Biomedical subjects

T Kuwahara

Publications and source records attributed to T Kuwahara.

At least 37 records · Page 2Linked to original sources

PubMed2001

Outbreak of Chinese herb nephropathy in Japan: are there any differences from Belgium?

OBJECTIVE: The purpose of this article was to study and clarify the features of Chinese herb nephropathy (CHN) in Japan. PATIENTS AND METHODS: The subjects consisted of patients diagnosed as having CHN in Saiseikai Nakatsu Hospital and of those reported in the literature in Japan. We investigated the clinical and histological features of CHN patients in Japan and compared them with the Belgian cases. RESULTS: The remarkable differences were as follows: (1) high prevalence in males compared with Belgian cases, (2) Fanconi syndrome was found in most cases, (3) no patients had malignant tumors in the urinary tract. In addition, the ascribed Chinese medicines in Japan were divided into three groups: 'Tenshin-toki-shigyaku-ka-gosyuyu-syokyo-to', 'Boui-ougi-to', and others. CONCLUSION: CHN in Japan has some characteristics distinguished from Belgian nephropathy. One hypothesis is a susceptibility to aristolochic acids (AAs), which is considered to be a causative agent, may be different among races. Another is that there could be some other toxic substances affecting the clinical findings although they are not identified at present. Further studies must be undertaken to clarify these differences.

Aristolochic Acids↗

PubMed2001

PCR-dot blot hybridization based on the neuraminidase-encoding gene is useful for detection of Bacteroides fragilis.

Bacteroides fragilis is a Gram-negative obligate anaerobe frequently isolated from clinical specimens and sometimes causes severe septicemia in compromised hosts. Increasing interest has been shown in the enterotoxigenicity and drug resistance of B. fragilis in the field of medical microbiology. We previously reported rapid detection of this anaerobe by nested PCR targeting a neuraminidase-encoding gene nanH. In the present study, we synthesized a digoxigenin-labeled oligonucleotide probe, NH1, which is specific for nanH of B. fragilis, and we combined the hybridization assay using NH1 with the nanH-PCR to detect this anaerobe in a bacteremia model mice. In the specificity test, the oligonucleotide probe, NH1, hybridized only to amplification products from B. fragilis. PCR-dot blot hybridization based on nanH enabled detection of cells of B. fragilis in blood samples even when the number was as low as 2 x 10(3) colony-forming units/ml. These findings suggest that PCR-dot blot hybridization targeting nanH is a useful procedure for diagnosis of septicemia caused by B. fragilis when viable cells in blood cannot be detected by the traditional culture techniques.

Animals↗

PubMed2001

Inhibitory effects of bitter melon (Momordica charantia Linn.) on bacterial mutagenesis and aberrant crypt focus formation in the rat colon.

Antimutagenicity and chemopreventive activity of an 80%-ethanol extract of bitter melon (Momordica charantia Linn.) against the formation of azoxymethane (AOM)-induced aberrant crypt foci (ACF) was investigated. The bitter melon extract was nonmutagenic and inhibited the mutagenicity of heterocyclic amines 2-amino-3,4-dimethylimidazo[4,5-f]quinoline and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, and aflatoxin B1 in the Salmonella mutation assay. To examine the inhibitory effect of bitter melon on AOM-induced ACF formation, male F344 rats were fed various concentrations of the extract (0.1, 0.5, and 1.0 g/kg body weight) for five weeks during the initiation stage. One week after the administration of the plant extract, rats were subcutaneously given AOM at 15 mg/kg body weight once a week for two weeks. Three rats in each group were sacrificed 12 hr after the second AOM injection to analyze DNA adducts, O6-methylguanine (O6-meG) and N7-methylguanine in the liver and colon. The remaining rats were sacrificed 3 weeks after the second AOM injection to observe ACF. To examine the inhibitory effect of the extract on ACF formation in the postinitiation stage, rats were fed the extract at 0.1 and 1.0 g/kg body weight for 12 weeks starting two weeks after the second AOM injection. Treatment with bitter melon extract significantly inhibited ACF formation in the colon during the initiation stage and dose-dependently decreased the average of O6-meG DNA adduct in the colonic mucosa. During the postinitiation stage, bitter melon extract, at 1.0 g/kg body weight, significantly inhibited ACF formation in the colon, especially the formation of ACF with four or more crypts per focus. These findings suggest that bitter melon is a possible chemopreventive agent against colon carcinogenesis.

