Large studies on long-term kidney outcome in patients with anti-glomerular basement membrane (anti-GBM) GN are lacking. This study aimed to identify clinical and histopathologic parameters that ...predict kidney outcome in these patients.
This retrospective analysis included a total of 123 patients with anti-GBM GN between 1986 and 2015 from six centers worldwide. Their kidney biopsy samples were classified according to the histopathologic classification for ANCA-associated GN. Clinical data such as details of treatment were retrieved from clinical records. The primary outcome parameter was the occurrence of ESRD. Kidney survival was analyzed using the log-rank test and Cox regression analyses.
The 5-year kidney survival rate was 34%, with an improved rate observed among patients diagnosed after 2007 (
=0.01). In patients with anti-GBM GN, histopathologic class and kidney survival were associated (
<0.001). Only one of 15 patients with a focal class biopsy sample (≥50% normal glomeruli) developed ESRD. Patients with a sclerotic class biopsy sample (≥50% globally sclerotic glomeruli) and patients with 100% cellular crescents did not recover from dialysis dependency at presentation. In multivariable analysis, dialysis dependency at presentation (hazard ratio HR, 3.17; 95% confidence interval 95% CI, 1.59 to 6.32), percentage of normal glomeruli (HR, 0.97; 95% CI, 0.95 to 0.99), and extent of interstitial infiltrate (HR, 2.02; 95% CI, 1.17 to 3.50) were predictors of ESRD during follow-up.
Dialysis dependency, low percentage of normal glomeruli, and large extent of interstitial infiltrate are associated with poor kidney outcome in anti-GBM GN. Kidney outcome has improved during recent years; the success rate doubled after 2007.
This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_11_21_CJASNPodcast_18_1_v.mp3.
Determining candidacy for live kidney donation among obese individuals remains challenging. Among healthy non-donors, body mass index (BMI) above 30 is associated with a 16% increase in risk of ...end-stage renal disease (ESRD). However, the impact on the ESRD risk attributable to donation and living with only one kidney remains unknown. Here we studied the risk of ESRD associated with obesity at the time of donation among 119 769 live kidney donors in the United States. Maximum follow-up was 20 years. Obese (BMI above 30) live kidney donors were more likely male, African American, and had higher blood pressure. Estimated risk of ESRD 20 years after donation was 93.9 per 10 000 for obese; significantly greater than the 39.7 per 10 000 for non-obese live kidney donors. Adjusted for age, sex, ethnicity, blood pressure, baseline estimated glomerular filtration rate, and relationship to recipient, obese live kidney donors had a significant 86% increased risk of ESRD compared to their non-obese counterparts (adjusted hazard ratio 1.86; 95% confidence interval 1.05–3.30). For each unit increase in BMI above 27 kg/m2 there was an associated significant 7% increase in ESRD risk (1.07, 1.02–1.12). The impact of obesity on ESRD risk was similar for male and female donors, African American and Caucasian donors, and across the baseline estimated glomerular filtration rate spectrum. These findings may help to inform selection criteria and discussions with persons considering living kidney donation.
Co-presentation with both ANCA and anti-GBM antibodies is thought to be relatively rare. Current studies of such ‘double-positive’ cases report small numbers and variable outcomes. To study this ...further we retrospectively analyzed clinical features and long-term outcomes of a large cohort of 568 contemporary patients with ANCA-associated vasculitis, 41 patients with anti-GBM disease, and 37 double-positive patients with ANCA and anti-GBM disease from four European centers. Double-positive patients shared characteristics of ANCA-associated vasculitis (AAV), such as older age distribution and longer symptom duration before diagnosis, and features of anti-GBM disease, such as severe renal disease and high frequency of lung hemorrhage at presentation. Despite having more evidence of chronic injury on renal biopsy compared to patients with anti-GBM disease, double-positive patients had a greater tendency to recover from being dialysis-dependent after treatment and had intermediate long-term renal survival compared to the single-positive patients. However, overall patient survival was similar in all three groups. Predictors of poor patient survival included advanced age, severe renal failure, and lung hemorrhage at presentation. No single-positive anti-GBM patients experienced disease relapse, whereas approximately half of surviving patients with AAV and double-positive patients had recurrent disease during a median follow-up of 4.8 years. Thus, double-positive patients have a truly hybrid disease phenotype, requiring aggressive early treatment for anti-GBM disease, and careful long-term follow-up and consideration for maintenance immunosuppression for AAV. Since double-positivity appears common, further work is required to define the underlying mechanisms of this association and define optimum treatment strategies.
HCV-infected patients with cirrhosis achieve high sustained virological response (SVR) rates with direct-acting antivirals (DAAs) even after hepatic decompensation. We aimed to assess the clinical ...outcome following DAAs among patients with compensated and decompensated cirrhosis in relation to SVR and changes in model for end-stage liver disease (MELD) score.
