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Background: Kidney involvement in systemic sclerosis (SSc) is common with altered kidney function present in approximately half of the patients [1]. Scleroderma renal crisis (SRC), the most severe kidney manifestation, occurs in about 20% of patients with this autoimmune disorder [1]. SRC mainly affects patients with the diffuse cutaneous systemic sclerosis (dcSSc) subtype of the disease, and particularly in those who are seropositive to anti RNA polymerase III antibodies [2]. In recent years, the prevalence of SRC has decreased following the initiation of medication therapy with angiotensin-converting-enzyme inhibitors (ACE-i). Previously, SRC mortality rates were as high as 78%. Contemporary studies in the post-ACE-i era suggest lower rates, with mortality rate ranging from 30% to 36% [3]. Nevertheless, progression to end-stage renal disease (ESRD) is evident and may require renal replacement therapies (RRTs). While renal transplant rates in SSc have increased, they constitute a small proportion of SSc-SRC patients (3-8%) and SSc-ESRD patients (4-17%).

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., (© 2024. The Author(s).)

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., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Vital, Siman-Tov, Shlomai, Davidov, Cohen-Hagai, Shashar, Askenasy, Ghinea, Mor and Hod.)

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.

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., Competing Interests: B.R.Z. received consultation fees from Fresenius, Novartis, and Sanofi, and speaker fees from AstraZeneca. The other authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hod, Oberman, Scott, Levy, Shlomai, Beckerman, Cohen-Hagai, Mor, Grossman, Zimlichman and Shashar.)

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., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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 &gt;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., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hod, Ben-David, Olmer, Scott, Ghinea, Mor, Levy, Indenbaum, Lustig, Grossman and Rahav.)

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)., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

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.

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., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: This study aimed to evaluate short- and long-term outcomes of kidney transplantation over 37 years in a national referral center and compare outcomes between Israeli Jewish and Arab children., Methods: Data on 599 pediatric transplantations performed in 545 children during 1981-2017, including demographic parameters, kidney failure disease profile, and pre-transplant dialysis duration, were retrieved from our computerized database and patient files. Patient and graft survival were estimated using the Kaplan-Meier method., Results: Twenty-year patient survival was 91.4% for live donor (LD) and 80.2% for deceased donor (DD) kidney recipients. Respective 10-year and 20-year graft survival rates for first kidney-only transplants were 75.2% and 47.0% for LD and 60.7% and 38.4% for DD grafts. Long-term graft survival improved significantly (p < 0.001) over the study period for recipients of both LD and DD allografts and reached 7-year graft survival of 92.0% and 71.3%, respectively. The proportion of DD transplantations was higher in the Arab subpopulation: 73.8% vs. 48.4% (p < 0.001). Graft survival was not associated with age at transplantation and did not differ between the Arab (N = 202) and Jewish children (N = 343). Median (IQR) waiting time on dialysis did not differ significantly between the Arab and Jewish children: 18 (10-30) and 15 (9-30) months, respectively (p Mann-Whitney = 0.312)., Conclusions: Good and progressively improving long-term results were obtained in pediatric kidney transplantation at our national referral center, apparently due to expertise gained over time and advances in immunosuppression. Equal access to DD kidney transplant and similar graft survival were found between ethnic groups.

