Monoallelic Loss-of-Function IFT140 Pathogenic Variants Cause Autosomal Dominant Polycystic Kidney Disease: A Confirmatory Study With Suspicion of an Additional Cardiac Phenotype.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. While biallelic variants affecting IFT140 are responsible for Mainzer-Saldino syndrome (characterized by severe ciliopathy causing skeletal abnormalities, kidney disease, and cysts), monoallelic loss-of-function (LoF) variants have been recently reported as an important cause of ADPKD beyond PKD1/2 genes. Herein, we report 6 non-family-related cases of monoallelic IFT140 LoF variants, identified from 1,340 exomes sequenced for nephrological indications in our local database. Every patient presented with polycystic kidney disease. Furthermore, the mother of a boy diagnosed with Mainzer-Saldino syndrome with a biallelic variant affecting IFT140 presented with several bilateral cysts, revealed after kidney imaging, and was found to carry a pathologic frameshift IFT140 variation. As well as this particular Mainzer-Saldino case, our 6 additional patients confirm that heterozygous IFT140 frameshift variants are responsible for the cystic phenotype and kidney failure. Interestingly, of the 6 patients, 2 also exhibited dilated cardiomyopathy, which was of unknown origin, as no genetic cause was found after exome sequencing analysis, suggesting a potential connection between IFT140 and heart disease.

Influence on quality of life from an early cinacalcet prescription for secondary hyperparathyroidism in dialysis.

OBJECTIVE: The goal of this study is to compare patient-reported quality of life (PRQOL) evolution between two groups of end-stage renal disease patients with secondary hyperparathyroidism (SHPT). The first with a cinacalcet prescription within 3 months after a diagnosis of SHPT (early group) and a second group of patients with a later or no cinacalcet prescription (nonearly group). PATIENTS AND METHODS: From 2009 to 2012, we conducted a multicenter pharmaco-epidemiologic study in Lorraine region (France) including all consecutive patients on maintenance dialysis for at least 3 months with a diagnosis of SHPT (PTH > 500 pg/ml or first cinacalcet prescription). PRQOL was estimated using the Kidney Disease Quality Of Life-Short Form questionnaire, at baseline and at 6 and 12 months follow-up. Change in PRQOL was compared between the groups and adjusted with a propensity score. RESULTS: We included 124 patients: 44 in the early group and 80 in the nonearly group. The mental component summary score was lower in the early group, at baseline (43.6 ± 6.6 vs 46.6 ± 7.6; p = 0.030), and at the follow-up assessment (42.6 ± 6.9 vs 45.7 ± 7.9; p = 0.033). We found no difference between the groups in change in PRQOL, for all dimensions, even after adjustment with the propensity score. Mean serum alkaline phosphatase levels were normal in both groups at baseline (80.9 ± 32.5 vs 95.1 ± 39.6; p = 0.41). CONCLUSION: Cinacalcet prescription immediately following diagnosis of SHPT does not seem to be associated with better PRQOL evolution at 1 year. Mean serum alkaline phosphatase levels suggest that physicians should consider waiting for another PTH assay result before starting cinacalcet in case of a PTH rise.

The Green Nephrology Group of the SFNDT: initial reflections / Groupe Néphrologie verte de la SFNDT : premières réflexions

Preserving the environment is becoming a universal priority. Human activities must be redesigned to best adapt them to available resources and to reduce their deleterious impact on the planet. The Green Nephrology Group of the "Société française de néphrologie, dialyse et transplantation" (SFNDT) has started a reflection on these issues, in particular on dialysis, a vital treatment but with high carbon production, associated with high water consumption. The data available on these points are presented such as, among others, the collection of indicators and action plans, the recycling of waste from water treatment, the reduction of dialysate flow, the reuse and regeneration of spent dialysate as well as calculations of carbon emission by dialysis activity. Architectural experiences are reported as well as the regulatory constraints applying to manufacturers and organizations in the sector. Potential solutions require the mobilization of all stakeholders, ranging from patients to health authorities, including caregivers, pharmacists, technicians, nephrologists and facility managers. They will be formalized very soon in a guide being prepared by the SFNDT Green Nephrology Group.

La préservation de l'environnement devient une priorité universelle. Les activités humaines doivent être repensées pour les adapter au mieux aux ressources disponibles et réduire leur impact délétère sur la planète. Le groupe Néphrologie verte de la Société francophone de néphrologie, dialyse et transplantation (SFNDT) a entamé une réflexion sur ces problématiques, en particulier sur la dialyse, traitement à caractère vital mais à production de carbone élevée, associée à une consommation d'eau importante. Les données disponibles sur ces points sont présentées comme, entre autres, le recueil d'indicateurs et les plans d'action, le recyclage du rejet du traitement d'eau, la réduction de débit du dialysat, la réutilisation et régénération du dialysat usé ainsi que les calculs d'émission de carbone par l'activité de dialyse. Les expériences architecturales sont rapportées de même que les contraintes réglementaires s'appliquant aux industriels et établissements du secteur. Les solutions potentielles nécessitent la mobilisation de tous les acteurs, allant des patients aux autorités de santé, en passant par les soignants, pharmaciens, techniciens, néphrologues et les directions d'établissement. Elles seront formalisées très prochainement dans un guide en cours de préparation par le groupe Néphrologie verte de la SFNDT.

