Serum permeability activity in steroid-resistant minimal change nephrotic syndrome is abolished by treatment of Hodgkin disease.

A circulating permeability factor is present in some patients with minimal change nephrotic syndrome (MCNS) or focal segmental glomerulosclerosis. Nephrotic syndrome occurs in less than 1% of patients with Hodgkin disease. A substance derived from T lymphocytes may be responsible for proteinuria in these patients, but a circulating permeability factor was not shown. Serum permeability activity (P(alb)) of a young man who presented with MCNS was tested over 11 years. He first was treated with oral prednisone, then cyclosporine (CsA; 4 mg/kg/d). Two years after the initial diagnosis, during CsA-induced remission of nephrotic syndrome, Hodgkin disease was diagnosed and he underwent systemic chemotherapy with doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine and radiation therapy. P(alb) was 0.67 before CsA therapy. Although CsA treatment decreased proteinuria to protein less than 100 mg/d, P(alb) did not change. P(alb) decreased to 0.19 within 2 weeks of initiation of chemotherapy for Hodgkin disease and has remained at less than 0.17 for the last 9 years. The patient, in remission from Hodgkin disease, has normal renal function and no detectable proteinuria. This is the first demonstration of the presence of P(alb) in a patient with MCNS and subsequent Hodgkin disease. It also is the first report that aggressive chemotherapy abolishes P(alb). Although the potential causal relationship between nephrotic syndrome and Hodgkin disease in this patient is not clear, the immediate decrease in P(alb) during treatment suggests that aggressive chemotherapy may be an effective treatment for patients with high P(alb) in steroid-resistant MCNS or focal segmental glomerulosclerosis.

A pilot study of the effect of sodium thiosulfate on urinary lithogenicity and associated metabolic acid load in non-stone formers and stone formers with hypercalciuria.

BACKGROUND AND OBJECTIVES: Sodium thiosulfate (STS) reduced calcium stone formation in both humans and genetic hypercalciuric stone forming (GHS) rats. We sought to measure urine chemistry changes resulting from STS administration in people. DESIGN SETTING PARTICIPANTS MEASUREMENTS: STS was given to healthy and hypercalciuric stone forming adults. Five normal non-stone forming adults (mean age 33 years), and 5 people with idiopathic hypercalciuria and calcium kidney stones (mean age 66 years) participated. Two baseline 24-hour urine collections were performed on days 2 and 3 of 3 days of self-selected diets. Subjects then drank STS 10 mmol twice a day for 7 days and did urine collections while repeating the self-selected diet. Results were compared by non-parametric Wilcoxon signed rank test. The primary outcome was the resulting change in urine chemistry. RESULTS: STS administration did not cause a significant change in urinary calcium excretion in either group. In both groups, 24 hour urinary ammonium (P = 0.005) and sulfate excretion (P = 0.007) increased, and urinary pH fell (P = 0.005); citrate excretion fell (P<0.05) in hypercalciuric participants but not in non-stone formers. Among stone formers with hypercalciuria, 3 of 5 patients had measurement of serum HCO3 concentration after the STS period: it did not change. The net effect was an increase in supersaturation of uric acid, and no change in supersaturation of calcium oxalate or calcium phosphate. CONCLUSIONS: The basis for studies demonstrating that STS prevented stones in rats and people was not reflected by the changes in urine chemistry reported here. Although serum HCO3 did not change, urine tests suggested an acid load in both non-stone forming and hypercalciuric stone-forming participants. The long term safety of STS needs to be determined before the drug can be tested in humans for long-term prevention of stone recurrence.

Lack of nephrotoxicity of gadodiamide in unselected hospitalized patients.

BACKGROUND: The nephrotoxicity of gadolinium-based magnetic resonance contrast media has not been adequately studied. METHODS: We evaluated the nephrotoxicity of gadolinium-based contrast media in hospitalized patients who underwent magnetic resonance imaging (MRI) as part of routine clinical care. Subjects who had a serum creatinine measurement during the 7 days before MRI and at least 1 other measurement 2 to 3 days after MRI were included. Patients who underwent noncontrasted MRI served as controls. RESULTS: There were 162 subjects (mean age, 57.8 +/- 16.9 years; 91 men and 71 women) and 125 controls (mean age, 64.6 +/- 18 years; 62 men and 63 women). All contrast-enhanced MRI studies utilized gadodiamide (Omniscan; GE Healthcare, Waukesha, WI). Subjects who received gadodiamide showed no difference in the incidence of acute renal insufficiency compared with controls (increase in serum creatinine >or= 25%, 11.1% vs 12.9%, respectively; P = 0.6; increase in serum creatinine by 0.5 mg/dL, 5.6% vs 3.2%, respectively; P = 0.4). There was no significant increase in serum creatinine baseline versus 48 hours in either the subjects who received gadodiamide (0.95 +/- 0.58 vs 0.96 +/- 0.65 mg/dL; P = 0.7) or controls (0.96 +/- 0.65 vs 0.88 +/- 0.43 mg/dL; P = 0.7). CONCLUSION: Our findings showed a lack of significant nephrotoxicity of gadodiamide in unselected hospitalized patients.