Influence of carvedilol on chronic renal failure progression in spontaneously hypertensive rats with adriamycin nephropathy

Background: In this study, the effects of carvedilol, antihypertensive (alpha-beta blocker) agent with antiproliferative and antioxidative properties, on slowing down of chronic renal failure (CRF) progression in spontaneously hypertensive rats (SHR) with adriamycin (ADR) nephropathy were examined. Methods: Eighty adult (24 weeks) SHR were divided into four groups: Control group: 20 SHR; ADR group: 20 SHR treated with ADR (2 mg/kg i.v. twice in 20 days); ADR-C group: 20 SHR treated with ADR and with carvedilol (30 mg/kg/day); ADR-CC group: 20 SHR treated with carvedilol and captopril (60 mg/kg/day). Systolic blood pressure was measured every two weeks, renal blood flow (RBF), mean arterial pressure (MAP) and renal vascular resistance (RVR) were determined at Weeks 6 and 12, creatinine clearance and proteinuria at Weeks -3 (see measurements), 6 and 12. The rats were sacrificed at Weeks 6 and 12 after the second ADR injection. Glomerular sclerosis, tubulointerstitial and blood vessel changes were determined by semiquantitative scoring. Results: Carvedilol decreased systolic blood pressure. It decreased RVR and MAP, and increased RBF significantly. Carvedilol also significantly decreased interstitial infiltration in the early phase of the study, slowed down the development of interstitial fibrosis and tubular atrophy and decreased blood vessel changes. The hemodynamic and morphological effects of carvedilol were associated with slowing down the CRF progression as well as a mild decrease in proteinuria. Captopril addition to carvedilol improved its effects especially on prevention of tubulointerstitial changes. Conclusions: Results of this experimental study showed beneficial effect of carvedilol and its combination with captopril on CRF progression, indicating that clinical Studies are warranted

Serum cystatin C as a measure of GFR in renal transplant patients

INTRODUCTION Assessment of renal function is of great importance in clinical medicine, especially in renal transplant patients requiring frequent controls of renal function. Therefore, continuous efforts have been made in searching precise and simple method for determination of glomerular filtration rate (GFR). Serum level of cystatin C (CyC), protein of low molecular weight, has been proposed as measure of GFR, but the data of its value in renal transplant patients are scarce [8-10]. PURPOSE The aim of this study was to compare the serum levels of low molecular weight proteins CyC and ß2-microglobulin (ß2-MG) with creatinine clearance, as well known measure of GFR, in renal transplant patients and control group of patients with different renal disease. PATIENTS AND METHODS The study included 36 patients divided into two groups. Group 1: 20 renal transplant patients (12 men and 8 women) aged between 22 and 63 (40.4±10.1) years with creatinine clearance from 7.1 to 77.7 ml/min. Group 2: 16 controls (5 men and 11 women) with various renal diseases, aged between 24 and 63 (41.5±12.5) years with creatinine clearance from 60.5 to 116.8 ml/min. N Latex Cystatin C and ß2-microglobulin for the Behring Nephelometer System was used in this study. Creatinine was determined with Jaffe-reaction in serum and urine. RESULTS In renal transplant patients as well as in control group of patients the significant correlation between creatinine clearance and reciprocal values of the serum CyC (rt=0.828; pt<0.001; rc=0.603; pc<0.05) and reciprocal values of the serum ß2-MG levels (rt=0.791; pt<0.001; rc=0.627 pc<0.05) was found (Graph 1). There was a slightly better correlation between creatinine clearance and reciprocal values of the serum CyC than the one between creatinine clearance and reciprocal values of the serum ß2-MG without statistical significance in renal transplant patients. There was no difference in correlation coefficients between both low molecular weight proteins and creatinine clearance in Group 2. The correlation coefficient between serum CyC and ß2-MG was r=0.839(p<0.001)in renal transplant patients and r=0.835 (p<0.05) in control group. There were no significant differences in correlation coefficients between reciprocal values of serum CyC and creatinine clearance (p=0,2043) as well as reciprocal values of serum ß2-MG and creatinine clearance (p=0.3717) between Group 1 and Group 2. DISCUSSION In renal transplant patients rapid assessment of graft function is necessary. This allows early recognition of rejection as well as differential diagnosis of different renal graft disorders. Study of Risch and co [16] suggested that serum CyC was very good marker for GFR in renal transplant patients which was confirmed by the other authors too [20-22]. During inflammatory process or other pathological conditions, especially during acute rejection or infections, CyC also provided precise assessment of GFR while creatinine clearance varied dramatically [16], Serum concentration of ß2-MG, another low molecular weight protein, also depends both on its production rate and the GFR [5,19]. Its production is dramatically different in patients with infections [5] as well as while immunosuppressive drugs are used [16], Therefore, ß2-MG is impractical as GFR marker in patients with renal transplants. So, serum CyC was considered as better marker for GFR than ß2-MG and creatinine clearance in renal transplant patients with different complications [16], In this study serum CyC was slightly better marker for GFR than ß2-MG, without statistical significance (Graph 1). Renal transplant patients, however, were in the stable condition at the time of the study. CONCLUSION Serum CyC was moderately better marker of GFR than ß2-MG in renal transplant patients when they were in the stable condition. Serum CyC and ß2-MG were the same markers of GFR in control group of patients with various renal diseases. There was no significant difference in correlation coefficients between reciprocal values of the serum CyC and creatinine clearance (p=0.2043) as well as reciprocal values of the serum ß2-MG levels and creatinine clearance (p=0.3717) between two examined groups of patients. The studies on renal transplant patients with acute graft rejection or infections are warranted

