Banff 2022 pancreas transplantation multidisciplinary report: Refinement of guidelines for T cell-mediated rejection, antibody-mediated rejection and islet pathology. Assessment of duodenal cuff biopsies and noninvasive diagnostic methods.

The Banff pancreas working schema for diagnosis and grading of rejection is widely used for treatment guidance and risk stratification in centers that perform pancreas allograft biopsies. Since the last update, various studies have provided additional insight regarding the application of the schema and enhanced our understanding of additional clinicopathologic entities. This update aims to clarify terminology and lesion description for T cell-mediated and antibody-mediated allograft rejections, in both active and chronic forms. In addition, morphologic and immunohistochemical tools are described to help distinguish rejection from nonrejection pathologies. For the first time, a clinicopathologic approach to islet pathology in the early and late posttransplant periods is discussed. This update also includes a discussion and recommendations on the utilization of endoscopic duodenal donor cuff biopsies as surrogates for pancreas biopsies in various clinical settings. Finally, an analysis and recommendations on the use of donor-derived cell-free DNA for monitoring pancreas graft recipients are provided. This multidisciplinary effort assesses the current role of pancreas allograft biopsies and offers practical guidelines that can be helpful to pancreas transplant practitioners as well as experienced pathologists and pathologists in training.

Effect of End-Stage Renal Disease Prospective Payment System on Utilization of Peritoneal Dialysis in Patients with Kidney Allograft Failure.

INTRODUCTION: The Center for Medicare and Medicaid Services introduced an End-Stage Renal Disease Prospective Payment System (PPS) in 2011 to increase the utilization of home dialysis modalities, including peritoneal dialysis (PD). Several studies have shown a significant increase in PD utilization after PPS implementation. However, its impact on patients with kidney allograft failure remains unknown. METHODS: We conducted an interrupted time series analysis using data from the US Renal Data System (USRDS) that include all adult kidney transplant recipients with allograft failure who started dialysis between 2005 and 2019. We compared the PD utilization in the pre-PPS period (2005-2010) to the fully implemented post-PPS period (2014-2019) for early (within 90 days) and late (91-365 days) PD experience. RESULTS: A total of 27,507 adult recipients with allograft failure started dialysis during the study period. There was no difference in early PD utilization between the pre-PPS and the post-PPS period in either immediate change (0.3% increase; 95% CI: -1.95%, 2.54%; p = 0.79) or rate of change over time (0.28% increase per year; 95% CI: -0.16%, 0.72%; p = 0.18). Subgroup analyses revealed a trend toward higher PD utilization post-PPS in for-profit and large-volume dialysis units. There was a significant increase in PD utilization in the post-PPS period in units with low PD experience in the pre-PPS period. Similar findings were seen for the late PD experience. CONCLUSION: PPS did not significantly increase the overall utilization of PD in patients initiating dialysis after allograft failure.

Serum ß2-Microglobulin Predicts Time to Recovery of Delayed Graft Function in Kidney Transplant Recipients.

BACKGROUND: Delayed graft function (DGF) after kidney transplantation is associated with adverse patients and allograft outcomes. A longer duration of DGF is predictive of worse graft outcomes compared to a shorter duration. Posttransplant serum ß2-microglobulin (B2M) is associated with long-term graft outcomes, but its relationship with DGF recovery is unknown. METHODS: We included all kidney-only transplant recipients with DGF enrolled in the E-DGF trial. Duration of DGF was defined as the interval between the transplant and the last dialysis session. We analyzed the association of standardized serum creatinine (Scr) and B2M on postoperative Days (POD) 1-7 during the subsequent days of DGF with the recovery of DGF. RESULTS: A total of 97 recipients with DGF were included. The mean duration of DGF was 11.0 ± 11.2 days. Higher Scr was not associated with the duration of DGF in unadjusted or adjusted models. Higher standardized B2M, in contrast, was associated with a prolonged duration of DGF. This association remained in models adjusting for baseline characteristics from POD 2 (3.19 days longer, 95% CI: 0.46-5.93; p = 0.02) through Day 6 of DGF (4.97 days longer, 95% CI: 0.75-9.20; p = 0.02). There was minimal change in mean Scr (0.01 ± 0. 10 mg/dL per day; p = 0.32), while B2M significantly decreased as the time to recovery approached (-0.14 ± 0.05 mg/L per day; p = 0.006), among recipients with DGF. CONCLUSION: B2M is more strongly associated with DGF recovery than Scr. Posttransplant B2M may be an important biomarker to monitor during DGF. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03864926.

