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Biomedical subjects

M Kanauchi

Publications and source records attributed to M Kanauchi.

At least 37 records · Page 2Linked to original sources

[Diagnostic significance of urinary immunoglobulin G in diabetic nephropathy].

An early manifestation of diabetic nephropathy, increased excretion of albumin, is now generally believed to be sufficiently specific, particularly in subjects with diabetes mellitus, to predict the subsequent development of clinically overt diabetic nephropathy. However, certain other proteins besides albumin may also be excreted in abnormal amounts during this early phase of diabetic nephropathy. We evaluated the diagnostic utility of urinary immunoglobulin G (IgG) in patients with diabetic nephropathy by comparing the findings with the clinical stage and renal biopsy specimen. Using 24-hour urine samples, IgG was measured by an enzyme-linked immunosorbent assay. In addition, urine samples were assayed for albumin, transferrin, beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase. Serum IgG concentration and HbA1c were also evaluated. A total of 197 patients with non-insulin-dependent diabetes mellitus were enrolled in this study. Subjects were grouped according to the rate of urinary albumin excretion (clinical stage). Fifty of these cases were also divided into four groups according to the severity of diffuse glomerular lesions using Gellman's criteria. The urinary excretion of IgG was significantly increased in diabetic patients as compared with the healthy controls. Among diabetic patients, IgG level showed a significant increase with respect to the clinical stage of nephropathy and the progress of glomerular diffuse lesions. In the stage of normoalbuminuria, the urinary excretion of IgG showed a significant increase in parallel with the progress of glomerular diffuse lesions, whereas there was no relationship between the urinary excretion of albumin and the progress of glomerular diffuse lesions. While the excretion of IgG correlated with that of albumin and transferrin, there was no correlation between the excretion of IgG and the other laboratory indices evaluated. These findings indicate that measurement of urinary IgG may be more useful than albuminuria in detecting the early stage of diabetic nephropathy.

Aged↗

Increased excretion of urinary transforming growth factor beta 1 in patients with diabetic nephropathy.

The accumulation of extracellular matrix in the glomeruli of human and experimental models of diabetic nephropathy is associated with disease progression. Transforming growth factor beta 1 (TGF-beta1), which is a multifunctional peptide growth factor, plays a key role in the synthesis of extracellular matrix protein in vitro, and the expression of TGF-beta1 is elevated in human and rat diabetic nephropathy. In this study, we measured the urinary TGF-beta1 excretion in 57 patients with non-insulin-dependent diabetes mellitus and in 20 healthy volunteers to examine whether the determination of urinary TGF-beta1 excretion would facilitate the evaluation of the degree of mesangial expansion in patients with diabetic nephropathy. Both active and total TGF-beta1 levels in 24-hour urine samples collected from patients with diabetes mellitus and normal controls were measured using an enzyme-linked immunosorbent assay. We observed a higher excretion of urinary TGF-beta1 in patients with diabetes mellitus than in normal controls. In addition, the urinary TGF-beta1 excretion was elevated in patients with severe mesangial expansion. These results suggest that urinary TGF-beta1 may represent one parameter that can be used to evaluate the progression of diabetic nephropathy.

Biomarkers↗

Discordance between retinopathy and nephropathy in type 2 diabetes.

The aim of this study was to investigate the relationship between the grade of retinopathy and the severity of glomerular lesions in patients with type 2 diabetes and to describe 5 patients without diabetic retinopathy for whom renal biopsy specimens demonstrated advanced diabetic nephropathy. A total of 221 patients with type 2 diabetes (139 males and 82 females) who consectively underwent renal biopsy between 1982 and 1996 were investigated. The severity of diffuse glomerular lesions was graded using the criteria of Gellman and coworkers, and diabetic retinopathy was classified as absent, nonproliferative, or proliferative. The incidence of advanced nephropathy without retinopathy for all 221 cases was 2.3%. Advanced nephropathy was present in 5 of the 122 (4.1%) patients without retinopathy. These 5 patients were all males and aged 50-70 (mean 61) years. Their clinical characteristics were not uniform, and no special clinical features distinguished the patients who were regarded as having possible advanced nephropathy without retinopathy. In our study, although concordance of retinopathy and nephropathy is relatively common, a little discordance was pronounced in Japanese type 2 diabetic patients. Our findings are consistent with the hypothesis that there are important differences in some aspects of the pathogenesis of retinopathy and nephropathy.

