Risk factors for lower renal compensation after nephrectomy: an analysis of living kidney donors in an Amazonian cohort / Fatores de risco para menor compensação renal pós-nefrectomia: análise de doadores de rim vivo em uma coorte amazônica

Abstract Introduction: Living donor kidney transplantation is considered the ideal renal replacement therapy because it has a lower complication rate and allows an efficient response to the high demand for grafts in the healthcare system. Careful selection and adequate monitoring of donors is a key element in transplantation. Individuals at greater risk of developing kidney dysfunction after nephrectomy must be identified. Objective: To identify risk factors associated with a renal compensation rate (CR) below 70% 12 months after nephrectomy. Methods: This observational retrospective longitudinal study included living kidney donors followed up at the Lower Amazon Regional Hospital between 2016 and 2022. Data related to sociodemographic variables, comorbid conditions and kidney function parameters were collected. Results: The study enrolled 32 patients. Fourteen (43.75%) had a CR < 70% 12 months after kidney donation. Logistic regression found obesity (Odds Ratio [95%CI]: 10.6 [1.7-65.2]), albuminuria (Odds Ratio [95%CI]: 2.41 [1.2-4.84]) and proteinuria (Odds Ratio [95%CI]: 1.14 [1.03-1.25]) as risk factors. Glomerular filtration rate was a protective factor (Odds Ratio [95% CI]: 0.92 [0.85-0.99]). Conclusion: Obesity, albuminuria and proteinuria adversely affected short-term renal compensation rate. Further studies are needed to uncover the prognostic implications tied to these risk factors. Our findings also supported the need for careful individualized assessment of potential donors and closer monitoring of individuals at higher risk.

Resumo Introdução: O transplante de rim de doador vivo é considerado a terapia renal substitutiva ideal por oferecer menor taxa de complicações e possibilitar uma resposta eficiente à grande demanda por enxertos no sistema de saúde. A seleção criteriosa e o acompanhamento adequado dos doadores constituem um pilar fundamental dessa modalidade terapêutica, sendo essencial a identificação dos indivíduos em maior risco de disfunção renal pós-nefrectomia. Objetivo: Identificar fatores de risco para uma Taxa de Compensação (TC) da função renal inferior a 70% 12 meses após a nefrectomia. Métodos: Estudo observacional, retrospectivo e longitudinal conduzido com doadores de rim vivo acompanhados no Hospital Regional do Baixo Amazonas entre 2016 e 2022. Foram coletados dados correspondentes a variáveis sociodemográficas, comorbidades e parâmetros de função renal. Resultados: Foram incluídos 32 pacientes na amostra final. Destes, 14 (43,75%) obtiveram TC < 70% 12 meses após a doação. A regressão logística identificou a obesidade (Odds Ratio [IC95%]: 10.6 [1.7-65.2]), albuminúria (Odds Ratio [IC95%]: 2.41 [1.2-4.84]) e proteinúria (Odds Ratio [IC95%]: 1.14 [1.03-1.25]) como fatores de risco. A taxa de filtração glomerular atuou como fator de proteção (Odds Ratio [IC95%]: 0.92 [0.85-0.99]). Conclusão: Obesidade, albuminúria e proteinúria demonstraram impacto negativo na taxa de compensação renal em curto prazo, o que reitera a necessidade de estudos acerca das implicações prognósticas desses fatores. Além disso, reforça-se a necessidade de avaliação cuidadosa e individualizada dos possíveis doadores, com acompanhamento rigoroso, especialmente para indivíduos de maior risco.

