Endothelial progenitor cells and asymmetric dimethylarginine after renal transplantation.

Levels of the endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) are elevated and endothelial progenitor cells (EPCs) decreased in patients undergoing renal transplantation (Tx) and may contribute to cardiovascular complications. In this study, we tested the hypothesis that elevated ADMA and decreased EPC can be positively influenced with regular physical exercise early after Tx. Blood samples for analysis of ADMA and EPC were obtained from randomly selected 64 patients after Tx who agreed to participate in a supervised aerobic exercise program for 6 months (group I). Samples were collected before the training began, 1 month after surgery (with stabilized renal function), and at 6 months after initiation. Sixty-two age, sex, human leukocyte antigens (HLA) typing, duration of previous dialysis, history of cardiovascular disease, and immunosupression regimen-matched transplant patients who did not exercise regularly were examined as controls (group II). There were no differences in ADMA levels and EPC count between both groups before the training program began. After 6 months of exercise, ADMA concentration in the group I decreased (3.50 ± 0.45 vs. 2.11 ± 0.35 µmol/L; P < .01) and was also lower comparing with group II (2.11 ± 0.23 vs. 3.25 ± 0.35 µmol/L; P < .01). In the same period, EPC cells increased from 2.085 ± 650 cells/mL versus 3.991 ± 560 cells/mL, P < .01 in group I; but in group II, changes were nonsignificant (P = .11). Blood lipids, HbA1c, insulin, and systolic blood pressure were also affected by the training program. Elevated ADMA level and decreased EPC count were significantly influenced by early regular exercise in patients after Tx.

[Investigation of tubular reabsorption of phosphates in patients with chronic kidney disease]. / Vysetrování tubulární resorpce fosfátu u pacientu s chronickým onemocnením ledvin.

INTRODUCTION: Moderate to medium decrease in glomerular filtration (GFR) in individuals with chronic kidney disease (CKD) does not need to be associated with hyperphosphatemia due to an adaptive decrease in tubular reabsorption of phosphates (TRPi) in residual nephrons. The clinical assessment of this function is performed based on the measurement of fractional phosphate excretion (FEPi), which is a quantity specifying the proportion of the filtered amount of phosphates which is excreted in the urine. This quantity may provide useful information about the involvement of kidneys in phosphate homeostasis of the internal environment. This study focuses on the comparison of a kr(FEPi) value examined based on a ratio of a phosphate clearance (CPi) and a creatinine clearance (CKr) marked kr(FEPi), and a value calculated based on a ratio of CPi and an exactly measured GFR as an inulin clearance (Cin), marked as in(FEPi).The goal of comparing the two methods of examining FEPi was to establish to what extent it is possible to evaluate the degree of inhibition of tubular phosphate transport in residual nephrons based on a simple examination of kr(FEPi) . METHODOLOGY: The examination of in(FEPi) and kr(FEPi) was carried out for 53 patients with CKD. The values of the examined quantities were as follows: SKr 199±45 µmol/l; SPi 1.41±0.29 mmol/l; CKr 0,95±0.36 ml/s/1.73 m2; Cin 0.71±0.25 ml/s/1.73 m2. For the purpose of comparison a cohort of 18 healthy volunteers was examined. RESULTS: For individuals with CKD an average value of kr(FEPi) equalled 29.1±10.9% and in(FEPi) 52.4±4.3%. The values of in(FEPi) were higher than kr(FEPi) (p<0.001) for all patients, although an average CPi value for patients with CKD did not significantly differ from the control cohort (0.22 vs 0.21 ml/s/1.73 m2). The values of in(FEPi) increased proportionally to SKr values and at higher values SKr (>300 µmol/l) they gradually approached 100% (indicating the complete inhibition of tubular reabsorption of phosphates in residual nephrons). The values of in(FEPi) were higher in all patients with CKD than kr(FEPi) as expected, likely because the value CKr decreases at a slower rate than Cin (GFR) in individuals with CKD as a result of increased tubular secretion of creatinine in residual nephrons. CONCLUSION: The results of this study support the assumption that, provided the values of kr(FEPi) which are easily measurable in clinical practice have reached 50-60%, almost complete inhibition of tubular reabsorption of phosphates in residual nephrons must be assumed and no favourable effect of phosphatonins on renal phosphate excretion can be expected. When looking for new possibilities of inhibition of tubular phosphate reabsorption, potential adverse effects of phosphatonins on organs must be considered.

