Hitoshi Tagawa

Increased excretion of nitric oxide in exhaled air of patients with chronic renal failure

Nitric oxide exerts multiple effects on renal function. It remains unclear whether endogenous nitric oxide production is increased or decreased in patients with chronic renal failure. To evaluate endogenous nitric oxide production in these patients we studied exhaled nitric oxide output by an ozone chemiluminescence method and plasma NO2(-)/NO3(-) levels by the Griess method in 40 patients with end-stage chronic renal failure who underwent regular continuous ambulatory peritoneal dialysis (n=30) or haemodialysis (n=10), and in 28 healthy subjects. Patients with chronic renal failure had a higher exhaled nitric oxide concentration [39+/-3 versus 19+/-1 parts per billion, (mean+/-S.E.M.), P<0.0001], a greater nitric oxide output (177+/-11 versus 96+/-7 nl.min-1.m-2, P<0.001) and a higher plasma NO2(-)/NO3(-) concentration (96+/-14 versus 33+/-4 micromol, P<0.01) than controls. These values did not differ between patients on haemodialysis and those on continuous ambulatory peritoneal dialysis. Patients with chronic renal failure had significantly higher plasma concentrations of both interleukin-1beta and interferon-gamma than controls. The exhaled nitric oxide output did not correlate with plasma NO2(-)/NO3(-) or with peritoneal dialysate NO2(-)/NO3(-), but plasma NO2(-)/NO3(-) correlated with dialysate NO2(-)/NO3(-) in patients who underwent continuous ambulatory peritoneal dialysis (r=0.77, P<0.01). Haemodialysis for 4 h acutely decreased plasma NO2(-)/NO3(-) (92+/-17 versus 50+/-8 micromol, P<0.05) and cGMP concentration (16.5+/-4.3 versus 5.1+/-1. 7 pmol/ml, P<0.01), but did not decrease exhaled nitric oxide output. The increase in exhaled nitric oxide with the simultaneous increase in circulating cytokines suggests that nitric oxide synthase seems to be induced significantly in patients with chronic renal failure. Increased endogenous nitric oxide production may have a pathophysiological role in patients with uraemia.

Diffuse Hepatic Calcification as a Sequela to Shock Liver

A 31-yr-old Japanese woman who was on chronic hemodialysis for 3 yr died of intractable congestive heart failure. Three years before death, the patient was in a state of shock for 48 h due to ventricular tachycardia and gastrointestinal bleeding, which was followed by marked elevation of serum transaminase. Four months later, abdominal plain radiography demonstrated diffuse hepatic calcification. At autopsy, microscopic examination of the liver revealed parenchymal necrosis and tiny calcifications in the central to midzonal area of the lobule. Calcification in the degenerative area of the hepatic lobule occurred subsequent to parenchymal ischemia after overt shock that lasted for 2 days. Although a definitive explanation for the calcification was not obtained, it may be related to the disturbances of intracellular Ca2+ homeostasis as a result of ischemic liver injury or it may be related to an elevated calcium-phosphorus product in the uremic state.

Clinical Significance of Cerebral Aneurysm in Renovascular Hypertension due to Fibromuscular Dysplasia: Two Cases in Siblings

Two cases, in siblings, of renovascular hypertension caused by fibromuscu lar dysplasia (FMD) of the renal artery associated with cerebral aneurysms are reported. Both of the cases were found to have cerebral aneurysm, as well as multiple stenotic or occluded lesions in arteries such as renal, mesenteric, celiac, and internal carotid arteries. One case died of subarachnoid hemorrhage and the other case was successfully operated on for the aneurysm. This report sug gests that FMD should be considered to be a systemic angiopathy including the cerebral artery, as well as the renal artery. Thus, cerebral angiography is rec ommended to detect the association with cerebral aneurysm, at least, in cases with multiple lesions of FMD. Occurrence of FMD in siblings also indicates that a genetic factor might be involved in the pathogenesis of FMD.

