The use of plasma exchange (PE) for induction treatment of anti-neutrophil cytoplasm autoantibody (ANCA)-associated vasculitis (AAV), including Wegener's granulomatosis (WG), is still controversial. ...The use of PE in AAV is not commonly accepted in patients with a plasma creatinine <500 μmol/L (5.7 mg/dL) despite experimental support for involvement of ANCA in the pathogenesis of vasculitis.
In a single-centre study from a tertiary referral centre, 32 patients with ANCA-positive WG were treated with standard immunosuppressive therapy, prednisolone and cyclophosphamide (CYC). In addition, they were randomized to treatment with or without initial PE. After 3 months, they were further randomized in a Latin square design to continue CYC or to change to cyclosporine A (CyA) for 9 months. The renal follow-up was at least 5 years.
Renal survival after 1, 3 and 12 months, and 5 years was significantly better in the PE groups. For all groups, the kidney/patient survival was 87.5%/93.7% at 1 year and 72%/56% at 5 years. All patients who were on dialysis when recruited were dialysis dependent 5 years later. There was no difference in morbidity or mortality between PE and control groups. Multivariate analysis demonstrated that PE improved renal survival (P < 0.01) at initial plasma creatinine levels >250 µmol/L (2.85 mg/dL). Change from CYC to CyA did not influence rate of relapses or time to relapse.
PE is recommended for induction therapy in WG patients at creatinine levels >250 µmol/L (2.85 mg/dL), whereas previous randomized studies have limited PE to patients with creatinine >500 µmol/L (5.65 mg/dL).
Chronic kidney diseases imply an ongoing need to remove toxins, with hemodialysis as the preferred treatment modality. We derive analytical expressions for phosphate clearance during dialysis, the ...single pass (SP) model corresponding to a standard clinical hemodialysis and the multi pass (MP) model, where dialysate is recycled and therefore makes a smaller clinical setting possible such as a transportable dialysis suitcase. For both cases we show that the convective contribution to the dialysate is negligible for the phosphate kinetics and derive simpler expressions. The SP and MP models are calibrated to clinical data of ten patients showing consistency between the models and provide estimates of the kinetic parameters. Immediately after dialysis a rebound effect is observed. We derive a simple formula describing this effect which is valid both posterior to SP or MP dialysis. The analytical formulas provide explanations to observations of previous clinical studies.
Infections and malignancies are the most common non-cardiovascular causes of death in patients on chronic renal replacement therapy (RRT). Here, we aimed to quantify the mortality risk attributed to ...infections and malignancies in dialysis patients and kidney transplant recipients when compared with the general population by age group and sex.
We followed 168 156 patients included in the ERA-EDTA registry who started RRT in 1993-2007 until 1 January 2012. Age- and cause-specific mortality rates per 1000 person-years (py) and mortality rate ratios (MRRs) compared with the European general population (WHO) were calculated. To identify risk factors, we used Cox regression.
Infection-related mortality was increased 82-fold in dialysis patients and 32-fold in transplant recipients compared with the general population. Female sex, diabetes, cancer and multisystem disease were associated with an increased risk of infection-related mortality. The sex difference was most pronounced for dialysis patients aged 0-39 years, with women having a 32% (adjusted HR 1.32 95% CI 1.09-1.60) higher risk of infection-related mortality than men. Mortality from malignancies was 2.9 times higher in dialysis patients and 1.7 times higher in transplant recipients than in the general population. Cancer and multisystem disease as primary causes of end-stage renal disease were associated with higher mortality from malignancies.
Infection-related mortality is highly increased in dialysis and kidney transplant patients, while the risk of malignancy-related death is moderately increased. Young women on dialysis may deserve special attention because of their high excess risk of infection-related mortality. Further research into the mechanisms, prevention and optimal treatment of infections in this vulnerable population is required.
Essentials
Mortality due to bleeding vs. arterial thrombosis in dialysis patients is unknown.
We compared death causes of 201 918 dialysis patients with the general population.
Dialysis was ...associated with increased mortality risks of bleeding and arterial thrombosis.
Clinicians should be aware of the increased bleeding and thrombosis risks.