Aged↗

[A case of Bartter's syndrome with chronic renal failure due to chronic interstitial nephritis].

We report a case of 45-year-old women with Bartter's syndrome and concomitant renal dysfunction. In 1986, the patient demonstrated muscle weakness and serum potassium levels as low as 1.1 mEq/l. She was suspected of having Bartter's syndrome because of hypokalemia, metabolic alkalosis, hyperreninemia, hyperaldosteronism and normotension. Pretibial edema developed in 1989 for which she received 40 to 100 mg/week of furosemide intermittently for the next 5 years. Her serum potassium level ranged from 1.5 to 3.9 mEq/l. In 1991, her serum creatinine level rose to 2.1 mg/dl, then continued to increase gradually. She was admitted to our hospital in 1994 for evaluation of the renal dysfunction. Decreased creatinine clearance (44 ml/min) and a defect in urinary concentrating capacity (Fishberg's test, 370 mOsm/kg.H2O) were detected. Renal biopsy revealed juxtaglomerular cell hyperplasia. These findings resulted in the diagnosis of Bartter's syndrome. The renal biopsy also showed diffuse interstitial fibrosis and marked tubular atrophy. We postulate in this case that long-term hypokalemia due to Bartter's syndrome and the administration of furosemide led to chronic interstitial nephritis and renal dysfunction.

Bartter Syndrome↗

[Successful treatment for pulmonary hypertension with angiotensin 1 converting enzyme inhibitor in a patient with mixed connective tissue disease].

This report described a 44 years-old female mixed connective tissue disease (MCTD) patient presenting pulmonary hypertension, successfully treated with angiotensin I converting enzyme (ACE) inhibitor. The patient was diagnosed as having MCTD because of Raynaud's phenomenon, swollen hand, and elevated level of anti-U 1 RNP antibodies. She was admitted to our hospital one year after the diagnosis of MCTD, because she experienced dyspnea and pretibial edema. A diagnosis of pulmonary hypertension was made by echocardiography and catheterization study. Pulmonary artery pressure and pulmonary artery resistance declined and returned gradually to normal during a period of three months with prednisolone and enalapril (10 mg/day) therapy. Pulmonary hypertension is one of fetal complications with MCTD, and 5 year mortality rate is reported less than 50%. However, a successful therapy for the pulmonary hypertension with MCTD has not been established yet. We considered that ACE inhibitor might be useful to control the pulmonary hypertension with MCTD and could improve the prognosis of MCTD.

Adult↗

Quantification of glomerular TGF-beta 1 mRNA in patients with diabetes mellitus.

Transforming growth factor-beta 1 (TGF-beta 1) is a primary determinant of the mesangial expansion observed in diabetic nephropathy. In this study, we quantitated the levels of intraglomerular TGF-beta 1 mRNA in patients with diabetes mellitus using a competitive polymerase chain reaction (PCR) method. Renal biopsy specimens were obtained from 29 patients with non-insulin-dependent diabetes mellitus. Total RNA was extracted from the glomeruli and reverse transcribed into cDNA with reverse transcriptase. To prepare samples containing identical amounts of beta-actin cDNA (8 pg), we performed competitive PCR by co-amplifying mutant templates of beta-actin with a unique EcoRI site. We also used this competitive PCR method to measure TGF-beta 1 cDNA by co-amplifying mutant templates of TGF-beta 1. We observed higher expression of TGF-beta 1 mRNA in glomeruli of patients with diabetic nephropathy as compared with normal glomeruli. Intraglomerular TGF-beta 1 mRNA was elevated, even in the early stage of diabetic nephropathy. Moreover, levels of intraglomerular TGF-beta 1 mRNA correlated with values of HbA1c. These data suggest that hyperglycemia induces intraglomerular TGF-beta 1 mRNA expression in vivo, and that TGF-beta 1 overproduction may be associated with the progression of diabetic nephropathy.