Early changes in serum visfatin after abdominal surgery: a new pro-inflammatory marker in diagnosis?

BACKGROUND: Visfatin is an adipocytokine produced primarily by visceral adipose tissue. In addition to its effect on the insulin receptor, it is a proinflammmatory cytokine with accumulating evidence for its rise in circulation, accompanying systemic inflammation. The aim of this study was to evaluate changes in serum visfatin levels in the early post-abdominal surgery period with serum levels of other proinflammatory cytokines, to determine whether it could be used as a marker of inflammation. METHODS AND RESULTS: This was a prospective cross-sectional study of 42 patients undergoing elective laparotomic right hemicolectomy for adenocarcinoma colon. The parameters determined were visfatin, leptin, adiponectin, TNF α, interleukin-6 and C-reactive protein levels. The dynamics of change in these markers were assessed at +12, +24, +48, and +72 h after surgery. Serum levels of visfatin peaked as early as 24 h post-surgery, returning to normal after 72 h. TNF α and IL-6 levels reached their maximum 12 to 24 h later while CRP levels peaked after 72 h. CONCLUSIONS: Significantly increased serum levels of visfatin detected in the early period after abdominal surgery preceded increase in the levels of other proinflammatory markers including TNF α, IL-6, and CRP. Given its dynamics, visfatin could serve as an early predictor of the development of inflammatory changes in patients undergoing surgery, particularly those with obesity (BMI > 30 kg/m(2)).

The relationship between estimated GFR based on the CKD-EPI formula and renal inulin clearance in potential kidney donors.

It is not yet clear whether or not renal function in the living donor can be sufficiently assessed by estimated glomerular filtration rate (GFR) using creatinine-based equations. The present paper investigates the relationship between GFR values determined using renal inulin clearance (Cin) and those estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Our study was performed in 287 potential kidney donors with a mean age of 48 ± 10 years. Mean Cin was 1.47 ± 0.28 (1.10 - 2.50) mL/s/1.73 m2. Total bias when using the CKDEPI formula was -0.0183 mL/s/1.73 m2, precision 0.263 mL/s/1.73 m2, and accuracy 90.6% within ± 30% of Cin. The sensitivity of CKD-EPI to estimate a decrease in Cin below 1.33 mL/s/1.73 m2 was 50.5%, with an 85% specificity of detecting a value above the cutoff. Receiver-operating curve analysis for the above produced an area under the curve of 0.766 ± 0.0285 (CI 0.712 - 0.813). For donor screening purposes, CKD-EPI should be interpreted with great caution.

Early exercise training after renal transplantation and asymmetric dimethylarginine: the effect of obesity.

BACKGROUND/AIMS: To assess, in a prospective cohort study of 238 renal transplant patients, our hypothesis that elevated ADMA levels may be influenced by physical exercise and obesity. METHODS: Blood samples before and after six months were obtained from 116 transplant patients participating in an aerobic exercise (Group I). A control group consisted of 122 matched transplant patients who did not exercise regularly (Group II). RESULTS: There were no significant differences in ADMA levels between both groups before the training program (Group IB vs. Group IIB). After six months of exercise, ADMA levels in Group I decreased (Group IB vs. Group IA : 3.50 ± 0.45 vs. 2.11 ± 0.35 µmol/L; p< 0.01) and were lower compared to those in Group II (Group IA vs. Group IIA : 2 11 ± 0 23 vs 3 25 ± 0 34 µmol/L; p< 0 01) Analysis of our results in obese renal transplant recipients (BMI B 30 kg/m(2)) confirmed a smaller effect of exercise training (Group IBO vs Group IAO : 3 75 ± 0 52 vs 3 45 ± 0 45; p< 0 05 and Group IAO vs. Group IIAO : 3.45 ± 0.45 vs. 3.74 ± 0.62; p<0.05). Blood lipids, HbA1C, insulin, and systolic BP were also affected by the training program. CONCLUSION: Elevated ADMA levels were significantly decreased by early exercise after renal transplantation. The effect of exercise was smaller in obese patients.

