Risk stratification of renal transplant recipients using routine parameters: Implication of learning from SARS-CoV-2 into transplant follow-up program

BACKGROUND Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is a global pandemic that is associated with a high risk of morbidity and mortality among recipients of solid organ transplantation.In the course of acute SARS-CoV-2 infection,various laboratory markers have been identified as predictors for high risk of mortality.AIM To risk stratify renal transplant recipients(RTxR)using general demographic parameters,comorbidities and routine laboratory markers for the severity of the disease and its outcomes.We believe that learning about these routinely monitored parameters can help us plan better strategies for the RTxR follow-up program.METHODS This present study includes RTxR who acquired SARS-CoV-2 infection from March 2020 to February 2021.We recorded the basic demographics,comorbidities and routine laboratory markers.We investigated the impact of SARS-CoV-2 infection on RTxRs and risk-stratified the progression of disease severity and outcomes in terms of recovery or mortality.RESULTS From 505 RTxRs in our renal transplant follow-up program,29(7.75%)RTxRs had PCR-positive SARS-CoV-2 infection.We recorded 8 deaths from SARS-CoV-2 infection giving an overall mortality rate of 1.6%but a significant 27.6%mortality in SARS-CoV-2 positive recipients.Age more than 68 years,non-Caucasian ethnicity and male gender were associated with a significant drop in survival probability;P≤0.001.<0.001 and<0.0001 respectively.87.5%of the deceased were diabetic;P≤0.0.0001.Estimated glomerular filtration rate of less than 26 mL/min/1.73 m2,serum albumin less than 20 g/L,Hemoglobin less than 9.6 g/L and serum calcium less than 1.70 mmol/L were all associated with significantly increased risk of mortality;P=0.0128,<0.001,<0.0001 and 0.0061 respectively.CONCLUSION This study has identified some routinely used modifiable parameters in predicting a higher risk of mortality and morbidity.This knowledge can be used in RTxR follow-up programs by addressing these parameters early to help reduce the morbidity and mortality in RTxRs.

An Evaluation of the Benefit of Cytomegalovirus Prophylaxis with Acyclovir on Post-Transplant Cytomegalovirus Infection Prevention in a Population of Renal Transplant Recipients in Nigeria

Background: Cytomegalovirus (CMV) is an important infection in renal transplant recipients and may significantly impact recipients’ long-term outcome and graft survival. Objective: This study aimed to evaluate the benefit of prophylaxis with acyclovir on post-transplant CMV infection prevention in a population of renal transplant recipients in Lagos, Nigeria. Subjects and Methods: The study was a cross-sectional design involving renal transplant recipients attending post-transplant follow-up clinics in Lagos, Nigeria between October 2004 and July 2005. Data on the use of CMV prophylaxis were obtained from the hospital case records of the study subjects. Enzyme-Linked Immunosorbent Assay (ELISA) was employed to detect CMV IgM antibodies for the diagnosis of post-transplant CMV infection and Microsoft Excel and EPI-Info 2002 statistical software were used for data entry and analysis. Results: Forty (40) renal transplant recipients were studied, 32 recipients were males and 8 were females with M:F ratio of 4:1. The mean age of the recipients was 39 ± 11.6 years old. The recipients’ post-transplant duration ranged from 2 to 80 months (Mean 17.6 ± 18.6 months). Fifteen (37.5%) of the transplant recipients received acyclovir prophylaxis for six months, one recipient (2.5%) received ganciclovir prophylaxis for three weeks while 24 recipients (60%) received no prophylactic therapy. There was no significant difference in the prevalence of seropositive CMV-IgM between transplant recipients who used CMV prophylaxis and those who did not (Fisher exact p = 0.45). Conclusion: Prophylaxis with acyclovir for six months showed no significant benefit on post-transplant CMV infection prevention in renal transplant recipients.

Risk factors for standard Tac-related nephrotoxicity in renal transplant recipients

Objective To investigate the factors for standard TAC - related nephrotoxicity in Tac - related nephrotoxicity in renal transplant recipients. Methods Clinical data of 132 patients in TAC - based regiment with a dose of 0. 15 - 0. 3 mg.kg -1.day -1and a trough level of 8 - 11 ug /L during the first 2 years post renal transplanta-

Pathologic analysis of donor grafts in 482 cases of renal transplantation recipients

Objective To evaluate the correlation between the pathologic findings of donor renal grafts and the post-transplantative diseases throuth the biopsies of donor grafts in 482 cases. Methods The renal structures of biopsies of the donor grafts in 482 cases were observed under microscope, and the pathologic findings combined with the post-transplantative conditions were analysed. Results After transplantation, acute rejection occurred in 71 cases,of when 16(22.5%) had adverse changes in donor grafts; chronic allograft nephropahty developed in 17 cases, of whom 7 (41.2% ) had adverse changes in donor grafts; elevated sera creatinine levels with unknown causes occurred in 39 cases, of whon 7(18.0% ) had adverse changes in donor grafts. The lesion of donor renal grafts had nothing to do with the acute rejection or other abnormalities after operation ( r≤ 0.3) but some kind of lesion had certain correlation with chronic allograft nephropathy(CAN, r 】0.3). Conclusion Routine biopsy of donor renal graft is

