Mutations in MAPKBP1 Cause Juvenile or Late-Onset Cilia-Independent Nephronophthisis.

Nephronophthisis (NPH), an autosomal-recessive tubulointerstitial nephritis, is the most common cause of hereditary end-stage renal disease in the first three decades of life. Since most NPH gene products (NPHP) function at the primary cilium, NPH is classified as a ciliopathy. We identified mutations in a candidate gene in eight individuals from five families presenting late-onset NPH with massive renal fibrosis. This gene encodes MAPKBP1, a poorly characterized scaffolding protein for JNK signaling. Immunofluorescence analyses showed that MAPKBP1 is not present at the primary cilium and that fibroblasts from affected individuals did not display ciliogenesis defects, indicating that MAPKBP1 may represent a new family of NPHP not involved in cilia-associated functions. Instead, MAPKBP1 is recruited to mitotic spindle poles (MSPs) during the early phases of mitosis where it colocalizes with its paralog WDR62, which plays a key role at MSP. Detected mutations compromise recruitment of MAPKBP1 to the MSP and/or its interaction with JNK2 or WDR62. Additionally, we show increased DNA damage response signaling in fibroblasts from affected individuals and upon knockdown of Mapkbp1 in murine cell lines, a phenotype previously associated with NPH. In conclusion, we identified mutations in MAPKBP1 as a genetic cause of juvenile or late-onset and cilia-independent NPH.

Treatment tolerance and patient-reported outcomes favor online hemodiafiltration compared to high-flux hemodialysis in the elderly.

Large cohort studies suggest that high convective volumes associated with online hemodiafiltration may reduce the risk of mortality/morbidity compared to optimal high-flux hemodialysis. By contrast, intradialytic tolerance is not well studied. The aim of the FRENCHIE (French Convective versus Hemodialysis in Elderly) study was to compare high-flux hemodialysis and online hemodiafiltration in terms of intradialytic tolerance. In this prospective, open-label randomized controlled trial, 381 elderly chronic hemodialysis patients (over age 65) were randomly assigned in a one-to-one ratio to either high-flux hemodialysis or online hemodiafiltration. The primary outcome was intradialytic tolerance (day 30-day 120). Secondary outcomes included health-related quality of life, cardiovascular risk biomarkers, morbidity, and mortality. During the observational period for intradialytic tolerance, 85% and 84% of patients in high-flux hemodialysis and online hemodiafiltration arms, respectively, experienced at least one adverse event without significant difference between groups. As exploratory analysis, intradialytic tolerance was also studied, considering the sessions as a statistical unit according to treatment actually received. Over a total of 11,981 sessions, 2,935 were complicated by the occurrence of at least one adverse event, with a significantly lower occurrence in online hemodiafiltration with fewer episodes of intradialytic symptomatic hypotension and muscle cramps. By contrast, health-related quality of life, morbidity, and mortality were not different in both groups. An improvement in the control of metabolic bone disease biomarkers and ß2-microglobulin level without change in serum albumin concentration was observed with online hemodiafiltration. Thus, overall outcomes favor online hemodiafiltration over high-flux hemodialysis in the elderly.

Two Years' Experience of Intensive Home Hemodialysis with the Physidia S3 System: Results from the RECAP Study.

