Cyclosporine therapy in steroid-dependent or steroid-resistant idiopathic focal and segmental glomerulosclerosis.

Focal and segmental glomerulosclerosis (FSGS) is a heterogeneous entity. Previous few studies have evaluated the efficacy of calcineurin inhibitors in primary FSGS and have suggested positive benefit. In this single-center, retrospective study (1975-2014), we report our experience in Tunisian adults with primary FSGS treated with cyclosporine A (CsA). It includes patients histologically proven FSGS and managed in the Charles Nicolle Hospital at Tunis, Tunisia. The dose of CsA was adjusted to maintain a whole blood trough level of 80-150 ng/mL. The observation period was 6.8 ± 3.7 years after CsA treatment. Twenty-three patients with idiopathic FSGS, treated with CsA, were studied. The mean age was 26.69 ± 10.1 years, and the sex ratio was 2.83. Eight patients (35%) had a steroid-dependent nephrotic syndrome (NS), and 15 patients (65%) had for steroid-resistant NS. After a median follow-up of 16.5 months on CsA, we noticed complete remission of the NS in eight cases (35%) after 12.12 ± 8 months, partial remission in five (22%) after 3 ± 0.7 months, dose-dependent remission to CsA (2.87 mg/kg/day) in four (17%), and a no response in six patients (26%). Eleven patients (48%) showed improvement of renal function, while eight (35%) developed end-stage renal disease (ESRD) after 35.7 ± 20.9 months. Predictive factors of progression to ESRD were creatinine clearance <90 mL/min before introduction of CsA (P = 0.0054) and CsA-resistance (P = 0.053). Our study suggests that CsA is effective in the treatment of patients with idiopathic FSGS. Initial renal function and cyclosporineresistance are the predictive factors of ESRD in steroid-resistant or -dependent FSGS.

Steroid and calcineurin inhibitor-sparing protocols in kidney transplantation.

Recent improvements in kidney transplantation have been driven largely by lower acute rejection rates attributed to better immunosuppressive agents. In an effort to reduce the long-term toxicities of immunosuppressant drugs, corticosteroid- and calcineurin inhibitor (CNI)-sparing immunosuppression protocols have become increasingly popular in managing kidney transplant recipients. Nevertheless, these strategies may increase the risk of acute and chronic allograft injury (CAI) that may worsen the fate of transplant recipients. This article focuses on steroid and CNI sparing protocols to elucidate their safety and efficacy in patients receiving a kidney transplant. Steroid avoidance protocols are rapidly and increasingly being used. Studies have shown that corticosteroids are not essential to achieve excellent short- and intermediate-term results. However, the role of steroid withdrawal is only marginally beneficial and very often benefit overstated. CNI-sparing strategies have been used to help maintain the balance between allograft survival and nephrotoxicity. Trials evaluating CNI minimization have shown reduced incidence of CAI and preservation of allograft function. CNI withdrawal within 3 to 12 months after kidney transplantation improved graft function despite increased risk of acute rejection. This approach may be feasible with adequate exposure and proper usage of mammalian target of rapamacin inhibitors. Late withdrawal or conversion did not show a clear benefit. Timing and degree of renal dysfunction are key determining factors. With regards to CNI avoidance, earlier trials, such as the Symphony study, did not support the use of a CNI-free regimen of low-dose sirolimus as initial immunosuppression. However, recent studies using costimulatory blockade-based immusouppression showed that CNI avoidance is possible. The best maintenance immunosuppressive with CNI- or steroid-sparing is a work in progress and awaits longer term follow-up. The availability of newer biologics for costimulatory blockade and new immunosuppressive agents with novel mechanisms of action have the potential of using CNI- and steroid-sparing protocols to minimize the incidence of CAI and improve long-term outcomes in kidney transplant recipients.

Short- and long-term outcomes of living donors in Tunisia: a retrospective study.

Despite initiatives to increase cadaveric donation, there is still a shortfall in donor organs. Kidneys from living donors now makes a significant contribution to increasing the number of organs available for transplantation in Tunisia. We performed a retrospective study of 405 kidney transplantations, including 321 (79.3%) from living donors performed from June 1986 to December 2007. We obtained information on only 162 (50.4%), namely, 64 men (39.5%) and 98 women (60.5%), whose mean age at the time of donation was 42.3 ± 12.2 years. Twelve (8.22%) perioperative complications occurred: wound infections (n = 4), pneumothorax (n = 4), phlebitis (n = 1), hematomas (n = 2), and urinary infection (n = 1). The mean follow-up period was 117.4 ± 74.4 months. Hypertension occurred in 42 donors (25.9%) with mean values of 134 ± 20 for systolic and 79 ± 10 for diastolic blood pressure. Twelve donors (7.4%) developed proteinuria (mean proteinuria, 0.08 ± 1.25 g/d). Renal insufficiency was found in 28 donors (19.44%), 2 of whom developed chronic renal failure requiring dialysis at intervals of 36 and 84 months. In both cases, we diagnosed a familial form of focal segmental glomerulosclerosis. Two donors (1.2%) died within 10 years after kidney donation due to senility. The relatively favorable outcomes suggest that living-donor kidney transplantation is an acceptable approach, in view of the superior results it yields in recipients. However, efforts to increase the number of cadaveric donors in Tunisia should be made. It is also important to develop a registry of long-term kidney function after kidney donation.

