Abstract
Background and Aims
Lower estimated glomerular filtration rate (eGFR) and higher proteinuria are the most sensitive predictor of the development of progressive renal insufficiency in various glomerular diseases. On the other hand, the onset of idiopathic membranous nephropathy (iMN) shows insidious progression, and the prognosis varies significantly. Therefore, it is difficult to predict the renal outcome in MN, using only the severity of proteinuria. Fractional excretion of total protein (FETP), which was protein clearance divided by creatinine clearance (Ccr), may be a better indicator of protein leak per functioning nephron. A recent study has also reported that FETP accurately predicted transplant failure and was more sensitive and specific than protein creatine ratio (PCR). Few studies, however, have analyzed the FETP to evaluate their relationship with renal function and histologic lesions in glomerular diseases. Thus, this study aims to assess the relationship between FETP and the clinicopathological findings and whether FETP predicts outcome in iMN.
Method
This study included patients with iMN that underwent kidney biopsies during the period from 2002 to 2020. We analyzed 24-h urinary protein excretion, FETP, and other clinicopathological findings at the kidney biopsy. The FETP was determined by the standard clearance technique based on 24-h urine collection: FETP = (urinary total protein / serum total protein) / (urinary creatinine / serum creatinine) × 100. A 30% decrease in eGFR or the occurrence of ESRD were the endpoints. The multivariate factors affecting the prognosis were analyzed with the Cox proportional-hazards model, and the cumulative risk of risk factors was analyzed by Kaplan‑Meier curve.
Results
A total of 153 subjects with MN were identified and were followed up for a median of 5.4 years. (age 64.9±13.6 [mean ± SD] years, male 73.2 %, hypertension 42.5 %, diabetes 10.5 %, nephrotic Syndrome 67.3 %, chronic kidney disease [CKD: eGFR<60ml/min/1.73m2] 51.9 %, eGFR 61.6±22.6 mL/min/1.73m2, urinary protein excretion [u-TP] 4.3±3.6 g/day, PCR 5.4±4.5 g/gCr, FETP 0.12±0.18 %, Selectivity Index [S.I] 0.23±0.39, fractional excretion of IgG [FEIgG] 0.065±0.170 %, glomerulosclerosis [GS] 13.9±13.7 %, interstitial fibrosis and tubular atrophy [IFTA] 12.2±10.0 %). FETP was more significantly associated with clinical parameters than PCR and FEIgG (Table.1). The high FETP group had a significantly worse renal prognosis during the follow-up periods than the low FETP group (Figure.1). Using Cox proportional hazards models, with FETP entered, and age, sex, eGFR,u-TP as covariates, FETP predict the primary endpoint with a hazards ratio of 0.343 (P<0.05).
Conclusion
These results suggest that FETP would be superior to PCR, the standard measure of proteinuria, in predicting outcome in patients with iMN. FETP could indicate the increased glomerular protein permeability and decreased glomerular filtration function in iMN.
Effects of Metreleptin on Proteinuria in Patients With Lipodystrophy