Animals↗

PubMed2000

Inhibitory effects of tea extracts on the mutagenicity of 1-methyl-1, 2,3,4-tetrahydro-beta-carboline-3-carboxylic acid on treatment with nitrite in the presence of ethanol.

It has been shown that the mutagenicity of 1-methyl-1,2,3, 4-tetrahydro-beta-carboline-3-carboxylic acid (MTCCA), a major mutagen precursor in soy sauce on treatment with nitrite and ethanol, was strongly decreased by the addition of hot water extracts of green, black and oolong teas in the reaction mixture when it was treated with 50mM nitrite at pH3.0, 37 degrees C for 60min in the presence of 7.5% ethanol. The mutagenicity-decreasing activity of the teas was scarcely decreased by washing the teas with chloroform and benzene and was partly decreased by butanol and ethyl acetate. Typical polyphenols such as catechins were shown to have the antimutagenicity dose dependently. The antimutagenicity and the reducing power of tea extracts gave a positive good correlation. The results suggest that the mutagenicity of MTCCA on treatment with nitrite in the presence of ethanol may be decreased by the mixed fractions of lyophilic components such as polyphenols, which have high reducing power such as catechins and the other compounds which have little reducing power including the derivatives of the catechins and so on. Although the antimutagenicity of teas and catechins was also considerably effective when they were added after the nitrosation, that of black tea and some catechins was less effective.

Carbolines↗

PubMed2000

Clinical and genetic studies of CLCN5 mutations in Japanese families with Dent's disease.

BACKGROUND: Dent's disease is an X-linked renal tubular disorder that is characterized by low molecular weight proteinuria, hypercalciuria, nephrolithiasis, and renal failure. The disease is caused by inactivation of a renal chloride channel gene, CLCN5, that encodes a 746-amino acid protein with 12 to 13 transmembrane domains. The Japanese variant of Dent's disease has been observed to be less severe, and we have investigated two unrelated Japanese families for CLCN5 mutations. METHODS: Six patients from two unrelated families were studied. Leukocyte DNA from probands was used with CLCN5-specific primers for polymerase chain reaction (PCR) amplification of the coding region and exon-intron boundaries, and the DNA sequences of the products were determined to identify abnormalities in the gene. RNA extracted from the kidney, leukocytes, or urine sediments was used to characterize further the effects of the identified mutations. RESULTS: beta2-microglobulinuria was detected in five patients, hypercalciuria in two patients, nephrolithiasis in three patients (2 of whom were females), and one 51-year-old man had renal failure. Two novel CLCN5 mutations consisting of an a to g transition at the invariant ag acceptor splice site of intron 5 and an intragenic deletion that encompassed the region between intron 3 and intron 6 were identified. The acceptor splice site mutation led to the utilization of two alternative cryptic splice sites in exon 6 that resulted in a frameshift or skipping of the exon 6. The deletional mutation, which resulted in a loss of exons 4, 5, and 6, is predicted to lead to a loss of domains 1 through 4. Both mutations predict truncated chloride channels that are likely to result in a functional loss. CONCLUSIONS: The observations of renal failure in one male and nephrolithiasis in two females represent important new findings in this Japanese variant of Dent's disease that is associated with CLCN5 mutations. In addition, our study is the first to demonstrate the use of urinary sediment cells and renal tissue for the detection of CLCN5 transcript abnormalities. These results help to expand the spectrum of CLCN5 mutations associated with Dent's disease.

Adult↗

PubMed2000

Transient U wave inversion during treadmill exercise testing in patients with left anterior descending coronary artery disease.

The transient U wave inversion during exercise is specific for detecting left anterior descending coronary artery (LAD) disease. In a homogeneous patient group restricted to LAD disease, however, the significance of the electrocardiographic finding has not yet been clarified. Thus, clinical characteristics in patients with angiographically documented one-vessel disease of the LAD and exercise-induced U wave inversion were delineated. Symptom-limited treadmill exercise testing was performed in 60 patients (43 men, 17 women; mean age 64 +/- 8 years) with angina pectoris whose culprit lesion was located only in the LAD. U wave polarity and amplitude were determined before, during, and after exercise with the P-Q segment as the isoelectric line. Exercise-induced transient U wave inversion was defined as positive when there was a discrete negative deflection > or = 0.05 mV within the T-P segment. Of all patients, 16 (27%) had exercise-induced U wave inversion. There were no differences in age, male gender, antianginal medication use, and coronary angiographic data between the two patients groups: patients with and without U wave inversion. Heart rate and double product of heart rate and systemic systolic blood pressure at peak exercise were also similar. Prevalence of abnormal exercise-induced S-T segment shift was 94% (15 of 16 patients) and 61% (27 of 44 patients) of patients with and without U wave inversion, respectively. The difference was statistically significant (p = 0.02). Among patients with exercise-induced S-T segment shift, the proportion of patients with S-T segment elevation to all the patients was larger in patients with U wave inversion than in patients without U wave inversion [3 (20%) of 15 patients vs 0 (0%) of 27 patients, p = 0.03)]. In conclusion, the exercise-induced U wave inversion in patients with one-vessel disease of the LAD indicates the severe degree of myocardial ischemia induced in the territory perfused by the LAD. However, the electrocardiographic finding does not appear to have independent significance since it closely correlates with the presence of S-T segment shift.

