Relevance of the tubuloglomerular feedback mechanism in pathophysiology

The balance between a high filtration rate and high reabsorption rate in the kidney is critical in the maintenance of extracellular fluid volume. One of the mechanisms that maintain this balance is the tubuloglomerular feedback (TGF) mechanism, which operates at the level of the macula densa assessing the load and/or solute concentration coming out of the loop of Henle and controlling this load by adjusting the GFR. This review discusses the potential role of the TGF system with respect to volume homeostasis in various conditions where GFR is maintained, decreased, or increased. In most of the states discussed, the TGF system seems to act appropriately regarding volume control; however, trade-off effects occasionally occur. After acetazolamide administration, during extracellular fluid volume contraction or expansion or acute hyperkalemia, the TGF mechanism responds appropriately with regard to volume balance. After a large reduction of renal mass, the system adjusts to function at a higher level of GFR and distal delivery. In chloride-depletion metabolic alkalosis, glomerulonephritis, diabetes mellitus, and acute renal failure, the adaptation of the TGF system appears to be appropriate with regard to volume control; however, it may lead to trade-off effects, such as maintenance of metabolic alkalosis, glomerular hypertension and sclerosis, or depression of GFR, respectively. Because the TGF mechanism often contributes to compensatory adjustments to or development of disease, it can be appreciated that any in-depth evaluation of the mechanisms responsible for various pathophysiologic conditions should include an assessment of the potential role of the TGF mechanism.