Non diabetic renal disease in type 2 diabetes mellitus

AIM: The aim of this analysis of renal biopsies in people with type 2 diabetes was to know the prevalence and nature of non-diabetic renal disease (NDRD) and to note its correlation with the duration of diabetes, extent of proteinuria and presence or absence of retinopathy. METHODS: From January 2000 to December 2004, 160 people with type 2 diabetes with clinically suspected NDRD underwent renal biopsy reported by a single pathologist. The case records of these patients were retrospectively analysed. Based on the biopsy findings, patients were grouped as Group I, isolated NDRD; Group II, NDRD with underlying diabetic glomerulosclerosis; and Group III, isolated diabetic glomerulosclerosis. The relation of histology with clinical profile in each group was noted and statistically analysed using strata 6 software. RESULTS: Of the 160 patients studied, 118 were males and 42 were females (2.8:1). The average age was 51.35 years (30-79). Indications for renal biopsy included: nephrotic syndrome in 55 (34.37%), acute renal failure (ARF) in 49 (30.62%), rapidly progressive renal failure (RPRF) in 24 (15%), absent retinopathy in 19 (11.87%), haematuria in 10 (6.25%) and acute on chronic renal failure (CRF) in three (1.87%) patients. Group I included 68 patients (42.50%), Group II included 48 patients (30%) and Group III included 44 patients (27.50%). The mean duration of diabetes was 5.37, 10.12 and 6.86 years in Groups I, II and III respectively. The duration of diabetes was significantly less in Group I compared with Group II and III combined (5.37 vs 8.53; P < 0.001). Diabetic retinopathy was absent in 61 (38.13%) patients, of whom 41 (67.21%) had isolated NDRD. The most common NDRD were acute interstitial nephritis (18.1%), post infectious glomerulonephritis (17.24%), membranous nephropathy (11.20%) and focal segmental glomerulosclerosis (7.75%). CONCLUSIONS: Prevalence of NDRD (either isolated or superimposed on underlying diabetic glomerulosclerosis) is very high in appropriate clinical settings. The shorter duration of diabetes and the absence of retinopathy, especially when associated with nephrotic proteinuria, strongly predict NDRD.     

Vitamin C augments the renal response to L-arginine in smokers.

BACKGROUND: In the coronary and the forearm circulations, endothelium-dependent vasomotion is impaired in smokers, but can be augmented by -arginine or vitamin C. We examined whether smoking similarly affects the renal circulation. METHODS: In 20 smokers (age 26 +/- 4 years) and in 20 non-smokers (age 28 +/- 3 years) changes of renal plasma flow (RPF), glomerular filtration rate (GFR), blood pressure and heart rate in response to the subsequent intravenous infusions of N(G)-monomethyl--arginine (L-NMMA), -arginine and -arginine plus vitamin C were studied by use of a constant infusion input clearance technique. RESULTS: Systemic haemodynamic parameters did not differ between smokers and non-smokers during each experimental phase. At baseline, RPF and GFR were similar between the groups. The infusion of L-NMMA led to a similar decrease of RPF, while GFR did not change in either group. During the infusion of -arginine RPF increased similarly. Finally, the co-infusion of -arginine plus vitamin C led to a significantly greater increase of RPF (+277 +/- 395 vs +79 +/- 76 ml/min, P = 0.03) and GFR (+12.1 +/- 10.6 vs +3.4 +/- 11.2 ml/min, P = 0.02) in smokers as compared to non-smokers. CONCLUSIONS: L-NMMA-induced vasoconstriction of the renal vasculature was similar in smokers compared to non-smokers. -arginine alone induced a similar increase of RPF. The co-infusion of vitamin C and -arginine led to a greater increase of RPF and GFR in smokers. This might suggest that oxidative stress is increased in the renal vasculature of smokers.     

Increased frequency of angiotensin-converting enzyme DD genotype in patients with type 2 diabetes in Taiwan.

