Early renal and vascular damage within the normoalbuminuria condition

Abstract

Objective: A continuous association between albuminuria and cardiorenal risk exists further below moderately increased albuminuria ranges. If only based in albumin to creatinine ratio (ACR) higher than 30 mg/g, a significant percentage of individuals may be out of the scope for therapeutic management. Despite epidemiological outcomes, the identification of biochemical changes linked to early albuminuria is underexplored, and normoalbuminuric individuals are usually considered at no risk in clinical practice. Here, we aimed to identify early molecular alterations behind albuminuria development. Methods: Hypertensive patients under renin–angiotensin system (RAS) suppression were classified as control, (ACR < 10 mg/g) or high-normal (ACR = 10–30 mg/g). Urinary protein alterations were quantified and confirmed by untargeted and targeted mass spectrometry. Coordinated protein responses with biological significance in albuminuria development were investigated. Immunohistochemistry assays were performed in human kidney and arterial tissue to in situ evaluate the associated damage. Results: A total of 2663 identified proteins reflect inflammation, immune response, ion transport and lipids metabolism (P value ≤ 0.01). A1AT, VTDB and KNG1 varied in high-normal individuals (P value < 0.05), correlated with ACR and associated with the high-normal condition (odds ratio of 20.76, 6.00 and 7.04 were found, respectively (P value < 0.001)). After 12 months, protein variations persist and aggravate in progressors to moderately increased albuminuria. At tissue level, differential protein expression was found in kidney from individuals with moderately increased albuminuria and atherosclerotic aortas for the three proteins, confirming their capacity to reflect subclinical organ damage. Conclusion: Early renal and vascular damage is molecularly evidenced within the normoalbuminuria condition.

The Lower Limit of Reference of Urinary Albumin/Creatinine Ratio and the Risk of Chronic Kidney Disease Progression in Patients With Type 2 Diabetes Mellitus

“…Furthermore, in a recent study by Santiago-Hernandez et al. ( 26 ), early renal and vascular damage was shown in patients with normal albuminuria. Hence, in accordance with our findings, a UACR >10 mg/g was associated with the risk of CKD progression.…”

Gene replacement therapy for Lafora disease in theEpm2a-/-mouse model

“…For differential quantitation in the proteomic and phosphoproteomic analysis, peptides were labeled with the Tandem Mass Tag 11 Plex (TMT11-Plex) technique. Identification and quantification of proteins were performed using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) 46,47 .…”

“…Data were analyzed using a logarithmic statistical model (log2), enabling the estimation of peptide and protein abundances (Zq). For the quantification of changes in peptide phosphorylation, the abundance of phospho-peptides was assessed using the corresponding standardized log2 ratio (Zp) 46,47 .…”

Association of high‐normal albuminuria and vascular aging: Hanzhong adolescent hypertension study

“…Most studies found that the incidence of subclinical atherosclerosis or arterial stiffness is increased with a mild elevated but normal UACR level in patients with hypertension or diabetes. [18][19][20] Logtransformed UACR with base 10 (lg-UACR) was found to be related to PWV in high-normal albuminuria participants especially in male, elderly over 65 years old, or normotensives in Chinese population. 21 However, few studies have investigated the association between highnormal albuminuria and vascular aging in Chinese general people with middle age.…”