Harold I. Feldman

Mortality and Cardiovascular Disease Among Older Live Kidney Donors

Over the past two decades, live kidney donation by older individuals (≥55 years) has become more common. Given the strong associations of older age with cardiovascular disease (CVD), nephrectomy could make older donors vulnerable to death and cardiovascular events. We performed a cohort study among older live kidney donors who were matched to healthy older individuals in the Health and Retirement Study. The primary outcome was mortality ascertained through national death registries. Secondary outcomes ascertained among pairs with Medicare coverage included death or CVD ascertained through Medicare claims data. During the period from 1996 to 2006, there were 5717 older donors in the United States. We matched 3368 donors 1:1 to older healthy nondonors. Among donors and matched pairs, the mean age was 59 years; 41% were male and 7% were black race. In median follow‐up of 7.8 years, mortality was not different between donors and matched pairs (pu2009=u20090.21). Among donors with Medicare, the combined outcome of death/CVD (pu2009=u20090.70) was also not different between donors and nondonors. In summary, carefully selected older kidney donors do not face a higher risk of death or CVD. These findings should be provided to older individuals considering live kidney donation.

Association of dialyzer reuse with hospitalization and survival rates among U.S. hemodialysis patients: do comorbidities matter?

The objective of this study was to determine whether the associations between reuse of hemodialyzers and higher rates of death and hospitalization persist after adjustment for comorbidity. This was a nonconcurrent cohort study of survival and hospitalization rates among 1491 U.S. chronic hemodialysis patients beginning treatment in 1986 and 1987. The impact of dialyzer reuse was compared across three survival models: an unadjusted model, a base model adjusted only for demographics and renal diagnosis, and an augmented model additionally adjusted for comorbidities. We found that reuse of dialyzers was associated with a similarly higher rate of death in analyses unadjusted for confounders (relative risk [RR] 1.25, 95% confidence interval [CI] 0.97-1.61), adjusted for demographics and renal diagnosis (RR 1.16, 95% CI 0.96-1.41), and analyses additionally adjusted for comorbidities (RR = 1.25, CI, 1.03, 1.52). Reusing dialyzers was also associated with a greater rate of hospitalization that was stable regardless of adjustment procedures. We conclude that higher rates of death and hospitalization associated with dialyzer reuse persist regardless of adjustment for demographic characteristics or baseline comorbidities. These findings amplify concerns that there exists elevated morbidity among hemodialysis patients treated in facilities that reuse hemodialyzers. Although the association we observed was not confounded by comorbidity, a cause-and-effect relationship between dialyzer reuse and morbidity could not be proved because of the inability to control for aspects of care other than dialyzer reuse.

Functional Status, Time to Transplantation, and Survival Benefit of Kidney Transplantation Among Wait-Listed Candidates

BACKGROUNDnIn the context of an aging end-stage renal disease population with multiple comorbid conditions, transplantation professionals face challenges in evaluating the global health of patients awaiting kidney transplantation. Functional status might be useful for identifying which patients will derive a survival benefit from transplantation versus dialysis.nnnSTUDY DESIGNnRetrospective cohort study of wait-listed patients using data for functional status from a national dialysis provider linked to United Network for Organ Sharing registry data.nnnSETTING & PARTICIPANTSnAdult kidney transplantation candidates added to the waiting list between 2000 andxa02006.nnnPREDICTORnPhysical Functioning scale of the Medical Outcomes Study 36-Item Short Form Health Survey, analyzed as a time-varying covariate.nnnOUTCOMESnKidney transplantation; survival benefit of transplantation versus remaining wait-listed.nnnMEASUREMENTSnWe used multivariable Cox regression to assess the association between physical function with study outcomes. In survival benefit analyses, transplantation status was modeled as a time-varying covariate.nnnRESULTSnThe cohort comprised 19,242 kidney transplantation candidates (median age, 51 years; 36% black race) receiving maintenance dialysis. Candidates in the lowest baseline Physical Functioning score quartile were more likely to be inactivated (adjusted HR vs highest quartile, 1.30; 95% CI, 1.21-1.39) and less likely to undergo transplantation (adjusted HR vs highest quartile, 0.64; 95% CI, 0.61-0.68). After transplantation, worse Physical Functioning score was associated with shorter 3-year survival (84% vs 92% for the lowest vs highest function quartiles). However, compared to dialysis, transplantation was associated with a statistically significant survival benefit by 9 months for patients in every function quartile.nnnLIMITATIONSnFunctional status is self-reported.nnnCONCLUSIONSnEven patients with low function appear to live longer with kidney transplantation versus dialysis. For wait-listed patients, global health measures such as functional status may be more useful in counseling patients about the probability of transplantation than in identifying who will derive a survival benefit from it.

