Keisuke Hiraoka

A Rare Combination of Sites of Involvement by Mycobacterium intracellulare in a Hemodialysis Patient: Multifocal Synovitis, Spondylitis, and Multiple Skin Lesions

Purpose: Atypical mycobacterial infection is a rare but serious hazard in immunocompromised patients including those undergoing maintenance hemodialysis and immunosuppressive therapy. Recognition of unusual involvement patterns is important. Methods: We describe an extremely rare combination of complications caused by such an organism in a patient with end-stage renal disease: spinal osteolysis and multiple skin lesions associated with synovitis. Results: The patient had received a renal allograft 18 years previously but developed infection with Mycobacterium avium-M. intracellulare complex including dermatologic manifestations, spondylitis, and synovitis involving the wrist and lateral malleolus after initiation of hemodialysis when the transplanted kidney failed. An empirical antibiotic regimen failed to alleviate skin lesions or fevers, or to lower an elevated C-reactive protein concentration, until the patient’s dose of methylprednisolone was increased to treat mild adrenal insufficiency. The increase resulted in rapid resolution of skin lesions. A compression fracture 6 months later was attributed to spondylitis caused by the same organism. Conclusion: We suspect that spondylitis represented the primary focus of M. intracellulare infection.

Impairment of Vascular Responses to Reactive Hyperemia and Nitric Oxide in Chronic Renal Failure

Background: Cardiovascular events are the leading cause of morbidity and mortality in patients with end-stage renal disease. The role of endothelial dysfunction, an early marker of arteriosclerosis, in patients with chronic renal failure (CRF) before the initiation of maintenance hemodialysis (HD), and the factors affecting endothelial dysfunction in the setting of chronic renal failure remain poorly understood. Methods: We evaluated endothelial function by measuring flow-mediated vasodilation (%FMD) during reactive hyperemia in healthy individuals (HCS) and patients with chronic renal failure with (HD) or without (ND) hemodialysis. Nonspecific endothelium-independent vasodilation (%NTG) was measured after the administration of sublingual glyceryl trinitrate spray (0.3 mg). Factors affecting %FMD and %NTG were also tested. Results: In ND and HD, plasma homocysteine, cysteine and stable NO metabolite (NO–3) concentrations were significantly elevated. In ND and HD, reactive hyperemia as well as %NTG and %FMD were attenuated to a similar degree. On multivariate regression analysis, NO–3 concentration was directly correlated with both %FMD and %NTG, while the glutathione (GSH) concentration correlated with only %NTG. Conclusion: Our findings indicate that chronic renal failure before the initiation of maintenance hemodialysis impairs endothelial function and/or the response to NO, which is accompanied by the attenuated reactive hyperemia. Furthermore, the impairment might be related to the decreased synthesis or the dissipation of NO.

A Nitric Oxide-Generating Beta-Blocking Agent Prevents Renal Injury in the Rat Remnant Kidney Model

Background: The L-arginine-nitric oxide (NO) pathway plays an important role in the modulation of glomerular disease. We investigated whether β-blocking agents, with and without an NO-generating function, had renoprotective effects in the 5/6 nephrectomized rats (Nx), an animal model of glomerulosclerosis. Methods: Nipradilol, a β-blocker with an ONO2 group (5, 10 or 15 mg/kg/day) and propranolol, a β-blocker without this group (50 mg/kg/day) were administered for 12 weeks to Nx together with and without nitro-L-arginine methyl ester (L-NAME). We evaluated the effects of both drugs on proteinuria, hypertension, renal function, glomerulosclerosis and urinary excretion of NO metabolites (UNOx) and cyclic GMP (UcGMP). Results: Both drugs similarly attenuated the elevated blood pressure in Nx. However, nipradilol, at doses of 10 and 15 mg/kg/day, significantly decreased proteinuria and glomerulosclerosis, while propranolol did not. Nx showed reduced UNOx in comparison with the sham-operated rats. Nipradilol increased UNOx and UcGMP significantly and in a dose- dependent manner, whereas propranolol reduced them to levels lower than those in Nx. Nx receiving L-NAME reduced UNOx. The addition of nipradilol increased UNOx and decreased urinary protein excretion and glomerulosclerosis, suggesting that the NO released from the drug contributed to its renoprotective effect. Conclusion: These findings indicate that nipradilol exerts its renoprotective effect through NO generation, and not by lowering blood pressure. The β-adrenergic blocking action per se does not seem to be related to the renoprotective effect of these agents.