[First case report of Streptococcus equi subsp. zooepidemicus post-infectious acute glomerulonephritis in France]. / Glomérulonéphrite aiguë post-infectieuse à Streptococcus equi subsp. zooepidemicus : premier cas décrit en France.

Post-infectious glomerulonephritis has become exceptional in France because streptococcus infections are well-treated. When they appear, clinical and biological symptoms are mostly typical and associate acute nephritic syndrome, acute renal failure, proteinuria, hematuria and low complement. We are reporting the first French case of acute post-infectious glomerulonephritis related to Streptococcus equi subsp. zooepidemicus, which is commonly found in horses and rarely in human pathology, and of which contamination is by direct contact with sick horses or by ingestion of non-pasteurized milk.

Trajectories of CKD-MBD biochemical parameters over a 2-year period following diagnosis of secondary hyperparathyroidism: a pharmacoepidemiological study.

OBJECTIVES: To define groups of patients according to the changes of biochemical parameters, that is, serum calcium, phosphate and parathyroid hormone (PTH), over a 2-year follow-up period using group-based multi-trajectory modeling (GBMM) among a cohort of dialysis patients with newly diagnosed secondary hyperparathyroidism (SHPT) (ie, PTH≥500 ng/L for the first time) and to compare their patient characteristics and treatments. DESIGN: Pharmacoepidemiological study. SETTING: In the 12 dialysis units located in the French region of Lorraine. PARTICIPANTS: A total of 269 dialysis patients with newly diagnosed SHPT were prospectively included from December 2009 to May 2012 and followed-up for 2 years. RESULTS: We identified four distinct trajectory groups: 'rapid PTH drop' experiencing a rapid and sharp decrease (over weeks) in PTH level associated with decreasing phosphate level within normal range (n=34; 12.7%), 'gradual PTH decrease' experiencing a gradual and continuous decrease (over months) in PTH level and maintaining phosphate at a middle level throughout the study (n=98; 36.4%), 'slow PTH decrease with high phosphate' experiencing a slow decrease in PTH level associated with a relatively high phosphate level (n=105; 39.0%) and 'uncontrolled SHPT' with high levels of PTH and phosphate throughout the study (n=32; 11.9%). Patients in the 'uncontrolled SHPT' group were significantly (p<0.00001) younger than patients in other groups. Kidney Disease Improving Global Outcomes (KDIGO) targets for PTH, phosphate and calcium were reached simultaneously for 14.9% of patients at baseline and 16.7% at the end of the study. Patients were given cinacalcet more frequently at months 3 and 6 in the 'rapid PTH drop' and at month 24 in the 'uncontrolled SHPT' groups. CONCLUSIONS: Over 2 years following a new SHPT diagnosis, a younger age and a higher rate of alkaline phosphatase were associated to a continuous uncontrolled SHPT. Patients with the lowest PTH at the end of the follow-up tended to receive more often cinacalcet. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT02888639, post results.

Minimal impact of calcimimetics on the management of hyperparathyroidism in chronic dialysis.

BACKGROUND: The calcimimetic drug cinacalcet has changed the prescription patterns in patients with secondary hyperparathyroidism, despite the lack of randomized studies that compare cinacalcet with conventional treatment, including parathyroidectomy. The aim of this study was to evaluate current management of patients on chronic dialysis with incidental and parathyroid hormone (PTH) levels ≥ 500 ng/L. METHODS: Prospective pharmacoepidemiologic study of chronic dialysis patients with PTH level ≥ 500 ng/L. RESULTS: We studied 269 patients. Among the 186 patients who had 2-year follow-up, 125 (67%) were managed using cinacalcet. At 2 years, when comparing the cinacalet with the noncinacalet groups, we found that mean PTH values were 400 ± 318 versus 388 ± 251 ng/L (P = ns) and the percentage of patients following 2009 PTH Kidney Disease Improving Global Outcomes (KDIGO) guidelines were 79 versus 85% (P = ns). Eight patients (4%) underwent parathyroidectomy. On multivariate analysis, the use of cinacalcet was not a predictor for PTH within KDIGO guidelines at 2-year follow-up. CONCLUSION: Cinacalcet was used in the majority (67%) of patients on chronic dialysis with secondary hyperparathyroidism, but the use of cinacalcet did not affect mean PTH values nor the proportion of patients following KDIGO guidelines compared with patients not using calcimimetics.