Renal cell cancer after kidney transplantation.

PURPOSE: This study aims to identify modifiable risk factors for de novo renal cell carcinoma (RCC) after kidney transplantation in a matched-pair approach matching for unmodifiable factors. PATIENTS AND METHODS: One thousand six hundred fifty-five adults who underwent kidney transplantation in the period 1 January 2000 to 31 December 2012 were analyzed. Patients with RCC after kidney transplantation were matched in a 1:2 ratio with those without RCC using the indication for transplantation, age at transplantation (± 10 years), recipient sex (male/female), number of received transplants, living organ donor transplantation (yes/no), and time of follow-up in days as matching criteria. The paired t test was used to compare continuous variables and the Cochran-Mantel-Haenszel test for categorical variables. Multivariable conditional logistic regression modeling was used to identify independent risk factors for RCC. RESULTS: In matched-pair analysis, a total number of 26 incident cases with RCC after kidney transplantation could be matched. Post-transplant RCC was significantly associated with longer durations of pre-transplant hemodialysis (p = 0.007) and post-transplant immunosuppression with cyclosporine (p = 0.029) and/or mycophenolate mofetil (p = 0.020) and with larger proportions of post-transplant time on mycophenolate mofetil (p = 0.046) and/or prednisolone medication (p = 0.042). Multivariable conditional logistic regression modeling revealed a significant risk increasing multiplicative factor interaction between the duration of pre-transplant dialysis (years) and the time of prednisolone usage (percent/100). Cyclosporine A usage and mycophenolate mofetil usage were also revealed as independent, significant risk factors for RCC development. CONCLUSIONS: Longer pre-transplant dialysis, cyclosporine-based protocols and/or intensified immunosuppression with additional mycophenolate mofetil, and larger proportions of time of prednisolone treatment during follow-up increase de novo RCC risk.

Development and validation of a prognostic model for kidney function 1 year after combined pancreas and kidney transplantation using pre-transplant donor and recipient variables.

PURPOSE: The widening gap between demand and supply of organs for transplantation provides extraordinary challenges for ethical donor organ allocation rules. The transplant community is forced to define favorable recipient/donor combinations for simultaneous kidney-pancreas transplantation. The aim of this study is the development of a prognostic model for the prediction of kidney function 1 year after simultaneous pancreas and kidney transplantation using pre-transplant donor and recipient variables with subsequent internal and external validation. METHODS: Included were patients with end-stage renal failure due to diabetic nephropathy. Multivariable logistic regression modeling was applied for prognostic model design with retrospective data from Hannover Medical School, Germany (01.01.2000-31.12.2011) followed by prospective internal validation (01 Jan. 2012-31 Dec. 2015). Retrospective data from another German transplant center in Kiel was retrieved for external model validation via the initially derived logit link function. RESULTS: The developed prognostic model is able to predict kidney graft function 1 year after transplantation ≥ KDIGO stage III with high areas under the receiver operating characteristic curve in the development cohort (0.943) as well as the internal (0.807) and external validation cohorts (0.784). CONCLUSION: The proposed validated model is a valuable tool to optimize present allocation rules with the goal to prevent transplant futility. It might be used to support donor organ acceptance decisions for individual recipients.

Identification of patients at risk for renal impairment after living donor kidney transplantation.

PURPOSE: Outcome after living donor kidney transplantation is highly relevant, since recipient and donor were exposed to notable harm. Reliable identification of risk factors is necessary. METHODS: Three hundred sixty-six living donor kidney transplants were included in this observational retrospective study. Relevant risk factors for renal impairment 1 year after transplantation and delayed graft function were identified with univariable and multivariable binary logistic regression and ordinal regression analysis. RESULTS: Eighty-four patients (26.6 %) suffered from renal impairment KDIGO stage ≥4 1 year post-transplant; median estimated glomerular filtration rate was 35.3 ml/min. In multivariable ordinal regression, male recipient sex (p < 0.001), recipient body mass index (p = 0.006), donor age (p = 0.002) and high percentages of panel reactive antibodies (p = 0.021) were revealed as independent risk factors for higher KDIGO stages. After adjustment for post-transplant data, recipient male sex (p < 0.001), donor age (p = 0.026) and decreased early renal function at the first post-transplant outpatient visit (p < 0.001) were identified as independent risk factors. Delayed graft function was independently associated with long stay on the waiting list (p = 0.011), high donor body mass index (p = 0.043), prolonged warm ischemic time (p = 0.016) and the presence of preformed donor-specific antibodies (p = 0.043). CONCLUSIONS: Broadening the donor pool with non-blood related donors seems to be legitimate, although with respect to careful medical selection, since donor age in combination with male recipient sex were shown to be risk factors for decreased graft function. Warm ischemic time and waiting time need to be kept as short as possible to avoid delayed graft function. Transplantation across HLA and ABO borders did not affect outcome significantly.

