Jon J. Snyder

Diabetes Mellitus After Kidney Transplantation in the United States

New onset diabetes is a major complication after kidney transplantation. However, the incidence, risk factors and clinical relevance of post‐transplant diabetes mellitus (PTDM) vary among reports from single‐center observational studies and clinical trials. Using data from the United Renal Data System we identified 11 659 Medicare beneficiaries who received their first kidney transplant in 1996–2000. The cumulative incidence of PTDM was 9.1% (95% confidence interval = 8.6–9.7%), 16.0% (15.3–16.7%), and 24.0% (23.1–24.9%) at 3, 12, and 36 months post‐transplant, respectively. Using Coxs proportional hazards analysis, risk factors for PTDM included age, African American race (relative risk = 1.68, range: 1.52–1.85, p < 0.0001), Hispanic ethnicity (1.35, range: 1.19–1.54, p < 0.0001), male donor (1.12, range: 1.03–1.21, p = 0.0090), increasing HLA mismatches, hepatitis C infection (1.33, range: 1.15–1.55, p < 0.0001), body mass index ≥30 kg/m2 (1.73, range: 1.57–1.90, p < 0.0001), and the use of tacrolimus as the initial maintenance immunosuppressive medication (1.53, range: 1.29–1.81, p < 0.0001). Factors that reduced the risk for PTDM included the use of mycophenolate mofetil, azathioprine, younger recipient age, glomerulonephritis as a cause of kidney failure, and a college education. As a time‐dependent covariate in Cox analyses that also included multiple other risk factors, PTDM was associated with increased graft failure (1.63, 1.46–1.84, p < 0.0001), death‐censored graft failure (1.46, 1.25–1.70, p < 0.0001), and mortality (1.87, 1.60–2.18, p < 0.0001). We conclude that high incidences of PTDM are associated with the type of initial maintenance immunosuppression, race, ethnicity, obesity and hepatitis C infection. It is a strong, independent predictor of graft failure and mortality. Efforts should be made to minimize the risk of this important complication.

Cancer after Kidney Transplantation in the United States

Previous reports of cancer after kidney transplantation have been limited by small numbers of patients in single‐center studies and incomplete ascertainment of cases in large registries.

Spectrum of Cancer Risk Among US Solid Organ Transplant Recipients

CONTEXT Solid organ transplant recipients have elevated cancer risk due to immunosuppression and oncogenic viral infections. Because most prior research has concerned kidney recipients, large studies that include recipients of differing organs can inform cancer etiology. OBJECTIVE To describe the overall pattern of cancer following solid organ transplantation. DESIGN, SETTING, AND PARTICIPANTS Cohort study using linked data on solid organ transplant recipients from the US Scientific Registry of Transplant Recipients (1987-2008) and 13 state and regional cancer registries. MAIN OUTCOME MEASURES Standardized incidence ratios (SIRs) and excess absolute risks (EARs) assessing relative and absolute cancer risk in transplant recipients compared with the general population. RESULTS The registry linkages yielded data on 175,732 solid organ transplants (58.4% for kidney, 21.6% for liver, 10.0% for heart, and 4.0% for lung). The overall cancer risk was elevated with 10,656 cases and an incidence of 1375 per 100,000 person-years (SIR, 2.10 [95% CI, 2.06-2.14]; EAR, 719.3 [95% CI, 693.3-745.6] per 100,000 person-years). Risk was increased for 32 different malignancies, some related to known infections (eg, anal cancer, Kaposi sarcoma) and others unrelated (eg, melanoma, thyroid and lip cancers). The most common malignancies with elevated risk were non-Hodgkin lymphoma (n = 1504; incidence: 194.0 per 100,000 person-years; SIR, 7.54 [95% CI, 7.17-7.93]; EAR, 168.3 [95% CI, 158.6-178.4] per 100,000 person-years) and cancers of the lung (n = 1344; incidence: 173.4 per 100,000 person-years; SIR, 1.97 [95% CI, 1.86-2.08]; EAR, 85.3 [95% CI, 76.2-94.8] per 100,000 person-years), liver (n = 930; incidence: 120.0 per 100,000 person-years; SIR, 11.56 [95% CI, 10.83-12.33]; EAR, 109.6 [95% CI, 102.0-117.6] per 100,000 person-years), and kidney (n = 752; incidence: 97.0 per 100,000 person-years; SIR, 4.65 [95% CI, 4.32-4.99]; EAR, 76.1 [95% CI, 69.3-83.3] per 100,000 person-years). Lung cancer risk was most elevated in lung recipients (SIR, 6.13 [95% CI, 5.18-7.21]) but also increased among other recipients (kidney: SIR, 1.46 [95% CI, 1.34-1.59]; liver: SIR, 1.95 [95% CI, 1.74-2.19]; and heart: SIR, 2.67 [95% CI, 2.40-2.95]). Liver cancer risk was elevated only among liver recipients (SIR, 43.83 [95% CI, 40.90-46.91]), who manifested exceptional risk in the first 6 months (SIR, 508.97 [95% CI, 474.16-545.66]) and a 2-fold excess risk for 10 to 15 years thereafter (SIR, 2.22 [95% CI, 1.57-3.04]). Among kidney recipients, kidney cancer risk was elevated (SIR, 6.66 [95% CI, 6.12-7.23]) and bimodal in onset time. Kidney cancer risk also was increased in liver recipients (SIR, 1.80 [95% CI, 1.40-2.29]) and heart recipients (SIR, 2.90 [95% CI, 2.32-3.59]). CONCLUSION Compared with the general population, recipients of a kidney, liver, heart, or lung transplant have an increased risk for diverse infection-related and unrelated cancers.