[Dynamics of serum visfatin level after abdominal surgery: a new proinflammatory marker in the early diagnosis?]. / Dynamika zmen sérového visfatinu po abdominálním chirurgickém výkonu: nový proinflamacní marker v casné diagnostice?

BACKGROUND: Visfatin is a newly recognized adipocytokine produced mainly in visceral fat tissue. Beside its effect on insulin receptor, it serves as proinflammatory cytokine and its level can be changed during inflammatory processes. The aim of the study was to analyze dynamics of serum visfatine level in early period after abdominal surgery and compare it with other proinflammatory markers. METHODS AND RESULTS: In prospective cross-sectional study 20 patients after elective laparotomic abdominal surgery (partial colectomy) were enrolled and dynamics of visfatin, leptin, resistin, adiponectin, TNF-α , IL-6 and CRP in period +12, +24, +48 and + 72 hours was monitored. Serum visfatin was elevated already in +24 hrs period after surgery comparing the culmination of serum level of TNF-α and IL-6 12-24 hrs later and CRP even 48-72 hrs later. CONCLUSIONS: Serum visfatin was elevated very early after abdominal surgery and thus its dynamic may be an early predictor of inflammatory processes namely in patients with visceral obesity.

Muscle and fat metabolism in obesity after kidney transplantation: no effect of peritoneal dialysis or hemodialysis.

Our prospective study analyzed selected adipocytokines: adiponectin (ADPN), leptin, visfatin, and asymmetric dimethylarginine (ADMA) in the plasma of renal transplant recipients previously treated by peritoneal dialysis and hemodialysis. A total of 70 patients were on follow-up for 12 months after transplantation. Of these, 30 patients (group I) developed obesity, and 40 patients were nonobese (group II). All were receiving standard immunosuppressive therapy (cyclosporine A or tacrolimus and mycophenolate mofetil, with prednisone added in the early posttransplant period) and did not differ statistically in HLA typing, age, sex, duration of previous dialysis, history of cardiovascular disease, and rate of rejection episodes. At the end of the study period, there were significant differences between groups I and II (t test, analysis of variance) in plasma: ADPN, 22.30 ± 10.2 versus 14.3 ± 7.2 µg/mL; visfatin, 1.7 ± 0.1 versus 1.2 ± 0.1 ng/mL; ADMA, 3.60 ± 0.47 versus 2.10 ± 0.36 µmol/L; P < .01; leptin, 55.6 ± 10.2 versus 25.6 ± 8.3 ng/L; P < .01 (P < .02). In conclusion, an increase of body fat after renal transplantation was associated with an increase of ADMA and leptin, TNF-α, MCP-1, and visfatin and decrease of adiponectin. Our study documented there was now long-term beneficial metabolic effect of peritoneal dialysis in developing posttransplant obesity.

Increased proinflammatory cytokine production in adipose tissue of obese patients with chronic kidney disease.

