The association of center volume with transplant outcomes in selected high-risk groups in kidney transplantation.

BACKGROUND: In context of increasing complexity and risk of deceased kidney donors and transplant recipients, the impact of center volume (CV) on the outcomes of high-risk kidney transplants(KT) has not been well determined. METHODS: We examined the association of CV and outcomes among 285 U.S. transplant centers from 2000-2016. High-risk KT were defined as recipient age ≥ 70 years, body mass index (BMI) ≥ 35 kg/m2, receiving kidneys from donors with kidney donor profile index(KDPI) ≥ 85%, acute kidney injury(AKI), hepatitisC + . Average annual CV for the specific-high-risk KT categorized in tertiles. Death-Censored-Graft-Loss(DCGL) and death at 3 months, 1, 5, and 10 years were compared between CV tertiles using Cox-regression models. RESULTS: Two hundred fifty thousand five hundred seventy-four KT were analyzed. Compared to high CV, recipients with BMI ≥ 35 kg/m2 had higher risk of DCGL in low CV(aHR = 1.11,95%CI = 1.03-1.19) at 10 years; recipients with age ≥ 70 years had higher risk of death in low CV(aHR = 1.07,95%CI = 1.01-14) at 10 years. There was no difference of DCGL or death in low CV for donors with KDPI ≥ 85%, hepatitisC + , or AKI. CONCLUSIONS: Recipients of high-risk KT with BMI ≥ 35 kg/m2 have higher risk of DCGL and recipients age ≥ 70 years have higher risk of death in low CV, compared to high CV. Future studies should identify care practices associated with CV that support optimal outcomes after KT.

Survival After Simultaneous Pancreas-Kidney Transplantation in Type 1 Diabetes: The Critical Role of Early Pancreas Allograft Function.

Simultaneous pancreas-kidney transplantation (SPK) carries about a 7%-22% risk of technical failure, but the impact of early pancreas allograft loss on subsequent kidney graft and patient survival is not well-defined. We examined national transplant registry data for type 1 diabetic patients who received SPK between 2000 and 2021. Associations of transplant type (i.e., SPK, deceased-donor kidney transplant [DDKA], living-donor kidney transplant [LDKA]) with kidney graft failure and patient survival were estimated by multivariable inverse probability of treatment-weighted accelerated failure-time models. Compared to SPK recipients with a functioning pancreas graft 3 months posttransplant (SPK,P+), LDKA had 18% (Time Ratio [TR] 0.82, 95%CI: 0.70-0.95) less graft survival time and 18% (TR 0.82, 95%CI: 0.68-0.97) less patient survival time, DDKA had 23% (TR 0.77, 95%CI: 0.68-0.87) less graft survival time and 29% (TR 0.71, 95%CI: 0.62-0.81) less patient survival time, and SPK with early pancreas graft loss had 34% (TR 0.66, 95%CI: 0.56-0.78) less graft survival time and 34% (TR 0.66, 95%CI: 0.55-0.79) less patient survival time. In conclusion, SPK,P+ recipients have better kidney allograft and patient survival compared with LDKA and DDKA. Early pancreas graft failure results in inferior kidney and patient survival time compared to kidney transplant alone.

Corrigendum: Survival After Simultaneous Pancreas-Kidney Transplantation in Type 1 Diabetes: The Critical Role of Early Pancreas Allograft Function.

[This corrects the article DOI: 10.3389/ti.2022.10618.].

Renal function outcomes and kidney biopsy features of living kidney donors with hypertension.

