Outcome of transplantation in renal allograft recipients from cadaveric donors with standard and expanded criteria: a single-center experience.

INTRODUCTION: The increasing number of patients requiring kidney transplantation and the lack of available organs has led to the utilization of kidneys from expanded criteria donors (ECD). AIM: The comparison of the clinical outcome of renal transplantation, performed in a single center, between allograft recipients from standard (SCD) and expanded criteria donors (ECD). PATIENTS AND METHODS: Data from 215 cadaveric renal transplantations performed during a 16 year period at the University Hospital of Patras were retrospectively studied. Donors' and recipients' characteristics (gender, age, history of hypertension and diabetes mellitus, cold ischemia time, post-transplant and long term graft function) were analyzed. RESULTS: Grafts from donors with expanded criteria (ECD, n = 53) were allocated to older recipients whereas grafts from donors with standard criteria (SCD, n = 162) were allocated to younger recipients. The mean cold ischemia time was 1,146 min and was similar between the two groups of patients. Patients' survival rates were similar between allograft recipients from SCD and ECD up to the 5(th) post-transplant year of follow-up. Graft survival was significantly better in allograft recipients from SCD during a 5-year follow-up period. A significantly lower eGFR was noted in allograft recipients from ECD in comparison to those from SCD throughout the observation period. Cold ischemia time was positively correlated to the development of DGF, while patients with DGF had significantly worse graft function throughout the observation period. CONCLUSION: Patient survival from ECD is comparable to that from SCD but graft survival is significantly lower. However, since renal function of recipients from ECD is adequate for long term period, grafts from ECD should be used in older patients.

Parameters influencing blood erythropoietin levels of renal transplant recipients during the early post-transplantation period.

AIM: Renal transplantation is accompanied by restoration of renal function and endogenous erythropoietin production. The purpose of this study was to investigate the time-related changes of endogenous erythropoietin secretion in the early renal post-transplant period and the influence of various parameters to this process. METHODS: Fifty-eight patients were enrolled in the study and followed up for 3 months after successful renal transplantation. Erythropoietin levels were measured at regular intervals and correlated with renal function, cold ischemia time and immunosuppressive regimen used. RESULTS: Two peaks of serum erythropoietin levels were observed: an early peak that occurred within two days after transplantation and a late one, between weeks 2 and 4, which resulted in increased blood hemoglobin levels. Factors that were found to correlate with erythropoietin levels were delayed graft function, cyclosporine use and prolonged cold ischemia time. Serum creatinine did not correlate to erythropoietin levels although the reduction of serum creatinine preceded the rise of erythropoietin levels. Normal hemoglobin values were restored about three months after successful renal transplantation. CONCLUSION: Serum erythropoietin levels increase during the early post-transplantation period resulting in correction of anemia three months after a successful renal transplantation. Restoration of allograft function is a prerequisite for erythropoietin secretion, while cold ischemia time and immunosuppressive regimen affect graft function.

Gastrointestinal disorders after renal transplantation.

BACKGROUND: Gastrointestinal disorders (GDs) are common in renal transplant recipients. The main cause of GDs seems to be the use of immunosuppressive medications, especially mycophenolic acid in the form of mycophenolate mofetil (MMF). OBJECTIVE: The aim of this study was to estimate the frequency and severity of GDs in renal allograft recipients with the use of the Gastrointestinal Symptom Rating Scale (GSRS). METHODS: Eighty-five renal allograft recipients, 50 ± 12 years old, treated with methylprednisolone, calcineurin inhibitor (cyclosporine [CsA], n = 42; tacrolimus (TAC), n = 43), and MMF were studied. RESULTS: At the time of completion of the GSRS questionnaire, 38 of the 85 patients (45%) already had their MMF dose reduced because of GDs. Only 15 patients (18%) were totally free from GDs. The most frequent and severe GDs recorded were indigestion and diarrhea who were significantly more frequent in women (P = .045). GDs were recorded in patients receiving both standard and reduced dose of MMF. MMF dose was significantly associated only with diarrhea. Although TAC-treated patients had the highest mean GSRS scores, no statistically significant differences were observed compared with CsA-treated patients. In 31 patients, MMF was replaced by enteric-coated mycophenolate sodium (EC-MPS) and new questionnaires were completed 1 month later. Significant improvement in total and all subscores of GSRS was demonstrated (P < .001). Although EC-MPS dose tolerated by the patients was higher than MMF dose, the difference was not statistically significant. CONCLUSIONS: Female sex and the use of MMF, especially in combination with TAC, are related to the occurrence of severe gastrointestinal symptoms. Substitution of MMF with EC-MPS significantly reduces the severity of symptoms and permits the use of higher doses.

