Trajectory of GFR Decline and Fluctuation in Albuminuria Leading to End-Stage Kidney Disease in Patients With Biopsy-Confirmed Diabetic Kidney Disease.

Introduction: Data on longitudinal trajectory of kidney function decline and fluctuation in albuminuria leading to end-stage kidney disease (ESKD) is sparse in patients with type 2 diabetes. Methods: Using data from an observational study of patients with type 2 diabetes and biopsy-confirmed diabetic kidney disease (DKD), generalized additive mixed models (GAMMs) were performed to quantify patterns of longitudinal trajectory of estimated glomerular filtration rate (eGFR) decline to ESKD associated with repeated measures of urine albumin-to-creatinine ratio (ACR). Results: Over a median follow-up period of 3.3 years, 155 of 319 patients progressed to ESKD. Among these patients, 91.6% exhibited a curvilinear pattern in their eGFR trajectory. The median coefficient of variation for ACR, representing the variability in ACR measurements, was 48.9 (interquartile range: 36.9, 68.2). The median compound annual growth rate (CAGR) for ACR, reflecting the variation in ACR progression over time, was 43.6% (interquartile range: 0.0, 102.5); and 84.5% of patients developed nephrotic-range albuminuria, with a majority remaining nephrotic and subsequently progressing to ESKD. There was a positive association between the instantaneous speed of eGFR decline and ACR. Conclusion: The observed curvilinear pattern in eGFR trajectory, high variability in ACR progression over time, and positive correlation between the speed of eGFR decline and ACR highlight the complex dynamics of disease progression and emphasize close monitoring of ACR fluctuation over time in patients with DKD.

Association between Hypokalemia and Albuminuria in a Japanese General Population.

INTRODUCTION: Hypokalemia is associated with an increased risk of chronic kidney disease (CKD) and is a risk factor for mortality. Albuminuria is an early manifestation of CKD. We investigated the association between hypokalemia and the prevalence of albuminuria in a Japanese general population. METHODS: We analyzed the data of 18,289 subjects who underwent annual health checkups in 2018. We categorized them into four groups according to their concentration of serum potassium (sK) and performed a multivariate logistic regression analysis to determine the association between hypokalemia and the prevalence of albuminuria in this population. Hypokalemia was defined as having an sK = 3.1-3.5 mEq/L. After dividing the subjects into those with/without renal dysfunction, those with/without hypertension, and those with/without hyperglycemia, we examined the association between hypokalemia and albuminuria in each group. RESULTS: Compared to the subjects with sK = 4.1-4.5 mEq/L, the subjects with hypokalemia had a significantly high prevalence of albuminuria: multivariable-adjusted odds ratio (OR) = 2.70 (95% confidence interval [CI] 1.84-3.96). The subgroup analyses showed the following multivariable-adjusted ORs (95% CIs) of the subjects: without renal dysfunction, 3.08 (2.00-4.73); with renal dysfunction, 2.05 (0.89-4.69); without hypertension, 2.89 (1.36-6.16); with hypertension, 2.60 (1.67-4.04); without hyperglycemia, 2.49 (1.62-3.84); and with hyperglycemia, 3.55 (1.43-8.79). CONCLUSIONS: Hypokalemia was significantly associated with the high prevalence of albuminuria in general population. Regardless of the presence/absence of renal dysfunction, hypertension, or hyperglycemia, hypokalemia was positively associated with the prevalence of albuminuria, and the associations were significant except for the subjects with renal dysfunction.

Sex differences in risk factors for end-stage kidney disease and death in type 2 diabetes: A retrospective cohort study.

BACKGROUND: This study investigated the sex differences in the risk of end-stage kidney disease (ESKD) and mortality, as well as the effect modification of sex on associated factors in patients with type 2 diabetes. METHODS: This multicenter observational cohort study included 4328 patients with type 2 diabetes. Hazard ratios (HRs) with 95% confidence intervals (CIs) of sex for ESKD and death were estimated using Cox proportional regression with adjustment for baseline covariates. For assessing risk modification, HRs and incidence rates for ESKD and death were compared between sexes across patient characteristics using Cox proportional and Poisson regression models. RESULTS: During a median follow-up of 7 years, 276 patients (70% men) developed ESKD, and 241 patients (68% men) died. Men had higher risks of ESKD (HR 1.34; 95% CI 1.02-1.75; p = .034) and death (HR 1.64; 95% CI 1.24-2.16; p = .001) versus women after adjusting for multiple covariates. Among patients with microalbuminuria, men had a substantially higher risk of ESKD versus women, compared to those with normo- and macroalbuminuria (p for interaction .04). Incidence rates were also increased in men versus women with albuminuria of around 300 mg/g. No differences were detected in the association of sex and death across baseline patient subgroups. CONCLUSIONS: In type 2 diabetes, men had an increased risk of ESKD and death versus women. Moderately increased albuminuria was strongly associated with sex difference in developing ESKD.