BACKGROUND: Diabetes is one of the major causes of end-stage renal failure in the Taiwanese population. Previous studies have shown that angiotensin-converting enzyme (ACE) inhibitor can improve glucose utilization and suppress hepatic glucose production and the renin-angiotensin system may play an important role in the initiation and progression of diabetic nephropathy. Thus, ACE gene polymorphism may be associated with type 2 diabetes and diabetic nephropathy. METHODS: To investigate the distribution of ACE-I/D genotype in type 2 diabetes and diabetic nephropathy, we examined 336 patients with type 2 diabetes (157 without nephropathy and 179 with nephropathy) and 263 age-matched normal controls. The diagnosis of nephropathy was made when daily protein loss exceeded 500 mg. ACE gene polymorphism was analysed by use of polymerase chain reaction. RESULTS: Our study revealed that the frequency of the D allele of the ACE gene was 29.3% in normal controls. The frequency of ACE DD genotype was significantly higher in type 2 diabetics compared with normal controls (18.2 vs 9.1%, P<0.01). The frequency of ACE DD genotype in patients with diabetic nephropathy was significantly higher than in patients without nephropathy (22.3 vs 13.4%, P<0.05). To determine whether ACE gene polymorphism was associated with the severity of diabetic nephropathy, we divided patients with diabetic nephropathy into dialysis and non-dialysis groups. The frequency of ACE DD genotype in the dialysis group was significantly higher than in non-dialysis group (28.7 vs 15.3%, P<0.05). CONCLUSION: Our results indicate that the frequency of ACE DD genotype is markedly higher in patients with type 2 diabetes, and the ACE DD genotype is significantly associated with diabetic nephropathy.     

A multicentre study of registration on renal transplantation waiting list of the elderly and patients with type 2 diabetes.

BACKGROUND: Studies in the USA have shown that some patients (African-Americans, women, the elderly and diabetics) were less likely to receive renal transplants. In order to identify patient characteristics modifying the likelihood of being wait-listed, we studied registration on renal transplantation waiting list (WLR) focusing on elderly (age > or =60 years) and on patients with type 2 diabetes (D2) in three departments of nephrology in the Rh?ne-Alpes county in France. METHODS: In a cohort of 549 patients who reached end-stage renal disease (ESRD) between 1995 and 1998 in these units, we analysed the rates of pre-transplant evaluation (PTE), the duration of PTE, the rates of exclusion from transplantation by PTE and the rates of WLR. With Cox regression model, we identified the characteristics that have independent and significant effects on the likelihood of being registered after the first renal replacement therapy (RRT). RESULTS: In this cohort, 185 patients (33.7%) were wait-listed by 31.03.00 and no patient > or =70 years was evaluated or registered. In univariate analysis, PTE and WLR rates were lower in the elderly (21.5 and 20.0%, respectively) than those <60 years (79.1 and 70.2%, P < 0.001) and in D2 (33.0 and 24.2%) than in non-D2 (65.8 and 60.6%, P < 0.001). The duration of PTE was longer in D2 than in non-D2 (12.7 +/- 11.0 vs 7.5 +/- 7.1 months, P < 0.01). Among patients excluded from PTE, more patients without relevant co-morbidities [e.g. rapidly progressive ESRD, cardiovascular disease (CVD), malignancy] were present in the elderly (> or =70 years: 14.8%; 60-69 years: 17.0%; <60 years: 6.4%) and in D2 (18.0%) than in non-D2 (10.9%). The adjusted relative risks (aRR) of being wait-listed after first RRT were significantly lowered by age and D2 (aRR, 95% CI): 60-64 year olds (0.44%: 0.26-0.75), 65-69 year olds (0.07%: 0.03-0.20) and D2 (0.41%: 0.24-0.69). Other conditions associated with a lower aRR were rapidly progressive ESRD (0.21%: 0.08-0.55), CVD (0.59%: 0.36-0.94), malignancy (0.13%: 0.04-0.46) and psychosis (0.05%: 0.01-0.35). CONCLUSION: Advanced age and D2 were associated with low PTE and WLR rates even after adjustment for other patient characteristics.     

