Kidney Recipients Research Articles

Discrepant Outcomes between National Kidney Transplant Data Registries in the United States.

Effects of reduced access to external data by transplant registries to improve accuracy and completeness of the collected data are compounded by different data management processes at three US organizations that maintain kidney transplant-related datasets. This analysis suggests that the datasets have large differences in reported outcomes that vary across different subsets of patients. These differences, along with recent disclosure of previously missing outcomes data, raise important questions about completeness of the outcome measures. Differences in recorded deaths seem to be increasing in recent years, reflecting the adverse effects of restricted access to external data sources. Although these registries are invaluable sources for the transplant community, discrepancies and incomplete reporting risk undermining their value for future analyses, particularly when used for developing national transplant policy or regulatory measures. Central to a transplant registry's quality are accuracy and completeness of the clinical information being captured, especially for important outcomes, such as graft failure or death. Effects of more limited access to external sources of death data for transplant registries are compounded by different data management processes at the United Network for Organ Sharing (UNOS), the Scientific Registry of Transplant Recipients (SRTR), and the United States Renal Data System (USRDS). This cross-sectional registry study examined differences in reported deaths among kidney transplant candidates and recipients of kidneys from deceased and living donors in 2000 through 2019 in three transplant datasets on the basis of data current as of 2020. We assessed annual death rates and survival estimates to visualize trends in reported deaths between sources. The UNOS dataset included 77,605 deaths among 315,346 recipients and 61,249 deaths among 275,000 nonpreemptively waitlisted candidates who were never transplanted. The SRTR dataset included 87,149 deaths among 315,152 recipients and 60,042 deaths among 259,584 waitlisted candidates. The USRDS dataset included 89,515 deaths among 311,955 candidates and 63,577 deaths among 238,167 waitlisted candidates. Annual death rates among the prevalent transplant population show accumulating differences across datasets-2.31%, 4.00%, and 4.03% by 2019 from UNOS, SRTR, and USRDS, respectively. Long-term survival outcomes were similar among nonpreemptively waitlisted candidates but showed more than 10% discordance between USRDS and UNOS among transplanted patients. Large differences in reported patient outcomes across datasets seem to be increasing, raising questions about their completeness. Understanding the differences between these datasets is essential for accurate, reliable interpretation of analyses that use these data for policy development, regulatory oversight, and research. This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_10_24_JASN0000000000000194.mp3.

Evaluating anti-thymocyte globulin induction doses for better allograft and patient survival in Asian kidney transplant recipients

Anti-thymocyte globulin (ATG) is currently the most widely prescribed induction regimen for preventing acute rejection after solid organ transplantation. However, the optimal dose of ATG induction regimen in Asian kidney recipients is unclear. Using the Korean Organ Transplantation Registry, we performed a retrospective cohort study of 4579 adult patients who received renal transplantation in South Korea and divided them into three groups according to the induction regimen: basiliximab group (n = 3655), low-dose ATG group (≤ 4.5 mg/kg; n = 467), and high-dose ATG group (> 4.5 mg/kg; n = 457). We applied the Toolkit for Weighting and Analysis of Nonequivalent Groups (TWANG) package to generate high-quality propensity score weights for intergroup comparisons. During four-year follow-ups, the high-dose ATG group had the highest biopsy-proven acute rejection rate (basiliximab 20.8% vs. low-dose ATG 22.4% vs. high-dose ATG 25.6%; P < 0.001). However, the rates of overall graft failure (4.0% vs. 5.0% vs. 2.6%; P < 0.001) and mortality (1.7% vs. 2.8% vs. 1.0%; P < 0.001) were the lowest in the high-dose ATG group. Our results show that high-dose ATG induction (> 4.5 mg/kg) was superior to basiliximab and low-dose ATG induction in terms of graft and patient survival in Asian patients undergoing kidney transplant.

Shifting perspectives in liver diseases after kidney transplantation.

Liver diseases after kidney transplantation range from mild biochemical abnormalities to severe hepatitis or cirrhosis. The causes are diverse and mainly associated with hepatotropic viruses, drug toxicity and metabolic disorders. Over the past decade, the aetiology of liver disease in kidney recipients has changed significantly. These relates to the use of direct-acting antiviral agents against hepatitis C virus, the increasing availability of vaccination against hepatitis B and a better understanding of drug-induced hepatotoxicity. In addition, the emergence of the severe acute respiratory syndrome coronavirus 2 pandemic has brought new challenges to kidney recipients. This review aims to provide healthcare professionals with a comprehensive understanding of recent advances in the management of liver complications in kidney recipients and to enable them to make informed decisions regarding the risks and impact of liver disease in this population.