Aged↗

[Clinicopathological study of diabetic nephropathy in the elderly].

We studied the relationship between clinical characteristics and renal structural changes in 29 elderly patients in whom non-insulin-dependent diabetes mellitus was diagnosed when they were 60 years of age or older. The clinical stage of nephropathy was graded according to the criteria of the Ministry of Health and Welfare of Japan: stage 1 (12 patients), normoalbuminuria; stage 2 (11 patients), microalbuminuria; stage 3 (1 patient), persistent proteinuria; stage 4 (5 patients), chronic renal failure. Renal biopsy specimens were semiquantitatively evaluated with regard to diffuse glomerular lesions, nodular lesions, and vascular lesions. In patients at stage 1, minimal-to-moderate diffuse lesions were observed, and vascular lesions were already present. In patients at stage 2, various alterations in diffuse lesions were observed and were associated with prominent changes in the vascular lesions. More advanced changes in the diffuse and vascular lesions were noted in patients at stages 3 and 4, but nodular lesions were found in only one patient. These patients had a high incidence of hypertension and ischemic heart disease. We conclude that elderly diabetic patients with nephropathy of different clinical stages have different underlying diabetic renal lesions.

Aged↗

Role of tissue inhibitors of metalloproteinase in diabetic nephropathy.

We evaluated the role of tissue inhibitors of metalloproteinase-1 (TIMP-1) in patients with diabetic nephropathy by comparing the serum and urine TIMP-1 levels with those of renal biopsy specimens. A total of 35 diabetic patients were divided into four groups, D0, DI, DII and DIII-IV, according to the severity of diffuse glomerular lesions using Gellman's criteria. Using serum and 24-hour urine specimens, TIMP-1 was measured by a sandwich enzyme immunoassay. Serum and urinary TIMP-1 showed significant increases in association with the progress of glomerular diffuse lesions. There was no correlation between serum TIMP-1 and serum creatinine, creatinine clearance, serum and urinary beta 2-microglobulin, urinary NAG, HbA1c, or urinary TIMP-1. There was a significant correlation between urinary TIMP-1 and urinary albumin, and was a significant correlation between urinary TIMP-1 and urinary NAG. We conclude that TIMP-1 has a potential role in the regulation of glomerular matrix accumulation in diabetic nephropathy.

Adult↗

Hypergammaglobulinaemic purpura of Waldenström and Ro/SSA autoantibodies.

Seven out of nine patients (78%), seen over a 13-year period with hypergammaglobulinaemic purpura of Waldenström were found to have antibodies to Ro/SSA. Over this period we saw 175 patients who had antibodies to Ro/SSA. In six of the seven patients, associated diseases were recognized. Five had Sjögren's syndrome, and one had systemic lupus erythematosus with Sjögren's syndrome and thyroiditis (and died 19 years after initial presentation from cerebral infarction). Screening for antibodies to Ro/SSA is important in the diagnosis of patients with hypergamma-globulinaemic purpura, and is helpful in predicting prognosis.

Adult↗

Clinical and morphological predictors of renal outcome in adult patients with focal and segmental glomerulosclerosis (FSGS).

In this retrospective study, we examined 35 adult patients with biopsy-proven, primary focal and segmental glomerulosclerosis (FSGS) and nephrotic syndrome to determine whether any of the clinical and morphological features of FSGS were associated with a higher risk of a poor renal outcome. Clinical factors assessed were the age, sex, amount of urinary protein, and presence of microscopic hematuria, hypertension and renal dysfunction at onset in each patient. Morphological parameters included the number of segmental sclerosis and global sclerosis, sclerosis score, location of segmental sclerosis, mean glomerular diameter, grade of tubulo-interstitial changes, and presence of vascular lesions. Twenty-three patients (66%) were in complete or incomplete (partial) remission, and 12 (34%) were non-responders at the end of follow-up. On univariate analysis, the age at onset, sclerosis score, mean glomerular diameter, and grade of tubulo-interstitial changes in no response were significantly greater than those parameters in remission. Multivariate logistic regression analysis revealed that the degree of tubulo-interstitial changes and mean glomerular diameter were independent risk factors for a poor renal outcome. These findings suggest that the estimation of these latter two parameters allows the nephrologist to predict the probable course and prognosis of an adult with FSGS. Intensive and prolonged therapy is recommended for patients without these two morphological features.