OPTN/SRTR 2015 Annual Data Report: Kidney

The first full year of data after implementation of the new kidney allocation system reveals an increase in deceased donor kidney transplants among black candidates and those with calculated panel‐reactive antibodies 98%–100%, but a decrease among candidates aged 65 years or older. Data from 2015 also demonstrate ongoing positive trends in graft and patient survival for both deceased and living donor kidney transplants, but the challenges of a limited supply of kidneys in the setting of increasing demand remain evident. While the total number of patients on the waiting list decreased for the first time in a decade, this was due to a combination of a decrease in the number of candidates added to the list and an increase in the number of candidates removed from the list due to deteriorating medical condition, as well as an increase in total transplants. Deaths on the waiting list remained flat, but this was likely because of an increasing trend toward removing inactive candidates too sick to undergo transplant.

OPTN/SRTR 2015 Annual Data Report: Liver.

ABSTRACT  The current liver allocation system, introduced in 2002, decreased the importance of waiting time for allocation priorities; the number of active wait‐listed candidates and median waiting times were immediately reduced. However, the total number of adult wait‐listed candidates has increased since 2002, and median waiting time has increased since 2006. Pretransplant mortality rates have been stable, but the number of candidates withdrawn from the list as being too sick to undergo transplant nearly doubled between 2009 and 2011. Deceased donation rates have remained stable, with an increasing proportion of expanded criteria donors. Living donation has decreased over the past 10 years. Transplant outcomes remain robust, with continuously improving graft survival rates for deceased donor, living donor, and donation after circulatory death livers. Numbers of new and prevalent pediatric candidates on the waiting list have decreased. Pediatric pretransplant mortality has decreased, most dramatically for candidates aged less than 1 year. The transplant rate has increased since 2002, and is highest in candidates aged less than 1 year. Graft survival continues to improve for pediatric recipients of deceased donor and living donor livers. Incidence of acute rejections increases with time after transplant. Posttransplant lymphoproliferative disorder remains an important concern in pediatric recipients.

