Statins in Kidney Transplant Recipients: Usage, All-Cause Mortality, and Interactions with Maintenance Immunosuppressive Agents.

SIGNIFICANCE STATEMENT: Cardiovascular diseases account for 32% of deaths among kidney transplant recipients. Statin therapy is common in this population. However, its effect on mortality prevention remains unclear among kidney transplant recipients, whose clinical risk profile might be unique because of concomitant immunosuppressive therapy. In this national study of 58,264 single-kidney transplant recipients, statin use was associated with a 5% decrease in mortality. More importantly, this protective association was stronger among those who used a mammalian target of rapamycin (mTOR) inhibitor for immunosuppression (27% decrease in mTOR inhibitor users versus 5% in nonusers). Our results suggest that statin therapy may reduce mortality in kidney transplant recipients and that the strength of this protective association may vary by immunosuppression regimen. BACKGROUND: Cardiovascular diseases are the leading cause of mortality in kidney transplant (KT) recipients, accounting for 32% of deaths. Statins are widely used in KT recipients, but effectiveness for preventing mortality remains unclear in this population, especially because of interaction between statins and immunosuppressive agents. We analyzed a national cohort to assess the real-world effectiveness of statins for reducing all-cause mortality in KT recipients. METHODS: We studied statin use and mortality among 58,264 adults (18 years or older) who received single kidneys between 2006 and 2016 and had Medicare part A/B/D. Statin use was ascertained from Medicare prescription drug claims and deaths from Center for Medicare and Medicaid Services records. We estimated the association of statin use with mortality using multivariable Cox models, with statin use as a time-varying exposure and immunosuppression regimen as effect modifiers. RESULTS: Statin use increased from 45.5% at KT to 58.2% at 1-year post-KT to 70.9% at 5-year post-KT. We observed 9785 deaths over 236,944 person-years. Overall, statin use was significantly associated with lower mortality (adjusted hazard ratio [aHR], 0.95; 95% confidence interval [CI], 0.90 to 0.99). The strength of this protective association varied by calcineurin inhibitor use (among tacrolimus users, aHR, 0.97; 95% CI, 0.92 to 1.03 versus among calcineurin nonusers, aHR, 0.72; 95% CI, 0.60 to 0.87; interaction P =0.002), mammalian target of rapamycin (mTOR) inhibitor use (among mTOR inhibitor users, aHR, 0.73; 95% CI, 0.57 to 0.92 versus among nonusers, aHR, 0.95; 95% CI, 0.91 to 1.00; interaction P =0.03), and mycophenolate use (among mycophenolate users, aHR, 0.96; 95% CI, 0.91 to 1.02 versus among nonusers, aHR, 0.76; 95% CI, 0.64 to 0.89; interaction P =0.002). CONCLUSION: Real-world evidence supports statin therapy for reducing all-cause mortality in KT recipients. Effectiveness might be greater when combined with mTOR inhibitor-based immunosuppression.

Trends in the survival benefit of repeat kidney transplantation over the past 3 decades.

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; Pinteraction = .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; Pinteraction = .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; Pinteraction = .02; >80: aHR = 0.57; 95% CI, 0.53-0.61; Pinteraction< .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.

Secondary hyperparathyroidism (CKD-MBD) treatment and the risk of dementia.

