Group Of Renal Transplant Recipients Research Articles

M-TOR Inhibitors in Kidney Transplantation: A Comprehensive Review

Mammalian target of rapamaycin inhibitors (mTOR-I) has been in use in kidney transplantation for over two decades. Since their introduction, they have been used in different combination immunosuppressant for low risk group renal transplantation. They have been in use in the various (Calcineurin inhibitors) CNI-free protocols, either as De novo regiments, or by conversion from CNIs at a later stage. Many of these studies reported comparable graft rejection rate and a better kidney function (eGFR) compared to standard CNI protocols. Also mTOR-I when used in combination with CNIs, facilitated the use of lower doses of CNIs with the resultant reduction of CNI related side effects, without seriously compromising graft outcome. They are of particular interest among certain group of renal transplant recipients, including those with malignancy, post-transplant encapsulating peritoneal scelorosis, CMV and BK virus infections. Moreover, protocols containing mTOR-I showed comparable results to standard protocols among recipients of kidneys from extended-criteria transplantation. However, only few reports studied their use in high risk group renal transplantation, with variable outcomes. There is a noticeable drop in their popularity in the recent years, and their use was associated with multiple adverse events, in addition to a recent concern of their link to increased mortality. Also, a high discontinuation rate was demonstrated across many of the studies available to date. More studies are still needed to clarify the above-mentioned concerns.

RENAL TRANSPLANT RECIPIENTS

Introduction: Good glycemic control and lipid modification are potentiallyimportant intervention for improving outcome after kidney transplantation. Objective: Todetermine the frequency of dyslipidemia and its types in renal transplant recipients (RTRs),and to observe impact of hyperglycemia on their lipid profile. Design: Case control study.Period: June 2011 to May 2012. Setting: Kidney Dialysis Department of Jinnah HospitalLahore, Urology Department of Mayo Hospital Lahore and Pathology Department AllamaIqbal Medical College Lahore. Patients and Methods: A total of 40 RTR were included in thestudy. An equal number of sex and age matched healthy subjects were considered as controlgroup. The patients were on regular post transplant follow up in Kidney Dialysis Department ofJinnah Hospital Lahore and Urology Department of Mayo Hospital Lahore and had no clinicalor laboratory evidence of graft rejection, post-transplant diabetes mellitus, hypertension or intercurrent infection. Total cholesterol (TC), triglyceride (TG), High density Lipoprotein-Cholesterol(HDL-C), and Glycohemoglobin A1c (HbA1c) were estimated in all subjects. These subjectswere divided into Diabetic and non-diabetic groups, according to level of HbA1c. Results:The mean age of the RTR was 34.5± 9.02 years and the mean duration of transplant was36.70 ± 38.07 months. RTRs showed significantly high mean levels of TG (p< 0.002), TC (p<0.00), LDL-C (p< 0.01), and HDL-C (p< 0.05) as compared to the control subjects. ElevatedTC, TG, LDL-C and low HDL was observed in 32.5%, 72.5%, 52.5%, and 60% of total RTR,respectively. The mean levels of TC, TG and HDL-C were increased in Diabetic transplant groupas compared to non-diabetic RTR. Percentage of elevated TC, TG, LDL-C and decreased HDLin diabetic group of RTR versus non diabetic RTR was 43.7% Vs 25% , 81.2% Vs 66.6%, , 62.5%Vs 44.4%, and 50% Vs 66.6% respectively. There was a positive relationship between HbA1cand lipid profile (TC, TG, and LDL – C) in both Diabetic and Non Diabetic Group. A statisticallysignificant correlation of the mean HbA1c levels with TG level was observed in Diabetic RTR.Conclusion: Dyslipidemia in our RTRs was observed as elevated levels of TC, TG and LDL-C. Indiabetic RTR, a statistically significant positive correlation of the HbA1c levels with TG level wasobserved. More rigorous glycemic control and lipid modification will reduce the development ofmicrovascular complications.

Prevalence of benign cutaneous disease among Oxford renal transplant recipients

The burden of malignant and benign cutaneous disease among renal transplant recipients (RTR) is substantial. Little attention is given to non-malignant skin problems in the literature despite their potential impact on quality of life or on aesthetics - which may contribute to poor compliance with immunosuppressive medications post-transplantation. The aim of this study was to examine prevalence of benign cutaneous disease in a group of RTRs and identify risk factors for individual cutaneous conditions. All cutaneous findings were recorded in a single full body skin examination of 308 RTRs. Data on medical, transplant and medication history were obtained from questionnaire and medical records. Odds ratios were calculated to look at associations between benign cutaneous diseases and various potential risk factors after controlling for gender, age, time since transplantation and skin type. Cutaneous infections such as viral warts (38%), fungal infection (18%) and folliculitis (27%) were common and usually chronic. A range of pilosebaceous unit disorders were observed with hypertrichosis being strongly associated with ciclosporin (P<0.0001). Other iatrogenic cutaneous effects included gingival hyperplasia (27%) and purpura (41%). We identified seborrhoeic warts and skin tags in 55% and 33% respectively. Inflammatory dermatoses were rare (<2%) apart from seborrhoeic dermatitis (9.5%). In this first comprehensive study on prevalence of benign cutaneous diseases in a UK transplant population, a wide range of skin disorders was identified. It is therefore important that RTRs have access to dermatology services post-transplantation for appropriate management of benign cutaneous conditions as well as early detection of cutaneous malignancy and education regarding risks of sun exposure.

