Abstract
Early detection of obesity-related glomerulopathy in humans is challenging as it might not be detected by routine biomarkers of kidney function. This study’s aim was to use novel kidney biomarkers and contrast-enhanced ultrasound (CEUS) to evaluate the effect of obesity development and weight-loss on kidney function, perfusion, and injury in dogs. Sixteen healthy lean adult beagles were assigned randomly but age-matched to a control group (CG) (n = 8) fed to maintain a lean body weight (BW) for 83 weeks; or to a weight-change group (WCG) (n = 8) fed the same diet to induce obesity (week 0–47), to maintain stable obese weight (week 47–56) and to lose BW (week 56–83). At 8 time points, values of systolic blood pressure (sBP); serum creatinine (sCr); blood urea nitrogen (BUN); serum cystatin C (sCysC); urine protein-to-creatinine ratio (UPC); and urinary biomarkers of glomerular and tubular injury were measured. Glomerular filtration rate (GFR) and renal perfusion using CEUS were assayed (except for week 68). For CEUS, intensity- and time-related parameters representing blood volume and velocity were derived from imaging data, respectively. At 12–22% weight-gain, cortical time-to-peak, representing blood velocity, was shorter in the WCG vs. the CG. After 37% weight-gain, sCysC, UPC, glomerular and tubular biomarkers of injury, urinary immunoglobulin G and urinary neutrophil gelatinase-associated lipocalin, respectively, were higher in the WCG. sBP, sCr, BUN and GFR were not significantly different. After 23% weight-loss, all alterations were attenuated. Early weight-gain in dogs induced renal perfusion changes measured with CEUS, without hyperfiltration, preceding increased urinary protein excretion with potential glomerular and tubular injury. The combined use of routine biomarkers of kidney function, CEUS and site-specific urinary biomarkers might be valuable in assessing kidney health of individuals at risk for obesity-related glomerulopathy in a non-invasive manner.
Highlights
Besides diabetes and hypertension, excess weight in the form of adipose tissue increases the risk of developing obesity-related glomerulopathy and chronic kidney disease in humans [1]
Values of serum creatinine and blood urea nitrogen (BUN) for all dogs were
Of the other kidney-related measurements, an increase in body fat % was related to an increase in urine protein-to-creatinine ratio (UPC), urinary immunoglobulin G (uIgG)/c and uNGAL/c, and a decrease in mGFR (P < 0.05)
Summary
Excess weight in the form of adipose tissue increases the risk of developing obesity-related glomerulopathy and chronic kidney disease in humans [1]. The mechanism of how excess weight can lead to chronic kidney disease is not fully understood, physical (e.g., fat accumulation and ectopic fat in kidney), inflammatory (e.g., adipokines like leptin) and renal hemodynamic factors (e.g., increased glomerular filtration rate (GFR) and renal blood flow due to increased tubular sodium reabsorption) might play important roles [2]. Because of the kidney’s compensatory ability, obesity-related kidney injury can develop asymptomatically and might not be detected either by routine kidney function biomarkers (e.g., serum creatinine, blood urea nitrogen (BUN)) or by GFR measurements early in the disease [4]. More sensitive and/or site-specific biomarkers of kidney injury and function that can aid in the early detection, monitoring, and potentially prevention of obesityrelated glomerulopathy are needed [4]. UIgG, uRBP, and uNGAL can detect diabetic nephropathy in an early stage [11]
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