Emerging Urinary Markers of Renal Injury in Obstructive Nephropathy

Lucarelli, Giuseppe; Mancini, Vito; Galleggiante, Vanessa; Rutigliano, Monica; Vavallo, Antonio; Battaglia, Michele; Ditonno, Pasquale

doi:10.1155/2014/303298

Cited by 65 publications

(58 citation statements)

References 63 publications

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“…Neutrophil gelatinase‐associated lipocalin (NGAL) is an early and sensitive marker of injury that is selectively expressed in the TALH and collecting ducts during obstruction‐induced renal injury (Lucarelli et al. ). NGAL kidney protein levels were increased 7, 14, and 21 days after UUO (Fig.…”

Section: Resultsmentioning

confidence: 99%

Uromodulin deficiency alters tubular injury and interstitial inflammation but not fibrosis in experimental obstructive nephropathy

et al. 2018

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Human GWAS and Mendelian genetic studies have linked polymorphic variants and mutations in the human uromodulin gene (UMOD) with chronic kidney disease. The primary function of this kidney‐specific and secreted protein remains elusive. This study investigated whether UMOD deficiency modified responses to unilateral ureteral obstruction (UUO)‐induced kidney injury. Kidneys harvested from groups of wild‐type (UMOD+/+) and knockout (UMOD−/−) male mice (n = 7–10 each) were studied on days 7, 14, and 21. Compared to sham kidneys, UMOD protein levels increased 9–13x after UUO and were associated with increased urinary UMOD levels. Kidney KIM‐1 protein levels were higher in the UMOD−/− groups at all time‐points (4–14x). The UMOD−/− groups also had higher KIM‐1 kidney‐to‐urine relative ratios (5–35x). In vitro studies using KIM‐1 expressing 769‐P cells showed lower KIM‐1 levels in the presence of UMOD protein. Levels of proapoptotic genes and the epithelial cell apoptotic protein marker M30 were significantly lower in the UMOD−/− groups. Both M30 and KIM‐1 colocalized with intraluminal UMOD protein deposits. Interstitial inflammation was less intense in the UMOD−/− groups. Renal fibrosis severity (kidney collagen mRNA and protein) was similar in both genotypic groups on days 7, 14, and 21. Our findings suggest a role for UMOD‐dependent inhibition of KIM‐1 expression and its apoptotic cell scavenging responses during chronic obstruction‐associated tubular injury.

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Section: Resultsmentioning

confidence: 99%

Uromodulin deficiency alters tubular injury and interstitial inflammation but not fibrosis in experimental obstructive nephropathy

et al. 2018

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“…Urinary biomarkers are recent candidates for alternative diagnostic modalities studied widely. The current study aimed to evaluate the relationship between biomarkers and severity of obstructions (5)(6)(7)(8)(9)(10)(11).…”

Section: Contextmentioning

confidence: 99%

The Role of Urinary Biomarker Levels in Assessing the Presence and Severity of Ureteropelvic Junction Obstruction in Children: A Systematic Review and Meta-Analysis

