Novel Urinary Biomarkers for Diagnosis of Acute Pyelonephritis in Children.

Urinary tract infection (UTI) is common among pediatric population. Pyelonephritis, especially in young infants, is associated with a significant morbidity. Usually, clinical manifestations, laboratory findings, and imaging are used to differentiate between lower and upper UTI. Lack of specific clinical findings and commonly used nonspecific blood indices are important hamper differentiation between lower and upper UTI in early stages. Imaging techniques are neither cost benefit nor safe for detection of UTI. Recent efforts have focused on characterization of novel serum and urinary biomarkers for early detection of acute pyelonephritis in children. It seems that urinary NGAL, NAG, TNF-α and IL-8 may be used as novel markers for early diagnosis of acute pyelonephritis in children.

New biomarkers defining a novel early stage of Fabry nephropathy: A diagnostic test study.

BACKGROUND: Renal involvement in Fabry disease is a major determinant of overall disease prognosis and early enzyme replacement therapy seems effective in preventing progression of kidney injury. Gb3 storage, glomerular sclerosis and tubulo-interstitial fibrosis may occur with minimal or no changes on standard renal tests, hence alternative markers of renal dysfunction are crucial. In this study we compared several biomarkers with albuminuria in the identification of incipient Fabry nephropathy and their diagnostic accuracy to identify chronic kidney disease (CKD) stage≥2. METHODS: In this multicentre, prospective, cross-sectional and diagnostic test study, a cohort of 78 Fabry patients and 25 healthy controls was consecutively recruited. Patients were grouped by severity of nephropathy: 1) albuminuria<30mg/g; 2) albuminuria 30-299mg/g; 3) albuminuria>300mg/g; 4) glomerular filtration rate (GFR)<60mL/min/1.73m2. Several index tests, namely biomarkers of glomerular (transferrin and type IV collagen) and tubular (α1-microglobulin, N-acetyl-ß-glucosaminidase and alanine aminopeptidase) dysfunction were compared with the reference standard (albuminuria). RESULTS: Significant increase of all tested biomarkers in Fabry patients, even in the subgroup of patients without evidence of nephropathy. We also found inverse significant correlations between estimated GFR and collagen type IV (ρ=-0.289; p=0.003) or N-acetyl-ß-glucosaminidase (ρ=-0.448; p<0.001), which were stronger than with albumin (ρ=-0.274; p=0.019). There was also better diagnostic accuracy of N-acetyl-ß-glucosaminidase to predict CKD stage≥2. CONCLUSIONS: These results suggest that studied biomarkers may overcome the limitations of albuminuria as sensitive marker of early renal dysfunction and as marker for CKD progression risk. These biomarkers may also define novel early stages of nephropathy characterized by mesangial expansion and/or tubular damage.

Renal tubular dysfunction increases mortality in the Japanese general population living in cadmium non-polluted areas.

The aim of this study was to establish the cause-effect relationship between renal tubular dysfunction and mortality. A 19-year cohort study was conducted in 900 men and 1313 women in 1993 or 1994 who lived in two cadmium non-polluted areas in Japan. Hazard ratio (HR) and 95% confidence interval (95% CI) of urinary ß2-microglobulin (ß2-MG) and N-acetyl-ß-glucosaminidase (NAG) for mortality were calculated using a proportional hazard regression. Forward stepwise model selection was applied to the potential covariates such as age, body mass index, mean arterial pressure, various lifestyle factors and present illness. Simultaneously, the dose-effect relationship between renal tubular markers and urinary cadmium at baseline was evaluated using multiple regression analyses. In men, HR was significant for ß2-MG (HR corresponding to an increase of 100 µg/g cre: 1.02) and NAG (HR corresponding to an increase of 1 IU/g cre: 1.05). In women, a significant HR was observed for ß2-MG (HR corresponding to an increase of 100 µg/g cre: 1.01) and NAG (HR corresponding to an increase of 1 IU/g cre: 1.02). Dose-effect relationships were significant for urinary cadmium and all renal tubular markers in men and women. The present study indicated that renal tubular dysfunction was significantly related to mortality in the general population of cadmium non-polluted areas in Japan.

Acute kidney injury induced by aristolochic acid in patients with primary glomerular nephritis.

BACKGROUND: Acute kidney injury induced by aristolochic acid (AA) might occur in patients with chronic glomerular nephritis (CGN). In this study, the clinical and pathological features of patients with acute aristolochic acid nephropathy (AAN) superimposing CGN (AAN-CGN) were investigated. METHODS: Eighteen patients diagnosed as acute AAN were included in this retrospective study, from January 2001 to December 2009. According to the pre-existing CGN, 13 patients were identified as the AAN-CGN group, and 5 isolated AAN patients as the control group. Clinical and pathological features were compared between the two groups. RESULTS: In the AAN-CGN group, six patients complained with gastrointestinal symptoms, such as nausea, vomiting, or loss of appetite. The rest of seven cases were asymptomatic or minimally uncomfortable, who were found with elevated serum creatinine (Scr) in the follow up of CGN. Compared with the control group, the patients in AAN-CGN group had higher levels of serum uric acid, urine n-acetyl-ß-d-glucosaminidase, and urine protein excretion (366.2 ± 122.8 vs. 218.0 ± 125.8 µmol/L, p = 0.037; 9.74 ± 4.4 vs. 1.38 ± 1.01 g/d, p = 0.001; 61.2 ± 21.9 vs. 27.4 ± 15.8 µ/g c cr, p = 0.007, respectively). In addition to, the AAN-CGN patients had an absolutely prominent percentage of macromolecule substance in the urine protein electrophoresis (25.0 ± 6.32 vs. 15.8 ± 7.8%, p = 0.029). The occurrence of hypokalemia and excretion of aminoaciduria were lower than that in the control group. Pathologically, 84.6% of patients were found with tubular brush border dropping, 30.8% with naked tubular basement membrane, and 15.4% with different stages of vascular lesion. There were no statistical differences in the above-mentioned pathological parameters between the two groups. In the follow-up, 10 patients with AAN-CGN recovered with normal Scr, accounting for 76.9%, which was better than the recovery in the control group. CONCLUSION: Patients with acute AAN-CGN manifested with a great mass of urine protein excretion, low incidence of hypokalemia and aminoaciduria, however, the tubular-interstitial lesions were similar to the isolated AAN.

