Resumen

MASCHERONI, Claudio A. PATHOPHYSIOLOGY OF GLOMERULAR HYPERFILTRATION IN DIABETES: PART II. Rev. nefrol. dial. traspl. [online]. 2014, vol.34, n.4, pp.208-229. ISSN 2346-8548.

Glomerular hyperfiltration (HF) in diabetic renal disease is a complex hemodynamic phenomenon that occurs early in the course of the disease and most likely has associated with poor prognosis with respect to the development of microalbuminuria and overt diabetic nephropathy. The factors involved in its pathophysiology are multiple and include the diabetic milieu and the effects of several humoral factors such as nitric oxide, prostaglandins, renin angiotensin aldosterone system, atrial natriuretic peptide, reactive oxygen species and other humoral and growth factors that act basically causing or enhancing the afferent arteriole vasodilation (AA) or vasoconstriction over the efferent arteriola, all considered primary vascular factors. However, these factors could not entirely explain other observed abnormalities that include primary tubular abnormalities such as increased reabsorption in the proximal tubule probably influenced by renal growth and cotransporter SGLT2 upregulation. This increased proximal reabsorption elicit a lower solute delivery to the macula densa (MD), which would be incompatible with glomerulotubular balance function, but would with actions mediated by tubuloglomerular feedback (TGF) that would sense low NaCl concentration at the MD, deactivating TGF and producing AA vasodilation, thereby increasing the glomerular filtration rate (GFR) and renal plasma flow (RPF), characteristic of the HF process. These two (vascular and tubular) processes could act synergistically or simultaneously, depending on the metabolic and evolutionary conditions of diabetic kidney disease. Similar mechanisms may explain the salt paradox, that is, a low-salt diet exacerbates the phenomenon of HF and a high-salt diet decreases GFR and RPF, which could have unexpected clinical implications. To the usually used therapeutic tools of strict metabolic control, low protein diet and ACE inhibitors or AT1receptor blockers use, not tested clinically for this purpose, but widely used in clinical settings, seems add new specific cotransporter SGLT2 inhibitors. These agents have shown beneficial effects in the treatment of many aspects of the diabetic disease, and recent works focused specifically on the effects over HF appear to be encouraging. Potential therapeutic benefits of peptide-C needs to be probed in clinical trials. It is essential to persevere in improving our knowledge to identify the pathophysiologic mechanisms involved in HF, what will allow a better understanding of this complex phenomenon and a better therapeutic approach.

Palabras clave : pathophysiology; glomerular hyperfiltration; diabetes.

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