Evaluation of histologic changes in the urinary tract of hypercalciuric rats

Abstract

Idiopathic hypercalciuria (IH) has been speculated to have a predisposing role in the development of urinary tract infection (UTI), due to the uroepithelial cell damage it leads to. In this study, we aimed to investigate the effects of hypercalciuria on the bladder, ureters, and kidneys in rats with experimentally induced hypercalciuria.Normocalcemic hypercalciuria was induced by furosemide (60 mg/100 mL of drinking water) administration to 16-week-old male Wistar Albino rats for 14 days. Calciuria (calcium/creatinine ratio, mg/mg, Ca/Cr) increased from 0.07+/-0.01 at the beginning of administration to 0.41+/-0.1 on day 14 (p=0.000). The Ca/Cr ratio was 0.14+/-0.06 at the beginning of the study and 0.25+/-0.06 on day 14 in the control group rats (p=0.002 vs. the hypercalciuric group rats on day 14). Bladder, ureter, and kidney specimens of the rats, dissected on the 14th day, were fixed in 10% formalin and 2.5% gluteraldehyde solutions for light and electron microscopic examination, respectively. Histopathological and ultrastructural examination of the hypercalciuric rats revealed proliferation and apical cytoplasmic vacuole formation in transitional epithelial cells, mitotic activity in the intermediate cell line, vasodilatation, edema, and separation of collagen fibers in the bladder and ureter specimens. Light microscopic examination of the kidney specimens revealed a lot of erythrocyte in the glomerular capillary lumen, while electron microscopy revealed vacuolization of proximal and distal tubules, tubular degeneration, interstitial edema, and vasodilatation.In this study, hypercalciuria was observed to have adverse effects on the cell architecture of the uroepithelium and disruption of the epithelial barrier of the bladder and ureters and all kidney structures, especially on the proximal epithelial cells.

Low‐dose thiazide diuretics in children with idiopathic renal hypercalciuria

“…We observed a high incidence of UTI (32%) in patients with renal hypercalciuria, implicating IH might be a major contributing factor to UTI in children. In rat models, hypercalciuria significantly affected on the cell architecture of the uroepithelium and disruption of the epithelial barrier of the bladder, ureter and all kidney structures, especially on the proximal epithelial cells (15). Therefore, this complication should also be considered when managing patients with IH in clinical practice.…”

Hypercalciuria, a promoting factor to urinary tract infection in children

“…Akil et al, showed that hypercalciuric rats revealed proliferation and apical cytoplasmic vacuole formation in transitional epithelial cells of bladder and ureter specimens, and also vacuolization of proximal and distal tubules, tubular degeneration, interstitial edema and vasodilatation of the kidney. [10] According to Vachvanichsanong et al, decreasing urinary calcium excretion was associated with decreased symptoms of dysfunctional voiding. [6] Kaminska et al, showed that treatment of preurolithiasis state could decrease the recurrence rate of UTI.…”

“…Different mechanisms have been shown as responsible mechanism for UTI, such as uroepithelial damage by calcium oxalate monohydrate, the balance between bacterial virulence and host resistance, an inflammatory response to lipopolysaccharide (LPS) and low urinary secretory IgA (sIgA). [10][11][12][13] Hypercalciuria can predispose patients to UTI due to uroepithelial damage. Akil et al, showed that hypercalciuric rats revealed proliferation and apical cytoplasmic vacuole formation in transitional epithelial cells of bladder and ureter specimens, and also vacuolization of proximal and distal tubules, tubular degeneration, interstitial edema and vasodilatation of the kidney.…”

High Concentration of Calcium Stimulates Calcium Oxalate Crystal Attachment to Rat Tubular Epithelial NRK Cells Through Osteopontin

“…2 A recent study shows that hypercalciuria has adverse effect on cell architecture of the uroepithelium and disruption of the epithelial barrier of the bladder and ureters and all kidney structures, especially on the proximal epithelial cells in hypercalciuric rats. 3 Taken together, these observations suggest that hypercalciuria maybe exert multiple functions in the kidney stone formation.…”