Elevated hemoglobin levels in renal transplant recipients with polycystic kidney disease versus other etiologies: exploring mechanisms and implications for outcomes.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD)-related end-stage kidney disease (ESKD) often necessitates transplantation. However, the impact of ADPKD on post-transplant outcomes, specifically hemoglobin levels, remains unknown. METHODS: We retrospectively analyzed 513 Kidney Transplant Recipients (KTRs), of whom 81 had ESKD due to ADPKD (20 with pre-transplant native nephrectomy and 61 without). Hemoglobin levels were evaluated at multiple time intervals post-transplant. RESULTS: Kidney transplant recipients with ADPKD vs. KTRs with ESKD due to other causes exhibited significantly higher hemoglobin levels in repeated measurement analysis. Multivariable analyses confirmed ADPKD as an independent predictor for elevated hemoglobin levels. In a multivariable logistic regression analysis, the odds for maximum hemoglobin > 15 mg/dL at 3-12 months post-transplant were more than twice as high in ADPKD patients vs. all the other KTRs (Odds Ratio [OR] 2.31, 95% Confidence Interval [CI] 1.3-4.13, p < 0.001). Pre-transplant native nephrectomy revealed a trend toward lower hemoglobin levels. Elevated hemoglobin levels were linked to improved estimated glomerular filtration rate (eGFR) at one year post-transplant. Patient survival was enhanced among KTRs with ADPKD compared to other ESKD causes. CONCLUSIONS: Kidney transplant recipients with ADPKD exhibited elevated hemoglobin levels post-transplant, possibly due to prolonged native kidney erythropoietin production. These elevated hemoglobin levels were linked to improved outcomes, including allograft function and patient survival. Future research should further investigate the underlying mechanisms driving favorable ADPKD KTR outcomes.

Assessing Health-Related Quality of Life in Non-Directed Versus Directed Kidney Donors: Implications for the Promotion of Non-Directed Donation.

Living kidney donation has increased significantly, but little is known about the post-donation health-related quality of life (HRQoL) of non-directed donors (NDs) vs. directed donors (DDs). We thus examined the outcomes of 112 living kidney donors (82 NDs, 30 DDs). For the primary outcomes-namely, the mean physical component summary (PCS) and mental component summary (MCS) scores of the 12-item Short Form Survey (SF-12) questionnaire-scores were significantly higher for the NDs vs. the DDs (PCS: +2.69, MCS: +4.43). For secondary outcomes, NDs had shorter hospital stays (3.4 vs. 4.4 days), returned to physical activity earlier (45 vs. 60 days), exercised more before and after donation, and continued physical activity post-donation. Regression analyses revealed that donor type and white blood cell count were predictive of the PCS-12 score, and donor type was predictive of the MCS-12 score. Non-directed donation was predictive of a shorter hospital stay (by 0.78 days, p < 0.001) and the odds of having PCS-12 and MCS-12 scores above 50 were almost 10 and 16 times higher for NDs, respectively (p < 0.05). These findings indicate the safety and potential benefits of promoting non-directed donation. However, careful selection processes must be maintained to prevent harm and exploitation.

The Impact of the Donor Card Holder Prioritization Program on Kidney Allocation in Israel.

BACKGROUND: Since 2014, as part of a priority program within the Israeli Transplant Law, additional points were given to waitlisted candidates with donor cards. We assessed the impact on deceased donor kidney allocation. METHODS: This study enrolled all patients older than 18 y who underwent deceased donor kidney transplantation (January 2016-December 2019). Data were obtained from the National HLA Tissue Laboratory registry at the Sheba Medical Center. Patients were grouped by donor card status (ADI group) (not signed, 0 points; relative signed, 0.1 points; patient signed, 2 points; and relative donated, 9 points). The primary outcome was waiting time until kidney transplantation with and without the additional score. RESULTS: Four hundred forty-four patients underwent kidney transplantation during the study period: 281 (63%) were donor card holders (DCH) and 163 (37%) were not DCH. DCH with extra points waited 68.0 (±47.0) mo on average, compared with 94.6 (±47.3) mo for not DCH ( P  < 0.001). Donor card signers had a shorter time until transplant in a multivariable model. Without extra points, 145 recipients (32.6%) would have missed organs allocated to higher-scored candidates. Allocation changes occurred in 1 patient because of an additional 0.1 points, in 103 candidates because of an additional 2 points, and in 41 candidates because of an additional 9 points. CONCLUSIONS: Additional DCH scores improved allocation and reduced waiting time for donor card signers and those with donating relatives. To enhance fairness, consideration should be given to reducing the score weight of this social criterion and raising scores for other factors, especially dialysis duration.