Synergistic deterioration of prognosis associated with decreased grip strength and hyporesponse to erythropoiesis-stimulating agents in patients undergoing hemodialysis.

INTRODUCTION: We examined the combined effect of erythropoietin (EPO) hyporesponsiveness and low handgrip strength (HGS) on the prognosis of patients undergoing hemodialysis (HD). METHODS: We recruited patients with chronic kidney disease (CKD) Stage 5, who were undergoing HD at our dialysis clinic between January 2015 and March 2015 (n = 182). Patients of ≥20 years of age and who had been undergoing HD for ≧3 months at enrollment were eligible for inclusion. Seven patients treated with epoetin-ß pegol were excluded. First, the erythropoietin resistance index (ERI) and HGS were measured. The patients were stratified by the ERI of 9.44 (U/kg/week/g/dL), and by the HGS of 28 kg for men and 18 kg for women. We then observed death and cardiovascular disease (CVD), composite endpoint (deaths or CVD) for a median of 2 years. RESULTS: A total of 175 patients (male, n = 122; female, n = 53; age, 34-92 years) were included in the analysis. During the observation period of 24 months, 57 events (14 deaths and 43 CVD) were observed. High ERI and low HGS were associated with a high incidence of endpoints compared to low ERI and high HGS. Among the four groups classified by ERI and HGS values, the highest risk group was the high ERI/low HGS group (HR: 4.20 95% CI 2.12-8.33). CONCLUSIONS: EPO hyporesponsiveness combined with low HGS were found to be significant predictors of a poor outcome, and the synergistic effects of the two factors had stronger predictive ability than either single factor.

Effects of Body Weight Change on Development of Chronic Kidney Disease in Obese Metabolic Phenotypes.

INTRODUCTION: Obesity is a risk factor for chronic kidney disease (CKD), but whether the reduction of body mass index (BMI) helps prevent CKD is controversial. Recently, obese metabolic phenotypes have raised considerable interest. We thus investigated the effect of BMI change on CKD development. METHODS: We analyzed the data of 6,959 subjects who underwent annual health checkups in both 2013 and 2018. The subjects were categorized into five groups according to their BMI percentage change (ΔBMI) and classified into four obese metabolic phenotypes. By a multivariate logistic regression analysis, we investigated the association between BMI change and CKD development within the 5 years. RESULTS: In total subjects, compared with the maintained BMI group (ΔBMI ≥0% but <2.5%), the odd ratios (ORs) and 95% confidence intervals (CIs) of CKD development were 0.70 (95% CI 0.54-0.91) for the severe BMI decrease group (ΔBMI <-2.5%), and 1.40 (95% CI 1.08-1.81) for the severe BMI increase group (ΔBMI ≥5%). In the metabolically healthy obese (MHO) phenotype, the risks of CKD development were significantly higher in the moderate BMI increase group (ΔBMI ≥2.5% but <5%) (OR 3.04, 95% CI 1.19-7.78) and a severe BMI increase group (OR 2.88, 95% CI 1.13-7.35). Regarding the metabolically unhealthy nonobese (MUNO) phenotype, the risks of CKD development were significantly lower in the severe BMI decrease group (OR 0.43, 95% CI 0.25-0.74) and the moderate BMI decrease group (ΔBMI ≥-2.5% but <0%) (OR 0.58, 95% CI 0.35-0.98). CONCLUSIONS: In the MHO phenotype, an increased BMI deteriorated CKD development, and a decreased BMI ameliorated CKD development in the MUNO phenotype.

Combined changes in albuminuria and kidney function and subsequent risk for kidney failure in type 2 diabetes.

