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Biomedical subjects

I Matl

Publications and source records attributed to I Matl.

At least 19 recordsLinked to original sources
PubMed2004

[Initial experience with protocol biopsies in transplanted kidneys].

BACKGROUND: The aim of protocol biopsy after renal transplantation was to assess the prevalence of chronic allograft nephropathy (CTN) and to correlate the degree of CTN with clinical and laboratory data. METHODS AND RESULTS: In 105 patients with a stabilized graft function, a protocol biopsy was carried out at 1 year after transplantation. CAN was found in 75% of patients, and in 6% an acute subclinical rejection was revealed. Statistically significant correlation was confirmed between CAN and recipient's age, development of acute rejection in the first year posttransplant, serum creatinine, clearance of creatinine, and proteinuria. There was no significant difference in CAN degree distribution between patients treated with cyclosporine-A or with tacrolimus. Twelve months after the biopsy, there was no significant change in kidney graft function. In patients treated with tacrolimus, cholesterol and triglycerides levels were significantly lower than in cyclosporine treated patients Over the next year, these values significantly decreased in both subgroups. CONCLUSIONS: The CAN was found in the majority of protocol biopsies at 1 year after kidney transplantation; subclinical acute rejection was revealed rarely.

Biopsy, Needle↗
PubMed2003

TGF-beta1 expression and chronic allograft nephropathy in protocol kidney graft biopsy.

Chronic allograft nephropathy (CAN) represents a frequent and irreversible cause of long-term renal graft loss. TGF-beta1 is a key profibrogenic cytokine associated with CAN pathogenesis. Because of clinical diagnostic inaccuracy, protocol biopsy has been suggested to be a beneficial method for early CAN detection. Protocol core biopsy was carried out in 67 consecutive cyclosporine-based immunosuppression-treated kidney transplant recipients with stable renal function 12 months after renal transplantation. Biopsy specimens were analyzed morphologically according to Banff-97' criteria and immunohistologically for TGF-beta1 staining. The data obtained were correlated with plasma TGF-beta1 levels and clinical data. CAN (grade I-III) was found in 51 patients (76 %). CAN grade I was found to be the most frequent one (44 %). A normal finding within the graft was made in only 12 patients (18 %). Clinically silent acute rejection Banff IA was present in 4 patients (6 %). In 8 patients (12 %) with CAN, borderline changes were present. We found a significant correlation between CAN grade and creatinine clearance, as measured by the Cockroft-Gault formula (p<0.01) as well as body mass index (p<0.01). There was a significant correlation between chronic vasculopathy (Banff cv) and creatinine clearance, and between the degree of TGF-beta1 staining and chronic vasculopathy (p<0.01). There were no relations between morphological findings and TGF-beta1 plasma levels, cyclosporine levels, plasma lipids, HLA-mismatches, panel reactive antibodies (PRA), proteinuria, and the donor's age. In conclusion, CAN is a frequent finding in protocol kidney graft biopsies 12 months after transplantation. TGF-beta1 tissue expression is linked with chronic vasculopathy.

Adult↗
PubMed2002

[Transforming growth factor (TGF-beta) and kidney transplantation].

Transformation growth factor (TGF-beta) is a cytokine, which takes part in many clinical conditions linked to different chronic disease states. Its production is regulated by genes and polymorphism of TGF-beta gene individually predetermines levels of its production. TGF-beta is produced by a number of normal, predominately haemopoietic and tissue cells. Moreover, it controls cell proliferation and differentiation, and namely it stimulates fibrogenesis. Profibrogenic efficacy plays a physiological role in wound healing and it is implicated in a spectrum of disease states, such as diabetic nephropathy, chronic glomerulonepthritis, lung fibrosis, or postirradiation fibrosis. In kidney transplant recipients. TGF-beta has been suggested to be involved in the chronic rejection pathogenesis by enhancing fibrogenesis.

Fibrosis↗
PubMed2001

[Nitric oxide (NO) in a model of renal ischemia and cyclosporine toxicity].