Histological predictors for renal prognosis in diabetic nephropathy in diabetes mellitus type 2 patients with overt proteinuria

Aim: Although several clinical risk factors for end‐stage renal disease in diabetic nephropathy are known, the pathological findings that may help predict renal prognosis have not yet been defined. Methods: We enrolled 69 diabetes mellitus type 2 patients with overt proteinuria and biopsy‐confirmed diabetic nephropathy with mesangial expansion, and retrospectively examined the association of histological and clinical findings with renal outcome. The median follow‐up duration was 52 months. Histological scoring was made according to that of Tervaert et al. Patients were divided into four groups according to glomerular classification (class 2a, mild mesangial expansion, n = 11; class 2b, severe mesangial expansion without nodular sclerosis, n = 15; class 3, nodular sclerosis, n = 36; class 4, global glomerulosclerosis observed in more than 50% of glomeruli, n = 7). Interstitial and vascular lesions were scored for each patient. A renal event was defined as a condition requiring the initiation of chronic dialysis or doubling of the serum creatinine level. Results: Cox proportional hazard analysis showed that the glomerular classes were not significant variables, while interstitial fibrosis, tubular atrophy and interstitial inflammation were independent variables associated with renal end‐point (HR: 3.36 (95% confidence interval: 1.21–9.32), 4.74 (1.26–17.91)). There were no significant differences in the renal survival rates between the glomerular classes 2a and 2b combined group and the glomerular class 3 group (P = 0.17, log‐rank test). Conclusion: Interstitial lesions but not glomerular lesions were a significant predictor for renal prognosis in diabetic nephropathy in type 2 diabetes patients with overt proteinuria.     

功能MRI评估2型糖尿病早期肾损害研究进展

糖尿病肾病（DKD）是糖尿病微血管并发症,亦为导致终末期肾脏病的主要原因。早期诊断、及时干预可有效控制DKD病情进展并改善预后。近年来,功能MRI （fMRI）逐渐用于定量评估2型糖尿病（T2DM）患者早期肾损害。本文就fMRI评估T2DM早期肾损害研究进展进行综述。     

The signification of stress in the aetiopathogenesis of type2 diabetes mellitus

The present study investigated the possible involvement of stress in the aetiopathogenesis of type 2 diabetes mellitus by using three different approaches: the role of chronic and subacute stress, assessed by a clinical interview in 300 newly discovered diabetic patients; the role of acute stress, by analysing the incidence of diabetes mellitus in connection with the earthquake of 4 March 1977; and investigating the autonomic reactivity of patients in whom stress was or was not involved in the onset of diabetes. The results showed: a chronic psychosocial stress was encountered in 44 per cent of 300 newly discovered type 2 diabetes mellitus patients; the number of newly registered diabetic cases was significantly (p < 0.001) higher in the month of May in 1977 (two months after the earthquake) as against the years preceding (1976) or following (1978) the earthquake; an autonomic hyperreactivity was found in the patients in whom stress was involved in the onset of diabetes as against the controls or diabetics in whom this factor was not involved in the onset of the disease.     

The burden of anaemia in type 2 diabetes and the role of nephropathy: a cross-sectional audit.

