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Preview: Nephrology Dialysis Transplantation - current issue

Nephrology Dialysis Transplantation Current Issue

Published: Fri, 30 Jun 2017 00:00:00 GMT

Last Build Date: Mon, 03 Jul 2017 06:49:12 GMT




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Effect of renal transcatheter arterial embolization on quality of life in patients with autosomal dominant polycystic kidney disease


Background. Currently, there are few strategies for improving the quality of life (QOL) in patients with autosomal dominant polycystic kidney disease (ADPKD) and massive kidneys. Renal transcatheter arterial embolization (TAE) reduces kidney volume, but its impact on QOL in ADPKD patients on hemodialysis is unknown. This study investigated the influence of renal TAE on QOL in ADPKD patients with massive kidneys receiving hemodialysis.Methods. This prospective observational study enrolled 188 ADPKD patients on hemodialysis (92 men and 96 women; mean age 56.7 ± 9.1 years) who underwent renal TAE at Toranomon Hospital between August 2010 and July 2014. The 36-item Short Form Health Survey (SF-36) and our original 15-item questionnaire were used to evaluate QOL.Results. Using a linear mixed model, the least squares mean values of the SF-36 physical component summary (PCS), mental component summary (MCS) and role/social component summary (RCS) before renal TAE were calculated as 38.21 [95% confidence interval (CI) 36.50–39.91], 48.45 (47.05–49.86) and 43.04 (40.70–45.37), respectively. These values improved to 42.0 (40.22–43.77; P < 0.001 versus before TAE), 51.25 (49.78–52.71; P = 0.001) and 49.67 (47.22–52.12; P < 0.001), respectively, 1 year after renal TAE. Scores for abdominal fullness, poor appetite and heartburn showed marked improvement after renal TAE, while scores for fever, bodily pain and sleep disorder also improved slightly, but significantly. Scores for constipation and use of analgesics/sleeping medications/laxatives did not improve significantly. All of the SF-36 scores and the scores for specific symptoms (except bodily pain, snoring and constipation) were significantly correlated with the sequential decrease of the height-adjusted total kidney volume.Conclusions. In ADPKD patients on hemodialysis, renal TAE was effective in improving abdominal fullness, appetite, heartburn and SF-36 scores (MCS and RCS scores), but not for sleep disturbance, constipation and physical strength (PCS score).

Clinical practice recommendations for treatment with active vitamin D analogues in children with chronic kidney disease Stages 2–5 and on dialysis


In patients with chronic kidney disease (CKD), renal synthesis of active vitamin D [1,25-dihydroxyvitamin D (1,25(OH)2D)] declines and is associated with hypocalcaemia, secondary hyperparathyroidism and the spectrum of CKD–mineral and bone disorder (MBD). In advanced CKD, active vitamin D analogues, including alfacalcidol, calcitriol and paricalcitol, are routinely administered. There are few studies on the use of vitamin D analogues in children with CKD and on dialysis. It is difficult to define bone-specific outcomes that can guide treatment with active vitamin D analogues in children with CKD-MBD. A core working group (WG) of the European Society for Paediatric Nephrology (ESPN) CKD-MBD and Dialysis WGs has developed recommendations for the use of active vitamin D therapy in children with CKD and on dialysis. A second document in parallel with this one covers treatment recommendations for native vitamin D therapy. The WGs have performed an extensive literature review to include systematic reviews and randomized controlled trials in adults and children with CKD and prospective observational studies in children with CKD. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system was used to develop and grade the recommendations. In the absence of applicable study data, the opinion of experts from the ESPN CKD-MBD and Dialysis WGs is provided, but clearly GRADE-ed as such and must be carefully considered by the treating physician and adapted to individual patient needs as appropriate.

