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Summary: Anemia and vitamin D deficiency are associated with allograft failure, and hence, are potential therapeutic targets among kidney transplant recipients (KTRs). We conducted a multicenter, two‐by‐two factorial, open‐label, randomized clinical trial to examine the effects of anemia correction and vitamin D supplementation on 2‐year change in eGFR among KTRs (CANDLE‐KIT). We enrolled 153 patients with anemia and >1‐year history of transplantation across 23 facilities in Japan, and randomly assigned them to either a high or low hemoglobin target (>12.5 vs. <10.5 g/dl) and to either cholecalciferol 1000 IU/day or control. This trial was terminated early based on the planned interim intention‐to‐treat analyses (α = 0.034). Among 125 patients who completed the study, 2‐year decline in eGFR was smaller in the high vs. low hemoglobin group (i.e., −1.6 ± 4.5 vs. −4.0 ± 6.9 ml/min/1.73 m2; P = 0.021), but did not differ between the cholecalciferol and control groups. These findings were supported by the fully adjusted mixed effects model evaluating the rate of eGFR decline among all 153 participants. There were no significant between‐group differences in all‐cause death or the renal composite outcome in either arm. In conclusion, aggressive anemia correction showed a potential to preserve allograft kidney function. [ABSTRACT FROM AUTHOR]

Background: Hypoalbuminemia is a strong predictor of hospitalization and mortality among adult dialysis patients. However, data are scant on the association between serum albumin and hospitalization among children new to dialysis. Methods: In a retrospective cohort study of children 1–17 years old with end-stage renal disease receiving dialysis therapy in a large US dialysis organization 2007–2011, we examined the association of serum albumin with hospitalization frequency and total hospitalization days using a negative binomial regression model. Results: Among 416 eligible patients, median (interquartile range) age was 14 (10–16) years and mean ± SD baseline serum albumin level was 3.7 ± 0.8 g/dL. Two hundred sixty-six patients (64%) were hospitalized during follow-up with an incidence rate of 2.2 (95%CI, 1.9–2.4) admissions per patient-year. There was a U-shaped association between serum albumin and hospitalization frequency; hospitalization rates (95%CI) were 2.7 (2.2–3.2), 1.9 (1.5–2.4), 1.6 (1.3–1.9), and 2.7 (1.7–3.6) per patient-year among patients with serum albumin levels < 3.5, 3.5– < 4.0, 4.0– < 4.5, and ≥ 4.5 g/dL, respectively. Case mix-adjusted hospitalization incidence rate ratios (IRRs) (95%CI) were 1.63 (1.24–2.13), 1.32 (1.10–1.58), and 1.25 (1.06–1.49) at serum albumin levels 3.0, 3.5, and 4.5 g/dL, respectively (reference: 4.0 g/dL). Similar trends were observed in hospitalization days. These associations remained robust against further adjustment for laboratory variables associated with malnutrition and inflammation. Conclusions: Both high and low serum albumin were associated with higher hospitalization in children starting dialysis. Because the observed association is novel and not fully explainable especially for high serum albumin levels, interpreting the results requires caution and further studies are needed to confirm and elucidate this association before clinical recommendations are made. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is common among dialysis patients and may impact blood concentrations of calcium, phosphorus, intact parathyroid hormone (iPTH), and alkaline phosphatase (ALP). Seasonal variation of serum 25-hydroxyvitamin D [25(OH)D] concentrations has been well established for the general population; however, less is known about circannual variation in 25(OH)D as well as other parameters of mineral and bone disorder among dialysis patients. Based on 57,500 serum 25(OH)D measurements collected over two years from January 2009 to December 2010 among 25,025 dialysis patients, we evaluated the circannual variations in serum concentrations of 25(OH)D, calcium, phosphorus, iPTH, and ALP by a linear regression model with a cosinor function for the time period (month). We adjusted for potential confounders including case-mix variables, and ultraviolet index. Serum 25(OH)D concentrations showed significant circannual variation and mean serum 25(OH)D was 3.2 ng/mL higher in summer than in winter. Furthermore, 25(OH)D concentration increased steadily by 1.3 ng/mL per year. While serum calcium concentrations showed statistically significant but clinically negligible seasonal variation (0.02 mg/dL in peak-trough difference), serum phosphorus did not follow such a pattern. Serum iPTH concentrations also showed a modest seasonal variation with 9% higher values in winter than in summer. Concordantly, ALP concentrations in the winter were 2% higher than in the summer time. Seasonal variation of 25(OH)D was greater in male (vs. female), African-American (vs. non-African-American), and younger (vs. older) dialysis patients. Serum 25(OH)D and iPTH concentrations show seasonal variation among dialysis patients while the variation in other parameters of mineral and bone disorder was clinically irrelevant, if any. Serum 25(OH)D also showed a gradual increase over time. Clinicians and researchers should be aware of these changes when interpreting laboratory results in dialysis patients. • Among ESRD patients, 25(OH)D concentrations followed seasonal variation during two consecutive years. • 25(OH)D concentrations were higher in the summer and lower in the winter time with a peak-trough difference of 3.2 ng/mL. • 25(OH)D concentrations increased steadily by 1.3 ng/mL/year. • IPTH, ALP and calcium concentrations also showed seasonal variation in contrast to phosphorus concentrations. • Clinicians and researchers should be aware of these variations when interpreting laboratory results in dialysis patients. [ABSTRACT FROM AUTHOR]

Background: Greater variability in estimated glomerular filtration rate (eGFR) is associated with mortality in patients with chronic kidney disease (CKD). However, the association between eGFR variability and cardiovascular (CV) mortality and/or end-stage kidney disease (ESKD) in the CKD population is not very clear. This study aimed to clarify whether such an association exists. Methods: We analyzed a final cohort of 2869 eligible Asian patients with CKD. Patients were stratified into three groups according to eGFR variability during the first year and were followed-up for a median of 3.15 years. Primary CV composite endpoints were hospitalization or death due to CV events, and renal composite endpoints were doubling of serum creatinine levels or ESKD. Multivariate Cox hazard models adjusted for classical risk factors and eGFR slope were used to examine the CV and renal risk associated with eGFR variability. Results: CV endpoints were observed in 14 (2.89%), 25 (5.69%), and 41 (10.79%) patients and renal endpoints were observed in 165 (27.6%), 235 (39.0%), and 298 patients (50.9%) in the lowest, intermediate, and highest tertiles of eGFR variability, respectively. Patients in the highest tertile were at a significantly higher risk for CV events (hazard ratio 1.90; 95% confidence interval 1.03–3.71) than those in the lowest tertile. However, there was no association between eGFR variability and renal endpoints. Conclusions: Variability in eGFR can predict CV outcomes among patients with CKD. [ABSTRACT FROM AUTHOR]

Background Abnormally high estimated glomerular filtration rates (eGFRs) are associated with endothelial dysfunction and frailty. Previous studies have shown that low eGFR is associated with increased morbidity, but few reports address high eGFR. The purpose of this study is to evaluate the association of high eGFR with surgical outcomes in patients undergoing surgery for gastrointestinal malignancies. Methods We identified patients who underwent elective surgery for gastrointestinal malignancies from 2005 to 2015 in the American College of Surgeons National Surgical Quality Improvement Program database. We evaluated associations of eGFR with surgical outcomes by Cox or logistic models with restricted cubic spline functions, adjusting for case mix variables (i.e. age, gender, race and diabetes). Results The median eGFR is 83 (interquartile range 67–96) mL/min/1.73 m2. Thirty-day mortality was 1.9% (2555/136 896). There is a U-shaped relationship between eGFR and 30-day mortality. The adjusted hazard ratios (95% confidence intervals) for eGFRs of 30, 60, 105 and 120 mL/min/1.73 m2 (versus 90 mL/min/1.73 m2) are 1.73 (1.52–1.97), 1.00 (0.89–1.11), 1.42 (1.31–1.55) and 2.20 (1.79–2.70), respectively. Similar associations are shown for other surgical outcomes, including return to the operating room and postoperative pneumonia. Subgroup analyses show that eGFRs both higher and lower than the respective medians are consistently associated with a higher risk of adverse outcomes across age, gender and race. Conclusions High and low eGFRs are associated with more adverse surgical outcomes in patients undergoing surgery for gastrointestinal malignancies. The eGFR associated with the lowest postoperative risk is approximately at the median eGFR of a given population. [ABSTRACT FROM AUTHOR]

