James V. Donadio

A Controlled Trial of Fish Oil in IgA Nephropathy

BACKGROUND The n-3 fatty acids in fish oil affect eicosanoid and cytokine production and therefore have the potential to alter renal hemodynamics and inflammation. The effects of fish oil could prevent immunologic renal injury in patients with IgA nephropathy. METHODS In a multicenter, placebo-controlled, randomized trial we tested the efficacy of fish oil in patients with IgA nephropathy who had persistent proteinuria. The daily dose of fish oil was 12 g; the placebo was a similar dose of olive oil. Serum creatinine concentrations, elevated in 68 percent of the patients at base line, and creatinine clearance were measured for two years. The primary end point was an increase of 50 percent or more in the serum creatinine concentration at the end of the study. RESULTS Fifty-five patients were assigned to receive fish oil, and 51 to receive placebo. According to Kaplan-Meier estimation, 3 patients (6 percent) in the fish-oil group and 14 (33 percent) in the placebo group had increases of 50 percent or more in their serum creatinine concentrations during treatment (P = 0.002). The annual median changes in the serum creatinine concentrations were 0.03 mg per deciliter (2.7 mumol per liter) in the fish-oil group and 0.14 mg per deciliter (12.4 mumol per liter) in the placebo group. Proteinuria was slightly reduced and hypertension was controlled to a comparable degree in both groups. The cumulative percentage of patients who died or had end-stage renal disease was 40 percent in the placebo group after four years and 10 percent in the fish-oil group (P = 0.006). No patient discontinued fish-oil treatment because of adverse effects. CONCLUSIONS In patients with IgA nephropathy, treatment with fish oil for two years retards the rate at which renal function is lost.

Treatment of Diffuse Proliferative Lupus Nephritis with Prednisone and Combined Prednisone and Cyclophosphamide

To evaluate the effectiveness of cyclophosphamide in the treatment of lupus nephritis, we designed a prospective study of patients with diffuse proliferative lupus nephritis. Twenty-six patients received prednisone (average dose, 40 mg per day) and 24 combined prednisone (average dose, 29 mg per day) and cyclophosphamide (average dose, 107 mg per day) for six months. Thereafter, all patients received maintenance doses of prednisone. Most of the patients improved (84 per cent) after six months of initial treatment with either program. Early progression of disease, ending mainly in end-stage renal disease, was equally frequent in the two treatment groups in patients with already advanced disease. In a four-year follow-up study there was a higher incidence (P approximately 0.04) and average rate (P approximately 0.02) of clinical recurrence of nephritis in the group initially given only steroid than in the group initially given both drugs. However, the proportion of patients alive after four years with stable or improved renal function was similar in the two treatment groups.

Membranoproliferative glomerulonephritis. A prospective clinical trial of platelet-inhibitor therapy

Forty patients with Type I membranoproliferative glomerulonephritis were treated for one year with dipyridamole, 225 mg per day, and aspirin, 975 mg per day, in a prospective, randomized, double-blind, placebo-controlled study. At the base line, the half-life of 51Cr-labeled platelets was reduced in 12 of 17 patients. The platelet half-life became longer and renal function stabilized in the treated group, as compared with the placebo group, suggesting a relation between platelet consumption and the glomerulopathy. The glomerular filtration rate, determined by iothalamate clearance, was better maintained in the treated group (average decrease, 1.3 ml per minute per 1.73 m2 of body-surface area per 12 months) than in the placebo group (average decrease, 19.6). Fewer patients in the treated group than in the placebo group had progression to end-stage renal disease (3 of 21 after 62 months as compared with 9 of 19 after 33 months). The data suggest that dipyridamole and aspirin slowed the deterioration of renal function and the development of end-stage renal disease.

