HIVICK spectrum.




Long-term outcomes of persistent disease and relapse in primary membranous nephropathy

2016-12-08T23:49:54-08:00

Background

Primary membranous nephropathy is associated with variable clinical course ranging from spontaneous remission to slow progression to end stage renal failure. Achieving remission confers better renal survival in primary membranous nephropathy (PMN). Longer term outcomes such as patient survival and relapse of active disease remain poorly understood.

Methods

We performed a retrospective study of 128 consecutive adult patients diagnosed with biopsy proven PMN at a single UK centre between 1980 and 2010. These patients were followed prospectively over a median of 128 months. We assessed impact of persistent disease and relapse on Stage 5 chronic kidney disease (CKD-5) and patient survival and present longer term cumulative incidences of different end points.

Results

One hundred patients achieved partial remission (PartRem) and 28 patients did not achieve remission (NoRem). Nine per cent of patients achieving first remission developed CKD-5 and 75% of those with NoRem developed CKD-5 [hazard ratio (HR) 0.07, 95% confidence interval 0.03–0.19). Relapse following PartRem occurred in 31 patients (31%) during follow-up and was significantly associated with progression to CKD-5. Progression to CKD-5 was strongly associated with death (47 versus 6%, HR 23.4; P < 0.01). Cumulative incidence at 15 years following first presentation included: death, 14%; CKD-5, 28%; and relapse 40% (in patients who achieved first remission).

Conclusions

Our data strongly suggest that mortality in PMN is seen in patients with disease progression to CKD-5. Achieving remission is strongly associated with improved renal survival after first presentation and following relapse. We suggest that patients who achieve remission should be followed up in longer term, and better strategies to help improve outcomes are needed in clinical practice.




Permanent cardiac pacing in patients with end-stage renal disease undergoing dialysis

2016-12-08T23:49:54-08:00

Background

Studies investigating the risk of cardiac dysrhythmia warranting permanent pacemaker therapy for end-stage renal disease (ESRD) patients are limited. This study investigated the incidence rate of permanent cardiac pacing in dialysis patients.

Methods

Using the Taiwan National Health Insurance Database, we identified 28 471 newly diagnosed ESRD patients in 2000–2010 [9700 on peritoneal dialysis (PD) and 18 771 on hemodialysis (HD)] and 113 769 randomly selected controls without kidney disease, frequency-matched by sex, age and diagnosis date. We also established propensity score-matched HD and PD cohorts with 9700 patients each. Incidence rates and hazard ratios (HRs) of implantation were evaluated by the end of 2011. Complications were also evaluated among patients with implantation.

Results

The incidence rates of permanent pacemaker implantation were 5.93- and 3.50-fold greater in HD and PD patients than in controls (1.44 and 0.85 versus 0.24 per 1000 person-years, respectively). The adjusted HRs (aHRs) of implantation were 3.26 [95% confidence interval (CI) = 2.41–4.42] and 2.36 (95% CI = 1.56–3.58) for HD and PD patients, respectively, compared with controls. The pacemaker implantation rate was 0.33 per 1000 person-years greater in the propensity score-matched HD cohort than in the PD cohort, with an aHR of 1.30 (95% CI = 0.82–2.05) for the HD cohort compared with the PD cohort.

Conclusions

Dialysis patients are at an increased risk of dysrhythmia requiring pacemaker implantation compared with the general population. The risks are not significantly different between HD and PD patients.




Atypical haemolytic uraemic syndrome and pregnancy: outcome with ongoing eculizumab

2016-12-08T23:49:54-08:00

Background

A therapeutic strategy based on complement blockade by eculizumab is widely used to treat atypical haemolytic uraemic syndrome (aHUS). Recent data are available on the administration of eculizumab during pregnancy in patients treated for paroxysmal nocturnal haemoglobinuria but there are very few data for aHUS patients.

Methods

We analysed the use of eculizumab for the treatment of aHUS during five pregnancies in three patients and studied an additional pregnancy without eculizumab. Obstetrical data and maternal and foetal complications during pregnancy, at delivery, and during the post-partum period were recorded.

Results

The mean age at pregnancy was 28.5 (range 25–33) years. The mean serum creatinine before pregnancy was 189 (range 130–300) µmol/L and the mean eGFR was 32 (range 18–45) mL/min/1.73 m2. One patient who stopped eculizumab 3 weeks after conception had a termination due to a relapse of HUS at 12 weeks of gestation (WG) during a first pregnancy and an intrauterine death at 24 WG despite continuous eculizumab treatment during a second pregnancy. In the other four pregnancies, treatment stabilized clinical and laboratory markers until 29–34 WG, but did not prevent hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome in one patient or pre-eclampsia in two other patients. All babies were born preterm and two presented with growth retardation. The mean body weight was 1632.5 (range 1070–2500) g. The dose of eculizumab had to be increased during all pregnancies due to incomplete complement blockade.

Conclusions

Eculizumab therapy during pregnancy displayed no overt safety issues but did not appear to prevent HELLP syndrome or pre-eclampsia in these high-risk chronic kidney disease patients.




Potential role of effector memory T cells in chronic T cell-mediated kidney graft rejection

2016-12-08T23:49:54-08:00

Background

Chronic T cell-mediated rejection (TCMR) in kidney graft is characterized by reduction of the vessel lumen with marked intimal thickening, fibrous hyperplasia of the small renal arteries and leukocyte infiltrates. The aim of this study was to find specific gene expression profiles in chronic TCMR kidney biopsies.

Methods

RNA extracted from archival formalin-fixed, paraffin-embedded renal biopsies was used for gene expression profiling. Our study included 14 patients with chronic TCMR and 10 with acute TCMR. Fifty-two cadaveric donors were used as controls. The results were validated in an independent set of kidney biopsies.

Results

We identified 616 and 243 differentially expressed genes with a fold change ≥1.5 and a false discovery rate <0.05 in chronic and acute TCMR, respectively. Pathway analysis revealed upregulation of OX40 signalling. This pathway is involved in the generation of CD8+ effector memory T cells and the upregulation of killer cell lectin-like receptor G1 (KLRG-1), B lymphocyte-induced maturation protein 1 (BLIMP-1) and CD25, which characterize CD8+ effector memory T cells. However, the enhanced OX40 signalling pathway was specific to chronic TCMR; a significant increase of KLRG-1+/CD8+ and BLIMP-1+/CD8+ was only detected in these specimens.