INTRODUCTION: Changes in albuminuria or estimated glomerular filtration rate (eGFR) can be used as a surrogate endpoint of end-stage kidney disease (ESKD) in people with type 2 diabetes. We investigated whether the combined changes in albuminuria and eGFR are more strongly associated with future risk of ESKD. RESEARCH DESIGN AND METHODS: Using data from a multicenter observational cohort study of people with type 2 diabetes, we evaluated the association of percentage change in urine albumin to creatinine ratio (UACR) and/or annual change in eGFR over 2 years with subsequent ESKD risk. RESULTS: Among 1417 patients with repeated albuminuria and eGFR over 2 years, 129 (9.1%) developed ESKD. Patients with >30% UACR decline had lower ESKD risk (HR 0.47; 95% CI 0.29 to 0.77), whereas those with >30% UACR increase had higher ESKD risk (HR 2.31; 95% CI 1.52 to 3.51), compared with those with minor UACR change. Patients with greater eGFR decline had an increased ESKD risk than those with minor eGFR change (a decline of <2.5 mL/min/1.73 m2/year): HR 4.19 (95% CI 1.87 to 9.38) and 2.89 (95% CI 1.32 to 6.33) for those with a decline of >5 and 2.5-5 mL/min/1.73 m2/year, respectively. When the combined changes in UACR and eGFR were used, the highest ESKD risk (HR 5.60; 95% CI 2.08 to 15.09) was observed among patients with >30% UACR increase and an eGFR decline of >5 mL/min/1.73 m2/year compared with those with a minor change in UACR and eGFR. CONCLUSIONS: Combined changes in albuminuria and eGFR over 2 years were strongly associated with future risk of kidney failure in patients with type 2 diabetes.

Quantitative sonographic assessment of quadriceps muscle thickness for fall injury prediction in patients undergoing maintenance hemodialysis: an observational cohort study.

BACKGROUND: Accidental fall risk is high in patients undergoing maintenance hemodialysis. Falls are associated with fatal injury, comorbidities, and mortality. Risk assessment should be a primary component of fall prevention. This study investigated whether quadriceps muscle thickness measured using ultrasonography can predict fall injury among dialysis patients. METHODS: Using an observational cohort study design, 180 ambulatory hemodialysis patients were recruited from 2015 to 2016 from four dialysis clinics. The sum of the maximum quadriceps muscle thickness on both sides and the average of the maximum thigh circumference and handgrip strength after hemodialysis were calculated. Patients were stratified according to tertiles of quadriceps muscle thickness. Fall injury was surveyed according to the patient's self-report during the one-year period. RESULTS: Among the 180 hemodialysis patients, 44 (24.4%) had fall injuries during the 12-month follow-up period. When the quadriceps muscle thickness levels were stratified into sex-specific tertiles, patients in the lowest tertile were more likely to have a higher incidence of fall injury than those in the higher two tertiles (0.52 vs. 0.19 and 0.17 fall injuries/person-year). After adjusting for covariates, lower quadriceps muscle thickness was found to be an independent predictor of fall injury (hazard ratio [95% confidence interval], 2.33 [1.22-4.52], P < 0.05). Receiver operating characteristic curves were constructed to determine the optimal cutoffs of quadriceps muscle thickness, thigh circumference, and handgrip strength that best predicted fall injury (quadriceps muscle thickness, 3.37 cm and 3.54 cm in men and women; thigh circumference, 44.6 cm and 37.2 cm in men and women; and handgrip strength, 23.3 kg and 16.5 kg in men and women). Using these cutoff values, the areas under the curve were 0.662 (95% CI, 0.576-0.738), 0.625 (95% CI, 0.545-0.699), and 0.701 (95% CI, 0.617-0.774), for quadriceps muscle thickness, thigh circumference, and handgrip strength, respectively. Quadriceps muscle thickness was a more precise predictor of fall injury than thigh circumference and had similar diagnostic performance as handgrip strength tests in dialysis patients. CONCLUSIONS: Quadriceps muscle thickness can be measured easily at the bedside using ultrasonography and is a precise predictor of fall injury in patients undergoing maintenance hemodialysis.

Subclinical hypothyroidism is associated with albuminuria in Japanese nondiabetic subjects.

