Living Donor Renal Transplant Recipients Research Articles

High Atherogenic Index of Plasma Associated With Delayed Graft Function in Living Donor Renal Transplant Recipients: A Single-Center Study in Vietnam.

To determine the predictive value of the atherogenic index of plasma before transplant for delayed graft function. A cross-sectional, longitudinal, non-interventional, non-controlled study of 167 patients undergoing kidney transplantation from living donors, with a mean age of 39.34 ± 11.86 years old, 53.3% male, and a pre-transplant hemodialysis time of 14 (7-36) months. Delayed graft function was defined as decreased blood creatinine < 25% within the first 24 h compared to pre-transplantation, and the patients needed hemodialysis in the first 7 days. The atherogenic index of plasma was calculated based on pre-transplant plasma triglycerides and high-density lipoprotein cholesterol concentrations. The ratio of delayed graft function in renal transplant recipients from living donors was 13.8% (23/167 patients). Hemodialysis time, the ratio of hepatitis infection, overweight and obese, atherosclerosis, positive PRA, and acute rejection in the DGF (+) group were higher than those of the DGF (-) group, p < 0.05 and < 0.001. In particular, plasma CRP-hs level and AIP also were higher in DGF (+) patients compared to those of DGF (-) ones, p < 0.001. Long hemodialysis time, obesity, high plasma CRP-hs, and high AIP in pre-transplant patients were independent factors related to DGF and had predictive value for DGF after kidney transplantation, in which AIP had good predictive value: AUC = 0.859, p < 0.001. Delayed graft function was relatively common in renal transplant recipients from living donors. AIP before kidney transplant was a good predictor for delayed graft function.

P.199: A cross sectional study of the medium term outcomes in living donor renal transplant recipients developing ATN in the immediate post transplant period.

P.199: A cross sectional study of the medium term outcomes in living donor renal transplant recipients developing ATN in the immediate post transplant period.

Immunosuppression withdrawal in living-donor renal transplant recipients following induction with antithymocyte globulin and rituximab: Results of a prospective clinical trial

Durable tolerance in kidney transplant recipients remains an important but elusive goal. We hypothesized that adding B cell depletion to T cell depletion would generate an immune milieu postreconstitution dominated by immature transitional B cells, favoring tolerance. The Immune Tolerance Network ITN039ST Research Study of ATG and Rituximab in Renal Transplantation was a prospective multicenter pilot study of live donor kidney transplant recipients who received induction with rabbit antithymocyte globulin and rituximab and initiated immunosuppression (IS) withdrawal (ISW) at 26 weeks. The primary endpoint was freedom from rejection at 52 weeks post-ISW. Six of the 10 subjects successfully completed ISW. Of these 6 subjects, 4 restarted immunosuppressive medications due to acute rejection or recurrent disease, 1 remains IS-free for over 9 years, and 1 was lost to follow-up after being IS-free for 42 weeks. There were no cases of patient or graft loss. CD19+ B cell frequencies returned to predepletion levels by 26 weeks posttransplant; immunoglobulin D+CD27--naïve B cells predominated. In contrast, memory cells dominated the repopulation of the T cell compartment. A regimen of combined B and T cell depletion did not generate the tolerogenic B cell profile observed in preclinical studies and did not lead to durable tolerance in the majority of kidney transplant recipients.

Incidence of postoperative cytomegalovirus and BK-polyoma virus infections and graft loss in ABO-incompatible renal transplant recipients: a multicenter retrospective study.