BACKGROUND: Elevated parathyroid hormone (PTH) levels have been reported as a potential risk factor for cognitive impairment. Compared with the general population, older adults with end-stage renal disease (ESRD) who are frequently affected by secondary hyperparathyroidism (SHPT) are at increased risk of developing dementia. The main objective of our study was to evaluate if the risk of dementia in older (age ≥66 years) ESRD patients differed if they were treated for SHPT. METHODS: Using the United States Renal Data System and Medicare claims, we identified 189 433 older adults without a diagnosis of dementia, who initiated dialysis between 2006 and 2016. SHPT treatment was defined as the use of vitamin D analogs, phosphate binders, calcimimetics or parathyroidectomy. We quantified the association between treated SHPT and incident dementia during dialysis using a multivariable Cox proportional hazards model with inverse probability weighting, considering SHPT treatment as a time-varying exposure. RESULTS: Of 189 433 older ESRD adults, 92% had a claims diagnosis code of SHPT and 123 388 (65%) were treated for SHPT. The rate of incident dementia was 6 cases per 100 person-years among SHPT treated patients compared with 11 cases per 100 person-years among untreated patients. Compared with untreated SHPT patients, the risk of dementia was 42% lower [adjusted hazard ratio (aHR) = 0.58, 95% confidence interval (CI): 0.56-0.59] among SHPT treated patients. The magnitude of the beneficial effect of SHPT treatment differed by sex (Pinteraction = .02) and race (Pinteraction ≤ .01), with females (aHR = 0.56, 95% CI: 0.54-0.58) and those of Asian (aHR = 0.51, 95% CI: 0.46-0.57) or Black race (aHR = 0.51, 95% CI: 0.48-0.53) having a greatest reduction in dementia risk. CONCLUSION: Receiving treatment for SHPT was associated with a lower risk of incident dementia among older patients with ESRD. This work provides additional support for the treatment of SHPT in older ESRD patients.

Comparing outcomes of third and fourth kidney transplantation in older and younger patients.

Performing third or fourth kidney transplantation (3KT and 4KT) in older patients is rare due to surgical and immunologic challenges. We aimed to analyze and compare the outcomes of younger (18-64 years) and older (≥65 years) recipients of 3KT and 4KT. Between 1990 and 2016, we identified 5816 recipients of 3KTs (153 were older) and 886 recipients of 4KTs (18 were older). The incidences of delayed graft function (24.3% vs. 24.8%, p = .89), primary non-function (3.2% vs. 1.3%, p = .21), 1-year acute rejection (18.6% vs. 14.8%, p = .24), and 5-year death censored graft failure (DCGF) (24.8% vs. 17.9%, p = .06) were not different between younger and older recipients of 3KT. However, 5-year mortality was higher in older recipients (14.0% vs. 33.8%, p < .001) which remained significant after adjustment (aHR = 3.21, 95% CI: 2.59-3.99). Similar patterns were noted in the 4KT cohort. When compared with waitlisted patients, 3KT and 4KT are associated with a lower risk of mortality; aHR = 0.37, 95% CI: 0.33-0.41 and aHR = 0.31, 95% CI: 0.24-0.41, respectively. This survival benefit did not differ by recipient age (younger vs. older, p for interaction = 3KT: .49 and 4KT: .58). In the largest cohort described to date, we report that there is a survival benefit of 3KT and 4KT even among older patients. Although a highly selected cohort, our results support improving access to 3KT and 4KT.

Ambient air pollution and posttransplant outcomes among kidney transplant recipients.

Fine particulate matter (PM2.5 ), a common form of air pollution which can induce systemic inflammatory response, is a risk factor for adverse health outcomes. Kidney transplant (KT) recipients are likely vulnerable to PM2.5 due to comorbidity and chronic immunosuppression. We sought to quantify the association between PM2.5 and post-KT outcomes. For adult KT recipients (1/1/2010-12/31/2016) in the Scientific Registry of Transplant Recipients, we estimated annual zip-code level PM2.5 concentrations at the time of KT using NASA's SEDAC Global PM2.5 Grids. We determined the associations between PM2.5 and delayed graft function (DGF) and 1-year acute rejection using logistic regression and death-censored graft failure (DCGF) and mortality using Cox proportional hazard models. All models were adjusted for sociodemographics, recipient, transplant, and ZIP code level confounders. Among 87 233 KT recipients, PM2.5 was associated with increased odds of DGF (OR = 1.59; 95% CI: 1.48-1.71) and 1-year acute rejection (OR = 1.31; 95% CI: 1.17-1.46) and increased risk of all-cause mortality (HR = 1.15; 95% CI: 1.07-1.23) but not DCGF (HR = 1.05; 95% CI: 0.97-1.51). In conclusion, PM2.5 was associated with higher odds of DGF and 1-year acute rejection and elevated risk of mortality among KT recipients. Our study highlights the importance of considering environmental exposure as risk factors for post-KT outcomes.

