Thrombotic microangiopathy due to acquired complement factor I deficiency in a male receiving interferon-beta treatment for multiple sclerosis.

AIMS: Interferon-beta (IFNß), the most widely prescribed medication for multiple sclerosis, is generally considered safe. Nevertheless, rare serious and/or life-threatening side effects have been reported such as thrombotic microangiopathy. A few mechanisms have been proposed to explain how interferon causes thrombotic microangiopathy, but immunological studies have been unable to pin this phenomenon down to a single pathophysiologic pathway. The aim of this article was to report a new mechanism explaining Interferon beta related thrombotic microangiopathy. METHODS: We report thrombotic microangiopathy in a 28-year-old male receiving interferon-beta treatment for multiple sclerosis. RESULTS: After three years of starting interferon beta therapy, the patient presented with malignant hypertension causing seizures, rapidly progressive renal failure requiring haemodialysis and haemolytic anaemia. Corticosteroid and plasma exchange sessions permitted haemolysis control. Nonetheless, the patient remained hemodialysis-dependent. Exploration of the complement system found a complement factor I deficiency whose activity normalized at the control carried out after 2 years. CONCLUSION: IFNß treatment may cause complement factor I deficit, which can lead to thrombotic microangiopathy and severe renal failure.

The evaluate and compare the effects of the Tacrolimus and Sirolimus on the intestinal system using an intestinal cell culture model.

Tacrolimus (TAC) and Sirolimus (SRL) are produced by Streptomyces sp and effective immunosuppressive drugs commonly used in organ transplantation. Therefore, strategies for minimizing the toxicity of immunosuppressant molecules are our interest. This study was conducted to evaluate the interactive effects and the possible underlying mechanism of TAC and SRL on HCT116 cells. It was found that TAC and SRL alone inhibited cell viability. Also, it induced reactive oxygen species (ROS) formation, loss of mitochondrial membrane potential (Δψm), and able to increase DNA fragmentation in a concentration-dependent manner. The use of combined SRL and TAC showed a reservation in all toxicity observed with the two immunosuppressive drugs separately. Our result demonstrated that the mechanisms of TAC and SRL at high concentration are closely connected with oxidative stress. Furthermore, SRL at low concentration plays a protective effect against TAC (IC50) which induced cytotoxicity and genotoxicity. However, using the combination of the SRL/TAC at high concentrations (IC30) appears as an antagonist response.

Prevalence and Predictive Factors of Urinary Tract Infection in Kidney Transplant Recipients: A 10-Year Study.

OBJECTIVES: Urinary tract infections are the main infectious complications among kidney transplant recipients and are considered as a potential risk factor for poor graft outcomes. However, the risk factors of urinary tract infections are controversial. The purpose of our study was to estimate the incidence and predisposing factors of urinary tract infections in patients undergoing kidney transplant in our teaching hospital of Sahloul, Tunisia. MATERIALS AND METHODS: We retrospectively analyzed the charts of 141 consecutive adult kidney transplants that were performed at the Department of Nephrology, University Hospital of Sahloul, Tunisia, between January 2007 and April 2016. RESULTS: Of 141 patients, 72 (51.1%) had urinary tract infections after kidney transplant. Mean age was 32.54 ± 12.1 years; 47.6% were male patients, and 52.4% were female patients. The average time between transplant and early urinary tract infections was 11 days (range, 1-30 days). Among our patient group, 87.8% of urinary tract infections occurred within the first 6 months posttransplant. We collected 205 episodes of urinary tract infections: 66.3% were asymptomatic bacteriuria, 10.2% acute cystitis, and 23.4% pyelonephritis. The estimated risk factors for urinary tract infection included only female sex (P < .05); older age (P = .32), longer duration of catheter (P = .34), and high body mass index (P = .46) were not correlated with urinary tract infection. CONCLUSIONS: Despite preventive measures, urinary tract infections remain an important cause of morbidity among kidney transplant recipients. In fact, more than half of kidney transplant recipients had at least 1 urinary tract infection after surgery. Female sex was statistically associated with higher risk of urinary tract infection.

Dermatological Conditions Seen in Kidney Transplant Recipients: Prevalence and Risk Factors.

