Urine Biomarkers Combined With Ultrasound for the Diagnosis of Obstruction in Pediatric Hydronephrosis

Introduction: To establish the efficacy of ultrasound (US) combined with urine biomarkers in differentiating patients who require surgical management from those who do not, avoiding invasive investigations.Materials and Methods: From February 2019 to February 2021, all pediatric patients who presented with hydronephrosis were selected for the study. All renal units (RU) were evaluated by US, and fresh frozen voided urine samples were collected at the time of inclusion. Hydronephrosis grade was evaluated by the Society for Fetal Urology (SFU) and an alternative grading system (AGS). Patients who had high-grade hydronephrosis on US were referred to renal scan (RS) or intervention, when there was an increase of dilatation in subsequent follow-up images. Fresh frozen urine from the control group with no history of renal diseases and no renal anomalies on US was collected. We compared differences of US parameters combined with urine biomarkers between surgically and non-surgically managed patients and between the groups of patients when they were stratified by different RS findings and analyzed whether urinary biomarkers give any additional value to US. Instead of the anterior–posterior diameter (APD), we used its ratio with mid-parenchymal thickness. The additional efficacy of biomarkers to US was calculated when the US component was derived to a cumulative APD/mid-parenchymal ratio.Results: Sixty-four patients with hydronephrosis were prospectively included in the study accounting for a total of 81 patient visits and 162 RUs evaluated. A control group of 26 patients was collected. The mean age at inclusion in the hydronephrosis group was 43.7(±45.5) months, and a mean age in a control group was 61.2(±41.3) months. The cumulative APD/mid-parenchymal ratio combined with urinary albumin, β2 microglobulin (β2-M), and urinary neutrophil gelatinase-associated lipocalcin may have a better performance in the prediction of surgical intervention than the cumulative APD/mid-parenchymal ratio alone (p = 0.1). The best performance to detect the increased tissue transit time and obstructive curve on RS was demonstrated by the β2-M creatinine ratio. An increased cumulative APD/mid-parenchymal ratio with biomarkers together had a fairly good sensitivity and specificity for detection of DRF < 40%.Conclusions: According to our data, the APD/mid-parenchymal ratio alone has good efficacy in prediction of surgery and abnormal RS findings especially when combined with urine biomarkers.

Exposure to an Extended-Interval, High-Dose Gentamicin Regimen in the Neonatal Period Is Not Associated With Long-Term Nephrotoxicity

Objectives: To assess the association between gentamicin exposure and subclinical signs of nephrotoxicity in school children who were exposed to a high-dose gentamicin regimen in the neonatal period.Methods: Children receiving three or more doses (6 mg/kg) of gentamicin as neonates were invited to a follow-up in school age. We evaluated potential signs of subclinical nephrotoxicity with four validated urine biomarkers: protein-creatinine ratio (PCR), albumin-creatinine ratio (ACR), kidney injury molecule-1 (KIM-1), and N-acetyl-beta-D-glucosaminidase (NAG) normalized for urine creatinine (NAG-Cr). In addition, blood pressure was measured. The measures of gentamicin exposure were cumulative dose (mg/kg) and highest trough plasma concentration (TPC) in mg/L. We used logistic and linear regression and non-parametric kernel regression to analyze the relationship between gentamicin exposure and the urine biomarkers.Results: A total of 222 gentamicin exposed children were included. As neonates, the children were exposed to a median (interquartile range-IQR) cumulative gentamicin dose of 36 (26–42) mg/kg and the median (IQR) TPC was 1.0 (0.7–1.3) mg/L. At follow-up, 15 children (6.8%) had either one abnormal urine biomarker value (13 children) or two abnormal urine biomarker values (2 children). These 17 biomarker values were all marginally above the suggested upper cutoff, and included the following markers; KIM-1 (n = 2), NAC-Cr (n = 5), ACR (n = 6), and PCR (n = 4). All other 207 children had normal sets of all four urine biomarkers. One child had hypertension. There were no differences in gentamicin exposure, gestational age (GA) at birth or birth weight between the group of 15 children with one or two abnormal urine biomarker values compared to the other 207 children who had normal biomarker values. Using different regression analyses, we did not find any association between gentamicin exposure (cumulative dose and/or TPC) and the urine biomarker values.Conclusions: Exposure to an extended-interval, high-dose gentamicin regimen in the neonatal period was not associated with signs of subclinical nephrotoxicity in schoolchildren. We therefore suggest that the gentamicin treatment regimen evaluated in this study is safe in terms of long-term nephrotoxicity.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT03253614.

Relationship between Urine Creatinine and Urine Osmolality in Spot Samples among Men and Women in the Danish Diet Cancer and Health Cohort

Assays of urine biomarkers often use urine creatinine to account for urinary dilution, even though creatinine levels are influenced by underlying physiology and muscle catabolism. Urine osmolality—a measure of dissolved particles including ions, glucose, and urea—is thought to provide a more robust marker of urinary dilution but is seldom measured. The relationship between urine osmolality and creatinine is not well understood. We calculated correlation coefficients between urine creatinine and osmolality among 1375 members of a subcohort of the Danish Diet, Cancer, and Health Cohort, and within different subgroups. We used linear regression to relate creatinine with osmolality, and a lasso selection procedure to identify other variables that explain remaining variability in osmolality. Spearman correlation between urine creatinine and osmolality was strong overall (ρ = 0.90; 95% CI: 0.89–0.91) and in most subgroups. Linear regression showed that urine creatinine explained 60% of the variability in urine osmolality, with another 9% explained by urine thallium (Tl), cesium (Cs), and strontium (Sr). Urinary creatinine and osmolality are strongly correlated, although urine Tl, Cs, and Sr might help supplement urine creatinine for purposes of urine dilution adjustment when osmolality is not available.

Nephroprotective Activity of Sophora interrupta bedd. against Gentamicin Induced Acute Renal Toxicity in Wistar Rats: An Experimental Study

Background: Based on ayurvedic/folklore medicine majority of the medicinal plants are used for treatment of different ailments. Sophora interrupta as traditional medicine focused to do the research work for protection of renal injury. Aim: The present study was investigated the nephroprotective activity of Sophora interrupta bedd. against gentamicin-induced acute renal toxicity in wistar rats. Study Design Rats have received gentamicin (40 mg/kg) intraperitoneally (i.p.) once daily for 5 days of the study to induce nephrotoxicity along with test extract of Sophora interrupta bedd. at a dose of 200 &400 mg/kg, p.o. for 21 days. Urinary parameters like Creatinine, Urea, and Uric acid; Biochemical parameters like Alanine transaminase (ALT), Aspartate transaminase (AST), Lactate dehydrogenase (LDH), and Gamma Glutamyl Transferase (GGT), Creatinine, Total protein, and Albumin were measured along with tissue parameters and histopathological observations were carried out. Results: The test extracts Sophora interrupta bedd. showed a prominent protective role against the gentamicin-induced nephrotoxicity with significant (P=.001) restoration in abnormal plasma & urine biomarkers as compared to the gentamicin-induced group. Treatment with both the doses (200 & 400 mg/kg) of Sophoria extract showed significantly (P=.001; P=0.01) modified levels of antioxidant enzymes when compared to gentamicin-induced animals evidenced by structural restoration of the kidney. Conclusion: These findings concluded that, Sophora interrupta bedd. exhibits a protective role against Gentamicin induced nephrotoxicity.