High (≥6.5) Spontaneous and Persistent Urinary pH Is Protective of Renal Function at Baseline and during Disease Course in Idiopathic Membranous Nephropathy

Metabolic acidosis correction in advanced renal failure slows renal function decline attributed to tubulointerstitial damage (TID) reduction. No study evaluated if spontaneous baseline high urinary pH (UpH) is renoprotective in patients with normal renal function and without metabolic acidosis. The study tested this hypothesis in idiopathic membranous nephropathy (IMN). Eighty-five patients (follow-up 81 ± 54 months) measured UpH, serum creatinine, eGFR, protein/creatinine ratio, fractional excretion of albumin, IgG, α1-microglobulin, and urinary N-acetyl-β-D-glucosaminidase (β-NAG)/creatinine ratio. Twenty-eight patients (33%) had UpH ≥ 6.5 and 57 (67%) pH < 6.5; high versus low UpH patients had significantly lower values of the tubulointerstitial damage (TID) markers FE α1m and β-NAG and significantly better baseline renal function. These differences persisted over time in a subset of 38 patients with 5 measurements along 53 ± 26 months. In 29 patients with nephrotic syndrome (NS) treated with supportive therapy (follow-up: 80 ± 52 months) renal function was stable in 10 high and significantly worse in 19 low UpH patients. Steroids + cyclophosphamide treatment in 35 NS patients masks the renoprotection of high UpH. Conclusions. In IMN high and persistent UpH is associated with reduction of the proteinuric markers of tubulointerstitial damage and baseline better renal function in all patients and in NS patients treated only with supportive therapy during disease course. The factors associated with high pH-dependent renoprotection were lower values of TID markers, eGFR ≥ 60 mL/min, BP < 140/90 mmHg, and age < 55 years.