Functional status and survival after kidney transplantation

Background Older patients constitute a growing proportion of U.S. kidney transplant recipients and often have a high burden of comorbidities. A summary measure of health such as functional status might enable transplant professionals to better evaluate and counsel these patients about their prognosis after transplant. Methods We linked United Network for Organ Sharing registry data about posttransplantation survival with pretransplantation functional status data (physical function [PF] scale of the Medical Outcomes Study Short Form-36) among individuals undergoing kidney transplant from June 1, 2000 to May 31, 2006. We examined the relationship between survival and functional status with multivariable Cox regression, adjusted for age. Using logistic regression models for 3-year survival, we also estimated the reduction in deaths in the hypothetical scenario that recipients with poor functional status in this cohort experienced modest improvements in function. Results The cohort comprised 10,875 kidney transplant recipients with a mean age of 50 years; 14% were ≥65. Differences in 3-year mortality between highest and lowest PF groups ranged from 3% among recipients <35 years to 14% among recipients ≥65 years. In multivariable Cox regression, worse PF was associated with higher mortality (hazard ratio, 1.66 for lowest vs. highest PF quartiles; P<0.001). Interactions between PF and age were nonsignificant. We estimated that 11% fewer deaths would occur if kidney transplant recipients with the lowest functional status experienced modest improvements in function. Conclusions Across a wide age range, functional status was an independent predictor of posttransplantation survival. Functional status assessment may be a useful tool with which to counsel patients about posttransplantation outcomes.

Association of Dialyzer Reuse and Hospitalization Rates among Hemodialysis Patients in the US

Objectives: To determine if reuse of hemodialyzers is associated with higher rates of hospitalization and their resulting costs among end-stage renal disease (ESRD) patients. Methods: Noncurrent cohort study of hospitalization rates among 27,264 ESRD patients beginning hemodialysis in the United States in 1986 and 1987. Results: Dialysis in free-standing facilities reprocessing dialyzers was associated with a greater rate of hospitalization than in facilities not reprocessing (relative rate (RR) = 1.08, 95% confidence interval (CI), 1.02–1.14). This higher rate of hospitalization was observed with dialyzer reuse using peracetic/acetic acids (RR = 1.11, CI 1.04–1.18) and formaldehyde (RR = 1.07, CI 1.00–1.14), but not glutaraldehyde (p = 0.97). There was no difference among hospitalization rates in hospital-based facilities reprocessing dialyzers with any sterilant and those not reprocessing. Hospitalization for causes other than vascular access morbidity in free-standing facilities reusing dialyzers with formaldehyde was not different from hospitalization in facilities not reusing. However, reuse with peracetic/acetic acids was associated with higher rates of hospitalization than formaldehyde (RR = 1.08, CI 1.03–1.15). Conclusions: Dialysis in free-standing facilities reprocessing dialyzers with peracetic/acetic acids or formaldehyde was associated with greater hospitalization than dialysis without dialyzer reprocessing. This greater hospitalization accounts for a large increment in inpatient stays in the USA. These findings raise important concerns about potentially avoidable morbidity among hemodialysis patients.

Acid Load and Phosphorus Homeostasis in CKD

BACKGROUNDnThe kidneys maintain acid-base homeostasis through excretion of acid as either ammonium or as titratable acids that primarily use phosphate as a buffer. In chronic kidney disease (CKD), ammoniagenesis is impaired, promoting metabolic acidosis. Metabolic acidosis stimulates phosphaturic hormones, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) inxa0vitro, possibly to increase urine titratable acid buffers, but this has not been confirmed in humans. We hypothesized that higher acid load and acidosis would associate with altered phosphorus homeostasis, including higher urinary phosphorus excretion and serum PTH and FGF-23.nnnSTUDY DESIGNnCross-sectional.nnnSETTING & PARTICIPANTSn980 participants with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study.nnnPREDICTORSnNet acid excretion as measured in 24-hour urine, potential renal acid load (PRAL) estimatedxa0from food frequency questionnaire responses, and serum bicarbonate concentrationxa0< 22 mEq/L.nnnOUTCOME & MEASUREMENTSn24-hour urine phosphorus and calcium excretion and serum phosphorus, FGF-23, and PTH concentrations.nnnRESULTSnUsing linear and log-linear regression adjusted for demographics, kidney function, comorbid conditions, body mass index, diuretic use, and 24-hour urine creatinine excretion, we found that 24-hour urine phosphorus excretion was higher at higher net acid excretion, higher PRAL, and lower serum bicarbonate concentration (each P<0.05). Serum phosphorus concentration was also higherxa0with higher net acid excretion and lower serum bicarbonate concentration (each P=0.001). Only higher net acid excretion associated with higher 24-hour urine calcium excretion (P<0.001). Neither net acid excretion nor PRAL was associated with FGF-23 or PTH concentrations. PTH, but notxa0FGF-23, concentration (P=0.2) was 26% (95% CI, 13%-40%) higher in participants with a serumxa0bicarbonate concentrationxa0<22 versusxa0≥22 mEq/L (P<0.001). Primary results were similar if stratified by estimated glomerular filtration rate categories or adjusted for iothalamate glomerular filtration rate (n=359), total energy intake, dietary phosphorus, or urine urea nitrogen excretion, when available.nnnLIMITATIONSnPossible residual confounding by kidney function or nutrition; urine phosphorus excretion was included in calculation of the titratable acid component of net acid excretion.nnnCONCLUSIONSnIn CKD, higher acid load and acidosis associate independently with increased circulating phosphorus concentration and augmented phosphaturia, but not consistently with FGF-23 or PTH concentrations. This may be an adaptation that increases titratable acid excretion and thus helps maintain acid-base homeostasis in CKD. Understanding whether administration of base can lower phosphorus concentrations requires testing in interventional trials.