BACKGROUND: The role of nitric oxide (NO) after the cadaveric kidney transplantation has not been fully clarified yet. The aim of our study was to examine benefits of the administration of a NO precursor--L-arginine in the model of renal ischaemia and after the subsequent cyclosporine (CsA) treatment, which simulates the state resulting from the kidney transplantation. METHODS AND RESULTS: 60 male rats of the Wistar strain were exposed to ischaemia for 45 minutes. Then they were divided into six groups: 1. Controls, 2. Rats administered by gastric sonde with 300 mg/kg of L-arginine since the first day after ischaemia, 3. Rats administered in a similar way with 10 mg/kg of cyclosporine A, 4. Group of rats receiving both drugs in the same doses, 5. Rats receiving 10 mg/kg of cyclosporine A since the first day after ischaemia and L-arginine in the dose 300 mg/kg since the seventh day, 6. Group of animals administered with L-arginine and cyclosporin A in the same doses with nonselective blocker of NO synthesis--L-NNA in the dose of 5 mg/kg. We examined renal functions (blood and urine levels of creatinine, urea, Na, K, Cl, osmolality, proteinuria), blood and urine levels of NO metabolites (NO2- and NO3-) in the fourth week after ischaemia. We found that L-arginine administration (when groups 1 and 2 were compared) decreased S-creatinine (< 0.05), it increased U-osmolality (p < 0.01), tubular resorption (p < 0.001), and blood levels of NO metabolites (p < 0.05). Changes in urine levels of NO metabolites (U-NOx/U-Cr) and in proteinuria were not found. In animals with renal ischaemia treated with cyclosporine (comparison of groups 3 and 4), L-arginine administration brought about a decrease of blood creatinine levels (p < 0.05), higher creatinine clearance (p < 0.05) and higher blood levels of NO metabolites (S-NOx; p < 0.01). However, differences in tubular functions, proteinuria and U-NOx/U-Cr were not detected. When L-arginine was added 7 days after the beginning of cyclosporine treatment, no significant difference was found between groups 5 and 3 and differences between groups 5 and 4 were similar to those between groups 4 and 3. Animals of the group 6 were not tested due to high mortality indicating high toxicity of the combination ischaemia + cyclosporine + L-arginine + L-NNA. CONCLUSION: Our study shows the benefits of L-arginine treatment in the renal ischaemia and during cyclosporine administration. The treatment should start immediately after the ischaemic period and at the same time as the cyclosporine administration. L-arginine added later has no positive effect.

Animals↗
PubMed2001

[Rapamycin: a new immunosuppressive agent capable of inhibiting chronic rejection?].

Chronic rejection represents the most common cause of transplanted graft loss in the long term. Rapamycin (sirolimus), and it's derivate RAD, are new and potent, immunosuppressive drugs. They inhibit cell proliferation driven by various growth factors. These drugs were successfully tested in some experimental models of the chronic rejection. Results of the first clinical trials have defined rapamycin pharmacokinetics and proved immunosuppressive efficacy. Rapamycin acts synergistically with cyclosporin A. The side effects are a dose-dependent thrombocytopenia and leukopenia but the most frequent is hyperlipidemia. The question, if rapamycin and RAD inhibit development of chronic rejection in man, will be solved by the prospective clinical trials over years.

Chronic Disease↗
PubMed2001

[Nitric oxide in patients after cadaveric kidney transplantation].

BACKGROUND: The role of nitric oxide (NO) after cadaveric renal graft transplantation has not been yet fully clarified. The aim of our study was to examine NO production into the urine of patients following cadaveric renal graft transplantation with a normal course and complications (acute rejection and cyclosporin toxicity). METHODS AND RESULTS: Production of stabile NO metabolites (NO2 and NO3) into urine (U-NOx) was examined in recipients of cadaveric renal transplantation. Only patients with standard triple immunosuppressive therapy (cyclosporin, azathioprine, prednisone) were include into the study. Patients receiving other immunosuppressive agents or drugs affecting NO formation (nitrates, ACE inhibitors) were excluded from the study, as were those with infectious or other serious post-transplant complications. Overall, we examined 33 patients (21 men and 12 women), with acute rejection and cyclosporin-induced toxicity in ten each, and a normal course with no complications in 13. The mean age of the patients was 50.96_11.13 years. U-NOx was examined by biochemistry using Griesse reaction every day after transplantation both in a morning urine sample and in a sample from 24-hour collection over the preceding day and calculated to 1 mmol/l of urinary creatinine (U-Cr). The levels of U-NOx/U-Cr in patients with acute rejection over the past 2 days before its development were lower compared with those in patients with a normal course (p_0.05). No difference was found between the groups of patients with cyclosporin-induced toxicity and a normal course. The levels of U-NOx were inversely correlated (p_0.01) to the levels of serum creatinine (S-Cr), but did not correlate with the blood levels of cyclosporin A. CONCLUSIONS: The study demonstrated a decrease in urinary U-NOx production within the past 2 days before renal transplant rejection. The levels of U-NOx in patients with cyclosporin-induced toxicity remain unaltered. U-NOx/U-Cr could possibly become a non-invasive marker of rejection.