PURPOSE: Thyroid dysfunction is a risk factor of cardiovascular disease (CVD), and albuminuria is a predictor of CVD. For preventing the CVD, it is essential to clarify from which stage of thyroid dysfunction the risk of CVD starts developing. We thus investigated the association between subclinical thyroid dysfunction and albuminuria, focusing on a nondiabetic general population. METHODS: We analyzed the data of 17,221 nondiabetic subjects who underwent annual health checkups by multivariate logistic regression analyses. RESULTS: Compared with the subjects with euthyroidism, those with subclinical hypothyroidism presented a higher prevalence of albuminuria. By a multivariate logistic regression analysis, subclinical hypothyroidism showed a significant and independent association with the high prevalence of albuminuria compared with euthyroidism (OR 1.64, 95% CI 1.21-2.21, p = 0.001). In accord with this result, the analysis in which the lowest quartile of thyroid stimulating hormone (TSH) concentration (<0.96 µIU/mL) was used as a reference revealed that the highest quartile (>2.07 µIU/mL) had a significant and independent association with the prevalence of albuminuria (OR 1.23, 95% CI 1.01-1.51, p = 0.04). One microliter unit per milliliter increase of the serum concentration of TSH also had a significant and independent association with the prevalence of albuminuria (OR 1.07, 95% CI 1.02-1.12, p = 0.006). The association between subclinical hyperthyroidism and the prevalence of albuminuria was not significant. CONCLUSION: Our data indicated that subclinical hypothyroidism was significantly and independently associated with the high prevalence of albuminuria.

Association of Thyrotropin Concentration with Chronic Kidney Disease in a Japanese General Population Cohort.

BACKGROUND: Previous studies have indicated an association between hypothyroidism and kidney dysfunction; however, few studies have investigated whether thyroid dysfunction is a risk factor for chronic kidney disease (CKD) development. And their result is not consistent. OBJECTIVES: We evaluated the association of thyroid dysfunction with CKD prevalence and development by a multivariate logistic regression analysis. METHOD: In cross-sectional and longitudinal studies, 16,390 subjects and 7,609 subjects, respectively, who underwent annual health check-ups were analyzed. We categorized the subjects into the following 4 groups based on their serum thyrotropin (TSH) -concentrations: below-normal (TSH < 0.54 mU/L), lower-normal -(0.54-2.40 mU/L), higher-normal (2.41-4.26 mU/L) and above-normal (> 4.26 mU/L). Subjects with eGFR <60 mL/min/1.73 m2 were determined to have CKD. RESULTS: The cross-sectional study revealed a positive correlation between TSH concentration and CKD -prevalence. Compared with the lower-normal TSH group, the ORs and 95% CIs of CKD prevalence were 0.61 (0.45-0.82, p = 0.001) for the below-normal group, 1.49 (1.33-1.67, p < 0.001) for the higher-normal group, and 1.90 (1.57-2.30, p < 0.001) for the above-normal group. The longitudinal study revealed that the risk of CKD development within 3 years was significantly higher in the above-normal TSH group than in the lower-normal TSH group (OR 1.58, 95% CI 1.02-2.45, p = 0.04). CONCLUSIONS: Our data indicate that higher TSH concentrations are positively correlated with CKD prevalence and that a high TSH concentration is a risk factor for CKD development.

Estimated glomerular filtration rate decline and risk of end-stage renal disease in type 2 diabetes.

BACKGROUND: According to studies by the National Kidney Foundation and Food and Drug Administration, 30% and 40% declines in estimated glomerular filtration rate (eGFR) could be used as surrogate endpoints of end-stage renal disease (ESRD). However, the benefits of using these endpoints in diabetic patients remain unclear. METHODS: This cohort study comprised Japanese patients with type 2 diabetes; those with repeated serum creatinine measurements during a baseline period of 2 years (n = 1868) or 3 years (n = 2001) were enrolled. Subsequent risks of ESRD following eGFR declines were assessed. RESULTS: In the 2-year baseline analysis, the cumulative prevalence of -20%, -30%, -40%, and -53% changes in eGFR were 23.9%, 11.1%, 6.8%, and 3.7%, respectively. There were 133 cases (7.1%) of subsequent ESRD during a median follow-up period of 6.5 years. In the 3-year baseline analysis, the corresponding proportions were 28.1%, 14.0%, 7.7%, and 3.9%, respectively, with 110 participants (5.5%) reaching ESRD during a median follow-up period of 5.5 years. The adjusted hazard ratios of subsequent ESRD following -53%, -40%, -30%, and -20% changes in eGFR during the 2-year baseline period were 22.9 (11.1-47.3), 12.8 (6.9-23.7), 8.2 (4.3-15.5), and 3.9 (2.2-7.0), respectively when compared with the no changes in eGFR. In the 3-year baseline analysis, the corresponding risks were 29.7 (10.8-81.9), 18.4 (7.6-44.7), 12.8 (5.2-32.2), and 5.4 (2.3-12.8), respectively. In the subgroup analysis, similar trends were observed in patients with macroalbuminuria at baseline. CONCLUSIONS: Declines in eGFR were strongly associated with subsequent risk of ESRD in Japanese type 2 diabetic patients. In addition to 30% and 40% declines, a 20% decline in eGFR over 2 years could be considered as a candidate surrogate endpoint of ESRD in diabetic kidney disease.

