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Preview: Nephrology Dialysis Transplantation - current issue

Nephrology Dialysis Transplantation Current Issue





Published: Wed, 10 Jan 2018 00:00:00 GMT

Last Build Date: Fri, 12 Jan 2018 01:51:04 GMT

 



Announcements

Wed, 10 Jan 2018 00:00:00 GMT

News from ERA-EDTA:



Big data in nephrology—a time to rethink

Thu, 14 Dec 2017 00:00:00 GMT

Big data are abundant in nephrology. We celebrate big data; we embrace them because of their sample sizes and give them space in the most respected journals. We make policy and funding decisions based on big data. But what happened to the interventional studies? Could the ready presence of big data be a bane of nephrology? What if the interpretations of the big data are flawed? Few of us really understand the statistical methods that underlie these big data, so all we read is the conclusion. We will take the example of a study published in this issue of NDT to note that the interpretation of big data by another set of nephrologists could lead to a conclusion quite contrary to that of the authors.



Creatinine generation from kinetic modeling with or without postdialysis serum creatinine measurement: results from the HEMO study

Mon, 13 Nov 2017 00:00:00 GMT

John T. Daugirdas and Thomas A. Depner; Nephrol Dial Transplant 2017; gfx038. doi: 10.1093/ndt/gfx038



Strategies to manage cardiovascular risk in chronic kidney disease

Thu, 09 Nov 2017 00:00:00 GMT

blood pressurechronic kidney diseasedialysislipidsvascular calcification



Increased mortality in haemodialysis patients administered high doses of erythropoiesis-stimulating agents: a propensity score-matched analysis

Wed, 25 Oct 2017 00:00:00 GMT

Rafael Pérez-García, Javier Varas, Alejandro Cives, Alejandro Martín-Malo, Pedro Aljama, Rosa Ramos, Julio Pascual, Stefano Stuard, Bernard Canaud and José Ignacio Merello on behalf of the ORD group; Nephrol Dial Transplant 2017; gfx269. doi: 10.1093/ndt/gfx269



New-onset diabetes after kidney transplantation: can the risk be modified by choosing immunosuppression regimen based on pretransplant viral serology?

Mon, 16 Oct 2017 00:00:00 GMT

Abstract
Background
This study aimed to analyze adult kidney transplant recipients (KTRs) for the risk of new-onset diabetes after transplantation (NODAT) associated with viral serologies and immunosuppression regimens [tacrolimus (Tac) + mycophenolate (MPA), cyclosporine (CSA) + MPA, sirolimus (SRL) + MPA, SRL + CSA or SRL +Tac].
Methods
Cox regression models were used to examine the risk of NODAT in the first posttransplant year associated with: (i) CSA + MPA, SRL + MPA, SRL + MPA or SRL + Tac versus reference, Tac + MPA; (ii) pretransplant viral serology [+ or −; hepatitis B core (HBc), hepatitis C (HCV), cytomegalovirus (CMV) or Epstein Barr Virus (EBV)]; and (iii) interactions between immunosuppression regimens and the viral serology found significant in the main analysis.
Results
Adult KTRs (n = 97 644) from January 1995 through September 2015 were studied. HCV+ [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.31–1.68] or CMV+ (HR 1.12, 95% CI 1.06–1.19) serology was a risk factor and HBc+ (HR 1.04, 95% CI 0.95–1.15) or EBV+ (HR 1.06, 95% CI 0.97–1.15) serology was not a risk factor for NODAT. Regardless of associated HCV or CMV serology, risk of NODAT relative to the reference regimen (Tac + MPA) was lower with CSA + MPA [HCV−: HR 0.74, 95% CI 0.65–0.85; HCV+: HR 0.47, 95% CI 0.28–0.78; CMV−: CSA + MPA HR 0.68, 95% CI 0.54–0.86; CMV+: (CSA + MPA) HR 0.73, 95% CI 0.63–0.85] and similar with SRL + CSA or SRL + MPA. In KTRs with HCV− or CMV+ serology, SRL + Tac was associated with a higher risk of NODAT relative to reference [HCV− (HR 1.43, 95% CI 1.17–1.74) and CMV+ (HR 1.44, 95% CI 1.14–1.81), respectively]. The risk for NODAT-free graft loss was lower with Tac + MPA than the other regimens.
Conclusions
Tailoring immunosuppression regimen based on HCV or CMV serology may modify the risk of developing NODAT in KTRs.