Consecutive DAA-treated chronic HCV-infected patients with cirrhosis from 4 hepatology clinics were included. The primary endpoint in survival analyses was clinical disease progression, defined as liver failure, hepatocellular carcinoma, liver transplantation or death.
In total, 868 patients were included with a median age of 59 (IQR 54–65) years; 719 (83%) with Child-Pugh A cirrhosis and 149 (17%) with Child-Pugh B/C cirrhosis. SVR was attained by 647 (90%) Child-Pugh A patients and 120 (81%) Child-Pugh B/C patients. During a median follow-up of 28 (IQR 20–36) months, 102 (14%) Child-Pugh A patients and 96 (64%) Child-Pugh B/C patients experienced clinical disease progression. SVR was independently associated with an improved event-free survival in patients with Child-Pugh A cirrhosis (adjusted hazard ratio HR 0.47; 95% CI 0.27–0.82, p = 0.007), but not in patients with Child-Pugh B/C cirrhosis (adjusted HR 1.23; 95% CI 0.67–2.26; p = 0.51). Twelve weeks post-DAAs, 28 (19%) patients with Child-Pugh B/C cirrhosis had ≥2-point MELD decline, but their 2-year event-free survival did not differ from those with a stable MELD (47.9%; 95% CI 28.7–67.1 vs. 48.9%; 95% CI 38.1–59.7, respectively, p = 0.99).
Among patients with chronic HCV infection, DAA-induced SVR was associated with a reduced risk of clinical disease progression in patients with Child-Pugh A cirrhosis but not in patients with Child-Pugh B/C cirrhosis. In Child-Pugh B/C cirrhosis, a ≥2-point MELD decline did not translate into improved clinical outcome.
Chronic HCV infection can be cured with antiviral therapy. In this study, we evaluated the long-term effects of antiviral therapy on liver-related complications in patients with cirrhosis. Our results suggest that patients with compensated cirrhosis who were cured of their HCV infection have a lower rate of complications. In contrast, the rate of complications was not related to virological cure among those with decompensated cirrhosis. While these patients seem to remain in need of liver transplantation, antiviral therapy may lower their priority on the liver transplantation waiting list.
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•SVR following DAA therapy was associated with lower risk of cirrhosis-related complications in patients with compensated but not decompensated cirrhosis.•A proportion of patients with decompensated cirrhosis showed a sustained MELD score decline following DAA-induced SVR.•A MELD score decline following DAAs did not translate into a beneficial clinical outcome among patients with decompensated cirrhosis.•HCV-infected patients with decompensated cirrhosis who are successfully treated with DAAs may be at risk of a persisting need of LT at a lower priority on the LT waiting list.
Autosomal-dominant polycystic kidney disease (ADPKD) affects up to 12 million individuals and is the fourth most common cause for renal replacement therapy worldwide. There have been many recent ...advances in the understanding of its molecular genetics and biology, and in the diagnosis and management of its manifestations. Yet, diagnosis, evaluation, prevention, and treatment vary widely and there are no broadly accepted practice guidelines. Barriers to translation of basic science breakthroughs to clinical care exist, with considerable heterogeneity across countries. The Kidney Disease: Improving Global Outcomes Controversies Conference on ADPKD brought together a panel of multidisciplinary clinical expertise and engaged patients to identify areas of consensus, gaps in knowledge, and research and health-care priorities related to diagnosis; monitoring of kidney disease progression; management of hypertension, renal function decline and complications; end-stage renal disease; extrarenal complications; and practical integrated patient support. These are summarized in this review.
Diabetic kidney disease and diabetic nephropathy are the leading cause of end-stage kidney disease in the United States and most developed countries. Diabetes accounts for 30% to 50% of the incident ...cases of end-stage kidney disease in the United States. Although this represents a significant public health concern, it is important to note that only 30% to 40% of patients with diabetes develop diabetic nephropathy. Specific treatment of patients with diabetic nephropathy can be divided into 4 major arenas: cardiovascular risk reduction, glycemic control, blood pressure control, and inhibition of the renin-angiotensin system (RAS). Recommendations for therapy include targeting a hemoglobin A1c concentration < 7% and blood pressure < 140/90mmHg with therapy anchored around the use of a RAS-blocking agent. The single best evidence-based therapy for diabetic nephropathy is therapy with a RAS-blocking medication. This Core Curriculum outlines and discusses in detail the epidemiology, pathophysiology, diagnosis, and management of diabetic nephropathy.
Despite recent advances in chronic kidney disease (CKD) and end-stage renal disease (ESRD) management, morbidity and mortality in this population remain exceptionally high. Persistent, low-grade ...inflammation has been recognized as an important component of CKD, playing a unique role in its pathophysiology and being accountable in part for cardiovascular and all-cause mortality, as well as contributing to the development of protein-energy wasting.
