Biomedical subjects

H Kiyomoto

Publications and source records attributed to H Kiyomoto.

At least 19 recordsLinked to original sources

PubMed2006

Interferon-gamma enhances superoxide production in human mesangial cells via the JAK-STAT pathway.

Immune reactive cytokines, such as interferon (IFN)-gamma, have multiple effects in glomerulonephritis. Superoxide anions (O(2)(-)), which are associated with the progression of glomerulonephritis, are mainly generated by nicotinamide adenine dinucleotide phosphate (reduced form) NAD(P)H oxidases. We determined the effects of IFN-gamma on O(2)(-) production, phosphorylation of signal transducer and activator of transcription (STAT)-1alpha, and the mRNA and protein expressions of p22phox and Nox1, components of NAD(P)H oxidases, in human mesangial cells (HMCs). Significant increases in O(2)(-) production with IFN-gamma were completely abolished by the flavin-containing enzyme inhibitor, diphenyleneiodonium (10 micromol/l), and the Janus-activated kinase (JAK)2 inhibitor, AG490 (100 micromol/l). Phosphorylated STAT-1alpha was detected after 5 min of IFN-gamma stimulation using Western blot analysis, and binding to the gamma-activating site was observed from 30 min to 4 h, thereafter by electrophoretic mobility shift assay (EMSA). Super-shift analysis in EMSA revealed that the main transcription factor was STAT-1alpha. IFN-gamma significantly increased the expression of p22phox mRNA and protein, although expression was inhibited by AG490. These data suggest that IFN-gamma stimulates O(2)(-) production in HMCs via the JAK-STAT pathway and NAD(P)H oxidase.

Cells, Cultured↗

PubMed2003

Long-term evaluation of nutritional status using dual-energy X-ray absorptiometry in chronic hemodialysis patients.

BACKGROUND: Hemodialysis patients very often suffer from malnutrition with net loss of body muscle and fat stores. Since protein-calorie malnutrition has been considered to be highly associated with increased morbidity and mortality, it is important that the nutritional status is evaluated accurately and that long-term evaluation of the nutritional status is performed to obtain good outcome. PATIENTS AND METHODS: Forty-six patients (28 men and 18 women) undergoing maintenance hemodialysis were studied. Nutritional status of the patients was examined by dual-energy X-ray absorptiometry (DXA) and anthropometry measurements after a hemodialysis session and 4 years after the initial measurement. RESULTS: Percent fat, the ratio of body fat (BF) to weight, determined by DXA correlated positively with body mass index (BMI) calculated from weight and height. There was also a significant positive correlation between lean body mass (LBM) determined by DXA and arm muscle circumference (AMC) calculated using the anthropometric method. In the study period of 4 years, LBM and bone mineral content (BMC) observed at the end point were significantly lower than those at the start. In contrast, BF and %fat at the end point were significantly higher as compared with those at the initial measurement. CONCLUSION: These results indicate that DXA is a reliable method for body composition analysis in chronic hemodialysis patients. Because the detection of early alterations in body composition may provide an early indication of the development of malnutrition, serial evaluation of body composition using DXA should be valid for assessment of the nutritional status.

Absorptiometry, Photon↗

PubMed2000

Alteration in left ventricular diastolic filling and accumulation of myocardial collagen at insulin-resistant prediabetic stage of a type II diabetic rat model.