Immune complexes containing serum B-cell activating factor and immunoglobulin G correlate with disease activity in systemic lupus erythematosus

Tue, 08 Aug 2017 00:00:00 GMT

Abstract
Background. B-cell activating factor belonging to the TNF family (BAFF) is important for the survival of autoreactive B-cells in systemic lupus erythematosus (SLE). However, the association between serum BAFF levels and SLE disease activity is controversial. Independently, autoantibodies targeting BAFF [immunoglobulin G (IgG) anti-BAFF] have also been described in SLE patients and were associated with increased disease activity. The aim of our study was to analyse the relationship between SLE disease manifestations and serum levels of BAFF, IgG anti-BAFF and BAFF–IgG complexes.
Methods
Levels of serum BAFF, IgG anti-BAFF and BAFF–IgG complexes were quantified by enzyme-linked immunosorbent assay. IgG anti-BAFF and BAFF–IgG complexes were further characterized using serum fractions obtained by fast protein liquid chromatography. To study the association of serum BAFF, IgG anti-BAFF and BAFF–IgG complex levels with SLE manifestations, 373 visits from 178 patients prospectively included in the Swiss SLE Cohort Study were analysed.
Results
While IgG anti-BAFF levels were not associated with clinical manifestations of SLE, serum BAFF levels correlated with disease activity and were higher in patients with renal involvement. Interestingly, we could also demonstrate the occurrence of BAFF–IgG complexes of different sizes in the sera of SLE patients, which were not due to treatment with belimumab and differed from complexes constructed in vitro. Most strikingly, the levels of these BAFF–IgG complexes were found to strongly correlate with overall disease activity, low complement levels and a history of lupus nephritis.
Conclusion
BAFF–IgG complexes strongly correlate with disease activity in SLE patients, suggesting a pathogenic role in SLE.



Vitamin K antagonist use and mortality in dialysis patients

Wed, 02 Aug 2017 00:00:00 GMT

Abstract
Background
The risk–benefit ratio of vitamin K antagonists for different CHA2DS2-VASc scores in patients with end-stage renal disease treated with dialysis is unknown. The aim of this study was to investigate the association between vitamin K antagonist use and mortality for different CHA2DS2-VASc scores in a cohort of end-stage renal disease patients receiving dialysis treatment.
Methods
We prospectively followed 1718 incident dialysis patients. Hazard ratios were calculated for all-cause and cause-specific (stroke, bleeding, cardiovascular and other) mortality associated with vitamin K antagonist use.
Results
Vitamin K antagonist use as compared with no vitamin K antagonist use was associated with a 1.2-fold [95% confidence interval (95% CI) 1.0–1.5] increased all-cause mortality risk, a 1.5-fold (95% CI 0.6–4.0) increased stroke mortality risk, a 1.3-fold (95% CI 0.4–4.2) increased bleeding mortality risk, a 1.2-fold (95% CI 0.9–1.8) increased cardiovascular mortality risk and a 1.2-fold (95% CI 0.8–1.6) increased other mortality risk after adjustment. Within patients with a CHA2DS2-VASc score ≤1, vitamin K antagonist use was associated with a 2.8-fold (95% CI 1.0–7.8) increased all-cause mortality risk as compared with no vitamin K antagonist use, while vitamin K antagonist use within patients with a CHA2DS2-VASc score ≥2 was not associated with an increased mortality risk after adjustment.
Conclusion
Vitamin K antagonist use was not associated with a protective effect on mortality in the different CHA2DS2-VASc scores in dialysis patients. The lack of knowledge on the indication for vitamin K antagonist use could lead to confounding by indication.



Inflammation induces osteoclast differentiation from peripheral mononuclear cells in chronic kidney disease patients: crosstalk between the immune and bone systems

Fri, 21 Jul 2017 00:00:00 GMT

Abstract
Background
Inflammation and immune system alterations contribute to bone damage in many pathologies by inducing the differentiation of osteoclasts (OCs), the bone resorbing cells. This link is largely unexplored in chronic kidney disease (CKD) and haemodialysis (HD) patients, in which reduced renal function is accompanied by an increased inflammatory state and skeletal abnormality.
Methods
We used ex vivo culture experiments to investigate the osteoclastogenic potential of peripheral blood mononuclear cells (PBMCs) of CKD and HD patients, focusing on immune cell subsets and inflammatory cytokines such as LIGHT and receptor activator of nuclear factor κB ligand (RANKL).
Results
We observed spontaneous osteoclastogenesis with a significant increase in OC formation and bone resorbing activity in late-stage CKD and HD patients when compared with early-stage CKD patients and healthy donors, likely due to an increased expression of RANKL and LIGHT (homologous to Lymphotoxins exhibiting Inducible expression and competing with herpes simplex virus Glycoprotein D for herpes virus entry mediator [HVEM], a receptor expressed by T lymphocytes) in PBMCs. Specific inhibition of these cytokines in PBMCs isolated from CKD stages 3b–5 and HD patients induced the reduction of OC formation in vitro. The phenotypic characterization of peripheral blood cells revealed a significant increase of OC precursors (CD14+CD11b+CD51/61+) and CD14+CD16+ monocytes in advanced CKD and HD patients compared with the control group.
Conclusions
Our results suggest that circulating inflammatory monocytes from advanced CKD or HD patients trans differentiate into OCs in vitro and play a relevant role in mineral bone disorders and that LIGHT and RANKL represent new potential therapeutic targets in these settings.



