Sex differences in the 10-year survival of patients undergoing maintenance hemodialysis in the Q-Cohort Study.

Women have a longer life expectancy than men in the general population. However, it has remained unclear whether this advantage is maintained in patients undergoing maintenance hemodialysis. The aim of this study was to compare the risk of mortality, especially infection-related mortality, between male and female hemodialysis patients. A total of 3065 Japanese hemodialysis patients aged ≥ 18 years old were followed up for 10 years. The primary outcomes were all-cause and infection-related mortality. The associations between sex and these outcomes were examined using Cox proportional hazards models. During the median follow-up of 8.8 years, 1498 patients died of any cause, 387 of whom died of infection. Compared with men, the multivariable-adjusted hazard ratios (95% confidence interval) for all-cause and infection-related mortality in women were 0.51 (0.45-0.58, P < 0.05) and 0.36 (0.27-0.47, P < 0.05), respectively. These findings remained significant even when propensity score-matching or inverse probability of treatment weighting adjustment methods were employed. Furthermore, even when the non-infection-related mortality was considered a competing risk, the infection-related mortality rate in women was still significantly lower than that in men. Regarding all-cause and infection-related deaths, women have a survival advantage compared with men among Japanese patients undergoing maintenance hemodialysis.

Stronger Effect of Azilsartan on Reduction of Proteinuria Compared to Candesartan in Patients with CKD: A Randomized Crossover Trial.

INTRODUCTION: Angiotensin receptor blockers (ARBs) are preferably used in hypertensive patients with CKD. Azilsartan is a strong antihypertensive ARB, but its antiproteinuric effects are not well understood. We compared the antiproteinuric effect of azilsartan and candesartan in CKD patients in an open-label, randomized, crossover trial. METHODS: A total of 111 patients were treated with 20 mg of azilsartan daily for 2 months as a run-in period. After the run-in period, patients were randomized into 2 arms and received either 20 mg of azilsartan or 8 mg of candesartan daily for 3 months in a crossover trial. The primary outcome was the percent change in urinary protein-to-Cr ratio (UPCR). RESULTS: Ninety-five patients completed the trial. The mean age was 64.3 years. The estimated glomerular filtration rate (eGFR) and UPCR were 41.5 mL/min/1.73 m2 and 1.8 g/gCr, respectively. The baseline systolic and diastolic blood pressures were 131.4 and 71.0 mm Hg, respectively. The mean percent change in the UPCR was -3.8% in the azilsartan group and 30.8% in the candesartan group at the 1st endpoint (p = 0.0004), and 6.1% in the azilsartan group and 25.8% in the candesartan group at the 2nd (final) endpoint (p = 0.029). The incidence of adverse events, including eGFR levels and serum potassium levels, was not significantly different between the groups. CONCLUSION: A 20 mg azilsartan dose had potent antiproteinuric effects compared with an 8 mg candesartan dose, without an increase in adverse events. Azilsartan may provide renal protection in addition to antihypertensive effects in CKD patients.

Association of normalized protein catabolic rate (nPCR) with the risk of bone fracture in patients undergoing maintenance hemodialysis: The Q-Cohort Study.

