Renal Transplant Patients Research Articles

Kidney-transplanted Adolescents-Nonadherence and Graft Outcomes During the Transition Phase: A Nationwide Analysis, 2000-2020.

The transition from pediatric to young adult care is a vulnerable period for the renal transplant patient. We aimed to identify medication nonadherence (noninitiation, nonimplementation, and nonpersistence) and graft loss rates among adolescents and young adults and elucidate the influence of the transition phase on transplant outcomes. A retrospective nationwide cohort analysis of all renal transplantations in Norway from 2000 to 2020 was performed. Data were retrieved from the Norwegian Renal Registry, and adherence data from hospital charts. Patients transplanted aged <50 y, with functioning graft at 6 mo, were included. Recipients transplanted aged <26 y were compared with recipients transplanted aged 26-50 y. Graft loss, acute rejection, and development of de novo donor-specific antibodies were assessed in relation to the transition phase, defined as 14-26 y. Data from 1830 kidney recipients were included: 371 (20%) transplanted <26 y (64% male, 68% living donor) versus 1459 transplanted 26-50 y (63% male, 44% living donor). There were 298 graft losses, 78 (21%) in the <26-y group versus 220 (15%) in the 26- to 50-y group. During the transition phase, 36 grafts were lost, 29 (81%) after transfer to the adult service. Medication nonadherence was the reason for 58% (21 of 36) of the losses during the transition phase, versus 12% (27 of 220) in the 26- to 50-y group ( P < 0.001). The 5-y graft survival rate was 89% (95% confidence interval, 85%-92%) and 94% (92%-95%), respectively ( P = 0.01). Nonadherence was verified as the main cause of kidney graft loss in the transition phase.

Avascular Necrosis in Renal Transplant Patients

Kidney transplant recipients are at increased risk for avascular necrosis due to steroid use and accompanying comorbidities. Concerning risk factors, uncertainty still exists. We evaluated the clinical characteristics and risk factors of avascular necrosis in kidney transplant recipients. Symptomatic avascular necrosis was found by magnetic resonance imaging in 33 of 360 kidney transplant patients between 2005 and 2021. The patients' clinical characteristics, biochemical testing, and medications were evaluated. We found the frequency of avascular necrosis to be 9.7% during the follow-up period. If the total steroid dosage used was more than 4 g in the first 3 months, the risk of developing avascular necrosis increased 4.08 times, and the presence of cytomegalovirus disease increased the risk by 4.03 times. Avascular necrosis was observed bilaterally in 60.6% of cases and at the femoral head in 66.7%. The frequency of avascular necrosis was highest in the first and second years posttransplant. We found that avascular necrosis appears most frequently in the first 2 years after kidney transplant and the most important risk factors are cumulative steroid dose and cytomegalovirus disease. In the follow-up of kidney transplant patients, it is important to use low-dose steroid doses if possible. Of note, preventing the development of cytomegalovirus disease by screening and prophylaxis for cytomegalovirus is also important in reducing the development of avascular necrosis.

Hashimoto's thyroiditis and renal transplant rejection.

Hashimoto's thyroiditis (HT) is a common autoimmune thyroid disorder that can disrupt thyroid function and homeostasis. As HT results from a dysregulated immune system, we hypothesized that these patients might be more susceptible to transplant failure; however, literature on this association is limited. The purpose of this study is to examine the association of HT with the risk of renal transplant failure. We utilized the United States Renal Database System dataset collected from 2005 to 2014 and compared the time from first renal transplant to transplant failure in end-stage renal disease (ESRD) patients with a HT diagnosis to ESRD patients without a HT diagnosis that underwent renal transplant. A total of 144 ESRD patients had International Classification of Disease-9 claim codes for HT prior to renal transplant, amongst a total cohort of 90,301 renal transplant patients aged 18-100 and meeting criteria. Patients with HT were significantly more likely to be female, white, and to have a diagnosis of cytomegalovirus compared to patients without. ESRD patients with a HT diagnosis that underwent renal transplant had a significantly increased risk of renal transplant failure compared to those ESRD renal transplant patients without an HT diagnosis. There was a significantly increased adjusted hazard ratio for graft failure in patients with a HT diagnosis compared to those without. Thyroid health and HT may play a significant role in the development of the increased risk of renal transplant failure observed in this study. Additional studies are needed to investigate the underlying mechanisms for this association.