Modulation of leucocytic angiotensin-converting enzymes expression in patients maintained on high-permeable haemodialysis

Wed, 19 Jul 2017 00:00:00 GMT

Abstract
Background
High mortality of haemodialysis patients is associated with systemic chronic inflammation and overactivation of the renin–angiotensin system (RAS). Insufficient elimination of pro-inflammatory immune mediators, especially in the molecular weight range of 15–45 kDa, may be one of the reasons for this. Employment of haemodialysis membranes with increased permeability was shown to ameliorate the inflammatory response and might modulate the effects of local RAS. In this study, we tested the impact of high cut-off (HCO), medium cut-off (MCO) and high-flux (HF) dialysis on leucocytic transcripts of angiotensin-converting enzymes (ACE and ACE2). Additionally, the impact of HCO, MCO and HF sera and dialysates on local ACEs and inflammation markers was tested in THP-1 monocytes.
Methods
Patients’ leucocytes were obtained from our recent clinical studies comparing HCO and MCO dialysers with HF. The cells were subjected to quantitaive polymerase chain reaction (qPCR) analyses with TaqMan probes specific for ACE, ACE2 and angiotensin II (AngII) and Ang1–7 receptors. Sera and dialysates from the clinical trials as well as samples from in vitro dialysis were tested on THP-1 monocytic cells. The cells were subjected to qPCR analyses with TaqMan probes specific for ACE, ACE2, interleukin-6 and tumour necrosis factor α and immunocytochemistry with ACE and ACE2 antibodies.
Results
Leucocytes obtained from patients treated with HCO or MCO demonstrated decreased transcript expression of ACE, while ACE2 was significantly upregulated as compared with HF. Receptors for AngII and Ang1–7 remained unchanged. THP-1 monocytes preconditioned with HCO and MCO patients’ or in vitro dialysis sera reflected the same expressional regulation of ACE and ACE2 as those observed in HCO and MCO leucocytes. As a complementary finding, treatment with HCO and MCO in vitro dialysates induced a pro-inflammatory response of the cells as demonstrated by elevated messenger RNA expression of tumour necrosis factor α and interleukin-6, as well as upregulation of ACE and decreased levels of ACE2.
Conclusions
Taken together, these data demonstrate that employment of membranes with high permeability eliminates a spectrum of mediators from circulation that affect the RAS components in leucocytes, especially ACE/ACE2.



Relationships between iron dose, hospitalizations and mortality in incident haemodialysis patients: a propensity-score matched approach

Thu, 13 Jul 2017 00:00:00 GMT

Abstract
Background
Intravenous iron management is common in the haemodialysis population. However, the safest dosing strategy remains uncertain, in terms of the risk of hospitalization and mortality. We aimed to determine the effects of cumulative monthly iron doses on mortality and hospitalization.
Methods
This multicentre observational retrospective propensity-matched score study included 1679 incident haemodialysis patients. We measured baseline demographic variables, haemodialysis clinical parameters and laboratory analytical values. We compared outcomes among quartiles of cumulative iron dose (mg/kg/month). We implemented propensity-score matching (PSM) to reduce confounding due to indication. In the PSM cohort (330 patients), we compared outcomes between groups that received cumulative iron doses above and below 5.66 mg/kg/month.
Results
Kaplan–Meier analyses showed that the high iron dose group had significantly worse survival than the low iron dose group. A univariate analysis indicated that the monthly iron dose could significantly predict mortality. However, a multivariate regression did not confirm that finding. The multivariate regression analysis revealed that iron doses  >5.58 mg/kg/month were not associated with elevated mortality risk, but they were associated with elevated risks of all-cause and cardiovascular-related hospitalizations. These results were ratified in the PSM population.
Conclusions
Intravenous iron administration is advisable for maintaining haemoglobin levels in patients that receive haemodialysis. Our data suggested that large monthly iron doses, adjusted for body weight, were associated with more hospitalizations, but not with mortality or infection-related hospitalizations.