Conclusions

These results suggest the involvement of memory-committed CD8+ effector T cells in chronic TCMR. The generation of effector memory T cells is mediated by the OX40 gene pathway, and could be considered a future target for the specific treatment of chronic TCMR.




Immunologic outcome in elderly kidney transplant recipients: is it time for HLA-DR matching?

2016-12-08T23:49:54-08:00

Background

The Eurotransplant Senior Program (ESP) neglects HLA matching for elderly (≥65 years) kidney transplant recipients (KTR). Few data regarding the influence of DR matching on clinical and immunologic outcome in elderly KTR exist.

Methods

This retrospective long-term observational study included 244 elderly out of n = 972 adult KTR between 2004 and 2014. Data analysis included patient and graft survival, biopsy-proven rejections [T-cell-mediated rejections (TCMR) and antibody-mediated rejections] and development of de novo donor-specific HLA antibodies (DSA). Outcome data were assessed over a maximum period of 10 years.

Results

Due to the nature of the ESP, elderly KTR showed significantly more HLA mismatches, shorter time on dialysis and shorter cold ischaemia time. Elderly KTR had significantly worse graft and patient survival, and after 7 years, the rate of de novo DSA (33 versus 25%, P = 0.034) and TCMR (39 versus 27%, P < 0.001) was significantly higher compared with younger KTR. Multivariate analysis identified donor age, delayed graft function and HLA-DR mismatches as independent risk factors for TCMR. Within the group of elderly KTR, HLA-DR mismatches were associated with a significantly higher incidence of TCMR and development of de novo DSA. Occurrence of TCMR and de novo DSA in elderly KTR resulted in significantly worse graft survival.

Conclusions

In elderly KTR, HLA-DR mismatches are independent risk factors for TCMR and the development of all classes of de novo DSA, both of which significantly impair graft survival. Introduction of HLA-DR matching in elderly KTR might significantly improve immunologic and overall outcome.




Cancer risk and mortality after kidney transplantation: a population-based study on differences between Danish centres using standard immunosuppression with and without glucocorticoids

2016-12-08T23:49:54-08:00

Background

Kidney recipients receive immunosuppression to prevent graft rejection, and long-term outcomes such as post-transplant cancer and mortality may vary according to the different protocols of immunosuppression.

Methods

A national register-based historical cohort study was conducted to examine whether post-transplant cancer and all-cause mortality differed between Danish renal transplantation centres using standard immunosuppressive protocols including steroids (Centres 2, 3, 4) or a steroid-free protocol (Centre 1). The Danish Nephrology Registry, the Danish Civil Registration System, the Danish National Cancer Registry and the Danish National Patient Register were used. A historical cohort of 1450 kidney recipients transplanted in 1995–2005 was followed up with respect to post-transplant cancer and death until 31 December 2011.

Results

Compared with Center 1 the adjusted post-transplant cancer risk was 6–39% lower in Centre 3 [hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.67–1.32], in Centre 2 (HR 0.72, 95% CI 0.52–0.98) and in Centre 4 (HR 0.61, 95% CI 0.44–0.83). Compared with Center 1, the adjusted post-transplant mortality was 21–55% higher in Centre 4 (HR 1.21, 95% CI 0.91–1.61), in Centre 3 (HR 1.35, 95% CI 0.98–1.86) and in Centre 2 (HR 1.55, 95% CI 1.17–2.05). On average, post-transplant cancer was associated with a 4-fold increase in the risk of death (HR 4.25, 95% CI 3.36–5.38).

Conclusions

There was a tendency of a higher post-transplant cancer occurrence, but lower all-cause mortality, in the Danish transplantation centre that adhered to a standard steroid-free immunosuppressive protocol.




Announcements

2016-12-08T23:49:54-08:00



















Pro: STOP immunosuppression in IgA nephropathy?

2016-11-02T00:05:41-07:00

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest a 6-month course of corticosteroids (CS) for IgA nephropathy (IgAN) patients with persistent proteinuria ≥1 g/day despite 3–6 months of renin–angiotensin system (RAS) blockers and glomerular filtration rate (GFR) >50 mL/min/1.73 m2. In December 2015, Rauen et al. (N Engl J Med 2015; 373: 2225–2236) published an article entitled ‘Intensive supportive care plus immunosuppression in IgA nephropathy’ (STOP-IgAN), which presented results from 379 IgAN patients from 32 nephrology centres in Germany. During a run-in phase of 6 months, patients received supportive care therapy including RAS blockers, dietary counselling, advice to stop smoking and avoid nephrotoxic drugs, and statins if required. After 6 months, 177 patients with proteinuria >0.75 g/day (non-responder patients) were randomized to either receive continued supportive care or supportive care plus immunosuppression (monotherapy with CS or combined therapy with three immunosuppressants). The authors reported that, after 36 months of observation, the addition of immunosuppressants to ongoing comprehensive supportive care was not beneficial in IgAN patients with moderate proteinuria and chronic kidney disease stages 1–3. These conclusions are questionable for several reasons: (i) studies on time-average proteinuria have shown that beneficial effects on renal survival, not evident after 36 months, emerge over the course of longer observation periods; (ii) supportive care in the STOP-IgAN study resulted in a small loss of renal function during the 36 months of observation (annual decrease in the estimated GFR of 1.6 mL/min/1.73 m2), but was unable to reduce proteinuria below 1 g/day; in contrast, 6 months of steroid therapy lowered proteinuria below 1 g/day; and (iii) the lack of any assessment of the histological data does not allow the importance of the morphological lesions on renal survival and therapy effects to be monitored. Further evaluation with a longer follow-up period is needed to obtain more reliable answers than the weak evidence of this study.




Opponent's comments

2016-11-02T00:05:41-07:00




Con: STOP immunosuppression in IgA nephropathy

2016-11-02T00:05:41-07:00

A comprehensive supportive therapy approach constitutes the mainstay treatment of IgA nephropathy (IgAN) patients. In our recent Supportive versus immunosuppressive Therapy Of Progressive IgA Nephropathy (STOP-IgAN) trial, we systematically selected for patients at high risk of a progressive disease course and evaluated the effect of immunosuppression, combined with supportive care, on renal end points in these patients. There was a higher rate of full clinical remission and transient proteinuria reduction in immunosuppressed patients. However, deterioration of renal function (i.e. number of patients with an estimated glomerular filtration rate (eGFR) decrease of at least 15 mL/min over the 3-year trial phase) was remarkably slow in both groups, compared with previous studies, and was not slowed further by adding immunosuppression to supportive care. Here, we address several concerns raised on the design and interpretation of our trial. In our randomized patients, we confirmed a lower baseline proteinuria to be predictive of clinical remission in IgAN. However, the observed transient drop in proteinuria in the immunosuppressed patients did not translate into an improved overall renal outcome in these patients. Although longer follow-up would be desirable, there was not even a trend for the eGFR course to diverge between our two treatment arms during the trial phase. Finally, it is important to note that we excluded specific infrequent patient groups during our run-in phase. Therefore, IgAN patients with a rapidly progressing course and those with persistent proteinuria >3.5 g/day would require further evaluation regarding potential benefits of immunosuppressive therapies.