Urinary Tract Infection 1 Year After Kidney Transplant: Effect on Kidney Transplant Outcomes.

Transplant is the gold standard treatment for end-stage renal disease, and yet infectious complications frequently arise in kidney recipients in the context of immunosuppression therapy, with urinary tract infection being the most common. We aimed to assess the prevalence of posttransplant urinary tract infections in kidney transplant recipients and assess the effects on kidney allograft and overall patient outcomes. We performed a retrospective analysis of data from State University of New York Upstate University Hospital from January 2016 to November 2022 to assess transplant outcomes in patients who underwent a kidney transplant at our center and met the inclusion criteria. There were 507 renal allograft recipients who met our inclusion criteria and were assessed for the incidence of urinary tract infection within the first year after transplant. Urinary tract infection was recurrent in 113 transplant recipients (55.6%) within the first year, and 118 (58.1%) were on prophylactic antibiotics at urinary tract infection diagnosis. We observed no relation between recurrence of urinary tract infection and use of prophylactic antibiotics (P = .21). Overall allograft survival rate was 92.1% in the urinary tract infection group and 96.7% in the group without urinary tract infection, which was significantly different (P = .02). Urinary tract infection significantly affected allograft survival (hazard ratio, 3.51; 95% CI, 1.49-8.23; P = .004). Overall patient survival rates were 86.7% and 91.4% in the groups with and without urinary tract infection, respectively (P = .08). We determined that allograft survival was significantly greater in the group without urinary tract infection versus the urinary tract infection group. We found no relation between urinary tract infection recurrence and prophylactic antibiotics. We also found that overall patient survival was not significantly different in the group with urinary tract infection versus the group without urinary tract infection.

Cytomegalovirus High-risk Kidney Transplant Recipients Show No Difference in Long-term Outcomes Following Preemptive Versus Prophylactic Management.

Following kidney transplantation (KT), cytomegalovirus (CMV) infection remains an important challenge. Both prophylactic and preemptive antiviral protocols are used for CMV high-risk kidney recipients (donor seropositive/recipient seronegative; D+/R-). We performed a nationwide comparison of the 2 strategies in de novo D+/R- KT recipients accessing long-term outcomes. A nationwide retrospective study was conducted from 2007 to 2018, with follow-up until February 1, 2022. All adult D+/R- and R+ KT recipients were included. During the first 4 y, D+/R- recipients were managed preemptively, changing to 6 mo of valganciclovir prophylaxis from 2011. To adjust for the 2 time eras, de novo intermediate-risk (R+) recipients, who received preemptive CMV therapy throughout the study period, served as longitudinal controls for possible confounders. A total of 2198 KT recipients (D+/R-, n = 428; R+, n = 1770) were included with a median follow-up of 9.4 (range, 3.1-15.1) y. As expected, a greater proportion experienced a CMV infection in the preemptive era compared with the prophylactic era and with a shorter time from KT to CMV infection ( P < 0.001). However, there were no differences in long-term outcomes such as patient death (47/146 [32%] versus 57/282 [20%]; P = 0.3), graft loss (64/146 [44%] versus 71/282 [25%]; P = 0.5), or death censored graft loss (26/146 [18%] versus 26/282 [9%]; P = 0.9) in the preemptive versus prophylactic era. Long-term outcomes in R+ recipients showed no signs of sequential era-related bias. There were no significant differences in relevant long-term outcomes between preemptive and prophylactic CMV-preventive strategies in D+/R- kidney transplant recipients.

Characterization of the stanford integrated psychosocial assessment for transplant for heart, liver, and kidney transplant candidates in Japan

