Clinical relevance of membrane attack complex deposition in children with IgA nephropathy and Henoch-Schönlein purpura.

BACKGROUND: IgA nephropathy (IgAN) and Henoch-Schönlein purpura are common glomerular disorders in children sharing the same histopathologic pattern of IgA deposits within the mesangium, even if their physiopathology may be different. Repeated exposure to pathogens induces the production of abnormal IgA1. The immune complex deposition in the renal mesangium in IgAN or potentially in small vessels in Henoch-Schönlein purpura induces complement activation via the alternative and lectin pathways. Recent studies suggest that levels of membrane attack complex (MAC) in the urine might be a useful indicator of renal injury. Because of the emerging availability of therapies that selectively block complement activation, the aim of the present study is to investigate whether MAC immunostaining might be a useful marker of IgA-mediated renal injury. METHODS: We conducted immunohistochemistry analysis of the MAC on renal biopsies from 67 pediatric patients with IgAN and Henoch-Schönlein purpura. We classified their renal biopsies according to the Oxford classification, retrieved symptoms, biological parameters, treatment, and follow-up. RESULTS: We found MAC expression was significantly related to impaired renal function and patients whose clinical course required therapy. MAC deposits tend to be more abundant in patients with decreased glomerular filtration rate (p = 0.02), patients with proteinuria > 0.750 g/day/1.73 m2, and with nephrotic syndrome. No correlation with histological alterations was observed. CONCLUSIONS: We conclude that MAC deposition could be a useful additional indicator of renal injury in patients with IgAN and Henoch-Schönlein purpura, independent of other indicators.

INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy.

BACKGROUND: Charcot-Marie-Tooth neuropathy has been reported to be associated with renal diseases, mostly focal segmental glomerulosclerosis (FSGS). However, the common mechanisms underlying the neuropathy and FSGS remain unknown. Mutations in INF2 were recently identified in patients with autosomal dominant FSGS. INF2 encodes a formin protein that interacts with the Rho-GTPase CDC42 and myelin and lymphocyte protein (MAL) that are implicated in essential steps of myelination and myelin maintenance. We therefore hypothesized that INF2 may be responsible for cases of Charcot-Marie-Tooth neuropathy associated with FSGS. METHODS: We performed direct genotyping of INF2 in 16 index patients with Charcot-Marie-Tooth neuropathy and FSGS who did not have a mutation in PMP22 or MPZ, encoding peripheral myelin protein 22 and myelin protein zero, respectively. Histologic and functional studies were also conducted. RESULTS: We identified nine new heterozygous mutations in 12 of the 16 index patients (75%), all located in exons 2 and 3, encoding the diaphanous-inhibitory domain of INF2. Patients presented with an intermediate form of Charcot-Marie-Tooth neuropathy as well as a glomerulopathy with FSGS on kidney biopsy. Immunohistochemical analysis revealed strong INF2 expression in Schwann-cell cytoplasm and podocytes. Moreover, we demonstrated that INF2 colocalizes and interacts with MAL in Schwann cells. The INF2 mutants perturbed the INF2-MAL-CDC42 pathway, resulting in cytoskeleton disorganization, enhanced INF2 binding to CDC42 and mislocalization of INF2, MAL, and CDC42. CONCLUSIONS: INF2 mutations appear to cause many cases of FSGS-associated Charcot-Marie-Tooth neuropathy, showing that INF2 is involved in a disease affecting both the kidney glomerulus and the peripheral nervous system. These findings provide new insights into the pathophysiological mechanisms linking formin proteins to podocyte and Schwann-cell function. (Funded by the Agence Nationale de la Recherche and others.).

Mutations in INF2 are a major cause of autosomal dominant focal segmental glomerulosclerosis.

The recent identification of mutations in the INF2 gene, which encodes a member of the formin family of actin-regulating proteins, in cases of familial FSGS supports the importance of an intact actin cytoskeleton in podocyte function. To determine better the prevalence of INF2 mutations in autosomal dominant FSGS, we screened 54 families (78 patients) and detected mutations in 17% of them. All mutations were missense variants localized to the N-terminal diaphanous inhibitory domain of the protein, a region that interacts with the C-terminal diaphanous autoregulatory domain, thereby competing for actin monomer binding and inhibiting depolymerization. Six of the seven distinct altered residues localized to an INF2 region that corresponded to a subdomain of the mDia1 diaphanous inhibitory domain reported to co-immunoprecipitate with IQ motif-containing GTPase-activating protein 1 (IQGAP1). In addition, we evaluated 84 sporadic cases but detected a mutation in only one patient. In conclusion, mutations in INF2 are a major cause of autosomal dominant FSGS. Because IQGAP1 interacts with crucial podocyte proteins such as nephrin and PLCε1, the identification of mutations that may alter the putative INF2-IQGAP1 interaction provides additional insight into the pathophysiologic mechanisms linking formin proteins to podocyte dysfunction and FSGS.

