Association of Recipient APOL1 Kidney Risk Alleles With Kidney Transplant Outcomes.

BACKGROUND: Kidney transplant survival in African American recipients is lower compared with non-African American transplant recipients. APOL1 risk alleles (RA) have been postulated as likely contributors. We examined the graft outcomes in kidney transplant recipients (KTRs) stratified by APOL1 RA status in a multicenter observational prospective study. METHODS: The Renal Transplant Outcome Study recruited a cohort of incident KTRs at 3 transplant centers in the Philadelphia area from 1999-2004. KTRs were genotyped for APOL1 RA. Allograft and patient survival rates were compared by the presence and number of APOL1 RA. RESULTS: Among 221 participants, approximately 43% carried 2 APOL1 RA. Recipients carrying 2 APOL1 RA demonstrated lower graft survival compared with recipients with only 1 or none of APOL1 RA at 1 y posttransplant, independently of other donor and recipient characteristics (adjusted hazard ratio 3.2 [95% confidence interval, 1.0-10.4], P = 0.05). There was no significant difference in overall survival or graft survival after 3 y posttransplantation. There was no difference in death by APOL1 -risk status ( P = 0.11). CONCLUSIONS: Recipients with 2 APOL1 high-risk alleles exhibited lower graft survival 1 y posttransplantation compared with recipients with only 1 or 0 APOL1 RA. Further research is required to study the combined role of the recipient and donor APOL1 genotypes in kidney transplantation.

Vitamin D Analogues and Coronary Calcification in CKD Stages 3 and 4: A Randomized Controlled Trial of Calcitriol Versus Paricalcitol.

RATIONALE & OBJECTIVE: Mineral and bone disorder in chronic kidney disease (CKD) is associated with progression of coronary artery calcification (CAC). Mineral and bone disorder often is treated with calcitriol and other vitamin D receptor activators, including paricalcitol, agents that may have differential effects on calcium, phosphate, and parathyroid hormone levels. Accordingly, we investigated whether these agents have differential effects on CAC progression in patients with CKD. STUDY DESIGN: Randomized, double-concealed, 48-week clinical trial. SETTING & PARTICIPANTS: CKD stage 3 or 4 with secondary hyperparathyroidism with CAC score > 0 and no prior treatment with activated vitamin D. INTERVENTION: Calcitriol versus paricalcitol. OUTCOMES: The primary outcome was log-transformed CAC change. Secondary outcomes included percent change in CAC volume, valvular calcifications, and bone mineral metabolism markers. RESULTS: Among 44 individuals randomly assigned, mean age was 65 years and mean estimated glomerular filtration rate was 27 mL/min/1.73 m2. Median CAC score was 140 (IQR, 55-277) Agatston units at baseline. There was no significant difference in CAC progression between treatment arms (P = 0.06). After adjustment for baseline CAC score (log), treatment group remains nonsignificant (P = 0.08). Further adjustment for creatinine level and/or CKD stage did not change the association. In secondary analyses adjusting for dose level of activated vitamin D, treatment group was significant (P = 0.01), and when dose level was also included in the model, the coefficient for individuals in the paricalcitol group was significantly associated with CAC progression (P = 0.02). An interaction term between dosing level and CKD stage was significant at the highest dosing level (P = 0.04). LIMITATIONS: Pilot single-center study. CONCLUSIONS: In patients with CKD with secondary hyperparathyroidism naive to activated vitamin D therapy, there was no difference in CAC or valvular progression in participants receiving calcitriol compared with paricalcitol during a 48-week period. FUNDING: Abbvie, Inc. TRIAL REGISTRATION: NCT00752102.

Effects of Smoking on Solid Organ Transplantation Outcomes.

Tobacco smoking is the leading preventable cause of death worldwide. Both donor and recipient smoking have been shown to increase graft loss and mortality in solid organ transplant recipients in many studies. Only in lung transplants is smoking a universal contraindication to transplantation. Transplant centers implement different policies regarding smoking recipients and allografts from smoking donors. Due to scarcity of available allografts, the risks of smoking have to be weighed against the risks of a longer transplant waitlist period. Although transplant centers implement different strategies to encourage smoking cessation pre- and post-transplant, not many studies have been published that validate the efficacy of smoking cessation interventions in this vulnerable population. This article summarizes the results of studies investigating prevalence, impact on outcomes, and cessationinterventions for smoking in the transplant population. We report herein a review of the elevated risks of infection, malignancy, graft loss, cardiovascular events, and mortality in solid organ transplant populations.

Diabetes and the solid organ transplant recipient.

Solid organ transplant candidates undergo very strict screening for cardiovascular risk. Such screening has permitted significant decreases in cardiovascular morbidity and mortality over the ensuing decades of follow up. Long term follow-up has enabled us to identify an increasing incidence of pulmonary and urinary tract infections with or without sepsis as competing factors of morbidity and mortality. Indeed, all-cause mortality may now be dominated by infection-related endpoints. No population of transplant recipients is more naturally susceptible to infection as a diabetic subset, now submitted to immunosuppression. The current review details infection risk for kidney, liver, heart, and lung allograft recipients. A specific feature of this report emphasizes the enhanced risk for bacterial and fungal infection found in diabetic allograft recipients on immunosuppression therapy. The risk of repeated prescription of antibiotics in terms of evolutions of resistant strains of infectious pathogens is emphasized.

Traumatic complex splenic arteriovenous fistula causing prehepatic portal hypertension and variceal bleeding: the importance of the diagnosis for the endovascular treatment approach.

We report a case of a 68-year-old female patient presenting with portal hypertension and variceal bleeding in the absence of any liver disease. After performing a computed tomography angiogram, the cause of her condition was identified to be a splenic arteriovenous fistula (SAVF). After confirming the findings with angiography, we opted to treat the condition with coil embolization as an alternative to a more invasive surgical treatment. Coil embolization of the SAVF was performed successfully resulting in the improvement of the patient's variceal congestion. Our case highlights the importance of identifying SAVF as a potentially curable cause of variceal bleeding in the absence of liver disease. Seeking this diagnosis is of utmost importance since it completely changes the endovascular approach and management of these patients with variceal bleeding. We describe a minimally invasive endovascular technique for treatment of these critically ill patients.