BACKGROUND: Anaemia is a common finding in patients with diabetes and constitutes an additional burden in patients with advancing age and comorbid vascular disease. This study examines the prevalence and predictors of anaemia in long-term outpatients with type 2 diabetes from three large clinical centres. METHODS: A full blood count was obtained in addition to routine testing in a cross-sectional survey of all patients with type 2 diabetes in long-term follow-up at the Austin Medical Centre, Melbourne (n = 670) and the Royal Prince Alfred Hospital (n = 915) and the Royal North Shore Hospital (n = 540), Sydney, Australia. The prevalence and correlates of anaemia (haemoglobin < 130 g/l in men and < 120 g/l in women) were identified using multivariate logistic regression. RESULTS: Roughly, one in five patients in each centre had anaemia. Patients at greatest risk could be readily identified by the presence of renal disease, manifested as impaired renal function and/or albuminuria in > 75% of patients with anaemia. Patients with diabetes and mild renal impairment [creatinine clearance (CCr) 60-90 ml/min/1.73 m(2)] were twice as likely to have anaemia as those with normal renal function (CCr > 90 ml/min/1.73 m(2)). Diabetics with moderate renal impairment (CCr < 60 ml/min/1.73 m(2)) were also twice as likely to have anaemia as those with mild renal impairment. Patients with anaemia were also more likely to have macrovascular disease, reflecting the high prevalence of nephropathy in these patients. CONCLUSIONS: Anaemia is a prevalent finding in patients with type 2 diabetes and represents a significant unrecognized burden. Patients at greatest risk can be identified by the presence of renal disease, either in the form of renal impairment and/or albuminuria.     

Time trends in the epidemiology of renal transplant patients with type 1 diabetes mellitus over the last four decades.

BACKGROUND: Diabetes mellitus (DM) type 1 is an important contributor to end-stage renal disease (ESRD) among younger transplant recipients. However, little is known about the changes in epidemiological characteristics of this population. Especially, time to reach ESRD may have changed in type 1 diabetic patients referred for transplantation, resulting in higher age at time of grafting. Such time trends may allow anticipating future developments regarding the demand for organ replacement in this patient group. METHODS: We retrospectively analysed 173 patients with type 1 DM undergoing renal transplantation at our institution, stratified into four groups according to year of reaching ESRD (A = 1973-1983, B = 1984-1990, C = 1991-1995 and D = 1996-2002). For each group we determined age at diagnosis of DM, age at time of reaching ESRD and age at time of transplantation. From these data, the interval from diagnosis of DM to ESRD and from ESRD to transplantation was calculated. The results were analysed in relation to gender, year of and age at onset of diabetes. RESULTS: Patients reaching ESRD in more recent years (group D) tended to be both younger at diagnosis of DM and older when reaching ESRD, resulting in higher mean age at transplantation (35.0, 37.5, 39.6 and 41.0 years in groups A, B, C and D, respectively). Accordingly, median duration to ESRD has significantly been prolonged over the last five decades in patients with type 1 DM undergoing renal transplantation (group A: 21.0, B: 20.7, C: 22.3 and D: 28.5 years; P < 0.0001), this finding being more pronounced in female patients. CONCLUSIONS: The results of our analysis are compatible with a change in epidemiology in patients undergoing kidney transplantation. Older age at time of reaching ESRD may impact significantly on the demand for renal grafts, as patients are already clearly older nowadays when being transplanted. From our data it cannot be concluded whether this development is due to a change in the progression of diabetic nephropathy or may simply reflect a change in the selection of type 1 diabetic patients referred for transplantation.     

Insufficient renal 1-alpha hydroxylase and bone homeostasis in aged rats with insulin resistance or type 2 diabetes mellitus