BACKGROUND: The medium- to long-term outcomes of living kidney donors with hypertension compared to normotensive donors are not well understood, especially with the recent changes in hypertension guidelines. METHODS: We studied a cohort of 950 living kidney donors using different definitions of hypertension based on either ≥140/90 or ≥130/80 mmHg thresholds and based on either office or ambulatory blood pressure readings. Microstructural features on kidney biopsy at the time of donation were compared using different definitions of hypertension. RESULTS: After adjusting for years of follow-up, age, sex, and baseline eGFR, hypertension (by any definition) did not significantly predict an eGFR < 45 ml/min/1.73 m2 at a median follow-up of 10 years postdonation, though there was a borderline association with ambulatory blood pressure ≥ 130/80 mmHg predicting a 40% decline in eGFR (OR = 1.53, 1.00-2.36; p = .051). Proteinuria was predicted by office blood pressure ≥ 140/90 mmHg and by nondipper profile on nocturnal ambulatory blood pressure measurements. At the time of donation, larger glomeruli and arterial hyalinosis on biopsy were associated with hypertension defined by either ≥140/90 or ≥130/80 mmHg (by office or ambulatory measurements). Nocturnal nondipper status was associated with larger glomeruli size but not arteriolar hyalinosis when compared to dippers. CONCLUSIONS: In programs that accept donors with controlled hypertension, various definitions of hypertension are associated with histological findings in the donated kidney, but none predict a clinically significant decline in kidney function 10 years after donation. These data support allowing healthy individuals with controlled hypertension to donate a kidney. However, donors with office hypertension (≥140/90 mmHg) and nondippers (regardless of hypertension status) are at greater long-term risk for proteinuria, and particularly for these donors, longer follow-up is warranted.

Mesangial expansion at 5 years predicts death and death-censored graft loss after renal transplantation.

Death with a functioning graft and death-censored renal allograft failure remain major problems for which effective preventative protocols are lacking. The retrospective cohort study aimed to determine whether histologic changes on a 5-year surveillance kidney biopsy predict adverse outcomes after transplantation in recipients who had: both Type 2 diabetes (T2DM) and obesity (BMI ≥ 30 kg/m2 ) at the time of transplantation (T2DM/Obesity, n = 75); neither (No T2DM/No obesity, n = 78); No T2DM/Obesity (n = 41), and T2DM/No obesity (n = 47). On 5-year biopsies, moderate-to-severe mesangial expansion was more common in the T2DM/Obesity group (Banff mm score ≥2 = 49.3%; Tervaert classification MS ≥ 2b = 26.7%) compared to the other groups (p < .001 for both scores). Risk factors included older age, higher BMI, HbA1C, and triglycerides at 1-year post-transplant. Moderate-to-severe mesangial expansion correlated with death with function (HR 1.74 (1.01, 2.98), p = .045 Banff and 1.89 (1.01, 3.51) p = .045 Tervaert) and with death-censored graft loss (HR 3.2 (1.2, 8.8), p = .02 Banff and HR 3.8 (1.3, 11.5), p = .01 Tervaert) over a mean of 11.6 years of recipient follow-up post-transplant. These data suggest that mesangial expansion in recipients with T2DM and obesity may reflect systemic vascular injury and might be a novel biomarker to predict adverse outcomes post renal transplant.

Kidney Structural Features from Living Donors Predict Graft Failure in the Recipient.

BACKGROUND: Nephrosclerosis, nephron size, and nephron number vary among kidneys transplanted from living donors. However, whether these structural features predict kidney transplant recipient outcomes is unclear. METHODS: Our study used computed tomography (CT) and implantation biopsy to investigate donated kidney features as predictors of death-censored graft failure at three transplant centers participating in the Aging Kidney Anatomy study. We used global glomerulosclerosis, interstitial fibrosis/tubular atrophy, artery luminal stenosis, and arteriolar hyalinosis to measure nephrosclerosis; mean glomerular volume, cortex volume per glomerulus, and mean cross-sectional tubular area to measure nephron size; and calculations from CT cortical volume and glomerular density on biopsy to assess nephron number. We also determined the death-censored risk of graft failure with each structural feature after adjusting for the predictive clinical characteristics of donor and recipient. RESULTS: The analysis involved 2293 donor-recipient pairs. Mean recipient follow-up was 6.3 years, during which 287 death-censored graft failures and 424 deaths occurred. Factors that predicted death-censored graft failure independent of both donor and recipient clinical characteristics included interstitial fibrosis/tubular atrophy, larger cortical nephron size (but not nephron number), and smaller medullary volume. In a subset with 12 biopsy section slides, arteriolar hyalinosis also predicted death-censored graft failure. CONCLUSIONS: Subclinical nephrosclerosis, larger cortical nephron size, and smaller medullary volume in healthy donors modestly predict death-censored graft failure in the recipient, independent of donor or recipient clinical characteristics. These findings provide insights into a graft's "intrinsic quality" at the time of donation, and further support the use of intraoperative biopsies to identify kidney grafts that are at higher risk for failure.