Urinary interleukin-6 (IL-6) and transforming growth factor (TGF-ß) levels in corticosteroidtreated patients with IgA nephropathy.

BACKGROUND: Interleukin-6 (IL-6) and transforming growth factor-ß (TGF-ß) are implicated in the progression of IgA nephropathy, which is usually treated with corticosteroids. PATIENTS AND METHODS: Urinary IL-6 and TGF-ß were measured in 21 proteinuric patients with IgA nephropathy, before and after treatment with corticosteroids, to estimate the activity of the disease after remission of proteinuria. RESULTS: Urinary IL-6 and TGF-ß levels at diagnosis were significantly higher in patients with IgA nephropathy compared to healthy subjects. TGF-ß levels, were significantly higher in patients with proteinuria > 1 g/24 h and/or severe mesangial proliferation. Although a significant reduction of proteinuria was observed with corticosteroid treatment, urinary IL-6 and TGF-ß levels remained elevated. Deterioration of renal function over a period of 5 years was observed in 3 patients. High urinary IL-6 levels at diagnosis represent a significant parameter distinguishing patients with progressive course in comparison to those with favorable clinical outcome (p = 0.01). CONCLUSION: Treatment of patients with IgA nephropathy with corticosteroids is followed by remission of proteinuria but still increased urinary IL-6 and TGF-ß excretion. This may be related to an ongoing inflammatory process within the kidney, and further research is required to estimate the value of urinary IL-6 and TGF-ß as markers of activity of the disease.

Expression of transgelin in human glomerulonephritis of various etiology.

BACKGROUND/AIMS: Activation of myofibroblasts occurs during kidney injury. Genomic and proteomic studies suggest that transgelin represents a protein that may be involved in renal injury. The purpose of this study was to estimate transgelin expression in the renal tissue of patients with glomerulonephritis. METHODS: Transgelin was identified in biopsy sections of 67 patients by immunohistochemistry and immunofluorescence. Its distribution was compared to that of α-smooth muscle actin (α-SMA), a marker of myofibroblast activation in the kidney. RESULTS: Transgelin and α-SMA expression was identified within glomeruli and interstitium. In patients with IgA nephropathy and focal segmental glomerulosclerosis, glomerular expression of transgelin was higher than that of α-SMA. The extent of transgelin immunostaining was related to mesangial proliferation (p = 0.034), glomerular sclerosis (p = 0.035), interstitial fibrosis (p = 0.047) and to the clinical course (p = 0.009). Colocalization studies showed that in some areas of kidney tissue both proteins were expressed with comparable intensity, whereas in other areas expression of either transgelin or α-SMA was predominant. CONCLUSION: Strong transgelin expression was observed in renal tissue of patients with glomerulonephritis. The observed differences in the pattern of transgelin and α-SMA expression suggest that either different subpopulations of myofibroblasts exist, or that these proteins are activated at different stages of renal injury/scarring.

The nucleus basalis of Meynert of the human brain: a Golgi and electron microscope study.

The nucleus basalis of Meynert of normal brains, aged from 15 to 73 years was studied in Golgi preparations and in electron microscopy. The nucleus is composed of large triangular, polyhedral and bipolar cells which are intermixed with numerous small or medium-sized spiny neurons. All of the neurons form a dense three dimensional dendritic arborization, with numerous secondary and tertiary dendritic branches studded with spines. The ultrastructural analysis revealed numerous axodendritic and axosomatic synapses between the spines. The ultrastructural analysis revealed numerous axodendritic and axosomatic synapses between the spiny neurons and the large triangular and polyhedral neurons. The presynaptic axonic profiles are plenty of ellipsoid and round synaptic vesicles. Large presynaptic terminals are seen frequently surrounded by numerous dendritic spines forming synaptic glomeruli, in all the areas of the nucleus basalis of Meynert. An age depended decrease of the number of neurons was noticed affecting mainly the population of the spiny neurons. Although in senile and presenile dementias an impressive loss of the cholinergic neurons of the nucleus basalis was reported, in normal aging the large cholinergic neurons of the nucleus basalis seems to be intact, whereas the medium and small shaped spiny neurons are decreased in number suggesting that the GABA-ergic neurons are principally affected.