BackgroundThe Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a comprehensive psychosocial assessment proven useful for predicting the outcomes of organ transplantation that is expected to be useful in Japan. However, the characteristics of organ-specific SIPAT scores for organ transplant recipient candidates in Japan are unclear and, to date, the SIPAT has not been properly utilized in clinical practice. The purpose of this study was to present basic data that can be used to establish the relation between SIPAT scores and post-transplantation psychosocial outcomes as well as organ-specific outcomes.MethodsThis study included 167 transplant recipient candidates (25 heart, 71 liver, and 71 kidney) who completed a semi-structured interview based on the Japanese version of SIPAT (SIPAT-J) prior to transplantation. The differences between organs in terms of SIPAT scores and differences in SIPAT scores based on demographic data were comparatively analyzed.ResultsThe total SIPAT scores were higher for liver recipient candidates than for heart recipient candidates (P = .019). Regarding the subscales, SIPAT B (social support system) scores were higher for liver and kidney recipient candidates than for heart recipient candidates (P = .021), whereas SIPAT C (psychological stability and psychopathology) scores were higher for liver recipient candidates than for kidney recipient candidates (P = .002). Recipient candidates with a history of psychiatric treatment and those who were unemployed had higher SIPAT scores, regardless of the transplant organ, than recipient candidates without a history of psychiatric treatment and those who were employed (P < .001, P = .016, respectively).ConclusionsThere were notable differences in the total SIPAT-J and subscale scores among the liver, heart, and kidney recipient candidates. Each organ was associated with specific psychosocial issues that should be addressed before transplantation. Interventions such as information provision and patient education based on SIPAT assessment results for each organ may improve recipient post-transplant outcomes.

Donor-derived Transmission of Hepatitis A Virus Following Kidney Transplantation: Clinical Course of Two Cases From One Donor.

In 2018, 2 kidneys and a liver were procured from a deceased donor resident of Kentucky, one of many states that was experiencing an HAV outbreak associated with person-to-person transmission through close contact, primarily among people who reported drug use. Both kidney recipients, residents of Virginia, subsequently developed acute HAV infections. We report the results of an investigation to determine the source of transmission and describe the clinical course of HAV infection in the infected kidney recipients. The liver recipient had evidence of immunity to HAV and did not become infected. The donor and both kidney recipients were found to have a genetically identical strain of HAV using a next-generation sequencing-based cyber molecular assay (Global Hepatitis Outbreak Surveillance Technology), confirming donor-derived HAV infections in kidney recipients. At least 1 kidney recipient experienced delayed development of detectable hepatitis A anti-IgM antibodies. By 383 and 198 d posttransplant, HAV RNA was no longer detectable in stool specimens from the left and right kidney recipients, respectively. Adherence to current guidance for hepatitis A vaccination may prevent future morbidity due to HAV among organ recipients. http://links.lww.com/TXD/A548.

The effect of the BK polyomavirus large T antigen on the function and maturity of the CD4+ T cell subsets in kidney transplant recipients

BackgroundIn kidney transplant recipients (KTRs) who are immunosuppressed, human BK polyomavirus (BKPyV) infection can be reactivated, resulting in BKPyV-associated nephropathy (BKPyVN). Considering that BKPyV inhibits CD4+ T cell differentiation, we investigated the effect of BKPyV large T antigen (LT-Ag) on the maturation of CD4+ T cell subsets during active BKPyV infection. MethodsIn this cross-sectional study, we examined the following groups: 1) five KTRs with active viral infection (BKPyV+ KTRs), 2) five KTRs without active viral infection (BKPyV−KTRs), and 3) five healthy controls. We measured the frequency of CD4+ T cells and their different subsets, such as naive T cells, central memory T cells (Tcm), and effector memory T cells (Tem). All these subsets were analyzed by flow cytometry in peripheral blood mononuclear cells (PBMCs) stimulated with the overlapping BKPyV LT-Ag peptide pool. In addition, CD4+ T cell subsets were analyzed by flow cytometry for the presence of CD4, CCR7, CD45RO, CD107a, and granzyme B (GB). In addition, mRNA expression of transcription factors (TFs) such as T-bet, GATA-3, STAT-3, and STAT-6 was examined. The probability of inflammation with perforin protein was examined by SYBR Green real-time PCR. ResultsAfter stimulation of PBMCs, naive T cells (CD4+CCR7+CD45RO−) (p = 0.9) and CD4+ T cells which release CD107a+ (CD4+CD107a+Geranzyme B−) (p = 0.9) T cells were more abundant in BKPyV+ KTRs than in BKPyV− KTRs. In contrast, central memory T cells (CD4+CCR7+CD45RO+) (p = 0.1) and effector memory T cells (CD4+CCR7−CD45RO+) (p = 0.1) were more abundant in BKPyV− KTRs than in BKPyV+ KTRs.The mRNA expression levels of T-bet, GATA-3, STAT-3, and STAT-6 were significantly higher (p < 0.05) in BKPyV− KTRs than in BKPyV+ KTRs which may be due to a higher differentiation level of CD4+ T cells. Due to inflammation, the mRNA expression level of perforin was higher in BKPyV+ KTRs, than in BKPyV− KTRs, but the difference was not significant (p = 0.175). ConclusionsThe high number of naive T cells after PBMC stimulation with the LT-Ag peptide pool was observed in BKPyV+ KTRs due to the interaction of LT-Ag with T cells. This means that BKPyV by using its LT-Ag can inhibit the naive T cell differentiation to other T cell subsets like central and effector memory T cells. However, the frequency of CD4+ T cell subsets and the combination of the activities of these cells with the expression profile of the target genes in this study may be efficient in treating and diagnosing BKPyV infections in kidney recipients.

