Effect of ovariectomy on glomerular injury in hypercholesterolemic female Imai rats.

To clarify the pathogenesis of focal and segmental glomerulosclerosis, we investigated the effect of ovariectomy in hypercholesterolemic female Imai rats. At 5 weeks of age, control female (group 1) and control male rats (group 3) were sham-operated, female rats (group 2) were ovariectomized and male rats (group 4) were castrated. Body weight, blood pressure, urinary protein and serum constituents were checked every 2 months from 2 through 12 months of age. All groups were studied morphologically at 6 months of age and further female groups (1 and 2) studied at 12 months. Both control female and control male rats developed marked proteinuria, to a significantly greater extent in the male rats. Castration reduced proteinuria, while ovariectomy did not influence it and there were no significant differences in proteinuria among the control females, the ovariectomized females and the castrated males. Control male rats had significantly lower serum albumin levels, higher cholesterol levels and a significantly greater impairment of renal function in blood urea nitrogen (BUN) levels than did the control female rats at 6 months. Castration significantly increased serum albumin levels and lowered BUN levels, while ovariectomy did not basically influence these values in the female rats. The glomerulosclerosis index at 6 months of age was significantly higher in the control males than in the control females. Castration attenuated glomerular injury, while ovariectomy aggravated glomerular injury to the same levels as found in the castrated males. This aggravating effect of ovariectomy observed at 6 months, however, disappeared at 12 months. These results suggested that sex-related factors regulated by the ovaries may play an inhibitory role in the development of glomerulosclerosis before 6 months of age, but not thereafter, in hypercholesterolemic female Imai rats.

Ovariectomy attenuates proteinuria and glomerular injury in unilaterally nephrectomized female Sprague-Dawley rats.

To determine the contribution of the ovary to the development of glomerulo-sclerosis, we investigated the effect of ovariectomy on glomerulosclerosis, using the unilaterally nephrectomized (Nx) female Sprague-Dawley rat. At 6 weeks of age, groups 2 and 3 underwent unilateral right nephrectomy and group 3 was simultaneously ovariectomized, while group 1 underwent a sham operation. Body weight, blood pressure, urinary protein, serum albumin, cholesterol, blood urea nitrogen and serum creatinine were checked every 2 months from 2 to 12 months after right nephrectomy. Control group 1, the Nx group 2 and the ovariectomized (Nx + ovariectomized) group 3 were studied morphologically at 6 and 12 months after nephrectomy. Body weight significantly increased in ovariectomized rats as compared with control and Nx rats. Nx rats became proteinuric with age. Ovariectomy significantly reduced proteinuria to the same levels in the controls. The glomerulosclerosis index was significantly higher in Nx rats than in either controls or ovariectomized rats. Ovariectomy attenuated glomerular injury in Nx rats, though not to the same levels in the control rats. Three groups showed no significant differences in either blood pressure or plasma somatomedin C. Growth hormone (GH) was significantly decreased by ovariectomy. The severity of glomerular injury and the glomerular tuft volume correlated with GH levels. Our results suggested that a decrease in plasma GH may contribute to the attenuating effect of ovariectomy on the development of glomerular injury in aging unilaterally Nx female Sprague-Dawley rats.

Estrogen attenuates progressive glomerular injury in hypercholesterolemic male Imai rats.

Hypercholesterolemic Imai rats spontaneously develop proteinuria and glomerulosclerosis, especially in males. A sex difference in glomerular injury has been recognized, but the role of sex hormones in glomerular injury remains unclear. Therefore, we investigated whether estrogen administration influences the progressive glomerular injury in male Imai rats. Estrogen produced a significant decrease in body weight. Systolic blood pressure in estrogen-treated rats was significantly lower than that in controls. Estrogen attenuated the progression of glomerular injury by significantly reducing proteinuria and glomerular sclerosis. The glomerulosclerosis index was significantly higher in controls than in estrogen-treated rats. Estrogen suppressed serum testosterone levels, whereas it increased GH levels. Results suggest that estrogen appears to play an inhibitory role on the development of glomerular injury, by itself or in association with sex-related factors regulated by estrogen and testosterone.

[A case of polyarteritis nodosa who developed rapidly progressive glomerulonephritis and presented with a tumor-like shadow on head CT in the remission stage].

