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Data binding the expression of Toll-like 4 receptor (TLR4), transplanted kidney (KT) function, and symptomatic CMV infection (CMV+) are scarcely available. Objective To investigate the relationship between TLR4 expression (TLR4ex) in patients who had a relapse of CMV and transplant function. Materials and Methods TLR4ex was measured in peripheral blood mononuclear cells of KT recipients. We compared TLR4ex among 30 CMV+ patients and 87 patients without CMV infection (CMVneg). At the beginning (day 0) TLR4ex, as well as concentrations of cyclosporin A and tacrolimus were determined. All patients, CMV+ and CMVneg patients were divided according to the respective median of TLR4ex into groups of low-TLR4 expression (L-TLR4ex) and high-TLR4 expression (H-TLR4ex). Estimated glomerular filtration rate (EGFR) was assessed on day 0 and after the follow-up (F-up). The magnitudes of EGFR change (ΔEGFR) were evaluated. Stable treatment along the F-up period (median 11.9 months) was applied. Results TLR4ex of CMV+ in 67% was below median for all patients. For day 0, in CMV+: no link of TLR4ex with EGFR was found; TLR4ex was lower but day 0 EGFR did not differ from H-TLR4ex. In CMVneg, a GFR-TLR4ex link was present. Post F-up. In CMV+ with L-TLR4ex, EGFR declined, with no change in H-TLR4ex. In CMVneg with H-TLR4ex, EGFR increased, with no change in L-TLR4ex. Both regression and receiver operating characteristic curve analyses points out the impact of CMV+ and TLR4ex on eGFR and ΔEGFR. Conclusion In CMV+, low TLR4ex increases the risk of EGFR deterioration. In CMVneg, high TLR4ex raises the chance of EGFR improvement.

Posttransplant diabetes mellitus (PTDM) adversely affects renal graft and patient survival. Fasting plasma glucose (FPG) alone underestimates diagnosis of glucose metabolism disorders (GMD) detected using the oral glucose tolerance test (OGTT-75). Prediabetes including impaired fasting glucose (IFG): 100 to 125 mg/dL (5.6–6.9 mmol/L) and impaired glucose tolerance (IGT): 140 to 199 mg/dL (7.8–11 mmol/L) 2 hours post 75-g OGTT in the pretransplant period can have a connection with the occurrence of PTDM after renal transplantation (RTx). The aim of our study was to assess the benefit of performing OGTT-75 in dialyzed chronic kidney disease (stage 5) patients on the waiting list for kidney transplantation as a useful tool to prevent PTDM. Materials and Methods Pretransplant glucose testing using OGTT-75 was performed in nondiabetic dialyzed chronic kidney disease patients on the waiting list for renal transplantation in the southwest region of Poland. GMD were diagnosed according to current criteria. Patients with recognized prediabetic stage were recommended a low carbohydrate diet, lifestyle modification, and increased physical activity. In the 12-month posttransplant period we estimated the prevalence of PTDM in the study group based on FPG >126 mg/dL (7 mmol/L) in 2 measurements or random blood glucose >200 mg/dL (11.1 mmol/L). Results A total of 80 nondiabetic dialysis patients (65 hemodialysis/15 peritoneal dialysis; 47 male/33 female) met initial entry criteria. In pretransplant glucose testing prediabetes was found in 31 out of 80 patients (39%). Among them, 5 patients (6.25%) had combined IGT/IFG, 18 patients (22.5%) had IGT, and 8 patients (10%) had IFG. One year after RTx we recognized PTDM in 14% of all analyzed patients (11/80) and noticed a significant frequency of glucose disorders status change after RTx ( P = .002). Conclusion Our findings suggest early detection of prediabetes using the OGTT-75 test in nondiabetic dialysis patients waiting for RTx to prevent occurrence of PTDM.

