[Acquired cystic kidney hemorrhage in peritoneal dialysis patients: A report of three cases].

Spontaneous renal cyst hemorrhage is one of the clinical emergencies in peritoneal dialysis (PD) patients and is potentially life-threatening. The main complaints are sudden low back pain, paleness, and hypotensive shock with or without vomiting or fever. In contrast to inherited polycystic kidney disease, acquired cystic kidney disease (ACKD) secondary to chronic kidney disease is easily overlooked or delayed in clinical diagnosis and treatment, leading to severe clinical outcomes. We report three patients with spontaneous hemorrhage of ACKD in the peritoneal dialysis center at Peking University First Hospital. The common features are as follows, long history of dialysis, mild to severe low back pain, decrease in hemoglobulin, negative PD solutions, diagnosis established through computed tomography (CT), and continuing PD during treatment of ACKD hemorrhage. Treatments vary from conservative to unilaterally selective renal artery embolization. In this study, ACKD morbidity was investigated in PD patients. A total of 316 patients who had an abdominal ultrasound, CT, or magnetic resonance imaging (MRI) in the past 1 year were enrolled. Among them, 103 cases (32.9%) met the diagnostic criteria of ACKD. The morbidity rates were 27.5%, 37.8%, 43.8%, 59.1%, and 88.6%, when the dialysis history ranged from ≤3, >3 & ≤5, >5 & ≤7, >7 & ≤9, >9 years, respectively, showing a increasing trend. Most ACKD hemorrhages could be healed and got an acceptable prognosis after treatment, including rest, blood transfusion, selective renal artery embolization, or nephrectomy. We summarize the risk factors, including a long history of dialysis, anticoagulation or antiplatelet, and inflammation or stones of the urinary system, but with no difference in initial kidney diseases and gender. ACKD hemorrhage mainly includes intracapsular hemorrhage, cyst rupture, and spontaneous retroperitoneal hemorrhage. In addition, we also recommend an adaptive process for spontaneous kidney hemorrhage of diagnosis and treatment in peritoneal dialysis patients. The significance of these cases lies in the fact that patients with ACKD are potentially associated with complications such as cyst hemorrhage and malignancy. Thus, peritoneal dialysis physicians should place great importance on the surveillance of ACKD.

Microangiopathic Lesions in IgA Nephropathy: A Cohort Study.

RATIONALE & OBJECTIVE: Renal arteriolar microangiopathic lesions may occur in immunoglobulin A nephropathy (IgAN), but their role in disease progression remains unclear. We sought to understand the prevalence and character of microangiopathic lesions in IgAN and their role in disease progression. STUDY DESIGN: A retrospective cohort study. SETTING & PARTICIPANTS: In this study, we enrolled a Chinese cohort with 944 adult patients with IgAN who had been followed up for at least 1 year. PREDICTORS: Renal arteriolar microangiopathic lesions. OUTCOMES: Composite kidney end point event defined as a>50% reduction in estimated glomerular filtration rate, end-stage kidney disease, or death. ANALYTICAL APPROACH: All kidney biopsies were independently reviewed by 2 investigators. Renal arteriolar microangiopathic lesions were detected using light microscopy. Multivariable Cox regression analysis was used to test the association between microangiopathic lesions and the outcomes. RESULTS: Overall, 194 (20.6%) patients had renal arteriolar microangiopathic lesions. Patients with microangiopathic lesions presented with higher blood pressures, more severe proteinuria, and lower estimated glomerular filtration rates (all P<0.001) than patients without microangiopathic lesions. After a median follow-up of 4.2 years, 75 (38.7%) patients with microangiopathic lesions and 83 (11.1%) patients without these lesions reached the composite kidney end point (P<0.001). In a multivariable Cox regression model adjusting for clinical and pathologic variables available at the time of biopsy, the presence of microangiopathic lesions was an independent risk factor for kidney failure (HR, 1.95; 95% CI, 1.34-2.83; P<0.001). Renal vascular sclerosis (arterial intimal fibrosis or arteriolar hyalinosis) was not a risk factor for kidney disease progression (P = 0.5). LIMITATIONS: A single Chinese center's experience, retrospective study, most patients were not tested for hemolytic markers (for example, haptoglobin level, lactate dehydrogenase level, and schistocytes). CONCLUSIONS: Renal arteriolar microangiopathic lesions are frequent in IgAN and their presence is independently associated with progression to kidney failure. If confirmed in other patient cohorts, such lesions could be considered for inclusion in formal classification schemes of IgAN.