The current study aimed to examine the incidence of perioperative infections and graft viability in ABO-compatible and ABO-incompatible renal transplant recipients. We included 643 living donor renal transplant recipients registered in the Michinoku Renal Transplant Network from 1998 to 2021. Patients were divided into the ABO-compatible and ABO-incompatible kidney transplantation groups. We compared the characteristics of the two groups and evaluated the incidence of postoperative viral infections (cytomegalovirus and BK virus), graft loss-free survival, and overall survival between the two groups. Of 643 patients, 485 (75%) and 158 (25%) were ABO-compatible and ABO-incompatible renal transplant recipients, respectively. Postoperative viral infections, rituximab use, and plasma exchange were significantly more common in ABO-incompatible than in ABO-compatible transplant recipients. However, there were no significant differences in terms of other background characteristics. The ABO-incompatible group was more likely to develop viral infections than the ABO-compatible group. Graft loss-free survival and overall survival did not significantly differ between the two groups. According to the multivariate Cox regression analysis, ABO compatibility was not significantly associated with graft loss-free survival and overall survival. Although the incidence of postoperative viral infections in ABO-incompatible renal transplant recipients increased, there was no significant difference in terms of rejection events, graft loss-free survival, and overall survival.

Risk Factors and Outcome of Gram-Negative Bloodstream Infection in Living-Donor Renal Transplant Recipients: A Case-Control Study From Pakistan.

Gram-negative rods are the most common cause of bloodstream infection in renal transplant recipients. Acute rejection, urologic abnormalities, and ureteral stents are risk factors. Graft dysfunction is independently associated with gram-negative rod bloodstream infection. Our aim is to investigate the incidence, risk factors, and outcome among living donor renal transplant recipients from Pakistan. In this case-control study, we reviewed the medical records until June 2021 of renal transplant recipients seen from 2015 to 2019 for gram negative bacteremia. For every case, controls were matched by age, date of transplant, and sex. Demographics, risk factors, graft function, and mortality were compared. Clinical features, immunosuppression, source of blood stream infection, and microbiology were noted in cases. Of 1677 renal transplant recipients, 44 developed gram negative bacteremia. The incidence was 5.9 per 1000 person-years. Median time since transplant was 5 months. The most common source was urinary tract infection. On univariate analysis, antithymocyte globulin, urinary tract infection, and recurrent urinary tract infections were associated with gram negative bacteremia. On multivariate analysis, urinary tract infection (adjusted odds ratio = 3.46; 95% CI, 1.27-9.37) and recurrent urinary tract infections (adjusted odds ratio = 4.03; 95% CI, 1.15-14.15) were significant risk factors. We found no difference in 30-day mortality and estimated glomerular filtration rate on last follow-up between cases and controls. Kaplan-Meier survival curves showed significant differences in graft survival in patients with gram negative bacteremia. Escherichia coli was the most common organism, with 75% ceftriaxone and 13% imipenem resistance. The most significant risk factor for gram negative rod bloodstream infection was recurrent urinary tract infections. Timely treatment and prevention of recurrent urinary tract infections areimperative for prevention of gram negative bacteremia.

Hypoglycemia with insulin in post-transplant diabetes mellitus

IntroductionTo prevent hypoglycemic episodes, the management of insulin therapy against post-transplant diabetes mellitus (PTDM) is important. We compared glargine (long-acting insulin) versus NPH isophane (intermediate-acting insulin) as an armamentarium against PTDM. Indeed, the study evaluated PTDM patients with hypoglycemic episodes treated with isophane or glargine. Material and methodsWe evaluated a total number of 231 living-donor renal transplant recipients with PTDM of age ≥ 18 years admitted to the hospital between January 2017 and September 2021. However, patients taking hypoglycemic agents before transplantation were excluded from this study. Out of 231 patients, 52 (22.15%) suffered from PTDM out of whom 26 were treated with glargine or isophane. ResultsAfter applying exclusion criteria, out of 52 PTDM patients 23 were included in the study: 13 PTDM patients were treated with glargine, whereas 10 PTDM patients with isophane. Our analysis revealed 12 episodes of hypoglycemia in glargine-treated PTDM patients compared to 3 in isophane-treated PTDM patients (p = 0.056). Clinically, 9 out of 15 hypoglycemic episodes were nocturnal (60%). Furthermore, no other risk factors were observed in our study population. Detailed analysis showed that both groups had equivalent doses of immunosuppressants and oral hypoglycemic agents. The odds ratio for hypoglycemia in the group treated with isophane compared to that treated with glargine was 0.224 (95% CI, 0.032–1.559). Glargine users recorded significantly lower blood sugar levels before lunch, dinner and at bedtime with p-values of 0.001, 0.009 and 0.001 respectively. A better hemoglobin A1c (HbA1c) level was seen in the glargine vs. isophane group (6.98 ± 0.52 vs. 7.45 ± 0.49, p-value 0.03). ConclusionThe study shows better blood sugar control with long-acting insulin analog, glargine, than with intermediate-actin analog, isophane. Overall, a higher number of hypoglycemic episodes was nocturnal. Long term safety of long-acting insulin analogs needs to be further studied.