Preemptive Kidney Transplantation: The Advantage and the Advantaged

It remains unclear whether preemptive transplantation is beneficial, and if so, who benefits. A total of 38,836 first, kidney-only transplants between 1995 and 1998 were retrospectively studied. A surprising 39% of preemptive transplants were from cadaver donors, and the proportions of cadaver donor transplants that were preemptive changed little, from 7.3% in 1995 to 7.7% in 1998. Preemptive transplants using cadaver donors were more likely among recipients aged 0 to 17 yr versus 18 to 29 yr (odds ratio [OR], 2.48; 95% confidence interval [CI], 1.94 to 3.17), white versus black (OR, 2.33; 95% CI, 2.03 to 2.68), able to work versus unable to work (OR, 1.42; 95% CI, 1.26 to 1.61), covered by private insurance versus Medicare (OR, 4.77; 95% CI, 4.26 to 5.32), or recipients with a college degree versus no college degree (OR, 1.34; 95% CI, 1.17 to 1.54). Preemptive transplants were less likely for Hispanics versus non-Hispanics (OR, 0.57; 95% CI, 0.50 to 0.67), patients with type 2 versus type 1 diabetes (OR, 0.76; 95% CI, 0.61 to 0.96), and for 2 to 5 HLA mismatches compared with 0 HLA mismatches (OR range, 0.77 to 0.82). In adjusted Cox proportional hazards analysis, the relative risk of graft failure for preemptive transplantation was 0.75 (0.67 to 0.84) among 25,758 cadaver donor transplants and 0.73 (0.64 to 0.83) among 13,078 living donor transplants, compared with patients who received a transplant after already being on dialysis. Preemptive transplantation was associated with a reduced risk of death: 0.84 (0.72 to 0.99) for cadaver donor transplants and 0.69 (0.56 to 0.85) for living donor transplants. Thus, preemptive transplantation, which is associated with improved patient and graft survival, is less common among racial minorities, those who have less education, and those who must rely on Medicare for primary payment. Alterations in the payment system, emphasis on early referral, and changes in cadaver kidney allocation could increase the number of patients who benefit from preemptive transplantation.

OPTN/SRTR 2013 Annual Data Report: Kidney: OPTN/SRTR 2013 Annual Data Report

A new kidney allocation system, expected to be implemented in late 2014, will characterize donors on a percent scale (0%‐100%) using the kidney donor profile index (KDPI). The 20% of deceased donor kidneys with the greatest expected posttransplant longevity will be allocated first to the 20% of candidates with the best expected posttransplant survival; kidneys that are not accepted will then be offered to remaining 80% of candidates. Waiting time will start at the time of maintenance dialysis initiation (even if before listing) or at the time of listing with an estimated glomerular filtration rate of 20 mL/min/1.73 m2 or less. Under the current system, the number of candidates on the waiting list continues to increase, as each year more candidates are added than are removed. Median waiting times for adults increased from 3 years in 2003 to more than 4.5 years in 2009. Donation rates have not increased. Short‐term outcomes continue to improve; death‐censored graft survival at 90 days posttransplant was 97% or higher for deceased donor transplants and over 99% for living donor transplants. In 2013, 883 pediatric candidates were added to the waiting list; 65.8% of pediatric candidates on the list in 2013 underwent deceased donor transplant. Five‐year graft survival was highest for living donor recipients aged younger than 11 years (89%) and lowest for deceased donor recipients aged 11 to 17 years (68%).

Excerpts From the US Renal Data System 2009 Annual Data Report

This 21st US Renal Data System Annual Data Report covers data through 2007, and again includes a section on chronic kidney disease (CKD) in the United States. Using NHANES and employer group health plan data, we estimate the relationship between kidney disease markers and mortality risk and the likelihood of blood pressure and lipid control by CKD stage; illustrate use of the new ICD-9-CM CKD diagnosis codes; and report on morbidity, mortality, care and costs during the transition to ESRD. New chapters address CKD patient care, the transition to ESRD, and acute kidney injury. In 2007, 111,000 patients started end-stage renal disease (ESRD) therapy, and the prevalent population reached 527,283 (including 368,544 dialysis patients); 17,513 transplants were performed, and 158,739 patients had a functioning graft at year’s end. Program expenditures reached

OPTN/SRTR 2012 Annual Data Report: Pancreas: OPTN & SRTR Annual Data Report 2012

35.3 billion, with

Propensity-Matched Mortality Comparison of Incident Hemodialysis and Peritoneal Dialysis Patients

23.9 billion from Medicare (accounting for 5.8% of total Medicare expenditures). The incident rate fell 2.1%, to 354 per million. Fistula use in prevalent patients declined 2.6 percent; catheter use continues to be a concern. The percentage of patients with hemoglobin levels above 13 g/dl has fallen since 2006, but levels in the incident population frequently exceed 12. First-year mortality and morbidity among hemodialysis patients—particularly the increasing rate of hospitalizations due to infections—continue to be major concerns, and pediatric patient survival has not improved. The public health impact of kidney disease is larger than previously appreciated, and early detection, education, intervention, and risk factor control need to address the heavy burden of cardiovascular disease and adverse events in this vulnerable population.