Donor antigen-specific regulatory T cell administration to recipients of live donor kidneys: A ONE Study consortium pilot trial

Regulatory T cells (Tregs) can inhibit cellular immunity in diverse experimental models and have entered early phase clinical trials in autoimmunity and transplantation to assess safety and efficacy. As part of the ONE Study consortium, we conducted a phase I-II clinical trial in which purified donor antigen reactive (dar)-Tregs (CD4+CD25+CD127lo) were administered to 3 patients, 7 to 11 days after live donor renal transplant. Recipients received a modified immunosuppression regimen, without induction therapy, consisting of maintenance tacrolimus, mycophenolate mofetil, and steroids. Steroids were weaned off over 14 weeks. No rejection was seen on any protocol biopsy. Therefore, all patients discontinued mycophenolate mofetil 11 to 13 months posttransplant, per protocol. An early for-cause biopsy in 1 patient, 5 days after dar-Treg infusion, revealed absence of rejection and accumulation of Tregs in the kidney allograft. All patients had Treg-containing lymphoid aggregates evident on protocol biopsies performed 8 months posttransplant. The patients are now all >6 years posttransplant on tacrolimus monotherapy with excellent graft function. None experienced rejection episodes. No serious adverse events were attributable to Treg administration. These results support a favorable safety profile of dar-Tregs administered early after renal transplant, suggest early biopsy might be an instructive research endpoint and provide preliminary evidence of potential immunomodulatory activity.

Impact of CYP3A5 Genotype on De-novo LCP Tacrolimus Dosing in Kidney Transplantation

The CYP3A5 gene encodes an enzyme called cytochrome P450 3A5, which is involved in the metabolism of many drugs, including tacrolimus. Tacrolimus is an immunosuppressive medication commonly used in kidney transplantation to prevent organ rejection. The CYP3A5 genotype can influence the metabolism and clearance of tacrolimus, leading to variations in the drug levels and response. LCP tac (an extended-release form of tacrolimus) has a recommended starting dose of 0.14 mg/kg/day in kidney transplants. Rao et al assessed the influence of CYP3A5 genotypes on perioperative LCP tac dosing and monitoring in adult kidney recipients receiving de-novo LCP tac. CYP3A5 genotype was measured, and 90-day pharmacokinetic and clinical were assessed. Patients were classified as CYP3A5 expressors (*1 homozygous or heterozygous) or nonexpressors (LOF *3/*6/*7 allele). They concluded that CYP3A5*1 expressors require higher doses of LCP tac to achieve therapeutic concentrations and are at higher risk of subtherapeutic trough concentrations, persisting for 30-day posttransplant. LCP tac dose changes in CYP3A5 expressors are more likely to be under-adjusted by providers. Pharmacogenet Genomics. 2023 Apr 1;33(3):59-65. doi: 10.1097/FPC.0000000000000494.

Outcomes of Patients Undergoing Combined Heart–Kidney Transplantation With or Without Prior Ventricular Assist Device

Both combined heart-kidney transplantation and ventricular assist devices (VADs) pose significant challenges, including sensitization, immunosuppressive treatment, and infrastructure demands. Despite these challenges, we hypothesized that the recipients of combined heart-kidney transplants with and without VADs would have equivalent survival. We aimed to compare the survival of heart-kidney transplant recipients with and without prior VAD placement. We retrospectively analyzed all patients enrolled in the United Network for Organ Sharing database who underwent heart-kidney transplants. We created a matched cohort of patients undergoing heart-kidney transplantation with or without prior VAD using 1:1 nearest propensity-score matching with preoperative variables. In the propensity-matched cohort, 399 patients underwent heart-kidney transplantation with prior VAD, and 399 underwent heart-kidney transplantation without prior VAD. The estimated survival of heart--kidney recipients with prior VAD was 84.8% at one year, 81.2% at 3 years, and 75.3% at 5 years. The estimated survival of heart-kidney recipients without prior VAD was 86.8.7% at one year, 84.0% at 3 years, and 78.8% at 5 years. There was no statistically significant difference in the survival of heart-kidney transplant recipients with or without prior VAD at one year (P=.42; Figure 2), 3 years (P=.34), or 5 years (P=.30). Despite the increased challenge of heart-kidney transplantation in recipients with prior VAD, we demonstrated that these patients have similar survival to those who underwent heart-kidney transplantation without previous VAD placement.