Aged↗

PubMed2000

Apical hypertrophic cardiomyopathy associated with life-threatening paroxysmal atrial flutter with a slow ventricular response: a case report.

A 58-year-old male patient had apical hypertrophic cardiomyopathy (HCM) associated with a life-threatening tachycardia due to atrial flutter. Following palpitation and dyspnea for 2-3 h, he became unconscious because of circulatory catastrophe, but was fully resuscitated. An electrocardiogram recorded just before the loss of consciousness revealed atrial flutter at a rate of 260 beats/min with a 2:1 ventricular response. He was diagnosed as having apical HCM based on the echocardiographic and left ventriculographic findings. Atrial stimulation at a rate of 150 pacings/min for 1 min caused a marked drop in systemic systolic blood pressure from 170 to 120 mmHg. The patient was treated with 150 mg of cibenzoline per day to prevent supraventricular tachyarrhythmias and to improve left ventricular diastolic function. At the time of the recent follow-up at 2 and a half years, he felt quite well.

Atrial Flutter↗

PubMed2000

Effect of beta-blocker on left ventricular function and natriuretic peptides in patients with chronic heart failure treated with angiotensin-converting enzyme inhibitor.

To evaluate whether or not beta-blockers can improve the condition of patients with heart failure treated with a combination of diuretics, digitalis and angiotensin-converting enzyme inhibitor (ACEI), 52 patients with chronic heart failure who have been treated with ACEI for more than 6 months were enrolled. They were divided into 2 groups: 26 patients continued the same therapy another 6 months or more (group A), and 26 patients were given oral metoprolol for 6 months or more, in addition to the ACEI (group B). Echocardiographic parameters and atrial and brain natriuretic peptides (ANP, BNP) were measured. The left ventricular dimensions at end-diastole and end-systole were significantly decreased and fractional shortening was significantly increased in group B after 6 months' treatment with the beta-blocker, but these parameters remained unchanged in group A. Plasma levels of both ANP and BNP were significantly decreased in group B, but remained unchanged in group A. These results indicate that concomitant beta-blocker therapy can improve left ventricular function and attenuate plasma ANP and BNP levels in patients with chronic heart failure treated with ACEI.

Adrenergic beta-Antagonists↗

PubMed2000

Chinese herb nephropathy in Japan presents adult-onset Fanconi syndrome: could different components of aristolochic acids cause a different type of Chinese herb nephropathy?

BACKGROUND: We encountered two cases of Chinese herb-induced Fanconi syndrome in Japan. One component of the chinese medicine was "Kan-mokutsu" (Aristolochia manshuriensis) in which aristolochic acids (AAs) were detected. METHODS: Renal biopsy showed flattening of proximal tubular epithelial cells and paucicellular interstitial fibrosis without glomerular lesions, all of which were in accordance with Chinese herb nephropathy (CHN). To date, many cases of CHN have been reported mainly as progressive renal failure in western countries. RESULTS: However, our cases were different from those in that they presented Fanconi syndrome. The detected AAs in our cases consisted of aristolochic acid (AA)-I, II and D. In contrast, in Belgium, the incriminated agent was Aristolochia fangchi which consisted of AA-I, B, C, and aristolactum. CONCLUSION: These findings could indicate that different components of AAs could cause different clinical lesions, or that the amount of ingested AAs might reflect clinical pictures, that is to say, our patients took lower volume of Chinese herbs and might be in an early stage of CHN. Furthermore, it is likely that susceptibility to this substance may be different among races. CHN would include two clinical aspects: subacute renal failure and adult-onset Fanconi syndrome. It is important to bear in mind that CHN could present Fanconi syndrome.