Immunosuppressive agents in adult kidney transplantation in the National Health Service: a model-based economic evaluation


Background. Immunosuppression is required in kidney transplantation to prevent rejection and prolong graft survival. We conducted an economic evaluation to support England’s National Institute for Health and Care Excellence in developing updated guidance on the use of immunosuppression, incorporating new immunosuppressive agents, and addressing changes in pricing and the evidence base.Methods. A discrete-time state transition model was developed to simulate adult kidney transplant patients over their lifetime. A total of 16 different regimens were modelled to assess the cost-effectiveness of basiliximab and rabbit anti-thymocyte globulin (rabbit ATG) as induction agents (with no antibody induction as a comparator) and immediate-release tacrolimus, prolonged-release tacrolimus, mycophenolate mofetil, mycophenolate sodium, sirolimus, everolimus and belatacept as maintenance agents (with ciclosporin and azathioprine as comparators). Graft survival was extrapolated from acute rejection rates, graft function and post-transplant diabetes rates, all estimated at 12 months post-transplantation. National Health Service (NHS) and personal social services costs were included. Cost-effectiveness thresholds of £20 000 and £30 000 per quality-adjusted life year were used.Results. Basiliximab was predicted to be more effective and less costly than rabbit ATG and induction without antibodies. Immediate-release tacrolimus and mycophenolate mofetil were cost-effective as maintenance therapies. Other therapies were either more expensive and less effective or would only be cost-effective if a threshold in excess of £100 000 per quality-adjusted life year were used.Conclusions. A regimen comprising induction with basiliximab, followed by maintenance therapy with immediate-release tacrolimus and mycophenolate mofetil, is likely to be effective for uncomplicated adult kidney transplant patients and a cost-effective use of NHS resources.

Clinical practice recommendations for native vitamin D therapy in children with chronic kidney disease Stages 2–5 and on dialysis


Vitamin D deficiency is widely prevalent and often severe in children and adults with chronic kidney disease (CKD). Although native vitamin D {25-hydroxyvitamin D [25(OH)D]} is thought to have pleiotropic effects on many organ systems, its skeletal effects have been most widely studied. The 25(OH)D deficiency is causally linked with rickets and fractures in healthy children and those with CKD, contributing to the CKD–mineral and bone disorder (MBD) complex. There are few studies to provide evidence for vitamin D therapy or guidelines for its use in CKD. A core working group (WG) of the European Society for Paediatric Nephrology (ESPN) CKD–MBD and Dialysis WGs have developed recommendations for the evaluation, treatment and prevention of vitamin D deficiency in children with CKD. We present clinical practice recommendations for the use of ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) in children with CKD Stages 2–5 and on dialysis. A parallel document addresses treatment recommendations for active vitamin D analogue therapy. The WG has performed an extensive literature review to include meta-analyses and randomized controlled trials in healthy children as well as children and adults with CKD, and prospective observational studies in children with CKD. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system has been used to develop and grade the recommendations. In the absence of applicable study data, the opinion of experts from the ESPN CKD–MBD and Dialysis WGs is provided, but clearly GRADE-ed as such and must be carefully considered by the treating physician, and adapted to individual patient needs as appropriate.

Transcatheter arterial embolization: an underappreciated alternative to nephrectomy in autosomal dominant polycystic kidney disease?


Autosomal dominant polycystic kidney disease (ADPKD) is well-known for its association with renal function decline that is caused by cyst formation in both kidneys. The majority of patients also have liver cysts (94%) [1]. However, due to enlargement of the kidneys or liver, these patients can also develop symptoms associated with abdominal distension, such as abdominal fullness, dyspepsia, and early satiety [2, 3]. Treatment for these symptoms is limited to either cyst aspiration or fenestration, which in most cases will not provide significant volume reduction, or a nephrectomy, with all its associated risks [4]. An alternative may be renal transcatheter arterial embolization (TAE). In renal TAE, coils are placed into the main renal arteries to obstruct blood flow, resulting in renal ischaemia and shrinkage of the kidney. Renal TAE has been used for certain indications, including gross haematuria, renal trauma and tumours. Reduction of kidney volume in ADPKD is a relatively novel indication. This procedure was first introduced in Japan in the late 1990s [5] and some experience has recently been obtained in France [6, 7].