Renal Involvement in Primary Sjögren's Syndrome: A Clinicopathologic Study

BACKGROUND & OBJECTIVES Renal pathology and clinical outcomes in patients with primary Sjögrens syndrome (pSS) who underwent kidney biopsy (KB) because of renal impairment are reported. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Twenty-four of 7276 patients with pSS underwent KB over 40 years. Patient cases were reviewed by a renal pathologist, nephrologist, and rheumatologist. Presentation, laboratory findings, renal pathology, initial treatment, and therapeutic response were noted. RESULTS Seventeen patients (17 of 24; 71%) had acute or chronic tubulointerstitial nephritis (TIN) as the primary lesion, with chronic TIN (11 of 17; 65%) the most common presentation. Two had cryoglobulinemic GN. Two had focal segmental glomerulosclerosis. Twenty patients (83%) were initially treated with corticosteroids. In addition, three received rituximab during follow-up. Sixteen were followed after biopsy for more than 12 mo (median 76 mo; range 17 to 192), and 14 of 16 maintained or improved renal function through follow-up. Of the seven patients presenting in stage IV chronic kidney disease, none progressed to stage V with treatment. CONCLUSIONS This case series supports chronic TIN as the predominant KB finding in patients with renal involvement from pSS and illustrates diverse glomerular lesions. KB should be considered in the clinical evaluation of kidney dysfunction in pSS. Treatment with glucocorticoids or other immunosuppressive agents appears to slow progression of renal disease. Screening for renal involvement in pSS should include urinalysis, serum creatinine, and KB where indicated. KB with characteristic findings (TIN) should be considered as an additional supportive criterion to the classification criteria for pSS because it may affect management and renal outcome.

The Risks of Unilateral Nephrectomy: Status of Kidney Donors 10 to 20 Years Postoperatively

We received requested follow-up information from 105 (73%) of our 144 kidney donors who had undergone unilateral nephrectomy 10 to 20 years previously. Five donors had died of unrelated causes 6 or more years postoperatively. Studies in the remaining 100 donors showed that the current mean serum creatinine concentration was 1.2 mg/dl and the mean 24-hour urinary protein value was 89 mg. Hypertension (defined as 160 mm Hg or more systolic, 95 mm Hg or more diastolic, or both) was present in 19% of the donors. In a subgroup of 66 donors who had had serial serum creatinine determinations, the renal function, as estimated on the basis of these serum creatinine values, had not deteriorated with time. Thus, we consider unilateral nephrectomy in this group of patients relatively safe. Subsequent evaluation will be necessary to ascertain whether these findings prevail.

Clinical Trial to Evaluate Omega-3 Fatty Acids and Alternate Day Prednisone in Patients with IgA Nephropathy: Report from the Southwest Pediatric Nephrology Study Group

This randomized, placebo-controlled, double-blind trial evaluated the role of prednisone and omega 3 fatty acids (O3FA) in patients with IgA nephropathy. Entry criteria were (1) biopsy-proven IgA nephropathy, (2) estimated GFR > or = 50 ml/min per 1.73 m2, and (3) moderate to severe proteinuria. Thirty-three patients were randomly assigned to receive prednisone 60 mg/m2 every other day for 3 mo, then 40 mg/m2 every other day for 9 mo, then 30 mg/m2 every other day for 12 mo (prednisone group); 32 were randomly assigned to receive O3FA 4 g/d for 2 yr (1.88 g eicosapentaenoic acid, 1.48 g docosahexaenoic acid; O3FA group); and 31 were randomly assigned to receive placebo (placebo group). Most (73%) patients completed 2 yr of treatment. Randomly assigned patients who were hypertensive were given enalapril 2.5 to 40 mg/d. The primary end point was time to failure, defined as estimated GFR <60% of baseline. An overall significance level of 0.10 was used. The three groups were comparable at baseline except that the O3FA group had higher urine protein to creatinine (UP/C) ratios than the placebo group (P = 0.003). Neither treatment group showed benefit over the placebo group with respect to time to failure, with 14 patient failures overall (two in the prednisone group, eight in the O3FA group, and four in the placebo group). The primary factor associated with time to failure was higher baseline UP/C ratios (P = 0.009). Superiority of prednisone or O3FA over placebo in slowing progression of renal disease was not demonstrated in this study. However, the relatively short follow-up period, inequality of baseline UP/C ratios, and small numbers of patients precludes definitive conclusions.