Transitioning to peritoneal dialysis: it does not matter where you come from / Transição para diálise peritoneal: não importa de onde

Introduction: Patients with end-stage renal disease (ESRD) frequently change renal replacement (RRT) therapy modality due to medical or social reasons. We aimed to evaluate the outcomes of patients under peritoneal dialysis (PD) according to the preceding RRT modality. Methods: We conducted a retrospective observational single-center study in prevalent PD patients from January 1, 2010, to December 31, 2017, who were followed for 60 months or until they dropped out of PD. Patients were divided into three groups according to the preceding RRT: prior hemodialysis (HD), failed kidney transplant (KT), and PD-first. Results: Among 152 patients, 115 were PD-first, 22 transitioned from HD, and 15 from a failing KT. There was a tendency for ultrafiltration failure to occur more in patients transitioning from HD (27.3% vs. 9.6% vs. 6.7%, p = 0.07). Residual renal function was better preserved in the group with no prior RRT (p < 0.001). A tendency towards a higher annual rate of peritonitis was observed in the prior KT group (0.70 peritonitis/year per patient vs. 0.10 vs. 0.21, p = 0.065). Thirteen patients (8.6%) had a major cardiovascular event, 5 of those had been transferred from a failing KT (p = 0.004). There were no differences between PD-first, prior KT, and prior HD in terms of death and technique survival (p = 0.195 and p = 0.917, respectively) and PD efficacy was adequate in all groups. Conclusions: PD is a suitable option for ESRD patients regardless of the previous RRT and should be offered to patients according to their clinical and social status and preferences.

Introdução: Pacientes com doença renal em estágio terminal (DRET) frequentemente mudam de modalidade de terapia renal substitutiva (TRS) por razões médicas ou sociais. Nosso objetivo foi avaliar desfechos de pacientes em diálise peritoneal (DP) segundo a modalidade anterior de TRS. Métodos: Realizamos estudo retrospectivo observacional unicêntrico, em pacientes prevalentes em DP, de 1º de janeiro de 2010 a 31 de dezembro de 2017, acompanhados por 60 meses ou até saírem de DP. Pacientes foram divididos em três grupos de acordo com a TRS anterior: hemodiálise prévia (HD), transplante renal malsucedido (TR) e DP como primeira opção (PD-first). Resultados: Entre 152 pacientes, 115 eram PD-first, 22 transitaram da HD e 15 de TR malsucedido. Houve tendência à maior ocorrência de falência de ultrafiltração em pacientes em transição da HD (27,3% vs. 9,6% vs. 6,7%; p = 0,07). A função renal residual foi melhor preservada no grupo sem TRS prévia (p < 0,001). Observou-se tendência à maior taxa anual de peritonite no grupo TR prévio (0,70 peritonite/ano por paciente vs. 0,10 vs. 0,21; p = 0,065). Treze pacientes (8,6%) tiveram um evento cardiovascular maior, cinco dos quais haviam sido transferidos de um TR malsucedido (p = 0,004). Não houve diferenças entre PD-first, TR prévio e HD prévia em termos de óbito e sobrevida da técnica (p = 0,195 e p = 0,917, respectivamente) e a eficácia da DP foi adequada em todos os grupos. Conclusões: A DP é uma opção adequada para pacientes com DRET, independentemente da TRS anterior, e deve ser oferecida aos pacientes de acordo com seu status clínico e social e suas preferências.

Proteomic Changes Induced by the Immunosuppressant Everolimus in Human Podocytes.

mTOR inhibitors (mTOR-Is) may induce proteinuria in kidney transplant recipients through podocyte damage. However, the mechanism has only been partially defined. Total cell lysates and supernatants of immortalized human podocytes treated with different doses of everolimus (EVE) (10, 100, 200, and 500 nM) for 24 h were subjected to mass spectrometry-based proteomics. Support vector machine and partial least squares discriminant analysis were used for data analysis. The results were validated in urine samples from 28 kidney transplant recipients receiving EVE as part of their immunosuppressive therapy. We identified more than 7000 differentially expressed proteins involved in several pathways, including kinases, cell cycle regulation, epithelial-mesenchymal transition, and protein synthesis, according to gene ontology. Among these, after statistical analysis, 65 showed an expression level significantly and directly correlated with EVE dosage. Polo-Like Kinase 1 (PLK1) content was increased, whereas osteopontin (SPP1) content was reduced in podocytes and supernatants in a dose-dependent manner and significantly correlated with EVE dose (p < 0.0001, FDR < 5%). Similar results were obtained in the urine of kidney transplant patients. This study analyzed the impact of different doses of mTOR-Is on podocytes, helping to understand not only the biological basis of their therapeutic effects but also the possible mechanisms underlying proteinuria.

