Efficacy of xanthine oxidase inhibitor for chronic kidney disease patients with hyperuricemia.

BACKGROUND: Hyperuricemia is a known risk factor for end-stage renal disease. Although xanthine oxidase (XO) inhibitors are expected to protect the kidney function, evidence to this end is insufficient at present. METHODS: This study was a multi-center, open-labeled, randomized study conducted in Mie Prefecture in Japan. Patients were included if they were between 20 and 80 years old and had a serum uric acid (sUA) level ≥ 7.0 mg/dl with or without gout, estimated glomerular filtration rate (eGFR) of 15-60 ml/min/1.73 m2, and urinary protein creatinine ratio (uPCR) of 0.15-3.5 g/gCr. Patients were randomly assigned to a Topiroxostat or Febuxostat group, and the treatment target for the sUA level was < 6.0 mg/dl. The primary outcome was the change in the uPCR after 24 weeks. RESULTS: The change in the median uPCR after 24 weeks was not statistically significant after treatment in the Topiroxostat or Febuxostat group (0.05 g/gCr and - 0.04 g/gCr, respectively). However, the sUA levels decreased significantly in both groups (Topiroxostat group: 8.6 ± 1.1 at baseline to 6.0 ± 1.1 mg/dl at 24 weeks, Febuxostat group: 8.4 ± 1.1 mg/dl at baseline to 5.9 ± 1.3 mg/dl at 24 weeks). No significant change in the eGFR after 24 weeks was noted in either the Topiroxostat or Febuxostat group (- 0.04 ± 4.59 ml/min/1.73 m2 and 0.31 ± 4.70 ml/min/1.73 m2, respectively). CONCLUSIONS: In this study, XO inhibitors did not significantly reduce the uPCR in chronic kidney disease stage 3 and 4 patients with hyperuricemia.

Echocardiographic Assessment of Cardiac Structural and Functional Abnormalities in Patients With End-Stage Renal Disease Receiving Chronic Hemodialysis.

BACKGROUND: The aim of this study was to assess the echocardiographic characteristics of chronic hemodialysis (HD) patients with end-stage renal disease (ESRD) in a multicenter prospective cohort study.Methods and Results:Three hundred and fifteen patients with ESRD (67.9±10.6 years, 47.6% male) on chronic HD for ≥1 year were examined on transthoracic echocardiography, including Doppler-derived aortic valve area (AVA) measurement. Only 11.5% and 3.4% of all patients had normal left ventricular (LV) geometry and normal LV filling pattern, respectively. The majority of patients had aortic and mitral valvular calcification, and approximately 50% of all 315 patients had aortic valve narrowing with AVA <2.0 cm2. Patients were divided into 3 groups according to AVA index tertile: group 1, highest tertile; group 2, middle tertile; and group 3, lowest tertile. Group 3 was older, had a greater cardiothoracic ratio on chest X-ray, higher plasma brain natriuretic peptide and total LV afterload, and lower stroke volume index than the other 2 groups. Age and intact parathyroid hormone (PTH) level were independently associated with low AVA index. CONCLUSIONS: Patients with ESRD on chronic HD have a high prevalence of cardiac structural and functional abnormalities including calcified aortic sclerosis. High age and PTH were associated with aortic valve narrowing in these patients.

Collagenofibrotic Glomerulopathy.

Collagenofibrotic glomerulopathy or LMX1B-associated nephropathy is a rare disease in which type III collagen accumulates in the glomeruli. We herein report a 64-year-old Japanese woman with an elevated serum creatinine level and persistent proteinuria for 7 years. An electron microscopic study using tannic acid showed curved and frayed collagen fibers within mesangial and subendothelial regions compatible with type III collagen depositions. The distribution of type IV collagen α1-6 chains was normal. Since no pathogenic mutations were identified in the LMX1B gene, she was diagnosed with collagenofibrotic glomerulopathy and treated with angiotensin II receptor blocker and calcium antagonist to control her blood pressure.

A Case of Lipoprotein Glomerulopathy with apoE Chicago and apoE (Glu3Lys) Treated with Fenofibrate.

Lipoprotein glomerulopathy (LPG) is characterized by the accumulation of lipoprotein thrombi within glomerular capillaries. This rare disorder is associated with various types of mutations in the apolipoprotein E gene (apoE). Herein, we present a case of LPG with a combination of apoE Chicago (Arg147Pro) and apoE (Glu3Lys) mutations. A 51-year-old Japanese woman presented with severe (3+) proteinuria. The initial renal biopsy showed glomerular capillary dilation and occlusion with lipid granules, a specific characteristic of LPG. Phenotype, genotype, and apoE DNA sequence analyses detected 2 mutations as described above within the same allele. Although both mutations had already been reported in 1 case of LPG each, this is the first time that the combination of the 2 mutations was identified in the same case. Familial analysis detected the same mutations in the patient's mother. However, she has not suffered LPG thus far. In addition, a re-analysis of the previous LPG case with apoE (Glu3Lys) also identified the apoE Chicago mutation, as was observed in our case. Treatment with fenofibrate and irbesartan was initiated, and urinary protein excretion ceased within 1 year; recurrence was not observed after an additional 2 years of follow-up. A second biopsy after 2 years showed great improvement, with lipoprotein thrombi identified only in 2 of 18 glomeruli.

Successful creation of an anemia management algorithm for hemodialysis patients.

INTRODUCTION: Several anemia guidelines for hemodialysis patients have recommended a target hemoglobin (Hb) range of 10-12 g/dL. However, maintaining Hb values continuously within a narrow target has been difficult, and there has been no generally accepted anemia management algorithm for hemodialysis patients. METHODS: In our study, we created an anemia management algorithm that considers the length of erythrocyte lifetimes, focuses on the combination of erythropoiesis-stimulating agent management and iron administration, and prevents iron deficiency and overload. Our algorithm established a target Hb range of 10-12 g/dL. RESULTS: We evaluated our algorithm in 49 patients for 6 months. The mean Hb values were approximately 11 g/dL during our study period. The percentage of patients in the target Hb range of 10-12 g/dL increased from 77.6% (38 of 49) at baseline to 85.7% (42 of 49) at 4-6 months. Throughout monthly regular blood tests during 1-6 months after we introduced our algorithm, Hb values remained within the target range in 55.1% (27 of 49) of patients. The standard deviation of Hb values significantly decreased at 5 and 6 months (P=0.013 and P=0.047, respectively; 1 g/dL at 0 month, 0.7 g/dL at 5 months, and 0.7 g/dL at 6 months). Our algorithm also succeeded in suppressing cumulative doses of iron (≤800 mg) and decreasing the ferritin values significantly (P=0.011). There were no significant differences in erythropoiesis-stimulating agent doses between 0 and 6 months (P=0.357). CONCLUSION: Our anemia management algorithm successfully increased the number of patients in the target Hb range, significantly decreased the Hb standard deviation, suppressed cumulative doses of iron, and decreased ferritin values. These results suggest a better prognosis for hemodialysis patients. Further studies are required to evaluate our algorithm.