MP31-10 MANAGEMENT OF MYCOTIC PSEUDOANEURYSMS IN RENAL TRANSPLANT PATIENTS - A LITERATURE REVIEW AND PROPOSAL FOR A NOVEL MANAGEMENT PATHWAY

You have accessJournal of UrologyCME1 Apr 2023MP31-10 MANAGEMENT OF MYCOTIC PSEUDOANEURYSMS IN RENAL TRANSPLANT PATIENTS - A LITERATURE REVIEW AND PROPOSAL FOR A NOVEL MANAGEMENT PATHWAY Alexandra Bain, Gerrit Winkelaar, and Max Levine Alexandra BainAlexandra Bain More articles by this author , Gerrit WinkelaarGerrit Winkelaar More articles by this author , and Max LevineMax Levine More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003264.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Vascular complications represent the main cause of early graft loss in renal transplantations—with less than 1% of these cases developing mycotic pseudoaneurysms. The morbidity and mortality associated with this complication is significant with an overall mortality rate of 15-20% and a graft loss rate of 55-70%. Currently the gold standard treatment for mycotic pseudoaneurysms is undefined. Recently there have been three renal transplant patients at the University of Alberta Hospital who developed mycotic pseudoaneurysms with different surgical repairs and outcomes. We performed a quality assurance review and a literature review of the surgical management of mycotic pseudoaneurysms. Based on this review, we have proposed a novel management pathway which may help reduce post-operative complications. METHODS: The databases MEDLINE and SCOPUS were searched for all case reports describing management of mycotic pseudoaneurysms in renal transplant patients between years 1990-2022. RESULTS: Twenty-two articles were reviewed which described forty-one case reports of mycotic pseudoaneurysms in renal transplant recipients. Repair techniques included patch repair in 61% of cases (25/41), endovascular stenting in 22% of cases (9/41), and extra-anatomical bypass in 12% of cases (5/41), 5% of patients (2/41) had a post-mortem diagnosis. The failure rates of patch repair resulting in death or repeat surgery was 44% (11/25), failure rates for stents was 22% (2/9), failure rates of extra-anatomical bypass was 0%. Every patient who required a takeback operative procedure was managed with an extra-anatomical bypass. Overall patient mortality was 17% (7/41), overall graft loss rate was 68% (28/41). CONCLUSIONS: Considering the high failure rates of patch repairs and endovascular stents, we suggest the first-line strategy for repair should be an extra-anatomical bypass with the assistance of Vascular Surgery when possible. If an extra-anatomical bypass cannot be performed, we suggest a wide surgical debridement with autologous in-line reconstruction. These surgical approaches may help decrease the incidence of surgical failure rates and mortalities. Having a standardized management pathway utilized by Transplant Urology and Vascular Surgery may allow for improved patient surgical outcomes and graft survival outcomes in the future. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e433 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexandra Bain More articles by this author Gerrit Winkelaar More articles by this author Max Levine More articles by this author Expand All Advertisement PDF downloadLoading ...

(536) Outcomes After Renal Transplantation in Patients with Reduced Left Ventricular Ejection Fraction

(536) Outcomes After Renal Transplantation in Patients with Reduced Left Ventricular Ejection Fraction

Management of Bone and Mineral Disease in Renal Transplant Patients

Mineral and bone disease in the posttransplantation patient is common and requires thorough evaluation for appropriate management. This includes secondary renal osteodystrophy, rickets, osteomalacia, osteoporosis, and osteonecrosis. Biochemical markers along with imaging and bone biopsy help to establish the diagnosis and treatment planning. Lack of appropriate management plan can lead to chronic pains, fractures, and osteonecrosis affecting long-term bone health. Tailoring immunosuppressants with appropriate medical therapy, nutritional supplements, and anti-resorptive agents is the mainstay of treatment. Here, we discuss the current management strategies with illustrative cases.