This study aimed to explore the relationship between insufficient renal 1-alpha hydroxylase (IRH) and bone homeostasis in type 2 diabetes mellitus (T2DM) or insulin resistance (IR) and to investigate whether IR plays a major role in the pathogenesis of both IRH and bone loss in T2DM. The experimental animal models of T2DM, IR, IR treated with vitamin D (VD), IR treated with 1-alpha hydroxyvitamin D (1α(OH) D, the product of renal 1-alpha hydroxylase), T2DM treated with VD, and T2DM treated with 1α(OH) D were established on 18-month-old male Wistar rats. For rats in each animal model and normal control rats, IR was detected by euglycemic insulin clamp technique (EICT) and glucose infusion rate (GIR, an index of IR) was calculated. Levels of serum 25-hydroxyvitamin D (25(OH)D) and serum active vitamin D (1,25(OH)₂D) were determined by radioimmunoassay (RIA), and 1,25(OH)₂D/25(OH)D ratio (1,25-25-R, an index of renal 1-alpha hydroxylase activity in vivo) was calculated; and bone mineral density (BMD) in femoral bone and lumbar vertebrae was measured by dual-energy X-ray absorption (DEXA). No significant difference was observed among the levels of 25(OH)D in all the rats. In IR rats, 1,25(OH)₂D level, 1,25-25-R, and BMD level were significantly higher than those in T2DM rats and were lower than those in normal control rats. In the aged rats with T2DM or IR, administration of VD had no effect on 25(OH)D level, 1,25(OH)₂D level, 1,25-25-R, and BMD level. Administration of 1α(OH) D had also no effect on 25(OH)D level but increased 1,25(OH)₂D level, 1,25-25-R, and BMD level. For the aged rats with T2DM or IR, GIR positively correlated with both levels of 1,25(OH)₂D and BMD, and 1,25-25-R positively and significantly correlated with levels of BMD. In T2DM or IR, IRH is a precipitating factor for bone loss. IR seems to play a major role in the pathogenesis of both IRH and bone loss in T2DM.     

Nephropathy in type 2 diabetes: current therapeutic strategies

Diabetic nephropathy is currently the commonest cause of end‐stage renal failure in most countries with a Western lifestyle. In addition to progressing to end‐stage renal disease, patients with type 2 diabetes and nephropathy are at especially high risk of cardiovascular death. A multifaceted approach, aiming not only to slow the progression of renal dysfunction but also to reduce the risk of associated complications, particularly cardiovascular disease, is advocated. Current evidence‐based guidelines serve a useful adjunctive role in providing target levels for therapeutic intervention.     

2型糖尿病合并肾脏损害的病理与临床分析

目的 分析2型糖尿病患者出现肾脏病变时病理诊断与临床表现的关系.探讨肾活检在2型糖尿病伴有肾脏病变诊断的意义.方法 分析52例尿检异常和（或）Scr升高的2型糖尿病患者的临床特征和病理改变特点.结果 52例2型糖尿病患者经肾活检,32例确诊为糖尿病肾病（DN）,占61.5%,其中3例为糖尿病肾病合并非糖尿病性肾脏疾病（NDRD）;余20例为非糖尿病性肾脏疾病,占38.5%.肾活检前后诊断符合率46.15%,误诊率19.23%.两组间除BUN、Scr、糖尿病病程和是否伴有糖尿病性视网膜病变有显著差异外,其他临床表现和实验室检查的差异均无统计学意义.结论 2型糖尿病伴肾脏病变时相当部分是非糖尿病性肾脏病变,单纯依靠临床资料常难以鉴别,肾活检对明确糖尿病伴肾病变的性质具有重要的意义.     

Efficacy of surgery in the management of obesity-related type 2 diabetes mellitus

BACKGROUND: It is estimated that up to 80% of persons with diabetes mellitus type 2 are overweight and in these patients it is recognized that effective weight control can lead to improvement or even resolution of their diabetes (Colagiuri et al.). All currently carried out operations for morbid obesity have been shown to improve diabetes, but there appears to be a variable response to surgery depending on several surgical and patient factors. METHODS: In this prospective review, we analysed the change in the diabetic status in 72 patients undergoing three different bariatric procedures in a single institution over 30 months. A review of the published work comparing the efficacy of the various procedures in achieving improvement or resolution of diabetes was also carried out and correlated to our findings. RESULTS: At an average follow up of 13 months, 50% of patients who had placement of laparoscopic adjustable gastric band had an improvement or resolution of their diabetes, compared with 95% of patients who had had laparoscopic sleeve gastrectomy or Roux-en-Y gastric bypass. Two of 12 (17%) laparoscopic adjustable gastric band patients had normal blood glucose levels off all diabetic medications compared with 7 of 21 (33%) laparoscopic sleeve gastrectomy and 27 of 39 (69%) Roux-en-Y gastric bypass patients. There was no significant association between the amount of weight lost and the return to euglycaemia. CONCLUSION: Direct comparison has shown a significant difference in the effects of different forms of bariatric surgery on type 2 diabetes, this is in keeping with evidence that surgery can lead to improvement in diabetes additional to that obtained by weight loss alone.     

