Anatole Besarab

Effect of albumin and free calcium concentrations on calcium binding in vitro.

In vivo equilibrium dialysis studies were performed to define further the characteristics of calcium binding to bovine albumin. The concentration range for albumin (1 to 9 g/dl) as well as ultrafilterable calcium (0.5 to 2.5 mM) studied encompassed those that might be ordinarily encountered in most clinical situations. Major differences in the regressions of total calcium on ultrafilterable calcium occurred at albumin concentrations of 1, 2, and 9 g/dl but only small differences at albumin concentrations between 3, 5 and 7 g/dl. When albumin concentration was kept constant, the amount of calcium bound to albumin varied directly with ultrafilterable calcium. At any constant ultrafilterable calcium concentration albumin bound calcium varied inversely with the albumin concentrations when albumin was greater than 3 g/dl. Analysis of the data to determine association constants and molar calcium to albumin binding ratios showed that both parameters were dependent on the absolute albumin concentrations. Our results indicate that calcium binding to albumin is a complex process characterised by multiple binding sites whose affinity and binding capacity are variable. These properties suggest that correction of total serum calcium using clinical formulations with fixed calcium to albumin binding ratios may be inappropriate, particularly in hypoalbuminaemic states.

A POSSIBLE ROLE FOR PROPRANOLOL IN THE TREATMENT OF RENAL OSTEODYSTROPHY

The effect of propranolol upon parathyroid hormone (P.T.H) concentrations was investigated in patients undergoing chronic haemodialysis. 9 patients receiving propranolol for the treatment of hypertension or angina pectoris were compared with 25 similar patients not taking the drug. P.T.H. and alkaline phosphatase concentrations were lower in patients receiving propranolol and there was less radiological evidence of renal osteodystrophy in these patients. Prospective studies are needed to determine whether propranolol may be helpful as an adjunct to other therapy in reversing or preventing renal osteodystrophy.

Prostaglandin E and hypercalcemia in breast carcinoma: Only a tumor marker?: A need for perspective

Prostaglandin E concentrations were measured in a patiet with breast carcinoma, hypercalcemia, undetectable parathyroid hormone (PTH) and no evidence of bone metastases. Catheterization of the drainage bed of her tumor documented production of E series prostaglandins. Treatment with the largest recommended doses of indomethacin for 10 days failed to lower her plasma prostaglandin E (PGE) concentrations or to correct the hypercalcemia, but it normalized urinary excretion of PGE. Subsequent chemotherapy reduced prostaglandin concentrations toward normal values concomitant with a reduction of clinically estimated tumor burden. During this period of time, serum calcium concentrations had no consistent relationship to the plasma PGE levels. We suggest that PGE merely reflected the tumor burden of this patient and did not directly contribute to the genesis of her hypercalcemia. The pertinent literature relating PGE and hypercalcemia is reviewed.

Increased absolute calcium binding to albumin in hypoalbuminaemia.

The amount of calcium bound to protein was measured in 30 patients with differing diseases and varying degrees of hypoalbuminaemia. Total serum calcium increased directly with both serum albumin and ultrafilterable calcium concentrations. The estimated amount of calcium bound per gram of albumin varied inversely with the albumin concentration, decreasing from 2.1 to 1.0 mg calcium/g albumin as albumin concentration increased from 1.7 to 3.1 g/dl. Circulating parathyroid hormone (PTH) concentrations varied inversely with measured ultrafilterable calcium concentrations. The frequency of raised PTH concentrations decreased as serum albumin increased. Use of a conventional correction factor for albumin binding (0.88 mg calcium bound per gram of albumin) to calculate corrected total calcium led to major errors in estimating ultrafilterable calcium in these patients. The PTH concentrations in turn correlated with the degree of deviation between estimated and measured ultrafilterable calcium concentrations. Ionised calcium was low in seven of ten additional hypoalbuminaemic patients studied whereas correction of total calcium for albumin indicated normocalcaemia in all. Thus correction of total calcium in patients with hypoalbuminaemia by formulae which use a fixed binding ration of calcium to albumin may give an erroneous impression of normocalcaemia. The increase in calcium binding ratio during hypoalbuminaemia needs to be considered during assessment of calcium status in these patients.

