Prognostic Significance of 1‐Year Serum Albumin Levels Within the Normal Range After Kidney Transplantation

Hypoalbuminemia is associated with poor outcomes in kidney transplantation (KT). However, what level is optimal in serum albumin is not clear for the long‐term prognosis. To determine whether the long‐term outcomes are different even between the normal ranges of serum albumin after KT, we analyzed data from 404 renal allograft recipients whose 1‐year post‐transplant serum albumin levels were within the normal limits (3.5–5.5 g/dL). During a follow‐up of 122 ± 56 months, 97 graft losses, 20 patient deaths, and 50 cardiovascular (CV) events occurred. Based on 1‐year serum albumin levels, the patients were divided into high normal (≥4.6 g/dL, n = 209) and low normal (<4.6 g/dL, n = 195) groups. Kaplan–Meier analyses revealed that the low normal group had poorer allograft survival (P = 0.01), patient survival (P < 0.001), and CV event‐free survival (P < 0.001) than the high normal group. Cox regression analysis confirmed that 1‐year serum albumin was inversely associated with the risk of graft loss (hazard ratio [HR] 0.414, 95% confidence interval [CI] 0.200–0.856), patient death (HR 0.097, 95% CI 0.019–0.484), and CV events (HR 0.228, 95% CI 0.074–0.702). In conclusion, a relatively low 1‐year post‐transplant serum albumin level within the normal limits (<4.6 g/dL) significantly predicts poor long‐term outcomes.     

Retrospective Analysis of the Kidney Donor Profile Index to Predict Patient and Graft Survival at 5 Years Posttransplantation in a Colombian Cohort

BackgroundThe Kidney Donor Profile Index (KDPI) has been used to predict patient and graft outcomes in deceased donor kidney transplantation. We aimed to evaluate the impact of KDPI on transplantation major outcomes applied to a Colombian cohort.MethodsWe retrospectively assessed 260 adult patients who underwent kidney transplantation (KT) from January 2011 to June 2014 at our center and compared their KDPIs with graft and patient outcomes at 5 years posttransplantation. Kaplan-Meier survival method and Cox analysis were fitted to analyze the impact of the 3 KDPI categories on graft and patient outcomes.ResultsA total of 18.4% of transplants were from donors with a KDPI ≥75%. There was a significant decrement in renal function with increasing KDPI at 5 years posttransplantation (P < .05). The final model indicates that donor diabetes was associated with elevated risk for graft loss (hazard ratio [HR], 6.5; 95% confidence interval [CI] 1.35-31.8; P = .019) at 5 years posttransplantation. Recipient age (HR, 2.3; 95% CI, 1.1-4.5; P = .001), diabetes status (HR, 2.17; CI, 1.04-5.5; P = .003), dialysis duration (HR, 1.08; 95% CI, 1.00-1.16; P = .003), and operating room time (HR, 1.47; 95% CI, 1.02-2.12; P = .003) were associated with elevated risk for death at 5 years posttransplantation. KDPI categories were not significantly associated with graft loss or death.ConclusionsWe found limited KDPI power to predict graft and patient survival when applied to a Latin American population in Colombia. Our findings highlight the importance of analyzing the application of KDPI in different populations. Therefore, our findings may not be generalizable to other regions outside of Colombia.     

The impact of early-diagnosed new-onset post-transplantation diabetes mellitus on survival and major cardiac events

The impact of early-diagnosed new-onset post-transplantation diabetes mellitus (PTDM) on cardiovascular (CV) disease is not well described. The objectives of the present prospective single-center observational study were to assess the long-term effects of early-diagnosed new-onset PTDM on major cardiac events (MCE; cardiac death or nonfatal acute myocardial infarction) and patient survival. Diabetic status and CV risk factors were assessed in 201 consecutive renal allograft recipients 3 months after transplantation (baseline) during a period of 16 months (1995-96). Follow-up data until January 1, 2004 were obtained from the Norwegian Renal Registry. The 8-year (range 7-9 years) cumulative incidence of MCEs was 7% (nine out of 138) in recipients without diabetes, 20% (seven out of 35) in patients with new-onset PTDM and 21% (six out of 28) in patients with diabetes mellitus before transplantation (DM). Proportional hazards regression analyses (forward stepwise regression) revealed that patients with PTDM had an approximately three-fold increased risk of MCEs as compared with nondiabetic patients (hazard ratio (HR)=3.27, 95% confidence interval (CI)=1.22-8.80, P=0.019). A total of 61 patients (30%) died. Eight-year patient survival was 80% in the nondiabetic group, 63% in the PTDM group and 29% in the DM group, respectively. Pretransplant diabetes (HR=5.09, 95% CI=2.60-9.96, P<0.001), age (HR=1.03, 95% CI=1.01-1.05, P=0.016), cytomegalovirus (CMV) infection (HR=2.66, 95% CI=1.27-5.53, P=0.009), and creatinine clearance (HR=0.98, 95% CI=0.96-1.00, P=0.046), but not PTDM (HR=1.20, 95% CI=0.58-2.49, P=0.621), were independent predictors of death in the multiple Cox regression model. Early-diagnosed PTDM is a predictor of MCEs, but not of all-cause mortality, the first 8 years after renal transplantation.     

