Faculty Bibliography

BACKGROUND:Frailty predicts adverse post-kidney transplant (KT) outcomes, yet the impact of frailty assessment on center-level outcomes remains unclear. We sought to test whether transplant centers assessing frailty as part of clinical practice have better pre- and post-KT outcomes in all adult patients (≥18 years) and older patients (≥65 years). METHODS:In a survey of US transplant centers (11/2017-4/2018), 132 (response rate = 65.3%) centers reported their frailty assessment practices (frequency and specific tool) at KT evaluation and admission. Assessment frequency was categorized as never, sometime, and always; type of assessment tool was categorized as none, validated (for post-KT risk prediction), and any other tool. Center characteristics and clinical outcomes for adult patients during 2017-2019 were gleaned from the transplant national registry (Scientific Registry of Transplant Recipients). Poisson regression was used to estimate incidence rate ratios (IRRs) of waitlist outcomes (waitlist mortality, transplantation) in candidates and IRRs of post-KT outcomes (all-cause mortality, death-censored graft loss) in recipients by frailty assessment frequency. We also estimated IRRs of waitlist outcomes by type of assessment tool at evaluation. All models were adjusted for case mix and center characteristics. RESULTS:Assessing frailty at evaluation was associated with lower waitlist mortality rate (always IRR = 0.91,95%CI:0.84-0.99; sometimes = 0.89,95%CI:0.83-0.96) and KT rate (always = 0.94,95%CI:0.91-0.97; sometimes = 0.88,95%CI:0.85-0.90); the associations with waitlist mortality rate (always = 0.86,95%CI:0.74-0.99; sometimes = 0.83,95%CI:0.73-0.94) and KT rate (always = 0.82,95%CI:0.77-0.88; sometimes = 0.92,95%CI:0.87-0.98) were stronger in older patients. Furthermore, using validated (IRR = 0.90,95%CI:0.88-0.92) or any other tool (IRR = 0.90,95%CI:0.87-0.93) at evaluation was associated lower KT rate, while only using a validated tool was associated with lower waitlist mortality rate (IRR = 0.89,95%CI:0.83-0.96), especially in older patients (IRR = 0.82,95%CI:0.72-0.93). At admission for KT, always assessing frailty was associated with a lower graft loss rate (IRR = 0.71,95%CI:0.54-0.92) but not with mortality (IRR = 0.93,95%CI:0.76-1.13). CONCLUSIONS:Assessing frailty at evaluation is associated with lower KT rate, while only using a validated frailty assessment tool is associated with better survival, particularly in older candidates. Centers always assessing frailty at admission are likely to have better graft survival rates. Transplant centers may utilize validated frailty assessment tools to secure KT access for appropriate candidates and to better allocate health care resources for patients identified as frail, particularly for older patients.

BACKGROUND:In older adults (≥65) access to and outcomes following kidney transplantation (KT) have improved over the past three decades. It is unknown if there were parallel trends in re-KT. We characterized the trends, changing landscape, and outcomes of re-KT in older adults. METHODS:Among the 44,149 older kidney-only recipients (1995-2016) in the Scientific Registry of Transplant Recipients, we identified 1,743 who underwent re-KT. We analyzed trends and outcomes (mortality, death-censored graft failure [DCGF]) by eras (1995-2002, 2003-2014 and 2015-2016) that were defined by changes to the ECD and KDPI policies. RESULTS:Among all older kidney-only recipients during 1995-2002, 2003-2014, 2015-2016 the proportion that were re-KTs increased from 2.7%-4.2%-5.7% p<0.001, respectively. Median age at re-KT (67-68-68, p=0.04), years on dialysis after graft failure (1.4-1.5-2.2, p=0.003), donor age (40.0-43.0-43.5, p=0.04), proportion with PRA 80-100 (22.0%-32.7%-48.7%, p<0.001) and donations after circulatory death (1.1%-13.4%-19.5%, p<0.001) have increased. Despite this, the 3-year cumulative incidence for mortality (22.3%-19.1%-11.5%, p=0.002) and DCGF (13.3%-10.0%-5.1%, p=0.01) decreased over time. Compared with deceased donor re-transplant recipients during 1995-2002, those during 2003-2014 and 2015-2016 had lower mortality hazard (aHR=0.78, 95%CI:0.63-0.86 and aHR=0.55, 95%CI:0.35-0.86, respectively). These declines were noted but not significant for DCGF and in living donor re-KTs. CONCLUSIONS:In older re-transplant recipients, outcomes have improved significantly over time despite higher risk profiles; yet they represent a fraction of the KTs performed. Our results support increasing access to re-KT in older adults; however, approaches to guide the selection and management in those with graft failure need to be explored.

