Early Steroid Withdrawal Compared With Standard Immunosuppression in Kidney Transplantation - Interim Analysis of the Amsterdam-Leiden-Groningen Randomized Controlled Trial

Nephrolog

Towards a standardised informed consent procedure for live donor nephrectomy: The PRINCE (Process of Informed Consent Evaluation) project-study protocol for a nationwide prospective cohort study

Introduction: Informed consent is mandatory for all (surgical) procedures, but it is even more important when it comes to living kidney donors undergoing surgery for the benefit of others. Donor education, leading to informed consent, needs to be carried out according to certain standards. Informed consent procedures for live donor nephrectomy vary per centre, and even per individual healthcare professional. The basis for a standardised, uniform surgical informed consent procedure for live donor nephrectomy can be created by assessing what information donors need to hear to prepare them for the operation and convalescence. Methods and analysis: The PRINCE (Process of In formed Consent Evaluation) project is a prospective, multicentre cohort study, to be carried out in all eight Dutch kidney transplant centres. Donor knowledge of the procedure and postoperative course will be evaluated by means of pop quizzes. A baseline cohort (prior to receiving any information from a member of the transplant team in one of the transplant centres) will be compared with a control group, the members of which receive the pop quiz on the day of admission for donor nephrectomy. Donor satisfaction will be evaluated for all donors who completed the admission pop-quiz. The primary end point is donor knowledge. In addition, those elements that have to be included in the standardized format informed consent procedure will be identified. Secondary end points are donor satisfaction, current informed consent practices in the different centres (eg, how many visits, which personnel, what kind of information is di

Genetic loci influencing kidney function and chronic kidney disease

Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10 10 to 10 15). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 × 10 5 and P = 3.6 × 10 4, respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease

Predictive performance of renal function equations in renal transplant recipients: An analysis of patient factors in bias

Creatinine-based equations are available to estimate GFR. After renal transplantation body composition usually changes, thus specific validation is required for transplant recipients. Nine equations were compared with iothalamate glomerular filtration rate (GFR) at 1 year after transplantation in 798 recipients. Equations were analyzed for precision, bias and accuracy. Sources of bias were analyzed by univariate and multivariate analysis, with body mass index (BMI), age and sex as independent variables and bias as dependent variable. Four hundred and seventy-eight patients were studied to assess whether the equations can be used to monitor renal function over time. Predictive performance was modest for all equations. MDRD and Jelliffe 2 were the best predictors of GFR. Bias was significantly related to BMI, age and gender in most equations. Multivariate analysis confirmed their independent contribution to the bias of MDRD, Jelliffe 2 and most other equations. Over time, bias was relatively stable at group level, but predictive performance in individuals was modest. The predictive performance of renal function equations is modest in renal transplants, which hampers their use for accurate assessment of renal function in the individual. The role of patient factors in the systematic error suggests that development of better equations should be feasible by better incorporation of these factor

Body mass index is associated with altered renal hemodynamics in non-obese healthy subjects

Weight excess is associated with increased renal risk. Data in overt obesity suggest a role for altered renal hemodynamics. Whether body mass index (BMI) is also relevant to renal function in non-obese subjects is unknown. We studied the relation between BMI and renal hemodynamics in 102 healthy, non-obese (BMI <30 kg/m2) subjects [59 males, 43 females, mean age 39 (18-69) years] in a post-hoc analysis of subjects evaluated as prospective kidney donors or as healthy volunteers in renal hemodynamic studies. Mean (+/-SD) BMI was 24.0 +/- 2.8 kg/m2, mean arterial pressure (MAP) 93 +/- 11 mm Hg, glomerular filtration rate (GFR, iothalamate clearance) 111 +/- 19 mL/min/1.73 m2, effective renal plasma flow (ERPF, hippuran clearance) 458 +/- 108 mL/min/1.73 m2, FF (GFR/ERPF) 0.25 +/- 0.04. On univariate analysis, BMI correlated negatively with ERPF/1.73 m2 body surface area (BSA) (r=-0.46; P <0.001), GFR/1.73 m2 BSA (r=-0.24, P= 0.013) and positively with FF (r= 0.45, P <0.001), and age (r= 0.47, P <0.001). On multivariate analysis both BMI and age were independent predictors of ERPF/1.73 m2 BSA (negative) and FF (positive, all P <0.05). Age was the only predictor of GFR/1.73 m2 BSA (negative). Analyzed for renal function indexed for height (h), BMI correlated negatively with ERPF/h (r=-0.274, P= 0.005), but not with GFR/h (r= 0.13, P= 0.899). On multivariate analysis both BMI (positive) and age (negative) were independent predictors for GFR/h (both P <0.001). Age was the only predictor for ERPF/h (negative). Predictors for FF (BMI and age, both positive) were by definition unaltered. The impact of BMI on renal function is not limited to overt obesity, as in subjects with BMI <30 kg/m2 a higher BMI is associated with higher FF, that is, a higher GFR relative to ERPF. This suggests an altered afferent/efferent balance and higher glomerular pressure (i.e., a potentially unfavorable renal hemodynamic profile) that may confer enhanced renal susceptibility when other factors, such as hypertension or diabetes are superimpose

