Protection from the nephrotoxicity of contrast dye.

Previous studies have reported a 4%-50% incidence of acute renal failure (ARF) following the use of radiocontrast media in patients with preexisting chronic renal insufficiency. In these studies, ARF was defined as a rise of the serum creatinine of at least 1 mg/dl above baseline. Using the same criteria, we studied 214 patients undergoing various intravascular radiocontrast media procedures. Patients were infused with a specially prepared cocktail solution (NSMF) containing 1000 ml half-normal saline, 12.5 g of mannitol (M), I ampule NaHCO3, and 200 mg of furosemide (F) at 100 ml/h from one hour prior to two hours after the procedure. Urinary output was replaced with normal saline for at least 6 h after the procedure. Seven percent of the patients developed acute renal insufficiency. Only 3% of the patients had a rise in serum creatinine greater than 2 mg/dl. No patient required dialysis therapy after the procedure. There was one unrelated death caused by acute myocardial infarction postangioplasty. Risk factors for development of ARF despite cocktail administration included the presence of diabetes mellitus and angiotensin converting enzyme (ACE) inhibitor therapy. We concluded that the properly administered NSMF solution protects against radiocontrast dye induced renal failure. In select patients with chronic renal insufficiency, consideration should be given to withholding ACE inhibitor therapy for 24-48 h prior to administration of intravenous radiocontrast dye. A large controlled trial will be required to establish whether the NSMF solution offers benefit beyond that of saline hydration alone.

Foscarnet alters antidiuretic hormone-mediated transport.

Therapy with foscarnet is associated with acute renal failure. Prior studies have emphasized foscarnet's proximal tubular toxicity, but there have been isolated reports of foscarnet-induced nephrogenic diabetes insipidus. As a phosphate analog, foscarnet is a competitive inhibitor of NaPO4 cotransport. However, foscarnet's effect on antidiuretic hormone (ADH)-induced transport has not been previously investigated. We studied foscarnet's modulation of transport in the toad urinary bladder. Foscarnet at 10 microM to 10 mM did not alter basal water or urea flux. Urea transport induced by a maximal dose of ADH (24 mIU/ml) was inhibited by 0.1 to 5.0 mM foscarnet. In tissues challenged with 0.5 to 1.0 mIU of ADH per ml, 1.0 to 10 mM foscarnet increased water flow but did not alter urea flux. Foscarnet also increased water flow induced by 1.0 to 10 microM forskolin. In tissues pretreated with 10 microM naproxen, foscarnet did not alter water flow induced by 0.5 to 1.0 mIU of ADH per ml or forskolin. These results indicate that foscarnet stimulates water flow induced by 0.5 to 1.0 mIU of ADH per ml at a site proximal to that of the generation of cyclic AMP and inhibits urea flux induced by a maximal dose of ADH at a separate site. In humans, foscarnet nephrotoxicity is likely not limited to the proximal nephron, but extends to the collecting duct. Patients receiving foscarnet should be closely monitored for disorders of urinary concentration.

Dialysis-related amyloidosis manifested as masses in the buttocks.

A 40-year-old man had enlarging painful gluteal masses that developed after 17 years of hemodialysis. Pathologic examination revealed extensive deposition of beta 2-microglobulin amyloid. A bladder biopsy done during evaluation for possible transplantation also showed amyloid deposits. This constellation of findings has not been reported in a patient with beta 2-microglobulin amyloidosis. Patients with dialysis-related amyloidosis should be carefully assessed for systemic involvement. Renal transplantation may prevent further amyloid deposition and provide relief of pain.

The use of fluconazole in the management of Candida peritonitis in patients on peritoneal dialysis.

In patients receiving peritoneal dialysis, fungal peritonitis is generally impossible to eradicate with previously available therapy in the absence of catheter removal. Corbella et al. described a patient with fungal peritonitis treated with fluconazole without catheter removal. We studied this drug's effectiveness in the treatment of 5 patients with peritonitis secondary to Candida species. Patients received a loading dose of 200-400 mg fluconazole, followed by 50-200 mg fluconazole daily. Patients improved initially after therapy with fluconazole. Abdominal pain and fever abated, dialysis returns cleared, cell counts decreased, and, in four cases, cultures were sterilized. Dialysate fluconazole levels were adequate. However, despite maintenance of fluconazole therapy, all patients had recurrent peritonitis within 1 month. Complete cure did not occur unless the Tenckhoff catheter was removed. When the catheter was removed, tip cultures grew pure Candida species, and microscopic examination of catheter sections revealed abundant yeast. Although there may be continued isolated reports of successful eradication of fungal peritonitis without catheter removal, we conclude that in the vast majority of cases catheter removal is required.

Effect of magnesium ion (Mg2+) and the magnesium adenosine triphosphate ion (MgATP2-) on pigeon liver pyruvate carboxylase.

Kinetic methods have been used to determine whether Mg2+ and MgATP2- play an important role in regulating pigeon liver pyruvate carboxylase [pyruvate: CO2 ligase (ADP), EC 6.4.1.1]. Mg2+ not only forms a complex with ATP4- (MgATP2-) but is also required for the enzyme activation (and probably for the binding of MgATP2- to this enzyme). Contrary to the results of other investigators, the MgATP2- complex was not found to activate pigeon liver pyruvate carboxylase. We could not demonstrate homotropic cooperativity with MgATP2-. Excess Mg2+ induced allosteric stimulation of the enzymatic activity at different concentrations of MgATP2-. With different Mg2+ concentrations, changes also occurred in the apparent Km, Vmax and Rs values. Without excess of Mg2+ (heterotropic effector) only about 2% of the total enzymic activity available could be demonstrated in the presence of MgATP2-. It is concluded that Mg2+ exhibits a homotropic cooperative effect and is required for the activation of this enzyme. Mg2+ may bind either to a specific effector site, at the active site, or at the binding site for MgATP2- which is capable of functioning as an effector site and in this way facilitates the carboxylation of pyruvate.