Tubular reabsorption and diabetes-induced glomerular hyperfiltration.
Elevated glomerular filtration rate (GFR) is a common observation in early diabetes mellitus and closely correlates with the progression of diabetic nephropathy. Hyperfiltration has been explained to be the result of a reduced load of sodium and chloride passing macula densa, secondarily to an increased proximal reabsorption of glucose and sodium by the sodium-glucose co-transporters. This results in an inactivation of the tubuloglomerular feedback (TGF), leading to a reduced afferent arteriolar vasoconstriction and subsequently an increase in GFR. This hypothesis has recently been questioned due to the observation that adenosine A(1)-receptor knockout mice, previously shown to lack a functional TGF mechanism, still display a pronounced hyperfiltration when diabetes is induced. Leyssac demonstrated in the 1960s (Acta Physiol Scand58, 1963:236) that GFR and proximal reabsorption can work independently of each other. Furthermore, by the use of micropuncture technique a reduced hydrostatic pressure in Bowman's space or in the proximal tubule of diabetic rats has been observed. A reduced pressure in Bowman's space will increase the pressure gradient over the filtration barrier and can contribute to the development of diabetic hyperfiltration. When inhibiting proximal reabsorption with a carbonic anhydrase inhibitor, GFR decreases and proximal tubular pressure increases. Measuring intratubular pressure allows a sufficient time resolution to reveal that net filtration pressure decreases before TGF is activated which highlights the importance of intratubular pressure as a regulator of GFR. Taken together, these results imply that the reduced intratubular pressure observed in diabetes might be crucial for the development of glomerular hyperfiltration.
Persson
P
P
Division of Integrative Physiology, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Hansell
P
P
Palm
F
F
D000042:Absorption; D000818:Animals; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D025461:Feedback, Physiological; D005919:Glomerular Filtration Rate; D006439:Hemodynamics; D006801:Humans; D006874:Hydrostatic Pressure; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000503:physiopathology; D007684:Kidney Tubules / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D015854:Up-Regulation