OBJECTIVES: In kidney transplant, the use of immunosuppressive drugs, indispensable to avoid organ rejection, implies an increased risk of several infectious and neoplastic diseases. Cutaneous infections have a high incidence in kidney transplant recipients and are diagnosed in 55% to 97% of these patients. The objectives of this study were to identify the most frequent skin diseases and their clinical risk factors within a population of kidney transplant recipients. MATERIALS AND METHODS: We reviewed the medical records of 200 kidney transplant recipients at Sahloul Teaching Hospital, Tunisia, between November 2007 and January 2018. We analyzed the clinical data of patients who sought skin consultations with either dermatologists or plastic surgeons within the hospital. We collected patient sociodemographic data, type of donor, and type of immunosuppressive therapy used by recipients. We also obtained history of skin lesions and examination findings. RESULTS: Among 200 patients included in our study cohort, 131 were male and 69 were female. Age ranged from 6 to 75 years with a mean age of 30.51 ± 12 years. Patients had received kidneys from either living or deceased donors, with available data indicating 96.5% living donors and 3.5% deceased donors. The mean time interval from transplant to first skin consultation was 31 month (range, 3 months to 10 years). Prevalence of various skin conditions was 48.5%. We found that 62.9% of cases were skin infections, 59.8% were drug-induced skin conditions, and 2.9% were skin cancers. The estimated risk factors for skin lesions include use of cyclosporin and duration of immunosuppression. CONCLUSIONS: Our study demonstrated the spectrum of skin conditions that can be expected after kidney transplant. Careful dermatological screening and long-term follow-up are needed for these patients to reduce posttransplant skin complications.

Role of recombinant human erythropoietin in mitomycin C-induced genotoxicity: analysis of DNA fragmentation, chromosome aberrations and micronuclei in rat bone-marrow cells.

Mitomycin C (MMC) is one of the most effective chemotherapeutic agents. However, during clinical use several side effects may occur. Recombinant human erythropoietin (rhEPO), a glycoprotein that regulates haematopoiesis, has been shown to exert an important cyto-protective effect in many tissues. The aim of this study was to explore whether rhEPO protects against MMC-induced genotoxicity in rat bone-marrow cells. Adult male Wistar rats were divided into six groups of 18 animals each: a control group, a 'rhEPO alone' group, an 'MMC alone' group and three 'rhEPO+MMC' groups (pre-, co- and post-treatment conditions). Our results show that MMC induced a noticeable genotoxic effect in rat bone-marrow cells. rhEPO reduced the effects of MMC significantly in every type of experiment conducted, such as the frequency of micronuclei, the percentage of chromosome aberrations and the level of DNA damage measured with the comet assay. The protective effect of rhEPO was more efficient when it was given 24h prior to MMC treatment.

In vitro interaction of the pesticides flupyradifurone, bupirimate and its metabolite ethirimol with the ATP-binding cassette transporter G2 (ABCG2).

ABCG2 is an ATP-binding cassette efflux transporter that is expressed in absorptive and excretory organs such as liver, intestine, kidney, brain and testis where it plays a crucial physiological and toxicological role in protecting cells against xenobiotics, affecting pharmacokinetics of its substrates. In addition, the induction of ABCG2 expression in mammary gland during lactation is related to active secretion of many toxicants into milk. In this study, the in vitro interactions between ABCG2 and three pesticides flupyradifurone, bupirimate and its metabolite ethirimol were investigated to check whether these compounds are substrates and/or inhibitors of this transporter. Using in vitro transepithelial assays with cells transduced with murine, ovine and human ABCG2, we showed that ethirimol and flupyradifurone were transported efficiently by murine Abcg2 and ovine ABCG2 but not by human ABCG2. Bupirimate was not found to be an in vitro substrate of ABCG2 transporter. Accumulation assays using mitoxantrone in transduced MDCK-II cells suggest that none of the tested pesticides were efficient ABCG2 inhibitors, at least in our experimental conditions. Our studies disclose that ethirimol and flupyradifurone are in vitro substrates of murine and ovine ABCG2, opening the possibility of a potential relevance of ABCG2 in the toxicokinetics of these pesticides.

Nephrotic syndrome with Minimal Change Disease and Atopy in NorthAfrican adults.