Genetics of nephrotic syndrome: connecting molecular genetics to podocyte physiology.

Urinary losses of macromolecules in nephrotic syndrome (NS) reflect a dysfunction of the highly permselective glomerular filtration barrier. Genetic studies of hereditary forms of NS have led to the identification of proteins playing a crucial role in slit-diaphragm signalling, regulation of actin cytoskeleton dynamics, maintenance of podocyte integrity and cell-matrix interactions. This review will focus on recent molecular and clinical findings in the field of genetics of NS, thereby providing a better understanding of the complex glomerular filtration barrier physiology.

Mutational analysis of the PLCE1 gene in steroid resistant nephrotic syndrome.

BACKGROUND: Mutations in the PLCE1 gene encoding phospholipase C epsilon 1 (PLCepsilon1) have been recently described in patients with early onset nephrotic syndrome (NS) and diffuse mesangial sclerosis (DMS). In addition, two cases of PLCE1 mutations associated with focal segmental glomerulosclerosis (FSGS) and later NS onset have been reported. METHOD: In order to better assess the spectrum of phenotypes associated with PLCE1 mutations, mutational analysis was performed in a worldwide cohort of 139 patients (95 familial cases belonging to 68 families and 44 sporadic cases) with steroid resistant NS presenting at a median age of 23.0 months (range 0-373). RESULTS: Homozygous or compound heterozygous mutations were identified in 33% (8/24) of DMS cases. PLCE1 mutations were found in 8% (6/78) of FSGS cases without NPHS2 mutations. Nine were novel mutations. No clear genotype-phenotype correlation was observed, with either truncating or missense mutations detected in both DMS and FSGS, and leading to a similar renal evolution. Surprisingly, three unaffected and unrelated individuals were also found to carry the homozygous mutations identified in their respective families. CONCLUSION: PLCE1 is a major gene of DMS and is mutated in a non-negligible proportion of FSGS cases without NPHS2 mutations. Although additional variants in 19 candidate genes (16 other PLC genes, BRAF,IQGAP1 and NPHS1) were not identified, it is speculated that other modifier genes or environmental factors may play a role in the renal phenotype variability observed in individuals bearing PLCE1 mutations. This observation needs to be considered in the genetic counselling offered to patients.

Genotype-phenotype correlations in non-Finnish congenital nephrotic syndrome.

Mutations in NPHS1, which encodes nephrin, are the main causes of congenital nephrotic syndrome (CNS) in Finnish patients, whereas mutations in NPHS2, which encodes podocin, are typically responsible for childhood-onset steroid-resistant nephrotic syndrome in European populations. Genotype-phenotype correlations are not well understood in non-Finnish patients. We evaluated the clinical presentation, kidney histology, and disease progression in non-Finnish CNS cases by mutational screening in 107 families (117 cases) by sequencing the entire coding regions of NPHS1, NPHS2, PLCE1, WT1, LAMB2, PDSS2, COQ2, and NEPH1. We found that CNS describes a heterogeneous group of disorders in non-Finnish populations. We identified nephrin and podocin mutations in most families and only rarely found mutations in genes implicated in other hereditary forms of NS. In approximately 20% of cases, we could not identify the underlying genetic cause. Consistent with the major role of nephrin at the slit diaphragm, NPHS1 mutations associated with an earlier onset of disease and worse renal outcomes than NPHS2 mutations. Milder cases resulting from mutant NPHS1 had either two mutations in the cytoplasmic tail or two missense mutations in the extracellular domain, including at least one that preserved structure and function. In addition, we extend the spectrum of known NPHS1 mutations by describing long NPHS1 deletions. In summary, these data demonstrate that CNS is not a distinct clinical entity in non-Finnish populations but rather a clinically and genetically heterogeneous group of disorders.

Hereditary nephrotic syndrome: a systematic approach for genetic testing and a review of associated podocyte gene mutations.