Background Both dialysis dose and residual kidney function (RKF) contribute to solute clearance and are associated with outcomes in hemodialysis patients. We hypothesized that the association between dialysis dose and mortality is attenuated with greater RKF. Methods Among 32 251 incident hemodialysis patients in a large US dialysis organization (2007–11), we examined the interaction between single-pool Kt / V (sp Kt / V) and renal urea clearance (rCLurea) levels in survival analyses using multivariable Cox proportional hazards regression model. Results The median rCLurea and mean baseline sp Kt / V were 3.06 [interquartile range (IQR) 1.74–4.85] mL/min/1.73 m2 and 1.32 ± 0.28, respectively. A total of 7444 (23%) patients died during the median follow-up of 1.2 years (IQR 0.5–2.2 years) with an incidence of 15.4 deaths per 100 patient-years. The Cox model with adjustment for case-mix and laboratory variables showed that rCLurea modified the association between sp Kt / V and mortality (Pinteraction = 0.03); lower sp Kt / V was associated with higher mortality among patients with low rCLurea (i.e. <3  mL/min/1.73 m2) but not among those with higher rCLurea. The adjusted mortality hazard ratios (aHRs) and 95% confidence intervals of the low (<1.2) versus high (≥1.2) sp Kt / V were 1.40 (1.12–1.74), 1.21 (1.10–1.33), 1.06 (0.98–1.14), and 1.00 (0.93–1.08) for patients with rCLurea of 0.0, 1.0, 3.0 and 6.0 mL/min/1.73 m2, respectively. Conclusions Incident hemodialysis patients with substantial RKF do not exhibit the expected better survival at higher hemodialysis doses. RKF levels should be taken into account when deciding on the dose of dialysis treatment among incident hemodialysis patients. [ABSTRACT FROM AUTHOR]

Sodium‐glucose cotransporter (SGLT)‐2 inhibitors have recently been approved for chronic kidney disease (CKD) based on their ability to lower proteinuria and slow CKD progression independent of diabetes status. In diabetic renal disease, modulation of tubuloglomerular feedback (TGF) leading to lower intraglomerular pressure has been postulated as one of the mechanisms of renal protection with SGLT2 inhibition; however, this mechanism has not been sufficiently explored in non‐diabetic CKD. We hypothesized that SGLT2 inhibition exerts renoprotection in CKD through increasing TGF despite normoglycemia. To test this hypothesis, we used an integrative mathematical model of human physiology, HumMod. Stage 3 CKD conditions were simulated by reducing nephron mass which was associated with hypertension, low glomerular filtration rate (GFR) (55 mL/min), hyperfiltration of remnant nephrons, elevated albuminuria (500 mg/day), and minimal levels of urinary glucose (0.02 mmol/L). SGLT2 inhibition was associated with acute reductions in GFR associated with afferent arteriolar vasoconstriction due to TGF. After 12 months, glomerular pressure, nephron damage, and chronic GFR decline were reduced with SGLT2 inhibition with additional SGLT1 inhibitory effects further enhancing these effects. This model supports the use of SGLT2 inhibitors to reduce hyperfiltration in CKD and mitigate renal disease progression, even in the absence of diabetes. [ABSTRACT FROM AUTHOR]

While many patients have substantial residual kidney function (RKF) when initiating hemodialysis (HD), most patients with end stage renal disease in the United States are initiated on 3-times per week conventional HD regimen, with little regard to RKF or patient preference. RKF is associated with many benefits including survival, volume control, solute clearance, and reduced inflammation. Several strategies have been recommended to preserve RKF after HD initiation, including an incremental approach to HD initiation. Incremental HD prescriptions are personalized to achieve adequate volume control and solute clearance with consideration to a patient's endogenous renal function. This allows the initial use of less frequent and/or shorter HD treatment sessions. Regular measurement of RKF is important because HD frequency needs to be increased as RKF inevitably declines. We narratively review the results of 12 observational cohort studies of twice-weekly compared to thrice-weekly HD. Incremental HD is associated with several benefits including preservation of RKF as well as extending the event-free life of arteriovenous fistulas and grafts. Patient survival and quality of life, however, has been variably associated with incremental HD. Serious risks must also be considered, including increased hospitalization and mortality perhaps related to fluid and electrolyte shifts after a long interdialytic interval. On the basis of the above literature review, and our clinical experience, we suggest patient characteristics which may predict favorable outcomes with an incremental approach to HD. These include substantial RKF, adequate volume control, lack of significant anemia/electrolyte imbalance, satisfactory health-related quality of life, low comorbid disease burden, and good nutritional status without evidence of hypercatabolism. Clinicians should engage patients in on-going conversations to prepare for incremental HD initiation and to ensure a smooth transition to thrice-weekly HD when needed. [ABSTRACT FROM AUTHOR]

Introduction: Hypoalbuminemia is a predictor of poor outcomes in dialysis patients. Among hemodialysis patients, there has not been prior study of whether residual kidney function or decline over time impacts serum albumin levels. We hypothesized that a decline in residual kidney function is associated with an increase in serum albumin levels among incident hemodialysis patients. Methods: In a large national cohort of 38,504 patients who initiated hemodialysis during 1/2007-12/2011, we examined the association of residual kidney function, ascertained by urine volume and renal urea clearance, with changes in serum albumin over five years across strata of baseline residual kidney function, race, and diabetes using case-mix adjusted linear mixed effects models. Findings: Serum albumin levels increased over time. At baseline, patients with greater urine volume had higher serum albumin levels: 3.44 ± 0.48, 3.50 ± 0.46, 3.57 ± 0.44, 3.59 ± 0.45, and 3.65 ± 0.46 g/dL for urine volume groups of <300, 300-<600, 600-<900, 900-<1,200, and ≥1,200 mL/day, respectively (Ptrend < 0.001). Over time, urine volume and renal urea clearance declined and serum albumin levels rose, while the baseline differences in serum albumin persisted across groups of urinary volume. In addition, the rate of decline in residual kidney function was not associated with the rate of change in albumin. Discussion: Hypoalbuminemia in hemodialysis patients is associated with lower residual kidney function. Among incident hemodialysis patients, there is a gradual rise in serum albumin that is independent of the rate of decline in residual kidney function, suggesting that preservation of residual kidney function does not have a deleterious impact on serum albumin levels. [ABSTRACT FROM AUTHOR]

Background. The association between serum uric acid (SUA) andmortality has been conflicting among studies using hemodialysis (HD) patients. Given the close link between purine and protein in foods, we hypothesized that normalized protein catabolic rate (nPCR), a dietary protein intake surrogate, modifies the SUA-mortality association in the HD population. Methods. We identified 4298 patients who initiated HD and had one or more SUA measurement in a contemporary cohort of HD patients over 5 years (1 January 2007-31 December 2011), and examined survival probability according to the first uric acid measurement, adjusting for dialysis vintage, case-mix andmalnutrition-inflammation complex-related variables. Results. Mean SUA concentration was 6.6±1.8mg/dL. There was a consistent association of higher SUA with better nutritional status and lower all-cause mortality irrespective of adjusted models (Ptrend<0.001). In the case-mix adjusted model, the highest SUA category (≥8.0mg/dL) compared with the reference group (>6.0-7.0mg/dL) showed no significant mortality risk [hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.72 - 1.13], while the lowest category (<5.0mg/dL) was associated with higher mortality (HR 1.42, 95% CI 1.16-1.72). The hypouricemia-mortality association was significantly modified by nPCR (Pinteraction =0.001). Mortality risk of low SUA (<5.0mg/dL) persisted among patients with low nPCR (<0.9 g/kg/day; HR 1.73, 95% CI 1.42-2.10) but not with high nPCR (≥0.9 g/kg/day; HR 0.99, 95% CI 0.74-1.33). Conclusions. SUA may be a nutritional marker in HD patients. Contrary to the general population, low but not high SUA is associated with higher all-cause mortality in HD patients, especially in those with low protein intake. Nutritional features of SUA warrant additional studies. [ABSTRACT FROM AUTHOR]