Steroid-tacrolimus drug-drug interaction and the effect of CYP3A genotypes.

AIMS: Tacrolimus, metabolized by CYP3A4 and CYP3A5 enzymes, is susceptible to drug-drug interactions (DDI). Steroids induce CYP3A genes to increase tacrolimus clearance, but the effect is variable. We hypothesized that the extent of the steroid-tacrolimus DDI differs by CYP3A4/5 genotypes. METHODS: Kidney transplant recipients (n = 2462) were classified by the number of loss of function alleles (LOF) (CYP3A5*3, *6 and *7 and CYP3A4*22) and steroid use at each tacrolimus trough in the first 6 months post-transplant. A population pharmacokinetic analysis was performed by nonlinear mixed-effect modelling (NONMEM) and stepwise covariate modelling to define significant covariates affecting tacrolimus clearance. A stochastic simulation was performed and translated into a Shiny application with the mrgsolve and Shiny packages in R. RESULTS: Steroids were associated with modestly higher (3%-11.8%) tacrolimus clearance. Patients with 0-LOF alleles receiving steroids showed the greatest increase (11.8%) in clearance compared to no steroids, whereas those with 2-LOFs had a negligible increase (2.6%) in the presence of steroids. Steroid use increased tacrolimus clearance by 5% and 10.3% in patients with 1-LOF and 3/4-LOFs, respectively. CONCLUSIONS: Steroids increase the clearance of tacrolimus but vary slightly by CYP3A genotype. This is important in individuals of African ancestry who are more likely to carry no LOF alleles, may more commonly receive steroid treatment, and will need higher tacrolimus doses.

Intracardiac vascular access in haemodialysis: A last resort for exhausted traditional access.

Depletion of veins for dialysis access is a challenging life threatening situation for patients in need of haemodialysis. The utilisation of intracardiac catheter is a rare procedure with scarce reported experience. We describe the case of a 68-year-old male that contributes to the limited knowledge of performing a life-saving intracardiac catheter placement for emergency haemodialysis in a patient without immediate alternative renal replacement therapy available. We also retrospectively analyse the experience reported so far and summarise complications and outcomes. In our case, the patient was able to pursue haemodialysis after intracardiac catheter placement without any complications. Two weeks later, the patient successfully received a kidney transplant from a deceased donor and has a serum creatinine of 1.7 mg/dL after 2 years of follow-up. There are only four reported cases of kidney transplantation after the procedure, including our own. Intracardiac catheter is an emerging option that could be considered in certain patients as the last resort. Further investigation with regards to patient candidacy and procedure security are necessary.

Presumed Monozygotic Twin Kidney Transplantation with a Thin Basement Membrane Nephropathy Donor: A Case Report.

Identical or Monozygotic twin kidney transplant usually possess an excellent immunological match and provide the opportunity to minimize or even avoid immunosuppression toxicity. However, there are concerns regarding disease recurrence among end stage kidney disease (ESKD) patients with an unknown etiology. Together with the risk of inherent, familial disease affecting donors and recipients alike, more invasive tests such as a pretransplant biopsy are being considered to ascertain renal prognosis. A 30-year-old female, known case of CKD Stage 5D from an unknown etiology, with secondary hyperparathyroidism and heart failure, presented at our OPD for kidney transplantation. Her donor is her identical twin who is asymptomatic and denies comorbidities. The recipient discloses a previous history of blood transfusion. Immunological workup revealed the following: matched blood type, zero HLA mismatch, negative T-cell tissue crossmatch but with a positive Class I HLA antigen screen. Antibody specificity revealed the presence of donor specific antibodies (DSA). After workup completion, the patient underwent a right kidney transplant with a preimplantation wedge biopsy on the donor kidney. Immediate graft function was noted post operatively. The wedge biopsy revealed a thinned glomerular basement membrane, consistent with Thin Basement Membrane Nephropathy (TBMN). The patient was started on immunosuppression and prophylaxis during the duration of the post operative period without any complications. Five months post-transplant, both the recipient and donor maintain an adequate renal function without any signs of allograft rejection. In this case report, we have demonstrated that TBMN may serve as a viable donor for a presumed monozygous twin kidney transplantation. When a live donor with TBMN is being considered, a thorough work-up and identification of high-risk features are essential to exclude other progressive renal diseases during the pretransplant evaluation.