Several genes have been implicated in genetic forms of nephrotic syndrome occurring in children. It is now known that the phenotypes associated with mutations in these genes display significant variability, rendering genetic testing and counselling a more complex task. This review will focus on the recent clinical findings associated with those genes known to be involved in isolated steroid-resistant nephrotic syndrome in children and, thereby, propose an approach for appropriate mutational screening. The recurrence of proteinuria after transplantation in patients with hereditary forms of nephrotic syndrome will also be discussed.

Analysis of recessive CD2AP and ACTN4 mutations in steroid-resistant nephrotic syndrome.

Mutations in podocyte genes have been identified in patients with steroid-resistant nephrotic syndrome (SRNS). Point mutations in the ACTN4 gene cause an autosomal dominant form of human focal segmental glomerular sclerosis (FSGS); however, reports of CD2AP mutations remain scarce. Based on the phenotype of Actn4 and Cd2ap null mice, we aimed to define the role of recessive CD2AP and ACTN4 mutations in a cohort of children with SRNS for which NPHS1, NPHS2, and PLCE1 mutations had been previously excluded. CD2AP and ACTN4 mutational analysis was performed in 42 children from 35 unrelated families. The median age of disease onset was 20 (range 0-102) months. Sixteen patients reached end-stage kidney disease at a median age of 84 (range 4-161) months. Renal histology showed FSGS lesions and minimal glomerular changes in 49% and 20% of patients, respectively. Microsatellite marker analysis excluded linkage to the CD2AP locus in 26 families and to the ACTN4 locus in 31 families. No disease-causing mutations were identified in the remaining families. Recessive CD2AP and ACTN4 mutations are rare in children with SRNS. The absence of mutations in this study suggests that there are other genetic causes of SRNS that still need to be identified.

Hypertension Canada's 2020 Comprehensive Guidelines for the Prevention, Diagnosis, Risk Assessment, and Treatment of Hypertension in Adults and Children.

Hypertension Canada's 2020 guidelines for the prevention, diagnosis, risk assessment, and treatment of hypertension in adults and children provide comprehensive, evidence-based guidance for health care professionals and patients. Hypertension Canada develops the guidelines using rigourous methodology, carefully mitigating the risk of bias in our process. All draft recommendations undergo critical review by expert methodologists without conflict to ensure quality. Our guideline panel is diverse, including multiple health professional groups (nurses, pharmacy, academics, and physicians), and worked in concert with experts in primary care and implementation to ensure optimal usability. The 2020 guidelines include new guidance on the management of resistant hypertension and the management of hypertension in women planning pregnancy.

Antibiotic prophylaxis for childhood urinary tract infection: a national survey.

AIMS: To describe attitudes of paediatricians and paediatric nephrologists regarding antibiotic prophylaxis for urinary tract infection (UTI) and determine the factors associated with its use. METHOD: A self-administered questionnaire was mailed to Canadian paediatricians (1136) and paediatric nephrologists (42). RESULTS: The response rate was 58.1% (684 physicians); 436 who had made a decision about antibiotic prophylaxis for childhood UTI in the previous year were included in the analysis. Of these, 407 (93.3%) were certified in paediatrics and 29 (6.7%) were paediatric nephrologists. Most respondents prescribed prophylaxis for children with grade III-V vesicoureteral reflux (VUR) (96.5%-98%); 69.8 and 92.8% prescribed it for children with grades I and II VUR, respectively. Factors significantly associated with use of prophylaxis for children with grade I VUR were frequency of decision-making about prophylaxis, city size and province. Fifteen percent of physicians felt that their practice regarding antibiotic prophylaxis for children with VUR was evidence based. A hundred one respondents (24.3%) prescribed prophylaxis for infants with a first febrile UTI in the absence of VUR. Nineteen percent felt that their practice regarding antibiotic prophylaxis for these infants was evidence based. Prescription of prophylaxis for children >12 months with recurrent UTI in the absence of VUR was influenced by frequency of pyelonephritis (88.5% of respondents) and presence of voiding dysfunction (53.8%). Nine percent of physicians felt that their practice for these children was evidence based. CONCLUSION: Opinions of Canadian paediatricians and paediatric nephrologists regarding antibiotic prophylaxis for UTI in children vary widely, probably because of the paucity of solid evidence about prophylaxis.

[Candidemia and granulomatous tubulointerstitial nephritis]. / Candidose et néphrite tubulo-interstitielle granulomateuse.