The reduction of heparan sulphate in the glomerular basement membrane does not augment urinary albumin excretion

Sat, 08 Jul 2017 00:00:00 GMT

Abstract
Background
Heparan sulphate proteoglycan (HSPG) is present in the glomerular basement membrane (GBM) and is thought to play a major role in the glomerular charge barrier. Reductions and structural alterations of HSPG are observed in different types of kidney diseases accompanied by proteinuria. However, their causal relations remain unknown.
Methods
We generated podocyte-specific exostosin-like 3 gene (Extl3) knockout mice (Extl3KO) using a Cre-loxP recombination approach. A reduction of HSPG was expected in the GBM of these mice, because EXTL3 is involved in its synthesis. Mice were separated into three groups, according to the loads on the glomeruli: a high-protein diet group, a high-protein and high-sodium diet group and a hyperglycaemic group induced by streptozotocin treatment in addition to maintenance on a high-protein and high-sodium diet. The urinary albumin:creatinine ratio was measured at 7, 11, 15 and 19 weeks of age. Renal histology was also investigated.
Results
Podocyte-specific expression of Cre recombinase was detected by immunohistochemistry. Moreover, immunofluorescent staining demonstrated a significant reduction of HSPG in the GBM. Electron microscopy showed irregularities in the GBM and effacement of the foot processes in Extl3KO. The values of the urinary albumin:creatinine ratio were within the range of microalbuminuria in all groups and did not significantly differ between the control mice and Extl3KO.
Conclusions
The reduction of HSPG in the GBM did not augment urinary albumin excretion. HSPG’s anionic charge appears to contribute little to the glomerular charge barrier.



Local delivery of liposomal prednisolone leads to an anti-inflammatory profile in renal ischaemia–reperfusion injury in the rat

Sat, 08 Jul 2017 00:00:00 GMT

Abstract
Background
Treatment of inflammatory kidney diseases with systemic high-dose glucocorticoids (GCs) has severe side effects. Liposomal encapsulation could facilitate local delivery of GCs to the inflamed kidney, as liposomes encapsulate their payload until extravasation at sites of inflammation, potentially resulting in local bioactivity. Our aim was to evaluate the ability of liposomes to accumulate locally after renal ischaemia–reperfusion injury in the rat and to study its effect on macrophages.
Methods
In vitro, human macrophages were incubated with fluorescent liposomes, liposomal prednisolone, prednisolone, empty liposomes or saline. Uptake was studied microscopically and treatment effect was assessed by interkeukin 6 (IL-6) enzyme-linked immunosorbent assay. The mechanism of action was evaluated by analysing GC receptor activation by microscopy and quantitative polymerase chain reaction (qPCR). In vivo, rats were subjected to ischaemia–reperfusion injury and were injected intravenously with fluorescent liposomes, liposomal prednisolone, prednisolone, empty liposomes or saline. Uptake was measured by the FLARE camera and the treatment effect by immunohistochemistry for myeloid cells and qPCR for inflammatory markers.
Results
In vitro, macrophages internalized liposomes after 8 hours. Prednisolone or liposomal prednisolone treatment reduced IL-6 production and both compounds induced translocation of the GC receptor to the nucleus and upregulation of PER1 messenger RNA (mRNA), indicating a similar mechanism of action. In vivo, fluorescent liposomes accumulated in the inflamed kidney. Liposomal prednisolone treatment increased the presence of ED2-positive anti-inflammatory macrophages and both prednisolone and liposomal prednisolone reduced monocyte chemoattractant protein-1 (MCP-1) mRNA production, indicating a reduced pro-inflammatory profile in the kidney.
Conclusions
Liposomal encapsulation is a promising strategy for local delivery of glucocorticoids to the inflamed kidney.



Effect of renin–angiotensin–aldosterone system blockade in adults with diabetes mellitus and advanced chronic kidney disease not on dialysis: a systematic review and meta-analysis