Effect of Statins on Kidney Disease Outcomes: A Systematic Review and Meta-analysis.

BACKGROUND: The effects of statin administration on kidney disease outcomes remain controversial. We undertook a systematic review and meta-analysis to assess the efficacy of statins on kidney outcomes. STUDY DESIGN: We conducted a meta-analysis of randomized controlled trials (RCTs) using MEDLINE (1946 to August 31, 2015), EMBASE (1966 to August 31, 2015), and the Cochrane Library database (no date restriction). SETTING & POPULATION: Adults who were not receiving dialysis, for whom kidney disease outcomes were reported. SELECTION CRITERIA FOR STUDIES: RCTs in which statins were given for at least 6 months and kidney outcomes were measured. INTERVENTION: Statins versus control, including placebo, usual care, and different types or doses of statins. OUTCOMES: Kidney failure events, rate of change in estimated glomerular filtration rate (eGFR) per year, change in proteinuria or albuminuria, and, in patients with chronic kidney disease, major cardiovascular events. RESULTS: 57 eligible studies with 143,888 participants were included. Statin treatment did not produce an apparent beneficial effect for kidney failure events (OR, 0.98; 95% CI, 0.87-1.10; P=0.7) or end-stage renal disease events (OR, 0.98; 95% CI, 0.90-1.07; P=0.7). However, mean difference for rate of decline in eGFR (0.41 [95% CI, 0.11-0.70] mL/min/1.73m(2) per year slower in statin recipients) and standardized mean difference for change in proteinuria or albuminuria (-0.65 [95% CI, -0.94 to -0.37] standard deviation units, statin recipients vs controls) were statistically significant. In addition, statin therapy significantly reduced the risk for cardiovascular events (OR, 0.69; 95% CI, 0.61-0.79; P<0.001) in patients with chronic kidney disease. LIMITATIONS: Inclusion of several post hoc analyses from large RCTs and substantial heterogeneity in secondary outcome analyses. CONCLUSIONS: Statin therapy does not reduce the risk for kidney failure events in adults not receiving dialysis for whom kidney disease outcomes were reported, but may modestly reduce proteinuria and rate of eGFR decline.

Renin-Angiotensin System Inhibitors and Kidney and Cardiovascular Outcomes in Patients With CKD: A Bayesian Network Meta-analysis of Randomized Clinical Trials.

BACKGROUND: There is much uncertainty regarding the relative effects of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) in populations with chronic kidney disease (CKD). STUDY DESIGN: Systematic review and Bayesian network meta-analysis. SETTING & POPULATION: Patients with CKD treated with renin-angiotensin system (RAS) inhibitors. SELECTION CRITERIA FOR STUDIES: Randomized trials in patients with CKD treated with RAS inhibitors. PREDICTOR: ACE inhibitors and ARBs compared to each other and to placebo and active controls. OUTCOME: Primary outcome was kidney failure; secondary outcomes were major cardiovascular events, all-cause death. RESULTS: 119 randomized controlled trials (n = 64,768) were included. ACE inhibitors and ARBs reduced the odds of kidney failure by 39% and 30% (ORs of 0.61 [95% credible interval, 0.47-0.79] and 0.70 [95% credible interval, 0.52-0.89]), respectively, compared to placebo, and by 35% and 25% (ORs of 0.65 [95% credible interval, 0.51-0.80] and 0.75 [95% credible interval, 0.54-0.97]), respectively, compared with other active controls, whereas other active controls did not show evidence of a significant effect on kidney failure. Both ACE inhibitors and ARBs produced odds reductions for major cardiovascular events (ORs of 0.82 [95% credible interval, 0.71-0.92] and 0.76 [95% credible interval, 0.62-0.89], respectively) versus placebo. Comparisons did not show significant effects on risk for cardiovascular death. ACE inhibitors but not ARBs significantly reduced the odds of all-cause death versus active controls (OR, 0.72; 95% credible interval, 0.53-0.92). Compared with ARBs, ACE inhibitors were consistently associated with higher probabilities of reducing kidney failure, cardiovascular death, or all-cause death. LIMITATIONS: Trials with RAS inhibitor therapy were included; trials with direct comparisons of other active controls with placebo were not included. CONCLUSIONS: Use of ACE inhibitors or ARBs in people with CKD reduces the risk for kidney failure and cardiovascular events. ACE inhibitors also reduced the risk for all-cause mortality and were possibly superior to ARBs for kidney failure, cardiovascular death, and all-cause mortality in patients with CKD, suggesting that they could be the first choice for treatment in this population.