Candida infection is a relatively common cause of nosocomial bloodstream infection in immunosuppressed patients. However, renal involvement is infrequent. Moreover, direct Candida identification on kidney biopsy is rarely possible. We present a case of renal insufficiency secondary to Candida albicans tubulointerstitial nephritis.

Two Cases of Mistaken Polyuria and Nephrocalcinosis in Infants with Glucose-Galactose Malabsorption: A Possible Role of 1,25(OH)2D3
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BACKGROUND/AIMS: Glucose-galactose malabsorption (GGM) is a rare and potentially fatal disorder. The autosomal recessive mutation of the SGLT1 gene interferes with the active glucose transport in the gut resulting in osmotic diarrhea and failure to thrive (FTT). Two nonrelated infants with GGM are presented as well as a novel mutation in SGLT1. CASE PRESENTATION: The first case consulted for FTT and presented with hypercalcemia and hypercalciuria. His mother had self-medicated with high doses of vitamin D. The second case consulted for macroscopic hematuria, and presented with dehydration and secondary acute kidney injury. In both cases, the profuse diarrhea, initially mistaken for polyuria, promptly resolved after the introduction of glucose-galactose-free milk. Investigations showed bilateral nephrocalcinosis and high levels of 1,25(OH)2D3 in both patients. We hypothesize that the upregulation of epithelial calcium channels (TRPV6) and 1,25(OH)2D3 are possible factors involved in the pathophysiology of nephrocalcinosis sometimes seen in GGM. Furthermore, a novel intronic SGLT1 mutation (c.207+2dup) is described. CONCLUSION: These 2 cases demonstrate that a malabsorption disorder such as GGM can present with nephrocalcinosis and/or hypercalcemia, with increased 1,25(OH)2D3 levels in infants. Prompt recognition of GGM is sometimes difficult but crucial.
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Setting New Directions for Research in Childhood Nephrotic Syndrome: Results From a National Workshop.

BACKGROUND: We report on the proceedings of a national workshop held in Canada with the aims to identify priorities for research in childhood nephrotic syndrome and to develop a national strategy to address these priorities. METHODS: A diverse group of participants attended the meeting, including patients, family members, researchers, and health care providers. We used small group discussions to explore priorities as perceived by patients and families and by health care providers and researchers. RESULTS: Research evaluating glucocorticoid minimization or glucocorticoid-sparing regimens was a consistent theme in the patient and family discussion group. Families also indicated the need for precise prognostic information at diagnosis, more information to help them choose the best available therapy, and more resources for disease management. Health care providers emphasized the importance of better disease characterization including genotyping and phenotyping patients, better understanding the pathogenesis, and the need of providing targeted therapy and precise prognostic information. CONCLUSIONS: These priorities will inform the development and future directions of the Canadian Childhood Nephrotic Syndrome (CHILDNEPH) project, a national research initiative to improve care and outcomes of patients with childhood onset nephrotic syndrome.

CONTEXTE: Nous rapportons les travaux d'un atelier national qui s'est tenu au Canada et qui avait pour objectif de définir les priorités dans la recherche sur le syndrome néphrotique de l'enfant et d'élaborer une stratégie nationale pour répondre à celles-ci. MÉTHODOLOGIE: Un groupe diversifié de participants a assisté à la réunion, notamment des patients, des membres de leurs familles, des chercheurs et des fournisseurs de soins de santé. Nous avons utilisé de petits groupes de discussion pour explorer les priorités telles que perçues par les patients et leurs familles, de même que par les fournisseurs de soins et les chercheurs. RÉSULTATS: La recherche évaluant la minimisation des glucocorticoïdes ou les traitements substituant les glucocorticoïdes a été un thème récurrent dans le groupe de discussion constitué des patients et de leurs familles. De plus, les familles ont souligné le besoin d'obtenir des informations précises sur le pronostic au moment du diagnostic. Ils ont notamment parlé d'obtenir plus d'informations pour aider à choisir le meilleur traitement disponible et davantage de ressources pour la gestion de la maladie. Les fournisseurs de soins de santé ont quant à eux insisté sur l'importance d'une meilleure caractérisation de la maladie, incluant le génotypage et le phénotypage des patients, une meilleure compréhension de la pathogenèse de la maladie et la nécessité de fournir des thérapies ciblées et des renseignements précis sur le pronostic. CONCLUSIONS: Ces priorités guideront le développement et les futures orientations du Canadian Childhood Nephrotic Syndrome project (CHILDNEPH), une initiative de recherche nationale visant à améliorer les soins et les résultats des patients atteints du syndrome néphrotique apparu durant l'enfance.