Effect of Maintaining Immunosuppression After Kidney Allograft Failure on Mortality and Retransplantation.

Few studies have addressed immunosuppression management after allograft failure (AF). Immunosuppression withdrawal to minimize complications must be balanced with the risk of sensitization and potentially reduced retransplantation. We aimed to determine relationships between immunosuppression, death, sensitization, and retransplantation among patients with AF. Methods: We performed a single-center retrospective study of patients transplanted from October 2007 to May 2017 with AF. We collected data on demographics, immunosuppression, calculated panel reactive antibody (cPRA) levels, death, retransplantation, and dialysis. Cox regression models were used to evaluate factors associated with death and retransplantation. Results: From October 2007 to May 2017, 1354 solitary ABO-compatible transplants were performed, of which 97 failed. Ten percent of patients received a preemptive retransplant. Among those who returned to dialysis (n = 87), 35% died, 25% received another transplant, and 30% remained on dialysis. After AF, 46% of patients discontinued immunosuppression. The cPRA was unchanged if immunosuppression was maintained, but immunosuppression discontinuation was associated with increased cPRA from a median (interquartile range) of 18 (0-99) to 96 (88.5-100.0; P = 0.003). Age at failure (hazard ratio, 1.1; confidence interval, 1.0-1.1) and cardiovascular disease were associated with death (hazard ratio, 2.9; confidence interval, 1.2-7.0) in multivariate analysis. Importantly, immunosuppression maintenance was not associated with increased death or retransplantation despite the increase in cPRA that occurred when immunosuppression was discontinued. Conclusions: Kidney transplant recipients with AF have a high mortality rate after dialysis initiation. Although immunosuppression withdrawal was associated with increased cPRA, it was not associated with reduced retransplantation. Therefore, it is reasonable to discontinue immunosuppression after AF despite sensitization if retransplantation is delayed.

Patterns in Use and Transplant Outcomes Among Adult Recipients of Kidneys From Deceased Donors With COVID-19.

