Effects of Wuzhi capsules on tacrolimus concentration in renal transplant recipients with different CYP3A5 genotypes / 中华泌尿外科杂志

Objective:To study the effect of Wuzhi capsules on tacrolimus trough concentration in kidney transplant recipients with different CYP3A5 genotypes.Methods:From June 2015 to October 2019, 162 patients who underwent renal transplantation for the first time were retrospectively analyzed. The patients were divided into two groups, combined and uncombined, according to whether combined with Wuzhi capsules. There were 81 cases in the uncombined group (55 males and 26 females), and 81 in the combined group (62 males and 19 females). There was no significant difference between the two groups( P=0.219). The ages of the uncombined group and the combined group were (39.26±11.91) years old and (37.21±10.88) years old ( P=0.103), the weights were (62.39±11.64) kg and (66.18±13.89)kg ( P=0.298), systolic blood pressure were (147.28±20.24) mmHg and (145.00±16.42) mmHg (1 mmHg=0.133 kPa)( P=0.276), diastolic blood pressure were (92.25±13.87) mmHg and (92.20±12.53) mmHg ( P=0.886), alanine aminotransferase were (12.24±8.59) U/L and (17.06±13.11) U/L ( P=0.015), aspartate aminotransferase were (17.76±9.12) U/L and (16.57±8.37) U/L ( P=0.463), fasting blood glucose were (8.70±3.48) mmol/L and (7.18±2.74)mmol/L ( P=0.006), hemoglobin were (98.96±17.53) g/L and (101.05±18.67) g/L ( P=0.789), creatinine were (665.22±296.55) μmol/L and (797.32±279.32) μmol/L ( P=0.007), estimated glomerular filtration rate were (11.47±14.11) ml/(min·1.73m 2) and (8.85±3.71) ml/(min·1.73m 2) ( P=0.130)in the kidney transplant recipients before surgery. Among the 162 cases in this study, there were 86 cases (53.09%) of CYP3A5*1*3 genotype, 17 cases (10.49%) of CYP3A5*1*1 genotype, 59 cases (36.42%) of CYP3A5*3*3 genotype, and the minimum allele frequency of CYP3A5*1 was 37.04%. In the uncombined group, CYP3A5*1*3 genotype 39 cases (48.15%), CYP3A5*1*1 genotype 5 cases (6.17%), and CYP3A5*3*3 genotype 37 cases (45.68%). In the combined group, CYP3A5*1*3 genotype 47 cases (58.02%), CYP3A5*1*1 genotype 12 cases (14.81%), and CYP3A5*3*3 genotype 22 cases (27.16%), with statistically significant differences in the two groups ( P=0.024). The patients were treated with a triple immunosuppressive regimen (tacrolimus+ mycophenolate mofetil+ glucocorticoid) based on tacrolimus [initial dose: 0.15-0.30 mg/(kg·d)], combination of Wuzhi capsules in the combination group (11.25 mg, twice a day). The trough concentration of tacrolimus was detected by enzyme-linked immunosorbent assay, compare the difference in the trough concentration of tacrolimus between the two groups. The relationship between the effect of Wuzhi capsules and CYP3A5 gene polymorphism was compared, and compare the changes before and after the application of CYP3A5 genotype combined with Wuzhi Capsules. The influencing factors of tacrolimus trough concentration were analyzed by multiple linear regression. Results:In the combined with Wuzhi capsules, the dose corrected trough concentration (C 0/D) of tacrolimus was higher than that in patients without Wuzhi capsules, and the extent of increase was related to genotype. The C 0/D of tacrolimus in patients with CYP3A5*3*3 genotype in the combination and non-combination groups were (12.15±2.95) (ng·ml -1/0.1mg·kg -1·d -1) and (9.99±2.33) (ng·ml -1/0.1mg·kg -1·d -1) ( P=0.004), CYP3A5*1*3 genotype were (11.11±3.20) (ng·ml -1/0.1mg·kg -1·d -1) and (6.86±1.62) (ng·ml -1/0.1mg·kg -1·d -1) ( P<0.001), and there were significant difference. However, CYP3A5*1*1 genotype were(8.29±2.64) (ng·ml -1/0.1mg·kg -1·d -1) and (6.16±2.87) (ng·ml -1/0.1mg·kg -1·d -1) ( P=0.160), there was no significant difference. The tacrolimus C 0/D of the combined group before and after the Wuzhi capsule were as follows: CYP3A5*3*3 genotype: (7.18±2.33)(ng·ml -1/0.1mg·kg -1·d -1) and (13.33±3.09) (ng·ml -1/0.1mg·kg -1·d -1) ( P<0.001); CYP3A5*1*3 genotype: (5.14±2.14) (ng·ml -1/0.1mg·kg -1·d -1) and (10.61±3.20) (ng·ml -1/0.1mg·kg -1·d -1) ( P<0.001); CYP3A5*1*1 genotype: (5.17±3.75) (ng·ml -1/0.1mg·kg -1·d -1) and (8.31±2.74) (ng·ml -1/0.1mg·kg -1·d -1)( P=0.002), and the differences were statistically significant. The results of multiple linear regression showed that the combination of Wuzhi capsules (β=0.508, P<0.001) and CYP3A5 genotype(CYP3A5*1*3 and CYP3A5*3*3: β=-0.361, P<0.001; CYP3A5*1*1 and CYP3A5*3*3: β=-0.425, P<0.001)could influence the trough concentration. The sex (β=-0.100, P=0.124) and age (β=-0.003, P=0.967) of renal transplant recipients had no statistical significance to tacrolimus C 0/D. Conclusions:In the renal transplant patients, CYP3A5 genotype and combined use of Wuzhi capsules are the main factors affecting tacrolimus C 0/D. In order to achieve the expected trough concentration as soon as possible, the interaction between CYP3A5 genotypes and drug combination should be considered.