Interaction between PLA2R1 and HLA-DQA1 variants associates with anti-PLA2R antibodies and membranous nephropathy.

Risk alleles at genome loci containing phospholipase A2 receptor 1 (PLA2R1) and HLA-DQA1 closely associate with idiopathic membranous nephropathy (IMN) in the European population, but it is unknown whether a similar association exists in the Chinese population and whether high-risk alleles promote the development of anti-PLA2R antibodies. Here, we genotyped 2132 Chinese individuals, including 1112 patients with IMN and 1020 healthy controls, for three single nucleotide polymorphisms (SNPs) within PLA2R1 and three SNPs within HLA genes. We also selected 71 patients, with varying genotypes, to assess for circulating anti-PLA2R antibody and for PLA2R expression in glomeruli. Three SNPs within PLA2R1 and one SNP within HLA-DQA1 strongly associated with IMN, and we noted gene-gene interactions involving these SNPs. Furthermore, these risk alleles strongly associated with the presence of anti-PLA2R antibodies and glomerular PLA2R expression. Among individuals who carried risk alleles for both genes, 73% had anti-PLA2R antibodies and 75% expressed PLA2R in glomeruli. In contrast, among individuals who carried protective genotypes of both genes, none had anti-PLA2R antibodies and glomerular expression of PLA2R was weak or absent. In conclusion, the interaction between PLA2R1 and HLA-DQA1 risk alleles associates with the development of IMN in the Chinese population. Individuals carrying risk alleles are predisposed to the generation of circulating anti-PLA2R autoantibodies, which may contribute to the development of IMN.

Effect of statin therapy on cardiovascular and renal outcomes in patients with chronic kidney disease: a systematic review and meta-analysis.

AIMS: The effects of statin therapy in patients with chronic kidney disease (CKD) remain uncertain. We undertook a systematic review and meta-analysis to investigate the effects of statin on major clinical outcomes. METHODS AND RESULTS: We systematically searched MEDLINE, Embase, and the Cochrane Library for trials published between 1970 and November 2011. We included prospective, randomized, controlled trials assessing the effects of statins on cardiovascular outcomes in people with kidney disease. Summary estimates of relative risk (RR) reductions were calculated with a random effects model. Thirty-one trials that include at least one event were identified, providing data for 48 429 patients with CKD, including 6690 major cardiovascular events and 6653 deaths. Statin therapy produced a 23% RR reduction (16-30) for major cardiovascular events (P<0.001), an 18% RR reduction (8-27) for coronary events, and 9% (1-16) reduction in cardiovascular or all-cause deaths, but had no significantly effect on stroke (21%, -12 to 44) or no clear effect on kidney failure events (5%, -1 to 10). Adverse events were not significantly increased by statins, including hepatic (RR 1.13, 95% CI 0.92-1.39) or muscular disorders (RR 1.02, 95% CI 0.95-1.09). Subgroup analysis demonstrated the relative effects of statin therapy in CKD were significantly reduced in people with advanced CKD (P < 0.001) but that the absolute risk reductions were comparable. CONCLUSION: Statin therapy reduces the risk of major cardiovascular events in patients with chronic kidney disease including those receiving dialysis.

