Effect of CYP3A4*22, CYP3A5*3 and POR*28 genetic polymorphisms on calcineurin inhibitors dose requirements in early phase renal transplant patients.

OBJECTIVE: This study aimed to investigate the combined effect of CYP3A5*3, CYP3A4*22, and POR*28 genetic polymorphisms on tacrolimus and cyclosporine dose requirements. METHODS: One hundred thirty renal transplant patients placed on either tacrolimus or cyclosporine were recruited, where the effect of CYP3A5*3, CYP3A4*22, and POR*28 genetic polymorphisms on their dose requirements were studied at days 14, 30, and 90 post-transplantations. RESULTS: The POR*28 allele frequency in the studied population was 29.61%. The tacrolimus dose-adjusted trough concentration ratio (C0/D) was significantly lower in the fast metabolizers group ( CYP3A5*1/POR*28(CT/TT ) carriers) than in the poor metabolizers group ( CYP3A5*3/*3/CYP3A4*22 carriers) throughout the study (14, 30, and 90 days) ( P = 0.001, <0.001, and 0.003, respectively). Meanwhile, there was no significant effect of this gene combination on cyclosporine C0/D. CONCLUSION: Combining the CYP3A5*3, POR*28 , and CYP3A4*22 genotypes can have a significant effect on early tacrolimus dose requirements determination and adjustments. However, it does not have such influence on cyclosporine dose requirements.

Infections in the first year of living related kidney transplantation in a young transplant cohort.

BACKGROUND: Infection after a kidney transplant is a serious cause of morbidity and mortality. Weighing the risks and benefits of immunosuppression is of paramount importance for patient wellbeing and transplant survival. METHODS: This is a prospective observational study exploring the variety of bacterial, viral and fungal infections occurring within the first year of living related kidney transplantation in a young transplant cohort. Fifty-one kidney transplant recipients (KTR) between the age of 18 and 45 who had a kidney transplant between Jan 2020 and Jan 2022 were enrolled and followed up for one year. Primary outcome was the occurrence of infection. RESULTS: Twenty-four patients (47%) recorded a collective 33 episodes of infection. Seven patients had repeated infections and 17 had single infections. Twenty-seven patients had an uneventful year with no infections recorded. Commonest infection was lower urinary tract infection (UTI) (27.3%) followed by SARS-COV2 and Herpes Zoster (15.2%). The commonest pathogens causing lower UTI were Escherichia coli (E coli) (21.2%) and Klebsiella (18.2%). Median Tacrolimus level was (7.8) ng/ml in KTR with infection and (8.95) ng/ml in KTR without infection, p = 0.21. Median Haemoglobin (IQR) was (10.2) g/dl (7.8-14) gm/dl in KTR with infection compared to (10.8) g/dl (7.3-15.3) in KTR without infection odds ratio (OR) = 0.78, confidence interval (CI) (0.5-1.1); p = 0.16.In KTR with infection 25% had donors above the age of 60 compared to 11% in KTR without infection ( OR 2.6,CI (0.5-12), p = 0.2). Post transplant diabetes (PTDM) occurred in (25%) in KTR with infection compared to those without, but that was not statistically significant p = 0. 365.In KTR without infection, 59.3% had a preemptive transplant compared to 20.8% in the group with infection (OR = 0.18; 95% CI: 0.052-0.631; p = 0.007). Median tacrolimus was 7.8 ng/ml in KTR with single infection compared to 7.7 ng/ml in KTR with repeated infections. CONCLUSION: This study shows that the commonest infection occurring in the first-year post kidney transplant was lower urinary tract infection followed by SARS-COV2 and Herpes Zoster. There was no difference in trough tacrolimus or haemoglobin levels between KTR who developed infection with those who did not.

High-Flux dialyzer 2.6 m2 is promising for free light chains removal in high-flux hemodialysis and in hemodiafiltration.