Detection of cytomegalovirus disease by real-time quantitative PCR targeting immediate early gene (ppUL83) in different samples among post-renal-transplant recipients

Renal transplantation is a treatment option for end-stage renal disease (ESRD). Cytomegalovirus (CMV) infection was analysed among symptomatic and asymptomatic post-renal-transplant recipients (PRTRs). A total of 30 PRTRs were enrolled. DNA was extracted and quantitative real-time PCR for CMV (CMV R-Gene, France) targeting ppUL83 gene was performed on whole blood, urine and saliva. The detection rate of CMV was found to be 27% (n = 8) in different samples, including whole blood, urine and saliva. Among 30 PRTRs, 53% (n = 16) of the PRTRs did not shed virus in saliva. About 7% of CMV was detected only in saliva among PRTRs who were symptomatic.

Association of Genetic Polymorphism in ABCC2 with Cyclosporine Induced Liver Injury in Renal Transplant Recipients / 中国药师

Objective: To investigate the association between ABCC2 gene polymorphisms and cyclosporine-induced liver injury in re-nal transplant recipients. Methods: The renal transplant recipients were divided into the liver injury group and the control group. Five single nucleotide polymorphisms ( rs4919395, rs2804398, rs4148394, rs4148397 and rs3740065) of ABCC2 were detected by high-throughput technique. The genotypes and haplotypes were analyzed between the groups. Results: There were 35 patients and 182 patients respectively in the liver injury group and the control group. No significant differences in alleles and genotypes were found between the groups (P>0. 05), and the SNP haplotypes showed no significant difference between the groups (P>0. 05). Conclusion: There is no association of ABCC2 polymorphisms (rs4919395, rs2804398, rs4148394, rs4148397 and rs3740065) with the liver injury induced by cy-closporine.

Determination of plasma concentration of mycophenolic acid and mycophenolic acid glucuronide by HPLC / 中国生化药物杂志

Objective To develop an HPLC method for the determination of mycophenolic acid(MPA), mycophenolic acid glucuronide(MPAG) in plasma.Methods The samples were precipitated with zinc sulphate-methanol solution before injection.Carbamazepine was selected as internal standard,ZORBAX XDB C18 (4.6 mm ×250 mm,5 μm) column was used and the flow rate was 1 mL/min.The mobile phase consisted of methanol-acetonitrile-potassium dihydrogen phosphate buffer solution(gradient elution) .The column temperature was 30℃ and the detective wave length was 254 nm.And then the MPA,MPAG concentration of 32 patients in 7-14 days after renal transplantion were determined.Results The assay was linear within 0.2-50μg/mL for MPA, 2.5-500 μg/mL for MPAG(r>0.999).Absolute recovery rates of MPA,MPAG were more than 80%, the recoveries were between 90%-110%.The intra-day and inter-day RSDs were both lower than 10%.Totally 32 cases of renal transplantion patiens were with mycophenolate mofetil at the dose of 1-1.5 g/d,and MPA in plasma was within the range of 0.32-6.19μg/mL,MPAG in plasma was within the range of 9.52-149.25μg/mL.Conclusion The method is accurate, convenient and rapid, which could be used in the quantitative determination of plasma concentration of MPA,MPAG in renal transplantion patients.

