Use of the kidney injury molecule-1 as a biomarker for early detection of renal tubular dysfunction in a population chronically exposed to cadmium in the environment

MicroRNAs (miRNAs) are small noncoding RNAs of 18–23 nucleotides that regulate gene expression. Recently, plasma miRNAs have been investigated as biomarkers for various physiological and pathological conditions. The present study details the conserved miRNA expression profiles of tubular tissues, and discusses whether they could be used to distinguish between proximal tubule injury, diagnose acute kidney injury (AKI), and the early-stage renal tubular dysfunction. miRNA expression was assessed with miRNA array and real-time reverse transcription polymerase chain reaction using the TaqMan system. The expression profiles of miR-200a/b/c, miR-145, miR-192, miR-194, miR-216a/b, miR-217, and miR-449a in human and rat tubular tissues such as the kidneys, lung, small intestine, and various exocrine glands were adequate for discriminating tubular tissues. In the kidney, miR-192 and miR-194 were highly expressed, whereas miR-145 and miR-449a were absent. miR-145 and miR-449a were relatively specifically expressed in small intestine and lung, respectively. Therefore, the combined levels of miR-200a/b/c, miR-192, and miR-194 in plasma were very useful in diagnosing AKI induced by contact freezing in mice. Moreover, urinary miR-200a levels were useful for the diagnosis of renal tubular dysfunction in Dahl salt-sensitive rat with high salt administration. Our results indicate that miRNA expression profiles are useful as biomarkers for identification of various kidney injuries.

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Tenofovir-induced renal tubular dysfunction among human immunodeficiency virus patients on antiretroviral therapy in Nigeria: Prospects for early detection of presymptomatic nephrotoxicity

Kidney Research and Clinical Practice ◽

10.23876/j.krcp.2018.37.3.230 ◽

2018 ◽

Vol 37 (3) ◽

pp. 230-238 ◽

Cited By ~ 1

Author(s):

Irikefe Paul Obiebi ◽

Ebube Amalachukwu Nwannadi

Keyword(s):

Human Immunodeficiency Virus ◽

Antiretroviral Therapy ◽

Early Detection ◽

Tubular Dysfunction ◽

Renal Tubular Dysfunction ◽

Immunodeficiency Virus ◽

Renal Tubular

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Serial Quantification of Urinary Protein Biomarkers to Predict Drug-induced Acute Kidney Injury

Current Drug Metabolism ◽

10.2174/1389200220666190711114504 ◽

2019 ◽

Vol 20 (8) ◽

pp. 656-664 ◽

Cited By ~ 4

Author(s):

Yi Da ◽

K. Akalya ◽

Tanusya Murali ◽

Anantharaman Vathsala ◽

Chuen-Seng Tan ◽

...

Keyword(s):

Acute Kidney Injury ◽

Cystatin C ◽

Calcineurin Inhibitors ◽

Kidney Injury ◽

Tubular Dysfunction ◽

Renal Tubular Dysfunction ◽

Protein Biomarkers ◽

Drug Induced ◽

Beta 2 ◽

Beta 2 Microglobulin

Background: : Drug-induced Acute Kidney Injury (AKI) develops in 10-15% of patients who receive nephrotoxic medications. Urinary biomarkers of renal tubular dysfunction may detect nephrotoxicity early and predict AKI. Methods:: We prospectively studied patients who received aminoglycosides, vancomycin, amphotericin, or calcineurin inhibitors, and collected their serial urine while on therapy. Patients who developed drug-induced AKI (fulfilling KDIGO criteria) were matched with non-AKI controls in a 1:2 ratio. Their urine samples were batch-analyzed at time-intervals leading up to AKI onset; the latter benchmarked against the final day of nephrotoxic therapy in non- AKI controls. Biomarkers examined include clusterin, beta-2-microglobulin, KIM1, MCP1, cystatin-C, trefoil-factor- 3, NGAL, interleukin-18, GST-Pi, calbindin, and osteopontin; biomarkers were normalized with corresponding urine creatinine. Results:: Nine of 84 (11%) patients developed drug-induced AKI. Biomarkers from 7 AKI cases with pre-AKI samples were compared with those from 14 non-AKI controls. Corresponding mean ages were 55(±17) and 52(±16) years; baseline eGFR were 99(±21) and 101(±24) mL/min/1.73m2 (all p=NS). Most biomarker levels peaked before the onset of AKI. Median levels of 5 biomarkers were significantly higher in AKI cases than controls at 1-3 days before AKI onset (all µg/mmol): clusterin [58(8-411) versus 7(3-17)], beta-2-microglobulin [1632(913-3823) versus 253(61-791)], KIM1 [0.16(0.13-0.76) versus 0.07(0.05-0.15)], MCP1 [0.40(0.16-1.90) versus 0.07(0.04-0.17)], and cystatin-C [33(27-2990) versus 11(7-19)], all p<0.05; their AUROC for AKI prediction were >0.80 (confidence intervals >0.50), with average accuracy highest for clusterin (86%), followed by beta-2-microglobulin, cystatin-C, MCP1, and KIM1 (57%) after cross-validation. Conclusion: : Serial surveillance of these biomarkers could improve the lead time for nephrotoxicity detection by days.