Outcomes of Deceased Donor Kidney Recipients From the Same Donor Based on Donor-Recipient Sex Discordance.

INTRODUCTION: Outcomes of deceased donor kidney transplant (DDKT) recipients from the same donor with donor-recipient sex discordance have been studied with inconsistent results. METHODS: Adult DDKT where both kidneys from the same donor occurred at our center in two different recipients of different sexes were included. Outcomes were analyzed separately for male and female donors, based on the concordance or discordance between donor-recipient sex: Male-male (M-m) versus Male to female (M-f) or vice versa, F-f versus F-m. Acute rejection (AR) and uncensored graft failure were primary outcomes of interest. The univariate and multivariate risks for AR and graft failure were conducted using the Cox proportional hazards model and log-rank tests. RESULTS: A total of 130 donors, 84 male and 46 female fulfilled our selection criteria and were transplanted in 260 recipients. With respect to the concordant groups (M-m or F-f), sex discordance was not significantly associated with the risk of rejection in multivariate analysis (M-f vs. M-m HR 1.15 [0.53-2.53, P = 0.72]; F-m vs. F-f HR 1.77 [0.71-4.39, P = 0.23]). Sex discordance was also not significantly associated with graft failure in multivariate analysis. Interestingly, risk factors for AR differed among male donors and female donors. The higher calculated panel reactive antibodies (cPRA) and nonwhite recipients were at increased risk for AR in F-m, but not in M-f. CONCLUSIONS: Donor-recipient sex discordance was not significantly associated with AR or graft failure. Risk factors for AR may differ across male and female donors.

Potassium-lowering effects of sodium zirconium cyclosilicate in the early post-transplant period.

PROBLEM: Hyperkalemia is a serious condition among intra-abdominal transplant recipients, and the safety and efficacy of sodium zirconium cyclosilicate (SZC) for its management during the early post-transplant period are not well-established. METHODS: Adults who received at least one 10-g dose of SZC within 14 days after an intra-abdominal transplant between January 2020 and July 2022 were included in our study. The primary outcome was the change in potassium (K+) levels following the first SZC dose. Other analyses explored adjunctive potassium-lowering therapies, potential gastrointestinal complications, and patient subgroups based on therapy and transplant type. RESULTS: Among the recipients (n = 46), 11 were kidney recipients, 26 were liver recipients, seven were simultaneous liver/kidney recipients, and two were simultaneous pancreas/kidney recipients. The mean time to first dose post-transplant was 7.6 (±4) days, and the mean change in serum K+ after the initial SZC dose was -.27 mEq (p = .001). No gastrointestinal complications were observed following the SZC dose. The mean increase in serum bicarbonate was .58 mEq (p = .41) following the first dose of SZC. Four kidney recipients required dialysis following the SZC dose. CONCLUSION: This study represents the largest investigation on the use of SZC in transplant recipients. A single 10-g dose of SZC reduced serum K+ levels in all subgroups, while the use of adjunctive K+-lowering therapies did not provide additional reduction beyond the effects of SZC. Importantly, no gastrointestinal complications were observed. These findings suggest that SZC may be a safe and promising therapeutic option for hyperkalemia management following solid organ transplantation.

Risk factors and outcomes of persistent post-transplant hypotension among simultaneous pancreas and kidney transplant recipients.

BACKGROUND: The risk factors and outcomes associated with post- transplant hypotension after simultaneous pancreas and kidney (SPK) Transplantation are poorly defined. METHODS: SPK recipients at our center between 2010 and 2021 with functioning pancreas and kidney grafts for >6 months were included. Recipients were then divided into three groups based on active medications for the treatment of hypo-or hypertension at 6-months post-transplant: those with normal blood pressure (NBP) not requiring medication (NBP group), those on antihypertensive medications (HTN group), and those on medications for hypotension (fludrocortisone and/or midodrine) (Hypotensive group). RESULTS: A total of 306 recipients were included in the study: 54 (18%) in the NBP group, 215 (70%) in the HTN group, and 37 (12%) in the Hypotensive group. On multivariate analysis, the use of T-depleting induction (aHR = 9.64, p = .0001, 95% Cl = 3.12-29.75), pre-transplant use of hypotensive medications (aHR = 4.53, p = .0003, 95% Cl = 1.98-10.38), and longer duration of dialysis (aHR = 1.02, p = .01, 95% Cl = 1.00-1.04) were associated with an increased risk of post-transplant hypotension. Post-transplant hypotension was not associated with an increased risk of death-censored kidney or pancreatic allograft failure, or patient death. CONCLUSION: Hypotension was common even 6 months post-SPK transplantation. With appropriate management, hypotension was not associated with detrimental graft or patient outcomes.