A new pathological scoring system by the Japanese classification to predict renal outcome in diabetic nephropathy.

BACKGROUND AND OBJECTIVES: The impact of the newly proposed pathological classification by the Japan Renal Pathology Society (JRPS) on renal outcome is unclear. So we evaluated that impact and created a new pathological scoring to predict outcome using this classification. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A multicenter cohort of 493 biopsy-proven Japanese patients with diabetic nephropathy (DN) were analyzed. The association between each pathological factor-Tervaert' and JRPS classifications-and renal outcome (dialysis initiation or 50% eGFR decline) was estimated by adjusted Cox regression. The overall pathological risk score (J-score) was calculated, whereupon its predictive ability for 10-year risk of renal outcome was evaluated. RESULTS: The J-scores of diffuse lesion classes 2 or 3, GBM doubling class 3, presence of mesangiolysis, polar vasculosis, and arteriolar hyalinosis were, respectively, 1, 2, 4, 1, and 2. The scores of IFTA classes 1, 2, and 3 were, respectively, 3, 4, and 4, and those of interstitial inflammation classes 1, 2, and 3 were 5, 5, and 4 (J-score range, 0-19). Renal survival curves, when dividing into four J-score grades (0-5, 6-10, 11-15, and 16-19), were significantly different from each other (p<0.01, log-rank test). After adjusting clinical factors, the J-score was a significant predictor of renal outcome. Ability to predict 10-year renal outcome was improved when the J-score was added to the basic model: c-statistics from 0.661 to 0.685; category-free net reclassification improvement, 0.154 (-0.040, 0.349, p = 0.12); and integrated discrimination improvement, 0.015 (0.003, 0.028, p = 0.02). CONCLUSIONS: Mesangiolysis, polar vasculosis, and doubling of GBM-features of the JRPS system-were significantly associated with renal outcome. Prediction of DN patients' renal outcome was better with the J-score than without it.

Uric Acid Is a Strong Risk Marker for Developing Hypertension From Prehypertension: A 5-Year Japanese Cohort Study.

Prehypertension frequently progresses to hypertension, a condition associated with high morbidity and mortality from cardiovascular diseases and stroke. However, the risk factors for developing hypertension from prehypertension remain poorly understood. We conducted a retrospective cohort study using the data from 3584 prehypertensive Japanese adults (52.1±11.0 years, 2081 men) found to be prehypertensive in 2004 and reexamined in 2009. We calculated the cumulative incidences of hypertension over 5 years, examined risk factors, and calculated odds ratios (ORs) for developing hypertension after adjustments for age, sex, body mass index, smoking and drinking habits, baseline systolic and diastolic blood pressure, pulse rate, diabetes mellitus, dyslipidemia, chronic kidney disease, and serum uric acid levels. The additional analysis evaluated whether serum uric acid (hyperuricemia) constituted an independent risk factor for developing hypertension. The cumulative incidence of hypertension from prehypertension over 5 years was 25.3%. There were no significant differences between women and men (24.4% versus 26.0%; P=0.28). The cumulative incidence of hypertension in subjects with hyperuricemia (n=726) was significantly higher than those without hyperuricemia (n=2858; 30.7% versus 24.0%; P<0.001). After multivariable adjustments, the risk factors for developing hypertension from prehypertension were age (OR, 1.023; P<0.001), female sex (OR, 1.595; P<0.001), higher body mass index (OR, 1.051; P<0.001), higher baseline systolic (OR, 1.072; P<0.001) and diastolic blood pressure (OR, 1.085; P<0.001), and higher serum uric acid (OR, 1.149; P<0.001). Increased serum uric acid is a strong risk marker for developing hypertension from prehypertension. Further studies are needed to determine whether treatment of hyperuricemia in prehypertensive subjects could impede the onset of hypertension.

Paratubular basement membrane insudative lesions predict renal prognosis in patients with type 2 diabetes and biopsy-proven diabetic nephropathy.