BACKGROUND & AIMS: Normalized protein catabolic rate (nPCR) is used as a surrogate for daily dietary protein intake and nutritional status in patients receiving maintenance hemodialysis. It remains uncertain whether the nPCR level is associated with the incidence of bone fracture. METHODS: A total of 2869 hemodialysis patients registered in the Q-Cohort Study, a multicenter, prospective, observational study, were followed up for 4 years. The primary outcome was bone fracture at any site. The main exposure was the nPCR level at baseline. Patients were assigned to four groups based on their baseline nPCR levels (G1: <0.85, G2: 0.85≤, <0.95, G3: 0.95≤, <1.05 [reference], G4: ≥1.05 g/kg/day). We examined the relationship between the nPCR levels and the risk for bone fracture using Cox proportional hazards models. RESULTS: During the follow-up period, 136 patients experienced bone fracture at any site. In the multivariable analyses, the risk for bone fracture was significantly higher in the lowest (G1) and highest (G4) nPCR groups than the reference (G3) group (hazard ratio [95% confidence intervals]: G1, 1.93 [1.04-3.58]; G2, 1.27 [0.67-2.40]; G3 1.00 (reference); G4, 2.21 [1.25-3.92]). The association remained almost unchanged, even when patients were divided into sex-specific nPCR quartiles, when analysis was limited to patients with a dialysis vintage ≥2 years, assumed to have lost residual kidney function, or when a competing risk model was applied. CONCLUSIONS: Our results suggest that both lower and higher nPCR levels are associated with an increased risk for bone fracture in hemodialysis patients.

Development and validation of a risk score for the prediction of cardiovascular disease in living donor kidney transplant recipients.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of death in kidney transplant (KT) recipients. To improve their long-term survival, it is clinically important to estimate the risk of CVD after living donor KT via adequate pre-transplant CVD screening. METHODS: A derivation cohort containing 331 KT recipients underwent living donor KT at Kyushu University Hospital from January 2006 to December 2012. A prediction model was retrospectively developed and risk scores were investigated via a Cox proportional hazards regression model. The discrimination and calibration capacities of the prediction model were estimated via the c-statistic and the Hosmer-Lemeshow goodness of fit test. External validation was estimated via the same statistical methods by applying the model to a validation cohort of 300 KT recipients who underwent living donor KT at Tokyo Women's Medical University Hospital. RESULTS: In the derivation cohort, 28 patients (8.5%) had CVD events during the observation period. Recipient age, CVD history, diabetic nephropathy, dialysis vintage, serum albumin and proteinuria at 12 months after KT were significant predictors of CVD. A prediction model consisting of integer risk scores demonstrated good discrimination (c-statistic 0.88) and goodness of fit (Hosmer-Lemeshow test P = 0.18). In a validation cohort, the model demonstrated moderate discrimination (c-statistic 0.77) and goodness of fit (Hosmer-Lemeshow test P = 0.15), suggesting external validity. CONCLUSIONS: The above-described simple model for predicting CVD after living donor KT was accurate and useful in clinical situations.

Association of Lower Serum Bilirubin With Loss of Residual Kidney Function in Peritoneal Dialysis Patients.

Bilirubin is recognized as an endogenous antioxidant, and low serum bilirubin is reported to be associated with the progression of kidney disease. However, it is unclear whether serum bilirubin levels are associated with the loss of residual kidney function (RKF) in peritoneal dialysis (PD) patients. This study investigated the relationship between serum total bilirubin and loss of RKF. We prospectively followed 94 PD patients who started PD in our hospital between June 2006 and May 2016. Ten patients who had chronic liver disease or cirrhosis were excluded. Patients were divided into three groups based on serum total bilirubin concentration tertiles: tertile 1 (T1) < 0.3, T2 = 0.3, and T3 ≥ 0.4 mg/dL. We estimated the relationship between serum bilirubin and loss of RKF, defined as daily urine volume (<100 mL) within 3 years after starting PD, using a Cox proportional hazards model. During the 3-year observation period, 22 patients lost RKF. The incidence rate of loss of RKF increased linearly with the decrease in serum total bilirubin levels (P for trend < 0.05). After adjusting for confounding factors, low serum total bilirubin level was shown to be an independent predictor of loss of RKF (hazard ratio [HR] for every 0.1 mg/dL decrease, 1.50; 95% confidence interval [CI], 1.01-2.51; HR [95%CI] for T2 and T1 [vs. T3] 2.03 [0.65-7.88] and 3.70 [1.00-15.9]). This study suggests that low serum total bilirubin levels are associated with the loss of RKF in PD patients.

