Subject(s)
Humans , Infant, Newborn , Polycystic Kidney, Autosomal Dominant/diagnosis , Polycystic Kidney, Autosomal Dominant/etiology , Polycystic Kidney, Autosomal Dominant/pathology , Polycystic Kidney, Autosomal Dominant , Polycystic Kidney, Autosomal Recessive/diagnosis , Polycystic Kidney, Autosomal Recessive/etiology , Polycystic Kidney, Autosomal Recessive/pathology , Polycystic Kidney, Autosomal Recessive , Diagnosis, Differential , Diagnostic Imaging , Polycystic Kidney Diseases/classification , Polycystic Kidney Diseases/genetics , Genetic CounselingABSTRACT
Autosomal recessive polycystic kidney disease (ARPKD) is an inherited disease characterized by a malformation complex which includes cystically dilated tubules in the kidneys and ductal plate malformation in the liver. The disorder is observed primarily in infancy and childhood, being responsible for significant pediatric morbidity and mortality. All typical forms of ARPKD are caused by mutations in a single gene, PKHD1 (polycystic kidney and hepatic disease 1). This gene has a minimum of 86 exons, assembled into multiple differentially spliced transcripts and has its highest level of expression in kidney, pancreas and liver. Mutational analyses revealed that all patients with both mutations associated with truncation of the longest open reading frame-encoded protein displayed the severe phenotype. This product, polyductin, is a 4,074-amino acid protein expressed in the cytoplasm, plasma membrane and primary apical cilia, a structure that has been implicated in the pathogenesis of different polycystic kidney diseases. In fact, cholangiocytes isolated from an ARPKD rat model develop shorter and dysmorphic cilia, suggesting polyductin to be important for normal ciliary morphology. Polyductin seems also to participate in tubule morphogenesis and cell mitotic orientation along the tubular axis. The recent advances in the understanding of in vitro and animal models of polycystic kidney diseases have shed light on the molecular and cellular mechanisms of cyst formation and progression, allowing the initiation of therapeutic strategy designing and promising perspectives for ARPKD patients. It is notable that vasopressin V2 receptor antagonists can inhibit/halt the renal cystic disease progression in an orthologous rat model of human ARPKD.
Subject(s)
Humans , Animals , Rats , Mutation , Polycystic Kidney, Autosomal Recessive/genetics , Polycystic Kidney, Autosomal Recessive/pathology , Receptors, Cell Surface/genetics , Cilia/pathology , Cytoplasm/pathology , Disease Models, Animal , Exons , PhenotypeABSTRACT
Autosomal Recessive Polycystic Kidney (ARPKD) is a very rare entity (1 in 15,000 live births) and mostly not compatible with life. Early diagnosis and genetic councelling may help prevent such births. Two interested cases are presented.
Subject(s)
Adult , Female , Fetal Death/pathology , Humans , Kidney/pathology , Liver/pathology , Polycystic Kidney, Autosomal Recessive/pathology , PregnancyABSTRACT
Los quistes renales son dilataciones anormales de túbulos, conductos o glomérulos, o estructuras similares a divertículos posiblemente en continuidad con el nefrón. La enfermedad quística renal puede comprometer ambos riñones en forma difusa como en el riñón poliquístico o enfermedad autosómica dominante, o un área particular de ambos riñones como los riñones en esponja, o sólo un riñón o parte de él como en el riñón multiquístico. También hay un tumor quístico que puede reemplazar el parénquima renal normal como es el quiste multilocular. Finalmente el quiste simple puede ocurrir solo o junto a más quistes en cualquier lugar del riñón. La clasificación de los quistes con el propósito de simplificar conceptos no provee nacesariamente un marco práctico y clínico para tan diversos procesos patológicos. El advenimiento de la ecografía, la resonancia nuclear magnética y la tomografía computarizada ha mejorado drásticamente la habilidad del clínico para diagnosticar y diferenciar la variedad de enfermedad renal quística. Sin embargo, la importancia de una cuidadosa historia familiar es enfatizada por la clasificación de esa patología en categorías genéticas.