Delayed kidney function risk score: donor factors versus ischemia/reperfusion injury.
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Hemodynamics↗
Biomedical subjects
L Paczek
Publications and source records attributed to L Paczek.
Suppressed activities of cathepsins and metalloproteinases in the chronic model of puromycin aminonucleoside nephrosis.
Glomerulosclerosis and tubulointerstitial fibrosis are the hallmarks of chronic renal diseases. In the present study, we have investigated the potential involvement of various proteinases in these alterations in the model of puromycin aminonucleoside (PAN) nephrosis. Two groups of male Wistar rats were given either three or seven injections of PAN (2.0 mg/100 g body weight) over a 4- and 12-week period, respectively. The two control groups received saline injections. Activities of cathepsins (B, H and L) were determined in isolated glomeruli and proximal tubules. Moreover, collagenase-like and gelatinase-like activities were analyzed in isolated glomeruli. Three weeks after weekly PAN injection, the rats developed heavy proteinuria (140.8+/-22.0 vs. 13.5+/-3.29 mg/day; p<0.001), and at week 11 protein excretion reached 606.6+/-23.00 vs. 22.8+/-1.5 mg/day. Renal morphology revealed minimal glomerular mesangial changes at the 4th week after PAN administration. At the 12th week a marked mesangial matrix accumulation as well as severe tubulointerstitial infiltration and fibrosis associated with tubular dilation and atrophy were observed. Glomerular cathepsins B, H, and L and gelatinase-like activities decreased at the 4th week after the first PAN injection and remained at this low level throughout the entire study period. Glomerular collagenase-like activity decreased at the 4th week (p<0.05) and was still mildly lower than that of the control group at the 12th week, but without significance. In the isolated proximal tubules, the activities of cathepsins B, H, and L showed the same pattern of decreases as those found in the glomeruli over the whole experimental period. Taken together, our data in the model of chronic PAN nephrosis suggest that the suppressed activities of cathepsins as well as the decreased gelatinase- and collagenase-like activities participate in the accumulation of extracellular matrix and thereby may contribute to the development of glomerulosclerosis and tubulointerstitial fibrosis.
Animals↗
[The intermediate uveitis with systemic symptoms: a case report].
The case of 26-year old male patient with typical clinical intermediate uveitis (vitritis, periphlebitis) with accompanying leucopenia, bradycardia and demyelination focal areas in brain of unknown etiology is presented. The asymptomatic periphlebitis was also found in the eyes of his twin brothers (30 years old) and sister (20 years old).
Adult↗
Identification of cytomegalovirus (CMV) infection by different laboratory methods in renal transplant recipients undergoing triple-drug immunosupressive treatment.
Early diagnosis of CMV infection is very important mainly in transplant recipients because CMV infection is a frequent complication after transplantation. In this work we compared different laboratory methods: ELISA (IgG, IgM), Western blot,shell vial, antigenemia assay (pp65), the immunofluorescent method with epithelial cells from urine (IF), DNA in leukocytes by PCR and DNA in leukocytes by hybridization (HCS) to estimate the most proper method for diagnosis of CMV in renal transplant recipients. This preliminary study showed that HCS, PCR and Western blot are sensitive methods for detecting CMV infection. Using HCS in quantitative variant we obtained a very good correlation between DNA load and clinical symptoms.
Adult↗
[Autoimmune liver diseases. Part I].
Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) belong to the group of liver diseases which are believed to be caused by autoimmune reactions. The primary causes of these diseases remain unknown. However, thanks to the recent studies in immunogenetics, progress has been made in understanding the mechanisms underlying these pathologies. Moreover, studies are being held on identification of specific autoantigens in these diseases. The results of these studies are criteria of diagnosis and treatment of those diseases. As there is still no specific treatment of PBC and PSC, in many cases best results are achieved with allogenic orthotropic liver transplantation.
Autoantigens↗
[Autoimmune liver diseases. Part II].
