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Background: Immunosuppressive therapy is the backbone of kidney transplantation in preventing acute rejection. T-cell depletion after doses of thymoglobulin is dose-dependent, as are their side effects. At the same time, basiliximab and other maintenance immunosuppressive drugs act at different signals on T lymphocytes. Therefore, studying the pattern of lymphocyte subset depletion depending on the induction regime given at transplantation could be an added tool in managing post-transplant recipients., Methodology: This prospective observational study recruited kidney transplant recipients from August 2019 through April 2021 at the University of Malaya Medical Centre. Blood tests for lymphocyte subsets were taken at pre-transplant, 1 week, 1 month, 3 months, and 6 months post-transplantation. At transplantation, recipients received either basiliximab, low-dose thymoglobulin (cumulative dose: 1.5 mg/kg), or standard-dose thymoglobulin (cumulative dose: 5 mg/kg)., Results: A total of 39 patients were recruited: 38.5% received basiliximab (15 of 39), 15.4% received low-dose thymoglobulin (6 of 39), and 46.2% received standard-dose thymoglobulin (18 of 39). Absolute lymphocyte counts 1 week post-transplantation were 1.5 ± 0.84 × 10 9 /L for basiliximab, 0.7 ± 0.57 × 10 9 /L for low-dose thymoglobulin, and 0.1 ± 0.08 × 10 9 /L for standard-dose thymoglobulin (P < .001). The CD4+ and CD8+ counts were severely depleted in the standard-dose thymoglobulin group, with a statistically significant differenceup to 6 months post-transplantation. In the low-dose thymoglobulin group, the CD4+ and CD8+ counts were depleted at 1 week post-transplantation and recovered at 1 month post-transplantation. There was no difference in allograft function and incidence of allograft rejection across groups., Conclusions: The effects on lymphocyte counts, CD4+ and CD8+, vary depending on the type and dose of induction immunosuppression. This could be a guiding tool in managing immunosuppression post-transplantation depending on the patient's immunologic risk., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Proteinuria and metabolic acidosis adversely affect long term renal allograft outcome and are highly prevalent in reported studies. The role of dietary intake in influencing proteinuria and metabolic acidosis remained uncertain. This study aims to determine the prevalence rate of proteinuria and metabolic acidosis among kidney transplant recipients (KTRs) and to study their relationship with dietary intake., Methods: We performed a cross-sectional study on KTRs with functioning renal allograft and at least 3 months post transplant. Dietary protein, salt, and dietary acid load were estimated using 24-hour urine collection. Demographic characteristics, concomitant medications, medical history, and laboratory results were obtained from electronic medical records., Results: A total of 204 KTRs were recruited with median age of 48 years (interquartile range [IQR], 18 years); male to female ratio was 61:39. A total of 79.9% (n = 163) were living related kidney transplants. The median duration after transplant was 71 months (IQR, 131 months), and median eGFR was 65 mL/min/1.73 m 2 (IQR, 25 mL/min/1.73 m 2 ). The prevalence rates of proteinuria (defined as ≥ 0.5 g/d) and metabolic acidosis (defined as at least 2 readings of serum bicarbonate ≤ 22 mmol/L in the past 6 months) were 17.7 % and 6.2%, respectively. High dietary protein of > 1.2 g/kg ideal body weight (adjusted odds ratio, 3.13; 95% CI, 1.35-7.28; P = .008) was significantly associated with proteinuria. Dietary protein, salt, and acid load did not correlate with chronic metabolic acidosis., Conclusions: The prevalence rate of proteinuria is consistent with published literature, but metabolic acidosis rate is extremely low in our cohort. High protein intake (> 1.2 g/kg ideal body weight) is a risk factor of proteinuria and may have negative impact on KTR outcome., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Allograft rejection remains a significant challenge in managing post-transplant recipients despite the improvement in immunologic risk assessment and immunosuppressive therapy. Published literature including animal studies has demonstrated that the cells responsible for rejection are beyond the innate T and B cells, and other studies revealed evidence supporting natural killer (NK) cells' role in kidney allograft injury. This study aims to find the association between