Importance: While the COVID-19 pandemic enters a new phase and the proportion of individuals with a previous COVID-19 diagnosis increases, the national patterns in kidney use and medium-term kidney transplant (KT) outcomes among patients receiving kidneys from active or resolved COVID-19-positive donors remain unknown. Objective: To evaluate the patterns in kidney use and KT outcomes among adult recipients of kidneys from deceased donors with active or resolved COVID-19. Design, Setting, and Participants: This retrospective cohort study was conducted using national US transplant registry data from 35 851 deceased donors (71 334 kidneys) and 45 912 adult patients who received KTs from March 1, 2020, to March 30, 2023. Exposure: The exposure was donor SARS-CoV-2 nucleic acid amplification test (NAT) results, with positive NAT results within 7 days before procurement defined as active COVID-19 and positive NAT results 1 week (>7 days) before procurement defined as resolved COVID-19. Main Outcomes and Measures: Primary outcomes were kidney nonuse, all-cause kidney graft failure, and all-cause patient death. Secondary outcomes were acute rejection (ie, rejection in the first 6 months after KT), transplant hospitalization length of stay (LOS), and delayed graft function (DGF). Multivariable logistic regression analyses were performed for kidney nonuse, rejection, and DGF; multivariable linear regression analyses were performed for LOS; and multivariable Cox regression analyses were performed for graft failure and all-cause death. All models were adjusted for inverse probability treatment weighting. Results: Among 35 851 deceased donors, the mean (SD) age was 42.5 (15.3) years; 22 319 (62.3%) were men and 23 992 (66.9%) were White. Among 45 912 recipients, the mean (SD) age was 54.3 (13.2) years; 27 952 (60.9%) were men and 15 349 (33.4%) were Black. The likelihood of nonuse of kidneys from active or resolved COVID-19-positive donors decreased over time. Overall, kidneys from active COVID-19-positive donors (adjusted odds ratio [AOR], 1.55; 95% CI, 1.38-1.76) and kidneys from resolved COVID-19-positive donors (AOR, 1.31; 95% CI, 1.16-1.48) had a higher likelihood of nonuse compared with kidneys from COVID-19-negative donors. From 2020 to 2022, kidneys from active COVID-19-positive donors (2020: AOR, 11.26 [95% CI, 2.29-55.38]; 2021: AOR, 2.09 [95% CI, 1.58-2.79]; 2022: AOR, 1.47 [95% CI, 1.28-1.70]) had a higher likelihood of nonuse compared with kidneys from donors without COVID-19. Kidneys from resolved COVID-19-positive donors had a higher likelihood of nonuse in 2020 (AOR, 3.87; 95% CI, 1.26-11.90) and 2021 (AOR, 1.94; 95% CI, 1.54-2.45) but not in 2022 (AOR, 1.09; 95% CI, 0.94-1.28). In 2023, kidneys from both active COVID-19-positive donors (AOR, 1.07; 95% CI, 0.75-1.63) and resolved COVID-19-positive donors (AOR, 1.18; 95% CI, 0.80-1.73) were not associated with higher odds of nonuse. No higher risk of graft failure or death was found in patients receiving kidneys from active COVID-19-positive donors (graft failure: adjusted hazard ratio [AHR], 1.03 [95% CI, 0.78-1.37]; patient death: AHR, 1.17 [95% CI, 0.84-1.66]) or resolved COVID-19-positive donors (graft failure: AHR, 1.10 [95% CI, 0.88-1.39]; patient death: AHR, 0.95 [95% CI, 0.70-1.28]). Donor COVID-19 positivity was not associated with longer LOS, higher risk of acute rejection, or higher risk of DGF. Conclusions and Relevance: In this cohort study, the likelihood of nonuse of kidneys from COVID-19-positive donors decreased over time, and donor COVID-19 positivity was not associated with worse KT outcomes within 2 years after transplant. These findings suggest that the use of kidneys from donors with active or resolved COVID-19 is safe in the medium term; further research is needed to assess longer-term transplant outcomes.

Bone marrow derived long-lived plasma cell phenotypes are heterogeneous and can change in culture.

Bone marrow-derived long-lived plasma cells (LLPCs) are thought to be a major source of alloantibody in sensitized transplant patients. However, studies of LLPCs have been hampered not only by the fact that they are rare and difficult to isolate and culture but also due to the lack of consensus regarding a definitive cell-surface phenotype. The goal of the current study was to determine if LLPCs have a specific, stable cell-surface phenotype. PCs were isolated from high-volume (120cc) bone marrow aspirates that were enriched first by negative selection then positive selection using anti-CD38 antibody-coated beads and purified by cell sorting. A typical isolation resulted in >100,000 PCs that were sorted into 4 populations with variable numbers of PCs: CD19+/CD138+/CD38Hi (64.1% of the PCs), CD19-/CD138+/CD38Hi (20.9%), CD19+/CD138-/CD38Hi (10.7%), and CD19-/CD138-/CD38Hi (4.3%). The purity of each subset was 96-99%. Each subset contained PCs secreting IgG and IgA. Measles- and tetanus-specific PCs (i.e. putative IgG secreting, antigen-specific LLPCs). LLPCs were identified in both the CD19+/CD138+/CD38Hi and CD19-/CD138+/CD38Hi subsets and in the smaller CD138- subsets (when pooled). Thus, all CD38Hi subsets contained LLPCs. Cultured PCs maintained viability (>50%) and function and could be retrieved for analyses. During 7 days of culture, cell surface expression changed from baseline in many PCs. For example, approximately 20% of CD19 + CD138+/CD38Hi cells (the largest PC subset) became CD19-. CFSE assays showed no division and only a small percentage of LLPCs were Ki-67 positive suggesting that the cells did not divide in culture and that the antibody detected was not from plasmablasts. We conclude that human bone marrow LLPCs have a heterogeneous expression of CD19 and CD138, which can change during cell culture. The fact that LLPCs were found in all four subsets raises the possibility that a large percentage of PCs in the bone marrow may be LLPCs.

