Albuminuria in individuals whose body mass index exceeds 40 kg/m(2) is associated with the presence of large glomeruli, thickened basement membrane and epithelial cellular (podocyte) distortion.
Obstructive sleep apnea magnifies glomerular injury as well, probably through a vasoconstrictive mechanism.
Insulin resistance from excess
fatty acids is exacerbated by decreased secretion of high molecular weight
adiponectin from adipose cells in the obese state.
Adiponectin potentiates
insulin in its post-receptor signaling resulting in
glucose oxidation in mitochondria. Recent studies of podocyte physiology have concentrated on the structural and functional requirements that prevent glomerular
albumin leakage. The architecture of the podocyte involves
nephrin and
podocin,
proteins that cooperate to keep slit pores between foot processes competent to retain
albumin.
Insulin and
adiponectin are necessary for high-energy
phosphate generation. When
fatty acids bind to
albumin, the toxicity to proximal renal tubules is magnified.
Albumin and
fatty acids are elevated in urine of individuals with
obesity related
nephrotic syndrome.
Fatty acid accumulation and
resistin inhibit
insulin and
adiponectin. Study of
cytokines produced by adipose tissue (
adiponectin and
leptin) and macrophages (
resistin) has led to a better understanding of the relationship between weight and
hypertension.
Leptin, is presumably secreted after food intake to inhibit the midbrain/hypothalamic appetite centers. Resistance to
leptin results in excess signaling to hypothalamic sympathetics leading to
hypertension. Demonstration of the existence of a cerebral receptor mutation provide evidence for a role in
hypertension of a central nervous reflex
arc in humans. Further understanding of
obesity-related renal dysfunction has been accomplished recently using experimental models. Rapid
weight loss following
bariatric surgery may reverse renal pathology of
obesity with restoration of normal blood pressure.