HDL Cholesterol Efflux Predicts Graft Failure in Renal Transplant Recipients

High-density lipoprotein (HDL) particles are involved in the protection against cardiovascular disease by promoting cholesterol efflux, in which accumulated cholesterol is removed from macrophage foam cells. We investigated whether HDL cholesterol efflux capacity is associated with cardiovascular mortality, all-cause mortality, and graft failure in a cohort of renal transplant recipients (n=495, median follow-up 7.0 years). Cholesterol efflux capacity at baseline was quantified using incubation of human macrophage foam cells with apolipoprotein B–depleted plasma. Baseline efflux capacity was not different in deceased patients and survivors (P=0.60 or P=0.50 for cardiovascular or all-cause mortality, respectively), whereas recipients developing graft failure had lower efflux capacity than those with functioning grafts (P<0.001). Kaplan–Meier analysis demonstrated a lower risk for graft failure (P=0.004) but not cardiovascular (P=0.30) or all-cause mortality (P=0.31) with increasing gender-stratified tertiles of efflux capacity. Cox regression analyses adjusted for age and gender showed that efflux capacity was not associated with cardiovascular mortality (hazard ratio [HR], 0.89; 95% confidence interval [95% CI], 0.67 to 1.19; P=0.43). Furthermore, the association between efflux capacity and all-cause mortality (HR, .79; 95% CI, 0.63 to 0.98; P=0.031) disappeared after further adjustment for potential confounders. However, efflux capacity at baseline significantly predicted graft failure (HR, 0.43; 95% CI, 0.29 to 0.64; P<0.001) independent of apolipoprotein A-I, HDL cholesterol, or creatinine clearance. In conclusion, this prospective study shows that cholesterol efflux capacity from macrophage foam cells is not associated with cardiovascular or all-cause mortality but is a strong predictor of graft failure independent of plasma HDL cholesterol levels in renal transplant recipients.     

Mycophenolate mofetil vs. azathioprine is associated with decreased acute rejection, late acute rejection, and risk for cardiovascular death in renal transplant recipients with pre-transplant diabetes

Outcomes specifically in mycophenolate mofetil (MMF)-treated diabetic renal transplant patients have not been previously reported. This study compared acute rejection (AR), late acute rejection (LAR), patient survival [and specifically death from cardiovascular (CV), infectious and malignant causes], incidence of post-transplant malignancies, and graft loss in MMF- or azathioprine (AZA)-treated renal transplant patients with pre-transplant diabetes. Outcomes were compared between MMF- (n = 14 144) and AZA- (n = 3001) treated diabetic patients using the Scientific Registry of Transplant Recipients data on all U.S. adult renal transplants performed between 1995 and 2002. Statistical analyses included Kaplan-Meier survival analysis, Cox multivariable regression and chi-square tests. MMF patients had less AR compared with AZA-treated patients (23.5% vs. 28.3%, p < 0.001) and less risk for LAR over 4 yr [hazard ratio (HR): 0.64, 95% CI 0.44, 0.92; p = 0.02]. While time to any-cause death did not differ between the groups, MMF treatment was associated with a 20% decreased risk of CV death (HR: 0.80, 95% CI 0.67, 0.97; p = 0.020) compared with AZA treatment. MMF patients also had a lower incidence of malignancies than AZA patients (2.2% vs. 3.7%, p < 0.001). These results suggest treatment with MMF compared with treatment with AZA in diabetic transplant patients is associated with less AR, less risk of LAR, a decreased risk of CV death, and a lower incidence of malignancies.     

Angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor antagonist therapy is associated with prolonged patient and graft survival after renal transplantation

Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type 1 receptor blockers (ARB) reduce cardiovascular death in the general population, but data for renal transplant recipients remain elusive. Similarly, ACEI/ARB have been shown to reduce proteinuria, but data on graft survival are lacking. Therefore a retrospective open cohort study was conducted of 2031 patients who received their first renal allograft at the Medical University of Vienna between 1990 and 2003 and survived at least 3 mo. Patient and graft survival was compared between patients with versus without ACEI and/or ARB therapy. Data were analyzed with and without propensity score models for ACEI/ARB therapy. Medication and comorbidities were analyzed as time-dependent variables in the Cox regression analyses. Ten-year survival rates were 74% in the ACEI/ARB group but only 53% in the noACEI/ARB group (P<0.001). The hazard ratio (HR) of ACEI/ARB use for mortality was 0.57 (95% confidence interval [CI] 0.40 to 0.81) compared with nonuse. Ten-year actual graft survival rate was 59% in ACEI/ARB patients but only 41% in nonusers (P=0.002). The HR of actual graft failure for ACEI/ARB recipients was 0.55 (95% CI 0.43 to 0.70) compared with nonusers; the HR of functional graft survival was 0.56 (95% CI 0.40 to 0.78). Ten-year unadjusted functional graft survival rates were 76% among ACEI/ARB patients and 71% in noACEI/ARB recipients (P=0.57). In summary, the use of ACEI/ARB therapy was associated with longer patient and graft survival after renal transplantation. More frequent use of these medications may reduce the high incidence of death and renal allograft failure in these patients.     

The Detrimental Effect of Poor Early Graft Function After Laparoscopic Live Donor Nephrectomy on Graft Outcomes

We undertook this study to assess the rate of poor early graft function (EGF) after laparoscopic live donor nephrectomy (lapNx) and to determine whether poor EGF is associated with diminished long-term graft survival. The study population consisted of 946 consecutive lapNx donors/recipient pairs at our center. Poor EGF was defined as receiving hemodialysis on postoperative day (POD) 1 through POD 7 (delayed graft function [DGF]) or serum creatinine ≥ 3.0 mg/dL at POD 5 without need for hemodialysis (slow graft function [SGF]). The incidence of poor EGF was 16.3% (DGF 5.8%, SGF 10.5%), and it was stable in chronologic tertiles. Poor EGF was independently associated with worse death-censored graft survival (adjusted hazard ratio (HR) 2.15, 95% confidence interval (CI) 1.34–3.47, p = 0.001), worse overall graft survival (HR 1.62, 95% CI 1.10–2.37, p = 0.014), worse acute rejection-free survival (HR 2.75, 95% CI 1.92–3.94, p < 0.001) and worse 1-year renal function (p = 0.002). Even SGF independently predicted worse renal allograft survival (HR 2.54, 95% CI 1.44–4.44, p = 0.001). Risk factors for poor DGF included advanced donor age, high recipient BMI, sirolimus use and prolonged warm ischemia time. In conclusion, poor EGF following lapNx has a deleterious effect on long-term graft function and survival.     

Death in the first year after kidney transplantation: implications for patients on the transplant waiting list

BACKGROUND: As the kidney transplant waiting list continues to expand, maintaining the medical fitness of transplant candidates will become increasingly difficult. METHODS: To identify patients who are at greatest risk during the wait-list period, we performed a Cox regression analysis to determine risk factors for mortality in the first posttransplantation year among 23,546 adult first kidney transplant recipients recorded in the United States Renal Data System between January 1995 and September 1997. RESULTS: In this study population, 4.6% of the patients died in the first posttransplantation year, and cardiac causes were the leading cause (27%) of death. Patients with diabetes (hazard ratio [HR]=1.58; 95% confidence interval [CI], 1.39-1.80), peripheral vascular disease (HR=1.41; 95% CI, 1.11-1.80), or angina (HR=1.38; 95% CI, 1.15-1.65), and patients with a longer duration of end-stage renal disease (HR=1.06 per year; 95% CI, 1.04-1.09) had a higher risk for mortality. Additionally, patients with early acute rejection (HR=1.47; 95% CI, 1.23-1.76), delayed graft function (HR=1.46; 95% CI, 1.25-1.71), and a lower glomerular filtration rate after transplantation were also at increased risk for death within the first posttransplantation year. CONCLUSIONS: Patients with comorbid disease, patients with a long duration of end-stage renal disease, and potential recipients of organs at high risk for graft dysfunction should be carefully screened for medical complications before transplantation to achieve the most favorable outcomes. Alternate organ allocation strategies that facilitate patient assessment close to the time of transplantation or that prioritize high-risk patients may also improve outcomes.     