[ORGAN TRANSPLANT HISTORY IN ISRAEL].

INTRODUCTION: Organ transplantation is an innovative field that was pioneered in the middle of the last century with the development of surgical techniques, advances in the understanding of immunological processes that cause rejection, introduction of drugs to prevent rejection and improved methods for organ preservation. In Israel, the first heart transplantation and kidney transplantation were performed in the mid-1960's followed by pancreas, lung and liver transplantation that were conducted for the first time in the late 1980's and early 1990's. The significant change that has led to an increase in the number of transplants in Israel and rising success rates after transplant has occurred with the introduction of the new generation of anti-rejection drugs, Cyclosporine and subsequently Tacrolimus (Prograf ®). Another milestone was the founding of The National Transplant Center in 1994. This led to the formation of national transplant candidate lists for each organ, the establishment of professional committees that determine organ allocation policy and the creation of a governmental ethics committee to oversee the performance of live-donor transplantation. In 2008, about a month before the signing of the Istanbul Declaration, the Transplantation Law was enacted to regulate organ transplantation in Israel, which included clauses restricting organ trade in the spirit of the Istanbul Declaration. These measures increased the number of transplants performed in Israel and significantly reduced the number of transplants of Israelis abroad. The establishment of Matanat Chaim Organization in 2012 is another milestone that has led to a significant increase in the number of kidney transplants, most of which are currently performed from altruistic donations. However, today there is still a shortage of organs for transplantation from deceased donors and there is a long way to go to close the gap between organ need and supply. This review will indicate the introduction of the first transplants performed in Israel and the measures undertaken to increase the number of transplants. In addition, the review will note the laws and regulations of organ allocation.

Bariatric Surgery in Severely Obese Kidney Donors Before Kidney Transplantation: A Retrospective Study.

BACKGROUND: Bariatric surgery (BS) is the optimal approach for sustained weight loss and may alter donation candidacy in potential donors with obesity. We evaluated the long-term effects of nephrectomy after BS on metabolic profile, including body mass index, serum lipids and diabetes, and kidney function of donors. METHODS: This was a single-center retrospective study. Live kidney donors who underwent BS before nephrectomy were matched for age, gender, and body mass index with patients who underwent BS alone and with donors who underwent nephrectomy alone. Estimated glomerular filtration rate (eGFR) was calculated according to Chronic Kidney Disease Epidemiology Collaboration and adjusted to individual body surface area to create absolute eGFR. RESULTS: Twenty-three patients who underwent BS before kidney donation were matched to 46 controls who underwent BS alone. At the last follow-up, the study group showed significantly worse lipid profile with low-density lipoprotein of 115 ± 25 mg/dL versus the control group with low-density lipoprotein of 99 ± 29 mg/dL ( P = 0.036) and mean total cholesterol of 191 ± 32 versus 174 ± 33 mg/dL ( P = 0.046). The second control group of matched nonobese kidney donors (n = 72) had similar serum creatinine, eGFR, and absolute eGFR as the study group before nephrectomy and 1 y after the procedure. At the end of follow-up, the study group had significantly higher absolute eGFR compared with the control group (86 ± 21 versus 76 ± 18 mL/min; P = 0.02) and similar serum creatinine and eGFR. CONCLUSIONS: BS before live kidney donation is a safe procedure that could increase the donor pool and improve their health in the long run. Donors should be encouraged to maintain their weight and avoid adverse lipid profile and hyperfiltration.

The Clinical Manifestation of Immunosuppressive Therapy as a Tool to Improve Immune Monitoring in Renal Transplant Recipients.

