Dataset Information

Urinary MMP-9/UCr association with albumin concentration and albumin-creatinine-ratio in Mexican patients with type 2 diabetes mellitus.

ABSTRACT:

Background

Chronic kidney disease is one of the most common complications of type 2 diabetes mellitus (T2DM), causing an increased risk of cardiovascular morbidity and mortality. Matrix metalloproteinase (MMP) activity has been proposed as useful biomarker for diabetic renal and vascular complications.

Methods

A cross-sectional study was conducted among T2DM patients who attended a public secondary hospital in Mexico. We performed clinical, biochemical, and microbiological assessments, as well chronic kidney disease diagnosis according to the KDIGO guideline. Urinary MMP-9 was quantified by ELISA and adjusted using urinary creatinine (UCr).

Results

A total of 111 patients were included. Most participants were women (66%). Mean age was 61 ± 10 years and median T2DM duration was estimated at 11 years. Through multivariate analysis, MMP-9/UCr was found to be associated with albumin concentration and albumin to creatinine ratio.

Discussion

Validation of non-invasive biomarkers of chronic kidney disease among T2DM patients is necessary. Here, we demonstrate MMP-9/UCr as a potential biomarker of albumin concentration and albumin to creatinine ratio in Mexican patients with T2DM.

SUBMITTER: Arcos-Sacramento VG

PROVIDER: S-EPMC7749659 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Urinary MMP-9/UCr association with albumin concentration and albumin-creatinine-ratio in Mexican patients with type 2 diabetes mellitus.

Arcos-Sacramento Víctor Gildardo VG Sampieri Clara Luz CL Sandoval-Lozano Víctor Hugo VH Orozco-Ortega Rubén Arturo RA Acuña-Hernández Mariel Alejandra MA Morales-Romero Jaime J Hernández-Hernández Magda Elena ME Rodríguez-Hernández Arturo A

PeerJ 20201216

<h4>Background</h4>Chronic kidney disease is one of the most common complications of type 2 diabetes mellitus (T2DM), causing an increased risk of cardiovascular morbidity and mortality. Matrix metalloproteinase (MMP) activity has been proposed as useful biomarker for diabetic renal and vascular complications.<h4>Methods</h4>A cross-sectional study was conducted among T2DM patients who attended a public secondary hospital in Mexico. We performed clinical, biochemical, and microbiological assessm ...[more]

PMID: 33362965

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Project description:BackgroundDiabetic kidney disease is the most common cause of chronic kidney disease (CKD). An early event in diabetic kidney disease is alteration of the glomerular basement membrane and the mesangial expansion. Matrix metalloproteinases (MMP) are a family of endopeptidases responsible for controlling the pathophysiological remodeling of tissues, including renal tissues. MMP-9 in human urine has been proposed as a marker of diabetic nephropathy and urinary tract infections (UTI).MethodsA cross-sectional study was conducted in type 2 diabetes mellitus (T2DM) patients who receive first level medical attention in Mexico. We used ELISA to measure MMP-9 levels in the urine of subjects with T2DM ≥ 18 years of age, who fulfilled the clinical requirements for calculation of glomerular filtration rate (GFR), according to the K/DOQI guide, in an attempt to identify whether MMP-9 levels in T2DM differ in patients with and without renal impairment. Univariate and multivariable analyses were performed in order to identify the association between MMP-9 and renal impairment.ResultsIncluded in the study were 34 (45%) subjects with renal impairment and 42 (55%) without. In the group with renal impairment, 10 subjects corresponded to stages 1-2 and 24 subjects corresponded to stage 3, according to their values of GFR and urinary albumin, following that proposed by the K/DOQI. No differences were found relating to sex, age, having or not having a partner, education, being able to read and write a message and duration of T2DM. Moreover, no differences were found between the groups in terms of weight, height, body mass index, waist size in general and frequency of UTI. In contrast, serum creatinine and urinary albumin were higher in the group with renal impairment, while GFR was greater in the group without renal impairment. Levels of MMP-9 were greater in women compared to men. Through univariate analysis in the general population, the presence of MMP-9 and that of its percentile 90 (P90) P90 were associated with the renal impairment group; however, in patients without UTI, only the presence of MMP-9 was associated with the renal impairment group, and no association was found with its P90. Multivariate analysis revealed an association between MMP-9 and its P90 with renal impairment.DiscussionIt is necessary to validate sensitive and non-invasive biological markers of CKD. We demonstrate that the presence and P90 of urinary MMP-9 are associated with renal impairment in Mexican patients with T2DM. While high levels of MMP-9 were associated to females and UTI, the presence of UTI was not associated with the incidence of renal impairment.