the peripheral blood lymphocyte subset counts, primarily NK cells, and the kidney allograft biopsy findings., Methods: This is a prospective cross-sectional study among a total of 100 kidney allograft biopsies in 61 kidney transplant recipients. The peripheral blood for the lymphocyte subset was sent just before the allograft biopsy. The patients' immunosuppression and other laboratory investigations were managed as per clinical practices by the attending nephrologist., Results: Overall, the mean age of our patients was 43.72 ± 10.68 years old, and 55.7% of recipients were male. Higher counts of T cells (CD4+; 658.8 ± 441.4 cells/µL; P = .043) and NK cells (CD3-CD16+CD56+; 188 [interquartile range = 133.0-363.0 cells/µL]; P = .002) were associated with higher risk of allograft rejection in the initial analysis. Patients with an allograft age <12 months had significantly higher total T cells, CD4+ T cells, and NK cells in the rejection groups. However, after assessing factors associated with rejection in the multivariate analysis, we only found that being ABO-incompatible and having >497 CD4+ cells/µL had a higher odds of allograft rejection., Conclusions: Higher CD4± counts were associated with a higher risk of allograft rejection. However, there was no significant increase in CD8±, CD19±, and NK cells count in our cohort with allograft rejection., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Evaluation of donor renal function as glomerular filtration rate (GFR) is a crucial part of pretransplant workup. Most guidelines recommend measured GFR (mGFR) using exogenous markers with creatinine clearance (CrCl) as an alternative. However, exogenous markers are difficult to obtain and perform, and CrCl may overestimate GFR., Objective: We explore the use of CrCl and combined urea and creatinine clearance as an alternative for GFR assessment., Methods: A retrospective study involving 81 kidney donors from 2007 to 2020, with mGFR collected by chromium 51-labeled ethylenediaminetetraacetic acid ( 51 Cr-EDTA) and CrCl and combined urea and creatinine clearance. We analyzed the performance of CrCl and combined urea and creatinine clearance against 51 Cr-EDTA. Adequacy of urine volume was taken into consideration., Results: A total of 81 candidates with a mean age of 44.80 ± 10.77 years were enrolled. Mean mGFR from 51 Cr-EDTA was 123.66 ± 26.91 mL/min/1.73 m 2 , and combined urea and creatinine clearance and CrCl were 122.13 ± 47.07 and 133.40 ± 36.32 mL/min/1.73 m 2 , respectively. CrCl overestimated 51 Cr-EDTA. Though combined urea and creatinine clearance had minimal bias, it had a lower correlation coefficient (0.25 vs 0.43), lower precision (49.51 vs 38.10), and slightly lower accuracy within 30% of 51 Cr-EDTA (74.07% vs 76.54%)., Conclusions: Combined urea and creatinine clearance did not improve the performance of CrCl. Nevertheless, it can potentially be used as first-line GFR assessment, followed by mGFR in selected donors, to ascertain threshold of safe kidney donation. A stringent urine collection method is essential to ensure accurate measurement., (Copyright © 2021. Published by Elsevier Inc.)

Living-kidney transplantation increases with years, however, the rate is comparatively low to support local needs. Marginal living donors like the elderly were used to increase the donor pool. We retrospectively evaluate the outcome of 25 elderly living kidney donors (eLKDs) who were ≥60 years old at the time of donation in our center. Their medical history and laboratory results were analyzed retrospectively from e-medical records. There are 16 females (64.0%) with a median age of 63 (60.5-66.0). The mean follow-up duration was 4.36 ± 2.46 years. Their mean body mass index increased from 23.70 ± 3.07 kg/m 2 to 24.21 ± 2.93 kg/m 2 (t[14] = -2.176, P = .047) post donation. Systolic blood pressure (SBP) increased from 133.33 ± 11.65 mm Hg to 140.56 ± 17.78 mm Hg (t[17] = -2.124, P = .049). However, the prevalence of overweight and hypertension were not significant. Only 5.56% of the eLKDs developed proteinuria post nephrectomy (P =1.000). Serum creatinine increased from 62.33 ± 14.39 mmol/L to 104.63 ± 28.53 mmol/L post 1-month donation (t[23] = -9.720, P = .000) and decreased to 99.67 ± 22.39 mmol/L post 1-year donation (t[17] = -8.415, P = .006), and latest results were 94.28 ± 20.74mmol/L (t[17] = -6.630, P = .033). Fasting blood glucose and HbA1c level recorded no significant changes post donation. We noted that 47.62% of the eLKDs had dyslipidemia pre