Cystic kidney diseases in children.

Cystic kidney disease comprises a broad group of heterogeneous diseases, which differ greatly in age at onset, disease manifestation, systemic involvement, disease progression, and long-term prognosis. As our understanding of these diseases continues to evolve and new treatment strategies continue to emerge, correctly differentiating and diagnosing these diseases becomes increasingly important. In this review, we aim to highlight the key features of the most relevant cystic kidney diseases, underscore important diagnostic characteristics of each disease, and present specific management options if applicable.

Iatrogenic Cushing syndrome in a child due to erroneous compounding of omeprazole containing glucocorticoid: A case report and literature review.

A 3-month-old infant was examined for inconsolable crying with polydipsia, polyuria, and rapid weight gain. Unexpectedly, the symptoms resolved spontaneously during hospitalization but were aggravated 2 weeks after discharge, with the patient presenting a Cushingoid appearance. Investigations ruled out diabetes mellitus and nephrogenic diabetes insipidus but indicated adrenocortical suppression by exogenous glucocorticoids, which were discovered via toxicologic analysis of her previously compounded omeprazole suspension. After discontinuing the omeprazole suspension, the infant recovered fully and the laboratory results normalized. This case shows us that the assumption of appropriate medication intake may conceal unexpected medication errors. Following this case, the current literature on the benefits and risks of compounding and its impact on patient health is discussed.

[Autosomal dominant polycystic kidney disease : a pediatric perspective]. / Polykystose rénale autosomique dominante : perspective pédiatrique.

Polycystic kidney disease (PKD) is the most prevalent inherited kidney disease. The disease is usually asymptomatic until adulthood. End-stage renal disease occurs generally after the age of 55 years, with a large inter-individual variability. Renal cyst formation begins early in life, and animal models have shown that treatments able to prevent the cyst growth slow down the renal function decline. A treatment by tolvaptan is currently used in adults to decelerate PKD progression. Until now there is no consensus about the appropriate time to screen for PKD in children. However, these scientific progresses raise the interest of determining early (i.e. pediatric) predictive markers of renal function decline.

La polykystose rénale autosomique dominante (PRAD) est la maladie rénale génétique la plus fréquente. Le développement insidieusement progressif des kystes rénaux fait que la PRAD est, le plus souvent, asymptomatique jusqu'à l'âge adulte, mais la croissance kystique survient très précocement. L'insuffisance rénale terminale survient, généralement, après l'âge de 55 ans, avec, cependant, une grande variabilité interindividuelle. Les modèles animaux montrent que les traitements ralentissant la croissance du volume rénal freinent parallèlement le déclin de la fonction rénale. Par ailleurs, un traitement récemment utilisé chez l'adulte (le tolvaptan) permet de ralentir la progression de la PRAD. A ce jour, il n'y a pas de consensus sur l'âge de dépistage de la PRAD chez les enfants. Toutefois, les récentes avancées scientifiques suggèrent l'intérêt de déterminer des marqueurs prédictifs précoces, y compris pédiatriques, du déclin de la fonction rénale.

Polycystins and cellular Ca2+ signaling.

The cystic phenotype in autosomal dominant polycystic kidney disease is characterized by a profound dysfunction of many cellular signaling patterns, ultimately leading to an increase in both cell proliferation and apoptotic cell death. Disturbance of normal cellular Ca(2+) signaling seems to be a primary event and is clearly involved in many pathways that may lead to both types of cellular responses. In this review, we summarize the current knowledge about the molecular and functional interactions between polycystins and multiple components of the cellular Ca(2+)-signaling machinery. In addition, we discuss the relevant downstream responses of the changed Ca(2+) signaling that ultimately lead to increased proliferation and increased apoptosis as observed in many cystic cell types.

Polycystin-1 and polycystin-2 are both required to amplify inositol-trisphosphate-induced Ca2+ release.

Autosomal dominant polycystic kidney disease is caused by loss-of-function mutations in the PKD1 or PKD2 genes encoding respectively polycystin-1 and polycystin-2. Polycystin-2 stimulates the inositol trisphosphate (IP(3)) receptor (IP(3)R), a Ca(2+)-release channel in the endoplasmic reticulum (ER). The effect of ER-located polycystin-1 is less clear. Polycystin-1 has been reported both to stimulate and to inhibit the IP(3)R. We now studied the effect of polycystin-1 and of polycystin-2 on the IP(3)R activity under conditions where the cytosolic Ca(2+) concentration was kept constant and the reuptake of released Ca(2+) was prevented. We also studied the interdependence of the interaction of polycystin-1 and polycystin-2 with the IP(3)R. The experiments were done in conditionally immortalized human proximal-tubule epithelial cells in which one or both polycystins were knocked down using lentiviral vectors containing miRNA-based short hairpins. The Ca(2+) release was induced in plasma membrane-permeabilized cells by various IP(3) concentrations at a fixed Ca(2+) concentration under unidirectional (45)Ca(2+)-efflux conditions. We now report that knock down of polycystin-1 or of polycystin-2 inhibited the IP(3)-induced Ca(2+) release. The simultaneous presence of the two polycystins was required to fully amplify the IP(3)-induced Ca(2+) release, since the presence of polycystin-1 alone or of polycystin-2 alone did not result in an increased Ca(2+) release. These novel findings indicate that ER-located polycystin-1 and polycystin-2 operate as a functional complex. They are compatible with the view that loss-of-function mutations in PKD1 and in PKD2 both cause autosomal dominant polycystic kidney disease.

Survey of first-year medical students to assess their knowledge and attitudes toward organ transplantation and donation.

BACKGROUND: The important shortage of organ donors is still a fundamental public health problem in France. Improving the knowledge and attitudes of health care professionals could help to promote organ donation. The aim of this survey was to evaluate the level of knowledge of medical students and their gaps about organ donation prior to any medical course. MATERIALS AND METHODS: A survey was conducted among 571 first-year medical students at a medical faculty in Lyon. Their knowledge, attitudes, personal views, and perceptions toward organ donation and transplantation were investigated prior to any medical course. A 31-item anonymous questionnaire including queries about personal views of organ donation, factual knowledge, and awareness of French law was distributed to the students. RESULTS: To "willingness to donate a kidney to a relative," 97.7% of respondents consented, 0.9% objected, and 1.4% did not answer. Their attitudes toward cadaveric organ donation were different: 81.1% agreed, 13.5% refused, and 5.4% did not answer. Regarding their knowledge about which organs could be transplanted, 95% of the respondents were aware of the possibility to transplant a face and 14% thought that xenotransplantation was performed nowadays. CONCLUSIONS: First-year medical students have a good knowledge level regarding the organ donation and transplantation system prior to their medical course. Some gaps remain which could be improved. The results of this study supported a greater emphasis on providing information regarding transplantation in medical schools to improve the knowledge of future health care professionals. A follow-up survey of the participants at the end of their medical course will be interesting to assess the progress of their attitudes.