Changes in Donor-Derived Cell-Free DNA Before and After Rejection and De Novo DSA Detection in Primary and Repeat Kidney Transplant Recipients.

BACKGROUND: Serial monitoring of dd-cfDNA and change from baseline can provide meaningful information beyond absolute thresholds. We describe dd-cfDNA trajectories from the baseline before and after acute rejection (AR) and de novo donor-specific antibodies (dnDSA) detection in kidney transplant recipients (KTRs). METHODS: We included KTR from 02/2019 to 03/2022 with serial dd-cfDNA. The primary analysis compared the time-varying change in dd-cfDNA from baseline in KTR first AR on biopsy [AR] to patients with no-AR on biopsy [no-AR]. RESULTS: 151 KTR were analyzed (AR = 56 KTR, no-AR = 95 KTRs). In the AR group, dd-cfDNA rose ahead of diagnosis: median rise from baseline was 75% at -3 months, 32% at -2 months, and 325% at -1 month before biopsy. At the time of biopsy, the median rise in dd-cfDNA from baseline was 291% (IQR [interquartile range] 88%-1081%) in AR and 17% (IQR 0%- 194%) in no-AR (p < 0.0001). Following treatment, dd-cfDNA values fell in the AR group with a median change from baseline of 94.7% at +1 month, 10.5% at +2 months, and 0% at +3 months. These trajectories were not observed in the no-AR group. Similarly, there were no significant differences in eGFR (estimated glomerular filtration rate) trajectories between the two groups. The median change from baseline to dnDSA detection was 141% (IQR 112%-574%). In KTRs with persistent rejection, median dd-cfDNA was 0.95% (IQR 0.44-1.8) compared to 0.19% (IQR 0.12-0.31) in subjects with no rejection on follow-up (p < 0.001). CONCLUSION: The significant changes from baseline observed before and after AR show how serial monitoring enhances dd-cfDNA utility and allows for earlier identification of evolving injury and monitoring treatment response.

Incidence and outcomes of fever of unknown origin after kidney transplant in the modern era.

BACKGROUND: While presumably less common with modern molecular diagnostic and imaging techniques, fever of unknown origin (FUO) remains a challenge in kidney transplant recipients (KTRs). Additionally, the impact of FUO on patient and graft survival is poorly described. METHODS: A cohort of adult KTRs between January 1, 1995 and December 31, 2018 was followed at the University of Wisconsin Hospital. Patients transplanted from January 1, 1995 to December 31, 2005 were included in the "early era"; patients transplanted from January 1, 2006 to December 31, 2018 were included in the "modern era". The primary objective was to describe the epidemiology and etiology of FUO diagnoses over time. Secondary outcomes included rejection, graft and patient survival. RESULTS: There were 5590 kidney transplants at our center during the study window. FUO was identified in 323 patients with an overall incidence rate of .8/100 person-years. Considering only the first 3 years after transplant, the incidence of FUO was significantly lower in the modern era than in the early era, with an Incidence Rate Ratio (IRR) per 100 person-years of .48; 95% CI: .35-.63; p < .001. A total of 102 (31.9%) of 323 patients had an etiology determined within 90 days after FUO diagnosis: 100 were infectious, and two were malignancies. In the modern era, FUO remained significantly associated with rejection (HR = 44.1; 95% CI: 16.6-102; p < .001) but not graft failure (HR = 1.21; 95% CI: .68-2.18; p = .52) total graft loss (HR = 1.17; 95% CI: .85-1.62; p = .34), or death (HR = 1.17; 95% CI: .79-1.76; p = .43. CONCLUSIONS: FUO is less common in KTRs during the modern era. Our study suggests infection remains the most common etiology. FUO remains associated with significant increases in risk of rejection, warranting further inquiry into the management of immunosuppressive medications in SOT recipients in the setting of FUO.