Recurrent Urinary Tract Infection in Living Donor Renal Transplant Recipients and the Role of Behavioral Education Program in Management: A Single-Center Experience

Urinary tract infections (UTIs) are the most prevalent type of kidney transplant (KT) recipients. We aimed to investigate the incidence, causes, and clinical impact of early recurrent UTI post-living donor KT and to examine the role of behavioral education program in management. This retrospective cohort chart-review study included all KT recipients with recurrent UTI necessitating hospital admission between September 2017 and August 2021. All patients with recurrent UTI were subjected to behavioral education for a month. UTI was found in 14 of 145 patients (9.6%), with recurrent UTI in 11 (7.6%). A total of 93% of UTIs occurred during the first 6 months post-transplant and represented 52% of KT readmissions during the same period. A total of 64.3% of patients were older than 50 years. The mean (SD) length of hospital stay was 5 (2.5) days, with an equal incidence in both sexes. The most common bacterial isolates in early recurrent UTI were Escherichia coli in 80.9%. Both Extended-spectrum beta-lactamases and multidrug-resistant organisms (resistance in ≥3 drugs) were seen in 82.4% of isolates. Furthermore, the most effective antibiotic was meropenem, with 86.7% effectiveness. A total of 65% of UTIs were managed with a single antibacterial course. A total of 64.3% of patients were older than 50 years. In patients who developed UTI, the mean (SD) serum creatinine was 1.31 (0.52) mg/dL, with a mean increase in serum creatinine of 0.19 mg/dL on having the episodes; at 1 year post-transplant, serum creatinine declined to 1.23 (0.43) mg/dL. Four patients (36%) had no recurrence of UTI after behavioral education. The multidrug-resistant bacterial isolates account for 82.4% of the UTIs. Therefore, antibiotic prescription should follow the antimicrobial stewardship guidelines. Behavioral education significantly reduced the incidence of recurrent UTI.

215.8: Long-term Follow-up of a Phase 2 Clinical Trial to Induce Tolerance in Living Donor Renal Transplant Recipients

215.8: Long-term Follow-up of a Phase 2 Clinical Trial to Induce Tolerance in Living Donor Renal Transplant Recipients

P8.012: The Impact of a Positive B-Cell Flow Crossmatch in Living Donor Renal Transplant Recipients

