Toshikazu Takizawa

AT1 RECEPTOR ANTAGONIST, TCV 116, DOES NOT PREVENT CARDIAC HYPERTROPHY IN SALT-LOADED DAHL SALT-SENSITIVE RATS

1. We investigated the effects of direct blockade of angiotensin II (AngII) by a potent, non‐peptide angiotensin II type 1 (AT1) receptor antagonist, TCV 116, on the development of cardiac hypertrophy in salt‐loaded Dahl salt‐sensitive rats.

Progression of glomerulosclerosis, renal hypertrophy, and an increased expression of fibronectin in the renal cortex associated with aging and salt-induced hypertension in Dahl salt-sensitive rats.

Aging and hypertension are known to be closely related with the pathogenesis and development of glomerulosclerosis. In this study, we examined the time course changes in the glomerulus associated with salt-induced hypertension using the inbred Dahl salt-sensitive rats. For this purpose, 5-week-old Dahl salt-sensitive rats (n=36) were fed either 4% NaCl diet (n=18) or 0.3% NaCl diet (n=18) up to 17 weeks of age. The high salt diet caused a dramatic increase in systolic blood pressure and also a dramatic renal hypertrophy as shown by a significant increase in the kidney weight. Histological examination revealed an age-dependent progression of glomerulosclerosis as documented by a quantitative scoring. This age-dependent progression was further accelerated by the co-existence of salt-induced hypertension in the high salt diet group. Northern blot analysis revealed an increase in the steady state mRNA levels of fibronectin, an important component of mesangial matrices, in the renal cortex, but not in the renal medulla, only in salt-loaded Dahl salt-sensitive rats. These findings indicate that salt-induced hypertension accelerates the age-dependent progression of glomerulosclerosis in Dahl salt-sensitive rats, and fibronectin may play a role in the pathogenesis, development, and progression of glomerulosclerosis associated with salt-induced hypertension.

NEPHROTIC SYNDROME ASSOCIATED WITH MALIGNANT MESOTHELIOMA

Sumi Tanaka, MD, 2nd Department of Internal Medicine, Urafune Hospital, 3-46 Urafune-cho, Minami-ku, Yokohama 232 (Japan) Discharge Admission Total protein ‘Albumin November 1991 Dear Sir, The association between nephrotic syndrome and malignancy has been well documented [1-3]. Several types of glomerular injury have been noted in patients with cancer [2], and the neoplasms that have been implicated include a variety of histological types from different primary sites [3]. We present a case with nephrotic syndrome associated with malignant mesothelioma. A 77-year-old man was admitted to our hospital with systemic edema, generalized weakness, and fatigue. Two years previously he had a pneumonia, at which time urinalysis showed no protein. He had not been receiving any medications. He had been working as an engineer on a ship and had been exposed to asbestos approximately 40 years prior to admission. Physical examination: On auscultation of his lungs, there were decreased breath sounds and some moist rales on the left. Heart sounds and abdomen were normal, and there was no lymphadenopathy. There was pitting edema of the whole body. Laboratory values included the following: total serum protein 5.4 g/dl, serum albumin 1.3 g/dl, total serum bilirubin 0.2 mg/ dl, serum glutamic-oxaloacetic transaminase 32 IU/1, serum glutamic-pyruvic transaminase 22, alkaline phosphatase 556IU/1, blood urea nitrogen 14 mg/dl, serum creatinine 0.8 mg/dl, Na 130 mEq/1, K 3.7 mEq/1, Ca 6.4 mg/dl, P 2.8, serum glucose 141, total cholesterol 184, triglycerides 107 mg/dl, eryth-rocyte sedimentation rate 50 mm/h, hemoglobin 8.9 g/dl, hematocrit 27.4%, white blood cell count 11.1 × lOVμl (with an increase in

Impaired renal function in a patient with diuretic abuse

A 31-year-old woman was diagnosed as having Bartters syndrome in 1978, although suspicions remained that she had been taking diuretics surreptitiously. Careful observation and repeated urinary drug analyses revealed no clue that she had been taking diuretics, until 20 years later, when the urine samples at last disclosed traces of furosemide. At this time she showed proteinuria, of 2 g/day, and hypercholesteremia. The glomerular filtration rate had decreased to 66 ml/min per 1.73 m2. The 24-h urinary concentrations of β2-microglobulin, N-acetyl-β-d-glucosaminidase (NAG) activity, and other urinary enzymes that are indicators of damage in proximal tubular cells, were increased, showing proximal tubular damage. The function of the loop of Henle was evaluated by a hypotonic saline loading test. The fractional distal chloride reabsorption, an index of the solute conservation rate in the loop of Henle, was 65.4%, which was lower than the normal value (88.9 ± 6.2%). The maximal urinary concentrating ability was 357 mOsm/kg·H2O, and a short ammonium chloride loading test showed impairment in the acidification of the urine. The third renal biopsy specimens showed some obsolescent glomeruli, marked juxtaglomerular cell hyperplasia, intraluminal calcification, interstitial infiltration of lymphocytes with fibrosis, and thickening of arteriolar walls with narrow lumens. Patients often attempt to hide their use of diuretics from medical staff, leading to them to make a misdiagnosis of Bartters syndrome. Although the patient described here has not experienced life-threatening adverse effects from furosemide abuse, some findings appear to be irreversible, suggesting the deterioration of renal function. Patients should realize that longstanding abuse of diuretics causes not only metabolic abnormalities but also the risk of renal damage.

Development of nodular lesions in amyloidosis with reference to diabetic nephropathy

BackgroundOne characteristic histologic change in diabetic glomerulopathy is nodular and diffuse mesangial expansion, which resembles the alterations seen in renal amyloidosis. We addressed the questions of whether the morphologic changes seen in renal amyloidosis are related to the biochemical amyloid type, and whether there is a histologic analogy in diabetic glomerulopathy.MethodsWe examined kidney specimens obtained from autopsies on 30 patients with systemic amyloidosis and 34 with diabetes mellitus.ResultsThe mean age at death of the patients with amyloidosis was 60.6±10.9 years. All samples were positively stained by Congored and direct fast scarlet stains. All nonnephrotic patients showed minimal diffuse or nodular lesions. Most of the lesions found in the patients with nephrosis were severe. We also assessed the histologic glomerular changes in 34 cases of diabetes mellitus. The mean age at death of the patients in this group was 62.3±12.3 years. In diabetic nephropathy, severe nodular lesions did not appear until there was progression of diffuse lesions. By contrast, in the amyloid kidney, nodular mesangial expansion could be seen in glomeruli even when the diffuse mesangial expansion was slight.ConclusionsThere is no significant relationship between histologic amyloid deposition patterns and biochemical amyloid types. Although, in both diabetic nephropathy and renal amyloidosis, the histologic alterations of the kidneys include diffuse and nodular mesangial expansion. these alterations progress separately in amyloidosis, while in diabetic nephropathy, the nodular lesions appear after progression of diffuse mesangial thickening.