Clinical characteristics and outcomes of COVID-19 in solid organ transplant recipients: A cohort study.

Solid organ transplant recipients (SOTr) with coronavirus disease 2019 (COVID-19) are expected to have poorer outcomes compared to nontransplant patients because of immunosuppression and comorbidities. The clinical characteristics of 47 SOTr (38 kidneys and 9 nonkidney organs) were compared to 100 consecutive hospitalized nontransplant controls. Twelve of 47 SOTr managed as outpatients were subsequently excluded from the outcome analyses to avoid potential selection bias. Chronic kidney disease (89% vs 57% P = .0007), diabetes (66% vs 33% P = .0007), and hypertension (94% vs 72% P = .006) were more common in the 35 hospitalized SOTr compared to controls. Diarrhea (54% vs 17%, P < .0001) was more frequent in SOTr. Primary composite outcome (escalation to intensive care unit, mechanical ventilation, or in-hospital all-cause mortality) was comparable between SOTr and controls (40% vs 48%, odds ratio [OR] 0.72 confidence interval [CI] [0.33-1.58] P = .42), despite more comorbidities in SOTr. Acute kidney injury requiring renal replacement therapy occurred in 20% of SOTr compared to 4% of controls (OR 6 CI [1.64-22] P = .007). Multivariate analysis demonstrated that increasing age and clinical severity were associated with mortality. Transplant status itself was not associated with mortality.

Prolonged persistence of a novel replication-defective HIV-1 variant in plasma of a patient on suppressive therapy.

BACKGROUND: Cell-free residual HIV-1 virions (RVs) persist in plasma below 20-50 vRNA copies/ml in most patients on suppressive antiretroviral therapy (ART). How RVs are produced in the body during therapy is not fully clear. In this study, we have attempted to characterize these viruses of an ART-treated patient in vitro in order to gain insights into the mechanism of their production in vivo. METHODS: We have reconstructed almost the entire genomes of RVs as DNA forms using the patient's residual plasma vRNA by an overlapping RT-nested PCR method, and then sequence-analyzed the cloned genomes and tested them for their biological activities in vitro. RESULTS: We found that the reconstructed molecular clones of RVs lacked antiretroviral drug-resistant mutations, as well as G-to-A hypermutations. The vDNA clones, when transfected into TZM-bl cells, released HIV-p24 into the culture media at extremely low levels. This low-level virus production was found to be due to the presence of a unique mutation (GU-to-GC) in the conserved 5'-major splice donor (MSD) motif of the corresponding vRNAs. We found that the incorporation of this point mutation by itself could cause defects in the replication of a standard HIV strain (JRCSF) in vitro. However, this novel viral variant was intermittently detected at 5 of 7 time-points in the patient's plasma over a period of 39 months during therapy. CONCLUSIONS: This is the first identification of a natural point mutation (GU-to-GC) in the conserved 5'-MSD motif of HIV genomic RNA. The intermittent but prolonged detection of this replication-defective HIV variant in the patient's plasma among other viral populations strongly suggests that this variant is released from highly stable productively infected cells present in vivo during therapy. The potential implication of this observation is that the elimination of such productively infected cells that contribute to residual viremia during suppressive therapy could be an important first step towards achieving a cure for HIV.

Evaluating Global and Temporal Trends in Pancreas and Islet Cell Transplantation: Public Awareness and Engagement.

BACKGROUND: Pancreas transplantation is a crucial surgical intervention for managing diabetes, but it faces challenges such as its invasive nature, stringent patient selection criteria, organ scarcity, and centralized expertise. Despite the steadily increasing number of pancreas transplants in the United States, there is a need to understand global trends in interest to increase awareness of and participation in pancreas and islet cell transplantation. METHODS: We analyzed Google Search trends for "Pancreas Transplantation" and "Islet Cell Transplantation" from 2004 to 14 November 2023, assessing variations in search interest over time and across geographical locations. The Augmented Dickey-Fuller (ADF) test was used to determine the stationarity of the trends (p < 0.05). RESULTS: Search interest for "Pancreas Transplantation" varied from its 2004 baseline, with a general decline in peak interest over time. The lowest interest was in December 2010, with a slight increase by November 2023. Ecuador, Kuwait, and Saudi Arabia showed the highest search interest. "Islet Cell Transplantation" had its lowest interest in December 2016 and a more pronounced decline over time, with Poland, China, and South Korea having the highest search volumes. In the U.S., "Pancreas Transplantation" ranked 4th in interest, while "Islet Cell Transplantation" ranked 11th. The ADF test confirmed the stationarity of the search trends for both procedures. CONCLUSIONS: "Pancreas Transplantation" and "Islet Cell Transplantation" showed initial peaks in search interest followed by a general downtrend. The stationary search trends suggest a lack of significant fluctuations or cyclical variations. These findings highlight the need for enhanced educational initiatives to increase the understanding and awareness of these critical transplant procedures among the public and professionals.

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.

Clinically adjudicated deceased donor acute kidney injury and graft outcomes.