Background: The 2006 Kidney Disease Outcomes Quality Initiative guidelines suggest twice-weekly or incremental hemodialysis for patients with substantial residual kidney function (RKF). However, in most affluent nations de novo and abrupt transition to thrice-weekly hemodialysis is routinely prescribed for all dialysis-naïve patients regardless of their RKF. We review historical developments in hemodialysis therapy initiation and revisit twice-weekly hemodialysis as an individualized, incremental treatment especially upon first transitioning to hemodialysis therapy. Summary: In the 1960's, hemodialysis treatment was first offered as a life-sustaining treatment in the form of long sessions (≥10 hours) administered every 5 to 7 days. Twice- and then thrice-weekly treatment regimens were subsequently developed to prevent uremic symptoms on a long-term basis. The thrice-weekly regimen has since become the 'standard of care' despite a lack of comparative studies. Some clinical studies have shown benefits of high hemodialysis dose by more frequent or longer treatment times mainly among patients with limited or no RKF. Conversely, in selected patients with higher levels of RKF and particularly higher urine volume, incremental or twice-weekly hemodialysis may preserve RKF and vascular access longer without compromising clinical outcomes. Proposed criteria for twice-weekly hemodialysis include urine output >500 ml/day, limited interdialytic weight gain, smaller body size relative to RKF, and favorable nutritional status, quality of life, and comorbidity profile. Key Messages: Incremental hemodialysis including twice-weeklyregimens may be safe and cost-effective treatment regimens that provide better quality of life for incident dialysis patients who have substantial RKF. These proposed criteria may guide incremental hemodialysis frequency and warrant future randomized controlled trials. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Vitamin D is an important nutrient involved in bone mineral metabolism, and vitamin D status is reflected by serum total 25-hydroxyvitamin D (25[OH]D) concentrations. Vitamin D deficiency is highly prevalent in patients with chronic kidney disease (CKD), and nutritional vitamin D supplementation decreases elevated parathyroid hormone concentrations in subgroups of these patients. Furthermore, vitamin D is supposed to have pleiotropic effects on various diseases such as cardiovascular diseases, malignancies, infectious diseases, diabetes, and autoimmune diseases. Indeed, there is cumulative evidence showing the associations of low vitamin D with the development and progression of CKD, cardiovascular complication, and high mortality. Recently, genetic polymorphisms in vitamin D-binding protein have received great attention because they largely affect bioavailable 25(OH)D concentrations. This finding suggests that the serum total 25(OH)D concentrations would not be comparable among different gene polymorphisms and thus may be inappropriate as an index of vitamin D status. This finding may refute the conventional definition of vitamin D status based solely on serum total 25(OH)D concentrations. [ABSTRACT FROM AUTHOR]

The article informs on the need of personalized dialysis treatment and prevailing dogma in the management of patients with end stage renal disease (ESRD). Topics include use of hemodialysis schedule as the standard of care for preventing uremic symptoms and increase mortality, association of residual kidney clearance with survival among ESRD patients on hemodialysis and peritoneal dialysis, and decline to patients on peritoneal dialysis if using on-line hemodiafiltration.

Background:: Nonadherence to treatment regimens for immunosuppressive agents is one of the major risk factors for allograft failure in kidney transplant recipients. The aim of this study was to estimate the relative effect of daily dosing on treatment adherence, not to identify how patients are non-adherent, in long-term kidney transplant recipients. Methods:: In January 2009, a cross-sectional, anonymous, and voluntary questionnaire survey was given to kidney transplant recipients who regularly visited Inoue Hospital. A self-reporting questionnaire underestimates nonadherence, but we reasoned that the effect of the dosing regimen should be estimated with relative accuracy by using the generalized ordered logit/partial proportional hazard odds model given that the distribution patterns in the degree of nonadherence have been shown to be similar with other measures. Results:: Of 336 eligible patients, 312 (92.9 %) participated in this study. Two hundred seventy-four patients (87.8 %) were more than 3 years post-transplant. Univariate analysis revealed that a single daily dose was significantly associated with better adherence. After controlling for age, sex, time since transplantation, and the number of prescribed drugs, the effect of a single daily dose still remained significant [odds ratio, 0.40 (95 % confidence interval, 0.19-0.81); p = 0.011]. Several sensitivity analyses yielded similar results. Conclusions:: To our knowledge, this is the first report that, in long-term kidney transplant recipients, a single daily regimen-one of few modifiable factors-might improve treatment adherence and allograft survival. [ABSTRACT FROM AUTHOR]

Background. Both chronic kidney disease (CKD) and post-angiographic acute kidney injury (AKI) are regarded as risks factors for long-term mortality after coronary angiography. On the other hand, acute haemodynamic disturbances requiring haemodynamic support have a strong impact on both the incidence of AKI and on prognosis after coronary angiography. The aim of this study was to determine the impact of CKD and AKI on long-term prognosis after coronary angiography among hospital survivors and to determine relationships with haemodynamic variables.Methods. We studied 2439 patients who underwent coronary angiography or percutaneous coronary intervention. Relationships between both CKD and AKI and mortality or cardiovascular diseases were measured using unadjusted and adjusted Cox models for case-mix and laboratory variables.Results. Multivariable Cox regression analysis identified CKD as an independent predictor of long-term mortality [adjusted hazard ratio (AHR) 1.51; 95% confidence interval (95% CI) 1.07–2.13] and composite end points (AHR 1.72; 95% CI 1.40–2.11). Lower estimated glomerular filtration ratio levels below 50 mL/min/1.73 m2 were significantly associated with mortality after adjustments. A similar association was found even in haemodynamically stable patients. AKI was also a predictor of long-term composite end points (AHR 1.64; 95% CI 1.09–2.46); however, its impact was attenuated in haemodynamically stable patients.Conclusions. Among hospital survivors, CKD is an independent predictor for both long-term mortality and composite end points, regardless of haemodynamic conditions. AKI is also a predictor of long-term prognosis; however, its impact may be attenuated in haemodynamically stable hospital survivors. [ABSTRACT FROM AUTHOR]

In this multicentre double-blind randomized clinical trial, we investigated the effects of oral cholecalciferol supplementation on serum hepcidin and parameters related to anaemia and CKD-MBD among haemodialysis patients. Participants were assigned in a 2:2:1:1 ratio to either (1) thrice-weekly 3,000-IU cholecalciferol, (2) once-monthly cholecalciferol (equivalent to 9,000 IU/week), (3) thrice-weekly placebo, or (4) once-monthly placebo. We also examined the effect modifications by selected single nucleotide polymorphisms in vitamin D-related genes. Out of 96 participants, 94 were available at Month 3, and 88 completed the 6-month study. After adjustment for baseline values, serum hepcidin levels were higher at Day 3 in the combined cholecalciferol (vs. placebo) group, but were lower at Month 6 with increased erythropoietin resistance. Cholecalciferol increased serum 1,25(OH)2D levels, resulting in a greater proportion of patients who reduced the dose of active vitamin D at Month 6 (31% vs. 10% in the placebo group). Cholecalciferol also suppressed intact PTH only among patients with severe vitamin D deficiency. In conclusion, cholecalciferol supplementation increases serum hepcidin-25 levels in the short term and may increase erythropoietin resistance in the long term among haemodialysis patients. Both thrice-weekly and once-monthly supplementation effectively increases serum 1,25(OH)2D levels, and hence, reduces active vitamin D drugs. Clinical Trial Registry: This study was registered at ClinicalTrials.gov and University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as NCT02214563 (registration date: 12/08/2014) and UMIN000011786 (registration date: 15/08/2014), respectively (please refer to the links below). ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/record/NCT02214563. UMIN-CTR: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000017152&language=E. [ABSTRACT FROM AUTHOR]