AIMS: Glomerular insudative lesions are a pathological hallmark of diabetic nephropathy (DN). However, paratubular basement membrane insudative lesions (PTBMIL) have not attracted much attention, and the association between such lesions and the renal prognosis remains unclear. METHODS: Among 142 patients with biopsy-proven DN and type 2 diabetes encountered from 1998 to 2011, 136 patients were enrolled in this study. Patients were classified into 3 groups (Group 1: mild, Group 2: moderate, Group 3: severe) according to the extent of cortical and medullary PTBMIL. The endpoint was a decline of the estimated glomerular filtration rate (eGFR) by ≥ 40% from baseline or commencement of dialysis for end-stage renal disease. The Cox proportional hazard model was employed to calculate hazard ratios (HRs) and 95% confidence interval (CIs) for the death-censored endpoint. RESULTS: During a median follow-up period of 1.8 years (IQR: 0.9-3.5), the endpoint occurred in 104 patients. Baseline mean eGFR was 43.9 ± 22.8 ml/min/1.73 m2, and 125 patients (92%) had overt proteinuria. After adjusting for known indicators of DN progression, the HR for the endpoint was 2.32 (95% CI: 1.20-4.51) in PTBMIL Group 2 and 3.12 (1.48-6.58) in PTBMIL Group 3 versus PTBMIL Group 1. Furthermore, adding the PTBMIL Group to a multivariate model including known promoters of DN progression improved prediction of the endpoint (c-index increased by 0.02 [95% CI: 0.00-0.04]). CONCLUSIONS: PTBMIL may be useful for predicting the renal prognosis of patients with biopsy-proven DN, but further investigation of these lesions in various stages of DN is needed.

Nodular lesions in diabetic nephropathy: Collagen staining and renal prognosis.

AIMS: Nodular lesions are one of the most characteristic pathological changes of advanced diabetic nephropathy (DN). Previous studies have demonstrated that the pattern of both routine and collagen staining of nodular lesions changes during their development. However, the association between such changes of staining and the renal prognosis remains unclear. METHODS: Among 252 patients with biopsy-proven DN, 67 met the selection criteria and were enrolled to investigate this relationship. In all patients, nodular lesions were stained with periodic acid Schiff, periodic acid methenamine silver, and Masson trichrome stains, and immunostaining was done for type I, III, IV, V, and VI collagen. The endpoint was commencement of dialysis due to end-stage renal disease. RESULTS: At least one mesangiolytic nodular lesion (MNL) that showed faint staining for PAS and PAM was found in 61% of the patients. MNLs were negative for type IV collagen staining, unlike the strong positivity of non-MNLs, while type V and VI collagen staining were strongly positive in all nodular lesions. Cox proportional hazards regression analysis revealed that the hazard ratio (HR) for the endpoint was significantly higher in patients with at least one MNL than in patients with no MNLs after adjustment for known promoters of renal progression (HR: 2.94; 95% confidence interval: 1.24-7.07). CONCLUSIONS: MNLs may reflect characteristic differences of collagen production and could be a useful prognostic indicator in patients with nodular lesions. Further investigation of the mechanism underlying these differences of collagen production could contribute to finding new therapeutic targets for DN.

A new peritoneal dialysis fluid for Japanese patients: a randomized non-inferiority clinical trial of safety and efficacy.

BACKGROUND: We report here two new peritoneal dialysis fluids (PDFs) for Japan [BLR 250, BLR 350 (Baxter Limited, Japan)]. The PDFs use two-chamber systems, and have bicarbonate and lactate buffer to a total of 35 mmol/L. In separate trials, the new PDFs were compared to two "standard" systems [PD-4, PD-2 (Baxter Limited, Japan)]. The trials aimed to demonstrate non-inferiority of peritoneal creatinine clearance (pCcr), peritoneal urea clearance (pCurea) and ultrafiltration volume (UF), and compare acid-base and electrolyte balance. METHODS: We performed randomized, multicenter, parallel group, controlled, open-label clinical trials in stable continuous ambulatory peritoneal dialysis (CAPD) patients. The primary endpoints were pCcr and UF. The secondary endpoints were serum bicarbonate and peritoneal urea clearance. The active phase was 8 weeks. These trials were performed as non-inferiority studies, with the lower limit of non-inferiority for pCcr and UF set at 3.2 L/week/1.73 m2 and 0.12 L/day, respectively. RESULTS: 108 patients (28 centers) and 103 patients (29 centers) took part in the two trials. Groups were well balanced at baseline. The investigative PDFs were non-inferior to the "standard" ones in terms of primary endpoints, comparable in terms of pCurea, and superior in terms acid-base balance, especially correcting those with over-alkalinization at baseline. CONCLUSIONS: We demonstrated fundamental functionality of two new PDFs and showed superior acid-base balance. Given the propensity of Japanese CAPD patients for alkalosis, it is important to avoid metabolic alkalosis which is associated with increased cardiovascular mortality risk and accelerated vascular calcification. The new PDFs are important progress of CAPD treatment for Japanese patients.