Cadaver↗
PubMed2000

[Chronic renal allograft rejection. Part 2. Therapeutic possibilities] .

Chronic rejection represents an important cause of renal allograft loss in the long term follow up. New insights into etiopathogenesis of the chronic rejection offer possibilities for experimental therapy. Novel immunosuppressants, such as mycophenolic acid, tacrolimus or rapamycin as well as lipid lowering drugs, angiotensin-converting enzyme inhibitors or AT-1 receptor blockers, may reduce of effects the risk factors on the progression of chronic rejection. In the future, gene therapy may offer additional possibilities to prevent chronic rejection. This review deals with possibilities of prevention of the chronic renal allograft rejection based on experimental evidences and current therapeutic concepts and puts these options into a rational perspective.

Chronic Disease↗
PubMed2000

[Withdrawal of prednisone from a triple combination of immunosuppressive agents after kidney transplantation].

BACKGROUND: Triple-drug immunosuppression may not be necessary in a majority of stabilized patients over 1 year after kidney transplantation. In contrary steroid withdrawal may be beneficial for the patient by elimination of side-effects. The primary aim of this study was assessment of the risk of rejection after the prednisone withdrawal. METHODS AND RESULTS: 88 patients 1 year after the first renal transplantation with stable graft function and serum creatinine < 160 mumol/l treated with cyclosporine-A, azathioprine and prednisone were randomized into group A (n = 46) with a prednisone withdrawal and group B (n = 42) on triple-drug therapy without change. At the time of randomization, fine-needle biopsy was carried out in all of the patients. In group A, the dose of prednisone was gradually reduced to zero in the course of six months and the patients were followed up for the next 12 months. In the group B, patients on triple-drug therapy were followed for the corresponding period of time. 3 patients (6.6%) in group A, and 2 (4.8%) in group B experienced rejection (NS). Mean values of serum creatinine were in the course of follow-up in both groups without any statistical difference. Suspect immunological activity or proved immunological activity in aspiration biopsy was present in 4 patients in each group, but one of them rejected the graft. In comparison with group B, a significant decrease of cholesterol and leukocytes was observed in group A. Prednisone withdrawal had no influence on hypertension and triglyceride. CONCLUSIONS: Gradual withdrawal of steroids is not associated with higher risks of rejection and has a beneficial effect on cholesterol levels. Aspiration biopsy was of no use for the prediction of rejection.

Azathioprine↗
PubMed2000

Withdrawal of steroids from triple-drug therapy in kidney transplant patients.

BACKGROUND: In renal transplant patients with stable graft function, triple-drug immunosuppression may not be necessary, while withdrawal of steroids may eliminate side effects. The primary aim of this study was to assess the risk of rejection after steroid withdrawal. METHODS: A total of 88 patients with stable graft function and serum creatinine <160 micromol/l, treated with cyclosporin A, azathioprine and prednisone were randomized into group A (n=46) with a gradual prednisone reduction to zero in the course of 6 months, and group B (n=42) on triple-drug therapy without change. At the time of randomization, fine-needle aspiration biopsy (FNAB) was carried out in all of the patients. After stopping steroids, the patients were followed up for a period of 12 months. RESULTS: Four patients failed to complete steroid withdrawal, three due to rejection, and one due to leukopenia. The proportion of rejection in three patients in group A (6.6%) was not significantly different from rejection in two patients in group B (4.8%). The mean value of serum creatinine was not significantly different in both groups in the course of follow-up. A finding of some degree of immunological activity in FNAB was made in four patients in each group, but none of these patients developed rejection. Compared with group B, significant decreases in serum cholesterol and blood leukocytes were observed in group A. Prednisone withdrawal did not have any influence on hypertension and serum triglycerides. CONCLUSIONS: Gradual withdrawal of steroids is not associated with a higher risk for rejection and has a beneficial effect on serum total cholesterol levels. FNAB was not a useful tool for predicting rejection.