Oxalate Nephropathy After Kidney Transplantation: Risk Factors and Outcomes of Two Phenotypes.

Describing risk factors and outcomes in kidney transplant recipients with oxalate nephropathy (ON) may help elucidate the pathogenesis and guide treatment strategies. We used a large single-center database to identify patients with ON and categorized them into delayed graft function with ON (DGF-ON) and late ON. Incidence density sampling was used to select controls. A total of 37 ON cases were diagnosed between 1/2011 and 1/2021. DGF-ON (n = 13) was diagnosed in 1.05% of the DGF population. Pancreatic atrophy on imaging (36.4% vs. 2.9%, p = 0.002) and gastric bypass history (7.7% vs. 0%; p = 0.06) were more common in DGF-ON than with controls with DGF requiring biopsy but without evidence of ON. DGF-ON was not associated with worse graft survival (p = 0.98) or death-censored graft survival (p = 0.48). Late ON (n = 24) was diagnosed after a mean of 78.2 months. Late ON patients were older (mean age 55.1 vs. 48.4 years; p = 0.02), more likely to be women (61.7% vs. 37.5%; p = 0.03), have gastric bypass history (8.3% vs. 0.8%; p = 0.02) and pancreatic atrophy on imaging (38.9% vs. 13.3%; p = 0.02). Late ON was associated with an increased risk of graft failure (HR 2.0; p = 0.07) and death-censored graft loss (HR 2.5; p = 0.10). We describe two phenotypes of ON after kidney transplantation: DGF-ON and late ON. Our study is the first to our knowledge to evaluate DGF-ON with DGF controls without ON. Although limited by small sample size, DGF-ON was not associated with adverse outcomes when compared with controls. Late ON predicted worse allograft outcomes.

Analysis of Rejection, Infection and Surgical Outcomes in Type I Versus Type II Diabetic Recipients After Simultaneous Pancreas-Kidney Transplantation.

Given the increasing frequency of simultaneous pancreas-kidney transplants performed in recipients with Type II diabetes and CKD, we sought to evaluate possible differences in the rates of allograft rejection, infection, and surgical complications in 298 Type I (T1D) versus 47 Type II (T2D) diabetic recipients of simultaneous pancreas-kidney transplants between 2006-2017. There were no significant differences in patient or graft survival. The risk of biopsy-proven rejection of both grafts was not significantly different between T2D and T1D recipients (HRpancreas = 1.04, p = 0.93; HRkidney = 0.96; p = 0.93). Rejection-free survival in both grafts were also not different between the two diabetes types (ppancreas = 0.57; pkidney = 0.41). T2D had a significantly lower incidence of de novo DSA at 1 year (21% vs. 39%, p = 0.02). There was no difference in T2D vs. T1D recipients regarding readmissions (HR = 0.77, p = 0.25), infections (HR = 0.77, p = 0.18), major surgical complications (HR = 0.89, p = 0.79) and thrombosis (HR = 0.92, p = 0.90). In conclusion, rejection, infections, and surgical complications after simultaneous pancreas-kidney transplant are not statistically significantly different in T2D compared to T1D recipients.

Early clearance of BK polyomavirus-DNAemia among kidney transplant recipients may lead to better graft survival.

INTRODUCTION: BK polyomavirus (BKPyV)-DNAemia is a common complication in kidney transplant recipients (KTRs). The significance of achieving viral clearance at different time intervals is not well understood. METHODS: All adult KTRs transplanted between January 1, 2015 and December 31, 2017 who developed BKPyV-DNAemia were included. Outcomes were analyzed based on persistent clearance of BKPyV-DNAemia at 3-month intervals up to 2 years after initial detection, and for recipients with persistent BKPyV-DNAemia at last follow-up. Uncensored graft failure, death-censored graft failure (DCGF), and a composite outcome of DCGF or fall in estimated glomerular filtration rate (eGFR) by ≥50% from the time of initial BKPyV-DNAemia were outcomes of interest. RESULTS: Of 224 KTRs with BKPyV-DNAemia, 58 recipients (26%) achieved viral clearance by 3 months after initial detection, 105 (47%) by 6 months, 120 (54%) by 9 months, 141 (63%) by 12 months, 155 (69%) by 15 months, 167 (75%) by 18 months, 180 (80%) by 21 months, and 193 (86%) by 24 months. Nine recipients (4%) had persistent BKPyV-DNAemia at last follow-up. Compared to recipients who achieved viral clearance by 3 months, those who achieved clearance by 6 months (adjusted odds ratio [aOR]: 3.15; 95% confidence interval [CI]: 1.22-8.12; p = .02) and 9 months (aOR: 3.69; 95% CI: 1.02-13.43; p = .04) had significantly increased risk for uncensored graft failure. There was no significant association between time to viral clearance and DCGF or composite outcomes. CONCLUSIONS: We found a trend of increased risk for uncensored graft failure among those who cleared BKPyV-DNAemia more slowly. Aiming to clear viremia early, without risking rejection, may be beneficial for allograft function and patient morbidity and mortality.