Summary
Background
Dialysis has been associated with both bleeding and thrombotic events. However, there is limited information on bleeding as a cause of death versus arterial thrombosis as a cause of death.
Objectives
To investigate the occurrence of bleeding, myocardial infarction and stroke as causes of death in the dialysis population as compared with the general population.
Methods
We included 201 918 patients from 11 countries providing data to the ERA‐EDTA Registry who started dialysis treatment between 1994 and 2011, and followed them for 3 years. Age‐standardized and sex‐standardized mortality rate ratios for bleeding, myocardial infarction and stroke as causes of death were calculated in dialysis patients as compared with the European general population. Associations between potential risk factors and these causes of death in dialysis patients were investigated by calculating hazard ratios (HRs) with 95% confidence intervals (CIs) by the use of Cox proportional‐hazards regression.
Results
As compared with the general population, the age‐standardized and sex‐standardized mortality rate ratios in dialysis patients were 12.8 (95% CI 11.9–13.7) for bleeding as a cause of death (6.2 per 1000 person‐years among dialysis patients versus 0.3 per 1000 person‐years in the general population), 13.4 (95% CI 13.0–13.9) for myocardial infarction (22.5 versus 0.9 per 1000 person‐years), and 12.4 (95% CI 11.9–12.9) for stroke (14.3 versus 0.7 per 1000 person‐years).
Conclusion
Dialysis patients have highly increased risks of death caused by bleeding and arterial thrombosis as compared with the general population. Clinicians should be aware of the increased mortality risks caused by these conditions.
Background. Nephrogenic systemic fibrosis may be caused by gadolinium (Gd)-containing magnetic resonance imaging contrast agents. Most reported cases were associated with one particular agent, ...gadodiamide. Yet, unidentified cofactors might explain why only a minority of renal failure patients exposed to gadodiamide develop nephrogenic systemic fibrosis. Methods. We conducted a case-control study of 19 histologically verified cases and 19 sex- and age-matched controls. All subjects had chronic renal failure when exposed to gadodiamide. Clinical, biochemical and pharmacological data were retrieved from medical records. Results. Cases had been exposed to a mean gadodiamide dose of 0.29 mmol/kg (range 0.18–0.50) shortly before first signs of nephrogenic systemic fibrosis. Controls had been exposed to 0.28 mmol/kg (0.13–0.49). Cumulative gadodiamide exposure while in chronic kidney disease stage 5 was significantly higher among cases compared with controls (0.41 vs 0.31 mmol/kg, P = 0.05) and among severe cases (n = 9) compared with non-severe cases (0.49 vs 0.33 mmol/kg, P = 0.02). Severe cases developed primarily among patients in regular haemodialysis therapy at exposure. Cases had higher serum concentrations of ionized calcium and phosphate than controls and tended to receive higher doses of epoietin-β than controls at time of exposure. Severe cases were treated with higher doses of epoietin-β than non-severe cases at exposure (10.8 vs 4.4 103 IU/week, P = 0.02). Conclusions. Increasing cumulative gadodiamide exposure, high-dose epoietin-β treatment, and higher serum concentrations of ionized calcium and phosphate increase the risk of gadodiamide-related nephrogenic systemic fibrosis in renal failure patients. Severe cases seem to develop primarily among patients in regular haemodialysis therapy at exposure.
In recent years, increased efforts have been undertaken to address the needs of patients with rare diseases by international initiatives and consortia devoted to rare disease research and management. ...However, information on the overall prevalence of rare diseases within the end-stage renal disease (ESRD) population is limited. The aims of this study were (i) to identify those rare diseases within the ERA-EDTA Registry for which renal replacement therapy (RRT) is being provided and (ii) to determine the prevalence and incidence of RRT for ESRD due to rare diseases, both overall and separately for children and adults.
The Orphanet classification of rare disease was searched for rare diseases potentially causing ESRD, and these diagnosis codes were mapped to the corresponding ERA-EDTA primary renal disease codes. Thirty-one diagnoses were defined as rare diseases causing ESRD.
