J. Hachicha

A Homozygous Missense Mutation in the Ciliary Gene TTC21B Causes Familial FSGS

Several genes, mainly involved in podocyte cytoskeleton regulation, have been implicated in familial forms of primary FSGS. We identified a homozygous missense mutation (p.P209L) in the TTC21B gene in seven families with FSGS. Mutations in this ciliary gene were previously reported to cause nephronophthisis, a chronic tubulointerstitial nephropathy. Notably, tubular basement membrane thickening reminiscent of that observed in nephronophthisis was present in patients with FSGS and the p.P209L mutation. We demonstrated that the TTC21B gene product IFT139, an intraflagellar transport-A component, mainly localizes at the base of the primary cilium in developing podocytes from human fetal tissue and in undifferentiated cultured podocytes. In contrast, in nonciliated adult podocytes and differentiated cultured cells, IFT139 relocalized along the extended microtubule network. We further showed that knockdown of IFT139 in podocytes leads to primary cilia defects, abnormal cell migration, and cytoskeleton alterations, which can be partially rescued by p.P209L overexpression, indicating its hypomorphic effect. Our results demonstrate the involvement of a ciliary gene in a glomerular disorder and point to a critical function of IFT139 in podocytes. Altogether, these data suggest that this homozygous TTC21B p.P209L mutation leads to a novel hereditary kidney disorder with both glomerular and tubulointerstitial damages.

Clinical and diagnostic value of ribosomal P autoantibodies in systemic lupus erythematosus

OBJECTIVE To analyse prospectively the diagnostic sensitivity and specificity as well as the clinical relevance of ribosomal P (anti-P) autoantibodies in a large cohort of SLE patients. METHODS The anti-P autoantibodies were evaluated in the serum of 200 Tunisian SLE patients at disease onset and 130 various control subjects by a sensitive immunodot assay. A complete laboratory evaluation and clinical examination were performed in each SLE patient. During the follow-up, the patients were regularly monitored for clinical parameters. Global SLE activity was measured by the ECLAM. RESULTS The sensitivity and specificity of anti-P testing for SLE were 23.5 and 98.4%, respectively. The anti-P-positive samples 14/47 (29.8%), 27/47 (57.4%) and 5/47 (10.6%) were negative for anti-dsDNA, anti-Sm or both antibodies, respectively. The anti-P-positive patients showed more active disease activity and a much higher prevalence of arthritis. An association between IgG aCLs and anti-P antibodies was also found. However, anti-P antibodies were not associated with neuropsychiatric manifestations or lupus nephritis. CONCLUSION This study does not seem to confirm the described association of anti-P antibodies with neuropsychiatric manifestations of SLE. However, it supports the anti-P antibody association with arthritis and disease activity as well as the presence of aCL. Based on our study and other related studies, we propose that, akin to anti-Sm and anti-dsDNA, anti-P antibodies detected by one agreed method may be considered for inclusion as a criterion for the classification of SLE.

Sirolimus for the Treatment of Kaposi Sarcoma After Renal Transplantation: A Series of 10 Cases

The incidence of Kaposi sarcoma (KS) has substantially increased among immunocompromised patients, suggesting a role for immunosuppressive drugs. The aim of this study was to evaluate the incidence, features, and outcome of KS among 307 kidney transplantation patients at our center between January 1994 and June 2010. During the study period, the 10 patients who developed KS (3.25%) showed a mean age at transplantation of 35.8 ± 8.7 years (range, 22 to 49 years). The mean interval between transplantation and occurrence of KS was 24.7 ± 21.36 months (range, 6 to 64 months). The mean time of antithymocyte globulin induction was 9.5 days (range, 6 to 13 days). KS was restricted to the skin in 7 cases, among which, one presented with associated Hodgkin lymphoma. Visceral involvement (one lung and one colon) was observed in two cases. One patient presented with a gastric KS without skin lesions. Immunosuppressive treatment was reduced, then withdrawn in three cases, resulting in regression of KS a few weeks later, but with graft loss requiring hemodialysis at 1, 3 and 4 months. Among the remaining 7 cases, we stopped mycophenalate mofetil (MMF) and switched from calcineurin inhibitors to sirolimus. Allograft function remained stable after the switch. Only one patient who already had allograft dysfunction due to biopsy-proven chronic allograft nephropathy. Deteriorated progressively, undergoing hemodialysis at 2 years after KS diagnosis. In conclusion, we observed a relatively high incidence of KS among our cases. The introduction of sirolimus resulted in complete regression of KS lesions with preserved graft function.

