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Monitoring of serum alkaline phosphatase (ALP) is recommended in the management of chronic kidney disease-mineral and bone disorder (CKD-MBD). However, unlike calcium, phosphate or parathyroid hormone, the relationship between serum ALP and patient outcome receiving hemodialysis (HD) in Japan is unknown.Baseline data of 185 277 HD patients with duration90 days (66 ± 12 years, males 61.9%, and median HD duration of 5.8 years) were extracted from a nationwide dialysis registry at the end of 2009 in Japan. Outcomes were then evaluated using the registry at the end of 2010 using a multivariate logistic regression analysis.During 1-year follow-up, 14 230 (7.9%) patients died of all causes, including 6396 (3.6%) cardiovascular deaths. In addition, 1586 patients (1.0%) were newly diagnosed as hip fractures. All-cause and cardiovascular mortality and the incidence of hip fracture were higher in line with the increase in baseline serum ALP. On multivariate analysis, patients with the highest ALP quartile had higher all-cause and cardiovascular mortalities and a higher incidence of hip fracture than those with the lowest quartile [odds ratio (OR) 1.46, 95% confidence interval (CI) 1.33-1.60; OR 1.25, 95% CI 1.10-1.42; and OR 1.71, 95% CI 1.33-2.18, respectively].In this large cohort study, higher serum ALP levels were independently associated not only with mortality but also with the incidence of hip fracture in Japanese HD patients. Further study is needed to test whether serum ALP measurements could improve the patient outcomes.

BACKGROUND The adverse histological features predicting a progressive loss of renal function in idiopathic membranous nephropathy (IMN), before the establishment of impaired renal function with advanced glomerulosclerosis and/or interstitial fibrosis, are still poorly understood. The present study examined the relationship between the glomerular density (GD; non-sclerotic glomerular number/renal cortical area of biopsy) and the renal prognosis in IMN patients, especially in those without any apparent renal dysfunction at the time of diagnosis. METHODS The predictive value of the factors at biopsy, including the GD, on the renal outcome was retrospectively analyzed in the 65 IMN patients with an estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/1.73 m(2) (mean, 80 mL/min/1.73 m(2)) at biopsy. RESULTS The individual values for GD ranged from 1.6 to 6.5/mm(2) with 4-fold variation. A lower GD was associated with progression based on a ≥ 50% reduction in eGFR or reaching to end-stage renal disease. An association between a lower GD and progression was observed, especially in patients with persistent proteinuria of ≥ 1 g/day at follow-up. In contrast, any patients who achieved proteinuria of

Background Although there have been many reports on clinicopathological studies of IgAN, information is limited regarding the long-term evolution of a renal histology by analysing samples obtained not only during normal renal function but also after the establishment of an impaired renal function in individual patients. Methods We analysed 18 pairs of serial biopsy specimens from 18 patients with IgA nephropathy (IgAN) in whom the first renal biopsies were performed while normal renal function was still present and the second biopsies were performed after impaired renal function was established. The glomerular density (GD, number of non-sclerotic glomeruli per renal cortical area) and mean glomerular area (MGA) were compared between the specimens. Results The GD at the first biopsy of each patient showed a striking variation (1.3-5.2/mm(2)). As a whole, the GD decreased (2.7 +/- 1.2 versus 1.4 +/- 0.7/mm(2)) and the MGA increased (19.7 +/- 4.2 x 10(3) versus 23.5 +/- 4.5 x 10(3) mm(2)) between the biopsies, respectively. The degrees of change in the GD and the MGA between the biopsies differed remarkably among the individuals. The patients with a high GD in the first biopsy progressed slowly, but showed a large decrease in the GD and a large increase in the MGA between the biopsies, respectively. The patients with a low GD, who already had enlarged glomeruli in the first biopsy, tended to progress rapidly. Conclusions Our results suggest that both the nephron number and glomerular enlargement play a crucial role as compensatory mechanisms against renal functional deterioration in progressive IgAN. The GD during normal renal function may determine these compensatory changes and thereby make it possible to predict the renal prognosis in IgAN.

Background. Soy protein ameliorates rat polycystic kidney disease with concomitant renal enrichment of ω3polyunsaturated fatty acids. A study was conducted to examine the effects of eicosapentaenoic acids (EPA) on renal volume and function in patients with autosomal dominant polycystic kidney disease (ADPKD). Methods.Non-azotemicpatientswererandomizedtoeither a control group (n = 20) or an EPA group (n = 21). EPA capsules (2.4 g/day) were administered in the EPA group for 2 years. Twenty-four hours of urine was collected for the creatinine clearance (Ccr) measurement every year. At baseline and 24 months, fatty acid compositions in erythrocytes were measured and computerized tomographies were obtained for calculation of renal volume by the modified ellipsoid and volumetric methods. Results. In the EPA group, the EPA concentration (1.80 ± 0.99 versus 4.40 ± 1.79 area%, P < 0.001) and the ω3/ω6 ratiointheerythrocyteincreased,butdocosahexaenoicacid (DHA) (6.76 ± 1.19 versus 5.64 ± 1.45 area%, P < 0.010) concentration decreased. Ccr decreased by 8.5 ± 9.5 and 9.0 ± 13.0 ml/min/1.73 m 2 /2 years in the control and EPA groups, respectively (NS). The increases in renal volume calculated by either method were not significantly different between the two groups. Conclusions. A beneficial effect of EPA on renal function and kidney volume in ADPKD patients could not be confirmed in the present study. Administration of EPA with DHA supplementation and/or longer intervention might be necessary to demonstrate preventive effects of ω3polyunsaturated fatty acids on progression of ADPKD.