Background: The aim of this study is to determine the incidence of early acute rejection and graft outcomes in living donor renal transplants with an isolated positive B-Cell Flow-Cytometry Crossmatch (B-FCXM). Methods: We performed a retrospective analysis of graft outcomes in 152 adults who received living donor renal transplants between January 2019 and March 2021 at Mount Sinai Hospital in New York CIty. Pre-transplant histocompatibility was assessed with flow cytometric crossmatch (FCXM) and Luminex single-antigen beads. Positive B- FCXM is was defined as median channel shift of ≥ 40. A mean fluorescence intensity (MFI) ≥ 1400 defined positive donor-specific HLA Class I and/or II antibody (DSA). Most patients received induction immunosuppression consisting of rabbit anti-thymocyte globulin, steroids and intravenous immunoglobulin. Estimated glomerular filtration rate (eGFR) and biopsy-proven rejection at six months’ post-transplant were compared between patients with and without a positive B-FCXM, and positive and negative DSA. Results: Of 152 patients, 89 (59%) were males and 63 (41%) females; the mean age was 44 years (SD ± 13.8). 45 donor B-FCXMs (30%) were positive and 107 (70%) were negative. 42 (28%) positive donor B-FCXM had no DSA and 3 (2%) had DSA. 91 (85%) negative donor B-FCXMs did not have DSA, and 16 (15%) had DSA. Thirty-six (80%) out of 45 patients with positive donor B-FCXM, including the 3 patients with DSA, received intravenous-immunoglobulin (IVIG) as part of induction immunosuppression. None of the patients with both positive donor B-FCXM and DSA had rejection. eGFR and rejection rate at 6 months were similar between patients with positive and negative donor B-FCXM [median 58.9 (IQR= 50.2-70.8) vs 57.6 (48.8-76.6), p=0.88; 6.8% vs 5.6%, p=0.7, respectively]. Comparison by combination of donor B-FCXM and DSA status (B-FCXM- DSA-, B-FCXM- DSA+, B-FCXM+ DSA-, B-FCXM+ DSA+) did not show statistically significant differences in eGFR or rejection rate at 6 months [median 57.4 (IQR= 48.5-74.3) vs 59.3 (52.6-83.3) vs 58.2 (50.1-70.8) vs 76.6 (58.3-102.5) p=0.4; 3.3% vs 18.7% vs 7.3% vs 0% p=0.09, respectively]. Conclusion: In our cohort, there was no statistical difference in early acute rejection and graft function at 6 months between living donor transplant recipients with positive and negative donor B-FCXM even after accounting for DSA status. Peri-transplant treatment with IVIG for a positive donor B-FCXM might be a helpful adjunct in this setting.

Study Design: Human Leukocyte Antigen Class I Molecule A∗02-Chimeric Antigen Receptor Regulatory T Cells in Renal Transplantation

IntroductionCell therapy with regulatory T cells (Tregs) in solid organ transplantation is a promising approach for the prevention of graft rejection and induction of immunologic tolerance. Previous clinical studies have demonstrated the safety of Tregs in renal transplant recipients. Antigen-specific Tregs, such as chimeric antigen receptor (CAR)-Tregs, are expected to be more efficacious than polyclonal Tregs in homing to the target antigen. We have developed an autologous cell therapy (TX200-TR101) where a human leukocyte antigen (HLA) class I molecule A∗02 (HLA-A∗02)-CAR is introduced into autologous naive Tregs from a patient with HLA-A∗02-negative end-stage renal disease (ESRD) awaiting an HLA-A∗02-positive donor kidney.MethodsThis article describes the design of the STEADFAST study, a first-in-human, phase I/IIa, multicenter, open-label, single-ascending dose, dose-ranging study to assess TX200-TR101 in living-donor renal transplant recipients. Up to 15 transplant recipients will receive TX200-TR101 and will be followed up for a total of 84 weeks post-transplant, alongside a control cohort of up to 6 transplant recipients. All transplant recipients will receive a standard of care immunosuppressive regimen, with the intent of intensified tapering of the regimen in the TX200-TR101 cohort.ResultsThe primary end point is the incidence and severity of treatment-emergent adverse events (AEs) within 28 days post–TX200-TR101 infusion. Other end points include additional safety parameters, clinical and renal outcome parameters, and the evaluation of biomarkers.ConclusionThe STEADFAST study represents the next frontier in adoptive cell therapies. TX200-TR101 holds great potential to prevent immune-mediated graft rejection and induce immunologic tolerance after HLA-A∗02-mismatched renal transplantation.

