Impact of education on APOL1 testing attitudes among prospective living kidney donors

It is unknown how providing prospective living donors with information about APOL1, including the benefits and drawbacks of testing, influences their desire for testing. In this study, we surveyed 102 participants with self-reported African ancestry and positive family history of kidney disease, recruited from our nephrology waiting room. We assessed views on APOL1 testing before and after presentation of a set of potential benefits and drawbacks of testing and quantified the self-reported level of influence individual benefits and drawbacks had on participants' desire for testing in the proposed context of living donation. The majority of participants (92%) were aware of organ donation and more than half (56%) had considered living donation. And though we found no significant change in response following presentation of the potential benefits and the drawbacks of APOL1 testing by study end significance, across all participants, "becoming aware of the potential risk of kidney disease among your immediate family" was the benefit with the highest mean influence (3.3±1.4), while the drawback with the highest mean influence (2.9±1.5) was "some transplant centers may not allow you to donate to a loved one". This study provides insights into the priorities of prospective living donors and suggests concern for how the information affects family members may strongly influence desires for testing. It also highlights the need for greater community engagement to gain a deeper understanding of the priorities that influence decision making on APOL1 testing

Renal transplantation using kidneys from hepatitis C-infected donors: A review of 30-years’ experience

Kidney transplantation is the optimal therapy for end-stage kidney disease but limited by the available number of organs. Using HCV+ donors, both in HCV+ and HCV− recipients, is a rational response to the organ shortage. We review the historic experience using HCV+ donors in HCV+ recipients and assess long-term results. We also discuss contemporary practices, including the transplantation of HCV-viremic kidneys into HCV− recipients with different approaches to posttransplant HCV therapy. Resumen: El trasplante renal es el tratamiento óptimo de la insuficiencia renal terminal pero está limitado por el número de órganos disponibles. El uso de los riñones de los donantes VHC+, tanto en receptores VHC+ como VHC−, es una respuesta racional a la escasez de órganos. En este artículo revisamos la experiencia histórica usando riñones de donantes VHC+ en receptores VHC+ y evaluamos los resultados a largo plazo. Además, discutiremos las prácticas contemporáneas incluyendo el trasplante de órganos VHC+ virémicos en receptores VHC− con diferentes opciones de tratamiento VHC postrasplante

Expanding the use of hepatitis C-viremic kidney donors

Direct-acting antivirals have revolutionized the treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease, with implications for the timing of antiviral treatment among kidney transplant candidates and for the use of HCV viremic donors. A recent consensus conference reviewed the available data on the safety and cost-effectiveness of expanding access to HCV-positive organs to HCV-negative recipients. Early trials are promising, but larger trials and a plan for obtaining HCV therapy in the posttransplantation period are needed. Implications for the larger transplant community also need to be considered

Sex hormone levels by presence and severity of cirrhosis in women with chronic hepatitis C virus infection

Cirrhosis is associated with hormonal dysregulation, as evidenced by secondary amenorrhoea in reproductive-aged women, and feminization of cirrhotic men. Whether hormone levels vary by severity of cirrhosis in women is not known. If identified, such changes may have important clinical relevance, particularly, as low sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) are known to promote metabolic and cardiovascular disease in women. In a cohort of post-menopausal women with chronic hepatitis C virus (HCV) infection, we compared comprehensive sex hormone levels by presence of cirrhosis, as well as across Child-Turcotte-Pugh (CTP) class. Results: There were n = 18 cirrhotic and n = 21 noncirrhotic women with a median age of 57 years (interquartile range [IQR] 53-62). Compared to noncirrhotics, cirrhotic women had higher oestradiol (11.0 vs 6.0 pg/mL, P = 0.05) and oestrone levels (32.0 vs 8.0 ng/mL, P < 0.001), and lower sex hormone binding globulin (SHBG) (69.2 vs 155.6 nmol/L, P = 0.001), and FSH levels (4.9 vs 89.6 mIU/mL, P < 0.001). Among cirrhotic women, there was a progressive decline in FSH and SHBG and concurrent rise in oestrone levels from CTP class A to C (test of trend, P values ≤0.02). Cirrhosis is associated with lower FSH and SHBG levels in cirrhotic compared to noncirrhotic women with HCV infection. In cirrhotic women, these levels demonstrate steady decline by disease severity. Given known associations of low SHBG and FSH with cardio-metabolic disease, the clinical implications of hormonal changes by cirrhosis severity in HCV-infected women warrants investigation

Estimating the causal effect of treatment with direct-acting antivirals on kidney function among individuals with hepatitis C virus infection.

