Pre-transplantation assessment of renal viability with 31P magnetic resonance spectroscopy.

As acute tubular necrosis (ATN) is still an important cause for postoperative malfunction of renal grafts, it would be useful to have a method predicting such a complication. We investigated the possibility to predict ATN by measuring the ratio of phosphomonoesters (PME, largely consisting of adenosine monophosphate) and inorganic phosphate (Pi) in the renal tissue, using 31P magnetic resonance spectroscopy (MRS) during the cold ischemia period. Assuming that this ratio reflects the tissue high-energy phosphate status, we studied five kidneys from living related donors (LRD), 28 kidneys from heart beating donors (HBD) and nine kidneys from non-heart beating donors (non-HBD). All kidneys were preserved with a phosphate free solution. We found an inverse relation between the time of 31P MRS and the PME/Pi ratio, suggesting a graded decay of tissue high energy phosphates during cold ischemia. The PME/Pi ratio was highest in grafts from LRD (2.65 +/- 0.50, no ATN), intermediate in grafts from HBD (1.65 +/- 0.41, 21% ATN) and lowest in those derived from non-HBD (1.05 +/- 0.47, 56% ATN). The differences in PME/Pi ratio between the groups was statistically significant (P < 0.01). Moreover, the ratio was significantly lower in grafts developing ATN (1.73 +/- 0.41 vs. 1.35 +/- 0.29 in the HBD group, 1.41 +/- 0.24 vs. 0.76 +/- 0.36 in the non-HBD group, P < 0.05). These observations point to a general relation between the pre-transplant kidney PME/Pi ratio and the development of ATN. However, the predictive value of a low PME/Pi ratio was too low (36%) to reliably predict development of ATN in individual cases.(ABSTRACT TRUNCATED AT 250 WORDS)

No effect of APD (amino hydroxypropylidene bisphosphonate) on hypercalcemia in patients with renal osteodystrophy.

Hypercalcemia, due to autonomous functioning of the parathyroids following long standing secondary hyperparathyroidism, is a well known complication in patients with renal osteodystrophy, which can on most cases be treated by parathyroidectomy only. While patients with renal osteodystrophy react favorably to supplementation of active vitamin D metabolites to prevent or reverse renal osteodystrophy, the use of these drugs is bound to result in greater hypercalcemia in those patients who are already hypercalcemic. The question rose if the bisphosphonate amino hydroxypropylidene bisphosphonate (APD) would decrease plasma calcium concentration sufficiently in order to create room for the use of vitamin D to cure the osteomalacia component of the osteodystrophy and simultaneously block the excessive bone resorption. Therefore, five patients with renal osteodystrophy and hypercalcemia were treated for up to 9 months with APD. Three of them, who were on chronic hemodialysis, received 15 mg APD i.v. 3 times a week, the 2 other patients with severe renal failure received 200 mg APD orally. Ionized calcium in plasma did not decrease. Histological investigation of bone samples, obtained before and after therapy, showed an increase of fibrous tissue and a remarkable increase in the number of osteoclasts or osteoclast-like cells not only along the bone-margin, but mainly within the bone-marrow. We conclude that in patients with renal failure with hypercalcemia, APD in the doses used had no effect on plasma calcium level, but caused a striking change in bone histology. Although the consequences of these findings are not yet clear, they do not seem to indicate improvement of bone structure.

Suppressed diluting segment reabsorption in Bartter's syndrome: studies in 1 patient and synthesis of literature data.