Immunoglobulin light chains are classified as middle molecule uremic toxins and its removal through effective dialyzer is needed with less albumin loss. This study assessed the free light chains (FLC) removal using dialyzer surface area (SA) 2.6m2 in high-flux dialysis (HF-HD) versus hemodiafiltration (HDF) and its relation to cumulative dialysate albumin loss. This pilot cross-over study included 25 patients who underwent hemodialysis (HD) using dialyzer surface area 2.6m2 on HF-HD followed by online post-dilution HDF with washout period of 2 weeks using high-flux dialyzers (max 2.0 m2 SA). All patients were subjected to single session measurement of dialysate albumin every hour and pre/post dialysis levels of FLC Kappa (Κ) and Lambda (λ) by ELISA. Dialyzer (SA) 2.6m2 showed a significant reduction in post-dialysis kappa and lambda level in comparison to pre-dialysis level on HF-HD and hemodiafiltration (P<0.001). HDF showed higher kappa and lambda FLC reduction ratio (45.16 ± 6.53 %, 28.68 ± 4.36 %, respectively compared to HF-HD (29.52 ± 6.38 %, 19.48 ± 1.96, respectively, P<0.001 for both). Patients on HDF dialysis had significant total albumin loss in dialysate [median (IQR) 2.97; 1.98 - 3.37 gm] compared to HF-HD [median (IQR) 0.67; 0.49 - 1.13 gm] (P <0.001). In conclusion, high-flux dialyzer 2.6 m2 (SA) may be effective in free light chains removal especially with online post-dilution hemodiafiltration with acceptable albumin loss.

Egyptian practical guidance in lipid management 2020.

BACKGROUND: Numerous epidemiological investigations and randomized clinical studies have determined that dyslipidemia is a major contributor to atherosclerotic cardiovascular disease (ASCVD). Consequently, the management of serum cholesterol and low-density lipoprotein levels has become a central objective in the effort to prevent cardiovascular events. MAIN BODY: Many guidelines were issued by different organizations and societies to define patient risk and establish important recommendations for management strategies. Newer cholesterol-lowering agents (non-statin drugs) are described, and their use is directed primarily to secondary prevention in patients at very high risk of new ASCVD. CONCLUSION: The present guidance summarizes the current methods for risk estimation and outlines the most recent data on lipid management in a simple user-friendly format, to improve physician awareness and help implement guidelines in the daily practice.

Esomeprazole vs pantoprazole effects on cyclosporine levels in kidney transplantation: A randomized clinical trial.

Renal allograft survival requires multiple immunosuppressive drugs. This strategy may lead to gastric complications that necessitate gastro-protective medications, notably, proton pump inhibitors (PPI). This study aimed to compare the influence of pantoprazole and esomeprazole on serum cyclosporine trough levels (C0 ) in renal transplant recipients (RTR). A prospective, parallel, open-label trial was conducted on 47 adult RTR receiving cyclosporine doses adjusted to attain trough concentrations of 100 to 150 µg/L, mycophenolate mofetil (MMF) 750 mg q12 hour and prednisolone at 5 mg daily at Nasser Institute, Cairo, Egypt from January to September 2016. Patients were randomized into the esomeprazole group (25) or pantoprazole group (22) receiving the same dose (40 mg once daily). The study outcomes included clinical signs of rejection and renal function decline, assessed by elevations in serum creatinine, caused by cyclosporine level variations in either of the two study groups. Renal function, C0 and CBC measurements were measured at baseline and monthly for 6 months. The mean C0 values were higher in the pantoprazole group than in the esomeprazole group in the sixth month only (P = .007). Serum creatinine level was lower in the sixth month than at baseline in the esomeprazole group (P = .004). There were no signs of rejection biochemical or clinical in any of the study groups. In conclusion, PPIs should be used with caution and doses should be titrated to reach the C0 targets in RTR, which is of more importance in pantoprazole than esomeprazole to avoid C0 level elevation or decline affecting the allograft function.

Proteinuria in Egyptian renal transplant recipients.

To evaluate the prevalence, risk factors, possible etiology, prognosis and management of proteinuria in renal transplant recipients, we studied 435 adult renal transplant recipient patients randomly selected from our center; 394 patients were reviewed retrospectively and 41 patients were followed-up prospectively for a period of one year. The patients were classified into three groups according to the results of urinalysis and spot urinary albumin creatinine ratio: Group A patients with normoalbuminuria; Group B patients with microalbuminuria; and Group C patients with macroalbuminuria. Persistent post-transplantation proteinuria was detected in 125 (28.8%) patients. The etiology of post-transplantation proteinuria included chronic allograft dysfunction in 44 (35.2%) patients, acute rejection in 40 (32%) patients, transplant glomerulopathy in eight (6.4%) patients, glomerular disease in 16 (12.8%) patients and other etiology in 17 (13.6%) patients. Proteinuric patients demonstrated significantly lower graft survival rates than did those without proteinuria (48.3% versus 51.7%, respectively; P = 0.017; Risk Ratio = 0.403; 95% confidence interval 0.188-0.862). We conclude that proteinuria is prevalent after kidney transplant in our population, and that it is most commonly associated with chronic allograft nephropathy, transplant glomerulopathy, glomerulonephritis and acute rejection. Post-transplant proteinuria is associated with decreased allograft survival.