donation, which increased to 76.20% post donation (P = .031). eLKDs with hyperuricemia increased significantly from 5.88% to 52.94%; with uric acid level from 306.12 ± 68.67 umol/L to 412.24 ± 74.14 umol/L (t[16] = -7.726, P = .000). None of the eLKDs were diagnosed with metabolic syndrome pre and post kidney donation. Postdonation kidney function of the eLKDs compensated well and were stable in the short term. We noted statistically significant increments of weight, body mass index, SBP, uric acid, and lipid levels, which did not translate to clinical significance post donation. Elderly living-kidney donation can be done safely with close monitoring post donation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The aim of induction therapy in the management of kidney transplant is to reduce the incidence of acute rejection and delayed graft function after kidney transplant. The agent for induction therapy differs depending on the recipient risks. The regimen can be either polyclonal (rabbit antithymocyte globulin [rATG]) or monoclonal antibody (basiliximab). Basiliximab is commonly used in patients with low immunologic risk. However, to date we know that the use of rATG on T cell depletion is dose dependent and more potent antirejection therapy. Therefore, we would like to look at 1-year graft function of very low-dose rATG in low immunologic risk recipients. All low immunologic risk patients who received low-dose rATG (0.5 mg/kg of body weight daily) during transplant (day 0) and on days 1 and 2 were recruited. Their renal function, HLA donor-specific antibodies, lymphocyte counts, protocol biopsy results, and cytomegalovirus (CMV) polymerase chain reaction were monitored as per clinical practice. All 10 patients had immediate graft function. Low-dose rATG caused lymphocyte counts to deplete immediately on day 0, and the effect lasted about 1 month post-transplant. All the patients had stable graft function without any significance episode of rejection. Only one patient had de novo HLA-DQ antibody. It is good to know that without prophylaxis antiviral in CMV + donor to CMV + recipient, the incidence of CMV viremia is considerably low in our cohort. Very low-dose rATG is an effective induction immunosuppression in low immunologic risk patients with acceptable infection risk., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The shortage of deceased donors led to an increase of living related renal transplant performed in the presence of donor-specific antibodies (DSAs) or ABO incompatibilities. There are various desensitization protocols that have been proposed. Here, we describe the outcome of these sensitized patients. This is a prospective cohort study recruiting all kidney transplant recipients from August 2016 until June 2018. Deceased donations, ABO incompatible patients, and sensitized patients who were not prescribed on our desensitization protocol were excluded. Recipients were screened for the presence of HLA-antibodies 1 month before transplant. Those with positive DSA will undergo flow cytometry (risk stratification). We are using a protocol that consisted of intravenous rituximab 200 mg (day -14), intravenous antithymocyte globulin 5mg/kg (day 0-4), plasma exchange post transplant for patients with mean fluorescent intensity (MFI) < 3000, and negative flow cytometry. Those patients with MFI ≥ 3000 or positive flow cytometry need extra cycles pretransplant. A total of 40 patients were recruited, and 20 were sensitized patients. Among the sensitized group 4 of 20 had flow cytometry crossmatch positive, while all had preformed HLA-DSA. A total of 8 of 20 had class I HLA-DSA, 11 of 20 had class II HLA-DSA, and 1of 20 was positive for both class I and II HLA-DSA. Mean immunodominant MFI was 2133.4 (standard deviation [SD], 4451.24) and 1383.7 (SD, 2979.02) for class I and class II, respectively. At 1 year, mean serum creatinine was 108.90 (SD, 25.95) and 118.42 (SD, 31.68) in sensitized and unsensitized patients, respectively. One of 20 unsensitized patients had Banff 1B rejection at 3 months, and there was no significant rejection in sensitized patients at 6 months and 1 year. There was no difference in the occurrence of de novo HLA-DSA between the groups. Desensitization protocols may help to overcome incompatibility barriers in living donor renal transplant. The combination of low-dose rituximab, antithymocyte globulin, and judicious use of plasma exchange has worked well for our cohort., (Copyright © 2020 Elsevier Inc. All rights reserved.)