Alipour¹,

Mohammadjafari

Rafiei³

et al. 2016

J Pediatr Rev

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Context: Ureteropelvic junction obstruction (UPJO) is the most common obstructive disease of the urinary tract in infancy and childhood with a prevalence of 15% -45% in neonates with antenatal hydronephrosis. The diagnosis of UPJO should be confirmed by imaging studies -most of which have a propensity to radiation exposure. Objectives:The current study aimed to present a review protocol to assess the role of measuring urinary biomarkers to distinguish severe UPJO from milder forms of the disease. Data Sources:The database of UPJO studies was searched and studies that compared the levels of urinary biomarkers with the gold standard (i e, dynamic renal scans) for UPJO diagnosis were selected. Severity assessment was done quantitatively.Study Selection: Three hundred fifty-eight articles were identified across the electronic databases. Twenty-seven articles were selected for the final analyses.Data Extraction: Data were extracted independently by three reviewers and analyzed using STATA software version 12.Results: Meta-analysis of studies showed that patients with severe UPJO had significantly higher biomarker levels than those with mild to moderate obstruction, with a pooled standardized mean difference (SMD) of 0.5 (confidence interval (CI) 95%, 0.34 -0.67; P < 0.001); and significantly higher biomarker standardized to urinary creatinine levels than those with mild to moderate obstruction, with a pooled SMD of 1.02 (95% CI, 0.88 -1.16; P < 0.001). Meta-analysis showed that patients with severe UPJO had significantly higher biomarker levels than healthy children, with a pooled SMD of 1.27 (CI 95%, 1.16 -1.39; P < 0.001); and significantly higher biomarker standardized to urinary creatinine levels than healthy children, with a pooled SMD of 1.14 (CI 95%, 0.95 -1.32; P < 0.001). Conclusions:The assessment of urinary biomarkers is a helpful tool to assess the presence and severity of UPJO, but there is little published data on each of the studied biomarkers. It is suggested to perform future larger multicenter studies.

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“…Increased urinary excretion of MCP-1 have been observed in various glomerular diseases with correlations observed between urinary levels and degree of tubulointerstitial involvement [11,12]. On the other hand, epidermal growth factor (EGF), a peptide growth factor produced by the ascending loop of Henle and the distal convoluted tubule, seem to have a protective role in tubulointerstitial damage.…”

Section: Introductionmentioning

confidence: 99%

Urine Epidermal Growth Factor, Monocyte Chemoattractant Protein-1 or Their Ratio as Biomarkers for Interstitial Fibrosis and Tubular Atrophy in Primary Glomerulonephritis

Worawichawong

Radinahamed

et al. 2016

Kidney Blood Press Res

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Background/Aims: The degree of tubular atrophy and interstitial fibrosis (IFTA) is an important prognostic factor in glomerulonephritis. Imbalance between pro-inflammatory cytokines such as monocyte chemoattractant protein-1 (MCP-1) and protective cytokines such as epidermal growth factor (EGF) likely determine IFTA severity. In separate studies, elevated MCP-1 and decreased EGF have been shown to be associated with IFTA severity. In this study, we aim to evaluate the predictive value of urinary EGF/MCP-1 ratio compared to each biomarker individually for moderate to severe IFTA in primary glomerulonephritis (GN). Methods: Urine samples were collected at biopsy from primary GN (IgA nephropathy, focal and segmental glomerulosclerosis, minimal change disease, membranous nephropathy). MCP-1 and EGF were analyzed by enzyme-linked immunosorbent assay. Results: EGF, MCP-1 and EGF/MCP-1 ratio from primary GN, all correlated with IFTA (n=58). By univariate analysis, glomerular filtration rate, EGF, and EGF/MCP-1 ratio were associated with IFTA. By multivariate analysis, only EGF/ MCP-1 ratio was independently associated with IFTA. EGF/MCP-1 ratio had a sensitivity of 88% and specificity of 74 % for IFTA. EGF/MCP-1 had good discrimination for IFTA (AUC=0.85), but the improvement over EGF alone was not significant. Conclusion: EGF/MCP-1 ratio is independently associated IFTA severity in primary glomerulonephritis, but the ability of EGF/ MCP-1 ratio to discriminate moderate to severe IFTA may not be much better than EGF alone.

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Emerging Urinary Markers of Renal Injury in Obstructive Nephropathy

Cited by 65 publications

References 63 publications

Uromodulin deficiency alters tubular injury and interstitial inflammation but not fibrosis in experimental obstructive nephropathy

Uromodulin deficiency alters tubular injury and interstitial inflammation but not fibrosis in experimental obstructive nephropathy

The Role of Urinary Biomarker Levels in Assessing the Presence and Severity of Ureteropelvic Junction Obstruction in Children: A Systematic Review and Meta-Analysis

Urine Epidermal Growth Factor, Monocyte Chemoattractant Protein-1 or Their Ratio as Biomarkers for Interstitial Fibrosis and Tubular Atrophy in Primary Glomerulonephritis

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