MP53-05 RISK OF ACUTE KIDNEY INJURY AFTER LOWER URINARY TRACT RECONSTRUCTION WITH EARLY NSAID THERAPY: A PROPENSITY MATCHED RETROSPECTIVE ANALYSIS

You have accessJournal of UrologyCME1 Apr 2023MP53-05 RISK OF ACUTE KIDNEY INJURY AFTER LOWER URINARY TRACT RECONSTRUCTION WITH EARLY NSAID THERAPY: A PROPENSITY MATCHED RETROSPECTIVE ANALYSIS Darren Ha, Eliza D. Blanchette, Duncan T. Wilcox, Vijaya M. Vemulakonda, Daniel N. Wood, and Kyle O. Rove Darren HaDarren Ha More articles by this author , Eliza D. BlanchetteEliza D. Blanchette More articles by this author , Duncan T. WilcoxDuncan T. Wilcox More articles by this author , Vijaya M. VemulakondaVijaya M. Vemulakonda More articles by this author , Daniel N. WoodDaniel N. Wood More articles by this author , and Kyle O. RoveKyle O. Rove More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003301.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Response to the opioid epidemic led to increased use of postoperative, non-opioid analgesia. Some pediatric urologists do not routinely use NSAIDs for fear of causing acute kidney injury (AKI). While previous studies have demonstrated the safety and efficacy of NSAIDs in children, safety after lower urinary tract reconstruction has not been well characterized. Using the Kidney Disease Improving Global Outcomes (KDIGO) criteria for AKI (increase in creatinine ≥0.3 mg/dL or increase in creatinine ≥1.5× baseline or urine output <0.5 mL/kg/hr for 6 hours), we hypothesized there would be a difference in incidence of postoperative AKI between patients who did and did not receive NSAIDs after these operations. METHODS: Patients 2–18 years old who underwent lower urinary tract reconstruction (i.e., bladder augmentation and/or creation of a catheterizable channel) from 2009 to 2021 and had documented urine were reviewed. CKD and stage were calculated from creatinine and cystatin C within 6 months of surgery using the CKiD U25 equations. Patients who received NSAIDs were propensity matched on 19 characteristics in a 2:1 ratio with patients undergoing similar surgeries who did not receive NSAIDs in the operating room or in the first 6 hours postoperatively. The primary outcome was incidence of AKI during 48 hours after surgery. RESULTS: The unmatched cohorts included 260 patients. After propensity matching, there were no meaningful differences in most characteristics among 118 in the NSAID arm and 59 in the no NSAID arm. 54 CKD and 4 renal transplant patients were included. There was no difference in the incidence of postoperative AKI based on any KDIGO criteria (18.6% no NSAID vs 15.3% NSAID, p=0.71). Median postoperative opioids fell from 0.75 mg/kg in the no NSAID arm to 0.30 mg/kg morphine equivalents in the NSAID arm (p=0.02). Log-rank testing by Kaplan-Meier analysis demonstrated no difference in time to incidence of low urine output between the groups (p=0.38). In the whole population not stratified by NSAID use, no differences were seen in AKI between those with and without CKD (16.6% vs 16.4%). CONCLUSIONS: There was no difference in the incidence of postoperative AKI among patients who did and did not receive NSAIDs after lower urinary tract reconstruction. These results support that postoperative NSAIDs were an unlikely source of AKI and result in lower opioid usage, but also indicate a proportion of patients undergoing these operations may be susceptible to AKI, likely owing to underlying disease, longer operations, and fluid shifts. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e713 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Darren Ha More articles by this author Eliza D. Blanchette More articles by this author Duncan T. Wilcox More articles by this author Vijaya M. Vemulakonda More articles by this author Daniel N. Wood More articles by this author Kyle O. Rove More articles by this author Expand All Advertisement PDF downloadLoading ...