BACKGROUND: Considerable controversy exists regarding impairment of cardiac function in diabetes mellitus (DM). We investigated the serial changes in left ventricular (LV) histopathology and LV filling dynamics in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which have been established as an animal model of type II DM. METHODS AND RESULTS: In 54 OLETF and 54 non-DM rats, body weight, blood pressure, heart rate, and transmitral pulsed Doppler examinations were performed from 5 to 47 weeks of age. An oral glucose tolerance test was performed at 10, 20, and 30 weeks of age. The hearts were excised for histopathology, including immunohistochemistry and histomorphometry of collagen, and measurement of hydroxyproline at baseline and each stage of developing DM. In the prediabetic stage (15 weeks of age), in which fast blood glucose remained normal, OLETF rats manifested mild obesity, postprandial hyperglycemia, and hyperinsulinemia, and early diastolic transmitral inflow exhibited prolonged deceleration time (OLETF, 59+/-10 ms versus non-DM, 49+/-8 ms, P<0.01) and low peak velocity (OLETF, 73+/-11 cm/s versus non-DM, 88+/-11 cm/s, P<0.01). Histopathology revealed extracellular fibrosis and abundant transforming growth factor-beta(1) receptor II in LV myocytes of OLETF rats. At 15 weeks of age, the ratio of collagen area/visual field of LV wall in OLETF rats (8.3+/-1.3%) was larger than that in non-DM rats (4.9+/-1.8%, P<0.0001), and the collagen content/dry tissue weight ratio of heart was significantly higher in OLETF (2. 0+/-0.5 mg/g) than non-DM (1.3+/-0.2 mg/g, P<0.01) rats. CONCLUSIONS: A metabolic abnormality present in the prestage of type II DM may produce LV fibrosis and alteration in cardiac function.

Animals↗

PubMed2000

A new approach for glomerular lesions: evaluation of scanning acoustic microscopy (SAM) for experimental glomerular disease in rats.

Most pathological evaluations using ordinary optical microscopy are usually qualitative and subjective. The beneficial properties of scanning acoustic microscopy (SAM) include not only observation of microstructure but also quantitative measurement of acoustic propagation speed, indicating the tissue elasticity. In this study, we examined the capability of SAM to evaluate pathological findings in glomeruli using anti-Thy.1 glomerulonephritis. Light microscopic observations of the glomeruli showed severe cell proliferation and mesangial matrix expansion at 10 days after induction of glomerulonephritis and, yet, to a lower extent at day 21 with onset of healing. C-mode scanning of SAM enabled imaging of glomerular structure compatible to findings of ordinary light microscopy. In addition, glomerular propagation speed in nephritic rats was significantly increased at day 10, and then decreased at day 21. These results indicate that SAM evaluation may be a new, useful technique for quantitative evaluation of proliferative glomerular lesions.

Animals↗

PubMed2000

Effects of troglitazone on collagen accumulation and distensibility of aortic wall in prestage of non-insulin-dependent diabetes mellitus of Otsuka Long-Evans Tokushima Fatty rats.

We investigated the effect of troglitazone (TG) on aortic distensibility and histopathology at the preclinical stage in the non-insulin-dependent diabetes mellitus (NIDDM) model. Twenty male diabetic and 20 male nondiabetic rats were each divided into two groups: treated-DM, untreated-DM, treated-nonDM, and untreated-nonDM. TG (0.2%) was mixed in chow in the treated groups. From age 5 to 15 weeks, fast blood glucose and insulin were monitored. At 15 weeks, oral glucose tolerance test results, aortic wall histopathology, and collagen content were studied, and intravascular ultrasound images and aortic pressure were recorded. Aortic diameter was measured during the cardiac cycle, and the stiffness parameter beta was calculated. Blood glucose (mg/dl) 2 h after loading in treated-DM (139+/-20) was normalized (untreated-DM, 188+/-27; p<0.05). Insulin concentration (ng/ml) in treated-DM (3.2+/-0.4) was lower than that in untreated-DM (8.1+/-1.5; p<0.01). At 15 weeks, beta in untreated-DM (2.4+/-0.8) was larger than those in untreated-nonDM (1.5+/-0.4; p<0.0001) and in treated-DM (1.9+/-0.4, p = 0.0081). Aortic wall collagen (mg/g dry weight) increased in untreated-DM (32.8+/-3.3) as compared with treated-DM (28.1+/-3.8; p = 0.048). Histomorphometry showed decreased medial area (mm2) in treated-DM (0.55+/-0.05) compared with untreated-DM (0.78+/-0.12; p<0.0001). This study suggests that TG may prevent metabolic abnormalities and the deterioration of aortic distensibility at an early prediabetic stage.

