Prognosis in IgA nephropathy: 30-year analysis of 1,012 patients at a single center in Japan

Abstract

Background: Little is known about the long-term prognosis of patients with IgA nephropathy (IgAN).

Methods: This retrospective cohort analysis evaluated clinical and histological findings at the time of renal biopsy, initial treatment, patient outcomes over 30 years, and risk factors associated with progression in 1,012 patients diagnosed with IgAN at our center since 1974.

Results: Of the 1,012 patients, 40.5% were male. Mean patient age was 33±12 years and mean blood pressure was 122±17/75±13 mmHg. Mean serum creatinine concentration was 0.89±0.42 mg/dL, and mean estimated glomerular filtration rate (eGFR) was 78.5±26.2 ml/min/1.73 m2. Mean proteinuria was 1.19±1.61 g/day, and mean urinary red blood cells were 36.6±35.3/high-powered field. Histologically, mesangial hypercellularity was present in 47.6% of patients, endothelial hypercellularity in 44.3%, segmental sclerosis in 74.6%, and tubular atrophy/interstitial fibrosis in 28.8% by Oxford classification. Initial treatment consisted of corticosteroids in 26.9% of patients, renin-angiotensin-aldosterone system inhibitor in 28.9%, and tonsillectomy plus steroids in 11.7%. The 10-, 20-, and 30-year renal survival rates were 84.3, 66.6, and 50.3%, respectively. Tonsillectomy plus steroids dramatically improved renal outcome. Cox multivariate regression analysis showed that higher proteinuria, lower eGFR, and higher uric acid at the time of renal biopsy were independent risk factors for the development of end stage renal disease (ESRD).

Conclusions: IgAN is not a benign disease, with about 50% of patients progressing to ESRD within 30 years despite treatment.

Figure 1. Cumulative renal survival rate from renal biopsy until ESRD in all 1,012 patients with IgAN.

Figure 2. Cumulative renal survival rates in IgAN patients categorized by initial treatment.

Figure 3. Cumulative renal survival rates in IgAN patients categorized by eGFR, U-Prot, U-RBC and uric acid concentration.

(a) The 30-year survival rates of patients with eGFR >80 ml/min/1.73m², between 80 and 60 ml/min/1.73m², and between 60 and 40 ml/min/1.73m² were 80.1%, 43.1%, and 34.6%, respectively. The survival rates of patients with eGFR between 40 and 20 ml/min/1.73m² and <20 ml/min/1.73m² were 24.8% over 18 years and 40.0% over 7 years, respectively. The difference among groups was statistically significant (P<0.0001). (b) The 30-year renal survival rates of patients with U-Prot <0.5 g/day, between 0.5 and 1 g/day, and between 1 and 3 g were 62.6%, 55.6%, and 49.0%, respectively. The survival rates of patients with U-Prot between 3 and 5 g/day and >5 g/day were 29.9% over 20 years and 34.4% over 15 years, respectively. The difference among groups was statistically significant (P<0.0001). (c) The 30-year renal survival rates of patients with U-RBC <10 counts/HF, between 10 and 49 counts/HF, and ≥100 counts/HF were 50.2, 49.0, and 41.7%. The survival rates of patients with U-RBC between 50 and 99 counts/HF was 29.6% over 25 years. The difference among groups was not statistically significant (P = 0.1122). (d) The 30-year renal survival rates of patients with uric acid <6 mg/dl, between 6 and 8 mg/dl, and >8 mg/dl were 62.3, 35.1, and 41.2%, respectively (P<0.0001).

Figure 4. Renal survival rates in IgAN patients diagnosed between 1974 and 1991 and between 1992 and 2001.

The 10(86.6% vs. 79.1%) and 20 year (75.2% vs. 59.0%) renal survival rates were significantly higher in patients diagnosed between 1992 and 2011 than in between 1974 and 1991 (P = 0.0002).