Subclinical Cognitive Impairment and Listing for Kidney Transplantation.

BACKGROUND AND OBJECTIVES: Cognitive impairment is common in patients with kidney disease and can affect physicians' perception and/or patients' ability to complete the pretransplant evaluation. We examined whether cognitive impairment influences the likelihood for transplant listing and whether patients with cognitive impairment take longer to be listed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a single-center longitudinal cohort study. Patients presenting for their index kidney transplant evaluation were screened for cognitive impairment using the Montreal Cognitive Assessment. A score <26 indicated cognitive impairment. The transplant selection committee was blinded to the scores. Kaplan-Meier analysis assessed time to active listing by level of cognition. A Cox proportional hazards model that included age, sex, race/ethnicity, smoking, coronary artery disease, and diabetes was constructed to evaluate the association between Montreal Cognitive Assessment score and listing for transplant. RESULTS: In total, 349 patients who underwent Montreal Cognitive Assessment testing at their initial visit were included in the analysis. Patients with cognitive impairment were more likely to be older, black, and smokers. The time to listing in patients with cognitive impairment was longer than the time to listing in those with no cognitive impairment (median time, 10.6 versus 6.3 months; log rank test P=0.01). Cognitive impairment was independently associated with a lower likelihood of being listed for transplant (hazard ratio, 0.93 per unit lower Montreal Cognitive Assessment score; 95% confidence interval, 0.88 to 0.99; P=0.02). A lower proportion of patients with cognitive impairment were listed compared with patients without cognitive impairment at 1 month (2% versus 11%), 6 months (17% versus 37%), and 1 year (23% versus 41%), (P<0.001 for all). CONCLUSIONS: Cognitive impairment is associated with a lower likelihood of being listed for kidney transplant, and is associated with longer time to transplant listing.

Donor PNPLA3 rs738409 genotype affects fibrosis progression in liver transplantation for hepatitis C.

UNLABELLED: The rs738409 G>C single nucleotide polymorphism occurring in the patatin-like phospholipase 3 gene has been identified as a novel genetic marker for hepatic steatosis. Recent studies also associated rs738409 with fibrosis in hepatitis C (HCV). Therefore, we sought to determine the impact of donor and recipient rs738409 genotype on the progression of fibrosis after liver transplantation for HCV. This cohort study included 101 patients infected with HCV who underwent liver transplantation between January 2008, and June 2011. Donor and recipient rs738409 genotypes were determined from donor wedge biopsies and recipient explants. The time to Ishak stage 3 fibrosis, or HCV-related mortality/graft loss was analyzed by the Cox model adjusting for HCV-Donor Risk Index, warm ischemic time, pretransplant Model for Endstage Liver Disease (MELD) and viral load. The rs738409 CC variant was present in 56% of donors and 57% of recipients. The median follow-up period was 620 days. A total of 39 patients developed the primary outcome of ≥stage 3 fibrosis or HCV-related mortality/graft loss, the time to which differed by donor (P = 0.019) but not recipient (P = 0.89) genotype. In the multivariate model, donor GC or GG variants had 2.53 times the risk (95% confidence interval [CI] 1.25-5.02, P = 0.008) compared to CC variants. In the alternative endpoint: stage 3 fibrosis or all-cause mortality/graft loss, the effect of donor genotype was attenuated but remained significant at 1.98 (95% CI 1.11-3.53). CONCLUSIONS: The rs738409 genotype is an important predictor of posttransplant outcome in HCV. Liver, and not adipocytes, is the site at which this effect occurs. Our finding may be useful in donor selection for liver transplantation with HCV, and may guide decisions regarding early antiviral treatment.