INTRODUCTION: Metrics for posttransplant immune monitoring to prevent over or under immunosuppression in renal transplant recipients (RTRs) are lacking. METHODS: We surveyed 132 RTRs, 38 in the first year posttransplant and 94 >1-year posttransplant, to study the clinical expression of immunosuppressive therapy. A questionnaire administered to these RTRs was divided into physical (Q physical) and mental (Q mental) symptoms. RESULTS: In multivariable models for the association between the calculated Q physical and Q mental scores and different clinical and biochemical variables in the 38 RTRs who filled out the questionnaire 130 times during the first year posttransplant, it was found that mycophenolic acid (MPA) and prednisone use increased the mean Q physical score by 0.59 (95% CI: 0.21-0.98, p = 0.002) and 0.53 (95% CI: 0.26-0.81, p = 0.00), respectively, while MPA use increased the mean Q mental score by 0.72 (95% CI: 0.31-1.12, p = 0.001). Among the 94 RTRs who each completed the questionnaire only once, the odds for the mean Q mental score to be above the median value were more than 3 times higher for RTRs treated versus non-treated with MPA (OR 3.38, 95% CI: 1.1-10.3, p = 0.03). MPA-treated RTRs had higher mean scores for questions related to sleep disorders (1.83 ± 1.06 vs. 1.32 ± 0.67 for not treated, p = 0.037), to difficulty falling asleep (1.72 ± 1.11 vs. 1.16 ± 0.5, p = 0.02), and to depression and anxiety. CONCLUSION: We concluded that prednisone and MPA use are associated with an increased Q physical and Q mental scores in RTRs. Routine monitoring of physical and mental status of RTRs should be implemented to improve the diagnosis of overimmunosuppression. Dose reduction or discontinuation of MPA should be considered in RTRs who report sleep disorders, depression, and anxiety.

Predictors and Adverse Outcomes of Acute Kidney Injury in Hospitalized Renal Transplant Recipients.

Data about in-hospital AKI in RTRs is lacking. We conducted a retrospective study of 292 RTRs, with 807 hospital admissions, to reveal predictors and outcomes of AKI during admission. In-hospital AKI developed in 149 patients (51%). AKI in a previous admission was associated with a more than twofold increased risk of AKI in subsequent admissions (OR 2.13, p < 0.001). Other major significant predictors for in-hospital AKI included an infection as the major admission diagnosis (OR 2.93, p = 0.015), a medical history of hypertension (OR 1.91, p = 0.027), minimum systolic blood pressure (OR 0.98, p = 0.002), maximum tacrolimus trough level (OR 1.08, p = 0.005), hemoglobin level (OR 0.9, p = 0.016) and albumin level (OR 0.51, p = 0.025) during admission. Compared to admissions with no AKI, admissions with AKI were associated with longer length of stay (median time of 3.83 vs. 7.01 days, p < 0.001). In-hospital AKI was associated with higher rates of mortality during admission, almost doubled odds for rehospitalization within 90 days from discharge and increased the risk of overall mortality in multivariable mixed effect models. In-hospital AKI is common and is associated with poor short- and long-term outcomes. Strategies to prevent AKI during admission in RTRs should be implemented to reduce re-admission rates and improve patient survival.

Humoral Response to the Fourth BNT162b2 Vaccination and Link Between the Fourth Dose, Omicron Infection, and Disease Severity in Renal Transplant Recipients.

BACKGROUND: The effectiveness of the fourth BNT162b2 vaccination in reducing the rate and severity of coronavirus disease 2019 (COVID-19) caused by the Omicron variant in renal transplant recipients (RTRs) is unknown. METHODS: Interviews were conducted with 447 RTRs regarding the status and timing of the fourth vaccination, prior vaccinations, and preceding COVID-19 infection. RTRs with polymerase chain reaction-confirmed COVID-19 infection from December 1, 2021, to the end of March 2022 were considered to have been infected with the Omicron variant and were interviewed to determine their disease severity. In a subgroup of 74 RTRs, the humoral response to the fourth dose was analyzed. In 30 RTRs, microneutralization assays were performed to reveal the humoral response to wild-type, Delta, and Omicron variant isolates before and after the fourth dose. RESULTS: Of 447 RTRs, 144 (32.2%) were infected with the Omicron variant, with 71 (49.3%) of the infected RTRs having received the fourth vaccine dose. RTRs who did not receive the fourth dose before the infection had more serious illness. In a subgroup of 74 RTRs, the fourth dose elicited a positive humoral response in 94.6% (70/74), with a significant increase in geometric mean titer for receptor-binding domain immunoglobulin G and neutralizing antibodies ( P < 0.001). The humoral responses to the Omicron variant before and after the fourth dose were significantly lower than the responses to the wild-type and the Delta variants. CONCLUSIONS: Overall, the fourth BNT162b2 dose was effective in reducing the rate and severity of Omicron disease in RTRs, despite the reduced humoral response to the variant.