Clinical characteristics of renal transplant recipients who developed de novo donor-specific antigen in Kyoto University Hospital: a case series

BackgroundThe clinical significance of de novo donor-specific antigen (DSA) in renal transplant recipients is not yet fully understood. This study aimed to report the prevalence of de novo DSA detected in antihuman leukocyte antigen (HLA) antibody testing and to evaluate the association between de novo DSA and renal transplant prognosis in living-donor renal transplant recipients at our hospital.MethodsOf the 110 patients who underwent living-donor renal transplantation from 1980 to 2019, 80 patients who underwent anti-HLA antibody screening tests were retrospectively reviewed for the development of de novo DSA and outcomes regarding graft function.ResultsThe mean age at transplantation was 43.2 ± 14.6 years. Of the 80 patients, 43 (53.8%) were men and 68 (85.0%) underwent ABO-compatible transplantation. Anti-HLA antibody was detected in 14 patients (17.5%), including eight (10.0%) with de novo DSA. Graft loss occurred in two (25%) of the eight patients with de novo DSA, none of the six patients with non-DSA anti-HLA antibody and no anti-HLA antibody (P = 0.0419, log-rank test). The mean estimated glomerular filtration rate at the time of the anti-HLA antibody test was 45.1 ± 14.4 mL/min/1.73m2 in the 66 patients with no anti-HLA antibody, while it was 35.0 ± 11.5 mL/min/1.73m2 in the eight patients with de novo DSA (P = 0.0702) and 39.3 ± 15.3 mL/min/1.73m2 in the six patients with non-DSA anti-HLA antibody (P = 0.3921). The mean monthly cyclosporin A trough concentration for the past year from the anti-HLA antibody test was 59.2 ± 24.8 ng/ml in the seven patients with no anti-HLA antibody, while it was 61.9 ± 12.5 ng/ml in the five patients with de novo DSA (P = 0.5670) and 36.3 ± 9.0 ng/ml in a patient with non-DSA anti-HLA antibody (P = 0.3921). The mean monthly tacrolimus trough concentration for the past year from the anti-HLA antibody test was 4.62 ± 1.20 ng/ml in the 55 patients with no anti-HLA antibody, while it was 4.09 ± 1.10 ng/ml in the three patients with de novo DSA (P = 0.0027) and 4.21 ± 1.14 ng/ml in the four patients with non-DSA anti-HLA antibody (P = 0.0722).ConclusionsThe optimal treatment for patients with de novo DSA has not been established, and immunosuppressive management that suppresses the development of de novo DSA is essential.

Health-Related Quality of Life Score and Outcomes in Living Donor Renal Transplant Recipients With COVID-19.

Renal transplant recipients with severe COVID-19 may have sequelae that can affect their quality of life and can have poor patient and graft outcomes. We conducted a prospective, observational study between April 1, 2020, and December 31, 2020, to assess patient and graft outcomes and quality of life using the EQ-5D quality of life survey score at baseline and at follow-up of at least 12 weeks. Of the 3100 renal transplant recipients with follow-up, 104 patients had COVID-19. Of these patients, 75 (72.1%) had mild-moderate disease and 29 (27.9%) had severe disease. In addition, 78 patients (75.0%) were hospitalized, with 43 patients (41.3%) in the intensive care unit. Remdesivir was used in 46 of the 78 hospitalized patients (58.9%) without any mortality benefitin the severe group. Sixteen patients (17.5%) were rehospitalized with opportunistic infection (n = 7), persistent graft dysfunction (n = 6), pulmonary sequelae (n = 2), and angina (n = 1). Thirteen patients (12.5%) died. On follow-up, the overall EQ-5D score was significantly lower, particularly the pain and anxiety/depression scores in patients with mild-moderate disease, whereas all components of the EQ-5D score were significantly affected in patients with severe COVID-19. Renal transplant recipients with severe COVID-19 are at high risk of mortality, acute graft dysfunction, and residual disability, severely affecting their quality of life score and requiring rehabilitation.

Two Decades Outcomes of Posttransplant Immunoglobulin A Nephropathy in Live Donor Renal Transplantation.