[Lymphoceles after renal transplantation: Study of risk factors]. / Facteurs de risque de la lymphocèle post-greffe rénale.

AIM: To identify the risk factors of post renal transplant lymphocele. PATIENTS AND METHOD: Over a period of 20 years (1986-2006) we carried out 377 renal transplants on 372 patients. Thirty cases of lymphocele were recorded (8%). The medical history of patients was retrospectively examined in order to identify the risk factors of this complication among the data relating to recipents, donors, the operation itself and post operative incidents. The different parameters liable to correlate with the incidence of lymphocele were subjected to a univaried then multivaried statistical study. RESULTS: Unifactorial analysis identified four predictive factors related to the incidence of lymphocele. They were the age of the recipient greater or equal to 35 years old, the cadaverous origin of the transplanted organ, the duration of ischemy greater or equal to 24hours for the kidneys of deceased donors, and immunosuppressor treatment associated with Mycophenolate mofetil-Cyclosporine. The only independent risk factor significant in multifactorial analysis was the cadaverous origin of the transplanted organ. CONCLUSION: Our study showed that the cadaverous origin of the transplanted organ would appear to play an important role in the genesis of post renal transplant lymphocele. A better preparation of the organs of cadaverous origin before their implantation with meticulous ligature of the hilum of lymph nodes could reduce the incidence of this complication. This observation, as well as the benefit of such a procedure, remains to be confirmed by studies on a larger scale.

[Variations of troponin T in chronic hemodialysis patients: study of 52 cases]. / Variation de la troponine Tc chez les hémodialyses chroniques: etude a propos de 52 cas.

BACKGROUND: Patients with severe renal dysfunction have unexplained elevated serum concentrations of cardiac troponin T. AIM: Study the frequency of elevated cTnT in hemodialysis patients and investigated whether cTnT is elevated. METHODS: The patient population consisted of 52 patients on maintenance hemodialysis and 20 healthy subjects. cTnT was measured before and after hemodialysis by using immunoenzymatic method. cTnT were undetectable in 7 cases(< 0.01 ng/ml) and higher than normal range (up to 0.1 ng/ml) in 9 cases. 32 cases have a level of cTnT > 0.01 and < 0.1 ng/ml. In addition, TnTc levels are significantly associated with cardiac dysfunction (p < 0.05) and inflammation (p 0.01). RESULTS: After hemodialysis sessions, TnTc was less than 0.01 ng/1 in 11 patients (21.2%), between 0.01 and 0.1 ng/ml in 32 subjects (61.5%) and greater than 0.1 ng/ml in 9 subjects (17.3%). In the control group, only 1 subject (5%) had a rate of TnTc between 0.01 and 0.1 ng/ml, whereas it was less than 0.01 ng/ml for all others. We aim a statistically significant positive correlation between the rate of TnTc and heart failure (p < 0.05) on the one hand and serum CRP (p < 0.01) on the other. CONCLUSION: The causes of elevated cTnT levels in hemodialysis patients was multiple: cardiac dysfunction, left ventricular dysfunction and inflammation.

The first year renal function as a predictor of long-term graft survival after kidney transplantation.

This study examined the impact of graft function at the end of the first year after kidney transplantation on long-term graft survival. We analyzed the roles of serum creatinine (Scr) and other variables as predictors of graft survival among 235 adult kidney transplant patients. The subjects were divided into 3 groups according to their Scr at the end of the first year: group 1, Scr < 100 micromol/L; group 2, 100 micromol/L < or = Scr < or = 150 micromol/L; and group 3, Scr >150 micromol/L. The annual rate of graft loss of 0.7% (95% confidence interval [CI], 0.63-0.77) in group 1, was lower than those in group 2 (2.1%; 95% CI, 2.02-2.18; P < .0001) and group 3 (6%; 5.74-6.26; P < .0001). Regression analysis showed the role of recipient age at the time of operation, and Scr level at the end of the first year to be independent predictors of graft loss. Graft survival was not influenced by any other studied parameter, including donor age, year of procedure, warm ischemia time, history of acute tubular necrosis, and occurrence of an acute rejection episode. We conclude that the 1-year Scr value predicts long-term renal graft survival, representing a simple, practical tool to identify recipients with an high risk for late graft failure.