Background: Persistent hyperparathyroidism (pHPT) is frequently seen after transplantation contributing to post-transplant complications., Methods: We conducted a retrospective single center analysis to explore the relationship of early pHPT and long-term allograft outcome. Patients were divided into high (N = 153) and low (N = 252) PTH groups based on serum parathyroid hormone (PTH) level 3 months post-transplant (PTH ≥ 150 and < 150 pg/mL, respectively)., Results: High PTH was found to be an independent predictor for reduced kidney allograft function up to 3 years post-transplant. eGFR decreased by 11.4 mL/min (P < .001) and the odds of having an eGFR < 60 mL/min 3 years post-transplant were sixfold higher (P < .01) in the high compared to the low PTH group. Subgroup analysis based on eGFR 1 year post-transplant, presence of slow graft function (SGF), and transplant type revealed similar results. High PTH three months post-transplant was also independently associated with an increased risk for overall mortality and for death with a functioning graft (P < .05)., Conclusions: pHPT three months post-renal transplantation is an independent predictor for a worse allograft function up to 3 years post-transplant and a risk factor for mortality. This relationship remains statistically significant after accounting for baseline allograft function, presence of SGF and serum mineral levels abnormalities., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Perfusion decellularization has been proposed as a promising method for generating nonimmunogenic organs from allogeneic or xenogeneic donors. Several imaging modalities have been used to assess vascular integrity in bioengineered organs with no consistency in the methodology used. Here, we studied the use of fluoroscopic angiography performed under controlled flow conditions for vascular integrity assessment in bioengineered kidneys. Porcine kidneys underwent ex vivo angiography before and after perfusion decellularization. Arterial and venous patencies were defined as visualization of contrast medium (CM) in distal capillaries and renal vein, respectively. Changes in vascular permeability were visualized and quantified. No differences in patency were detected in decellularized kidneys compared with native kidneys. However, focal parenchymal opacities and significant delay in CM clearance were detected in decellularized kidneys, indicating increased permeability. Biopsy-induced leakage was visualized in both groups, with digital subtraction angiography revealing minimal CM leakage earlier than nonsubtracted fluoroscopy. In summary, quantitative assessment of vascular permeability should be coupled with patency when studying the effect of perfusion decellularization on kidney vasculature. Flow-controlled angiography should be considered as the method of choice for vascular assessment in bioengineered kidneys. Adopting this methodology for organs premodified ex vivo under normothermic machine perfusion settings is also suggested., (© 2020 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background: There is no consensus on the optimal management of immunosuppression during bacterial infections among solid organ transplant recipients., Methods: A multicenter, cross-sectional survey, of high-volume kidney and liver transplant centers across US and Europe. Structured questionnaires including six multiple-choice questions concerning the management of immunosuppression during infection were distributed among 381 centers., Results: A total of 124 (33%) centers fully completed the questionnaire: 67 liver, 57 kidney centers. Participating centers reported heterogenous approaches to immunosuppression management for all types of immunosuppressive drugs. Notably, kidney centers reported similar frequencies of either discontinuation (19%), continuation (19%), or dose reduction (17.5%) of antimetabolites; discontinuation only for life-threatening infection (17.5%) or case by case decisions (27%). Calcineurin inhibitors (CNI) management was heterogenous mostly among liver centers, with 8% discontinuing the CNI, 18% continuing, and 22% reducing dose. Heterogenous approaches to management of steroids and inhibitors of the mammalian target of rapamycin were also demonstrated., Conclusions: Immunosuppression management during bacterial infection is heterogenous in US and European centers. Immunosupression reduction (ISR) during infection is a common practice, though supported by limited evidence. Demonstrating high heterogeneity in the approach to ISR, together with the equivocal results of clinical studies, support consideration of an interventional clinical trial., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Immunosuppression reduction is a common practice in the management of bacterial infection among kidney transplant recipients (KTRs). This practice, however, is based on limited evidence., Methods: Retrospective study comparing clinical outcomes of KTRs whose antimetabolite was discontinued vs continued during hospitalization due to bacterial infection, considering calcineurin inhibitors (CNI) levels. Primary outcome was a composite of clinical failure at day 5; all-cause mortality; and/or re-hospitalization at 90 days. Multivariable analysis of risk factors for the primary outcome was performed using a propensity-matched cohort., Results: We included 183 KTRs hospitalized with bacterial infection. Neither discontinuation of antimetabolites nor lower levels of CNI at infection onset were associated with a significant decrease the composite primary outcome. No significant difference in graft loss or rejection was demonstrated between patients with low vs high CNI levels or discontinuation vs continuation of antimetabolite. In multivariable analysis, CNI levels and management of antimetabolite were not significantly associated with adverse outcome., Conclusions: Immunosuppression reduction in hospitalized KTRs with bacterial infection did not offer a clinical advantage in terms of mortality, re-hospitalization, or clinical success. An interventional study evaluating continuation of immunosuppression vs reduction should be considered., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The surgical risk of morbidly obese patients is high and even higher for kidney transplant candidates. A BMI > 35-40 kg/m 2 is often a contraindication for that surgery. The safety, feasibility, and outcome of bariatric surgery for those patients are inconclusive., Methods: We conducted a retrospective chart review of prospectively collected data on morbidly obese renal transplant candidates who underwent laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB) in our institution between January 2009 and September 2017. The reported outcome included body weight and graft status after a mean follow-up of 47 months (range 0.5-5 years)., Results: Twenty-four patients (8 females, 16 males, average age 54 years, average preoperative BMI 41 kg/m 2 [range 35-51]) underwent LSG (n = 17) or LRYGB (n = 7). Sixteen of them (67%) proceeded to kidney transplantation. Of the 8 pre-transplant and post-bariatric surgery patients, 5 are on the waitlist, and 2 patients died (one of staple line leakage, and one from sepsis unrelated to the bariatric surgery). The average time from bariatric surgery to transplantation was 1.5 years (range 1 month to 4.3 years). The average pre-transplantation BMI was 28 kg/m 2 (range 19-36). The mean percentage of excess weight loss was 66% (n = 21), and the total percentage of weight loss was 29% (n = 21). Comorbidities (type 2 diabetes, hypertension, and dyslipidemia) improved significantly following both surgical approaches., Conclusions: LSG and LRYGB appear to effectively address obesity issues before kidney transplantation and improve surgical access. Morbidly obese transplant candidates would benefit from prior bariatric surgery.

Purpose: High tacrolimus trough drug level variability was found to be associated with reduced graft survival. The primary goal of this study was to find whether reduction of exposure to high tacrolimus trough level variability in patients in which previously had high variability was associated with better graft survival., Methods: All tacrolimus drug level values in patients that underwent kidney transplantation at our center between 2006 and 2015 were collected. Exposure to variability was calculated using a time-weighted coefficient of variability (TWCV). Time-dependent univariate and multivariate Cox proportional hazard models were used to analyze the primary outcome of graft survival and to determine a cutoff value for TWCV as a predictor of this outcome., Results: A total of 878 patients were included in the study with a median follow-up of 1263 days. TWCV above 25% was significantly associated with reduced graft survival (HR3.66, 95% CI 2.3-5.8, p < 0.001). Of the 480 patients (54.7%) who had a cumulative TWCV of > 25% at a certain time during the follow-up, 110 (22.9%) later returned to a cumulative TWCV of less than 25%. Reduction of TWCV to values below 25% was associated with a hazard of graft loss that was not different from patients who had cumulative TWCV of less than 25% during the entire follow-up period (HR 1.81, 95% CI 0.71-4.62, p = 0.218 and HR 1.08, 95% CI 0.39-2.99, p = 0.780) in univariate and multivariate analyses, respectively., Conclusions: Monitoring TWCV can help detect the high-risk patients. Interventions intended to reduce variability on long-term graft survival may have a positive effect on graft survival.