The link between phenotype and fatty acid metabolism in advanced chronic kidney disease


Background. The kidney plays a central role in elimination of metabolic waste products and regulation of low-molecular weight metabolites via glomerular filtration, tubular secretion and reabsorption. Disruption of these processes results in profound changes in the biochemical milieu of the body fluids, which contribute to complications of chronic kidney disease (CKD) by inducing cytotoxicity and inflammation. Insight into the changes of the composition of metabolites and dysregulation of target genes and proteins enhances the understanding of the pathophysiology of CKD and its complications, and the development of novel therapeutic strategies. Chronic interstitial nephropathy is a common cause of CKD. The present study was designed to determine the effect of chronic interstitial nephropathy on the composition of serum metabolites and regulation of oxidative, inflammatory, fibrotic and cytoprotective pathways.Methods. Male Sprague−Dawley rats were randomized to the CKD and control groups (n = 8/group). CKD was induced by administration of adenine (200 mg/kg body weight/day) by oral gavage for 3 weeks. The control group was treated with the vehicle alone. The animals were then observed for an additional 3 weeks, at which point they were sacrificed and kidney and serum samples were collected. Serum metabolomic and lipidomic analyses were performed using ultra-performance liquid chromatography-quadrupole time-of-flight high-definition mass spectrometry. Kidney tissues were processed for histological and molecular biochemical analyses.Results. CKD rats exhibited increased plasma urea and creatinine concentrations, renal interstitial fibrosis, tubular damage and up-regulation of pro-inflammatory, pro-oxidant and pro-fibrotic pathways. Comparison of serum from CKD and control rats revealed significant differences in concentrations of amino acids and lipids including 33 metabolites and 35 lipid species. This was associated with marked abnormalities of fatty acid oxidation, and γ-linolenic acid and linoleic acid metabolism in CKD rats. Logistic regression analysis identified tetracosanoic acid, docosatrienoic acid, PC(18:3/14:1) and l-aspartic acid, tetracosanoic acid and docosatrienoic acid as novel biomarkers of chronic interstitial nephropathy.Conclusions. Advanced CKD in rats with adenine-induced chronic interstitial nephropathy results in profound changes in the serum metabolome, activation of inflammatory, oxidative and fibrotic pathways, and suppression of cytoprotective and antioxidant pathways.

Assessment of acute kidney injury in rhabdomyolytic mice by transcutaneous measurement of sinistrin excretion


Background. Early and accurate assessment of renal function is required for the successful detection and treatment of acute kidney injury (AKI). However, only retention parameters such as plasma urea and creatinine, and the indirect estimation of glomerular filtration rate are commonly available.Methods. Here, we measured the kinetics of plasma fluorescein isothiocyanate (FITC)-sinistrin excretion to detect alterations of renal function over time in a murine model of rhabdomyolysis-induced AKI. The half-life of FITC-sinistrin was evaluated using a transcutaneous device at different time points in conscious mice, from 4 days before renal damage up to 30 days after. Retention markers were also evaluated, in parallel.Results. Evaluation of the FITC-sinistrin half-life revealed early reduction of renal filtration, observed as early as 6 h after renal damage, and maintained up to 12 h following AKI. Plasma creatinine and urea levels correlated with the transcutaneous measurements of sinistrin excretion. Evaluation of sinistrin excretion also demonstrated that glycerol-treated animals did not develop AKI. Finally, histological analysis showed the presence of renal parenchymal lesions, which developed following the reduced renal filtration and persisted over time, highlighting the causative role of vascular dysfunction and myoglobin toxicity on the subsequent induction of tissue damage.Conclusions. Taken together, the results of this study provide important insights into the pathophysiology of kidney injury in rhabdomyolytic mice, and indicate that the transcutaneous measurement of FITC-sinistrin is an efficient and simple method to assess renal function precisely. This method also allows reduction of the required number of experimental animals by monitoring the same mouse over time.

Adverse kidney effects of epidermal growth factor receptor inhibitors


The epidermal growth factor receptor (EGFR) is implicated in various malignancies. The past decade has seen the development and widespread use of EGFR inhibitors for the successful treatment of such cancers. Available EGFR inhibitors include small molecule tyrosine-kinase inhibitors and monoclonal antibodies. Class-related renal adverse events result in dual toxicity including tubular/electrolyte disorders and glomerulopathies. Tubular injury is common and mainly due to monoclonal antibodies while glomerulopathy is rare and related to various anti-EGFR agents. The exact pathogenesis of anti-EGFR agents associated with kidney disorders remains to be elucidated.