Kidney transplantation (KT) experts did not support the use of subjective unintentional weight loss to measure shrinking in the physical frailty phenotype (PFP); a clinically feasible and predictive measure of shrinking is needed. To test whether unintentional weight loss could be replaced by an assessment of sarcopenia using existing CT scans, we performed a prospective cohort study of adult KT recipients with original PFP (oPFP) measured at admission (December 2008-February 2020). We ascertained sarcopenia by calculating skeletal muscle index from available, clinically obtained CTs within 1-year pre-KT (male < 50 cm² /m² ; female < 39 cm² /m² ) and combined it with the original four components to determine new PFP (nPFP) scores. Frailty was classified by frailty score: 0: non-frail; 1-2: pre-frail; ≥3: frail. Mortality and graft loss hazard ratios (HRs) were estimated using adjusted Cox proportional hazard models. Model discrimination was quantified using Harrell's C-statistic. Among 1113 recipients, 18.6% and 17.1% were frail by oPFP and nPFP, respectively. Compared to non-frail recipients, frail patients by either PFP had higher risks of mortality (oPFP HR = 1.67, 95% CI: 1.07-2.62, C = 0.710; nPFP HR = 1.68, 95% CI: 1.06-2.66, C = 0.710) and graft loss (oPFP HR = 1.67, 95% CI: 1.17-2.40, C = 0.631; nPFP HR = 1.66, 95% CI: 1.15-2.40, C = 0.634) with similar discriminations. oPFP and nPFP are equally useful in risk prediction for KT recipients; oPFP may aid in screening patients for pre-KT interventions, while nPFP may assist in nuanced clinical decision-making.

Background/UNASSIGNED:Posttransplant diabetes (PTD), a major complication after kidney transplantation (KT), is often attributable to immunosuppression. The risk of PTD may increase with more potent steroid maintenance and older recipient age. Methods/UNASSIGNED:Using United States Renal Data System data, we studied 12 488 adult first-time KT recipients (2010-2015) with no known pre-KT diabetes. We compared the risk of PTD among recipients who underwent early steroid withdrawal (ESW) versus continued steroid maintenance (CSM) using Cox regression with inverse probability weighting to adjust for confounding. We tested whether the risk of PTD resulting from ESW differed by recipient age (18-29, 30-54, and ≥55 y). Results/UNASSIGNED:). Conclusions/UNASSIGNED:The beneficial association of ESW with decreased PTD was more pronounced among recipients aged ≥55, supporting an age-specific assessment of the risk-benefit balance regarding ESW.

Rationale & Objective/UNASSIGNED:Posttransplant diabetes mellitus (DM) after kidney transplantation increases morbidity and mortality, particularly in older and obese recipients. We aimed to examine the impact of immunosuppression selection on the risk of posttransplant DM among both older and obese kidney transplant recipients. Study Design/UNASSIGNED:Retrospective database study. Setting & Participants/UNASSIGNED:Kidney-only transplant recipients aged ≥18 years from 2005 to 2016 in the United States from US Renal Data System records, which integrate Organ Procurement and Transplantation Network/United Network for Organ Sharing records with Medicare billing claims. Exposures/UNASSIGNED:Various immunosuppression regimens in the first 3 months after transplant. Outcomes/UNASSIGNED:Development of DM >3 months-to-1 year posttransplant. Analytical Approach/UNASSIGNED:We used multivariable Cox regression to compare the incidence of posttransplant DM by immunosuppression regimen with the reference regimen of thymoglobulin (TMG) or alemtuzumab (ALEM) with tacrolimus + mycophenolic acid + prednisone using inverse propensity weighting. Results/UNASSIGNED:(aHR, 0.63; 95% CI, 0.46-0.87). Limitations/UNASSIGNED:Retrospective study and lacked data on immunosuppression levels. Conclusions/UNASSIGNED:The beneficial impact of steroid avoidance using tacrolimus on posttransplant DM appears to differ by patient age and induction regimen.

BACKGROUND:Cognitive impairment is common among persons with chronic kidney disease (CKD) due in part to reduced kidney function. Given that physical activity (PA) is known to mitigate cognitive decline, we examined whether associations between CKD stage and global/domain-specific cognitive function differs by PA. METHODS:We leveraged 3,223 participants (aged≥60years) enrolled in National Health and Nutrition Examination Survey (NHANES,2011-2014), with at least one measure of objective cognitive function (immediate recall [CERAD-WL], delayed recall [CERAD-DR], verbal fluency [AF], executive function/processing speed [DSST], global [average of 4 tests]) or self-perceived memory decline [SCD]. We quantified the association between CKD stage (no CKD: eGFR≥60 mL/min/1.73m2 and albuminuria(ACR)<30 mg/g; stage G1-G3: eGFR≥60mL/min/1.73m2 and ACR≥30mg/g or eGFR 30-59mL/min/1.73m2; stage G4-G5: eGFR<30mL/min/1.73m2) and cognitive function using linear regression (objective measures) and logistic regression (SCD), accounting for sampling weights for nationally-representative estimates. We tested whether associations differed by physical activity (Global Physical Activity Questionnaire, high PA≥600MET*min/week vs. low PA<600MET*min/week) using a Wald test. RESULTS:Among NHANES participants, 34.9% had CKD stageG1-G3, 2.6% had stageG4-G5, and 50.7% had low PA. CKD stageG4-G5 was associated with lower global cognitive function (difference = -0.38SD, 95%CI:-0.62,-0.15). This association differed by PA (pinteraction = 0.01). Specifically, among participants with low PA, those with CKD stageG4-G5 had lower global cognitive function (difference = -0.57SD, 95%CI: -0.82,-0.31) compared to those without CKD. Among those with high PA, no difference was found (difference = 0.10SD, 95%CI:-0.29,0.49). Similarly, CKD stage was only associated with immediate recall, verbal fluency, executive function, and processing speed among those with low PA; no associations were observed for delayed recall or self-perceived memory decline. CONCLUSIONS:CKD is associated with lower objective cognitive function among those with low, but not high PA. Clinicians should consider screening older patients with CKD who have low PA for cognitive impairment and encourage them to meet PA guidelines.