Background: Desensitization protocols have been developed in order to overcome the immunological barrier of donor-specific anti-HLA antibodies (DSA)., Methods: During 2006-2012, we implemented a program for desensitizing sensitized (positive DSA, negative NIH-CDC crossmatch) living-donor recipients. The long-term outcome of 36 sensitized recipients, treated with IVIG and plasmapheresis (PP), with or without rituximab (added when > 7500 MFI), was compared to 252 non-sensitized living-donor recipients., Results: Median peak DSA level before desensitization was 7223 (range 3567-16 000) MFI. During a mean follow-up of 121.9 months, graft loss occurred in 6/36 (17%) of the sensitized and 15/251 (6%) of the non-sensitized recipients (P = 0.021). Five-year and 10-year death-censored graft survival rates were 85% and 81% compared to 95% and 92%, respectively, for the non-sensitized recipients. There was no difference in recipients' survival. Slightly more episodes of acute rejection occurred in the sensitized group but had not influence on graft survival. At the last follow-up, 28 recipients had functioning graft; seventeen (47%) did not have detectable DSA. Eleven recipients had excellent graft function despite having detectable DSA., Conclusion: The long-term outcomes of sensitized recipients who underwent desensitization are encouraging. Adding rituximab to PP + IVIG in candidates with very high titers may result in improved outcome., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Post transplantation anemia (PTA) is common among kidney transplant patients. PTA is associated with increased graft loss and in most studies with increased mortality. However, the effect of the severity of anemia on this associations was not thoroughly evaluated., Methods: Patients who underwent kidney transplantation in Rabin Medical Center (RMC) were included in the study. Data were collected during the years 2002-2016. Anemia was defined as hemoglobin (Hb) level less than 12 g/dL in women and less than 13 g/dL in men, in accordance with World Health Organization (WHO) criteria. Severe anemia was defined as hemoglobin lower than 11 g/dL. Primary outcome was a composite of patient and graft survival. We used univariate and multivariate models to evaluate association between severity and specific causes of anemia with the outcomes. As the risk associated with anemia changed over time we analyzed the risk separately for the early and the late period (before and after 1251 days)., Results: Our cohort included 1139 patients, 412 (36.2%) of which had PTA and 134 (11.7%) had severe anemia. On multivariable analysis, severe anemia was highly associated with the primary outcome at the early period (HR 6.26, 95% CI 3.74-10.5, p < 0.001). Anemia due to either AKI & acute rejection (11.9% of patients) or infection (16.7%), were associated with primary outcome at the early period (HR 9.32, 95% CI 5.3-26.41, p < 0.001 and HR 3.99, 95% CI 2.01-7.95, p < 0.001, respectively). There was non-significant trend for association between anemia due to Nutritional deficiencies (29.1%) and this outcome (HR 3.07, 95% CI 0.93-10.17, p = 0.067)., Conclusion: PTA is associated with graft loss and mortality especially during the first three years. Anemia severity affects this association. An anemia workup is recommended for PTA.

Background: Acute kidney injury (AKI) was found to be associated with an increased risk of major adverse cardiovascular events (MACE) in the general population. Patients after kidney transplantation are prone to AKI events and are also at an increased risk of cardiovascular (CV) disease. The association between AKI and MACE in kidney transplant patients is yet to be studied., Methods: This retrospective single-center cohort study reviewed 416 adult renal allograft recipients transplanted between 2005 and 2010. AKI events were recorded starting 2 weeks after transplantation, or following discharge with a functioning graft. AKI was defined, according to the KDIGO criteria. The primary outcome was the composite of MACE starting 6 months after transplantation and all-cause mortality. For survival analysis, we used univariate and multivariate time varying Cox proportional hazard model., Results: One hundred and twenty-four patients (29.8%) had at least one episode of AKI. During the median follow-up time of 7.2 years (interquartile range 4.3-9.1), 144 outcome events occurred. By time varying Cox regression analysis, AKI was associated with an increased rate of CV outcomes or death (hazard ratio [HR] 1.96, 95% CI 1.36-2.81, p < 0.001), and the association remained significant by multivariate adjusted model (HR 1.76, 95% CI 1.18-2.63, p = 0.005). As for the different components of MACE, all-cause mortality and CV mortality were the only outcomes that were significantly associated with AKI. No interaction between AKI timing and MACE was found., Conclusion: AKI in kidney transplant recipient is associated with an increased risk of CV disease., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Aim: To assess the incidence of acute kidney injury (AKI) and its common etiologies in kidney transplant recipients and the effect of AKI's characteristics on graft survival., Methods: In a retrospective longitudinal cohort study, all serum creatinine (SCr) values of patients that had kidney transplantation between 01/2002-12/2010 were retrieved. AKI was defined as a 50% increase in SCr. Etiologies, recurrence, timing, and kidney function dynamics during the event were evaluated. The primary endpoint was defined as graft loss. Time-varying Cox model was used for the analysis., Results: Of 659 patients, 208 (31.6%) patients had 321 documented AKI events. Of these, 138 (66.4%) patients had one event, and 70 (33.6%) patients had recurrent events. The leading etiologies of the first AKI event were as follows: infection (33.4%), hypovolemia (14.3%), and unknown etiology (16.8%). Both first and recurrent AKI events were associated with an increased risk of graft loss (HR: 2.76, 95% CI: 1.95-3.89) and (HR: 4.54, 95% CI: 2.59-7.93), respectively. This deleterious association was lower within three months after transplantation, compared to later events. Patients in whom kidney function returned to baseline were less prone to graft loss., Conclusions: Late-onset, incomplete recovery, and recurrent AKI events are associated with increased graft loss., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Guidelines for bladder augmentation (BA) in kidney transplantation (KT) recipients are not well-defined. In our center, simultaneous BA with KT (BA-KT) is performed. We assessed transplantation outcomes of this unique extensive procedure., Methods: A case-control single center retrospective study. Transplantation outcomes were compared with those of KT recipients who did not need BA., Results: Compared with 22 patients who underwent KT only, for 9 who underwent BA-KT, surgical complications and the need for revision in the early posttransplantation period were similar; early graft function was better: estimated glomerular filtration rate, 96.5 ± 17.1 versus 79.4 ± 16.6 mL/min at 0 to 6 months (P = 0.02); posttransplantation clean intermittent catheterization was more often needed: by 78% (7/9) versus 13% (3/22); and asymptomatic bacteriuria was more common: 100% versus 9% during the first 6 months (P < 0.001), 55% versus 9% (P = 0.02) and 66.6% versus 9% during the first and second years, respectively (P = 0.004). Urinary tract infection (UTI) incidence was also higher: 100% versus 23% during the first 6 months and 44% versus 9% during the second year posttransplantation. Graft function deteriorated significantly in the BA-KT group by the fifth posttransplantation year: estimated glomerular filtration rate was 47.7 ± 39.7 mL/min versus 69 ± 21.3 mL/min, with only 6 (66%) of 9 functioning grafts versus 100% in the KT only group. Causes of graft loss were noncompliance with drug therapy in 2 patients and recurrent UTIs in 2 patients., Conclusions: Excellent short-term outcome for simultaneous BA-KT is threatened by graft loss due to a high prevalence of UTIs and patient noncompliance with the demanding complex posttransplantation therapy.

