Microalbuminuria and C-reactive protein: Similar messengers of cardiovascular risk?

■ AbstractOBJECTIVES: Oxidative stress can contribute to microvascular complications in diabetes. A decisive event associated with this condition may be the decrease in the synthesis of zinc-containing antioxidant enzymes such as superoxide dismutase and glutathione peroxidase. This consideration led us to investigate the effect of zinc supplementation versus placebo on microalbuminuria in diabetic patients in a randomized double blind clinical trial. METHODS: Fifty diabetic patients with microalbuminuria were enrolled. Fasting plasma glucose, HbA1c, lipid profiles, plasma zinc levels and random urine for albumin and creatinine were measured. Patients randomly received 30 mg elemental zinc (group 1) or placebo (group 2) for 3 months. After a 4 week wash-out period, the groups were crossed over (i.e. the zinc group were given placebo, and the placebo group were given zinc) and the protocol was repeated. RESULTS: From an initial number of 50 selected patients (25 in each of two groups), 39 patients (21 in group 1 and 18 in group 2) completed the study. In group 1, after zinc supplementation, urinary albumin excretion decreased significantly from 86.5 ± 57 to 75 ± 71 mg/g (p = 0.01). After placebo, patients in group 1 showed no significant reduction in microalbuminuria (85 ± 72 mg/g to 83 ± 63 mg/g creatinine). In group 2, no change in albumin excretion was observed after placebo treatment (90.5 ± 63 mg/g to 90 ± 60 mg/g creatinine). After zinc supplementation, a significant reduction was observed in albumin excretion, from 90 ± 60 mg/g to 85 ± 57 mg/g creatinine (p = 0.003). CONCLUSIONS: Zinc supplementation reduced albumin excretion in microalbuminuric type 2 diabetic patients. This outcome may be due to the antioxidant effect of zinc.

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“…However, the correlation between CRP and albuminuria has already been reported to be low [27]. Zinc may also affect the alpha-cell function.…”

Section: Discussionmentioning

confidence: 98%

Effect of Zinc Supplementation on Microalbuminuria in Patients With Type 2 Diabetes: A Double Blind, Randomized, Placebo-Controlled, Cross-Over Trial

Parham¹,

Amini²,

Aminorroaya³

et al. 2008

Rev Diabet Stud

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“…This mechanism could explain the strong association between endothelial albuminuria and cardiovascular disease, 1 and the value of vascular inflammatory markers such as Creactive protein in predicting the progression of cardiovascular and renal disease. 63 The glycocalyx as a therapeutic target Angiotensinconvertingenzyme (ACE) inhibitors and angiotensinreceptor blockers are among the drugs used for renal and cardiovascular protection. These drugs are known to change endothelial haemodynamic function, 64,65 but their exact mechanisms of action in this context are unknown.…”

Section: The Renal-cardiovascular Linkmentioning

confidence: 99%

The glycocalyx—linking albuminuria with renal and cardiovascular disease

2015

Self Cite

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Albuminuria is commonly used as a marker of kidney disease progression, but some evidence suggests that albuminuria also contributes to disease progression by inducing renal injury in specific disease conditions. Studies have confirmed that in patients with cardiovascular risk factors, such as diabetes and hypertension, endothelial damage drives progression of kidney disease and cardiovascular disease. A key mechanism that contributes to this process is the loss of the glycocalyx--a polysaccharide gel that lines the luminal endothelial surface and that normally acts as a barrier against albumin filtration. Degradation of the glycocalyx in response to endothelial activation can lead to albuminuria and subsequent renal and vascular inflammation, thus providing a pathophysiological framework for the clinical association of albuminuria with renal and cardiovascular disease progression. In this Review, we examine the likely mechanisms by which glycocalyx dysfunction contributes to kidney injury and explains the link between cardiovascular disease and albuminuria. Evidence suggests that glycocalyx dysfunction is reversible, suggesting that these mechanisms could be considered as therapeutic targets to prevent the progression of renal and cardiovascular disease. This possibility enables the use of existing drugs in new ways, provides an opportunity to develop novel therapies, and indicates that albuminuria should be reconsidered as an end point in clinical trials.

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“…As putative explanatory variables, we took into account factors known to influence urinary albumin loss and also known to be altered by weight changes, such as the classical CV and metabolic risk factors [17], high sensitive (hs)-CRP [18][19][20][21][22], sodium and protein intake [23,24], and creatinine clearance [25]. We used data obtained from a prospective, observational cohort study derived from general population.…”

Section: Introductionmentioning

confidence: 99%

Impact of weight change on albuminuria in the general population

Bello

Zeeuw

Nahas

et al. 2007

Nephrology Dialysis Transplantation

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Background. Increased levels of albuminuria have been recognized as a feature of obesity and the metabolic syndrome, and to be associated with an increased risk for cardiovascular and renal disease. The impact of weight change on albuminuria and its possible mechanism has not been studied yet in the general population. We investigated this issue in a cohort of the Northern European population. Methods. A total of 6894 participants of the Prevention of Renal and Vascular Endstage Disease (PREVEND) study were evaluated from baseline to a mean period of follow-up of 4.2 years for weight change (gain/loss), and its impact on albuminuria, renal function and cardiovascular risk factors. Participants were categorized into three groups based on absolute change in weight from baseline to follow-up: significant weight loss (>10 kg reduction in weight), stable weight, or significant weight gain (>10 kg increase). Multivariate regression analysis was used to evaluate the effect of baseline characteristics and time-dependent changes in these characteristics on the relationship of weight change with urine albumin excretion (UAE). Results. At follow-up 101 subjects experienced significant weight loss (mean change ¼ À14.2 kg), 348 had significant weight gain (mean change ¼ þ13.4 kg) and the remaining were defined stable in weight (mean change ¼ þ1.4 kg). Weight loss was associated with significant improvement in systolic blood pressure (À11 AE 15 mmHg), diastolic blood pressure (À5 AE 8 mmHg), and cholesterol (À0.7 AE 1.3 mmol/l), even after adjustment for the use of medications (P < 0.001). These parameters worsened significantly in those who substantially gained weight (P < 0.001). Similarly, weight loss was significantly associated with a reduction in UAE (mean À2.2 AE 1.1 mg/24 h), whereas weight gain was associated with a rise in UAE (mean þ0.42 AE 2.0 mg/24 h). Notably, no changes were observed in GFR (assessed as 24 h urinary creatinine clearance) in subjects with weight loss or weight gain. Multivariate regression modelling with changes in UAE as dependent variable-correcting for factors that might explain the association-showed that only part of the relationship between weight changes and changes in UAE was explained by effect of weight change on blood pressure and cholesterol, whereas the association disappeared with changes in CRP in the model (P ¼ 0.50). Conclusion. This is the first population-based longitudinal study to show that changes in weight are associated with parallel changes in albuminuria. This relationship cannot be fully explained by the association between weight and classical cardiovascular risk factors and renal function. Based on our data we hypothesize that weight-induced changes in vascular inflammation may cause changes in albuminuria.

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Microalbuminuria and C-reactive protein: Similar messengers of cardiovascular risk?

Cited by 23 publications

References 64 publications

Effect of Zinc Supplementation on Microalbuminuria in Patients With Type 2 Diabetes: A Double Blind, Randomized, Placebo-Controlled, Cross-Over Trial

Effect of Zinc Supplementation on Microalbuminuria in Patients With Type 2 Diabetes: A Double Blind, Randomized, Placebo-Controlled, Cross-Over Trial

The glycocalyx—linking albuminuria with renal and cardiovascular disease

Impact of weight change on albuminuria in the general population

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