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The effect of lithium chloride administration on urinary acidification was studied in dogs. Lithium-treated dogs developed hyperchloremic metabolic acidosis with alkaline urine. Bicarbonate loading resulted in a normal increase in urinary Pco2 in normal dogs but failed to produce the same response in lithium-treated dogs. The bicarbonate titration curve of lithium-treated dogs revealed a small leak of bicarbonate at low plasma levels of bicarbonate; at high plasma levels bicarbonate reabsorption was significantly higher in lithium-treated dogs. This pattern of bicarbonate reabsorption is identical to that described in classic distal renal tubular acidosis. Sodium sulfate administration resulted in a normal urinary acidification ilithium-treated dogs. It is possible that lithium administration induces distal renal tubular acidosis by allowing excessive back-diffusion of acid. This excessive back-diffusion of acid would result in a low urinary Pco2 during bicarbonate loading. Sodium sulfate administration, by increasing the negative intratubular potential, would restrict back-diffusion of hydrogen ion and thereby result in a normal acidification in lithium-treated dogs. We previously demonstrated that postureteral obstruction of the kidney fails to increase urinary Pco2 during bicarbonate loading and to lower urinary pH with sodium sulfate. It is possible that a low urinary Pco2 during HCO3 loading can occur as a consequence of either diminished hydrogen ion secretion (postobstructed kidney) or excessive back-diffusion of acid (lithium administration). Further studies are indicated to determine whether both mechanisms may be found in patients with distal renal tubular acidosis.

The renal effects of the radiographic contrast agent meglumine iothalamate (Conray; C) were evaluated in rats. C produced a 42% fall in glomerular filtration rate (p less than 0.05) and a 44% fall in effective renal plasma flow (p less than 0.05). The effects of C were blunted by both acute and chronic volume expansion. Equiosmolar mannitol produced similar hemodynamic responses as C. The fractional excretions of sodium and potassium were similar in rats given C or mannitol. The renal effects of C appear to be due to its hypertonicity. These effects may be modified by volume expansion.

The renal handling of Ca in response to Na intake was evaluated in 12 patients with hypercalciuria and active kidney stone disease. There was no depression of urinary Ca excretion in response to the hypocalciuric effect of metolazone. Patients were hospitalized and their Ca and Na excretions measured while on a 190-mEq Na, 800-mg Ca, 1200-mg PO4- diet. These measurements were then repeated after Na intake decreased to 35 mEq/day while other variables, including diuretic dose and Ca intake, were unchanged. Two distinct responses were elicited by patients after Na restriction. In group I or the "responders" (n = 4), Ca excretion was reduced from 255 +/- 31 to 62 +/- 6 mg/24 hr. In the control group (n = 4), Ca excretion decreased from 95 +/- 8 to 57 +/- 11 mg/24 hr at similar levels of Na excretion. In group II or the "nonresponders" (n = 8), Ca excretion fell from 317 +/- 31 to 154 +/- 17 mg/24 hr when Na excretion was less than 50 mEq/24 hr. Metolazone with Na restriction normalized urine Ca excretion to the same order as in control subjects in group I. This is indicative of a mild Ca leak or a salt-sensitive leak. Despite diuretic and Na restriction most of the patients with hypercalciuria (group II) did not reabsorb Ca in a normal manner. This is indicative of a severe reabsorptive defect for Ca despite normal Na handling.

The phosphaturic effect of parathyroid hormone (PTH), cyclic adenosine monophosphate (cAMP), acetazolamide (Az), and HCO3 loading was studied in normal, thyroparathyroidectomized (TPTX), and Li-treated dogs. PTH administration to normal animals markedly increased fractional excretion (F) of PO4 but had a blunted effect on FPO4 in the Li-treated animals. Cyclic AMP likewise markedly increased FPO4 in the normal animals but had a markedly blunted effect in the Li-treated animals. Az led to a significant increase in FNa, FHCO3, and FPO4 in the normal animals. In the Li-treated dogs, Az induced a significant natriuresis and bicarbonaturia but failed to increase phosphaturia. HCO3 loading in normal dogs caused a significant phosphaturia while having little effect on FPO4 in Li-treated dogs. HCO3 loading to TPTX dogs was associated with a lower FPO4 as compared to normal HCO3-loaded animals. These data suggest that Li administration not only blocks the adenyl cyclase-cAMP system in the renal cortex, but it may also interfere with a step distal to the formation of cAMP, since the phosphaturic effect of both PTH and cAMP was markedly diminished in Li-treated animals.