Risk Factors Affecting Graft and Patient Survivals After Transplantation From Deceased Donors in a Developing Country: A Single-Center Experience

Aim

The aim of this study was to evaluate risk factors affecting graft and patient survival after transplantation from deceased donors.

Serum phosphate and calcium concentrations are associated with reduced patient survival following kidney transplantation

Moore J, Tomson CRV, Tessa Savage M, Borrows R, Ferro CJ. Serum phosphate and calcium concentrations are associated with reduced patient survival following kidney transplantation.
Clin Transplant 2011: 25: 406–416. © 2010 John Wiley & Sons A/S. Abstract: The impact of disordered mineral and bone metabolism following kidney transplantation is not well defined. We studied the association of serum phosphate and calcium concentrations, and surrogate measures of arterial stiffness (augmentation index: AIx and Timing of the reflected wave: Tr), with long‐term kidney transplant recipient and allograft survival. Prevalent adult renal transplant patients (n = 270) were prospectively studied over a median 88‐month follow‐up. Detailed demographic, clinical and laboratory data, in addition to both peripheral and central non‐invasive blood pressure measurements, were recorded. Higher serum phosphate and calcium levels were associated with increased all‐cause mortality (HR: 1.21; 95% CI 1.09,1.35, p < 0.001 and HR: 1.22; 95% CI 1.01,1.48; p < 0.04, respectively; adjusted Cox model) and death‐uncensored graft loss (p < 0.001 and p = 0.03, respectively). In addition, serum calcium and phosphate were associated with death‐censored graft loss on univariable analysis (p < 0.001 and p = 0.02, respectively), but did not retain significance on multivariable analysis. AIx and Tr were not associated with mortality or graft loss on multivariable analysis. This is the first report to demonstrate that both higher serum phosphate and calcium levels are associated with increased mortality in kidney transplant recipients. It highlights the need for randomized trials assessing current interventions available for improving disordered mineral–bone metabolism post transplantation.     

透析开始残余肾功能与维持性透析患者预后的关系

目的 评估终末期肾病患者透析开始残余肾功能与维持性透析预后的关系.方法 收集2005年1月1日至2009年9年30日新进入血透或腹透治疗的终末期肾病成年患者资料,随访至2010年3月31日.根据透析开始时估算肾小球滤过率(eGFR)分为≥10.5、8～＜10.5、6～＜8、＜6 ml· min-1·(1.73 m2)-1 4组.eGFR评估采用MDRD简化公式.终点事件为全因死亡和心脑血管死亡.结果 (1)共562例患者入选,透析开始中位eGFR为5.60(2.26～12.62) ml· min-1·(1.73 m2)-1;中位随访时间为17(0～58)个月 ;死亡141例,中位生存期为45.48(43.05 ～47.90)个月.随着透析开始eGFR下降,4组患者Scr、BUN、血尿酸(SUA)、血前白蛋白、血磷、血钙磷乘积、整段甲状旁腺激素(iPTH)、平均动脉压(MAP)逐渐升高 ;血红蛋白(Hb)、男性患者比例、并发糖尿病比例、Charison并发症指数≥5比例逐渐下降,差异均有统计学意义(均P＜ 0.05).随着透析开始eGFR下降,并发左室肥大比例有逐渐升高趋势,但差异无统计学意义.(2)Kaplan-Meier生存曲线显示4组患者总体生存率差异无统计学意义.Cox回归分析显示透析开始eGFR与透析预后无显著关系.对透析非早期(＞3个月)死亡患者进行Kaplan-Meier生存曲线分析,4组患者1年生存率差异无统计学意义.多因素Cox回归分析显示透析开始eGFR是透析1年生存预后的保护因素(HR =0.791,95％CI 0.669～0.935,P＜0.01).(3)以心脑血管死亡为终点事件,多因素Cox回归分析显示,透析开始eGFR是心脑血管生存预后(HR =0.868,95％CI 0.777～0.971,P＜0.05)和1年心脑血管生存预后(HR=0.937,95％CI 0.851～0.992,P＜0.05)的保护因素.(4)多因素Cox回归分析显示,透析开始eGFR增高1 ml·min-1·(1.73 m2)-1,腹膜透析患者死亡风险下降10％(HR=0.90,95％CI 0.81～0.99,P＜ 0.05).血液透析方式4组患者Kaplan-Meier生存率分析显示,差异有统计学意义(Log-rank检验,P=0.047),8～＜10.5组生存率最低,与6～＜8组、＜6组差异有统计学意义(Log-rank检验,P=0.033,P=0.005).多因素Cox回归分析并未显示透析开始eGFR与预后相关.多因素Cox回归分析提示透析开始eGFR增高1 ml·min-1·(1.73 m2)-1,慢性肾小球肾炎患者和慢性肾小球肾炎腹膜透析患者死亡风险分别降低16.6％(HR=0.834,95％CI 0.736～0.946,P＜0.01)和32.1％(HR=0.679,95％CI 0.535～0.862,P＜0.01).以心脑血管死亡为终点,多因素Cox回归分析显示透析开始eGFR增高1 ml·min-1·(1.73 m2)-1,慢性肾小球肾炎患者心脑血管死亡风险下降18.2％(HR=0.818,95％CI 0.669～0.999,P＜0.05).结论 本组患者透析时机明显晚于国际透析指南的标准.随着透析开始eGFR降低,并发症增多及程度加重.早期透析可能无法提高透析患者的总体生存率,但可能有助于改善患者心脑血管及1年总体生存预后和腹膜透析、慢性肾小球肾炎患者的预后.     