INTRODUCTION: In adults, minimal change disease (MCD) accounts for 15 to 25% of nephrotic syndrome (NS). Numerous reports have suggested a link between NS and atopy. However, data on treatment and prognosis of NS associated with allergy are limited. AIM: To examine the presenting characteristics, treatments and outcomes of adults with allergic MCD in a North African center. METHODS: This was an observational study using retrospectively collected data. Patients were recruited from the Nephrology department of Sahloul Hospital (Sousse, Tunisia) from January 2006 to December 2020. Adults with a biopsy proved MCD, which was associated with atopy, were included. RESULTS: Fifteen patients (eight males, age mean±SD: 34±13 years) were included. High eosinophil and immunoglobulin E (IgE) levels were noted in three and twelve patients respectively. The IgE mean level at the initial presentation was 1431 IU/ml. Allergic skin tests were positive in nine patients. All patients were treated with corticosteroids, five had anti-histamine therapy and five had hyposensitization therapy, which was successful in two patients. Thirteen patients had relapsed during follow-up. Mean eosinophil level was significantly higher in patients with frequent relapses compared to those with infrequent relapses (5415/mm³ vs. 239.12/mm³, respectively, p=0.022). Two patients had progressed to chronic renal failure. CONCLUSION: It is important to search for atopic disorders in patients with MCD to better control this disease and use specific treatments. However, the efficacy of anti-allergic therapies has to be proven.

Bromuconazole caused genotoxicity and hepatic and renal damage via oxidative stress process in Wistar rats.

Bromuconazole is a triazole pesticide used to protect vegetables and fruits against diverse fungi pathologies. However, its utilization may be accompanied by diverse tissue injuries. In this study, we evaluated the biochemical and histopathological modifications, and we analyzed genotoxic and oxidative stress, in the aim to examine bromuconazole effects in the liver and kidney. We subdivided animals into four groups, each one contains six adult male Wistar rats. Untreated rats received daily a corn oil (vehicle) orally. Three oral bromuconazole doses were tested (1, 5, and 10 % of LD50) daily for 28 days. Bromuconazole increased the plasma activities of alkaline phosphatase, lactate dehydrogenase, and transaminases. It also increased the plasma levels of creatinine and uric acid. Histopathological check showed that bromuconazole caused organ damage. This study makes known that bromuconazole caused conspicuous DNA damage either in hepatic or kidney tissues, with a significant increase in the levels of malondialdehyde and protein carbonyl followed by an enhancement in catalase and superoxide dismutase enzymatic activities, and these increases are in a dose-dependent manner. In other side, we found that Glutathione-S-transferase and peroxidase activities raised. Our outcomes highlight that bromuconazole exposure induced genotoxic damage and organ damage which may be caused by the disturbances of oxidative stress statue in the liver and kidney.

Estimating the cost of home dialysis in Tunisia: Application of the Activity-based costing methodology.

INTRODUCTION: In Tunisia, in-centre haemodialysis (ICHD) is the most common type of dialysis. Despite the increasing demand, the number of haemodialysis machines per 100,000 inhabitants is still low. Home Haemodialysis (HHD) is a candidate solution to this problem. Despite its confirmed benefits over ICHD, HHD has not taken place in Tunisia. AIM: To describe the processes of home dialysis modalities, especially HHD, evaluate their costs, analyse them, in the context of medical practice in public health structures in Tunisia. METHOD: The Activity-Based Costing technique was applied: the processes of home dialysis modalities were modelled, the main activity and resource cost drivers identified, and cost equations developed. Based on data from the nephrology department of Sahloul hospital, the cost per session and annual costs for each home dialysis modality were calculated and analyzed. RESULTS: Home Peritoneal Dialysis, already implemented in Tunisia; presented the lowest annual cost per patient 25344 TND versus 29232 TND for Conventional HHD and 54144 TND for Short-Daily HHD. The cost per session of the Short-Daily HHD (188,8 TND) was comparable to ICHD (180 TND). Consumables presented the most expensive resource for these modalities. Finally, the cost structure of HHD was comparable in Tunisia and France as well as in previous costing studies. CONCLUSION: The cost of one session of HHD is estimated to 188,8 TND. The Tunisian ministry of health could adopt a flexible policy to start HHD program by implementing Conventional HHD first.

New-Onset Diabetes as a Complication After Kidney Transplant: Incidence and Outcomes.