Among kidney disease patients ≥80 years progressing to end-stage renal disease, there is growing interest in conservative nondialytic management approaches. However, among those who have initiated hemodialysis, little is known about the impact of withdrawal from dialysis on mortality, nor the patient characteristics associated with withdrawal from dialysis. Historical cohort study. We examined 133,162 incident hemodialysis patients receiving care within a large national dialysis organization from 2007 to 2011. We identified patients who withdrew from dialysis, either as a listed cause of death or censor reason. Incidence rates and subdistribution hazard ratios for withdrawal from dialysis as well as 4 other censoring reasons were examined across age groups. In addition, demographic and clinical characteristics associated with withdrawal from dialysis therapy among patients ≥80 years old was assessed using logistic regression analysis. Among 17,296 patients aged ≥80 years, 10% of patients withdrew from dialysis. Duration from the last hemodialysis treatment to death was 10 [interquartile range 6-16] days in patients with available data. Withdrawal from dialysis was the second and third most common cause of death among patients aged ≥80 years and <80 years, respectively. Among patients ≥80 years, minorities were much less likely than non-Hispanic whites to stop dialysis. Other factors associated with higher odds of dialysis withdrawal included having a central venous catheter compared to an arteriovenous fistula at dialysis start, dementia, living in mid-west regions, and less favorable markers associated with malnutrition-inflammation-cachexia syndrome such as higher white blood cell counts and lower body mass index, albumin, and normalized protein catabolic rate. Among very-elderly incident hemodialysis patients, dialysis therapy withdrawal exhibits wide variations across age, race and ethnicity, regions, cognitive status, dialysis vascular access, and nutritional status. Further studies examining implications of withdrawal from dialysis in older patients are warranted [ABSTRACT FROM AUTHOR]

Background Higher estimated glomerular filtration rate (eGFR) at dialysis initiation, known as earlier start of dialysis, is often a surrogate of poor outcomes including higher mortality. We hypothesized that earlier dialysis initiation is associated with a faster decline in residual kidney function (RKF), which is also associated with higher mortality among incident hemodialysis (HD) patients. Methods In a cohort of 4911 incident HD patients who initiated HD over a 5-year period (July 2001 to June 2006), we examined the trajectories of RKF, ascertained by renal urea clearance (KRU), over 2 years after HD initiation across strata of eGFR at HD initiation using case-mix adjusted linear mixed-effect models. We then investigated the association between annual change in RKF and mortality using Cox proportional hazard models. Results The median (interquartile range) baseline KRU was 2.20 (1.13–3.63)  mL/min/1.73 m2. The decline of KRU was faster in patients who initiated HD at higher eGFR. The relative changes with 95% confidence intervals (CIs) in KRU at 1 year after HD initiation were −1.29 (−1.28 to −1.30), −1.17 (−1.16 to −1.18), −1.11 (−1.10 to −1.12) and −0.78 (−0.78 to −0.79)  mL/min/1.73 m2 in the eGFR categories of ≥10, 8–<10, 6–<8 and <6 mL/min/1.73 m2, respectively. The faster decline of KRU at 1 year was associated with higher all-cause mortality (reference: ≥0 mL/min/1.73 m2): hazard ratios (95% CIs) for change in KRU of −1.5 to <0, −3 to less than −1.5 and less than −3 mL/min/1.73 m2 were 1.20 (1.03–1.40), 1.42 (1.17–1.72) and 1.88 (1.47–2.40), respectively. Conclusions The faster decline of RKF happens with earlier dialysis initiation and is associated with higher all-cause mortality. [ABSTRACT FROM AUTHOR]

Vitamin D receptor activators (VDRA) may exert pleiotropic effects on cardiovascular disease, malignancy, and infections among dialysis patients, but recent studies have mainly focused on cardiovascular outcomes. Among 8,675 patients who started dialysis in 2007 and who survived until January 1, 2010, listed in the Renal Data Registry of the Japanese Society for Dialysis Therapy, 5,365 VDRA users were matched to 3,203 non-users based on clinically relevant variables at the end of 2009 using the coarsened exact matching procedure. Until December 31, 2011, a total of 1,128 deaths occurred, of which 468 (42%) were cardiovascular deaths, 229 (20%) were infection-related deaths, and 141 (12%) were malignancy-related deaths. Multivariable survival analyses accounting for intra-region correlation revealed that VDRA use was significantly associated with lower rates of infection- and malignancy-related deaths [subhazard ratio 0.62 (95% CI, 0.52-0.73) and 0.70 (95% CI, 0.50-0.97), respectively] but not with cardiovascular death [subhazard ratio 0.86 (95% CI, 0.72-1.04)]. Future randomized clinical trials with a sufficient sample size and an adequate follow-up period are warranted to test the clinical effectiveness of VDRA on infection and malignancy, rather than cardiovascular disease, among dialysis patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Dietary acid reduction with fruits and vegetables or sodium bicarbonate reduces kidney injury in subjects with moderately reduced GFR due to hypertensive nephropathy," by Nimrit Goraya and colleagues in the 2012 issue.

Background Hyperkalemia is associated with kidney function decline in patients with non-dialysis dependent chronic kidney disease, but this relationship is unclear for residual kidney function (RKF) among hemodialysis (HD) patients. Methods We conducted a retrospective cohort study of 6655 patients, who started HD January 2007 and December 2011 and who had data on renal urea clearance (KRU). Serum potassium levels were stratified into four groups (i.e. ≤4.0, >4.0 to ≤4.5, >4.5 to ≤5.0 and >5.0 mEq/L) and 1-year KRU slope for each group was estimated by a linear mixed-effects model. Results Higher serum potassium was associated with a greater decline in KRU, and the greatest decrease in KRU (–0.20, 95% confidence interval –0.50 to –0.06) was observed for baseline potassium >5.0 mEq/L in the fully adjusted model. Mediation analysis showed that KRU slope mediated 1.78% of the association between serum potassium and mortality. Conclusions Hyperkalemia is associated with a decline in RKF amongst incident HD patients. These findings may have important clinical implications in the management of hyperkalemia in advanced CKD if confirmed in additional clinical trials. [ABSTRACT FROM AUTHOR]

The combination of serum 25-hydroxyvitamin D (25D) and fibroblast growth factor 23 (FGF23) levels predict hard renal outcomes in patients with chronic kidney disease (CKD), independent of classical markers of mineral and bone disorders, including serum phosphorus, parathyroid hormone, 1,25-dihydroxyvitamin D levels, and active vitamin D therapy. In a prospective cohort study of 738 Japanese pre-dialysis outpatients with CKD, we examined potentially non-linear associations between 25D and FGF23 levels and estimated glomerular filtration rate (eGFR) changes in 727 patients with at least a 6-month observation period and no history of admission by acute kidney injury. We used multiple regression analyses with restricted cubic spline functions using annualized eGFR decline as a dependent variable. A significantly non-linear positive relationship between 25D and eGFR changes was observed. The annualized eGFR decline was greater in patients with 25D concentrations <25 and 23 ng/ml in univariate and multivariate analyses, respectively. Above this threshold, the eGFR decline plateaued. FGF23 showed a linear negative association with eGFR changes. After dividing the patients into four groups according to median 25D and FGF23 levels, the annualized eGFR changes in the Low FGF23-Low 25D, High FGF23-High 25D, and High FGF23-Low 25D groups were 0.49 (95% confidence intervals: −2.83 to 3.81), −1.24 (−5.00 to 2.52), −4.77 (−8.85 to −0.69), respectively, relative to the Low FGF23-High 25D group (P for trend, 0.02). Thus, combined use of FGF23 and 25D is useful to predict eGFR change in patients with CKD as well as hard renal outcomes. [ABSTRACT FROM AUTHOR]

Background Constipation is highly prevalent in patients with chronic kidney disease (CKD), particularly among those with end-stage renal disease (ESRD), partly due to their dietary restrictions, comorbidities and medications. Laxatives are typically used for constipation management; however, little is known about laxative use and its associated factors in patients with advanced CKD transitioning to ESRD. Methods In a retrospective cohort of 102 477 US veterans transitioning to dialysis between October 2007 and March 2015, we examined the proportion of patients who filled a prescription for any type of laxative within each 6-month period over 36 months pre- and post-transition to ESRD. Factors associated with laxative use during the last 1-year pre-ESRD period were identified by multivariable logistic regression. Results The proportion of patients prescribed laxatives increased as patients progressed to ESRD, peaking at 37.1% in the 6 months immediately following ESRD transition, then remaining fairly stable throughout the post-ESRD transition period. Among laxative users, stool softeners were the most commonly prescribed (∼30%), followed by hyperosmotics (∼20%), stimulants (∼10%), bulk formers (∼3%), chloride channel activator (<1%) and several combinations of these. The use of anticoagulants, oral iron supplements, non-opioid analgesics, antihistamines and opioid analgesics were among the factors independently associated with pre-ESRD laxative use. Conclusion The use of laxatives increased considerably as patients neared transition to ESRD, likely mirroring the increasing burden of drug-induced constipation during the ESRD transition period. Findings may provide novel insight into better management strategies to alleviate constipation symptoms and reduce medication requirements in patients with advanced CKD. [ABSTRACT FROM AUTHOR]