Higher Expression of Activated CD8+ T Lymphocytes (CD8+CD25+, CD8+CD69+ and CD8+CD95+) Mediate Early Post-Transplant Acute Tubular Injury in Kidney Recipients.

Acute kidney injury (AKI) is a leading cause of early post-transplant kidney damage. Furthermore, acute tubular necrosis (ATN) is appointed as the most prevalent form of AKI, a frequent multifactorial process associated with high morbidity and mortality, yet giving rise to delayed graft function (DGF) and, ultimately, allograft dysfunction. Common factors such as prolonged cold ischemia time, advanced donor age, cadaveric versus living donor, donor history of hypertension, as well as donation after cardiac death have all been deemed risk factors for ATN. With the increasing number of older cadaveric and cardiac donors in the donation process, ATN could have a detrimental impact on patient welfare. Therefore understanding the underlying process would benefit the transplant outcome. We aimed to prospectively monitor several T cell subsets in a cohort of kidney transplant recipients (KTrs) to investigate whether there is an adaptive immune-mediated involvement in the ATN process. Peripheral blood was collected from 31 KTrs at different time points within the first-year post-transplantation for in vitro stimulation with Concanavalin-A (Con-A) in a humidified 5% CO2 incubator at 37 °C for 72 hours. Upon cell stimulation, flow cytometry was applied to quantify the surface expression through the median fluorescence intensity (MFI) of CD4+CD25+, CD8+CD25+, CD4+CD38+, CD8+CD38+, CD4+CD154+, CD8+CD154+, CD4+CD69+, CD8+CD69+, CD4+CD95+, and CD8+CD95+ T cells. Statistical analysis was carried out with SPSS Statistics IBM v.25 (IBM Corp, Armonk, NY, USA). MFIs values were compared using a univariate analysis by a nonparametric U-Mann Whitney test. ROC analysis was applied to define cut-off values most capable of stratifying patients at high risk of ATN. Spearman's rank-order coefficient test was applied to correlate biomarkers with allograft function. Multivariate regression independently validated CD8+ T lymphocytes as surrogate biomarkers of ATN. A p-value < 0.05 was considered statistically significant. KTrs who developed ATN upon transplantation had significantly higher expression of CD25, CD69, and CD95 on CD8+ and lower expression of CD95 on CD4+ T lymphocytes than patients with stable graft function. ROC curve analysis showed that MFIs ≥1015.20 for CD8+CD25+, ≥2489.05 for CD8+CD69+, ≥4257.28 for CD8+CD95+, and ≤1581.98 for CD4+CD95+ were capable of stratifying KTrs at high risk of ATN. Furthermore, patients with an MFI below any cut-off were significantly less likely to develop ATN than those with other values. The allograft function was correlated with the CD4+CD95+/CD8+CD95+ ratio in KTrs who developed ATN. The multivariate analysis confirmed that, within the first-month post-transplant, MFI values of CD8+CD25+, CD4+CD95+, and CD8+CD95+ T lymphocytes, along with donor age, serum creatinine, and GFR were independent risk factors to ATN. Moreover, we were also able to corroborate previous immune factors of importance in immune-mediated response to the allograft, such as the patient's maximum panel reactive antibody (PRA) or the maintenance immunosuppression therapy. Our results demonstrate evidence for the implication of CD8+ T lymphocytes in the development of ATN early in the post-transplant phase. Post-transplant monitoring of activated CD8+ T lymphocytes may help identify which patients require further clinical intervention to prevent graft damage.

Diagnostic policies on nephrolithiasis/nephrocalcinosis of possible genetic origin by Italian nephrologists: a survey by the Italian Society of Nephrology with an emphasis on primary hyperoxaluria