Urinary vanin-1 as a novel biomarker for early detection of drug-induced acute kidney injury.

Drug-induced nephrotoxicity is a serious problem in patients with hospital-acquired acute kidney injury (AKI). A new renal biomarker is needed because traditional markers are not sensitive for early detection of drug-induced AKI. In a recent study, we demonstrated that vanin-1 is a novel candidate biomarker of nephrotoxicant-induced kidney injury. The objective of the present study is to determine whether the increase in urinary vanin-1 is detected before the elevations of serum creatinine or urinary N-acetyl-ß-glucosaminidase (NAG), kidney injury molecule-1 (Kim-1), and neutrophil gelatinase-associated lipocalin (NGAL) in the two well established animal models of drug-induced AKI. After the administration of a higher dose of cisplatin (10 mg/kg, a single intraperitoneal dose) or gentamicin (120 mg/kg per day, once daily intraperitoneal dose for 9 days), urinary vanin-1 was detected earlier than the other biomarkers. In rats treated with a lower dose of cisplatin (5 mg/kg, a single intraperitoneal dose) or gentamicin (40 mg/kg per day, once daily intraperitoneal dose for 9 days), serum creatinine and urinary NAG were not changed throughout the study period, whereas urinary vanin-1, Kim-1, and NGAL were significantly increased. The renal vanin-1 protein levels were significantly decreased in rats treated with the higher dose of cisplatin on day 5 and gentamicin on day 9, and the immunofluorescence analyses confirmed that vanin-1 immunoreactivity in tubular cells was reduced with the time after the dose of cisplatin, indicating that urinary vanin-1 was leaked from tubular cells. These results suggest that, compared with urinary Kim-1 and NGAL, urinary vanin-1 is an earlier and equally sensitive biomarker for drug-induced AKI.

Prevalence of chronic kidney disease in a middle and old-aged population of Beijing.

BACKGROUND: Chronic kidney disease (CKD) was epidemic worldwide. The prevalence of CKD indicators, including proteinuria, hematuria/uninfectious leukocyturia and reduced GFR, was investigated in the middle and old-aged population of Beijing Shijingshan district. METHODS: Subjects of 2310 aged > or =40 y were enrolled. Their health conditions were taken by questionnaires and physical check-ups. Spot urine albumin to creatinine ratio, spot urine dipstick and microscopy for urine red cell and leukocyte, and serum creatinine was determined. Using simplified Modification of Diet in Renal Disease Study equation estimated GFR assessed renal function. The associations between age, gender, diabetes mellitus, and hypertension, and indicators of kidney damage were examined. RESULTS: Through the questionnaires, the history of diabetes mellitus, hypertension and CKD were found in 28%, 47.1% and 3.6% of subjects, respectively. Albuminuria was detected in 8.4% of subjects, hematuria and uninfectious leukocyturia in 0.7%, and reduced GFR in 4.9%. Approximately 12.9% had at least 1 indicator of CKD. The known rate of CKD in the studied population was 7.1%. Age, diabetes mellitus, hyper fasting blood glucose and hypertension were independently associated with albuminuria; age, gender, hyper uric acid and albuminuria with reduced GFR. When proteinuria and reduced GFR were determined using spot urine dipstick protein > or =25 mg/dl and serum creatinine > or =133 micromol/l, the prevalence of proteinuria and reduced GFR were 4.7% and 0.8%, respectively. CONCLUSION: The prevalence of CKD is common in middle and old-aged population of Beijing, especially in the elderly, but the known rate was relatively low. These findings highlight the clinical and public health importance of CKD.

p38-MAPK inhibition and endotoxin induced tubular dysfunction in men.

BACKGROUND: To evaluate the possibility of preventing endotoxin induced renal damage by p38-MAPK inhibition in a human model. DESIGN AND METHODS: Twenty-one healthy young male volunteers received 4 ng/kg Escherichia coli endotoxin as a single dose. Four groups of volunteers received an oral dose of placebo or 350, 700 or 1400 mg RWJ-67657, a p38-MAPK inhibitor, 20 min before endotoxin infusion. Urine samples were collected at set time intervals. The urinary excretion rate of beta(2)-microglobulin and N-acetyl-beta-D-glucosaminidase, as indicators of tubular dysfunction was determined. RESULTS: There was a significant increase of beta(2)-microglobulin and N-acetyl-beta-D-glucosaminidase urine excretion rate after endotoxin infusion in the placebo group. p38-MAPK inhibition prevented the increase of markers for tubulopathy. CONCLUSIONS: Endotoxin infusion induces measurable tubular damage. Blocking the p38-MAPK may prevent this damage. The mechanism is unclear, but blocking TNF-alpha release is a possible explanation.