Combined Urinary Reconstruction During en Bloc Kidney Transplantation From a Pediatric Donor to an Adult Recipient: A Case Report.

Urinary reconstruction during en bloc kidney transplantation is challenging, with different techniques described. Here, we report a case of combined urinary reconstruction using modified Lich ureteroneocystostomy and ureteroureterostomy.

Successful Kidney Transplantation Using Elderly Living Donor with Extremely Large Renal Cyst and Double Arteries.

The authors describe a kidney transplant procedure using a living donor with a large cyst and double arteries. Due to the lack of regular transplant activity from a deceased donors, we decided to use the, so called, expanded criteria living donors, which means older age (more than 65 years), hypertension, some structural anomalies of the kidneys (cysts, multiple renal arteries), ABO incompatible kidney transplant, etc. The surgical procedure was the unroofing of a large cyst and wadding with perirenal fat. The 10 years survival rate is quite successful and we can recommend it.

A novel nomogram for predicting the risk of persistent hyperparathyroidism after kidney transplantation.

PURPOSE: Persistent hyperparathyroidism (PTHPT) in kidney transplant recipients is associated with bone loss, graft dysfunction and cardiovascular mortality. There is no clear consensus on the management of PTHPT. Accurate risk prediction of the disease is needed to support individualized treatment decisions. We aim to develop a useful predictive model to provide early intervention for hyperparathyroidism in these patients. METHODS: We retrospectively analyzed 263 kidney transplantations in the urology department of China-Japan Friendship Hospital from January 2018 to December 2022. The overall cohort was randomly assigned 70% of the patients to the training cohort and 30% to the validation cohort. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for PTHPT and to construct the predictive model. This model was assessed regarding discrimination, consistency, and clinical benefit. RESULTS: The occurrence of PTHPT was 25.9% (68 out of 263 patients) in this study. Dialysis duration, postoperative 3-month intact parathyroid hormone (iPTH), 3-month corrected calcium (cCa), and 3-month phosphorus (P) are independent risk factors for the development of PTHPT. The nomogram showed good discrimination with the area under the curve (AUC) value of 0.926 in the training cohort and 0.903 in the validation cohort. The calibration curve and decision curve also showed that the model was well-evaluated. CONCLUSION: We developed a validated nomogram model to predict PTHPT after kidney transplantation. This can help the clinic prevent and control PTHPT early and improve patients' prognosis.

Sarcopenia as a predictor of mortality in kidney transplant recipients: A 5-year prospective cohort study with propensity score matching.

BACKGROUND: Sarcopenia is known to bring about adverse outcomes in elderly populations and dialysis patients. However, whether it is a risk factor in kidney transplant recipients (KTRs) has not yet been established. In the present study, the association of sarcopenia with mortality was investigated in KTRs. METHODS: We conducted a single-center prospective cohort study and recruited KTRs who were more than 1-year posttransplant from August 2017 to January 2018. The participants were followed for 5 years, and the Kaplan-Meier method and Cox proportional hazards model were used to assess patient survival. RESULTS: A total of 212 KTRs with a median age of 54 years and median transplant vintage of 79 months were enrolled in this study. Among them, 33 (16%) had sarcopenia according to the Asia Working Group for Sarcopenia 2019 at baseline. During the 5-year follow-up period, 20 (9.4%) died, 5 returned to dialysis after graft loss, and 4 were lost to follow-up. The 5-year overall survival rate was 90%. After 1:1 propensity score matching, a matched cohort with 60 KTRs was generated. The overall survival rate was significantly lower in the sarcopenia group compared to the non-sarcopenia group (p = 0.025, log-rank test). Furthermore, mortality risk was significantly higher in the sarcopenia group compared to the non-sarcopenia group (hazard ratio = 7.57, 95% confidence interval = 0.94-62). CONCLUSION: Sarcopenia was a predictor of mortality in KTRs. KTRs with suboptimal muscle status who were at risk for poor survival could have a clinical benefit by interventions for sarcopenia.

