The hyperfiltration theory: A paradigm shift in nephrology

Abstract

Experimental studies incriminate glomerular hypertension in mediating progressive renal damage after any of a variety of initiating injuries. Prevention of glomerular hypertension by dietary protein restriction or antihypertensive therapy lessens progressive glomerular damage in several experimental models of chronic renal disease. Glomerular hypertension and hyperfiltration also occur in humans with diabetes mellitus, solitary or remnant kidneys, and various forms of acquired renal disease. Clinical studies indicate that dietary protein restriction and antihypertensive therapy also slow progression in many of these disorders. Large multicenter trials confirm the beneficial effects of these therapeutic maneuvers on the rate of progression of chronic renal disease.

A developmental nephron deficit in rats is associated with increased susceptibility to a secondary renal injury due to advanced glycation end-products

“…To the extent that AGE accumulation is a strong predictor of adverse renal outcomes in patients with diabetes, it is possible to speculate that reduced nephron endowment may be associated with accelerated AGE accumulation, and therefore more aggressive renal disease, in the setting of diabetes. This is consistent with the Brenner hypothesis, which links the observed association of reduced nephron number with the subsequent increased risk of renal disease in adults [18]. In support of this concept, Jones et al report exacerbated renal and glomerular hypertrophy in adult LPD rat offspring following induction of streptozotocininduced diabetes and that these glomerular abnormalities persist even when insulin is administered [28].…”

“…In the Brenner hypothesis, one of the key links between reduced nephron endowment and renal disease is systemic hypertension [18]. In a carefully conducted stereological autopsy analysis of kidneys, Keller et al demonstrated that patients with primary hypertension had fewer glomeruli per kidney than their normotensive controls [34].…”

“…It has been proposed previously that a congenital nephron deficit is associated with an increased risk of adult renal disease [18]. However, the precise mechanisms behind this link remain to be established.…”

Reduced Krüppel-Like Factor 2 Aggravates Glomerular Endothelial Cell Injury and Kidney Disease in Mice with Unilateral Nephrectomy

“…1 A reduction in the number of functional nephrons, whether induced genetically, surgically, or by acquired renal disease, contributes to the progression of CKD, likely secondary to glomerular hyperfiltration and hypertrophy. 2 However, the precise mechanism that mediates the progression of CKD in these patients remains unclear.…”

Avaliação da relação proteína-creatinina urinária em gatos com doença renal crônica

“…Essa hiperfiltração leva à esclerose glomerular e proteinúria (Brenner et al 1996). A proteinúria tem sido considerada um importante fator na progressão da DRC em humanos (Willians et al 1988), em cães (Jacob et al 2005) e em gatos (Syme et al 2006).…”