Adaptive changes in GFR, tubular morphology, and transport in subtotal nephrectomized kidneys: modeling and analysis.
Removal of renal mass stimulates anatomical and functional adaptations in the surviving nephrons, including elevations in single-nephron glomerular filtration rate (SNGFR) and tubular hypertrophy. A goal of this study is to assess the extent to which the concomitant increases in filtered load and tubular transport capacity preserve homeostasis of water and salt. To accomplish that goal, we developed computational models to simulate solute transport and metabolism along nephron populations in a uninephrectomized (UNX) rat and a 5/6-nephrectomized (5/6-NX) rat. Model simulations indicate that nephrectomy-induced SNGFR increase and tubular hypertrophy go a long way to normalize excretion, but alone are insufficient to fully maintain salt balance. We then identified increases in the protein density of Na+-K+-ATPase, Na+-K+-2Cl-cotransporter, Na+-Cl-cotransporter, and epithelial Na+channel, such that the UNX and 5/6-NX models predict urine flow and urinary Na+and K+excretions that are similar to sham levels. The models predict that, in the UNX and 5/6-NX kidneys, fractional water and salt reabsorption is similar to sham along the initial nephron segments (i.e., from the proximal tubule to the distal convoluted tubule), with a need to further reduce Na+reabsorption and increase K+secretion primarily along the connecting tubules and collecting ducts to achieve balance. Additionally, the models predict that, given the substantially elevated filtered and thus transport load among each of the surviving nephrons, oxygen consumption per nephron segment in a UNX or 5/6-NX kidney increases substantially. But due to the reduced nephron population, whole animal renal oxygen consumption is lower. The efficiency of tubular Na+transport in the UNX and 5/6-NX kidneys is predicted to be similar to sham.
Department of Mathematics, Duke University, Durham, North Carolina; alayton@math.duke.edu.
Anita T
AT
Layton
Centre National de la Recherche Scientifique, ERL 8228, Paris, France.|Department of Bioengineering, Boston University, Boston, Massachusetts.
Aurélie
A
Edwards
Departments of Medicine and Pharmacology, University of California San Diego, La Jolla, California; and.|San Diego Veterans Affairs Healthcare System, San Diego, California.
Volker
V
Vallon
D000222:Adaptation, Physiological; D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D053503:Epithelial Sodium Channels / Q000378:metabolism; D005919:Glomerular Filtration Rate; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D023421:Models, Animal; D008954:Models, Biological; D009392:Nephrectomy / Q000009:adverse effects / Q000379:methods*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D065667:Renal Elimination; D065608:Renal Reabsorption; D012964:Sodium / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D064486:Solute Carrier Family 12, Member 3 / Q000378:metabolism
D053503:Epithelial Sodium Channels; C578876:Slc12a3 protein, rat; D028021:Sodium-Potassium-Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium
epithelial transport; homeostasis; remnant kidney