Corrigendum: Impaired antigen-specific B-cell responses after Influenza vaccination in kidney transplant recipients receiving co-stimulation blockade with Belatacept.

[This corrects the article DOI: 10.3389/fimmu.2022.918887.].

Persisting Hypercalcemia and Hyperparathyroidism after Kidney Transplantation Have a Negative Impact on Graft and Patient Survival.

Hyperparathyroidism (HPT) with hypercalcemia, often deemed irreversible and detrimental to graft survival post-kidney transplantation (KT), prompts pre-transplant parathyroidectomy in hypercalcemic patients. In this retrospective analysis of 1212 kidney transplant recipients (KTRs) between 2006 and 2019, the incidence and effect of persistent HPT and hypercalcemia on graft and patient survival, and risk factors for persistence were analyzed until 60 months of follow up (FU). At KT, 5.7% (n = 69) had no HPT, 32.7% (n = 396) had HPT without hypercalcemia and 37.0% (n = 448) had HPT with hypercalcemia. At 2 years FU, 26.4% (n = 320) of patients had no HPT and 6% (n = 73) had HPT with hypercalcemia. Dialysis and dialysis duration were linked to HPT development, while dialysis, KT waiting time and donor type correlated with persisting hypercalcemia after KT. KTRs with normalized PTH and recovered hypercalcemia had improved death-censored graft survival (p < 0.001) and overall patient survival (p < 0.001). HPT with hypercalcemia is frequent at time of KT with normalization of PTH and calcium in a substantial proportion of patients after a KT. These findings question the routine pre-KT parathyroidectomy for suspected parathyroid autonomy. Persisting HPT, especially with hypercalcemia, adversely affects graft and patient survival, suggesting the need for more aggressive treatment of HPT, especially in cases of persisting hypercalcemia.

Are There Differences in Skin Autofluorescence-Measured Advanced Glycation End-Product Levels between Chronic Kidney Disease and Kidney Transplant Recipients?

The aim of this cross-sectional study was to evaluate the differences in the levels of advanced glycation end products (AGE) between patients with chronic kidney disease (CKD) and kidney transplant recipients (KTRs) and to investigate the risk factors for the AGE levels in each group of these patients. There were 217 participants total, of which 99 (45.6%) were KTRs and 118 (54.4%) had CKD. Data on the levels of AGE, body mass composition, anthropometric parameters, central and peripheral blood pressure, and clinical and laboratory parameters were gathered for each study participant. The AGE values of the CKD and KTRs groups did not differ from one another. In both groups, a lower estimated glomerular filtration rate, male sex, and older age were positive predictors for increased AGE values. Furthermore, higher levels of AGE were linked to lower central systolic blood pressure (cSBP) in the CKD group, whilst, in the KTRs group, higher levels of AGE were linked to a shorter time since kidney transplantation (KTx), more years of dialysis prior to KTx, lower levels of trunk visceral fat, the presence of arterial hypertension, and the absence of prescriptions for the antihypertensive medications urapidil and angiotensin II receptor blockers. Further studies are needed to better understand the above associations. Consequently, a personalised multidisciplinary approach to assess the cardiovascular as well as dietary and lifestyle risk factors to reduce the AGE levels in both KTRs and CKD patients may be implemented.

Longitudinal monitoring of Torque Teno virus DNAemia in kidney transplant recipients correlates with long-term complications of inadequate immunosuppression.