Hypertension Canada's 2017 Guidelines for the Diagnosis, Assessment, Prevention, and Treatment of Pediatric Hypertension.

After the 2016 guidelines for blood pressure measurement, diagnosis, and investigation of pediatric hypertension, we now present evidence-based guidelines for the prevention and treatment of hypertension in children. These guidelines were developed by Hypertension Canada's Guideline Committee pediatric subgroup after thorough evaluation of the available literature. Included are 10 guidelines specifically addressing health behaviour management, indications for drug therapy in children with hypertension, choice of therapy for children with primary hypertension, and goals of therapy for children with hypertension. Although the pediatric literature is inherently limited by small numbers of participants, fewer trials, and a prolonged latency to the development of vascular outcomes, this report reflects the current and highest level of evidence and provides guidance for primary care practitioners on the management of pediatric hypertension. Studies of therapeutic lifestyle modifications in children are available to guide current management and more antihypertensive drugs have been studied in children since the Food and Drug Administration Modernization Act. Consistent with Hypertension Canada's guideline policy, diagnostic and therapeutic algorithm tools will be developed and the guidelines will be reviewed annually and updated according to new evidence.

Hypertension Canada's 2016 Canadian Hypertension Education Program Guidelines for Blood Pressure Measurement, Diagnosis, and Assessment of Risk of Pediatric Hypertension.

We present the inaugural evidence-based Canadian recommendations for the measurement of blood pressure in children and the diagnosis and evaluation of pediatric hypertension. Rates of pediatric hypertension are increasing concomitant with increased rates of childhood obesity. With this, there is growing awareness of the need to measure blood pressure in children. Consequently, the present recommendations have been developed to address an important gap and improve the clinical care of children. For 2016, a total of 15 recommendations are presented. These are categorized in a fashion similar to that of the existing adult recommendations. Specifically, we present recommendations on (1) accurate measurement of blood pressure in children, (2) criteria for diagnosis of hypertension in children, (3) assessment of overall cardiovascular risk in hypertensive children, (4) routine laboratory tests for the investigation of children with hypertension, (5) ambulatory blood pressure measurement in children, and (6) the role of echocardiography. We discuss the rationale for the recommendations and present additional supporting material for the clinician, including tables with standardized techniques for blood pressure measurement and determination of normative blood pressure values for children. Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force will update the recommendations annually and develop future evidence-based recommendations to guide prevention and treatment of pediatric hypertension.

The Canadian Childhood Nephrotic Syndrome (CHILDNEPH) Project: overview of design and methods.

BACKGROUND: Nephrotic syndrome is a commonly acquired kidney disease in children that causes significant morbidity due to recurrent episodes of heavy proteinuria. The management of childhood nephrotic syndrome is known to be highly variable among physicians and care centres. OBJECTIVES: The primary objective of the study is to determine centre-, physician-, and patient-level characteristics associated with steroid exposure and length of steroid treatment. We will also determine the association of dose and duration of steroid treatment and time to first relapse as a secondary aim. An embedded qualitative study utilizing focus groups with health care providers will enrich the quantitative results by providing an understanding of the attitudes, beliefs and local contextual factors driving variation in care. DESIGN: Mixed-methods study; prospective observational cohort (quantitative component), with additional semi-structured focus groups of healthcare professionals (qualitative component). SETTING: National study, comprised of all 13 Canadian pediatric nephrology clinics. PATIENTS: 400 patients under 18 years of age to be recruited over 2.5 years. MEASUREMENTS: Steroid doses for all episodes (first presentation, first and subsequent relapses) tracked over course of the study. Physician and centre-level characteristics catalogued, with reasons for treatment preferences documented during focus groups. METHODS: All patients tracked prospectively over the course of the study, with data comprising a prospective registry. One focus group at each site to enrich understanding of variation in care. LIMITATIONS: Contamination of treatment protocols between physicians may occur as a result of concurrent focus groups. CONCLUSIONS: Quantitative and qualitative results will be integrated at end of study and will collectively inform strategies for the development and implementation of standardized evidence-based protocols across centres.