A 70-year-old woman was admitted to our hospital because of weight loss, fever of unknown origin and rapid deterioration of renal function. Polyarteritis nodosa was diagnosed based on the findings of fever, weight loss, thrombocytosis, arthralgia and crescentic glomerulonephritis with vasculitis in the kidney biopsy specimens. Renal function progressively deteriorated and the patient underwent peritoneal dialysis (PD). Methylprednisolone pulse therapy and subsequent oral prednisolone (PSL) therapy combined with cyclophosphamide (CY) was instituted. Renal function gradually recovered and PD was discontinued 2 weeks later. She was discharged after about 2 months of hospitalization and received a monthly follow-up with daily administration of 10mg of PSL and 25mg of CY. Six months after discharge, PN activity was well controlled by PSL and CY, but mental disturbance gradually developed and head CT disclosed a low-density mass shadow that was enhanced with a ring-like appearance by contrast medium similar to a brain tumor. The follow-up CT did not show any enlargement of the mass shadow. One year later, the patient died of uremia and concomitant dementia. Autopsy disclosed cerebral infarct in the relevant site of the mass on CT and the healed stage of angitis in other tissues.

Segmental glomerular necrosis as an active index of IgA nephropathy: a study with 100 serial sections of 128 cases.

One hundred serial sections from each of 128 cases with immunoglobulin A (IgA) nephropathy were examined by light microscopy to clarify the relationship between segmental glomerular necrosis (SGN) and progression of glomerular injury. The cases were divided into five groups according to the percentage of glomeruli with cellular/fibrocellular (C/F) crescents, fibrous adhesion and/or sclerosis: grade I, 0%; grade II, < 20%; grade III, 20-50%; grade IV, 50-80%; and grade V, 80% or more. The serial sections revealed unequivocally focal occurrence of SGN in 39 cases (30%). Segmental glomerular necrosis was never found in the cases of grade I (0%, 0/28), while it appeared in those of grade II (33%, 12/36), grade III (46%, 13/28), grade IV (48%, 13/27) and grade V (11%, 1/9). The incidence of the cases with C/F crescents showed a similar tendency among the groups. In addition, focal C/F crescents were more frequent in cases with SGN (82%) than in those without SGN (24%). In particular, cellular crescents in 26 cases were formed in close proximity to SGN. These results suggested that SGN in IgA nephropathy was a more common finding than formerly evaluated and that it potentially participated in the progression of glomerular injuries closely associated with crescent formation. Unequivocally, focal occurrence of SGN corresponded well with the slowly progressive course of the glomerular disease.

[Severe proteinuria in IgA nephropathy. Clinicopathological study of 8 cases with 100 serial sections].

Using 100 serial sections for light microscopy, we studied the clinicopathologic characteristics of IgA nephropathy with severe proteinuria. Eight out of 128 cases with IgA nephropathy exhibited severe proteinuria of 3.0g/day or more. These cases consisted of 5 males and 3 females with an age range from 15 to 73 years. Daily proteinuria ranged from 3.3 to 7.1 g. At the time of biopsy, the serum creatinine level was 1.2 mg/dl or more in 6 cases; two of these developed end-stage renal failure during the follow-up period. In most of the cases, routine sections for light microscopy revealed moderate to severe mesangial proliferation and tubulointerstitial damage. In 7 cases, variable percentages of glomeruli, ranging from 20% to 95%, were involved by chronic lesion represented by sclerosis and fibrous crescents/adhesion, while only 2 cases exhibited active lesion characterized by segmental glomerular necrosis and/or cellular/fibrocellular crescents. In contrast, thorough observation of 100 additional serial sections disclosed the focal presence of active lesion in all except one case with features of endstage kidney. In addition, the highest percentage of glomeruli with active lesion in the serial sections correlated well with the severity of proteinuria. The results suggested that severe proteinuria in IgA nephropathy depends on, at least in part, focal outbreak of active lesion characterized by segmental glomerular necrosis and cellular/fibrocellular crescents.

[Clinicopathological study of membranous glomerulonephritis in patients with rheumatoid arthritis].

Of 103 patients with membranous glomerulonephritis proved by renal biopsy, 11 (10.7%) had rheumatoid arthritis. Nine of these 11 patients received systemic treatment with anti-rheumatic remedies including gold, D-penicillamine and bucillamine. Two others were administered only token of nonsteroidal antiinflammatory drugs. Renal function of the patients was well maintained and within normal limits. Four patients showed nephrotic syndrome, while mild to moderate proteinuria was found in the other 7. Hematuria was minimal to mild, and it was not a major symptom. Six patients resolved proteinuria completely and 2 patients incompletely after discontinuation of chrysotherapy. Nine cases of the membranous lesion in patients with rheumatoid arthritis were stage 1. Thus it was often difficult to identify the glomerular change only by light microscopy. IgA nephropathy and AA amyloidosis were associated in one patient respectively. Our data lead us to conclude that chrysotherapy would cause membranous lesions, but rheumatoid arthritis itself also induce membranous glomerulonephritis.