Purpose: Anemia has been reported to be associated with diabetes, but the association between new-onset diabetes after transplantation (NODAT) and anemia has not been reported., Methods: Patients who underwent kidney transplantation and did not have diabetes prior to transplantation were included in this study. Hemoglobin levels and the prevalence of anemia (hemoglobin <12 g/dL in females and <13 g/dL in males) were evaluated at three time points (prior to transplantation, 6 months following transplantation or 1 month before the development of NODAT, 2 years following transplantation, or following the development of NODAT) and were compared between those who developed NODAT and those who did not. Variables associated with the development of anemia were compared between the two groups., Results: A total of 266 kidney transplant recipients were included, of which 71 (27%) developed NODAT during the time of the follow-up. Hemoglobin and hematocrit levels and the prevalence of anemia were similar in those with and without NODAT at all three time points evaluated. Ferritin levels, prior to transplantation and mean corpuscular volume (MCV) posttransplantation post-NODAT development, were slightly but significantly lower in those with NODAT, although both were within the normal range., Conclusions: Pretransplantation ferritin levels and posttransplantation post-NODAT development MCV are inversely associated with the development of NODAT in kidney transplants.

Ureteral stents are routinely used in renal transplant and are associated with reduced urological complications but increased urinary tract infections (UTIs). There is no agreement on the preferred time to removal of stents after transplantation. We performed a systematic review and meta-analysis of all randomized controlled trials (RCTs) comparing stent duration of <14 days vs > =14 days. Electronic databases were searched to identify RCTs that compared early vs late stent removal. Primary outcome was urinary tract infections. Secondary outcomes included various urological complications. No significant difference in UTI rates was demonstrated between short and long stent duration (relative risk (RR) 0.85, 95% confidence interval (CI) 0.44-1.64), with significant heterogeneity (I 2  = 86%). Sensitivity analysis evaluating studies with low risk of bias for allocation concealment demonstrated statistically significant lower rates of UTI with short stent duration (RR 0.48, 95% CI 0.32-0.71) with no heterogeneity. No significant difference was demonstrated for the outcome of major urological complications (RR 0.72, 95% CI 0.50-1.05), without heterogeneity. Ureteral stenosis rates were significantly lower in the short duration arm (RR 0.42, 95% CI 0.18-0.98). Early removal of ureteral stents after renal transplant may be associated with reduced rates of UTI and ureteral stenosis. Additional RCTs are needed.

Objective: Clinical outcomes in individuals with new onset diabetes after transplantation (NODAT) and the optimal treatment for this complication are poorly characterized. This study was intended to better define these issues., Methods: Patients who underwent kidney transplantation and did not have diabetes prior to transplantation were included in the study. Clinical outcomes were compared between those who developed NODAT and those who did not. In those who developed NODAT, oral therapy was compared with insulin based therapy., Results: A total of 266 kidney transplant recipients were included, of which 71 (27%) developed NODAT during the time of the follow-up. Using Cox multivariate analysis adjusted for age and gender, hazard ratio for overall mortality among patients with NODAT versus those without NODAT was 2.69 (95% CI 1.04-7.01). Among patients who developed NODAT, 29 patients (40%) were treated with an insulin-based regimen. At the end of follow-up, no difference was found in mean HbA1c, and therapy regimen was not associated with greater mortality., Conclusions: New onset diabetes in kidney transplanted patients is associated with increased mortality compared with kidney transplanted patients without NODAT., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: Current data regarding the outcome of kidney transplantation in patients with familial Mediterranean fever (FMF) who reach end-stage renal disease (ESRD) due to reactive amyloidosis A (AA) are scarce and inconclusive., Methods: The outcomes of 20 patients with FMF and biopsy-proven AA amyloidosis that were transplanted between 1995 and 2014 were compared with 82 control patients (32 with diabetes mellitus and 50 with nondiabetic kidney disease). Major outcome data included overall patient and graft survivals., Results: During a mean overall follow-up of 116.6 ± 67.5 months 11 patients (55%) with FMF died versus 26 patients (31%) in the control group. Median time of death for patients with FMF was 61 months (range, 16-81) after transplantation. Estimated 5-year, 10-year, and actuarial 15-year overall patients survival rates were 73%, 45%, and 39%, respectively, for patients with FMF, versus 84%, 68% and 63%, respectively, for the control group (P = 0.028). FMF was associated with more than twofold increased risk for death after transplantation, and with a threefold increased risk for hospitalization because of infections during the first year. Infections and cardiovascular disease were the cause of death in the majority of patients with FMF. Overall graft survival was similar between the groups. Recurrence of AA amyloidosis was diagnosed in 2 patients during the first year after transplantation., Conclusions: FMF is associated with increased risk of mortality after kidney transplantation.

We sought to assess the frequency and predictors of early and late posttransplantation anemia (PTA). In addition, we aimed to assess the outcomes of patients with anemia and to assess the impact of anemia on mortality, graft function, and graft failure.Patients who underwent kidney transplantation in a single center during a 4-year period were included. Predictors associated with the development of anemia at 6 months (early PTA) or 2 years (late PTA) were evaluated in a univariate and multivariate analyses. The effects of anemia and other variables on mortality and graft function were assessed.A total of 266 kidney transplant recipients were included. The prevalence of PTA at 6 months (early PTA) was 51.3% and at 2 years (late PTA) was 36.6%. Female sex was significantly associated with early PTA. Patients with early PTA proceeded to late PTA. Patients with both early and late PTA had a higher mortality rate at 4 years compared to patients without anemia. On multivariable analysis, lower Hb at 2 years posttransplantation (hazard ratio [HR] 0.716, 95% confidence intervals [CI] 0.541-0.948, for every increment of 1 g/dL) was significantly associated with mortality. Patients with late PTA suffered a decline in eGFR compared to patients without anemia (P = .026). Furthermore, a lower Hb at 2 years posttransplantation was also associated with graft failure (HR 0.775, 95% CI 0.619-0.969, for every increment of 1 g/dL).Post-transplantation anemia is significantly associated with late mortality, with a decline in graft function and with an increased incidence of graft failure.