Prognostic significance of serum lactate dehydrogenase in patients undergoing radical cystectomy for bladder cancer

BackgroundTo investigate the prognostic significance of preoperative serum lactate dehydrogenase (LDH) in patients undergoing radical cystectomy for bladder cancer (BCa).Patients and methodsA cohort of 263 patients undergoing open or laparoscopic radical cystectomy between 2011 and 2016 was studied. Baseline characteristics, hematological variables, follow-up data were collected. Kaplan-Meier curves and Cox proportional hazard regression model were applied to assess the relationship between LDH and overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS).ResultsAfter a median 34.2 (22.9–45.8) months follow-up, all-cause death, cancer-specific death, and disease recurrence occurred in 66 patients, 50 patients, and 91 patients. The elevation of serum LDH was associated with several unfavorable parameters, including advanced age, continent cutaneous urinary diversion, increased neutrophil-to-lymphocyte ratio, decreased lymphocyte-to-monocyte ratio. Patients with a higher serum LDH (> 220 U/L) had a worse OS (P < 0.001), CSS (P < 0.001) and DFS (P < 0.001). Multivariate Cox analysis suggested that elevated LDH was an independent predictor for OS (hazard ratio [HR]: 3.113, 95% confidence interval [CI]: 1.524–6.358; P = 0.002), CSS (HR: 4.564, 95% CI: 2.008–10.373; P < 0.001), DFS (HR: 2.051, 95% CI: 1.125–3.739; P = 0.019). Medical history of diabetes, high pT stage, and positive lymph node also were adverse predictors for oncological outcomes of BCa patients in multivariate analysis.ConclusionsPreoperative serum LDH is an independent prognostic biomarker for OS, CSS, and DFS in patients undergoing radical cystectomy for BCa, which can be incorporated into prognostic models.     

Risk factors for allograft failure in United kingdom renal transplant recipients treated with cyclosporine A

BACKGROUND: After the introduction of cyclosporine A (CsA), 2-year graft survival of transplanted kidneys improved from less than 60% to more than 80%, but long-term graft survival and graft half-life have shown less change. This study investigates the impact of a range of demographic and treatment factors on long-term graft survival in renal recipients treated with CsA from all renal transplant centers in the United Kingdom. METHODS: Data were obtained from the Long-Term Efficacy and Safety Surveillance study of renal transplant recipients receiving CsA (Neoral; Novartis, Basel, Switzerland). A total of 1,757 de novo patients with a functioning graft at 1 year were evaluated. The endpoints considered were the need for regular dialysis or death. A stepwise stratified Cox model was used to identify the factors associated with outcome. RESULTS: Seven independent risk factors for allograft failure were identified: older recipient (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.2-2.6), male recipient (HR 1.8, 95% CI 1.2-2.7), younger donor (HR 1.7, 95% CI 1.2-2.5), above average creatinine (HR 1.9, 95% CI 1.3-2.8), chronic allograft nephropathy (HR 7.0, 95% CI 4.7-10.4), diabetic recipient (HR 2.2, 95% CI 1.2-4.1), and neoplasm after transplant (HR 1.7, 95% CI 1.2-2.6). CONCLUSION: Seven independent risk factors were found to influence graft survival. Only two of these can be modified by clinical intervention, elevated serum creatinine at 1 year and the occurrence of chronic allograft nephropathy. To influence these two factors, the optimization of immunosuppressive therapy is essential.     