Evaluating the Effect of CYP3A4 and CYP3A5 Polymorphisms on Cyclosporine, Everolimus and Tacrolimus Pharmacokinetics in Renal Transplantation Patients

Nephrolog

Alcohol consumption, new onset of diabetes after transplantation, and all-cause mortality in renal transplant recipients

Background. Renal transplant recipients (RTR) are often advised to refrain from alcohol because of possible interaction with their immunosuppressive medication. Although moderate alcohol consumption is associated with reduced risk of diabetes and mortality in the general population, this is unknown for RTR. Therefore, we investigated the association of alcohol consumption with new onset of diabetes after transplantation (NODAT), mortality, and graft failure in RTR. Method. RTR were investigated between 2001 and 2003. Alcohol consumption was assessed by self-report. Mortality and graft failure was recorded until May 2009. Results. Six hundred RTR were studied (age 51 +/- 12 years, 55% men). Of these RTR, 48% were abstainers, 38% had light alcohol intake, 13% had moderate intake, and 1% were heavy consumers. Moderate alcohol consumption was associated with a lower risk of developing NODAT over the follow-up period than was abstention (OR=0.36 [0.2-0.6], P=<0.001). During follow-up for 7.0 years [6.2-7.5 years], 133 recipients died. In Cox regression analyses, moderate alcohol consumption was associated with lower mortality period than was abstention (hazard ratio=0.40 [0.2-0.8], P=0.009). Adjustment for confounders, including age and smoking, did not materially change this association. No association was found between alcohol consumption and graft failure. Conclusions. Moderate alcohol consumption is associated with low prevalence of NODAT and reduced risk for mortality in RTR, in line with findings in the general population. These findings refute the common advice to refrain from alcohol in RTR

Alcohol consumption, new onset of diabetes after transplantation, and all-cause mortality in renal transplant recipients

Background. Renal transplant recipients (RTR) are often advised to refrain from alcohol because of possible interaction with their immunosuppressive medication. Although moderate alcohol consumption is associated with reduced risk of diabetes and mortality in the general population, this is unknown for RTR. Therefore, we investigated the association of alcohol consumption with new onset of diabetes after transplantation (NODAT), mortality, and graft failure in RTR. Method. RTR were investigated between 2001 and 2003. Alcohol consumption was assessed by self-report. Mortality and graft failure was recorded until May 2009. Results. Six hundred RTR were studied (age 51 +/- 12 years, 55% men). Of these RTR, 48% were abstainers, 38% had light alcohol intake, 13% had moderate intake, and 1% were heavy consumers. Moderate alcohol consumption was associated with a lower risk of developing NODAT over the follow-up period than was abstention (OR=0.36 [0.2-0.6], P=<0.001). During follow-up for 7.0 years [6.2-7.5 years], 133 recipients died. In Cox regression analyses, moderate alcohol consumption was associated with lower mortality period than was abstention (hazard ratio=0.40 [0.2-0.8], P=0.009). Adjustment for confounders, including age and smoking, did not materially change this association. No association was found between alcohol consumption and graft failure. Conclusions. Moderate alcohol consumption is associated with low prevalence of NODAT and reduced risk for mortality in RTR, in line with findings in the general population. These findings refute the common advice to refrain from alcohol in RTR

Impact of depression on long-term outcome after renal transplantation: a prospective cohort study

Background. Renal transplantation is the treatment of choice for end stage renal disease. Although there is more depression in wait-listed versus transplant patients, depression persists after transplantation. We investigated the determinants of depression in renal transplantation recipients (RTRs) and the association with cardiovascular (CV) and all-cause-mortality and graft failure. Methods. RTR were investigated between 2001 and 2003. Depression was assessed using the Depression Subscale of the Symptom Checklist (SCL-90). Mortality and graft failure were recorded until May 2009. Results. A total of 527 RTR (age, 51 +/- 12 years; 55% men) were studied; 31% of the RTR were indicated with depression. Independent variables associated with depression were medically unfit for work, proteinuria, lower physical activity level, and longer dialysis duration. During follow-up for 7.0 (6.2-7.5) years, 114 RTR (59 CV) died. In Cox regression analyses, depression was strongly associated with increased risk for CV (HR=2.12 [1.27-3.53], P=0.004) and all-cause mortality (HR=1.96 [1.36-2.84], P<0.001). Adjustments for confounders did not materially change these associations. The association with graft failure (HR=1.77 [1.01-3.10]. P=0.047) disappeared after adjustment for kidney function (P=0.6). Conclusions. Although our study has several limitations, including the lack of pretransplant depression status, we identified medically unfit for work, proteinuria, lower physical activity level, and longer dialysis duration as independent variables associated with depression. We furthermore found that depression is associated with CV and all-cause mortality in RTR