Induction immunosuppression and the risk of incident malignancies among older and younger kidney transplant recipients: A prospective cohort study.

BACKGROUND: Older (≥65) KT recipients differ from their younger counterparts in their immune response to immunosuppression (IS) and may have a different risk of malignancy after receiving induction. METHODS: We identified 66 700 adult KT recipients treated with anti-thymocyte globulin (ATG) (n = 40 443) or interleukin-2 receptor antagonist (IL-2RA) (n = 26 327) induction (1/1/1999-12/31/2014) using USRDS/Medicare data. We estimated the risk of first-diagnosed post-KT malignancy associated with induction (ATG vs. IL-2RA) using Cox proportional hazard models. We then tested whether these risks differed between older and younger recipients (Wald test for interaction). Models incorporated inverse probability of treatment weights to adjust for confounders. RESULTS: The 3-year cumulative incidences of any diagnosed malignancy were 11.5%. ATG was associated with a higher malignancy risk (HR = 1.12, 95%CI:1.06-1.18). This association differed (pinteraction  = 0.04) between younger (HR = 1.12, 95%CI:1.06-1.18) and older recipients (HR = 1.03, 95%CI:0.96-1.09). ATG was also associated with higher risk of skin (HR = 1.18, 95%CI:1.08-1.29), lung (HR = 1.24, 95%CI:1.05-1.47), and ovary malignancies (HR = 1.94, 95%CI:1.08-3.48). However, only the association of ATG with post-KT skin malignancy differed (pinteraction  = 0.01) between younger (HR = 1.18; 95%CI:1.08-1.29) and older (HR = 1.01; 95%CI:0.93-1.09) recipients. CONCLUSIONS: Compared with IL-2RA induction, ATG was associated with elevated post-KT malignancy risk but only among younger recipients. Transplant centers may need to tailor induction IS for younger recipients to mitigate malignancy risk.

Age Disparities in Access to First and Repeat Kidney Transplantation.

BACKGROUND: Evidence suggests that older patients are less frequently placed on the waiting list for kidney transplantation (KT) than their younger counterparts. The trends and magnitude of this age disparity in access to first KT and repeat KT (re-KT) remain unclear. METHODS: Using the US Renal Data System, we identified 2 496 743 adult transplant-naive dialysis patients and 110 338 adult recipients with graft failure between 1995 and 2018. We characterized the secular trends of age disparities and used Cox proportional hazard models to compare the chances of listing and receiving first KT versus re-KT by age (18-64 y versus ≥65 y). RESULTS: Older transplant-naive dialysis patients were less likely to be listed (adjusted hazard ratio [aHR] = 0.18; 95% confidence interval [CI], 0.17-0.18) and receive first KT (aHR = 0.88; 95% CI, 0.87-0.89) compared with their younger counterparts. Additionally, older patients with graft failure had a lower chance of being listed (aHR = 0.40; 95% CI, 0.38-0.41) and receiving re-KT (aHR = 0.76; 95% CI, 0.72-0.81). The magnitude of the age disparity in being listed for first KT was greater than that for re-KT ( Pinteraction < 0.001), and there were no differences in the age disparities in receiving first KT or re-KT ( Pinteraction = 0.13). Between 1995 and 2018, the age disparity in listing for first KT reduced significantly ( P < 0.001), but the age disparities in re-KT remained the same ( P = 0.16). CONCLUSIONS: Age disparities exist in access to both first KT and re-KT; however, some of this disparity is attenuated among older adults with graft failure. As the proportion of older patients with graft failure rises, a better understanding of factors that preclude their candidacy and identification of appropriate older patients are needed.

Gabapentin, Concomitant Prescription of Opioids, and Benzodiazepines among Kidney Transplant Recipients.