Adult↗

PubMed2000

A functional proteomics screen of proteases in colorectal carcinoma.

BACKGROUND: Proteases facilitate several steps in cancer progression. To identify proteases most suitable for drug targeting, actual enzyme activity and not messenger RNA levels or immunoassay of protein is the ideal assay readout. MATERIALS AND METHODS: An automated microtiter plate assay format was modified to allow detection of all four major classes of proteases in tissue samples. Fifteen sets of colorectal carcinoma biopsies representing primary tumor, adjacent normal colon, and liver metastases were screened for protease activity. RESULTS: The major proteases detected were matrix metalloproteases (MMP9, MMP2, and MMP1), cathepsin B, cathepsin D, and the mast cell serine proteases, tryptase and chymase. Matrix metalloproteases were expressed at higher levels in the primary tumor than in adjacent normal tissue. The mast cell proteases, in contrast, were at very high levels in adjacent normal tissue, and not detectable in the metastases. Cathepsin B activity was significantly higher in the primary tumor, and highest in the metastases. The major proteases detected by activity assays were then localized in biopsy sections by immunohistochemistry. Mast cell proteases were abundant in adjacent normal tissue, because of infiltration of the lamina propria by mast cells. Matrix metalloproteases were localized to the tumor cells themselves; whereas, cathepsin B was predominantly expressed by macrophages at the leading edge of invading tumors. Although only low levels of urinary plasminogen activator were detected by direct enzyme assay, immunohistochemistry showed abundant protein within the tumor. CONCLUSIONS: This analysis, surveying all major classes of proteases by assays of activity rather than immunolocalization or in situ hybridization alone, serves to identify proteases whose activity is not completely balanced by endogenous inhibitors and which may be essential for tumor progression. These proteases are logical targets for initial efforts to produce low molecular weight protease inhibitors as potential chemotherapy.

Biopsy↗

PubMed2000

The characteristic pattern of aminoaciduria in patients with aristolochic acid-induced Fanconi syndrome: could iminoaciduria be the hallmark of this syndrome?

BACKGROUND: In Japan the patients with Chinese herbs nephropathy (CHN), aristolochic acids-(AAs) associated renal failure, often present Fanconi syndrome. The aim of this study was to investigate the pattern of aminoaciduria in patients with AAs-induced Fanconi syndrome and to clarify whether it is different from other Fanconi syndromes reported in the literature. SUBJECTS AND METHODS: The subjects consisted of 4 patients with Fanconi syndrome due to AAs. We studied biochemical data and urinary excretion of amino acids in the 4 patients. Amino acids in their urine were analyzed by high performance liquid chromatography (HPLC). RESULTS: Three out of 4 patients showed in common very increased excretion ofproline, hydroxyproline and citruline. Last patient showed the very increased levels of proline and valine. Regarding glycine, which is considered to belong to the same group as imino acid and to be shared with high-affinity transport system ofproline, there was not very increased excretion. CONCLUSION: These findings suggest that AAs would predominantly affect the low-affinity transport system of proline in the brushborder membrane of proximal tubules because the low-affinity system is considered not to be shared with glycine transport.

Adult↗

PubMed1999

Effects of beta-glucuronidase-deficient and lycopene-producing Escherichia coli strains on formation of azoxymethane-induced aberrant crypt foci in the rat colon.

We tried to inhibit the formation of azoxymethane-induced aberrant crypt foci (ACF) in the rat intestine by feeding a culture of a beta-glucuronidase-deficient Escherichia coli strain or a cell suspension of a lycopene-producing E. coli strain. Feeding of the former culture to F344 rats did not decrease fecal beta-glucuronidase activity or the number of ACF compared with the control beta-glucuronidase-proficient groups. However, a significant positive correlation between the fecal beta-glucuronidase activity and the ACF number was observed among groups treated with cultures of beta-glucuronidase-proficient and -deficient strains. In the group treated with lycopene-producing cells, the number of ACF was significantly lower than that in the control group. A vegetable juice containing a larger amount of lycopene than a cell suspension of the lycopene-producing E. coli also decreased the number of ACF to the same extent as a cell suspension of the lycopene-producing bacteria. These results suggest that feeding of the beta-glucuronidase-deficient E. coli is not very effective in preventing colon carcinogenesis, although activity of the fecal beta-glucuronidase is associated with AOM-induced ACF formation, and that lycopene-producing intestinal bacteria can effectively prevent colon carcinogenesis.

