Tubular expression of Toll-like receptor 9 in lupus and primary membranous nephropathy.

INTRODUCTION: Toll-like- receptors (TLR) control important aspects of innate and adaptive immune responses. Renal cells are among the non-immune cells that express (TLR). Therefore, their activation might be implicated in renal tubulo-interstitial injury. AIM: The study aimed to compare TLR9 expression in patients with primary membranous nephropathy (MN) to patients with lupus membranous nephropathy. METHODS: Kidney sections from 10 Lupus nephritis (LN) patients and ten patients with primary MN were analyzed by immunohistochemistry using anti-human TLR9 antibody. RESULTS: Results showed that TLR9 expression was weak and exclusively tubular in primary MN patients' biopsies. There was a significant difference between LN patients' biopsies and primary MN patients' biopsies. TLR9 expression was more diffused in LN patients' specimen than in those with primary MN. CONCLUSION: This study focuses on molecular level pathogenesis of MN. The data suggest that the receptors TLR9 may play role in tubulointerstitial injury in the pathogenesis of LN but not primary membranous nephropathy.

Melatonin intake before intradialytic exercise reverses oxidative stress and improves antioxidant status in hemodialysis patients.

PURPOSE: The present study aimed to investigate for the first time the effects of melatonin (MEL) intake on oxidative stress and cellular damage during intradialytic exercise (IEX). METHODS: Thirteen hemodialysis (HD) patients volunteered to participate in the current randomized crossover trial. Participants performed four HD sessions in four different conditions: (Exercise (EX)-MEL), (EX-Placebo (PLA)), (Control (C)-MEL), and (C-PLA). 3 mg of MEL or PLA were taken 60 min before starting exercise, or at the equivalent time in the C conditions. Blood samples were taken before HD (T0), immediately after the end of IEX (T1), 60 min after IEX (T2), or at the corresponding times in the C conditions to measure free radicals damage, antioxidant biomarkers, as well as biomarkers of muscle and liver damage. RESULTS: Malondialdehyde and Advanced Oxidation Protein Products decreased in (C-MEL) (p < 0.05, d = 2.19; p < 0.01, d = 0.99, respectively) at T2 compared to T0. Catalase and total thiol levels increased in (C-MEL) (p < 0.01, d = 1.51; p < 0.01, d = 1.56, respectively) and in (EX-MEL) (p = 0.01, d = 1.28; p < 0.01, d = 1.52, respectively) at T1 compared to T0. Total bilirubin levels increased in (EX-MEL) and (C-MEL) at T2 compared to T0 (p < 0.001, d = 2.77; p < 0.001, d = 1.36, respectively), but only at T2 compared to T1 in (EX-MEL) (p < 0.001, d = 1.67). In all conditions, uric acid levels decreased at T1 compared to T0 and at T2 compared to T1, while biomarkers of muscle and liver damage remained unchanged. CONCLUSION: This pilot study is the first to show that MEL ingestion, alone or combined with IEX, could improve oxidant-antioxidant balance during HD.

Effects of intradialytic exercise in combination with melatonin supplementation on functional capacity, postural balance, and quality of life in hemodialysis patients.

INTRODUCTION: We evaluated the effect of intradialytic concurrent (resistance-endurance) training combined with melatonin (MEL) supplementation on functional capacity, muscle strength, postural balance, and quality of life (QoL) in hemodialysis (HD) patients. METHODS: Thirty-three HD patients were randomized into three groups: Exercise (EX)-MEL (n = 11); EX-Placebo (PLA) (n = 11) and Control (C)-PLA (n = 11). Participants included in the EX-MEL and EX-PLA groups were submitted to concurrent training for 12 weeks. RESULTS: EX-MEL and EX-PLA improved functional capacity, muscle strength, QoL, and postural balance parameters in eyes open and eyes closed conditions. Parameters of postural balance in the dual task condition were improved only in EX-MEL. EX-MEL induced better results in some domains of QoL compared with EX-PLA. CONCLUSION: Intradialytic concurrent training induced beneficial effects on physical function, muscle strength, postural balance, and QoL in HD patients. MEL supplementation combined with intradialytic exercise lead to better improvements in postural balance and QoL.

