Summary
A decade ago, observations suggested that post‐transplant diabetes mellitus (PTDM) was linked to allograft loss and shorter patient survival. Increasing awareness, improvements in care, and ...changes in the immunosuppressive regimen may have modified this association. Single‐center analysis of 1990 (age>18; transplantation date 1996–2012) primary kidney recipients (KTR). Patients with <12 months follow‐up were excluded. Diabetes was diagnosed according to ADA criteria and characterized as follows: No diabetes, PTDM in the first post‐transplant year not treated with glucose‐lowering medications (GLM) at 12 months, PTDM in the first post‐transplant year treated with GLM at 12 months, and pretransplant diabetes. Cox proportional hazards models were used to examine the relationship of PTDM with allograft and patient survival. Mean follow‐up time was 6.8 years for allograft survival and 7.4 years for patient survival. PTDM treated with medication at year one was not associated with allograft survival (HR 1.28, 95% CI 0.97–1.69), but was significantly associated with overall mortality and death with functioning graft (DWFG) (HR overall: 1.81, 95% CI 1.36–2.39; HR DWFG: 1.59 95% CI 1.05–2.38). In this cohort, KTR with PTDM being treated with glucose‐lowering medication at 12 months experienced significantly shorter overall survival and survival with functioning graft.
BACKGROUNDUnited 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.
METHODSWe 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.
RESULTSThere 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.
CONCLUSIONSKidney 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.
New-onset diabetes has long been recognized as a common complication of kidney transplantation, promoting cardiovascular disease, death, and graft failure. Studies in recent years have begun to ...highlight the very high posttransplantation prevalence of the prediabetic states of impaired fasting glucose and impaired glucose tolerance and the significant repercussions of these states on cardiovascular health. Therefore, the overall burden of transplant-associated hyperglycemia (TAH), which encompasses new-onset diabetes and the prediabetic states, is far greater than previously appreciated. The kidney transplant population is predisposed to insulin resistance and to additional insults of hypertension and hyperlipidemia that, together with hyperglycemia, compose the metabolic syndrome and promote atherosclerosis. When recipients with an underlying, frequently nonmodifiable predisposition to glucose dysregulation encounter transplant-specific, often modifiable, diabetogenic exposures, TAH manifests. Aggressive screening will effectively detect TAH, whereas risk factor modification, lifestyle intervention, and, when appropriate, drug therapy may decrease its impact. Topics of future investigation should include the use of emerging diabetes therapies and avenues for the prevention and reversal of TAH.
The relationship between commonly occurring genetic variants (G1 and G2) in the APOL1 gene in African Americans and different disease traits, such as kidney disease, cardiovascular disease, and ...pre-eclampsia, remains the subject of controversy. Here we took a genotype-first approach, a phenome-wide association study, to define the spectrum of phenotypes associated with APOL1 high-risk variants in 1,837 African American participants of Penn Medicine Biobank and 4,742 African American participants of Vanderbilt BioVU. In the Penn Medicine Biobank, outpatient creatinine measurement-based estimated glomerular filtration rate and multivariable regression models were used to evaluate the association between high-risk APOL1 status and renal outcomes. In meta-analysis of both cohorts, the strongest phenome-wide association study associations were for the high-risk APOL1 variants and diagnoses codes were highly significant for “kidney dialysis” (odds ratio 3.75) and “end stage kidney disease” (odds ratio 3.42). A number of phenotypes were associated with APOL1 high-risk genotypes in an analysis adjusted only for demographic variables. However, no associations were detected with non-renal phenotypes after controlling for chronic/end stage kidney disease status. Using calculated estimated glomerular filtration rate -based phenotype analysis in the Penn Medicine Biobank, APOL1 high-risk status was associated with prevalent chronic/end stage kidney disease /kidney transplant (odds ratio 2.27, 95% confidence interval 1.67-3.08). In high-risk participants, the estimated glomerular filtration rate was 15.4 mL/min/1.73m2; significantly lower than in low-risk participants. Thus, although APOL1 high-risk variants are associated with a range of phenotypes, the risks for other associated phenotypes appear much lower and in our dataset are driven by a primary effect on renal disease.
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Introduction
The new kidney allocation system (KAS) prioritizes patients based on date of dialysis initiation or waitlisting, whichever is earlier. We hypothesized that this change would increase ...transplant rates for patients with prolonged pretransplant dialysis times (DT) and aimed to assess the impact of prolonged DT on post‐transplant outcomes.
Methods
We used United Network for Organ Sharing registry data to assess outcomes for patients added to the renal transplant waitlist from January 1, 1998 to December 31, 2010 and patients transplanted from January 1, 1998 to December 3, 2012.
Results
Compared with patients transplanted pre‐emptively, patients with <5 years, 5‐9 years, and ≥10 years DT had progressively decreased graft and patient survival (P < .001). The rates of short‐term complications including delayed graft function, graft loss within 30 days, and patient death within 30 days were significantly higher in cohorts with ≥10 years DT than in cohorts with less DT (P < .001).
Conclusions
Patients with pretransplant DT of ≥10 years had worse outcomes than patients pre‐emptively transplanted or transplanted with shorter DT. Durations of dialysis dependence beyond 10 years were associated with further deterioration in short‐term but not long‐term post‐transplant outcomes.