Project description:ImportanceAlthough cumulative evidence suggests that elevated urinary albumin-to-creatinine ratio (UACR) in the normal range (<30 mg/g) may be associated with an increased risk of mortality, few studies have investigated whether cardiovascular health (CVH) modifies the harmful outcomes of high-normal UACR.ObjectiveTo investigate associations of traditionally normal UACR and CVH with all-cause mortality.Design, setting, and participantsThis cohort study used National Health and Nutrition Examination Survey data from 2005 through 2018 and linked mortality information until 2019. Data were analyzed from March 1 through October 31, 2023. The study included adult participants aged 20 to 79 years with a normal UACR (<30 mg/g) based on Kidney Disease: Improving Global Outcomes criteria.ExposuresThe UACR was treated as a continuous variable and categorized into tertiles delineated as low (<4.67 mg/g), medium (4.67-7.67 mg/g), and high (7.68 to <30 mg/g). Cardiovascular health was assessed using Life's Essential 8 scores and grouped as poor (0-49 points), moderate (50-79 points), and ideal (80-100 points).Main outcomes and measuresMultivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of UACR with all-cause mortality in total participants and as stratified by CVH groups.ResultsThe study included 23 697 participants (mean [SD] age, 45.58 [15.44] years; 11 806 women [49.7%] and 11 891 men [50.3%]). During the median 7.8 years (range, 4.5-11.1 years) of follow-up, 1403 deaths were recorded. Near-linear associations were observed for continuous UACR and CVH with all-cause mortality. Compared with the low UACR group, high UACR in the normal range showed an increased mortality risk in the moderate and poor CVH groups (CVH [50-79]: HR, 1.54 [95% CI, 1.26-1.89]; CVH [0-49]: HR, 1.56 [95% CI, 1.10-2.20]), with a significant multiplicative interaction of UACR and CVH (P < .001).Conclusions and relevanceThe findings suggest that high UACR within the normal range is associated with a significantly increased risk of all-cause mortality, with the association more pronounced in adults with poor CVH status. These findings highlight the importance of risk management for early kidney dysfunction, particularly among individuals with poor CVH.

Project description:Aims/hypothesisWe examined whether candidate biomarkers in serum or urine can improve the prediction of renal disease progression in type 1 diabetes beyond prior eGFR, comparing their performance with urinary albumin/creatinine ratio (ACR).MethodsFrom the population-representative Scottish Diabetes Research Network Type 1 Bioresource (SDRNT1BIO) we sampled 50% and 25% of those with starting eGFR below and above 75 ml min-1 [1.73 m]-2, respectively (N = 1629), and with median 5.1 years of follow-up. Multiplexed ELISAs and single molecule array technology were used to measure nine serum biomarkers and 13 urine biomarkers based on our and others' prior work using large discovery and candidate studies. Associations with final eGFR and with progression to <30 ml min-1 [1.73] m-2, both adjusted for baseline eGFR, were tested using linear and logistic regression models. Parsimonious biomarker panels were identified using a penalised Bayesian approach, and their performance was evaluated through tenfold cross-validation and compared with using urinary ACR and other clinical record data.ResultsSeven serum and seven urine biomarkers were strongly associated with either final eGFR or progression to <30 ml min-1 [1.73 m]-2, adjusting for baseline eGFR and other covariates (all at p<2.3 × 10-3). Of these, associations of four serum biomarkers were independent of ACR for both outcomes. The strongest associations with both final eGFR and progression to <30 ml min-1 [1.73 m]-2 were for serum TNF receptor 1, kidney injury molecule 1, CD27 antigen, α-1-microglobulin and syndecan-1. These serum associations were also significant in normoalbuminuric participants for both outcomes. On top of baseline covariates, the r2 for prediction of final eGFR increased from 0.702 to 0.743 for serum biomarkers, and from 0.702 to 0.721 for ACR alone. The area under the receiver operating characteristic curve for progression to <30 ml min-1 [1.73 m]-2 increased from 0.876 to 0.953 for serum biomarkers, and to 0.911 for ACR alone. Other urinary biomarkers did not outperform ACR.Conclusions/interpretationA parsimonious panel of serum biomarkers easily measurable along with serum creatinine may outperform ACR for predicting renal disease progression in type 1 diabetes, potentially obviating the need for urine testing.

Dataset Information

Urinary MMP-9/UCr association with albumin concentration and albumin-creatinine-ratio in Mexican patients with type 2 diabetes mellitus.

Background

Methods

Results

Discussion

Publications

Urinary MMP-9/UCr association with albumin concentration and albumin-creatinine-ratio in Mexican patients with type 2 diabetes mellitus.

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