Opponent's comments

2016-11-02T00:05:41-07:00




Moderator's view: Treatment of IgA nephropathy--getting comfortable with uncertainty

2016-11-02T00:05:41-07:00

A Polar Views discussion by Pozzi and Rauen et al. on the interpretation and clinical application of the recently published Supportive Versus Immunosuppressive Therapy of Progressive IgA Nephropathy (STOP-IgAN) trial has elucidated important points concerning potential strengths and weaknesses of this landmark randomized trial. This critical examination of the impact of steroid monotherapy or steroid plus an immunosuppressive (IS) agent compared with ‘supportive’ therapy with inhibitors of the renin–angiotensin system (RAS) has enhanced our appreciation of the importance of rigorous application of titrated RAS inhibition in high-risk patients with persistent proteinuria >0.75 g/day. At the same time, it brings a new level of uncertainty concerning the overall value and risk of steroid or steroid plus IS therapy in patients failing such ‘supportive' therapy. Some of these uncertainties revolve on issues of study design, such as the duration of follow-up, participant stratification (particularly underlying pathology) and dosing regimens. It is hoped that additional trials, better methods of patient selection, improved surrogate end points and safer regimens will lead to less uncertainty over the best treatment practices. On balance, the STOP-IgAN trial raises some key concerns about the merits of steroid alone or steroid plus IS therapy for selected subjects with IgAN, but it does not by itself close the door on the utility of steroid monotherapy in subjects with high-risk IgAN, even as it further degrades the value of steroid plus IS, at least with sequential cyclophosphamide and azathioprine.




Midkine, a heparin-binding growth factor, and its roles in atherogenesis and inflammatory kidney diseases

2016-11-02T00:05:41-07:00

The heparin-binding protein midkine is a potent growth factor with emerging roles in numerous inflammatory diseases. Beyond its characterization in embryogenesis and organ development, ample insights into its function have been collected from experimental disease models using knockout animals or knockdown intervention strategies. Here a comprehensive overview on midkine and its functions in atherogenesis and kidney diseases is provided. Molecular clues to key signalling pathways (Akt, ERK, HIF1α) and key events in atherosclerotic vessels link midkine expression with vascular smooth muscle proliferation and (neo)angiogenesis. In acute and chronic kidney diseases, midkine expression is upregulated in tubular as well as endothelial cells. Experimental disease models that mimic diabetic nephropathy and/or immunologic glomerular damage indicate dichotomous midkine activities, with cytoprotective as well as injurious effects. This review also pinpoints the commonalities of the disease models. An understanding of the underlying molecular events will be required in order to design a targeted intervention into cardiovascular or renal diseases as well as inflammatory processes.




Sex hormones in women with kidney disease

2016-11-02T00:05:41-07:00

Menstrual disorders, infertility and premature menopause are common but often underrecognized phenomena among women with chronic kidney disease. Hypothalamic, rather than ovarian dysfunction, may be the cause of the abnormal reproductive milieu, which can be at least partially reversed by kidney transplantation and increased intensity of hemodialysis. Endogenous sex hormones, and specifically estradiol, appear to be renoprotective in women, although the effects of exogenous estradiol (as an oral contraceptive and postmenopausal hormone therapy) on kidney function are more controversial. Treatment with postmenopausal hormone therapy in women with end-stage kidney disease (ESKD) has been associated with improved quality of life, bone health and markers of cardiovascular risk, as well as an increased risk of arteriovenous access thrombosis. The selective estrogen receptor modulator raloxifene has been associated with both a decreased fracture risk as well as renoprotection in women with kidney disease. Young women with ESKD are more likely to die from infection or develop malignancy, suggesting an immunomodulatory role of estrogen. Whether the premature menopause commonly observed in female patients with kidney disease results in increased cardiovascular morbidity and mortality is unknown, although preliminary studies have suggested a possible therapeutic role for manipulation of the sex hormone milieu to mitigate risk in this population. Large, prospective, randomized studies examining the role of sex hormones in women with kidney disease are required to address the question.




Should chronic metabolic acidosis be treated in older people with chronic kidney disease?

2016-11-02T00:05:41-07:00

Metabolic acidosis is common in advanced chronic kidney disease and has been associated with a range of physiological derangements of importance to the health of older people. These include associations with skeletal muscle weakness, cardiovascular risk factors, and bone and mineral disorders that may lead to fragility fractures. Although metabolic acidosis is associated with accelerated decline in kidney function, end-stage renal failure is a much less common outcome in older, frail patients than cardiovascular death. Correction of metabolic acidosis using bicarbonate therapy is commonly employed, but the existing evidence is insufficient to know whether such therapy is of net benefit to older people. Bicarbonate is bulky and awkward to take, may impose additional sodium load with effects on fluid retention and blood pressure, and may cause gastrointestinal side effects. Trial data to date suggest potential benefits of bicarbonate therapy on progression of renal disease and nutrition, but trials have not as yet been published examining the effect of bicarbonate therapy across a range of domains relevant to the health of older people. Fortunately, a number of trials are now underway that should allow us to ascertain whether bicarbonate therapy can improve physical function, quality of life, and vascular, bone and kidney health in older people, and hence decide whether any benefits seen outweigh adverse effects and additional treatment burden in this vulnerable group of patients.




Genetic testing in steroid-resistant nephrotic syndrome: when and how?

