Urinary protein and enzyme excretion as markers of tubular damage

D’Amico, Giuseppe; Bazzi, Claudio

doi:10.1097/00041552-200311000-00011

Cited by 109 publications

(56 citation statements)

References 30 publications

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“…Recent studies suggest that damage to the proximal tubule is a determinant of early renal insufficiency in diabetes (54). A well-established noninvasive surrogate for proximal tubule damage is elevated excretion of NAGase, a 140-kDa brush border lysosomal enzyme that is released posttranslationally by proximal tubules after injury (13). Moreover, the high molecular weight of NAGase precludes glomerular filtration, making urine NAGase activity a relatively specific marker of tubular injury.…”

Section: Identification Of Differentially Expressed Genes In Db/db Kimentioning

confidence: 99%

“…Damage to the proximal tubule has emerged as a determinant of tubulo-interstitial inflammation and fibrosis in diabetic nephropathy (29,54). Elevated excretion of NAGase, a surrogate for proximal tubule damage (13), is associated with diminished eGFR in crosssectional (44) and longitudinal (29) studies of diabetes. We found that urine levels of ET-1, GDF15, and IL-6 are associated with NAGase.…”

Section: ϫ2mentioning

confidence: 99%

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The renal transcriptome of db/db mice identifies putative urinary biomarker proteins in patients with type 2 diabetes: a pilot study

Simonson

Tiktin

Debanne

et al. 2012

American Journal of Physiology-Renal Physiology

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The renal transcriptome of db/db mice identifies putative urinary biomarker proteins in patients with type 2 diabetes: a pilot study. Am J Physiol Renal Physiol 302: F820-F829, 2012. First published December 28, 2011 doi:10.1152/ajprenal.00424.2011.-We sought to identify novel urinary biomarkers of kidney function in type 2 diabetes. We screened the renal transcriptome of db/db and db/m mice for differentially expressed mRNA transcripts that encode secreted proteins with human orthologs. Whether elevated urine levels of the orthologous proteins correlated with diminished glomerular filtration rate was tested in a cross-sectional study of n ϭ 56 patients with type 2 diabetes. We identified 36 putative biomarker genes in db/db kidneys: 31 upregulated and 5 downregulated. Urinary protein levels of six selected candidates (endothelin-1, lipocalin-2, transforming growth factor-␤, growth and differentiation factor-15, interleukin-6, and macrophage chemoattractant protein-1) were elevated in type 2 diabetic patients with subnormal glomerular filtration rate (i.e., Ͻ90 ml·min Ϫ1 ·1.73 m Ϫ2 ), independent of microalbuminuria, age, sex, race, and use of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists. In contrast, urinary levels of fibroblast growth factor were not increased. A composite variable of urine albumin and any of the six candidate markers was associated with subnormal estimated glomerular filtration rate more closely than albumin alone. In addition, urinary endothelin-1, growth and differentiation factor-15, and interleukin-6 were associated with a marker of proximal tubule damage, N-acetyl-␤-D-glucosaminidase activity. These results suggest that gene expression profiling in diabetic mouse kidney can complement existing proteomic-based approaches for renal biomarker discovery in humans.

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Section: Identification Of Differentially Expressed Genes In Db/db Kimentioning

confidence: 99%

Section: ϫ2mentioning

confidence: 99%

The renal transcriptome of db/db mice identifies putative urinary biomarker proteins in patients with type 2 diabetes: a pilot study

Simonson

Tiktin

Debanne

et al. 2012

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

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“…These factors have been extensively studied in nephrotoxicity related to heavy metals, glomerulonephritis and diabetic nephropathy (35). Indeed, it has been demonstrated that excretion of larger amounts of tubular proteins may precede glomerular involvement in diabetic nephropathy, even before the appearance of microalbuminuria.…”

