Inflammatory mediators in the adipo-renal axis: leptin, adiponectin, and soluble ICAM-1

Abstract

Background: A lower 24-h urine pH (24h-pH), i.e., a higher renal excretion of free protons, at a given acid load to the body, denotes a reduction in the kidney's capacity for net acid excretion (NAE). There is increasing evidence - not only for type 2 diabetes patients, but also for healthy individuals - that higher body fatness or waist circumference (WC) negatively impact on renal function to excrete acids (NAE). We hypothesized that adiposity-related inflammation molecules may mediate this relation between adiposity and renal acid excretion function. Methods: Twelve biomarkers of inflammation were measured in fasting blood samples from 162 adult participants (18-25y) of the DONALD study, who had undergone anthropometric measurements and collected 24-h urine samples. Both Baron and Kenny's steps (B&Ks) to test mediation and causal mediation analysis were conducted to examine the potential mediatory roles of biomarkers of inflammation in the WC-24h-pH relationship after strictly controlling for lab-measured NAE. Results: In B&Ks mediation analysis, leptin, soluble intercellular adhesion molecule-1 (sICAM-1), and adiponectin significantly associated with the outcome 24h-pH and attenuated the WC-pH relation. In agreement herewith, causal mediation analysis estimated the "natural indirect effects" of WC on 24h-pH via leptin (P=0.01) and adiponectin (P=0.03) to be significant with a trend for sICAM-1 (P=0.09). The calculated proportions mediated by leptin, adiponectin and sICAM-1 were 64%, 23%, and 12%, respectively. Conclusion: Both mediation analyses identified an inflammatory (leptin) and an anti-inflammatory (adiponectin) cytokine along with sICAM-1 as being potentially involved in mediating adiposity-related influences on renal acid excretion capacity.

Protein intake and risk of urolithiasis and kidney diseases: an umbrella review of systematic reviews for the evidence-based guideline of the German Nutrition Society

“…Even with HPI of around 80 to 100 g/d, mean 24-h urine pH can be kept at ≥ 6 through moderate alkali equivalent ingestion [ 33 , 64 ]. Besides this, HPI with a higher NAE, higher age (> 50 years) [ 67 ], higher BMI or body fat [ 66 , 68 , 69 ], and other features of the metabolic syndrome including insulin resistance [ 68 , 70 ] each contribute to urine pH reductions. Thus, the NutriGrade rating of ‘low’ obtained for a potential constancy of the urine pH along with rises in protein intake [ 18 ] suggests that HPI does not necessarily increase renal “free proton stress”.…”

Higher Renal Net Acid Excretion, but Not Higher Phosphate Excretion, during Childhood and Adolescence Associates with the Circulating Renal Tubular Injury Marker Interleukin-18 in Adulthood

“…After an overnight fast, venous blood samples (<20 mL) were collected, centrifuged at 4 • C within 15 min, and stored at −80 • C. Serum IL-18 (Human IL-18 ELISA, MBL, Nagoya, Japan) and serum or plasma concentrations of 10 other biomarkers of inflammation were measured at the Institute for Clinical Diabetology (German Diabetes Center, Düsseldorf, Germany) using highly sensitive ELISAs as previously described (leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), omentin, IL-1 receptor antagonist (IL-1RA), chemerin, fetuin-A, IL-6, fibroblast growth factor-21 (FGF21), soluble Eselectin (sE-selectin)) [41]. Plasma glucose, LDL and HDL cholesterol, as well as uric acid were determined at the clinic lab of the pediatric clinic Dortmund, Germany, and high-sensitivity C-reactive protein (hsCRP) at the lab of Institute for Clinical Diabetology with a Roche/Hitachi Cobas c311 analyser (Roche diagnostics, Mannheim, Germany).…”

The Leptin-to-Adiponectin Ratio in Inflammation

“…Given that it is still unclear if all methods for quantifying leptin and adiponectin yield similar results, additional studies are needed to make this determination. Finally, various previous human studies have measured leptin and adiponectin in plasma/serum, saliva, hair, and/or urine [30,31,[64][65][66][67][68][69][70][71][72][73][74]. There may be methods that would allow the comparison of levels of leptin and adiponectin across sample types, but additional studies are needed to explore this possibility.…”