BACKGROUND: Obesity is a known high-risk factor for the development of vascular diseases and chronic kidney disease (CKD). In this study we aimed to elucidate the impact of adipose tissue on the inflammatory state in CDK patients with obesity. PATIENTS AND METHODS: A cohort of 40 patients with CKD (stages 3-4) with mild proteinuria (2.3-3.5 g/day) were analyzed in a prospective cross-sectional study: single blood samples and visceral and subcutaneous samples of adipose tissue were taken from 20 patients with obesity and 20 without obesity (control group) during elective abdominal surgery (laparoscopic cholecystectomy). Serum concentrations of asymmetric dimethylarginine (ADMA), adiponectin, C-reactive protein, interleukin-6, tumor necrosis factor-alpha, pentosidine and monocyte chemoattractant protein-1 were measured. Messenger RNA expression of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, adiponectin receptors 1 and 2, and immunocompetent cell marker CD68 was measured in subcutaneous and visceral fat samples using real-time PCR. Adipose tissue was examined immunohistochemically for CD68-positive cells. Other biochemical parameters (insulin, glycated hemoglobin, cholesterol, LDL cholesterol, and triglycerides) were assessed in the two groups of patients at the same time. RESULTS: Serum concentrations of ADMA, C-reactive protein, pentosidine, interleukin-6, tumor necrosis factor-alpha and monocyte chemoattractant protein-1 were significantly higher in obese CKD patients than in the control group; adiponectin was lower in the obese group. Subcutaneous and visceral mRNA expressions of tumor necrosis factor-alpha, CD68, adiponectin receptor-1, and monocyte chemoattractant protein-1 were significantly increased in the obese patients, whereas expression of adiponectin, interleukin-6, and adiponectin receptor-2 did not significantly differ between the patient groups. In general, mRNA expressions were higher in visceral than in subcutaneous samples (P < 0.01 vs. P < 0.05). Increased infiltration of subcutaneous and visceral adipose tissue by CD68-positive immunocompetent cells was found in the obese CKD group. With respect to lipid metabolism parameters, a small but significant increase in levels was found in the obese patients (P < 0.02). Changes in triglycerides were more marked in this group (P < 0.01) and a similar increase was noted in insulin and HbA1c levels (P < 0.02). CONCLUSION: Increased expression of proinflammatory cytokines and increased infiltration by immunocompetent cells were found in adipose tissue of obese patients with CKD stages 3-4. This upregulated inflammation may contribute to the induction of a systemic proinflammatory state in patients with CKD and could accelerate the progression of renal dysfunction.

Gender-related determinants of advanced subclinical atherosclerosis in patients undergoing kidney transplantation.

BACKGROUND: Cardiovascular disease caused by atherosclerosis remains a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD). We evaluated the potential association of cardiovascular risk factors including asymmetric dimethyl L-arginine (ADMA) and the soluble receptor for advanced glycation end products (sRAGE) with preclinical atherosclerosis in patients undergoing kidney transplantation. PATIENTS AND METHODS: In 92 males and 47 females undergoing the first cadaveric renal transplantation, ADMA, sRAGE and common risk factors including lipid parameters were evaluated as potential predictors of preclinical atherosclerosis defined as the Belcaro score (focused on advanced atherosclerotic changes) measured by ultrasound. RESULTS: The prevalence of atherosclerotic changes was approximately 70% in men and women. In logistic regression, age, history of smoking, presence of diabetes mellitus, and plasma triglycerides were the strongest independent predictors for advanced atherosclerosis in the whole group. In unadjusted analyses advanced atherosclerosis was also associated with sRAGE in men and with the atherogenic index of plasma in women. CONCLUSION: Apart from traditional cardiovascular risk factors, plasma triglycerides were found to be strong and independent predictors of advanced atherosclerosis in patients with ESRD. In addition, sRAGE was associated with atherosclerosis in men and the atherogenic index of plasma in women.

Nutritional consequences of renal transplantation.