We analyzed renal sodium handling in a patient with Bartter's syndrome after equilibration on diets containing 200 and 700 mmol NaCl/day. No potassium supplements were given. Clearance studies were performed during maximal water diuresis, maximal free water clearance was taken as measure of diluting segment sodium reabsorption. A normal reference frame of diluting segment NaCl reabsorption at varying delivery rates to that segment was drawn from data collected in similarly studied normal subjects after equilibration on low (20 and 200 mmol/day) or very high (916-1,224 mmol/day) sodium intakes. The results were compatible with a defect in diluting segment reabsorption in the patient, which appeared more pronounced during the high sodium intake. Recent reports do not agree with the existence of such a defect in Bartter's syndrome. One of the reasons of this difference may be the lack of a proper reference frame in previously published studies. We, therefore, compared clearance data in adults with Bartter's syndrome published by others with our studies in normals. Our analysis showed that in Bartter's syndrome (1) a moderate diluting segment NaCl reabsorption defect is often present, and (2) the proximal reabsorption is frequently elevated relative to sodium intake. Severely suppressed diluting segment reabsorption and relatively low proximal reabsorption may also occur, particularly in association with salt loading or reduced glomerular filtration. It seems, therefore, that much of the continuing controversy on renal sodium handling in Bartter's syndrome may be solved by using the proper frame of reference.

Effect of high-dose aldosterone infusions on renal electrolyte excretion in patients with renal insufficiency.

We investigated the effect of aldosterone infusion (0.5 mg/h for 6 h) on electrolyte excretion in 11 patients with severe renal insufficiency (creatinine clearance 6-20 ml/min), with normal or elevated serum potassium levels and a wide range of plasma aldosterone levels, and compared the data with those obtained in 7 healthy subjects. The studies were done under conditions of fixed sodium and potassium intake. In the normal subjects, aldosterone infusion caused a significant rise in potassium excretion and a significant fall in sodium and chloride excretion (p less than 0.01). In 1 patient with a high plasma aldosterone, virtually no response occurred to the aldosterone infusion. In the others, the increase in potassium excretion and reduction in chloride excretion were not different from the changes observed in the normals, but the fall in sodium excretion was less due to a higher urinary sodium before infusion in the normals (p less than 0.05). Fractional electrolyte excretions as well as the changes in fractional excretion by aldosterone were larger in the patients (p less than 0.05). Apparently, the renal tubules of patients with chronic renal failure are still responsive to maximal stimulation with aldosterone, in spite of their basically elevated fractional electrolyte output. These findings suggest that, with some exceptions, the hyperkalemia in patients with chronic renal failure is in part due to relative hypoaldosteronism.

Adaptation to chronic potassium loading in normal man.

To analyze factors involved in the maintenance of potassium balance during increased intake, 6 healthy males were studied on a normal (80 mEq) and high (300 mEq) potassium diet. After 18 days of potassium-rich diet, urinary potassium excretion had increased from 50 +/- 12 to 233 +/- 45 mEq/day. Plasma renin activity and body weight were unchanged, serum potassium and plasma aldosterone somewhat increased, and the ratio of plasma aldosterone to renin activity consistently elevated. Acetazolamide injection (1 g i.v.) increased sodium and potassium excretion rates equally on the two diets indicating that a sudden increase in distal solute delivery was not handled differently after potassium loading. The reaction to a high dose of aldosterone (1 mg i.v. followed by 0.5 mg/h infusion) in terms of sodium retention and potassium excretion was also comparable, indicating no altered sensitivity to aldosterone after adaptation to the potassium-rich diet. By contrast, the aldosterone antagonist canrenoate (100 mg i.v.) acutely raised NaCl excretion without changing the potassium excretion during the high potassium diet, but did not affect NaCl excretion during the normal diet. Subsequent oral administration of spironolactone for 5 days (200 mg daily) caused a more negative sodium balance associated with more weight loss and rise in renin activity during the potassium rich diet. Surprisingly we noticed no fall in renal potassium excretion in this period, but mean serum potassium was raised by 0.3-0.4 mEq/l at the end. These results suggest that adaptation of a healthy subject to a potassium-rich diet does not involve intrinsic changes of the distal tubule, but a shift of sodium reabsorption from a proximal to a distal (aldosterone-sensitive) nephron level.(ABSTRACT TRUNCATED AT 250 WORDS)