Kidney in Long-Term Fasting

As fasting continues into early starvation and beyond, the kidney plays important roles. The renal cortex expresses the enzymes of gluconeogenesis, including glucose 6-phosphatase, and, in late fasting, ~50% of gluconeogenesis occurs here. [Note: A portion of this glucose is used by the kidney itself.] The kidney also provides compensation for the acidosis that accompanies the increased production of ketone bodies (organic acids). The glutamine released from the muscle’s metabolism of BCAA is taken up by the kidney and acted upon by renal glutaminase and glutamate dehydrogenase , producing α-ketoglutarate, which can be used as a substrate for gluconeogenesis, plus ammonia (NH₃₎. The NH₃ picks up protons from ketone body dissociation and is excreted in the urine as ammonium (NH₄⁺), thereby decreasing the acid load in the body (Fig. 1). Therefore, in long-term fasting, there is a switch from nitrogen disposal in the form of urea to disposal in the form of NH₄⁺. [Note: As ketone body concentration rises, enterocytes, typically consumers of glutamine, become consumers of ketone bodies. This allows more glutamine to be available to the kidney.]

Figure 1: Use of glutamine from BCAA catabolism in muscle to generate ammonia (NH₃) used for the excretion of protons (H⁺) as ammonium (NH₄⁺) in the kidneys.