Successful kidney transplantation leads to restoration of renal function. Some metabolic disorders from chronic renal failure may persist and new metabolic abnormalities can develop (obesity, diabetes, hypertension, bone disease, and anemia). Additionally, influence of immunosuppressive drugs (corticosteroids, cyclosporine A, tacrolimus, and rapamycin) may aggravate the course of diabetes, hypertension, and dyslipidemia. Nutritional management of renal transplantation is divided into the pretransplant period, transplant surgery, and early and late posttransplant period. Patients in the pretransplant period in dialysis treatment may develop protein-energy malnutrition and negative nitrogen balance, with loss of lean body mass and fat deposits. Nutritional management in the early posttransplant period with a functioning kidney graft necessitates fluid and electrolyte balance control with protein intake of 1,2/kg BW/day and 30-35 kcal/kg BW/day. In a nonfunctioning kidney graft, dialysis treatment continues and the therapeutic dose of immunosuppressive drugs must be reduced. The principal objective in the late posttransplant period is the maintenance of optimal nutritional status. Nutrition is important in managing obesity, insulin resistance, diabetes, hyperlipidemia, and hypertension. Other posttransplant conditions for which diet and/or nutritional supplements may be beneficial include hypomagnesemia, hypophosphatemia, hyperuricemia, hyperkalemia, hyperhomocysteinemia, chronic renal allograft failure, renal anemia, and renal bone disease.

Reduction of plasma asymmetric dimethylarginine in obese patients with chronic kidney disease after three years of a low-protein diet supplemented with keto-amino acids: a randomized controlled trial.

BACKGROUND: Levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) are elevated in chronic kidney disease (CKD) and may contribute to vascular complications. In this study we tested the hypothesis that elevated ADMA can be reduced in obese CKD patients by long-term administration of a low-protein diet supplemented with keto-amino acids. PATIENTS AND METHODS: In a long-term prospective double-blind placebo-controlled randomized trial, we evaluated for a period of 36 months a total of 111 CKD patients (54 men, 57 women) aged 22-76 years with obesity (BMI >or= 30 kg/m(2)) and an inulin clearance rate (C(in)) of 22-40 ml/min/1.73 m(2). All patients were on a low-protein diet containing 0.6 g protein/kg BW per day and 120-125 kJ/kg BW per day. The diet was randomly supplemented with keto-amino acids at a dosage of 100 mg/kg BW per day (66 patients, Group I); 65 patients received placebo (Group II). RESULTS: During the study period, the glomerular filtration rate decreased slightly in Group I (C(in) from 32.4 +/- 12.6 to 29.8 +/- 8.6 ml/min/1.73 m(2)) and more markedly in Group II (from 33.2 +/- 12.6 to 23.2 +/- 98.4 ml/min/1.73 m(2), P < 0.01). BMI decreased significantly in Group I (from 32.0 +/- 3.3 to 26.1 +/- 4.0 kg/m(2), P < 0.01) and was linked to reduced volume of visceral fat measured by MRI (P < 0.01). Reduction of BMI in Group II was not significant. In Group I, there was a significant decrease in the plasma level of ADMA (from 2.5 +/- 0.5 to 1.3 +/- 0.4 micromol/l, P < 0.01), but ADMA remained unchanged in Group II. A further remarkable finding in Group I was reduction in the plasma concentration of pentosidine (from 480 +/- 170 to 320 +/- 120 microg/l, P < 0.01) and decrease of proteinuria (from 3.8 +/- 2.24 to 1.6 +/- 1.0 g/24 h, P < 0.02). Plasma adiponectin rose in Group I (P < 0.01). Analysis of the lipid spectrum revealed a mild but significant decrease in total cholesterol and LPD-cholesterol (P < 0.02), more pronounced in Group I. There was also a decrease in plasma triglycerides in Group I (from 3.9 +/- 1.6 down to 2.2 +/- 0.6 mmol/l, P < 0.01) and a decrease in glycated hemoglobin (from 7.2 +/- 1.4% to 4.2 +/- 0.8%, P < 0.02). CONCLUSION: Compared with the placebo group, long term co-administration of a low-protein diet and keto-amino acids in CKD patients with obesity led to decreases of ADMA, visceral body fat and proteinuria. Concomitant decreases of glycated hemoglobin, LDL-cholesterol and pentosidine may also contribute to the delay in progression of renal failure.

