Changes in urine proteome accompanying diabetic nephropathy progression

Lewandowicz, Andrzej; Bakun, Magda; Kohutnicki, Rafał; Fabijańska, Agnieszka; Kistowski, Michał; Imiela, Jacek; Dadlez, Michał

doi:10.20452/pamw.2640

Cited by 18 publications

(17 citation statements)

References 10 publications

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“…However, there is still need for novel markers of renal function deterioration, and both serum and urine markers are being studied in this context. 33,34 A strong correlation between serum uromodulin concentrations and eGFR allows us to assume that serum uromodulin levels may potentially be an alternative indicator of renal function with a similarly high diagnostic accuracy. It may be hypothesized that serum uromodulin levels reflect the number or function of renal tubules.…”

Section: Resultsmentioning

confidence: 99%

Serum uromodulin concentrations correlate with glomerular filtration rate in patients with chronic kidney disease

Fedak¹,

Kuźniewski²,

Fugiel³

et al. 2016

Polish Archives of Internal Medicine

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INTROduCTION Urinary uromodulin excretion has been associated with kidney diseases. However, serum uromodulin concentrations have not been extensively studied in patients with chronic kidney disease (CKD), and the results of published studies are inconsistent.ObjECTIvEs The aims of the study were to evaluate serum uromodulin concentrations in patients with CKD and to assess the utility of serum uromodulin measurements for diagnosing CKD stages.PATIENTs ANd mEThOds This observational study included 170 patients with CKD stages 1 to 5, not treated by renal replacement therapy, and 30 healthy individuals. The serum levels of creatinine, cystatin C, and uromodulin were measured, and estimated glomerular filtration rate (eGFR) was calculated according to the 2012 CKD Epidemiology Collaboration cystatin -creatinine equation.REsuLTs Among patients with CKD, serum uromodulin concentrations were significantly lower than in controls, and were strongly negatively correlated with renal retention markers (ie, serum creatinine and cystatin C) and strongly positively correlated with eGFR. An inverse, hyperbolic relationship between serum creatinine and uromodulin levels was analogous to the well -known association between serum creatinine concentrations and eGFR. A receiver -operating characteristic curve analysis showed a high diagnostic accuracy of the measurement of serum uromodulin concentrations in the assessment of CKD stages.CONCLusIONs Serum uromodulin concentrations are closely correlated with eGFR, which is the recommended measure of renal function. As uromodulin is produced exclusively by renal tubular cells, the assessment of uromodulin levels in patients with CKD may be an alternative method for evaluating the number of functioning nephrons.

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Section: Resultsmentioning

confidence: 99%

Serum uromodulin concentrations correlate with glomerular filtration rate in patients with chronic kidney disease

Fedak¹,

Kuźniewski²,

Fugiel³

et al. 2016

Polish Archives of Internal Medicine

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“…Urine can be obtained noninvasively and is stable enough for proteomic analysis; therefore, some factors identified in the urine through proteomic analysis could provide new tools for the diagnosis and prognosis of glomerular diseases . Lewandowicz et al . applied iTRAQ technology coupled to LC‐MS/MS to analyze changes in urine protein excretion based on the stage of diabetic kidney disease.…”

Section: Discussionmentioning

confidence: 99%

Comparative proteomic analysis of urine and laser microdissected glomeruli in IgA nephropathy

Ning

Yin

et al. 2017

Clin Exp Pharma Physio

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The purpose of the present study was to identify the differential proteins that synchronously change in urine and glomeruli and could be used to monitor glomerular lesions of IgA nephropathy (IgAN). The proteomes of urine and glomeruli from four IgAN patients who were graded III/IV according to the grading system of Lee et al. were compared to the urine proteomes of four healthy volunteers and the glomeruli proteomes of adjacent normal tissue from four patients with renal tumors, respectively. Western blot, enzyme-linked immunosorbent assay and immunofluorescence assay were applied to verify the results of the proteomic analysis. In the proteomic analysis of urine from IgAN patients and healthy volunteers, 714 proteins were identified, with 246 proteins identified as differential proteins. In the proteomic analysis of glomeruli from renal biopsy tissue of IgAN patients and from adjacent normal tissue of patients with renal tumors, 161 proteins were identified altogether, and 20 proteins of these were recognized as differential proteins. After comparatively analyzing the differential proteins identified in the urine and glomeruli, five synchronously changed differential proteins were found: complement C9, Ig kappa chain C region and three cytoskeleton proteins. In summary, our findings indicate that certain immunological indices in urine appear to be associated with glomerular lesions of IgAN.