Complications After Hand-Assisted Laparoscopic Living Donor Nephrectomy.

OBJECTIVE: To study the complications of hand-assisted laparoscopic living donor nephrectomy (HALLDN) with an emphasis on complications occurring early after hospital discharge up to 120 days after surgery. PATIENTS AND METHODS: We retrospectively categorized complications using the Clavien-Dindo classification in 3002 HALLDNs performed at 1 center from January 1, 2000, through December 31, 2019. In addition to overall summaries, modeling was used to identify correlates of complications before and after living donation. RESULTS: Of these donors, 87% were White, 59% were female, the mean age was 45 years (range, 18-77 years), 30.3% had a body mass index of at least 30, and 36.3% had previous abdominopelvic surgery. There were no deaths related to the surgery. The incidence of major complications (intraoperative complications plus Clavien-Dindo grade ≥III postoperatively) was 2.5% (n=74). The overall complication rate was 12.4% (n=371), including 15 intraoperative, 76 postoperative before discharge, and 280 after discharge to 120 days. Reoperation was required in 1.8% of patients (n=54), and all but 1 of these were incision-related problems. Seventy-six percent of all complications occurred after discharge, including 85% of the reoperations. For major complications, no risk factor was found. Risk factors for any complication included paramedian incision (hazard ratio [HR], 2.54; 95% CI, 1.49 to 4.34; P<.001); a history of abdominopelvic surgery (HR, 1.37; 95% CI, 1.07 to 1.76; P=.01), male sex (HR, 1.37; 95% CI, 1.07 to 1.76; P=.01), non-White race (HR, 1.40; 95% CI, 1.05 to 1.88; P=.02), and early era of the experience. CONCLUSION: Most major complications of HALLDN occur after discharge, suggesting that close follow-up is warranted and that the current literature may underestimate the true incidence.

Clinical and Kidney Structural Characteristics of Living Kidney Donors With Nephrolithiasis and Their Long-term Outcomes.

BACKGROUND: Nephrolithiasis in living kidney donors is concerning due to the potential impact on long-term postdonation kidney function. METHODS: We performed a cohort study of living kidney donors from 2 centers with a baseline computed tomography scan and implantation renal biopsy. Donors (>5 y since donation) completed a follow-up survey or underwent chart review to assess eGFR and incident hypertension. Stone formers were classified as symptomatic if they had a past symptomatic episode or asymptomatic if only incidental radiographic kidney stones were identified during donor evaluation. We compared baseline clinical, imaging, and biopsy characteristics by stone former status including review of metabolic evaluations in stone formers. Long-term risks of renal complications (low eGFR and hypertension) by stone former status were evaluated. RESULTS: There were 12 symptomatic and 76 asymptomatic stone formers among 866 donors. Overall, baseline clinical characteristics and implantation biopsy findings were similar between stone formers and non-stone formers. After a median follow-up of 10 y, stone former status was not associated with eGFR <60 mL/min/1.73 m2, eGFR <45 mL/min/1.73 m2, or hypertension. CONCLUSIONS: Both asymptomatic and symptomatic SF have favorable histology findings at baseline. Long-term kidney outcomes were favorable in select stone formers with no evident increased long-term risk for decreased kidney function or hypertension after donation.

Death With Function and Graft Failure After Kidney Transplantation: Risk Factors at Baseline Suggest New Approaches to Management.