Purpose of review Antibody-mediated rejection is the leading cause of deterioration of graft function and graft loss after kidney transplantation. Recent studies have reported an increasing role of non-HLA antibodies in the humoral injury after kidney transplantation. We decided to present the influence of non-HLA antibodies - anti-endothelin II type A receptor (ETAR) on a transplanted kidney and characterize the significance of their receptor. Recent findings The role of non-HLA antibodies is still uncertain. Many studies suggest that the presence of non-HLA antibodies, including anti-ETAR antibodies, is among the risk factors for antibody-mediated rejection, graft injury, and graft loss. The discovery of new antigen targets and antibodies, which participate in the humoral response, has provided a significantly better understanding of the mechanism of antibody-mediated rejection after organ transplantation. Summary Endothelin and its receptors play an important role in physiology and pathophysiology after solid organ transplantation. ETAR and antibodies against ETAR may participate in humoral rejection and graft damage. The measurement of anti-ETAR antibodies may identify patients with an increased risk of rejection and even loss of a transplanted organ. Expression of ETAR detected in biopsy of transplant could become an additional tool used to better understand humoral activity. More research is needed to address many questions about non-HLA directed rejection and graft damage.

The occurrence of anti-angiotensin II type 1 receptor (AT1R) antibodies is thought to be a risk factor for transplant injury, but the relationship of AT1R to graft loss in renal transplantation has not been assessed. The aim of our study was to evaluate the expression of AT1R and its relationship with graft loss in patients who had a renal transplant biopsy for cause. Methods AT1R immunoreactivity was analyzed in 170 renal transplant biopsies. Immunohistochemical evaluation of AT1R expression was performed on 4 μm-thick paraffin sections mounted on silanized slides. AT1R expression was analyzed in 5 compartments: 1. glomeruli, 2. renal blood vessels (small and intermediate arteries), 3. peritubular capillaries, 4. tubular epithelium, and 5. interstitium based on a 3-step scale. Results Initially we checked 170 consecutive samples of biopsies for the immunoreactivity of the AT1R. The study finally included 118 renal transplant patients in 1-year observation after the biopsy. The renal allograft biopsy was performed between 6 days and 24 years after transplantation and the diagnosis was based on Banff criteria. We observed positive immunostaining of AT1R in tubular epithelium in 26.3% (42/118) of patients. A total of 7 patients had staining assessed as 2 and 35 as 1. One year post-biopsy graft loss in the AT1R (+) patients was 35.7 % (15/42) compared to 14.5% (11/76) in the AT1R (-) group (P = .008). Conclusions The expression of AT1R in tubular epithelium of the biopsy for cause was associated with significantly higher graft loss. The relevance of AT1R should be considered for better transplant immunological risk assessment.

Data binding the expression of Toll-like 4 receptor (TLR4ex), transplanted kidney function, and the cause of pre-transplant end-stage renal disease are scarcely available. Objective To investigate the relationship between pre-transplant chronic interstitial nephritis (CIN), TLR4ex and transplanted kidney function. Materials and methods TLR4ex was measured in peripheral blood mononuclear cells of 43 CIN kidney transplant recipients. We compared TLR4ex among 33 patients with pre-transplant chronic non-infectious interstitial nephritis (NIN) and 10 patients with pre-transplant chronic pyelonephritis (Py). At the beginning (Day-0) TLR4ex, as well as concentrations of cyclosporin A (CyA) and tacrolimus (TAC) were determined. Both CIN and NIN patients were divided according to the respective median of TLR4ex into groups of low-TLR4 expression (L-TLR4ex) and high-TLR4 expression (H-TLR4ex). Serum creatinine/glomerular filtration rate (sCr/EGFR) was assessed on Day-0 and after the follow-up (F-up). The magnitudes of sCr/EGFR change (ΔsCr/ΔEGFR) were evaluated. The treatment was maintained stable along the F-up period (median 11.9 months). Results Day-0: in CIN with L-TLR4ex TAC was lower but sCr/EGFR were not different from H-TLR4ex; in Py TLR4ex and TAC were lower than in NIN with no difference in sCR/eGFR. After F-up: in CIN with L-TLR4ex sCR/EGFR and ΔsCr/ΔEGFR were worse than in H-TLR4ex; in Py sCR/EGFR and ΔsCr/ΔEGFR were worse than in NIN. The regression analysis points out prospective impact of Py and TLR4ex on sCR/eGFR and ΔsCr/ΔeGFR. Conclusion In CIN, both TLR4ex and Tac appear to be a useful positive predictor of the effectiveness of immunosuppression. Chronic pyelonephritis indirectly promotes faster progression of chronic transplanted kidney disease.

