Claus Brun

THE MECHANISM OF FORMATION OF OSMOTICALLY CONCENTRATED URINE DURING THE ANTIDIURETIC STATE

The present study is concerned with the operation by which the kidney, during antidiuresis, conserves water for the body by elaborating a urine osmotically more concentrated than the blood. It is appropriate to emphasize that in the mammals the osmotic pressure of the plasma and the interstitial fluid is one of the most closely guarded of all the homeostatic states, and that the kidney is chiefly responsible for the regulation of this osmotic pressure within narrow limits. Osmotic dilution of the plasma is normally offset by the excretion of a urine osmotically more dilute than the plasma, as in water diuresis, while an increase in osmotic concentration of the plasma is offset by the excretion of urine osmotically more concentrated than the plasma. The present paper is concerned only with the mechanism of the excretion of a hypertonic urine. That no osmotic concentration is achieved in the separation of the glomerular filtrate is established, to the satisfaction of all investigators, by the well known micropuncture studies of Richards and his coworkers in the Amphibia, and Walker, Oliver, and their coworkers in the guinea pig, rat and opossum. These studies have also demonstrated, at least under the recorded experimental conditions, that the urine remains isosmotic with the plasma, ,or nearly so, throughout the length of the proximal segment, at a time when the bladder urine may be concentrated osmotically to a considerable extent. Unfortunately, such icropuncture studies as are

Diabetic nephropathy: Kidney biopsy and renal function tests☆

Abstract Kidney biopsy findings in twelve patients with diabetes mellitus have been compared with the clinical and laboratory findings in these cases, and the results of discrete renal function tests. In six cases the biopsy specimen revealed solely diffuse glomerular changes; in four cases nodular-diffuse changes; and in one case completely hyalinized glomeruli with remnants of nodules; in one case the biopsy showed normal renal tissue in a patient in whom the further course of the disease showed that the renal symptoms must have been due to cardiac failure. The kidney biopsy method made possible correction of clinically misdiagnosed diabetic nephropathy in one case, and in four cases which did not show definite clinical signs of diabetic renal disease it revealed the presence of glomerular changes (diffuse in three cases and nodular-diffuse in one case). Biopsy of the kidney, therefore, has some diagnostic value in diabetic nephropathy. Its value in the differential diagnosis of chronic pyelonephritis, on the other hand, seems to be very limited. The present kidney biopsy experience apparently supports the theory that diabetic nephropathy originates as diffuse hyalinization in the basement membranes of the glomerular tufts, and that the nodular changes may be considered a further development of the diffuse form. The discrete renal function tests, which do not per se permit any safe diagnostic conclusions with regard to the degree and nature of diabetic nephropathy, seem to indicate that glomeruli with rather pronounced changes of diabetic origin, at least in some instances, have a higher filtration capacity than might be supposed from the histologic picture.

Lithium: long-term effects on the kidney. II: Structural changes

Forty-six patients treated with lithium for an average of 8 yr participated in a follow-up study involving a kidney biopsy. The results were compared with renal biopsy specimens from an age-matched group of controls never treated with lithium. The average number of totally scelerotic glomeruli and atrophic tubuli was higher in lithium-treated patients. The histopathological changes showed significant correlations with lithium dosage schedule. Both the proportions of sclerotic glomeruli, atrophic tubuli and focally distributed interstitial fibrosis were higher in patients receiving their lithium two or three times a day than when lithium was given in a single daily dose.

TWO CASES OF CALCINOSIS RENIS, STUDIED BY MEANS OF RENAL BIOPSY AND RENAL FUNCTION TESTS

Nephrocalcinosis may either be due to calcification of necrotic tubular epithelial cells and of precipitates such as occur in corrosive sublimate poisoning, in tubular nephritis (lower nephron nephrosis) (1) and rarely in chronic glomerulonephritis (1-3), or it may appear as part of a metastatic calcification due to mobilization of skeletal calcium in such conditions as hyperparathyroidism, hypervitaminosis D, osseous metastases (4), myelomatosis, osteomalacia, and long-term immobilization of bones (trauma, tuberculosis, and osteomyelitis). Finally, it may be seen following abnormalities of the blood chemistry (other than hypercalcemia) such as hyperchloremic acidosis and hypochloremic alkalosis. A comprehensive review of nephrocalcinosis in human pathology has recently been given by Geraci, Harris, and Keith (5), and the literature concerning experimental metastatic calcification in the kidneys has been collected by Dick and Prior (6). In the present paper two cases of calcinosis renis are reported. One patient suffered from a parathyroid adenoma with hyperparathyroidism, the other from calciferol poisoning. In both cases there was a secondary renal disease, and the renal biopsy method afforded essential information about its nature. Differentiated renal function studies were also made in these two patients; the results could be compared with the histological examination undertaken simultaneously.

Long-term effects of lithium on the kidney: Functional-morphological correlations

Correlations between quantitative kidney biopsy findings and clinical renal function in 46 unselected patients treated with lithium for an average of eight years were studied. A significant relationship between maximum renal concentrating capacity and degree of tubular atrophy was found. GFR correlated significantly with sclerotic glomeruli as well as atrophic tubules in patients on a multiple dosage schedule, whereas no relationship was seen in patients receiving lithium in a single daily dose. Thus, renal dysfunction may have a structural basis in a subgroup of lithium-treated patients on a multiple dosage schedule.