Incidence and predictors of myocardial infarction after kidney transplantation

The risk and predictors of post-kidney transplantation myocardial infarction (PTMI) are not well described. Registry data collected by the United States Renal Data System were used to investigate retrospectively PTMI among adult first renal allograft recipients who received a transplant in 1995 to 2000 and had Medicare as the primary payer. PTMI events were ascertained from billing and death records, and participants were followed for up to 3 yr after transplant or until the end of observation (December 31, 2000). Extended Cox's hazards analysis was used to identify independent clinical correlates of PTMI (hazard ratio [HR]) and to examine PTMI as an outcomes predictor. Among 35,847 eligible participants, the cumulative incidence of PTMI was 4.3% (95% confidence interval [CI], 4.1 to 4.5%), 5.6% (95% CI, 5.3 to 5.8%), and 11.1% (95% CI, 10.7 to 11.5%) at 6, 12, and 36 mo, respectively. Risk factors for PTMI included older recipient age, pretransplantation comorbidities (diabetes, angina, peripheral vascular disease, and MI), transplantation from older donors and deceased donors, and delayed graft function. Women, blacks, Hispanics, and employed recipients experienced reduced risk. The hazard of PTMI rose after a diagnosis of posttransplantation diabetes (HR, 1.60; 95% CI, 1.35 to 1.88) and markedly increased after graft failure (HR, 2.78; 95% CI, 2.41 to 3.19). In separate analyses, PTMI predicted death-censored graft failure (HR, 1.89; 95% CI, 1.63 to 2.20) and strongly predicted death in a manner that declined with time after PTMI. Risk factors for PTMI include potentially modifiable posttransplantation complications. Because PTMI in turn predicts graft failure and death, reducing the risk for PTMI may improve outcomes after kidney transplantation.     

Effects of serum magnesium level on mortality in maintenance hemodialysis patients

Objective To investigate the effects of serum magnesium level on all-cause mortality and cardiovascular and cerebrovascular diseases mortality in maintenance hemodialysis (MHD) patients. Methods Clinical data of MHD patients in Shaoxing People's Hospital from June 1, 2016 to June 30, 2018 were collected retrospectively. The patients were divided into low magnesium group (serum magnesium≤0.96 mmol/L), medium magnesium group (serum magnesium 0.97-1.07 mmol/L) and high magnesium group (serum magnesium≥1.08 mmol/L) according to the tertile of mean serum magnesium level. The differences of clinical data and laboratory results were compared among the three groups. Kaplan-Meier method was used to draw the survival curves, and log-rank test was used to compare the survival rate differences. Multivariate Cox regression was used to analyze the relationship between serum magnesium and all-cause mortality and cardiovascular and cerebrovascular diseases mortality in MHD patients. Results A total of 332 patients [194 males (58.4%)] were included in this study, with a median age of 63(51, 72) years and a median follow-up time of 36(20, 45) months. Kaplan-Meier survival analysis showed that the all-cause survival rate and cardiovascular and cerebrovascular diseases survival rate in the low magnesium group were lower than those in the medium magnesium group and the high magnesium group (Log-rank χ2=36.286, P＜0.001; Log-rank χ2=20.145, P＜0.001; respectively). After adjusting for multiple confounding factors, the results of multivariate Cox regression analysis suggested that low serum magnesium was an independent risk factor for all-cause death and cardiovascular and cerebrovascular diseases death in MHD patients. The risk of all-cause death and cardiovascular and cerebrovascular diseases death in the low magnesium group were significantly higher than those in the high magnesium group (HR=2.925, 95%CI 1.352-6.330, P=0.006; HR=3.821, 95% CI 1.394-10.473, P=0.009; respectively). Conclusions Hypomagnesemia may be an independent risk factor for all-cause death and cardiovascular and cerebrovascular diseases death in MHD patients. Low serum magnesium level increases the risk of all-cause death and cardiovascular and cerebrovascular diseases in MHD patients.     

