The role of the kidney in erythropoiesis

Abstract

SummaryThe relationship between the kidney and erythropoiesis has been investigated.Bilateral nephrectomy abolishes erythropoiesis in dogs maintained by peritoneal lavage. Removal of both kidneys is followed by a rapid depletion of erythroblasts from the marrow; often none could be found after 72 hours.Ferrokinetic agrees completely with marrow observations; iron59 T/2 is increased : 299 minutes (90 minutes in controls); plasma iron turnover is lowered: 0,24 mg/kg/day (0,64 mg/kg/day in con-trols); Fe59 uptake into red cells is strongly reduced: 6,1 % against 70 % in normal dogs.Severe bleedings performed immediatly after bilateral nephrectomy do not enhance erythropoiesis; despite this stimulation the same pattern of erythroblasts disappearance and of iron measurement is observed as in unbled nephrectomized dogs.Although bilateral ureteral ligation results in the same elevation of blood urea nitrogen and the same degree of starvation as in the nephrectomized group, erythropoiesis is essentially normal in ureter ligated dogs : iron59 T/2 averages 96 minutes and plasma iron turnover 0,48 mg/kg/day; Fe59 uptake into red cells reaches 61,3%.An active erythropoietic factor is demonstrated in plasma and urine of bled dogs by Fe59 red cells in corporation assay on starved rats. A very striking erythropoietic factor response is obtained when severe anemia is produced (hematocrit less than 15%). Urine erythropoietic activity follows plasma activity.Bilateral nephrectomy abolishes capacity of anemic dogs to produce erythropoietin. This is not observed after ureteral ligation.Homogenates of kidney, liver and spleen tissue from anemic dogs are assayed for erythropoietic activity. A slightly but significantly higher incorporation of Fe59 into rat red cells results from administration of an extract of anemic kidney than from extracts of normal kidney or anemic liver or anemic spleen.Erythropoiesis is investigated in chronic uremic patients and in acute anuric patients.Severe erythroblastopenia (5%) follows rapidly acute renal failure; a moderately lowered erythroblasts percentage (13%) is observed in chronic uremic patients.Plasma iron turnover is slightly lowered and Fe59 maximal incorporation into red cells is definitely reduced in both conditions.The Fe59 uptake averages 57 % in chronic patients and 42 % in the acute anuric group (controls: 84%). Some patients with acute renal failure disclose Fe59 uptake into red cells as low as uptake observed in bilaterally nephrectomized dogs, while others have a normal uptake despite similar erythroblastopenia. This discrepancy is not understood.Red cells survival measured by chromium51 method is reduced in chronic uremic patients. Hemodialysis prevents this investigation in anuric patients.These studies strongly suggest that the kidney is involved in erythropoietin production. The hypothesis that renal anemia results from marrow intoxication can hardly be supported in the light of these observations.Therapeutic considerations are outlined.