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Biomedical subjects

Akira Hishida

Publications and source records attributed to Akira Hishida.

At least 73 records · Page 4Linked to original sources

Rapid improvement of acute pulmonary edema with angiotensin converting enzyme inhibitor under hemodialysis in a patient with renovascular disease.

A 71-year-old man with bilateral renovascular disease was admitted to Hamamatsu University hospital because of appetite loss and acute shortness of breath due to acute pulmonary edema (APE) with accelerated hypertension and renal failure. Hypertension and APE were controlled by an angiotensin converting enzyme inhibitor (ACEI) and four sessions of hemodialysis with reduction of 1.8 kg bodyweight. Renal function was later stabilized and the patient required no ACEI or hemodialysis. A trial of right renal angioplasty 1 month after admission failed and renal function deteriorated (serum creatinine 7.1 mg/dL) with accelerated hypertension, gain of bodyweight and APE. Even after four sessions of hemodialysis with adequate reduction of bodyweight, APE was not controlled, but it rapidly improved after administration of an ACEI, without major bodyweight change. As no apparent cardiac dysfunction was evident, APE might have been caused by a direct action of angiotensin II on hyperpermeability in pulmonary capillaries. Blocking of angiotensin II should be considered in such patients even after introduction of hemodialysis.

Acute Disease↗

Supplementation with Alfacalcidol increases protein intake and serum albumin concentration in patients undergoing hemodialysis with hpoalbumineamia.

BACKGROUND: We have reported that vitamin D deficiency may be implicated in the pathogenesis of hypoalbuminemia observed in patients with end-stage renal disease, but the mechanism remains to be clarified. The aim of the present study was to determine whether supplementation with alfacalcidol might increase protein intake in hemodialyzed patients with hypoalbuminemia. METHODS: Twelve patients with hypoalbuminemia under 3.5 g/dl undergoing maintenance hemodialysis and not taking active forms of vitamin D were orally supplemented with 0.5 microg of alfacalcidol daily for 8 weeks. Normalized protein catabolic rate (nPCR), an index of protein intake, and serum concentrations of albumin, interleukin-6 (IL-6), IL-1beta, and soluble tumor necrosis factor-alpha receptor-II (sTNFR-II), an index of tumor necrosis factor-alpha activity, were determined before and after supplementation with alfacalcidol. RESULTS: Supplementation with alfacalcidol increased nPCR from 0.96 +/- 0.20 to 1.16 +/- 0.15 g/kg/day (p < 0.005), thereby increasing serum albumin concentration from a baseline of 3.13 +/- 0.35 to 3.32 +/- 0.29 g/dl (p < 0.05). The baseline serum concentrations of sTNFR-II and IL-6 were markedly elevated, whereas those of IL-1beta were under the detection limit. Supplementation with alfacalcidol significantly decreased serum concentration of sTNFR-II from 23.8 +/- 4.38 to 19.7 +/- 3.93 ng/ml (p < 0.001) but did not alter serum IL-6 concentration. CONCLUSION: Supplementation with alfacalcidol can increase protein intake and serum albumin concentration in hemodialyzed patients with hypoalbuminemia, probably through the suppressed tumor necrosis factor activity.

Aged↗

[Nephrotic syndrome: pathophysiology, classification and diagnostic criteria].

The nephrotic syndrome is defined by heavy proteinuria due to abnormal increase of glomerular permeability and following hypoalbuminemia, hyperlipidemia and edema. Disorders of size selective barrier, charge selective barrier, slit diaphragm and circulating permeability factors are thought to be the causes of proteinuria. Most patients with nephrotic edema have primary salt retention. Overproduction and impaired catabolism of lipoproteins are the causes of hyperlipidemia. Abnormality of coagulation factors is also associated with nephrotic syndrome. Nephrotic syndrome may be primary or secondary to systemic disorders. Once diagnosed, the cause for the nephrotic syndrome must be examined.

Edema↗

Dietary salt intake modulates progression of antithymocyte serum nephritis through alteration of glomerular angiotensin II receptor expression.