Role of Endogenous Serotonin in the Regulation of Blood Pressure in Patients with Chronic Renal Failure

Although the pathogenesis of hypertension in patients on maintenance haemodialysis is not completely understood, one of the important contributing factors is an increase in total peripheral vascular resistance (Kim et al. 1972). Page and McCubbin (1953) discovered the monoamine serotonin and suggested it may have a role in the regulation of blood pressure. However, its function in the regulation of blood pressure is still unclear. Clinical investigations of the serotonin S2-receptor antagonist ketanserin have shown that ketanserin reduces systemic vascular resistance and lowers blood pressure following acute or long term administration in patients with essential hypertension (De Cree et al. 1981; Fagard et al. 1984; Wenting et al. 1984). In this study, the acute effects of ketanserin on blood pressure and hormonal responses in 10 patients on maintenance haemodialysis with hypertension were determined in order to assess the role of endogenous serotonin in the regulation of blood pressure in such patients. The long term effect of ketanserin on pressor responsiveness to the £x,-adrenoreceptor agonist phenylephrine was also determined in 5 patients. 1. Methods

Improvement of MBD Parameters in Dialysis Patients by a Switch to, and Combined Use of Lanthanum Carbonate: Josai Dialysis Forum Collaborative Study

The effects of lanthanum carbonate on MBD parameters were investigated in 59 hemodialysis patients who were taking calcium carbonate. Lanthanum carbonate (initial dosage: 750 mg/day), as a replacement for or in combination with calcium carbonate and/or sevelamer hydrochloride, was administered for 12 months with increase/decrease of dosages. Lanthanum carbonate replaced calcium carbonate for 21 cases and was co‐administered in 38 cases. It replaced sevelamer hydrochloride in 20 cases and was co‐administered in 10 cases. Both the number of cases to which calcium carbonate was administered and their dosages decreased to about 70–80% 12 months after the initiation, and cases administered sevelamer decreased to about 30%. In the cases for which lanthanum carbonate was co‐administered, the dosages of calcium carbonate and sevelamer slightly decreased. A significant decrease in serum calcium level was observed. In the serum phosphorus levels (P levels), significant decrease compared with the initial level was observed only at six and nine months. Intact parathyroid hormone (iPTH) level remained stable at around 230 pg/mL without significant change. The dosage of vitamin D and cinacalcet remained without significant change. The results of this trial suggest that, if dosages of vitamin D and cinacalcet are adequately controlled, a switch to lanthanum carbonate and its concomitant use are effective to control the Ca and P levels without changing iPTH levels.

Potential factors regulating serum parathyroid hormone in maintenance hemodialysis patients: 4-year retrospective study

AbstractBackground. This study was carried out to evaluate potential factors affecting long-term parathyroid function in patients on maintenance hemodialysis. Methods. Biochemical parameters, including intact parathyroid hormone (i-PTH) and intact osteocalcin (i-OC) were analyzed retrospectively in 120 outpatients receiving hemodialysis, for the 4 years between 1992 and 1996. Patients were classified into the following three groups according to their serum i-PTH levels in 1996: low PTH (<100 pg/ml), normal PTH (100–450 pg/ml), and high PTH (≧450 pg/ml). Results. Among the three PTH groups, no differences were found in age, sex, duration of dialysis, and laboratory parameters, except for serum levels of alkaline phosphatase (ALP), i-PTH, and i-OC. The percentage of diabetic patients was higher in the low PTH group than in the other two PTH groups. Both serum ALP and i-PTH levels increased in the high PTH group, and serum i-PTH level decreased in the low PTH group during the 4 years. The change in serum calcium (Ca) level was negatively correlated with that in serum i-PTH level (1994–1996, r = −0.623, 1992–1996, r = −0.565; P <0.0001). A higher correlation coefficient was observed in the low PTH group than in the other PTH groups, although the difference was not significant. A weak positive correlation of the changes in serum inorganic phosphorus (IP) level (1994–1996) and i-PTH level (1994–1996) was found in the high PTH group (r = 0.379, P < 0.05). Conclusion. Serum Ca level may play a determinant role in suppressing serum i-PTH level in hemodialysis patients. Serum IP level may stimulate serum i-PTH level in patients with hyperparathyroidism, although the physiological role of serum IP is yet to be established.

Percutaneous transluminal angioplasty for venous stenosis of hemodialysis fistula: Indication and prognosis

BackgroundPercutaneous transluminal angioplasty is an acceptable procedure for insufficient hemodialysis fistula flow, but the factors affecting the patency after angioplasty remain to be clarified.MethodsPercutaneous transluminal angioplasty was performed 29 times in 24 patients undergoing hemodialysis who had insufficient blood flow arising from stenosis in the venous limb of the arterio-venous fistula. We retrospectively investigated factors affecting patency of stenotic lesions after the angioplastic procedure.ResultsCumulative patency rate after angioplasty in all patients, by using Kaplan-Meiers plot, amounted to 58% at 1 year and 54% at 2 years. Analysis by the Cox proportional hazard model showed that length of the stenotic lesions was the only significant factor for patency. The 1-year patency rate after percutaneous transluminal angioplasty was identified as 81% when original stenosis length had been less than 1 cm, 42% when stenosis length had been between 1 and 2 cm, and 16% when stenosis length had exceeded 2 cm.ConclusionShort venous stenotic lesions in hemodialysis fistulas can be treated successfully with percutaneous transluminal angioplasty.