BACKGROUND: Improving both patient and graft survival after kidney transplantation are major unmet needs. The goal of this study was to assess risk factors for specific causes of graft loss to determine to what extent patients who develop either death with a functioning graft (DWFG) or graft failure (GF) have similar baseline risk factors for graft loss. METHODS: We retrospectively studied all solitary renal transplants performed between January 1, 2006, and December 31, 2018, at 3 centers and determined the specific causes of DWFG and GF. We examined outcomes in different subgroups using competing risk estimates and cause-specific Cox models. RESULTS: Of the 5752 kidney transplants, graft loss occurred in 21.6% (1244) patients, including 12.0% (691) DWFG and 9.6% (553) GF. DWFG was most commonly due to malignancy (20.0%), infection (19.7%), cardiac disease (12.6%) with risk factors of older age and pretransplant dialysis, and diabetes as the cause of renal failure. For GF, alloimmunity (38.7%), glomerular diseases (18.6%), and tubular injury (13.9%) were the major causes. Competing risk incidence models identified diabetes and older recipients with higher rates of both DWFG and nonalloimmune GF. CONCLUSIONS: These data suggest that at baseline, 2 distinct populations can be identified who are at high risk for renal allograft loss: a younger, nondiabetic patient group who develops GF due to alloimmunity and an older, more commonly diabetic population who develops DWFG and GF due to a mixture of causes-many nonalloimmune. Individualized management is needed to improve long-term renal allograft survival in the latter group.

Association of Ambient Fine Particulate Matter Air Pollution With Kidney Transplant Outcomes.

Importance: Increased levels of ambient fine particulate matter (PM2.5) air pollution are associated with increased risks for detrimental health outcomes, but risks for patients with kidney transplants (KTs) remain unknown. Objective: To investigate the association of PM2.5 exposure with KT outcomes. Design, Setting, and Participants: This retrospective cohort study was conducted using data on patients who received KTs from 2004 to 2016 who were identified in the national US transplant registry and followed up through March 2021. Multiple databases were linked to obtain data on PM2.5 concentration, KT outcomes, and patient clinical, transplant, and contextual factors. Data were analyzed from April 2020 through July 2021. Exposures: Exposures included post-KT time-dependent annual mean PM2.5 level (in 10 µg/m3) and mean PM2.5 level in the year before KT (ie, baseline levels) in quartiles, as well as baseline annual mean PM2.5 level (in 10 µg/m3). Main Outcomes and Measures: Acute kidney rejection (ie, rejection within 1 year after KT), time to death-censored graft failure, and time to all-cause death. Multivariable logistic regression for kidney rejection and Cox analyses with nonlinear assessment of exposure-response for death-censored graft failure and all-cause death were performed. The national burden of graft failure associated with PM2.5 levels greater than the Environmental Protection Agency recommended level of 12 µg/m3 was estimated. Results: Among 112 098 patients with KTs, 70 522 individuals (62.9%) were older than age 50 years at the time of KT, 68 117 (60.8%) were men, and the median (IQR) follow-up was 6.0 (3.9-8.9) years. There were 37 265 Black patients (33.2%), 17 047 Hispanic patients (15.2%), 48 581 White patients [43.3%]), and 9205 patients (8.2%) of other race or ethnicity. The median (IQR) baseline PM2.5 level was 9.8 (8.3-11.9) µg/m3. Increased baseline PM2.5 level, compared with quartile 1 baseline PM2.5 level, was not associated with higher odds of acute kidney rejection for quartile 2 (adjusted odds ratio [aOR], 0.99; 95% CI, 0.92-1.06) but was associated with increased odds for quartile 3 (aOR, 1.11; 95% CI, 1.04-1.20) and quartile 4 (aOR, 1.13; 95% CI, 1.05-1.23). Nonlinear assessment of exposure-response for graft failure and death showed no evidence for nonlinearity. Increased PM2.5 levels were associated with increased risk of death-censored graft failure (adjusted hazard ratio [aHR] per 10 µg/m3 increase, 1.17; 95% CI, 1.09-1.25) and all-cause death (aHR per 10 µg/m3 increase, 1.21; 95% CI, 1.14-1.28). The national burden of death-censored graft failure associated with PM2.5 above 12 µg/m3 was 57 failures (95% uncertainty interval, 48-67 failures) per year among patients with KTs. Conclusions and Relevance: This cohort study found that PM2.5 level was an independent risk factor associated with acute rejection, graft failure, and death among patients with KTs. These findings suggest that efforts toward decreasing levels of PM2.5 concentration may be associated with improved outcomes after KT.

