SIRT3 attenuates palmitate-induced ROS production and inflammation in proximal tubular cells.

Free fatty acid (FFA)-mediated renal lipotoxicity is associated with the progression of tubulointerstitial inflammation in proteinuric kidney disease. SIRT3 is an antiaging molecule regulated by calorie restriction and mitochondria-localized NAD(+)-dependent deacetylase. In this study, we investigated whether SIRT3 reversed renal lipotoxicity-mediated ROS and inflammation. In the kidney of the FFA-bound BSA-overloaded mouse, which is a well-established experimental model of FFA-associated tubulointerstitial inflammation, mRNA expression of SIRT3 was significantly decreased and negatively correlated with mRNA expression of an inflammatory cytokine, monocyte chemoattractant protein-1 (MCP-1). In cultured proximal tubular (mProx) cells, the saturated FFA palmitate stimulated ROS accumulation and expression of MCP-1. These effects were ameliorated by retrovirus-mediated overexpression of SIRT3, whereas they were exacerbated by either overexpression of a dominant-negative form of SIRT3(N87A) lacking deacetylase activity or knockdown of SIRT3 by siRNA transfection. Furthermore, we showed that SIRT3 positively regulated both mitochondrial oxidative capacity and antioxidant gene expression, thereby reducing ROS accumulation in mProx cells, which suggests a mechanism that underlies SIRT3-mediated reversal of palmitate-induced inflammation. In conclusion, these results highlight a new role for SIRT3 in lipotoxicity/ROS-related inflammation, reveal a new molecular mechanism underlying calorie restriction-mediated antioxidant and anti-inflammatory effects, and could aid in the design of new therapies for the prevention of tubulointerstitial lesions in proteinuric kidney disease.

Acute interstitial nephritis associated with etanercept.

We encountered an adult patient with rheumatoid arthritis who developed acute interstitial nephritis associated with an anti-tumor necrosis factor alpha agent, etanercept.

The occurrence of systemic lupus erythematosus in an asymptomatic carrier of human T-cell lymphotropic virus type I.

A 63-year-old asymptomatic carrier of human T-cell lymphotropic virus type I (HTLV-1) infection was admitted because of chest oppression, a high-grade fever, polyarthralgia, and erythematous rashes. Laboratory examination revealed lymphocytopenia, proteinuria, and high titers of antinuclear antibodies and antidouble-stranded DNA antibody; thus, she was diagnosed as having systemic lupus erythematosus (SLE). This case indicates that HTLV-1 infection might be related with the pathogenesis of SLE.

A case of myeloperoxidase-antineutrophil cytoplasmic antibody positive-polyarteritis nodosa complicated by interstitial pneumonia and rapidly progressive renal failure.

A 73-year-old woman was admitted to our hospital because of persistent high fever and cough, generalized myalgia, and renal dysfunction. Laboratory examination revealed severe inflammatory signs, pulmonary fibrosis, progression of renal impairment with active nephritic urinary sediments, and a high titer of myeloperoxidase-antineutrophil cytoplasmic antibody, indicating that she might have microscopic polyangiitis with interstitial pneumonia and rapidly progressive glomerulonephritis. Her renal biopsy, however, showed tubulointerstitial changes with mild glomerular abnormalities, and renal angiography revealed that she had vascular lesions of medium-sized arteries, which were compatible with classical polyarteritis nodosa. Tissue biopsy of the clinically affected organ should be considered in anyone suspected to have vasculitis.

Incidence of intraoperative floppy iris syndrome in patients on either systemic or topical alpha(1)-adrenoceptor antagonist.

PURPOSE: To evaluate the incidence of Intraoperative Floppy Iris syndrome (IFIS) in relation to the usage of alpha(1)-adrenoceptor antagonists. DESIGN: Prospective, interventional case series. METHODS: In 2,643 consecutive eyes of 1,968 patients undergoing cataract surgery, occurrence of IFIS and use of alpha(1) antagonists were recorded. RESULTS: IFIS was observed in 29 eyes (1.1%) of 25 male patients, all of whom were receiving alpha(1) antagonists. In those receiving systemic tamsulosin, alpha(1A) selective antagonist, IFIS developed in 25 (43.1%) of 58 eyes. In those receiving systemic naftopidil, alpha(1A) and alpha(1D) antagonists, IFIS was found in 4 (19.0%) of 21 eyes. There was no case of IFIS in patients who received other systemic alpha(1) antagonists and in eyes treated with bunazosin eyedrops, a nonselective alpha(1) antagonist. CONCLUSIONS: IFIS occurred in 1.1% of cases treated with systemic alpha(1A)-adrenoceptor antagonists for benign prostatic hypertrophy. Topical nonselective alpha(1) antagonist did not induce IFIS.

Lupus vasculopathy combined with renal infarction: unusual manifestation of lupus nephritis.

A 30-year-old woman with a 10-year history of systemic lupus erythematosus was admitted to our hospital because of the onset of hypertension and renal dysfunction. Renal arteriogram revealed multiple renal infarctions, and cut-off or tapering-stenosis in the interlobular arteries. Renal biopsy showed concentric intimal thickening with narrowed lumen in some arterioles and deposition of IgG/IgM/complement 3 in the wall of arteriole without any active lesions or immune complex deposition in glomeruli. The present case indicates that this type of renal vascular lesion in lupus nephritis, lupus vasculopathy, may cause renal infarction and the loss of renal function without active glomerular lesions.