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Microvascular endothelial dysfunction may predict albuminuria in Asians with T2D

Pearl Toh
13 Apr 2018

Impaired endothelial-dependent microvascular reactivity appears to be predictive of albuminuria progression in Asian patients with type 2 diabetes (T2D) who have normal urine albumin levels at baseline, but not in those with microalbuminuria, a prospective longitudinal cohort study suggests.

“Albuminuria progression could reflect changes in the pathophysiology of the leakage of proteins and serves as a biomarker for progression of renal dysfunction … Clinical and epidemiological studies have reported that albuminuria predicts not only the progression of chronic kidney disease, but also cardiovascular morbidity in diabetes patients,” according to the researchers led by Dr Lim Su Chi from Khoo Teck Puat Hospital in Singapore.

After following up 1,098 T2D patients for a median of 3.2 years, 226 patients (20.6 percent) had albuminuria progression, defined as transition from normo- to micro-/macroalbuminuria, or micro- to macroalbuminuria*. [Microcirculation 2018;doi:10.1111/micc.12453]

Endothelial-dependent microvascular reactivity—as indicated by change in blood flow from baseline in response to acetylcholine (ACh)-induced vasodilation, measured using laser Doppler flowmetry—was significantly lower among T2D patients with albuminuria progression than those without (72 percent vs 80 percent; p=0.04).

For every one standard deviation (SD) increase in response to ACh, there was a 15 percent decreased risk of albuminuria progression (odds ratio [OR], 0.85; p=0.04) in univariate analysis, although the association was no longer significant in multivariate analysis (p=0.08).    

Nonetheless, a stratified analysis revealed that a 1-SD increase in response to ACh remained significantly associated with a lower risk of albuminuria progression among patients with baseline normoalbuminuria (OR, 0.76; p=0.03), but not in patients with microalbuminuria (OR, 1.18; p=0.39).

Other predictors for albuminuria progression include insulin use (OR, 2.03; p=0.01 and 2.31; p<0.001 for patients with baseline normoalbuminuria and microalbuminuria, respectively) and poor kidney function, as indicated by LnACR** (OR, 2.32; p<0.001 and 4.49; p<0.001, respectively) and eGFR*** (OR,0.99; p=0.02 and 0.98; p<0.001, respectively).

In contrast, no significant association was found between albuminuria progression and microvascular reactivity independent of the endothelium—as assessed by response to sodium nitroprusside.

“We found that only impaired response to ACh could independently predict albuminuria progression, suggesting that the impaired microvascular function was primarily limited to the endothelium. Although ... we could not exclude possible contribution of endothelium-independent vasodilation completely,” said Lim and co-authors.

According to the researchers, the findings are clinically relevant as previous studies have shown that certain interventions, such as L-arginine (a precursor of nitric oxide for endothelium-dependent vasodilation) and lifestyle modifications involving change in diet and exercise, can potentially reverse endothelial dysfunction. [Kidney Int 2017;92:313-323] 

“Therefore, extensive treatment of microvascular endothelial dysfunction early during the natural history of glucose intolerance might have the potential to retard or prevent the onset of albuminuria in T2D patients,” they suggested.

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Pearl Toh, 3 days ago
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Rachel Soon, 05 Dec 2018

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