Panduranga S. Rao

A comprehensive risk quantification score for deceased donor kidneys: the kidney donor risk index.

Background. We propose a continuous kidney donor risk index (KDRI) for deceased donor kidneys, combining donor and transplant variables to quantify graft failure risk. Methods. By using national data from 1995 to 2005, we analyzed 69,440 first-time, kidney-only, deceased donor adult transplants. Cox regression was used to model the risk of death or graft loss, based on donor and transplant factors, adjusting for recipient factors. The proposed KDRI includes 14 donor and transplant factors, each found to be independently associated with graft failure or death: donor age, race, history of hypertension, history of diabetes, serum creatinine, cerebrovascular cause of death, height, weight, donation after cardiac death, hepatitis C virus status, human leukocyte antigen-B and DR mismatch, cold ischemia time, and double or en bloc transplant. The KDRI reflects the rate of graft failure relative to that of a healthy 40-year-old donor. Results. Transplants of kidneys in the highest KDRI quintile (>1.45) had an adjusted 5-year graft survival of 63%, compared with 82% and 79% in the two lowest KDRI quintiles (<0.79 and 0.79–<0.96, respectively). There is a considerable overlap in the KDRI distribution by expanded and nonexpanded criteria donor classification. Conclusions. The graded impact of KDRI on graft outcome makes it a useful decision-making tool at the time of the deceased donor kidney offer.

Evaluating the survival benefit of kidney retransplantation.

Background. The magnitude of the survival benefit associated with kidney retransplantation has not been well studied. Methods. Using data from the Canadian Organ Replacement Register (CORR), we studied patients (n=3,067) initiating renal replacement therapy during 1981–1998 who had received a transplant and experienced graft failure (GF). Such patients were followed until death, loss to follow-up or the end of the observation period (December 31, 1998). Using Cox regression, we estimated the post-GF covariate-adjusted hazard ratio (HR) for retransplant versus dialysis, and determined whether the contrast differed across patient subgroups. Through nonproportional hazards models, we also examine patterns in the retransplant/dialysis HR with time following retransplant. Results. Overall, retransplantation is associated with a covariate-adjusted 50% reduction in mortality, relative to remaining on dialysis (HR=0.50; P<0.0001). This benefit is most pronounced in the 18- to 59-year age group. Retransplanted patients were at significantly higher risk of death relative to patients on dialysis only during the first month posttransplant (HR=1.66; P=0.047), and experienced significantly reduced mortality thereafter. Conclusions. Following primary graft failure, retransplantation is associated with significantly reduced mortality rates among Canadian end-stage renal disease patients. Further study should be undertaken to assess the applicability of our findings to other patient populations.

The role of donor-recipient relationship in long-term outcomes of living donor renal transplantation.

Background. Graft failure related to acute and chronic rejection remains an important problem in transplantation. An association has been reported between microchimerism and the development of tolerance. Since it has been established that cells of fetal origin can be found in maternal tissues long after parturition, and cells of maternal origin may persist for years in offspring, we hypothesized that this fetal-maternal microchimerism may confer tolerance and thus less graft loss for kidneys transplanted between mothers and their offspring. Methods. We used data from the Scientific Registry of Transplant Recipients to compare death-censored graft survival among recipients of living-related renal transplants sharing at least one human leukocyte antigen (HLA) haplotype with their donor. A total of 23,064 such transplants were reported from 1995 to 2004. A Cox proportional hazards model was constructed to compare death-censored graft survival among the following donor-recipient pairings: child-to-mother, child-to-father, mother-to-child, father-to-child, 1-haplotype matched siblings, and HLA-identical siblings. Results. HLA-identical sibling recipients had the best survival, but results for the child-to-father group were not significantly worse (hazard ratio=1.07, P=0.47). Mother-to-child transplants had the poorest graft survival (hazard ratio=2.61, P<0.0001). We found no evidence of tolerance to kidneys transplanted between mothers and offspring. Conclusions. Our analysis of 1-haplotype matched living-related renal transplants argues against tolerance to organs based on fetal-maternal microchimerism. Mechanistic studies examining the relationship between chimerism and immune sensitization would be useful to explore our results, and may contribute to a better understanding of tolerance.

Evaluation of characteristics, associations and clinical course of isolated spontaneous renal artery dissection

BACKGROUND Spontaneous renal artery dissection (SRAD) is a rare entity of unknown etiology. We aimed to study the clinical course and outcomes and compare the characteristics of patients with SRAD with those of the general population. METHODS All cases of isolated renal artery dissection diagnosed at the University of Michigan Hospitals between January 2000 and July 2012 were identified by the ICD-9 code. Cases were matched by age, gender and race with individuals from the 2009-2010 National Health and Nutrition Examination Survey (NHANES). Characteristics and awareness of comorbid conditions were compared. Information about the clinical course after diagnosis was retrieved from the case group to ascertain their outcomes. RESULTS Overall, 17 patients with SRAD with a mean age of 38.6 years (SD = 8.3) were identified. Eleven patients were male and 14 were white. The most common presenting symptom was excruciating sudden-onset flank pain ipsilateral to the site of dissection. Fibromuscular dysplasia, Ehlers-Danlos and polyarteritis nodosa were present in 4, 4 and 1 patients, respectively. After adjusting in a multivariable model, the case group was more likely to report history of hypertension, cancer and connective tissue disorders (P < 0.001), and less likely to have obesity (BMI ≥30 kg/m(2)) compared with the general population. Supportive medical treatment, endovascular intervention and surgery were required in 8, 5 and 4 cases, respectively. After discharge from the hospital, hypertension was adequately controlled in all the patients but one. CONCLUSION SRAD may be part of a syndrome having multi-organ involvement. With appropriate medical or surgical management, long-term clinical outcome appears favorable.