Optimization of individual immunosuppression, which reduces the risks of both graft loss and patients' death, is considered the best approach to improve long-term outcomes of renal transplantation. Torque Teno Virus (TTV) DNAemia has emerged as a potential biomarker reflecting the depth of therapeutic immunosuppression during the initial year post-transplantation. However, its efficacy in long-term monitoring remains uncertain. In a cohort study involving 34 stable kidney transplant recipients and 124 healthy volunteers, we established lower and upper TTV DNAemia thresholds (3.75-5.1 log10 cp/mL) correlating with T-cell activatability, antibody response against flu vaccine, and risk for subsequent serious infections or cancer over 50 months. Validation in an independent cohort of 92 recipients confirmed that maintaining TTV DNAemia within this range in >50% of follow-up time points was associated with reduced risks of complications due to inadequate immunosuppression, including de novo DSA, biopsy-proven antibody-mediated rejection, graft loss, infections, or cancer. Multivariate analysis highlighted "in-target" TTV DNAemia as the sole independent variable significantly linked to decreased risk for long-term complications due to inadequate immunosuppression (odds ratio [OR]: 0.27 [0.09-0.77]; p = 0.019). Our data suggest that the longitudinal monitoring of TTV DNAemia in kidney transplant recipients could help preventing the long-term complications due to inadequate immunosuppression.

Influence of ensitrelvir or nirmatrelvir/ritonavir on tacrolimus clearance in kidney transplant recipients: a single-center case series.

BACKGROUND: Among the oral antivirals used for treating patients with mild-to-moderate novel coronavirus disease 2019 (COVID-19), nirmatrelvir/ritonavir (NMV/RTV) and ensitrelvir (ESV) are inhibitors of cytochrome P450 (CYP) 3A, and therefore, can cause drug-drug interactions with concomitant medications. Tacrolimus (TAC), a substrate of CYP3A4/5, is administered for a long period to prevent rejection after kidney transplantation. TAC should be discontinued while using NMV/RTV because blood TAC levels significantly increase when these drugs are concomitantly administered. However, the influence of ESV on blood TAC levels has not yet been reported, and the management of TAC doses during the use of ESV remains unclear. CASE PRESENTATION: We experienced three kidney transplant recipients with COVID-19, whose blood trough levels of TAC increased by the concomitant use of NMV/RTV or ESV. In two patients administering NMV/RTV, blood trough levels of TAC increased more than tenfold after combination therapy, whereas in one patient administering ESV, TAC level increased approximately threefold. CONCLUSIONS: These cases suggest that TAC administration should be discontinued during NMV/RTV treatment to maintain blood TAC levels within the therapeutic range, and a reduced TAC dose is sufficient during ESV treatment.

Outcomes of kidneys used for transplantation: an analysis of survival and function.

Introduction: Kidney transplant recipients expect to survive the procedure with sufficient renal function for reliable dialysis freedom. Methods: Transplant outcomes (survival and estimated renal function) were assessed after live and deceased donor transplantation from the US national database. Outcomes were stratified by age (donor and recipient) and donor type. Results: Aggregate recipient outcomes were better transplanting living vs deceased donated kidneys. However, when stratified by the one-year renal function (within KDIGO CKD stage stratifications), surviving recipients had clinically similar dialysis-freedom, irrespective of donor type or age. The major outcome differences for recipients of age-stratified live and deceased kidneys was 1) the increasing frequency of one-year graft failures and 2) the increasing likelihood of severely limited renal function (CKD 4/5) with advancing donor age. Over 30% of recipients of deceased kidneys >65 years had either one-year graft failure or severely limited renal function contrasted to less than 15% of recipients of live kidneys aged >65 years. Conclusions: Evolving techniques to reduce adverse events after urgent vs elective procedures, plus improved transplant outcome predictability with increased-age deceased donor kidneys using advanced predictive analytics (using age-stratified live kidney transplantation outcomes as a relevant reference point) should facilitate similar kidney transplant outcomes, irrespective of donor type.

Monocyte-derived dendritic cells can be detected in urine of kidney transplant recipients with pathogenic asymptomatic bacteriuria.