[Lymphoproliferative disorders in kidney transplant recipients: incidence, clinical characteristics and outcome]. / Syndromes lymphoprolifératifs après transplantation rénale: incidence et particularités cliniques et évolutives.

PURPOSE: The aim of this study was to determine the epidemiological and the clinical characteristics of post-transplant lymphoproliferative disease (PTLD) and to evaluate its impact on patients' and grafts' survival. PATIENTS AND METHODS: Three hundred and sixteen adult kidney recipients, transplanted between June 1986 and May 2006, were included. The incidence rates were calculated by dividing the number of different events (PTLD, death and graft-loss) by the total duration of follow-up. The survival rates and the cumulated frequency of PTLD were calculated according to the actuarial method. RESULTS: Seven recipients developed PTLD during a cumulated follow-up of 2202 years. The annual incidence was of 0.32% (95% CI : 0.30-0.34). It was of 0.81% (0.70-0.92) in recipients of kidneys from deceased donors, and of 0.25% (0.23-0.27) in patients transplanted from living donors (NS). The delay after transplantation for the diagnosis of PTLD ranged from 7.4 months to 7.7 years. PTLD was a B cell lymphoma in six cases and affected extra nodal sites in most of the cases. The treatment, comprising the cessation of immunosuppressive therapy in all cases, resulted in complete remission in four patients. Three patients died, representing an annual death rate of 6.1%, versus 2.8% in patients without PTLD (NS). The annual incidence of graft loss was 6.1% versus 3.2% among patients without PTLD (NS). CONCLUSION: PTLD was observed in 2.2% of our patients, with an annual incidence of 0.32%. It resulted in a decrease of both patients' and grafts' survivals. Preventive measures, including the improvement of the monitoring of immunosuppressive drugs and the prevention of viral infections, should be considered to reduce the risk of PTLD.

Impact of dialysis modality on posttransplantation results in kidney transplantation.

Studies looking at the type of pretransplantation renal replacement therapy on graft and patient survivals after kidney transplantation have produced conflicting results. Therefore, we studied the effect of pretransplantation dialysis modality (peritoneal dialysis [PD] or hemodialysis [HD]) on transplant outcomes. We performed a retrospective study of 78 patients (39 PD and 39 HD) who had their first renal transplantation between January 1986 and December 2004. Comparisons between groups were made using chi-square tests for qualitative parameters and nonpaired Student t tests for continuous variables. Comparisons between actuarial curves of patient and technique survivals used log-rank tests. The percentages of recipient males, cadaveric donors, transplant-induced diabetes, mean period of dialysis, mean transplantation follow-up, mean duration of first hospital stay, first infection, acute tubular necrosis, and acute rejection episodes were not significantly different among PD versus HD patients, whereas recipient and donor mean ages were significantly higher in HD and PD patients, respectively. There were no differences in graft and recipient survivals among PD versus HD patients. After kidney transplantation, there was no difference between PD and HD patients concerning percentages of infection, acute tubular necrosis, acute rejection episodes or graft and recipient survivals.

[Renal manifestations in tuberous sclerosis]. / Atteinte rénale au cours de la sclérose tubéreuse de Bourneville.

BACKGROUND: Tuberous sclerosis is a rare inherited disease which can involve several organs. Renal involvement is one of the most severe manifestations of the disease. We analysed in this study renal involvement of tuberous sclerosis. METHODS: We studied retrospectively nine cases of tuberous sclerosis with renal involvement diagnosed between 1994 and 2005. The diagnosis was based on the presence of typical extra-renal manifestations and familial history of tuberous sclerosis. RESULTS: There were eight females and one male. Their mean age was 40.8+/-16.4 years (range: 15-62). At first presentation, we noted hypertension in three cases, proteinuria in seven cases, hematuria in eight cases and renal failure in five cases (end stage renal failure in four cases). By ultrasonography, we found angiomyolipoma in one case, cysts in four cases and angiomyolipoma associated to cysts in four cases. Nephrectomy was performed in two patients, in one case for hydronephrosis secondary to urolithiasis and in the other for hemorrhagic complication. In the later, pathological examination revealed renal carcinoma. At last evaluation, two patients were lost to follow-up, one had normal serum creatinine, five were on renal replacement therapy and the latter died from sepsis following kidney removal. CONCLUSIONS: In our patients, renal disease was diagnosed late at chronic renal failure stage. Patients with end-stage renal failure require dialysis and renal transplantation, but we recommend binephrectomy after starting dialysis and before transplantation due to the risk of cancer and bleeding related to angiomyolipomas.

Urine cartilage oligomeric matrix protein (COMP) measurement is useful in discriminating the osteoarthritic Thoroughbreds.