Adult↗
PubMed1999

[Chronic rejection of renal allografts. Part 1. Present knowledge of etiopathogenesis].

Chronic rejection is the most common cause of the long term renal graft loss. It is characterized by luminal thickening and obliteration, interstitial sclerosis, glomerulosclerosis and tubular atrophy development. The pathology is still unclear. Alloantigen-dependent factors (acute rejection, HLA mismatch) and allograft-independent factors (ischaemia-reperfusion, hyperlipidaemia, hypertension, infection, nephrotoxicity, reduced nephron dose) have been implicated in the etiology of chronic rejection. As a result of these factors, endothelial cells are activated and express a variety of adhesion molecules, cytokines and growth factors. Lymphocytes and macrophages infiltrate the areas of local damage and express other cytokines and growth factors (TGF, bFGF, PDGF). In the next step, vascular smooth muscle cells proliferate and migrate from the media into the vascular intima and produce local extracellular matrix. Which factors are the most important and which mechanisms are the key for the development of chronic rejection are in the focus of ongoing research.

Chronic Disease↗
PubMed1999

[Conversion from Consupren sol. to Consupren S capsules in kidney transplant patients].

In a group of patients after transplantation of the kidney with stabilized graft function treated by Consupren sol. combined with prednisone and azathioprin in 20 patients (group A) Consupren sol. was replaced by Consupren S capsules, in 17 patients (group B) Consupren sol. therapy proceeded without any change. To maintain the cyclosporin blood concentration within the therapeutic range it was necessary after the change of drug form in group A to adjust the dosage of the drug in 12 patients of group A while in group B only in one patient (p<0.01). The mean doses and levels of Cy-A however did not change significantly during the three-month investigation period in the two groups and and the bioequivalence of the two preparations was evident. Conversion from Consupren sol. to Consupren S capsules is not associated with the risk of rejection or undesirable effects. It can be implemented at a ratio of 1:1 or 1: the closest dose divisible by 25 (the smallest capsules are 25 mg) and after conversion a check-up or possible modification of the dose is necessary.

Administration, Oral↗
PubMed1998

[Light chain deposition disease as a cause of renal failure].

The objective of the paper is to draw attention to a rare cause of rapidly progressing renal failure which developed in the course of four months as a result of light chain deposition disease. The authors submit two case-histories of the disease assessed by renal biopsy after previous clinical and laboratory suspicion of monoclonal gammapathy. In one patient in the sternal punctate plasmacytoma was diagnosed and in the second case it was not possible to detect any type of monoclonal gammapathy or another possible cause of disease. Renal failure was in both cases irreversible and both patients were enlisted in regular haemodialyzation treatment.

Female↗
PubMed1998

[Repeat kidney transplantation].