BACKGROUND: Acute kidney injury (AKI) in deceased donors is not associated with graft failure (GF). We hypothesize that hemodynamic AKI (hAKI) comprises the majority of donor AKI and may explain this lack of association. METHODS: In this ancillary analysis of the Deceased Donor Study, 428 donors with available charts were selected to identify those with and without AKI. AKI cases were classified as hAKI, intrinsic (iAKI), or mixed (mAKI) based on majority adjudication by three nephrologists. We evaluated the associations between AKI phenotypes and delayed graft function (DGF), 1-year eGFR and GF. We also evaluated differences in urine biomarkers among AKI phenotypes. RESULTS: Of the 291 (68%) donors with AKI, 106 (36%) were adjudicated as hAKI, 84 (29%) as iAKI and 101 (35%) as mAKI. Of the 856 potential kidneys, 669 were transplanted with 32% developing DGF and 5% experiencing GF. Median 1-year eGFR was 53 (IQR: 41-70) ml/min/1.73m2. Compared to non-AKI, donors with iAKI had higher odds DGF [aOR (95%CI); 4.83 (2.29, 10.22)] and had lower 1-year eGFR [adjusted B coefficient (95% CI): -11 (-19, -3) mL/min/1.73 m2]. hAKI and mAKI were not associated with DGF or 1-year eGFR. Rates of GF were not different among AKI phenotypes and non-AKI. Urine biomarkers such as NGAL, LFABP, MCP-1, YKL-40, cystatin-C and albumin were higher in iAKI. CONCLUSION: iAKI was associated with higher DGF and lower 1-year eGFR but not with GF. Clinically phenotyped donor AKI is biologically different based on biomarkers and may help inform decisions regarding organ utilization.

Acute Kidney Injury in a Predominantly African American Cohort of Kidney Transplant Recipients With COVID-19 Infection.

BACKGROUND: Renal involvement in severe or critical acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is frequent. Acute kidney injury (AKI) in African American (AA) kidney transplant recipients (KTRs) with COVID-19 is not well described. We report our experience with a predominantly AA cohort (79%) of KTRs with COVID-19 infections in the Detroit Metropolitan area. METHODS: In this retrospective, single-center study, we identified 39 KTRs who tested positive for SARS-CoV-2 between March 16 and April 25, 2020. Data from electronic medical records were retrieved and compared between KTRs without AKI and KTRs with AKI. RESULTS: One patient was excluded due to delayed graft function. Final analysis of AKI in KTRs with proven COVID-19 was done on 38 patients of which 30 were AA (79%). AKI occurred in 71.1% of COVID-19 KTRs (n = 27), of whom 6 (22.2%) patients required HD. The incidence of AKI in our cohort was 71% (27/38). AKI rate among AA was 76.7% versus 50% in non-AA cohort (P = 0.195). In a univariate logistic regression analysis, AA race was not significantly associated with AKI odds ratio (3.4; CI, 0.68-17.4; P = 0.14). After risk adjustment by race, patients with diabetes showed a significantly higher risk of AKI (adjusted odds ratio, 19.85; CI, 1.65-58.66; P = 0.012). KTRs with AKI had more preexisting renin angiotensin aldosterone system inhibitor use than KTRs without AKI (P = 0.03). CONCLUSIONS: KTRs infected with SARS-CoV-2 have a high incidence of AKI, with associated increased morbidity and mortality. Although no racial differences in mortality were noted in our KTRs with AKI, we await data from registries to help elucidate this difference.

Epidemiology of parvovirus B19 and anemia among kidney transplant recipients: A meta-analysis.

BACKGROUND: Persistent anemia has been described in kidney transplant (KTx) recipients with parvovirus B19 virus infection. However, the epidemiology of parvovirus B19 and parvovirus B19-related anemia after KTx remains unclear. We conducted this systematic review (1) to investigate the incidence of parvovirus B19 infection after KTx and (2) to assess the incidence of parvovirus B19 among KTx patients with anemia. MATERIALS AND METHODS: A systematic review was conducted in EMBASE, MEDLINE, and Cochrane databases from inception to March 2019 to identify studies that reported the incidence rate of parvovirus B19 infection and/or seroprevalence of parvovirus B19 in KTx recipients. Effect estimates from the individual studies were extracted and combined using random-effects, generic inverse variance method of DerSimonian and Laird. The protocol for this systematic review is registered with PROSPERO (no. CRD42019125716). RESULTS: Nineteen observational studies with a total of 2108 KTx patients were enrolled. Overall, the pooled estimated seroprevalence of parvovirus B19 immunoglobulin G was 62.2% (95% confidence interval [CI]: 45.8%-76.1%). The pooled estimated incidence rate of positive parvovirus B19 DNA in the 1st year after KTx was 10.3% (95% CI: 5.5%-18.4%). After sensitivity analysis excluded a study that solely included KTx patients with anemia, the pooled estimated incidence rate of positive parvovirus B19 DNA after KTx was 7.6% (95% CI: 3.7%-15.0%). Among KTx with anemia, the pooled estimated incidence rate of positive parvovirus B19 DNA was 27.4% (95% CI: 16.6%-41.7%). Meta-regression analysis demonstrated no significant correlations between the year of study and the incidence rate of positive parvovirus B19 DNA (P = 0.33). Egger's regression asymmetry test was performed and demonstrated no publication bias in all analyses. CONCLUSION: The overall estimated incidence of positive parvovirus B19 DNA after KTX is 10.3%. Among KTx with anemia, the incidence rate of positive parvovirus B19 DNA is 27.4%. The incidence of positive parvovirus B19 DNA does not seem to decrease overtime.