BACKGROUND: Gabapentinoids, commonly used for treating neuropathic pain, may be misused and coprescribed with opioid and benzodiazepine, increasing the risk of mortality and dependency among kidney transplant recipients. METHODS: We identified adult kidney transplant recipients who enrolled in Medicare Part D in 2006-2017 using the United States Renal Data System/Medicare claims database. We characterized recipients' post-transplant concomitant prescription of gabapentinoids, opioids, and benzodiazepine stratified by transplant year and recipient factors (age, sex, race, and diabetes). We investigated whether concomitant prescriptions were associated with postkidney transplant mortality using Cox regression. Models incorporated inverse probability weighting to adjust for confounders. RESULTS: Among 63,359 eligible recipients, 13% of recipients filled at least one gabapentinoid prescription within 1 year after kidney transplant. The prevalence of gabapentinoid prescriptions increased by 70% over the study period (16% in 2017 versus 10% in 2006). Compared with nonusers, gabapentinoids users were more likely to have diabetes (55% versus 37%) and obesity (46% versus 34%). Of the 8509 recipients with gabapentinoid prescriptions, 45% were coprescribed opioids, 7% were coprescribed benzodiazepines, and 3% were coprescribed both opioids and benzodiazepines. Compared with no study prescriptions, gabapentinoid monotherapy (adjusted hazard ratio [aHR]=1.25; 95% confidence interval [CI], 1.16 to 1.32) and combination therapy (gabapentinoids and opioids [aHR=1.49; 95% CI, 1.39 to 1.60], gabapentinoids and benzodiazepines [aHR=1.46; 95% CI, 1.03 to 2.08], and coprescribing all three [aHR=1.88; 95% CI, 1.18 to 2.98]) were all associated with a higher risk of postkidney transplant mortality. CONCLUSIONS: Gabapentinoid coprescription with both benzodiazepines and opioids among kidney transplant recipients increased over time. Kidney transplant recipients prescribed gabapentinoids had a higher risk of post-transplant mortality, and the risk was higher with opioids or benzodiazepine coprescription.

Increasing rates of parathyroidectomy to treat secondary hyperparathyroidism in dialysis patients with Medicare coverage.

BACKGROUND: Secondary hyperparathyroidism affects nearly all patients with renal failure on dialysis. Medical treatment of secondary hyperparathyroidism has considerably evolved over the past 2 decades, with parathyroidectomy reserved for severe cases. The primary objective of our study was to understand how trends in medical treatments affected parathyroidectomy rates in patients with secondary hyperparathyroidism on dialysis. METHODS: We used the United States Renal Data System to identify 379,835 adult patients (age ≥18) who were on maintenance dialysis in the United States between 2006 and 2016 with Medicare as the primary payor and ascertained treatment for secondary hyperparathyroidism. Adjusted rate ratios for rates of parathyroidectomy were calculated using multivariable-adjusted Poisson regression. RESULTS: Of 379,835 secondary hyperparathyroidism patients, 4,118 (1.1%) underwent parathyroidectomy, 39,835 (10.5%) received cinacalcet, 243,522 (64.1%) received phosphate binders, 17,571 (4.6%) received vitamin D analogs, and 86,899 (22.9%) received no treatment during the 10 years of follow-up. Over the entire study period, there was a 3.5-fold increase in the use of calcimimetics and a 3.4-fold increase in rates of parathyroidectomy. Compared to 2006 through 2009, utilization of parathyroidectomy increased 52% (adjusted rate ratio = 1.52, 95% confidence interval: 1.39-1.65) between 2010 and 2013 and by 106% (adjusted rate ratio = 2.06, 95% confidence interval: 1.90-2.24) between 2014 and 2016. The greatest increase in parathyroidectomy utilization occurred in younger patients (age 18-64 years), Black patients, female patients, those living in higher poverty neighborhoods, those listed for kidney transplant, and those who live in the Southern region of the United States. CONCLUSION: Despite the evolution of medical treatments and an increase in the use of calcimimetics to treat secondary hyperparathyroidism, parathyroidectomy rates have been steadily increasing among dialysis patients with Medicare coverage.