OBJECTIVES: Diabetes after kidney transplant is a common complication. It may increase the risk of cardiovascular disease and mortality after kidney transplant. The aim of this study was to examine the effects of diabetes that developed after transplant on outcomes in kidney transplant recipients. MATERIALS AND METHODS: This study included renal allograft recipients without diabetes who received transplants from 2008 to 2019 in our Department of Nephrology at Sahloul Hospital (Tunisia). Demographic and clinical data at transplant time and clinical events during the study period were collected. Patient and graft survival rates were analyzed. Patients with and without diabetes after transplant were compared. RESULTS: In the 257 patients (median age of 36 years) included in our study, the overall incidence of diabetes after transplant was 21.8%. Laboratory data (serum cholesterol, serum creatinine at discharge, and 24-hour proteinuria) were similar in those with and without diabetes after transplant. We observed no significant differences in cardiovascular diseases and infectious complication rates between patients with and without diabetes after transplant. There was also no significant difference in graft loss at 5 years between those with and without diabetes after transplant (P = .582). The 5-year patient survival rate in kidney transplant recipients with diabetes after transplant was 87.5%. There was no significant difference in death rate between those with and without diabetes after transplant (P = .566). CONCLUSIONS: Diabetes after transplant affected graft and patient survival and increased the incidence of posttransplant cardiovascular disease. The incidence and impact of diabetes after transplant can be minimized through pre- and posttransplant screening to identify patients at higher risk.

Severe Acute Interstitial Nephritis, Dermatitis, and Hemolytic Anemia due to Polyparasitic Infection in an Immunocompetent Male Patient.

Acute interstitial nephritis (AIN) is a relevant cause of acute renal failure. Drugs are the predominant cause, followed by infections and idiopathic lesions. AIN, as a form of hypersensitivity reaction, is an uncommon manifestation in the setting of human parasitic infections. We report a case of a polyparasitic infection (Giardia lamblia, Entamoeba coli, and Endolimax nana) resulting in a severe biopsy-proven AIN in a 61-year-old male patient. Despite the antiparasitic treatment followed by corticosteroid therapy, and during the 6-month follow-up period, the patient remained dialysis-dependent, and he developed autoimmune hemolytic anemia. Extensive search for another infection or neoplasia was negative. Immunological tests were also negative. The resulting hypersensitivity reaction to the triple parasite infection would have led to fatal evolution for the kidneys affected by this unusual type of AIN.

Elizabethkingia meningoseptica: An Uncommon Cause of Peritonitis In Continuous Ambulatory Peritoneal Dialysis: A Case Report and Review of Literature.

Peritonitis is a major complication of peritoneal dialysis (PD) and due to its gravity, it remains the primary reason to switch from PD to hemodialysis. Elizabethkingia meningoseptica, a non-fermentative Gram-negative bacillus, is rarely encountered as a pathogen causing peritonitis in adults. We present here a case report of an acquired infection with this organism in adult on PD. To the best of our knowledge, this is the first report of infection with this organism in a continuous ambulatory PD patient in Tunisia.

Acute Kidney Injury due to Povidone-Iodine.

Povidone-iodine is a broad-spectrum antiseptic applied topically to treat wounds and prevent their infection. Despite the apparent innocuousness of this agent, several cases of acute kidney injury (AKI) due to iodine toxicity have been reported. We report a case of severe AKI that occurred in a 32-year-old female three days after a hysteroscopy for the diagnosis of primary sterility using povidone-iodine as the local antiseptic agent. We made a clinical diagnosis of tubular necrosis related to iodine toxicity in view of the clinical presentation and high blood iodine concentration. The patient was treated with hemodialysis until urine output and renal function improved. Physicians must be aware of the possible nephrotoxicity secondary to povidone-iodine use. Patients receiving povidone-iodine, especially those who already suffer from kidney failure, should be closely monitored. The discontinuation of this agent, with the use of hemodialysis, is usually effective.

Long-term clinical outcomes of peritoneal dialysis patients: 10-year experience of a single unit from Tunisia.