OBJECTIVE: To quantify the urinary concentration of cartilage oligomeric matrix protein (COMP), and to evaluate the relationship between urinary COMP concentration and the catabolic activity of synovial fluid (SF) in diseased horses. METHODS: COMP in horse urine was detected by immunoblotting with a monoclonal antibody (mAb; 14G4) raised against equine COMP from articular cartilage. Urine and serum samples were obtained from 83 Thoroughbred horses with aseptic joint diseases (AJD, 79 horses) or septic joint diseases (SJD, four horses) at the time of anesthesia induction, and samples of SF were obtained during surgery. Control samples of urine (n=111) were collected from normal horses free of any orthopedic diseases after they had been racing. COMP concentration was determined in all samples using inhibition enzyme-linked immunosorbent assay (ELISA) with mAb 14G4. SF samples were also used for the quantification of gelatinase activity. RESULTS: Positive bands of COMP fragments were determined on the immunoblots with mAb 14G4. The urinary COMP concentrations in AJD and SJD horses (1.02+/-0.75 and 1.55+/-1.17 microg/100mg creatinine, respectively) were significantly higher than normal (0.57+/-0.29 microg/100mg creatinine). In 55 horses with fractures in the AJD group there was a logarithmic relationship (r=-0.45, P<0.001) between the urinary and SF COMP measurements, while the urinary COMP level was positively correlated with matrix metalloproteinase (MMP)-2 and -9 activities (r=0.30, P<0.05 and r=0.51, P<0.001, respectively) in SF. CONCLUSIONS: The urinary COMP assay with mAb 14G4 is useful for discriminating horses with osteoarthritis. The higher COMP levels in urine from such horses would be indicative of enhanced proteolytic activity, in addition to the increased COMP levels in the diseased joints.

[Parvovirus B19 infection after renal transplantation]. / Infection à parvovirus B19 et transplantation rénale.

Despite improvements in the management of transplanted patients, viral infections following transplantation remain significant causes of morbidity and mortality. New laboratory techniques have improved the diagnosis of pathogenic viral infections following transplantation such as parvovirus B19 infections. Anemia is the principal abnormality associated with parvovirus B19 infection but other complications have been reported such as hepatitis, glomerulonephritis, myocarditis or arthritis. In immunocompromised patients, infection, which may remain undiagnosed by serological tests is usually assessed by PCR. Patients may spontaneously recover. However, in the absence of specific antiviral therapy, intravenous immunoglobulin appears to be the more efficacious treatment.

Relative sweetness of fructose compared with sucrose in healthy and diabetic subjects.

Fructose is credited with some advantages over sucrose: it causes less of an increment in plasma glucose and insulin response, and the taste is sweeter. We reevaluated the latter property with a new methodology (the "up and down" method adapted from Dixon) in 33 healthy subjects, 17 insulin-dependent diabetes mellitus (IDDM) patients, and 12 non-insulin-dependent diabetes mellitus (NIDDM) patients. Sweetening potency was determined over 2-3 test sessions in each subject. Results are expressed in percent as the relative sweetness (R) of fructose (F) over sucrose (S), taken as reference. In the first set of experiments, with a 30-g/L sucrose-water solution at pH 7, we found that R values were similar for healthy subjects (102 +/- 8%) and diabetic subjects (106 +/- 7%) (P less than .05). No significant difference between IDDM and NIDDM patients was observed. In a second set of experiments, performed in healthy subjects only, R was increased in acid water (114%; P less than .01), in lemon juice (136%; P less than .001), in water at 2 degrees C (130%; P less than .001), and in coffee at 2 degrees C (120%; P less than .02); mean values were decreased in grapefruit juice (77%; P less than .001), in water at 43 degrees C (88%; P less than .01), and in coffee at 53 degrees C (87%; P less than .001). We found that the test methodology had a very satisfactory intrasubject reproducibility (coefficient of variation [C.V.] less than 8%) but a very wide intersubject variability (C.V. congruent to 32%).(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition phenomena mechanisms in experimental obeliscoidosis in rabbits. II. Local and systemic antibody responses.

A series of experiments was carried out using adult outbred Polish race rabbits of both sexes infected, during spring or autumn, with 10,000 larvae of Obeliscoides cuniculi, either fresh or stored at 4 degrees C. Extracts of mucosal proteins and bile were collected at postmortem 6 or 12 weeks after infection. Antibody levels were determined in antisera, bile and stomach mucosa by haemagglutination and precipitation tests. Local antibody responses were demonstrated in the stomach and bile, and reactions were obtained with the tissue fluids by haemagglutination and precipitation tests with worm antigens and ES products. Additionally, some specific immunological response was observed in the circulation during the primary infection. These results suggest a clear-cut relationship between increased levels of these antibodies and either larval inhibition or worm expulsion during O. cuniculi infections.