Thrombospondin immune regulation and the kidney


Most therapeutic attempts to prevent the progression of kidney diseases have been based on interventions to inhibit the production of transforming growth factor-β (TGF-β). Thrombospondins (TSPs) play an important role in activating TGF-β. In the healthy kidney, two TSPs are expressed, TSP1 and TSP2, which exert contrasting effects. While TSP1 is a major activator of TGF‐β in renal cells and exerts pro-inflammatory effects both in vitro and in vivo, TSP2 lacks the ability for TGF‐β activation but regulates matrix remodeling and inflammation in experimental kidney disease. The effects of TSPs in the kidney have been mostly investigated by using the murine model of unilateral ureteral obstruction. In this model, TSP1 expression is increased along with the development of interstitial fibrosis and TGF-β. Relief of the obstruction gradually improves renal function and decreases the expression in TSP1 and TGF-β1. Several inhibitors of TSP1 prevented progressive interstitial fibrosis in murine models of ureteral obstruction, suggesting that control of latent TGF-β activation by inhibiting TSP1 might represent a novel potential target for preventing renal interstitial fibrosis. However, further studies are needed to assess whether TSP1‐mediated TGF‐β activation can be safely used in humans. In fact, TSPs normally act to suppress tumors in vivo. Moreover, TGF‐β can exert a pivotal function in the immune system, as it may induce the production of regulatory T cells and suppress B cell responses. Knowledge of the molecular mechanisms involved in TGF-β regulation may help in finding effective treatments of tissue fibrosis, cancer and autoimmune disease.

Acute genetic ablation of pendrin lowers blood pressure in mice


Background. Pendrin, the chloride/bicarbonate exchanger of β-intercalated cells of the renal connecting tubule and the collecting duct, plays a key role in NaCl reabsorption by the distal nephron. Therefore, pendrin may be important for the control of extracellular fluid volume and blood pressure.Methods. Here, we have used a genetic mouse model in which the expression of pendrin can be switched-on in vivo by the administration of doxycycline. Pendrin can also be rapidly removed when doxycycline administration is discontinued. Therefore, our genetic strategy allows us to test selectively the acute effects of loss of pendrin function.Results. We show that acute loss of pendrin leads to a significant decrease of blood pressure. In addition, acute ablation of pendrin did not alter significantly the acid-base status or blood K+ concentration.Conclusion. By using a transgenic mouse model, avoiding off-target effects related to pharmacological compounds, this study suggests that pendrin could be a novel target to treat hypertension.

Specific heparanase inhibition reverses glucose-induced mesothelial-to-mesenchymal transition


Background. Epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells induced by high glucose (HG) levels is a major biological mechanism leading to myofibroblast accumulation in the omentum of patients on peritoneal dialysis (PD). Heparanase (HPSE), an endoglycosidase that cleaves heparan sulfate chains, is involved in the EMT of several cell lines, and may have a major role in this pro-fibrotic process potentially responsible for the failure of dialysis. Its specific inhibition may therefore plausibly minimize this pathological condition.Methods. An in vitro study employing several biomolecular strategies was conducted to assess the role of HPSE in the HG-induced mesothelial EMT process, and to measure the effects of its specific inhibition by SST0001, a N-acetylated glycol-split heparin with a strong anti-HPSE activity. Rat mesothelial cells were grown for 6 days in HG (200 mM) culture medium with or without SST0001. Then EMT markers (VIM, α-SMA, TGF-β) and vascular endothelial growth factor (VEGF) (a factor involved in neoangiogenesis) were measured by real-time PCR and immunofluorescence/western blotting. As a functional analysis, trans-epithelial resistance (TER) and permeability to albumin were also measured in our in vitro model using a Millicell-ERS ohmmeter and a spectrophotometer, respectively.Results. Our results showed that 200 mM of glucose induced a significant gene and protein up-regulation of VEGF and all EMT markers after 6 days of culture. Intriguingly, adding SST0001 on day 3 reversed these biological and cellular effects. HPSE inhibition also restored the normal TER and permeability lost during the HG treatment.Conclusion. Taken together, our data confirm that HG can induce EMT of mesothelial cells, and that HPSE plays a central part in this process. Our findings also suggest that pharmacological HPSE inhibition could prove a valuable therapeutic tool for minimizing fibrosis and avoiding a rapid decline in the efficacy of dialysis in patients on PD, though clinical studies and/or trials would be needed to confirm the clinical utility of this treatment.

