Analysis of proteinuria in experimental model of ascending acute kidney injury.

Proteinuria accompanies kidney diseases of various etiology and correlates with the degree of organ damage. Analysis of proteinuria allows the location of pathophysiological process in the kidney, and assessment of the severity of the kidney disease in chronic and acute kidney injury (AKI). Ascending bacterial acute kidney injury develops as a consequence of pyelonephritis. It is a rare complication in patients with anatomical or functional dysfunctions of the urinary tract. AIM: The aim of the study was to perform the laboratory analysis of proteinuria in bacterial ascending AKI in an experimental model. MATERIALS AND METHODS: Female Wistar rats (n = 24) were intravesically administrated bacterial suspension of Escherichia coli (E. coli) to induce: pyelonephritis (group 1, 105 CFU/ml); AKI (group 2, 107 CFU/ml); AKI and urosepsis (group 3, 109 CFU/ml) respectively. Bacterial strain - E.coli, was isolated from a patient with acute pyelonephritis. The daily diuresis and urine protein excretion was measured the following days: 0, 7, 14 and 21. Moreover, electrophoretic separation of urine protein, densitometric analysis of albumin fraction and uromodulin concentration in urine were performed. Moreover, the key parameters for the diagnosis of AKI were assayed. RESULTS: Increased urinary protein excretion was observed in each of the study groups. Moreover, the study groups showed significant changes in protein selectivity in the urine. CONCLUSIONS: Moderately severe proteinuria was revealed while its selectivity suggested significant damage of glomeruli and renal tubules in groups with complications caused by AKI induced by ascending pyelonephritis.

Experimental model for acute kidney injury caused by uropathogenic Escherichia coli.

INTRODUCTION: Acute kidney injury (AKI) is the rapid deterioration of renal function, diagnosed on the basis of an increase in serum creatinine and abnormal urinary parameters. AKI is associated with increased risk of mortality or chronic kidney disease (CKD). The aim of the study was to develop an experimental model for AKI resulting from Escherichia coli-induced pyelonephritis. E. coli was isolated from a patient with clinical symptoms of urinary tract infection (UTI). MATERIAL/METHODS: The study included three groups of female Wistar rats (groups 1, 2 and 3), in which pyelonephritis was induced by transurethral inoculation with highly virulent E. coli (105, 107 and 109 cfu/ml, respectively). Urine and blood samples for analysis were obtained prior to the inoculation (day 0), as well as 7, 14 and 21 days thereafter. RESULTS: Aside from a microbiological examination of urine samples, daily urine output, serum creatinine (CreaS), creatinine clearance (CrCl), interleukin 6 (IL-6), fractional excretion of sodium (FENa) and fractional excretion of urea (FEUrea) were determined. A histopathological examination of kidney and urinary bladder specimens was conducted as well. While UTI-related pyelonephritis developed irrespective of E. coli inoculum size, AKI was observed only following transurethral administration of E. coli at the intermediate and high dose, i.e. 107 and 109 cfu/ml, respectively (group 2 and 3). DISCUSSION: An increase in CreaS and abnormal diuresis were accompanied by changes in parameters specific for various forms of AKI, i.e. FENa and FEUrea. Based on these changes, administration of E. coli at 107 cfu/ml was demonstrated to induce renal AKI, whereas inoculation with 109 cfu/ml seemed to cause not only ascending pyelonephritis, but perhaps also bacteremia and urosepsis (prerenal component of AKI).

Urinary kidney injury molecule-1 (KIM-1) excretion in rats with experimental cystitis induced by oxazaphosphorines.

Introduction: Oxazaphosphorine agents (cyclophosphamide - CP, ifosfamide - IF) are causative factors of cystitis and also exert a characteristic nephrotoxic effect, clinically manifested by a broad spectrum of disturbances. The aim of the study was to estimate the toxic effect of the abovementioned oxazaphosphorines on the renal tubules by assessment of diuresis and urinary concentration and daily urinary excretion of the kidney injury molecule-1 (KIM-1) in rats with induced and histologically confirmed cystitis. Material and Methods: The study involved 60 rats (equal amounts of ♀ and ♂), including animals treated with CP, administrated four times at the dose 75 mg/kg (group 1; n=10) and treated with IF, administrated four times at the dose 50 mg/kg IF (group 2; n=10) with the suitable control group A (group 3; n = 10), as well as animals receiving either a single dose 150 mg/kg of CP (group 4) or IF (group 5), with an appropriate control group B (group 6). Results: In both groups 1 and 4, a significant increase in the daily diuresis and decrease of the urinary pH were revealed, compared to the appropriate control group A (group 3) and B (group 6), while IF-treated animals, regardless of the applied doses (groups 2 and 5), were characterized by a urinary pH decrease. KIM-1 urinary concentration in rats from group 1 and 4 was almost three times higher compared to the appropriate control groups A or B, respectively, and the difference was statistically significant. In animals with chronic (group 2) and acute (group 5) ifosfamide- induced cystitis, no statistically significant difference concerning KIM- 1 urinary concentration compared to a control A and B groups was revealed, although a clear tendency of increase of the parameter was observed in the IF-treaded animals. Analysis of daily KIM-1 urinary excretion showed a statistically significant, almost six-fold increase in group 1 and almost two-fold increase in group 2. In the groups with acute model of cystitis, the highest, nearly eight-fold, daily KIM-1 urinary excretion, was revealed in animals treated with single CP dose, compared to the respective control B group, while rats treated with a single IF dose were characterized by a daily urinary KIM -1 excretion, comparable to animals with IF-induced chronic cystitis. The histopathological analysis confirmed cystitis in all animals treated with either CP or IF (groups 1,2,4,5), while no altered kidney microscopic morphology, compared to respective control groups A and B, was observed in those rats. Conclusions: The study confirmed the proximal tubular dysfunction in rats with both cyclophosphamide- and ifosfamide-induced cystitis, which was reflected by an increased urinary KIM-1 excretion. The disturbance was more emphasized in CP-treated animals, especially in those ones treated with the single, high CP dose. The functional tubulopathy was not accompanied by a structural kidney damage in rats treated with either CP or IF.