Smoking and proteinuria impair vasodilatory response of intrarenal arteries to nitroglycerine in patients with type 2 diabetes mellitus.

BACKGROUND: Few studies have addressed the effect of vasodilatory stimuli on the intrarenal arterial system in type 2 diabetes mellitus (DM), and factors affecting its responsiveness. METHODS: One hundred twenty-four patients with type 2 DM without renal failure were enrolled, and 25 subjects served as controls. Using duplex Doppler sonography, resistive indices (RI) of interlobar arteries were measured before and after sublingual nitroglycerine (NTG) (0.3 mg) spray over a 10-min period. RESULTS: Per cent changes in RI (%DeltaRI) in the DM group were significantly less than in controls (P<0.05), as was the area over the %DeltaRI-time curve (AOC-%DeltaRI, total responsiveness to nitroglycerine) (P<0.05). In the DM group, significant negative correlations were found between AOC-%DeltaRI and age (r=-0.492, P<0.0001). AOC-%DeltaRI in DM patients with proteinuria was significantly lower than without it (P<0.003). AOC-%DeltaRI in smokers was also significantly lower than in nonsmokers (P<0.05). By multiple regression analysis of the DM group, AOC-%DeltaRI was found to be significantly and independently affected by age (beta=-0.394), smoking (beta=-0.211), and the presence of proteinuria (beta=-0.270; R(2)=0.354, P<0.0001). CONCLUSIONS: Diabetic patients have a lower level of responsiveness to NTG. Advanced age, smoking, and proteinuria significantly affect response to NTG in DM patients, suggesting that advanced intrarenal arteriosclerosis may be contributory. Smoking is suggested to be a risk factor for progression of diabetic nephropathy, likely contributing to poor responsiveness of the intrarenal arterial system to vasodilatory stimuli.     

Albuminuria in type 2 diabetes mellitus: from remission to progression

Objective Albuminuria is an early marker of renal impairment and a powerful factor of progression of renal disease in type 2 diabetes (T2D). Approximately, one-third of patients with T2D have micro- or macroalbuminuria and these patients have a high risk of progression toward End Stage Renal Disease (ESRD) as well as increased cardiovascular disease. The aim of this study was to determine the prevalence of remission, regression, persistence, and progression of albuminuria, and to evaluate the impact of change in albuminuria on kidney disease and cardiovascular disease in a prospective cohort of patients with T2D. Methods This is a prospective study. The Ethics Committee of Morocco’s Mohammed V University in Rabat approved the study protocol. Inclusion criteria targeted patients who were type 2 diabetics with albuminuria?>30?mg/day, and who had been regularly followed-up in nephrology consultation for at least 36 months. Results Five-hundred twenty-four patients were included. 75.8 and 24.6% of all patients had micro- and macroalbuminuria at enrollment in the study. At the end of the study, 91, 141, 199, and 93 patients had remission, regression, persistence, and progression of albuminuria, respectively. Remission of microalbuminuria to normoalbuminuria was observed in 23.6% of cases. Regression of macroalbuminuria to micro- was observed in 29.9% of cases. Conclusion In our study, the incidence of remission and/or regression of micro- and macroalbuminuria was higher. The incidence of ESRD and the occurrence of cardiac events were greater in the regression, persistence, and progression groups than in the remission of albuminuria group.     

