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T Cieciura

Publications and source records attributed to T Cieciura.

At least 19 recordsLinked to original sources
PubMed2005

Serum TGF-beta1 correlates with chronic histopathological lesions in protocol biopsies of kidney allograft recipients.

INTRODUCTION: Transforming growth factor-beta (TGF-beta) is a well-known profibrotic factor playing a role in chronic kidney allograft nephropathy. Cyclosporine (CsA)-sparing immunosuppressive regimens may improve long-term graft function. Our aim was to study the influence of immunosuppressive treatment with versus without calcineurin inhibitors on serum TGF-beta levels and histological changes in protocol biopsies of kidney allograft recipients. PATIENTS AND METHODS: In this prospective, randomized study of 42 low-rejection risk patients we randomized two groups: group A: mycophenolate mofetil (MMF), prednisone, daclizumab, and reduced CsA dose for 7 months (5 mg per kg per day) followed by complete withdrawal (n = 21); and group B: normal CsA dose (10 mg per kg per day adjusted according to C2 levels), MMF, prednisone, and no daclizumab (n = 21). METHODS: In both groups we performed histological assessments (Banff 97) and measured serum TFG-beta levels before as well as, at 3 and 12 months after transplantation. RESULTS: We found a relationship between immunosuppressive regimen and the TGF-beta concentration over 1 year of observation. Before transplant the TGF-beta1 levels did not differ between the groups (P = .29); at 3 months they were 33 +/- 9 vs 49 +/- 15 pg per mL, respectively, in groups A and B (P = .08), and at 12 months they were 39.5 +/- 4 versus 55.5 +/- 11 pg per mL, respectively, in groups A and B (P = .03). Protocol biopsies at 12 months in group B showed chronic tubular lesions more pronounced than in group A. TGF-beta1 concentrations were significantly higher among group B than A. We conclude that TGF-beta1 concentration may predict the development of kidney graft fibrosis; early CsA withdrawal may achieve a reduction in chronic tubular and interstitial injury of cadaveric kidney allografts.

Antibodies, Monoclonal↗
PubMed2005

Tubular and glomerular proteinuria in diagnosing chronic allograft nephropathy with relevance to the degree of urinary albumin excretion.

The diagnosis of chronic allograft nephropathy (CAN) is based on pathological examination according to Banff 97 schema. The aim of the study was to evaluate the usefulness of tubular and glomerular proteinuria for noninvasive recognition of CAN. One hundred and thirty renal allograft recipients (at least 90 days after transplantation) who had undergone diagnostic allograft biopsy were included in the study. Beta2-microglobulin, alpha1-microglobulin, albumin, immunoglobulin G, total protein, and creatinine concentrations were obtained from the second morning urine specimen. Raw data and values calculated per 1 g of creatinine excreted in urine along with time after transplantation, serum creatinine, and its change over a period of 2 months prior to biopsy were taken for analysis. Urine proteins were measured using a nephelometric method. Statistical calculations were performed using MANOVA and stepwise discriminant analysis (SDA). Statistical diagnosis and staging of CAN matched the pathological method in 68% of a preliminary SDA. Therefore patients were divided into normoalbuminuric, microalbuminuric, and macroalbuminuric groups. There was no significant differences between protein excretion, except alpha1-microglobulinuria (CAN 0 vs 2, P = .018; CAN 1 vs 2, P = .041), beta2-microglobulinuria (CAN 0 vs 2, P = .026; CAN 1 vs 2, P = .0033), and total proteinuria (CAN 0 vs 2, P = .042) in the normoalbuminuric group. Nevertheless, diagnoses obtained using SDA were 89%, 91%, and 92% identical to the results of pathological examinations, for normoalbuminuric, microalbuminuric, and macroalbuminuric groups, respectively. In conclusion, tubular and glomerular proteinuria measurements may be useful for a noninvasive CAN diagnosis and staging only with regard to degree of urinary albumin excretion.

Albuminuria↗
PubMed2003

C4d complement split product expression in chronic rejection of renal allograft.

Chronic allograft rejection remains the major cause of late renal graft loss. Its pathogenesis is complex, depending on both immunological and nonimmunological factors. An important role in development of chronic rejection is ascribed to an ongoing immunological reaction mainly of the humoral type. C4d complement split product, as a stable fragment of complement degradation activated by antigen-antibody complexes, is considered to be an indicator of humoral activity in allografts. The aim of the present study was to establish a correlation between C4d expression and morphological findings specific for chronic rejection among biopsy specimens from patients with deteriorating graft function versus protocol biopsy specimens versus biopsy specimens of native kidneys with glomerular diseases. C4d deposits in peritubular capillaries and glomeruli were observed in 83% of patients with morphological changes of chronic rejection. No C4d expression was found in the protocol biopsy group. C4d deposits in glomeruli localizations were found in kidneys from patients with glomerulopathies; the pattern of distribution was similar to that for antibodies characteristic for glomerulonephritis. There was a positive correlation between C4d expression and morphological features of chronic rejection. In our opinion, only peritubular capillary localization is specific for a rejection process; glomerular localization is nonspecific and probably secondary to antigen-antibody complex deposition in course of some types of glomerulopathies.

Biopsy↗
PubMed2003

The role of the protocol biopsies in renal allograft recipients.