Malnutrition in solid organ transplant patients: A review of the literature.

Screening for malnutrition is of vital importance for solid organ transplant candidates to optimize nutrition status before transplant, to improve clinical outcomes and to inform selection committees of nutritional contraindications and risks. There are multiple criteria and screening tools available for determining malnutrition diagnosis and risk. Registered Dietitian Nutritionists use these tools for nutrition assessments to quantify the severity of malnutrition, provide patient-centered interventions, and monitor progression. Many transplant centers in the United States utilize the American Society of Parenteral and Enteral Nutrition and the Academy of Nutrition and Dietetics' Adult Malnutrition Criteria, though there is limited research using these criteria specifically in the transplant population. Malnutrition, utilizing other diagnostic and screening tools, has been associated with important complications, including longer length of hospital stay, increased mortality, decreased quality of life, worsened end-stage organ progression, and decreased functional status. Malnutrition typically results from sarcopenia and cachexia, and can ultimately lead to frailty, causing further negative impacts on transplant outcomes. This literature review summarizes the current research on malnutrition in solid organ transplant candidates and provides recommendations for future research and current practice implications.

Discordance in cytomegalovirus viremia in kidney recipients from the same donor is associated with the worst outcomes.

BACKGROUND: Cytomegalovirus (CMV) is a common viral infection in kidney transplant recipients (KTR) that has been associated with negative outcomes. The effect on outcomes of concordance versus discordance in CMV between two different recipients of kidneys from the same donor is largely unknown. METHODS: We reviewed all adult deceased donor kidney transplant recipients (DDKTs) for which both kidneys were transplanted to two different recipients at our center between 2014 and 2019. Recipient pairs from each donor were divided into groups based on concordance or discordance for the development of CMV viremia between the pair; concordant no CMV (cc-no-CMV) if neither KTR developed CMV, concordant CMV (cc-CMV) if both KTRs developed CMV. The discordant group was then further divided based on the individual development of CMV (dc-CMV) or lack of development of CMV (dc-no-CMV). Patient mortality and death-censored graft failure (DCGF) were outcomes of interest. RESULTS: Of 578 KTRs, 67% were cc-no-CMV, 5% were cc-CMV, 14% were dc-no-CMV, and 14% dc-CMV. Some of the baseline characteristics differ among the groups including a higher prevalence of high-risk serostatus (D+/R-) in cc-CMV (32%) and dc-CMV (32%). In multivariate analysis, with reference to cc-no-CMV, dc-CMV was associated with increased risk for DCGF (HR 3.13, 95% CI 1.58-6.19), and so was delayed graft function. Factors associated with increased risk of mortality were advanced recipient age and DGF. cc-CMV was neither associated with mortality nor DCGF. CONCLUSIONS: These findings support that in certain contexts, CMV viremia has adverse allograft outcomes, and this is highlighted when illustrated via discordance in CMV between pair kidneys from the same deceased donor.

Pre-transplant hypoalbuminemia is not associated with worse short-term outcomes among kidney transplant recipients.