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“…Moreover, another advantage of using urine, instead of blood, is its easy and non‐invasive collection that allows repeated sampling for disease monitoring. In the last years, several studies have been performed, in urines, aiming to identify biomarkers that can detect early stages of DN and progressive kidney function decline in diabetic patients, as well as biomarkers that can allow for a non‐invasive diagnosis of kidney disease (Chang et al ., ; Chu et al ., ; Manwaring et al ., ; Merchant et al ., ; Lewandowicz et al ., ; Siwy et al ., ; Vitova et al ., ; Wheelock et al ., ).…”

Section: Diabetic Nephropathymentioning

confidence: 99%

“…Lewandowicz et al . () analyzed, by quantitative untargeted proteomics, urine samples of T2DM patients with different DKD stages in order to identify changes in urinary protein excretion. The studied groups were respectively: T2DM patients with no nephropathy ( N = 33), T2DM patients with retinopathy ( N = 15), T2DM patients with overt nephropathy ( N = 24), and a control group of healthy subjects ( N = 27).…”

Section: Diabetic Nephropathymentioning

confidence: 99%

“…Moreover, another advantage of using urine, instead of blood, is its easy and non-invasive collection that allows repeated sampling for disease monitoring. In the last years, several studies have been performed, in urines, aiming to identify biomarkers that can detect early stages of DN and progressive kidney function decline in diabetic patients, as well as biomarkers that can allow for a non-invasive diagnosis of kidney disease (Chang et al, 2017;Chu et al, 2013;Manwaring et al, 2013;Merchant et al, 2013;Lewandowicz et al, 2015;Siwy et al, 2017;Vitova et al, 2017;Wheelock et al, 2017). Siwy et al (2017) by using CE-MS aimed to verify if urinary proteome analysis holds information on disease etiology and allows to discriminate among seven different types of CKD that in the current clinical practice are defined by pathological assessment of renal biopsies.…”

Section: Investigations On Urine Proteome and Metabolome In Dkdmentioning

confidence: 99%

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The role of mass spectrometry in studies of glycation processes and diabetes management

DaRonco

Crotti

Agostini

et al. 2018

Mass Spectrometry Reviews

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In the last decade, mass spectrometry has been widely employed in the study of diabetes. This was mainly due to the development of new, highly sensitive, and specific methods representing powerful tools to go deep into the biochemical and pathogenetic processes typical of the disease. The aim of this review is to give a panorama of the scientifically valid results obtained in this contest. The recent studies on glycation processes, in particular those devoted to the mechanism of production and to the reactivity of advanced glycation end products (AGEs, AGE peptides, glyoxal, methylglyoxal, dicarbonyl compounds) allowed to obtain a different view on short and long term complications of diabetes. These results have been employed in the research of effective markers and mass spectrometry represented a precious tool allowing the monitoring of diabetic nephropathy, cardiovascular complications, and gestational diabetes. The same approaches have been employed to monitor the non‐insulinic diabetes pharmacological treatments, as well as in the discovery and characterization of antidiabetic agents from natural products. © 2018 Wiley Periodicals, Inc. Mass Spec Rev 38:112–146, 2019.

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Changes in urine proteome accompanying diabetic nephropathy progression

Cited by 18 publications

References 10 publications

Serum uromodulin concentrations correlate with glomerular filtration rate in patients with chronic kidney disease

Serum uromodulin concentrations correlate with glomerular filtration rate in patients with chronic kidney disease

Comparative proteomic analysis of urine and laser microdissected glomeruli in IgA nephropathy

The role of mass spectrometry in studies of glycation processes and diabetes management

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