Purpose: Immunosuppressive therapy plays a major role in the development of post-transplant cancer. In this nested case-control study of kidney transplant recipients (KTRs), we investigated whether the incidence of post-transplant cancer is associated with the level of tacrolimus exposure over time., Methods: We screened the Rabin Medical Center database for adults who received kidney transplants between 2001 and 2014 and developed post-transplant cancer (excluding basal and squamous cell skin cancers). They were matched against KTRs without cancer. All patients received a maintenance immunosuppressive treatment with tacrolimus, mycophenolate mofetil and corticosteroids. The degree of exposure to tacrolimus was estimated as the time-weighted average (tTWA) value of tacrolimus blood levels. The tTWA was calculated as the area under the curve divided by time at 1, 6, and 12 months after transplantation and at time of cancer diagnosis., Results: Thirty-two cases were matched against 64 controls. tTWA values above 11 ng/mL at 6 and 12 months after transplantation were associated with odds ratio (OR) of 3.1 (95% CI 1.1-9) and 11.7 (95% CI = 1.3-106), respectively, for post-transplant cancer; and with OR of 5.2 (95% CI 1.3-20.5) and 14.1 (95% CI = 1.5-134.3), respectively, for cancer diagnosed more than 3 years after transplantation., Conclusion: Exposure to a tacrolimus time-weighted average level above 11 ng/mL at 6 or 12 months after kidney transplantation is associated with an increased risk of developing cancer.

Introduction: With the introduction of new therapies, the ABO barrier for kidney transplantation has been breached. In the recent decade the reported results with ABO incompatible (ABOi) kidney transplantation are similar to ABO compatible transplantation. We report on our initial experience with ABOi kidney transplantation performed at the Rabin Medical Center., Methods: During the period 3/2010 to 4/2015, 22 patients with PRA 0% underwent ABOi living-donor kidney transplantation. This group was compared to 325 non-sensitized live-donor transplant recipients of ABO-match transplants performed at the same period. The desensitization protocol included rituximab (375mg/kg/m2) and three sets of plasmapheresis every other day with IVIG (0.5g/kg) after each plasmapheresis. We compared graft and patient survivals, antibody mediated rejection (AMR) and graft function between the two groups., Results: Graft survival rates at 1, 3 and 5 years in the ABOi group were 95.5% at all intervals and 99.4% for the 1st year and 97.9% at 3 and 5 years after transplant (p=ns). Patient survival rates were 100% at all intervals and 100%, 98.3% and 97.5% at 1,3, and 5 years (p=ns). Two patients (9.1%) in the ABOi group experienced antibody mediated rejection (AMR), one lost his graft. In the ABO-matched group only two patients (0.85%) experienced AMR (p<0.05). Creatinine levels at followup were not statistically different between the groups., Conclusions: ABO incompatible kidney transplantation provides an additional option for transplant with excellent results. Strict monitoring of antibody levels should be conducted after ABOi transplantation to timely intervene and prevent AMR.

Background: Serum lactate dehydrogenase (LDH) levels may help to distinguish ischemic acute tubular necrosis (ATN) from acute rejection after kidney transplantation., Methods: All kidney biopsies performed in the years 2010 to 2012 were reviewed. Serum LDH, creatinine level, clinical variables, and presence of donor-specific antibodies were recorded before the biopsy., Results: Overall 150 biopsies were included. Ischemic ATN was diagnosed in 45 biopsies and acute cellular-mediated rejection and/or antibody-mediated rejection in 59 biopsies, 38 of which were accompanied by ATN. Serum LDH was elevated in 23 (51%) of 45 cases with ischemic ATN versus 15 (14%) of 105 cases with other diagnoses ( P < .0001). Median serum LDH was 478 U/L (range 277-2018) for ischemic ATN and 372 U/L (range 191-748) for all other diagnoses ( P < .001). When delayed graft function or primary nonfunctioning grafts were caused by ischemic ATN, serum LDH was elevated in 58% of cases, but when caused by acute rejection, LDH was normal in 88% of cases ( P = .02)., Conclusions: There is a strong association between elevated serum LDH 1 to 3 days before performing kidney biopsy and the diagnosis of ischemic ATN after kidney transplantation, especially at the immediate posttransplantation period. Normal serum LDH at this period should raise a suspicion of acute rejection.

Background: The variability of tacrolimus blood levels has been shown to be associated with inferior graft survival. However, the effect of variability during the early post-transplantation period has not been evaluated. We sought to evaluate the association between time-weighted variability in the early post-transplantation period and graft survival. We also explored the interaction between drug level variability and exposure to inadequate drug levels., Methods: This retrospective cohort study included all patients who underwent kidney transplantation in the Rabin Medical Center and were treated with tacrolimus. Time-weighted coefficient of variability (TWCV) was defined as time-weighted standard deviation divided by the mean drug level. Univariate and multivariate Cox proportional hazard model was used with the primary outcome of patients and graft survival., Results: The study population included 803 patients who underwent kidney transplantation between 1 January 2000 and 29 September 2013. The high tertile of TWCV of tacrolimus blood levels was associated with reduced graft survival by univariate and multivariate analyses [hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.14-2.53, P = 0.01 and HR 1.74, 95% CI 1.14-2.63, P = 0.01, respectively]. The interaction between high TWCV and exposure to inadequately low drug levels was significantly associated with reduced survival (P = 0.004), while the interaction between TWCV and high drug blood levels was not. One hundred and thirty patients (16.2%) had the combination of high TWCV and exposure to low drug values (<5 ng/mL). These patients had reduced graft survival by univariate and multivariate analyses (HR 2.42, 95% CI 1.57-3.74, P < 0.001 and HR 2.6, 95% CI 1.65-4.11, P < 0.001, respectively)., Conclusions: The combination of high TWCV and exposure to low drug levels might identify high-risk patients in the early post-transplantation period., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