The auxiliary table for GFR estimation according to the MDRD formula.

The best overall index of renal function is considered to be glomerular filtration rate (GFR) and the gold standard for its assessment is renal inulin clearance (Cin) Unfortunately, Cin cannot be routinely used in daily practice due to its complexity as a test. The most often used ones are the Cockcroft-Gault (CG) formula and the recently developed Modification of Diet in Renal Disease (MDRD) prediction equation. Calculation of MDRD (estimated GFR) according to this formula is simple but it requires a computer program. The following table is prepared for parts of the world where the computer program is not available as yet.

Metabolic syndrome after renal transplantation.

Obesity and hyperlipidemia are common findings after kidney transplantation (Tx), and may represent independent risk factors for development of atherosclerosis and chronic allograft nephropathy. In a prospective metabolic study, we monitored a total of 68 obese transplant patients (body mass index > 30 kg/m2) with dyslipidemia. We compared findings of a new therapeutic regimen 1 year (at baseline) and 2 years after renal transplantation. Using the Subjective Global Assessment, at the end of the first year an Individualized Hypoenergetic-Hypolipidemic diet was initiated. Subsequently, after withdrawal of corticosteroids IHHD was regularly supplemented with statins (atorvastatin 10-20 mg/day) and followed-up for 2 years. All patients were on a regimen of cyclosporin A or tacrolimus and mycophenolate mofetil. During the study period, there was a significant decrease in BMI (p<0.25) and an increase in adiponectin levels (p<0.01). Long-term therapy was associated with a significant decrease in serum leptin (p<0.01) and lipid metabolism parameters (p<0.01). Insulin clearance mean systolic and diastolic blood pressure, proteinuria and apo-lipoprotein E isoforms did not differ significantly. Based on our results, we can assume that obesity and hyperlipidemia after renal transplantation can be effectively treated by modified immunosuppression (corticosteroid withdrawal), statins and long-term diet (IHHD). The increased levels of adiponectin may be a marker of reduced atherosclerosis and chronic allograft nephropathy.

Estimation of glomerular filtration rate based on the modification of diet in renal disease equation in patients with chronic renal failure.

The list of indications for initiating regular dialysis treatment includes residual glomerular filtration rate (GFR). Under the current European Best Practice Guidelines for Hemodialysis, residual GFR (and the presence of one or more symptoms of uremia) should not decrease below 15 ml/min. The present article seeks to determine to what extent the modification of diet in renal disease (MDRD) equation enables the detection of this decrease in GFR. We tried to answer this question using a more detailed analysis of the relationship between MDRD and renal inulin clearance (C in). Residual GFR based on C in (under conditions of stable plasma levels and water loading) and GFR calculated using the MDRD equation was measured in 79 individuals with chronic renal failure (with mean C in = 19.1 +/- 10.1 ml/min/1.73 m2). Statistical evaluation was performed using regression analysis, the interchangeability of both methods (Bland-Altman) and receiver-operating characteristic (ROC) curve analysis. Regression analysis demonstrated a significant correlation between MDRD and C in (r = 0.892; p < 0.001). However, the regression equation line for the correlation differs significantly from the identity line (p < 0.001). The value of the regression coefficient (0.722) is significantly lower than 1.0 (CI50 0.63; 0.81). The mean MDRD -C in difference was 3.26 +/- 4.46 ml/min/1.73 m2 and the value was significantly different from zero (p < 0.001). The mean difference +2 SD was 12.2 ml/min/1.73 m2, and the mean - 2 SD was -5.7 ml/min/1.73 m2. ROC curve analysis (for a cutoff C in = 15 ml/min/1.73 m2) indicates an area under the curve (AUC) of 0.954 +/- 0.023. The best combination of sensitivity and specificity was obtained for a MDRD of 19.7 ml/min/1.73 m2, with a sensitivity of 90.5% and specificity of 87.5%. For cutoff value of C in = 10 ml/min/1.73 m2, the AUC was 0.939 +/- 0.026 (CI95 0.863-0.890). A combination of maximum sensitivity and specificity was obtained with an MDRD of 16.5 ml/min/1.73 m2. With this value, MDRD sensitivity was 100% and specificity 81.5%. A significant correlation between the MDRD equation and the measured creatinine clearance (C cr) was found (r = 0.883, p < 0.001). The mean difference of MDRD-C cr was -7.2 +/- 6.5 ml/min/1.73 m2. This is significantly different from that of MDRD-C in (p < 0.001). Our results suggest that MDRD and C in in individuals with chronic renal failure are not interchangeable methods for a GFR <15 ml/min/1.73 m2 determination. However, MDRD may furnish valuable information in terms of detecting a critical decrease in GFR; but, the MDRD equation for this decrease in GFR (15 ml/min/1.73 m2) will provide a somewhat higher value (19.7 ml/min/1.73 m2).

