Estimated GFR Trajectories in Pediatric and Adult Nephrotic Syndrome: Results From the Nephrotic Syndrome Study Network (NEPTUNE)

Abigail R Smith; Jarcy Zee; Nan Ji; Jonathan P Troost; Brenda W Gillespie; Viji Nair; Qian Liu; Keisha L Gibson; Matthias Kretzler; Laura H Mariani

doi:10.1016/j.xkme.2020.03.006

Estimated GFR Trajectories in Pediatric and Adult Nephrotic Syndrome: Results From the Nephrotic Syndrome Study Network (NEPTUNE)

Kidney Med. 2020 Jun 5;2(4):407-417. doi: 10.1016/j.xkme.2020.03.006. eCollection 2020 Jul-Aug.

Authors

Affiliations

¹ Arbor Research Collaborative for Health, Ann Arbor, MI.
² Michigan Institute for Clinical and Health Research, University of Michigan, Ann Arbor, MI.
³ Department of Biostatistics, University of Michigan, Ann Arbor, MI.
⁴ Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI.
⁵ Division of Pediatric Nephrology, Department of Nephrology and Hypertension, University of North Carolina, Chapel Hill, NC.

Abstract

Rationale & objective: Surrogate outcomes for end-stage kidney disease often assume linear changes, which may not reflect true estimated glomerular filtration rate (eGFR) trajectories. This study's objective was to characterize nonlinear eGFR trajectories in nephrotic syndrome.

Study design: Observational cohort study.

Setting & participants: Nephrotic Syndrome Study Network (NEPTUNE) is a multicenter study of adult and pediatric patients with proteinuria enrolled at clinically indicated kidney biopsy or initial presentation of disease (pediatric only).

Predictors: Patient demographic, clinical, and pathology variables at study enrollment and follow-up time.

Outcome: eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (patients ≥ 18 years old) or modified Chronic Kidney Disease in Children Study-Schwartz (patients < 18 years) formulas. The probability of nonlinearity (PNL) was calculated for individual eGFR trajectories.

Analytical approach: Associations between predictors and PNL were assessed using multivariable linear regression.

Results: 453 patients with ≥3 eGFR measurements and 1 or more year of follow-up were included (median follow-up, 3.6 years). Median PNL was 0.052; 56% and 16% had PNL < 10% and >50%, respectively. In both adults and pediatric patients, higher baseline eGFR was associated with higher PNL, whereas longer follow-up time was associated with lower PNL. Higher urine protein-creatinine ratio and steroid use were also associated with higher PNL in adults. Higher percentages of tubular atrophy and foot-process effacement were associated with lower and higher PNLs, respectively, in adults.

Limitations: Relatively short follow-up time, inability to assess acute kidney injury events, and variable eGFR measurement frequency across patients.

Conclusions: Although increasing follow-up time resulted in more linear trajectories, nonlinear eGFR trajectories were common in this cohort. Future studies in nephrotic syndrome should consider novel outcomes that do not rely on linearity assumptions.

Keywords: ESKD; Glomerular disease; non-linear eGFR; surrogate outcomes.

Grants and funding

K08 DK115891/DK/NIDDK NIH HHS/United States