Sun, 02 Jul 2017 00:00:00 GMT

Abstract
The presumed superiority of renin–angiotensin–aldosterone system (RAAS)-blocking agents over other antihypertensive agents in patients with diabetes to delay development of end-stage kidney disease (ESKD) has recently been challenged. In addition, there is ongoing uncertainty whether RAAS-blocking agents reduce mortality and/or delay ESKD in patients with diabetes and chronic kidney disease (CKD) stages 3–5. In this subgroup, there might be an expedited need for renal replacement therapy (RRT) when RAAS-blocking agents are used. We conducted a meta-analysis of randomized controlled trials (RCTs) of at least 6-months duration in adult patients with diabetes who also have non-dialysis CKD stages 3–5. RCTs comparing single RAAS-blocking agents to placebo or alternative antihypertensive agents were included. Outcomes of interest were all-cause mortality, cardiovascular morbidity, progression of renal function, ESKD and adverse events. A total of nine trials (n = 9797 participants with CKD stages 3–5) fit our inclusion criteria. There was no difference between the RAAS group and control group regarding all-cause mortality {relative risk [RR] = 0.97 [95% confidence interval (CI) 0.85–1.10]}, cardiovascular mortality [RR = 1.03 (95% CI 0.75–1.41)] and adverse events [RR = 1.05 (95% CI 0.89–1.25)]. There was a trend for a favourable effect for non-fatal cardiovascular events [RR = 0.90 (95% CI 0.81–1.00)] and a lower risk of the composite endpoint need for RRT/doubling of serum creatinine [RR = 0.81 (95% CI 0.70–0.92)] in the RAAS-blocking agents group versus the control group. We found evidence that in patients with diabetes mellitus and CKD stages 3–5, treatment with RAAS-blocking agents did not result in a clear survival advantage. The effect on renal outcomes did depend on the selected outcome measure. However, we did not find evidence that the use of RAAS-blocking agents expedited the need for RRT in patients with CKD stages 3–5.



Intradialytic hypotension, blood pressure changes and mortality risk in incident hemodialysis patients

Fri, 21 Apr 2017 00:00:00 GMT

Abstract
Background
Intradialytic hypotension (IDH) occurs frequently in maintenance hemodialysis (HD) patients and may be associated with higher mortality. We hypothesize that nadir intradialytic systolic blood pressure (niSBP) is inversely related to death risk while iSBP change (Δ) and IDH frequency are incrementally associated with all-cause mortality.
Methods
In a US-based cohort of 112 013 incident HD patients over a 5-year period (2007–11), using niSBP, ΔiSBP (pre-HD SBP minus niSBP) and IDH frequency (proportion of HD treatments with niSBP <90 mmHg) within the first 91 days of HD, we examined mortality-predictability at 1, 2 and 5 years using Cox models and restricted cubic splines adjusted for case-mix, comorbidities and laboratory covariates.
Results
We observed that niSBP of <90 and ≥140 mmHg had a 5-year mortality hazard ratio (HR) (95% confidence interval) of 1.57 (1.47–1.67) and 1.25 (1.18–1.33), respectively, compared with niSBP 110 to <120 mmHg. ΔiSBP of <15 and ≥50 compared with 21–30 mmHg had mortality HR of 1.31 (1.26–1.37) and 1.32 (1.24–1.39), respectively. Among patients with >40% IDH frequency, we observed a mortality HR of 1.49 (1.42–1.57) compared with 0% IDH frequency in fully adjusted models. These associations were robust at 1 and 2 years of follow-up.
Conclusion
In conclusion, we observed a U-shaped association between niSBP and ΔiSBP and mortality and a direct linear relationship between IDH frequency and mortality. Our findings lend some prognostic insight of HD blood pressure and hemodynamics, and have the potential to guide blood pressure management strategies among the HD population.



Urea and chronic kidney disease: the comeback of the century? (in uraemia research)

Wed, 12 Apr 2017 00:00:00 GMT

Abstract
Urea, a marker of uraemic retention in chronic kidney disease (CKD) and of adequacy of intradialytic solute removal, has traditionally been considered to be biologically inert. However, a number of recent experimental data suggest that urea is toxic at concentrations representative for CKD. First of all, at least five studies indicate that urea itself induces molecular changes related to insulin resistance, free radical production, apoptosis and disruption of the protective intestinal barrier. Second, urea is at the origin of the generation of cyanate, ammonia and carbamylated compounds, which as such all have been linked to biological changes. Especially carbamylation has been held responsible for post-translational protein modifications that are involved in atherogenesis and other functional changes. In observational clinical studies, these carbamylated compounds were associated with cardiovascular and overall morbidity and mortality. These findings shed new light on the validity of Kt/Vurea as a marker of dialysis adequacy. Yet, also the views that the kinetics of urea are not representative of the kinetics of several other uraemic retention solutes, and that urea cannot be held responsible for all complex metabolic and clinical changes responsible for the uraemic syndrome, still remain valid. Future efforts to improve the outcome of patients with CKD might be directed at further improving removal of solutes implied in the uraemic syndrome, including but not restricted to urea, also taking into account the impact of the intestine and (residual) renal function on solute concentration.