Special Issue: New Advances in Kidney Transplantation.

This Special Issue in renal transplantation covers a variety of clinical and research areas in kidney transplantation [...].

The Impact of Obesity and Associated Comorbidities on the Outcomes after Renal Transplantation with a Living Donor vs. Deceased Donor Grafts.

Background: Obesity among kidney transplant (KT) recipients can lead to metabolic comorbidity-associated deaths. This study compares post-KT survival between obese and non-obese patients and outcomes of living donor (LD) and deceased donor (DD) grafts. Methods: Between January 2005−May 2019, 1403 KT recipients from a single center were included in the study, as well as 314 patients (22.4%) with obesity (BMI > 30 kg/m2), 137 DD transplants, and 177 LD transplants. Of the 1089 (77.6%) in the control group (BMI ≤ 30 kg/m2), 384 were DD transplants and 705 LD transplants. The Kaplan−Meier method was used for survival analysis and a Cox regression was used to identify risk factors for graft loss and mortality. Propensity score matching analysis adjusting for age, IHD, and T2DM was performed. Results: The study group had higher incidence of obesity related comorbidities, delayed graft function and primary non function (p < 0.001). One-, 5-and 10-year patient and graft survival were lower in the study group (p < 0.001). Subgroup analysis of graft survival according to type of graft shows a difference in the DD (p = 0.002) but not in the LD group (p = 0.220). However, mortality was higher in both groups (LD, p = 0.045; DD, p = 0.004). Risk factors for mortality were age, T2DM, IHD, and DD, and for graft failure: IHD, BMI, donor age, re-transplant, and DD. Propensity score analysis shows an odds ratio of 0.81 for graft failure and 0.93 for death in the study group (95% CI = 0.55, 1.21, p = 0.3 and CI = 0.59, 1.46, p = 0.7, respectively). Conclusions: Recipient age and metabolic comorbidities should be emphasized when evaluating patients with obesity. We suggest considering weight loss interventions using the new GLP-1 inhibitors and bariatric procedures in selected patients to prepare overweight patients for transplant.

BNT162b2 Third Booster Dose Significantly Increases the Humoral Response Assessed by Both RBD IgG and Neutralizing Antibodies in Renal Transplant Recipients.

Background: An impaired humoral response to full dose of BNT162b2 vaccine was observed in renal transplant recipients (RTR). Methods: To reveal predictors for humoral response to third vaccine, patients were stratified to positive (N = 85) and negative (N = 14) response groups based on receptor-binding domain (RBD) IgG ≥1.1 and neutralizing antibodies (NA) ≥ 16 dilution versus RBD IgG <1.1 or NA < 16, respectively. NA were detected using a SARS-CoV-2 pseudo-virus. Results: Response rate increased from 32.3% (32/99) before the third dose to 85.9% (85/99) post-third vaccine with a significant rise in geometric mean titers (GMTs) for RBD IgG and NA [0.79 (95% CI 0.65-0.96) vs. 3.08 (95% CI 2.76-3.45), p < 0.001 and 17.46 (95% CI 12.38-24.62) vs. 362.2 (95% CI 220.7-594.6), p < 0.001 respective. 80.6% (54/67) seroconverted and 96.9% (31/32) remained positive following the vaccine with a significant increase in GMTs for RBD IgG and NA. Age, ESRD secondary to diabetic nephropathy (DN) and renal allograft function were independent predictors for antibody response in RTR. Mycophenolic acid (MPA) use and dose had no impact on humoral response following the third booster. AEs were recorded for 70.1% of RTR population. Systemic AEs were more common in recipients with a positive humoral response as opposed to non-responders (45.2% versus 15.4% respectively, p = 0.04). Conclusion: 85.9% of RTR develop NA to BNT162b2 third vaccine, found effective in both negative and positive responders prior to the vaccine. Antigenic re-exposure overcame the suppressive effect of MPA on antibody response in RTR.

A multidisciplinary nephrogenetic referral clinic for children and adults-diagnostic achievements and insights.