The most frequent cause of kidney allograft loss is chronic allograft injury, often with proteinuria as the clinical feature. Occurrence of proteinuria late after kidney transplantation is associated with worse graft function and patient survival.The aim of the study was to assess plasma and urine matrix metalloproteinases (MMP-2 and MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in proteinuric renal transplant recipients (RTRs). The factors were determined by enzyme-linked immunosorbent assay in 150 RTRs (51 women and 99 men), aged 49.2 ± 11.5 years, at mean 73.4 ± 41.2 months after kidney transplantation (range: 12 to 240 months).Proteinuric RTRs compared with non-proteinuric RTRs had higher median plasma MMP-2 (P = .012), TIMP-1 (P = .0003), and TIMP-2 (P = .0021) concentrations, as well as higher urine MMP-2 (P.0001) excretion. The presence of proteinuria had no impact on plasma MMP-9 and urine MMP-9, TIMP-1, and TIMP-2. Proteinuria and estimated daily proteinuria (uPr:uCr) correlated positively with plasma MMP-2 (rs = 0.226, P = .0054 and rs = 0.241, P = .003), TIMP-1 (rs = 0.305, P = .00015 and rs = 0.323, P = .000055), TIMP-2 (rs = 0.273, P = .0007 and rs = 0.269, P = .001) and urine MMP-2 (rs = 0.464, P.0001 and rs = 0.487, P.0001), respectively. Proteinuric RTRs had impaired graft function with higher median serum creatinine concentrations (1.91 [1.60-2.43] mg/dL versus 1.41 [1.20-1.65] mg/dL, P.00001) and lower estimated glomerular filtration rate (36 [28-45] mL/min/1.73 m(2) versus 53 [43-61] mL/min/1.73 m(2), P.00001) than RTRs without proteinuria.Our research revealed that in RTRs, proteinuria was significantly associated with increased concentrations of enzymes involved in extracellular matrix (ECM) degradation: plasma MMP-2, TIMP-1, TIMP-2, and urine MMP-2. Findings strongly emphasize increased plasma TIMPs in proteinuric RTRs that inhibit degradation of ECM by MMPs and favor excessive deposition of ECM proteins.

Introduction Non-HLA antibodies specific for angiotensin II type 1 receptor (anti-AT1R) and endothelin-1 type A receptor (anti-ETAR) of vascular cells activate signaling pathways leading to cell proliferation and vascular injury. The aim of this study was to evaluate the impact of non-HLA antibodies on kidney allograft morphology and function in patients who underwent a kidney biopsy due to renal function impairment. Patients and Methods The study included 65 consecutive renal transplant patients who were evaluated for the presence of non-HLA and anti-HLA antibodies at the time of transplant biopsy. Results of pre-transplant CDC cross-match were negative. A kidney allograft biopsy was performed between 6 days and 13 years (42 ± 49 months) after transplantation, and the diagnosis was made on the basis of the Banff criteria. The level >9 U/L of anti-AT1R and anti-ETAR antibodies was considered high. Results A high level of non-HLA antibodies (anti-AT1R and/or anti-ETAR) was found in 7 (10.7%) of 65 patients at the time of biopsy. Graft loss in the non–HLA-positive patients was significantly higher (71% in non–HLA-positive cases after 7.8 ± 2.6 months vs 11% after 6 months in non-HLA–negative cases [P = .00099]). In these non–HLA-positive patients, the mean anti-AT1R level was 15.3 ± 9.4 U/L and the mean anti-ETAR level was 13.8 ± 8.6 U/L. In only 2 of these patients were anti-HLA antibodies additionally detected: anti-class I in 1 and anti-class II in both patients. The mean serum creatinine level was 2.34 ± 0.6 mg/dL at the time of biopsy. Results of an early biopsy revealed acute vascular rejection (Banff grade IIB). Chronic allograft injury was found (grading cg1-3, cv1-2, ci1-2, ct1-2) in the remaining 6 patients. C4d was present in 3 of 7 patients. Conclusions High levels of anti-AT1R and/or anti-ETAR antibodies were associated with morphological and functional allograft injury and graft loss in these study patients. Non-HLA antibodies can be helpful in assessing the risk of graft failure.

