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.

Pregnancy in kidney transplanted women: what are the optimal conditions for a better pregnancy outcome?

BACKGROUND: Motherhood has long been not recommended for kidney transplanted women for fear of adverse effects on the graft and the risks to the fetus. AIMS: This article aimed to provide evidence based answer to the following questions regarding pregnancy in kidney transplanted women: 1. what are the nephrologic and obstetrical parameters that can influence the pregnancy outcome? 2. What is the impact of pregnancy on graft? 3. What are the optimal conditions for pregnancy planning in kidney transplanted women? METHODS: A literature search was conducted using as key words "pregnancy", "renal transplant", "renal graft survival" in the PubMed database over the period from January 1994 to December 2011. RESULTS: Recovery of renal function in kidney transplanted patients is followed by restoration of endocrine function. Knowledge of the initial nephropathy assesses the risk of recurrence after transplantation, which may affect the graft. Chronic glomerular nephropathies are the most frequent from 32 to 76.1%. Duration of hemodialysis (over 2 years) is associated with a risk of preterm delivery and growth retardation. A period of 1 year between renal transplantation and conception seems reasonable to stabilize renal function and reduce the doses of immunosuppressants. The number of unintended pregnancies remains high (50%). The incidence of pregnancy after renal transplantation varies between 3 and 21.2%. Graft survival in patients who carried a pregnancy is equivalent to that of patients who were not pregnant. CONCLUSIONS: Pregnancy in kidney transplanted patients is a highrisk pregnancy, but it does not seem to affect graft function through certain conditions.

Pre-emptive treatment of hepatitis B infection by lamivudine in two Tunisian renal transplant recipients.

Infection with hepatitis B virus has a major implication for transplant recipients due to the risk of reactivation under immunosuppression, progression to chronic liver disease, development of liver cirrhosis and hepatocellular carcinoma. We report two cases of renal transplantation patients who were hepatitis B surface antigen positive before transplantation and were treated by Lamivudine.

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.

Comparative study of perdialytic volemia variability in chronic dialysis patients between acetate- free biofiltration and bicarbonate hemodialysis.

We have developed since 1994 a new hemodialysis (HD) technique called acetate biofiltration 84% (AFB 84%) that is characterized by the absence of acetate in the dialysate and the complete correction of buffer balance by post- dilutional infusion of bicarbonate- based replacement solution. Our study aimed to compare the variability of perdialytic volemia [net ultrafiltration (UF) rate, total UF, Δweight (T4- T0)] during AFB 84% and bicarbonate dialysis (BD) for stable chronic hemodynamic patients. This was a prospective crossover study carried out on 14 patients for a total of 168 HD sessions (84 AFB 84% and 84 BD). Optical measurement of hemoglobin (Hb) concentration was incorporated into the dialysis monitor to allow the study of the relative blood volume. For both techniques, Hb measured by Hemoscan® correlated well with the laboratory measurements. Moreover, the comparison of the averages of the different indicators of the perdialytic volemia did not disclose any significant statistical differences. Nevertheless, the comparison of the variability of perdialytic volemia between both techniques showed less Δ volemia (T4- T0) during the AFB 84% than the BD (- 7.909% for BD and - 6.960% for ABF 84%, P = 0.0036). We conclude that the absence of acetate and maintaining an optimal osmolarity at the origin of a better plasma refilling rate are key factors that make AFB 84% a technique assuring a better perdialyitic hemodynamic tolerance in comparison with BD in chronic HD patients.

Visceral leishmaniasis in a renal transplant recipient treated with allopurinol.

Leishmaniasis is an infection caused by a protozoan parasite belonging to the genus Leishmania and transmitted by the Phlebotomus sandfly. We report a case of visceral leishmaniasis in a 49-year-old male renal transplant recipient, a resident of the western part of Tunisia, which is an endemic zone for the disease. Just before and after the transplantation, the patient resided in Tunis, which is non-endemic for leishmaniasis. Visceral leishmaniasis occurred eight years after renal transplantation, and the clinical picture was characterized by fever and pancytopenia. Leishmaniae were detected by bone marrow aspiration. Pentavalent antimonal was used for 28 days and was substituted by allopurinol (20 mg/kg per day). One year after the infection, the patient remains totally asymptomatic. Our report suggests that visceral leishmaniasis may complicate the clinical course of organ transplantation and can be fatal, particularly when untreated. Relapses may occur after completion of the apparently effective treatment. Allopurinol could be a solution to avoid these relapses.

Nephrotic syndrome and Guillan-Barré Syndrome: a rare association in child.

Only few cases of nephrotic syndrome associated with Guillain-Barre Syndrome (GBS) have been reported in the adult and pediatric literature. A 3-year-old boy was initially admitted to our hospital following five days of progressive weakness of his extremities, fatigue, right leg pain and numbness. There was no past history of renal or neurological disease. Cerebro-spinal fluid studies showed a protein level of 92 mg/dL and a white cell count of 1 per high-power field. The diagnosis of GBS was verified with a nerve conduction velocity test as well as. The GBS symptoms improved gradually on intravenous immunoglobulin. Three weeks later, he developed severe proteinuria and edema; laboratory investigation showed nephrotic syndrome which responded to steroid therapy. Renal biopsy showed minimal change glomerulonephritis. He remained free of proteinuria during his 20 months of follow-up.

