Hunt, James C.

Familial metaphysial dysostosis has been described as it occurred among 18 members of a family in seven generations. The roentgenologic changes were very similar to those seen in vitamin D resistant rickets. No biochemical defect could be detected. Studies of renal function with special reference to tubular reabsorption of phosphorus gave normal values. The treatment of choice is osteotomy, after epiphysial closure has occurred, to correct the pronounced bowing of the legs. Administration of vitamin D in high doses has no effect on the course of this disease.

Radioisotope renograms with orthoiodohippurate-I131 were obtained for 41 children who had known renal or renovascular disorders. (Two patients had hypertension but no evidence of renal disease.) Values determined for various components of the renogram curves were considered abnormal when they exceeded two standard deviations from the mean values for normal children of similar body surface area or when time B (from injection to the point of maximal radioactivity) exceeded 6.5 minutes or differed from the contralateral kidney by more than 1 minute. The renogram was clearly abnormal in all 17 patients who had unilateral or predominantly unilateral renal disorders. Abnormalities associated with bilateral renal disorders varied with the disease and its severity. The clinical severity of impairment of renal function could be estimated from the renogram. The isotope renogram proved to be a simple, reproducible technique for determination of function of the separate kidneys.

Isotope renograms (ortho-iodohippurate-I were obtained from 30 children who had no evidence of renal disease. Determinations were made by a standardized technique with the subjects in a state of relative dehydration; in 15 children the renogram was repeated under conditions of hydration (14 children) or further dehydration (1 child). Values for the point of initial peak (point A), point of maximal radioactivity (point B), and the differences between these points (B-A) were calculated. These values were plotted arithmetically against surface area to obtain regression lines and estimates of the variability of the observations about the line. The time from appearance of radioactivity to peak radioactivity was calculated and found to fall into a relatively narrow range. Similar attempts to correlate mathematically the height of timed segments of the decreasing slope of the renogram with surface area were successful in children with a body surface area of 1.15 m2 or greater. The state of hydration appeared to influence the excretory slope of the renogram; this effect was most pronounced in children whose total body surface area was less than 1.15 m2.

1. Hepatic metabolism of renin activity was studied in seven normal dogs, twelve dogs with acute hepatic allograft rejection, five dogs with chronic toxic hepatitis and in seven isolated canine liver preparations. 2. Renin activity was measured by radioimmunoassay in hepatic arterial, portal venous, and hepatic venous plasma (PRA), in bile (BRA) and in perfusate (PsRA). 3. There was a significant gradient of PRA across the normal liver (P < 0.03) and of PsRA across the isolated liver (P < 0.05). 4. There was no significant PRA gradient across the liver of dogs with allograft rejection (acute hepatic necrosis). 5. Dogs with chronic toxic hepatitis showed decreased fractional extraction of PRA but otherwise their data were normal. 6. There was a significant difference between portal venous PRA (8.69 ±1.51 ng ml−1h−1) and hepatic arterial PRA (5.67±1.91 ng ml−1h−1) (P < 0.05). 7. BRA accounted for only 0.04% of hepatic extraction of PRA, suggesting that more important mechanisms for hepatic renin metabolism are binding or destruction of renin by the hepatic tissue.

Renal performance of seven patients undergoing replacement of the aortic valve was investigated. The initial portion of cardiopulmonary bypass was characterized by low arterial blood pressure and anuria. With a subsequent rise in arterial pressure during bypass, urine flow suddenly increased in five patients. In two patients urine flow did not resume until immediately after cardiopulmonary bypass. The high rate of urine flow at these times is thought to be partially due to a glucose-induced osmotic diuresis. The glomerular filtration rate (inulin clearance) and the effective renal plasma flow (PAH clearance) fell with induction of anesthesia and opening of the chest, but there was no further drop in these functions as a result of total body perfusion. Urine osmolality fell significantly during and immediately after cardiopulmonary bypass. The changes in urine osmolality are thought to be due in part to the osmotic diuresis and in part to a temporary reduction in the renal medullary hyperosmolality secondary to hemodynamic changes. All of the alterations in renal function were reversible in the patients studied.

Sodium ortho-iodohippurate (Hippuran) I 131 renography has been performed by a standardized technic in patients with renal artery stenosis, pyelonephritis, primary aldosteronism, pheochromocytoma, and renal tubular acidosis with nephrocalcinosis, as well as in patients in whom the hypertension was apparently not secondary. Fifty of 94 patients studied were found to have abnormal renograms. In patients with renal artery stenosis, all of 37 patients studied had values on the renogram that were outside the range for normal subjects. Although the renographic findings were not considered diagnostic of renal artery stenosis, certain abnormalities of the renogram were commonly observed in the presence of such lesions. When a unilateral delay in the appearance of maximal radioactivity was associated with delayed disappearance ot the medium, renal artery stenosis was frequently observed. Less pronounced differences in the function of the two kidneys were observed in patients with bilateral renal artery stenosis. A state of antidiuresis was often found helpful in the detection of less severe differences in renal function. In patients with predominantly unilateral pyelonephritis, the renographic abnormalities were qualitatively consistent with the degree of impairment of renal function. Bilateral abnormalities were observed in two patients who had bilateral parenchymal disease. The abnormalities on the renogram did not permit distinction between renovascular and renal parenchynal disease. Pyelonephritis associated with obstructive uropathy revealed findings highly suggestive of renal artery stenosis. Distinction from renovascular lesions could be determined with the aid of urographic studies. Only three of 44 patients with essential hypertension had abnormal renograms. The renograms, normal and abnormal, revealed essentially equal function of the two kidneys. The patients with abnormal renograms were not found by other technics to have evidence of secondary hypertension. The patients who were found to have pheochromocytoma and primary aldosteronism had normal isotope renograms. The patient with renal tubular acidosis and nephrocalcinosis had a bilaterally abnormal renogram and severe impairment of total renal function. The presence of a normal isotope renogram, as performed in our laboratory, is considered strong evidence against the existence of a renal or renovascular cause for secondary hypertension.