BACKGROUND: The objective of the study was an analysis of results of repeated kidney transplantations (Tx2, Tx3) implemented during the first 29 years of activities of the Transplantation Centre of the Institute of the Clinical and Experimental Medicine in subjects with a different maintenance immunosuppression. METHODS AND RESULTS: The retrospective study pertains to 134 Tx2 and 17 Tx3 in 134 non-diabetic subjects: 43 of them had during Tx1 and Tx2 (1966-1981 and 1966-1985 resp.) immunosuppression on the basis of azathioprin (Aza, sub-group AA), 42 during Tx1 (1972-85), Aza, while during Tx2 (1984-85) immunosuppression on the basis of cyclosporin (CyA, subgroup AC) and 49 both during Tx1 and Tx2 (1985-93 and 1986-95 resp.) CyA (subgroup CC). Compared was survival of grafts by the actuarial method (with regard to all losses regardless of cause) by the end of the 4th year inside the subgroups (Tx2, vs. Tx1 and Tx3 vs. Tx2 in the same subjects) and between subgroups (Tx1 vs. Tx1 and Tx2 vs. Tx2 in different subjects). Moreover in paired investigations the survival of recipients and grafts after Tx2 was compared after immunosuppression on the basis of CyA with the same parameters after Tx1 in different subjects with the same immunosuppression, operated at approximately the same time (n = 81) and survival of subjects with Tx1 + Tx2 on the CC regime regardless whether the second grafts functioned at the time of the last examination, with survival of subjects after Tx1 where after graft failure Tx2 was not performed (n = 34). Prophylaxis with antilymphocyte globulins was not used. Survival of second and first grafts did not differ in any of the subgroups, third grafts survived at the end of the third year more frequently than second grafts (66 vs. 18%, p < 0.01). Second grafts in CC survived more than in AA (55 vs. 28%, p < 0.01). In the paired study Tx2 vs. Tx1 the survival of grafts and recipients was the same (88 vs. 89%, N.S. and 47 vs. 62% resp.), in the paired study Tx1 + Tx2 vs. Tx1 more subjects with Tx1 + Tx2 survived 10 years after Tx1 than subjects who did not have Tx2 (82 vs. 49%, p < 0.05). CONCLUSIONS: A further transplantation of the kidney after functional loss of the first graft is the method of choice: the mortality is low, the probability of several years' function is considerable and the prognosis as regards quality and length of life better than with regular dialysis treatment.

Adult↗
PubMed1998

[Evaluation of long-term monitoring of glomerular filtration in individuals with kidney transplantation].

BACKGROUND: Long-term follow-up of the glomerular filtration rate (GFR) in subjects with a transplanted kidney revealed that changes of this function in the course of time are frequently irregular and cannot be expressed by a simple mathematical function. This fact causes problems when evaluating the rate of progression of chronic transplant nephropathy. Characterization of changes of the GFR of the graft by values of this function at the beginning and at the end of the follow-up period does not take into account transient changes and the predominating level of GFR during the entire follow-up period. The authors tried to elaborate a method which would render it possible to evaluate in a simple manner the level of the GFR during the entire investigation period. The method is based on assessment of the area under the curve (AUC) of GFR. METHODS AND RESULTS: This method was used to investigate the time course of GFR in 22 subjects after transplantation of the kidney from a cadaverous donor. The investigated group included nine women and 13 men aged 30-65 years (mean 50 years). The time interval after transplantation was 1-84 months (mean 22 months). The GFR was assessed after 3-months intervals for a period of 9-21 months (mean 13.5 months). GFR was assessed on the basis of renal clearance of polyfructosan. The time course and level of GFR was evaluated in the common way based on GFR values at the beginning and end of the investigation period and according to the new method based on calculation of AUC. It was found that the two methods of evaluation of graft function do not provide the same results. In one third of the examined subjects the differences were higher than 20%. CONCLUSIONS: The results of this study provide evidence that evaluation of changes and the level of the GFR of the graft throughout the follow-up period based on AUC provides more detailed information then evaluation of the GFR only at the beginning and end of the follow-up period. The authors assume that this method of evaluation of the GFR of the graft could be helpful in a more accurate assessment of the effect of different therapeutic procedures.

Adult↗
PubMed1998

Long-term follow-up of the tubular secretion of creatinine in renal graft recipients.