Animals↗

PubMed1999

Isolation and characterization of CA XIV, a novel membrane-bound carbonic anhydrase from mouse kidney.

Carbonic anhydrase (CA) is involved in various physiological processes such as acid-base balance and transport of carbon dioxide and ions. In this study, we have succeeded in the isolation of a novel CA from the mouse kidney by use of the signal sequence trap method. It is a 337-amino acid polypeptide with a calculated molecular mass of 37.5 kDa, consisting of a putative amino-terminal signal sequence, a CA domain, a transmembrane domain, and a short hydrophilic carboxyl terminus, which we designated CA XIV. The CA domain of CA XIV is highly homologous with those of known CAs, especially extracellular CAs including CA XII, IX, VI, and IV. The expression study of an epitope-tagged protein has suggested that CA XIV is located on the plasma membrane. When expressed in COS-7 cells, CA XIV exhibits CA activity that is predominantly associated with the membrane fraction. By Northern blot analysis, the gene expression of CA XIV is most abundant in the kidney and heart, followed by the skeletal muscle, brain, lung, and liver. In situ hybridization has revealed that, in the kidney, the gene is expressed intensely in the proximal convoluted tubule, which is the major segment for bicarbonate reabsorption and also in the outer border of the inner stripe of the outer medulla. In conclusion, we have cloned a functional cDNA encoding a novel membrane-bound CA. This study will bring new insights into our understanding of carbon dioxide metabolism and acid-base balance.

Amino Acid Sequence↗

PubMed1999

Primary Non-Hodgkin's Lymphoma of the Male Breast: A Case Report.

A 69-year-old Japanese man presented with bilateral gynecomastia and a soft, mobile and clearly defined mass beneath the left nipple. A round radiopaque masswas revealed on mammography. The tumor was homogeneous, hypoechoic and measured2.4 x 3.9 cm on ultrasonography. Based on a diagnosis of malignant lymphoma by needle aspiration cytology, a modified radical mastectomy with ipsilateral axillary lymph node dissection was performed. Malignant diffuse large B-cell type lymphoma was diagnosed histologically. Whole body examinations revealed no evidenceof other tumors. Three courses of adjuvant CHOP therapy were subsequently performed. The patient is free of recurrence 12 months after surgery. Primary non-Hodgkin's lymphoma (NHL) of the male breast is extremely rare. The occurrence of lymphoma in this patient could be related to elevated estrogen levels.

Journal Article↗

PubMed1999

Effects of roselle (Hibiscus sabdariffa Linn.), a Thai medicinal plant, on the mutagenicity of various known mutagens in Salmonella typhimurium and on formation of aberrant crypt foci induced by the colon carcinogens azoxymethane and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in F344 rats.

The 80% ethanol extract of roselle (Hibiscus sabdariffa Linn.), a medicinal plant in Thailand, was examined for antimutagenic and chemopreventive activity in a colon carcinogenesis model. It reduced about 60-90% of the mutagenicity induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and other heterocyclic amines 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline(MelQ),2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline(MelQx),3-amino-1,4-dimet hyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2),2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1),2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2), at a concentration of 12.5 mg/plate in the Salmonella mutation assay. The extract showed no mutagenicity and no antibacterial activity below this dose. Mutagenicity of methylazoxymethanol (MAM) acetate, which, like PhIP, is a colon carcinogen,was also efficiently inhibited by the roselle extract. To investigate chemoprevention by roselle in a colon carcinogenesis model, we examined the inhibitory effects of the roselle extract in F344 rats in which aberrant crypt focus (ACF) formation was induced by azoxymethane (AOM) and PhIP. In the initiation stage, the number of AOM-induced ACF in the colon was significantly decreased by roselle (17-25%) compared with that in rats treated with AOM alone. The amount of O6-methylguanine in the colonic mucosa tended to be decreased in the roselle-treated rats. The number of PhIP-induced ACF was also significantly decreased by roselle treatment (22%) at a concentration of 1.0 g/kg body weight in the initiation stage. However, in the post-initiation stage of AOM-induced ACF formation, roselle increased the number of ACF, especially the number of foci which had more than three crypts/focus. These results indicate that roselle has antimutagenic activity against MAM acetate and heterocyclic amines and that it decreases the number of AOM- and PhIP-induced ACF in the initiation stage, although it rather increased the number of ACF in the post-initiation stage.

Animals↗

PubMed1999

Interruption of the aortic arch at the isthmus with DiGeorge syndrome and 22q11.2 deletion.