Animals↗

PubMed2000

Echocardiographic observation of acute myocarditis with systemic lupus erythematosus.

Although myocarditis from a series of autopsies of patients with systemic lupus erythematosus was frequently observed, the incidence of clinically apparent myocardial dysfunction was low. A 30-year-old woman with systemic lupus erythematosus was examined by echocardiography. An acoustic densitometry was followed at the left ventricular posterior wall throughout the clinical course. A decrease in the magnitude of cyclic variation of integrated backscatter (IB) was observed before treatment. Following the combined treatment, steroid and cyclophosphamide, a repeated ultrasonic tissue characterization showed an increase in the magnitude of cyclic variation of IB. It is thought that ultrasonic tissue characterization may be a useful method to evaluate the impairment of contraction, and to follow up the clinical course of myocardial involvement in systemic lupus erythematosus.

Adult↗

PubMed2000

Transesophageal echocardiographic observation of multiple myeloma involving the pericardium: a case report.

This report presents a case of multiple myeloma with a mass lesion on the pericardium and pericardial effusion. The response to intrapericardial combination chemotherapy (cisplatin and betamethasone) was evaluated by repeated transesophageal echocardiograms. Following the treatment, complete resolution of the tumor and effusion were observed for 6 months after which the patient died of bacterial pneumonia. Intrapericardial combination chemotherapy can be an effective treatment for myelomatous involvement of the pericardium.

Aged↗

PubMed1999

The effect of combination therapy with interferon and cryofiltration on mesangial proliferative glomerulonephritis originating from mixed cryoglobulinemia in chronic hepatitis C virus infection.

Cryofiltration, which has developed from double filtration plasmapheresis (DFPP) with a cooling unit, is an on-line technique to remove cryoglobulin. We report on a patient who suffered from progressive edema and renal insufficiency caused by cryoglobulinemic membranoproliferative glomerulonephritis (MPGN), probably due to chronic hepatitis C virus (HCV) infection. To remove cryoglobulins and terminate the HCV infection, we utilized combination therapy with cryofiltration and interferon-alpha injection with corticosteroids. Interferon-alpha was capable of decreasing proteinuria but not diminishing cryoglobulin. Additional cryofiltration could remove cryoglobulin to an undetectable level. This combination therapy was partially successful to reduce proteinuria and prevent the progressive deterioration of renal function. The major adverse effects of this therapy were bleeding and myelosuppression. We conclude that this combination therapy may be effective and should be considered as treatment for cryoglobulinemic MPGN.

Aged↗

PubMed1999

Alteration in aortic wall stiffness and accumulation of collagen during the prediabetic stage of type II diabetes mellitus in rats.

Aortic damage during the prediabetic stage of diabetes mellitus (DM) was investigated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, as an animal model of type II DM. In 30 OLETF and 30 nonDM rats, an oral glucose tolerance test was performed at 10, 20 and 30 weeks of age. At 15 and 30 weeks, intravascular ultrasound images and aortic pressure were recorded and the stiffness parameter beta was calculated. The aortic walls were excised at 5, 15 and 30 weeks for histopathology and the measurement of hydroxyproline. At 10 weeks, blood glucose (mg/dl) and insulin concentrations (ng/ml) of the OLETF rats (2h; 168+/-30 and 0.82+/-0.15) were significantly high (nonDM: 118+/-15; p = 0.02 and 0.16+/-0.64; p = 0.003). At the prediabetic stage (15 weeks), beta in the OLETF rats (2.5+/-0.9) was larger than in nonDM rats (1.4+/-0.4; p = 0.0006), and the collagen (hydroxyproline) content/dry weight (mg/g) of the aortic wall was significantly higher in OLETF (33.5+/-3.1) than in nonDM rats (28.7+/-3.5; p<.05). Histopathological examination showed that from 15 weeks of age the medial wall thickness increased gradually. In the prediabetic stage, collagen accumulation may contribute to impairment of aortic wall stiffness in the OLETF rats, which would accelerate the aging process in the aortic wall.