Background Cardiovascular disease is a major cause of mortality in solid organ allograft recipients. Hand transplantation is not a lifesaving procedure, thus the effect of long-term immunosuppression on the cardiovascular system in these patients should be monitored. The aim of this study was to evaluate the morphology and function of heart and blood vessels in patients after hand transplantation. Methods The study included 5 patients at ages 32 to 58 years, mean 39 years, who underwent hand transplantation between 2006 and 2010. Immunosuppressive treatment included basiliximab in induction and tacrolimus, mycophenolate mofetil, and prednisone. Cardiac status was assessed by echocardiography (according to the American Society of Echocardiography) and cardiac biomarkers. Blood vessels were estimated by carotid intima-media thickness, pulse wave velocity, and brachial artery flow-mediated dilatation (FMD). The examinations were performed at 28 to 79 (mean 43) months after transplantation. Results Cardiovascular risk factors were observed in all patients after transplantation: 2 had insulin-dependent diabetes, 3 developed dyslipidemia and hypertension, 2 had chronic kidney disease stage 3. Concentric left ventricular hypertrophy was found in 1 and ventricular concentric remodeling in 4 patients. Impaired diastolic function (E/e’ > 8) was observed in 2 patients. The index volume of the left atrium was higher in all patients. The cardiac biomarkers N-terminal pro-brain natriuretic peptide, C-reactive protein, and troponins were within normal range. Carotid intima-media thickness was higher in 1 patient and normal in 4 patients. Arterial stiffness measured by pulse wave velocity was not increased in all patients. Native brachial artery FMD response, an index of endothelium-dependent function, was abnormal in 2 patients, but in the transplanted extremity FMD was abnormal in 4 patients. Conclusions Pathologic changes in cardiac structures were found in all patients, but the arterial wall changes and endothelial dysfunction were observed in some patients. Patients after hand transplantation are at higher risk for cardiovascular disease.

Background Advanced age of renal transplant recipients (RTRs) has a negative impact on kidney allograft survival through impaired extracellular matrix degradation by the matrix metalloproteinases/tissue inhibitors of metalloproteinases (MMPs/TIMPs) system. Moreover, older RTRs are at risk of smoldering inflammation, known as inflammaging. Aim The aim of the study was to assess the impact of a RTR's age on plasma and urine concentrations of interleukin 6 (IL-6), chemokine ligand 2 (CCL2), and the MMPs/TIMPs system. Material and Methods One hundred fifty adult RTRs (8.7% ≥ 65 years) and 37 adult healthy volunteers (10.8% ≥ 65 years) were enrolled in the study. The studied factors (IL-6, CCL2, MMP-2, MMP-9, TIMP-1 and TIMP-2) were quantified in plasma and urine with enzyme-linked immunosorbent assay. The Mann-Whitney U test and Spearman's (r s ) rank correlation were applied, and differences with a P Results There was a weak but significant positive correlation between increasing RTR's age and plasma IL-6 (r s = 0.18, P = .028), CCL2 (r s = 0.27, P = .001), and MMP-2 (r s = 0.20, P = .017), as well as urine CCL2 (r s = 0.16, P = 0.050) and TIMP-1 (r s = 0.20, P = .014) concentrations. Conclusions Advancing age of RTRs correlates with increasing plasma IL-6 and CCL2 concentrations, reflecting smoldering inflammation (known as inflammaging) and alterations in MMPs/TIMPs profiles, especially with increased plasma MMP-2 and urine TIMP-1 concentrations.