Nationwide multicentre kidney biopsy study of Japanese patients with type 2 diabetes

Thu, 02 Mar 2017 00:00:00 GMT

Abstract
Background
The clinical and pathologic manifestations of nephropathy due to type 2 diabetes are diverse, but large-scale pathologic studies with long-term observations are limited.
Methods
Kidney biopsies and clinical data of 600 patients with type 2 diabetes were collected retrospectively from 13 centres across Japan. Thirteen pathologic findings (nine glomerular lesions, two interstitial lesions and two vascular lesions) were clearly defined and scored.
Results
During the observation period, there were 304 composite kidney events [dialysis, doubling of creatinine or reduction of estimated glomerular filtration rate (eGFR) by half], 31 instances of chronic kidney disease (CKD) G5D, 76 cardiovascular events and 73 deaths. The mean observation period was 72.4 months. The distribution of CKD heat map categories for the 600 patients was 103 green or yellow, 149 orange and 348 red. Even in the cases in the green and yellow category, diffuse lesions (81.6%), polar vasculosis (42.6%) and subendothelial space widening (35.1%) were commonly detected. Cox proportional hazard analysis revealed that the presence of nodular lesions [hazard ratio (HR) 21.1, 95% confidence interval (CI) 5.3–84.6], exudative lesions (HR 5.1, 95% CI 1.3–20.3) and mesangiolysis (HR 7.6, 95% CI 2.0–28.8) in cases in the green and yellow category were associated with significantly great impact on composite kidney events after adjustment for clinical risk factors.
Conclusions
This nationwide study on kidney biopsy of 600 cases with type 2 diabetes revealed that pathologic findings (presence of nodular lesions, exudative lesions and mesangiolysis) were strong predictors of kidney events in low-risk patients.



Chronic disease management interventions for people with chronic kidney disease in primary care: a systematic review and meta-analysis

Mon, 23 Jan 2017 00:00:00 GMT

Abstract
Background
Primary care providers manage the majority of patients with chronic kidney disease (CKD), although the most effective chronic disease management (CDM) strategies for these patients are unknown. We assessed the efficacy of CDM interventions used by primary care providers managing patients with CKD.
Methods
The Medline, Embase and Cochrane Central databases were systematically searched (inception to November 2014) for randomized controlled trials (RCTs) assessing education-based and computer-assisted CDM interventions targeting primary care providers managing patients with CKD in the community. The efficacy of CDM interventions was assessed using quality indicators [use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), proteinuria measurement and achievement of blood pressure (BP) targets] and clinical outcomes (change in BP and glomerular filtration rate). Two independent reviewers evaluated studies for inclusion, quality and extracted data. Random effects models were used to estimate pooled odds ratios (ORs) and weighted mean differences for outcomes of interest.
Results
Five studies (188 clinics; 494 physicians; 42 852 patients with CKD) were included. Two studies compared computer-assisted intervention strategies with usual care, two studies compared education-based intervention strategies with computer-assisted intervention strategies and one study compared both these intervention strategies with usual care.Compared with usual care, computer-assisted CDM interventions did not increase the likelihood of ACEI/ARB use among patients with CKD {pooled OR 1.00 [95% confidence interval (CI) 0.83–1.21]; I2 = 0.0%}. Similarly, education-related CDM interventions did not increase the likelihood of ACEI/ARB use compared with computer-assisted CDM interventions [pooled OR 1.12 (95% CI 0.77–1.64); I2 = 0.0%]. Inconsistencies in reporting methods limited further pooling of data.
Conclusions
To date, there have been very few randomized trials testing CDM interventions targeting primary care providers with the goal of improving care of people with CKD. Those conducted to date have shown minimal impact, suggesting that other strategies, or multifaceted interventions, may be required to enhance care for patients with CKD in the community.



Albuminuria is associated with a higher prevalence of depression in a population-based cohort study: the Maastricht Study

Tue, 13 Dec 2016 00:00:00 GMT

Abstract
Background
Depression is common in individuals with chronic kidney disease (CKD). However, data on the association of albuminuria, which together with reduced estimated glomerular filtration rate (eGFR) defines CKD, with depression are scarce and conflicting. In addition, it is not clear when in the course from normal kidney function to CKD the association with depression appears.
Methods
We examined the cross-sectional associations of albuminuria and eGFR with depressive symptoms and depressive episodes in 2872 and 3083 40- to 75-year-old individuals, respectively, who completed the baseline survey of an ongoing population-based cohort study conducted in the southern part of The Netherlands between November 2010 and September 2013. Urinary albumin excretion (UAE) was the average UAE in two 24-h urine collections and eGFR was calculated with the Chronic Kidney Disease Epidemiology Collaboration equation based on creatinine and cystatin C. Depressive symptoms were assessed with the 9-item Patient Health Questionnaire (PHQ-9) and the presence of a minor or major depressive episode was assessed with the MINI-International Neuropsychiatric Interview.
Results
In total, 5.4% had a minor or major depressive episode. UAE was <15 mg/24 h in 81.2%, 15–<30 mg/24 h in 10.3% and ≥30 mg/24 h in 8.6%. In a multivariable logistic regression analysis adjusted for potential confounders, and with UAE <15 mg/24 h as reference category, the odds ratio for a minor or major depressive episode was 2.13 [95% confidence interval (CI) 1.36–3.36] for UAE 15–<30 mg/24 h and 1.81 (95% CI 1.10–2.98) for UAE ≥30 mg/24 h. The average eGFR was 88.2 ± 14.7 mL/min/1.73 m2. eGFR was not associated with the presence of a minor or major depressive episode. Results were similar when we assessed associations with depressive symptoms or clinically relevant depressive symptoms (PHQ-9 score ≥10).
Conclusions
Albuminuria was associated with depressive symptoms and depressive episodes, even at levels of UAE that do not fulfil the CKD criteria. Future longitudinal studies should examine the direction of this association and whether albuminuria could serve as a biomarker to identify individuals at risk of depression.