Economic evaluation of a pre-ESRD pay-for-performance programme in advanced chronic kidney disease patients


Background: The National Health Insurance Administration in Taiwan initiated a nationwide pre-end-stage renal disease (ESRD) pay-for-performance (P4P) programme at the end of 2006 to improve quality of care for chronic kidney disease (CKD) patients. This study aimed to examine this programme's effect on patients' clinical outcomes and its cost-effectiveness among advanced CKD patients.Methods: We conducted a longitudinal observational matched cohort study using two nationwide population-based datasets. The major outcomes of interests were incidence of dialysis, all-cause mortality, direct medical costs, life years (LYs) and incremental cost-effectiveness ratio comparing matched P4P and non-P4P advanced CKD patients. Competing-risk analysis, general linear regression and bootstrapping statistical methods were used for the analysis.Results: Subdistribution hazard ratio (95% confidence intervals) for advanced CKD patients enrolled in the P4P programme, compared with those who did not enrol, were 0.845 (0.779–0.916) for incidence of dialysis and 0.792 (0.673–0.932) for all-cause mortality. LYs for P4P and non-P4P patients who initiated dialysis were 2.83 and 2.74, respectively. The adjusted incremental CKD-related costs and other-cause-related costs were NT$114 704 (US$3823) and NT$32 420 (US$1080) for P4P and non-P4P patients who initiated dialysis, respectively, and NT$-3434 (US$114) and NT$45 836 (US$1572) for P4P and non-P4P patients who did not initiate dialysis, respectively, during the 3-year follow-up period.Conclusions: P4P patients had lower risks of both incidence of dialysis initiation and death. In addition, our empirical findings suggest that the P4P pre-ESRD programme in Taiwan provided a long-term cost-effective use of resources and cost savings for advanced CKD patients.

Atrial fibrillation and chronic kidney disease: struggling through thick and thin


The prevalence of atrial fibrillation and the risk of stroke display an age-related increase in the chronic kidney disease (CKD) population. Evidence from large randomized controlled trials conducted in the general population supports the use of anticoagulation to reduce the risk of stroke in the setting of non-valvular atrial fibrillation. However, data in the non-dialysis-dependent and dialysis-dependent CKD populations are limited largely to observational studies, which demonstrate conflicting results regarding the risk–benefit profile of anticoagulation. The paradoxical increase in bleeding and thromboembolism that is observed in CKD further complicates decision-making on the use of anticoagulation. Several observational studies suggest an increased risk of bleeding that parallels the decline in renal function, with the highest rates of bleeding seen in the dialysis-dependent population, whereas other studies have not demonstrated any appreciable increase in bleeding risks with anticoagulation. Bleeding rates are largely driven by increased rates of gastrointestinal bleeding with anticoagulation, with minimal contribution of intra-cranial bleeding. Similarly, several studies have suggested lower rates of ischemic stroke and systemic thromboembolism with anticoagulation in people with CKD, whereas other studies have demonstrated no difference in rates of ischemic stroke. Given the paucity of high-quality evidence, and the high prevalence of atrial fibrillation in people with CKD, large randomized control trials are needed to provide recommendations for anticoagulation in this setting.