Background Non-HLA antibodies (Abs) targeting vascular receptors are considered to have an influence on renal transplant injury. Anti-endothelin-1 type A receptor (anti-ETAR) antibodies were associated with cellular and antibody-mediated rejection and early onset of vasculopathy in heart transplant patients but their role in renal transplantation remains unclear. The aim of our study was to assess the incidence and importance of anti-ETAR antibodies and their impact on renal transplant during the first year observation. Methods We evaluated the presence of anti-ETAR antibodies in 116 consecutive renal transplant recipients in pre- and post-transplant screening (before and in 1st, 3rd, 6th, 12th month after transplantation). Additionally, we assessed the presence of anti-HLA antibodies. Anti-ETAR antibodies were assayed by ELISA. The diagnosis of acute rejection was based on the Banff criteria. Results Anti-ETAR antibodies were observed in 55 (47.4%) of the analyzed recipients before transplantation. The function of renal transplant was significantly worse in the anti-ETAR(+) group compared to the anti-ETAR(−) group during the first post-transplant year. One month after transplantation the serum creatinine in anti-ETAR (+) patients (pts) was 1.86 ± 0.8 mg/dl and 1.51 ± 0.5 in anti-ETAR(−) pts (p = 0.009). Twelve months after transplantation the difference between the groups was still observed 1.70 ± 0.7 vs. 1.40 ± 0.4 (p = 0.04). Biopsy proven acute rejection was recognized in 8/55 (14.5%) in ETAR(+) and 9/61 (14.8%) in ETAR(−) patients but cases with mild to severe intimal arteritis (v1–v3) were more often observed in patients with the presence of anti-ETAR Abs 4/55 (7.2%) comparing with 1/61 (1.6%) in anti-ETAR(−) patients. The anti-ETAR antibody levels varied at different measurement intervals during the one-year follow-up. Conclusions The presence of anti-ETAR antibodies is associated with a worse renal transplant function during the first 12 months after transplantation. Including anti-ETAR antibodies in the diagnostics of renal transplant recipient immune status should be considered to provide comprehensive assessment of humoral alloimmunity.

Chronic allograft injury (CAI) is the most frequent cause of progressive kidney allograft impairment and eventual loss, which is due to interstitial fibrosis and tubular atrophy (IF/TA). Mechanisms of CAI are not fully understood. Chemokines, cytokines, metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) play roles in fibrosis development. The aims of this study were to evaluate plasma and urine TIMPs (TIMP-1 and TIMP-2), MMPs (MMP-2 and MMP-9), proinflammatory interleukin-6 (IL-6), chemokine (C-C motif) ligand 2 (CCL2 chemokines previously known as monocyte chemoattractant protein-1 [MCP-1]) among 150 recipients beyond 1 year post–renal transplantations and to explore the usefulness of these potential biomarkers of ongoing allograft injury. Renal transplant recipients compared with healthy volunteers (control group) showed significantly increased plasma and urine IL-6, MMP-9, TIMP-1, and TIMP-2, as well as lower plasma MMP-2 and urine CCL2 concentrations. Compared with recipients showing good function those with impairments displayed higher plasma TIMP-1 (P < .001) and TIMP-2 (P = .003) concentrations. The recipient estimated glomerular filtration rate (eGFR) values negatively correlated with plasma TIMP-1 and TIMP-2 levels (r = −0.43; P < .0001 and rs = −0.42; P < .0001, respectively) and with urine IL-6 excretion (rs = −0.33; P < .0001). Multivariate and receiver operating characteristic (ROC) analyses showed TIMP-1 plasma level assessments to be useful estimates of allograft injury.