Study of systemic fungal infections in renal transplant recipients

Background: Despite technical, immunological, and therapeutic advances in the field of renal transplantation, infections remain a major barrier to successful outcome. Fungal infections (14%) after renal transplantation, despite a lower incidence than bacterial and viral infections, remain a major cause of morbidity and mortality. This study was conducted to assess the impact of invasive fungal infections in our renal transplant recipients. Aim: To study the clinical profile, risk factors for acquiring fungal infections, its outcome and the factors influencing outcome in living and deceased donor renal transplant recipients. Materials and methods: Renal transplant recipients both cadaveric and living-related during the time period between August 2008 and May 2011 admitted with systemic fungal infections in nephrology ward were included in the study. Data gathered included age, sex, date of transplantation, date of diagnosis, fungal pathogen, organs affected by infection, treatment and patient outcome. Microsoft excel 2007, Binomial and Student t tests were used for statistical analysis. Observation: Twenty two patients were diagnosed with systemic fungal infections during this period. The mean age of the study patients was 35.55 years. The male to female ratio was 1.75:1.Candida species (62%) are the commonest organisms causing fungal infection. Fungal infections commonly occurred in gastrointestinal tract (GIT), lung and urinary tract, each 22%. Fifty percent of patients with fungal infections expired. Graft loss occurred in 41% of patients. Conclusion: The mortality rate was 50%. Bone marrow suppression {Leukopenia (50%)} and hypoalbuminemia (59%) contributed to high mortality. Overall immunosuppression should be monitored periodically and kept at optimal level just enough to avoid rejection, thereby avoiding opportunistic infections.

Outbreak of Pneumocystis jirovecii pneumonia in renal transplant recipients on prophylaxis: Our observation and experience.

Pneumocystis jirovecii is a life‑threatening opportunistic pathogen affecting immunocompromised hosts, especially renal transplant recipients. This study reports an outbreak of seven such cases, both inpatients and outpatients, occurring in our hospital over a period of 4 months (January–April 2013). All patients were male with a median age of 38 years (range, 28–58 years); the median period between transplantation and diagnosis was 39.5 months (range, 11–123 months). One patient succumbed to the infection. Two were breakthrough cases, developing the infection while on prophylaxis, highlighting the need to view prophylaxis in light of the immunosuppression and clinical picture of such patients.

Intestinal parasitic infections in renal transplant recipients

The impact of intestinal parasitic infection in renal transplant recipients requires careful consideration in the developing world. However, there have been very few studies addressing this issue in Iran. This study was conducted to determine the prevalence of intestinal parasitic infections in renal transplant recipients in Iran. Stool specimens from renal transplant recipients and control groups were obtained between June 2006 and January 2007. The samples screened for intestinal parasitic infections using direct smear, formalin-ether sedimentation, Sheather's flotation and modified Ziehl-Neelsen staining methods. Out of 150 renal transplant recipients, 33.3 percent (50), and out of 225 control group, 20 percent (45) were infected with one or more type of intestinal parasites. The parasites detected among patients included Entamoeba coli (10.6 percent), Endolimax nana (8.7 percent), Giardia lamblia (7.4 percent), Blastocystis spp. (4.7 percent), Iodamoeba butschlii (0.7 percent), Chilomastix mesnili (0.7 percent) and Ascaris lumbricoides (0.7 percent). Multiple infections were more common among renal transplant recipients group (p < 0.05). This study highlights the importance of testing for intestinal parasites among Iranian renal transplant recipients. Routine examinations of stool samples for parasites would significantly benefit the renal transplant recipients by contributing to reduce severe infections.

Skin lesions in renal transplant recipients: A single center analysis.