2016-11-02T00:05:41-07:00

Steroid-resistant nephrotic syndrome (SRNS) represents the second most frequent cause of chronic kidney disease in the first three decades of life. It manifests histologically as focal segmental glomerulosclerosis (FSGS) and carries a 33% risk of relapse in a renal transplant. No efficient treatment exists. Identification of single-gene (monogenic) causes of SRNS has moved the glomerular epithelial cell (podocyte) to the center of its pathogenesis. Recently, mutations in >30 recessive or dominant genes were identified as causing monogenic forms of SRNS, thereby revealing the encoded proteins as essential for glomerular function. These findings helped define protein interaction complexes and functional pathways that could be targeted for treatment of SRNS. Very recently, it was discovered that in the surprisingly high fraction of ~30% of all individuals who manifest with SRNS before 25 years of age, a causative mutation can be detected in one of the ~30 different SRNS-causing genes. These findings revealed that SRNS and FSGS are not single disease entities but rather are part of a spectrum of distinct diseases with an identifiable genetic etiology. Mutation analysis should be offered to all individuals who manifest with SRNS before the age of 25 years, because (i) it will provide the patient and families with an unequivocal cause-based diagnosis, (ii) it may uncover a form of SRNS that is amenable to treatment (e.g. coenzyme Q10), (iii) it may allow avoidance of a renal biopsy procedure, (iv) it will further unravel the puzzle of pathogenic pathways of SRNS and (v) it will permit personalized treatment options for SRNS, based on genetic causation in way of ‘precision medicine’.




Innate immunity in CKD-associated vascular diseases

2016-11-02T00:05:42-07:00

Chronic kidney disease (CKD) is associated with an increased risk for cardiovascular events. Therefore, the activation of the innate immune system plays an important role. In contrast to the adaptive immunity, unspecific recognition of conserved endogenous and exogenous structures by pattern recognition receptors (PRRs) represents a key feature of the innate immunity. Of these PRRs, Toll-like receptors (TLRs) as well as the inflammasome complex have been documented to be involved in the pathogenesis of cardiovascular diseases (CVDs). They are not only expressed in leukocytes but also in a variety of cell types such as endothelial cells or fibroblasts. While activation of TLRs on the cell surface leads to nuclear factor B-dependent expression of pro-inflammatory mediators, the inflammasome is a cytosolic multimeric protein complex, which cleaves cytokines such as interleukin-1β into their biologically active forms. Several endogenous ligands for these PRRs have been identified as contributing to the development of a CKD-specific pro-inflammatory microenvironment. Notably, activation of TLRs as well as the inflammasome is associated with arterial hypertension, formation of atherosclerotic vascular lesions and vascular calcification. However, detailed molecular mechanisms on how the innate immune system contributes to CKD-associated CVDs are as yet poorly understood. Currently, several agents modulating the activation of the innate immune system are the focus of cardiovascular research. Large clinical studies will provide further information on the therapeutic applicability of these substances to reduce cardiovascular morbidity and mortality in the general population. Further trials including patients with CKD will be necessary to assess their effects on CKD-associated CVD.







Resveratrol delays polycystic kidney disease progression through attenuation of nuclear factor {kappa}B-induced inflammation

2016-11-02T00:05:42-07:00

Background

Inflammation plays an important role in polycystic kidney disease (PKD). The current study aimed to examine the efficacy of the anti-inflammatory compound resveratrol in PKD and to investigate its underlying mechanism of action.

Methods

Male Han:SPRD (Cy/+) rats with PKD were treated with 200 mg/kg/day resveratrol or vehicle by gavage for 5 weeks. Human autosomal dominant (AD) PKD cells, three-dimensional (3D) Madin-Darby canine kidney cells and zebrafish were treated with various concentrations of resveratrol or the nuclear factor B (NF-B) inhibitor QNZ.

Results

Resveratrol treatment reduced blood urea nitrogen levels and creatinine levels by 20 and 24%, respectively, and decreased two-kidney/total body weight ratio by 15% and cyst volume density by 24% in Cy/+ rats. The proliferation index and the macrophage infiltration index were reduced by 40 and 43%, respectively, in resveratrol-treated cystic kidneys. Resveratrol reduced the levels of the pro-inflammatory factors monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α) and complement factor B (CFB) in Cy/+ rat kidneys in parallel with the decreased activity of NF-B (p50/p65). The activation of NF-B and its correlation with pro-inflammatory factor expression were confirmed in human ADPKD cells and kidney tissues. Resveratrol and QNZ inhibited the expression of MCP-1, TNF-α and CFB and reduced NF-B activity in ADPKD cells. Moreover, NF-B blockage minimized the inhibition of inflammatory factor production by resveratrol treatment. Furthermore, resveratrol or QNZ inhibited cyst formation in the 3D cyst and zebrafish models.

Conclusions

The NF-B signaling pathway is activated and partly responsible for inflammation in polycystic kidney tissues. Targeting inflammation through resveratrol could be a new strategy for PKD treatment in the future.




Impact of individual intravenous iron preparations on the differentiation of monocytes towards macrophages and dendritic cells

2016-11-02T00:05:42-07:00

Background

Treatment of iron deficiency with intravenous (i.v.) iron is a first-line strategy to improve anaemia of chronic kidney disease. Previous in vitro experiments demonstrated that different i.v. iron preparations inhibit differentiation of haematopoietic stem cells to monocytes, but their effect on monocyte differentiation to macrophages and mature dendritic cells (mDCs) has not been assessed. We investigated substance-specific effects of iron sucrose (IS), sodium ferric gluconate (SFG), ferric carboxymaltose (FCM) and iron isomaltoside 1000 (IIM) on monocytic differentiation to M1/M2 macrophages and mDCs.

Methods

Via flow cytometry and microRNA (miRNA) expression analysis, we morphologically and functionally characterized monocyte differentiation to M1/M2 macrophages and mDCs after monocyte stimulation with IS, SFG, FCM and IIM (0.133, 0.266 and 0.533 mg/mL, respectively). To assess potential clinical implications, we compared monocytic phagocytosis capacity in dialysis patients who received either 500 mg IS or IIM.

Results

Phenotypically, IS and SFG dysregulated the expression of macrophage (e.g. CD40, CD163) and mDC (e.g. CD1c, CD141) surface markers. Functionally, IS and SFG impaired macrophage phagocytosis capacity. Phenotypic and functional alterations were less pronounced with FCM, and virtually absent with IIM. In miRNA expression analysis of mDCs, IS dysregulated miRNAs such as miR-146b-5p and miR-155-5p, which are linked to Toll-like receptor and mitogen-activated protein kinase signalling pathways. In vivo, IS reduced monocytic phagocytosis capacity within 1 h after infusion, while IIM did not.

Conclusions

This study demonstrates that less stable i.v. iron preparations specifically affect monocyte differentiation towards macrophages and mDCs.