Dietary salt intake modulates the renin-angiotensin system (RAS); however, little is known about the effect of salt intake on the progression of glomerulonephritis. We investigated the glomerular expression of TGF-beta1 type I (TbetaRI) and II (TbetaRII) TGF-beta receptors and RAS components in rats with antithymocyte serum (ATS) nephritis on normal (NSI)-, low (LSI)-, and high-salt intake (HSI) and on HSI rats receiving candesartan cilexetil (CC) and LSI rats receiving PD-123319. Glomerular lesions were less severe in rats on LSI and aggravated in those on HSI compared with those on NSI. Intrarenal renin and glomerular ANG II levels were significantly higher in LSI and lower in HSI rats. In ATS nephritis, HSI increased glomerular TbetaRI, TbetaRII, and ANG II type 1 receptor (AT1R), and decreased glomerular ANG II type 2 receptor (AT2R), whereas LSI decreased glomerular TGF-beta1 and TbetaRI and increased glomerular AT2R. CC ameliorated glomerular lesions, reduced glomerular TGF-beta1 and TbetaRII, and increased glomerular AT2R. PD-123319 aggravated glomerular lesions and increased glomerular TGF-beta1 and TbetaRII. Our results suggest that dietary salt intake influences progression of ATS nephritis by modulating glomerular TGF-beta1 and TbetaR expression resulting, at least in part, from altered glomerular AT1R and AT2R expression.

Angiotensin II↗

Important role for fibronectin-EIIIA during renal tubular repair and cellular recovery in uranyl acetate-induced acute renal failure of rats.

The present study was designed to identify the source and kinetics of an alternatively spliced "embryonic" cellular fibronectin EIIIA (cFn-EIIIA) in relation to regenerating renal tubules in uranyl acetate (UA)-induced acute renal failure (ARF) in rats. Damage of the proximal tubules was found as early as day 2 after induction of ARF, peaked at day 5, and was almost substituted by epithelial relining by day 7. Immunohistochemistry showed de novo deposition of cFn-EIIIA in peritubular regions as early as day 2, then on the tubular basement membrane (TBM) after day 4. beta1 Integrin, the receptor for Fn, was mainly found at the basal side of tubules in the normal control and increased in the interstitium after induction of ARF, but the staining pattern gradually returned to the control after day 7. Immunoelectron microscopy revealed that cFn-EIIIA was produced initially by the peritubular endothelium and later by fibroblastic cells and was deposited to the TBM, on which regenerating tubules proliferated, probably with cFn-EIIIA production. beta1 Integrin was expressed in cFn-EIIIA-producing cells, especially in regenerating tubular cells, suggesting that cFn-EIIIA signal transduction affects regenerating tubules. Transforming growth factor (TGF)-beta1 was found in some damaged proximal tubules and interstitial cells after induction of ARF and later in the regenerating tubules. CFn-EIIIA and beta1 integrin mRNA levels were upregulated as early as day 2. TGF-beta1 mRNA level significantly increased after day 3, suggesting a modulatory role for TGF-beta1 on cFn-EIIIA production, but not by day 2. Our data suggest that cFn-EIIIA production by the endothelium during the very early response to tubular injury and by fibroblastic cells and regenerating tubules may play an important role in the cellular recovery of UA-induced ARF in rats.

Acute Disease↗

Temporary changes in macrophages and MHC class-II molecule-expressing cells in the tubulointerstitium in response to uranyl acetate-induced acute renal failure in rats.

The present study was designed to asses the dynamic changes in macrophages (Møs) with or without expression of major histocompatibility complex (MHC) class-II molecule in response to uranyl acetate-induced acute renal failure (ARF) in rats. ED1+ monocytes/Møs infiltrated into the interstitium as early as day 2, peaked in number on day 5 after uranyl acetate-induced ARF. ED1+ cells did not correlate with necrotic tubules but accumulated abundantly in the vicinity of the Ki67+ regenerating proximal tubules around days 4-5. Afterward, regeneration of proximal tubules was accelerated. After day 5, some ED1+ cells entered the tubular lumen, and became ED1+ giant cells, which had features of phagocytic Møs by immunoelectron microscopy, peaking in number on day 7. Most ED1+ cells did not incorporate [(3)H]-thymidine, indicating lack of active proliferation. The number of OX6+ cells (directed to MHC class-II molecule) in the interstitium significantly increased on day 4 and peaked on day 5. Double staining revealed that ED1+OX6- cells entered the tubular lumen while ED1+OX6+ cells remained in the peritubular regions. Osteopontin (OPN) protein and mRNA were significantly upregulated. No specific relationship could be found between OPN+ regenerating proximal tubules and ED1+ cells, but most ED1+ giant cells were OPN+ and intermingled among OPN+ cell debris. Our findings suggest that ED1+ Møs are actively associated with regenerating proximal tubules and, thus, might promote proximal tubular regeneration. ED1+OX6- Møs may function as scavengers and phagocytose cellular debris in the tubular lumen, cleaning the wound site. OPN might be involved in this process. ED1+OX6+ Møs in the peritubular regions may act as outpost of the defense system to monitor incoming antigens. Our data indicate that Møs with or without expressing MHC class-II molecule contribute to the defense and repair of injured proximal tubules in this ARF.