Evolving Trends in Risk Profiles and Outcomes in Older Adults Undergoing Kidney Retransplantation.

BACKGROUND: In older adults (≥65), access to and outcomes following kidney transplantation (KT) have improved over the past 3 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 1743 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 expanded criteria donors and Kidney Donor Profile Index 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% to 4.2% to 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 panel reactive antibody 80-100 (22.0%-32.7%-48.7%, P < 0.001), and donation after circulatory death (1.1%-13.4%-19.5%, P < 0.001) have increased. Despite this, the 3-y 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 retransplant recipients during 1995-2002, those during 2003-2014 and 2015-2016 had lower mortality hazard (aHR = 0.78, 95% confidence interval, 0.63-0.86 and aHR = 0.55, 95% confidence interval, 0.35-0.86, respectively). These declines were noted but not significant for DCGF and in living donor re-KTs. CONCLUSIONS: In older retransplant 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.

Effect of Early Steroid Withdrawal on Posttransplant Diabetes Among Kidney Transplant Recipients Differs by Recipient Age.

BACKGROUND: 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: 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: Of 12 488, 28.3% recipients received ESW. The incidence rate for PTD was 13 per 100 person-y and lower among recipients who received ESW (11 per 100 person-y in ESW; 14 per 100 person-y in CSM). Overall, ESW was associated with lower risk of PTD compared with CSM (adjusted hazard ratio [aHR] = 0.720.790.86), but the risk differed by recipient age (P interaction = 0.09 for comparison between recipients aged 18-29 and those aged 30-54; P interaction = 0.01 for comparison between recipients aged 18-29 and those aged ≥55). ESW was associated with lower risk of PTD among recipients aged ≥55 (aHR = 0.620.710.81) and those aged 30-54 (aHR = 0.730.830.95), but not among recipients aged 18-29 (aHR = 0.811.181.72). Although recipients who received ESW had a higher risk of acute rejection across the age groups (adjusted odds ratio = 1.011.171.34), recipients with no PTD had a lower risk of mortality (aHR = 0.580.660.74). CONCLUSIONS: 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.

Kidney Transplantation, Immunosuppression and the Risk of Fracture: Clinical and Economic Implications.

Rationale & Objective: Disorders of bone and mineral metabolism frequently develop with advanced kidney disease, may be exacerbated by immunosuppression after kidney transplantation, and increase the risk of fractures. Study Design: Retrospective database study. Setting & Participants: Kidney-only transplant recipients aged ≥18 years from 2005 to 2016 in the United States captured in US Renal Data System records, which integrate Organ Procurement and Transplantation Network/United Network for Organ Sharing records with Medicare billing claims. Exposures: Various immunosuppression regimens in the first 3 months after kidney transplantation. Outcomes: The development of fractures, as ascertained using diagnostic codes on Medicare billing claims. Analytical Approach: We used multivariable Cox regression with inverse propensity weighting to compare the incidence of fractures >3 months-to-3 years after kidney transplantation associated with various immunosuppression regimens compared to a reference regimen of antithymocyte globulin (TMG) or alemtuzumab (ALEM) with tacrolimus + mycophenolic acid + prednisone using inverse probability treatment weighting. Results: Overall, fractures were identified in 7.5% of kidney transplant recipients (women, 8.8%; men, 6.7%; age < 55 years, 5.9%; age ≥ 55 years, 9.3%). In time-varying regression, experiencing a fracture was associated with a substantially increased risk of subsequent death within 3 months (adjusted hazard ratio [aHR], 3.06; 95% confidence interval [CI], 2.45-3.81). Fractures were also associated with increased Medicare spending (first year: $5,122; second year: $10,890; third year: $11,083; [P < 0.001]). Induction with TMG or ALEM and the avoidance or early withdrawal of steroids significantly reduced the risk of fractures in younger (aHR, 0.63; 95% CI, 0.54-0.73) and older (aHR, 0.83; 95% CI, 0.74-0.94) patients. The avoidance or early withdrawal of steroids with any induction was associated with a reduced risk of fractures in women. Limitations: This was a retrospective study which lacked data on immunosuppression levels. Conclusions: Fractures after kidney transplantation are associated with significantly increased mortality risk and costs. The early avoidance or early withdrawal of steroids after induction with TMG or ALEM reduces the risk of fractures after kidney transplantation and should be considered for patients at high-risk of this complication, including older adults and women.

