Comparing Long-Term Outcomes in Glomerular Disease Patients Presenting with Nephrotic Syndrome Versus Nephrotic Range Proteinuria

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Background: Despite extensive research on proteinuria’s impact on chronic kidney disease progression, there is no direct comparison of outcomes in biopsy-diagnosed glomerular disease (GD) patients with nephrotic syndrome (NS) or nephrotic range proteinuria (NRP). Our study addresses this gap, comparing long-term outcomes between NS and NRP. Methods: We conducted a retrospective study on 240 kidney biopsy-proven GD patients, tracked from 2010 to 2015 until end-stage kidney disease (ESKD), death, or the study end in January 2022. Results: The median follow-up was 8.8 years. Diagnoses were predominantly nonproliferative (53%), proliferative (25%) nephropathies, diabetic nephropathy (12%), and paraprotein diseases (10%). NS was observed in 141 (59%) patients, presenting more frequently with arterial hypertension, higher eGFR, increased proteinuria, and dyslipidemia than NRP patients. NRP patients often had proliferative GD and diabetic nephropathy; their renal chronicity score was higher. The ESKD endpoint occurred in 35% NS and 39% NRP patients (p 0.4). The cohort’s mean kidney survival time was 8.2 years. In a multivariate analysis, NS, lower eGFR, a higher renal chronicity score, and diabetic nephropathy were associated with ESKD. A total of 64 patients (27%) died, 73% post-kidney replacement therapy initiation, and mostly from cardiovascular disease (63%). Mortality between proteinuria forms showed no difference. The multivariate analysis found lower eGFR, a higher Charlson comorbidity score, and diabetic nephropathy associated with mortality. Conclusions: Our study found no difference in all-cause mortality between NS and NRP in glomerular diseases. However, an adjusted analysis revealed poorer kidney survival for NS patients, emphasizing the need for personalized management to improve renal prognoses.