Acute Disease↗

The induction of heat shock protein-72 attenuates cisplatin-induced acute renal failure in rats.

Induction of heat shock proteins (HSPs) is thought to play a protective role in ischaemic acute renal failure (ARF). However the role of HSPs in nephrotoxic ARF is not well explored. The aim of this study was to clarify the effects of the induction of HSP70s on cisplatin (CDDP) (6 mg/kg i.v.)-induced ARF in rats. Uranyl acetate (UA) or sodium arsenite (SA) were administered i.v. 14 days or 1 day respectively before CDDP injection to induce HSPs. Serum creatinine (SCr), tubular damage score and the numbers of apoptotic (TUNEL-positive) cells were examined 5 days after CDDP injection. The expression of HSP72, B-cell lymphoma gene product-2 (Bcl-2) and Bax were evaluated by Western blot analysis. We also investigated the effect of co-administration of chelerythrine chloride (Chel), which inhibits the induction of HSPs, with SA on the expression of HSP72 and nephrotoxicity. Pretreatment with UA or SA significantly induced renal HSP72 expression. Both UA and SA attenuated the CDDP-induced increase in SCr and tubular damage scores. Co-administration of Chel with SA abolished the SA-induced increment of HSP72 and the beneficial effects of SA. The protective effects of the induction of HSP72 were associated with an increased renal Bcl-2/Bax ratio and the reduction of TUNEL-positive cells in the outer stripe of outer medulla. Our findings suggest that HSP72 attenuates CDDP-induced nephrotoxicity. The protective effects of HSP72 are associated with an increased Bcl-2/Bax ratio and less apoptosis.

Acute Kidney Injury↗

Longterm complete remission of AL-amyloid-related nephrotic syndrome.

We describe a 59-year-old man with nephrotic syndrome that was diagnosed as suspected minimal change nephrotic syndrome by the routine examination of renal tissues at first biopsy, because renal histology showed segmental mild mesangial expansion with argyrophilic staining and partial foot process fusion without any deposition. Prednisolone therapy induced complete remission of nephrotic syndrome. Relapse occurred after 4 years of complete remission, and the second renal biopsy revealed amyloid light-chain (AL)-amyloidosis. Re-examination of the first biopsy tissues by Congo red staining confirmed a small amount of amyloid deposition in the mesangial areas although the mesangial areas showed argyrophilic staining, which is atypical for amyloid deposition. This case raises a caution that even when renal histology is not suggestive of amyloidosis and prednisolone therapy is very effective, when a renal histology diagnosis is not confirmed, the clinician should suspect amyloidosis and should, at least, undertake Congo red staining to definitively rule out amyloidosis.

Amyloidosis↗

Ubiquitin-dependent degradation of Smad2 is increased in the glomeruli of rats with anti-thymocyte serum nephritis.

The overexpression of transforming growth factor (TGF)-beta and Smad-mediated intracellular TGF-beta signaling in the kidney underlies the development of renal scarring from pathological matrix accumulation. However, changes in the Smad proteins during the progression of kidney disease are unclear. In this study, we investigated the regulation of Smad proteins in the glomeruli of rats with anti-thymocyte serum nephritis. We found that Smad2 protein decreased markedly in nephritic glomeruli, whereas no significant changes were observed in the levels of Smad3 and Smad4 proteins. In contrast, the level of Smad2 mRNA in nephritic glomeruli did not differ significantly from that in control glomeruli. Based on recent reports of the ubiquitin-mediated degradation of Smad2, we investigated the degradation and ubiquitination activity directed against Smad2 in glomerular extracts. Both the degradation and ubiquitination of Smad2 were markedly increased in glomerular extracts from rats with nephritis. We also found that Smurf2, a ubiquitin ligase for Smad2, was increased in the nephritic glomerular extracts. These data suggest that the decrease in Smad2 resulted from enhanced ubiquitin-dependent degradation of Smad2 mediated by Smurf2, and is involved in the regulation of Smad2-mediated TGF-beta signaling in nephritic glomeruli.

Animals↗

Isolated adrenocorticotropic hormone deficiency presenting with hypercalcemia in a patient on long-term hemodialysis.