MP53-03 UROLOGIC RISK FACTORS FOR URINARY TRACT INFECTION AND ALLOGRAFT FAILURE IN PEDIATRIC RENAL TRANSPLANTATION

You have accessJournal of UrologyCME1 Apr 2023MP53-03 UROLOGIC RISK FACTORS FOR URINARY TRACT INFECTION AND ALLOGRAFT FAILURE IN PEDIATRIC RENAL TRANSPLANTATION Vinicius Seidel, Matthew Buell, Kai Wen Cheng, Cayde Ritchie, Adam Fisher, David Chamberlin, and Joshua Chamberlin Vinicius SeidelVinicius Seidel More articles by this author , Matthew BuellMatthew Buell More articles by this author , Kai Wen ChengKai Wen Cheng More articles by this author , Cayde RitchieCayde Ritchie More articles by this author , Adam FisherAdam Fisher More articles by this author , David ChamberlinDavid Chamberlin More articles by this author , and Joshua ChamberlinJoshua Chamberlin More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003301.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urinary tract infection (UTI) causes morbidity in children with end stage renal disease (ESRD) and may lead to allograft failure. Appropriate urologic evaluation is important before and after renal transplantation. The purpose of this study is to identify risk factors for UTI and allograft failure in children with ESRD. METHODS: A retrospective review of all pediatric renal transplant patients at a single transplant center from 2013 to 2022 was performed. Inclusion criteria were patients less than 18 years of age with ESRD who underwent their first renal transplantation. Patients with less than 6 months follow-up were excluded. The primary endpoints were UTI occurrence and allograft failure. Allograft failure was defined as rejection with return to dialysis. Statistical comparisons were made using the Chi Square test and the Wilcoxon signed rank test. RESULTS: 79 children underwent renal transplantation with a median follow-up time of 56 months (6-112 months). Etiologies for renal failure were identified as renal in 60 (76%) patients and bladder in 19 (24%) patients. Renal failure in patients with congenital anomaly of kidney and urinary tract (CAKUT) was seen in 33% of renal etiologies and 100% of bladder etiologies. Overall, the UTI rate was lower pre-transplant (8%) compared to post-transplant (28%) (p=0.002). Pre-transplant bladder etiology for renal failure had a higher UTI rate when compared to the renal etiology (26% vs 2%, p=0.002). Post-transplant there was no difference in UTI rate between bladder etiology and renal etiology (37% vs 25%, p=0.32). 27% of patients had pre-transplant native kidney vesicoureteral reflux (VUR) and 11% had transplant kidney VUR. Children with native kidney VUR had a higher UTI rate pre-transplant (48% vs. 21%, p<0.05). Children with transplant kidney VUR had a higher UTI rate than those without transplant VUR (67% vs. 23%, p<0.05). Patients with poor bladder compliance and capacity on urodynamics when medically and surgically optimized, did not have increased post-transplant UTI rates. 14 (17.7%) patients developed allograft rejection. Etiology and onset time of initial renal failure, number of UTI, CAKUT, and VUR were not associated with allograft rejection. CONCLUSIONS: Pediatric ESRD patients with pre-transplant native kidney VUR and renal transplant VUR are at increased risk for UTI and should be treated. Unsafe bladders when optimized may safely undergo transplantation. Renal allograft failure was not associated with etiology, onset time of initial renal failure, number of UTI, CAKUT, and VUR. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e712 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Vinicius Seidel More articles by this author Matthew Buell More articles by this author Kai Wen Cheng More articles by this author Cayde Ritchie More articles by this author Adam Fisher More articles by this author David Chamberlin More articles by this author Joshua Chamberlin More articles by this author Expand All Advertisement PDF downloadLoading ...