eMAP:CKD: electronic diagnosis and management assistance to primary care in chronic kidney disease

Thu, 27 Oct 2016 00:00:00 GMT

Abstract
Background
The increasing burden of chronic kidney disease (CKD) underpins the importance for improved early detection and management programs in primary care to delay disease progression and reduce mortality rates. eMAP:CKD is a pilot program for primary care aimed at addressing the gap between current and best practice care for CKD.
Methods
Customized software programs were developed to integrate with primary care electronic health records (EHRs), allowing real-time prompting for CKD risk factor identification, testing, diagnosis and management according to Kidney Health Australia's (KHA) best practice recommendations. Primary care practices also received support from a visiting CKD nurse and education modules. Patient data were analyzed at baseline (150 910 patients) and at 15 months (175 917 patients) following the implementation of the program across 21 primary care practices.
Results
There was improvement in CKD risk factor recognition (29.40 versus 33.84%; P < 0.001) and more complete kidney health tests were performed (3.20 versus 4.30%; P < 0.001). There were more CKD diagnoses entered into the EHR (0.48 versus 1.55%; P < 0.001) and more patients achieved KHA's recommended management targets (P < 0.001).
Conclusion
The eMAP:CKD program has shown an improvement in identification of patients at risk of CKD, appropriate testing and management of these patients, as well as increased documentation of CKD diagnosis entered into the EHRs. We have demonstrated efficacy in overcoming the verified gap between current and best practice in primary care. The success of the pilot program has encouraging implications for use across the primary care community as a whole.



Radical versus partial nephrectomy, chronic kidney disease progression and mortality in US veterans

Tue, 25 Oct 2016 00:00:00 GMT

Abstract
Background
Partial nephrectomy is considered the preferred care for localized kidney tumors and may yield better patient and kidney survival and similar oncological outcomes compared with radical nephrectomy. We sought to reexamine these hypotheses in a large nationally representative cohort of US veterans who underwent radical or partial nephrectomy.
Methods
We identified 7073 US veterans who had a partial or radical nephrectomy between 2004 and 2013. We collected data on estimated glomerular filtration rate (eGFR) prior to admission for nephrectomy surgery, immediately after surgery and 180 days postsurgery. We evaluated the association of nephrectomy type and eGFR at different time points with long-term mortality risk in adjusted survival models.
Results
Patients who underwent radical (compared to partial) nephrectomy had a 2-fold greater decline in eGFR (−21.8 ± 17.7 versus −10.3 ± 17.4 mL/min/1.73 m2) immediately after surgery. This larger drop in eGFR resulted in a larger proportion of radical nephrectomy patients having an eGFR <60 mL/min/1.73 m2 at ≥180 days postsurgery. Radical (compared to partial) nephrectomy patients also exhibited a 2.2-fold higher mortality [adjusted death hazard ratio 2.21 (95% confidence interval 1.91–2.55)]. Low eGFRs prior to surgery and 180 days postsurgery were associated with higher risk of postnephrectomy death.
Conclusions
Worse postnephrectomy kidney function and higher mortality were observed with radical nephrectomy, and a low presurgical eGFR and a greater decrease in eGFR postsurgery were associated with worse mortality irrespective of the type of nephrectomy. Additional studies are needed to examine predictors of postnephrectomy outcomes.