Analysis of donor selection for living related kidney transplantation and their postoperative outcome

Lack of cadaveric organs for transplantation resulted in increased number of living related kidney donors examinations and consequent transplantations in our Department. Donor procedure, selection, drop-outs and final results for living related donors (LRD) were retrospectively analyzed in this paper. Between 1987 and 1994 202 potential LRD were examined. Most of them were females (59%) and about 30% were older than 60 years. The family relation between LRD and recipients were: parents (95%), siblings (3%), grandmother grandfather (1.5%) and uncle (0.5%). Potential LRD were informed on risks advantages and procedure of living donor transplantation. After primary information 26% of potential LRD gave up further examinations. Following immunological and clinical evaluations 48% of LRD actually donated a kidney. The other 26% were excluded during the selection procedure. High immunological risks including ABO incompatibility, HLA mismatches and positive cross match test were the reasons for drop outs of 35 potential LRD (17%). Five more donors were excluded for medical reasons: one because of low creatinine clearance and four because of neoplasms, discovered during examination (kidney, laryngeal, lung). Fourteen transplantation were not realized due to different recipient reasons: 5 of them had clinical contraindications, two died and in 7 cadaveric kidney transplantations were performed. Mild hypertension, coronary disease and diabetes mellitus type 2 were presented in 5 LRD accepted for transplantation. Five more had to be operated before donation (abdominal or urological operation). Early complications after donor nephrectomy were acute renal failure, stress ulcus, pleuropneumonia in three and thromboflebitis in two donors. In conclusion, although kidney transplantation from LRD is highly successful careful examination during selection procedure is indispensable