The RECAP study reports results and outcomes (clinical performances, patient acceptance, cardiac outcomes, and technical survival) achieved with the S3 system used as an intensive home hemodialysis (HHD) platform over a three-year French multicenter study. Ninety-four dialysis patients issued from ten dialysis centers and treated more than 6 months (mean follow-up: 24 months) with S3 were included. A two-hour treatment time was maintained in 2/3 of patients to deliver 25 L of dialysis fluid, while 1/3 required up to 3 h to achieve 30 L. The additional convection volume produced by means of the SeCoHD tool (internal filtration backfiltration) was 3 L/session, and the net ultrafiltration produced to achieve dry weight was 1.4 L/session. On a weekly basis, an average 156 L of dialysate corresponding to 94 L of urea clearance when considering 85% dialysate saturation under low flow conditions was delivered. Such urea clearance was equivalent to 9.2 [8.0-13.0] mL/min weekly urea clearance and a standardized Kt/V of 2.5 [1.1-4.5]. The predialysis concentration of selected uremic markers remained remarkably stable over time. Fluid volume status and blood pressure were adequately controlled by means of a relatively low ultrafiltration rate (7.9 mL/h/kg). Technical survival on S3 was 72% and 58% at 1 and 2 years, respectively. The S3 system was easily handled and kept by patients at home, as indicated by technical survival. Patient perception was improved, while treatment burden was reduced. Cardiac features (assessed in a subset of patients) tended to improve over time. Intensive hemodialysis relying on the S3 system offers a very appealing option for home treatment with quite satisfactory results, as shown in the RECAP study throughout a two-year follow-up time, and offers the best bridging solution to kidney transplantation.

Safety and Efficacy of Short Daily Hemodialysis with Physidia S3 System: Clinical Performance Assessment during the Training Period.

BACKGROUND: A growing body of scientific evidence indicates that clinical outcomes of hemodialysis patients can be improved with short daily dialysis treatment. Current in-center hemodialysis machines do not fulfill the requirements needed for self-care home hemodialysis (HHD) treatment. In line with the reviviscence of home therapy, several hemodialysis devices have been developed and deployed for treatment. Physidia S3 is one of these new dialysis delivery systems featuring an appealing design and functionalities intended for daily HHD treatment. METHODS: In this French multicenter proof-of-concept study enrolling 13 training centers, we report our preliminary experience with a special focus on quantifying clinical performances in short daily HHD treatment performed during the training period of the patients. RESULTS: Among the 80 patients included in this study, a total of 249 sessions could be analyzed. Dialysis dose, estimated from weekly standardized Kt/V, was maintained at 2.22 [1.95-2.61] with a normalized protein catabolic rate of 0.93 [0.73-1.18] g/kg/24 h. Furthermore, anemia and nutritional status were adequately controlled as indicated by 11.6 ± 1.4 g/dL of hemoglobin level and 39.4 ± 5.7 g/L of serum albumin as well as electrolyte disorders. CONCLUSIONS: The safety and efficacy of the S3 therapy concept relying on a short daily hemodialysis treatment using a bagged delivery system are in total agreement with daily HHD recommendations. Clinical performances are aligned to the metabolic needs of the vast majority of HHD patients. Currently ongoing studies at home will provide further evidence and value of this therapeutic approach.

[Acute kidney injury in thromboangiitis obliterans disease]. / Ischémie rénale bilatérale par thrombis de la micro-circulation rénale dans le cadre d'une maladie de Buerger.

Buerger's disease or thombo-angiitis obliterans disease is a small vessel's vasculitis, frequently observed in young and smoker's males. Diagnosis is based on both clinical and radiological arguments. There is no specific treatment designed for this disease. We report the case of 43 years old patient presenting with an acute kidney injury associated with Buerger's disease. We reviewed the different case of kidney disease in this rare disease.

Course of chronic kidney disease in French patients.

BACKGROUND: In 1998, a French survey showed that the referral of patients with chronic kidney disease to a nephrologist was delayed, resulting in many emergency initiations of dialysis. In 2009, the ORACLE study aimed to describe the renal course of dialysis patients from their first nephrology visit to their first dialysis session. METHODS: The ORACLE study was a multicentre retrospective study of all patients who started chronic dialysis. Data were collected at the first nephrology visit and at the first dialysis session. RESULTS: In total, 720 patients were included (69 centres). At the first nephrology visit, the mean Cockcroft-Gault (CG) indicator was 31.8 mL/min (22.7 in 1998) and 52.4% of patients (73% in 1998) had a CG <30. The mean time between the first nephrology visit and the first dialysis session was 48 months (35 months in 1998). CONCLUSION: In 2009, most patients were referred a long time before dialysis initiation, which likely allowed them to benefit from the impact of nephrology care on early outcomes when on dialysis. However, 34.2% of the dialysis sessions were still initiated under emergency conditions.