BACKGROUND: Genetic kidney diseases contribute a significant portion of kidney diseases in children and young adults. Nephrogenetics is a rapidly evolving subspecialty; however, in the clinical setting, increased use of genetic testing poses implementation challenges. Consequently, we established a national nephrogenetics clinic to apply a multidisciplinary model. METHODS: Patients were referred from different pediatric or adult nephrology units across the country if their primary nephrologist suspected an undiagnosed genetic kidney disease. We determined the diagnostic rate and observed the effect of diagnosis on medical care. We also discuss the requirements of a nephrogenetics clinic in terms of logistics, recommended indications for referral, and building a multidisciplinary team. RESULTS: Over 24 months, genetic evaluation was completed for a total of 74 unrelated probands, with an age range of 10 days to 72 years. The most common phenotypes included congenital anomalies of the kidneys and urinary tract, nephrotic syndrome or unexplained proteinuria, nephrocalcinosis/nephrolithiasis, tubulopathies, and unexplained kidney failure. Over 80% of patients were referred due to clinical suspicion of an undetermined underlying genetic diagnosis. A molecular diagnosis was reached in 42/74 probands, yielding a diagnostic rate of 57%. Of these, over 71% of diagnoses were made via next generation sequencing (gene panel or exome sequencing). CONCLUSIONS: We identified a substantial fraction of genetic kidney etiologies among previously undiagnosed individuals which influenced subsequent clinical management. Our results support that nephrogenetics, a rapidly evolving field, may benefit from well-defined multidisciplinary co-management administered by a designated team of nephrologist, geneticist, and bioinformatician. A higher resolution version of the Graphical abstract is available as Supplementary information.

The Effect of Priority Given to Donor Card Holders on the Allocation of Livers for Transplant-Evidence From 7 Years of the Israeli Priority Program.

BACKGROUND: The Israeli Transplant Law grants priority in organ allocation to patients signing a donor card. Liver transplant candidates get additional 2 points on their Model for End Stage Liver Disease score for signing a donor card, 0.1 points for a relative holding a card, and 5 points if a relative donated an organ. We studied the effect of the priority program on waiting list mortality and allocation changes due to priority. METHODS: Using Israeli Transplant data of 531 adult liver transplant candidates with chronic liver disease listed between 2012 and 2018 we compared waitlist mortality and transplant rate of candidates with and without priority. Then we analyzed liver allocations resulting from additional priority points and followed outcome of patients who were skipped in line. RESULTS: Of the 519 candidates, 294 did not sign a donor card, 82 signed, 140 had a relative sign, and for 3, a relative donated an organ. The rates of waitlist mortality in these 4 groups were 22.4%, 0%, 21.4%, and 0%, respectively, and the transplant rates were 50%, 59.8%, 49.3%, and 100%, respectively. Of the 30 patients who were skipped because of priority, 24 subsequently underwent transplant, 2 are on the waiting list, and 4 died within 0.75, 1.75, 7, and 17 mo. CONCLUSIONS: The 2 points added to the Model for End Stage Liver Disease score were associated with lower waitlist mortality and higher transplant rate for candidates signing a donor card without significantly affecting access to transplant during allocation. Further research and consideration of optimal policy when granting priority for candidates signing a donor card should continue.

Long-Term Results of Kidney Transplantation in the Elderly: Comparison between Different Donor Settings.

With scarce organ supply, a selection of suitable elderly candidates for transplant is needed, as well as auditing the long-term outcomes after transplant. We conducted an observational cohort study among our patient cohort >60 years old with a long follow up. (1). PATIENTS AND METHODS: We used our database to study the results after transplant for 593 patients >60 years old who underwent a transplant between 2000-2017. The outcome was compared between live donor (LD; n = 257) recipients, an old-to-old (OTO, n = 215) group using an extended criteria donor (ECD) kidney, and a young-to-old (YTO, n = 123) group using a standard-criteria donor. The Kaplan-Meir method was used to calculate the patient and graft survival and Cox regression analysis in order to find risk factors associated with death. (2). RESULTS: The 5- and 10-year patient survival was significantly better in the LD group (92.7% and 66.9%) compared with the OTO group (73.3% and 42.8%) and YTO group (70.9% and 40.6%) (p < 0.0001). The 5- and 10-year graft survival rates were 90.3% and 68.5% (LD), 61.7% and 30.9% (OTO), and 64.1% and 39.9%, respectively (YTO group; p < 0.0001 between the LD and the two DD groups). There was no difference in outcome between patients in their 60's and their 70's. Factors associated with mortality included: age (HR-1.060), DM (HR-1.773), IHD (HR-1.510), and LD/DD (HR-2.865). (3). CONCLUSIONS: Our 17-years of experience seems to justify the rational of an old-to-old allocation policy in the elderly population. Live-donor transplant should be encouraged whenever possible. Each individual decision of elderly candidates for transplant should be based on the patient's comorbidity and predicted life expectancy.