Introduction: Erythropoietin stimulating agents (ESA) hyporesposiveness has been associated with increased mortality in hemodialysis (HD) patients. However, the impact of decline of residual kidney function (RKF) on ESA hyporesposiveness has not been adequately elucidated among patients receiving HD. Methods: The associations of RKF decline with erythropoietin resistance index (ERI; average weekly ESA dose [units])/post‐dialysis body weight [kg]/hemoglobin [g/dL]) were retrospectively examined across four strata of annual change in RKF (residual renal urea clearance [KRU] < −3.0, −3.0 to <−1.5, −1.5 to <0, ≥0 mL/min/1.73 m2 per year; urinary volume < −600, −600 to<−300, −300 to <0, ≥0 mL/day per year) using logistic regression models adjusted for clinical characteristics and laboratory variables in 5239 incident HD patients in a large US dialysis organization between 1 January 2007 and 31 December 2011. Findings: The median values of the annual change in KRU and urinary volume were −1.2 (interquartile range [IQR]: −2.8 to 0.1) mL/min/1.73 m2 per year and −250 (IQR: −600 to 100) mL/day per year. A faster KRU decline in the first year of HD was associated with higher odds for ESA hyporesponsiveness: KRU decline of <−3.0, −3.0 to <−1.5, and −1.5 to <0/min/1.73 m2 per year were associated with adjusted odds ratios (OR) of 2.07 (95% confidence interval [CI]: 1.66–2.58), 1.54 (95%CI: 1.28–1.85), and 1.26 (95%CI: 1.07–1.49), respectively (reference: ≥0 mL/min/1.73 m2 per year). These associations were consistent across strata of baseline KRU, age, sex, race, diabetes, congestive heart failure, hemoglobin, and serum albumin. Sensitivity analyses using urinary volume as another index of RKF showed consistent associations. Discussion: A faster RKF decline during the first year of dialysis was associated with ESA hyporesponsiveness and low hemoglobin levels among incident HD patients. [ABSTRACT FROM AUTHOR]

Summary: Adolescent age may be a high‐risk period for kidney allograft failure. However, the knowledge on this topic is limited mostly to the first transplant. Among 20 960 patients aged ≤21 years at the first kidney transplantation from the US Renal Data System, we evaluated the association of age at the first kidney transplant with risk for the first and subsequent graft failures (1st, 2nd, and 3rd) using the conditional risk set model for recurrent time‐to‐event data. The median age was 15 (interquartile range: 9–18) years, and 18% received transplants twice or more during a median follow‐up of 9.7 years. The risk for graft failures was highest in 16 to <18 years old with an adjusted hazard ratio (aHR) of 1.93 (95% CI, 1.73–2.15; reference: <3 years). When separately analyzed, the highest risk was observed in 17, 19, and 21 years old for the first, second, and third transplant, respectively. Those 16 to <18 years were also strongly associated with the highest risk for death after returning to dialysis (aHR, 4.01; 95% CI, 2.82–5.71). Adolescent recipients remain at high risk for allograft failure for a long time, which may result in high mortality risk, even though they surpass this high‐risk period soon after the first transplant. [ABSTRACT FROM AUTHOR]

Separate assessment of mineral bone disorder (MBD) parameters including calcium, phosphate, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D (1,25D) predict renal outcomes in kidney transplant recipients (KTRs), with conflicting results. To date, data simultaneously evaluating these parameters and interwoven relations on renal outcomes are scarce. We conducted a prospective long-term follow-up cohort study included 263 KTRs with grafts functioning at least 1 year after transplantation. The outcome was a composite of estimated GFR halving and graft loss. Cox regression analyses were employed to evaluate associations between a panel of six MBD parameters and renal outcomes. The outcome occurred in 98 KTRs during a median follow-up of 10.7 years. In a multivariate Cox analysis, intact PTH (iPTH), phosphate, and 1,25D levels were associated with the outcome (hazard ratio, 1.60 per log scale; 95% confidence interval, 1.19–2.14, 1.60 per mg/dL; 1.14–2.23 and 0.82 per 10 pg/mL; 0.68–0.99, respectively). Competing risk analysis with death as a competing event yielded a similar result. After stratification into four groups by iPTH and phosphate medians, high risks associated with high iPTH was not observed in KTRs with low phosphate levels (P-interaction < 0.1). Only KTRs not receiving active vitamin D, poor 1,25D status predicted the worse outcome (P-interaction < 0.1). High iPTH, phosphate, and low 1,25D, but not FGF23, levels predicted poor renal outcomes. Simultaneous evaluation of PTH and phosphate levels may provide additional information regarding renal allograft prognosis. [ABSTRACT FROM AUTHOR]

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) is associated with a slower progression to end-stage renal disease (ESRD) in pre-dialysis patients. However, little is known about the associated mortality risks after transitioning to dialysis. Methods: This retrospective cohort study included 0–21 year-old incident dialysis patients from the United States Renal Data System starting dialysis between 1995 and 2016. We examined the association of CAKUT vs. non-CAKUT with all-cause mortality, using Cox regression adjusted for case mix variables. We also examined the mortality risk associated with 14 non-CAKUT vs. CAKUT ESRD etiologies and under stratification by estimated glomerular filtration rate (eGFR). Results: Among 25,761 patients, the median (interquartile range) age was 17 (11–19) years, and 4780 (19%) had CAKUT. CAKUT was associated with lower mortality, with an adjusted hazard ratio (aHR) of 0.72 (95%CI, 0.64–0.81) (reference: non-CAKUT). In age-stratified analyses, CAKUT vs. non-CAKUT aHRs (95%CI) were 0.66 (0.54–0.80), 0.56 (0.39–0.80), 0.66 (0.50–0.86), and 0.97 (0.80–1.18) among patients < 6, 6–< 13, 13–< 18, and ≥ 18 years at dialysis initiation, respectively. Among non-CAKUT ESRD etiologies, the risk of mortality associated with primary glomerulonephritis (aHR, 0.93; 95%CI 0.80–1.09) and focal segmental glomerulosclerosis (aHR, 0.89; 95%CI, 0.75–1.04) were comparable or slightly lower compared to CAKUT, whereas most other primary causes were associated with higher mortality risk. While the CAKUT group had lower mortality risk compared to the non-CAKUT group patients with eGFR ≥5 mL/min/1.73m2, CAKUT was associated with higher mortality in patients with eGFR < 5 mL/min/1.73 m2. Conclusions: CAKUT is associated with lower mortality among children < 18 years old, but showed comparable mortality with non-CAKUT among patients ≥ 18 years old. ESRD etiology should be considered in risk assessment for children initiating dialysis. [ABSTRACT FROM AUTHOR]

Background Red blood cell distribution width (RDW) is found to be associated with different types of anemia and has recently been studied as a prognostic marker of mortality in hemodialysis patients. However, the relationship of RDW with mortality and hospitalization rate in peritoneal dialysis (PD) patients is less known. Methods Among 14 323 incident PD patients between 2007 and 2011 in the USA, we examined the relationship of baseline and time-varying RDW with the risk of mortality and time to first hospitalization using adjusted Cox models. In addition, we examined the relationship of baseline RDW and hospitalization rate using an adjusted negative-binomial regression model. Sensitivity analyses included competing risk models and subgroup analyses. Results The study population comprised patients 56 ± 16 years of age, including 43% females, 23% African Americans and 62% diabetics, with a mean RDW of 15.3 ± 1.6%. In models adjusted for clinical characteristics and laboratory parameters, RDW exhibited an incremental relationship with the mortality risk, where RDW ≥16.5% had a 40% and 69% higher risk of death in baseline and time-varying analyses, respectively, compared with an RDW of 14.5–15.5%. Moreover, higher baseline RDW ≥16.5% was also associated with a higher risk of time to first hospitalization {hazard ratio 1.22 [95% confidence interval (CI) 1.14–1.29]} and a higher rate of hospitalizations [incidence rate ratio 1.16 (95% CI 1.09–1.23)]. These results were consistent across numerous sensitivity analyses. Conclusions Higher RDW is associated with a higher risk of mortality and hospitalizations among incident PD patients. Further studies are needed to examine the mechanism behind RDW and adverse outcomes. [ABSTRACT FROM AUTHOR]