Urinary tract infections (UTI) are an important clinical problem in kidney transplant recipients (KTR). Asymptomatic bacteriuria (ASB) is frequent in these patients and often resolved by the immune system, but a significant proportion may progress to complicated UTI, which may compromise allograft function and survival. It is essential to determine the involvement of the immune system in the infectious process. Dendritic cells (DCs) are recognised as playing a pivotal role in initiating inflammatory responses capable of priming antigen-specific T cells, a crucial step in determining the fate of local inflammation. Little is known about their role in the control of UTI. In this brief communication, we report an incidental finding in a group of 16 stable KTR in which monocyte-derived dendritic cells (ModDCs), analysed by flow cytometry, were found in urine of patients with ASB and high bacterial counts >107 cfu/ml. Within this group, one patient developed pyelonephritis in the following days. These findings suggest that the immune system, in particular DCs, may be recruited during the course of a UTI and, to our knowledge, present for the first time evidence that inflammatory ModDCs can be detected in urine. Their frequency may reflect the degree of infection. This finding suggests the potential for exploring whether these cells may be useful in distinguishing between pathogenic ASB and those that can be resolved by the immune system.

Bridging the gap: assessing CMV DNAemia in kidney transplant recipients with previous solid organ transplants.

Cytomegalovirus (CMV) infection poses a significant threat to solid organ transplant (SOT) recipients and can lead to various complications and adverse outcomes. In an effort to prevent CMV infection, it is common to utilize prophylactic strategies, including antiviral medications such as valganciclovir, especially for high-risk patients. Risk factors for CMV infection in kidney transplant recipients (KTRs) include CMV mismatch between donor and recipient (i.e., donor positive, recipient negative), and intensity of immunosuppression, such as the use of T-cell depleting agents. However, little attention has been given to KTRs with a history of prior SOTs, despite their prolonged exposure to immunosuppressive regimens. The aim of this retrospective single-center study was to investigate the incidence and implications of CMV DNAemia in KTRs with prior SOTs. The study included 97 KTRs with prior SOTs and 154 KTRs with no prior transplants as a control group. In the study group, the most common SOT before the current kidney transplantation (KT), was a previous KT. Patients in the KTR group with prior SOTs were more sensitized than those in the control group [calculated panel-reactive antibody > 30%: 49 (50.5%) vs. 30 (19.45%) patients, p = 0.001]. There was a 39.2% incidence of CMV DNAemia in the previous SOT group compared to 48.7% in the control group [non-significant (NS)]. Patients with prior SOTs demonstrated a shorter post-transplant time to CMV DNAemia [median time 1.6 months (interquartile range, IQR 0.7-5.8) in the KTRs with prior SOTs vs. 2.6 months (IQR 1.5-8.1) in the control group (p = 0.001)]. Although the study highlights the need for tailored prophylaxis strategies and vigilant monitoring in KTRs with prior SOTs, its limitations, such as its retrospective nature and single-center design, call for further multicenter research to establish comprehensive guidelines for managing CMV DNAemia in this unique patient population. Despite these limitations, this study underscores the importance of recognizing the heightened risk of CMV infection or reactivation in KTRs overall and the potential benefits of proactive intervention to mitigate associated morbidity and mortality.

High burden of CMV infections after simultaneous pancreas-kidney transplantation-a nationwide cohort study.

Cytomegalovirus (CMV) infections remain a common problem after solid-organ transplantation. We characterized the burden of CMV infections, and adverse events of CMV prophylaxis after simultaneous pancreas-kidney transplantation (SPK). We included all SPK patients (n = 236) since 2010 in our country. Immunosuppression was ATG, tacrolimus, mycophenolate, and steroids. Valganciclovir prophylaxis was given to all CMV D+/R- patients for six months, and to seropositive SPK patients for three months since February 2019. CMV DNAemia was monitored with quantitative PCR from plasma. Among D+/R- SPK recipients, post prophylaxis CMV infection was detected in 41/60 (68%) during follow-up. In seropositive SPK recipients with no prophylaxis, CMV infection was detected in 53/95 (56%), vs. 28/78 (36%) in those who received 3 months of prophylaxis (P = 0.01). CMV was symptomatic in 35 (15%) patients, of which 10 required hospitalization. Mean duration of viremia was 28 days (IQR 21-41). Leukopenia was detected in 63 (46%) of the 138 patients with valganciclovir prophylaxis. 7/122 (6%) of the CMV infections detected were defined as refractory to treatment, and three patients had confirmed ganciclovir resistance. SPK recipients experience a high burden of CMV infections despite CMV prophylaxis. Leukopenia is common during valganciclovir prophylaxis.