Background. Pteridine metabolism is impaired in the uraemic state. This may affect cardiovascular function and contribute to malnutrition. We wished to clarify further the impact of impaired pteridine metabolism. Methods. Using the HPLC method, the plasma concentrations of endogenous pteridines were determined in 64 patients with chronic renal failure (33 on intermittent haemodialysis (HD) treatment vs 31 not yet on renal replacement therapy), and in 18 healthy controls. The patients were classified into three groups on the basis of creatinine clearance (Ccr): group (a), Ccr )60 mlumin; group (b), Ccrs10‐60 mlumin; group (c), all patients receiving HD. Results. Total neopterin (NP) and biopterin (BP) levels and the NPuBP ratio (a biomarker for macrophage activity) were significantly higher, whereas tetrahydrobiopterin (BH4)udihydrobiopterin (BH2) ratio (a biomarker for nitric oxide synthase and phenylalanine hydroxylase activities) was significantly lower in group (c) (118.9"11.7 nguml, 18.8"1.2 nguml, 6.79"0.53, and 0.26"0.06) than in healthy subjects (5.17"0.29 nguml, 2.83"0.19 nguml, 1.92"0.13, and 1.15"0.11; P-0.01). These significant differences were also observed between control and group (b) (12.4"2.20 nguml, 4.48"0.36 nguml, 2.81"0.48, and 0.74"0.08; P-0.01). In groups (a) and (b), significant negative correlations were found between Ccr and the total NP level (rs0.663, P-0.01), the total BP level (rs0.492, P-0.01), the BH2 level (rs0.677, P-0.01), and the NPuBP ratio (rs0.493, P-0.01). Conversely, significant positive correlations were found between Ccr and the BH4uBH2 ratio (rs0.602, P-0.01). Conclusion. The reduction of quinoid-type BH2 to BH4 is modified in patients with advanced chronic renal failure, before and after the initiation of regular HD treatment. These metabolic alterations may play a role in the impaired macrophage, endothelial constitutive nitric oxide synthase, or phenylalanine hydroxylase (PH) activities observed in such patients.

The common intact parathyroid hormone (i-PTH) assay detects not only PTH (1-84) but also the PTH (7-84) fragment. Recently, it was reported that the PTH (7-84) fragment is an antagonist to the biological action of PTH (1-84). It was also reported that the accumulation of the PTH (7-84) fragment plays a role in skeletal resistance in haemodialysis (HD) patients. However, the role of accumulation of the PTH (7-84) fragment in continuous ambulatory peritoneal dialysis (CAPD) patients, with a different clearance rate from that of HD patients, is still unclear. Therefore, we have measured only the active form of PTH (1-84) using a new method of whole PTH (w-PTH) assay in 20 CAPD patients (15 male and five female; mean age 51.0+/-13.0 years). The mean w-PTH value was 88.5 +/-14.2 pg/ml in CAPD patients, which was 42.1% of i-PTH (152.6+/-23.6 pg/ml). The approximate value of w-PTH was calculated using the following formula (w-PTH=0.58 x iPTH-0.4, R(2)=0.94). PTH (7-84) fragment was calculated by the formula i-PTH-w-PTH. The PTH (7-84) fragment/w-PTH ratio as an index of skeletal resistance, and serum alkaline phosphatase activity as an osteoblastic marker were negatively correlated (P=0.02). From these results, we concluded that the i-PTH level as calculated using the common assay method might lead to an overestimation of parathyroid function and bone turnover in CAPD patients similarly to HD patients. The w-PTH assay may be useful for more precise evaluation of PTH activity in end-stage renal disease patients.

Sir, Cardiovascular disease (CVD) is the most important complication for patients with end-stage renal disease including continuous ambulatory peritoneal dialysis (CAPD) patients. Oxidative stress recently has been proposed to be a major contributor to CVD among these patients [1]. Albumin is the most abundant protein in the extracellular fluid. Chemically, human serum albumin (HSA) can be divided into at least three forms according to the redox state of the cysteine residue at portion 34 from the N-terminus: not oxidized (human mercaptoalbumin or HMA); reversibly oxidized (human non-mercaptoalbumin-1 or HNA-1) and strongly oxidized (human non-mercaptoalbumin-2 or HNA-2). These three forms can be distinguished by highperformance liquid chromatography (HPLC) using a Shodex–Asahipak ES-502N 7C column (Showa Denko, Tokyo, Japan) [2]. We thus measured oxidative stress in 21 stable CAPD patients using the redox state of serum albumin (HSA-redox) as a marker. All patients were undergoing CAPD with exchanges of 2l four times daily. Total oxidized albumin (HNA-1 þ HNA-2, or HNA-total) accounted for 35–55% of serum albumin, similar to the percentage in predialysis patients with stage 5 chronic kidney disease [3]. Considering that HNA-total constitutes 20–25% in healthy subjects [3,4], oxidative stress in CAPD patients is greater than that in normal subjects. Simple regression analysis, in which HNA-total as a percentage [ f(HNA-total)] was taken as the dependent variable, indicated that f(HNA-total) correlated significantly with serum urea nitrogen but not with other variables considered (Table 1). The regression plot for f(HNA-total) and urea nitrogen is shown in the Figure 1. Given the significant correlation of f(HNA-total) with urea nitrogen but not with urinary volume or serum b-2 microglobulin level, oxidation of serum albumin among CAPD patients would appear to be induced not by middlesized but by small uremic molecules.