Why is erythropoietin made in the kidney? The kidney functions as a critmeter

Erythropoietin is distinct among the hematopoietic growth factors because i t is produced primarily in the kidneys rather than the bone marrow. The kid ney functions as a critmeter in that it senses oxygen tension and extracell ular volume. By regulating red cell mass through erythropoietin and plasma volume through excretion of salt and water, the kidney sets the hematocrit at a normal value of 45%. This is not a random number, but a value that max imizes oxygen delivery to peripheral tissues. The ability of the kidney to coordinate these two volumes to generate a hematocrit of 45% establishes it as the logical site for erythropoietin production. The kidney has the uniq ue ability to translate a measure of plasma volume as tissue oxygen pressur e required to regulate erythropoietin production. I hypothesize that the cr itmeter is a functional unit that regulates the hematocrit. The critmeter i s found at the tip of the juxtamedullary region of the cortical labyrinth i n the kidney, where erythropoietin is made physiologically. Renal vasculatu re and nephron segment heterogeneity in sodium reabsorption generate the ma rginal tissue oxygen pressure required to trigger the production of erythro poietin. The balance of the oxygen consumption for sodium reabsorption and the oxygen delivery to the proximal tubule is reflected by the tissue oxyge n pressure that determines red blood cell mass adjusted to plasma volume. F actors that affect blood supply and sodium reabsorption in a discordant man ner may modulate the critmeter(eg, angiotensin II). Examples of clinical di sorders caused by dysfunction or resetting of the critmeter are described. (C) 2001 by the National Kidney Foundation, Inc.