Evaluation of Plasma Concentrations of Mycophenolic Acid in Renal Transplant Patients Using LM1010 High-performance Liquid Chromatography

Plasma concentrations of mycophenolic acid (MPA), an immunosuppressive agent, have been measured in clinical settings using immunoassay methods or HPLC. However, immunoassay methods show cross-reactivity with metabolites of MPA glucuronide. Recently, the LM1010 high-performance liquid chromatography instrument was approved as a new general medical device. In this study, we compared the results of MPA plasma concentrations analyzed using the LM1010 method and the previously described HPLC method. Plasma samples obtained from 100 renal transplant patients (32 women and 68 men) were evaluated using both HPLC instruments. Deming regression analyses showed a very high correlation between the two instruments, with a slope of 0.9892 and an intercept of 0.0235 µg/mL (r2=0.982). Bland-Altman analysis showed an average of -0.0012 µg/mL between the LM1010 method and the previously described HPLC method. For the LM1010 method, the total run time for MPA analysis was 7 min, and the analytical time was short; however, the extraction recovery when using a spin column was extremely low for frozen plasma samples stored at -20°C for 1 month, and the volume required for the assay (150 µL) could not be collected. Thus, for the LM1010 method, analysis using fresh plasma samples was optimal. Overall, our findings showed that the LM1010 method was a rapid, accurate HPLC assay for MPA analysis and could be used in clinical practice for routine monitoring of MPA in fresh plasma samples.

Choroidal Vascularity Index and Choroidal Thickness Changes Following Renal Transplantation.

This study aimed to evaluate changes in subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), estimated glomerular filtration rate (GFR), mean arterial pressure (MAP), and intraocular pressure (IOP) after renal transplantation. A total of 49 renal transplantation patients were included in this prospective study. CVI and SFCT on enhanced-depth imaging optic coherence tomography (EDI-OCT), MAP at the cubital fossa, GFR, and IOP were measured preoperatively and at postoperative 1 week and 1 month. In the analysis of EDI-OCT images, luminal area (LA) and stromal area of the choroid were determined using the image binarization method. CVI was defined as the ratio of LA to total choroid area. The effects of GFR, IOP, and MAP on CVI and SFCT were investigated. The study included 23 women (47%) and 26 men (53%) with a mean age of 26.28±8.25 years (range: 18-52). Changes between preoperative, postoperative 1-week, and postoperative 1-month GFR values, CVI, and SFCT measurements were evaluated. There were significant differences between preoperative and postoperative GFR and SFCT measurements (p<0.001), but no significant differences between preoperative and postoperative CVI (p=0.09), MAP (p=0.14), or IOP (p=0.84) measurements. The present study demonstrated that SFCT increased significantly with GFR, while there was no change in CVI values.

A RARE PRESENTATION OF MYCOPHENOLATE MOFETIL-INDUCED SEGMENTAL COLITIS MASQUERADING AS ISCHEMIC COLITIS

Mycophenolate mofetil (MMOF) is an immunosuppressive pro-drug commonly used to prevent rejection in recipients of solid organ transplants. It is hepatically converted to mycophenolic acid which then acts to reversibly inhibit inosine monophosphate dehydrogenase, thereby preventing B and T lymphocyte proliferation, B cell antibody formation, and leukocyte recruitment to sites of inflammation. Diarrhea is the most common gastrointestinal side effect of MMOF usage with up to 40% of renal transplant patients on MMOF reporting this symptom and colonoscopy not infrequently shows injurious changes that range from edema and erythema to ulcerations and diffuse colitis. Isolated reports note that colonic histopathology from patients on MMOF sometimes mimic graft-versus-host disease, inflammatory bowel disease, or ischemic colitis. However, there are very few cases that describe segmental colitis in MMOF patients. We present a rare case of a renal transplant patient presenting with MMOF-induced segmental colitis after 4 years of medication usage.