Animals↗

PubMed1999

Effect of histamine H2-receptor antagonist on the phosphorus-binding abilities of calcium carbonate and calcium lactate in hemodialysis patients.

The effect of histamine H2-receptor antagonist (famotidine) on the phosphorus-binding abilities of calcium carbonate and calcium lactate were examined in 13 chronic hemodialysis patients. In seven patients receiving calcium carbonate, famotidine (20 mg/d) was given because of gastroduodenal disorders, and calcium carbonate was replaced with calcium lactate as a phosphorus binder after 4 wk of treatment with famotidine. With the 4-wk administration of famotidine accompanied by calcium carbonate, the serum phosphorus level increased from 6.3+/-0.9 to 7.1+/-0.5 mg/dl (P<0.05). However, with the substitution of calcium lactate, the serum phosphorus level decreased significantly when compared to that before substitution (6.3+/-0.2 and 6.0+/-0.9 mg/dl after 4 and 8 wk of substitution, respectively), despite continued administration of famotidine. Serum calcium, creatinine, alkaline phosphatase, high sensitive parathyroid hormone, blood urea nitrogen, arterial blood pH, and bicarbonate were not significantly altered during the trial period. In six control patients treated with calcium carbonate alone, there were no statistical changes in serum calcium and phosphorus levels after substitution of calcium lactate for calcium carbonate. These results suggest that famotidine significantly affects the phosphorus-binding ability of calcium carbonate, but not that of calcium lactate. A careful observation of changes in the serum phosphorus level should be required in hemodialysis patients receiving calcium carbonate and histamine H2-receptor antagonists. Calcium lactate may be useful as a phosphorus binder in such hemodialysis patients.

Adult↗

PubMed1998

Preferential expression of insulin-like growth factor binding proteins-1, -3, and -5 during early diabetic renal hypertrophy in rats.

The renal insulin-like growth factor-I (IGF-I) system has been implicated in the pathogenesis of renal hypertrophy, altered hemodynamics, and extracellular matrix expansion associated with early diabetes. The relative abundance of IGF binding proteins (IGFBPs) in the renal microenvironment may modulate IGF-I actions. However, the precise IGFBPs expressed in the glomerular and tubulointerstitial compartments during diabetic renal growth have not been characterized. In the present study, in situ hybridization studies were performed to examine the expression of IGFBP-1 to -6 messenger RNAs (mRNAs) 3, 7, and 14 days after streptozotocin (STZ) injection in rats. In control, nondiabetic kidneys, all six IGFBP mRNAs were differentially expressed with a predominance of IGFBP-5. The onset of renal hypertrophy in STZ-induced diabetes was associated with a rapid and site-specific induction of IGFBP-1, -3, and -5 mRNAs. In contrast, basal expression of IGFBP-2, -4, and -6 mRNAs was not altered in diabetic rats. IGFBP-5 mRNA expression increased in diabetic glomeruli, cortical, and inner medullary peritubular interstitial cells at days 3, 7, and 14. Although normal glomeruli failed to express IGFBP-3, it was induced concomitantly with IGFBP-5 in diabetic glomeruli and cortical peritubular interstitial cells. IGFBP-1 mRNA levels also increased in cortical tubular cells at each time point tested. Peak induction of IGFBP-3 and -5 was observed at day 3, whereas IGFBP-1 was delayed until day 7. IGFBP-1, -3, and -5 mRNA levels declined by day 14, but remained persistently elevated above control. By immunoperoxidase staining, similar alterations in the pattern of IGFBP-3 and -5 protein expression were observed at each time point. The preferential and site-specific increase in IGFBP-1, -3, and -5 suggest that these IGFBPs may regulate the local autocrine and/or paracrine actions of IGF-I and contribute to the pathogenesis of the early manifestations of diabetic nephropathy.

Animals↗

PubMed1998

Evaluation of acoustic properties of the live human smooth-muscle cell using scanning acoustic microscopy.