Subclinical rejection and long-term cyclosporine nephrotoxicity are well-known risk factors of chronic allograft nephropathy. In a prospective study 32 low-risk patients were randomized to either a reduced CsA dose (5 mg/kg/d) and daclizumab (group A, n = 16) for 7 months posttransplant with subsequent CsA tapering/withdrawal, or to a normal CsA dose (10 mg/kg/day) without daclizumab (group B, n = 16). Both groups received MMF and prednisone. Protocol biopsies were obtained at engraftment and 3 and 12 months after Tx. The number of rejection episodes was the primary endpoint. The secondary endpoints were: renal function, histological parameters related to CsA, and serum levels of TGF-beta and PDGF-BB. A low incidence of clinically suspected rejection episodes was observed (19% in group A and 12.4% in group B; P = NS). Although protocol biopsies showed 12 subclinical rejection episodes (six in group A, six in group B), serum creatinine levels were not different between the examined groups at 3 months. However, at 12 months, there was a statistically improved mean creatinine level in group A patients (1.2 mg/dL +/- 0.5 in group A vs 1.54 mg/dL in group B; P <.05). Chronic histopathologic changes were significant for biopsies at 3 and 12 months in both groups compared to the baseline findings for protocol biopsies (with no differences between groups, or between 3 and 12 months in both groups). Serum TGF-beta and PDGF-BB did not differ between the groups. Protocol biopsies may be useful to monitor safety and efficiency of new immunosuppressive protocols. Immunosuppressive regimens with low CsA doses followed by the drug's complete withdrawal seem to be efficient and safe in low-risk kidney allograft recipients.

Adult↗
PubMed2003

Polyomavirus BK infection.

Because it is an important factor affecting renal transplant function, BK infections are significant problem in posttransplant. BK nephropathy develops in 5% of renal allograft recipients, in most cases within the first year after the procedure. The gold standard for BK nephropathy diagnosis is still immunohistochemical staining for large T antigen in graft biopsy specimens. The aim of the present study was to evaluate the incidence of and factors influencing BK nephropathy in our renal allograft population. Among 89 renal or pancreas/kidney allograft recipients, BKV DNA was detected in 1 or more serum samples in 17 patients but BK nephropathy was diagnosed in only 1 case. Plasmacytic tubulitis was an exclusive feature in PCR-positive patients with 2 (20%) cases but no such findings in the PCR-negative group. In 40% of patients in the PCR-positive group at least 1 rejection episode was diagnosed versus 22% in the PCR-negative group. There were no significant differences in both groups according to total ischemia time, immunosuppressive treatments, or mean serum creatinine at 1 year after transplantation.

BK Virus↗
PubMed2000

Randomised open clinical trial of conversion from mycophenolate mofetil to azathioprine in cadaveric renal transplantation.

Mycophenolate mofetil (MMF) is a powerful immunosuppressive drug with established efficacy and safety. The search for a less expensive immunosuppressive protocol has led to an open randomised clinical trial of conversion from MMF to azathioprine (Aza). A total of 28 renal allograft recipients treated with prednisone, cyclosporine, and MMF was randomised into two groups: converted (early conversion) and control (late conversion). Conversion from MMF to Aza was conducted at the end of the 4th post-transplant month in the converted group and after the 12th month in the control. During the 20-month observation period, biopsy-proven acute rejection occurred more frequently in the converted than in the control group, although the difference was not statistically significant. Early conversion from MMF to Aza increased the risk of subsequent rejection in those patients who underwent at least one episode of acute rejection prior to conversion.

Adult↗
PubMed1999

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↗
PubMed1997

Higher exposure to cyclosporine A with unchanged tolerability in patients converted from Sandimmun to Sandimmun Neoral.

Neoral (NEO) is claimed to have better pharmacokinetics than standard preparation of cyclosporine (SIM) thus providing more reliable immunosuppression. We estimated safety and tolerability of NEO and compared pharmacokinetic parameters in 20 stable renal allograft recipients (RARs) converted from SIM to NEO treatment. Another 20 stable RARs continuously treated with SIM created a control group. Whole blood through CsA level (C0) did not differ after conversion (SIM: 136.2 +/- 33 ng/ml and NEO: 142.6 +/- 34 ng/ml). During therapy with NEO peak blood concentration (Cmax) was significantly higher (935.6 +/- 368 ng/ml) and occurred earlier (Tmax 1 hr. 36 min. +/- 30 min) as compared to the period on SIM (Cmax 598 +/- 309 ng/ml, p = 0.01), Tmax = 3 hr. +/- 1 h 36 min., (p = 0.01) respectively. AUC increased from 2975.4 +/- 1020 ngxhr/ml to 4236.1 +/- 1188 ngxhr/ml (p < 0.0001). Correlation coefficient between AUC and C0 was higher during NEO (r = 0.52) than SIM therapy (r = 0.32). The only noticeable change in laboratory tests after switch to NEO was slight increase of serum triglyceride concentration (119.5 +/- 44.7 mg/dL vs. 148.4 +/- 67.0 mg/dl). The mean serum creatinine concentration did not change significantly (1.42 +/- 0.32 mg/dL and 1.46 +/- 0.31 mg/dL). Tolerance of NEO was good and 1:1 switch from SIM to NEO is clinically safe. Higher bioavailability of NEO was not associated with decreased tolerability or increased nephrotoxicity. Better correlation between C0 and AUC during NEO administration makes CsA treatment monitoring more reliable.

Adult↗