The impact of induction therapy on the risk of posttransplant lymphoproliferative disorder in adult kidney transplant recipients with donor-recipient serological Epstein-Barr virus mismatch.

Posttransplant lymphoproliferative disorder (PTLD) poses a significant concern in Epstein-Barr virus (EBV)-negative patients transplanted from EBV-positive donors (EBV R-/D+). Previous studies investigating the association between different induction agents and PTLD in these patients have yielded conflicting results. Using the Organ Procurement and Transplant Network database, we identified EBV R-/D+ patients >18 years of age who underwent kidney-alone transplants between 2016 and 2022 and compared the risk of PTLD with rabbit antithymocyte globulin (ATG), basiliximab, and alemtuzumab inductions. Among the 6620 patients included, 64.0% received ATG, 23.4% received basiliximab, and 12.6% received alemtuzumab. The overall incidence of PTLD was 2.5% over a median follow-up period of 2.9 years. Multivariable analysis demonstrated that the risk of PTLD was significantly higher with ATG and alemtuzumab compared with basiliximab (adjusted subdistribution hazard ratio [aSHR] = 1.98, 95% confidence interval [CI] 1.29-3.04, P = .002 for ATG and aSHR = 1.80, 95% CI 1.04-3.11, P = .04 for alemtuzumab). However, PTLD risk was comparable between ATG and alemtuzumab inductions (aSHR = 1.13, 95% CI 0.72-1.77, P = .61). Therefore, the risk of PTLD must be taken into consideration when selecting the most appropriate induction therapy for this patient population.

Distinct phenotypes of kidney transplant recipients aged 80 years or older in the USA by machine learning consensus clustering.

Objectives: This study aimed to identify distinct clusters of very elderly kidney transplant recipients aged ≥80 and assess clinical outcomes among these unique clusters. Design: Cohort study with machine learning (ML) consensus clustering approach. Setting and participants: All very elderly (age ≥80 at time of transplant) kidney transplant recipients in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database database from 2010 to 2019. Main outcome measures: Distinct clusters of very elderly kidney transplant recipients and their post-transplant outcomes including death-censored graft failure, overall mortality and acute allograft rejection among the assigned clusters. Results: Consensus cluster analysis was performed in 419 very elderly kidney transplant and identified three distinct clusters that best represented the clinical characteristics of very elderly kidney transplant recipients. Recipients in cluster 1 received standard Kidney Donor Profile Index (KDPI) non-extended criteria donor (ECD) kidneys from deceased donors. Recipients in cluster 2 received kidneys from older, hypertensive ECD deceased donors with a KDPI score ≥85%. Kidneys for cluster 2 patients had longer cold ischaemia time and the highest use of machine perfusion. Recipients in clusters 1 and 2 were more likely to be on dialysis at the time of transplant (88.3%, 89.4%). Recipients in cluster 3 were more likely to be preemptive (39%) or had a dialysis duration less than 1 year (24%). These recipients received living donor kidney transplants. Cluster 3 had the most favourable post-transplant outcomes. Compared with cluster 3, cluster 1 had comparable survival but higher death-censored graft failure, while cluster 2 had lower patient survival, higher death-censored graft failure and more acute rejection. Conclusions: Our study used an unsupervised ML approach to cluster very elderly kidney transplant recipients into three clinically unique clusters with distinct post-transplant outcomes. These findings from an ML clustering approach provide additional understanding towards individualised medicine and opportunities to improve care for very elderly kidney transplant recipients.

Use of Machine Learning Consensus Clustering to Identify Distinct Subtypes of Black Kidney Transplant Recipients and Associated Outcomes.