INTRODUCTION: Serum albumin is an indicator of overall health status, but it remains unclear how pre-transplant hypoalbuminemia is associated with early post-transplant outcomes. METHODS: This study included all adult kidney transplant recipients (KTRs) at our center from 01/01/2001-12/31/2017 with serum albumin measured within 30 days before transplantation. KTRs were grouped based on pretransplant albumin level normal (≥4.0 g/dL), mild (≥3.5 - < 4.0g/dL), moderate (≥3.0 - < 3.5g/dL), or severe hypoalbuminemia (<3.0g/dL). Outcomes of interest included: length of hospital stay (LOS), readmission within 30 days, delayed graft function(DGF), and re-operation related to post-transplant surgical complications. We also analyzed rejection, graft failure, and death within 6 months post-transplant. RESULTS: A total of 2807 KTRs were included 43.6% had normal serum albumin, 35.3% mild, 16.6% moderate, and 4.5% severe hypoalbuminemia. Mild and moderate hypoalbuminemia were associated with a shorter LOS by 1.22 (p < 0.001) and 0.80 days (p = 0.01), respectively, compared to normal albumin. Moderate (HR: 0.58; 95% CI: 0.37-0.91; p = 0.02) and severe hypoalbuminemia (HR: 0.21; 95% CI: 0.07-0.68; p = 0.01) were associated with significantly lower rates of acute rejection within 6 months post-transplant. CONCLUSION: Patients with pre-transplant hypoalbuminemia have post-transplant outcomes similar to those with normal serum albumin, but with a lower risk of acute rejection based on the degree of hypoalbuminemia.

Hypoalbuminemia is a risk factor for invasive fungal infections and poor outcomes in infected kidney transplant recipients.

INTRODUCTION: Invasive fungal infections (IFI), are estimated to occur in 2%-14% of kidney transplant recipients (KTRs) in the current era of immune suppression and are associated with high mortality rates. We hypothesized that hypoalbuminemia in KTRs is a risk factor for IFI and would be associated with poor outcomes. METHODS: In this study, using data from a prospective cohort registry, we describe the frequency of IFI due to Blastomycosis, Coccidioidomycosis, Histoplasmosis, Aspergillosis, and Cryptococcus in KTRs with serum albumin levels measured 3-6 months before diagnosis. Controls were selected based on incidence density sampling. KTRs were divided into three groups based on the pre-IFI serum albumin level: normal (≥4 g/dL), mild (3-4 g/dL), or severe (<3 g/dL) hypoalbuminemia. Outcomes of interest were uncensored graft failure after IFI and overall mortality. RESULTS: A total of 113 KTRs with IFI were compared with 348 controls. The incidence rate of IFI among individuals with normal, mild, and severe hypoalbuminemia was 3.6, 8.7, and 29.3 per 100 person-years, respectively. After adjustment for multiple variables, the trend for risk of uncensored graft failure following IFI was greater in KTRS with mild (HR = 2.1; 95% CI, .75-6.1) and severe (HR = 4.47; 95% CI, 1.56-12.8) hypoalbuminemia (P-trend < .001) compared to those with normal serum albumin. Similarly, mortality was higher in severe hypoalbuminemia (HR = 1.9; 95% CI, .67-5.6) compared to normal serum albumin (P-trend < .001). CONCLUSION: Hypoalbuminemia precedes the diagnosis of IFI in KTRs, and is associated with poor outcomes following IFI. Hypoalbuminemia may be a useful predictor of IFI in KTRs and could be incorporated into screening algorithms.

Comprehensive review: Frailty in pancreas transplant candidates and recipients.

Well-selected patients with kidney disease and diabetes mellitus who undergo simultaneous kidney-pancreas transplantation often experience dramatic improvements in quality of life and long-term survival compared to those who remain on medical therapy. Over the past several years the importance of frailty in the pancreas transplant candidate and recipient populations has grown. More patients with advanced age have entered the waitlist, and complications from prolonged diabetes, even in younger patients, have created increased evidence of risk for frailty. Given these concerns, and the broad challenges facing pancreas transplantation volumes overall, we generated this review to help establish the impact and implications. We summarize the interplay of immunological factors, aging, environmental factors, diabetes mellitus, and chronic kidney disease that put these patients at risk for frailty. We discuss its measurement and recommend a combination of two instruments (both well-validated and one entirely objective). We describe the outcomes for patients before and after pancreas transplantation who may have frailty, and what interventions can be taken to mitigate its effects. Broader investigation into frailty in the pancreas transplant population is needed to better understand how to select patients for pancreas transplantation and to how manage its consequences thereafter.

The Perspectives of General Nephrologists Toward Transitions of Care and Management of Failing Kidney Transplants.

