Kukla, Aleksandra

The Hispanic population of the United States is the second largest racial or ethnic group, comprising 18.7% of the population. However, this population is incredibly heterogeneous differing in genetic traits, cultural upbringing, educational backgrounds, and financial status. The impact of this heterogeneity on the prevalence and outcomes of renal disease and kidney transplantation is understudied compared with non-Hispanic White and Black populations. What is known appears to be underrecognized. This review aims to critically assess current medical literature on Hispanic individuals, focusing on etiological factors, disease progression, and outcomes related to CKD and kidney transplantation. By doing so, we aim to underscore key areas for further in-depth investigation.

Key Points Morphometry allows for a more prognostic multidimensional quantification of interstitial fibrosis and tubular atrophy (IFTA) in kidneys than does visual inspection. The density of IFTA foci is determined by dividing the number of contiguous IFTA patches in the kidney cortex by the area of cortex. Higher density of IFTA foci significantly predicted renal allograft failure beyond %IFTA and other biopsy and clinical characteristics. Background Contraction of interstitial fibrosis and tubular atrophy (IFTA) may cause %IFTA to under-represent the severity of nephron loss. Higher density of IFTA foci is an important predictor of progressive CKD in native kidneys independent of %IFTA. Methods We studied kidney transplant recipients transplanted between 2000 and 2013 who had a 5-year surveillance kidney biopsy and subsequent follow-up. Banff ci score (interstitial fibrosis) was obtained from the pathology reports. After digitizing the biopsies, we traced cortex area and each distinct IFTA focus on a single trichrome-stained section. Percent IFTA area and IFTA foci density (count of IFTA foci/cortex area) were calculated. Cox models assessed the risk of death-censored graft failure after the 5-year biopsy with Banff ci score, morphometric %IFTA, and IFTA foci density. Results There were 58 death-censored allograft failures among 835 kidney recipients during the 5 years of follow-up. Biopsies from grafts that failed had higher mean Banff ci score (1.5 versus 0.7, P < 0.0001), %IFTA (22.6% versus 7.0%, P < 0.0001), and IFTA foci density (1.3/mm 2 versus 0.4/mm 2 , P < 0.0001). After adjusting for other Banff scores or clinical variables, Banff ci did not correlate with allograft failure, but both higher %IFTA (hazard ratio = 1.56, P < 0.0001) and higher IFTA foci density (hazard ratio = 2.34, P < 0.0001) did. All but four allograft failures by 10 years had biopsies in the top quartile of either %IFTA or IFTA foci density at 5 years. A model using just these two morphometric measures without clinical characteristics resulted in a c-statistic of 0.891 with respect to allograft failure. Conclusions Morphometric characterization of IFTA foci density is a strong predictor of death-censored allograft failure not captured in current Banff classification for grading of kidney fibrosis.

Background. Mesangial expansion (ME) is an understudied histologic lesion in renal allografts. The current Banff mm score is not reproducible and may miss important ME features. The study aimed to improve the quantification of ME using morphometry, assess changes over time, and determine its association with allograft loss. Methods. We studied ME in 1-y and 5-y surveillance biopsies in 835 kidney transplants performed between January 2000 and December 2013. ME was assessed using the Banff mm score by a central pathologist and by morphometry. We derived 3 different morphometric measures: (1) %ME mm (%glomeruli with ME in ≥2 lobules, like Banff mm); (2) %MEany (%glomeruli with any ME lesion); and (3) %ME area (sum of all ME areas/all glomerular tuft areas). Unadjusted and adjusted Cox models assessed the risk of death-censored allograft loss. Results. From 1- to 5-y biopsies, the mean Banff mm score increased from 0.18 to 0.34, whereas %ME mm increased from 2.5% to 13.3%. Banff mm score had modest correlations with morphometric ME measures. Moderate-severe %ME mm was present in 20.1% of 5-y biopsies, whereas only 6.6% of Banff mm scores were. In general, higher ME on both 1- and 5-y biopsies was associated with a deceased donor, older recipient age, recipient diabetes/obesity (present in >50% of severely affected biopsies), higher hemoglobin A1c at 5 y posttransplant, and recurrent kidney disease. Higher ME on 5-y biopsies was associated with delayed graft function. A higher Banff mm score at 1-y biopsy and morphometry ME measures at 5-y biopsy were associated with rejection during the first year posttransplant. Morphometric ME measures were associated with allograft loss independent of Banff scores and all clinical characteristics, including kidney function and recurrent disease. The model with %MEany had the highest c-statistic (0.872). Conclusions. Banff mm score underestimates the pervasiveness of ME in 5-y biopsies. ME is common and associated with alloimmune and nonalloimmune causes of graft loss.