Repeat kidney transplantation (re-KT) is the preferred treatment for patients with graft failure. Changing allocation policies, widening the risk profile of recipients, and improving dialysis care may have altered the survival benefit of a re-KT. We characterized trends in re-KT survival benefit over 3 decades and tested whether it differed by age, race/ethnicity, sex, and panel reactive assay (PRA). By using the Scientific Registry of Transplant Recipient data, we identified 25 419 patients who underwent a re-KT from 1990 to 2019 and 25 419 waitlisted counterfactuals from the same year with the same waitlisted time following graft failure. In the adjusted analysis, a re-KT was associated with a lower risk of death (adjusted hazard ratio [aHR] = 0.63; 95% confidence interval [CI], 0.61-0.65). By using the 1990-1994 era as a reference (aHR = 0.77; 95% CI, 0.69-0.85), incremental improvements in the survival benefit were noted (1995-1999: aHR = 0.72; 95% CI, 0.67-0.78: 2000-2004: aHR = 0.59; 95% CI, 0.55-0.63: 2005-2009: aHR = 0.59; 95% CI, 0.56-0.63: 2010-2014: aHR = 0.57; 95% CI, 0.53-0.62: 2015-2019: aHR = 0.64; 95% CI, 0.57-0.73). The survival benefit of a re-KT was noted in both younger (age = 18-64 years: aHR = 0.63; 95% CI, 0.61-0.65) and older patients (age ≥65 years: aHR = 0.66; 95% CI, 0.58-0.74; P_interaction = .45). Patients of all races/ethnicities demonstrated similar benefits with a re-KT. However, it varied by the sex of the recipient (female patients: aHR = 0.60; 95% CI, 0.56-0.63: male patients: aHR = 0.66; 95% CI, 0.63-0.68; P_interaction = .004) and PRA (0-20: aHR = 0.69; 95% CI, 0.65-0.74: 21-80: aHR = 0.61; 95% CI, 0.57-0.66; P_interaction = .02; >80: aHR = 0.57; 95% CI, 0.53-0.61; P_interaction< .001). Our findings support the continued practice of a re-KT and efforts to overcome the medical, immunologic, and surgical challenges of a re-KT.

Purpose of Review: Irreversible cognitive impairment is a contraindication to liver transplantation, but growing evidence suggests many etiologies of liver disease have cognitive manifestations independent of hepatic encephalopathy and with variable reversibilities. Recent Findings: While cognitive sequelae of chronic alcohol use have long been recognized, cognitive dysfunction associated with other liver disease etiologies such as chronic hepatitis C infection, non-alcoholic fatty liver disease, and primary biliary cirrhosis has been recognized. While mechanisms vary and are incompletely understood, inflammation appears to play a central role in causing cognitive dysfunction associated with these diseases. Summary: Further research is needed to determine optimal cognitive assessment tools for patients with liver disease, identify patients at greatest risk for cognitive impairment, determine which elements of cognitive impairment are reversible, and identify effective therapies. This information will inform neurologic evaluation at time of liver transplant evaluation as well as expectations for neurologic recovery post-transplant.

BACKGROUND:Early post-kidney transplantation (KT) changes in physiology, medications, and health stressors likely impact body mass index (BMI) and likely impact all-cause graft loss and mortality. METHODS:/month) using adjusted Cox proportional hazards models. RESULTS:), BMI increase was associated with higher all-cause mortality (aHR = 1.09, 95% CI: 1.05-1.14), all-cause graft loss (aHR = 1.05, 95% CI: 1.01-1.09), and mortality with functioning graft (aHR = 1.10, 95% CI: 1.05-1.15) risks, but not death-censored graft loss risks, relative to stable weight. Among individuals without obesity, BMI increase was associated with lower all-cause graft loss (aHR = .97, 95% CI: .95-.99) and death-censored graft loss (aHR = .93, 95% CI: .90-.96) risks, but not all-cause mortality or mortality with functioning graft risks. CONCLUSIONS:BMI increases in the 3 years post-KT, then decreases in years 3-5. BMI loss in all adult KT recipients and BMI gain in those with obesity should be carefully monitored post-KT.