Cancers after renal transplantation: multicenter experience.

Renal transplant recipients are at higher risk of certain tumors such as lymphomas and skin cancers and than the general and dialysis populations. We retrospectively studied the prevalence of tumors in adult renal transplant recipients in four Tunisian centers of transplantation in Tunis, Monsatir and Sfax from January 1986 to January 2005. The study included 36 patients; 19 men and 17 women with a mean age of 34.6 years (range from 18-54 years). The mean time since dialysis to transplantation was 43 months (6-131months). Maintenance therapy was based on calcineurin inhibitors (CNI) in 86 % of cases, on antimetabolites and corticosteroids in 100 % of cases. Anti-thymoglobulin was administered in a mean course of 12.4 days in 78 % of the patients. Acute rejection occurred in 25 cases and was treated with polyclonal or monoclonal antibodies on 40 % of cases. Incidence of cancer among our population was 7 % and occurred after a mean period of 54 months of transplantation (range from 4-160 months). Eighty three percent of the tumors were solid, and the rest were in the skin. Kaposi sarcoma formed 41.6 % and non-Hodgkin or Hodgkin lymphoma 27.7 % of the solid tumors, while spinocellular carcinoma formed 83% and basocellular carcinoma 17% of the skin tumors. Switching CNI to sirolimus in 8.3% cases was associated with a favorable outcome. Mortality was the outcome in 33.3% of the patients with cancer, while partial or complete regression of cancers was observed in 55.5% cases after decreasing the doses of the immunosuppressive medications. We conclude that post renal transplant cancer is mainly characterized by the predominance of Kaposi sarcoma favored by solar exposure and rigorously induced and maintained immunosuppression. Careful follow-up may results in early intervention and decrease mortality.

Variability of acid-base status in acetate-free biofiltration 84% versus bicarbonate dialysis.

The ultimate goal of hemodialysis (HD) treatment is to achieve the highest level of efficacy in the presence of maximal clinical tolerance. With an aim to offer good hemodynamic stability, as observed during the acetate-free biofiltration 14% (AFB 14%) to patients who are intolerant to bicarbonate dialysis (BD) and with less cost, we have developed since June 1994, a new HD technique, namely AFB 84%. This study was carried out to analyze acid-base variations during the AFB 84% in comparison to BD in hemodynamically stable patients on regular HD. This was a prospective randomized crossover study carried out on 12 patients (6 males and 6 females) for a total of 144 HD sessions (72 BD and 72 AFB 84%). Patients with decompensated cardiomyopathy, respiratory diseases or uncontrolled hypertension were not included in the trial. All the patients were treated with BD or AFB 84%; the latter is characterized by the absence of acetate in the dialysate and a complete correction of buffer balance by post-dilutional infusion of bicarbonate-based replacement solution. The comparison of pre-dialysis arterial acid-base and blood-gas parameters revealed no significant differences of pH, HCO(3)(-) and paCO(2) levels between the two techniques. Analysis of post-dialysis parameters showed that, among patients dialyzed with BD, there was over correction of metabolic acidosis with a tendency towards metabolic alkalosis. In contrast, in patients dialyzed with AFB 84%, we observed a significant improvement in pH and HCO(3)(-) levels but the increase in paCO(2) level was not significant. A comparison of these parameters between the two techniques showed statistically significant difference in pH, HCO(3)(-) and paCO(2) levels, but not for paO(2) level. AFB 84% can offer some important advantages with the complete absence of acetate from the substitution fluids, and permits a better correction of metabolic acidosis than BD, without causing alkalosis.

Acute renal failure due to lymphomatous infiltration: an unusual presentation.

Renal lymphoma occurs most often as a part of a multi-systemic disseminated lymphoma or as a recurrence of the tumor. Renal involvement usually occurs late in the course of the disease and is clinically silent. Acute renal failure (ARF) from lymphomatous infiltration has been described but is quite rare. We report a 50-year-old Caucasian woman, who presented with features of ARF. Physical examination showed that her arterial blood pressure was 190/100 mm Hg with no lymphadenopathy or hepatosplenomegaly. Her urine output was about 100 ml/day, and urinanalysis revealed + proteinuria and microscopic hematuria. Biochemical findings revealed severely impaired renal function with a serum creatinine of 693 micromol/L. The patient's lactate dehydrogenase was elevated at 632 U/L. An abdominal ultrasound showed bilateral, large non-obstructed kidneys and a hypoechoic mass arising in the right lobe of the liver. An ultrasound-guided percutaneous liver biopsy showed typical features of B-cell lymphoblastic lymphoma. The patient expired two days later, even before any specific treatment could be started.