Dorfman-Chanarin Syndrome with Renal Involvement: A Rare Case Report and Literature Review.

Dorfman-Chanarin syndrome (DCS) is a rare autosomal recessive disease. It is a multisystemic disease in which renal involvement is uncommon. We report the case of a woman with nephrotic syndrome associated with DCS. A 36-year-old woman was referred to the nephrology department for edema with known history for DCS. On physical examination, she had ichthyosiform erythroderma with generalized scaly skinand ascites. The ophthalmologic examination revealed a cataract in the right eye. Abdominal ultrasound examination showed hepatomegaly and splenomegaly. Laboratory tests showed normal renal and liver function. The blood cell count showed pancytopenia. Immunologic exams showed the presence of anti-mitochondrial antibodies. Kidney biopsy showed mesangial proliferative glomerulonephritis with extensive lipid vacuoles in the tubular epithelial cells. Immunofluorescence study showed mesangial deposits of IgG, C3, kappa, and lambda. To the best of our knowledge, this is the first case of DCS with renal involvement reported in an adult.

Acinetobacter lwoffi peritonitis in peritoneal dialysis: two cases report.

Peritonitis is an important cause of morbidity and technique failure in peritoneal dialysis. Herein, we report peritonitis related to Acinetobacter lwoffi in two patients on peritoneal dialysis. The first case is a 63-year-old patient treated by automated peritoneal dialysis admitted with abdominal pain. The peritoneal effluent White Blood Cells count consisted of 280 cells/mm3. Then culture identified a multisensitive Acinetobacter lwoffi. Treatment with ceftazidime and ciprofloxacin had been started. The control dialysate culture was sterile after three weeks. The second patient is a 59-year-old female admitted because of diffuse abdominal pain and cloudy dialysate. The peritoneal effluent White Blood Cells count consisted of countless leukocytes, with predominantly polynuclear and culture identified Acinetobacter lwoffi. He received intraperitoneal ceftazidim and amikacin for three weeks. The control dialysate was sterile. Acinetobacter lwoffi is a rare cause of peritonitis and it can be treated successfully with early recognition and appropriate antibiotic therapy based on culture instead of catheter removal.

Differential Expression of Anti-Inflammatory RNA Binding Proteins in Lupus Nephritis.

Lupus nephritis (LN) is a type of immunological complex glomerulonephritis characterized by chronic renal inflammation which is exacerbated by infiltrating leukocytes and fueled by a variety of pro-inflammatory cytokines. A profound understanding of the pathogenesis of LN is necessary to identify the optimal molecular targets. The role of RNA-binding proteins (RBPs) in post-transcriptional gene regulation in the immune system is being explored in greater depth to better understand how this regulation is implicated in inflammatory and autoimmune diseases. Tristetraprolin (TTP), Roquin-1/2, and Regnase-1 are 3 RBPs that play a critical role in the regulation of pro-inflammatory mediators by gating the degradation and/or translational silencing of target mRNAs. In this study, we proposed to focus on the differential expression of these RBPs in immune cells and renal biopsies from LN patients, as well as their regulatory impact on a specific target. Herein, we highlight a novel target of anti-inflammatory treatment by revealing the mechanisms underlying RBP expression and the interaction between RBPs and their target RNAs.

[Cutaneous leishmaniasis after renal transplantation: Report of 7 cases and review of the literature]. / Leishmaniose cutanée après transplantation rénale : à propos de 7 cas et revue de la littérature.

Leishmaniasis is a zoonosis acquired from the bite of a sandfly that introduces the amastigote forms of leishmania into the bloodstream. It is a frequent infection in the countries of the Mediterranean basin and in Tunisia, where it is rife in an endemo-epidemic mode. However, it is rare after kidney transplantation. It constitutes a challenge due to the diagnostic difficulty, the variability and the polymorphism of the clinical picture in immunocompromised patients. We report seven observations of cutaneous leishmaniasis after kidney transplantation through which we try to identify diagnostic and therapeutic difficulties.

Primary membranoproliferative glomerulonephritis in Sfax, Tunisia: epidemiologic profile and prognostic factors.