Association between salivary microbiota and renal function in renal transplant patients during the perioperative period.

Renal transplantation is an effective treatment for the end stage renal disease (ESRD). However, how salivary microbiota changes during perioperative period of renal transplant recipients (RTRs) has not been elucidated. Five healthy controls and 11 RTRs who had good recovery were enrolled. Saliva samples were collected before surgery and at 1, 3, 7, and 14 days after surgery. 16S rRNA gene sequencing was performed. There was no significant difference in the composition of salivary microbiota between ESRD patients and healthy controls. The salivary microbiota of RTRs showed higher operational taxonomic units (OTUs) amount and greater alpha and beta diversity than those of ESRD patients and healthy controls, but gradually stabilized over time. At the phylum level, the relative abundance of Actinobacteria, Tenericutes and Spirochaetes was about ten times different from ESRD patients or healthy controls for RTRs overall in time. The relative abundance of Bacteroidetes, Fusobacteria, Patescibacteria, Leptotrichiaceae and Streptococcaceae was correlated with serum creatinine (Scr) after renal transplantation. In short, salivary microbiota community altered in the perioperative period of renal transplantation and certain species of salivary microbiota had the potential to be a biomarker of postoperative recovery.

Disseminated Strongyloidiasis in Renal Transplant Recipient Complicated with Neurological Manifestations

Introduction: Infections caused by Strongyloides stercoralis are quite difficult to detect. It can remain silent long before manifesting, which used to occur when patients were under immunosuppressed conditions. This scenario makes the patient’s treatment and recovery hard to deal with. Case Presentation: This paper reports the case of a renal transplant patient who presented disseminated strongyloidiasis infection complicated with neurological manifestations. In order to eliminate Strongyloides stercoralis, the patient initially received oral Ivermectin treatment, and as the infection persisted, parenteral treatment was provided. The patient developed flaccid tetraparesis and increased cerebrospinal fluid protein with albumin- cytological dissociation, initially suggesting the diagnosis of Guillain-Barré syndrome. Conclusions: This clinical report highlights the need for early diagnosis and treatment in cases of immunosuppressed patients with strongyloidiasis infection, as the diagnosis might be neglected.

Transplant renal artery stenosis: utilization of machine learning to identify ancillary sonographic and doppler parameters to predict stenosis in patients with graft dysfunction

To determine if ancillary sonographic and Doppler parameters can be used to predict transplant renal artery stenosis in patients with renal graft dysfunction. IRB-approved, HIPAA-compliant retrospective study included 80 renal transplant patients who had renal US followed by renal angiogram between January 2018 and December 2019. A consensus read of two radiologists recorded these parameters: peak systolic velocity, persistence of elevated velocity, grayscale narrowing, parvus tardus, delayed systolic upstroke, angle of the systolic peak (SP angle), and aliasing. Univariate analysis using t-test or chi-square was performed to determine differences between patients with and without stenosis. P values under 0.05 were deemed statistically significant. We used machine learning algorithms to determine parameters that could better predict the presence of stenosis. The algorithms included logistic regression, random forest, imbalanced random forest, boosting, and CART. All 80 cases were split between training and testing using stratified sampling using a 75:25 split. We found a statistically significant difference in grayscale narrowing (p=0.0010), delayed systolic upstroke (p=0.0002), SP angle (p=0.0005), and aliasing (p =0.0024) between the two groups. No significant difference was found for an elevated peak systolic velocity (p =0.1684). The imbalanced random forest (IRF) model was selected for improved accuracy, sensitivity, and specificity. Specificity, sensitivity, AUC, and normalized Brier score for the IRF model using all parameters were 73%, 81%, 0.82, and 69 in the training set, and 78%, 58%, 0.78, and 80 in the testing set. VIMP assessment showed that the combination of variables that resulted in the most significant change of the training set performance was that of grayscale narrowing and SP angle. Elevated peak systolic velocity did not discriminate between patients with and without TRAS. Adding ancillary parameters into the machine learning algorithm improved specificity and sensitivity similarly in the training and testing sets. The algorithm identified the combination of lumen narrowing coupled with the angle of the systolic peak as better predictor of TRAS. This model may improve the accuracy of ultrasound for transplant renal artery stenosis.