A Pilot Randomized Trial of Financial Incentives or Coaching to Lower Serum Phosphorus in Dialysis Patients

OBJECTIVEnAmong chronic hemodialysis patients, hyperphosphatemia is common and associated with mortality. Behavioral economics and complementary behavior-change theories may offer valuable approaches to achieving phosphorus (PO4) control. The aim was to determine feasibility of implementing financial incentives and structured coaching to improve PO4 in the hemodialysis setting.nnnDESIGN AND METHODSnThis pilot randomized controlled trial was conducted in 3 urban dialysis units for 10xa0weeks among 36 adults with elevated serum PO4 (median >5.5xa0mg/dL over 3xa0months).nnnINTERVENTIONSnTwelve participants each were randomized to: (1) financial incentives for lowering PO4, (2) coaching about dietary and medication adherence, or (3) usual care. PO4 was measured during routine clinic operations. Each incentives arm participant received the equivalent of

Measures of Global Health Status on Dialysis Signal Early Rehospitalization Risk after Kidney Transplantation

1.50/day if the PO4 was ≤5.5xa0mg/dL or >5.5xa0mg/dL but decreased ≥0.5xa0mg/dL since the prior measurement. The coach was instructed to contact coaching arm participants at least 3 times per week.nnnMAIN OUTCOME MEASURESnThe outcome measures included: (1) enrollment rate, (2) dropout rate, and (3) change in PO4 from beginning to end of 10-week intervention period.nnnRESULTSnOf 66 eligible patients, 36 (55%) enrolled. Median age was 53xa0years, 83% were black race, and 78% were male. Median baseline PO4 was 6.0 (interquartile range 5.6, 7.5). Using stratified generalized estimation equation analyses, the monthly decline in PO4 was -0.32xa0mg/dL (95% CI -0.60, -0.04) in the incentives arm, -0.40xa0mg/dL (-0.60, -0.20) in the coaching arm, and -0.24xa0mg/dL (-0.60, 0.08) in the usual care arm. No patients dropped out. All intervention arm participants expressed interest in receiving similar support in the future.nnnCONCLUSIONSnThis pilot trial demonstrated good feasibility in enrollment and implementation of novel behavioral health strategies to reduce PO4 in dialysis patients.

Effect of dialyzer reuse on survival of patients treated with hemodialysis.

Background Early rehospitalization (<30 days) after discharge from kidney transplantation (KT) is associated with poor outcomes. We explored summary metrics of pre-transplant health status that may improve the identification of KT recipients at risk for early rehospitalization and mortality after transplant. Materials and Methods We performed a retrospective cohort study of 8,870 adult (≥ 18 years) patients on hemodialysis who received KT between 2000 and 2010 at United States transplant centers. We linked Medicare data to United Network for Organ Sharing data and data from a national dialysis provider to examine pre-KT (1) Elixhauser Comorbidity Index, (2) physical function (PF) measured by the Short Form 36 Health Survey, and (3) the number of hospitalizations during the 12 months before KT as potential predictors of early rehospitalization after KT. We also explored whether these metrics are confounders of the known association between early rehospitalization and post-transplant mortality. Results The median age was 52 years (interquartile range [IQR] 41, 60) and 63% were male. 29% were rehospitalized in <30 days, and 20% died during a median follow-up time of five years (IQR 3.6–6.5). In a multivariable logistic model, kidney recipients with more pre-KT Elixhauser comorbidities (adjusted odds ratio [aOR] 1.09 per comorbidity, 95% Confidence Interval [CI] 1.07–1.11), the poorest pre-KT PF (aOR 1.24, 95% CI 1.08–1.43), or >1 pre-KT hospitalizations (aOR 1.32, 95% CI 1.17–1.49) were more likely to be rehospitalized. All three health status metrics and early rehospitalization were independently associated with post-KT mortality in a multivariable Cox model (adjusted hazard ratio for rehospitalization: 1.41, 95% CI 1.28–1.56) Conclusions Pre-transplant metrics of health status, measured by dialysis providers or administrative data, are independently associated with early rehospitalization and mortality risk after KT. Transplant providers may consider utilizing metrics of pre-KT global health status as early signals of vulnerability when transitioning care after KT.