A simple care bundle for use in acute kidney injury: a propensity score-matched cohort study

2016-11-02T00:05:42-07:00

Background

Consensus guidelines for acute kidney injury (AKI) have recommended prompt treatment including attention to fluid balance, drug dosing and avoidance of nephrotoxins. These simple measures can be incorporated in a care bundle to facilitate early implementation. The objective of this study was to assess the effect of compliance with the AKI care bundle (AKI-CB) on in-hospital case–fatality and AKI progression.

Methods

In this larger, propensity score-matched cohort of multifactorial AKI, we examined the impact of compliance with an AKI-CB in 3717 consecutive episodes of AKI in 3518 patients between 1 August 2013 and 31 January 2015. Propensity score matching was performed to match 939 AKI events where the AKI-CB was completed with 1823 AKI events where AKI-CB was not completed.

Results

The AKI-CB was completed in 25.6% of patients within 24 h. The unadjusted case–fatality was higher when the AKI-CB was not completed versus when the AKI-CB was completed (24.4 versus 20.4%, P = 0.017). In multivariable analysis, AKI-CB completion within 24 h was associated with lower odds for in-hospital death [odds ratio (OR): 0.76; 95% confidence interval (95% CI): 0.62–0.92]. Increasing age (OR: 1.04; 95% CI: 1.03–1.05), hospital-acquired AKI (OR: 1.28; 95% CI: 1.04–1.58), AKI stage 2 (OR: 1.91; 95% CI: 1.53–2.39) and increasing Charlson's comorbidity index (CCI) [OR: 3.31 (95% CI: 2.37–4.64) for CCI of more than 5 compared with zero] had higher odds for death, whereas AKI during elective admission was associated with lower odds for death (OR: 0.29; 95% CI: 0.16–0.52). Progression to higher AKI stages was lower when the AKI-CB was completed (4.2 versus 6.7%, P = 0.02).

Conclusions

Compliance with an AKI-CB was associated with lower mortality and reduced progression of AKI to higher stages. The AKI-CB is simple and inexpensive, and could therefore be applied in all healthcare settings to improve outcomes.




Atherosclerotic renal artery stenosis is associated with elevated cell cycle arrest markers related to reduced renal blood flow and postcontrast hypoxia

2016-11-02T00:05:42-07:00

Background

Atherosclerotic renal artery stenosis (ARAS) reduces renal blood flow (RBF), ultimately leading to kidney hypoxia and inflammation. Insulin-like growth factor binding protein-7 (IGFBP-7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) are biomarkers of cell cycle arrest, often increased in ischemic conditions and predictive of acute kidney injury (AKI). This study sought to examine the relationships between renal vein levels of IGFBP-7, TIMP-2, reductions in RBF and postcontrast hypoxia as measured by blood oxygen level–dependent (BOLD) magnetic resonance imaging.

Methods

Renal vein levels of IGFBP-7 and TIMP-2 were obtained in an ARAS cohort (n= 29) scheduled for renal artery stenting and essential hypertensive (EH) healthy controls (n = 32). Cortical and medullary RBFs were measured by multidetector computed tomography (CT) immediately before renal artery stenting and 3 months later. BOLD imaging was performed before and 3 months after stenting in all patients, and a subgroup (N = 12) underwent repeat BOLD imaging 24 h after CT/stenting to examine postcontrast/procedure levels of hypoxia.

Results

Preintervention IGFBP-7 and TIMP-2 levels were elevated in ARAS compared with EH (18.5 ± 2.0 versus 15.7 ± 1.5 and 97.4 ± 23.1 versus 62.7 ± 9.2 ng/mL, respectively; P< 0.0001); baseline IGFBP-7 correlated inversely with hypoxia developing 24 h after contrast injection (r = –0.73, P< 0.0001) and with prestent cortical blood flow (r = –0.59, P= 0.004).

Conclusion

These data demonstrate elevated IGFBP-7 and TIMP-2 levels in ARAS as a function of the degree of reduced RBF. Elevated baseline IGFBP-7 levels were associated with protection against postimaging hypoxia, consistent with ‘ischemic preconditioning’. Despite contrast injection and stenting, AKI in these high-risk ARAS subjects with elevated IGFBP-7/TIMP-2 was rare and did not affect long-term kidney function.




Primary care physicians perceived barriers, facilitators and strategies to enhance conservative care for older adults with chronic kidney disease: a qualitative descriptive study

2016-11-02T00:05:42-07:00

Background

Although primary care physicians (PCPs) are often responsible for the routine care of older adults with chronic kidney disease (CKD), there is a paucity of evidence regarding their perspectives and practice of conservative (non-dialysis) care. We undertook a qualitative study to describe barriers, facilitators and strategies to enhance conservative, non-dialysis, CKD care by PCPs in the community.

Methods

Semi-structured telephone and face-to-face interviews were conducted with PCPs from Alberta, Canada. Participants were identified using a snowball sampling strategy and purposively sampled based on sex, age and rural/urban location of clinical practice. Eligible participants had managed at least one patient ≥75 years with Stage 5 CKD (estimated glomerular filtration rate <15 mL/min/1.73 m2, not on dialysis) in the prior year. Participant recruitment ceased when data saturation was reached. Transcripts were analyzed thematically using conventional content analysis.

Results

In total, 27 PCPs were interviewed. The majority were male (15/27), were aged 40–60 years (15/27) and had practiced in primary care for >20 years (14/27). Perceived barriers to conservative CKD care included: managing expectations of kidney failure for patients and their families; dealing with the complexity of medical management of patients requiring conservative care; and challenges associated with managing patients jointly with specialists. Factors that facilitated conservative CKD care included: establishing patient/family expectations early; preserving continuity of care; and utilizing a multidisciplinary team approach. Suggested strategies for improving conservative care included having: direct telephone access to clinicians familiar with conservative care; treatment decision aids for patients and their families; and a conservative care clinical pathway to guide management.

Conclusions

PCPs identified important barriers and facilitators to conservative care for their older patients with Stage 5 CKD. Further investigation of potential strategies that address barriers and enable facilitators is required to improve the quality of conservative care for older adults in the community.




Selective screening for distal renal tubular acidosis in recurrent kidney stone formers: initial experience and comparison of the simultaneous furosemide and fludrocortisone test with the short ammonium chloride test

2016-11-02T00:05:42-07:00

Background

Distal renal tubular acidosis (dRTA) is associated with renal stone disease, and it often needs to be considered and excluded in some recurrent calcium kidney stone formers (KSFs). However, a diagnosis of dRTA, especially when ‘incomplete’, can be missed and needs to be confirmed by a urinary acidification (UA) test. The gold standard reference test is still the short ammonium chloride (NH4Cl) test, but it is limited by gastrointestinal side effects and occasionally failure to ingest sufficient NH4Cl. For this reason, the furosemide plus fludrocortisone (F+F) test has been proposed as an easier and better-tolerated screening test. The aim of the present study was to assess the usefulness of the F+F test as a clinical screening tool for dRTA in a renal stone clinic.