CONTEXTE: Le syndrome néphrotique est une néphropathie fréquente chez l'enfant, qui cause une morbidité considérable en raison de la récurrence d'épisodes de protéinurie importante. La gestion du syndrome néphrotique de l'enfant varie énormément d'un médecin et d'un centre de soins à l'autre. OBJECTIFS: L'objectif principal de cette étude est de déterminer les caractéristiques associées à l'exposition et la durée du traitement aux stéroïdes, liées au centre, au médecin et au patient. En deuxième lieu, nous déterminerons la corrélation entre la dose et la durée du traitement aux stéroïdes, puis la durée avant la première rechute. À cette étude s'ajoutera une étude qualitative avec des groupes de discussion composés de professionnels de la santé qui viendra enrichir les résultats quantitatifs en favorisant une meilleure compréhension des attitudes, des croyances et des facteurs contextuels locaux qui entraînent des variations dans les soins. TYPE D'ÉTUDE: Une étude méthodologique mixte; étude d'observation de cohorte prospective (composante quantitative), combinée avec des groupes de discussion semi-structurés composés de professionnels de la santé (composante qualitative). CONTEXTE/ÉCHANTILLON: Étude nationale, constituée des 13 cliniques canadiennes de néphrologie pédiatrique. PARTICIPANTS: 400 patients âgés de moins de 18 ans, à recruter sur une période de 2,5 années. MESURES: Suivi des doses de stéroïdes pour chacun des épisodes (première présentation, première rechute et suivantes), tout au long de l'étude. Catalogage des caractéristiques liées au médecin ou au centre, et attestation des raisons justifiant les préférences de traitement au cours des séances avec les groupes de discussion. MÉTHODES: Tous les patients suivis de manière prospective dans le cadre de l'étude, dont les données constituent un registre prospectif. Un groupe de discussion à chaque endroit, afin d'enrichir la compréhension des variations dans les soins. LIMITES DE L'ÉTUDE: La contamination des protocoles de traitement entre les médecins peut se produire en raison de la tenue simultanée de groupes de discussions. CONCLUSIONS: Les résultats quantitatifs et qualitatifs seront intégrés à la fin de l'étude et permettront de mettre en place des stratégies de développement et de mise en œuvre de protocoles normalisés et fondés sur des données probantes.

Hyperoxia exposure impairs nephrogenesis in the neonatal rat: role of HIF-1α.

Preterm neonates are exposed at birth to high oxygen concentrations relative to the intrauterine environment. We have previously shown in a rat model that a hyperoxic insult results in a reduced nephron number in adulthood. Therefore, the aim of this study was to determine the effects of transient neonatal hyperoxia exposure on nephrogenesis. Sprague-Dawley rat pups were raised in 80% O2 or room air from P3 to P10. Pups (n = 12/group, 6 males and 6 females) were sacrificed at P5 (during active nephrogenesis) and at P10 (after the completion of nephrogenesis). Hyperoxia exposure resulted in a significant reduction in both nephrogenic zone width and glomerular diameter at P5, and a significantly increased apoptotic cell count; however, nephron number at P10 was not affected. HIF-1α expression in the developing kidney was significantly reduced following hyperoxia exposure. Systemic administration of the HIF-1α stabilizer dimethyloxalylglycine (DMOG) resulted in enhanced expression of HIF-1α and improved nephrogenesis: kidneys from hyperoxia-exposed pups treated with DMOG exhibited a nephrogenic zone width and glomerular diameter similar to room-air controls. These findings demonstrate that neonatal hyperoxia exposure results in impaired nephrogenesis, which may be at least in part HIF-1α-mediated. Although nephron number was not significantly reduced at the completion of nephrogenesis, early indicators of maldevelopment suggest the potential for accelerated nephron loss in adulthood. Overall, this study supports the premise that prematurely born neonates exposed to high oxygen levels after birth are vulnerable to impaired renal development.

Hereditary kidney diseases: highlighting the importance of classical Mendelian phenotypes.

A Mendelian inheritance underlies a nonnegligible proportion of hereditary kidney diseases, suggesting that the encoded proteins are essential for maintenance of the renal function. The identification of genes involved in congenital anomalies of the kidney and in familial forms of nephrotic syndrome significantly increased our understanding of the renal development and kidney filtration barrier physiology. This review will focus on the classical phenotype and clinical heterogeneity observed in the monogenic forms of these disorders. In addition, the role of susceptibility genes in kidney diseases with a complex inheritance will also be discussed.