BackgroundPrimary hyperoxaluria is a genetic disorder of the metabolism of glyoxylate, the precursor of oxalate. It is characterized by high endogenous production and excessive urinary excretion of oxalate, resulting in the development of calcium oxalate nephrolithiasis, nephrocalcinosis, and, in severe cases, end-stage kidney disease and systemic oxalosis. Three different forms of primary hyperoxaluria are currently known, each characterized by a specific enzymatic defect: type 1 (PH1), type 2 (PH2), and type 3 (PH3). According to currently available epidemiological data, PH1 is by far the most common form (about 80% of cases), and is caused by a deficiency of the hepatic enzyme alanine:glyoxylate aminotransferase.MethodsA survey on rare forms of nephrolithiasis and nephrocalcinosis with a focus on primary hyperoxaluria in the setting of Italian Nephrology and Dialysis Centers, using an online questionnaire, was recently conducted by the Project Group “Rare Forms of Nephrolithiasis and Nephrocalcinosis” of the Italian Society of Nephrology, with the aim of assessing the impact and management of this disorder in clinical practice in Italy.ResultsForty-five public and private Italian Centers participated in the survey, and responses to the questionnaire were provided by 54 medical professionals. The survey results indicate that 21 out of the 45 participating Centers are managing or have managed primary hyperoxaluria patients, most of whom are on dialysis, or are recipients of kidney transplants.ConclusionsThe data of this survey indicate the need to implement genetic testing in suspected cases of primary hyperoxaluria, not only in the setting of dialysis or transplantation, but also with the aim of encouraging early diagnosis of PH1, which is the only type of primary hyperoxaluria for which specific drug therapy is currently available.Graphical abstract

Microchimerism as Post-Transplant Marker of a Chronic Rejection Process

The risk of losing a transplanted organ is high, and non-invasive markers to warn of this phenomenon are still being sought. We investigated the impact of post-transplant microchimerism on the function of the transplanted kidney. The study included 100 kidney transplant recipients, mostly women. All transplanted organs were from opposite-sex deceased donors. Microchimerism was assessed using multiplex PCR. Male DNA was detected in all urine samples from female recipients and in 13/56 blood samples from female kidney recipients. Female DNA was found in 31/44 urine samples from male recipients, but in none of the blood samples. Microchimerism in the urine of female recipients correlated positively with blood urea (Rs = 0.45; p = 5.84 × 10−4) and K+ ions (Rs = 0.29; p = 0.03), while microchimerism in the blood of female recipients also correlated positively with blood urea (Rs = 0. 28; p = 0.04), cystatin C (Rs = 0.31; p = 0.02) and the number of incompatible HLA alleles (Rs = 0.42; p = 0.01). A history of DGF was associated with higher urinary donor DNA concentrations in female recipients.: Post-transplant microchimerism may serve as a potential marker of chronic kidney rejection.

Simultaneous Lung-Kidney Transplantation in the United States

BackgroundSimultaneous lung-kidney transplantation is rarely performed. Contemporary national practice trends and outcomes are unclear. MethodsFrom the United Network for Organ Sharing database, we identified 108 lung-kidney transplant recipients (2005-2022). They were compared with isolated lung recipients with pretransplantation dialysis or estimated glomerular filtration rate (eGFR) ≤30 mL/min per 1.73 m2 (n = 372) and isolated non–dialysis-dependent lung recipients with 30 < eGFR < 50 mL/min per 1.73 m2 (n = 1416), respectively. Lung-kidney recipients were also compared with recipients of the contralateral kidney from the same donors (n = 90). ResultsLung-kidney transplantation was performed by 36 centers, with increasing annual volume (1 in 2005, 16 in 2022; P < .01). Forty percent (44/108) of lung-kidney recipients received pretransplantation dialysis, and of those without pretransplantation dialysis, median eGFR was 30.7 mL/min per 1.73 m2. Lung-kidney recipients had improved survival compared with isolated lung recipients with eGFR ≤30 mL/min per 1.73 m2 or pretransplantation dialysis (adjusted hazard ratio, 0.59; 95% CI, 0.38-0.92). However, no survival benefit was observed when lung-kidney recipients were compared with isolated lung recipients with 30 < eGFR < 50 mL/min per 1.73 m2 and no pretransplantation dialysis (adjusted hazard ratio, 0.88; 95% CI, 0.55-1.41). Compared with isolated kidney recipients using the contralateral kidney from the same donors, lung-kidney recipients had a higher risk of kidney allograft loss (adjusted hazard ratio, 3.27; 95% CI, 1.22-8.78), a difference largely accounted for by patient death with a functioning kidney allograft. ConclusionsRecipients of lung-kidney transplants had improved survival compared with isolated lung recipients with eGFR ≤30 mL/min per 1.73 m2 or pretransplantation dialysis. However, lung-kidney recipients had a higher rate of kidney allograft loss than recipients of the contralateral kidney allograft from the same donors.

Helical TomoTherapy Total Lymphoid Irradiation and Hematopoietic Cell Transplantation for Kidney Transplant Tolerance in Rhesus Macaques.