INTRODUCTION: membranoproliferative glomerulo nephritis (MPGN) is a rare kidney disease with a poor prognosis as 50% of patients attend the end stage renal failure after 10 years of follow up. Several factors have been described associated with poor renal prognosis. The aim of our study is to determine the epidemiologic profile and to identify prognostic factors of MPGN. METHODS: our study is retrospective over a period of 16 years (January 1996 - December 2011) including all cases of primary MPGN aged more than 15 years, collected at the nephrology department of Hedi Chaker University Hospital, Sfax, Tunisia. RESULTS: we collected 118 cases of primary MPGN, with mean age of 45 (SD 19) years. The incidence of MPGN has decreased from 10 cases/year between 1996 and 1999 to 5 cases/year between 2008 and 2011. Seventy-nine percent of patients (n=93) had renal failure at the moment of diagnosis (e-GFR less than 60 ml/min/1.73m2;). After a mean follow-up of 51.9 (SD 44) months, progression to end stage renal failure was observed in 43.5% of followed cases (n=20). On univariate analysis, factors associated with death or progression to end stage renal failure were initial renal failure and sclerotic glomeruli (respectively p at 0.040 and 0.032). Multivariate analysis indicated that initial renal failure was significantly correlated with death or progression to end stage renal failure (HR: 0.14, 95% CI (0.033-0.593), p=0.008). CONCLUSION: there has been a decline in the number of cases of MPGN diagnosed in our hospital. The presence of renal failure at diagnosis was associated with death or progression to end stage renal failure.

Treatment of chronic hepatitis C with sofosbuvir in a hemodialysis patient: a case report.

The treatment of chronic hepatitis C virus (HCV) infection in chronic hemodialysis patients remains an issue of great concern for nephrologists. In 2008 the kidney disease improving global outcomes working group suggested the use of pegylated interferon in end stage kidney disease patients treated by dialysis. Since then, series and some clinical trials on different direct-acting antiviral agents have shown better efficacy and tolerance than interferon-based regimens. Data on the efficacy, tolerance and the right dose of sofosbuvir in this population are still unclear. We report a case of chronic HCV genotype 1b infection in a 47-year-old patient on maintenance hemodialysis successfully treated by a combination of sofosbuvir and ledipasvir for 12 weeks. Evolution was marked by the complete regression of the hepatic cytolysis, a complete and sustained virologic response with HCV viral load undetectable for a 24 months follow-up period. No adverse reaction was found. The treatment of HCV genotype 1 or 4 infection in patients on maintenance hemodialysis is possible with sofosbuvir based regimens with a good efficacy/safety ratio in the absence of current recommended drugs for patients with eGFR<30ml/min/1.73m2. The prescription of sofosbuvir should be encouraged amongst this population in this setting.

Next-generation sequencing in patients with familial FSGS: first report of collagen gene mutations in Tunisian patients.

Focal segmental glomerulosclerosis (FSGS) is a histological lesion with many causes, including inherited genetic defects, with significant proteinuria being the predominant clinical finding at presentation. FSGS is considered as a podocyte disease due to the fact that in the majority of patients with FSGS, the lesion results from defects in the podocyte structure. However, FSGS does not result exclusively from podocyte-associated genes. In this study, we used a genetic approach based on targeted next-generation sequencing (NGS) of 242 genes to identify the genetic cause of FSGS in seven Tunisian families. The sequencing results revealed the presence of eight distinct mutations including seven newly discovered ones: the c.538G>A (p.V180M) in NPHS2, c.5186G>A (p.R1729Q) in PLCE1 and c.232A>C (p.I78L) in PAX2 and five novel mutations in COL4A3 and COL4A4 genes. Four mutations (c.209G>A (p.G70D), c.725G>A (p.G242E), c.2225G>A (p.G742E), and c. 1681_1698del) were detected in COL4A3 gene and one mutation (c.1424G>A (p.G475D)) was found in COL4A4. In summary, NGS of a targeted gene panel is an ideal approach for the genetic testing of FSGS with multiple possible underlying etiologies. We have demonstrated that not only podocyte genes but also COL4A3/4 mutations should be considered in patients with FSGS.

Unusual Cause of Peritonitis in Peritoneal Dialysis Patient Related to Streptococcus salivarius.

