WhizBang

For years, we nephrologists have taught physiology as if the kidney were one giant nephron. We know it isn’t, and that function varies from section to section of the kidney at any given time. We are born with more nephrons than needed, because life damages them. By the time you turn 40, about 10% of your original filtering units have scarred and gone to nephron heaven.

Likewise, we tend to think of the glomerulus as a single capillary when really it is a knot of vessels that split after the afferent arteriole and the come back together by the efferent vessel. Flow and pressure dynamics within these vessels have not been studied adequately for technical reasons. Two abstracts at Experimental Biology aim to help fill this gap.

First, a brief review.

Now that we are straight on terminology and some physics, let’s approach these abstracts in the order I viewed them

E549 748.11 The Distribution of Blood in Renal Glomerular
Capillaries Is a New Physiological Parameter, Which Is Affected
by Diabetes and ACE-inhibition. J.S. Engbjerg, D. Sardella,
L. Bordoni, F. Trepiccione, G. Capasso, L. Østergaard,
G. George Rhodes, R. Sandoval, T. Ring, B. Molitoris, S.
Frische. Aarhus University, Denmark, University of Campania
“Luigi Vanvitelli”, Italy and Indiana University.

In this study, two-photon in vivo microscopy was used to measure velocity in glomerular capillaries after plasma labeling with dextran. Red blood cell shadows could be observed over time as dark (unlabelled) spots. They examined velocities in 2582 capillaries from 253 glomeruli in 38 rats. In addition to normal rats, a group with early diabetes induced by streptozocin 7 days earlier and a group made hyperglycemic by glucose infusion were examined. Studies were also performed in an aging model of chronic kidney disease (CKD), with and without 10 weeks of lisinopril treatment.

Control rats showed a velocity of 3.74 mm/s. Velocity was reduced in diabetes and to a lesser degree in acute hyperglycemia. When variation in velocity throughout the glomerulus was studied, it was significantly lower in diabetic and acutely hyperglycemic rats as well. In the CKD group, velocity and variation were similar to younger controls, but lisinopril treatment reduced both velocity and variation.

We always think about flow in capillaries, and that is not what was measured here. We do not know the capillary areas, so we cannot go there. Relatively subtle changes in velocity may result in similar flows because of differences in capillary diameters. Nor do we now what the function of these glomeruli and kidneys are at the time of study. Future work with single nephron GFR is planned, I am assured by the authors.

Next up we have an in silico approach to the problem.

E551 748.13 Glomerular Capillary Hypertrophy in the
Diabetic Rat Normalizes Wall Shear Stress: A Modeling Study.
O. Richfield, R. Cortez, L.G. Navar. Tulane University and
Tulane University School of Medicine.

Diabetes results in impairment of autoregulation in the kidney, with increases in glomerular pressure and plasma flow. It is assumed that this results in increased sSS in the capillaries, but over time capillary diameter increases, so SS may b reduced. However, that means an increase in HS is sustained, and that may impact podocytes. That which is adaptive may be maladaptive in the long run.

Using previously published models of rat glomerular capillary beds and earlier micropuncture work and modeling, the authors have developed and validated an anatomically accurate mathematical model of glomerular filtration in vivo. I won’t go into the mathematics here because my eyes will glaze over, and I will just write gibberish. However, this model may provide important data to examine others’ in vivo data (see abstract above; these two authors were already plotting) as well as sending adequate mechanical signals to cells in vitro (see earlier post).

A fascinating day for the mechanically minded in physiology running about the poster sessions. More fun and knowledge clearly lies ahead.