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High sucrose diet induces morphological, structural and functional impairments in the renal tubules of Drosophila melanogaster: A model for studying type-2 diabetes mediated renal tubular dysfunction

Insect Biochemistry and Molecular Biology ◽

10.1016/j.ibmb.2020.103441 ◽

2020 ◽

Vol 125 ◽

pp. 103441

Author(s):

Lavi Rani ◽

Sanjay Saini ◽

Neha Shukla ◽

Debapratim Kar Chowdhuri ◽

Naveen Kumar Gautam

Keyword(s):

Type 2 Diabetes ◽

Tubular Dysfunction ◽

Renal Tubular Dysfunction ◽

Renal Tubules ◽

Functional Impairments ◽

Sucrose Diet ◽

High Sucrose Diet ◽

Renal Tubular ◽

High Sucrose

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Renal Sodium Handling in Relation to Environmental and Genetic Factors in Untreated Chinese

American Journal of Hypertension ◽

10.1093/ajh/hpaa160 ◽

2020 ◽

Author(s):

Yuan-Yuan Kang ◽

Yi-Bang Cheng ◽

Qian-Hui Guo ◽

Chang-Sheng Sheng ◽

Qi-Fang Huang ◽

...

Keyword(s):

Blood Pressure ◽

Multiple Testing ◽

Genetic Factors ◽

Blood Pressure Monitoring ◽

Lithium Concentration ◽

Tubular Dysfunction ◽

Renal Tubular Dysfunction ◽

Renal Sodium Handling ◽

Renal Tubular ◽

Sodium Handling

Abstract Background We investigated proximal and distal renal tubular sodium handling, as assessed by fractional excretion of lithium (FELi) and fractional distal reabsorption rate of sodium (FDRNa), in relation to environmental and genetic factors in untreated patients. Methods Our study participants were suspected hypertensive patients being off antihypertensive medication for ≥2 weeks and referred for 24-hour ambulatory blood pressure monitoring. We collected serum and 24-hour urine for measurement of sodium, creatinine and lithium concentration, and calculated FELi and FDRNa. We genotyped 19 SNPs associated with renal sodium handling or blood pressure using the ABI SNapShot method. Results The 1409 participants (664 men, 47.1%) had a mean (±SD) age of 51.0±10.5 years. After adjustment for host factors, both FELi and FDRNa were significantly (P≤0.01) associated with season and humidity, explaining ~1.3% and ~3.5% of the variance, respectively. FELi was highest in autumn and lowest in summer and intermediate in spring and winter (P=0.007). FDRNa was also highest in autumn but lowest in winter and intermediate in spring and summer (P<0.001). Neither FELi nor FDRNa was associated with outdoor temperature or atmospheric pressure (P≥0.13). After adjustment for host and environmental factors and Bonferroni multiple testing, among the 19 studied genetic variants, only rs12513375 was significantly associated with FELi and FDRNa (P≤0.004) and explained about 1.7% of the variance. Conclusions Renal sodium handling as measured by endogenous lithium clearance was sensitive to major environmental and genetic factors. Our finding is towards the use of these indexes for the definition of renal tubular dysfunction.

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