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Hypoxia-inducible factor prolyl hydroxylase inhibitors improve anemia in CKD and dialysis patients and were approved for anemia treatment with these populations in Japan. An 89 year-old man with anemia and on maintenance hemodialysis was successfully treated with a dose-up of darbepoetin alfa from 10 to 20 μg per week, and the dose was gradually tapered to 5 μg. Later, serum hemoglobin levels decreased with the newly occurring sustained inflammation and left pleural effusion of an unknown cause, and the darbepoetin alfa dose was increased again to 20 μg per week, which was not effective. Darbepoetin alfa was switched to 4 mg of daprodustat daily, which was fairly effective under sustained inflammation, with serum hemoglobin levels maintained at 11-12 g/dL. The increase in hemoglobin levels was ascribed to the increase in the number of red blood cells, not the mean corpuscular hemoglobin level. During the inflammatory state, despite the contrasting effect on anemia by the 20 μg of darbepoetin alfa weekly and 4 mg of daprodustat daily, the reticulocyte counts were equivalent. The serum erythropoietin levels during daprodustat administration were within the physiological range (8.5-18.8 mIU/mL). For anemia treatment in hemodialysis patients, daprodustat is less influenced by the inflammatory status than darbepoetin alfa, and one of the possible reasons for this includes the extended red blood cell lifespan.

Mechanisms of impaired fatty acid metabolism may not be the same in nondialysis and hemodialysis patients. Correlations between the serum free carnitine concentration (FC), acylcarnitine concentration (AC), acyl to free carnitine ratio (AC/FC) and estimated glomerular filtration rate (eGFR) in the nondialysis population and the duration of hemodialysis in hemodialysis patients were investigated. As the eGFR decreased, the FC and AC increased, and as the duration of hemodialysis became longer, the FC and AC decreased. The AC/FC increased consistently as the eGFR decreased and the duration of hemodialysis increased. As an exception, the AC/FC decreased in the patients with a hemodialysis duration less than 90 days, which was not explained by carnitine removal by hemodialysis. In nondialysis patients, a functional, rather than an absolute, carnitine deficiency is a main cause of impaired fatty acid metabolism. Long-term hemodialysis exacerbates absolute carnitine deficiency, whereas hemodialysis treatment may improve impaired fatty acid metabolism. This article is protected by copyright. All rights reserved.

Background Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare hereditary disease caused by a variety of genetic mutations. Carriers of a mutation in the responsible genes are at risk of reaching end-stage kidney disease typically in middle age. The frequency of this disease is assumed to be underestimated because of a lack of disease-specific signs. Pathological findings obtained from kidney of uromodulin related ADTKD (ADTKD-UMOD) patients are regarded as non-specific and less-informative for its diagnosis. This research was undertaken to evaluate the significance of kidney biopsy in ADTKD-UMOD patients. Methods Thirteen patients from 10 families with nine identified uromodulin (UMOD) gene mutations who underwent kidney biopsy in the past were studied. Their kidney tissues were stained with anti-UMOD antibody in addition to conventional methods such as PAS staining. When positive, the numbers of tubules with visible UMOD protein accumulations were calculated based on the total numbers of UMOD expressing tubules. Pathological findings such as tubulointerstitial fibrosis, atrophy, inflammation and glomerulosclerosis were also evaluated and analyzed. Results Interstitial fibrosis and tubular atrophy were present in all 13 patients. Most atrophic tubules with thickening and lamellation of tubular basement membranes showed negative UMOD staining. In all but two patients with C94F mutations, massive accumulation of UMOD proteins was observed in the renal endoplasmic reticulum. UMOD accumulations were also detectable by PAS staining as polymorphic unstructured materials in the 11 patients at frequencies of 2.6–53.4%. 80.4% of the UMOD accumulations were surrounded by halos. The detection rate of UMOD accumulations positively correlated with eGFR. Glomerulosclerosis was detected in 11/13 patients, with a frequency of 20.0 to 61.1%, while no cystic dilatations of glomeruli were detected. Conclusions Massively accumulated UMOD proteins in ADTKD-UMOD kidneys are detectable not only by immunostaining using anti-UMOD antibody but also by conventional methods such as PAS staining, although their detection is not easy. These findings can provide important clues to the diagnosis of ADTKD-UMOD. Kidney biopsy in ADTKD-UMOD may be more informative than assumed previously.