The authors report on a 44-year-old female hemodialysis (HD) patient who presented with hypercalcemia secondary to isolated adrenocorticotropic hormone (ACTH) deficiency. She had been suffering from nausea and abdominal pain caused by recurrent esophageal ulcer. Blood calcium (Ca) adjusted for serum albumin concentration was increased to 14.9 mg/dL (3.72 mmol/L) concurrently with fever and hypotension. Serum intact parathyroid hormone (PTH)-related peptide was not elevated, but serum intact PTH and 1,25-(OH)2 vitamin D3 were decreased to 31 pg/mL (ng/L) and 8.1 pg/mL (2.6 pmol/L), respectively. Endocrinologic examination found that plasma ACTH was reduced below 5.0 pg/mL (0.22 pmol/L). A single ACTH stimulation normally increased blood cortisol, whereas a single corticotropin-releasing hormone injection failed to increase plasma ACTH and cortisol. Pituitary magnetic resonance imaging disclosed no enlargement of pituitary gland. Circulating bone formation and absorption markers were not elevated. Blood Ca was normalized shortly after pamidronate disodium administration without glucocorticoid supplementation. This case suggested that secondary adrenal insufficiency caused by isolated ACTH deficiency could be an occult cause of severe hypercalcemia in HD subjects.

Adrenal Insufficiency↗

Anti-glomerular basement membrane antibody-induced glomerulonephritis with periglomerular granulomatous reaction and massive renal eosinophilic infiltration.

We present a case of a 68-year-old man with anti-glomerular basement membrane (anti-GBM) antibody-induced glomerulonephritis accompanied by periglomerular granulomatous reaction and massive eosinophilic infiltration. Periglomerular granulomatous giant cells were derived from macrophages, shown by positive staining for monoclonal antibody against cluster of differentiation 68. Staining for eosinophil cationic protein indicated that activated eosinophils were involved in the tubulitis, as well as in the glomerular injury. The patient was admitted to the hospital with fever, loss of appetite, edema of the extremities, abnormal urinalysis results, and rapid progressive renal failure. At an examination 8 months before admission, his serum creatinine level (1.0 mg/dL [88.4 micromol/L]) and urinalysis results were normal. On admission, an elevated serum creatinine level (5.1 mg/dL [450.8 micromol/L]) and marked eosinophilia (eosinophils, 5.00 x 10(3)/microL [5.00 x 10(9)/L]; 37.2% of total white blood cell count) were observed. Serum anti-GBM antibody titer was high (43 EU), measured by means of an enzyme-linked immunosorbent assay. No respiratory or ophthalmological abnormalities were seen. Intravenous steroid pulse therapy followed by oral prednisolone (PSL) was effective for reducing the fever, eosinophilia, anti-GBM antibody titer, and C-reactive protein level, but did not improve renal function because renal tissue already was irreversibly damaged. Oral PSL dose was tapered off without relapse. The patient underwent long-term hemodialysis therapy, which dissipated the edema. He was discharged from our hospital 65 days after admission. Three months later, his anti-GBM antibody level was less than 10 EU, and the number of peripheral eosinophils stayed with the normal range.

Acute Kidney Injury↗

Impact of carotid atherosclerosis on long-term mortality in chronic hemodialysis patients.

BACKGROUND: Cardiovascular event is the major cause of mortality in patients on maintenance hemodialysis. We prospectively tested the predictive values of atherosclerotic parameters for all-cause and cardiovascular outcomes in 219 hemodialysis patients (age, 58 +/- 13 years; time on hemodialysis, 13 +/- 7 years; male/female, 144/75). METHODS: We measured blood homocysteine (Hcy), ultrasound carotid artery intima media thickness (IMT) and % aortic wall calcification at L2/3 region [% of calcification index in the abdominal aortic wall (%ACI)] by computed tomography (CT) scan, and followed all patients for 5 years. RESULTS: During the follow-up periods, 54 patients (25%) died, 40 (74%) of them of cardiovascular causes. IMT was significantly higher in patients who expired (0.75 +/- 0.02 mm) than in those who survived (0.62 +/- 0.01 mm). IMT was significantly correlated with age (r = 0.47, P < 0.01) and %ACI (r = 0.27, P < 0.01). The survival rate during the observation was significantly lower in the final IMT third (58%) than in the first (90%) and the middle IMT third (80%) (P < 0.01). Multivariate Cox proportional hazards analysis revealed that diabetes and IMT became independent determinants of all-cause and cardiovascular death. Adjusted hazards ratios of all-cause and cardiovascular mortality for an increase of 0.1 mm in IMT were 1.31 (95% CI, 1.07 to 1.59) and 1.41 (95% CI, 1.12 to 1.76). In contrast, %ACI at abdominal aorta and blood Hcy did not affect their 5-year mortality. CONCLUSION: These findings suggested that measurement of carotid artery IMT is useful for predicting long-term mortality in patients receiving maintenance hemodialysis.