Amylase/Creatinine Clearance Fraction in Patients on Chronic Hemodialysis

Excerpt The importance of the amylase/creatinine clearance fraction (Cam/Ccr) in differentiating acute pancreatitis from the hyperamylasemia of renal failure was first shown in 1969 by Levitt, Rapo...

EFFECT OF DELAYED GRAFT FUNCTION AND ALG ON THE CIRCASEPTAN (ABOUT 7-DAY) RHYTHM OF HUMAN RENAL ALLOGRAFT REJECTION

Postimplantation records of 157 kidney transplant recipients with first rejection episodes within 50 days of surgery were studied. Of these 36 had living-related and 121 cadaver donors. Recipients of cadaver donor kidneys were divided into four subgroups: with and without postoperative acute renal failure (ARF), and with and without approximately two weeks of immunosuppression by antilymphoblast globulin (ALG) added to conventional therapy. All recipients with immediate function without ALG showed evidence of periodicity in probability of occurrence of rejection that was highly significant for a 7-day period beginning at the time of surgery. The remaining groups showed less significant periodicity or no significant periodicity beginning at the time of surgery, but they did show a highly significant circaseptan rhythm of rejection episodes beginning with cessation of ALG treatment or with onset of diuresis following ARF in the absence of ALG. It is suggested that clinical manifestation of the immunologic attack of recipient upon graft has an intrinsic development period of about 7 days beginning with implantation. However, initiation of the first period may be blocked by ALG or by low renal blood flow during ARF.

Suppression of Secondary Hyperparathyroidism by Propranolol in Renal Failure Patients

Renal osteodystrophy in part due to secondary hyperparathyroidism, is one of the major unresolved problems affecting patients on chronic hemodialysis. In addition, evidence has shown that parathyroid hormone (PTH) is toxic to other organ systems besides bone. The results of a prospective study on the effect of propranolol in reducing PTH levels in chronic renal failure patients on hemodialysis are reported. Propranolol administration reduced PTH levels by over 50-75%. The levels of calcium, phosphorus, alkaline phosphatase and hematocrit were variable, but patients with severe derangements in these measurements also seemed to benefit from propranolol. It should now be determined by larger and longer studies whether these biochemical improvements can be translated into clinical benefits.

Effect of plasma proteins and buffer in flushing solutions on rat kidney preservation by cold storage.

The isolated rat kidney perfused at 37 C was used to evaluate the effect of adding plasma proteins to, and varying osmolality of, cold-storage flushing solutions with or without buffering. Addition of albumin improved immediate poststorage kidney function (glomerular filtration rate [GFR], fractional sodium reabsorption, and fractional protein clearance) of all flushing solutions tested after 6 hr and 24 hr of storage. At 6 hr, these improvements also correlated with less weight gain. Flushing solutions containing citrate and sulfate produced significantly better return of function after 24 hr of cold storage than Krebs or Collins-derived solutions. Osmolality was unimportant with solutions containing citrate. Collins solution with reduced MgSO4 yielded better poststorage function than conventional solution. An all-citrate isotonic solution buffered with 15 mmol THAM preserved poststorage function at 48 hr better than a similarly buffered solution containing both citrate and sulfate. Loss of dry weight during storage and subsequent perfusion appeared to correlate, in these experiments, with loss of poststorage function. The isolated rat kidney provides discrimination among various flushing solutions. The technique might be useful in the assay of additional variables that might affect the quality of kidney preservation.

Diagnostic and prognostic significance of an increase in fractional protein clearance ratio before and during rejection of renal transplant.

We measured prospectively changes in fractional protein clearance ratio (CPr/CCr) in 21 live-related (LR) and 41 cadaver donor (CD) renal transplants before and during onset of first rejections. Fifty-three recipients manifested a rejection within the first post-transplant month. Fractional protein clearance increased in all patients during rejection. An increase in CPr/CCr prior to other evidence of impending rejection, and therefore clinically useful, required at least a 10-day rejection-free interval dated from onset of diuresis (whether diuresis was immediate or delayed by acute tubular necrosis (ATN)). Twenty-three of 25 nonantilymphocyte globulin (ALG)-treated CD transplants manifested clinical and laboratory signs of the first rejection episode prior to the 10th day of diuresis compared with 5 of 21 LR and none of 16 ALG-treated CD transplants. Persistence of elevated CPr/CCr despite treatment forecast graft loss (11 of 13), whereas a decrease in this ratio was associated with ultimate reversal of the rejection process.