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.

[Post-infectious glomerulonephritis: unusual etiology of postpartum acute renal failure]. / La glomérulonéphrite aiguë postinfectieuse : une cause inhabituelle d'insuffisance rénale aiguë du post-partum.

Severe pre-eclampsia and acute tubular necrosis due to hemorrhagic shock are the major causes of postpartum acute renal failure. Cortical necrosis and haemolytic uraemic syndrome are less frequently. Post-infectious glomerulonephritis as a cause of postpartum acute glomerular disease and renal failure has been rarely reported. We report a patient with postpartum acute glomerulonephritis who presented nephritic syndrome, the diagnosis of which was confirmed by renal biopsy.

Brown tumors in dialyzed patients with secondary hyperparathyroidism: report of 16 cases.

Brown tumors (BTs) are relatively uncommon but they are serious complications of renal osteodystrophy. The objective of this study was to analyze the clinical, biological, and radiological characteristics of 16 patients with BTs provoked by secondary hyperparathyroidism (sHPT) and its response to the decrease in parathyroid hormone levels after parathyroidectomy (PTX). The management of that uncommon condition was also reviewed. We conducted a retrospective study including 16 end-stage renal disease patients who underwent subtotal PTX between 1997 and 2007 for severe sHPT with BTs. Our study included 10 men and 6 women, whose average age was 34 years. All patients were on dialysis. Ten of them were on dialysis for more than 5 years. The median duration on dialysis was 84 months. Patients included suffered from swellings associated with functional limitations. BTs had multiple locations in 7 patients. Jaw was the most frequent location (62%). Radiography and tomodensitometry demonstrated a mixed radio lucent and radio-opaque lesions with an expansion of the cortical bone. Bone scan demonstrated an increased uptake of lesions. Chirurgical treatment was indicated in all cases because of severe refractory sHPT with functional limitations and/or disfiguring deformities. In all cases, BTs stopped its progression and even decreased in size. However, it was insufficient in four cases, which required a surgical resection. PTX remains an efficacious approach in resistant cases of sHPT with persistent BTs.

[Surgical treatment of secondary hyperparathyroidism in patients with chronic renal failure]. / Traitement chirurgical de l'hyperparathyroïdie secondaire chez l'insuffisant rénal chronique.

OBJECTIVE: To identify the indications for subtotal parathyroidectomy (PTX) in secondary hyperparathyroidism (SHPT) and report postoperative, early and late complications of PTX. PATIENTS AND METHODS: We conducted a retrospective study of subjects with chronic renal failure operated in Tunisian hospitals who received subtotal PTX over 10 years from January 1997 to December 2007. We analyzed the clinical, biological and radiological parameters pre- and postoperatively. RESULTS: We included 70 patients with average age of 39.4 years, 55.7% men and 44.3% in dialysis for 7.75 ± 4.8 years before PTX. The initial nephropathy was interstitial in 50% of cases. No cases of diabetic nephropathy have been reported. The clinical signs were bone pain (88.6%), muscle pain (85.6%), pruritus (81.4%). Radiological signs of osteitis fibrosa were observed in the majority of patients mainly resorption of extremities (92.9%), thinning of cortical (85.7%) and osteosclerosis (87.1%). The most common indication of PTX (85.7% of cases) was the persistence of serum PTH of more than 800 pg/ml associated with hypercalcemia and/or hyperphosphatemia refractory to medical treatment. A subtotal PTX (3/4 or 7/8) was performed after ultrasound and scintigraphy in the majority of cases. The histology of the parathyroid glands showed diffuse hyperplasia (51.4%), nodular hyperplasia (45.7%) and adenoma (2.8%). The postoperative evolution was marked by an improvement of the clinical and radiological criteria in 80% of cases. A PTH level of less than 15 pg/ml was rarely observed (10% of cases), and a PTH level of more than 300 pg/ml concerned 13% of patients. We noted a low morbidity and mortality (no cases laryngeal paralysis or cervical hematoma). CONCLUSION: Surgical treatment of SHPT in Tunisia is very effective in our experience. The biological results are comparable to treatment with calcimimetics, not available in Tunisia and whose price is higher. An early treatment of disorders of bone and mineral metabolism should reduce the incidence of SHPT.

[Acute renal failure and fungus ball: A case report]. / Insuffisance rénale aiguë et obstacle mycélien : à propos d'un cas.

Fungus ball is rarely associated with acute renal failure (ARF). We report the case of a 65-year-old diabetic patient who has been admitted for a right kidney infection. Urinary exam showed a leucocyturia with a negative urine culture. Ultrasonography showed pelvicaliceal dilation. Nephroscopy revealed a fungal material in ureter. Culture of this material was positive for Candida tropicalis. After endoscopic and antifongic therapy, the serum creatinin decreased from 336 micromol/L to 150 micromol/L, indicating the good evolution of his renal function.

[Haemodialysis and its impact on the quality of life]. / L'hémodialyse et son impact sur la qualité de vie.

The haemodialysis has considerably transformed the evolution of chronic renal failure which usually has a precarious evolution. However, this palliative treatment disturbed in several manners the universe of the patient. Our purposes were to evaluate the quality of life of patient on haemodialysis and to identify the risk factors that can deteriorate it. Our work was a transversal study realized in four centers of haemodialysis during a period of three months (2004). One hundred and sixty-two patients participated. The quality of life was assessed with a specific scale Kidney Disease Quality of Life Short-Form (KDQDL-SF). A standardization of the initial average scores of SF-36 was realized. The global average score, according to KDQOL-SF, was 55,2. The standardization showed a physical component more alterated than the mental one with respective scores 36,8 and 44,7. The logistic regression permitted us to identify that the quality of life's alteration was correlated with an absent autonomy, a diabetic origin of renal insufficiency, a predialytic serum creatine concentration inferior to 800micromol/l and haemodialysis demographic social features. This clinimetric approach not only precises the more deteriorated sectors through the regard of patient, but also reintroduces its point of view about the treatment permitting a personalization of therapies and consequently a better adhesion.

[Twin pregnancy after renal transplantation: first case reported in Tunisia]. / La grossesse gemellaire et la transplantation renale a propos d'une premiere observation Tunisienne.

Women with end-stage renal disease or on regular dialysis have low fertility. Renal transplantation restores not only normal renal and endocrine functions but also the reproductive function as well and this conception becomes possible. Pregnancy in transplanted women is at higher risk and necessitates a multidisciplinary follow up. We report the course and out come of two successful pregnancies, the second was the first case of twin pregnancy in Tunisia in a transplanted woman. Our patient is 35 years old had a chronic renal insufficiency, secondary to interstitial nephropathy. After six years of hemodialysis, she had received a renal graft from a living donor (his brother). A double drug immunosuppression was given (Prednisolone - Azathioprine). Two years later, she became pregnant and delivered a normal baby at term, and one year later she had a twin pregnancy that ended successfully and delivered by caesarian section a two babies with different sex. Pregnancy after renal transplantion must be considered as a risk factor for any subsquent pregnancy, and the risk nicreases in case of twin pregnancy.