Autoimmune hepatis along with primary biliary cirrhosis, primary sclerosing cholagitis and some other not classified primary hepatobiliary pathologies belong to the group of liver diseases which are believed to be caused by autoimmune reactions. The primary causes of those pathological states remain unknown. However, thanks to the recent studies in immunogenetics and on autoantigens, progress has been made in understanding the mechanisms underlying these pathologies. The results of these studies are criteria of diagnosis and treatment of those diseases. In spite of some beneficial results of immunosuppressive treatment of AIH, the disease in some cases progresses and those states are one of the classical indications for allogenic liver transplantation.
Autoimmune Diseases↗
[Lipocytes--their importance in physiology and pathology of the liver].
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Acute Disease↗
Factors affecting reactivation of Epstein-Barr virus infection after kidney allograft transplantation.
OBJECTIVES: Reactivation of Epstein-Barr virus (EBV) infection in renal transplant recipients may cause significant morbidity and mortality. To evaluate factors associated with activation of EBV replication we followed prospectively a group of 65 recipients of cadaveric kidney for 12 months. METHODS: Sera were collected periodically from these patients and analyzed for the presence of specific anti-EBV antibodies. Control group consisted of renal (n=35) and healthy blood donors (n=35). Enzyme-linked immunoassays based on recombinant EBV proteins were used to detect the following antibody specificities: early antigen (EA) IgA, IgM, and IgG, nuclear antigen (EBNA) IgG. RESULTS: During first year after transplantation, primary infection developed in 4 (6.15%) recipients and reactivation occurred in 18 (27.7%) recipients. Analysis did not show the association of reactivation with type of basic immunosuppressive therapy, prophylactic or therapeutic use of anti-lymphocyte antibodies, as well as acute rejection episodes. There was a borderline association (p=0.068) between the incidence of CMV infection and EBV reactivation. CONCLUSIONS: Our data suggest casual relationship between CMV infection and EBV reactivation.
Adult↗
Perioperative single high dose ATG-Fresenius S administration as induction immunosuppressive therapy in cadaveric renal transplantation--preliminary results.
Monoclonal and polyclonal antilymphocyte antibodies have been used successfully in organ transplantation as induction therapy and in the treatment of acute graft rejection. Used for induction the medication is generally given for the first 7-10 days. The aim of this study was to assess the safety and efficacy of single high dose (9 mg/kg) ATG Fresenius S given perioperatively, before revascularization, to kidney allograft recipients. During last twelve months seventy six, first cadaveric kidney adult recipients were included into the study in two centers (center A-64, center B-12). All patients received triple drug immunosuppression (Neoral, steroids and Cellcept which was replaced by azathioprine after 4 months), and were randomized to receive ATG or not. The follow-up period ranged from 1 month up to 1 year. The preliminary results are very promising, the rejection rate in bolus group was significantly lower than in control. No significant side effects or serious adverse events in both groups were observed.
Acute Disease↗
Activity of glutathione S-transferases in the urine of kidney transplant recipients during the first week after transplantation.
UNLABELLED: Glutathione S-Tranferases (GST) are the enzymes which are strictly specific for epithelial cells of the proximal and distal tubules in the kidney. These enzymes are detected in the urine when some tubular damage process is found. In healthy people urine GST is hardly detected. The goal of this study was to evaluate the release of two isoenzymes -- alpha and pi GST in the urine of kidney graft recipients during the first week after kidney transplantation, aiming to differentiate the cause of the delayed function (DF) of transplanted kidney. MATERIAL AND METHODS: 50 cadaveric kidneys were procured using standard technique with "in situ" cooling using UW solution. All kidneys were machine perfused. After preservation kidneys were transplanted to 50 ERSD patients. Standard triple drug immunosuppression was applied (steroids, CsA, Cell-Cept or Aza.). Graft function and the release of alpha and pi GST in the urine were measured 1, 3 and 7 days after transplantation. RESULTS: immediate function (IF) was found in 72% (36pts), DF in 28% (14pts). 5 of DF patients had ATN, 4 had acute rejection (REJ) and the remaining 5 had ATN and acute rejection (see table below). CONCLUSIONS: High alpha and pi GST concentrations were found in pts with DF graft function during the first 7 days after Tx. Elevated pi GST and low alpha GST in the urine indicates acute rejection. High alpha and pi GST in pts with DF should raise suspicion of graft rejection.