Methods

We studied 124 patients retrospectively in whom incomplete dRTA was suspected: 71 had kidney stones only, 9 had nephrocalcinosis only and 44 had both. A total of 158 UA tests were performed: 124 F+F and 34 NH4Cl; both tests were completed in 34 patients.

Results

The mean age was 45.4 ± 15 years, and 49% of patients were male. The prevalence of complete and incomplete dRTAs was 7 and 13.7%, respectively. Of the 34 patients tested using both tests, 17 (50%) were abnormal and 4 (12%) were normal. Thirteen (39%) patients were abnormal by F+F, but normal by NH4Cl [sensitivity 100% (95% CI 80–100), specificity 24% (95% CI 7–50), positive predictive value 57% (95% CI 37–75), negative predictive value 100% (95% CI 40–100)].

Conclusions

The F+F test is characterized by an excellent sensitivity and negative predictive value, and the diagnosis of incomplete dRTA can be excluded reliably in a patient who acidifies their urine normally with this test. However, its lack of specificity is a drawback, and if there is any doubt, an abnormal F+F test may need to be confirmed by a follow-up NH4Cl test. Ideally, a prospective blinded study in unselected KSFs is needed to accurately assess the reliability of the F+F test in diagnosing, rather than excluding, dRTA.




Development and initial validation of prescribing quality indicators for patients with chronic kidney disease

2016-11-02T00:05:42-07:00

Background

Quality assessment is a key element for improving the quality of care. Currently, a comprehensive indicator set for measuring the quality of medication treatment in patients with chronic kidney disease (CKD) is lacking. Our aim was to develop and validate a set of prescribing quality indicators (PQIs) for CKD care, and to test the feasibility of applying this set in practice.

Methods

Potential indicators were based on clinical practice guidelines and evaluated using the RAND/UCLA Appropriateness Method. This is a structured process in which an expert panel assesses the validity of the indicators. Feasibility was tested in a Dutch primary care database including >4500 diabetes patients with CKD.

Results

An initial list of 22 PQIs was assessed by 12 experts. After changing 10 PQIs, adding 2 and rejecting 8, a final list of 16 indicators was accepted by the expert panel as valid. These PQIs focused on the treatment of hypertension, albuminuria, mineral and bone disorder, statin prescribing and possible unsafe medication. The indicators were successfully applied to measure treatment quality in the primary care database, but for some indicators the number of eligible patients was too small for reliable calculation. Results showed that there was room for improvement in the treatment quality of this population.

Conclusions

We developed a set of 16 PQIs for measuring the quality of treatment in CKD patients, which had sufficient content and face validity as well as operational feasibility. These PQIs can be used to point out priority areas for improvement.




Albuminuria and tolvaptan in autosomal-dominant polycystic kidney disease: results of the TEMPO 3:4 Trial

2016-11-02T00:05:42-07:00

Background

The TEMPO 3:4 Trial results suggested that tolvaptan had no effect compared with placebo on albuminuria in autosomal-dominant polycystic kidney disease (ADPKD) patients. However, the use of categorical ‘albuminuria events’ may have resulted in a loss of sensitivity to detect changes. The aim of this study is to investigate the effects of tolvaptan on albuminuria as a continuous variable.

Methods

Post hoc analysis of a 3-year prospective, blinded randomized controlled trial, including 1375 ADPKD patients. Albuminuria was measured in a spot morning urine sample prior to tolvaptan dosing and expressed as albumin-to-creatinine ratio (ACR).

Results

Baseline median (interquartile range) ACR was 3.2 (1.7–7.1) mg/mmol. Of note, 47.9% of ADPKD patients had normal, 48.7% moderately increased and 3.4% severely increased ACR. Subjects with higher baseline ACR had higher blood pressure and total kidney volume (TKV) and lower estimated glomerular filtration rate (eGFR). During follow-up, higher baseline ACR was associated with more rapid eGFR loss (P < 0.0001 for trend), but not with rate of growth in TKV. During the 3-year trial, ACR rose in placebo- and decreased in tolvaptan-treated patients (+0.23 versus –0.40 mg/mmol). The difference ACR increased over time, reaching a maximum of 24% at Month 36 (P < 0.001). At that time only a minor difference in blood pressure was observed (mean arterial pressure –1.9 mmHg for tolvaptan). The decrease in ACR was similar in all subgroups investigated, and remained after withdrawal of study drug. The beneficial effect of tolvaptan on TKV growth and eGFR loss was stronger in patients with higher baseline ACR.

Conclusions

In ADPKD, higher baseline albuminuria was associated with more eGFR loss. Tolvaptan decreased albuminuria compared with placebo, independent of blood pressure. Treatment efficacy of tolvaptan on changes in TKV and eGFR was more readily detected in patients with higher albuminuria.




Association between low birth weight and childhood-onset chronic kidney disease in Japan: a combined analysis of a nationwide survey for paediatric chronic kidney disease and the National Vital Statistics Report

2016-11-02T00:05:42-07:00

Background

Although numerous epidemiological surveys performed across several continents and ethnic groups have linked low birth weight (LBW) to increased risk of chronic kidney disease (CKD) in adulthood, the effects of birth weight and prematurity on development of CKD in childhood have not been clearly established.

Methods

Data on sex, LBW incidence and gestational age were compared between paediatric CKD cases and a control group. Paediatric CKD cases were obtained from a nationwide survey conducted by the Pediatric CKD Study Group in Japan. The population attributable fraction was calculated to evaluate the effects of reducing the prevalence of LBW infants (LBWI).

Results

Of 447 individuals born between 1993 and 2010 that fulfilled the eligibility criteria, birth weight data were obtained for 381 (85.2%) (231 boys and 150 girls), 106 (27.8%) of whom were LBWI. The proportion of LBWI in the general population during the same period was much lower (8.6%). Therefore, the risk ratio (RR) for paediatric CKD was significantly higher in the LBW group [crude RR: 4.10; 95% confidence interval (CI) 3.62–5.01], and the overall impact on paediatric CKD for removal of LBW amounted to 21.1% (95% CI 16.0–26.1%). In addition, 82 patients (21.9%) with paediatric CKD were born prematurely (before 37 weeks of gestation), and as with LBW, a strong correlation was observed between prematurity and CKD (RR: 4.73; 95% CI 3.91–5.73).