BNT162b2 mRNA COVID-19 vaccination in immunocompromised patients: A prospective cohort study.

BACKGROUND: Trials of the Pfizer-BioNTech BNT162b2 mRNA vaccine showed 95% efficacy in preventing symptomatic disease; however, the trials excluded immunocompromised patients (ICPs). We aim at analyzing antibody response in ICPs. METHODS: A prospective cohort study was conducted at Sheba Medical Center, Israel, between January and April 2020, in 1274 participants who received the vaccine, including 1002 ICPs and 272 immunocompetent healthcare workers (HCWs). Antibodies were measured two-four weeks after vaccination by SARS-CoV-2 anti-receptor binding domain IgG antibodies (RBD IgG) and pseudo-virus neutralization assays. Multivariable logistic regression analyses were used to identify factors associated with vaccine-induced antibody response. Adverse events (AEs) were monitored. FINDINGS: RBD-IgG antibodies were detected in 154/156 (98.7%) of patients with HIV, 75/90 (83.3%) with solid malignancies, 149/187 (79.7%) with myeloma, 83/111 (74.8%) following hematopoietic stem cell transplants, 25/36 (69.4%) following liver transplantation, 26/43 (60.5%) with myelodysplastic syndrome, 96/188 (51.0%) with chronic lymphocytic leukemia/non-Hodgkin's lymphoma, 50/110 (45.5%) following kidney transplantation, 15/80 (18.8%) following heart transplantation, and 269/272 (98.9%) in controls. There was a significant correlation r = 0.74 (95%CI 0.69,0.78) between RBD-binding IgG and neutralizing antibodies in all groups. Multivariate logistic regression analysis showed that age > 65 years (OR 0.41,95%CI 0.30,0.57) and underlying immunosuppression (OR 0.02,95%CI 0.01,0.07) were significantly associated with a non-reactive response of IgG antibodies. HIV patients showed a similar immunological response as healthy adults. The vaccine was safe without any episodes of rejection, graft-versus-host disease (GVHD) or allergy. Immunocompetent HCWs experienced significantly more AEs than ICPs. INTERPRETATION: Antibody response to the Pfizer-BioNTech vaccine was highly variable among different ICPs; thus, individual recommendations should be provided for the different immunosuppression states.

Short versus prolonged antibiotic treatment for complicated urinary tract infection after kidney transplantation.

There is no consensus regarding the optimal duration of antibiotic therapy for urinary tract infection (UTI) following kidney transplantation (KT). We performed a retrospective study comparing short (6-10 days) versus prolonged (11-21 days) antibiotic therapy for complicated UTI among KT recipients. Univariate and inverse probability treatment weighted (IPTW) adjusted multivariate analysis for composite primary outcome of all-cause mortality or readmissions within 30 days and relapsed UTI 180 days were performed. Overall, 214 KT recipients with complicated UTI were included; 115 short-course treatment (median 8, interquartile range [IQR] 6-9 days), 99 prolonged course (median 14, IQR 12-21 days). The composite outcome occurred in 33 (28.6%) in the short-course group and 30 (30%) in the prolonged-course group; relapsed UTI occurred in 19 (16.5%) vs. 21 (21%), respectively. Duration of antibiotic treatment was not associated with any of these outcomes. The only risk factor for mortality/readmissions in multivariate analysis was deceased donor. No differences between groups were demonstrated for length of hospital stay, rates of bacteraemia, resistance development, and serum creatinine at 30 and 90 days. In conclusion, we found no difference in clinical outcomes between KT recipients treated for complicated UTI with short-course antibiotic (6-10 days) versus longer course (11-21 days).

Can uric acid blood levels in renal transplant recipients predict allograft outcome?