Elevated Tacrolimus Blood Concentration Due to the Interaction with Nirmatrelvir/Ritonavir During COVID-19 Treatment: A Case Report

Nirmatrelvir/ritonavir, a newly authorized drug for the treatment of COVID-19, is a strong CYP3A4 inhibitor that can interact with many drugs, such as tacrolimus, reducing its metabolism. The reported case is a renal transplant patient who experienced a strong increase in tacrolimus blood concentration (up to 112ng/mL, more than ten times above the target range) when treated with both drugs at the same time, which caused a neurologic condition that required hospital admission for its control and treatment. The resolution of the symptoms was rapid, but the elevation of tacrolimus concentration remained for several days, even after discontinuing both drugs. This case shows the importance of developing a protocol for managing this interaction to guarantee the efficacy and safety of treatment with nirmatrelvir/ritonavir in transplant patients.

A transitional B-cell cytokine biomarker for risk stratifying renal transplant patients with borderline rejection

Borderline allograft rejection can promote acute rejection and graft loss in some, but not all, patients. In this issue, Cherukuri etal. use a novel test based on peripheral blood transitional T1 B cells producing interleukin-10 and tumor necrosis factor-α, which identifies patients at high risk for poor outcomes. The potential mechanisms by which transitional T1 B cells might modulate alloreactivity need exploration, but following appropriate validation, this biomarker could risk stratify patients in need of early intervention.

Cyclosporine A-induced gingival overgrowth in renal transplant patients accompanied by epithelial-to-mesenchymal transition.

To investigate the association between the prevalence of cyclosporin A-induced gingival overgrowth and the expression of the epithelial-to-mesenchymal transition factors in the gingival tissues of renal transplant patients. Gingival overgrowth (GO) is a frequent complication in organ transplant patients treated with the immunosuppressant cyclosporin A (CsA). The epithelial-to-mesenchymal transition (EMT) is considered a factor contributing to CsA-induced GO. However, current knowledge on this topic is sparse. Sixty-three renal transplant patients were divided into two groups according to the occurrence of GO: those with gingival overgrowth (GO+ group) and those without gingival overgrowth (GO- group). Data on age, sex, and use of immunosuppressant and calcium channel blocker medications, serum creatinine values, peak concentrations of blood CsA, and gingival hyperplasia scores were recorded to identify clinically pathogenic factors. Gingival tissues from five patients with CsA-induced GO and five healthy subjects were selected for histomorphological observation with hematoxylin-eosin staining, Masson staining, and immunohistochemical staining. The mRNA expression of EMT factors was detected with reverse transcription-quantitative PCR. The use of CsA significantly increased the prevalence of GO in renal transplant patients. The expression of α-SMA, SMAD4, and TGM2 was upregulated and that of E-cadherin was downregulated in the gingival tissues of patients with CsA-induced GO compared with those of the corresponding controls. Treatment with CsA is closely related to the occurrence of GO in renal transplant patients and EMT plays an important role in CsA-induced gingival tissue hyperplasia.

Case Report: Successful Treatment of Recurrent Urinary Tract Infection Due to Extensively Drug-Resistant Klebsiella Pneumoniae in a Kidney Transplant Recipient Using Chloramphenicol

Effective therapies for multidrug-resistant (MDR) microorganisms, especially Gram-negative bacteria, are becoming rare. Also, solid-organ transplant recipients are at high risk of MDR Gram-negative bacilli infection. Urinary tract infections are the most frequent bacterial infections in kidney transplant recipients and are an important cause of mortality after renal transplantation. We describe a case of complicated urinary tract infection in a kidney transplant patient due to extensively drug-resistant (XDR) K. pneumoniae treated successfully with a regimen comprising a combination of chloramphenicol and ertapenem. We do not recommend chloramphenicol as a first-line choice for treating complicated urinary tract infections. Still, we believe it is an alternative for infections caused by MDR and/or XDR pathogens in renal transplant patients, as other options are nephrotoxic.

