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Biomedical subjects

Leszek Paczek

Publications and source records attributed to Leszek Paczek.

At least 37 records · Page 2Linked to original sources

Serum growth factors in hemodialyzed patients.

The contact of chronic hemodialysis patients' blood with components of extracorporeal circulation leads to mobilization of several systemic reactions. The purpose of this study was to determine the activity of transforming growth factor (TGF-beta1) and platelet derived growth factor (PDGF) in serum of patients on long-term hemodialysis program and to compare these results with ones obtained in healthy volunteers. Twenty-five patients on dialysis carried out on polysulfone membrane dialyzer, and 16 patients on dialysis with the used of cuprophan membrane dialyzer on long-term hemodialysis program participated in the study. TGF-beta1 level in serum of healthy volunteers (12.06 +/- 7.56 ng/mL) was lower than in serum of patients dialyzed on polysulfone membrane dialyzers (26.56 +/- 14.83 ng/mL). Differences in PDGF concentrations in serum of control group and hemodialyzed patients were not statistically significant. The strong correlation between TGF-beta1 and PDGF in serum of both studied groups of patients was demonstrated.

Adult↗

Pretransplant and early posttransplant predictors of chronic allograft nephropathy in cadaveric kidney allograft--a single-center analysis of 1112 cases.

This retrospective series reviews risk factors for chronic allograft nephropathy (CAN) based on the 10-year experience of a single institution. One thousand one hundred and twelve primary cadaveric renal transplant recipients whose graft survived for more than 6 months were followed for a mean of 4.6 years. The data were analyzed using the multivariate Cox proportional hazards model. CAN was defined as an irreversible rise of serum creatinine (SCr) by 30% in the absence of other causes and occurred in 42% of the patients. The risk of CAN was significantly increased in patients who experienced late rejections. Recipients of organs from donors that were older than 50 years and from such who died secondary to cerebrovascular accident were at increased risk of incurring CAN. Early markers of progression to CAN found at 6 months after transplantation included SCr levels of greater than 1.8 mg/ml, proteinuria, hypoalbuminemia, and hypertension. In conclusion, immune and non-immune factors affect progression to CAN in renal allograft recipients.

Adult↗

Long-term improvement in renal function with sirolimus after early cyclosporine withdrawal in renal transplant recipients: 2-year results of the Rapamune Maintenance Regimen Study.

INTRODUCTION: The purpose of this study was to evaluate early cyclosporine (CsA) withdrawal from a sirolimus (SRL)-CsA-steroid (ST) regimen. METHODS: Within 48 hr after transplantation, 525 primary (90%) or secondary (10%) renal allograft recipients with cadaveric (89%) or living (11%) donors received 2 mg of SRL (troughs >5 ng/mL; immunoassay), CsA, and ST. Those eligible (430) were randomly assigned (1:1) at 3 months +/- 2 weeks to remain on triple-drug therapy (SRL-CsA-ST group) or to have CsA withdrawn and SRL trough concentrations targeted to 20 to 30 ng/mL (SRL-ST group) until month 12, and 15 to 25 ng/mL thereafter. RESULTS: At 24 months, there were no statistically significant differences in patient survival (94.0% vs. 95.3%), graft survival (91.2% vs. 93.5%), acute rejection after randomization (5.1% vs. 9.8%) or discontinuations (34% vs. 33%) for SRL-CsA-ST versus SRL-ST, respectively. Serum creatinine level was significantly better in patients who had CsA withdrawn (167 vs. 128 micromol/L, P<0.001), as was the slope of 1/creatinine. Similarly, systolic blood pressure was lower in patients who had CsA withdrawn (141 vs. 134 mm Hg, P<0.001). High-density lipoprotein cholesterol was significantly higher in the SRL-ST group, whereas total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were not significantly different. Hypertension, creatinine increase, abnormal kidney function, toxic nephropathy, edema, hyperuricemia, cataracts, Herpes zoster, and malignancy were reported significantly more often in patients continuing CsA. Thrombocytopenia, hypokalemia, abnormal liver function tests, abnormal wound healing, ileus, and pneumonia were reported significantly more frequently with SRL-ST. CONCLUSION: Data at 2 years confirm that early CsA withdrawal followed by an SRL-ST maintenance regimen results in long-term improvement in both renal function and blood pressure, without increased risk of graft loss or late acute rejection.

Blood Pressure↗

A prospective randomized multicenter study of tacrolimus in combination with sirolimus in renal-transplant recipients.