The differences in glomerular filtration rate (GFR) based on creatinine clearance (Ccr) or obtained by the more exact methods are caused mainly by tubular creatinine secretion. In this study, we monitored creatinine clearance (Ccr), GFR on the basis of polyfructosan renal clearance (C(PF)) and parameters characterizing tubular creatinine secretion (Ccr/C(PF), Ccr - C(PF), Tcr/C(PF) x 100) in 12 individuals with renal grafts (Group A), 12 kidney graft donors for related transplantation (Group B), and in 27 individuals undergoing nephrectomy for a pathological process in one kidney (Group C). In the monitored groups, C(PF) and Ccr values were within the limits consistent with the normal function of a single kidney in a healthy individual. The values characterizing tubular creatinine secretion in Group A did not differ significantly from those obtained in Groups B and C. However, the parameters showed a wide range in all groups. In seven individuals with a renal graft, all the above functional parameters were monitored at three-month intervals for a period of 24 months. Significant differences in the time courses of Ccr and C(PF) due to marked intra-individual fluctuations were found in tubular creatinine secretion. The findings suggest that the rate of tubular creatinine secretion in the renal graft does not differ significantly from that in individuals with a single native (normally functioning) kidney. However, there are large inter-individual differences. The large intra-individual fluctuations in tubular creatinine secretion in the kidney graft result in significant differences in the time courses of Ccr and C(PF) and a possibility of erroneous evaluation of graft function if based exclusively on Ccr.

Adolescent↗
PubMed1998

[Renal excretion of potassium in individuals with stabilized function of a transplanted kidney].

From previous work it is known that in subjects with a transplanted kidney treated with cyclosporin A hyperkalaemia may develop even if the glomerular filtration rate is within the normal range or only slightly reduced. The mechanism of this defect was not elucidated so far. In the present work the authors try to study the question whether and how renal potassium excretion by the transplanted kidney is influenced by the intensity of sodium excretion. Focused on renal excretion of potassium, sodium, chlorides, all osmotically active substances, glomerular filtration rate (polyfructosan clearance) and renal plasma flow (paraaminohippuric acid clearance) the authors examined 12 patients after transplantation of the kidney from a cadaverous donor (group A), 11 subjects after unilateral nephrectomy for the purpose of donorship for transplantation (group B) and 27 subjects after nephrectomy on account of a pathological process in one kidney (group C). The glomerular filtration rate in the investigated groups was greater than 1.0 ml/s/1.73 m2. The mean value of the fractional potassium excretion (FEK) in group A was 15.2 (+/- 6.3)%, in group B 18.4 (+/- 6.6)% and in group C 20.1 (+/- 8.6)%. The value of FEK in group A was significantly lower than in group C (p < 0.01). Groups B and C did not differ significantly in the mean value of FEK. Between values of FEK and FENA a significant direct correlation was found (r = 0.621, p < 0.001) in the group of subjects with a single kidney of their own (B + C). On the other hand, this correlation was not found in subjects with a transplanted kidney (A). The achieved results support the idea that in subjects with a transplanted kidney treated with cyclosporin A there are deviations in tubular potassium transport even when its serum level is not elevated. This deviation is manifested by lower FEK values and also by and inadequate response of the distal tubule to an increased sodium supply by increased tubular potassium secretion. The authors assume that when drugs with a potential potassium retaining effect are administered to subjects with a transplanted kidney it is important to check carefully the serum potassium level even when the glomerular filtration rate is within normal limits or only slightly reduced.

Adult↗
PubMed1998

[Hyperlipidemia after kidney transplantation and its control by individualized therapy: evaluation of the first years' trial].

Secondary hyperlipidaemia (HLP) is one of the most serious metabolic complications in patients after transplantations of the kidney. In its development a number of factors may participate, the most important ones being immunosuppressive drugs (cyclosporin A and prednisone) and the patients dietary habits. In a prospective metabolic trial a group of 248 patients after transplantation of the kidney with a long-term stable function of the graft were followed up for 12 months. Group I (128 patients) was systematically followed up in the Institute of Clinical and Experimental Medicine and the patients were treated by individualized dietetic and pharmacological intervention. Group II (120 patients) were out-patients who were treated according to current procedures in other departments than the Institute of Clinical and Experimental Medicine. The cholesterol and LDL-cholesterol increased significantly in both groups starting with the 3rd month of the follow-up. A subsequent decline was observed in group I from the 9th month onward, while in group II both values rose steadily. The triacylglycerol level rose in both groups during the 6th month, there were however great interindividual differences. There was a significant rise of the HDL-cholesterol. The Lp(a) level changed also significantly--its values--after an initial drop during the 3rd month--rose significantly in group II.

Adult↗