Infuence of donor specific transfusion on renal allograft outcome

Donor specific transfusion (DST) is proclaimed to improve graft survival in living related kidney transplantation (LRTx). The aim of the present study was to estimate the influence of DST on LRTx graft function, acute rejection rate (AR) and survival in the early and late post transplant period. Fifty-five LRTx patients (grafted in the same year, and matched for recipients' and donor's age, sex) were included into the study. Ninety pts received DST: 4 patients were excluded from further evaluation (3 developed positive cross match reaction and one patients received cadaver graft) and 15 patients subsequently underwent LRTx from their respective blood donors (group 1). Their outcome was compared with 15 patients who had never been transfused before (group 2) and 25 random transfused patients (group 3). Besides similar patients' and donors' sex and age, kidney transplantations were performed in the same period. Graft functions were followed-up 6-60 months after LRTx. DST protocol consists of 3x150 ml potentially related donor's fresh whole blood at 2-week intervals (DST1, DST2, DST3) with 3 days azathioprine administration (2 mg/kg bw, one day before to one day after DST administration). Donor specific citotoxic antibodies were determined before DST1, at the day of DST2, DST3 and 14 and 28 days after DST3. All patients were grafted at least one month after the DST3. Immunosuppressive protocol consisted of three drugs. There is no difference in HLA mismatches, MLC answer, and pretransplant panel reactive antibodies level between groups. One patient from group 2 lost their graft in the first postTx month (acute tubular necrosis). A better graft function was preserved in patients from groups 1 and 3 than group 2 in the observed periods. Number of patients with acute rejection was unsignificantly different: 5/15 from group 1,12/25 from group 3 but 8/10 patients from group 2. However, the acute rejection rate was lower in patients from group 1. One and five-year graft survival was 100% for grafts from groups 1 and 3, while it is gradually decreased for group 2 grafts: 84.5% and 57%. Our results confirmed the beneficial effect of blood transfusion on LRTx renal graft function and survival and DST on the incidence of acute rejection

Transforming Growth Factor-beta(1) in Balkan Endemic Nephropathy

Background/Aim: The aim of this study was to compare plasma and urine transforming growth factor-beta(1) (TGF-beta(1)) levels in patients with different stages of Balkan endemic nephropathy (BEN) with those in patients with primary glomerulonephritis (GN) and healthy controls. Methods: The study involved 47 patients with BEN (30 with manifest BEN and 17 in the early stage of BEN), 12 patients with GN and 10 healthy controls. Plasma and urine TGF-beta(1) was assayed by enzyme-linked immunosorbent assay. Results: The median plasma TGF-beta(1) levels differed nonsignificantly between the groups (4,908-6,442 pg/ml), but individual plasma TGF-beta(1) levels in BEN patients exhibited the highest dispersion. Median urinary TGF-beta(1) excretion (pg/mg creatinine) was significantly higher in patient groups (manifest BEN: 203, early-stage BEN: 341, GN: 775) than in healthy controls (42). No correlation was found between plasma and urine TGF-beta(1) levels or between plasma TGF-beta(1) levels and creatinine clearance for any of the examined groups. Conclusion: Plasma TGF-beta(1) levels in BEN patients extended over the widest range, but no significant differences were found between the median values for the groups. Median urinary TGF-beta(1) excretion was significantly higher in patients with BEN and GN than in healthy controls. Copyright (C) 2009 S. Karger AG, BaselMinistry of Science and Ecology of Serbia [145037

Transforming Growth Factor-beta(1) in Balkan Endemic Nephropathy

Background/Aim: The aim of this study was to compare plasma and urine transforming growth factor-beta(1) (TGF-beta(1)) levels in patients with different stages of Balkan endemic nephropathy (BEN) with those in patients with primary glomerulonephritis (GN) and healthy controls. Methods: The study involved 47 patients with BEN (30 with manifest BEN and 17 in the early stage of BEN), 12 patients with GN and 10 healthy controls. Plasma and urine TGF-beta(1) was assayed by enzyme-linked immunosorbent assay. Results: The median plasma TGF-beta(1) levels differed nonsignificantly between the groups (4,908-6,442 pg/ml), but individual plasma TGF-beta(1) levels in BEN patients exhibited the highest dispersion. Median urinary TGF-beta(1) excretion (pg/mg creatinine) was significantly higher in patient groups (manifest BEN: 203, early-stage BEN: 341, GN: 775) than in healthy controls (42). No correlation was found between plasma and urine TGF-beta(1) levels or between plasma TGF-beta(1) levels and creatinine clearance for any of the examined groups. Conclusion: Plasma TGF-beta(1) levels in BEN patients extended over the widest range, but no significant differences were found between the median values for the groups. Median urinary TGF-beta(1) excretion was significantly higher in patients with BEN and GN than in healthy controls. Copyright (C) 2009 S. Karger AG, BaselMinistry of Science and Ecology of Serbia [145037