Importance: Among kidney transplant recipients, Black patients continue to have worse graft function and reduced patient and graft survival. Better understanding of different phenotypes and subgroups of Black kidney transplant recipients may help the transplant community to identify individualized strategies to improve outcomes among these vulnerable groups. Objective: To cluster Black kidney transplant recipients in the US using an unsupervised machine learning approach. Design, Setting, and Participants: This cohort study performed consensus cluster analysis based on recipient-, donor-, and transplant-related characteristics in Black kidney transplant recipients in the US from January 1, 2015, to December 31, 2019, in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Each cluster's key characteristics were identified using the standardized mean difference, and subsequently the posttransplant outcomes were compared among the clusters. Data were analyzed from June 9 to July 17, 2021. Exposure: Machine learning consensus clustering approach. Main Outcomes and Measures: Death-censored graft failure, patient death within 3 years after kidney transplant, and allograft rejection within 1 year after kidney transplant. Results: Consensus cluster analysis was performed for 22 687 Black kidney transplant recipients (mean [SD] age, 51.4 [12.6] years; 13 635 men [60%]), and 4 distinct clusters that best represented their clinical characteristics were identified. Cluster 1 was characterized by highly sensitized recipients of deceased donor kidney retransplants; cluster 2, by recipients of living donor kidney transplants with no or short prior dialysis; cluster 3, by young recipients with hypertension and without diabetes who received young deceased donor transplants with low kidney donor profile index scores; and cluster 4, by older recipients with diabetes who received kidneys from older donors with high kidney donor profile index scores and extended criteria donors. Cluster 2 had the most favorable outcomes in terms of death-censored graft failure, patient death, and allograft rejection. Compared with cluster 2, all other clusters had a higher risk of death-censored graft failure and death. Higher risk for rejection was found in clusters 1 and 3, but not cluster 4. Conclusions and Relevance: In this cohort study using an unsupervised machine learning approach, the identification of clinically distinct clusters among Black kidney transplant recipients underscores the need for individualized care strategies to improve outcomes among vulnerable patient groups.

Outcomes of kidney retransplantation in recipients with prior posttransplant lymphoproliferative disorders: An analysis of the 2000-2019 UNOS/OPTN database.

This study utilized the UNOS database to assess clinical outcomes after kidney retransplantation in patients with a history of posttransplant lymphoproliferative disease (PTLD). Among second kidney transplant patients from 2000 to 2019, 254 had history of PTLD in their first kidney transplant, whereas 28,113 did not. After a second kidney transplant, PTLD occurred in 2.8% and 0.8% of patients with and without history of PTLD, respectively (p = .001). Over a median follow-up time of 4.5 years after a second kidney transplant, 5-year death-censored graft failure was 9.5% vs. 12.6% (p = .21), all-cause mortality was 8.3% vs. 11.8% (p = .51), and 1-year acute rejection was 11.0% vs. 9.3% (p = .36) in the PTLD vs. non-PTLD groups, respectively. There was no significant difference in death-censored graft failure, mortality, and acute rejection between PTLD and non-PTLD groups in adjusted analysis and after propensity score matching. We conclude that graft survival, patient survival, and acute rejection after kidney retransplantation are comparable between patients with and without history of PTLD, but PTLD occurrence after kidney retransplantation remains higher in patients with history of PTLD.

Degree of Glomerulosclerosis in Procurement Kidney Biopsies from Marginal Donor Kidneys and Their Implications in Predicting Graft Outcomes.

Background: This study aimed to assess the association between the percentage of glomerulosclerosis (GS) in procurement allograft biopsies from high-risk deceased donor and graft outcomes in kidney transplant recipients. Methods: The UNOS database was used to identify deceased-donor kidneys with a kidney donor profile index (KDPI) score > 85% from 2005 to 2014. Deceased donor kidneys were categorized based on the percentage of GS: 0-10%, 11-20%, >20% and no biopsy performed. The outcome included death-censored graft survival, patient survival, rate of delayed graft function, and 1-year acute rejection. Results: Of 22,006 kidneys, 91.2% were biopsied showing 0-10% GS (58.0%), 11-20% GS (13.5%), >20% GS (19.7%); 8.8% were not biopsied. The rate of kidney discard was 48.5%; 33.6% in 0-10% GS, 68.9% in 11-20% GS, and 77.4% in >20% GS. 49.8% of kidneys were discarded in those that were not biopsied. Death-censored graft survival at 5 years was 75.8% for 0-10% GS, 70.9% for >10% GS, and 74.8% for the no biopsy group. Among kidneys with >10% GS, there was no significant difference in death-censored graft survival between 11-20% GS and >20% GS. Recipients with >10% GS had an increased risk of graft failure (HR = 1.27, p < 0.001), compared with 0-10% GS. There was no significant difference in patient survival, acute rejection at 1-year, and delayed graft function between 0% and 10% GS and >10% GS. Conclusion: In >85% KDPI kidneys, our study suggested that discard rates increased with higher percentages of GS, and GS >10% is an independent prognostic factor for graft failure. Due to organ shortage, future studies are needed to identify strategies to use these marginal kidneys safely and improve outcomes.