Effect of high-protein meals during hemodialysis combined with lanthanum carbonate in hypoalbuminemic dialysis patients: findings from the FrEDI randomized controlled trial


Background: Inadequate protein intake and hypoalbuminemia, indicators of protein-energy wasting, are among the strongest mortality predictors in hemodialysis patients. Hemodialysis patients are frequently counseled on dietary phosphorus restriction, which may inadvertently lead to decreased protein intake. We hypothesized that, in hypoalbuminemic hemodialysis patients, provision of high-protein meals during hemodialysis combined with a potent phosphorus binder increases serum albumin without raising phosphorus levels.Methods: We conducted a randomized controlled trial in 110 adults undergoing thrice-weekly hemodialysis with serum albumin <4.0 g/dL recruited between July 2010 and October 2011 from eight Southern California dialysis units. Patients were randomly assigned to receive high-protein (50–55 g) meals during dialysis, providing 400–500 mg phosphorus, combined with lanthanum carbonate versus low-protein (<1 g) meals during dialysis, providing <20 mg phosphorus. Prescribed nonlanthanum phosphorus binders were continued over an 8-week period. The primary composite outcome was a rise in serum albumin of ≥0.2 g/dL while maintaining phosphorus between 3.5–<5.5 mg/dL. Secondary outcomes included achievement of the primary outcome's individual endpoints and changes in mineral and bone disease and inflammatory markers.Results: Among 106 participants who satisfied the trial entrance criteria, 27% (n = 15) and 12% (n = 6) of patients in the high-protein versus low-protein hemodialysis meal groups, respectively, achieved the primary outcome (intention-to-treat P-value = 0.045). A lower proportion of patients in the high-protein versus low-protein intake groups experienced a meaningful rise in interleukin-6 levels: 9% versus 31%, respectively (P = 0.009). No serious adverse events were observed.Conclusion: In hypoalbuminemic hemodialysis patients, high-protein meals during dialysis combined with lanthanum carbonate are safe and increase serum albumin while controlling phosphorus.

Serum sodium and mortality in a national peritoneal dialysis cohort


Background: Sodium disarrays are common in peritoneal dialysis (PD) patients, and may be associated with adverse outcomes in this population. However, few studies of limited sample size have examined the association of serum sodium with mortality in PD patients, with inconsistent results. We hypothesized that both hypo- and hypernatremia are associated with higher death risk in a nationally representative cohort of US PD patients.Methods: We sought to examine the association of serum sodium over time and mortality among 4687 adult incident PD patients from a large US dialysis organization who underwent one or more serum sodium measurements within the first 3 months of dialysis over January 2007 to December 2011. We examined the association of time-dependent and baseline sodium with all-cause mortality as a proxy of short- and long-term sodium–mortality associations, respectively. Hazard ratios were estimated using Cox models with three adjustment levels: minimally adjusted, case-mix adjusted, and case-mix + laboratory adjusted.Results: In time-dependent analyses, sodium levels <140 mEq/L were associated with incrementally higher death risk in case-mix models (ref: 140 to <142 mEq/L); following laboratory covariate adjustment, associations between lower sodium and higher mortality remained significant for levels <136 mEq/L. In analyses using baseline values, sodium levels <140 mEq/L were associated with higher mortality risk across all models (ref: 140 to <142 mEq/L).Conclusions: In PD patients, lower time-dependent and baseline sodium levels were independently associated with higher death risk. Further studies are needed to determine whether correction of dysnatremia improves longevity in this population.

Serum sclerostin: relation with mortality and impact of hemodiafiltration


Background: The glycoprotein sclerostin (Scl; 22 kDa), which is involved in bone metabolism, may play a role in vascular calcification in haemodialysis (HD) patients. In the present study, we investigated the relation between serum Scl (sScl) and mortality. The effects of dialysis modality and the magnitude of the convection volume in haemodiafiltration (HDF) on sScl were also investigated.Methods: In a subset of patients from the CONTRAST study, a randomized controlled trial comparing HDF with HD, sScl was measured at baseline and at intervals of 6, 12, 24 and 36 months. Patients were divided into quartiles, according to their baseline sScl. The relation between time-varying sScl and mortality with a 4-year follow-up period was investigated using crude and adjusted Cox regression models. Linear mixed models were used for longitudinal measurements of sScl.Results: The mean (±standard deviation) age of 396 test subjects was 63.6 (±13.9 years), 61.6% were male and the median follow-up was 2.9 years. Subjects with the highest sScl had a lower mortality risk than those with the lowest concentrations [adjusted hazard ratio 0.51 (95% confidence interval, CI, 0.31–0.86, P = 0.01)]. Stratified models showed a stable sScl in patients treated with HD (Δ +2.9 pmol/L/year, 95% CI −0.5 to +6.3, P = 0.09) and a decreasing concentration in those treated with HDF (Δ −4.5 pmol/L/year, 95% CI −8.0 to −0.9, P = 0.02). The relative change in the latter group was related to the magnitude of the convection volume.Conclusions: (i) A high sScl is associated with a lower mortality risk in patients with end-stage kidney disease; (ii) treatment with HDF causes sScl to fall; and (iii) the relative decline in patients treated with HDF is dependent on the magnitude of the convection volume.