Prediction of Three-Year Mortality After Deceased Donor Kidney Transplantation in Adults with Pre-Transplant Donor and Recipient Variables.

BACKGROUND Prognostic models for 3-year mortality after kidney transplantation based on pre-transplant donor and recipient variables may avoid futility and thus improve donor organ allocation. MATERIAL AND METHODS There were 1546 consecutive deceased-donor kidney transplants in adults (January 1, 2000 to December 31, 2012) used to identify pre-transplant donor and recipient variables with significant independent influence on long-term survival (Cox regression modelling). Detected factors were used to develop a prognostic model for 3-year mortality in 1289 patients with follow-up of >3 years (multivariable logistic regression). The sensitivity and specificity of this model's prognostic ability was assessed with the area under the receiver operating characteristic curve (AUROC). RESULTS Highly immunized recipients [hazard ratio (HR: 2.579, 95% CI: 1.272-4.631], high urgency recipients (HR: 3.062, 95% CI: 1.294-6.082), recipients with diabetic nephropathy (HR: 3.471, 95% CI: 2.476-4.751), as well as 0, 1, or 2 HLA DR mismatches (HR: 1.349, 95% CI: 1.160-1.569) were independent and significant risk factors for patient survival. Younger recipient age ≤42.1 years (HR: 0.137, 95% CI: 0.090-0.203), recipient age 42.2-52.8 years (HR: 0.374, 95% CI: 0.278-0.498), recipient age 52.9-62.8 years (HR: 0.553, 95% CI: 0.421-0.723), short cold ischemic times ≤11.8 hours (HR: 0.602, 95% CI: 0.438-0.814) and cold ischemic times 11.9-15.3 hours (HR: 0.736, 95% CI: 0.557-0.962) reduced this risk independently and significantly. The AUROC of the derived model for 3-year post-transplant mortality with these variables was 0.748 (95% CI: 0.689-0.788). CONCLUSIONS Older, highly immunized or high urgency transplant candidates with anticipated longer cold ischemic times, who were transplanted with the indication of diabetic nephropathy should receive donor organs with no HLA DR mismatches to improve their mortality risk.

Timing of parathyroidectomy in kidney transplant candidates with secondary hyperparathryroidism: effect of pretransplant versus early or late post-transplant parathyroidectomy.

BACKGROUND: The timing of parathyroidectomy in kidney transplant candidates suffering from secondary hyperparathyroidism before versus early or late after transplantation remains controversial. METHODS: The short-term follow-up cohort comprised 66 patients with 1-year post-transplant follow-up, while the long-term follow-up cohort contained 123 patients. Risk-adjusted identification of independent risk factors for compromised renal graft function (KDIGO stage ≥ IV) was performed using multivariable regression analysis adjusted for propensity score logits for parathyroidectomy before versus after renal transplantation. Intra-individual matched-pairs analyses were used to identify significant effects of post-transplant parathyroidectomy on graft function as assessed by estimated glomerular filtration rate (eGFR) and paired t tests. RESULTS: Donor kidney function KDIGO stage III (P = .030; OR = 5.191, 95% CI: 1.100-24.508), donor blood group 0 (P = .005; OR = 0.176, 95% CI: 0.048-0.642), and post-transplant parathyroidectomy (P = .032; OR = 17.849, 95% CI: 1.086-293.268) were revealed as independent significant risk factors for compromised renal graft function in the short-term follow-up cohort using propensity score risk adjustment while post-transplant parathyroidectomy had no independent influence in the long-term follow-up cohort (P = .651). Parathyroidectomy after renal transplantation compromised graft function early after parathyroidectomy and at last follow-up in all post-transplant parathyroidectomy cases (P ≤ .004). Parathyroidectomy within the first post-transplant year was associated with compromised renal graft function until last follow-up (P = .004), while parathyroidectomy late post-transplant was not. CONCLUSION: Parathyroidectomy should be conducted before transplantation or, if this is not possible, preferably after the first post-transplant year.