BackgroundDirect-acting antivirals (DAA) are highly effective at treating Hepatitis C virus (HCV) infection, with a cure rate >95%. However, the effect of DAAs on kidney function remains debated.MethodsWe analyzed electronic health record data for DAA-naive patients with chronic HCV infection engaged in HCV care at Boston Medical Center between 2014 and 2018. We compared the following hypothetical interventions using causal inference methods: 1) initiation of DAA and 2) no DAA initiation. For patients with normal kidney function at baseline (eGFR>90 ml/min/1.73m2), we estimated and compared the risk for reaching Stage 3 chronic kidney disease (CKD) (eGFR≤60 ml/min/1.73m2) under each intervention. For patients with baseline CKD Stages 2-4 (15ResultsFirst, among 1390 patients with normal kidney function at baseline the estimated 2-year risk difference (95% CI) of reaching Stage 3 CKD for DAA initiation versus no DAA was -1% (-3, 2). Second, among 733 patients with CKD Stage 2-4 at baseline the estimated 2-year mean difference in change in eGFR for DAA initiation versus no DAA therapy was -3 ml/min/1.73m2 (-8, 2).ConclusionsWe found no effect of DAA initiation on kidney function, independent of baseline renal status. This suggests that DAAs may not be nephrotoxic; furthermore, in the short-term, HCV clearance may not improve CKD

A Paired Kidney Analysis of Multiorgan Transplantation: Implications for Allograft Survival

Background. United Network for Organ Sharing multiorgan transplantation allocation policy allows sequestration of a kidney by another solid organ regardless of the priority of the candidate for the kidney allograft. The implications of this policy for kidney allograft survival are not well understood. Methods. We conducted a retrospective cohort analysis of pairs of deceased donor kidney transplants where 1 kidney was allocated to a simultaneous liver-kidney (SLK) or simultaneous heart-kidney (SHK) recipient and the contralateral kidney to a kidney transplant alone (KTA) recipient (cohort from February 2002 to December 2010). Graft and patient survivals were assessed with Cox regression models. Results. There were 1998 SLK and 276 SHK transplants with matching KTA transplants. Five-year kidney graft (64% [SLK] vs 75% [KTA], P < 0.001) and patient survivals (66% [SLK] vs 81% [KTA], P < 0.001) were significantly lower in SLK versus KTA recipients of the contralateral kidney. Among the entire cohort of SLK in this analysis, the cumulative difference in graft survival 1 year after transplant was 115 years, and by 5 years, the difference increased to 1062 years. Among the SHK arm of our study, 5-year graft survival (72% [SHK] vs 73% [KTA], P = 0.71) did not significantly differ, although patient survival (75% [SHK] vs 84% [KTA], P = 0.02) was higher in KTA recipients. Conclusions. Kidney graft survival is inferior among SLK relative to KTA, but not SHK. Multiorgan transplantation allocation may not be congruent with the intention of new kidney allocation policies that attempt to maximize survival after kidney transplantation

Mortality and Kidney Transplantation Outcomes among Chronic Dialysis Patients who are Seropositive for Hepatitis C Virus

INTRODUCTIONThe end stage renal disease (ESRD) population is enriched with patients with HCV infection. However, lack of information about HCV serostatus in large ESRD and transplant registries in the United States (US) has limited research about outcomes among dialysis patients who have been infected with HCV and HCV-seropositive patients’ access to renal transplantation. MATERIALS AND METHODSWe linked detailed clinical data, that included HCV sersostatus, from a large dialysis provider with US transplant registry data and examined outcomes among patients receiving chronic dialysis between 1/1/2004 – 12/31/2014. Using Cox and cause-specific hazards regression, we evaluated adjusted hazard (aHR) and subhazard ratios (SHR) of all-cause mortality, transplant wait-listing, and kidney transplantation associated with HCV seropositivity status. RESULTSAmong 442,171 chronic dialysis patients, 31,624 (7.2%) were seropositive for HCV. HCV infection was associated with a small elevation in the risk of death (aHR 1.09, 95% CI 1.07-1.11) but a substantial reduction in access to the kidney transplant waitlist (SHR 0.67, 95% CI 0.61 - 0.73). Once waitlisted, HCV+ patients underwent transplantation as rapidly as seronegative patients (SHR 1.11, 95% CI 0.97-1.29) and derived a substantial survival benefit from kidney transplantation (aHR 0.37, 95% CI 0.31-0.46) compared to dialysis (Figure 1). Additionally, the strategy of accepting an HCV+ donor kidney provided a survival advantage (aHR 0.67, 95% CI 0.51-0.87) compared to remaining on the waitlist to wait for a HCV-negative donor kidney. DISCUSSION AND CONCLUSIONDialysis patients with HCV have reduced access to kidney transplantation, despite deriving a significant survival benefit from transplantation. Future research must focus on identifying and removing barriers to waitlisting for these patients.NIH R21 DK108045.(Figure is included in full-text article.