This study was performed to measure the acoustic propagation speed in live human aortic smooth-muscle cells (HASMC), using scanning acoustic microscopy (SAM) and a novel measurement theory that permits the measurement of the acoustic propagation speed in biological samples of unknown thickness. C-mode and X-Z-mode images of HASMC under three different conditions: growing (G); differential (D); and on hypotonic loading (H), were acquired using 100-MHz, 450-MHz and 600-MHz ultrasound. The images exhibit features related to the cell surface curvature and intracellular structure. The theory supporting the methodology is derived in this article and makes use of the interference fringes within the focusing lens of the high-frequency transducer. The propagation speed in the cells was calculated from the location of the interference fringe on the C-mode images and the fringe shift on the X-Y-mode images with 450-MHz ultrasound. The propagation speed in D (1624 +/- 16 m/s) was significantly higher than those in G (1571 +/- 14 m/s, p < 0.05) and H (1585 +/- 8 m/s, p < 0.05). Scanning acoustic microscope measurements, along with the described theory, are useful for studying the acoustic properties of live cells ex vivo and have applications in both pathophysiology and biomechanics.

Acoustics↗

PubMed1998

A simple and early prognostic index for acute renal failure patients requiring renal replacement therapy.

Recent advances in technology have not substantially changed the high mortality rate associated with acute renal failure (ARF). To obtain a simple, valid prognostic index, we retrospectively evaluated the relative importance of demographic data, causes (acute insults) of renal failure, and comorbid clinical conditions for the outcome in 102 ARF patients who received renal replacement therapy with an overall mortality rate of 65% (66 of 102). There were no significant differences between survivors and nonsurvivors in age and gender. Mortality according to acute insults was similar to that of the whole population studied. Of the 10 clinical conditions at the time of the first renal replacement therapy, mechanical ventilation (p = 0.0002), cardiac failure (p = 0.0006), hepatic failure (p = 0.003), central nervous system dysfunction (p = 0.005), and oliguria (p = 0.04) were found to be significantly related to mortality by univariate analysis. Furthermore, multivariate analysis demonstrated that only mechanical ventilation, cardiac failure, and hepatic failure were significant risk factors. Survival was directly related to the number of significant variables in univariate analysis: zero, 89% (8 of 9); one, 62% (21 of 34); two, 19% (5 of 27); three, 10% (2 of 20); four, 0% (0 of 8); five, 0% (0 of 4). This simple and early prognostic index, derived from the assessment of clinical conditions which were easily determined at the patient's bedside, could be useful for outcome prediction in ARF patients requiring renal replacement therapy.

Acute Kidney Injury↗

PubMed1997

Expression of transforming growth factor-beta and type IV collagen in early streptozotocin-induced diabetes.

The earliest manifestations of type I diabetic nephropathy include mesangial matrix expansion, basement membrane thickening, and renal hypertrophy. Transforming growth factor (TGF)-beta, a potent inducer of matrix protein synthesis, is a prime candidate to mediate the glomerular changes observed in diabetes. However, the temporal expression of TGF-beta and matrix proteins during the early stage of diabetic nephropathy has not been clearly defined. Using in situ hybridization and immunohistochemistry, we determined the expression of TGF-beta and type IV collagen mRNAs and proteins in glomeruli and interstitium of diabetic rats 3, 7, and 14 days after streptozotocin (STZ) administration. There was a marked increase in the expression of TGF-beta and alpha1(IV) procollagen mRNAs in glomerular and tubulointerstitial cells as early as 3 days after induction of diabetes, an effect that persisted for 14 days. A concomitant increase in TGF-beta and type IV collagen proteins was also observed at each time point. Insulin treatment substantially inhibited the increased expression of TGF-beta and collagen type IV mRNAs and proteins. We conclude that TGF-beta is increased in glomeruli during the early phase of rapid renal growth in diabetes. These findings suggest that TGF-beta may be a key factor involved in the pathogenesis of basement membrane thickening and extracellular matrix accumulation. Inhibition of TGF-beta and type IV collagen expression by insulin treatment suggests that they may be useful structural markers for determining the efficacy of therapeutic intervention during early diabetic nephropathy.