From 1 January 2007 to 31 December 2011, 7194 patients started RRT for a rare disease (10.6% children). While some diseases were exclusively found in adults (e.g. Fabry disease), primary oxalosis, cystinosis, congenital anomalies of the kidney and urinary tract (CAKUT) and medullary cystic kidney disease affected young patients in up to 46%. On 31 December 2011, 20 595 patients (12.4% of the total RRT population) were on RRT for ESRD caused by a rare disease. The point prevalence was 32.5 per million age-related population in children and 152.0 in adults. Only 5.8% of these patients were younger than 20 years; however, 57.7% of all children on RRT had a rare disease, compared with only 11.9% in adults. CAKUT and focal segmental glomerulosclerosis were the most prevalent rare disease entities among patients on RRT.
More than half of all children and one of nine adults on RRT in the ERA-EDTA Registry suffer from kidney failure due to a rare disease, potentially with a large number of additional undiagnosed or miscoded cases. Comprehensive diagnostic assessment and the application of accurate disease classification systems are essential for improving the identification and management of patients with rare kidney diseases.
Background
For 10 consecutive years, the ESPN/ERA-EDTA Registry has included data on children with stage 5 chronic kidney disease (CKD 5) receiving kidney replacement therapy (KRT) in Europe. We ...examined trends in incidence and prevalence of KRT and patient survival.
Methods
We included all children aged <15 years starting KRT 2007–2016 in 22 European countries participating in the ESPN/ERA-EDTA Registry since 2007. General population statistics were derived from Eurostat. Incidence and prevalence were expressed per million age-related population (pmarp) and time trends studied with JoinPoint regression. We analyzed survival trends using Cox regression.
Results
Incidence of children commencing KRT <15 years remained stable over the study period, varying between 5.5 and 6.6 pmarp. Incidence by treatment modality was unchanged over time: 2.0 for hemodialysis (HD) and peritoneal dialysis (PD) and 1.0 for transplantation. Prevalence increased in all age categories and overall rose 2% annually from 26.4 pmarp in 2007 to 32.1 pmarp in 2016. Kidney transplantation prevalence increased 5.1% annually 2007–2009, followed by 1.5% increase/year until 2016. Prevalence of PD steadily increased 1.4% per year over the entire period, and HD prevalence started increasing 6.1% per year from 2011 onwards. Five-year unadjusted patient survival on KRT was around 94% and similar for those initiating KRT 2007–2009 or 2010–2012 (adjusted HR: 0.98, 95% CI:0.71–1.35).
Conclusions
We found a stable incidence and increasing prevalence of European children on KRT 2007–2016. Five-year patient survival was good and was unchanged over time. These data can inform patients and healthcare providers and aid health policy makers on future resource planning of pediatric KRT in Europe.
Bone disease is common after renal transplantation. The main syndromes are bone loss with a consequent fracture rate of 3% per year, osteonecrosis of the hip, and bone pain. The causes of disease ...include preexisting uremic osteodystrophy (hyperparathyroidism, aluminum osteomalacia, beta2-associated amyloidosis, and diabetic osteopathy), postoperative glucocorticoid therapy, poor renal function, and ongoing hyperparathyroidism, as the result of either autonomous transformation of the parathyroid gland or ongoing physiologic stimuli. Cyclosporine A treatment, hyperphosphaturia, and a pathogenic vitamin D allele have also been implicated. Bone loss is particularly pronounced during the first year after operation, amounting to up to 9% of bone mass. The clinical and biochemical picture is consistent with a high turnover bone disease, but histomorphometric studies do not completely support this. Principal prophylactic options include preoperative osteodystrophy prophylaxis; postoperative calcium, vitamin D, or calcitriol therapy; estrogen therapy for postmenopausal women; and parathyroidectomy for medically intractable hyperparathyroidism. Recently, prophylactic biphosphonate treatment has shown promise, but the exact indications for treatment remain to be determined.
This study examines the time trends in incidence, prevalence, patient and kidney allograft survival and causes of death (COD) in patients receiving renal replacement therapy (RRT) in Europe.
Eighteen ...national or regional renal registries providing data to the European Renal Association-European Dialysis and Transplant Association Registry between 1998 and 2011 were included. Incidence and prevalence time trends between 2001 and 2011 were studied with Joinpoint and Poisson regression. Patient and kidney allograft survival and COD between 1998 and 2011 were analysed using Kaplan-Meier and competing risk methods and Cox regression.