A 6-day-old male with interruption of the aortic arch at the isthmus (type A) had the typical phenotype of DiGeorge syndrome. There was also a doubly committed juxta-arterial ventricular septal defect and an unobstructed left ventricular outflow tract. Hypoplasia of the thymus was confirmed during a modified Blalock-Park operation. He had persistent hypocalcemia, and was susceptible to infection. He was subsequently revealed by the use of fluorescence in situ hybridization analysis to have 22q11.2 deletion. Interruption of the aortic arch at the isthmus is presumed to reflect abnormal fetal hemodynamics, and is considered a distinct pathogenetic entity from interruption between the left common carotid and subclavian arteries, the latter being the variant more frequently associated with DiGeorge syndrome. In our case, the 22q11.2 deletion likely played a major role in the etiology of the interrupted aortic arch.

Aorta, Thoracic↗

PubMed1999

Rest-redistribution thallium-201 myocardial scintigraphic study in cardiac amyloidosis.

BACKGROUND: Histopathological study in amyloid heart demonstrates that myocyte destructed by the extracellular deposition of amyloid protein together with viable myocyte is present. We hypothesized that rapid thallium washout may be found in amyloid heart as in regions which have a mixture of viable myocyte and scar tissue in patients with myocardial infarction. Thus, the purpose of this study was to evaluate the extent and severity of myocardial damage due to amyloid deposits using the washout rate of the tracer on rest-redistribution thallium-201 (201Tl) myocardial scans in cardiac amyloidosis patients. METHODS: Rest-redistribution 201Tl myocardial scintigraphy was performed in 5 patients with biopsy-proved systemic amyloidosis with cardiac involvement (amyloidosis group). The initial and delayed images were obtained 15 min and 4 h, respectively, after intravenous injection of the tracer of 111 MBq. Washout rate of the tracer was calculated. Twelve patients with no apparent heart disease served as controls (control group). RESULTS: Mean washout rate of the whole heart was higher in the amyloidosis group than in the control group (56 +/- 9% vs 36 +/- 6%, p < 0.001). Particularly, 4 of the 5 patients in the amyloidosis group presented a very high rate of thallium clearance which ranged from 57 to 61%, and died in less than a year. In the remaining 1 patient who had a normal washout rate of the tracer in the first study, it changed from 40 to 53% during the 5-year follow-up period. CONCLUSIONS: Washout rate in the setting of rest and delayed 201Tl images may represent the severity of amyloid depositions in the myocardium and may provide prognostic information.

Aged↗

PubMed1999

Low density lipoprotein apheresis therapy for steroid-resistant nephrotic syndrome. Kansai-FGS-Apheresis Treatment (K-FLAT) Study Group.

BACKGROUND: The pathogenic role of hyperlipidemia in long-standing nephrotic syndrome (NS) is known to be responsible for both the progression of glomerulosclerosis and tubulointerstitial injury, especially in focal segmental glomerulosclerosis (FGS). METHODS: Aggressive lipid lowering treatment by low density lipoprotein (LDL) apheresis (LDL-A) using a dextran sulfate cellulose column to treat patients with steroid-resistant or frequently recurrent severe NS was performed first without fixing the protocol in eight patients with FGS and one with minimal change nephrotic syndrome (MCNS). The period of NS before LDL-A, number and average intervals of LDL-A until the end of the therapy, and the prognosis were investigated. Next, a multicenter study with a fixed protocol of LDL-A treatment was designed in combination with steroid therapy for treatment twice a week for three weeks and weekly for six weeks, and was performed in 17 patients with FGS. The effects on the state of NS in addition to the change of urinary eicosanoid metabolites and remission rates were evaluated. RESULTS: In the preliminary study, along with a rapid improvement of hyperlipidemia, a high incidence of remission was achieved by LDL-A performed at relatively short intervals. In the multicenter study with a fixed protocol, there was a significant decrease of urinary protein (P < 0.001) and increase of serum albumin (P < 0.02) as well as a decrease of thromboxane B2 (TXB2) excretion (P < 0.05) after the treatment. Urinary excretion of TXB2 was significantly reduced after LDL-A (P < 0.05). The rate of entering into complete or incomplete remission was 71% with a relatively short duration of nephrotic-range proteinuria using the LDL-A therapy in comparison with steroid therapy alone. CONCLUSION: The rapid improvement of hypercholesterolemia with LDL-A treatment may provide a new approach for a high rate of improvement in the degree of NS in steroid-resistant NS of FGS and MCNS.

Adolescent↗