Salivary creatinine and urea are higher in an experimental model of acute but not chronic renal disease

<div><p>Plasma creatinine and urea are commonly used markers of kidney function in both acute and chronic renal failure. The needed repeated blood collection is associated with pain, stress and might lead to infections. Saliva has the potential to be a non-invasive alternative diagnostic fluid. The use of saliva in clinical practice is limited, since many factors affect the concentration of salivary biomarkers. The aim of our study was to analyze salivary creatinine and urea in the animal models of acute and chronic renal disease. Bilateral nephrectomy and adenine nephropathy were induced in adult male mice. Both, plasma creatinine and urea were higher in animals with renal failure compared to controls. Salivary creatinine was higher by 81% and salivary urea by 43% in comparison to the control group, but only in animals with bilateral nephrectomy and not in adenine nephropathy. Our results indicate that the increase of salivary creatinine and urea depends on the experimental model of renal failure and its severity. Further studies are needed to monitor the dynamics of salivary markers of renal function and to reveal determinants of their variability.</p></div

Correlation between plasma creatinine and urea and their salivary levels.

<p>Correlation between plasma creatinine and salivary creatinine levels in (A) control group (p>0.05) and (B) BNX group (p<0.05). Correlation between plasma urea and salivary urea levels in (C) control group (p>0.05) and (D) BNX group (p<0.05) (by Pearson’s correlation analysis).</p

Plasma and salivary concentrations of creatinine and urea in CKD.

<p>Concentration of plasma (A) creatinine and (B) urea, and salivary (C) creatinine and (D) urea after 3 weeks of CKD induction. Results are expressed as mean + SD. * denotes p<0.05 in comparison to control group (by Student’s unpaired t test, n = 15 for each group).</p

Correlation between plasma creatinine and urea and their salivary levels.

<p>Correlation between plasma creatinine and salivary creatinine levels in (A) control group (p>0.05) and (B) Adenine group (p>0.05). Correlation between plasma urea and salivary urea levels in (C) control group (p>0.05) and (D) Adenine group (p>0.05) (by Pearson’s correlation analysis).</p

Plasma and salivary concentrations of creatinine and urea in AKI.

<p>Concentration of plasma (A) creatinine and (B) urea, and salivary (C) creatinine and (D) urea 24 hours after AKI induction. Results are expressed as mean + SD. * denotes p<0.05 and *** denotes p<0.001 in comparison to control group (by Student’s unpaired t test, n = 10 for each group).</p

Datasheet1_Neutrophil extracellular traps in urinary tract infection.pdf

BackgroundUrinary tract infections (UTI) are common types of bacterial infection in children. UTI treatment is aimed to prevent complications including hypertension, proteinuria, and progression to chronic kidney disease. Activated neutrophils release chromatin-based structures associated with antimicrobial proteins called neutrophil extracellular traps (NETs). We aimed to describe the role of NET-associated markers in children with UTI as well as the role of NETs formation in a mouse model of UTI.Materials and methodsMarkers of NETs including extracellular DNA (ecDNA), myeloperoxidase (MPO) and cathelicidin were analyzed in children with febrile UTI caused by E.coli (n = 98, aged 0.3–1.3 years) and in healthy controls (n = 50, 0.5–5.2 years). Moreover, an acute experimental model of UTI was performed on PAD4 knock-out mice with diminished NETs formation (n = 18), and on wild-type mice (n = 15).ResultsChildren with UTI had significantly higher urinary NETs markers including total ecDNA, nuclear DNA and mitochondrial DNA, altogether with MPO and cathelicidin. The concentrations of MPO and cathelicidin positively correlated with ecDNA (r = 0.53, p ≤ 0.001; r = 0.56, p ≤ 0.001, respectively) and the number of leukocytes in the urine (r = 0.29, p ≤ 0.05; r = 0.27, p ≤ 0.05, respectively). Moreover, urinary MPO was positively associated with cathelicidin (r = 0.61, p ≤ 0.001). In the experimental model, bacterial load in the bladder (20-fold) and kidneys (300-fold) was significantly higher in PAD4 knock-out mice than in wild-type mice.ConclusionHigher urinary NETs makers—ecDNA, MPO and cathelicidin and their correlation with leukocyturia in children with UTI confirmed our hypothesis about the association between NETs and UTI in children. Higher bacterial load in mice with diminished NETs formation suggests that NETs are not only a simple consequence of UTI, but might play a direct role in the prevention of pyelonephritis and other UTI complications.</p