Extra-renal Erythropoietin Secretion After Bilateral Nephrectomy

Serum concentrations of erythropoietin and soluble transferrin receptor were examined immediately after removal of the remaining kidney in a patient with a history of unilateral radical nephrectomy. Unexpectedly, the erythropoietin concentration increased from 18.2 U/L to 42.5 within 6 h after the operation. Soluble transferrin receptor (TfR) concentration rapidly decreased from 2725 µg/L to 1548 during the 12-h postoperative period. Extra-renal erythropoietin secretion could increase to more than twice as much as the renal secretion of erythropoietin immediately after the loss of renal tissue, and the rise in erythropoietin could accelerate the recycling of TfR, thus causing a decrease in its serum concentration.

Tuberculosis in diabetic patients on maintenance hemodialysis.

1978年から1991年までの14年間に, 血液透析へ導入された糖尿病性腎症を原疾患とする透析患者, 男性72例, 女性34例の計106例を対象として, 結核症の合併について検討した. 年齢は58±10歳, 透析導入までの糖尿病歴は16±8年, インスリン使用例は56例であった. 菌排出, 生検, 剖検により結核症と確定診断した5例と, ツベルクリン反応陽性, 赤沈亢進, 炎症反応, 不明熱を認め, 抗結核剤投与により症状改善を認めた疑診例10例, 計15例 (14.4%) を結核合併症とし, 結核非合併症91例との比較を行った. 年齢, 糖尿病歴, インスリン使用例, 糖尿病合併症等には両群間に差はなかった. 結核症合併例15例中9例に結核既往歴が認められ, 非合併例の91例中10例よりも高頻度に認められた. また, 結核症合併例15例中13例は透析導入後6月以内に発症した.

Evaluation of overhydration in diabetic patients at the beginning of regular dialysis treatment.

糖尿病性腎症由来の腎不全患者においては, 慢性腎炎由来の腎不全患者よりも, 慢性透析導入時に溢水状態にある患者の多いことが知られている. これらの溢水状態にある糖尿病性腎症患者の, 慢性透析導入時の病態と治療成績を検討した. 本院において慢性透析に導入した糖尿病性腎症患者69例 (男40例, 女29例, 平均年齢59歳, 平均糖尿病罹病期間16年) を, 導入時点において溢水を伴う症例と溢水を伴わない症例に分け検討した. 溢水症例としては肺水腫23例, 心胸比の拡大24例, 胸水貯留13例, 腹水貯留14例, 心嚢液貯留7例を認めた. これらのいずれかを有する症例33例を溢水症例とした.溢水症例は非溢水症例よりも導入時のクレアチニン, 血中総蛋白, 酸素分圧が低値であり, 1日尿蛋白の排泄量が高値であった. 一方, 性, 年齢, 糖尿病罹病期間, インスリン使用に関しては両群間に差はみられなかった. 導入3か月目までの死亡は6例にみられ, 全例溢水症例であった. 死因は, 心不全2例, 感染症2例, 脳出血, 消化管出血各1例であった. 溢水症例においては, 直接穿刺による緊急透析例が多く, 導入後10日間における透析回数, 透析時間, 総除水量が多かった. 溢水状態にある症例に対してはより早期の導入を心がけた, 1984年以後の症例の導入期死亡例は23例中3例と, それ以前の10例中3例より若干減少した.以上, 溢水状態にある糖尿病性腎不全患者は, 温水のない症例よりも導入時死亡の頻度が高く, より早期に透析療法に導入し, 溢水の是正をはかる必要があると考えられた.

Clinical study of gastrointestinal bleeding in patients with chronic hemodialysis.

1974年から1989年までに本院において経験した, 消化管出血を合併した慢性透析患者32例, 33回, 平均年齢53歳, 男性21例, 女性11例, 平均透析歴26か月を対象として, 慢性透析患者の消化管出血に関する病態および治療成績の検討を行った. 消化管出血の原因としては, 胃潰瘍14例, 胃癌2例, Mallory-Weiss症候群2例, 腸結核2例, 食道静脈瘤, 出血性胃炎, 十二指腸潰瘍, 下行結腸ポリープ, 下行結腸潰瘍, S状結腸癌各1例, 不明7例であった. 死亡例は11例 (死亡率34%) で, 消化管出血の持続による者が8例, 感染症2例, 房室ブロック1例であった. 6例に開腹手術による止血が試みられたが, 4例は術後合併症のために死亡した. 1984年以降の症例に対しては, メシル酸ガベキサートやメシル酸ナファモスタットを使用する非ヘパリン透析により十分な血液浄化を行い, 上部消化管病変に対してはH2受容体拮抗剤の使用, さらにより早期から高カロリー輸液による十分な熱量の補給に心掛けた. その結果, 1984年以降の症例の死亡率は11%と, それ以前の死亡率64%より減少した.以上, 非ヘパリン透析による十分な透析, 高カロリー輸液による栄養管理, 上部消化管病変に対するH2受容体拮抗剤の使用等を総合的に行うことにより, 慢性透析患者における消化管出血に対する治療成績の改善が得られた.