Cyclosporine↗
Urine activity of cathepsin B, collagenase and urine excretion of TGF-beta 1 and fibronectin in membranous glomerulonephritis.
In 30% of cases nephrotic syndrome is caused by membranous glomerulonephritis (MG). Protein accumulation in glomeruli leads to progressive loss of kidney function and damage of structure in MG. The role of tissue proteolytic systems and growth factors in this process is not known. The purpose of the study was to estimate urine cathepsin B, collagenase activity and urine excretion of TGF-beta 1 and fibronectin in MG. Cathepsin B activity was greater in the urine of MG patients than in the control group (10.58 +/- 8.73 pmol AMC/mg creatinine per min-1 vs control 7.11 +/- 2.05 pmol AMC/mg creatinine per min-1; P < 0.05). Urine collagenase activity was higher in the group of patients than in the control group (8.59 +/- 4.26 pmol AMC/mg creatinine per min-1 vs control 3.84 +/- 2.09 pmol AMC/mg creatinine per min-1 P < 0.02). Urine excretion of fibronectin (45.60 ng/mg creatinine vs control 10.30 ng/mg creatinine; P < 0.04) and TGF-beta 1 levels in the urine were higher than in controls (283.55 +/- 248.13 pg/ml vs 36.11 +/- 48.01 pg/ml; P < 0.01). Results suggest glomerular overproduction of TGF-beta 1 and urinary leak of proteolytic enzymes (PE). This may result in decreased glomerular PE activity in MG and, with time, may lead to protein accumulation in renal glomeruli and to progressive loss of kidney function and damage of structures as the course of MG progresses. PE urine composition as well as ECM protein and cytokine urine excretion may allow noninvasive glomerulopathy course monitoring in humans in the future.
Adult↗
Abnormal adhesion of T cells to extracellular matrix proteins in hemodialysis patients.
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Adult↗
Effect of chronic therapy with proteolytic enzymes on hypertension-induced renal injury in the rat model of Goldblatt hypertension.
This study investigated the possible beneficial effect of intraperitoneal proteolytic enzyme administration on the development of hypertension-induced renal injury in the rat model of 2-kidney 1-clip (2K1C) Goldblatt hypertension. Male Wistar rats (120-150 g) underwent either sham surgery (control, n = 5) or clipping of the left renal artery. From day one 2K1C rats were randomized into 2 groups, placebo treatment (n = 7), and proteolytic enzyme treatment (n = 9). To the verum group a fixed mixture of trypsin (2.42 mg), bromelain (4.54 mg), and rutin (5.04 mg) dissolved in 2 ml of sterile 0.9% NaCl was administered intraperitoneally daily, while the placebo group received only vehicle. Rats were pair-fed. The duration of the study was 7 weeks. All 2K1C rats developed hypertension and the mean values of systolic blood pressure (SBP) did not differ significantly between the groups at any time recorded (SBP at sacrifice: controls 122.0 +/- 8.5 mm Hg; placebo 191.4 +/- 7. 6 mm Hg; enzyme 180.5 +/- 6.5 mm Hg). Enzyme treatment prevented the rise in proteinuria (controls 12.4 +/- 2.6 mg/24 h; placebo 19.7 +/- 3.9 mg/24 h; enzyme 12.2 +/- 1.3 mg/24 h; p < 0.05) and ameliorated the increase in serum urea concentrations. Histomorphologically, signs of malignant nephrosclerosis were not found in control rats, while they were present in 4/7 (57%) of placebo-treated rats, but only in 1/9 (11%) of the enzyme-treated group. The volume fraction of renocortical interstitium was increased in both 2K1C groups in comparison with controls; however, enzyme treatment decreased the accumulation of interstitial tissue significantly (-22%) compared to placebo treatment. Cellular infiltration with mononuclear cells was also lower in the protease-treated group. To summarize, in the rat model of 2K1C hypertension, systemic treatment with proteases ameliorates the severity of nephrosclerosis and tubulointerstitial fibrosis in the non-clipped kidney, as well as proteinuria, without affecting high blood pressure.