Animals↗

PubMed1997

[Long-term follow-up study of bone mineral density in a patient with adult idiopathic Fanconi syndrome].

A 64-year-old woman complaining of severe lumbar pain was admitted to our hospital because of the finding of pre-existing mitral valve regurgitation on examination. Laboratory data revealed the proximal type of renal tubular acidosis, renal glucosuria, phosphaturia, generalized aminoaciduria and low-molecular-weight proteinuria. She did not have any cause of these tubular dysfunctions, and was diagnosed as adult idiopathic Fanconi syndrome. Dual energy X-ray absorptiometry (DEXA) revealed a reduction of bone mineral density in the lumbar spine to about 65% of the age-and gender-matched control value. Alkali agents (sodium citrate and potassium citrate), calcium lactate and 1 alpha-hydroxyvitamin D3 were administered. Bone mineral density estimated with DEXA improved with a reduction of serum alkali phosphate and disappearance of lumbar pain, and was restored to 82% of the age-and gender-matched control value after about 30 months of treatment. DEXA is useful for the long-term follow-up study of bone mineral density in a patient with Fanconi syndrome.

Absorptiometry, Photon↗

PubMed1997

[Mechanism mediating hypertension induced by chronic inhibition of nitric oxide synthesis].

Although the inhibition of nitric oxide (NO) synthesis is known to induce systemic hypertension, the underlying mechanisms mediating this type of hypertension are incompletely understood. In the present study we investigated the influence of sodium intake on the pressor effect of long-term administration of the NO synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 16 mg/dl in drinking fluid for 8 weeks), in conscious Sprague-Dawley rats. Urinary excretion rates of catecholamine during NO synthesis inhibition were also examined. Long-term administration of L-NAME produced a sustained elevation in tail-cuff pressure without altering urine flow, or sodium excretion rate. L-NAME-induced hypertension was accompanied by a decreased urinary excretion of the stable NO metabolites, NO2- and NO3-, and was aggravated when rats drank 0.9% saline in place of tap water. Thus, inhibition of NO synthesis resulted in a rightward shift of the pressure natriuresis relationship and a significant decrease in the slope of this relationship. Urinary excretion of epinephrine and norepinephrine, but not that of dopamine, in L-NAME-treated rats significantly increased within the first week of the study when compared with those observed in control rats. A natriuretic index of the sympathetic nervous system, the ratio of dopamine to norepinephrine excretion, was significantly less in L-NAME-treated rats than in control rats. After 8-week treatment with L-NAME, renal morphologic evaluation revealed significant narrowing and obliteration of the arterioles. L-arginine (2 g/dl in drinking fluid) completely reversed the elevation of blood pressure as well as the decrease in urinary NO2- and NO3- excretion and the increased urinary excretion of catecholamines associated with L-NAME treatment after 3 weeks of concomitant administration. These results suggest that the inhibition of chronic NO synthesis produces sodium-sensitive hypertension and that changes in sympathetic nerve activity may, at least in part, contribute to the sodium sensitivity in this type of hypertension.

Animals↗

PubMed1996

PDGF stimulates tyrosine phosphorylation of JAK 1 protein tyrosine kinase in human mesangial cells.