Section: Tubular Proteins As Early Markers Of Ta/if Developmentmentioning

confidence: 99%

Proximal tubular dysfunction as an indicator of chronic graft dysfunction

Câmara¹,

Williams

Pacheco-Silva³

2009

Braz J Med Biol Res

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New strategies are being devised to limit the impact of renal sclerosis on graft function. Individualization of immunosuppression, specifically the interruption of calcineurin-inhibitors has been tried in order to promote better graft survival once chronic graft dysfunction has been established. However, the long-term impact of these approaches is still not totally clear. Nevertheless, patients at higher risk for tubular atrophy and interstitial fibrosis (TA/IF) development should be carefully monitored for tubular function as well as glomerular performance. Since tubular-interstitial impairment is an early event in TA/IF pathogenesis and associated with graft function, it seems reasonable that strategies directed at assessing tubular structural integrity and function would yield important functional and prognostic data. The measurement of small proteins in urine such as α-1-microglobulin, Nacetyl-beta-D-glucosaminidase, alpha/pi S-glutathione transferases, β-2 microglobulin, and retinol binding protein is associated with proximal tubular cell dysfunction. Therefore, its straightforward assessment could provide a powerful tool in patient monitoring and ongoing clinical assessment of graft function, ultimately helping to facilitate longer patient and graft survival associated with good graft function.

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“…Moreover, urinary NAG increases significantly during necrosis of the tubular epithelium, and this change occurs much earlier than do changes in blood urea nitrogen and Cr. 35 Jiang et al demonstrated that urine NAG levels were more sensitive than serum creatinine levels for predicting AKI development in the early postop period of unilateral PNL operations. 2 Moreover, in the current study, we observed progressive increases in urine NAG levels during the post-PNL period.…”

Section: Discussionmentioning

confidence: 99%

Potential biomarkers for the early detection of acute kidney injury after percutaneous nephrolithotripsy

et al. 2015

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This study aims to investigate the role of urinary biomarkers in the determination of the potential risks of renal parenchymal tubular damage in adult patients who underwent percutaneous nephrolithotomy (PNL) with the indication of renal stone. A randomized and prospective controlled study was performed between June and December 2013. We enrolled 29 consecutive patients with renal calculi42 cm and who underwent PNL, as well as 47 healthy control subjects. Urine samples, including 2 h before surgery, 2 and 24 h after surgery were collected from the patient group. Freshly voided urine samples were collected from the control group. Kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-glucosaminidase (NAG), and liver-type fatty acid binding protein (LFABP) levels were measured from these urine samples. The mean KIM-1/Cr value that measured 24 h after the operation was statistically significant, higher than its preoperative (preop) level (p ¼ 0.045). A significant difference was detected between the mean preop and postoperative (postop) 24 h NAG/Cr values (p50.001). Also, postop 24 h NGAL/Cr levels were statistically significant, higher than its preop levels (p ¼ 0.013). According to the comparison of preop and postop levels, an increase in LFABP/Cr values secondary to surgical intervention was observed without any statistically significant difference. Besides the LFABP/Cr levels do not change after percutaneous kidney surgery, KIM-1/Cr, NAG/Cr, and NGAL/Cr levels increase postop period, especially at 24 h. Further studies with a larger series and repeated measurements should be performed to clarify if they can be used to demonstrate renal damage after percutaneous surgery or not.

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Urinary protein and enzyme excretion as markers of tubular damage

Abstract: The measurement of urinary excretion of tubular enzymes and microproteins may be clinically useful in several different kidney diseases (such as acute tubular necrosis, glomerulonephritis) both for diagnosis and prediction of fractional outcome.

Cited by 109 publications

References 30 publications

The renal transcriptome of db/db mice identifies putative urinary biomarker proteins in patients with type 2 diabetes: a pilot study

The renal transcriptome of db/db mice identifies putative urinary biomarker proteins in patients with type 2 diabetes: a pilot study

Proximal tubular dysfunction as an indicator of chronic graft dysfunction

Potential biomarkers for the early detection of acute kidney injury after percutaneous nephrolithotripsy

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