Is Remote Ischemic Conditioning of Benefit to Patients Undergoing Kidney Transplantation?

Renal ischemia-reperfusion injury (IRI), an inevitable event during kidney transplantation procedure, can result in delayed graft function or even primary nonfunction. In addition to strategies to limit IRI such as advancements in organ allocation systems and preservation of organs, and reduction in cold and warm ischemia time, remote ischemic conditioning (RIC) has attracted much attention in recent years. With promising findings and data suggesting a potential benefit of RIC in animal kidney transplantation models, a few clinical trials have investigated the use of RIC in human kidney transplantation. Unfortunately, the findings from these investigations have been inconclusive due to a number of factors such as diverse time points of RIC, limited sample size, and complexity of kidney transplant patients. This brief commentary aims to discuss the effects of RIC on clinical outcomes and proinflammatory cytokines in patients undergoing kidney transplantation.

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.

Reactivation of BK polyomavirus during pregnancy, vertical transmission, and clinical significance: A meta-analysis.

BACKGROUND: Studies have shown conflicting results on the prevalence and the risks of BK reactivation among pregnant women. In addition, the prevalence of vertical transmission and its clinical significance during pregnancy are not well studied. OBJECTIVES: The study's aims were (1) to investigate the prevalence, and (2) to assess the risk of BK Polyomavirus reactivation and its clinical significance in pregnant women and fetuses. STUDY DESIGN: A literature search was performed using MEDLINE, EMBASE and Cochrane Database from inception through May 31, 2017. We included studies that reported prevalence, relative risks, odds ratios, or hazard ratios of BK Polyomavirus reactivation during pregnancy. Pooled odds ratios (ORs) and 95% CI were calculated using a random-effect model. The protocol for this study is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017063919). RESULTS: 17 observational studies with a total of 2553 pregnant women were enrolled. The estimated prevalence of BK seropositivity and BK in urine (viruria) among pregnant women were 79.2% (95%CI: 69.6%-86.4%) and 18.9% (95%CI: 10.4%-31.8%). When compared to non-pregnant women, the pooled ORs of BK seropositivity and BK viruria in pregnant women were 1.84 (95%CI: 1.05-3.22) and 6.02 (95%CI: 2.43-14.92), respectively. The estimated prevalence of positive BK-specific IgM antibody in cord blood was 4.9% (95%CI: 0.5%-36.2%). The data on the fetal effects of BK virus were limited. Although BK was detected in fetal organs, available data suggested no association between BK infection and adverse consequences such as miscarriage during pregnancy or childhood malignancy. CONCLUSION: Our meta-analysis demonstrates a significantly increased risk of BK Polyomavirus reactivation during pregnancy. Although vertical transmission can occur with an overall estimated prevalence of 4.9%, there are currently no data suggesting harm to pregnant women and fetuses from BK Polyomavirus.

Epidemiology and Prognostic Importance of Atrial Fibrillation in Kidney Transplant Recipients: A Meta-Analysis.

This meta-analysis was conducted with the aims to summarize all available evidence on (1) prevalence of pre-existing atrial fibrillation (AF) and/or incidence of AF following kidney transplantation; (2) the outcomes of kidney transplant recipients with AF; and (3) the trends of estimated incidence of AF following kidney transplantation over time. A literature search was conducted utilizing MEDLINE, EMBASE, and the Cochrane Database from inception through March 2018. We included studies that reported (1) prevalence of pre-existing AF or incidence of AF following kidney transplantation or (2) outcomes of kidney transplant recipients with AF. Effect estimates from the individual study were extracted and combined utilizing random-effect, generic inverse variance method of DerSimonian and Laird. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018086192). Eight cohort studies with 137,709 kidney transplant recipients were enrolled. Overall, the pooled estimated prevalence of pre-existing AF in patients undergoing kidney transplantation was 7.0% (95% CI: 5.6⁻8.8%) and pooled estimated incidence of AF following kidney transplantation was 4.9% (95% CI: 1.7⁻13.0%). Meta-regression analyses were performed and showed no significant correlations between year of study and either prevalence of pre-existing AF (p = 0.93) or post-operative AF after kidney transplantation (p = 0.16). The pooled odds ratios (OR) of mortality among kidney transplant recipients with AF was 1.86 (3 studies; 95% CI: 1.03⁻3.35). In addition, AF is also associated with death-censored allograft loss (2 studies; OR: 1.55, 95% CI: 1.02⁻2.35) and stroke (3 studies; OR: 2.54, 95% CI: 1.11⁻5.78) among kidney transplant recipients. Despite advances in medicine, incidence of AF following kidney transplant does not seem to decrease over time. In addition, there is a significant association of AF with increased mortality, allograft loss, and stroke after kidney transplantation.