From 2001 to 2008, the adjusted incidence of RRT rose by 1.1% (95% CI: 0.6, 1.7) annually to 131 per million population (pmp). During 2008-2011, the adjusted incidence fell by 2.2% (95% CI: -4.2, -0.2) annually to 125 pmp. This decline occurred predominantly in patients aged 45-64 years, 65-74 years and in the primary renal diseases diabetes mellitus type 1 and 2, renovascular disease and glomerulonephritis. Between 2001 and 2011, the overall adjusted prevalence increased from 724 to 1032 pmp (+3.3% annually, 95% CI: 2.8, 3.8). The adjusted 5-year patient survival on RRT improved between 1998-2002 and 2003-2007 adjusted hazard ratio (HRa) 0.85, 95% CI: 0.84, 0.86. Comparing these time periods, the risk of cardiovascular deaths fell by 25% (HRa 0.75, 95% CI: 0.74, 0.77). However the risk of malignant death rose by 9% (HRa 1.09, 95% CI: 1.03, 1.16) in patients ≥65 years.
This European study shows a declining RRT incidence, particularly in patients aged 45-64 years, 65-74 years and secondary to diabetic nephropathy. Encouragingly, the adjusted RRT patient survival continues to improve. The risk of cardiovascular death has decreased, though the risk of death from malignancy has increased in the older population.
Background. Hypoalbuminaemia is common in peritoneal dialysis (PD) patients and has an associated high mortality. An excess morbidity and mortality has previously been found in patients with high ...peritoneal transport. A high peritoneal large pore fluid flux (JvL) results in increased peritoneal loss of protein that possibly contributes to patient morbidity. Alternatively, hypoalbuminaemia and high transport status could be just a marker of capillary pathology associated with atherosclerotic comorbidity. Methods. Peritoneal dialysis capacity computer modelling of peritoneal transport, based on Rippe's three-pore model, was performed to measure JvL in 155 incident PD patients 2–4 weeks after PD initiation. Patient clinical and biochemical status was determined −6, −3, −1, 1 and 6 months after PD initiation, and every 6 months thereafter. JvL was redetermined in prevalent patients 2 and 4 years after PD initiation. Results. JvL was 0.106±0.056 ml/min/1.73 m2 (median 0.094, interquartile range 0.068–0.128). It was correlated to age*** (*P<0.05; **P<0.01; ***P<0.001) (20–30 years 0.079±0.04; 70 years 0.121±0.071), but not to gender. No correlation to diabetic or preexisting renal replacement therapy was seen, but patients with atherosclerosis had higher JvL (0.123±0.06 vs 0.100±0.056*) as had patients with other systemic disease (0.121±0.68 vs 0.100±0.051*). JvL was positively correlated to area parameter (r = 0.41***), and negatively correlated to plasma albumin (−0.36***). Patients were divided into three equal groups: group 1, JvL <0.075 ml/min/1.73 m2; group 2, 0.075–0.11; group 3: >0.11. There was no difference between the groups in p-albumin prior to PD. Immediately after PD start, differences between the three groups appeared (1 month p-albumin: (μmol/l) group 1, 548±83; group 2, 533±86; group 3, 497±78**), and persisted for up to 6 years. No significant change in JvL was seen at 2 and 4 years. Patients with significant albuminuria also had hypoalbuminaemia (<1 g/day: 546±81 μmol/l; >2 g/day: 503±54 μmol/l). Intermittent PD ameliorated the effect of JvL on albumin losses and clearance. Mortality was increased significantly with raised JvL, independently of age (2 year mortality: group 1, 10%, group 3, 32%*). There was no overall effect on technique survival, but hypoalbuminaemic group 3 patients had a higher failure rate*. Conclusion. JvL is related to hypoalbuminaemia and mortality after PD initiation. A high JvL seems to be a marker of preexisting vascular pathology, and to cause hypoalbuminaemia after PD initiation. It is suggested that peritoneal albumin loss can have an identical pathogenic effect as urinary albumin loss, by causing an iatrogenic ‘nephrotic’ syndrome.
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