Animals↗
[Mechanisms of action of angiotensin II].
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Angiotensin II↗
[Protein glycosylation end products].
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Alzheimer Disease↗
The effect of cyclosporine on regulators of fibrinolysis in plasma from renal allograft recipients.
Fibrinolytic disturbances are thought to play an important role in processes leading to deterioration of renal allograft function. We investigated the effect of CsA therapy on the regulation of fibrinolysis in kidney graft recipients by measuring plasma concentration and activity of plasminogen activators (tPA, uPA) and their inhibitors (PAI-1, 2). We found an increase in tPA activity and in PAI-1 concentration as well as a decrease in PAI-1 activity in renal allograft recipients as compared to healthy controls, but did not confirm a correlation between these observations and CsA administration. tPA and PAI-2 concentrations as well as uPA activity did not significantly differ between the studied groups. We showed a significant decrease in uPA plasma concentration in patients treated with azathioprine. The significance of this finding is unknown.
Adult↗
[The role of proteolytic enzymes in the pathogenesis of primary glomerulonephritis].
There are many evidences that nonimmunologic factors contribute to pathogenesis of primary glomerulonephritides. Proteolytic enzymes plays important role in glomerular protein turn-over and their altered activities may have influence on glomerular function. The purpose of this paper was to review the role of proteolytic enzymes in initiation and progression of idiopathic glomerular diseases.
Animals↗
[The effect of hypolipidemia treatment on the function of kidney transplanted from cadavers].
The high prevalence of hypercholesterolemia (HCh) in kidney transplant recipients probably contributes to the high cardiovascular mortality of these patients. Additionally, HCh is a contributing factor to the progression of renal failure. We conducted a prospective, randomised study with low dose Lovastatin in 42 kidney transplant recipients during 32 weeks, focusing on side effect and kidney function 42 consecutive patients with kidney transplanted in our Institute, with stable renal function (creatinine level < 160 mmol/l) treated with ciclosporine, azathioprine, prednisone were enrolled for the study (regardless of the initial cholesterol level). Every second patient was given Lovastatin 20 mg/night. In the Lovastatin group total cholesterol (TC) and LDL concentration were significantly lower after 6 months of treatment (TC was reduced from 242.5 +/- 12.8 to 220 +/- 15.4 mg/dl, p < 0.05) in Lovastatin group whereas in control group it increased nonsignificantly. Similarly LDL in Lovastatin group decreased from 140.0 +/- 7.0 to 121.3 +/- 10.8 mg/dl, p < 0.02 whereas in control group it increased from 143.6 +/- 5.4 to 169.9 +/- 10.3 mg/dl, p < 0.01. HDL and trigliceride concentrations were unchanged. The Lovastatin treatment did not results in more adverse events than the placebo treatment. Notably, the tendency to increase creatinine level in Lovastatin group was observed from 1.59 +/- 0.17 to 1.74 +/- 0.22 in Lovastatin group versus 1.89 +/- 0.22 to 2.21 +/- 0.35 mg/dl (NS). Low dose Lovastatin treatment seems to be safe and efficient cholesterol-lowering procedure. However we did not observe beneficial effect on kidney graft function.
Adult↗