From 1982 to 2011, 53 kidney transplantations (KT) for pediatric focal segmental glomerulosclerosis (FSGS) were recorded in the National Israeli Kidney Transplant Registry (NIKTR): 22-primary (1◦) FSGS, 25-proved/suspected genetic-secondary (2◦) FSGS, six lost/incomplete files/other. Half (56%) of 23 patients with 2◦ FSGS were Israeli-Arabs vs 29% of 1◦ FSGS KT recipients. 1◦ FSGS recurrence occurred in 64% (14/22) of 22 KT in 17 patients aged (median) 14 years vs 1/25 of 2◦ FSGS (P<.001). Early graft days/nonfunction occurred in 9/14 (64%), 2/8 (25%) and 2/25 (4%) of recurrent 1◦ FSGS (rFSGS), nonr1◦ FSGS and 2◦ FSGS, respectively. Twelve biopsies performed in nine of these grafts at (median) 8 days (range 5-60 days) post-KT showed: ATN-5, suspected rejection-4, rFSGS-2, normal kidney-1; rFSGS was diagnosed eventually in 8/9. Dialysis need during the first month post-KT was significantly associated with FSGS recurrence: 6/14 (43%) for rFSGS vs 2/8 (25%) for non-rFSGS. Plasmapheresis (PP) achieved complete and partial rFSGS remission in 5/9 and 2/9 grafts, respectively. Three grafts were excised during the first 60 days post-KT for: nonfunction (1) and bleeding (2). Remaining grafts' GFR was: 78, 42, and 91 mL/min (median) at 5.3, 4.75, and 8 years follow-up for non-rFSGS, rFSGS, and 2◦ FSGS grafts, respectively., Conclusions: Early PP implementation should be considered after KT for 1◦ FSGS patients with early graft dysfunction despite delayed proteinuria and nonspecific biopsy., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The effect of cytomegalovirus (CMV) serology status on malignancy risk in kidney transplanted patients is not clear yet., Methods: In a nested case-control study, CMV serology status was compared between patients with a malignancy and 2:1 matched control patients without a malignancy. In a cohort study, the hazard of malignancy was compared between patients that were CMV-negative but had a CMV-positive donor and other patients, using Cox analysis., Results: Fifty-two of 599 patients transplanted in our center between 2001 and 2014 developed a malignancy. Nine (17.3%) of the 52 patients that developed cancer were CMV-negative but had a-CMV-positive donor compared with 6 (5.8%) of the 104 matched control patients (odd ratio 3.42, 95% confidence interval [CI] 1.15-10.2, P=.021). By univariate Cox model, there was a trend toward increased cancer risk in CMV-negative patients with a positive donor (hazard ratio [HR] 1.95, 95% CI 0.95-4.0, P=.07), but after adjusting for multiple covariates, CMV-negative status was significantly associated with increased risk of cancer (HR 2.55, 95% CI 1.23-5.26; P=.012)., Conclusions: CMV-negative patients that had a CMV-positive donor were found to have a higher risk of malignancy after kidney transplantation., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The prevalence of adrenal incidentalomas (AIs) in asymptomatic individuals is unknown. This study evaluated the prevalence of AIs in healthy kidney donors in whom pre-operative computed tomography (CT) is performed routinely., Methods: All potential kidney donors evaluated at the Rabin Medical Center who had routine abdominal CT were identified and their medical records were retrospectively reviewed. Subjects who had normal CT scans were compared with those with a finding of an AI, evaluating demographic (age, body mass index, systolic and diastolic blood pressure) and laboratory variables (glucose, sodium, potassium, calcium, phosphorus, albumin and creatinine). In addition, prevalence of hypertension, rate of donation and surgical mortality were compared between the two groups., Results: CT was performed in 673 potential kidney donors. Of these, 645 had a normal CT and 28 (4.2%) had evidence of an AI. Those with AIs had a similar prevalence of hypertension, kidney donation and surgical mortality as those with a normal CT. Those with AIs were older (50.93 ± 11.1 versus 43.76 ± 11.1 years) but other demographic variables were similar; laboratory variables were also similar except for slightly lower albumin and creatinine in those with AIs., Conclusions: The prevalence of AIs is high even in healthy asymptomatic individuals.

Background: Most previously published studies of patients with membranoproliferative glomerulonephritis type I are small or have short follow-up period. We report the outcome of a fairly large cohort of patients followed up for nearly 10 years., Methods: Retrospective cohort study. Graft survival, recurrence rate and risk factors for recurrence were analyzed for 43 patients transplanted between the years 1995 and 2012., Results: At a mean overall follow-up of 118 ± 61 months (median, 127.8; range, 4.9-217), 12 patients lost their graft (28%). Death-censored actuarial 15-year graft survival rate was 56%. Membranoproliferative glomerulonephritis recurred in eight patients (19%) at a median time of 15.4 months (range, 4.4-70 months). Recurrence led to graft loss in seven patients (88%) within a median of 11.6 months (range, 1.3-54 months) from diagnosis. Median graft survival was 30.5 months for recurrence (range, 7-86). Actuarial 15-year graft survival was 71% for nonrecurrent. The risk for recurrence was higher for patients with human leukocyte antigen (HLA) B49 (odds ratio, 16.9; 95% confidence interval, 1.1-246; P=0.038) and HLA DR4 (odds ratio, 15.9; 95% confidence interval, 1.07-237; P=0.044) alleles. A trend toward increased risk was found with shorter duration of dialysis before transplantation. Four of 16 (25%) living-related versus none of the living-unrelated donors' recipients recurred. The HLA B49, acute tubular necrosis after transplantation, previous transplantations, and Arab origin were all associated with decreased graft and patient survival., Conclusion: Patients without recurrence in the first years should expect an excellent graft survival. Nonrelated living donors should be preferred. The HLA B49 and DR4 alleles may increase the risk for recurrence.