Conclusions

Both birth weight and gestational age were strongly associated with childhood-onset CKD in this study.




Lipoprotein(a) concentrations, apolipoprotein(a) isoforms and clinical endpoints in haemodialysis patients with type 2 diabetes mellitus: results from the 4D Study

2016-11-02T00:05:42-07:00

Background

High lipoprotein(a) [Lp(a)] concentrations and low molecular weight (LMW) apolipoprotein(a) [apo(a)] isoforms are associated with cardiovascular disease and mortality in the general population. We examined the association of both with all-cause mortality and cardiovascular endpoints in haemodialysis patients with diabetes mellitus.

Methods

This is a post hoc analysis of the prospective 4D Study (German Diabetes Dialysis Study) that evaluated atorvastatin compared with placebo in 1255 haemodialysis patients with type 2 diabetes mellitus (median follow-up 4 years). The association of natural logarithm-transformed Lp(a) concentrations (increment one unit) and apo(a) isoforms with outcomes was analysed by Cox proportional hazards regression. The influence of age (median 66 years) was evaluated by stratified survival analyses.

Results

The median baseline Lp(a) concentration was 11.5 mg/dL (IQR 5.0–41.8). A quarter of patients had at least one LMW apo(a) isoform. Increased Lp(a) concentrations were associated with all-cause mortality in the total group [hazard ratio (HR) 1.09 (95% CI 1.03–1.16), P = 0.004]. LMW apo(a) isoforms were only associated with all-cause mortality in patients ≤ 66 years [HR 1.38 (95% CI 1.05–1.80), P = 0.02]. The strongest association for Lp(a) concentrations and LMW apo(a) isoforms was found for death due to infection in patients ≤ 66 years [HR 1.39 (95% CI 1.14–1.71), P = 0.001; HR 2.17 (95% CI 1.26–3.75), P = 0.005]. Lp(a) concentrations were also associated with fatal stroke in patients ≤66 years of age [HR 1.54 (95% CI 1.05–2.24), P = 0.03]. Neither Lp(a) nor LMW apo(a) isoforms were associated with other atherosclerosis-related events.

Conclusions

High Lp(a) concentrations and LMW apo(a) isoforms are risk predictors for all-cause mortality and death due to infection in haemodialysis patients with diabetes mellitus. These associations are modified by age.




A novel COL4A1 frameshift mutation in familial kidney disease: the importance of the C-terminal NC1 domain of type IV collagen

2016-11-02T00:05:42-07:00

Background

Hereditary microscopic haematuria often segregates with mutations of COL4A3, COL4A4 or COL4A5 but in half of families a gene is not identified. We investigated a Cypriot family with autosomal dominant microscopic haematuria with renal failure and kidney cysts.

Methods

We used genome-wide linkage analysis, whole exome sequencing and cosegregation analyses.

Results

We identified a novel frameshift mutation, c.4611_4612insG:p.T1537fs, in exon 49 of COL4A1. This mutation predicts truncation of the protein with disruption of the C-terminal part of the NC1 domain. We confirmed its presence in 20 family members, 17 with confirmed haematuria, 5 of whom also had stage 4 or 5 chronic kidney disease. Eleven family members exhibited kidney cysts (55% of those with the mutation), but muscle cramps or cerebral aneurysms were not observed and serum creatine kinase was normal in all individuals tested.

Conclusions

Missense mutations of COL4A1 that encode the CB3 [IV] segment of the triple helical domain (exons 24 and 25) are associated with HANAC syndrome (hereditary angiopathy, nephropathy, aneurysms and cramps). Missense mutations of COL4A1 that disrupt the NC1 domain are associated with antenatal cerebral haemorrhage and porencephaly, but not kidney disease. Our findings extend the spectrum of COL4A1 mutations linked with renal disease and demonstrate that the highly conserved C-terminal part of the NC1 domain of the α1 chain of type IV collagen is important in the integrity of glomerular basement membrane in humans.




Pregnancy in dialysis patients in the new millennium: a systematic review and meta-regression analysis correlating dialysis schedules and pregnancy outcomes

2016-11-02T00:05:42-07:00

Background

Advances have been made in the management of pregnancies in women receiving dialysis; however, single-centre studies and small numbers of cases have so far precluded a clear definition of the relationship between dialysis schedules and pregnancy outcomes. The aim of the present systematic review was to analyse the relationship between dialysis schedule and pregnancy outcomes in pregnancies in chronic dialysis in the new millennium.

Methods

Medline–PubMed, Embase and the Cochrane library were searched (1 January 2000–31 December 2014: MESH, Emtree, free terms on pregnancy and dialysis). A separate analysis was performed for case series (more than five cases) and case reports. Meta-regression was performed in case series dealing with the larger subset of haemodialysis (HD) patients; case reports were analysed separately [according to peritoneal dialysis (PD) versus HD; conception before or during dialysis].

Results

We obtained 190 full texts and 25 congress abstracts from 2048 references. We selected 101 full papers and 25 abstracts (36 series; 90 case reports), for a total of 681 pregnancies in 647 patients. In the case series (574 pregnancies in 543 patients), preterm delivery was extremely frequent (83%). Meta-regression analysis showed a relationship between hours of dialysis per week in HD and preterm delivery, and was significant for preterm deliveries (<37 gestational weeks: P = 0.044; r2 = 0.22) and for small for gestational age (SGA) (P = 0.017; r2 = 0.54). SGA was closely associated with the number of dialysis sessions per week (P = 0.003; r2 = 0.84). Case report analysis suggests a lower incidence of SGA on HD versus PD (31 versus 66.7%; P = 0.015). No evidence of an increased risk of congenital abnormality was found in the retrieved papers.

Conclusions

Data on pregnancy on dialysis are heterogeneous but rapidly accumulating; the main determinant of outcomes on HD is the dialysis schedule. The differences between PD and HD should be further analysed.




Solute solver 'what if module for modeling urea kinetics

2016-11-02T00:05:42-07:00

Background

The publicly available Solute Solver module allows calculation of a variety of two-pool urea kinetic measures of dialysis adequacy using pre- and postdialysis plasma urea and estimated dialyzer clearance or estimated urea distribution volumes as inputs. However, the existing program does not have a ‘what if’ module, which would estimate the plasma urea values as well as commonly used measures of hemodialysis adequacy for a patient with a given urea distribution volume and urea nitrogen generation rate dialyzed according to a particular dialysis schedule.