Manifestations cutanées chez les hémodialysés chroniques: Étude prospective de 363 cas

Resume Objectif Les manifestations cutanees chez les hemodialyses chroniques sont frequentes et variees. Leur pathogenie est souvent hypothetique. Le but de ce travail est d’evaluer la prevalence et la nature de ces lesions cutanees et de discuter certains mecanismes pathogeniques. Methodes Cette etude prospective a ete realisee du 1erfevrier au 30 avril 1996. Elle a interesse 363 patients hemodialyses dans 7 centres. Chaque patient a eu un interrogatoire et un examen dermatologique. Resultats Il y avait 210 hommes et 153 femmes. L’âge moyen etait de 50,6 ans. La duree totale de l’hemodialyse a varie de 1 a 192 mois avec une moyenne de 52,4 mois. Quatre-vingt huit pour cent des patients etudies avaient des manifestations cutanees et 44,9 % un prurit. Il est apparu apres le debut de l’hemodialyse chez 82,1 % d’entre eux. La xerose cutanee a ete trouvee chez 69 % des patients. Les alterations de la pigmentation cutanee ont ete observees dans 17 % des cas, representees essentiellement par une hyperpigmentation des zones photoexposees. Chez 6 patients, un blondissement de la peau, des cheveux et des phaneres est survenu 10 mois a 8 ans apres le debut de l’hemodialyse. L’hyperkeratose folliculaire a ete constatee chez 15 % des patients. Une seule patiente avait une pseudomaladie de Kyrle confirmee. Les troubles des phaneres representes essentiellement par les ongles amincis et les hemorragies sous-ungueales ont ete notes dans 18,5 % des cas. Les autres manifestations cutanees ont ete les petechies ou les ecchymoses (66 %), les infections cutanees a type de folliculite (9 %), les calcifications sous-cutanees (2 cas), une pseudoporphyrie cutanee (2 cas), un eczema en regard de la fistule (11,5 %) du essentiellement aux produits appliques localement. Conclusion Les manifestations cutanees chez les hemodialyses chroniques sont frequentes et polymorphes. Si la plupart sont connues de longue date, certaines, en particulier le blondissement, sont de connaissance plus recente. Leur pathogenie est le plus souvent mal elucidee. Le traitement est souvent symptomatique. La dialyse et la greffe renale constituent le meilleur traitement. Voir aussi dans ce numero l’editorial de Gerard Guillet, Les signes cutanes chez les hemodialyses: des marqueurs predictifs de morbidite ou de mortalite?.p 377-8.OBJECTIVE Chronic hemodialysis patients experience frequent and varied cutaneous manifestations, of often hypothetical pathogenesis. The aim of this work is to assess the prevalence and nature of these cutaneous lesions and discuss some pathogenic mechanisms. METHODS This prospective study was conducted from 1 February through 30 April 1996. It included 363 hemodialysis patients in seven centers. Each patient was interviewed and examined. RESULTS There were 210 men and 153 women. Their mean age was 50.6 years. The total duration of hemodialysis ranged from 1 to 192 months, with a mean of 52.4 months. 88% of the patients had cutaneous manifestations. Pruritus was reported by 44.8%. It appeared after hemodialysis began for 82.1% of them. Cutaneous xerosis was observed in 69%. Changes in pigmentation were observed in 17% of cases, primarily involving hyperpigmentation of photo-exposed areas. In 6 patients, skin, hair, and exoskeleton began to turn lighter 10 months to 8 years after hemodialysis. Follicular hyperkeratosis was observed in 15%. One patient had a confirmed case of perforating follicular dermatosis. Disorders of the exoskeleton (18.5% of cases) were represented mainly by thin nails and subungual hemorrhages. Other cutaneous manifestations included petechiae and ecchymoses (66%), folliculitis-type infections (9%), subcutaneous calcifications (2 cases), cutaneous pseudoporphyria (2 cases), and eczema around the fistula (11.5%), due essentially to locally-applied products. CONCLUSION Cutaneous manifestations in chronic hemodialysis patients are frequent and polymorphous. While most have long been known, lightening of skin, in particular, others have been discovered more recently. Their pathogenesis is most often poorly elucidated. Treatment is often symptomatic. Dialysis and renal transplantation constitute the best treatment.

Clinical significance of antinucleosome antibodies in Tunisian systemic lupus erythematosus patients

The aim of this study was to investigate the clinical significance of antinucleosome antibodies in Tunisian systemic lupus erythematosus (SLE) patients. IgG antinucleosome antibodies were detected by a qualitative enzyme immunoassay (immunodot) in the sera of SLE patients at onset of disease. The patients were divided into two groups according to the result of the antinucleosome antibodies test: positive (group A) and negative (group B). The two groups were also evaluated for clinical and biological parameters. Of 84 patients with SLE, 66 (78.6%) had antinucleosome antibodies. Among 21 patients negative for anti-double-stranded DNA (anti-dsDNA), 5 (23.8%) were antinucleosome positive. The most common initial features were haematological disorders (80.1%) and arthritis or arthralgias (79.8%). Renal disorders, observed in 59.5% of SLE patients, were more common in group A compared to group B (65 vs 38%) (p=0.04). The European Consensus Lupus Activity Measurement (ECLAM) mean score was higher in group A (6.42) than in group B (4.44) (p=0.002). Antinucleosome antibodies were positive in nearly one-fourth of SLE patients negative for anti-dsDNA. We found a correlation between antinucleosome antibodies, nephritis and SLE disease activity. Therefore, the determination of circulating antinucleosome antibodies could be a useful parameter for early diagnosis and follow-up of SLE patients.

