These data indicate that urinary angiotensinogen is a powerful tool for determining intrarenal RAS status and associated renal derangement in patients with IgA nephropathy.

We demonstrated previously that the blood pressure of patients with IgA nephropathy becomes salt sensitive as renal damage progresses. We also showed that increased urinary angiotensinogen levels in such patients closely correlate with augmented renal tissue angiotensinogen gene expression and angiotensin II levels. Here, we investigated the relationship between urinary angiotensinogen and salt sensitivity of blood pressure in patients with IgA nephropathy. Forty-one patients with IgA nephropathy consumed an ordinary salt diet (12 g/d of NaCl) for 1 week and a low-salt diet (5 g/d of NaCl) for 1 week in random order. The salt-sensitivity index was calculated as the reciprocal of the slope of the pressure-natriuresis curve drawn by linking 2 data points obtained during consumption of each diet. The urinary angiotensinogen:creatinine ratio was significantly higher in patients who consumed the ordinary salt diet compared with the low-salt diet (17.5 μg/g [range: 7.3 to 35.6 μg/g] versus 7.9 μg/g [range: 3.1 to 14.2 μg/g] of creatinine, respectively; P<0.001). The sodium sensitivity index in our patients positively correlated with the glomerulosclerosis score (r=0.43; P=0.008) and changes in logarithmic urinary angiotensinogen:creatinine ratio (r=0.37; P=0.017) but not with changes in urinary protein excretion (r=0.18; P=0.49). In contrast, changes in sodium intake did not alter the urinary angiotensinogen:creatinine ratio in patients with Ménière disease and normal renal function (n=9). These data suggest that the inappropriate augmentation of intrarenal angiotensinogen induced by salt and associated renal damage contribute to the development of salt-sensitive hypertension in patients with IgA nephropathy.

Tonsillectomy was associated with a favorable renal outcome of IgA nephropathy in terms of clinical remission and delayed renal deterioration even in non-steroid-treated patients.

Treatment with angiotensin II type 1 receptor blockers (ARBs) is the first-line therapy for hypertensive patients with diabetic nephropathy. However, emerging clinical evidence indicates that mineralocorticoid receptor (MR) blockers have blood pressure-independent antiproteinuric effects. We sought to determine whether treatment with an MR blocker, eplerenone, enhances the effects of an ARB, telmisartan, on podocyte injury and proteinuria in type 2 diabetic Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats. From 20 to 50 weeks old, diabetic OLETF rats showed higher systolic blood pressure (SBP) and urinary protein excretion (U protein V) than nondiabetic control Long-Evans-Tokushima-Otsuka rats. At 50 weeks old, OLETF rats also showed glomerular sclerosis and podocyte injury, whereas nephrin and podocin mRNA levels in isolated glomeruli were significantly decreased. Treatment with telmisartan (3 mg/ kg/day p.o.) decreased SBP and U protein V, increased nephrin and podocin mRNA levels, and attenuated glomerular sclerosis and podocyte injury. Eplerenone (100 mg/kg/day p.o.) did not alter SBP but elicited similar changes in renal parameters. However, greater reductions in U protein V and podocyte injury and greater increases in nephrin and podocin mRNA levels were observed in the combination treatment group. Hydralazine (25 mg/kg/day p.o.) decreased SBP but did not alter any renal parameters. These data indicate that MR blockade enhances the SBP-independent antiproteinuric effect of an ARB through inhibiting podocyte injury in type 2 diabetic rats.

A 76-year-old man with lung cancer and multiple metastases was admitted for purpura and rapidly progressive glomerulonephritis. Adenosquamous cell carcinoma of the lung had been diagnosed 6 months earlier.Two anti-cancer drug regimens had no effect. At admission, his survival with his malignancy was estimated to be several months. Renal biopsy revealed pauci-immune necrotizing crescentic glomerulonephritis (CrGN). Negative results were obtained for myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA) and proteinase-3-ANCA by enzyme-linked immunosorbent assay, and for peripheral-ANCA and cytoplasmic-ANCA by indirect immunofluorescence. He was diagnosed with ANCA-negative pauciimmune CrGN. Although steroids were initiated, the patient died of renal failure and intestinal bleeding 2 weeks later. It was later found that cancer cells were positive for interleukin (IL)-6 and that serum IL-6 levels were significantly elevated, concomitantly with increased IL-8, granulocyte-colony stimulating factor and transforming growth factor-b levels. Some kinds of lung cancer are known to produce IL-6 that activate neutrophils and are related to ANCA-associated CrGN. It appears that IL-6 can activate neutrophils in the pathogenesis of ANCA-negative pauciimmune CrGN with lung cancer. Therapy that blocks IL-6 may prove to be effective in vasculitis and cancer-related symptoms in such cases.