Obesity and hyperhomocysteinaemia after kidney transplantation.

Obesity and hyperhomocysteinaemia are found very frequently after kidney transplantation (Tx). They may independently represent risk factors for development of atherosclerosis and chronic allograft nephropathy. In a prospective metabolic study, we monitored, over a period of 24 months, a total of 118 obese transplant patients [body mass index (BMI) > or =30 kg/m(2)] with hyperhomocysteinaemia. We compared the findings of a new therapeutic regimen at 1 year (start of the study) and 2 years after renal transplantation. Based on a Subjective Global Assessment Scoring Sheet, we started at the end of the first year with an individualized hypoenergic-hypolipidaemic diet (IHHD). Subsequently, after corticoid withdrawal, IHHD was supplemented regularly with orlistat at a dose of up to 3 x 120 mg/day, statins (pravastatin 10-40 mg), folic acid 5 mg/day and vitamin B6 50 mg/day, and followed-up for up to 2 years. All patients were on a regimen of cyclosporin A and mycophenolate mofetil. During the study period, there was a significant decrease in BMI (P < 0.025) and total homocysteine level (P < 0.001). Long-term therapy was associated with a significant decrease in serum leptin (P < 0.001) and lipid metabolism parameters (P < 0.01). The mean values of serum folate and vitamin B6 also increased significantly (P < 0.01); creatinine clearance, mean blood pressure, proteinuria, lipoprotein(a) and apolipoprotein E isoforms did not differ significantly. Based on our results, we assume that obesity and hyperhomocysteinaemia after renal transplantation can be treated effectively by modified immunosuppression (corticosteroid withdrawal), long-term diet (IHHD), folic acid and vitamin B6 supplementation, and drugs suppressing digestion or absorption to reduce atherosclerotic and chronic allograft nephrop-athy processes.

Glomerular filtration rate estimation in patients with advanced chronic renal insufficiency based on serum cystatin C levels.

BACKGROUND: Cystatin C has an obvious advantage in the recognition of the initial stages of renal impairment. It is questionable whether cystatin C possesses the same benefit in follow-up of pre-dialysis patients. If cystatin C were also a sensitive marker of GFR in pre-dialysis patients, then it could be expected that, for the same degree of a decrease in GFR, the increase in S(cyst) would be higher than in S(cr) because of the significant increase in tubular secretion of creatinine in residual nephrons. The aim of this study was to evaluate whether S(cyst) in patients with GFR

Predicting the grade of Banff 97 classification of chronic allograft nephropathy based on examination of graft dysfunction (a preliminary report).