Renal α‐smooth muscle actin: A new prognostic factor for lupus nephritis

Aim:  Systemic lupus erythematosus (SLE) is the prototype of autoimmune disease where renal involvement is frequent and always severe. Histological prognostic factors proposed for lupus nephritis (LN) including the World Health Organization and International Society of Nephrology/Renal Pathology Society – Working Group on the Classification classifications, active (AI) and chronicity (CI) indices may not predict response to treatment. The aim of this study was to correlate α‐smooth muscle actin (α‐SMA) expression, an early marker of glomerular and interstitial response to injury, to AI and CI, renal scarring progression and response to treatment.

Association purpura rhumatoïde de l'adulte et carcinome épidermoïde du poumon

INTRODUCTION Association between Schönlein-Henoch purpura and neoplasm can suggest the responsibility of tumour antigens in the genesis of the vasculitis. We report a new case of squamous cell carcinoma associated with Schönlein-Henoch purpura and we discuss the reality of this association. CASE REPORT We report the case of a 50-year-old man who presents Schönlein-Henoch purpura with a purpura of lower limbs, joint involvement, gastrointestinal lesions and IgA renal mesangial deposits. The patient received three intravenous methylprednisolone pulses followed with oral corticosteroids. Six months later, while the vasculitis was in remission, the patient presented a squamous cell lung carcinoma. He was treated by chemotherapy and local radiotherapy. At the late follow-up, the neoplasm was incompletely resolved. CONCLUSION The neoplasm could be responsible of the development of the Schönlein-Henoch purpura. The discovery of this systemic vasculitis in an elderly patient should warrant a deep screening for an occult neoplasm.

Secondary oxalosis due to excess vitamin C intake: a cause of graft loss in a renal transplant recipient.

Renal oxalate deposition can be seen with primary hyperoxaluria, malabsorptive states, ethylene glycol toxicity and, rarely, with excessive vitamin C ingestion. We report a case of secondary hyperoxaluria in which the diagnosis was not considered initially because there was no past history of urinary calculi and no evidence of nephrocalcinosis on plain X-ray of the abdomen and ultrasonography. The disease was detected and diagnosed only after kidney transplantation. Secondary oxalosis can cause graft loss or delayed graft function. Biopsy of the allograft should be carefully examined for oxalate deposits even in the absence of a family history. When oxalosis is diagnosed, intensifying hemodialysis (HD) to eliminate calcium oxalate can help in the recovery of renal function in some cases. Systematic vitamin C supplementation in HD patients should be avoided as it can be a cause of secondary oxalosis.

Short- and long-term outcomes of kidney donors: A report from Tunisia

Kidney transplantation remains the best treatment option of end-stage renal disease. Kidney donations are of particular interest with the currently increasing practice of living-donor transplantation. The purpose of this study was to analyze retrospectively the general health status as well as renal and cardiovascular consequences of living-related kidney donation. A total of 549 living-related kidney donors had donated their kidneys between 1986 and 2007. We attempted to contact all donors to determine short- and long-term outcome following kidney donation. All kidney donors who responded underwent detailed clinical and biochemical evaluation. The data were compared with age-matched health tables of the Tunisian general population. In all, 284 donors (52%) had a complete evaluation. They included 117 men and 167 women with a mean age of 42 ± 12 years. The major peri-operative complications that occurred in these donors included four cases of pneumothorax, six cases of surgical site infection, one case of phlebitis and one case of pulmonary embolism. None of the study cases died. The median length of hospital stay after donor nephrectomy was 6.5 days (range: 3-28 days). The median follow-up period was eight years. The mean creatinine clearance after donation was 90.4 ± 25 mL/min in men and 81.5 ± 27.2 mL/min in women. Proteinuria was >300 mg/24 h in 17 cases (5.9%). Fifty-eight (20.4%) donors became hypertensive and 19.6% of the men and 37.2% of the women became obese. Diabetes mellitus developed in 24 (8.4%), and was more common in patients who had significant weight gain. Our study suggests that kidney donors have minimal adverse effects on overall health status. Regular follow-up identifies at-risk populations and potentially modifiable factors. Creation of a national registry of living donors and their monitoring are an absolute necessity.

Hypopigmentation in hemodialysis : acquired hair and skin fairness in a uremic patient undergoing maintenance hemodialysis : case report and review of the literature

With recent advances in medicine, uremic patients are living longer with an improving quality of life. Several skin diseases have been reported in patients with chronic renal failure, and the opportunity has been offered to elucidate newer cutaneous abnormalities among patients undergoing long-term hemodialysis. Hyperpigmentation was the most prevalent cutaneous abnormality observed in these patients, but hypopigmentation remains an exceptional event. We report here a case of a maintenance hemodialysis patient with an acquired hair and skin fairness. Although the true mechanism involved in this entity remains obscure, it can be correlated with a disturbance of phenylalanine metabolism on the basis of the current knowledge.