The management of failing kidney allograft and transition of care to general nephrologists (GN) remain a complex process. The Kidney Pancreas Community of Practice (KPCOP) Failing Allograft Workgroup designed and distributed a survey to GN between May and September 2021. Participants were invited via mail and email invitations. There were 103 respondents with primarily adult nephrology practices, of whom 41% had an academic affiliation. More than 60% reported listing for a second kidney as the most important concern in caring for patients with a failing allograft, followed by immunosuppression management (46%) and risk of mortality (38%), while resistant anemia was considered less of a concern. For the initial approach to immunosuppression reduction, 60% stop antimetabolites first, and 26% defer to the transplant nephrologist. Communicating with transplant centers about immunosuppression cessation was reported to occur always by 60%, and sometimes by 29%, while 12% reported making the decision independently. Nephrologists with academic appointments communicate with transplant providers more than private nephrologists (74% vs. 49%, p = 0.015). There are heterogeneous approaches to the care of patients with a failing allograft. Efforts to strengthen transitions of care and to develop practical practice guidelines are needed to improve the outcomes of this vulnerable population.

Delayed graft function: current status and future directions.

PURPOSE OF REVIEW: Delayed graft function is a common early posttransplant event predictive of adverse outcomes including hospital readmission, impaired long-term graft function, and decreased graft and patient survival. The purpose of this review is to summarize recent literature describing delayed graft function in hopes of better understanding and managing this condition. RECENT FINDINGS: Recent research efforts have been garnered towards risk factor modification, prevention, and earlier detection of delayed graft function. In this review, we aim to summarize current innovative approaches and future directions. SUMMARY: Delayed graft function portends worse graft and patient outcomes. Continued research to prevent, and detect early perturbations in allograft function, and more optimally manage this disease will hopefully improve graft function, along with graft/patient survival.

Factors affecting sensitization following kidney allograft failure.

INTRODUCTION: Management of immunosuppression in a kidney transplant recipient with a failed allograft is complex; continuation carries infectious and metabolic risks, and discontinuation can lead to sensitization. METHODS: We evaluated risk factors for sensitization in 89 kidney or simultaneous kidney-pancreas recipients, whose kidney transplant failed after January, 2013 and who were subsequently re-evaluated for kidney transplantation. RESULTS: Among recipients with pre graft failure cPRA < 50%, calcineurin inhibitor (CNI) continuation (OR .11, P = .003) and steroid continuation (OR .17, P = .04) were associated with significantly lower odds of developing an absolute increase in cPRA of ≥50%. Each additional HLA mismatch was associated with OR of 2.16 (P = .02). CNI use was associated with OR of .09 (P = .001) for increase in cPRA to ≥80% if pre graft failure cPRA was <50%, and OR of .08 (P = .02) for increase in cPRA to ≥98% if pre graft cPRA was <80%. Anti-metabolites were continued more often among recipients who had a <50% increase (P = .006); however, the association was lost on multivariate analyses. Weaning off immunosuppression and higher number of HLA mismatches are associated with greater likelihood of sensitization. CONCLUSION: While both CNI and steroid continuation conferred some protection against increase in cPRA, CNI continuation was the only factor protecting against becoming highly sensitized.

Kidney transplant outcomes among recipients with post-transplant hip or knee joint replacement surgery.

INTRODUCTION: Patients with end-stage renal disease (ESRD) are at a higher risk of needing hip or knee replacement (joint replacement) surgery due to the high prevalence of degenerative joint disease and other conditions. However, there remains a large debate about the timing of joint replacement surgery and whether it should be pre- vs post-transplant. METHODS: We conducted a retrospective study analyzing all adult kidney transplant recipients (KTRs) at our university hospital who had undergone subsequent joint replacement between 2001 and 2017. Transplant-specific outcomes of acute rejection, death censored graft failure (DCGF), and patient death post-joint replacement surgery were outcomes of interest. Controls were selected at a 1:3 ratio based on the incidence density sampling of post-transplant interval. RESULTS: There were 101 KTRs in the joint replacement group and were compared with 281 controls. In the multivariate analysis, the need for joint replacement was not associated with acute rejection (HR: 1.59; 95% CI: 0.77-3.29; P = 0.21); DCGF (HR: 0.89; 95% CI: 0.49-1.60; P = 0.70) or patient death (HR: 0.84, 95% CI: 0.55-1.38, P = 0.42). CONCLUSION: In selected KTRs, joint replacement surgery was not associated with detrimental transplant-specific outcomes.