Platelet-derived growth factor (PDGF) exerts multiple effects in glomerular mesangial cells, including transcription of genes that mediate its biological activity. We have partially characterized PDGF-mediated early mitogenic signal transduction pathways that include activation of protein kinase C alpha and phosphatidylinositol 3 kinase. However, the precise mechanism of PDGF-induced gene transcription is not yet clear. A family of cytoplasmic transcription factors referred to as signal transducers and activators of transcription (STAT) has recently been identified. This group of transcription factors is activated by different cytokines via tyrosine phosphorylation. We studied the effect of PDGF on STATs in human mesangial cells. Using a gel retardation assay, nuclear and cytoplasmic extracts from PDGF-stimulated mesangial cells contained protein factors that bind to a DNA sequence representing the sis-inducible element (SIE) present in the c-fos gene promoter. These protein factors also bind to the enhancer element present in interferon-gamma responsive genes, suggesting the involvement of STAT proteins. The addition of monoclonal antibody that recognizes STAT 1 results in "supershift" of the DNA-protein complex stimulated by PDGF indicating the presence of STAT 1. Immunoblotting experiments with a monoclonal STAT 1 antibody revealed the presence of STAT1 alpha and STAT1 beta in mesangial cells. Since certain cytokines activate STATs via tyrosine phosphorylation mediated by JAK family of tyrosine kinases, we studied the effect of PDGF on JAK kinases. Antiphosphotyrosine immunoblotting of JAK 1 immunoprecipitates from PDGF-stimulated mesangial cell lysate showed increased tyrosine phosphorylation of this tyrosine kinase. In vitro immune complex kinase assay of JAK 1 immunoprecipitates from PDGF-stimulated mesangial cell lysate revealed activation of this tyrosine kinase. Taken together, these data demonstrate that PDGF activates the transcription factor STAT 1 in mesangial cells. The data also provide the first evidence that PDGF stimulates tyrosine phosphorylation of JAK 1, the cytoplasmic tyrosine kinase stimulated by many other cytokines to activate transcription via STATs. These observations indicate that JAK 1 is a downstream tyrosine kinase in PDGF receptor signaling and is a candidate for activation of STAT 1.

Binding Sites↗

PubMed1996

[Effect of histamine H2-receptor antagonists on the phosphorus-binding ability of phosphate binders in hemodialysis patients].

We examined the effects of histamine H2-receptor antagonists on the phosphorus binding ability of phosphate binders. Serum calcium, phosphorus, ALP, PTH and arterial blood pH and bicarbonate were measured during treatment with histamine H2-receptor antagonists accompanied by calcium carbonate in sixteen patients undergoing maintenance hemodialysis. Seven patients receiving histamine H2-receptor antagonists without calcium carbonate were selected as controls. In the sixteen patients receiving calcium carbonate, serum calcium, ALP, PTH and arterial blood pH and bicarbonate were not significantly altered during treatment with histamine H2-receptor antagonists, but serum phosphorus levels increased significantly after four (5.6 +/- 1.1 mg/dl) and eight weeks (5.9 +/- 0.8 mg/dl) of treatment as compared with that before treatment (4.8 +/- 1.2 mg/dl). Furthermore, serum phosphorus levels decreased significantly eight weeks after the discontinuation of treatment with histamine H2-receptor antagonists. In the seven control patients there were no statistical differences in serum calcium and phosphorus levels measured before and after treatment with histamine H2-receptor antagonists. In seven other patients receiving histamine H2-receptor antagonists with calcium carbonate, calcium carbonate was replaced with calcium lactate as the phosphate binder after four weeks of treatment with histamine H2-receptor antagonists. With the 4-week administration of histamine H2-receptor antagonists accompanied by calcium carbonate, the serum phosphorus level increased, similarly to that of the first study (from 6.3 +/- 0.9 to 7.1 +/- 0.5 mg/dl). However, with the substitution of calcium lactate, the serum phosphorus level decreased significantly (6.3 +/- 0.2 and 6.0 +/- 0.9 mg/dl after four and eight weeks, respectively, despite continued administration of histamine H2-receptor antagonists). These results suggest that histamine H2-receptor antagonists significantly affect the phosphorus binding ability of calcium carbonate, but not of calcium lactate. Although the exact mechanism remains obscure, one possible explanation may be related to the rise in pH of the gastric juice. Careful observation of changes in the serum phosphorus level is required in hemodialysis patients receiving calcium carbonate and histamine H2-receptor antagonists. Calcium lactate may be useful as a phosphate binder in such hemodialysis patients.

Adult↗