Background Hypomagnesemia (Hypo-Mg) predicts mortality and chronic kidney disease (CKD) progression. However, in CKD, its prevalence, kidney-intrinsic risk factors, and the effectiveness of oral magnesium (Mg) therapy on serum Mg levels is uncertain. Methods In a cross-sectional study enrolling pre-dialysis outpatients with CKD, the prevalence of electrolyte abnormalities (Mg, sodium, potassium, calcium and phosphorus) was compared. In an open-label randomized controlled trial (RCT), we randomly assigned CKD patients to either the magnesium oxide (MgO) or control arm. The outcome was serum Mg levels at 1 year. Results In 5126 patients, Hypo-Mg was the most common electrolyte abnormality (14.7%) with similar prevalence across stages of CKD. Positive proteinuria was a risk factor of Hypo-Mg (odds ratio 2.2; 95% confidence interval 1.2–4.0). However, stratifying the analyses by diabetes mellitus (DM), it was not significant in DM (Pinteraction = 0.04). We enrolled 114 patients in the RCT. Baseline analyses showed that higher proteinuria was associated with higher fractional excretion of Mg. This relationship between proteinuria and renal Mg wasting was mediated by urinary tubular markers in mediation analyses. In the MgO arm, higher proteinuria or tubular markers predicted a significantly lower 1-year increase in serum Mg. In patients with a urinary protein-to-creatinine ratio (uPCR) <0.3 g/gCre, serum Mg at 1 year was 2.4 and 2.0 mg/dL in the MgO and control arms, respectively (P   <   0.001), with no significant between-group difference in patients whose uPCR was ≥0.3 g/gCre (Pinteraction=0.001). Conclusions Proteinuria leads to renal Mg wasting through tubular injuries, which explains the high prevalence of Hypo-Mg in CKD. [ABSTRACT FROM AUTHOR]

Background. Intradialytic hypotension (IDH) occurs frequently inmaintenance hemodialysis (HD) patients and may be associated with higher mortality. We hypothesize that nadir intradialytic systolic blood pressure (niSBP) is inversely related to death risk while iSBP change (D) and IDH frequency are incrementally associated with all-cause mortality. Methods. In a US-based cohort of 112 013 incident HD patients over a 5-year period (2007-11), using niSBP, DiSBP (pre-HD SBP minus niSBP) and IDH frequency (proportion of HD treatments with niSBP <90mmHg) within the first 91 days of HD, we examined mortality-predictability at 1, 2 and 5 years using Cox models and restricted cubic splines adjusted for case-mix, comorbidities and laboratory covariates. Results. We observed that niSBP of <90 and ≥140mmHg had a 5-year mortality hazard ratio (HR) (95% confidence interval) of 1.57 (1.47-1.67) and 1.25 (1.18-1.33), respectively, compared with niSBP 110 to <120mmHg. DiSBP of <15 and ≥50 compared with 21-30mmHg had mortality HR of 1.31 (1.26-1.37) and 1.32 (1.24-1.39), respectively. Among patients with >40% IDH frequency, we observed a mortality HR of 1.49 (1.42-1.57) compared with 0% IDH frequency in fully adjusted models. These associations were robust at 1 and 2 years of follow-up. Conclusion. In conclusion, we observed a U-shaped association between niSBP and DiSBP andmortality and a direct linear relationship between IDH frequency and mortality. Our findings lend some prognostic insight of HD blood pressure and hemodynamics, and have the potential to guide blood pressure management strategies among the HD population. [ABSTRACT FROM AUTHOR]

Incremental hemodialysis has been examined as a viable hemodialysis regimen for selected end-stage renal disease (ESRD) patients. Preservation of residual kidney function (RKF) has been the driving impetus for this approach given its benefits upon the survival and quality of life of dialysis patients. While clinical practice guidelines recommend an incremental start of dialysis in peritoneal dialysis patients with substantial RKF, there remains little guidance with respect to incremental hemodialysis as an initial renal replacement therapy regimen. Indeed, several large population-based studies suggest that incremental twice-weekly vs. conventional thrice-weekly hemodialysis has favorable impact upon RKF trajectory and survival among patients with adequate renal urea clearance and/or urine output. In this report, we describe a case series of 13 ambulatory incident ESRD patients enrolled in a university-based center's Incremental Hemodialysis Program over the period of January 2015 to August 2016 and followed through December 2016. Among five patients who maintained a twice-weekly hemodialysis schedule vs. eight patients who transitioned to thrice-weekly hemodialysis, we describe and compare patients' longitudinal case-mix, laboratory, and dialysis treatment characteristics over time. The University of California Irvine Experience is the first systemically examined twice-weekly hemodialysis practice in North America. While future studies are needed to refine the optimal approaches and the ideal patient population for implementation of incremental hemodialysis, our case-series serves as a first report of this innovative management strategy among incident ESRD patients with substantial RKF, and a template for implementation of this regimen. [ABSTRACT FROM AUTHOR]

Each year approximately 13,000 Veterans transition to maintenance dialysis, mostly in the traditional form of thrice-weekly hemodialysis from the start. Among >6000 dialysis units nationwide, there are currently approximately 70 Veterans Affairs (VA) dialysis centers. Given this number of VA dialysis centers and their limited capacity, only 10% of all incident dialysis Veterans initiate treatment in a VA center. Evidence suggests that, among Veterans, the receipt of care within the VA system is associated with favorable outcomes, potentially because of the enhanced access to healthcare resources. Data from the United States Renal Data System Special Study Center "Transition-of-Care-in-CKD" suggest that Veterans who receive dialysis in a VA unit exhibit greater survival compared with the non-VA centers. Substantial financial expenditures arise from the high volume of outsourced care and higher dialysis reimbursement paid by the VA than by Medicare to outsourced providers. Given the exceedingly high mortality and abrupt decline in residual kidney function (RKF) in the first dialysis year, it is possible that incremental transition to dialysis through an initial twice-weekly hemodialysis regimen might preserve RKF, prolong vascular access longevity, improve patients' quality of life, and be a more patient-centered approach, more consistent with "personalized" dialysis. Broad implementation of incremental dialysis might also result in more Veterans receiving care within a VA dialysis unit. Controlled trials are needed to examine the safety and efficacy of incremental hemodialysis in Veterans and other populations; the administrative and health care as well as provider structure within the VA system would facilitate the performance of such trials. [ABSTRACT FROM AUTHOR]

Background: It is not known whether asymptomatic cardiac troponin T (cTnT) elevation is associated with all-cause or cardiovascular mortality in non-diabetic and advanced chronic kidney disease (CKD) patients. Methods: We measured cTnT in 248 consecutive patients at 1-2 weeks before dialysis initiation between March 2005 and August 2010 and followed them prospectively. A Cox proportional hazard model was used to investigate the relationship between cTnT and all-cause and cardiovascular mortality on dialysis. Results: The median age of the patients was 67 years (male 59.3 %), and the prevalence of diabetic nephropathy (DN) was 38.3 %. Asymptomatic cTnT elevation (>0.01 ng/mL) was observed in 196 (79 %) and 111 (73 %) patients among the overall patients and among patients without DN, respectively. A total of 51 patients died during a median follow-up period of 31.6 months. The cTnT level was associated with all-cause [hazard ratio (HR) 1.453; 95 % confidence interval (CI) 1.093-1.931; P = 0.010] and cardiovascular mortality [HR 1.973; 95 % CI 1.127-3.454; P = 0.017] on dialysis after extensive adjustment in the overall patient population. Patients without DN showed similar associations as those for the overall patient population (all-cause mortality: HR 1.566; 95 % CI 1.048-2.339; P = 0.029 and cardiovascular mortality: HR 2.657; 95 % CI 1.115-6.328; P = 0.027). Conclusion: Asymptomatic cTnT elevation might be strongly associated with all-cause and cardiovascular mortality in patients without DN, as well as in the overall advanced CKD patients. We suggest that cardiovascular risk in patients with pre-dialysis CKD should be stratified according to cTnT levels. [ABSTRACT FROM AUTHOR]