CNI withdrawal for post‐transplant lymphoproliferative disorders in kidney transplant is an independent risk factor for graft failure and mortality

Post‐transplantation lymphoproliferative disorders (PTLD) are associated with poor patient and graft survival. The risk of rejection and subsequent graft loss are increased by the reduction of immunosuppression therapy, the cornerstone of PTLD treatment. This multicentre, retrospective, nonrandomized cohort study includes 104 adults who developed PTLD after renal or simultaneous renal/pancreatic transplantation between 1990 and 2007. It examines the effect of calcineurin inhibitor (CNI) withdrawal on long‐term graft and patient survival. At 10 years postonset of PTLD, the Kaplan–Meier graft loss rate was 43.9% and graft loss or death with functioning graft was 64.4%. Cox multivariate analysis determined risk factors of graft loss as PTLD stage greater than I‐II and CNI withdrawal, and for graft loss and mortality, these remained risk factors along with age over 60 years. Type and location of PTLD, year of diagnosis, and chemotherapy regime were not independent risk factors. Multivariate analysis determined CNI withdrawal as the most important risk factor for graft loss (HR = 3.07, CI 95%: 1.04–9.09; P = 0.04) and death (HR: 4.00, CI 95%: 1.77–9.04; P < 0.001). While long‐term stable renal function after definitive CNI withdrawal for PTLD has been reported, this review determined that withdrawal is associated with reduced graft and patient survival.     

Influence of time of rejection on long-term graft survival in renal transplantation

BACKGROUND: The aim of this analysis was to investigate the relationship of acute rejection episodes (ARE) at different times posttransplantation with reversibility of graft dysfunction and long-term graft failure using data from the Collaborative Transplant Study database. METHODS: A total of 28,867 patients receiving their graft between 1995 and 2005 from deceased donors were included in the analysis. The time from renal transplantation to first treated ARE was divided into intervals up to 3 years. Long-term graft survival and half-life rates were calculated and hazard ratios (HR) for failure were computed using multivariate Cox regression analysis. RESULTS: Compared with patients who did not receive rejection treatment during the first posttransplant year, HR for graft survival increased to 1.35 for patients with rejection 0 to 90 days (P<0.001), 2.05 with rejection 91 to 180 days (P<0.001), and 2.74 with rejection 181 to 365 days of posttransplantion (P<0.001). First rejections occurring during the second year were associated with HR 3.35 (P<0.001) and rejections during the third year with HR 3.17 (P<0.001). In addition to the time of rejection, the degree of functional recovery after rejection treatment was found to be important for subsequent graft survival. CONCLUSION: The time point of occurrence and the degree of functional recovery after rejection treatment were found to significantly influence the impact of ARE on long-term graft survival, and we were able to quantify the associated risks.     

Prediction of Fractures and Major Cardiovascular Events in Men Using Serum Osteoprotegerin Levels: The Prospective STRAMBO Study

Fragility fractures and cardiovascular diseases often coincide. However, data on shared risk factors and markers are scarce. Our aim was to assess the independent associations of serum osteoprotegerin (OPG) levels with the risk of fracture and cardiovascular outcomes (acute coronary syndrome, cardiac death) in older men. A cohort of 819 home‐dwelling men aged 60 to 87 years was followed prospectively for 8 years. Serum OPG was measured at baseline by ELISA. Bone mineral density (BMD) at femoral neck and Trabecular Bone Score (TBS) were assessed by DXA. Clinical risk factors and Fracture Risk Assessment Tool (FRAX) were assessed. The incident events (self‐reported peripheral fractures and acute coronary syndrome, cardiac death reported by a proxy) confirmed by a health professional were retained for the statistical analysis. Incident vertebral fractures were assessed on lateral DXA scans after 4 and 8 years. Hazard risk (HR) was assessed using the Cox model. After adjustment for FRAX corrected for femoral neck BMD and TBS, diabetes mellitus, ischemic heart disease, and prior falls, the risk of fracture was twofold higher in the highest versus the lowest OPG quartile (HR 2.35; 95% CI, 1.35 to 4.10). The risk of vertebral and nonvertebral fracture was higher in the highest versus the lowest OPG quartile (OR 2.76 [95% CI, 1.08 to 7.05] and HR 2.46 [95% CI, 1.23 to 4.92]). The risk of major osteoporotic fracture was higher in the fourth versus the first OPG quartile (HR 2.43; 95% CI, 1.16 to 5.10). The risk of cardiovascular outcome (adjusted for confounders) was higher in the highest versus the lowest OPG quartile (HR 3.93; 95% CI, 1.54 to 10.04). The risk of fracture and cardiovascular outcome was higher in the highest OPG quartile versus the lower quartiles combined (HR 2.06 [95% CI, 1.35 to 3.14] and HR 2.98 [95% CI, 1.60 to 5.54], respectively). In conclusion, in older men, higher serum OPG levels represent an independent risk factor for cardiovascular and fracture risk. © 2017 American Society for Bone and Mineral Research.     

