[Simultaneous familial occurrence of distal renal tubular acidosis, polycystic kidney and nephrogenic diabetes insipidus]. / Distalis renalis tubularis acidosis, polycystás vese és nephrogen diabetes insipidus együttes családi elöfordulása.

In five members of three generations in a family studied in 1972, 3 nephrological disorders occurred concurrently: distal renal tubular acidosis (dRTA), polycystic kidney and nephrogenic diabetes insipidus (with the exception of a five-year-old child in whom polycystic kidney was not detectable--yet?). Chromosoma studies revealed an increased rate of the occurrence of variations. The youngest patient was reinvestigated in 1993; the other four affected members of the family were already not alive. 7 offsprings in two generations of the 3 healthy members of the third "patient generation" were healthy. The autosomal dominant way of inheritance characteristic to both dRTA and polycystic kidney disease was obvious in this family. On the other hand the same degree of the concentrating defect found both in the patients of the familial dRTA and in 11 control patients with non familial (acquired) dRTA suggested that the nephrogenic diabetes insipidus as an acquired disorder was associated with the two congenital abnormalities. The clinical picture of the combined disease was dominated by the symptoms of polydipsia and polyuria. The vasopressin resistance with a variation in the degree interindividually seemed to be responsible for the nephrogenic diabetes insipidus. Functional insufficiency of the loop of Henle was excluded on the basis of normal responses to a "loop diuretic".

The antidiuretic action of 1-deamino-8-D-arginine vasopressin (DDAVP) in man.

1. After administration of a new vasopressin analogue (DDAVP), a marked and prolonged antidiuresis occurred in 10 patients with pituitary diabetes insipidus. 2. The antidiuretic effects of single intravenous doses of 0.04--24 mug DDAVP and single intranasal doses of 5--320 mug DDAVP were investigated. Time curves of the antidiuretic responses expressed in changes of urine osmolality (Uosm) and free water clearance per 100 ml GFR (CH2O X 100/GFR) are described. 3. Maximal "peak" response was obtained after an intravenous dose of 1 mug within the first 12 hrs (Uosm was 7--800 mOsm/KgH2O). Further increase of dosage resulted only in prolongation of duration of action (up to 48 hrs) and peak ("plateau") effect (up to 24 hrs). 4. There was a linear relationship between the log dose and log osmolality of urine collected in the second 12 hours after administration of single intravenous and intranasal doses of DDAVP. 5. Comparison of the effects of 1 mug lysine-vasopressin and 1 mug DDAVP revealed only slight differences in peak effects, but extreme differences in duration of action. 6. It is concluded that in the evaluation of a synthetic vasopressin analogue the maximal antidiuretic ability and the prolongation of action have to be analysed separately.

Application of a simple fluorometric method on absorption of canrenone.

The absorption of canrenone, the major metabolite of spironolactone, was studied by a simple fluorometric method in 30 healthy subjects. Two different pharmaceutical formulations were compared on absorption, and only a negligible difference was found between the micronized and balled-milled form. Canrenone in both formulations was well absorbed, whereas spironolactone absorption was slower. Mattingly's fluorometric assay proved to be a simple method to evaluate the absorption of canrenone.

Hyperkalemia unresponsive to massive doses of aldosterone and renal tubular acidosis in a patient with chronic interstitial nephritis: clinical and experimental studies.

A unique 53-year-old male patient is described in whom aldosterone-refractory hyperkalemia and renal tubular acidosis/RTA/ was due to chronic interstitial nephritis associated with peritubular hyaline deposits in the distal nephron. Hyperkalemia was not caused by an adrenal disorder or acidosis and could not be abolished by interventions enhancing K clearance; saline infusions, high doses of furosemide, cortisone, cortisol, long-acting synthetic ACTH and excessive doses of aldosterone. Glucocorticoids induced a marked decrease in sodium excreting capacity probably by an action on the ascending limb of Henle's loop while aldosterone elicited a paradoxical natriuretic response by unknown mechanism. The results of our experimental studies carried out on the hyperkalemic RTA patient as well as on various control subjects and patients suggest 1. a specific defect in renal K excretion associated with decreased aldosterone responsiveness of the tubules presumably due to the peritubular pathology, and 2. a disturbance in the cellular regulation of K distribution between fluid compartments of unknown origin.

Hyperkalemia unresponsive to massive doses of aldosterone in a patient with renal tubular acidosis.

In a 53-year-old male patient aldosterone-refractory hyperkalemia was associated with renal tubular acidosis (RTA) due to chronic interstitial nephritis accompanied by peritubular hyaline deposits in the distal nephron. The hyperkalemia was not caused by an adrenal disorder or acidosis and could not be abolished by diuretics, cortisone, longacting synthetic ACTH, excessive doses of DOCA and aldosterone. The results of our experimental studies carried out on the hyperkalemic RTA patient as well as on various control subjects and patients suggested the presence of a specific defect in renal K excretion associated with a decreased aldosterone responsiveness of the renal tubules presumably due to the peritubular pathology.