The Use of Donor-Derived Cell-Free DNA for Assessment of Allograft Rejection and Injury Status.

Patient monitoring after kidney transplantation (KT) for early detection of allograft rejection remains key in preventing allograft loss. Serum creatinine has poor predictive value to detect ongoing active rejection as its increase is not sensitive, nor specific for acute renal allograft rejection. Diagnosis of acute rejection requires allograft biopsy and histological assessment, which can be logistically challenging in some cases and carries inherent risk for complications related to procedure. Donor-derived cell-free DNA (dd-cfDNA), DNA of donor origin in the blood of KT recipient arising from cells undergoing injury and death, has been examined as a potential surrogate marker for allograft rejection. A rise in dd-cfDNA levels precedes changes in serum creatinine allows early detections and use as a screening tool for allograft rejection. In addition, when used in conjunction with donor-specific antibodies (DSA), it increases the pre-biopsy probability of antibody-mediated rejection (ABMR) aiding the decision-making process. Advancements in noninvasive biomarker assays such as dd-cfDNA may offer the opportunity to improve and expand the spectrum of available diagnostic tools to monitor and detect risk for rejection and positively impact outcomes for KT recipients. In this this article, we discussed the evolution of dd-cfDNA assays and recent evidence of assessment of allograft rejection and injury status of KT by the use of dd-cfDNA.

Recent Advances and Clinical Outcomes of Kidney Transplantation.

Recent advances in surgical, immunosuppressive and monitoring protocols have led to the significant improvement of overall one-year kidney allograft outcomes. Nonetheless, there has not been a significant change in long-term kidney allograft outcomes. In fact, chronic and acute antibody-mediated rejection (ABMR) and non-immunological complications following kidney transplantation, including multiple incidences of primary kidney disease, as well as complications such as cardiovascular diseases, infections, and malignancy are the major factors that have contributed to the failure of kidney allografts. The use of molecular techniques to enhance histological diagnostics and noninvasive surveillance are what the latest studies in the field of clinical kidney transplant seem to mainly focus upon. Increasingly innovative approaches are being used to discover immunosuppressive methods to overcome critical sensitization, prevent the development of anti-human leukocyte antigen (HLA) antibodies, treat chronic active ABMR, and reduce non-immunological complications following kidney transplantation, such as the recurrence of primary kidney disease and other complications, such as cardiovascular diseases, infections, and malignancy. In the present era of utilizing electronic health records (EHRs), it is strongly believed that big data and artificial intelligence will reshape the research done on kidney transplantation in the near future. In addition, the utilization of telemedicine is increasing, providing benefits such as reaching out to kidney transplant patients in remote areas and helping to make scarce healthcare resources more accessible for kidney transplantation. In this article, we discuss the recent research developments in kidney transplants that may affect long-term allografts, as well as the survival of the patient. The latest developments in living kidney donation are also explored.

Outcomes of kidney retransplantation after graft loss as a result of BK virus nephropathy in the era of newer immunosuppressant agents.

