Faculty Bibliography

OBJECTIVES: To describe the unusual occurrence of systemic lupus erythematosus (SLE) with nephritis in human immunodeficiency virus (HIV)-infected individuals. METHODS: Chart review-based report of a case of SLE with diffuse proliferative glomerulonephritis (DPGN) in an HIV-infected man, together with a literature review of previously published cases. We searched the English language medical literature from 1987 to 2009 using the following PubMed and Medline terms: "SLE," "HIV," "DPGN." In addition, we researched the role of mycophenolate mofetil (MMF) in the treatment of patients with HIV by using the keywords "MMF" and "HIV". RESULTS: An 18-year-old male patient with vertically transmitted HIV-1 infection presented with malaise, weight loss, malar rash, arthritis, proteinuria, and hematuria. Kidney biopsy confirmed the diagnosis of lupus nephritis (Class IV). He was treated successfully with high-dose corticosteroids and MMF, which were added to his baseline treatment of highly active antiretroviral therapy. The review of the literature identified a total of 18 cases of SLE appearing in HIV+ individuals, of which 11 patients had lupus nephritis. Among the latter, there were only 5 cases of proliferative (focal or diffuse) glomerulonephritis, and their treatment consisted mainly of high-dose corticosteroids. The short-term outcome was favorable in 4 cases and 1 patient died. CONCLUSIONS: Proliferative lupus nephritis is rare in HIV-infected patients. A detailed analysis of the cases may lead to important insights into the pathogenic mechanisms of both diseases. Considering its complex interaction with antiviral medications, MMF may be considered for the treatment of lupus with severe proliferative glomerulonephritis in HIV-infected individuals.

OBJECTIVES: Clinical and laboratory markers in current use have limited specificity and sensitivity for predicting the development of renal disease in lupus patients. In this longitudinal study, we investigated whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts active nephritis and renal flares in lupus patients with and without a history of biopsy-proven lupus nephritis. METHODS: Renal disease activity and flare status was determined by SLEDAI and BILAG scores. Random effects models were used to determine whether uNGAL was a significant predictor for renal disease activity in SLE patients, and for renal flares in patients with established nephritis. To assess the predictive performance of uNGAL, receiver operating characteristic (ROC) curves were constructed using the previous visit's uNGAL level. These curves were then compared with curves constructed with currently used biomarkers. Cut-offs determined by ROC curves were tested in an independent validation cohort. RESULTS: uNGAL was found to be a significant predictor of renal disease activity in all SLE patients, and a significant predictor for flare in patients with a history of biopsy-proven nephritis, in multivariate models adjusting for age, race, sex and anti-double-stranded (ds)DNA antibody titres. As a predictor of renal flare in patients with biopsy-proven nephritis, uNGAL outperformed anti-dsDNA antibody titres. These results were confirmed in an independent validation cohort. CONCLUSIONS: uNGAL predicts renal flare in patients with a history of biopsy-proven nephritis with high sensitivity and specificity. Furthermore, uNGAL is a more sensitive and specific forecaster of renal flare in patients with a history of lupus nephritis than anti-dsDNA antibody titres.

OBJECTIVE: To study the membrane expression of endothelial protein C receptor (mEPCR) in the renal microvasculature in lupus nephritis (LN) as a potential marker of injury and/or prognostic indicator for response to therapy. METHODS: mEPCR expression was analysed by immunohistochemistry in normal kidney and in 59 biopsies from 49 patients with LN. Clinical parameters were assessed at baseline, 6 months and 1 year. RESULTS: mEPCR was expressed in the medulla, arterial endothelium and cortical peritubular capillaries (PTCs) in all biopsies with LN but not in the cortical PTCs of normal kidney. Positive mEPCR staining in >25% of the PTCs was observed in 16/59 biopsies and associated with poor response to therapy. Eleven (84.6%) of 13 patients with positive staining for mEPCR in >25% of the PTCs and follow-up at 6 months did not respond to therapy, compared with 8/28 (28.6%) with mEPCR staining in < or =25% PTCs, P = 0.0018. At 1 year, 10 (83.3%) of 12 patients with positive mEPCR staining in >25% of the PTCs did not respond to therapy (with two progressing to end-stage renal disease) compared with 8/24 (33.3%) with positive staining in < or =25% of the PTCs, P = 0.0116. Although tubulo-interstitial damage (TID) was always accompanied by mEPCR, this endothelial marker was extensively expressed in the absence of TID suggesting that poor response could not be attributed solely to increased TID. mEPCR expression was independent of International Society of Nephrology/Renal Pathology Society class, activity and chronicity indices. CONCLUSION: Increased mEPCR expression in PTCs may represent a novel marker of poor response to therapy for LN