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.

Comparative effect of metals on antidiuretic hormone induced transport in toad bladder: specificity of mercuric inhibition of water channels.

We previously reported that HgCl2 inhibits water and urea flux in tissues fixed with glutaraldehyde after antidiuretic hormone (ADH) stimulation and suggested that the ADH-induced water channel may share characteristics of the red blood cell and proximal tubule water transport pathway. To determine the specificity of mercury's action, we examined the effect of numerous other metals. In tissues fixed after ADH stimulation, water flow and urea and sucrose permeabilities are maintained from mucosal bath pH 2.5 through pH 12. Several metals including Ba, Co, Fe, Sr and Zn did not alter flux. Al, Cd, La, Li, Pb and U inhibited urea permeability but not water flow. At pH 2.8, Cu inhibited water flow by 30% and urea permeability by 50%. At pH 4.9-7.4, Cu inhibited urea permeability but not water flow. At pH less than or equal to 3.0, Pt inhibited flow in ADH-pretreated tissues. The inhibitory effect was not present at pH greater than 3.0. At pH less than 3.0, Au inhibited flow by 90% in tissues fixed after pretreatment with ADH but increased the permeability of tissues fixed in the absence of ADH. Ag inhibited flow by 70% but also increased sucrose, urea, and basal permeabilities. This suggests that Ag and Au disrupt epithelial integrity. These results indicate that at physiologic pH, the ADH-induced water channel is specifically blocked by Hg but not by other metals. This specificity may reflect the presence of a large number of sulfhydryl groups in the water channel.

Persistent nocardemia following renal transplantation. Association with pulmonary nocardiosis.

Pulmonary nocardiosis occurred in a renal homotransplant patient and was diagnosed by persistently positive blood cultures. Infection developed at a time when efforts were being made with moderate dosages of immunosuppressive drugs to prevent rejection of the transplant. The subsequent nocardemia lasted for one week. The remaining kidney function was preserved, and the patient had a very favorable outcome because of early diagnosis and prompt treatment with sulfisoxazole.

Metabolic changes in diabetic uremic patients on hemodialysis.

By studying the metabolic values of a nondiabetic and diabetic uremic population we demonstrated the following: 1. Insulin is higher in diabetic than nondiabetic uremic patients. A slight arteriovenous difference across the dialyzer membrane suggests that insulin is dialyzable in small amounts in man. 2. C-peptides are highest in nondiabetics, lower in maturity onset diabetics, and lowest in juvenile diabetics. 3. Growth hormone is higher in diabetics than nondiabetics, decreased in both groups during hemodialysis, and returns to pre-dialysis levels 2 hrs after the completion of dialysis treatment. 4. Plasma triglycerides are elevated in both popualtions during the fasting state anddrop during hemodialysis, rising slowly towards the end of hemodialysis. 5. The majority of diabetics on hemodialysis have low renin levels and do not respond to volume reduction. In the high renin diabetics and high and low renin nondiabetics the plasma renin levels rise in response to volume reduction during hemodialysis. Renin is not dialyzable in man. 6. Thyroid function tests show that diabetic and nondiabetic patients have measurements in the low normal range. Our results reveal significant information concerning metabolic changes which take place in diabetic and nondiabetic uremic patients on hemodialysis and helps to characterize these populations. This report may have implications in better understanding the nature of the problems encountered in these populations and in their management (Table III).

Medical nephrectomy. The use of metallic salts for the control of massive proteinuria in the nephrotic syndrome.

Two patients with intractable massive proteinuria and uremia were followed and treated with standard mecial therapy and dialysis. After a period of study and demonstration of clinical deterioration both patients were given solutions containing sodium mercaptomerin. Within days there was a decline in urine protein excretion and a variable increase in serum protein concentration. The patients demonstrated an increase in blood pressure, which made hemodialysis treatment possible. No deleterious effects from the mercury salts were noted. These observations suggest that in selected cases nephrotoxic agents may be of value in decreasing massive proteinuria, and improving protein homeostasis in uremic patients. Table I: Possible advantages of medical nephrectomy. 1. Reversal of hypotension and shock 2. Ability to perform hemodialysis 3. No anesthesia or surgical risk 4. No angiography related complications 5. Preservation of endocrine function of kidney. Possible advantages of medical nephrectomy (Table I), are: 1) Correction of proteinuria and hypotension; 2) Ability to perform hemodialysis; 3) No anesthesia or surgical risk; 4) No angiography related complications; and 5) Preservation of remaining endocrine function of the kidney, including erythropoietic and vitamin D action. The ideal agent should be non-toxic to other organs and produce selective renal ablation. Obviously mercury is not the ideal agent, although in these cases it did not produce observable side effects. It appears that this agent should be used with caution and only in patients with irreversible renal failure.

The behavior of carbenicillin as a nonreabsorbable anion.

In order to study the mechanism of hypokalemic alkalosis which occurs in some patients being treated with disodium carbenicillin, renal clearance experiments were carried out in rats and observations were made on electrical changes in isolated toad bladders. In rats maintained on a sodium-free diet, intravenous infusion of carbenicillin at 40 mg. per hour resuited in an immediate diuresis characterized by a striking increase in K and NH4 excretion, and progressive acidification of the urine. In a control group of rats, also prepared with a sodium free diet, intravenous infusion of mannitol resulted in a comparable diuresis, but no significant changes in K and NH4 excretion, and no acidification of the urine. The urinary changes in the carbenicillin-treated rats could not be accounted for by any alterations in blood electrolytes, acid-base values, or glomerular filtration rate (GFR). Isonatric, isohydric substitution of carbenicillin for chloride in the mucosal bathing media of toad bladders mounted in Ussing chambers resulted in a reversible increase in electrical potential (PD) and resistance (R) without a comparable change in short-circuit current (SCC). Substitution in the serosal medium resulted in a reversal of polarity of PD and SCC in 4 of 9 experiments, a finding best explained by more rapid movement of chloride from M leads to S than carbenicillin movement from S leads to M (a chloride diffusion potential). The observations in both the rat and toad bladder experiments are consistent with the view that carbenicillin behaves as a nonreabsorbable anion. Hypokalemic alkalosis in patients receiving this drug can thus be attributed to increased electrical negativity of the distal nephron with subsequent enhancement of K and H secretion.