Faculty Bibliography

BACKGROUND:Patients undergoing hemodialysis are at high risk of falls, with subsequent complications including fractures, loss of independence, hospitalization, and institutionalization. Factors associated with falls are poorly understood in this population. We hypothesized that insights derived from studies of the elderly might apply to adults of all ages undergoing hemodialysis; we focused on frailty, a phenotype of physiological decline strongly associated with falls in the elderly. METHODS:In this prospective, longitudinal study of 95 patients undergoing hemodialysis (1/2009-3/2010), the association of frailty with future falls was explored using adjusted Poisson regression. Frailty was classified using the criteria established by Fried et al., as a combination of five components: shrinking, weakness, exhaustion, low activity, and slowed walking speed. RESULTS:Over a median 6.7-month period of longitudinal follow-up, 28.3% of study participants (25.9% of those under 65, 29.3% of those 65 and older) experienced a fall. After adjusting for age, sex, race, comorbidity, disability, number of medications, marital status, and education, frailty independently predicted a 3.09-fold (95% CI: 1.38-6.90, P=0.006) higher number of falls. This relationship between frailty and falls did not differ for younger and older adults (P=0.57). CONCLUSIONS:Frailty, a validated construct in the elderly, was a strong and independent predictor of falls in adults undergoing hemodialysis, regardless of age. Our results may aid in identifying frail hemodialysis patients who could be targeted for multidimensional fall prevention strategies.

BACKGROUND: Recipients of ABO-incompatible (ABOi) living-donor kidney transplants often undergo more intense immunosuppression than their ABO-compatible counterparts. It is unknown if this difference leads to higher cancer risk after transplantation. Single-center studies are too small and lack adequate duration of follow-up to answer this question. METHODS: We identified 318 ABOi recipients in the Transplant Cancer Match Study, a national linkage between the Scientific Registry of Transplant Recipients and population-based U.S. cancer registries. Seven cancers (non-Hodgkin lymphoma, Merkel cell carcinoma, gastric adenocarcinoma, hepatocellular carcinoma, thyroid cancer, pancreatic cancer, and testicular cancer) were identified among ABOi recipients. We then matched ABOi recipients to ABO-compatible controls by age, gender, race, human leukocyte antigen mismatch, retransplantation, and transplant year. RESULTS: There was no demonstrable association between ABOi and cancer in unadjusted (incidence rate ratio, 0.83; 95% confidence interval, 0.33-1.71; P=0.3) or matched control (incidence rate ratio, 0.99; 95% confidence interval, 0.38-2.23; P=0.5) analyses. CONCLUSION: To the extent that could be determined in this registry study, current desensitization protocols are not associated with increased risk of cancer after transplantation.

BACKGROUND:Living-donor kidney transplantation (KT) is encouraged for children with end-stage renal disease due to superior long-term graft survival compared with deceased-donor KT. Despite this, there has been a steady decrease in the use of living-donor KT for pediatric recipients. Due to their young age at transplantation, most pediatric recipients eventually require retransplantation, and the optimal order of donor type is not clear. METHODS:Using the Scientific Registry of Transplant Recipients, we analyzed first and second graft survival among 14,799 pediatric (<18 years old) recipients undergoing KT between 1987 and 2010. RESULTS:Living-donor grafts had longer survival compared with deceased-donor grafts, similarly among both first (adjusted hazard ratio [aHR], 0.78; 95% confidence interval [CI], 0.73-0.84; P<0.001) and second (aHR, 0.74; 95% CI, 0.64-0.84; P<0.001) transplants. Living-donor second grafts had longer survival compared with deceased-donor second grafts, similarly after living-donor (aHR, 0.68; 95% CI, 0.56-0.83; P<0.001) and deceased-donor (aHR, 0.77; 95% CI, 0.63-0.95; P=0.02) first transplants. Cumulative graft life of two transplants was similar regardless of the order of deceased-donor and living-donor transplantation. CONCLUSIONS:Deceased-donor KT in pediatric recipients followed by living-donor retransplantation does not negatively impact the living-donor graft survival advantage and provides similar cumulative graft life compared with living-donor KT followed by deceased-donor retransplantation. Clinical decision-making for pediatric patients with healthy, willing living donors should consider these findings in addition to the risk of sensitization, aging of the living donor, and deceased-donor waiting times.

The growth in living kidney donation has been accompanied by greater racial diversity. Most information on post-donation health comes from single-center studies of dominantly Caucasian cohorts. Recent linkage of U.S. donor registration data with death records demonstrated higher mortality risks among African American donors, but importantly, no differences in death compared with demographically matched, healthy controls. Within the donor population, some recent studies have also identified higher likelihoods of post-donation hypertension, diabetes mellitus and kidney failure in African American and Hispanic donors. Thus, based on concerns for higher risks of long-term end-organ damage, it may be reasonable to consider race within the living donor selection process, such as use of more stringent exclusion criteria among non-Caucasian living donors with baseline elevated blood pressure. Recently identified associations of coding variants in the apolipoprotein L1 (APOL1) gene with nondiabetic renal failure in African Americans raise promise of APOL1 genotyping as a novel tool for risk stratifying African American potential donors, but more data are needed to understand implications for post-donation outcomes. To tailor counseling and informed consent, focused attention to long-term medical outcomes among non-Caucasian living donors is needed, and should include assembly of healthy non-donor controls for assessment of attributable risks of donation.

BACKGROUND:Lifetime risk estimates of chronic kidney disease (CKD) can motivate preventative behaviors at the individual level and forecast disease burden and health care use at the population level. STUDY DESIGN/METHODS:Markov Monte Carlo model simulation study. SETTING & POPULATION/METHODS:Current US black and white population. MODEL, PERSPECTIVE, & TIMEFRAME/METHODS:Markov models simulating kidney disease development, using an individual perspective and lifetime horizon. OUTCOMES/RESULTS:Age-, sex-, and race-specific residual lifetime risks of CKD stages 3a+ (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m²), 3b+ (eGFR <45 mL/min/1.73 m²), 4+ (eGFR <30 mL/min/1.73 m²), and end-stage renal disease (ESRD). MEASUREMENTS/METHODS:State transition probabilities of developing CKD and of dying prior to its development were modeled using: (1) mortality rates from the National Vital Statistics Report, (2) mortality risk estimates from a 2-million person meta-analysis, and (3) CKD prevalence from National Health and Nutrition Examination Surveys. Incidence, prevalence, and mortality related to ESRD were supplied by the US Renal Data System. RESULTS:At birth, the overall lifetime risks of CKD stages 3a+, 3b+, 4+, and ESRD were 59.1%, 33.6%, 11.5%, and 3.6%, respectively. Women experienced greater CKD risk yet lower ESRD risk than men; blacks of both sexes had markedly higher CKD stage 4+ and ESRD risks (lifetime risks for white men, white women, black men, and black women, respectively: CKD stage 3a+, 53.6%, 64.9%, 51.8%, and 63.6%; CKD stage 3b+, 29.0%, 36.7%, 33.7%, and 40.2%; CKD stage 4+, 9.3%, 11.4%, 15.8%, and 18.5%; and ESRD, 3.3%, 2.2%, 8.5%, and 7.8%). Risk of CKD increased with age, with approximately one-half the CKD stage 3a+ cases developing after 70 years of age. LIMITATIONS/CONCLUSIONS:CKD incidence was modeled from prevalence estimates in the US population. CONCLUSIONS:In the United States, the lifetime risk of developing CKD stage 3a+ is high, emphasizing the importance of primary prevention and effective therapy to reduce CKD-related morbidity and mortality.