Uric Acid as a Predictor of Immunoglobulin A Nephropathy Progression: A Cohort Study of 1965 Cases

Abstract

Background: The role of serum uric acid (SUA) level in the progression of Immunoglobulin A nephropathy (IgAN) remains controversial. Methods: In a cohort of 1,965 cases with biopsy-proven IgAN, we examined the associations of SUA concentration with the primary outcome of a composite of all-cause mortality or kidney failure (defined as a reduction of estimated glomerular filtration rate [eGFR] by 40% from baseline, requirements for dialysis and transplantation), or the outcome of kidney failure alone, assessed using Cox and logistic regression models, respectively, with adjustment for confounders. Results: At baseline, the mean age was 33.37 ± 11.07 years, eGFR was 101.30 ± 30.49 mL/min/1.73 m², and mean uric acid level was 5.32 ± 1.76 mg/dL. During a median of 7-year follow-up, 317 cases reached the composite outcome of all-cause mortality (5 deaths) or kidney failure (36 cases of dialysis, 5 cases of renal transplantation, and 271 cases with reduction of eGFR by 40% from baseline). After adjustment for demographic and IgAN specific covariates and treatments, a higher quartile of uric acid was linearly associated with an increased risk of the primary outcome (highest versus lowest quartile, hazard ratio [HR] 2.39; 95% CI 1.52–3.75) and kidney failure (highest versus lowest quartile, HR 2.55; 95% CI 1.62–4.01) in the Cox proportional hazards regression models. In the continuous analysis, a 1 mg/dL greater uric acid level was associated with 16% increased risk of primary outcome (HR 1.16, 95% CI 1.07–1.25) and 17% increased risk of kidney failure (HR 1.17, 95% CI 1.08–1.27), respectively, in the fully adjusted model. The multivariate ­logistic regression analyses for the sensitive analyses drew consistent results. In the subgroup analyses, significant interactions were detected that patients with mean arterial pressure (MAP) < 90 mm Hg or mesangial hypercellularity had a higher association of SUA with the incidence of the primary outcome than those with MAP ≥90 mm Hg or those without mesangial hypercellularity respectively. Hyperuricemia was not significantly associated with the risk of developing the primary outcome in elder patients (≥32 years old), patients with eGFR < 90 mL/min or with tubular atrophy/interstitial fibrosis. Conclusions: SUA level may be positively associated with the progression of IgAN. It was noticeable that the association of hyperuricemia with IgAN progression was less significant in patients with elder age, lower eGFR, or tubular atrophy/interstitial fibrosis, which may be due to some more confounders in association with the IgA progression in these patients. Future prospective studies are warranted to confirm these findings and to investigate the underlying mechanisms.

The Correlation between Serum Uric Acid and Renal Function in Elderly Chinese Diabetes with Normoalbuminuria

“…With the increase in life expectancy and the large number of diabetic patients, diabetes has replaced chronic glomerulonephritis as the primary cause of new dialysis patients in Shanghai [7] and Beijing [12] which are the big cities in China although the control of blood glucose, blood lipids, and blood pressure [13–15] has been strengthened. Recently, studies have shown that a significant proportion of diabetes with normoalbuminuria have glomerular filtration rate (GFR) decrease [8, 16] while serum uric acid (SUA) has reentered the spotlight as a cause of renal insufficiency [17, 18].…”

Serum uric acid level is correlated with the clinical, pathological progression and prognosis of IgA nephropathy: an observational retrospective pilot-study

“…This study also has shown that, except for glomerulosclerosis percentage, there is no significant difference in the 2009 Oxford classification, crescentic percentage, and focal segmental sclerosis between the hyperuricemia group and the normo-uricemia group (Moriyama et al, 2015). Another study suggested that the relationship between hyperuricemia and IgAN progression was not very significant in patients with older age, lower eGFR, or interstitial lesion (Zhu et al, 2018). Similarly, this study did not use the updated Oxford classification of IgAN.…”

Fructose and Uric Acid: Major Mediators of Cardiovascular Disease Risk Starting at Pediatric Age

“…Uric acid internalization by URAT 1 is necessary for its deleterious and pro-apoptotic effect at the tubular level, and this is confirmed by the protective effect showed by losartan, which reduced TLR4, MCP1 and Nox4 expression [ 74 ]. Taken together with the association between increased serum uric acid levels and the more severe tubular atrophy and vascular damage described in different series of renal biopsy [ 75 , 76 , 77 , 78 , 79 , 80 ], these findings might explain, at least in part, the unfavorable renal outcomes related to hyperuricemia.…”