Complement factor H variants are associated with microangiopathy lesions in IgA nephropathy.

BACKGROUND: Thrombotic microangiopathy (TMA) occurs in immunoglobulin A nephropathy (IgAN), and the pathogenesis is not known behind the endothelium injury. The genetic studies have indicated that complement factor H (CFH) and complement factor H-related protein genes (CFHRs)play a key role in IgAN. We perform a study to investigate the CFH /CFHRs gene variants and their roles in IgAN with microangiopathy based on a previous genome-wide association study (GWAS). METHODS: We re-review microangiopathic lesions in 2055 IgAN patients by light microscopy. And 204 IgAN patients with MA and 1851 IgAN without MA are confirmed in this study. Nineteen single nucleotide polymorphisms (SNPs) across CFH and CFHRs genes information are extracted from GWAS data. RESULTS: The results show that 204 out of 2055(9.93 %) MA patients are screened from our IgAN cohort. Patients with MA lesions are strongly associated with more severe clinical conditions and higher serum complement factor H (FH) levels than IgAN without MA(MA vs IgAN-non MA:428.16 ± 141.05 vs 364.62 ± 139.06ug/mL, p = 0.004). The genetic association study indicates the frequency of rs800292-G in CFH was significantly higher in the MA group (0.441 vs 0.374, odds ratio1.37[1.07-1.62], p = 0.010) compared with IgAN without MA. In addition, patients with the rs412852-G allele in CFH become an independent risk factor for end-stage renal disease (ESRD)in MA patients (Hazard Ratio 2.77[1.17-6.65], p = 0.021). However, the gene variants did not correlate with serum FH, serum C3, and C3 deposits in the renal specimens. CONCLUSION: Our results indicated that variants in CFH are associated with the development and progression of IgAN with microangiopathy.

Evaluation of the Oxford classification in immunoglobulin A vasculitis with nephritis: a cohort study and meta-analysis.

BACKGROUND: Similarities in clinicopathological presentations in immunoglobulin A (IgA) nephropathy and IgA vasculitis with nephritis (IgAVN) raise the question of the utility of the Oxford classification in the latter. The aim of this study was to evaluate the Oxford classification in IgAVN. METHODS: We conducted a retrospective cohort study and meta-analysis following systematic searching of the MEDLINE and Excerpta Medica Database (EMBASE) databases between January 2009 and September 2019. We modeled the association of 30 and 50% decline in estimated glomerular filtration rate or end-stage renal disease with pathologic lesions of the Oxford classification including mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), interstitial fibrosis/tubular atrophy (T) and crescents (C). Results were pooled using random-effects meta-analysis. RESULTS: The cohort study included 132 patients, and only T lesion was an independently risk factor in IgAVN. The meta-analysis yielded six retrospective studies with 721 patients and 139 endpoints. In multivariate model, T lesion was significantly associated with renal outcome (hazard ratio = 2.45, P = 0.007). M and C lesions could not predict renal outcome without evidence of heterogeneity. E and S lesions could not predict renal outcome with evidence of heterogeneity (I 2 = 66.6%; P = 0.01, and I 2 = 65.8%; P = 0.03, respectively). Subgroup analysis showed that the possible reasons to the heterogeneity were from usage of immunosuppressant, sample size and follow-up time. CONCLUSIONS: The study suggests that the Oxford classification could not be fully validated in IgAVN. Higher portion of immunosuppressant especially before renal biopsy might be the main confounder for the predictive value of Oxford classification in IgAVN.

Glomerular C4d Deposition and Kidney Disease Progression in IgA Nephropathy: A Systematic Review and Meta-analysis.