Chronic Histologic Changes Are Present Regardless of HLA Mismatches: Evidence from HLA-Identical Living Donor Kidney Transplants.

BACKGROUND: At 5 and 10 y after kidney transplantation, chronic histologic changes such as arteriolar hyalinosis and mesangial expansion are common; however, determining cause is difficult. We compared surveillance biopsies in living donor kidney transplants (LDKTx) from HLA-matched siblings (termed HLA-identical [HLA-ID]) with HLA non-ID to investigate which histologic changes were likely due to alloimmune injury and which were due to nonalloimmune injury. METHODS: We performed a retrospective, cohort study comparing HLA-ID sibling LDKTx (n = 175) with HLA non-ID LDKTx (n = 175; matched for age, sex, and year of transplant ±2 y) performed at a single institution from March 1999 to November 2018. RESULTS: Baseline characteristics and maintenance immunosuppression were similar. Mortality rates were similar, but in the HLA-ID group, 10-y death-censored graft survival was higher (93.8% versus 80.9% HLA non-ID LDKTx; P < 0.001), rejection rates were lower (after 1 y 9.6% versus 27.1%; P < 0.001), and Banff inflammation scores including glomerulitis and peritubular capillaritis were lower on surveillance biopsies at 1, 5, and 10 y. In contrast, chronic Banff scores (interstitial fibrosis, arteriolar hyalinosis, mesangial expansion, etc) were similar in prevalence and severity on surveillance biopsies at 1, 5, and 10 y. CONCLUSIONS: HLA-ID LDKTx have less inflammation and less transplant glomerulopathy, but most chronic histologic changes were similar to less well-matched LDKTx. We conclude that these types of chronic changes are not associated with HLA mismatches and may be due to nonimmunologic causes (hypertension, obesity, etc), suggesting that new management approaches to prevent these lesions may be needed.

Trends in Discard of Kidneys from Hepatitis C Viremic Donors in the United States.

BACKGROUND AND OBJECTIVES: Kidneys from hepatitis C virus (HCV) viremic donors have become more commonly accepted for transplant, especially after effective direct-acting antiviral therapy became available in 2014. We examined the contemporary trend of kidney discard from donors with HCV seropositivity and viremia. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from the Organ Procurement and Transplantation Network were used to identify deceased donor kidneys recovered for transplant. The exposure was donor HCV antibody status in the first analyses, and donor HCV antibody and viremia status in the second analyses. Multilevel, multivariable logistic regression was used to assess the association of these HCV exposure measures with kidney discard, adjusted for donor characteristics. Multilevel analyses were conducted to account for similar kidney discard pattern within clusters of organ procurement organizations and regions. RESULTS: Among 225,479 kidneys recovered from 2005 to 2019, 5% were from HCV seropositive donors. Compared with HCV seronegative kidneys, the odds of HCV seropositive kidney discard gradually declined, from a multivariable-adjusted odds ratio (aOR) of 7.06 (95% confidence interval [95% CI], 5.65 to 8.81) in 2014, to 1.20 (95% CI, 1.02 to 1.42) in 2019. Among 82,090 kidneys with nucleic acid amplification test results in 2015-2019, 4% were from HCV viremic donors and 2% were from aviremic seropositive donors. Compared with HCV aviremic seronegative kidneys, the odds of HCV viremic kidney discard decreased from an aOR of 4.89 (95% CI, 4.03 to 5.92) in 2018, to 1.48 (95% CI, 1.22 to 1.81) in 2019. By 2018 and 2019, aviremic seropositive status was not associated with higher odds of discard (2018: aOR, 1.13; 95% CI, 0.88 to 1.45; and 2019: aOR, 0.97; 95% CI, 0.76 to 1.23). CONCLUSIONS: Despite the decrease in kidney discard in recent years, kidneys from viremic (compared with aviremic seronegative) donors still had 48% higher odds of discard in 2019. The potential of these discarded organs to provide successful transplantation should be explored.

Kidney Microstructural Features at the Time of Donation Predict Long-term Risk of Chronic Kidney Disease in Living Kidney Donors.