There are limited data regarding outcomes of patients underwent kidney autotransplantation. This study aims to investigate outcomes of such patients. The nationwide inpatient sample database was used to identify patients underwent kidney autotransplantation during 2002 to 2012. Multivariate analyses using logistic regression were performed to investigate morbidity predictors. A total of 817 patients underwent kidney autotransplantation from 2002 to 2012. The most common indication of surgery was renal artery pathology (22.7%) followed by ureter pathology (17%). Overall, 97.7 per cent of operations were performed in urban teaching hospitals. The number of procedures from 2008 to 2012 were significantly higher compared with the number of them from 2002 to 2007 (473 vs 345, P < 0.01). The overall mortality and morbidity of patients were 1.3 and 46.2 per cent, respectively. The most common postoperative complications were transplanted kidney failure (10.7%) followed by hemorrhagic complications (9.7%). Obesity [adjusted odds ratio (AOR): 9.62, P < 0.01], fluid and electrolyte disorders (AOR: 3.67, P < 0.01), and preoperative chronic kidney disease (AOR: 1.80, P = 0.03) were predictors of morbidity in patients. In conclusion, Kidney autotransplantation is associated with low mortality but a high morbidity rate. The most common indications of kidney autotransplantation are renal artery and ureter pathologies, respectively. A kidney transplant failure rate of 10.7 per cent was observed in patients with kidney autotransplantation. The most common postoperative complication was hemorrhagic in nature. [ABSTRACT FROM AUTHOR]

Background: The Agatston score, commonly used to quantify coronary artery calcification (CAC), is determined by the plaque area and density. Despite an excellent predictability of the Agatston score for cardiovascular events, the density of CAC has never been studied in patients with pre-dialysis chronic kidney disease (CKD). This study aimed to analyze the CAC density and its association with serum mineral levels in CKD. Methods: We enrolled patients with pre-dialysis CKD who had diabetes mellitus, prior cardiovascular disease history, elevated low-density lipoprotein cholesterol levels, or smoking history. The average CAC density was calculated by dividing the Agatston score by the total area of CAC. Results: The mean estimated glomerular filtration rate (eGFR) of 109 enrolled patients was 35.7 mL/min/1.73 m2. The correlation of the Agatston score with density was much weaker than that with the total area (R2 = 0.19, P < 0.001; and R2 = 0.99, P < 0.001, respectively). Multivariate analyses showed that serum magnesium level was inversely associated with the density, but not with the total area, after adjustment for demographics and clinical factors related to malnutrition-inflammation-atherosclerosis syndrome and mineral and bone disorders including fibroblast growth factor 23 (P = 0.006). This inverse association was pronounced among patients with higher serum phosphate levels (P for interaction = 0.02). Conclusion: CAC density was inversely associated with serum magnesium levels, particularly in patients with higher serum phosphate levels. [ABSTRACT FROM AUTHOR]

Carriage of high-risk APOL1 genetic variants is associated with increased risks for kidney diseases in people of African descent. Less is known about the variants' associations with blood pressure or potential moderators. We investigated these associations in a pregnancy cohort of 556 women and 493 children identified as African American. Participants with two APOL1 risk alleles were defined as having the high-risk genotype. Blood pressure in both populations was measured at the child's 4–6 years visit. We fit multivariate linear and Poisson regressions and further adjusted for population stratification to estimate the APOL1 -blood pressure associations. We also examined the associations modified by air pollution exposures (particulate matter ≤2.5 μ m in aerodynamic diameter [PM 2.5 ] and nitrogen dioxide) and explored other moderators such as health conditions and behaviors. Neither APOL1 risk alleles nor risk genotypes had a main effect on blood pressure in mothers or children. However, each 2-μg/m3 increase of four-year average PM 2.5 was associated with a 16.3 (95%CI: 5.7, 26.9) mmHg higher diastolic blood pressure in mothers with the APOL1 high-risk genotype, while the estimated effect was much smaller in mothers with the low-risk genotype (i.e., 2.9 [95%CI: -3.1, 8.8] mmHg; P interaction = 0.01). Additionally, the associations of APOL1 risk alleles and the high-risk genotype with high blood pressure (i.e., SBP and/or DBP ≥ 90th percentile) were stronger in girls vs. boys (P interaction = 0.02 and 0.005, respectively). This study sheds light on the distribution of high blood pressure by APOL1 genetic variants and informs regulatory policy to protect vulnerable population subgroups. • No association between APOL1 and blood pressure was shown in African American mothers or children. • Mothers with the APOL1 high-risk genotype were more vulnerable to higher DBP when exposed to PM 2.5. • Stronger associations of APOL1 risk variants with HBP were found in girls than in boys. [ABSTRACT FROM AUTHOR]

Osteoporosis is one of the major complications of glucocorticoid therapy. Osteoporosis is usually defined by the levels of bone mineral density (BMD) assessed by dual energy X-ray absorptiometry (DEXA); however, glucocorticoids often induce fractures in patients with normal BMD. Thus, novel diagnostic approaches are required. In this study, we examined whether multidetector-row computed tomography (MDCT) is useful to assess the bone status in glucocorticoid-induced osteoporosis (GIO). Because bisphosphonates have been proven to prevent bone fracture in GIO, we tried to detect the therapeutic effects of bisphosphonates in GIO by MDCT. Fifteen Japanese patients with immunoglobulin A nephropathy who had normal renal function were enrolled in this open-label randomized trial. Patients were randomly divided into three groups-calcitriol (VD), menatetrenone (VK), or bisphosphonate (Bis). Bone conditions were analyzed twice by three different methods-bone turnover markers, DEXA, and MDCT-at the start and 6 months after the start of therapy. Both bone markers and DEXA could not detect significant differences among the therapeutic groups; however, MDCT-based analyses detected the preventive effects of bisphosphonates in GIO. Compared to VD, Bis improved structural indices, such as bone volume fraction, trabecular separation, marrow star volume, and structure model index whereas the difference between VD and VK was not significant. Finite element analysis revealed that simulated fracture load in the Bis group was significantly improved. These findings suggested that MDCT-based assessment is superior to bone markers and/or DEXA in assessing the therapeutic effect of bisphosphonates on GIO. [ABSTRACT FROM AUTHOR]

The main objective of this study was to assess cardiac death (CD) kidney grafts before transplantation to determine whether blood oxygen level-dependent (BOLD) and diffusion MRI techniques can predict damage to these grafts after transplantation. We assessed CD kidney tissue by BOLD and diffusion MRI. We also examined pathological and gene expression changes in CD kidney grafts before and after transplantation. Although there was significantly more red cell congestion (RCC) in the inner stripe of the outer medulla (IS) in both 1 h after cardiac death (CD1h) and CD2h kidneys destined for grafts before transplantation compared with CD0h (p<0.05), CD2h, but not CD1h, kidney grafts had significantly different RCC in the IS 2 days after transplantation (p<0.05). Consistent with these pathological findings, tissue plasminogen activator (tPA) gene expression was increased only in the cortex and medulla of CD2h kidney grafts after transplantation. BOLD MRI successfully and non-invasively imaged and quantified RCC in the IS in both CD1h and CD2h kidney grafts (p<0.05). Diffusion MRI also non-invasively assessed increased the apparent diffusion coefficient in the IS and decreased it in the outer stripe (OS) of CD2h grafts, in concordance with interstitial edema in the IS and tubule cellular edema in the OS. These two types of edema in the outer medulla could explain the prolonged RCC in the IS only of CD2h kidney grafts, creating part of a vicious cycle inhibiting red cells coming out of capillary vessels in the IS. Perfusion with University of Wisconsin solution before MRI measurements did not diminish the difference in tissue damage between CD1h and CD2h kidney grafts. BOLD and diffusion MRI, which are readily available non-invasive tools for evaluating CD kidney grafts tissue damage, can predict prolonged organ damage, and therefore the outcome, of transplanted CD kidney grafts. [ABSTRACT FROM AUTHOR]

