Claudia Hura

Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis

Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m(2) in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.

Abetimus sodium for renal flare in systemic lupus erythematosus: Results of a randomized, controlled phase III trial†

OBJECTIVE To investigate whether treatment with abetimus delays renal flare in patients with lupus nephritis. Secondary objectives included evaluation of the effect of abetimus on C3 levels, anti-double-stranded DNA (anti-dsDNA) antibody levels, use of high-dose corticosteroids and/or cyclophosphamide, and major systemic lupus erythematosus (SLE) flare. METHODS We conducted a randomized, placebo-controlled study of treatment with abetimus at 100 mg/week for up to 22 months in SLE patients. Three hundred seventeen patients with a history of renal flare and anti-dsDNA levels >15 IU/ml were randomized to a treatment group (158 abetimus, 159 placebo); 298 (94%) were enrolled in the intent-to-treat (ITT) population (145 abetimus, 153 placebo), based on the presence of high-affinity antibodies for the oligonucleotide epitope of abetimus at baseline screening. RESULTS Abetimus did not significantly prolong time to renal flare, time to initiation of high-dose corticosteroid and/or cyclophosphamide treatment, or time to major SLE flare. However, there were 25% fewer renal flares in the abetimus group compared with the placebo group (17 of 145 abetimus-treated patients [12%] versus 24 of 153 placebo-treated patients [16%]). Abetimus treatment decreased anti-dsDNA antibody levels (P < 0.0001), and reductions in anti-dsDNA levels were associated with increases in C3 levels (P < 0.0001). More patients in the abetimus group experienced > or =50% reductions in proteinuria at 1 year, compared with the placebo group (nominal P = 0.047). Trends toward reduced rates of renal flare and major SLE flare were noted in patients treated with abetimus who had impaired renal function at baseline. Treatment with abetimus for up to 22 months was well tolerated. CONCLUSION Abetimus at 100 mg/week significantly reduced anti-dsDNA antibody levels but did not significantly prolong time to renal flare when compared with placebo. Multiple positive trends in renal end points were observed in the abetimus treatment group.

Hydralazine Induces Myeloperoxidase and Proteinase 3 Anti-Neutrophil Cytoplasmic Antibody Vasculitis and Leads to Pulmonary Renal Syndrome

We report a case of hydralazine-induced ANCA-associated glomerulonephritis with pulmonary hemorrhage. A 62-year-old Hispanic man with hypertension, who was being treated with hydralazine 100 mg three times a day for four and half years, presented to the hospital with severe anemia. He had acute kidney injury and urinalysis showed proteinuria, dysmorphic RBCs, and rare RBC cast. CT scan of the chest revealed bilateral pulmonary ground-glass infiltrates. Transbronchial biopsy was consistent with pulmonary hemorrhage. Serologic tests showed high titer PR3 ANCA and, to a lesser extent, MPO ANCA. Kidney biopsy revealed focal segmental necrotizing glomerulonephritis with crescents, without evidence of immune complex deposits. Hydralazine was discontinued and the patient was treated with corticosteroids and intravenous cyclophosphamide. At one-year follow-up, he had no symptoms and anemia had resolved. Kidney function improved dramatically. Serology showed undetectable PR3 ANCA and minimally elevated MPO ANCA. To our knowledge, hydralazine-associated PR3 ANCA has not been previously reported. The possibility of ANCA systemic vasculitis should be included in the differential diagnosis of any patient with hydralazine use and pulmonary renal syndrome. This is a potentially life threatening condition requiring prompt cessation of the drug and treatment with glucocorticoids and immunosuppression.

Tryptophan Metabolism in Patients With Chronic Kidney Disease Secondary to Type 2 Diabetes: Relationship to Inflammatory Markers:

Objective: Type 2 diabetes (T2D) is the primary case of chronic kidney disease (CKD). Inflammation is associated with metabolic dysregulation in patients with T2D and CKD. Tryptophan (TRP) metabolism may have relevance to the CKD outcomes and associated symptoms. We investigated the relationships of TRP metabolism with inflammatory markers in patients with T2D and CKD. Methods: Data were collected from a well-characterized cohort of type 2 diabetic individuals with all stages of CKD, including patients on hemodialysis. Key TRP metabolites (kynurenine [KYN], kynurenic acid [KYNA], and quinolinic acid [QA]), proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6]), and C-reactive protein were measured in plasma. The KYN/TRP ratio was utilized as a surrogate marker for indoleamine 2,3-dioxygenase 1 (IDO1) enzyme activity. Results: There was a significant inverse association between circulating TRP level and stages of CKD (P < 0.0001). Downstream bioactive TRP metabolites KYN, KYNA, and QA were positively and robustly correlated with the severity of kidney disease (P < 0.0001). In multiple linear regression, neither TNF-α nor IL-6 was independently related to KYN/TRP ratio after adjusting for estimated glomerular filtration rate (eGFR). Only TNF-α was independently related to KYN after taking into account the effect of eGFR. Conclusions: Chronic kidney disease secondary to T2D may be associated with accumulation of toxic TRP metabolites due to both inflammation and impaired kidney function. Future longitudinal studies to determine whether the accumulation of KYN directly contributes to CKD progression and associated symptoms in patients with T2D are warranted.

Quality of Life and Depression Among Mexican Americans on Hemodialysis: A Preliminary Report

Health‐related quality of life (QOL) and depression burden of Mexican Americans with end‐stage renal disease (ESRD) are not known. This observational cross‐sectional study assessed QOL and depression and examined their inter‐relatedness in Mexican Americans with type 2 diabetes and ESRD on maintenance hemodialysis (HD) treatment. Prevalent Mexican Americans on HD (N = 40) completed the Kidney Disease Quality of Life‐Short Form (KDQOL‐SF) and the Beck Depression Inventory II. The overall median scores for the mental component summary and the physical component summary scales in the KDQOL‐SF were 40.9 and 34.0, respectively. The prevalence of severe depression was 40%. The most significant differences between depressed and non‐depressed groups were symptom/problem list, cognitive function, and emotional well‐ being (P < 0.0001 for all). Mexican Americans with depression endure a more dismal QOL compared to non‐depressed peers. Significant negative correlations between depression and several QOL scales underscore plausible interactions between the two conditions which warrants further evaluation.