男性2型糖尿病伴代谢综合征患者血清维生素D水平的研究

目的观察男性2型糖尿病(T2DM)患者血清25-羟维生素D[25(OH) D]水平与代谢综合征(MS)及其组分的关系。方法收集2018年3月至2019年6月在遵义医科大学附属医院内分泌科住院的男性T2DM患者203例及同期健康男性对照组(NC组) 42例,糖尿病患者中根据有无MS分为T2DM+MS组(122例)、T2DM+非MS组(81例),另根据符合MS诊断标准数目分为T2DM组(单纯糖尿病组)、T2DM+1组(除血糖异常外另加一个组分)、T2DM+2组(除血糖异常外另加两个组分)、T2DM+3组(除血糖异常外另加三个组分)、T2DM+4组(具备MS的所有组分),分析WC、BMI、SBP、DBP、FBG、Hb Alc、HOMAIR、TG、TC、LDL-C、HDL-C和25(OH) D水平。结果 T2DM+MS组及T2DM+非MS组血清25(OH) D水平均较NC组显著降低(P0.05),T2DM+MS组血清25(OH) D水平较T2DM+非MS组显著降低(P0.05)。NC组、T2DM组、T2DM+1组、T2DM+2组、T2DM+3组、T2DM+4组血清25(OH) D水平逐渐降低,差异有统计学意义(P 0.05)。Pearson相关分析显示血清25(OH) D水平与WC、BMI、SBP、DBP、HOMA-IR、FBG、TG、TC、LDL-C呈负相关(P0.05),与HDL-C呈正相关(P0.05)。多元线性回归提示HOMA-IR是血清25(OH) D水平的独立影响因素(P0.05)。二元Logistic回归分析显示血清25(OH) D是T2DM伴MS患者的独立保护因素(P0.05)。结论血清维生素D水平在男性T2DM患者代谢综合征的发生发展中可能起着一定作用。低水平维生素D与MS组分数目增加存在一定相关性。     

Effects of antioxidant supplementation on blood cyclosporin A and glomerular filtration rate in renal transplant recipients.

BACKGROUND: Transplant recipients have elevated oxidative stress, which has prompted suggestions that supplementary antioxidants may be beneficial. However, only a small number of clinical trials have investigated antioxidant supplementation in transplant recipients, with very few data on their effects on patients' immunosuppressive therapy. METHODS: A randomized placebo-controlled single-blind crossover trial was conducted in 10 renal transplant recipients (RTRs) taking cyclosporin A (CsA) as part of their immunosuppressive therapy. Each phase of the trial lasted 6 months, with a 6 month wash-out period in between. During one of the phases, patients consumed a tablet twice per day which delivered 400 IU/day of vitamin E, 500 mg/day of vitamin C and 6 mg/day of beta-carotene. RESULTS: During antioxidant supplementation, there was no change in CsA dose. Antioxidant supplementation resulted in a significant decrease (P<0.05) in blood trough CsA by 24% (mean+/-SD, pre- 127.3+/-38.9, post- 97.2+/-30.7 microg/ml) compared with no change while taking the placebo (pre- 132.2+/-50.6, post- 138.6+/-56.0 microg/ml). The glomerular filtration rate was significantly (P<0.05) improved by 12% during antioxidant supplementation (pre- 66.9+/-20.7, post- 75.0+/-20.1 ml/min/1.72 m2), with no change during the placebo phase (pre- 66.8+/-11.8, post- 66.7+/-16.1 ml/min/1.72 m2). There were no significant differences (P>0.05) in markers of oxidative stress (malondialdehyde, susceptibility of plasma to oxidation) or plasma antioxidant enzymes. CONCLUSION: In CsA-treated RTRs, antioxidant supplementation decreased blood CsA, which may affect adequacy of immunosuppression.