Methods

Conventional variable extracellular volume 2-pool urea kinetic equations were used.

Results

A javascript-HTML Web form was created that can be used on any personal computer equipped with internet browsing software, to compute commonly used Kt/V-based measures of hemodialysis adequacy for patients with differing amounts of residual kidney function and following a variety of treatment schedules.

Conclusions

The completed Web form calculator may be particularly useful in computing equivalent continuous clearances for incremental hemodialysis strategies.




Impact of the Banff 2013 classification on the diagnosis of suspicious versus conclusive late antibody-mediated rejection in allografts without acute dysfunction

2016-11-02T00:05:42-07:00

Background

The Banff classification is used worldwide to characterize pathological findings in renal allograft biopsies. During the 11th Banff meeting, relevant changes were introduced in the diagnostic criteria for Category 2 antibody-mediated rejection (ABMR). Here, we assess the effect of these changes on the diagnosis of late chronic ABMR.

Methods

Seventy-three indication renal graft biopsies (chronic dysfunction, proteinuria and/or the presence of de novo donor-specific antibodies) from 68 kidney transplant recipients initially classified following the Banff 2009 criteria were reviewed and reclassified as per the new Banff 2013 criteria.

Results

The diagnostic category changed in 18% of the study biopsies with Banff 2013. The reclassification mainly involved Category 2 cases, from which 23.5% of the biopsies from older patients with worse graft function were overlooked by Banff 2009. ABMR was ruled out in 13% of cases under the Banff 2009 criteria. A significant number of the study samples were conclusively diagnosed as ABMR (40% as per Banff 2009 and 74% as per Banff 2013; P = 0.006), because of the inclusion of microvascular inflammation and the acceptance of some ultrastructural diagnostic criteria. However, when following the criteria of the new classification, samples with histological signs of chronic ABMR, in which human leucocyte antigen donor-specific antibodies are not detected or ultrastructural studies are not performed, may be inadequately characterized.

Conclusions

The Banff 2013 classification helps in making a diagnosis of late ABMR, identifying cases, decreasing the percentage of suspected ABMR and making more conclusive diagnoses.




Epidemiology and management of hypertension in paediatric and young adult kidney transplant recipients in The Netherlands

2016-11-02T00:05:42-07:00

Introduction

Hypertension in kidney transplant recipients (KTRs) is a risk factor for cardiovascular mortality and graft loss. Data on the prevalence of hypertension and uncontrolled hypertension (uHT) in paediatric and young adult KTRs are scarce. Also, it is unknown whether ‘transition’ (the transfer from paediatric to adult care) influences control of hypertension. We assessed the prevalence of hypertension and uHT among Dutch paediatric and young adult KTRs and analysed the effects of transition. Additionally, we made an inventory of variations in treatment policies in Dutch transplant centres.

Methods

Cross-sectional and longitudinal national data from living KTRs ≤30 years of age (≥1-year post-transplant, eGFR >20 mL/min) were extracted from the ‘RICH Q’ database, which comprises information about all Dutch KTRs <19 years of age, and the Netherlands Organ Transplant Registry database for adult KTRs (≥18–30 years of age). We used both upper-limit blood pressure (BP) thresholds for treatment according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. uHT was defined as a BP above the threshold. A questionnaire on treatment policies was sent to paediatric and adult nephrologists at eight Dutch transplant centres.

Results

Hypertension and uHT were more prevalent in young adult KTRs (86.4 and 75.8%) than in paediatric KTRs (62.7 and 38.3%) according to the KDIGO definition. Time after transplantation was comparable between these groups. Longitudinal analysis showed no evidence of effect of transition on systolic BP or prevalence of uHT. Policies vary considerably between and within centres on the definition of hypertension, BP measurement and antihypertensive treatment.

Conclusion

Average BP in KTRs increases continuously with age between 6 and 30 years. Young adult KTRs have significantly more uHT than paediatric KTRs according to KDIGO guidelines. Transition does not influence the prevalence of uHT.




Pregnancy outcomes after kidney graft in Italy: are the changes over time the result of different therapies or of different policies? A nationwide survey (1978-2013)

2016-11-02T00:05:42-07:00

Background Kidney transplantation is the treatment of choice to restore fertility to women on renal replacement therapy. Over time, immunosuppressive, support therapies and approaches towards high-risk pregnancies have changed. The aim of this study was to analyse maternal–foetal outcomes in two cohorts of transplanted women who delivered a live-born baby in Italy in 1978–2013, dichotomized into delivery before and after January 2000. Methods A survey involving all the Italian transplant centres was carried out, gathering data on all pregnancies recorded since the start of activity at each centre; the estimated nationwide coverage was 75%. Data on cause of ESRD, dialysis, living/cadaveric transplantation, drug therapy, comorbidity, and the main maternal–foetal outcomes were recorded and reviewed. Data were compared with a low-risk cohort of pregnancies from two large Italian centres (2000–14; Torino and Cagliari Observational Study cohort). Results The database consists of 222 pregnancies with live-born babies after transplantation (83 before 2000 and 139 in 2000–13; 68 and 121 with baseline and birth data, respectively), and 1418 low-risk controls. The age of the patients significantly increased over time (1978–99: age 30.7 ± 3.7 versus 34.1 ± 3.7 in 2000–13; P < 0.001). Azathioprine, steroids and cyclosporine A were the main drugs employed in the first time period, while tacrolimus emerged in the second. The prevalence of early preterm babies increased from 13.4% in the first to 27.1% in the second period (P = 0.049), while late-preterm babies non-significantly decreased (38.8 versus 33.1%), thus leaving the prevalence of all preterm babies almost unchanged (52.2 and 60.2%; P = 0.372). Babies below the 5th percentile decreased over time (22.2 versus 9.6%; P = 0.036). In spite of high prematurity rates, no neonatal deaths occurred after 2000. The results in kidney transplant patients are significantly different from controls both considering all cases [preterm delivery: 57.3 versus 6.3%; early preterm: 22.2 versus 0.9%; small for gestational age (SGA): 14 versus 4.5%; P < 0.001] and considering only transplant patients with normal kidney function [preterm delivery: 35 versus 6.3%; early preterm: 10 versus 0.9%; SGA: 23.7 versus 4.5% (P < 0.001); risks increase across CKD stages]. Kidney function remained stable in most of the patients up to 6 months after delivery. Multipl[...]



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2016-11-02T00:05:42-07:00