Published data on the outcome of maintenance peritoneal dialysis (PD) since the initiation of PD in Tunisia is poor. The purpose of this study is to report long-term clinical outcomes of PD patients through a 10-year experience at a single unit. This is a retrospective review of the medical records of 182 PD patients who were followed up from January 2006 to June 2016. All patients were followed till death, renal transplant, switch over to hemodialysis (HD) or the end of the study in June 2016. The mean age of the incident patients was 43.93 ± 16.95 years. Nineteen (10.4%) were aged >65 years and 59.3% were male. The average duration of follow-up was 27.75 ± 26.18 months. The mean duration of PD treatment was 27.75 ± 26.18 months. There were 186 episodes of peritonitis that occurred over the total study period (54 episodes during the 1st year). The overall incidence of peritonitis during the 10-year study period was 1 per 27.25 patient months. Mechanical complications were noted in 31.2% of cases. Thirty- two (17.6%) patients had catheter displacement. Only 26 cases of hemoperitoneum (14.3%) were recorded. Death occurred in 23.1% of cases. Twenty-two patients (27.5%) were transplanted; 56 patients (70%) were transferred to HD, one patient had renal recovery and one case had voluntarily interrupted PD. In Kaplan-Meier curves of residual renal function (RRF) loss, there was a significant difference between peritonitis group and peritonitis-free group (P = 0.01). Technique and patient survival were associated with diabetes with a significant difference. The main cause of technique failure was peritonitis (61.4%). Moreover, the main repertoried causes of death were cardiovascular and septic causes. The mortality of diabetic and elderly PD patients was higher than mortality in nondiabetic and nonelderly groups, respectively, in our study. Peritonitis was associated with loss of RRF and technique failure.

Alternaria alternata peritonitis in a patient undergoing continuous ambulatory peritoneal dialysis.

Fungal peritonitis is a serious complication of peritoneal dialysis (PD) leading to loss of ultrafiltration and discontinuation of PD treatment. The most frequently isolated fungi are Candida albicans and, filamentous fungi such Alternaria alternata species are found only rarely. We report the case of a 75-year-old woman who developed peritonitis due to this black fungus.

Effect of intraperitoneal injection of sulodexide on peritoneal function and albumin leakage in continuous ambulatory peritoneal dialysis patients.

Peritoneal protein loss is one of the inevitable consequences during continuous ambulatory peritoneal dialysis (CAPD). Our objective was to study the effect of sulodexide on the protein loss and efficiency of dialysis. This study included six patients receiving CAPD treated with sulodexide at the dose of 600 IU/day given by intraperitoneal injection for 10 days. Clinical and biologic parameters were assessed before starting the treatment (D0 and after 10 days of treatment (D10. We also evaluated the benefit of therapy persisting 20 days after the end of treatment (D30. The sulodexide administration produced a significant improvement of the peritoneal function as determined by a significant increase in the following ratios measured at the 4 th h of dwell time on D0 and D30: dialysate-to plasma (D/P) creatinine from 0.63 ± 1.45 to 0.85 ± 0.073 (P = 0.028) and D/P urea from 0.63 ± 0.15 to 79 ± 0.2 (P = 0.048). A significant decrease of albumin leakage was observed, which was 0.90 ± 0.40 g/L at baseline, 0.67 ± 0.36 g/L on the 10 th day, and 0.43 ± 0.22g/L 20 days after the end of treatment. Within 10-day treatment period, use of sulodexide resulted in a reduction in the peritoneal loss of albumin, in addition to improvement of the quality of dialysis and the residual renal function among these patients.

Metabolic syndrome and chronic kidney disease.

To determine the prevalence of metabolic syndrome (MS) in chronic kidney disease (CKD) patients as well as its effects on the progression of CKD, we conducted a prospective, longitudinal study including 180 patients with chronic renal failure followed at the outpatient service of Nephrology at the Saloul's University Hospital of Sousse (Tunisia) over six months. Our study population consisted of 101 men and 79 women. Chronic glomerulonephritis (36.6%) was the most frequent nephropathy. The mean serum creatinine was 249 ± 200 mmol/L and the mean estimated glomerular filtration rate (eGFR) was 55.8 ± 49.2 mL/min. Cardiovascular (CV) impairment was found in 27.2% of the patients. The prevalence of MS was 42.2%. Women had significantly more abdominal obesity than men. Subjects with MS were significantly older and predominantly females who had higher blood pressure and body mass index (BMI). CV complications were more frequent among the MS subjects than among the controls. Glycemia, triglycerides, total cholesterol and low-density lipoprotein-cholesterol (LDL-c) were significantly higher in the group of CKD patients with MS. However, the occurrence of MS was not influenced by the nature of nephropathy, the degree of the CKD and the use of renin-angiotensin blockers or statins. In multivariate analysis, predictors of occurrence of MS in our series included older age, female gender and higher BMI and LDL-c levels. The prevalence of MS in patients with CKD is higher than the general population. These patients should receive special multidisciplinary care to limit CV complications.