Adult↗

Elevation of blood thioredoxin in hemodialysis patients with hepatitis C virus infection.

BACKGROUND: Thioredoxin (TRX) is a stress-inducible thiol-containing protein, which has been shown to be an indicator of oxidative stress in a variety of diseases. The association between oxidative stress and hepatitis C virus (HCV) infection, however, remains unknown in hemodialysis patients. METHODS: We measured serum TRX levels in 85 hemodialysis patients positive for anti-HCV antibodies (age, 60 +/- 1 years old; hemodialysis duration, 17 +/- 1 years; M/F = 57/28) by enzyme-linked immunosorbent assay (ELISA), and examined whether blood TRX may be associated with HCV-related hepatic injury. RESULTS: Serum TRX was significantly higher in hemodialysis patients with HCV infection (112.3 +/- 3.7 ng/mL, N = 85) than in those without HCV infection (69.7 +/- 3.3 ng/mL, N = 59) (age, 69 +/- 2 years old; hemodialysis duration, 6 +/- 1 years; M/F = 32/27, P < 0.01) or normal subjects (28.0 +/- 5.4 ng/mL, N = 9). TRX was significantly correlated with time on hemodialysis (r = 0.27, P = 0.01) in HCV-positive patients, while it was associated with the patient's age in HCV-negative patients (r = 0.42, P < 0.01). Blood TRX was significantly correlated with asparate aminotransferase in patients with HCV infection (r = 0.34, P < 0.01) and without HCV infection (r = 0.46, P < 0.01). However, serum TRX was not associated with blood alanine aminotransferase, a relatively specific marker of hepatic cellular damage, in HCV-infected hemodialysis patients. A significant relationship was found between serum ferritin and TRX (r = 0.25, P = 0.02) and malondialdehyde (MDA) values (r = 0.25, P = 002) in HCV-positive patients. Serum TRX was also higher in the patients receiving weekly iron supplement with HCV infection (135.3 +/- 10.2 ng/mL vs. 110.2 +/- 3.9 ng/mL, P = 0.06) and without HCV infection (91.8 +/- 12.1 ng/mL vs. 65.2 +/- 2.7 ng/mL, P < 0.01). CONCLUSION: There was a greater increase in serum TRX in hemodialysis patients with HCV viremia than without HCV viremia. However, there may not be an association between serum TRX and HCV-related hepatic injury. TRX increased with serum ferritin in HCV-infected patients and further increased by iron infusion. These findings indicate that HCV infection and iron loading may aggravate oxidative stress in dialysis patients.

Aged↗

Withdrawal of interferon-alpha results in prompt resolution of thrombocytopenia and hemolysis but not renal failure in hemolytic uremic syndrome caused by interferon-alpha.

This case report describes 2 patients with chronic myeloid leukemia in whom hemolytic uremic syndrome developed while being treated with interferon-alpha and hydroxycarbamide. Hemolytic uremic syndrome was recognized by progressive renal dysfunction, thrombocytopenia, microangiopathic hemolytic anemia, and histologic features of thrombotic microangiopathy in the kidney. Although renal dysfunction progressed to dialysis-dependent renal failure in one patient despite treatment with prednisolone and plasmapheresis but not in other, withdrawal of the treatment resulted in a prompt resolution of thrombocytopenia and microangiopathic hemolytic anemia in both patients.

Adult↗

Adrenal insufficiency due to isolated adrenocorticotropin deficiency complicated by autosomal recessive polycystic kidney disease.

We describe a 29-old-year Japanese man with autosomal recessive polycystic kidney disease who was frequently hypoglycemic. Insulinoma as a cause of hypoglycemia was denied because the ratio of plasma immunoreactive insulin to glucose was low. Adrenal insufficiency was diagnosed because of the low urinary excretion of 17-hydroxycorticosteroids, and both blunted responses of plasma cortisol to an intravenous injection of adrenocorticotropin and of plasma adrenocorticotropin to an intravenous injection of human corticotropin releasing hormone were observed, although basal plasma concentrations of cortisol and adrenocorticotropin were normal. The elusion profile of plasma sample from our patient chromatographed on a Sephadex G-75 column showed two peaks of (1-39)-ACTH and beta-lipotropin, with no evidence of high molecular weight form of ACTH. The plasma concentrations of thyroid stimulating hormone and growth hormone were within the normal range. These findings indicated that this patient with autosomal recessive polycystic kidney disease was associated with adrenal insufficiency due to isolated adrenocorticotropin deficiency.

17-Hydroxycorticosteroids↗