Lower Serum Albumin Level Is Associated With an Increased Risk for Loss of Residual Kidney Function in Patients Receiving Peritoneal Dialysis.

Preserving residual kidney function (RKF) is important in the management of patients on peritoneal dialysis. However, few studies have examined the association between serum albumin level and the risk of RKF loss. We prospectively recruited 104 patients who began peritoneal dialysis treatment at our hospital between 2006 and 2016. The primary outcome was complete RKF loss, defined as urine volume < 100 mL/day. Serum albumin level at baseline was the main exposure. During a median observation period of 24 months, 33 patients developed RKF loss. A Cox proportional hazards model showed that hypoalbuminemia was associated with an increased risk of RKF, even after adjustments for potential confounding factors. Multivariable-adjusted linear regression analysis also showed that hypoalbuminemia was associated with greater rates of decline in 24-h urine volume and in renal Kt/V urea. Our findings suggest that hypoalbuminemia is associated with an increased risk of RKF loss in patients with peritoneal dialysis.

Development of a risk prediction model for infection-related mortality in patients undergoing peritoneal dialysis.

BACKGROUND: Assessment of infection-related mortality remains inadequate in patients undergoing peritoneal dialysis. This study was performed to develop a risk model for predicting the 2-year infection-related mortality risk in patients undergoing peritoneal dialysis. METHODS: The study cohort comprised 606 patients who started and continued peritoneal dialysis for 90 at least days and was drawn from the Fukuoka Peritoneal Dialysis Database Registry Study in Japan. The patients were registered from 1 January 2006 to 31 December 2016 and followed up until 31 December 2017. To generate a prediction rule, the score for each variable was weighted by the regression coefficients calculated using a Cox proportional hazard model adjusted by risk factors for infection-related mortality, including patient characteristics, comorbidities, and laboratory data. RESULTS: During the follow-up period (median, 2.2 years), 138 patients died; 58 of them of infectious disease. The final model for infection-related mortality comprises six factors: age, sex, serum albumin, serum creatinine, total cholesterol, and weekly renal Kt/V. The incidence of infection-related mortality increased linearly with increasing total risk score (P for trend <0.001). Furthermore, the prediction model showed adequate discrimination (c-statistic = 0.79 [0.72-0.86]) and calibration (Hosmer-Lemeshow test, P = 0.47). CONCLUSION: In this study, we developed a new model using clinical measures for predicting infection-related mortality in patients undergoing peritoneal dialysis.

Association of B-Type Natriuretic Peptide Level With Residual Kidney Function in Incident Peritoneal Dialysis Patients.

BACKGROUND: Residual kidney function (RKF) is an important factor influencing both technique and patient survival in peritoneal dialysis (PD) patients. B-type natriuretic peptide (BNP) is considered a marker of cardio-renal syndrome. The relationship between BNP and RKF in PD patients remains unclear. METHODS: We conducted a prospective study of 89 patients who had started and continued PD for 6 months or more in Kyushu University Hospital between June 2006 and September 2015. Participants were divided into low BNP (≤ 102.1 ng/L) and high BNP (> 102.1 ng/L) groups according to median plasma BNP level at PD initiation. The primary outcome was RKF loss, defined as 24-hour urine volume less than 100 mL. We estimated the association between BNP and RKF loss using a Kaplan-Meier method and Cox proportional hazards model and compared the rate of RKF decline between the 2 groups. To evaluate the consistency of the association, we performed subgroup analysis stratified by baseline characteristics. RESULTS: During the median follow-up of 30 months, 30 patients lost RKF. Participants in the high BNP group had a 5.87-fold increased risk for RKF loss compared with the low BNP group after adjustment for clinical and cardiac parameters. A high plasma BNP level was more clearly associated with RKF loss in younger participants compared with older participants in subgroup analysis. CONCLUSIONS: B-type natriuretic peptide may be a useful risk marker for RKF loss in PD patients. The clinical importance of plasma BNP level as a marker of RKF loss might be affected by age.