allopurinol and Glomerulonephritis--IGA

Immunoglobulin A (IgA) nephropathy (IgAN) is the most common form of primary glomerulopathy worldwide. Various investigations have addressed the clinical and morphological risk factors related to the risk of progression. Recently, much attention has been made toward the prognostic implication of serum uric acid in patients with IgAN. It has been observed that treatment of hyperuricemia with allopurinol in chronic kidney failure has resulted in a fall in blood pressure and inhibition of the progression of kidney injury. Recent studies have documented that hyperuricemia is an independent risk factor for IgAN, and appropriate treatment by allopurinol is a reasonable modality in these patient. We believe that allopurinol should routinely be included to the treatment of IgAN patients; however, this hypothesis requires further investigation. Clinical studies are suggested to better understand kidney protective properties of allopurinol in IgAN.

Topics: Allopurinol; Disease Progression; Glomerulonephritis, IGA; Gout Suppressants; Humans; Hyperuricemia; Kidney; Kidney Failure, Chronic; Risk Factors; Treatment Outcome; Uric Acid

Topics: Allopurinol; Glomerulonephritis; Glomerulonephritis, IGA; Gout; Humans; Hyperuricemia; Lead Poisoning; Polycystic Kidney, Autosomal Dominant

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.. 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.. 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).. 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.

Topics: Adolescent; Adult; Aged; Allopurinol; Cohort Studies; Female; Follow-Up Studies; Glomerulonephritis, IGA; Humans; Hyperuricemia; Male; Middle Aged; Pilot Projects; Prospective Studies; Retrospective Studies; Treatment Outcome; Young Adult

Recent clinical studies have demonstrated the protective effect of xanthine oxidase (XO) inhibitors against chronic kidney diseases, although the underlying molecular mechanisms remain unclear. However, to date, neither clinical nor basic research has been carried out to elucidate the efficacy of XO inhibitor administration for IgA nephropathy. We thus investigated whether febuxostat, an XO inhibitor, exerts a protective effect against the development of IgA nephropathy, using gddY mice as an IgA nephropathy rodent model. Eight-week-old gddY mice were provided drinking water with (15 μg/mL) or without febuxostat for nine weeks and then subjected to experimentation. Elevated serum creatinine and degrees of glomerular sclerosis and fibrosis, judged by microscopic observations, were significantly milder in the febuxostat-treated than in the untreated gddY mice, while body weights and serum IgA concentrations did not differ between the two groups. In addition, elevated mRNA levels of inflammatory cytokines such as TNFα, MCP-1, IL-1β, and IL-6, collagen isoforms and chemokines in the gddY mouse kidneys were clearly normalized by the administration of febuxostat. These data suggest a protective effect of XO inhibitors against the development of IgA nephropathy, possibly via suppression of inflammation and its resultant fibrotic changes, without affecting the serum IgA concentration.

Topics: Animals; Anti-Inflammatory Agents; Chemokines; Disease Progression; Endoplasmic Reticulum Stress; Febuxostat; Female; Fibrosis; Gene Expression Regulation; Glomerulonephritis, IGA; Inflammation Mediators; Kidney; Mice, Inbred BALB C; Xanthine Oxidase