Predictors of atherosclerotic events in patients on haemodialysis: post hoc analyses from the AURORA study

Mon, 17 Oct 2016 00:00:00 GMT

Abstract
Background
Patients on haemodialysis (HD) are at high risk for cardiovascular events, but heart failure and sudden death are more common than atherosclerotic events. The A Study to Evaluate the Use of Rosuvastatinin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events (AURORA) trial was designed to assess the effect of rosuvastatin on myocardial infarction and death from any cardiac cause in 2773 HD patients. We studied predictors of the atherosclerotic cardiovascular events in AURORA.
Methods
We readjudicated all deaths and presumed myocardial infarctions according to the criteria used in the Study of Heart and Renal Protection (SHARP); these were specifically developed to separate atherosclerotic from non-atherosclerotic cardiovascular events. The readjudicated atherosclerotic end point included the first event of the following: non-fatal myocardial infarction, fatal coronary heart disease, non-fatal and fatal non-haemorrhagic stroke, coronary revascularization procedures and death from ischaemic limb disease. Stepwise Cox regression analysis was used to identify the predictors of such events.
Results
During a mean follow-up of 3.2 years, 506 patients experienced the new composite atherosclerotic outcome. Age, male sex, prevalent diabetes, prior cardiovascular disease, weekly dialysis duration, baseline albumin [hazard ratio (HR) 0.96; 95% confidence interval (CI) 0.94–0.99 per g/L increase], high-sensitivity C-reactive protein (HR 1.13; 95% CI 1.04–1.22 per mg/L increase) and oxidized low-density lipoprotein (LDL) cholesterol (HR 1.09; 95% CI 1.03–1.17 per 10 U/L increase) were selected as significant predictors in the model. Neither LDL cholesterol nor allocation to placebo/rosuvastatin therapy predicted the outcome.
Conclusions
Even with the use of strict criteria for end point definition, non-traditional risk factors, but not lipid disturbances, predicted atherosclerotic events in HD patients.



A two-pool kinetic model predicts phosphate concentrations during and shortly following a conventional (three times weekly) hemodialysis session

Thu, 13 Oct 2016 00:00:00 GMT

Abstract
Background
Previous studies have suggested that a conventional two-pool model cannot be used to predict intradialysis and early postdialysis phosphorus concentrations.
Methods
A conventional two-pool urea model was modified by increasing the distal compartment volume from two-thirds to three times the total body water and by the use of a dynamically variable intercompartmental phosphorus clearance during dialysis. The phosphate solver model parameters were derived from an examination of the results in the literature, and fine-tuned using a training set (F4) of 415 Hemodialysis (HEMO) Study patients studied during a dialysis session where phosphorus was measured at 4 months of follow-up. Validation was done in a group of 380 different HEMO Study patients plus 9 from the original F4 group, who were evaluated at 36 months of follow-up.
Results
The model predicted measured median early (1 h) intradialysis, end-dialysis and 30-min postdialysis serum phosphorus levels in the test and validation datasets with little apparent bias, including the highest and lowest deciles of predialysis serum phosphorus. The model tended to underestimate slightly intradialysis serum phosphorus when predialysis serum phosphorus was <3.0 mg/dL (0.97 mmol/L). There was a large scatter and standard deviation among patients, and whether aberrant values represent a patient-specific phenomenon is unclear.
Conclusions
A modified two-pool model using a slightly expanded distal compartment and a dynamically varying intercompartmental clearance, depending on the intradialysis phosphorus concentration, can be used to predict serum phosphorus level during and shortly after dialysis, in patients following a conventional three times per week dialysis prescription.



Long-term renal outcome in children with OCRL mutations: retrospective analysis of a large international cohort

Wed, 05 Oct 2016 00:00:00 GMT

Abstract
Background
Lowe syndrome (LS) and Dent-2 disease (DD2) are disorders associated with mutations in the OCRL gene and characterized by progressive chronic kidney disease (CKD). Here, we aimed to investigate the long-term renal outcome and identify potential determinants of CKD and its progression in children with these tubulopathies.
Methods
Retrospective analyses were conducted of clinical and genetic data in a cohort of 106 boys (LS: 88 and DD2: 18). For genotype–phenotype analysis, we grouped mutations according to their type and localization. To investigate progression of CKD we used survival analysis by Kaplan–Meier method using stage 3 CKD as the end-point.
Results
Median estimated glomerular filtration rate (eGFR) was lower in the LS group compared with DD2 (58.8 versus 87.4 mL/min/1.73 m2, P < 0.01). CKD stage II–V was found in 82% of patients, of these 58% and 28% had moderate-to-severe CKD in LS and DD2, respectively. Three patients (3%), all with LS, developed stage 5 of CKD. Survival analysis showed that LS was also associated with a faster CKD progression than DD2 (P < 0.01). On multivariate analysis, eGFR was dependent only on age (b = −0.46, P < 0.001). Localization, but not type of mutations, tended to correlate with eGFR. There was also no significant association between presence of nephrocalcinosis, hypercalciuria, proteinuria and number of adverse clinical events and CKD.
Conclusions
CKD is commonly found in children with OCRL mutations. CKD progression was strongly related to the underlying diagnosis but did not associate with clinical parameters, such as nephrocalcinosis or proteinuria.