Background. Microvascular inflammation (MVI) is a key feature of antibody-mediated rejection (AMR) among patients with HLA donor-specific antibody (DSA), but MVI at AMR thresholds (Banff glomerulitis [g] + peritubular capillaritis [ptc] score ≥ 2) without DSA has been increasingly recognized. We aimed to determine the incidence of MVI among highly sensitized kidney transplant recipients without DSA. Methods. We performed a single-center, retrospective, matched cohort study comparing outcomes of kidney transplant recipients with cPRA ≥90% with preexisting DSA (n = 49), cPRA ≥90% without preexisting DSA (n = 47), and matched controls with cPRA = 0 without preexisting DSA (n = 49). Controls were matched by age, donor type, and transplant date. Indication and surveillance biopsies combined with annual de novo DSA screening were obtained. Results. Kidney transplant recipients with a cPRA ≥90% and no evidence of preexisting or de novo DSA had a higher incidence of MVI (glomerulitis + peritubular capillaritis ≥ 2) than patients with cPRA = 0 [35% (17/49) versus 12% (6/49), P = 0.0003] over a median (interquartile range) follow-up of 5 (4–6) y posttransplant. Among this cPRA ≥90% group without DSA, MVI persisted in 54% of cases on follow-up biopsy (7/13), and 24% (4/13) of cases developed transplant glomerulopathy (Banff cg score > 0). Conclusions. Highly sensitized transplant recipients have a high incidence of persistent and progressive MVI, even without DSA. The mechanisms underlying these histologic features needs to be elucidated, but this information is important to consider when making decisions about transplantation among highly sensitized individuals.

Background. Pancreas transplant biopsy practices for the diagnosis of rejection or other pathologies are not well described. Methods. We conducted a survey of staff at US pancreas transplant programs (March 22, 2022, to August 22, 2022) to assess current program practices and perceptions about the utility and challenges in the performance and interpretation of pancreas allograft biopsies. Results. Respondents represented 65% (76/117) of active adult pancreas transplant programs, capturing 66% of recent pancreas transplant volume in the United States. Participants were most often nephrologists (52%), followed by surgeons (46%), and other staff (4%). Pancreas allograft biopsies were performed mostly by interventional radiologists (74%), followed by surgeons (11%), nephrologists (8%), and gastroenterologists (1%). Limitations in the radiologist’s or biopsy performer’s comfort level or expertise to safely perform a biopsy, or to obtain sufficient/adequate samples were the two most common challenges with pancreas transplant biopsies. Pancreas transplant biopsies were read by local pathologists at a majority (86%) of centers. Challenges reported with pancreas biopsy interpretation included poor reliability, lack of reporting of C4d staining, lack of reporting of rejection grading, and inconclusive interpretation of the biopsy. Staff at a third of responding programs (34%) stated that they rarely or never perform pancreas allograft biopsies and treat presumed rejection empirically. Conclusions. This national survey identified significant variation in clinical practices related to pancreas allograft biopsies and potential barriers to pancreas transplant utilization across the United States. Consideration of strategies to improve program experience with percutaneous pancreas biopsy and to support optimal management of pancreas allograft rejection informed by histology is warranted.

ABSTRACT Post-transplantation diabetes mellitus (PTDM) remains a leading complication after solid organ transplantation. Previous international PTDM consensus meetings in 2003 and 2013 provided standardized frameworks to reduce heterogeneity in diagnosis, risk stratification and management. However, the last decade has seen significant advancements in our PTDM knowledge complemented by rapidly changing treatment algorithms for management of diabetes in the general population. In view of these developments, and to ensure reduced variation in clinical practice, a 3rd international PTDM Consensus Meeting was planned and held from 6–8 May 2022 in Vienna, Austria involving global delegates with PTDM expertise to update the previous reports. This update includes opinion statements concerning optimal diagnostic tools, recognition of prediabetes (impaired fasting glucose and/or impaired glucose tolerance), new mechanistic insights, immunosuppression modification, evidence-based strategies to prevent PTDM, treatment hierarchy for incorporating novel glucose-lowering agents and suggestions for the future direction of PTDM research to address unmet needs. Due to the paucity of good quality evidence, consensus meeting participants agreed that making GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) recommendations would be flawed. Although kidney-allograft centric, we suggest that these opinion statements can be appraised by the transplantation community for implementation across different solid organ transplant cohorts. Acknowledging the paucity of published literature, this report reflects consensus expert opinion. Attaining evidence is desirable to ensure establishment of optimized care for any solid organ transplant recipient at risk of, or who develops, PTDM as we strive to improve long-term outcomes.

AbstractPancreas transplantation alone (PTA) is a β cell replacement option for selected patients with type 1 diabetes mellitus; concerns have been raised regarding deterioration in kidney function (KF) after PTA. This retrospective multicenter study assessed actual impact of transplantation and immunosuppression on KF in PTA recipients at three Transplant Centers. The primary composite endpoint 10 years after PTA was >50% eGFR decline, eGFR < 30 mL/min/1.73 m2, and/or receiving a kidney transplant (KT). Overall, 822 PTA recipients met eligibility. Median baseline and 10‐year eGFR (mL/min/1.73 m2) were 76.3 (58.1–100.8) and 51.3 (35.3–65.9), respectively. Primary composite endpoint occurred in 98 patients (53.5%) with 45 experiencing a >50% decrease in eGFR by 10 years post‐transplant, 38 eGFR < 30 mL/min/1.73 m2 and 49 requiring KT. KF declined most significantly within 6 months post‐PTA, more often in females and patients with better preserved GFR up to 5 years with 11.6% kidney failure at 10 years. Patient survival and death‐censored graft survival were both 68% at 10 years with overall graft thrombosis rate 8%. KF declined initially after PTA but stabilized with further slow progression. In conclusion, prospective intervention studies are needed to test renal sparing interventions while gathering more granular data.