Outcome of childhood-onset full-house nephropathy


Background: Patients with full-house nephropathy (FHN) present renal lesions that are indistinguishable from those of lupus nephritis (LN) but lack the systemic features necessary to meet diagnostic criteria for systemic lupus erithematosus (SLE). Some have been reported to develop a delayed SLE with time. The clinical outcome of children having FHN without SLE has never been reported.Methods: Children with biopsy-proven FHN were selected after excluding SLE cases by the absence of America College of Rheumatology criteria. The proportion of patients with complete (proteinuria <0.5 g/day) or partial remission (proteinuria ≤50% from baseline), relapse (estimated glomerular filtration rate <25% and/or proteinuria ≥50% from baseline) and progression to Stage III chronic kidney disease (CKD) was described according to age and gender groups with the Kaplan–Meier curve and compared with the Log-rank test. Entity of treatment was summarized by a score at induction (0–6 months) and maintenance (6–18 months). Cox-regression model was performed to test predictors of remission, relapse and progression to CKD.Results: Among 42 patients (28 pre-pubertal) who met the inclusion criteria, 39 (92.9%) achieved partial and 32 (76.2%) complete remission of nephropathy over 2.78 and 7.51 months of follow-up. At 10 years, the probability of progressing to CKD was 4.8%. Of those achieving remission, 18% had a renal flare mainly within 4 years after remission. Pre-pubertal males achieved complete remission more frequently than other patients but often relapsed; pre-pubertal females were treated more aggressively. Cox-regression analysis did not find independent predictors of remission or relapse.Conclusions: The outcome of the patients with FHN we investigated was encouraging. Recurrences are limited to the first 4 years following diagnosis, allowing progressive withdrawal of immunosuppression in patients achieving remission. Evaluation of risk factors for adverse outcome is necessary especially in pre-pubertal children.

Symptomatic fracture risk in the renal replacement therapy population


Background: Bone fractures are an important cause of morbidity and mortality in patients on renal replacement therapy (RRT). The aim of this multicentre observational study was to quantify the incidence of radiologically proven bone fracture by anatomical site in prevalent RRT groups and study its relationship to potential risk factors.Methods: We performed a retrospective analysis of electronic records of all 2096 adults prevalent on RRT in the West of Scotland on 7 July 2010 across all hospitals (except one where inception was 1 August 2011) to identify all subsequent radiologically proven fractures during a median 3-year follow-up.Results: There were 340 fractures, with an incidence of 62.8 per 1000 patient-years. The incidences were 37.6, 99.2 and 57.6 per 1000 patient-years in the transplant, haemodialysis (HD) and peritoneal dialysis (PD) groups, respectively (P < 0.05). In the multivariable model, age and HD (relative to transplant or PD) were independently associated with increased risk of fractures, while primary glomerular disease, increasing serum albumin and taking alfacalcidol or lanthanum were associated with decreased risk. In a multivariable model of only HD patients, age was independently associated with an increased risk of fractures, while glomerular disease, high serum albumin and being on alfacalcidol and lanthanum were associated with decreased risk. In a multivariable model in transplant patients, there were no significant independent predictors of fracture.Conclusions: The risk of symptomatic bone fracture is high in RRT patients and is ∼2.5 times higher in HD than in renal transplant patients, with the increased risk being independent of baseline factors. Fracture risk increases with age and lower serum albumin and is reduced if the primary renal diagnosis is glomerular disease. The possible protective role of alfacalcidol and lanthanum in HD patients deserves further exploration.

