Dataset Information

Mannose-binding lectin activation is associated with the progression of diabetic nephropathy in type 2 diabetes mellitus patients.

ABSTRACT:

Background

We aimed to investigate whether mannose-binding lectin (MBL) activation contributed to the progression of diabetic nephropathy (DN), and its role in predicting the renal prognosis of DN.

Methods

Seventy-seven patients who received renal biopsy in the First Affiliated Hospital, College of Medicine, Zhejiang University between August 2013 and September 2016 were enrolled in the study. These patients were followed up until the endpoint of end-stage renal disease (ESRD) or the last follow-up time of August 31, 2018. They were divided into ESRD group (33 patients) and non-ESRD group (44 patients). Their baseline characteristics and MBL levels (serum and urine) were compared between groups. The correlation between single nucleotide polymorphisms (SNPs) of the MBL2 gene and renal outcomes was also analyzed.

Results

The median (interquartile ranges) of serum and urine MBL levels were significantly higher in ESRD group than those in non-ESRD group [2,783.75 (1,244.28, 3,837.07) vs. 1,141.60 (652.67, 3,188.44) ng/mL, P=0.016; 1.02 (0.43, 2.05) vs. 0.27 (0.04, 0.58) ng/mg, P<0.01, respectively]. Both univariate and multivariate Cox analysis showed that serum MBL >1,108.75 ng/mL (stratified by maximum Youden index) was an independent predictor for ESRD [hazard ratio (HR) =4.164, 95% confidence interval (CI): 1.601-10.833, P=0.003; HR =4.644, 95% CI: 1.320-16.337, P=0.017; respectively]. For the patients with rs1800450 SNPs of MBL2 gene, patients with homozygous genotype (GG) had higher serum MBL level (median 2,963.52 ng/mL) compared with those with heterozygous genotype (GA) (median 665.38 ng/mL) (P<0.001). MBL2 rs1800450 GA genotype was an independent protective factor for ESRD with a HR of 0.485 (95% CI: 0.237-0.991; P=0.047).

Conclusions

Activation of MBL contributed to the progression of DN. The rs1800450 SNP of the MBL2 gene may be of value in predicting the progression to ESRD in DN patients.

SUBMITTER: Cai K

PROVIDER: S-EPMC7723547 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Mannose-binding lectin activation is associated with the progression of diabetic nephropathy in type 2 diabetes mellitus patients.

Cai Kedan K Ma Yanhong Y Wang Junni J Nie Wanyun W Guo Junmin J Zhang Minqiao M Yang Yi Y Chen Jianghua J Han Fei F

Annals of translational medicine 20201101 21

<h4>Background</h4>We aimed to investigate whether mannose-binding lectin (MBL) activation contributed to the progression of diabetic nephropathy (DN), and its role in predicting the renal prognosis of DN.<h4>Methods</h4>Seventy-seven patients who received renal biopsy in the First Affiliated Hospital, College of Medicine, Zhejiang University between August 2013 and September 2016 were enrolled in the study. These patients were followed up until the endpoint of end-stage renal disease (ESRD) or ...[more]

PMID: 33313144

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Project description:ObjectiveTo examine the association of bradykinin and related peptides with the development of diabetic nephropathy lesions in 243 participants with type 1 diabetes (T1D) from the Renin-Angiotensin System Study who, at baseline, were normoalbuminuric, normotensive and had normal or increased glomerular filtration rate (GFR).DesignPlasma concentrations of bradykinin and related peptides were measured at baseline by quantitative mass spectrometry. All participants were randomly assigned at baseline to receive placebo, enalapril or losartan during the 5 years between kidney biopsies. Kidney morphometric data were available from kidney biopsies at baseline and after 5 years. Relationships of peptides with changes in morphometric variables were assessed using multiple linear regression after adjustment for age, sex, diabetes duration, HbA1c, mean arterial pressure, treatment assignment and, for longitudinal analyses, baseline structure.ResultsBaseline median albumin excretion rate of study participants was 5.0 μg/min, and mean GFR was 128 mL/min/1.73 m2. After multivariable adjustment, higher plasma concentration of bradykinin (1-8) was associated with greater glomerular volume (partial r = 0.191, P = 0.019) and total filtration surface area (partial r = 0.211, P = 0.010), and higher bradykinin (1-7) and hyp3-bradykinin (1-7) were associated with lower cortical interstitial fractional volume (partial r = -0.189, P = 0.011; partial r = -0.164, P = 0.027 respectively). In longitudinal analyses, higher bradykinin was associated with preservation of surface density of the peripheral glomerular basement membrane (partial r = 0.162, P = 0.013), and for participants randomized to losartan, higher hyp3-bradykinin (1-8) was associated with more limited increase in cortical interstitial fractional volume (partial r = -0.291, P = 0.033).ConclusionsHigher plasma bradykinin and related peptide concentrations measured before clinical onset of diabetic nephropathy in persons with T1D were associated with preservation of glomerular structures, suggesting that elevations of these kinin concentrations may reflect adaptive responses to early renal structural changes in diabetic nephropathy.

Dataset Information

Mannose-binding lectin activation is associated with the progression of diabetic nephropathy in type 2 diabetes mellitus patients.

Background

Methods

Results

Conclusions

Publications

Mannose-binding lectin activation is associated with the progression of diabetic nephropathy in type 2 diabetes mellitus patients.

Similar Datasets

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