Treatment of Lupus Nephritis with Prednisone and Combined Prednisone and Azathioprine

Abstract The relative effectiveness of high-dose prednisone (group A) was compared with the same regimen plus azathioprine (group B) for the treatment of lupus nephritis of mild or moderate severit...

Immunosuppressive Drug Therapy in Lupus Nephritis

During the past two decades, the immunosuppressive drugs azathioprine and cyclophosphamide have been widely used in the treatment of patients with lupus nephritis. Their toxicities are well known and are mostly dose- and time-dependent. Complications that arise from these therapies stem from their immunosuppressive (susceptibility for infection) or pharmacologic (hemorrhagic cystitis, bladder cancer, and fibrosis from the alkylating agents) effects, or both. Uncontrolled studies reporting good results in treating patients with various combinations of corticosteroids and azathioprine and, especially, cyclophosphamide cannot be conclusively confirmed by the few controlled clinical trials that are available for review. Part of the problem of inconclusiveness has to do with timing treatment to different phases of the disease and the vast heterogeneity of lupus nephritis. Although these immunosuppressive agents may have favorable effects on the overall activity of systemic lupus erythematosus, their long-term effects per se on renal disease are in question and could be attributed to lower prednisone dosage and better medical management of hypertension, hyperlipidemia, infection, and other metabolic consequences of the disease.

MEMBRANOUS LUPUS NEPHROPATHY: A CLINICOPATHOLOGIC STUDY

Twenty-eight patients with SLE and distinct, well-defined renal morphologic lesions of membranous nephropathy were followed up for 4 years. These patients comprised approximately 8% of the patients evaluated for SLE during a 12-year period. The patients with membranous lupus nephropathy had typical systemic features of SLE, and most of them had positive LE cell tests and ANA, low serum complement concentrations, and mildly elevated serum antinative DNA levels. Proteniuria and microscopic hematuria were usually discovered years after systemic symptoms of SLE had developed, Only two patients had slowly progressive renal failure, and most patients continued to have proteinuria. Prednisone treatment did not influence either proteinuria or renal function. In only one patient, the renal character of the disease changed drastically, demonstrating membranoproliferative glomerulonephritis. Six patients died (21%); most of these died of cardiovascular illnesses. The relatively benign and stable renal course of membranous lupus nephropathy in patients with otherwise typical SLE suggests that the renal pathogenesis is different from that of proliferative lupus nephritis.

Enhanced absorption of n-3 fatty acids from emulsified compared with encapsulated fish oil.

Health benefits of n-3 fatty acids are well-established. However, consumption of adequate dietary sources of these fatty acids is inadequate. Oral fish oil supplements are an alternative means of consuming adequate long-chain n-3 fatty acids in individuals who do not consume sufficient dietary sources. However, palatability can present a problem with compliance. Emulsifying fish oil allows for production of a pleasant-tasting supplement and can enhance digestion and absorption of the fatty acids. We investigated the rate and extent of absorption of emulsified fish oil compared with capsular triglyceride fish oil supplements in humans. Participants subjectively rated palatability of these products. A randomized, crossover-designed, open-label trial was performed in which 10 healthy volunteers received emulsified fish oil and capsular triglyceride fish oil orally. Blood samples were collected at 0, 2, 4, 8, 24, and 48 hours to determine the absorption of individual fatty acids into plasma phospholipid fatty acids. At the completion of blood collection, subjects were asked to subjectively rate the tolerance and acceptability of the two supplements. During a 48-hour period, there was enhanced absorption of total n-3 and eicosapentaenoic acid (0.67%+/-0.16%, 0.45%+/-0.06%; P<0.01; 0.34%+/-0.05%, 0.23%+/-0.04%; P=0.05; emulsified fish oil and capsular triglyceride fish oil, respectively) observed for the emulsified fish oil treatment. Our findings indicate that a single dose of emulsified fish oil resulted in enhanced absorption of total n-3 eicosapentaenoic acid and docosahexaenoic acid as evidenced by changes in phospholipid fatty acids composition compared with the capsular triglyceride fish oil during the 48-hour observation period. Both supplements were subjectively rated and found to be well-tolerated by participants.