Somatostatin analogue attenuates estrogen-induced augmentation of glomerular injury in spontaneous hypercholesterolemic female Imai rats.

BACKGROUND: Aggravating effect of estrogen replacement therapy on glomerular injury associated with an elevation of growth hormone (GH) levels has been reported. Therefore, in the present study, to clarify an association between GH elevation and the aggravating effect of estrogen on glomerular injury, we investigated the effect of somatostatin, an inhibitor of GH secretion, on glomerular injury in estrogen-treated hypercholesterolemic female Imai rats. METHOD: Control female rats were assigned to group 1 (Cont, n = 10). Group 2 (Cont-E, n = 10) received estrogen, and groups 3 (Cont-E-LS, n = 10) and 4 (Cont-E-HS) received estrogen and either a low dose of somatostatin analogue or a high dose of somatostatin analogue. Body weight, urinary protein, serum albumin, total cholesterol, triglycerides, blood urea nitrogen and serum creatinine were investigated every 4 weeks from 10 weeks through 30 weeks of age. At 30 weeks of age, rats were studied morphologically. RESULTS: Estrogen administration resulted in an increase in urinary protein excretion rates and serum total cholesterol levels, and aggravated glomerular injury associated with an increase in GH. In contrast, somatostatin treatment reduced both urinary protein excretion rates and total cholesterol levels and attenuated glomerular injury to levels close to those of controls associated with a reduction of GH levels. CONCLUSION: The results suggest that increased GH levels may contribute to an enhancing effect of estrogen administration on glomerular injury.

Cellular crescents and segmental glomerular necrosis in IgA nephropathy are indicative of the beneficial effects of corticosteroid therapy.

OBJECTIVE: Recent reports have revealed that corticosteroid (PSL) therapy has a long-term beneficial effect for stabilization of renal function in progressive IgA nephropathy. PATIENTS AND METHODS: We analyzed serum creatinine (Cr), daily proteinuria and the results of other routine laboratory examinations during a short-term course of PSL therapy in 28 cases of progressive IgA nephropathy. The cases were divided into two groups according to changes in renal function during the PSL treatment period: group I (15 cases), improved renal function; group II (13 cases), no significant change in renal function. RESULTS: In group I, serum Cr and proteinuria were significantly decreased, with maximum effects observed at 3 months of PSL therapy, and remained low during the period of treatment. In contrast, group II showed no significant changes in serum Cr levels during the period of therapy, although proteinuria was transiently decreased after 3 months of therapy. Histologically, cellular/fibrocellular (C/F) crescents and/or segmental glomerular necrosis (SGN) occurred with a significantly higher incidence in group I (87%) than in group II (46%) (p < 0.05). CONCLUSIONS: These results suggested that the early response to PSL in reducing serum Cr and proteinuria by 3 months of treatment may be clinically useful to predict the prognosis of IgA nephropathy and that C/F crescents and/ or SGN may be histologically indicative of the beneficial effects of PSL therapy in IgA nephropathy.

Morphogenesis of MDCK cells in a collagen gel matrix culture under stromal adipocyte-epithelial cell interaction.

BACKGROUND: The stromal-epithelial cell interaction is essential for epithelial morphogenesis. Recently, the specific stromal cell type adipocytes, which abundantly exist in perirenal adipose tissue, have been suggested to affect the biological behavior of some epithelial cell types. However, adipocyte-renal epithelial cell interaction remains unclear. We thus examined the effects of adipocytes on the morphogenesis of renal epithelial cells. METHODS: The renal epithelial cell line, Madin-Darby canine kidney (MDCK), cells were cultured in three-dimensional collagen gel matrix with or without mature unilocular adipocytes. Cultures cells were examined by histochemistry, immunohistochemistry, and electron microscopy. RESULTS: Adipocytes extensively promoted the tubule formation of MDCK cells in two different manners. In the first type, after approximately 20% of MDCK cells actively adhered to adipocytes; they organized double-cell structured tubules between the adipocytes and the gel, contacting directly with the entire surface of the adipocytes. In the second type, approximately 70% of MDCK cells apart from adipocytes also formed tubules that had no contact with adipocytes. The component cells of both tubule types at the apical side showed microvilli and peanut agglutinin lectin-positive stain. These cells at the basal side had the basal lamina and type IV collagen-positive stain. CONCLUSIONS: These results indicate that the specific stromal cell type adipocytes cause MDCK cells to organize the well-polarized tubular structures in two different manners according to their direct and indirect interactions, suggesting that adipocytes may be involved in the regulatory mechanism of renal epithelial morphogenesis.

Attenuating effect of a semipurified alcohol extract of soy protein on glomerular injury in spontaneous hypercholesterolemic male Imai rats.