OBJECTIVE: To determine whether microstructural features on a kidney biopsy specimen obtained during kidney transplant surgery predict long-term risk of chronic kidney disease in the donor. PATIENTS AND METHODS: We studied kidney donors from May 1, 1999, through December 31, 2018, with a follow-up survey for the results of recent blood pressure and kidney function tests (estimated glomerular filtration rate [eGFR] and proteinuria). If not recently available, blood pressure and eGFRs were requested from a local clinic. Microstructural features on kidney biopsy at the time of donation were assessed as predictors of hypertension and kidney function after adjusting for years of follow-up, baseline age, sex, and clinical predictors. RESULTS: There were 807 donors surveyed a mean 10.5 years after donation. An eGFR less than 45 mL/min/1.73 m2 in 6.4% (43/673) of donors was predicted by larger glomerular volume per standard deviation (odds ratio [OR], 1.48; 95% CI, 1.08 to 2.04) and nephron number below the age-specific 5th percentile (OR, 3.38; 95% CI, 1.31 to 8.72). An eGFR less than 60 mL/min/1.73 m2 in 42.5% (286/673) of donors was not predicted by any microstructural feature. Residual eGFR (postdonation/predonation eGFR) was predicted by nephron number below the age-specific 5th percentile (difference, -6.07%; 95% CI, -10.24% to -1.89%). Self-reported proteinuria in 5.1% (40/786) of donors was predicted by larger glomerular volume (OR, 1.42; 95% CI, 1.08 to 1.86). Incident hypertension in 18.8% (119/633) of donors was not predicted by any microstructural features. CONCLUSION: Low nephron number for age and larger glomeruli are important microstructural predictors for long-term risk of chronic kidney disease after living kidney donation.

Renal Transplantation after Transcatheter Aortic Valve Replacement: Case Report.

Patients with chronic kidney disease (CKD) have an increased likelihood of developing calcific aortic stenosis (AS). These patients also often suffer from multiple comorbidities, potentially making them high-risk surgical candidates and limiting their treatment options. Transcatheter aortic valve replacement (TAVR) is the recommended therapeutic approach for severe AS in patients who are not suitable candidates for surgical aortic valve replacement (SAVR). TAVR is being increasingly considered as a viable alternative to SAVR. As such, its applications in patients with CKD and other chronic diseases, as well as methods to optimize peri- and postoperative results are of great interest and significance. We present the case of a successful renal transplant procedure, performed within a year following a TAVR, in a 52-year-old man who suffered from multiple comorbidities.

The Use of GLP1R Agonists for the Treatment of Type 2 Diabetes in Kidney Transplant Recipients.

Glucagon-like peptide-1 receptor agonists (GLP1RA) have been shown to improve glucose control and diabetes-related comorbidities in patients without solid organ transplants. The effectiveness, safety, and tolerability of GLP1RA after kidney transplantation have not been adequately studied. METHODS: We retrospectively reviewed data on kidney transplant recipients performed in our institution, who were initiated on GLP1RA either for the treatment of type 2 diabetes diagnosed before transplantation or posttransplant diabetes. We analyzed efficacy, safety, and the effect on kidney allograft function. RESULTS: Seventeen kidney transplant recipients were initiated on GLP1RA therapy, 14 of which remained on the medication for at least 12 months. The use of GLP1RA had no significant impact on weight loss, but was associated with a significant reduction in the total daily insulin dose, from the median of 63 [interquartile range 43-113] IU to 44 [interquartile range 25-88] and reduction in the risk of hypoglycemia in patients who were on therapy for at least approximately 12 months. Kidney function remained stable and none of the recipients experienced acute rejection. Tacrolimus dose was not significantly changed. Five patients (29%) discontinued GLP1RA therapy-4 due to side effects and 1 due to uncontrolled hyperglycemia. CONCLUSIONS: GLP1RA may be a relatively safe and effective treatment for kidney transplant recipients with type 2 diabetes that allows for a reduction in insulin requirements. More studies are needed to determine whether the use of these agents will translate into an improvement in allograft and patient survival.