Laura I. Rankin

Urinary Calcium Excretion at Extremes of Sodium Intake in Normal Man

To elucidate the relationship between the renal regulation of sodium and calcium excretion at extremes of sodium intake, we studied 6 normal men ingesting a fixed, 400 mg/day calcium intake and four levels of sodium intake from 10 to 1,500 mEq/day. Serum ionized calcium was not influenced by sodium intake. Blood pressure and cardiac index increased modestly. Urinary calcium excretion increased to 262 +/- 53 mg/day (mean +/- SE). Plasma norepinephrine concentration, serum PTH levels, hematocrit, total serum protein concentrations and CO2 content decreased with increasing sodium intake. Urinary cAMP increased as sodium intake was raised from 10 to 300 mEq/day, but subsequently decreased to basal values. Urinary calcium and sodium excretion were related (p less than 0.001) in a nonlinear fashion as were the fractional excretions of these cations (p less than 0.001). The filtered calcium load and the fractional calcium excretion were directly and linearly related (p less than 0.001). We conclude that the effect of sodium intake on urinary calcium excretion principally reflects changes in the filtered calcium load rather than changes in renal sodium handling. Calcium homeostasis at extremes of sodium intake does not appear to be critically dependent upon PTH-mediated mechanisms. The data suggest that the proximal tubule has a remarkable capacity to dissociate calcium resorption from that of sodium.

Atrial myxoma: a review of the neurological complications, metastases, and recurrences.

The neurological complications secondary to embolism from atrial myxoma are reviewed. A patient with intracranial and skeletal metastases is described to emphasise the malignant potentiality of this tumour. A classification of atrial myxoma metastases is presented.

The effects of age, race and heredity on glomerular filtration rate following volume expansion and contraction in normal man

To elucidate racial and age differences in natriuretic responses following volume expansion, we studied GFR, as reflected by endogenous creatinine clearance, in 446 normal persons including 99 blacks and 44 pairs of mono-and dizygotic twins. GFR was measured day and night, under basal conditions, following volume expansion with 2 L intravenous normal saline and volume contraction with 120 mg oral furosemide. Volume expansion and contraction altered GFR to similar degrees in whites and blacks. White exhibited a diurnal variation in GFR (day>night) under all conditions, which was not observed in blacks. Following saline, whites excreted more sodium during the day, but less sodium during the night, than blacks (p<0.05). In whites, UnaV and GFR were correlated only during the day, while in blacks the correlation persisted throughout the night. When the white population was divided into subjects < 40 years and ≥40 years, the responses of the older whites resembled those of blacks. The inverse relationship between GFR and age was steeper in blacks than whites. A twin analysis demonstrated that plasma creatinine, urinary creatinine excretion and creatinine clearance are heritable. The failure of GFR to decrease at night in blacks and older whites may be related to an altered natriuretic capacity. Decreases in GFR with aging are greater in blacks than whites. GFR is partially under the influence of genetic variance.

Metastatic Atrial Myxoma Presenting as Intracranial Mass

Metastases from atrial myxomas are uncommon. A patient with a left atrial myxoma that had been excised eight years earlier developed intracranial and skeletal metastases. The primary lesion had not recurred. The malignant potential of this neoplasm is discussed.

Recovery from Aminoglycoside Nephrotoxicity with Continued Drug Administration

To examine the nephrotoxicity of prolonged gentamicin administration compared to the effect obtained when a less toxic aminoglycoside is substituted during the course of treatment, we gave gentamicin (67.5 mg/kg per day) to rats for 21 days, gentamicin for 14 days followed by either netilmicin or tobramycin for 7 days, or gentamicin for 14 days followed by saline diluent. After initial tubular, necrosis, the animals recovered from renal injury whether the drug was continued or discontinued or another drug was substituted. These data are consistent with the observation that regenerating renal epithelium is resistant to continued or additional nephrotoxic insults. These findings suggest that improvement in renal function during aminoglycoside therapy cannot necessarily be attributed to the substitution of another aminoglycoside or other therapeutic interventions.

Protection from Gentamicin Nephrotoxicity by Cephalothin and Carbenicillin

In rats, cephalothin exerts a protective effect upon the nephrotoxicity of gentamicin. To examine the possibility that this effect is also observed with carbenicillin, we gave the following (milligrams per kilogram) to rats daily for 14 days: gentamicin alone, 60; gentamicin plus cephalothin, 100, 500, or 1,000; gentamicin plus carbenicillin, 50, 100, 250, 500, or 1,000. A 500-mg/kg dose of cephalothin afforded significant partial protection from gentamicin nephrotoxicity, as did a 100-mg/kg dose of carbenicillin. Increasing doses of either drug failed to increase protection. The data suggest that in rats not only does carbenicillin afford some protection from gentamicin nephrotoxicity, but also that it does so at a lower dose than cephalothin. These findings may in part explain the divergent observations regarding the nephrotoxicity of cephalothin-gentamicin combination therapy in rats and humans.

The Effects of Rapid Saline Infusion on Sodium Excretion, Renal Function, and Blood Pressure at Different Sodium Intakes in Man

To examine the effects of increasing dietary sodium intake on natriuresis, filtration rate, and renal blood flow following rapid volume expansion, we infused 2-liter normal saline over 2 hr into normal men in balance at 10, 300, 600, and 800 mEq/day sodium intake. Natriuresis and kaliuresis were related to prior sodium intake. Fractional excretion of sodium (6%-7%) was maximal at the 600 mEq/day sodium intake and increased no further at the 800 mEq/day sodium intake. Although blood pressure increased with rapid saline infusion, natriuresis and blood pressure were not associated. Creatinine clearance decreased or remained constant, while PAH clearance decreased during saline infusion at each level. The data suggest that although natriuresis following rapid saline infusion is dependent upon prior sodium intake, under given circumstances it may be independent of glomerular filtration rate, renal blood flow, or blood pressure.

Comparative nephrotoxicity of SCH 21420 and amikacin in rats.

The nephrotoxic potentials of the new aminoglycoside SCH 21420 and amikacin were compared in a rat model. Groups of rats received 100, 200, 300, or 600 mg of either drug per kg per day for 14 days. Enzymuria, urine osmolality, protein excretion, and blood urea nitrogen were monitored at periodic intervals, whereas creatinine clearance and pathological changes were determined at sacrifice. Amikacin caused more enzymuria at the two lower doses as well as greater proteinuria and blood urea nitrogen elevations at the highest dose than did SCH 21420 (P less than 0.05). Pathological changes were more severe with amikacin than with SCH 21420 at the three lower doses (P less than 0.05); however, at the 600 mg/kg per day dose, the pathological scores and creatinine clearances of animals receiving either drug were not significantly different (P greater than 0.05).

Effect of Cephalothin on Measurement of Creatinine Concentration

Cephalothin, an antibiotic implicated as nephrotoxic, falsely elevates the creatinine concentration as determined by the Jaffé reaction in vitro. We studied this effect in vivo and demonstrated variable degrees of interference in determinations of plasma and urinary creatinine concentrations by two automated methods. Clinicians should be aware of this phenomenon in patients receiving cephalothin, both when monitoring renal function and when assessing patient reliability in the collection of timed urine specimens.

Comparative nephrotoxicities of dibekacin, amikacin, and gentamicin in a rat model.

The nephrotoxicity of dibekacin was compared with those of gentamicin and amikacin in a rat model. The doses used were 3, 10, and 30 times the suggested human therapeutic dose on a weight basis. Indices of glomerular and tubular function failed to clearly differentiate the drugs. Dibekacin and gentamicin produced equally severe injury to the renal tissue. Slightly less damage occurred with amikacin.