Research progress on renal calculus associate with inborn error of metabolism / 浙江大学学报·医学版

Renal calculus is a common disease with complex etiology and high recurrence rate. Recent studies have revealed that gene mutations may lead to metabolic defects which are associated with the formation of renal calculus, and single gene mutation is involved in relative high proportion of renal calculus. Gene mutations cause changes in enzyme function, metabolic pathway, ion transport, and receptor sensitivity, causing defects in oxalic acid metabolism, cystine metabolism, calcium ion metabolism, or purine metabolism, which may lead to the formation of renal calculus. The hereditary conditions associated with renal calculus include primary hyperoxaluria, cystinuria, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis, Bartter syndrome, primary distal renal tubular acidosis, infant hypercalcemia, hereditary hypophosphatemic rickets with hypercalciuria, adenine phosphoribosyltransferase deficiency, hypoxanthine-guanine phosphoribosyltransferase deficiency, and hereditary xanthinuria. This article reviews the research progress on renal calculus associated with inborn error of metabolism, to provide reference for early screening, diagnosis, treatment, prevention and recurrence of renal calculus.

Long non-coding RNA CHCHD4P4 promotes epithelial-mesenchymal transition and inhibits cell proliferation in calcium oxalate-induced kidney damage

Kidney stone disease is a major cause of chronic renal insufficiency. The role of long non-coding RNAs (lncRNAs) in calcium oxalate-induced kidney damage is unclear. Therefore, we aimed to explore the roles of lncRNAs in glyoxylate-exposed and healthy mouse kidneys using microarray technology and bioinformatics analyses. A total 376 mouse lncRNAs were differentially expressed between the two groups. Using BLAST, 15 lncRNA homologs, including AU015836 and CHCHD4P4, were identified in mice and humans. The AU015836 expression in mice exposed to glyoxylate and the CHCHD4P4 expression in human proximal tubular epithelial (HK-2) cells exposed to calcium oxalate monohydrate were analyzed, and both lncRNAs were found to be upregulated in response to calcium oxalate. To further evaluate the effects of CHCHD4P4 on the cell behavior, we constructed stable CHCHD4P4-overexpressing and CHCHD4P4-knockdown HK-2 cells. The results showed that CHCHD4P4 inhibited cell proliferation and promoted the epithelial-mesenchymal transition in kidney damage and fibrosis caused by calcium oxalate crystallization and deposition. The silencing of CHCHD4P4 reduced the kidney damage and fibrosis and may thus be a potential molecular target for the treatment of kidney stones.

ClC-5 chloride channel and kidney stones: what is the link?

Nephrolithiasis is one of the most common diseases in the Western world. The disease manifests itself with intensive pain, sporadic infections, and, sometimes, renal failure. The symptoms are due to the appearance of urinary stones (calculi) which are formed mainly by calcium salts. These calcium salts precipitate in the renal papillae and/or within the collecting ducts. Inherited forms of nephrolithiasis related to chromosome X (X-linked hypercalciuric nephrolithiasis or XLN) have been recently described. Hypercalciuria, nephrocalcinosis, and male predominance are the major characteristics of these diseases. The gene responsible for the XLN forms of kidney stones was cloned and characterized as a chloride channel called ClC-5. The ClC-5 chloride channel belongs to a superfamily of voltage-gated chloride channels, whose physiological roles are not completely understood. The objective of the present review is to identify recent advances in the molecular pathology of nephrolithiasis, with emphasis on XLN. We also try to establish a link between a chloride channel like ClC-5, hypercalciuria, failure in urine acidification and protein endocytosis, which could explain the symptoms exhibited by XLN patients

Evaluacion metabolica ante el primer episodio de litiasis renal / Metabolic evaluation before of the first renal lithiasis episode

Existen pocas dudas acerca de la necesidad de estudiar en forma exhaustiva a todo paciente con litiasis renal recurrente. Sin embargo, es controvertida la conducta a adoptar ante el primer episodio. Por tal motivo nos propusimos responder a una serie de interrogantes al cabo de los cuales formularemos nuestro propio criterio. ?Cuál es la recurrencia luego del primer cálculo formado? ?Tienen la misma alteración alteración metabólica el recurrente que aquel que tuvo su primer episodio? ?Son similares los antecedentes familiares an ambos grupos de nefrolitiásicos? ?Cuál es el grado de morbilidad en ambos grupos? ?Son los estudios metabólicos de difícil realización? Luego de responder estos interrogantes con datos aportados por 200 de nuestros pacientes (100 LP y 100LR) y una revisión de la literatura, creemos que tanto los pacientes con un primer episodio como los recurrentes corresponden a una misma población, detectados en diferentes momentos evolutivos. Basándonos en esto, proponemos la siguiente conducta: 1) todo paciente con litiasis renal debe ser estudiado desde el punto de vista metabólico desde su primer espisodio; 2) el estudio metabólico inicial debe ser lo más exhaustivo posible con la finalidad de adecuar una terapéutica específica; 3) las posibilidades de encontrar una alteración metabólica pasible de ser tratada con éxito superan el 90 por ciento