The variety of factors contribute to chronic inflammatory status in CKD, including increased production and decreased clearance of pro-inflammatory cytokines, oxidative stress and acidosis, chronic and recurrent infections, including those related to dialysis access, altered metabolism of adipose tissue, and intestinal dysbiosis. Inflammation directly correlates with the glomerular filtration rate (GFR) in CKD and culminates in dialysis patients, where extracorporeal factors, such as impurities in dialysis water, microbiological quality of the dialysate, and bioincompatible factors in the dialysis circuit play an additional role. Genetic and epigenetic influences contributing to inflammatory activation in CKD are currently being intensively investigated. A number of interventions have been proposed to target inflammation in CKD, including lifestyle modifications, pharmacological agents, and optimization of dialysis. Importantly, some of these therapies have been recently tested in randomized controlled trials.
Chronic inflammation should be regarded as a common comorbid condition in CKD and especially in dialysis patients. A number of interventions have been proven to be safe and effective in well-designed clinical studies. This includes such inexpensive approaches as modification of physical activity and dietary supplementation. Further investigations are needed to evaluate the effects of these interventions on hard outcomes, as well as to better understand the role of inflammation in selected CKD populations (e.g., in children).
The relative immunosuppression and high prevalence of comorbidities in patients with ESKD on dialysis raise concerns that they may have an elevated risk of severe coronavirus disease 2019 (COVID-19), ...but outcomes for COVID-19 in such patients are unclear.
To examine presentation and outcomes of COVID-19 in patients with ESKD on dialysis, we retrospectively collected clinical data on 59 patients on dialysis who were hospitalized with COVID-19. We used Wilcoxon rank sum and Fischer exact tests to compare patients who died versus those still living.
Two of the study's 59 patients were on peritoneal dialysis, and 57 were on hemodialysis. Median age was 63 years, with high prevalence of hypertension (98%) and diabetes (69%). Patients who died were significantly older than those still living (median age, 75 versus 62 years) and had a higher median Charlson comorbidity index (8 versus 7). The most common presenting symptoms were fever (49%) and cough (39%); initial radiographs most commonly showed multifocal or bilateral opacities (59%). By end of follow-up, 18 patients (31%) died a median 6 days after hospitalization, including 75% of patients who required mechanical ventilation. Eleven of those who died had advanced directives against intubation. The remaining 41 patients (69%) were discharged home a median 8 days after admission. The median initial white blood cell count was significantly higher in patients who died compared with those still living (7.5 versus 5.7×10
/
l), as was C-reactive protein (163 versus 80 mg/L).
The association of COVID-19 with high mortality in patients with ESKD on dialysis reinforces the need to take appropriate infection control measures to prevent COVID-19 spread in this vulnerable population.
Background Sudden death is a leading cause of death in patients on maintenance hemodialysis therapy. During hemodialysis sessions, the gradient between serum and dialysate levels results in rapid ...electrolyte shifts, which may contribute to arrhythmias and sudden death. Controversies exist about the optimal electrolyte concentration in the dialysate; specifically, it is unclear whether patient outcomes differ among those treated with a dialysate potassium concentration of 3 mEq/L compared to 2 mEq/L. Study Design Prospective cohort study. Setting & Participants 55,183 patients from 20 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 1 to 5 (1996-2015). Predictor Dialysate potassium concentration at study entry. Outcomes Cox regression was used to estimate the association between dialysate potassium concentration and both all-cause mortality and an arrhythmia composite outcome (arrhythmia-related hospitalization or sudden death), adjusting for potential confounders. Results During a median follow-up of 16.5 months, 24% of patients died and 7% had an arrhythmia composite outcome. No meaningful difference in clinical outcomes was observed for patients treated with a dialysate potassium concentration of 3 versus 2 mEq/L (adjusted HRs were 0.96 95% CI, 0.91-1.01 for mortality and 0.98 95% CI, 0.88-1.08 for arrhythmia composite). Results were similar across predialysis serum potassium levels. As in prior studies, higher serum potassium level was associated with adverse outcomes. However, dialysate potassium concentration had only minimal impact on serum potassium level measured predialysis (+0.09 95% CI, 0.05-0.14 mEq/L serum potassium per 1 mEq/L greater dialysate potassium concentration). Limitations Data were not available for delivered (vs prescribed) dialysate potassium concentration and postdialysis serum potassium level; possible unmeasured confounding. Conclusions In combination, these results suggest that approaches other than altering dialysate potassium concentration (eg, education on dietary potassium sources and prescription of potassium-binding medications) may merit further attention to reduce risks associated with high serum potassium levels.
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