Five Sequential Evaluations of Renal Histology in a Patient with Light Chain Deposition Disease.

A 58-year-old man was referred to our institution for an evaluation of nephrotic range proteinuria. Renal biopsy showed a marked expansion of the mesangial matrix and thickening of glomerular basement membrane (GBM) in periodic acid-silver methenamine (PAM). Immunofluorescence (IF) revealed strong staining for the monoclonal kappa light chain. EM demonstrated massive subendothelial and mesangial dense deposits. As a result, light chain deposition disease (LCDD) was diagnosed. Melphalan and prednisolone (MP) therapy was started, which was continued for 10 years with minimal complications. Serial evaluations of renal histology revealed the resolution of nodular lesions and the glomeruli became nearly normal. MP therapy can therefore be an effective therapeutic option for LCDD if it is continued over the long term.

Impact of individual components and their combinations within a family history of hypertension on the incidence of hypertension: Toranomon hospital health management center study 22.

Although a family history (FH) of hypertension is a risk factor for the development of hypertension, only a few studies have investigated in detail the impact of individual components of an FH on incident hypertension. We investigated the impact of individual components and their combinations on the presence or development of hypertension considering obesity, smoking habits, physical activity, and other metabolic parameters.Studied were 12,222 Japanese individuals without hypertension (n = 9,766) and with hypertension (n = 2,456) at the baseline examination. The presence or incidence of hypertension during 5 years after a baseline examination was assessed by the presence of systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or a self-reported history of clinician-diagnosed hypertension. In this prospective study, the odds ratio for incident hypertension was 1.39 (95% confidence interval [CI], 1.22, 1.59) for individuals with any FH of hypertension compared with those without such an FH. Individuals with an FH of hypertension in both parents and one or more grandparents had an odds ratio of 3.05 (95% CI 1.74, 5.36) for hypertension compared with those without an FH of hypertension. FH was associated with incident hypertension independently of other modifiable risk factors such as obesity, smoking, physical inactivity, hyperglycemia, hyperuricemia, and hypertriglyceridemia.A parental history of hypertension was an essential component within an FH for incident hypertension. FH of hypertension over two generations with both parents affected was the most important risk factor for incident hypertension. Although an FH is not a modifiable risk factor, modifying other risk factors could contribute to reducing the risk of hypertension even among individuals with a family history of hypertension.

Assessment of kidney dysfunction with cystatin C- and creatinine-based estimated glomerular filtration rate and predicting type 2 diabetes: Toranomon Hospital Health Management Center Study 21.

OBJECTIVE: Whether early stages of kidney dysfunction assessed by the estimated glomerular filtration rate from cystatin C measurements (eGFRCysC) rather than from creatinine measurements (eGFRCr) would more precisely reflect the risk of developing type 2 diabetes (T2D) has not been clarified. We compared the risk of developing T2D associated with renal dysfunction indicated by eGFRCysC or eGFRCr measurements. METHODS: Studied were 2131 Japanese individuals without diabetes. Hazard ratios (HRs) for the development of T2D over 3-5 y were calculated across categories of eGFRCysC and eGFRCr, respectively. RESULTS: Reduced levels of eGFRCysC were associated with a step-wise increase in the cumulative incidence rate of T2D (p=0.007). In comparison with the eGFRCysC >85th percentile group (≥ 117.4 ml/min/1.73 m(2)), the lowest group, which was the eGFRCysC <15th percentile group (<86.2 ml/min/1.73 m(2)), had an adjusted HR of 2.30 (95% CI 1.13, 4.68) for T2D. Compared with the eGFRCr >85th percentile group, the lowest eGFRCr group (<15th percentile) had an HR of 1.19 (0.63, 2.24) for T2D. However, individuals with eGFRCr <60 ml/min/1.73 m(2) had a significantly increased risk of T2D. Clustering of both low eGFRCysC and low eGFRCr further elevated the HR for T2D compared with the presence of either. CONCLUSIONS: Although eGFRCr in ranges indicating chronic kidney disease reflected an elevated risk of developing diabetes, earlier stages of kidney dysfunction indicated by reduced eGFRCysC, which could not be captured by reduced eGFRCr, would be a marker for an elevated risk of developing T2D.

