Marked increase in urinary excretion of apolipoproteins in children with nephrolithiasis associated with hypercalciuria

Abstract

We provide proteomic data showing increased urinary excretion of lipid metabolism/transport-related proteins in children with kidney stones and hypercalciuria. These findings suggest that abnormalities in lipid metabolism might play a role in kidney stone formation.

Fatty Acid-Binding Protein 4—An “Inauspicious” Adipokine—In Serum and Urine of Post-Partum Women with Excessive Gestational Weight Gain and Gestational Diabetes Mellitus

“…Dubé et al [52] found decreased maternal plasma levels of total cholesterol, LDL, and HDL, which is in agreement with ours and other authors’ studies [42,43], and they concluded that these results could partly be due to the lack of excessive gestational weight gain in obese women and/or to the unchanged levels of triglycerides and free fatty acids in the venous cord blood despite the increased maternal plasma levels of triglycerides in obese pregnancies. Studies have reported mostly inflammatory changes in the placenta of obese women, such as an accumulation of the immune cells (macrophages and neutrophils) and an increase in the expression of several inflammatory cytokines, such as interleukin-1 (IL-1), IL-6, TNFα, IL-8 [52,54,55].…”

“…Due to its small molecular size, this protein may escape the glomerular sieves and be excreted in the urine if not reabsorbed by the renal tubules. FABP4 may also be produced by the tubular epithelial cells or adjacent tissue [42]. In the healthy kidneys, FABP4 is expressed in the endothelial cells of the tubulointerstitial peritubular capillary and vein in both the cortex and medulla, but not in the glomerular or arterial endothelial cells, under normal physiological conditions [24,43].…”

Fatty acid–binding protein 4 downregulation drives calcification in the development of kidney stone disease

“…39 In addition, urinary FABP4 levels correlate with severity of albuminuria, yearly decrease of glomerular filtration rate in healthy volunteers, 41 and prevalence of pediatric kidney stones. 42 Similar to other FABP4 studies for cardiovascular disease, 43 these studies suggest that upregulation of FABP4 is a risk factor and biomarker for the development of renal disease. On the contrary, we found that both mRNA and protein expression levels of FABP4 were downregulated in papillae with RP, which are considered to be in a pre-stoneforming state in the kidney.…”

“…Secreted FABP4 levels may serve as a marker or therapeutic target for renal diseases. [37][38][39][40][41][42] Circulating serum FABP4 levels have been associated with worsened renal dysfunction in patients with diabetes mellitus, 37,38 a history of cardiovascular events, decreased glomerular filtration rate, 40 or on chronic hemodialysis. 39 In addition, urinary FABP4 levels correlate with severity of albuminuria, yearly decrease of glomerular filtration rate in healthy volunteers, 41 and prevalence of pediatric kidney stones.…”

The Roles of Fatty Acids and Apolipoproteins in the Kidneys

“…ApoC-III plays an important role in triglyceride transport and triglyceride homeostasis [ 155 ]. The concentration of ApoC-III in urinary excretion is significantly associated with urinary calcium excretion in children [ 156 ], thus suggesting that abnormalities in lipid metabolism and APOC3 might play a role in kidney stone formation [ 156 ]. However, ApoC’s physiological role in the kidneys remains to be established.…”