The Effects of Different Induction Regimes on Serial Lymphocyte Subsets in Kidney Transplant Recipients: A Single Tertiary Center Experience.

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 × 109/L for basiliximab, 0.7 ± 0.57 × 109/L for low-dose thymoglobulin, and 0.1 ± 0.08 × 109/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.

Metabolic Changes In Living Kidney Donors After Donation In University Malaya Medical Centre.

The short- and long-term outcome of donations from living donors of kidneys (LKDs) remains controversial. Information regarding metabolic changes after donation in Malaysia remains limited despite Malaysia having the highest record prevalence of diabetes, obesity, and hypertension in Asia. There were 159 LKDs in our center from 2010 to 2020. We analyzed pre and post donation clinical data and laboratory results from 140 LKDs, retrospectively, from electronic medical records and looked for any metabolic changes. Among these 140 LKDs, 99 were women (70.7%), with a mean age of 47.23 ± 11.67 before donation. The median follow-up was 4 years (range, 2-6 years). Median body mass index increased from 24.35 kg/m2 (range, 22.11-26.93) to 25.56 kg/m2 (range, 22.78-28.57; Z=-3.934, P = .000) after donation. Prevalence of obesity increased from 24.18% to 30.77%. Only 2.8% of LKDs developed proteinuria postnephrectomy (P = .250). Serum creatinine increased from 60 mmol/L (range, 52-74) to 87 mmol/L (range, 74-108) 1 year after donation (P = .000), and the latest results decrease to 83 mmol/L (range, 73-101; P = .000). Systolic blood pressure increased from 127.83 ± 12.25 mm Hg to 131.30 ± 18.16 mm Hg, (t[97] = -2.012; P = .047); and prevalence of hypertension increased from 19.81% to 23.58% (P = .125), with 22.64% requiring treatment. We noted that 22.54% of the LKDs had dyslipidemia before donation, a number that increased to 50% after donation (P = .000). LKDs with hyperuricemia increased significantly from 7.92% to 34.65%, with uric acid level increasing from 311.94 ± 78.51umol/L to 381.87 ± 86.96 umol/L (t[94] = -10.805; P = .000). Fasting blood glucose and glycated hemoglobin level recorded no significant changes after donation. Post donation kidney function of LKDs compensated well and stable in short term. We noted statistically significant increment of weight, post donation body mass index, systolic blood pressure, uric acid, and lipids. We suggest prospective studies with longer follow-up and more subjects for clinical correlation.

Glycaemic control in type 2 diabetic patients with chronic kidney disease: the impacts on enzymatic antioxidants and soluble RAGE.

BACKGROUND: Chronic kidney disease (CKD) is characterised by long-term kidney damage and renal function decline. Diabetic CKD is the principal subtype of kidney disease in Malaysia and is associated with oxidative stress which plays an important role in development and progression of the disease. Glycaemic control slows down the progression of diabetic complications, including diabetic CKD. However, the implication of glycaemic control on enzymatic antioxidants and soluble RAGE (sRAGE) in CKD patients remains elusive. The aim of this study was to investigate the effect of glycaemic control on the levels or activities of glutathione peroxidase (GPx), superoxide dismutase (SOD) and sRAGE in CKD patients. METHODS: A total of 150 CKD patients and 64 non-CKD patients were enrolled. The type 2 diabetic patients in the recruited study participants were categorised based on their glycaemic control; poor glycaemic control (GC) with haemoglobin A1c (HbA1c) > 7% and good GC with HbA1c ≤ 7%. The levels or activities of GPx, SOD and sRAGE in plasma were measured. These biochemical parameters were analysed using Mann-Whitney U test and two-way analysis of variance (ANOVA). RESULTS: The activities of GPx and SOD as well as plasma level of sRAGE were not significantly different among the CKD patients with varying glycaemic control status. Irrespective of diabetes status and glycaemic control status, CKD patients also exhibited lower plasma SOD activities compared with non-CKD patients. Among the non-CKD patients, SOD activities were significantly higher in diabetic patients with good GC than diabetic patients with poor GC. Two-way ANOVA revealed that both CKD status and glycaemic control had an interaction effect on SOD activities in diabetic subjects with and without CKD. Follow-up analysis showed that SOD activities were significantly higher in non-CKD patients with good GC. There were no overall significant differences in GPx activities among the study participants. Furthermore, plasma sRAGE levels were higher in diabetic patients with CKD than those without CKD, regardless of glycaemic control status. There were no interaction effects between CKD status and glycaemic control status on GPx and sRAGE. Instead, CKD status showed significant main effects on these parameters, indicating significant differences between diabetic subjects with CKD and diabetic subjects without CKD. CONCLUSION: Glycaemic control did not quantitatively alter GPx, SOD and sRAGE in diabetic CKD patients. Despite the advantages of good glycaemic control, a well-controlled diabetes in CKD did not modulate the activities of enzymatic antioxidants and sRAGE levels, therefore may not be the primary mechanism to handle oxidative stress.