Posttransplant Diabetes Mellitus and Immunosuppression Selection in Older and Obese Kidney Recipients.

RATIONALE & OBJECTIVE: 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: Retrospective database study. SETTING & PARTICIPANTS: 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: Various immunosuppression regimens in the first 3 months after transplant. OUTCOMES: Development of DM >3 months-to-1 year posttransplant. ANALYTICAL APPROACH: 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: 12.7% of kidney transplant recipients developed posttransplant DM with higher incidences in older (≥55 years vs <55 years: 16.7% vs 10.1%) and obese (body mass index [BMI] ≥ 30 kg/m2 vs BMI < 30 kg/m2: 17.1% vs 10.9%) patients. The incidence of posttransplant DM was lower with steroid avoidance [TMG/ALEM + no prednisone (8.4%) and IL2rAb + no prednisone (9.7%)] than TMG/ALEM with triple therapy (13.1%). After adjustment for donor and recipient characteristics, TMG/ALEM with steroid avoidance was beneficial for all groups [age < 55 years: adjusted HR (aHR), 0.63 (95% confidence interval [CI], 0.54-0.72); age ≥ 55 years: aHR, 0.69 (95% CI, 0.60-0.79); BMI < 30 kg/m2: aHR, 0.69 (95% CI, 0.60-0.78); BMI ≥ 30 kg/m2: aHR, 0.67 (95% CI, 0.57-0.79)]. However, IL2rAb with steroid avoidance was beneficial only for older patients (aHR, 0.76; 95% CI, 0.58-0.99) and for those with BMI < 30 kg/m2 (aHR, 0.63; 95% CI, 0.46-0.87). LIMITATIONS: Retrospective study and lacked data on immunosuppression levels. CONCLUSIONS: The beneficial impact of steroid avoidance using tacrolimus on posttransplant DM appears to differ by patient age and induction regimen.

Association Between Treatment of Secondary Hyperparathyroidism and Posttransplant Outcomes.

BACKGROUND: Secondary hyperparathyroidism (SHPT) affects nearly all patients on maintenance dialysis therapy. SHPT treatment options have considerably evolved over the past 2 decades but vary in degree of improvement in SHPT. Therefore, we hypothesize that the risks of adverse outcomes after kidney transplantation (KT) may differ by SHPT treatment. METHODS: Using the Scientific Registry of Transplant Recipients and Medicare claims data, we identified 5094 adults (age ≥18 y) treated with cinacalcet or parathyroidectomy for SHPT before receiving KT between 2007 and 2016. We quantified the association between SHPT treatment and delayed graft function and acute rejection using adjusted logistic models and tertiary hyperparathyroidism (THPT), graft failure, and death using adjusted Cox proportional hazards; we tested whether these associations differed by patient characteristics. RESULTS: Of 5094 KT recipients who were treated for SHPT while on dialysis, 228 (4.5%) underwent parathyroidectomy, and 4866 (95.5%) received cinacalcet. There was no association between treatment of SHPT and posttransplant delayed graft function, graft failure, or death. However, compared with patients treated with cinacalcet, those treated with parathyroidectomy had a lower risk of developing THPT (adjusted hazard ratio, 0.56; 95% confidence interval, 0.35-0.89) post-KT. Furthermore, this risk differed by dialysis vintage (Pinteraction = 0.039). Among patients on maintenance dialysis therapy for ≥3 y before KT (n = 3477, 68.3%), the risk of developing THPT was lower when treated with parathyroidectomy (adjusted hazard ratio, 0.43; 95% confidence interval, 0.24-0.79). CONCLUSIONS: Parathyroidectomy should be considered as treatment for SHPT, especially in KT candidates on maintenance dialysis for ≥3 y. Additionally, patients treated with cinacalcet for SHPT should undergo close surveillance for development of tertiary hyperparathyroidism post-KT.