Efficacy of Prolonged-release Tacrolimus After Conversion From Immediate-release Tacrolimus in Kidney Transplantation: A Retrospective Analysis of Long-term Outcomes From the ADMIRAD Study.

A retrospective, noninterventional chart review study examined long-term graft survival in adult kidney transplant participants in the Adherence Measurement in Stable Renal Transplant Patients Following Conversion From Prograf to Advagraf (ADMIRAD) clinical trial at 4 Belgian sites. Patients were randomized to receive once-daily PRT or twice-daily IRT for 6 mo, followed by treatment as per real-world clinical practice. Data were collected retrospectively from randomization day until December 31, 2018. Primary endpoints included efficacy failure, defined as a composite endpoint of graft loss, biopsy-confirmed acute rejection, and graft dysfunction. Secondary endpoints included overall patient survival and course of kidney function. This analysis included 78.5% of patients from ADMIRAD (n = 108 PRT; n = 64 IRT). The Kaplan-Meier survival rate without efficacy failure from randomization to year 5 was 0.741 (95% confidence interval [CI]: 0.647, 0.813) for the PRT group (n = 80), and 0.667 (95% CI: 0.536, 0.768) for the IRT group (n = 42) and remained higher for PRT throughout 10 y follow-up (P = 0.041). The Kaplan-Meier estimate of overall survival from the time of last transplant was 0.981 (95% CI: 0.928, 0.995) and 0.880 (95% CI: 0.802, 0.928) at 5 and 10 y in the PRT group. Kidney function parameters and tacrolimus trough levels remained stable over the follow-up period. Patients in the ADMIRAD study who received PRT for up to 10 y had improved long-term outcomes compared with patients receiving IRT, with a consistent effect on both graft and patient survival.

Missed Opportunities to Diagnose and Treat Tertiary Hyperparathyroidism After Transplant

IntroductionTertiary hyperparathyroidism (3HPT) is common after renal transplant. However, guidelines for diagnosis are not clear and few patients are treated surgically. This study aims to determine rates of diagnosis and treatment of 3HPT in renal transplant patients with hypercalcemia. Materials and methodsThis retrospective chart review identified all renal transplant recipients at a single tertiary care institution between 2011 and 2021. Patients with post-transplant hypercalcemia (> 10.2 mg/dL) were identified. The time in months of index hypercalcemia was noted. Measurement of parathyroid hormone (PTH) levels after index hypercalcemia was determined and noted as elevated if > 64 pg/mL at least 6 mo after transplant. Documentation of symptoms of hyperparathyroidism, a diagnosis of hyperparathyroidism in the electronic medical record, and medical or surgical management of patients with classic 3HPT (elevated calcium and PTH) were determined. ResultsOf 383 renal transplant recipients, hypercalcemia was identified in 132 patients. The majority of hypercalcemic patients had PTH levels measured (127, 96.2%). PTH was elevated in 109 (82.6%). Among the 109 patients with classic 3HPT, 54 (49.5%) had a documented diagnosis of hyperparathyroidism in the electronic medical record (P = 0.01). Kidney stones or abnormal DEXA scan were present in 16 (14.7%) and 18 (16.5%), respectively. Most patients were managed non-surgically (101, 92.6%); calcimimetics were prescribed for 42 (38.5%, P = 0.01). Eight (7.3%) patients with classic 3HPT were referred to a surgeon (P = 0.35); all were initially prescribed calcimimetics (P = 0.001). Conclusions3HPT is underdiagnosed in patients with elevated calcium and PTH levels post-transplant. A significant percentage of these patients go without surgical referral and curative treatment.