Prognostic Value of Tubulointerstitial Lesions, Urinary N-Acetyl-ß-d-Glucosaminidase, and Urinary ß2-Microglobulin in Patients with Type 2 Diabetes and Biopsy-Proven Diabetic Nephropathy.

BACKGROUND AND OBJECTIVES: Some biomarkers of renal tubular injury are reported to be useful for predicting renal prognosis in the early stage of diabetic nephropathy (DN). Our study compared predictions of the renal prognosis by such biomarkers and by histologic tubulointerstitial damage. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 210 patients with type 2 diabetes and biopsy-proven DN managed from 1985 to 2011, 149 patients with urinary N-acetyl-ß-d-glucosaminidase (NAG) and urinary ß2-microglobulin (ß2-MG) data at the time of renal biopsy were enrolled. The primary outcome was a decline in eGFR of ≥50% from baseline or commencement of dialysis for ESRD. RESULTS: The median follow-up period was 2.3 years (interquartile range, 1.1-5.3), and the primary outcome was noted in 94 patients. Mean eGFR was 46.3±23.2 ml/min per 1.73 m(2), and 132 patients (89%) had overt proteinuria at baseline. Cox proportional hazards analysis revealed that the association of urinary NAG and ß2-MG with the outcome was attenuated after adjustment for known promoters of progression (+1 SD for log NAG: hazard ratio [HR], 1.14; 95% confidence interval [95% CI], 0.84 to 1.55; +1 SD for log ß2-MG: HR, 1.23; 95% CI, 0.94 to 1.62). In contrast, the interstitial fibrosis and tubular atrophy (IFTA) score was still significantly correlated with the outcome after adjustment for the same covariates (+1 for IFTA score: HR, 2.31; 95% CI, 1.56 to 3.43). Moreover, adding the IFTA score to a model containing known progression indicators improved prediction of the outcome (increase of concordance index by 0.02; 95% CI, 0.00 to 0.05; category-free net reclassification improvement by 0.54; 95% CI, 0.03 to 1.05; and relative integrated discrimination improvement by 0.07; 95% CI, -0.08 to 0.22). CONCLUSIONS: Adding urinary NAG and ß2-MG excretion to known promoters of progression did not improve prognostication, whereas adding the IFTA score did. The IFTA score may be superior to these tubulointerstitial markers for predicting the renal prognosis in advanced DN.

Relationship between Alcohol Intake and Risk Factors for Metabolic Syndrome in Men.

OBJECTIVE: The precise relationship between alcohol intake and metabolic syndrome (MetS) is still unclear, and the results from previous studies have been inconclusive. Thus, we examined the effect of alcohol intake on the risk of MetS in men in order to gain more information on a potential relationship. METHODS: This study included 22,349 men who were divided into four groups according to their average alcohol intake [non-, light (less than 20 g ethanol/day), heavy (equal or more than 20 g and less than 60 g ethanol/day) and very heavy (equal and greater than 60 g ethanol/day) drinkers]. We measured each subject's body mass index (BMI), waist circumference and blood pressure (BP) and conducted a blood test to obtain a complete blood count and biochemical panel. These results were used to obtain the MetS prevalence. Additionally, fatty liver was diagnosed using abdominal ultrasonography. RESULTS: Light drinkers had smaller waist circumferences. Heavy and very heavy drinkers had larger waist circumferences, a higher BMI, a higher BP, higher fasting plasma glucose levels, higher triglycerides (TG) levels and higher high-density lipoprotein (HDL) cholesterol levels while they had lower low-density lipoprotein cholesterol levels than nondrinkers. The prevalence of high BP, hyperglycemia and high TG was significantly higher in heavy and very heavy drinkers than in nondrinkers. The prevalence of low HDL cholesterol levels decreased with an increase in alcohol consumption. The prevalence of MetS was significantly lower in light drinkers and higher in very heavy drinkers compared with nondrinkers. CONCLUSION: Alcohol intake significantly influences the risk of MetS in men. A significant association was seen between an alcohol intake of 60 g/day or higher and the prevalence of MetS.