The Israeli transplantation law of 2008 stipulated that organ trading is a criminal offense, and banned the reimbursement of such transplants by insurance companies, thus decreasing dramatically transplant tourism from Israel. We evaluated the law's impact on the number and the socio-demographic features of 575 consecutive living donors, transplanted in the largest Israeli transplantation center, spanning 5 years prior to 5 years after the law's implementation. Living kidney donations increased from 3.5 ± 1.5 donations per month in the pre-law period to 6.1 ± 2.4 per month post-law (p < 0.001). This was mainly due to a rise in intra-familial donations from 2.1 ± 1.1 per month to 4.6 ± 2.1 per month (p < 0.001). In unrelated donors we found a significant change in their socio-demographic characteristics: mean age increased from 35.4 ± 7.4 to 39.9 ± 10.2 (p = 0.001), an increase in the proportion of donors with college level or higher education (31.0% to 63.1%; p < 0.001) and donors with white collar occupations (33.3% to 48.3%, p = 0.023). In conclusion, the Israeli legislation that prohibited transplant tourism and organ trading in accordance with Istanbul Declaration, was associated with an increase in local transplantation activity, mainly from related living kidney donors, and a change in the profile of unrelated donors into an older, higher educated, white collar population., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Cardiovascular-related mortality is 100-fold higher in pediatric renal transplant recipients than in the age-matched general population. Seventy-seven post-renal transplant children's charts were reviewed for cardiovascular risk factors at two and six months after transplantation (short term) and at two yr after transplantation and the last follow-up visit (mean 7.14 ± 3.5 yr) (long term). Significant reduction was seen in cardiovascular risk factors prevalence from two months after transplantation to last follow-up respectively: Hypertension from 52.1% to 14%, hypercholesterolemia from 48.7% to 33%, hypertriglyceridemia from 50% to 12.5%, anemia from 29.6% to 18.3%, hyperparathyroidism from 32% to 18.3% and hyperglycemia from 11.7% to 10%, and left ventricular hypertrophy from 25.8% at short term to 15%. There was an increase in the prevalence of obesity from 1.5% to 3.9% and of CKD 3-5 from 4.75% to 24%. The need for antihypertensive treatment decreased from 54% to 42%, and the percentage of patients controlled by one medication rose from 26% to 34%, whereas the percentage controlled by 2, 3, and 4 medications decreased from 21.9%, 5.5%, and 1.4% to 6%, 2%, and 0. Children after renal transplantation appear to have high rates of cardiovascular risk factors, mainly on short-term follow-up., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Using living donor organs for sequential liver and kidney transplantation (SeqLKT) in patients with primary hyperoxaluria type 1 (PH1) has emerged as a viable approach. Taking both organs from a single donor, however, is rare. There are 8 reported cases of SeqLKT in the literature, and in all but 1 case, children were the recipients. We present our experience with SeqLKT in 2 young adults with PH1. In the first case, with an interval between procedures of 4.5 months, SeqLKT was performed with a right liver lobe from a 47-year-old father for his 19-year-old son with PH1 who was on dialysis for 2 years before transplantation. Both the donor and the recipient had an uneventful recovery, although there was re-exploration for the control of bleeding in the recipient after liver transplantation. Thirty-three months after transplantation, the patient had normal liver and renal function. In the second case, with an interval between procedures of 22 days, SeqLKT was performed with organs from a 45-year-old father for his 19-year-old daughter with PH1 who was on dialysis for 8 months. The recipient procedures, including right liver lobe transplantation and kidney transplantation, were uneventful. The donor underwent percutaneous drainage of a subphrenic collection and subsequently fully recovered. Eighteen months after transplantation, the recipient's liver and renal allograft function was normal. In conclusion, because of the severe organ shortage, living related SeqLKT using the same donor should be carefully considered for young adults with PH1., (Copyright © 2013 American Association for the Study of Liver Diseases.)

The severe organ shortage in Israel has prompted many patients to undergo kidney transplantation abroad. In May 2008, the Israeli Knesset approved the Israel Transplant Law prohibiting organ trade and disallowing health insurers to reimburse the cost of illegal transplantation abroad. The aim of this study was to assess the initial effect of the law on kidney transplantations inside and outside the country. The number of kidney transplantations performed inside and outside Israel was compared between the 3-year periods before and after implementation of the transplant law (2006-2008 and 2009-2011). Further analysis compared the number of deceased-donor and live-donor transplantations performed in Israel during the same periods. The results showed that the number of transplants performed abroad dropped significantly, from a median of 143 per year during 2006-2008 to <45 per year during 2009-2011. There was a parallel increase in the number of kidney transplantations from living donors, from a median of 56 transplants per year in 2006-2008 to 78 per year in 2008-2011, with a peak of 117 transplants in 2011. In conclusion, the Israel Transplant Law has dramatically affected kidney transplantation practices in Israel by reducing transplantation tourism and increasing living-donor kidney transplantations., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aim: Haemoglobin (Hb) variability is associated with poor survival in patients with chronic kidney disease. Association of Hb variability after kidney transplantation with patients' and graft survival has not been adequetly studied., Methods: This retrospective study used registry data to examine the association between Hb variability in the early post-transplant period (first 6 months) and graft survival after kidney transplantatin. Kaplan-Meier and Cox regression analyses were used for univariate and multivariate associations between mortality, death censored graft survival and the composite outcome of both, in 752 patients after kidney transplantation. Hb values were collected each month during the first 6 months after transplantation, and Hb variavility was calculated using the residual standard deviation method., Results: The highest quartile of Hb variability was associated with inferior graft and patients' survival in univariate (hazard ratio (HR) 2.18; 95% confidence interval (CI) 1.51 to 3.13; P < 0.001) and multivariate models (HR 1.5; 95% CI 1.029 to 2.18; P = 0.035). This association was mainly due to increased death censored graft failure in the high variability group (HR 2.75; 95% CI 1.73 to 4.38; P < 0.001) and (HR 1.67; 95% CI 1.023 to 2.74; P = 0.04) in the univariate and multivariate models, respectively. There was no association between Hb variability and the risk of death (HR 1.51; 95% CI 0.88 to 2.57; P = 0.132)., Conclusion: High Hb variability is independently associated with inferior graft survival in patients after kidney transplantation., (© 2012 The Authors. Nephrology © 2012 Asian Pacific Society of Nephrology.)