Association of the receptor for advanced glycation end-products (RAGE) gene polymorphisms in Malaysian patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a condition associated with progressive loss of kidney function and kidney damage. The two common causes of CKD are diabetes mellitus and hypertension. Other causes of CKD also include polycystic kidney disease, obstructive uropathy and primary glomerulonephritis. The receptor for advanced glycation end-products (RAGE) is a multi-ligand cell surface receptor of the immunoglobulin superfamily and it has been associated with kidney disease in both non-diabetic and diabetic patients. Presently, data on the association between RAGE polymorphisms and CKD in the Malaysian population is limited, while numerous studies have reported associations of RAGE polymorphisms with diabetic complications in other populations. The present study aims to explore the possibility of using RAGE polymorphisms as candidate markers of CKD in Malaysian population by using association analysis. METHODS: A total of 102 non-diabetic CKD patients, 204 diabetic CKD patients and 345 healthy controls were enrolled in the study. DNA isolated from blood samples were subjected to genotyping of RAGE G82S, -374T/A, -429T/C, 1704G/T and 2184A/G polymorphisms using real-time polymerase chain reaction (PCR). The 63-bp deletion, a polymorphism in the RAGE gene promoter, was genotyped using conventional PCR method and visualized using agarose gel electrophoresis. The collective frequencies of genotypes with at least one copy of the minor alleles of the four polymorphisms were compared between the non-diabetic CKD patients, diabetic CKD patients and healthy controls. RESULTS: After adjustment of age, gender and ethnic groups in binary logistic regression analysis, the G82S CT + TT genotypes were associated with non-diabetic CKD patients when compared with diabetic CKD patients (p = 0.015, OR = 1.896, 95% CI = 1.132-3.176). After further adjustment of CKD comorbidities, the G82S CT + TT genotypes were still associated with non-diabetic CKD patients when compared with diabetic CKD patients (p = 0.011, OR = 2.024, 95% CI = 1.178-3.476). However, it cannot be suggested that G82S polymorphism was associated with CKD in non-diabetic patients in this study. This is because there were no significant differences in the frequencies of G82S CT + TT genotypes between non-diabetic CKD patients and healthy controls. In addition, the RAGE -374T/A, -429T/C, 1704G/T, 2184A/G and 63-bp deletion polymorphisms were also not associated with non-diabetic CKD patients and diabetic CKD patients in this study. CONCLUSION: The G82S, -374T/A, -429T/C, 1704G/T, 2184A/G and 63-bp deletion polymorphisms examined in this study were not associated with chronic kidney disease in the Malaysian patients.

A Study of Dielectric Properties of Proteinuria between 0.2 GHz and 50 GHz.

This paper investigates the dielectric properties of urine in normal subjects and subjects with chronic kidney disease (CKD) at microwave frequency of between 0.2 GHz and 50 GHz. The measurements were conducted using an open-ended coaxial probe at room temperature (25°C), at 30°C and at human body temperature (37°C). There were statistically significant differences in the dielectric properties of the CKD subjects compared to those of the normal subjects. Statistically significant differences in dielectric properties were observed across the temperatures for normal subjects and CKD subjects. Pearson correlation test showed the significant correlation between proteinuria and dielectric properties. The experimental data closely matched the single-pole Debye model. The relaxation dispersion and relaxation time increased with the proteinuria level, while decreasing with the temperature. As for static conductivity, it increased with proteinuria level and temperature.

Rothia dentocariosa repeat and relapsing peritoneal dialysis-related peritonitis: a case report and literature review.

Peritonitis is well recognized as the Achilles tendon of peritoneal dialysis (PD). Reoccurrence of peritonitis due to the same organism, defined as either repeat or relapsing peritonitis under the 2005 guidelines by the International Society for Peritoneal Dialysis, often results in PD technique failure. Rothia dentocariosa, a low-virulent human oropharynx commensal, is a rarely reported pathogen in human infection, particularly infective endocarditis. R. dentocariosa PD-related peritonitis is exceedingly uncommon yet potentially results in repeat or relapsing peritonitis which requires catheter removal. We report a case of R. dentocariosa repeat and relapsing peritonitis in a PD patient who was treated successfully with antimicrobial therapy.

Clinical predictors of non-diabetic renal disease and role of renal biopsy in diabetic patients with renal involvement: a single centre review.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is reportedly the leading cause of end-stage renal disease (ESRD) worldwide. However, non-diabetic renal diseases (NDRD) are not uncommon among T2DM patients with renal involvement. Our study aimed to examine the prevalence of NDRD in T2DM and clinical markers for diabetic nephropathy (DN) and NDRD and to determine the role of renal biopsy in T2DM patients and its impact on clinical practice. METHODS: We conducted a retrospective analysis of T2DM patients in whom renal biopsies were performed from January 2004 to March 2008 (n = 110). RESULTS: Biopsy results were divided into three groups: group I/pure DN (62.7%), group II/isolated NDRD (18.2%), and group III/mixed lesions (19.1%). The causes of NDRD in decreasing order of frequency were acute interstitial nephritis, glomerulonephritides, hypertensive renal disease, and acute tubular necrosis. Significant clinical markers for DN are presence of diabetic retinopathy and longer duration of diabetes. For NDRD, useful clinical markers include the presence of acute renal failure and microscopic hematuria. In the DN subgroup, Indians had significantly shorter duration of diabetes on biopsy compared with Malays and Chinese. CONCLUSIONS: NDRD is prevalent in T2DM patients, and given its potentially treatable nature, renal biopsy should be considered in T2DM patients with nephropathy, especially in those with atypical features.