Numerous studies have shown that circulating donor-specific antibodies targeting human leukocyte antigen (HLA) are associated with accelerated renal transplant failure, but many patients with these antibodies have good graft function. The aim of our study was to investigate the long-term graft function and survival in patients with de novo post-transplant donor-specific anti-HLA antibodies (DSA). Our prospective study included 78 consecutive recipients with a negative crossmatch before transplantation. Recipient serum samples were assayed for DSA in week 2 and 1, 3, 6, 9, 12 months after transplantation using a complement-dependent lymphocytotoxic technique with donor lymphocytes. Additionally, patients with DSA and stable renal function in the first year were tested with a more sensitive flow-panel-reactive antibody. DSA were present in 34 (44%) of our patients during the first 12 months after transplantation. Biopsy-proved acute rejection occurred in 11 DSA-positive and 10 DSA-negative patients. Seven DSA-positive patients had antibody-mediated rejection and no DSA-negative ones developed humoral rejection. The serum creatinine level in DSA-positive patients was significantly higher (2.48 vs 1.43 mg/dL) in year 5. The 13 (38%) DSA-positive patients with good graft function in month 12 were stable during a 5-year follow-up: their serum creatinine was 1.46 ± 0.4 in year 1 and 1.56 ± 0.4 mg/dL in year 5 and nobody lost their allograft. One- and 5- year graft survivals were appropriately 85% and 59% in DSA-positive patients compared to 93% and 93% in DSA-negative patients. To sum up, post-transplant DSA had a significant influence on kidney function and graft survival but in 38% of patients the presence of DSA did not decrease a 5-year renal function. A good renal allograft function in the presence of DSA in the first year after transplantation and cessation of their production in the subsequent years may be a good prognostic marker for a long-term allograft function and survival.

Background The proximal forearm antecubital fistula described by Gracz is a valuable option for autogenous vascular access for hemodialysis in patients with destroyed forearm veins or advanced arteriosclerotic and calcified radial arteries. Results obtained with a variant of the Gracz fistula are presented. Study Design Patients with forearm vein destruction or failed distal radiocephalic fistulas were selected to have a variant of the Gracz fistula created and were followed up for 36 months. In each patient, the radial artery was anastomosed side to end or end to end to the perforating vein. Additionally, in some patients, the median cephalic or basilic vein was relocated subcutaneously to increase the accessibility of veins for puncture. Setting & Participants Native arteriovenous fistulas (AVFs) in the cubital region using a perforating vein were created in 77 patients (34 women, 43 men) referred to the Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland, from 1992 to 2006. Outcomes & Measurements Percentages of successful fistula creation and primary patency rates, defined from fistula placement to any maintaining intervention, and cumulative patency, defined from placement to fistula abandonment, were assessed. Results AVF creation was successful in 56 patients (73%). Primary patency rates during the follow-up period were 47% after 1 year, 43% after 2 years, and 39% after 3 years. Cumulative patency rates were 67% after 1 year, 56% after 2 years, and 53% after 3 years. Limitations These results reflect performance of a single center and thus may not be generalizable to surgeons less experienced in this technique. Conclusions Radial artery–perforating vein fistulas have an acceptable survival rate and do not produce circulatory complications. This method may be applicable for AVF creation in patients with forearm vein destruction/abnormalities and as a rescue procedure for an old clotted fistula after kidney transplant failure.