Background: Recent experimental studies suggest that erythropoietin promotes beneficial myocardial remodeling during left ventricular hypertrophy (LVH); however, such compensatory capacity may be limited due to insufficient erythropoietin production in chronic kidney disease patients. Thus, this study aimed to explore the effect of pre-dialysis erythropoiesis-stimulating agent (ESA) use on the prognostic significance of LVH in dialyzed patients. Methods: This retrospective study included 404 consecutive patients who started dialysis between 2001 and 2009. The interaction of ESA with the association between left ventricular mass index (LVMI) observed at dialysis initiation and all-cause and cardiovascular mortality was analyzed at the end of 2010 using the Cox model. Results: During a median follow-up of 36.5 months, 164 patients died, 31 of them from heart failure. The frequency of pre-dialysis ESA use was 58.7 % and median LVMI was 160.3 g/m. Of interest, patients with the lowest tertile of LVMI had worse survival compared with those with each subsequent tertile. LVMI was inversely associated with all-cause mortality [hazard ratio (HR) 0.991, 95 % confidence interval (CI) 0.988-0.995, P = 0.000] after extensive adjustment including ejection fraction, whereas the prognostic value of LVMI for cardiovascular mortality was dependent on pre-dialysis ESA use [adjusted HR 1.010, 95 % CI 0.999-1.020, P = 0.065 for pre-dialysis ESA(+) and 0.978, 95 % CI 0.967-0.989, P = 0.000 for pre-dialysis ESA(−), respectively]. Conclusions: Our results suggest that reverse epidemiology may exist between LVH and mortality and that pre-dialysis ESA use may modify the prognostic significance of LVH observed at dialysis initiation for cardiovascular mortality in dialyzed patients. [ABSTRACT FROM AUTHOR]

Background As a cardiorenal syndrome, there is a dynamic interplay between the heart and the kidney. We conducted a prospective study to evaluate the prognostic impact of plasma B-type natriuretic peptide (BNP) level, a cardiac biomarker, on the long-term kidney prognosis in chronic kidney disease (CKD) patients. Methods We prospectively enrolled 508 patients with CKD Stages 3, 4 and 5 not on dialysis, from a single nephrology department between 2004 and 2010. The exclusion criteria were over 90 years of age, malignancy, active infection, low cardiac ejection fraction and rapid progressive glomerulonephritis. Relationships between BNP and kidney end point [defined as doubling of baseline serum creatinine and end-stage kidney disease (ESKD) requiring kidney replacement therapy] were measured using Cox models for case-mix and laboratory variables. Results The final analysis covered 485 participants with no loss to follow-up. The median follow-up period was 3.2 years. Two hundred and twenty-eight of the 485 patients reached ESKD requiring dialysis, and baseline serum creatinine levels doubled in another 31. The kidney end point was significantly poorer among patients with plasma BNP levels above, compared with below a cut-off value of 86.1 pg/mL indicated from receiver operating characteristic analysis. Multivariable Cox regression analysis identified the common logarithm BNP as a predictor of kidney end point (adjusted hazard ratio 1.78, 95% CI: 1.28–2.46, P < 0.01). Conclusions Elevation of BNP level is associated with an increased risk for accelerated progression of CKD ultimately to ESKD. Monitoring the BNP level could be helpful in the management of combined heart and kidney disease. [ABSTRACT FROM PUBLISHER]

Abstract: Purpose: Low 25-hydroxyvitamin D (25D), increased levels of fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), and alkaline phosphatase (ALP) were reported to be risk factors for mortality in chronic kidney disease (CKD). However, the independent associations of these factors with cardiovascular disease (CVD), the leading cause of death among CKD patients, remain unclear. Our purpose was to identify which of these factors predict incident CVD in CKD. Methods: In this prospective cohort study, we enrolled 738 predialysis outpatients in the two nephrology departments. We employed Cox proportional hazards analyses to elucidate predictors of the endpoint, defined as fatal or non-fatal cardiovascular event requiring hospitalization. Multiple imputation was performed for missing values. Results: Mean estimated glomerular filtration rate (eGFR) was 35mL/min/1.73m2. During a median duration of 4.4years, 86 patients developed the endpoint, of whom 62 patients achieved it before the initiation of dialysis. Multivariable analyses revealed that high serum intact FGF23 levels predicted the outcome preceding dialysis initiation (hazard ratio (HR) per lnFGF23 (SD), 1.64 (1.27–2.30)), while 25D, PTH, and bone-specific ALP did not. Adding FGF23 to the conventional model of age, sex, diabetes, prior CVD, pulse pressure, and eGFR, led to a net reclassification improvement of 6.87% (P =0.04). Not censoring the patients at the start of dialysis and continuing follow-up even after dialysis, FGF23 levels did not predict the outcome (HR, 1.16 (0.91–1.48)). Complete case analyses yielded similar results. Conclusions: Intact FGF23 levels in predialysis CKD predicted incident cardiovascular events requiring hospitalization before starting dialysis, but did not predict events during the entire follow-up period, including post dialysis initiation. [Copyright &y& Elsevier]

Background: Hypertension, which is affected by genetic and environmental factors, is one of the major risk factors for chronic kidney disease. Identification of the genetic factor contributing to hypertension in patients with chronic kidney disease may potentially refine a therapeutic strategy. Methods: In the present multicenter cross-sectional study, 240 patients were eligible (aged 15-50 years with urinary protein ≥0.25 g/day) out of 429 patients who were diagnosed as having immunoglobulin (Ig) A nephropathy (IgAN) by renal biopsy between 1990 and 2005 and enrolled in our previous study, PREDICT-IgAN. The outcome was hypertension defined as ≥140 and/or ≥90 mmHg of systolic and diastolic blood pressure and/or use of antihypertensives at renal biopsy. We assessed associations between hypertension and 28 polymorphisms with the frequency of minor genotype ≥10% among 100 atherosclerosis-related polymorphisms using the Chi-squared test in dominant and recessive models. We identified polymorphisms associated with hypertension in multivariate logistic regression models. Results: Baseline characteristics: hypertension 36.3%. Among 28 polymorphisms, the Chi-squared test revealed that CD14 (-159CC vs CT/TT, P = 0.03) and ACE (DD vs DI/II, P = 0.03) were significantly associated with hypertension after Bonferroni correction. Multivariate logistic regression models revealed that CD14 -159CC [vs CT/TT, odds ratio (OR) 3.58 (95% confidence interval (CI) 1.66-7.63)] and ACE DD [vs DI/II, OR 4.41 (95% CI 1.80-10.8), P = 0.001] were independently associated with hypertension. Conclusions: CD14 C-159T and ACE I/D contributed to hypertension in patients with IgAN. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic kidney disease (CKD) still frequently experience cardiovascular events despite recent progress in treatment. We examined whether nicorandil, a hybrid nitrate and adenosine triphosphate-sensitive potassium channel opener, could improve a biomarker and physiological markers of cardiovascular events. Methods: Patients with advanced stage CKD (stage III-V with or without peritoneal dialysis) were included in this trial if they were considered at high risk for cardiovascular events [past history of cardiovascular diseases, past history of coronary angiography, presence of endothelial dysfunction measured by reactive hyperemia peripheral arterial tonometry, and presence of high brain natriuretic peptide (BNP) values]. Patients were randomly assigned to be treated with or without oral nicorandil, 15 mg/day. BNP values and endothelial function (augmentation index, pulse wave velocity, and reactive hyperemia peripheral arterial tonometry) before and 1 month after the initiation of the trial were assessed. Results: Nineteen patients (15 men, 4 women) with a mean age of 61 ± 10 (SD) years were included. The median baseline BNP value was 75.3 (interquartile range, 32.1-138.8) pg/ml, and the BNP level was significantly reduced in the nicorandil group ( P < 0.05). Regression analysis demonstrated that only the use of nicorandil is related to a decrease of BNP levels [standardized β coefficient, −75.1 (95% CI, −19.7 to −130.6), P = 0.01]. There were no significant changes in the rest of the parameters in the nicorandil group in comparison to the control group. The change in BNP levels was correlated with changes in the augmentation index ( P < 0.01) and central pulse pressure ( P = 0.03). Conclusions: Nicorandil treatment may reduce the level of BNP by reducing the central blood pressure in CKD patients. [ABSTRACT FROM AUTHOR]