Albumin Urinary Excretion Is Associated with Increased Levels of Urinary Chemokines, Cytokines, and Growth Factors Levels in Humans.

Bengt Fellström,Lars Lind,Kim Kultima,Inga Soveri,Johanna Helmersson-Karlqvist,Johan Ärnlöv,Måns Thulin,Anders Larsson

doi:10.3390/biom11030396

Abstract

The aim of the present study was to study the associations between urine albumin excretion, and a large number of urinary chemokines, cytokines, and growth factors in a normal population. We selected 90 urine samples from individuals without CVD, diabetes, stroke or kidney disease belonging to the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females, all aged 75 years). Urinary cytokine levels were analyzed with two multiplex assays (proximity extension assays) and the cytokine levels were correlated with urine albumin. After adjustment for sex, body mass index (BMI), estimated glomerular filtration rate (eGFR), smoking and multiplicity testing, 11 biomarkers remained significantly associated with urine albumin: thrombospondin 2, interleukin 6, interleukin 8, hepatocyte growth factor, matrix metalloproteinase-12 (MMP-12), C-X-C motif chemokine 9, tumor necrosis factor receptor superfamily member 11B, osteoprotegerin, growth-regulated alpha protein, C-X-C motif chemokine 6, oncostatin-M (OSM) and fatty acid-binding protein, intestinal, despite large differences in molecular weights. In this study, we found associations between urinary albumin and both small and large urine proteins. Additional studies are warranted to identify cytokine patterns and potential progression markers in various renal diseases.

Highlights

The measurements of urinary albumin/total protein excretion play key roles in the detection and classification of renal disease [1]
After adjustment for sex, urinary creatinine, estimated glomerular filtration rate (eGFR), body mass index (BMI), smoking, exercise habits and multiplicity testing, 11 biomarkers remained significantly associated with urine albumin (thrombospondin 2, interleukin 6, interleukin 8, hepatocyte growth factor, matrix metalloproteinase-12 (MMP-12), C-X-C motif chemokine 9, tumor necrosis factor receptor superfamily member 11B, osteoprotegerin, growth-regulated alpha protein, C-X-C motif chemokine 6, oncostatin-M (OSM) and fatty acid-binding protein, intestinal) (Table 2)
The study subjects were recruited from a community living cohort without any prior diagnosed kidney injury or compromised eGFR

Summary

Introduction

The measurements of urinary albumin/total protein excretion play key roles in the detection and classification of renal disease [1]. Even small amounts of albumin, i.e., microalbuminuria, are associated with increased morbidity and mortality and are part of the chronic kidney disease staging according to the Kidney Disease: Improving. Global Out- comes (KIDGO) guidelines [2]. Water and small molecules can freely pass through the glomerular filter. The permeability is depending on the size. Under normal conditions the glomerular membrane is almost impermeable to albumin due to the size and charge of albumin [3,4]. The reference method for albuminuria is the measurement of albumin in a 24-h urine collection. Twenty-four-hour collections are burdensome for patients to perform and subject to errors resulting from erroneous collection periods or incomplete collections

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