Effects of Allopurinol on the Progression of Chronic Kidney Disease.

BACKGROUND: Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease who are at risk for progression is not known. METHODS: In this randomized, controlled trial, we randomly assigned adults with stage 3 or 4 chronic kidney disease and no history of gout who had a urinary albumin:creatinine ratio of 265 or higher (with albumin measured in milligrams and creatinine in grams) or an eGFR decrease of at least 3.0 ml per minute per 1.73 m2 of body-surface area in the preceding year to receive allopurinol (100 to 300 mg daily) or placebo. The primary outcome was the change in eGFR from randomization to week 104, calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. RESULTS: Enrollment was stopped because of slow recruitment after 369 of 620 intended patients were randomly assigned to receive allopurinol (185 patients) or placebo (184 patients). Three patients per group withdrew immediately after randomization. The remaining 363 patients (mean eGFR, 31.7 ml per minute per 1.73 m2; median urine albumin:creatinine ratio, 716.9; mean serum urate level, 8.2 mg per deciliter) were included in the assessment of the primary outcome. The change in eGFR did not differ significantly between the allopurinol group and the placebo group (-3.33 ml per minute per 1.73 m2 per year [95% confidence interval {CI}, -4.11 to -2.55] and -3.23 ml per minute per 1.73 m2 per year [95% CI, -3.98 to -2.47], respectively; mean difference, -0.10 ml per minute per 1.73 m2 per year [95% CI, -1.18 to 0.97]; P = 0.85). Serious adverse events were reported in 84 of 182 patients (46%) in the allopurinol group and in 79 of 181 patients (44%) in the placebo group. CONCLUSIONS: In patients with chronic kidney disease and a high risk of progression, urate-lowering treatment with allopurinol did not slow the decline in eGFR as compared with placebo. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; CKD-FIX Australian New Zealand Clinical Trials Registry number, ACTRN12611000791932.).

Recent evidence on the effect of urate-lowering treatment on the progression of kidney disease.

PURPOSE OF REVIEW: Several observational studies have shown that hyperuricemia is associated with chronic kidney disease (CKD) progression and is a potential therapeutic target in people with CKD. This review discusses the results of three recently published placebo-controlled randomized trials evaluating the effect of urate-lowering treatment on the progression of CKD with at least 2 years of follow-up. RECENT FINDINGS: The Febuxostat versus Placebo Randomized Controlled Trial Regarding Reduced Renal Function in Patients with Hyperuricemia Complicated by Chronic Kidney Disease Stage 3 trial evaluated the effect of febuxostat in 443 patients with stage 3 CKD (mean estimated glomerular filtration rate [eGFR] 45 mL/min/1.73 m2) and asymptomatic hyperuricemia (mean serum urate 7.8 mg/dL). The Controlled trial of slowing of Kidney Disease progression From the Inhibition of Xanthine oxidase and Preventing Early Renal Loss in Diabetes trials respectively evaluated the effect of allopurinol in 369 adults with stage 3 or 4 CKD (mean eGFR 31.7 mL/min/1.73 m2, mean serum urate 8.2 mg/dL) with high progression risk and 530 patients with type 1 diabetes and diabetic kidney disease (mean eGFR 74.7 mL/min/1.73 m2, mean serum urate 6.1 mg/dL). Despite the large and sustained reductions in serum urate levels in all 3 trials, urate-lowering treatment with febuxostat or allopurinol did not result in clinically meaningful improvement in kidney outcomes. SUMMARY: The results of large and well-designed placebo-controlled trials do not support the use of urate-lowering therapy to slow the progression of CKD.

Sex differences in chronic kidney disease prevalence in Asia: a systematic review and meta-analysis.

Background: Previous reports on the prevalence of chronic kidney disease (CKD) in Asia have suggested important sex disparities but have been inconsistent in nature. We sought to synthesize available sex-disaggregated CKD prevalence data in Asia to quantify sex disparities in the region. Methods: We systematically searched MEDLINE and Embase for observational studies involving ≥500 adults who reported sex-disaggregated CKD prevalence data in any of the 26 countries in East, Southeast and South Asia. For each study we calculated the female:male prevalence ratio (PR), with a ratio >1 indicating a higher female prevalence. For each country, log-transformed PRs were pooled using random effects meta-analysis. These were then combined using a fixed effects model, weighting by population size, to estimate a pooled PR for each of East, Southeast and South Asia and Asia overall. Results: Sex-disaggregated data were available from 171 cohorts, spanning 15 countries and comprising 2 550 169 females and 2 595 299 males. Most studies (75.4%) came from East Asia (China, Taiwan, Japan and South Korea). Across Asia, CKD prevalence was higher in females {pooled prevalence 13.0% [95% confidence interval (CI) 11.3-14.9]} compared with males [pooled prevalence 12.1% (95% CI 10.3-14.1)], with a pooled PR of 1.07 (95% CI 0.99-1.17). Substantial heterogeneity was observed between countries. The pooled PRs for East, Southeast and South Asia were 1.11 (95% CI 1.02-1.21), 1.09 (0.88-1.36) and 1.03 (0.87-1.22), respectively. Conclusions: Current evidence suggests considerable between-country and -region heterogeneity in the female:male PR of CKD. However, there remains a large part of the region where data on sex-specific CKD prevalence are absent or limited. Country-level assessment of the differential burden of CKD in females and males is needed to define locally relevant policies that address the needs of both sexes.

Significant infrarenal aortic stenosis in pregnancy: a case report.

BACKGROUND: Hypertension is common in pregnant women presenting with aortic coarctation or Takayasu's arteritis. Uncontrolled hypertension leads to increased adverse maternal and neonatal events. CASE PRESENTATION: A 36-year-old gravida 2, para 1 Caucasian woman presented at 9 weeks of gestation with headaches but normal blood pressure. She had a past medical history of an in vitro fertilization pregnancy complicated by preeclampsia at 27 weeks of gestation (birth weight 1900 g) and infrarenal aortic stenosis. In the current pregnancy, she received aspirin and calcium as preeclampsia prophylaxis, remained normotensive throughout pregnancy, and was delivered by elective cesarean section at 37 weeks without complications. CONCLUSIONS: This case demonstrates a significant chronic aortopathy in pregnancy with normal fetal growth and uterine blood flow through collateral supply from the internal mammary and epigastric arteries.