Five patients who developed eosinophilic peritonitis shortly after starting CAPD.

CAPDにおける腹膜炎の一部に, 無菌的に発症する好酸球性腹膜炎の存在が報告されている. 我々は, 三井記念病院でCAPDに導入した慢性腎不全患者60例のうち, 好酸球性腹膜炎と診断された5例を経験した. 全例が腹膜カテーテル挿入後3週間以内に排液の白濁にて発症し, 自覚症状はなく, 自然軽快を示した. 好酸球性腹膜炎の原因としてはCAPDのシステムに対するアレルギー反応が考えられているが, 今回経験した5症例のうち4例が導入直後に発症しており, うち2例は挿入時に使用した腹腔鏡の消毒薬がその原因と考えられることから, カテーテル挿入時の化学的, 機械的な刺激がその原因になり得るものと推論した. 本症は無治療にて自然軽快するため, 抗菌剤による治療は不要である.

Erythropoietin titers in patients on maintenance dialysis determined by a new radioimmunoassay technique

遺伝子組換えヒトエリスロポエチンを用いた放射免疫測定法を新たに開発し, 特異性, 感度, 再現性ともに優れた臨床応用可能な血中エリスロポエチン (EPO) 濃度の測定系を確立した. その容量反応曲線は3-250mU/mlの範囲で直接測定が可能であり, 最小測定限界は5mU/mlであった.本法によって測定したEPOは長期透析患者428例において16.1±8.6mU/ml (m±SD), 正常人86例において17.1±7.2mU/mlであり, 両群間に有意差を認めなかった. 透析患者のEPOは貧血の程度に比して相対的に極めて低値と考えられ, またEPOとHtとの間には相関を認めなかった. 大量の輸血を受けた患者群と非輸血群のEPOはほぼ同値であったが, 一部の高度貧血患者では低値の傾向があり, 輸血を繰り返す必要があった. 正常人, 透析患者ともにEPOは加齢にともなって増加する傾向があったが, 正常人では70歳以上でやや減少した. 透析期間が長いほどHtが高い症例が増加する傾向があるが, 透析期間とEPOの間には有意の相関を認めなかった. 腎不全の原因疾患別にみると, 多発性骨髄腫のEPDは他疾患の患者群よりも有意に高値であった. 多発性嚢胞腎では貧血は軽度であり, EPOはやや高値の傾向を示した. なお, 蛋白同化ステロイド・鉄剤投与の有無, 網状赤血球数, 血液尿素窒素, 血清クレアチニン, 血清鉄, 血清フェリチンとEPOとの間には, 相関を認めなかった.

A CASE OF HYPOKALEMIA IN ACUTE MONOCYTIC LEUKEMIA

急性単球性白血病はときに低カリウム血症を伴うことが知られている.われわれもその1例を経験し,低カリウム血症の発生機序を検討した.症例は61才,女,発熱,リンパ節腫脹,出血傾向,肝脾腫あり.白血球10.1万,単球様白血病細胞が末梢血で89%,骨髄で92.6%を占めた.血清Kは常2.9mEq/l以下.リゾチーム活性は血清357,尿3111μg/m1と高値であつた. VCMP療法3クールにて完全寛解となつた.リゾチーム活性は血清,尿ともに著減したが,血清Kは低値のままであつた.カリウム負荷により尿中K排泄が増加し,またナトリウム摂取を制限しても尿中K排泄が減少しないことから,近位尿細管あるいはHenle係蹄におけるカリウム再吸収の抑制が示唆される.トリアムテレン投与に対する反応は正常であり,遠位尿細管のNa・K交換部位はintactと判断された.また,血漿レニン活性,アルドステロン値が正常であり,スピロノラクトンが無効であることから,レニン・アルドステロン系の関与は否定された.以上から,崩壊した単球に由来する大量のリゾチームが近位尿細管で再吸収されたために,その部位のカリウム再吸収機構に傷害を与え,カリウム喪失をきたしたものと結論した.なお,その他の尿細管機能の異常は随伴しなかつた.