Tamm-Horsfall Protein (THP) is a 95 kD glycoprotein which is secreted in the thick ascending loop of Henle (TALH) of the kidney. After renal tubular damage the secretion of THP is reduced. In diabetes mellitus (DM), TALH has not been studied. To differentiate between glomerular (albumin), proximal tubular microglobulinuria (alpha 1-microglobulin), and TALH function (THP), we investigated 65 patients 4-61 years of age. In well-controlled DM, mean hemoglobin A1 equalled 7.4% and proximal tubular parameters indicated reversible damage early after onset. THP excretion (per 24 hrs or per day) was significantly elevated in DM duration of greater than ten years, suggesting enhanced TALH ion transport (glomerular hyperfiltration). THP secretion decreased in DM duration of greater than 15 years despite normal albumin excretion. Thus, renal THP excretion indicates early medullary dysfunction (TALH) in DM type I.

Adolescent↗

PubMedDate not supplied

Effects of thyroid hormones on heart and kidney functions.

Thyroid hormones affect the functions of several organs including the heart and kidney. Using isolated left papillary muscles we have investigated the action of thyroid hormones on the mechanical and electrical properties of the heart. We found that pure hypothyroidism causes a depression in contractile and electrical parameters, but we noticed that superimposed hypoparathyroidism accounts for the marked prolongation in contractile kinetics and action potential duration. At kidney level we have shown that thyroid hormones affect proximal tubular sodium transport and this effect is only partially mediated by the action of thyroid hormones on Na-K-ATPase activity. Using the micropuncture technique, we hypothesized that the early effect of thyroid hormone action is on the potassium permeability of proximal tubular cell membrane. This latter effect would explain the increase in isotonic fluid reabsorption through an increase in the driving force for sodium. Finally, hypothyroid patients have a decrease in glomerular filtration rate and renal plasma flow that are completely reversed by thyroxine administration. On the other hand, hyperthyroid subjects exhibit a significant increase in both parameters.

Animals↗

PubMedDate not supplied

The use of micropuncture, isolated tubule, and vesicle technique in the study of the action of thyroid hormones on the proximal tubule function.

In hypothyroid rats (TX), the isotonic fluid reabsorption (Jv), that is closely linked to the transepithelial sodium transport (JNa), is impaired. The administration of physiological doses (10 micrograms/kg body weight per day) of tri-iodothyronine (T3) doubles Jv in three days (TX+T3). This phenomenon could be explained by several mechanisms: a direct stimulation of Na-K-ATPase, an increase in the Na+ entry step, changes in the permeability properties of the luminal and/or basal lateral membranes. Using a kinetic microassay, Na-K-ATPase activity was measured in early (S1) and late (S2) proximal tubules segments isolated from control, TX, and TX+3T3 animals. In TX rats the enzyme activity was lower (70%) in both segments versus control rats, it remained unchanged after 3 days, and it increased after 7 days of T3 substitution. The Na+ permeability of brush border membrane (BBM) vesicles isolated from TX and TX+T3 rats was identical. However the valuation of the K+ membrane permeability by in vivo perfusion of the lumen and peritubular space of proximal tubules of TX rats, with perfusate containing the K+ ionophore valinomycin (1 microgram/ml), induced a significant increase in Jv that accounted for 40% of that elicited by T3. Taken together, the in vivo and in vitro experiments suggest that the early effect on Jv of physiological doses of T3 cannot be explained by a direct action of T3 either on the Na+ entry step across the BBM or on the Na+ exit step (i.e., the Na-K-ATPase), but rather by an increase in K+ permeability of proximal tubular cell membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