BACKGROUND: Recently, sirolimus (SRL) was introduced as an immunosuppressant in solid-organ transplantation. This study evaluated combinations of SRL and tacrolimus (Tac). METHODS: This 6-month study investigated the safety and efficacy of Tac and steroids in combination with three different doses of SRL in renal-transplant recipients. A total of 104 patients were randomized in four groups: one group received Tac and steroids (control n=28), and three groups also received the following daily SRL doses: 0.5 mg (TacSRL0.5, n=25), 1 mg (TacSRL1, n=25), or 2 mg (TacSRL2, n=26). Tac doses were adjusted to whole-blood trough levels. Steroids were tapered from 20 mg per day to 5 mg per day. The SRL groups underwent a second randomization to discontinue SRL at either month 3 or 5. RESULTS: At month 6, patient survival rates were 100%, 100%, 96.0%, and 100%, and graft survival rates were 96.4%, 84.0%, 88.0%, and 84.6%, respectively. The overall safety profile was similar in all groups. The incidences of infections during months 1 to 3 were similar in all groups (control 46.4%, TacSRL0.5 32.0%, TacSRL1 56.0%, TacSRL2 46.2%). The 3-month incidences of hypercholesteremia (cholesterol >240 mg/dL or low-density lipoprotein cholesterol >160 mg/dL) were 21.4%, 36.0%, 48.0%, and 50.0% (P=0.019). Lipid levels improved after withdrawal of SRL. The 3-month incidences of biopsy-proven acute rejection were 28.6% (control), 8.0% (TacSRL0.5), 8.0% (TacSRL1), and 3.8% (TacSRL2) (P=0.014). CONCLUSION: Tac in combination with low doses of SRL provides a very effective and safe regimen.

Adult↗

Prognostic significance of free radicals: mediated injury occurring in the kidney donor.

BACKGROUND: Brain death is associated with hemodynamic disturbances in systemic circulation and metabolic storm, and, thus, free radical-mediated injury to donor tissues was hypothesized. An assessment of oxidative stress in the donor and its effect on posttransplant kidney graft function comprised the scope of the study. METHODS: A prospective study was performed in 27 donors and 50 kidney transplant recipients. Sera from 27 brain-dead organ donors and preservation media were tested for malondialdehyde (MDA) and for total antioxidant status (TAS). Kidneys were preserved in University of Wisconsin-gluconate solution with machine perfusion. Mean ischemia time was 36.7+/-8 hours. Organs were transplanted to recipients on the Polish National Waiting List and posttransplant kidney function was monitored periodically. Posttransplant delayed graft function (DF) was diagnosed when a patient required at least one dialysis within first week after transplantation. Acute rejection was diagnosed clinically and confirmed with fine-needle biopsy if necessary. RESULTS: Thirty-two recipients had immediate graft function (IF), and 18 suffered from DF. MDA level in preservation solution at the end of machine perfusion was significantly higher in the DF group (52.6+/-31 vs. 25.3+/-19 micromol/L) whereas donor TAS activity was lower (1.14+/-0.2 vs. 0.97+/-0.3 mmol/mL). Patients who suffered from acute rejection received kidneys from donors with significantly higher serum MDA (66+/-73 micromol/ml vs. 23+/-49 for patients without rejection). Serum creatinine 12 to 48 months after transplantation correlated to donor- and preservation-solution MDA (P<0.006). CONCLUSIONS: Free-radical mediated injury occurring in the donor and during preservation is strictly correlated with immediate and long-term kidney function. It may also cause grafts to be prone to acute rejection.

Acute Disease↗

[The aging of the immune system].

As the expected lifespan of man still rises in modern societies, the problems of immunosenescence are getting constantly more and more interesting for scientists. According to the classical theory, cumulating microinjuries within the immune system cause overall immunodeficiency in elderly. However, recently the genetic background is more frequently used for explanation of this phenomenon. One of the main causes of immunosenesence is involution of the thymus. The results of this process are changes in subpopulations and functioning of T cells, as well as mainly secondary dysfunction of other types of immune cells. Although function of some cells (e.g. neutrophils or NK cells) seems to remain unaffected, the immune system in elderly is clearly less effective in comparison with the younger population. Hopefully, studies on this subject will help to find some effective strategies to prevent or to treat this dysfunction.

Aging↗

The impact of pretransplant erythropoietin therapy on late outcomes of renal transplantation.

OBJECTIVES: The introduction of recombinant erythropoietin (rHu-EPO) has been shown to reverse anemia of chronic renal failure and was able to almost completely obviate the need for repeated blood transfusions (BT), the most potent cause of allostimulation in renal transplant candidates. The series describes single center experience of the pretransplant BT and rHu-EPO therapy effects on late outcomes of cadaveric renal transplantation. METHODS: We retrospectively analyzed data of 502 adult recipients of primary renal allograft between 1990-1997 whose graft survived > 6 months. In the study group 51 patients were treated prior to transplantation with de novo rHu-EPO therapy, 207 patients received BT, 184 patients were switched from BT to rHu-EPO therapy, and 60 patients did not require treatment. The groups were compared in respect to pretransplant % PRA, frequency of acute rejections and graft survival. RESULTS: At one-year graft survival was similar between groups, however at five years recipients of de novo rHu-EPO and those who have converted from BT to rHu-EPO experienced only 7% graft loss, as compared to 22% of patients treated with BT, and 18% of patients who did not require treatment, p < 0.001. The pretransplant therapy with rHu-EPO was associated with decreased frequency of late episodes of rejection from 0.42 to 0.27, p = 0.03. There were no differences between groups in the number of highly sensitized (PRA > 20%) at the time of transplantation. CONCLUSIONS: The use of rHu-EPO as de novo therapy or conversion from BT treatment to rHu-EPO prior to transplantation was associated with a decline in late posttransplant alloreactivity and improved late renal graft survival.

Adult↗