Clinical outcome of hyperuricemia in IgA nephropathy: a retrospective cohort study and randomized controlled trial

Abstract

Background: Hyperuricemia is an independent risk factor for renal progression in IgA nephropathy (IgAN). However, no study has evaluated the effect of allopurinol on the clinical outcome in hyperuricemic IgAN.

Methods: First,a retrospective cohort study of 353 IgAN patients was conducted to explore the relationship between uric acid (UA) and the progression of renal disease over a mean period of 5 years. Then, 40 hyperuricemic IgAN patients were randomized to receive allopurinol (100-300 mg/day) or usual therapy for 6 months. The study outcomes were renal disease progression and/or blood pressure.

Results: Hyperuricemia independently predicted renal survival at 1, 3, and 5 years after adjustment for different baseline estimated glomerular filtration rates. In the randomized controlled trial, allopurinol did not significantly alter renal progression or proteinuria. The antihypertensive drug dosage was reduced in 7 of 9 cases with hypertension in the allopurinol group compared to 0 of 9 cases in the control group (p < 0.01). UA levels correlated with mean arterial pressure in normotensive patients (r = 0.388, p < 0.001).

Conclusion: Hyperuricemia predicts the progression of IgAN independently of baseline estimated glomerular filtration rate. Allopurinol may improve the control of blood pressure. Further studies are required to explore the effects of lowering UA on renal protection in IgAN.

Fig. 1

a Cumulative probability of renal survival for all CKD (stages 1–3) patients in relation to UA at the time of renal biopsy. The differences in the renal survival of patients with or without hyperuricemia were statistically significant, p < 0.0001. b Cumulative probability of renal survival for CKD (stage 1–2) patients with eGFR ≥ 60 min/ml in relation to UA at the time of renal biopsy. The differences in renal survival of patients with or without hyperuricemia were statistically significant, p < 0.001. c Cumulative probability of renal survival for CKD patients (stage 3) with eGFR < 60 min/ml in relation to UA at the time of renal biopsy. The differences in the renal survival of patients with or without hyperuricemia were statistically significant, p = 0.03. d Number of patients exposed to risk at the time point (a–c).

Fig. 2

Study algorithm. Enrollment of patients, treatment assignments, and outcomes in the study.

Fig. 3

a Baseline and repeated values of eGFR during the 6-month therapy for patients with eGFR < 60 ml/min/1.73 m² treated with allopurinol or control therapy. eGFR was not significantly changed at the end of 6 months. b Baseline and repeated values of eGFR during the 6-month therapy for patients treated with allopurinol or control therapy. eGFR was not significantly changed at the end of 6 months (p = 0.2 for allopurinol group vs. baseline value, p = 0.9 for control treatment group vs. baseline value and p = 0.2 compared with two treatment groups at the end of study, respectively). By the end of the first month, compared to baseline values before allopurinol treatment, eGFR was reduced (by 9.3 ± 1.4%, p = 0.2).

Fig. 4

Relationship between serum UA and MAP in patients without antihypertensive (r = 0.388, p < 0.001).