Adult↗

Diagnostic significance of urinary fibronectin in diabetic nephropathy.

We evaluated the diagnostic utility of urinary fibronectin (FN) in patients with diabetic nephropathy by comparing the findings with those of renal biopsy specimens. A total of 46 diabetic patients were divided into four groups, D0, DI, DII and DIII-IV, according to the severity of diffuse glomerular lesions using Gellman's criteria. Using 24-hour urine specimens, FN was measured by a solid phase enzyme-linked immunosorbent assay. The urinary excretion of FN was significantly higher in the overt proteinuric group than in the normo- and micro-albuminuric groups. Urinary FN level showed a significant increase with respect to the progress of glomerular diffuse lesions. There was a weak correlation between the urinary level of FN and serum creatinine level and a weak inverse correlation between the urinary level of FN and creatinine clearance. When patients with overt proteinuria were excluded from the analysis, there was no correlation between the urinary level of FN and serum creatinine level, creatinine clearance, or that of beta 2-microglobulin and NAG. The findings indicate that urinary FN may be useful in estimating pathologic conditions, especially the early stage of diabetic nephropathy.

Adult↗

Diagnostic significance of urinary transferrin in diabetic nephropathy.

We evaluated the diagnostic utility of urinary transferrin (Tf) in patients with diabetic nephropathy by comparing the diagnostic findings with those of clinical stage and renal biopsy specimens. According to the rate of urinary albumin excretion, a total of 60 patients with non-insulin-dependent diabetes mellitus were separated into normoalbuminuria (< 28.8 mg/day), microalbuminuria (28.8 approximately 288 mg/day), and overt proteinuria (> 288 mg/day). They were also divided into 5 groups, D0, DI, DII, DIII and DIV according to the severity of glomerular diffuse lesions using Gellman's criteria. Thirty-eight non-diabetic volunteers were used as controls. Using 24-hour urine specimens, Tf was measured by latex-immuno-turbidimetry. Urinary concentrations of albumin, alpha 1-microglobulin, beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG) were also evaluated. Urinary Tf was significantly increased in the diabetic patients relative to the non-diabetic controls. The incidence of microtransferrinuria (440 approximately 4,400 micrograms/day) was 33.3% in normoalbuminuria, 63.2% in microalbuminuria, and 18.2% in overt proteinuria. The incidence of overt transferrinuria (> 4,400 micrograms/day) was 0%, 36.8% and 81.8%, respectively. Among the diabetic patients, urinary Tf showed a significant increase with respect to the progress of glomerular diffuse lesions. The glomerular diffuse lesions of 10 normoalbuminuric cases with microtransferrinuria were graded as DI in 8 cases, DII in 1 case, and DIII in 1 case. There was a significant correlation between the urinary excretion of Tf and that of albumin, alpha 1-microglobulin or NAG. The findings indicate that urinary Tf may be useful in detecting diabetic nephropathy at an early stage.

Adult↗

Henoch-Schönlein purpura nephritis associated with polycythemia vera.

We present a 53-year-old man with rapidly progressive glomerulonephritis and Henoch-Schönlein purpura which developed during the course of treatment for polycythemia vera. An initial renal biopsy specimen showed mesangial proliferative glomerulonephritis. The patient was admitted to the hospital with cutaneous purpura and progressive renal failure after having received 700 mg of ranimustine over a 29 month period as therapy for the polycythemia vera. A second renal biopsy specimen revealed crescentic glomerulonephritis with deposition of immunofluorescent IgA. These data suggest that Henoch-Schönlein purpura nephritis may occur in response to ranimustine therapy.

Glomerulonephritis, Membranoproliferative↗