Renal digoxin clearance was compared in patients suffering from atrial fibrillation with well preserved cardiac function (n = 9; salt intake +/- 170 mmol daily) and patients with chronic congestive heart failure (n = 10; salt intake 50 mmol daily and maintenance treatment with diuretics). There was no difference between the groups concerning digoxin dosage, creatinine clearance, diuresis or sodium excretion in the urine. Digoxin clearance in chronic heart failure proved to be significantly lower than in atrial fibrillation (48 +/- 21 vs 71 +/- 36 ml X min-1, p less than 0.05), and Cdig/Ccreat was similarly reduced at 0.73 +/- 0.15 compared to 1.09 +/- 0.27 (p less than 0.005). Steady state serum digoxin concentration was significantly higher in patients with congestive heart failure (1.44 +/- 0.47 vs 0.87 +/- 0.33 micrograms X 1(-1), p less than 0.01). Chronic congestive heart failure is a state with reduced digoxin clearance by the kidney, which could lead to digoxin intoxication not explicable by overdose, reduced renal function or the effect of interacting drugs.
To evaluate the influence of different types of natriuresis on the renal clearance of digoxin (Cldig) and the Cldig/Clcr ratio, studies were performed in which sodium-depleted patients were placed on a moderately high sodium diet for 6 days. In another group natriuresis was evoked by furosemide. In the first study, in 10 patients, there was a 10-fold increase in Na excretion and a small rise in diuresis (V) and Clcr, which was accompanied by an increase in Cldig from 57.5 +/- 32, and 60.7 +/- 27.3 (duplicate measurements) to 103.9 +/- 55.4 (p less than 0.01) and 103.8 +/- 46.5 ml min-1 (p less than 0.01). Cldig/Clcr rose from 0.60 +/- 0.24 and 0.61 +/- 0.16 to 0.91 +/- 0.31 and 0.91 +/- 0.21, respectively (both p less than 0.005). Serum digoxin concentration declined from 1.24 +/- 0.35 and 1.19 +/- 0.40 to 1.02 +/- 0.35 and 0.97 +/- 0.32 micrograms/l (both p less than 0.01) during the high sodium diet. In the furosemide-induced natriuresis (6 patients), changes in Na excretion and V were a multiple of those caused by Na loading, but the Cldig/Clcr ratio was not increased. The results are in accordance with the concept of digoxin backdiffusion in the proximal tubules, which is dependent on proximal Na reabsorption. In the more distal segments of the nephron, where the action of furosemide occurs, there does not appear to be any transtubular movement of digoxin.
Abstract. Plasma cyclic AMP (PcAMP) concentration and the excretion of cyclic AMP dl GF were estimated in 11 thyrotoxic patients before and after medical treatment.
PcAMP concentrations were significantly higher during hyperthyroidism (2.30 ± 0.69 vs 1.88 ± 0.71 nmoldl; P < 0.05), and total urinary cyclic AMP (TcAMP) excretion showed no significant changes (3.24 ± 0.64 vs 3.44 ± 1.77 nmol/dl GF). Nephrogenous (NcAMP) excretion rose significantly (1.00 ±0.82 vs 1.68 ±1.31 mmol/dl GF; P < 0.025). The increase in NcAMP excretion correlated significantly with the decrease in serum T3 levels (r = -0.46; P < 0.05). Serum iPTH levels showed no significant change. Both the serum Ca, corrected for serum total protein and TmPO4 GFR declined after treatment (respectively 2.44 ± 0.13 vs 2.33 ± 0.08 mmol l; P <0.05 and 1.18 ± 0.29 vs 1.05 ±0.22 mmol/l; P < 0.05). It is concluded that the rise in NcAMP excretion corroborates the concept of increasing parathyroid activity following the treatment of hyperthyroidism.
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