Associations of dysnatremias with mortality in chronic kidney disease


Background: Hyponatremia and hypernatremia are associated with death in the general population and those with chronic kidney disease (CKD). We studied the associations between dysnatremias, all-cause mortality and causes of death in a large cohort of Stage 3 and 4 CKD patients.Methods: We included 45 333 patients with Stage 3 and 4 CKDs followed in a large healthcare system. Associations between hyponatremia (<136 mmol/L) and hypernatremia (>145), and all-cause mortality and causes of death (cardiovascular, malignancy related and non-cardiovascular/non-malignancy related) were studied using Cox proportional hazards and competing risk models.Results: Dysnatremias were found in 9.2% of the study population. In separate multivariable Cox proportional hazards models using baseline serum sodium levels and time-dependent repeated measures, both hyponatremia and hypernatremia were associated with all-cause mortality. In the competing risk analyses, hyponatremia was significantly associated with increased risk for various cause-specific mortality categories [cardiovascular (hazard ratio, HR 1.16, 95% confidence interval, CI: 1.04, 1.30), malignancy related (HR 1.48, 95% CI: 1.33, 1.65) and non-cardiovascular/non-malignancy deaths (HR 1.25, 95% CI: 1.13, 1.39)], while hypernatremia was significantly associated with higher non-cardiovascular/non-malignancy mortality only (HR 1.36, 95% CI: 1.08, 1.72).Conclusions: In those with CKD, hyponatremia was associated with all-cause mortality, cardiovascular, malignancy and non-cardiovascular/non-malignancy-related deaths. Hypernatremia was associated with all-cause and non-cardiovascular/non-malignancy-related deaths. Further studies are needed to elucidate the mechanisms of differences in cause-specific death among CKD patients with hyponatremia and hypernatremia.

As we grow old: nutritional considerations for older patients on dialysis


The number of older people on dialysis is increasing, along with a need to develop specialized health care to manage their needs. Aging-related changes occur in physiological, psychosocial and medical aspects, all of which present nutritional risk factors ranging from a decline in metabolic rate to assistance with feeding-related activities. In dialysis, these are compounded by the metabolic derangements of chronic kidney disease (CKD) and of dialysis treatment per se, leading to possible aggravation of protein–energy wasting syndrome. This review discusses the nutritional derangements of the older patient on dialysis, debates the need for specific renal nutrition guidelines and summarizes potential interventions to meet their nutritional needs. Interdisciplinary collaborations between renal and geriatric clinicians should be encouraged to ensure better quality of life and outcomes for this growing segment of the dialysis population.

The clinicopathological relevance of pretransplant anti-angiotensin II type 1 receptor antibodies in renal transplantation


Background: Anti-angiotensin II type 1 receptor antibodies (AT1R-Abs) have been suggested as a risk factor for graft failure and acute rejection (AR). However, the prevalence and clinical significance of pretransplant AT1R-Abs have seldom been evaluated in Asia.Methods: In this multicenter, observational cohort study, we tested the AT1R-Abs in pretransplant serum samples obtained from 166 kidney transplant recipients. Statistical analysis was used to set a threshold AT1R-Abs level at 9.05 U/mL.Results: Pretransplant AT1R-Abs were detected in 98/166 (59.0%) of the analyzed recipients. No graft loss or patient death was reported during the study period. AT1R-Abs (+) patients had a significantly higher incidence of biopsy-proven AR than AT1R-Abs (−) patients (27.6 versus 10.3%, P = 0.007). Recipients with pretransplant AT1R-Abs had a 3.2-fold higher risk of AR within a year of transplantation (P = 0.006). Five study subjects developed microcirculation inflammation (score ≥2). Four of them were presensitized to AT1R-Abs. In particular, three patients had a high titer of anti-AT1R-Abs (>22.7 U/mL).Conclusions: Pretransplant AT1R-Abs is an independent risk factor for AR, especially acute cellular rejection, and is possibly associated with the risk of antibody-mediated injury. Pretransplant assessment of AT1R-Abs may be useful for stratifying immunologic risks.