Development of a post-transplant kidney transplant tolerance induction protocol involving a novel total lymphoid irradiation (TLI) conditioning method in a rhesus macaque model is described. We examined the feasibility of acheiving tolerance to MHC 1-haplotype matched kidney transplants by establishing a mixed chimeric state with infusion of donor hematopoietic cells (HC) using TomoTherapy TLI. The chimeric state was hypothesized to permit the elimination of all immunosuppressive (IS) medications while preserving allograft function long-term without development of graft-versus-host-disease (GVHD) or rejection. An experimental group of 11 renal transplant recipients received the tolerance induction protocol and outcomes were compared to a control group (n = 7) that received the same conditioning but without donor HC infusion. Development of mixed chimerism and operational tolerance was accomplished in two recipients in the experimental group. Both recipients were withdrawn from all IS and continued to maintain normal renal allograft function for 4 years without rejection or GVHD. None of the animals in the control group achieved tolerance when IS was eliminated. This novel experimental model demonstrated the feasibility for inducing of long-term operational tolerance when mixed chimerism is achieved using a TLI post-transplant conditioning protocol in 1-haplotype matched non-human primate recipients of combined kidney and HC transplantation.

The in-vitro influence of urea concentration on thromboelastrography in patients with and without end stage renal disease

BackgroundEnd stage renal disease (ESRD) is associated with platelet dysfunction but also thromboembolic complications. The specific role of increased blood urea nitrogen (BUN) on coagulation is unclear. We aimed to characterize thromboelastography (TEG) parameters from males and females with ESRD and normal kidney function and evaluate if exogenous urea in vitro reproduced those TEG differences. MethodsWe collected blood samples from 20 living kidney donors and 20 kidney recipients. TEG was performed without and with two increasing urea concentrations in vitro. TEG parameters were compared between recipients and donors. ResultsBlood from kidney recipients showed baseline increased maximum amplitude (MA) and shortened time to maximum amplitude (TMA) compared to donors. These differences were not confirmed in females. In all patients, BUN was inversely correlated with TMA (r = −0.342; p = 0.031). In males, BUN and creatinine concentrations showed a direct correlation with MA (0.583; p = 0.007) and an inverse correlation with TMA (r = −0.520; p = 0.019). Urea in vitro decreased R-time (p = 0.005) and increased LY30 (p = 0.009) in donors but not recipients. ConclusionsESRD is associated with increased MA and decreased TMA on TEG. No change in MA was observed with increasing urea concentrations in vitro. Gender-specific variability in TEG parameters were observed.

Results of studying the diabetic retinopathy course in potential kidney and pancreatic recipients while on hemodialysis

Introduction. Kidney and pancreas transplantation is a surgical method for the treatment of patients with diabetes mellitus and terminal diabetic nephropathy. While waiting for surgical treatment, potential recipients receive maintenance hemodialysis. Dialysis initiates the loss of body fluid, which in turn can affect the state of the intraocular structures. Aim. To study the effect of long-term hemodialysis therapy on ophthalmic parameters in patients with terminal diabetic nephropathy. Material and methods. Sixty patients (120 eyes) were examined: group A included 30 patients with end-stage renal failure as a result of diabetic nephropathy, group B included 30 people without systemic and ocular pathologies. The ophthalmological status of group A was assessed at the stage of planned preparation for renal replacement therapy, at 3 and 6 months after the initiation of dialysis. Ophthalmological examination consisted of the use of traditional and special diagnostic methods (microperimetry, photorecording of the fundus, optical coherence tomography angiography). Results. Within 6 months of hemodialysis courses, the following was recorded: a decrease in the thickness of the retina (Me: from 348.5 to 306.1 µm; p &lt;0.05) and choroid (Me: from 330.3 to 294.9 µm; p &lt;0.05), the improvement of retinal perfusion in eyes with diabetic macular edema (Me in the superficial capillary plexus: from 10.6 to 15.8% in the fovea, from 19.7 to 25.4% in the parafovea; in the deep capillary plexus: from 15.4 to 20.9% in the fovea, from 27.5 to 33.5% in the parafovea; p &lt;0.05), a decrease in choroidal hemoperfusion (Me in the layer of choriocapillaries: from 59.0 to 54.2% in the fovea, from 59.3 to 54.7% in the parafovea; in the deep layer of the choroids: from 55.5 to 50.7% in the fovea, from 55.3 to 50.7% in the parafovea; p&lt;0.05),an improvement in retinal photosensitivity (Me: from 16.7 to 20.3 dB in eyes with diabetic macular edema; from 21.1 to 24.2 dB in eyes without diabetic macular edema; p&lt;0.05) and increased visual acuity in eyes with macular edema (Me: 0.1 to 0.3; p&lt;0.05). Conclusions. Against the background of maintenance hemodialysis hemodialysis in patients with terminal diabetic nephropathy, along with a decrease in hyperazotemia, there is an improvement in architectonics, hemodynamics of the retina and visual functions.