Impact of homocysteinemia on long-term renal transplant survival

AIM: We prospectively followed a cohort of 202 renal transplant recipients for 5 years to examine the impact of fasting homocysteinemia on long-term patient and renal allograft survival. METHODS: Cox proportional hazards regression analysis was used to identify independent predictors of all-cause mortality and graft loss. RESULTS: Hyperhomocysteinemia (tHcy >15 micromol/L) was present in 48.7% of the 202 patients, predominantly among men (55.8%) as opposed to women (37.1%). At the end of the follow-up period, 13 (6.4%) patients had died including 10 from cardiovascular disease, and 23 had (11.4%) had lost their grafts. Patient death with a functioning allograft was the most prevalent cause of graft loss (13 recipients). Levels of tHcy were higher among patients who died than among survivors (median 23.9 vs 14.3 micromol/L; P = .005). Median tHcy concentration was also higher among the patients who had lost their allografts than those who did not (median 19.0 vs 14.1 micromol/L; P = .001). In a Cox regression model including gender, serum creatinine concentration, transplant duration, traditional cardiovascular risk factors, and associated conditions, such as past cardiovascular disease, only tHcy concentration (ln) (HR = 5.50; 95% CI, 1.56 to 19.36; P = .008) and age at transplantation (HR = 1.07; 95% CI, 1.02 to 1.13; P = .01) were independent predictors of patient survival. After censoring data for patient death, tHcy concentration was not a risk factor for graft loss. CONCLUSIONS: This prospective study shows that tHcy concentration is a significant predictor of mortality, but not of graft loss, after censoring data for patient death.     

Is mycophenolate mofetil less safe than azathioprine in elderly renal transplant recipients?

BACKGROUND: Mycophenolate mofetil (MMF) is a potent immunosuppressive agent that has been shown to be superior to azathioprine in preventing early acute rejection in the general renal transplant population. However, it is uncertain whether these benefits also apply to older renal transplant recipients, who are known to be more susceptible to infectious complications and have considerably lower rates of rejection and immunological graft loss. METHODS: A retrospective analysis was undertaken of all elderly (> or =55 years old) renal transplant recipients who underwent renal transplantation at the Princess Alexandra Hospital (1994-2000) and received either MMF (n=60) or azathioprine (n=55) in combination with prednisolone and cyclosporin. Data were analyzed on an intention-to-treat basis using a multivariate Cox proportional hazards model. RESULTS: The azathioprine- and MMF-treated groups were well matched at baseline with respect to demographic characteristics, end-stage renal failure causes and transplant characteristics. Compared with the MMF cohort, azathioprine-treated patients experienced a shorter time to first rejection [hazard ratio (HR) 4.47, 95% CI 1.53-13.1, P<0.01]. However, azathioprine-treated patients were also less likely to develop opportunistic infections (HR 0.11, 95% CI 0.03-0.41, P=0.001). No differences were observed between the two groups with respect to hospitalization rates, intensive care admissions, hematological complications, or posttransplant malignancies. Actuarial 2-year survival rates for the azathioprine- and MMF-treated patients were 100 and 87%, respectively (P<0.001). The principal cause of death in the MMF cohort was infection. Using a multivariate Cox regression analysis of patient survival, an adjusted hazard ratio of 0.01 (95% CI 0.001-0.08, P=0.001) was calculated in favor of azathioprine. Overall graft survival also tended to be better in patients receiving azathioprine (HR 0.27, 95% CI 0.06-1.33, P=0.11), CONCLUSIONS: In elderly renal transplant recipients, the combination of MMF, cyclosporin, and prednisolone appears to result in a worse outcome compared with the less potent combination of azathioprine, cyclosporin, and prednisolone. Future prospective studies need to specifically evaluate the risk/benefit ratios of newer, more potent immunosuppressive protocols, such as MMF-based regimens, in this important and sizeable patient subgroup.