Complete Remission in the Nephrotic Syndrome Study Network

Abstract

Background and objectives This analysis from the Nephrotic Syndrome Study Network (NEPTUNE) assessed the phenotypic and pathology characteristics of proteinuric patients undergoing kidney biopsy and defined the frequency and factors associated with complete proteinuria remission (CRever).Design, setting, participants, & measurements We enrolled adults and children with proteinuria $0.5 g/d at the time of first clinically indicated renal biopsy at 21 sites in North America from April 2010 to June 2014 into a prospective cohort study. NEPTUNE central pathologists assigned participants to minimal-change disease (MCD), FSGS, membranous nephropathy, or other glomerulopathy cohorts. Outcome measures for this analysis were (1) CRever with urine protein-to-creatinine ratio (UPC) ,0.3 g/g with preserved native kidney function and (2) ESRD. Continuous variables are reported as median and interquartile range (IQR; 25th, 75th percentile). Cox proportional hazards modeling was used to assess factors associated with CRever.Results We enrolled 441 patients: 116 (27%) had MCD, 142 (32%) had FSGS, 66 (15%) had membranous nephropathy, and 117 (27%) had other glomerulopathy. The baseline UPC was 4.1 g/g (IQR, 1.9, 7.7) and the eGFR was 81 ml/min per 1.73 m 2 (IQR, 50, 105). Median duration of observation was 19 months (IQR,11, 30). CRever occurred in 46% of patients, and 4.6% progressed to ESRD. Multivariate analysis demonstrated that higher prebiopsy proteinuria (hazard ratio, 0.3; 95% confidence interval, 0.2 to 0.5) and pathology diagnosis (FSGS versus MCD; hazard ratio, 0.2; 95% confidence interval, 0.1 to 0.5) were inversely associated with CRever. The effect of immunosuppressive therapy on remission varied by pathology diagnosis.Conclusions In NEPTUNE, the high frequency of other pathology in proteinuric patients affirms the value of the diagnostic kidney biopsy. Clinical factors, including level of proteinuria before biopsy, pathology diagnosis, and immunosuppression, are associated with complete remission.

Renal matrix Gla protein expression increases progressively with CKD and predicts renal outcome

“…NEPTUNE is part of the National Institutes of Health (NIH) Rare Disease Clinical Research Network (RDCRN). The study design and cohort baseline description are published (Gadegbeku et al, 2013; Gipson et al, 2016). NEPTUNE was approved by collaborating center Institutional Review Boards, and subjects or guardians provided consent to participate.…”

“…eGFR (mL/min/1.73m 2 ) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula for participants ≥ 18 years old and the modified CKiD-Schwartz formula for children < 18 years old. CKD progression was evaluated with a composite of 40% decline in eGFR from baseline or end-stage renal disease (ESRD) (Mariani et al, 2017; Levey et al, 2014), defined as the initiation of dialysis, kidney transplant, or eGFR < 15 mL/min/1.73 m 2 on two measurements (Gipson et al, 2016). …”

The relatively poor correlation between random and 24-hour urine protein excretion in patients with biopsy-proven glomerular diseases

“…Full details of the study design and baseline description of the cohort have been published elsewhere. 28, 29 Eligibility criteria include: individuals of any age scheduled for a clinically-indicated renal biopsy with proteinuria ≥ 500 mg/day from a 24-hour or random (protein to creatinine ratio (UPCR) > 0.5 g/g) urine sample. Patients with sub-nephrotic proteinuria were included to capture the broad spectrum of clinical presentations.…”

The Incidence of Primary vs Secondary Focal Segmental Glomerulosclerosis: A Clinicopathologic Study

“…1–7 (Table 1) FSGS now accounts for 20 to 40% of all biopsy-proven glomerular diseases in adults. 3–8 However, the previous studies have important limitations. First, the majority of the studies reported trends in relative disease frequencies among biopsied patients rather than true population-based incidence rates of FSGS.…”

“…Another important limitation in the previous studies is the approach of reporting FSGS as a single disease entity. 2–8 We now know that FSGS is a histological pattern of injury that characterizes a broad spectrum of diseases with different pathophysiologies. Primary FSGS is presumed to be due to a circulating permeability factor diffusely toxic to podocytes, which may respond to immunosuppressive treatment.…”