Asymptomatic bacteriuria (AB) is frequent among kidney transplant patients during the first year post transplantation. Currently, there are no clear guidelines for the antibiotic treatment of AB among these patients. We examined the outcomes of treatment versus no treatment of AB in kidney transplant patients during the first year post transplantation. A retrospective cohort study including adults >16 years of age transplanted in one center between 1/2004 and 12/2010 was undertaken. The primary outcome was a composite of hospitalization for symptomatic urinary tract infection (UTI) or more than 25 % reduction in the estimated glomerular filtration rate (eGFR) 30 days after the documentation of AB. Secondary outcomes included symptomatic UTIs following the episode of AB, persistent recurrent AB, total days in hospital, mortality, adverse events, and resistance development. A total of 112 patients with AB fulfilled the inclusion criteria. Twenty-two patients received antibiotic treatment (19.6 %), while 90 patients did not. The primary outcome occurred in 4/22 (18.2 %) of the treated patients versus 5/90 (5.6 %) of the untreated patients [odds ratio (OR) = 3.78, 95 % confidence interval (CI) 0.9-15]. The risk of developing symptomatic UTI after AB was almost three times higher (p < 0.05) and the total number of hospitalization days at 6 months post AB was also significantly higher (p < 0.026) in the treated group. No patient died during the study period. UTI caused by bacteria resistant to the antibiotic used for the treatment of AB occurred in 36 % of the treated patients. We observed no benefit for the antibiotic treatment of AB in the short- and long-term follow-up. A prospective observational study is needed.

PTLD is the most common malignancy in pediatric kidney-transplant recipients. We examined the prevalence, clinical features, and outcome of PTLD in Israel. Twelve (4.4%) of 272 pediatric (<19 yr) kidney-transplant recipients retrieved from a search of the NIKTR for 1991-2008 had acquired PTLD at a median of 3.2 yr post-transplantation. PTLD-affected patients were younger at transplantation (4.2 vs. 12.5 yr, p = 0.02), had a higher rate of OKT3 therapy for acute rejection (25% vs. 4%, p = 0.015), and 5/12 were EBV-seropositive at transplantation. Graft dysfunction was the presenting sign in six (50%). PTLD was predominantly abdominal (83%) and B-cell type (67%); T-cell PTLD occurred exclusively in EBV-seropositive patients. Treatment consisted of immunosuppression cessation (6/12, 50%), antiviral agents (7/12, 58%), anti-CD20 monoclonal antibodies (4/12, 33%), and chemotherapy (6/12, 50%). Survival was 100% in the EBV-naïve patients and 40% in the EBV-seropositive patients. Graft loss occurred in three of eight survivors (37.5%). PTLD-associated mortality risk was older age: 11.2 vs. 3.4 yr, longer dialysis: 15 vs. 6.5 months, T-cell type disease (75%), later PTLD onset: 6.35 vs. 1.9 yr post-transplantation and era of transplantation (43% mortality before vs. 20% after 2001). Pretransplantation EBV-seronegative status might confer a survival benefit with early detected PTLD. EBV-seropositive patients are at risk for aggressive late-onset lethal PTLD., (© 2012 John Wiley & Sons A/S.)

Background: We sought to evaluate the effect of intravenous (IV) iron supplementation on hemoglobin (Hb) levels and detect predictors for response., Methods: This is a retrospective cohort study of 81 patients who were treated with IV iron post-transplant. We evaluated predictors of response to treatment defined as an increase in Hb value of more than 1 g/dL by linear regression analysis., Results: Three months after treatment, the mean Hb level increased significantly from 9.8 ± 1.4 g/dL to 11.1 ± 1.6 g/dL (p < 0.001). A lower baseline Hb value (OR: 0.51, 95% CI: 0.33-0.78 per 1 g/dL increase) was the only predictor of response at three months. The Hb value in the evaluable 60 patients at one yr increased from 9.9 ± 1.4 g/dL to 11.7 ± 1.7 g/dL (p < 0.001). Lower baseline Hb value (OR: 0.34, 95% CI: 0.18-0.65 per 1 g/dL increase) and a shorter time from transplantation (OR: 0.8, 95% CI: 0.68-0.94 per one yr increase) were predictors of response. Adverse events were reported in five patients (0.7% of doses). The rate of estimated glomerular filtration rate decline was reduced following the IV iron treatment -0.34 ± 1.05 mL/min/month after treatment compared with -0.81 ± 1.11 mL/min/month before treatment (p = 0.013)., Conclusions: IV iron treatment was safe and associated with Hb increase in a cohort of patients after kidney transplantation., (© 2012 John Wiley & Sons A/S.)

The aim of this study was to assess the prevalence and risk factors of AI in pediatric recipients of kidney or liver transplantation admitted because of a physiological stress episode and to identify patients that might be at risk of adrenal crises by clinical and laboratory parameters at admission. Adrenal function was prospectively evaluated by a standard (250 μg) adrenocorticotropin test in 48 recipients. Data on clinical and laboratory parameters were collected. AI was diagnosed in 11 patients: 10/32 (31.3%) children on long-term steroid treatment and 1/16 (6.25%) untreated. The only risk factor for AI was corticosteroids cumulative dose of >0.15 mg/kg/day during the last six months (p = 0.02, OR 6.67; 95% CI: 0.97-45.79). No correlation was found between clinical or laboratory signs of adrenal crisis on admission and the presence of AI. None of the patients with AI who did not receive stress dose (n = 8) developed adrenal crisis. AI is relatively common in children receiving prolonged corticosteroid treatment after kidney or liver transplantation. Clinical parameters on admission could not reliably identify patients with AI. Universal administration of a stress dose during physiological stress might not be required. However, at this point, the only method to identify patients that will benefit from a stress dose is through the ACTH test., (© 2011 John Wiley & Sons A/S.)