We investigated whether soy protein's alcohol-extractable components (SPEs; mainly consisting of isoflavones) have the ability to attenuate glomerular injury in male Imai rats of a spontaneous focal segmental glomerulosclerosis model. Male Imai rats were fed a casein-based diet with and without SPEs. Group 1 (Cont) was fed a standard diet without additional SPEs, and groups 2 (SPE-1) and 3 (SPE-2) were fed a standard diet supplemented with a semipurified alcohol extract of soy protein, 0.05 and 0.10 g/100 g of diet, respectively. Body weight, urinary protein level, serum constituents, and systolic blood pressure were evaluated every 4 weeks from 12 through 28 weeks of age. At 28 weeks of age, rats were studied morphologically. Growth rates were not different among the three groups throughout the experiment. SPE-supplemented diets resulted in less proteinuria and less hyperlipidemia. The decline in renal function shown by blood urea nitrogen and creatinine clearance was less marked in the animals fed the SPE-supplemented diets. Each SPE-supplemented diet equally induced less glomerular hypertrophy and less renal histological damage compared with nonsupplemented diets. The present study showed a beneficial effect of a semipurified alcohol extract of soy protein on glomerular disease.

Simultaneous occurrence of minimal change glomerular disease, sarcoidosis and Hashimoto's thyroiditis.

We herein report a very rare case of a patient suffering from simultaneous occurrence of three immune disorders, i.e. Hashimoto's thyroiditis, sarcoidosis and minimal change glomerular disease. A 66-year-old man was admitted to our hospital for evaluation of nephrotic syndrome. Six months before admission, he was pointed out as having positive proteinuria, hypoalbuminemia and associated pretibial pitting edema. Initial laboratory data showed high gammaglobulinemia, high titers of both antimicrosomal and antithyroglobulin antibodies with normal thyroid function. Chest X-ray and CT scan revealed bilateral hilar lymphadenopathy with interstitial shadow. Ga-citrate scan disclosed positive accumulation in the thyroid glands, the mediastinum, the lungs and the kidneys. The diagnosis of minimal change nephritic syndrome and pulmonary sarcoidosis was made, based on the findings of transbronchial lung biopsy and kidney biopsy. After one and a half months of admission, thyroid function had gradually deteriorated. The histological findings of the thyroid were consistent with the features of Hashimoto's thyroiditis. Treatment with prednisolone and cyclophosphamide resulted in a decrease in urinary protein excretion, reduction in the size of mediastinal lymphadenopathy and disappearance of positive findings of Ga-citrate scan in the thyroid glands and the kidneys. Simultaneous occurrence of minimal change-glomerular disease, sarcoidosis and Hashimoto's thyroiditis in our case suggests that similar immunological abnormalities may be involved in the pathogenesis of the diseases.

Recurrence of rapidly progressive glomerulonephritis probably associated with two different kinds of drugs.

We describe a rare case that developed a rapidly progressive glomerulonephritis twice in a 69-year-old man during a course of treatment, first with allopurinol and then with piperacillin. The cessation of each treatment was followed by spontaneous recovery in renal function. A renal biopsy showed crescentic glomerulonephritis with mild tubulointerstitial change and a skin biopsy showed leukocytoclastic vasculitis. This is, to our knowledge, a very rare case of crescentic glomerulonephritis, probably associated with vasculitis during a course of treatment with two different kinds of drugs.

Combined therapy with estrogen and testosterone eliminates the aggravating effect of estrogen replacement therapy on glomerular injury in hypercholesterolemic female Imai rats.

Hypercholesterolemic Imai rats spontaneously develop proteinuria and glomerulosclerosis, especially male animals. Ovariectomy aggravates glomerular injury in female Imai rats. However, estrogen replacement therapy did not abolish this aggravating effect of ovariectomy and rather aggravated glomerular injury with an increase in serum levels of lipids and growth hormone (GH). Whereas we have already reported that treatment with testosterone in addition to estrogen reduces GH levels and attenuates glomerular injury as compared with estrogen alone in male Imai rats, in the present study, to investigate whether increased GH levels may contribute to an enhancing effect of estrogen on glomerular injury, we treated ovariectomized female Imai rats with estrogen pulse testosterone. Group 1 was sham operated and group 2 was ovariectomized at 6 weeks of age. Groups 3, 4, and 5 were ovariectomized and received estrogen, testosterone, or estrogen plus testosterone, respectively. Body weight, urinary protein, and serum constituents were investigated every 4 weeks from 12 to 24 weeks of age. At 24 weeks of age, the rats were studied morphologically. Each treatment with estrogen or testosterone equally aggravated glomerular injury with an increase in both proteinuria and serum lipids with increased serum GH levels in estrogen-treated rats but without influencing GH levels in testosterone-treated rats; combined treatment with estrogen plus testosterone resulted in a reduction of both proteinuria and serum lipids to levels of the controls and attenuated glomerular injury to levels close to those of controls with a reduction of the elevated serum GH levels. These results suggest that increased GH levels may contribute to an enhancing effect of estrogen replacement therapy on glomerular injury and that testosterone, when administered to the estrogen-treated rats, seems to exert an attenuating effect on glomerular injury by suppressing GH levels.