1398-P: Contribution of New-Onset Diabetes after Organ Transplantation on the Incident Cardiovascular Disease and Malignancy in Korea—A Nationwide Population-Based Study

Background: In Korea, the number of solid organ transplantation (TPL) has been markedly increased; however, there has been limited data on the adverse effect on the cardiovascular disease and malignancy of new onset diabetes after transplantation (NODAT) in solid organ TPL other than kidney. Methods: Using the National Health Insurance Service (NHIS) database which covers the claims of 97.0% of the population in Korea, the recipients of kidney, liver, and heart TPL in 2009-2015 were identified and categorized into 3 groups: without NODAT (reference), with NODAT, and pre-existing diabetes mellitus (DM). The incidence of myocardial infarction (MI), stroke, and malignancy till December 2018 in each group were compared using Cox-regression analysis. Results: Among the entire 18,763 cases of TPL identified, NODAT was detected in 29.8% (27.2% [2,903 out of 10,687], 43.4% [3,247 out of 7,747], and 41.5% [250 out of 602] in kidney, liver, and heart TPL, respectively); and 77.3% of NODAT cases were detected within 3 months after TPL. NODAT increased the risk of MI, but not of stoke, by 2.3 times compared to the reference group after adjustment for age, sex, hypertension, dyslipidemia, and immunosuppressants (hazard ratio [HR], 2.34; 95% CI, 1.61-3.51), which was observed only in kidney TPL (HR, 2.44; 95% CI, 1.52-3.91) but not in liver TPL. A significant increment of the risk of malignancy by NODAT was found only in kidney TPL (HR, 1.30; 95% CI, 1.04-1.64), whose statistical significance was lost after adjusting confounders. During the same period, no association between pre-existing DM and malignancy was found, neither. Conclusion: NODAT independently increased the risk of MI after organ transplantation, which was more evident in the recipient of kidney TPL. There was no additional increased risk of stroke or malignancy by NODAT in solid-organ TPL. Disclosure B.Koo: None. M.Moon: None. S.Park: None. K.Han: None.

Kidney Transplantation in Nigeria: A Single Centre’s Early Surgical Experience and Outcomes

With the rise in the population of patients with End-stage Renal Disease (ESRD) in Nigeria, there is an increased demand for Renal Replacement Therapy (RRT) including kidney transplantation (KT). We present our initial surgical experience and early outcomes with KT at a Nigerian transplant center over 2 years. A 2-year retrospective review of patients who underwent KT was done. Data of both kidney donors and recipients were recorded in designed proformas. Extracted information included demographic characteristics, side of open donor nephrectomy (ODN), recipient anatomy, surgical techniques and postoperative outcomes. Data were analyzed using SPSS version 21. A total of 210 patients had KT during the period under review&lt;em&gt;. &lt;/em&gt;Donors had an age range of 19 to 53 years with a mean of 30.8 3 ± 8.43 years while recipients aged between 9 and 73 years with a mean of 45.97 ± 13.71 years. There were 190 (90.5%) male and 20 (9.5%) female donors. One hundred fifty-four recipients were males (73.3%) and 56 (26.7%) were females. Left ODN was performed in 152 (72.4%) of cases and the commonest indication for right ODN was multiple left renal arteries. The allograft was placed in the right iliac fossa in 187 (89.0%) recipients with the external iliac artery preferred for anastomosis with the allograft renal artery in end-to-side fashion in 182 (86.7%) cases. The internal iliac artery was used in end-to-end fashion anastomosis in 28 (13.3%) of cases. Ureteroneocystostomy using the Modified Lich-Gregoir technique over a double-J stent was performed in all but 5 patients who had uretero-ureterostomies. Significant peri-operative hemorrhage necessitating blood transfusion was experienced in 9 donors and 26 recipients. There was a low complication rate in kidney donors. Allograft renal artery thrombosis, venous thrombosis, and arterial pseudo-aneurysms were encountered in 3, 2 and 4 recipients respectively. Kidney transplantation can be safely and routinely carried out in Nigeria. The early surgical outlook of both kidney donors and recipients was found to be excellent in this study.