Metabolic and functional effects of exercise training in diabetic kidney transplant recipients

BACKGROUND Physical activity levels are significantly lower in kidney transplant(KT)recipients compared to the general population.The effects of exercise training in KT recipients with diabetes mellitus remain unclear,and so little is known about the role of increased exercise on cardiovascular risk and metabolic profile of KT patients.AIM To investigate the effects of a 6-mo home-based exercise training program on functional capacity,glucose levels and lipid profile of diabetic KT patients.METHODS In total,21 type II diabetic KT recipients were randomly assigned into two groups:Exercise(n=11,aged 52.9±10.1 years)and control(n=10,aged 53.01±9.5 years).All participants at baseline and the end of the study underwent biochemical tests for fasting plasma glucose levels,glycated hemoglobin and lipid profile and cardiopulmonary exercise testing for maximum oxygen uptake[(VO2)peak]estimation.The exercise group followed a 6-mo supervised home-based aerobic and progressive resistance exercise program of moderate intensity 3 times per week,while the control group continued to receive usual care.RESULTS At the end of the 6-mo study,the exercise group had significantly lower values in fasting plasma glucose by 13.4%(from 120.6±28.9 mg/dL to 104.8±21.9 mg/dL,P=0.01),glycated hemoglobin by 1.5%(from 6.7%±0.4 to 6.6%±0.4,P=0.01)and triglycerides by 8.5%(from 164.7±14.8 mg/dL to 150.8±11.6 mg/dL,P<0.05)and higher values in high-density lipoprotein by 10.2%(from 51.4±8.8 mg/dL to 57.2±8.7 mg/dL,P<0.05)and(VO_(2))_(peak)by 4.7%(from 22.7±3.3 to 23.8±4.2,P=0.02)than the control group.There were statistically significant differences between the two groups at the end of the study for fasting plasma glucose(decreased by 9.6%,P<0.05),triglycerides(decreased by 4.5%,P=0.04)and(VO_(2))_(peak)(increased by 4.4%,P=0.01).Finally,after training,there was a moderate,positive linear relationship between(VO_(2))_(peak)and glycated hemoglobin in the exercise group(r=0.408,P=0.03).CONCLUSION The results demonstrated that a 6-mo home-based mixed type exercise training program can improve the functional capacity,levels of glucose and lipid profile of diabetic KT recipients.

Pharmacokinetics of enteric-coated mycophenolate sodium in Chinese renal transplantation recipients

Background Mycophenolic acid （MPA） as an anti-proliferative immune-suppressive agent is used in the majority of immunosuppressive regimens in solid organ transplantation. This study aimed to investigate the pharmacokinetic （PK） characteristics of enteric-coated mycophenolate sodium （EC-MPS） and area under the curve （AUC） from 0 to 12 hours with limited sampling strategies （LSSs） in Chinese renal transplant recipients. Methods This study was conducted in 10 Chinese renal transplant patients receiving living donor and treated with EC-MPS, cyclosporine, and corticosteroids. MPA concentrations were measured by enzyme multiplied immunoassay technique （EMIT）. Whole 12-hour PK profiles were obtained on Day 4 after operation. LSSs with jackknife technique, multiple stepwise regression analysis, and Bland-Altman analysis were developed to estimate MPAAUC. Results The mean maximum plasma concentration, the mean time for it to reach peak （Tmax）, and the mean MPA AUC were （11.38±2.49） mg/L, （4.85±3.32） hours, and （63.19±13.54） mg.h.L1, respectively. Among the 10 profiles, MPA AUC of four patients was significantly higher than that of the other six patients, and the corresponding Tmax was significantly longer than that of the other six patients. No patient exhibited a second peak caused by enterohepatic recirculation. The best models were as follows： 27.46＋0.94C3＋3.24C8＋2.81C10 （f2=0.972）, which was used to predict AUC of fast metabolizer with a mean prediction error （MPE） of -0.21% and a mean absolute prediction error （MAE） of 2.59%; 36.65＋3.08Ce＋5.30C10-4.04C12 （r2=0.992）, which was used to predict AUC of slow metabolizer with a MPE of 0.58% and a MAE of 1.95%. Conclusions The PKs of EC-MPS had a high variability among Chinese renal transplant recipients. The preliminary PK data indicated the existence of slow and fast metabolizer. These findings may be associated with the enterohepatic rec.irculation.