Peritonitis remains the most common serious complication associated with peritoneal dialysis (PD). The Gram-positive peritonitis with Staphylococcus aureus and coagulase-negative Staphylococcus are the most frequent causes, whereas Gram-positive and Gram-negative species remain less frequent. We report an uncommon case of PD-related peritonitis due to Streptococcus salivarius, known as nonpathogen Gram-positive bacteria of oral flora.

[Urolithiasis of the kidney transplanted patient in south Tunisia: A 17-year experience]. / La lithiase urinaire du transplanté rénal dans le sud tunisien : expérience de 17 ans.

INTRODUCTION: Urolithiasis in a kidney transplanted patient is an uncommon but complex urological complication. Its potential severity comes from its occurrence on a solitary kidney and on a field of immunosuppression. The aim of our study is to assess the incidence, characteristics and course of urolithiasis in our series. METHODS: A retrospective study was performed. We included kidney transplanted patients between November 2002 and November 2019 and presenting lithiasis during their follow-up. Clinical, biological and radiological data were collected as well as lithiasis disease related data. The management of and patient's evolution were also specified. RESULTS: Seven of 416 kidney transplanted patients developed lithiasis during their follow-up with an incidence of 1.6 %. The mean age at lithiasis diagnosis was 36.5 years [24-55 years], the sex ratio was 1.3. They developed stones after mean follow-up of 67 months [4-168 months]. The stones' size varied from 2 to 18mm. Treatment was alkalisation in 3 cases, extracorporeal lithotripsy in 2 cases, a double J stent in 3 cases and pyelolithotomy in 2 cases. Four patients had multiple treatments. Three patients had 1 residual stone during evolution (7mm average diameter), 1 microlithiasis, 1 lost to follow-up after treatment and only 2 (out of 7) were "stone free". Furthermore, lithiasis didn't damage the graft survival after a median follow-up of 62 months post-treatment. CONCLUSION: Urolithiasis in the kidney transplanted patient requires an adapted multidisciplinary management. Its skill is a challenge for both the nephrologist and urologist.

[Pregnancy in patients on chronic haemodialysis: about 25 cases which occurred in the south of Tunisia]. / La grossesse en hémodialyse chronique: à propos de 25 cas survenus dans le Sud Tunisien.

INTRODUCTION: the occurrence of pregnancy in patients on chronic haemodialysis is rare. However, given the evolution in dialysis technique, improvement in fertility is possible. The purpose of our study was to report our experience concerning the occurrence of pregnancy in patients on dialysis and to identify factors involved in its success. METHODS: we conducted a retrospective study on 25 spontaneous pregnancies occurred in 19 patients treated with periodical hemodialysis in different hemodialysis centers in the south of Tunisia over a period of 34 years. RESULTS: maternal age at the onset of pregnancy was, on average, 35.6 years [23-44 years] with an average seniority in hemodialysis of 4.22 years [1-17 years]. Seven patients (37%) had residual diuresis (>500 ml/24h). The prescribed weekly number of hours of dialysis was ≥16 hours per week in 7 cases and ≥20 hours in 4 cases. Success of pregnancy (new-born surviving at least 28 days) was estimated at 56%. The median gestational age was 34 weeks of amenorrhea [28-38 WA]. The average neonatal weight was equal to 1970g [1500g-2300g]. Analytical study showed a significant correlation between the increase in the hours of dialysis per week and the success of pregnancy (R=0.59; p=0.002). CONCLUSION: it was noted that with adequate support and in particular, increasing the number of sessions of dialysis, materno-fetal complications can be minimized and the balance risk-benefit can turn the chance for a woman on dyalisis to become pregnant.

Twice weekly hemodialysis is safe at the beginning of kidney replacement therapy: the experience of the Nephrology Department at Hedi Chaker University Hospital, Sfax, south of Tunisia.