The Effect of Different Dialysate Magnesium Concentrations on QTc Dispersion in Hemodialysis Patients

Background: Electrolyte changes during dialysis affect corrected QT (QTc) and QTc dispersion (QTcd), a surrogate marker of arrhythmogenicity. The impact of magnesium on QTcd is not clear. Methods: Twenty-two stable patients on maintenance hemodialysis were enrolled in this study. Each underwent two consecutive hemodialysis sessions at least 2 days apart, the first against normal magnesium dialysate (with magnesium at 1.8 mg/dL) followed by a low magnesium dialysate (with magnesium at 0.6 mg/dL). Pre- and post-dialysis weights, blood pressure, electrolytes, and 12-lead surface EKG were recorded. The QT interval and the QTcd were calculated before and after dialysis in both sessions. Results: Of 22 patients, 16 were female. The mean age ± SD was 53.7 ± 18.0 years. The mean change of QTcd (pre- vs. post-dialysis) was 9.5 ms (p = 0.120) and 9.3 ms (p = 0.145) in low and normal magnesium groups, respectively. Using univariate analysis, there was a statistically significant decrease in the mean blood pressure, weight, potassium, magnesium, and QTc interval post-dialysis (compared to pre-dialysis) in both groups (p ≤ 0.049). Post-dialysis concentrations of sodium and calcium were unchanged (compared to pre-dialysis) but bicarbonate increased with both dialysate groups (p < 0.001). The mean change of QTcd was not significant pre- versus post-dialysis by univariate analysis in either group. Multiple linear regression analysis adjusting for pertinent factors did not change the results in either of the two groups. Conclusion: Using a low magnesium dialysate bath in hemodynamically stable hemodialysis patients without preexisting advanced cardiac disease does not significantly impact QTcd.

Quality of life of older patients undergoing renal transplantation: finding the right immunosuppressive treatment.

Kidney transplantation is currently the best treatment for end-stage renal disease, both in terms of mortality benefit and quality of life (QOL). Elderly patients are a rapidly growing subset of the kidney transplant waiting list. While it is clear that elderly individuals have a mortality benefit from kidney transplant, it is less clear how to make sure these individuals benefit from optimal QOL following transplant. Several studies demonstrate superiority of some immunosuppressive regimens over others in the QOL domain. Tacrolimus has been shown to be associated with better QOL than cyclosporine (ciclosporin), as has corticosteroid-free immunosuppressive regimens. Similarly, patients on drug regimens, which tend to lessen the side effects, report better QOL. However, these studies are observational or cross-sectional and not focused exclusively on the elderly patient. More studies are needed to determine optimal immunosuppression regimens for elderly individuals. Additionally, further studies on determinants of QOL in elderly kidney transplant recipients are also needed.

Does allograft failure impact infection risk on peritoneal dialysis: a North American Pediatric Renal Trials and Collaborative Studies Study.

BACKGROUND AND OBJECTIVES Several adult studies report that patients returning to peritoneal dialysis after allograft failure have increased infection-related morbidity. The impact of allograft failure on infection risk in children is uncertain. We compared peritonitis-free survival between pediatric peritoneal dialysis patients with prior allograft failure and those who were transplant naive. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We studied patients, 2-21 years of age, who initiated peritoneal dialysis from January 1, 1992, to December 31, 2007, in the North American Pediatric Renal Trials and Collaborative Studies registry. Demographic characteristics were compared between transplant naive and allograft failure patients using a chi-squared statistic. Peritonitis-free survival was compared between the two groups using Kaplan-Meier estimates. A Cox regression analysis was performed to adjust for covariates, which impact risk of peritonitis. RESULTS Of 2829 patients on peritoneal dialysis, 445 had a prior history of allograft failure and 2384 did not (transplant naive). Demographic characteristics including age at dialysis initiation, race, primary renal disease, and era of dialysis initiation were significantly different between the two groups. Peritonitis-free survival was poorer for the allograft failure group. After covariate adjustment, allograft failure showed borderline significance as a factor predictive of peritonitis. CONCLUSIONS Children initiating peritoneal dialysis after allograft failure may experience a slightly higher infection risk.