We conducted this study using the updated 2005-2016 Organ Procurement and Transplantation Network database to assess clinical outcomes of retransplant after allograft loss as a result of BK virus-associated nephropathy (BKVAN). Three hundred forty-one patients had first graft failure as a result of BKVAN, whereas 13 260 had first graft failure as a result of other causes. At median follow-up time of 4.70 years after the second kidney transplant, death-censored graft survival at 5 years for the second renal allograft was 90.6% for the BK group and 83.9% for the non-BK group. In adjusted analysis, there was no difference in death-censored graft survival (P = .11), acute rejection (P = .49), and patient survival (P = .13) between the 2 groups. When we further compared death-censored graft survival among the specific causes for first graft failure, the BK group had better graft survival than patients who had prior allograft failure as a result of acute rejection (P < .001) or disease recurrence (P = .003), but survival was similar to those with chronic allograft nephropathy (P = .06) and other causes (P = .05). The better allograft survival in the BK group over acute rejection and disease recurrence remained after adjusting for potential confounders. History of allograft loss as a result of BKVAN should not be a contraindication to retransplant among candidates who are otherwise acceptable.

BK polyomavirus genotypes in renal transplant recipients in the United States: A meta-analysis.

BACKGROUND: In the United States, increasing ethnic diversity has been apparent. However, the epidemiology and trends of BKV genotypes remain unclear. This meta-analysis was conducted with the aim to assess the prevalence of BKV genotypes among kidney transplant (KTx) recipients in the United States. METHODS: A comprehensive literature review was conducted through October 2018 utilizing MEDLINE, Embase, and Cochrane Database to identify studies that reported the prevalence of BKV subtypes and/or subgroups in KTx recipients in the United States. Pooled prevalence rates were combined using random effects, generic inverse variance method. The protocol for this study is registered with PROSPERO (no. CRD42019134582). RESULTS: A total of eight observational studies with a total of 193 samples (urine, blood, and kidney tissues) from 188 BKV-infected KTX recipients were enrolled. Overall, the pooled estimated prevalence rates of BKV subtypes were 72.2% (95% confidence of interval [CI]: 62.7-80.0%) for subtype I, 6.8% (95% CI: 2.5-16.9%) for subtype II, 8.3% (95% CI: 4.4-15.1%) for subtype III, and 16.1% (95% CI: 10.4-24.2%) for subtype IV, respectively. While metaregression analysis demonstrated a significant positive correlation between year of study and the prevalence of BKV subtype I (slopes = +0.1023, P = .01), there were no significant correlations between year of study and percentages of BKV subtype II-IV (P > .05). Among KTx recipients with BKV subtype I, the pooled estimated percentages of BKV subgroups were 22.4% (95% CI: 13.7-34.5%) for subgroup Ia, 30.6% (95% CI: 17.7-47.5%) for subgroup Ib1, 47.7% (95% CI: 35.8-59.9%) for subgroup Ib2, and 4.1% (95% CI:1.2-13.3%) for subgroup Ic, respectively. CONCLUSION: BKV subtype I is the most prevalent subtype among KTx recipients in the United States and its prevalence seems to increasing overtime. Subgroup Ib2 is the most common subgroup among BKV subtype I.

Incidence and Mortality of Renal Cell Carcinoma after Kidney Transplantation: A Meta-Analysis.

BACKGROUND: The incidence and mortality of renal cell carcinoma (RCC) after kidney transplantation (KTx) remain unclear. This study's aims were (1) to investigate the pooled incidence/incidence trends, and (2) to assess the mortality/mortality trends in KTx patients with RCC. METHODS: A literature search was conducted using the MEDLINE, EMBASE and Cochrane databases from inception through October 2018. Studies that reported the incidence or mortality of RCC among kidney transplant recipients were included. The pooled incidence and 95% CI were calculated using a random-effect model. The protocol for this meta-analysis is registered with PROSPERO; no. CRD42018108994. RESULTS: A total of 22 observational studies with a total of 320,190 KTx patients were enrolled. Overall, the pooled estimated incidence of RCC after KTx was 0.7% (95% CI: 0.5-0.8%, I2 = 93%). While the pooled estimated incidence of de novo RCC in the native kidney was 0.7% (95% CI: 0.6-0.9%, I2 = 88%), the pooled estimated incidence of RCC in the allograft kidney was 0.2% (95% CI: 0.1-0.4%, I2 = 64%). The pooled estimated mortality rate in KTx recipients with RCC was 15.0% (95% CI: 7.4-28.1%, I2 = 80%) at a mean follow-up time of 42 months after RCC diagnosis. While meta-regression analysis showed a significant negative correlation between year of study and incidence of de novo RCC post-KTx (slopes = -0.05, P = 0.01), there were no significant correlations between the year of study and mortality of patients with RCC (P = 0.50). Egger's regression asymmetry test was performed and showed no publication bias in all analyses. CONCLUSIONS: The overall estimated incidence of RCC after KTX was 0.7%. Although there has been a potential decrease in the incidence of RCC post-KTx, mortality in KTx patients with RCC has not decreased over time.