Determinants of enhanced thromboxane biosynthesis in renal transplantation

Despite great improvement in patient and graft survival, the long-term morbidity and mortality in renal transplant recipients (RTRs) are still significant, with a high incidence of cardiovascular disease-related deaths. We investigated thromboxane (TXA2) biosynthesis and endothelial and coagulative activation in 65 patients who received a renal transplant. The rate of TXA2 biosynthesis (urinary 11-dehydro-TXB2 excretion largely reflects platelet TXA2 production in vivo) was significantly (P < 0.0001) higher in RTRs than in healthy subjects. Plasma von Willebrand factor (vWF) and thrombin-antithrombin (TAT) complexes were significantly higher (P < 0.001) in RTRs compared with controls. Urinary 11-dehydro-TXB2 directly correlated with plasma vWF and cholesterol. We next examined the relative influence of cyclosporine A (CsA) on TXA2 biosynthesis and endothelial activation, comparing a group of RTRs not receiving CsA with an age- and sex-matched group of patients treated with CsA. Urinary excretion of 11-dehydro-TXB2 and plasma levels of vWF were significantly increased in RTRs who received CsA compared with those who did not. After an overall follow-up of 120 months, RTRs who experienced cardiovascular events had a higher frequency of abnormal plasma levels of vWF than patients who remained event free. Renal transplantation is associated with in vivo platelet activation highly related to endothelial activation. This is particularly evident in CsA-treated patients. Administration of drugs that are able to reduce or eliminate thromboxane-dependent platelet activation in vivo may be beneficial to reduce the risk of cardiovascular events in RTRs.

Prevalence of Superficial Dermatomycoses in 73 Renal Transplant Recipients

Background: Because of chronic immunosuppressive therapy, the skin of renal transplant recipients (RTR) is considered more liable to fungal infections. Aim: The aim of the study was to analyze the prevalence of superficial dermatomycoses in a chronically immunosuppressed group of RTR who live in northern Italy and to verify the eventual relationship between the onset of mycoses, the immunosuppressive regimen and the interval of time elapsed after the transplantation. Methods: 73 RTR were submitted to a complete dermatological examination for fungal infection. Skin scrapings were taken from the upper back, from the 4th toe web of all patients and from any suspicious lesion. Results: 31 patients (42.5%) were affected by dermatomycosis. Pityriasis versicolor (PV) was present in 20 RTR (27.4%), fungal infection of the 4th toe web in 10 patients (13.7%) and onychomycosis in 9 RTR (12.3%). Trichophyton mentagrophytes was the most common dermatophyte. The prevalence of dermatomycoses was higher in the group of patients treated with azathioprine-cyclosporine-steroids and in those who had received their renal transplant in the previous 1–5 years. Conclusions: PV was the most frequent dermatomycosis and showed a higher prevalence than in the normal population. The prevalence of fungal infection of the 4th toe web and onychomycosis was similar to that found in the immunocompetent population, but the length of interval after transplantation seemed to increase the probability of their occurrence and of mixed or simultaneous fungal infections in the same patient.

Urinary enzyme excretion by renal-transplant recipients in relation to interval after transplantation.

We determined the urinary excretion of the enzymes aminopeptidase (EC 3.4.11.2), alkaline phosphatase (EC 3.1.3.1), gamma-glutamyltransferase (EC 2.3.2.2), and N-acetyl-beta-glucosaminidase (EC 3.2.1.30) in two groups of renal-transplant recipients at different times after transplantation (1.8 months and 52 months, respectively). Both groups of patients showed a higher rate of enzyme excretion than did a reference group of healthy persons. More aminopeptidase and N-acetyl-beta-glucosaminidase were excreted during the early period after transplantation than later. The time-dependence of urinary enzyme excretion was confirmed in six renal-transplant recipients studied during the course of 15 months after transplantation. There was a general correlation between the extent of urinary enzyme excretion and both the time after transplantation and the daily dose of prednisolone. Therefore, it is necessary to take into account this influence on the extent of urinary enzyme in renal-transplant recipients if urinary enzyme excretion is used as an indicator of renal disorder and especially as an early predictor of transplant rejection.