Long-term follow-up of kidney transplant recipients: comparison of hospitalization rates to the general population

BackgroundKidney transplant recipients are recognized as a vulnerable population that is at increased risk of adverse health outcomes. However, there have been few studies that have compared hospital-related morbidity of these patients to the general population, and how this differs with respect to time since transplantation. Such analyses are useful in estimating the health burden in this patient population.MethodsWe assembled a population-based Canadian cohort (excluding Quebec) of 6,116 kidney transplant recipients who underwent transplantation between 1 April 2001 and 31 December 2008. Record linkage was used to identify hospital discharge records of these patients from 1 April 2001 through 31 March 2009. Hospital discharges were tabulated across the main disease chapters of the ICD10, and person-years of follow-up were calculated across age and sex strata. Comparisons of hospital-related morbidity to the general population were made by using a standardized hospitalization ratio (SHR). For those who underwent transplantation in 2004, stratified analyses were performed to explore differences in hospital discharge rates both before and after transplantation.ResultsAfter excluding hospitalizations due to complications from transplantation, when compared to the general population, transplant recipients were approximately 6.4 (95% CI: 6.3, 6.5) times more likely to be hospitalized during follow-up. The SHRs were highest during the time periods proximate to transplantation, and then decreased to approximately a five-fold increase from 3 years post transplantation onwards. The largest disease-specific excesses were observed with infectious diseases and diseases of the endocrine system. Among those who underwent transplantation in 2004, the SHR decreased from 11.2 to 5.0 in the periods before and after surgery, respectively.ConclusionsOur results indicate that, even more than 5-years post transplantation, there remains a more than six-fold difference in hospitalization rates relative to the general population. Additional work is needed to confirm these findings, and to develop strategies to reduce long-term morbidity in this patient population.

Does allograft failure impact school attendance in children? A NAPRTCS study

BACKGROUND Studies show that adult dialysis patients with allograft failure have increased mortality and morbidity on dialysis compared to transplant naïve patients. We previously showed comparable mortality risk in pediatric dialysis patients after allograft failure compared to transplant naïve patients; the impact on morbidity is less clear. Specifically, the effect of allograft failure on school attendance in pediatric patients has not previously been studied. METHODS Using the North American Pediatric Renal Trials and Collaborative Studies database, we compared school attendance between transplant naïve and allograft failure patients from 1 January 1992 to 31 December 2007. School attendance was compared between the two groups at 6 and 12 months after dialysis initiation using a chi-square test. Factors which can potentially impact on school attendance data were evaluated using a multivariate logistic regression analysis. RESULTS There were 2783 patients who had a follow-up at least 6 months after dialysis initiation and were capable of attending school during the study period. Patients were categorized by transplant history: previous allograft failure (n=576) and transplant naïve (n=2207). At 6 months, full-time school attendance was 67.2% in the allograft failure group and 72.3% in the transplant naïve group (P=0.0164). At 12 months, attendance was 68.6% in the allograft failure group and 72.5% in the transplant naïve group (P=0.103). After covariate adjustment, transplant failure did not impact school attendance at either 6 or 12 months follow-up [hazard ratio (HR) 1.12, confidence interval (CI) 0.91-1.39; HR 0.99, CI 0.78-1.27, respectively]. CONCLUSIONS Children with failed allografts who return to dialysis have comparable school attendance compared to their transplant naïve dialysis counterparts. These results suggest that transplant failure is not an adverse prognostic factor for quality of life as measured by full-time school attendance.

Health Behaviors in Younger and Older Adults With CKD: Results From the CRIC Study

Introduction A cornerstone of kidney disease management is participation in guideline-recommended health behaviors. However, the relationship of these health behaviors with outcomes, and the identification of barriers to health behavior engagement, have not been described among younger and older adults with chronic kidney disease. Methods Data from a cohort study of 5499 individuals with chronic kidney disease was used to identify health behavior patterns with latent class analysis stratified by age <65 and ≥65 years. Cox models, stratified by diabetes, assessed the association of health behavior patterns with chronic kidney disease (CKD) progression, atherosclerotic events, and death. Logistic regression was used to assess for barriers to health behavior engagement. Results Three health behavior patterns were identified: 1 “healthy” pattern, and 2 “less healthy” patterns comprising 1 pattern with more obesity and sedentary activity and 1 with more smoking and less obesity. Less healthy patterns were associated with an increased hazard of poor outcomes. Among participants <65 years of age, the less healthy patterns (vs. healthy pattern) was associated with an increased hazard of death in diabetic individuals (hazard ratio [HR] = 2.17, 95% confidence interval [CI] = 1.09–4.29; and HR = 2.50, 95% CI = 1.39–4.50) and cardiovascular events among nondiabetic individuals (HR = 1.49, 95% CI = 1.04–2.43; and HR = 2.97, 95% CI = 1.49–5.90). Individuals with the more obese/sedentary pattern had an increased risk of CKD progression in those who were diabetic (HR = 1.34, 95% CI = 1.13–1.59). Among older adults, the less healthy patterns were associated with increased risk of death (HR = 2.97, 95% CI = 1.43–6.19; and HR = 3.47, 95% CI = 1.48–8.11) in those who were nondiabetic. Potential barriers to recommended health behaviors include lower health literacy and self-efficacy. Conclusion Identifying health behavior patterns and barriers may help target high-risk groups for strategies to increase participation in health behaviors.