Background:The data on long-term outcomes of posttransplant immunoglobulin A nephropathy (IgAN) are confounding and vary with geography and ethnicity worldwide. We aimed to study the long-term graft outcomes of patients with posttransplant IgAN in the northern Indian cohort.Methods:The long-term graft outcomes of 51 live donor renal transplant recipients with biopsy-proven posttransplant IgAN (recurrence/de novo) were analyzed. The risk factors for graft failure in the posttransplant IgA groups were analyzed using the Cox regression analysis.Results:Out of the total of 51 patients who had posttransplant IgAN, 40 patients had a biopsy-proven native kidney IgAN. The mean duration of the clinical presentation of posttransplant IgAN was 62.4 months (5.2 years) posttransplant. Proteinuria at the time of biopsy was 3.03 ± 2.2 g/day, and 41.2% had proteinuria of more than 3 g/day at the time of biopsy. The estimated 1, 5, 10, and 20 years patient survival was 98%, 95.4%, 75.9%, and 25.2%, respectively, and the estimated 1, 5, 10, and 20 years graft survival was 98%, 88.5%, 44.6%, and 11.9%, respectively, in patients who had posttransplant IgA. Many of the traditional risk factors associated with progression in native kidney IgAN, such as the degree of proteinuria, Oxford MEST (mesangial and endocapillary hypercellularity, segmental sclerosis, and interstitial fibrosis/tubular atrophy) scoring, recipient's age, and sex were not predictive of early graft failure among patients with posttransplant IgAN. In our cohort, the only significant graft failure predictor was serum creatinine at 5 years. Chronic antibody-mediated rejection (ABMR) was seen in 21.6% of patients with posttransplant IgAN. Whether this coexistence of chronic ABMR is an incidental finding or posttransplant IgAN predisposes to chronic ABMR requires further investigation.Conclusion:Posttransplant IgAN is associated with poor long-term graft outcomes in live donor renal transplants. Proteinuria and MEST scoring were not predictive of graft failure in living donor posttransplant IgAN.

Comparison of Outcomes of Live and Deceased Donor Renal Transplantation-A Retrospective Study from a single center in South India

Background: Renal transplantation is the treatment modality of choice for patients with end-stage renal disease(ESRD). Living donors constitute the majority of the organ donor pool in India. Deceased donation program is only slowly evolving in the country. In this study, we aimed at comparing the outcome of live and deceased donor renal transplantation at our institute. Methods: This is a single-center, retrospective, observational study of renal transplant recipients from January 2010 to April 2016 conducted in a tertiary care centre in South India. The clinical profile, graft dysfunction, graft survival and patient survival rates of renal transplant recipients were analyzed. Results: Of 210 recipients, live donor renal transplant (LDRT) recipients were 176(83.80%) and deceased donor renal transplants (DDRT) were 34(16.19%). Delayed graft function was common in DDRT (64.7%) compared to LDRT (3.40%). Graft dysfunction episodes were commoner in DDRT (1.04 episodes/patient/year) compared to LDRT (0.43 episodes/patient/year). Higher rejection rate was seen in LDRT (25.56%) compared to DDRT (8.82%) with mean duration of follow up of 3.37± 1.80 years and 2.14 ± 1.12 years respectively. Modification of immunosuppression and noncompliance were the risk factors for rejection. Death censored graft survival rates at 6 months, 1 year and 5 years in LDRT were 98.9%, 97.2%, and 92.6% respectively and at 6 months, 1 year and 3.26 years in DDRT were 100%, 97%, and 94% respectively. Patient survival rates at 6 months, 1 and 5 years in LDRT were 94.3%, 91.5% and 86.4% respectively, and in DDRT patient survival rates at 6 months, 1 and 3.26 years were 91.2% 85.3% and 79.4% respectively. Though the patient survival rate was better in LDRT compared to DDRT, it did not reach statistical significance. Overall mortality rate was 14% and infection was the commonest (77.74%) cause of mortality. Mortality rates in LDRT and DDRT were 13.63% and 20.58% respectively. Conclusions: Live donors constitute the majority of the organ donor pool. DGF is commonly seen in DDRT. Rejection rate was higher in LDRT, with noncompliance and modification of immunosuppression being the risk factors. There is no difference in the patient and graft survival between LDRT and DDRT.

