Charles M. Elwood

Digoxin pharmacokinetics: Role of renal failure in dosage regimen design

Radioimmunoassayed serum concentration and urinary excretion data for digoxin from azotemic patients were characterized using a 2‐compartment open model. Urinary excretion rates of digoxin as well as serum concentration data are needed to accurately characterize the disposition of the drug. Seven patients with renal failure showed highly variable steady‐state volumes of distribution (VSSD = 195 to 489 liters/1.73 m2) and tÛβ values (1.5 to 5.2 days). This variability is a major limiting factor in the use of dosage regimen nomograms that assume a constant VSSD and a rigorous relationship between tÛβ and creatinine clearance (ClCR). Body clearance (ClB) is a parameter that is affected by both elimination and distribution of drugs. A linear relationship between ClB and renal clearance of digoxin or ClCR was found and was used to develop a model‐independent approach to calculation of maintenance doses of digoxin. Several methods for calculating steady‐state serum concentrations of digoxin (CSSD) were compared with actual measurements obtained in 16 chronically medicated patients. Optimum computation of CSSD is obtained by use of digoxin renal and body clearances. Variability in the digoxin: creatinine renal clearance ratio is the major limiting factor in prediction of digoxin dosage regimens.

Evolution of membranous nephropathy into anti-glomerular-basement-membrane glomerulonephritis.

Abstract In a patient with biopsy-proved membranous nephropathy (nephrotic syndrome) acute fatal renal failure suddenly developed. Autopsy revealed rapidly progressive glomerulonephritis superimposed on the previous membranous changes. IgG eluted from the kidney was shown by immunofluorescence technic to bind to the glomerular basement membrane of normal human and monkey kidneys, and was capable of producing an acute anti-glomerular-basement-membrane nephritis in two monkeys. The IgG antibody, by radioisotopic methods, was specifically directed against primate kidney. It is postulated that immune complexes responsible for the original membranous nephropathy induced release of antigenic glomerular-basement-membrane fragments into the circulation, stimulating formation of antibodies to the membrane and producing fatal acute glomerulonephritis. (N Engl J Med 290:1340–1344, 1974)

The measurement of glomerular filtration rate and effective renal plasma flow in man by iothalamate 125-I and iodopyracet 131-I.

In 21 patients, 90 simultaneous renal clearances of inulin and sodium iothalamate 125I, and para-amino-hippuric acid (PAH) and iodopyracet 131I were determined by a constant infusion technique. The activities of iothalamate 125I and iodopyracet 131I were determined simultaneously in a dual-channel scintillation counter. The concentrations of inulin and PAH were determined by standard chemical techniques. The ratio of iothalamate 125I to inulin clearance ranged from 0.93 to 1.09 with a mean of 1.00. The ratio of iodopyracet 131I to PAH clearance varied from 0.86 to 1.04 with a mean of 0.96. The chemical determination of PAH and inulin required approximately 8 hours of technician time as compared with 30 minutes by the radioactive technique. The determination of the renal clearances of iothalamate 125I and iodopyracet 131I is an accurate and time-saving technique for the measurement of glomerular filtration rate and effective renal plasma flow.

Tubular Lesions Produced by Autoantibodies to Tubular Basement Membrane in Human Renal Allografts

In two patients with chronic glomerulonephritis who received renal allografts, transplant failure was associated with binding of transplantation antibodies to the graft and with glomerular and vascula

The measurement of glomerular filtration rate with 125I-sodium iothalamate (Conray).

Abstract Simultaneous renal clearances of 125I-iothalamate and inulin were performed in ten patients. The mean 125Iiothalamate-to-inulin clearance ratio was 1·018. In two patients, the clearance of 131I-iothalamate was found to be similar to that of the 131I form which is known to be excreted by glomerular filtration only. 125I-iothalamate provides an accurate measurement of glomerular nitration rate in man.

The Measurement of Glomerular Filtration Rate with 125-Sodium Iothalamate (Conray)

Abstract Simultaneous renal clearances of 125I-iothalamate and inulin were performed in ten patients. The mean 125Iiothalamate-to-inulin clearance ratio was 1·018. In two patients, the clearance of 131I-iothalamate was found to be similar to that of the 131I form which is known to be excreted by glomerular filtration only. 125I-iothalamate provides an accurate measurement of glomerular nitration rate in man.

Immune deposits in the spleen of a patient with acute poststreptococcal glomerulonephritis (APSGN)

Abstract In a 17-year-old boy with biopsy-proven acute poststreptococcal glomerulonephritis (ASPGN) a splenectomy was performed because of traumatic rupture 49 days after the onset of gross hematuria and 24 days after percutaneous renal biopsy. Granular deposits of C 3 , properdin, and IgG were found in the walls of splenic venous sinuses and arterioles and in renal glomeruli. These findings support the hypothesis that APSGN is a systemic vascular disease characterixed by generalized capillary damage secondary to the deposition of immune complexes.

Effect of intramuscular pentazocine on renal hemodynamics in normal human subjects.

INTRODUCTION ENTAZOCINE* is a benzomorphan nucleus P derivative with analgesic properties comparable to those of morphine.1-6 Maximum analgesia is usually noted 30 to 60 minutes after the intramuscular administration of 30 to 60 mg., with a gradual diminution in effectiveness over the ensuing 2% hours. Although a potent analgesic, pentazocine does not appear to produce either the addiction or psychotomimetic effects seen with opiates. Since analgesic agents, premedicants, and anesthetic agents may alter renal hemodynamics, the effects of pentazocine on effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were studied in man.

Membranoproliferative glomerulonephritis with polyarteritis: A case report

A case of membranoproliferative glomerulonephritis with polyarteritis is described. The patient was a 68 year old male who had the disease for about four months. A kidney biopsy specimen taken just before the patient died was studied by light, immunofluorescence, and electron microscopy. Splitting of the basement membrane, IgG, IgA, BlC, Clq, fibrinogen, and electron dense deposits were found in the glomeruli. It is considered that perhaps some cases of membranoproliferative glomerulonephritis are produced by circulating immune complexes.