We re-examine the infrequent paradigm of a biweekly dialysis at the start of renal replacement therapy. The current method is to launch hemodialysis among patients using a 'full-dose' posology three times a week. As a matter of fact, recent data has suggested that frequent hemodialysis leads to high mortality at the onset of dialysis. The aim of our study is to show the factors affecting early mortality especially the hemodialysis frequency. We undertook an observational study in the hemodialysis unit of Sfax University Hospital (south Tunisia). We enrolled the incident patients during one year. Baseline demographic and clinical characteristics of patients were noted. The survival status of each patient is observed at 6 months after the onset of hemodialysis. We analyzed the factors associated with mortality, especially the hemodialysis frequency (twice or thrice weekly hemodialysis regimen). We enrolled 88 patients with mean age of 56 ± 18 years old. Thirty patients underwent twice weekly dialysis (Group 1) and 58 patients underwent thrice weekly dialysis (Group 2). The mortality at 6 months was similar in the 2 groups (the rate of death = 30% in group 1 vs 13.8% in group 2, p = 0.07). However, the mortality was lower in the group with preserved residual diuresis (35.3% vs 64.7% in the group without residual diuresis, p = 0.02). The mortality was higher in diabetes patients (64.7% vs 35.5%, p = 0.02). It was concluded that twice or threefold weekly treatment have some considerable similar outcomes on the patients survival (at 6 months).

A novel de novo splicing mutation c.1444-2A>T in the TSC2 gene causes exon skipping and premature termination in a patient with tuberous sclerosis syndrome.

Tuberous sclerosis complex (TSC) syndrome is a neurocutaneous syndrome that affects the brain, skin, and kidneys that has an adverse impact on the patient's health and quality of life. There have been several recent advances that elucidate the genetic complex of this disorder that will help understand the basic neurobiology of this disorder. We report a Tunisian patient with clinical manifestations of TSC syndrome. We investigated the causative molecular defect in this patient using PCR followed by direct sequencing. Subsequently, in silico studies and mRNA analysis were performed to study the pathogenicity of the new variation found in the TSC2. Bioinformatics tools predicted that the novel mutation c.1444-2A>T have pathogenic effects on splicing machinery. RT-PCR followed by sequencing revealed that the mutation c.1444-2A>T generates two aberrant transcripts. The first, with exon 15 skipping, is responsible for the loss of 52 amino acids, which causes the production of an aberrant protein isoform. The second, with the inclusion of 122 nucleotides of intron 14, is responsible for the creation of new premature termination codons (TGA), which causes the production of a truncated TSC2 protein. This study highlighted the clinical features of a Tunisian patient with TSC syndrome and revealed a splicing mutation c.1444-2A>T within intron 14 of TSC2 gene, which is present for the first time using Sanger sequencing approach, as a disease-causing mutation in a Tunisian patient with TSC syndrome.

[Epidemiological profile of terminal chronic renal failure in the region of Sfax]. / Profil épidémiologique de l'insuffisance rénale chronique terminale dans la région de Sfax.

INTRODUCTION: Terminal chronic renal failure is a truly global public health problem. In 2011, the cost of management of patients on dialysis has surpassed 90 million dinars (37.000 euro) in Tunisia, nearly 5% of the overall health spending. A better knowledge of the epidemiological profile of terminal chronic renal failure contributes to the implementation and evaluation of health strategies aimed to improve prevention and disease management. This study aimed to describe the epidemiological profile of incident cases in the Sfax Governorate over the period of 10 years. METHODS: We conducted a descriptive retrospective study over the period from January 2003 to December 2012. The incident cases of terminal chronic renal failure in the Sfax Governorate were included in the study. RESULTS: The diagnosis of terminal chronic renal failure was made in 1708 cases: 957 men and 751 women (sex-ratio = 1.27). The average age was 58.4 years [10-100 years]. The study of the evolution of the average age during the study period showed a tendency to increase with positive correlation coefficient (0.749) and p = 0.006. The main causal nephropathy was diabetic nephropathy (21.5%), with a significant increase in its frequency from one year to the other (positive correlation coefficient (0.770) with p = 0.009). Hemodialysis was the dialysis technique of choice, performed in 96% of patients. CONCLUSION: A national registry is indispensable in order to better understand the epidemiological profile of terminal chronic renal failure in Tunisia and to improve its management.

The Increased Expression of Toll-Like Receptor 4 in Renal and Skin Lesions in Lupus Erythematosus.