The role of cytomegalovirus (CMV) disease to induce chronic nephropathy using new immunosuppressive regimens is debated. This study sought to assess the influence of CMV disease on early and late graft function in relation to immunosuppressive therapy. Among 456 renal recipients transplanted from 1997 to 2003, 95 were diagnosed with CMV disease on the basis of clinical symptoms and the presence of pp65 protein. The patients were divided into 2 groups according to their immunosuppressive regimen: group I included 43 patients treated with cyclosporine (CsA), azathioprine (AZA), and prednisone (P); group II, 52 patients treated with calcineurin inhibitor (CI), mycophenolate mofetil (MMF), and P. A control group of 90 CMV disease-free renal recipients were transplanted in 2001. CMV disease occurred in 20.8% of renal recipients: 14.8% from group I and 25.5% from group II. CMV disease was diagnosed in 73 patients (76.8%) before the third month after transplantation. An acute rejection episode (ARE) appeared in 42 patients, of whom 31 had CMV disease diagnosed within 1 month after ARE, while 5 before an ARE. In six patients ARE was not time related to CMV disease. The serum creatinine values at 6 months after transplantation were significantly higher among the CMV versus control groups: 1.69 and 1.76 vs 1.49 (P < .05). In patients with ARE and CMV disease, the serum creatinine value was also higher at 6 and 12 months after transplantation compared with patients without an ARE (P < .03). One- and 3-year graft survival rates were 95.1% and 83.7% in group I versus 93.4% and 86.5% in group II versus 95.4% and 90.2% in the control group. In conclusion, CMV disease showed a negative impact on early graft function independent of the immunosuppressive regimen, an effect that was emphasized by an ARE.

The aim of this study was to evaluate the impact of sirolimus and cyclosporine (CsA) combined therapy on the incidence and duration of delayed graft function (DGF), and the impact of the latter on 1-year graft function. The study entailed 23 cadaveric renal recipients treated with sirolimus-CsA-prednisone regimen (sirolimus group). The reference group entailed 23 patients treated with CsA-azathioprine-prednisone. In the sirolimus group the frequency of DGF was 39% and was essentially the same as in reference group (34.8%). The duration of DGF was significantly longer in SRL group and lasted 21.2 +/- 12.2 days versus 6.8 +/- 2.5 in reference group (P = .004). Serum creatinine level decreased below 3.0 mg/dL after 36 +/- 22 days in sirolimus group versus 16.8 +/- 6 days in reference group (P.04). Cold ischemia was slightly longer and donors were older in DGF patients in both groups. Sirolimus dose during first month was higher in DGF patients (3.5 versus 2.6 mg), whereas level of CsA was lower (230 versus 310 ng/mL). Biopsy-proven acute rejection (AR) occurred in most of DGF patients and during the DGF period. Serum creatinine level at the 12th month posttransplant was higher in DGF versus non-DGF patients (2.0 +/- 0.5 versus 1.5 +/- 0.4 mg/dL). One-year patient and graft survival was 100% in sirolimus group and 100% and 95% in reference group. In conclusion, sirolimus significantly retards the recovery from posttransplant renal failure; however, it does not increase the incidence of DGF. Patients who suffered from posttransplant acute renal failure had worse renal function at 1 year after transplantation, independent of the treatment protocol.

Graft endothelial lesions resulting from acute rejection may be sustained by concomitant hypercholesterolemia, thus increasing the risk of chronic graft failure. The present study was undertaken to examine the influence of hypercholesterolemia and acute graft rejection (AGR) episodes on graft function and graft loss due to chronic nephropathy. A cohort of 336 patients transplanted between 1993 and 2000 having graft function at 12 months after transplantation were examined. Immunosuppressive therapy consisted of CsA, azathioprine, and corticosteroids in 90% with 10% of patients receiving mycophenolate mofetil in place of azathioprine. During the first year after transplantation, AGR occurred in 134 (39.8%) and hypercholesterolemia (6.2 mmol/L) in 132 (39.2%) of patients. The population was divided into four groups according to AGR occurrence and cholesterol concentrations during the first year after transplantation for analysis of serum creatinine concentrations and graft loss at 5 years of follow-up. Patients with AGR irrespective of cholesterol levels displayed significantly higher creatinine concentrations. Graft loss in these patients increased over twofold compared to the remaining groups. Patients without hypercholesterolemia and AGR showed normal creatinine concentrations and low graft loss rates during 5 years of follow-up.