Use of deceased diabetic donor kidneys has increased over recent decades. However, scarce patient and allograft survival data are available taking into account recipient diabetes status. Here we ...performed a retrospective cohort study using data from the United Network of Organ Sharing in patients transplanted from 1994 through 2013. Multivariable Cox regression assessed recipient outcomes of 9074 diabetic vs. 152,555 nondiabetic donor kidneys. Recipients of diabetic donor kidneys had elevated rates of all-cause allograft failure (hazard ratio 1.21, 95% confidence interval 1.16–1.26) and death (1.19, 1.13–1.24) compared to recipients of kidneys from nondiabetic donors. Younger recipients of diabetic donor kidneys had worse allograft survival than older recipients of nondiabetic donor kidneys. There was significant interaction between donor and recipient diabetes status. To minimize the effect of unmeasured confounders, we used paired analyses of recipients of mate-kidneys from the same donor, with one diabetic recipient and the other nondiabetic. Among discordant recipient pairs of diabetic donor kidneys, diabetic recipients had significantly higher risk of allograft failure (1.27, 1.05–1.53) and death (1.53, 1.22–1.93) than nondiabetic recipients. After stratifying by Kidney Donor Profile Index risk category, diabetic recipients of diabetic donor kidneys continued to have worse allograft survival compared to all other patients. Thus, risks are associated with the use of diabetic donor kidneys. Understanding these risks will enable clinicians to better educate potential recipients.
In patients with recent onset renal insufficiency, the decision to perform combined kidney/liver transplantation (CKLT) vs. orthotopic liver transplantation alone (OLTa) can be difficult. We ...hypothesized that duration of renal dysfunction may correlate with creatinine elevation after liver transplantation. We retrospectively identified 69 liver transplantation patients with pretransplantation creatinine ≥1.5 mg/dL (53 OLTa, 13 CKLT). Variables analyzed were presence of hepatorenal syndrome, creatinine, Model for End‐Stage Liver Disease score, albumin, age, race, gender, cause of liver disease, diabetes mellitus, hypertension, and history of ascites, spontaneous bacterial peritonitis, variceal bleeding, hepatic encephalopathy, renal replacement therapy (RRT), and transjugular intrahepatic portosystemic shunting. Duration of pretransplantation renal dysfunction was predictive of 6‐ and 12‐month creatinine post‐OLTa. Area under the receiver operating characteristic (ROC) curve for prediction of 12‐month renal insufficiency by renal dysfunction duration was 0.71; optimal duration cutoff was 3.6 weeks. We applied a multivariable model, derived from OLTa patients, to CKLT subjects with definite or possible hepatorenal syndrome. Predicted 12‐month creatinine without renal transplantation was >2.0 mg/dL for each patient. CKLT patients as opposed to OLTa patients had longer duration of renal dysfunction (median, 18.1 vs. 2.7 weeks, P < 0.001), higher creatinine (median 4.0 versus 1.7 mg/dL, P < 0.001), and higher rate of pretransplantation RRT (62% vs. 7%, P < 0.001). Adjusting for baseline characteristics, CKLT patients had lower creatinine than OLTa patients at 6 months (P =0.15) and 12 months (P =0.01) after transplantation. In conclusion, duration, but not cause, of renal dysfunction predicts renal outcome in OLTa recipients. Prospective studies may use duration of renal dysfunction to help identify CKLT candidates. (Liver Transpl 2005;11:1048–1055.)
Hepatitis C virus (HCV) seroconversion among HCV‐uninfected transplant recipients from HCV‐infected (NAT+/Antibody+) or HCV‐exposed (NAT−/Antibody+) donors has been reported. However, the origin of ...anti‐HCV antibody and the implications of seroconversion remain unknown. We longitudinally tested plasma from HCV‐uninfected kidney (n = 31) or heart transplant recipients (n = 9) of an HCV NAT+ organ for anti‐HCV antibody (both IgG and IgM isotypes). Almost half of all participants had detectable anti‐HCV antibody at any point during follow‐up. The majority of antibody‐positive individuals became positive within 1‐3 days of transplantation, and 6 recipients had detectable antibody on the first day posttransplant. Notably, all anti‐HCV antibody was IgG, even in samples collected posttransplant day 1. Late seroconversion was uncommon (≈20%‐25% of antibody+ recipients). Early antibody persisted over 30 days in kidney recipients, whereas early antibody dropped below detection in 50% of heart recipients within 2 weeks after transplant. Anti‐HCV antibody is common in HCV‐uninfected recipients of an HCV NAT+ organ. The IgG isotype of this antibody and the kinetics of its appearance and durability suggest that anti‐HCV antibody is donor derived and is likely produced by a cellular source. Our data suggest that transfer of donor humoral immunity to a recipient may be much more common than previously appreciated.
Serologic testing of HCV‐negative transplant recipients who receive an HCV+ organ requires careful interpretation because anti‐HCV IgG, potentially of donor origin, can be detected early after transplantation.
Advancing care has markedly improved survival after kidney transplantation, leaving patients susceptible to the effects of chronic transplant-associated morbidities. New-onset diabetes mellitus ...(NODM) is common in kidney recipients, threatening health and longevity by predisposing to microvascular and cardiovascular disease and by reducing graft survival. A strong rationale therefore exists for the aggressive treatment of NODM in kidney recipients to limit these complications. Screening for diabetes should be systematic and should span the pre- and posttransplantation periods. Once NODM is diagnosed in the kidney transplant patient, a comprehensive plan of therapy should be used to achieve treatment targets. As in the general population, treatment includes lifestyle modification and drug therapy as needed, but transplant-specific factors add complexity to the care of kidney recipients. Among these, minimizing immunosuppression-related toxicity without compromising graft outcomes is of paramount importance. Preexisting allograft functional impairment and the potential for significant interactions with immunosuppressive agents mandate that the expanding armamentarium of hypoglycemic agents be used with care. A team-oriented treatment approach that capitalizes on the collective expertise of transplant physicians, diabetologists, nurse-educators, and dieticians will optimize both glycemic control and the overall health of hyperglycemic kidney recipients.
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