Toll-like receptor 4 (TLR-4), a bacterial lipopolysaccharide sensor, is an innate immunity essential modulator. It is expressed on both immune and non-immune cells and may contribute to the cutaneous and renal manifestations during lupus erythematosus (LE). Our purpose is to evaluate TLR-4 expression and analyzing its role in lupus nephritis (LN) and chronic cutaneous lupus erythematosus (CLE) pathogenesis. TLR-4 immunohistochemical staining was performed on 30 LN renal biopsies compared with 11 healthy renal tissues and 30 skin biopsies from CLE patients compared with 15 normal individuals. CLE patients' biopsies showed a strong and diffuse TLR-4 expression throughout the epidermis and labeled inflammatory infiltrate and glands in the dermis whereas controls' skin expressed weakly TLR-4 only in the epidermis basal layer. LN glomeruli and tubules showed an increased and more intense TLR-4 expression compared with normal controls where TLR-4 expression was weak and rarely detected in glomeruli, diffuse and weak in tubules. A significant difference in TLR-4 expression between LN classes, both in glomeruli and tubules, was observed. These data confirm an up-regulation of TLR-4 expression in the affected tissues of CLE and LN patients and highlight the critical role of TLR-4 in the pathogenesis of cutaneous and renal disorders in LE.

Diet in chronic kidney disease in a Mediterranean African country.

BACKGROUND: Mediterranean diet is characterized by low to moderate consumption of animal protein and high consumption of fruits, vegetables, bread, beans, nuts, seeds and other cereals. It has been associated with reduced risk of cardiovascular disease. However, it is not suitable for chronic kidney disease because of high potassium intake. DISCUSSION: Tunisia is an emerging Mediterranean country with limited resources, a high prevalence of chronic hemodialysis treatment and high dialysis expenditures. In order to limit dialysis cost, primary and secondary prevention of chronic renal disease are of paramount importance. In addition to drugs, secondary prevention includes diet measures (e.g. salt diet, protein diet). The aims of diet practice in chronic kidney disease are to slow chronic renal failure progression and to prevent its complications like hyperphosphatemia and hyperkaliemiae. A few decades ago, a Tunisian diet was exclusively Mediterranean, and protein consumption was not excessive. However, today, protein consumption is more comparable to western countries. Salt consumption is also excessive. Some Tunisian diets still include food with high potassium intake, which are not suitable for patients with chronic kidney disease. Therefore, the role of the dietician is extremely important to help calculate and create a dietary regimen tailored to each of our patients. Advice about diets should be adapted to both the patient and population habits to improve adherence rate. As such, the purpose of this article is to provide our own experience regarding medical nutrition therapy in patients with chronic kidney disease in Tunisia, with some changes in food habits. Prevention is far better than treatment. In this perspective, dietary measures must be at the core of our intervention.

Ciprofloxacin-induced crystal nephropathy.

Ciprofloxacin is a commonly used antibiotic. Renal side effects are rare and are usually immune mediated. Clinical and experimental studies have suggested that crystalluria and crystal nephropathy occur in alkaline urine. Preexisting kidney function impairment, high dose of the medication, and advanced age predispose to this complication. We report a case of crystal nephropathy in a young woman treated with ciprofloxacin and a nonsteroidal anti-inflammatory drug.

Risk factors for acute decompensation of chronic kidney disease in hospitalized patients in the nephrology department: a case-control study.

OBJECTIVE: To investigate risk factors for acute kidney injury (AKI) in hospitalized patients with chronic kidney disease (CKD) a case-control study was conducted in the Nephrology Department of Hedi Chaker University Hospital in Sfax, Tunisia, for a 1-year period. METHODS: All patients with baseline renal insufficiency hospitalized for AKI were considered as cases. They were compared with control patients with CKD. A conditional logistic regression model was used to identify independent risk factors for AKI in patients with CKD. RESULTS: A total of 58 cases were compared with 114 control subjects. In multivariable models, baseline diabetes, cardiopathy disease, and exposure to non-steroidal anti-inflammatory drugs were independent risk factors for AKI in patients with CKD. However, exposure to calcium channel blockers (CCBs) was associated with decreased risk for AKI on CKD (OR = 0.4; CI 95%: 0.2 - 0.8, p = 0.007). CONCLUSIONS: Patients with CKD may benefit from more aggressive cardiovascular screening to prevent episodes of acute kidney injury. More efforts should be made to prevent prescription drug abuse and to demonstrate the role of CCBs in renal protection in these patients.