Characteristics and Prognosis of Stroke in Living Donor Renal Transplant Recipients.

Aims: We aimed to determine the characteristics and vascular outcomes of stroke in renal transplant (RT) recipients and compare them with those in patients on hemodialysis (HD) and those with no renal replacement therapy (RRT). Methods: In this prospective observational study, 717 patients (mean age, 70.8 years; male, 60.5%) with acute ischemic stroke within one week of onset were consecutively enrolled and followed for one year. The patients were classified into three groups: (1) living donor RT recipients (n=27); (2) patients on maintenance HD before the index stroke (n=39); and (3) those with no history of RRT (n=651). The primary outcome was a composite of major adverse cardiovascular events (MACE). Results: Diabetic nephropathy was the most common reason for RRT in both RT and HD patients. RT patients were more likely to have embolic stroke of undetermined source (33.3%) than others, whereas HD patients more often had cardioembolism (51.3%). No difference was observed in the MACE risk between the patients in RT and non-RRT groups (annual rate, 11.3% vs. 13.1%; log-rankP=0.82; hazard ratio [95% confidence interval], 0.92 [0.29-2.98]). In contrast, HD patients had a greater risk of MACE than those with no RRT (annual rate, 28.2% vs. 13.1%; log-rankP=0.019; hazard ratio [95% confidence interval], 2.24 [1.16-4.3]). Conclusions: The underlying etiologies of stroke differed in RT and HD patients. The one-year risk of MACE for stroke patients who had received an RT was lower than that for patients undergoing HD and comparable with that of patients with no RRT.

Subclinical Rejection and Immunosuppression in Pediatric Kidney Transplant Recipients : Single Centre Study

Background: By the time of histological confirmation of rejection is achieved, renal scarring may for treatment as a realistic option . This study aims to study the subclinical pathological graft data and to evaluate the histopathological impact of different immunosuppression protocols in pediatric renal transplant recipients. Methods: This is a case series that included twenty living donor renal transplant recipients. All included cases received the classic triple immunotherapy for at least one month post-transplantation [Steroids, calconurine inhibitors (CNI), and mycofenlolic mofetile (MMF)]. Based on their immunological risk stratification; included cases were divided into 2 groups: group (A) continued on CNI based triple therapy protocol; group (B) shifted to evirolimus /low dose CNI protocol. Surveillance biopsies were done for all cases at one and four month post-transplantation. Results: One and four month biopsies revealed subclinical rejection (including borderline changes) in 4 (20%) cases and 6 (30%) cases respectively. The number of patients received tacrolimus/MMF therapy significantly increased (p=0.02) while that of patients on everloimus/low dose CNI significantly decreased (p=0.014) due to drug modifications based on four month surveillance biopsy data. Conclusion: Subclinical rejection is not uncommon in pediatric renal graft recipients which makes surveillance biopsy might be of help. Early usage of evirolimus/low CNI protocol is associated with higher rejection rate than triple therapy.

Impact of C1q fixing donor-specific antibodies on renal transplant outcome.

Not all anti-HLA donor-specific antibodies (HLA-DSAs) are detrimental to renal allograft. In this context, the C1q complement activating ability of antibodies appears to be an important parameter to distinguish clinically inert versus detrimental DSAs. We evaluated sera of 206 consecutive primary live donor renal transplant recipients before transplant and at post-operative day 7, 30, 90, 180 and at the time of graft dysfunction for quantifying HLA-DSAs using single antigen bead assay on a Luminex platform. Patients positive for these antibodies with an MFI >500 were further screened for C1q fixing nature of DSA. Fourteen of the 18 antibody-positive patients had C1q fixing DSA with MFI value >5000. Only 4 antibody-positive patients did not have C1q fixing DSA. The MFI values of DSA detected by C1q assay were generally higher at least by 25% than those detected by the conventional IgG-SAB assay. Twelve of the 14 patients (85.71%) with C1q+ DSA developed antibody-mediated rejection during the mean follow-up period of 21.43±8.03months as compared to none of the four C1q-negative DSA (85.71% vs 0%; P=.001). These results suggest deleterious effect of C1q+ DSA vis-à-vis C1q-negative DSA on renal allograft.

