In a prospective survey, one hundred and eleven dogs with canine chronic renal disease, presenting to 24 veterinary practices in East Anglia and the West Midlands (geographical area 8,600 square miles) were identified. More than 20 different breeds were represented. In 76 cases, clinical details, blood and urine biochemistry, serology and kidney tissue for light and electron microscopy, and immunohistochemistry were obtained. Forty (52%) had glomerular (GN) and 36 (48%) non-glomerular (NGN) disease. Types of GN identified were (W.H.O. classification, number of cases in brackets): focal glomerulonephritis (gn) (5), diffuse mesangial proliferative gn (8), diffuse endocapillary proliferative gn (2), mesangiocapillary gn type I (8), diffuse crescentic gn (1), diffuse sclerosing gn (7), amyloid (6), unclassifiable gn (3). Eight dogs with GN and 13 with NGN had extra-renal lesions. In only one GN case (bacterial endocarditis) was the etiology clear. Proteinuria, but not age, breed, sex, serum creatinine or hematuria, discriminated between GN and NGN groups. This prospective survey identifies GN, with morphological types as found in humans, as a common cause of canine chronic renal disease.

Systemic lupus erythematosus (SLE) is a potentially fatal non–organ-specific autoimmune disease that predominantly affects women. Features of the disease include inflammatory skin lesions and widespread organ damage caused by deposition of anti-dsDNA autoantibodies. The mechanism and site of production of these autoantibodies is unknown, but there is evidence that interferon (IFN) γ plays a key role. We have used the involucrin promoter to overexpress IFN-γ in the suprabasal layers of transgenic mouse epidermis. There was no evidence of organ-specific autoimmunity, but transgenic animals produced autoantibodies against dsDNA and histones. Autoantibody levels in female mice were significantly higher than in male transgenic mice. Furthermore, there was IgG deposition in the glomeruli of all female mice and histological evidence of severe proliferative glomerulonephritis in a proportion of these animals. Our findings are consistent with a central role for the skin immune system, acting under the influence of IFN-γ, in the pathogenesis of SLE.

Activated macrophages synthesize nitric oxide (NO) from L-arginine. In culture, the major stable end product is nitrite (NO2). Activated macrophages accumulate in glomeruli and are responsible for injury in experimental immune complex glomerulonephritis. We examined NO2- production by isolated glomeruli and urinary NO2- in accelerated nephrotoxic nephritis in the rat. Normal glomeruli did not produce NO2- spontaneously or when stimulated with lipopolysaccharide (LPS) (1 microgram/ml) or A23187 (2 microgram/ml). Cultured mesangial cells at first or seventh passage did not produce NO2- spontaneously or when stimulated. Nephritic glomeruli spontaneously produced NO2 at all times studied; this production was maximal at 24 hours after induction of glomerulonephritis (158.4 +/- 8.4 nmol/48 hr/ml, N = 3). The production of NO2- was inhibited 75 to 100% by NG-monomethyl-L-arginine (L-NMMA), and this inhibition was reversed by L-arginine, indicating NO2- production from L-arginine via NO. The production of NO2- was increased by LPS (1 microgram/ml) at 2, 7 and 21 days. NO2- was undetectable in normal rat urine; however, it was present in urine of rats with glomerulonephritis (Day 0 to 1:8161 +/- 2605 nmol/24 hr. N = 12). The production of NO in nephritic glomeruli may have implications for both the mechanism of glomerular injury and glomerular hemodynamics.