Background: The chronic use of immunosuppressants in renal transplant recipients (RTRs) predisposes them to a variety of skin manifestations. Studies on skin lesions in RTRs from India have been limited. Aim: To study the prevalence and clinical spectrum of skin diseases in RTR in patients attending the Nephrology clinic of a tertiary care hospital in South India. Methods: Between October 2002 and June 2003, 365 RTRs were evaluated for skin lesions, including 280 examined after renal transplant (group A) and 85 examined once before and then monthly after transplant for a period of 6 months (group B). Results: A total of 1163 skin lesions were examined in 346 RTRs (94.7%) including lesions of aesthetic interest (LAI) [62.3%] followed by infections [27.3%]. All LAI were drug-related manifestations, making it the most common skin lesion, while fungal (58.7%) and viral (29.3%) infections constituted majority of lesions caused by infection. Lesions related to neoplasms were relatively uncommon (2.1%) and all lesions were benign. Miscellaneous lesions constituted 8.3% of skin lesions, which included vaccine-induced necrobiotic granulomas at the site of Hepatitis B vaccination and acquired perforating dermatoses. Conclusion: Skin lesions among RTRs from India consist predominantly of drug-related LAI and infections and are different from the West in view of the paucity of neoplastic lesions.

Epidemiological aspects of hepatitis C virus infection among renal transplant recipients in Central Brazil

An investigation was conducted involving 255 renal transplant recipients in the state of Goiás, Central Brazil, to determine the prevalence of hepatitis C virus (HCV), its risk factors, the genotypes involved, and the level of alanine aminotransferase (ALT) present in the patients. All serum samples were tested for anti-HCV antibodies and HCV RNA. Forty-one patients were anti-HCV and/or HCV RNA positive, resulting in an overall HCV infection prevalence of 16.1 percent (95 percent CI: 11.9-21.3). A multivariate analysis of risk factors showed that a history of blood transfusions without anti-HCV screening, the length of time spent on hemodialysis, and renal transplantation before 1994 are all associated with HCV positivity. In HCV-positive patients, only 12.2 percent had ALT levels above normal. Twenty-eight samples were genotyped as genotype 1, subtypes 1a (62.5 percent) and 1b (31.3 percent), and two samples (6.2 percent) were genotype 3, subtype 3a. These data show a high prevalence of HCV infection and low ALT levels in the studied population. The risk factor analysis findings emphasize the importance of public health strategies such as anti-HCV screening of candidate blood and organ donors, in addition to the stricter adoption of hemodialysis-specific infection control measures. The present study also demonstrates that HCV genotype 1 (subtype 1a) is predominant in this population.

Skin Lesions Developing in Renal Transplantation Recipients / 대한피부과학회지

BACKGROUND: As the renal transplantation is rapidly becoming a standard treatment of end stage renal disease, a varieties of skin lesions in renal transplant recipients are being encountered in Korea. However, there have been little studies concerning the incidence and clinical feature of skin lesions has not been well addressed yet. OBJECTIVE: We examined the skin manifestations in renal transplant recipients. METHOD: We attempted to assess the dermatologic problems in 58 renal transplant recipients, who had been managed at Keimyung University Medical center between December, 2001, and July, 2002. RESULTS: The results are summarized as follows; Among the 58 patients, the number of male and female patients were 31(53.4%) and 27(46.6%) respectively. The mean age was 38.3 years and the mean duration of renal transplatant was 38.7 months. They had one more skin lesions. Among the 58 patients, skin infection was found in 61(105%), drug-associated skin lesions in 31(53.4%), malignant skin tumor in 0(0%) and other skin lesions in 6(10.3%). Viral infections were VZV infection(15 cases, 25.9%), HPV infection(11 cases, 19%), HSV infection(7 cases, 12.1%) and molloscum contagiosum(2 cases, 3.4%). Fungal infections were superficial mycosis(16cases, 27.6%) and deep mycosis(1 case, 1.7%). Bacterial infection was found in 5(8.6%). Drug-associated skin lesions were hypertrichosis(17 cases, 29.3%), acne(11 cases, 19%), xerosis(7 cases, 12.1%), facial flusing, purpura and gingival hyperplasia(3 cases, 5.2%), respectively, telangiectasis and urticaria(2cases, 3.4%) respectively and alopecia(1 case, 1.7%). Other skin lesions included seborrheic dermatitis(8 cases, 13.8%), nummular dermatitis(3 cases, 5.2%), prurigo nodularis, scleredema, seborrheic keratosis and toxic erythema(1 case, 1.7%). CONCLUSION: Long term use of immunosuppresive agents is associated with high incidences of skin disease. Education of patients and medical staff for early detection and treatment of skin lesions is important.