Background: Based on observations of the clinical course in patients with IgA nephropathy (IgAN), D'Amico et al proposed the concept of the "point of no return (PNR)", after which progression to end-stage renal disease (ESRD) becomes inevitable. They reported that the approximate PNR is serum creatinine (sCr) 3.0 mg/dL.
Methods: To confirm the PNR and to clarify the factors affecting renal function deterioration in IgAN patients, we analyzed the sequential data of those with 1.2 <or= sCr <2.0 mg/dL at renal biopsy. Forty-seven patients with moderate to severe histological lesions and whose 36-month follow-up did not require renal replacement therapy were enrolled in this study.
Results: None of the patients who once exceeded sCr 2.0 mg/dL could return to <2.0 mg/dL during the observation period (103.3 +/- 54.3 (36-237) months). Kaplan-Meier analysis revealed that the renal outcome of patients with average mean blood pressure (MBP) >or= 102 mmHg and/or urinary protein (UP) score >or= 2.0 with sCr up to 2.0 mg/dL was significantly poor. Multivariate analysis using the Cox's proportional hazards model, identified only MBP and UP during the course until sCr reached 2.0 mg/dl as independent prognostic factors for ESRD, having hazard ratios of 2.56 (per 10 mmHg; 95% confidence interval (95% CI) 1.08-6.05) and 4.37 (per 0.5 point; 95% CI 1.36-14.1), respectively.
Conclusions: We confirmed PNR as a sCr level of 2.0 mg/dL (equivalent to estimated glomerular filtration rate (GFR) of 30-35 mL/min/1.73m2) during the course of IgAN in Japan. Proper management of both BP and UP until sCr has reached PNR is essential to arrest the progression to ESRD in IgAN.