The Risk of Postkidney Transplant Outcomes by Induction Choice Differs by Recipient Age.

BACKGROUND: Among adult kidney transplant (KT) recipients, the risk of post-KT adverse outcomes differs by type of induction immunosuppression. Immune response to induction differs as recipients age; yet, choice of induction is barely tailored by age likely due to a lack of evidence of the risks and benefits. METHODS: Using Scientific Registry of Transplant Recipients data, we identified 39336 first-time KT recipients (2010-2016). We estimated the length of stay (LOS), acute rejection (AR), graft failure, and death by induction type using logistic and Cox regression weighted by propensity score to adjust for confounders. We tested whether these estimates differed by age (65+ versus 18-64 y) using a Wald test. RESULTS: Overall, rabbit antithymocyte globulin (rATG) was associated with a decreased risk of AR (odds ratio = 0.79, 95% confidence interval [CI], 0.72-0.85) compared with basiliximab. The effect of induction on LOS and death (interaction P = 0.03 and 0.003) differed by recipient age. Discharge was on average 11% shorter in rATG among younger recipients (relative time = 0.89; 95% confidence interval [CI], 0.81-0.99) but not among older recipients (relative time = 1.01; 95% CI, 0.95-1.08). rATG was not associated with mortality among older (hazard ratio = 1.05; 95% CI, 0.96-1.15), but among younger recipients (hazard ratio = 0.87; 95% CI, 0.80-0.95), it was associated with reduced mortality risk. CONCLUSIONS: rATG should be considered to prevent AR, especially among recipients with high-immunologic risk regardless of age; however, choice of induction should be tailored to reduce LOS and risk of mortality, particularly among younger recipients.

Early Changes in Kidney Transplant Immunosuppression Regimens During the COVID-19 Pandemic.

BACKGROUND: Kidney transplant recipients have higher risk of infectious diseases due to their reliance on immunosuppression. During the current COVID-19 pandemic, some clinicians might have opted for less potent immunosuppressive agents to counterbalance the novel infectious risk. We conducted a nationwide study to characterize immunosuppression use and subsequent clinical outcomes during the first 5 months of COVID-19 pandemic in the United States. METHODS: Using data from the Scientific Registry of Transplant Recipients, we studied all kidney-only recipients in the United States from January 1, 2017, to March 12, 2020 ("prepandemic" era; n = 64 849) and from March 13, 2020, to July 31, 2020 ("pandemic" era; n = 5035). We compared the use of lymphocyte-depleting agents (versus basiliximab or no induction) and maintenance steroids (versus steroid avoidance/withdrawal) in the pandemic era compared with the prepandemic era. Then, we compared early posttransplant outcomes by immunosuppression regimen during the pandemic era. RESULTS: Recipients in the pandemic era were substantially less likely to receive lymphocyte-depleting induction agents compared with their prepandemic counterparts (aOR = 0.400.530.69); similar trends were found across subgroups of state-level COVID-19 incidence, donor type, and recipient age. However, lymphocyte-depleting induction agents were associated with decreased rejection during admission (aOR = 0.110.230.47) but not with increased mortality in the pandemic era (aHR = 0.130.471.66). On the other hand, the use of maintenance steroids versus early steroid withdrawal remained similar (aOR = 0.711.071.62). CONCLUSIONS: The use of lymphocyte-depleting induction agents has decreased in favor of basiliximab and no induction during the COVID-19 pandemic. However, this shift might have resulted in increases in rejection with no clear reductions in posttransplant mortality.

Immunosuppression Regimen Use and Outcomes in Older and Younger Adult Kidney Transplant Recipients: A National Registry Analysis.