BACKGROUND: Hyperuricemia is common after renal transplantation, especially in those receiving calcineurin inhibitors. Little, however, is known about the relationship between uric acid (UA) levels and allograft outcome. METHODS: We conducted a retrospective single-center analysis (N = 368) in order to assess UA blood levels post-transplant association with allograft outcome. For this study, a median serum UA level of all measured UA levels from 1 month to 1 year post renal transplantation was calculated. RESULTS: Patients were divided into 2 groups based on the median UA level measured between 1 and 12 months post-transplant. Those with median UA level ≥ 7 and ≥ 6 mg/dL (N = 164) versus median UA level < 7 and < 6 mg/dL for men and women respectively (N = 204) had lower GFR values at 1, 3 and 5 years posttransplant (mean GFR ± SD of 43.4 ± 20.6 and 58 ± 19.9 at 3 years post-transplant, p < 0.001). In multivariate models, UA levels were no longer significantly associated with renal allograft function. In a multivariate cox proportional hazard model, UA level was found to be independently associated with increased risk for death-censored graft loss (HR of 1.3, 95% CI 1.0-1.7, p < 0.05 for every increase of 1 mg/dL in UA level). CONCLUSION: Hyperuricemia was found to be associated with increased death- censored graft loss but not with allograft function. Increased UA levels were not found to be an independent predictor of long-term allograft function despite the known association of hyperuricemia with the progression of cardiovascular and renal disease.

Humoral Response of Renal Transplant Recipients to the BNT162b2 SARS-CoV-2 mRNA Vaccine Using Both RBD IgG and Neutralizing Antibodies.

BACKGROUND: Data about SARS-CoV-2 vaccines efficacy in renal transplant recipients (RTR) are lacking. METHODS: To reveal predictors for humoral response to BNT162b2 vaccine among RTR, patients were divided into positive (N = 42) and negative (N = 78) response groups based on receptor-binding domain (RBD) immunoglobulin G (IgG) ≥1.1 and neutralizing antibodies (NA) ≥16 dilution versus RBD IgG <1.1 or NA <16, respectively. NA were detected using a SARS-CoV-2 pseudo-virus. RESULTS: NA were detected in only 42 of 120 (35%) of RTR versus 197 of 202 (97.5%) immunocompetent controls (P < 0.001). NA geometric mean titers in RTR were significantly lower versus the control group {83.7 (95% confidence interval [CI], 50.5-138.8) versus 482 (95% CI, 411-566), P < 0.001}. In a multivariable analysis, mycophenolic acid (MPA) dose and hemoglobin level were found to be independent predictors for antibody response in RTR. A positive response rate of 27% versus 63% was observed in patients on and off MPA, respectively. An increase in MPA dose by 1 mg/kg weight reduced the odds for a positive response by 17% (odds ratio = 0.83; 95% CI, 0.75-0.92; P < 0.001). Geometric mean titers for RBD IgG were significantly reduced as MPA daily dose increased. Hemoglobin blood level <13 g/dL reduced the antibody response by 63% (P = 0.04). Pain at the injection site after the second vaccine dose was significantly higher in the responders versus nonresponders (20.5% versus 5.5%, P = 0.01). CONCLUSIONS: Only 35% of RTR develop NA to the BNT162b2 mRNA vaccine. MPA is a major suppressor of antibody response in RTR.

Generation of vascular chimerism within donor organs.

Whole organ perfusion decellularization has been proposed as a promising method to generate non-immunogenic organs from allogeneic and xenogeneic donors. However, the ability to recellularize organ scaffolds with multiple patient-specific cells in a spatially controlled manner remains challenging. Here, we propose that replacing donor endothelial cells alone, while keeping the rest of the organ viable and functional, is more technically feasible, and may offer a significant shortcut in the efforts to engineer transplantable organs. Vascular decellularization was achieved ex vivo, under controlled machine perfusion conditions, in various rat and porcine organs, including the kidneys, liver, lungs, heart, aorta, hind limbs, and pancreas. In addition, vascular decellularization of selected organs was performed in situ, within the donor body, achieving better control over the perfusion process. Human placenta-derived endothelial progenitor cells (EPCs) were used as immunologically-acceptable human cells to repopulate the luminal surface of de-endothelialized aorta (in vitro), kidneys, lungs and hind limbs (ex vivo). This study provides evidence that artificially generating vascular chimerism is feasible and could potentially pave the way for crossing the immunological barrier to xenotransplantation, as well as reducing the immunological burden of allogeneic grafts.