OBJECTIVES: Progression of chronic allograft nephropathy (CAN) is associated with a progressive decrease in graft function. Prediction of the Banff CAN grade on the basis of correlation between the grade of histological changes and Scr is difficult because of the big spread of individual values. This study sought to predict the Banff CAN grade based on Scr, Ccr and proteinuria using ROC analysis. METHODS: Graft protocol biopsy and functional testing (Scr, Ccr and proteinuria) were performed in 77 subjects (43 men, 34 women, mean age 48.4 +/- 12.8 years) at 33.8 +/- 1.0 months after their first renal transplantation. Immunosuppression was provided with the triple combination of cyclosporin A, prednisone and azathioprine (or mycophenolate mofetil). Statistical evaluation was performed using receiver-operating curve (ROC) analysis. The cut-off value of the Banff CAN score was set at 1. RESULTS: The mean values and SD of the investigated functional parameters in study subjects were as follows: Scr = 201.5 (+/- 100.0) mumol/l Ccr = 48.1 (+/- 21.2) ml/min/1.73 m2, proteinuria = 0.89 (+/- 1.96) g/24 h. ROC analysis showed the highest AUC (+/- SEM) for Scr 0.806 (+/- 0.063). The respective values were 0.790 (+/- 0.053) for Ccr and 0.643 (+/- 0.075) for proteinuria. The AUC (area under the ROC curve) for Scr was significantly higher (P < 0.043) compared with proteinuria. The values for sensitivity (specificity) were as follows: Scr 65.0 (91.2). Ccr 75.0 (82.5), proteinuria 60.0 (68.4). The best fit values (best combination of sensitivity and specificity) were 257.2 umol/l for Scr, 33.6 ml/min/1.73 m2 for Ccr and 0.40 g/24 hr for proteinuria. CONCLUSIONS: Our findings support the assumption that Scr > 275 mumol/l and Ccr < 33.6 ml/min/1.73 m2 suggest a Banff CAN grade higher than 1 (P < 0.001). Proteinuria had the lowest predictive values. Values > 0.40 g/24 hr were probably associated with a Banff CAN grade higher than 1 (p < 0.05).

Glomerular filtration rate assessment in individuals after orthotopic liver transplantation based on serum cystatin C levels.

Individuals after orthotopic liver transplantation (OLT) often show renal dysfunction, which may substantially affect the post-OLT course. Renal function after OLT is commonly assessed by means of serum creatinine (S(cr)) concentration or renal creatinine clearance (C(cr)). A glomerular filtration rate (GFR) estimate based on S(cr) level is not accurate enough because even a more marked decrease in GFR need not be associated with an increase in S(cr) level, especially in jaundiced patients. The study intends to try to estimate GFR in individuals after OLT by means of determining serum cystatin C (S(cyst)) concentrations. In 58 individuals (mean age, 49 +/- 7 years; 31 men, 27 women) at various intervals from OLT (mean, 14 +/- 10 months), GFR was estimated by using simultaneous determinations of S(cyst), S(cr), C(cr), and renal inulin clearance (C(in)). In most subjects (91.3%), C(in) was decreased to less than the lower limit of normal (80 mL/min/1.73 m(2)). A significant correlation (r = 0.70; P <.001) was found between 1/S(cyst) and C(in). Receiver operating characteristic analysis was performed on S(cyst) and S(cr) using a C(in) cutoff value of 80 mL/min/1.73 m(2). The area under the curve for S(cyst) was 0.912 +/- 0.044, and that for S(cr), 0.899 +/- 0.049. There was no statistically significant difference between these values. The sensitivity for a S(cyst) level of 1.20 mg/L (upper limit of normal value) to detect a decrease in GFR (measured as C(in)) below the lower limit of normal (80 mL/min/1.73 m(2)) was 96.1%. The sensitivity of S(cyst) level was significantly greater (P <.01) than the sensitivity of S(cr) level for men and at borderline significance for women (P =.05). Findings support the assumption that a S(cyst) level less than 1.2 mg/L indicates with a high degree of probability (P <.001) that GFR is not decreased to less than the normal limit. S(cyst) assessment in individuals after OLT could be proposed as a confirmatory test of a decrease in GFR in individuals with normal S(cr) levels.