BACKGROUND: Although the population of older transplant recipients has increased dramatically, there are limited data describing the impact of immunosuppression regimen choice on outcomes in this recipient group. METHODS: National data for US Medicare-insured adult kidney recipients (N = 67 362; 2005-2016) were examined to determine early immunosuppression regimen and associations with acute rejection, death-censored graft failure, and mortality using multivariable regression analysis in younger (18-64 y) and older (>65 y) adults. RESULTS: The use of antithymocyte globulin (TMG) or alemtuzumab (ALEM) induction with triple maintenance immunosuppression (reference) was less common in older compared with younger (36.9% versus 47.0%) recipients, as was TMG/ALEM + steroid avoidance (19.2% versus 20.1%) and mammalian target of rapamycin inhibitor (mTORi)-based (6.7% versus 7.7%) treatments. Conversely, older patients were more likely to receive interleukin (IL)-2-receptor antibody (IL2rAb) + triple maintenance (21.1% versus 14.7%), IL2rAb + steroid avoidance (4.1% versus 1.8%), and cyclosporine-based (8.3% versus 6.6%) immunosuppression. Compared with older recipients treated with TMG/ALEM + triple maintenance (reference regimen), those managed with TMG/ALEM + steroid avoidance (adjusted odds ratio [aOR], 0.440.520.61) and IL2rAb + steroid avoidance (aOR, 0.390.550.79) had lower risk of acute rejection. Older patients experienced more death-censored graft failure when managed with Tac + antimetabolite avoidance (adjusted hazard [aHR], 1.411.782.25), mTORi-based (aHR, 1.702.142.71), and cyclosporine-based (aHR, 1.411.782.25) regimens, versus the reference regimen. mTORi-based and cyclosporine-based regimens were associated with increased mortality in both older and younger patients. CONCLUSIONS: Lower-intensity immunosuppression regimens (eg, steroid-sparing) appear beneficial for older kidney transplant recipients, while mTORi and cyclosporine-based maintenance immunosuppression are associated with higher risk of adverse outcomes.

Effectiveness of corticosteroids for post-extubation stridor and extubation failure in pediatric patients: a systematic review and meta-analysis.

BACKGROUND: While the results of previous meta-analyses have shown beneficial effects of corticosteroid therapy on post-extubation stridor and extubation failure in adults, these results might not be generalizable to children because of the differences in anatomy and structure. We aimed to determine the benefits of corticosteroids on those outcomes in pediatric populations. METHODS: We searched PubMed, EMBASE, and reference lists of articles from inception until February 2019. Randomized controlled trials and observational studies on the efficacy of systemic corticosteroid administration given prior to elective extubation in mechanically ventilated pediatrics were eligible. Outcomes included post-extubation stridor indicating laryngeal edema and extubation failures. RESULTS: A total of ten randomized controlled trials with 591 pediatric patients were included: seven of the ten studies for post-extubation stridor/suspected upper airway obstruction and nine of the ten studies for extubation failure. The estimate of pooled odds ratios (ORs) for post-extubation stridor/suspected upper airway obstruction was 0.40 (95% CI: 0.21-0.79). When analysis was restricted to trials that had explicit data for infants and explicit data for pediatric patients under 5 years old excluding infants, the estimates of pooled ORs were 0.53 (95% CI: 0.20-1.40) and 0.68 (95% CI: 0.38-1.22), respectively. For pediatric patients who received corticosteroids, there was a 0.37-fold lower odds of extubation failure than that in pediatric patients who did not receive corticosteroids (OR, 0.37; 95% CI, 0.22-0.61). While three observational studies were included in this review, their estimates have a potential for bias and we did not perform a meta-analysis. CONCLUSIONS: Despite a relatively small sample size in each randomized controlled trial and wide ranges of ages and steroid administration regimens, our results suggest that the use of corticosteroids for prevention of post-extubation stridor and extubation failure could be considered to be acceptable in pediatric patients.