The mammalian kidney is a complex organ that has several metabolically active cell types to aid in filtration, salt-water balance, and electrolyte homeostasis in the body.

These functions are done primarily through the nephron, which relies on strict regulation of various metabolic pathways. Any deviations in the metabolic profile of nephrons or their precursor cells called nephron progenitors can lead to renal pathologies and abnormal development. Metabolism encompasses the mechanisms by which cells generate intermediate molecules and energy in the form of adenosine triphosphate (ATP).

ATP is required by all cells and is mainly produced through glycolysis, fatty acid oxidation, and oxidative phosphorylation. During kidney development, self-renewing or proliferating cells rely on glycolysis to a greater extent than the other metabolic pathways to supply energy, replenish reducing equivalents, and generate nucleotides.

However, terminally differentiated cell types rely more heavily on fatty acid oxidation and oxidative phosphorylation performed in the mitochondria to fulfill energy requirements. Further, the mature nephron is comprised of distinct segments, and each section utilizes metabolic pathways to varying degrees depending on the specific function. This review will focus on major metabolic processes performed by the nephron during health and disease.

Nephron metabolism

Nephron progenitors are proliferative and self-renewing until they receive signals to undergo differentiation, which involves metabolic reprogramming towards mitochondrial respiration. The nephron progenitors give rise to structures such as the glomerulus, proximal tubules, a loop of Henle, and distal tubules.

Although most of these structures have not been well characterized metabolically, studies predominantly done in the The 1970s and 1980s investigated enzyme abundance and function in segments of a nephron. These studies found that each section has a unique metabolic profile, which likely corresponds to its purpose. Based on these investigations, the specific metabolic pathways of each segment can be hypothesized.

A summary of the predicted metabolic pathways utilized along the nephron is Although the proteins are expressed and their function is known, future investigations into kidney metabolism should include experimentation to determine the types of definitively metabolism used along the nephron as well as by the other kidney compartments.

It is clear that metabolism plays a significant role in kidney development And pathological kidney conditions. Although metabolic processes are readily investigated, the mechanisms controlling metabolic regulation during kidney development is Not entirely understood. More research into the effect of critical  metabolic regulators on kidney development and nephrogenesis is needed to realize a renal disease better And cancer etiology.

Although challenging, interrogation of the interplay between these complex metabolic processes is critical for uncovering key regulators in developmental and pathological mechanisms.