Efficacy of blood purification therapy for heat stroke presenting rapid progress of multiple organ dysfunction syndrome: a comparison of five cases.

Five patients were admitted to our hospital because of classical heat stroke during the heat waves which attacked our country in the summers 1994 and 1995. The clinical and laboratory findings of all patients suggested the rapid progress of multiple organ dysfunction syndrome (MODS). Blood purification (BP) therapy, in addition to conventional treatment, was performed in three of the patients. Despite their disastrous general condition, all completely recovered or recovered sufficiently to be transferred to a rehabilitation hospital. Two additional patients were treated with conventional treatment only and both died in 1-3 days after admission. Clinical characteristics and laboratory findings on admission showed no differences between the cases receiving BP therapy and those not receiving BP therapy. These findings suggest that, in heat stroke patients, additional BP therapy may provide a better prognosis than conventional therapy only. These beneficial effects of BP may have been due mainly to the removal of proinflammatory cytokines related to heat stroke.

Acute renal failure due to hypokalemic rhabdomyolysis in Gitelman's syndrome.

A 46-year-old-male developed acute renal failure (ARF) secondary to hypokalemic rhabdomyolysis. Potassium supplementation restored renal function following improvement of the rhabdomyolysis. After recovery from ARF, further evaluation disclosed he had hypokalemic metabolic alkalosis, normotensive hyperreninemia, hyperaldosteronism, renal hypomagnesemia, hypocalciuria and hyperplasia of the juxtaglomerular apparatus which are a diagnostic set of disorders in Gitelman's syndrome, a variant of Bartter's syndrome. This is the first reported case of ARF due to hypokalemic rhabdomyolysis associated with Gitelman's syndrome.

Estrogen replacement therapy with its physiological dose does not eliminate the aggravating effect of ovariectomy on glomerular injury in hypercholesterolemic female Imai rats.

Hypercholesterolemic Imai rats spontaneously develop proteinuria and glomerulosclerosis, especially in males. Estrogen administration attenuated glomerular injury in male Imai rats, and the aggravating effect of ovariectomy in female rats is found. To clarify whether this aggravating effect of ovariectomy is due to a lack of estrogen, we administered estrogen to ovariectomized female Imai rats. At 6 weeks of age, group 1 (control) was sham-operated and group 2 was ovariectomized. Groups 3 and 4 were ovariectomized and received estrogen replacement therapy (0.1 mg in group 3 and 0.2 mg in group 4 once a month subcutaneously). Body weight, urinary protein and serum constituents were investigated every month from 3 to 6 months of age. At 6 months of age, rats were studied morphologically. Estrogen replacement therapy increased serum estrogen to levels close to those of controls when 0.1 mg was used, or higher when 0.2 mg was used. Estrogen replacement therapy with 0.1 mg did not eliminate the aggravating effect of ovariectomy on glomerular injury and rather aggravated it, but conversely therapy with 0.2 mg attenuated glomerular injury and abolished the aggravating effect of ovariectomy. Estrogen replacement therapy markedly elevated serum GH levels dose-dependently. These results suggested that other hormones as well as estrogen may play a protective role of the ovary for the development of glomerular injury, and that estrogen seems to exert a dual effect on glomerular injury.

End-stage renal failure due to crescentic glomerulonephritis in a patient with Behçet's syndrome. Review of the literature.

We report a rare case of a patient with Behçet's syndrome who developed end-stage renal failure due to crescentic glomerulonephritis (GN). A 20-year-old male patient had suffered from uveitis, aphthous mouth ulcers and genital ulceration for the past 7 years. His renal function rapidly deteriorated and renal biopsy specimens obtained when his serum creatinine level was 3 mg/dl showed diffuse proliferative GN with fibrous crescent formation in 75% of glomeruli excluding totally sclerotic glomeruli. Immune complexes were identified by demonstration of complement and immunoglobulins in the glomeruli. He developed end-stage renal failure during a 1-year course and received maintenance hemodialysis. We reviewed the literature on severe forms of GN in patients with Behçet's syndrome.

Fibrillar crystal structure in essential monoclonal IgM kappa cryoglobulinemia.

In monoclonal IgG cryoglobulinemia, two types of crystallization have been demonstrated with electron microscopy at high magnification. In contrast, little information is available on well-defined crystallization in cases of monoclonal IgM cryoglobulinemia. We present a case of pure monoclonal IgM kappa cryoglobulinemia and rapidly progressive glomerulonephritis occurring in a 75-year-old woman. We detected unequivocal formation of fibrillar crystal structure within intraglomerular macrophages on electron microscopy: the structure accords with that in a case of monoclonal IgG cyroglobulinemia described in the literature.