Prevalence of cancer in membranous nephropathy: a systematic review and meta-analysis of observational studies.

BACKGROUND: The association between membranous nephropathy (MN) and cancer has been well documented. However, the true prevalence and characteristics of cancer associated with MN have not been well described. METHODS: A systematic review and meta-analysis of cohort studies was conducted to summarize the prevalence of cancer-associated MN as well as patient characteristics and types of cancer in this population. We used a random-effects meta-analysis model to estimate the prevalence of cancer. RESULTS: We included 6 studies (n = 785). The estimated prevalence of cancer was 10.0% (95% CI, 6.1-14.6). The mean age of MN patients with cancer was 67 ± 7 years. The diagnosis of cancer preceded the diagnosis of MN in 20 ± 6.8%. Lung cancer was the most common type of tumor, accounting for 22 cases (26%), followed by prostate cancer (13 cases, 15%), hematologic malignancies (12 cases, 14%), colorectal cancer (9 cases, 11%), breast cancer (6 cases, 7%), and stomach and esophageal cancer (5 cases, 6%). CONCLUSION: The estimated prevalence of cancer in patients with MN is 10% (95% CI, 6.1-14.6). The vast majority of tumors associated with MN are lung and prostate cancer. Hematologic malignancies should also be considered as one of the potential cancers associated with MN. Our study was based on a largely Caucasian population; therefore, the findings might not be applicable to other populations.

Idiopathic granulomatous interstitial nephritis responsive to mycophenolate mofetil therapy.

Granulomatous interstitial nephritis (GIN) is a rare histologic disease. Various causes have been reported in the literature, including drugs, sarcoidosis, and infections. Other incidents have no discernible cause and are identified as idiopathic. We report a 68-year-old white man who presented with acute kidney injury and was given a diagnosis of idiopathic GIN. Mycophenolate mofetil treatment was elected because of steroid toxicity. He responded well to mycophenolate mofetil and has been in remission for more than 3 years. To our knowledge, this is the first report of successful treatment with mycophenolate mofetil of an adult patient with idiopathic GIN.

Clinical features of inflammatory myopathies and their association with malignancy: a systematic review in asian population.

Introduction. Idiopathic inflammatory myopathies (IIMs) are a group of chronic systemic autoimmune diseases that mainly affect the skeletal muscle. The common subtypes include adult dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM). Most of the earlier studies that described the clinical characteristics of IIM as well as their association with cancer were conducted in Western population. Our study is the first systematic review that summarizes the clinical data of DM/PM in Asian population. Methods. We identified 14 case series of DM/PM that met our eligibility criteria. We then compared this data with that from previous reports from Europe and North America. Results. Our systematic review included 2518 patients. Dermatomyositis is more common, with the ratio of dermatomyositis to polymyositis being 1.36 : 1. 69% of them were females with mean age of 45.5 years. Extramuscular manifestations, including arthritis/arthralgia, dysphagia, and interstitial lung disease, are found in one-third of the patients. Malignancy was found in 10% of patients, with lung and nasopharyngeal carcinomas being the most common malignancies associated with these myopathies. Conclusion. Clinical presentation of PM/DM appears to be similar in both Western and Asian populations. However, the type of associated malignancies in Asians differs from that in Caucasians. Ethnic background should be one of the factors that clinicians should consider while screening for malignancy.