BACKGROUND: Glomerular deposition of C4d is a widely used biomarker for activation of the lectin pathway in the complement system and is reported to be associated with kidney progression in immunoglobulin A nephropathy (IgAN). The aim of this study was to evaluate whether glomerular C4d deposition, as a new biomarker, improves the prediction of kidney prognosis in IgAN. STUDY DESIGN: Systematic review and meta-analysis. SETTING & POPULATION: Patients with biopsy-proven primary IgAN without age limitations.Selection Criteria for Studies: Cross-sectional or cohort studies reporting the prevalence of glomerular C4d deposition or evaluating its association with IgAN progression. PREDICTOR: Glomerular C4d deposition. OUTCOME: Composite progression event of a >30% decline in estimated glomerular filtration rate or end-stage kidney disease. RESULTS: 12 studies with 1,251 patients were included. The prevalence of glomerular C4d deposition was 34% (95% CI, 27%-41%), with large heterogeneity (I 2 = 86%; P < 0.001). Patients with C4d deposition had lower estimated glomerular filtration rates (mean difference [MD], -11.48; 95% CI, -18.27 to -4.70; P < 0.001) as well as higher urinary protein-creatinine ratios (MD, 0.87; 95% CI, 0.53-1.21; P < 0.001) or 24-hour urinary protein excretion (MD, 0.99; 95% CI, 0.50-1.47; P < 0.001) and higher risk for hypertension (relative risk [RR], 1.45; 95% CI, 1.06-1.99; P = 0.02) than patients without C4d deposition. Glomerular C4d deposition was associated with a high Oxford classification score, including M1, E1, S1, and T1/2 lesions (all P ≤ 0.006). Patients with C4d deposition had higher rates of use of renin-angiotensin system blockers and immunosuppressants. Glomerular C4d was found to be a risk factor for the composite kidney event (RR, 3.17; 95% CI, 2.29-4.40; P < 0.001; adjusted HR, 2.05; 95% CI, 1.53-2.76; P < 0.001) and end-stage kidney disease (RR, 4.37; 95% CI, 3.15-6.07; P < 0.001) without evidence of heterogeneity. LIMITATIONS: The definition of positive C4d was not uniform and not all studies provided data about kidney outcomes. CONCLUSIONS: Glomerular C4d deposition is associated with an adverse prognosis and may be a useful biomarker of disease prediction in IgAN.

Prevalence of Kidney Injury and Associations with Critical Illness and Death in Patients with COVID-19.

BACKGROUND AND OBJECTIVES: Coronavirus disease 2019 is spreading rapidly across the world. This study aimed to assess the characteristics of kidney injury and its association with disease progression and death of patients with coronavirus disease 2019. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a retrospective study. Two representative cohorts were included. Cohort 1 involved severe and critical patients with coronavirus disease 2019 from Wuhan, China. Cohort 2 was all patients with coronavirus disease 2019 in Shenzhen city (Guangdong province, China). Any kidney injury was defined as the presence of any of the following: hematuria, proteinuria, in-hospital AKI, or prehospital AKI. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria. The primary outcome was death at the end of follow-up. The secondary outcome was progression to critical illness during the study period. RESULTS: A total of 555 patients were enrolled; 42% of the cases (229 of 549) were detected with any kidney injury, 33% of the cases (174 of 520) were detected with proteinuria, 22% of the cases (112 of 520) were detected with hematuria, and 6% of the cases (29 of 520) were detected with AKI. Of the 29 patients with AKI, 21 cases were recognized as in-hospital AKI, and eight were recognized as prehospital AKI. Altogether, 27 (5%) patients died at the end of follow-up. The death rate was 11% (20 of 174) in patients with proteinuria, 16% (18 of 112) in patients with hematuria, and 41% (12 of 29) in the AKI settings. Multivariable Cox regression analysis showed that proteinuria (hazard ratio, 4.42; 95% confidence interval, 1.22 to 15.94), hematuria (hazard ratio, 4.71; 95% confidence interval, 1.61 to 13.81), and in-hospital AKI (hazard ratio, 6.84; 95% confidence interval, 2.42 to 19.31) were associated with death. Among the 520 patients with noncritical illness at admission, proteinuria (hazard ratio, 2.61; 95% confidence interval, 1.22 to 5.56) and hematuria (hazard ratio, 2.50; 95% confidence interval, 1.23 to 5.08) were found to be associated with progression to critical illness during the study period. CONCLUSIONS: Kidney injury is common in coronavirus disease 2019, and it is associated with poor clinical outcomes. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_09_18_CJN04780420.mp3.