Practicing With Uncertainty: Kidney Transplantation During the COVID-19 Pandemic

The coronavirus disease 2019 (COVID-19) pandemic required transplant nephrologists, surgeons, and care teams to make decisions about the full spectrum of transplant program operations and clinical practices in the absence of experience or data. Initially, across the country, there was a reduction in kidney transplant procedures and a striking pause in the conduct of living donation and living-donor transplant surgeries. Aspects of candidate evaluation and follow-up rapidly converted to telehealth. Months into the pandemic, much has been learned from experiences worldwide, yet many questions remain. In this Perspective, we reflect on some of the practice decisions made by the transplant community in the initial response to the pandemic and consider lessons learned, including those related to the risks, benefits, and logistical considerations of proceeding with versus delaying deceased-donor transplantation, living donation, and living-donor transplantation during the pandemic. We review the evolution of therapeutic strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their use in transplant recipients, current consensus related to immunosuppression management in infected transplant recipients, and emerging information on vaccination against SARS-CoV-2. We share our thoughts on research priorities, discuss the areas in which we are still practicing with uncertainty, and look ahead to the next phase of the pandemic response.

5-Year Long-Term Outcome of Live-Donor Renal Transplant Recipients With Enterocystoplasty and Ureterocystoplasty: An Age– and Sex-Matched Pair Analysis

To assess surgical complications, febrile UTI, graft function and 5-year graft survival after renal transplantation (RT) in patients with augmentation cytsoplasty (AC) and to compare them to RT patients with normal lower urinary tract. A case-control study of 34 RT patients with AC including 23 patients with enterocystoplasty (EC) and 11 patients with ureterocystoplasty (UC) was performed. The primary outcome was to determine the difference between both groups regarding postoperative surgical complications and febrile UTI episodes. Graft function was compared at 1, 3, and 5 years and 5-year graft survival was determined. The secondary outcome was to compare them to an age- and gender-matched control group (122 patients) with normal lower urinary tract. There was no significant difference regarding surgical complications or rates of hospital readmission between AC groups. Seventeen (73.9%) and 5 (45.5%) patients developed 33 and 14 episodes of febrile UTI in EC and UC groups, respectively (P= .5). Control group had shown lower incidence surgical complications (P=.001) and febrile UTIs (P=.02) compared to AC groups. At 3 and 5 years, UC had higher median eGFR than EC (P=.08, 0.008, respectively). The 5-year graft survival was 32 (94.1%) with no statistically significant difference between EC (95.7%) and UC (90.9%) (P=.5) or between AC and control (85.2%, P=.3). Although RT after AC was associated with higher surgical complications and UTI episodes, they had comparable 5-year graft survival to their control. When indicated, UC should be the preferred choice of AC whenever possible.

Plasma cytokine levels before and 1 year after successful living-donor renal transplantation

PurposeThis study aimed to evaluate cytokine levels in plasma samples over time from living-donor renal transplant recipients with no evidence of pathological and clinical rejection at least 1 year post-procedure.MethodsWe examined plasma cytokine levels in 15 living-donor renal transplant recipients who were treated at our hospital from 2015 to 2018 and who presented with no evidence of pathological or clinical rejection for 1 year or longer. We collected blood samples before renal transplantation and at 1 week and 1 year post-procedure. We evaluated levels of 40 cytokines in plasma using Bio-Plex Pro™ Human Chemokine Assay kit.ResultsWe detected no increase in plasma cytokine levels at either the 1 week or the 1 year time points. Plasma levels of 22 cytokines remained stable throughout and levels of 18 cytokine decreased after transplantation.ConclusionPlasma cytokine levels remained unchanged or were decreased in our patient cohort that included stable cases of living-donor renal transplantation. Our results suggest that renal transplantation may promote amelioration of chronic inflammation associated with end-stage renal failure and dialysis.