Prevalence of hyperkalemia among hemodialysis patients in Egypt.

INTRODUCTION: Hyperkalemia is a frequent problem in patients with end stage renal disease (ESRD) on maintenance hemodialysis and is often attributed as a cause of deaths in these patients. The aim of this study was to estimate the prevalence of hyperkalemia among Egyptian hemodialysis patients. PATIENTS AND METHODS: 400 ESRD patients on maintenance hemodialysis were enrolled in the study. They were allowed their usual diets and medications during the study periods. For all patients, history and clinical examinations and serum potassium level was measured three times--pre- and post-1st session and pre-next session--at two successive sessions of hemodialysis. RESULTS: The results of this study showed that the prevalence of hyperkalemia was 41.2%, 6.5%, and 66.9% of pre- and post-dialysis and before the next session of dialysis, respectively. Hyperkalemia significantly correlates with potassium-rich diets, non-compliant patients, two sessions of hemodialysis per week, and constipation in ESRD patients during the study periods. Serum potassium level was significantly higher in anuric ESRD patients than those who had residual renal function, patients using acetate dialysate than those using bicarbonate dialysate, and patients with low blood flow rate than those with higher blood flow rates. There was a non-significant correlation between serum potassium and ACEls, B-blockers, or diabetes. CONCLUSION: Hyperkalemia is a frequent problem in patients with end stage renal disease in Egypt. Hyperkalemia significantly correlates with a potassium-rich diet and inadequate dialysis either by prescription or non-compliance. Thrice weekly bicarbonate dialysis with higher blood pump flow rate had better elimination of potassium.

Effect of recombinant human erythropoietin on insulin resistance in hemodialysis patients.

Insulin resistance is a characteristic feature of uremia. Insulin resistance and concomitant hyperinsulinemia are present irrespective of the type of renal disease. Treatment with recombinant human erythropoietin (rHuEPO) was said to be associated with improvement in insulin sensitivity in uremic patients. The aim of this study was to compare insulin resistance in adult uremic hemodialysis (HD) patients including diabetic patients treated with or without rHuEPO. A total of 59 HD patients were studied, patients were divided into 2 groups of subjects: 30 HD patients on regular rHuEPO treatment (group A), and 29 HD patients not receiving rHuEPO (group B) diabetic patients were not excluded. Full medical history and clinical examination, hematological parameters, lipid profile, serum albumin, parathyroid horomone, Kt/V, fasting glucose, and insulin levels were measured in all subjects. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was used to compare insulin resistance. The results of this study showed that the mean insulin level of HD patients treated with rHuEPO (group A) (17.5 +/- 10.6 microU/mL) was significantly lower than patients without rHuEPO (group B) (28.8 +/- 7.7 microU/mL), (P<0.001). Homeostasis Model Assessment of Insulin Resistance levels in group A were significantly lower than in group B (3.8 +/- 2.97, 7.98 +/- 4.9, respectively, P<0.001). Insulin resistance reflected by HOMA-IR levels among diabetic patients in group A was significantly lower than among diabetic patients in group B (3.9 +/- 3.2, 9.4 +/- 7.2, respectively, P<0.001). Also, HOMA-IR levels among nondiabetic patients in group A were significantly lower than among nondiabetic patients in group B (3.7 +/- 2.85, 6.9 +/- 1.43, respectively, P<0.01). We found a statistically significant negative correlation between duration of erythropoietin treatment, fasting blood glucose, insulin levels, and insulin resistance (r=-0.62, -0.71, and -0.57, P<0.001). Patients treated with rHuEPO showed less insulin resistance compared with patients not treated with rHuEPO in diabetic and nondiabetic patients and, duration of erythropoietin treatment is negatively correlated with insulin levels and insulin resistance in HD patients.