Antithrombotic medications (AM) are mandatory for many hemodialysis patients, but the bleeding risk associated with this therapy is elevated. The frequency of bleeding events requiring discontinuation of AM, cessation of heparin use, and/or hospitalization was compared between hemodialysis patients with and without AM. All the hemodialysis patients in our clinic were investigated. AM were prescribed in 130 of 222 patients. Except for patients with cilostazol, those with AM had significantly more frequent bleeding events than those without AM (P

Oral iron preparations are useful for the treatment of anemia in hemodialysis patients; however, long-term changes in the iron dynamics and effects of anemia are unknown. Serum ferritin levels and erythropoietin-stimulating agent (ESA)/hemoglobin (Hb) ratios were investigated for 750 days in the following four groups: patients treated with sodium ferrous citrate (SF) (de novo 50 mg/day and 150 mg/day switched from 50 mg/day) and patients treated with 1500 mg/day of ferric citrate (FC) (de novo and switched from 50 mg/day of SF). Compared with the other groups, serum ferritin levels increased less apparently with de novo 50 mg/day SF. ESA/Hb ratios did not change in groups switched from 50 mg/day SF. Conversely, in groups with de novo iron, ESA/Hb ratios decreased and ultimately reached the same levels in all groups. Although more iron results in higher serum ferritin levels, 50 mg/day SF has an equivalent effect for anemia treatment.

Although cardiovascular disease (CVD) is an important cause of death in patients on hemodialysis, evidence of a beneficial effect of percutaneous intervention (PCI) on stable heart disease is scarce. We investigated the cardiovascular outcomes of hemodialysis patients under our policy of encouraging coronary artery screening tests to the extent possible. A total of 147 hemodialysis patients have been treated in our clinic so far. In 98 of them, coronary artery screening tests were performed, three in unstable and 95 in asymptomatic patients. Significant coronary artery stenosis was detected in 29 at the first tests and in 11 during subsequent tests (40/98, 40.8%), and PCI or coronary artery bypass grafting (CABG) was performed. Multiple PCIs were needed in 21 patients. In the other 49 patients, coronary artery screening tests were not undertaken based on the nephrologist's decision or patient refusal. At the end of the study, 73 (74.5%) patients with tests, and 14 (28.6%) without tests were still outpatients (P < 0.01). Of 40 patients transferred to other hospitals for medical reasons or who died before transfer, there was cerebrovascular accident in eight, malignancy in six, congestive heart failure without CVD in four, infection in three, sudden cardiac death in one, and others 18. No patient with tests died of CVD and the only patient who died of sudden cardiac death probably due to myocardial infarction was a patient who had declined the screening tests. Coronary artery screening tests, intervention and subsequent periodic tests for asymptomatic hemodialysis patients can reduce the occurrence of cardiovascular events in this population.

For iron therapy in hemodialysis patients, intravenous rather than oral administration is recommended. For hemodialysis patients with serum ferritin levels less than 200 ng/ml (less than 100 ng/ml: 67 patients, between 100 and 199 ng/ml: 20 patients) with no iron therapy for more than 3 months, iron was administered intravenously (40 mg of ferric oxide saccharate for ten times consecutively, N = 40) or orally (50 mg/day of sodium ferrous citrate N = 31, or 1500 mg/day of ferric citrate hydrate N = 16). We conducted the retrospective observational study to evaluate the changes in hemoglobin levels, the dose of erythropoietin-stimulating agents (ESAs), and the ratio of ESA dose/hemoglobin (Hb) levels for 28 weeks. During the first 8 weeks, hemoglobin levels increased and ESA/Hb ratio decreased uniformly with almost the same ESA dose. Subsequently, ESA/Hb ratio increased in patients with intravenous iron but decreased further in patients administered oral iron. ESA dose reduction at the end of the study in the patients receiving intravenous iron, sodium ferrous citrate, and ferric citrate hydrate were 12.2, 33.8, and 39.5 %, and ESA/Hb reduction ratios were 10.3, 34.5, and 37.4 %, respectively. In patients with serum ferritin levels less than 100 ng/ml at baseline, ESA/Hb ratio decreased especially in those receiving oral rather than intravenous iron (p

Compared with acetate dialysate, bicarbonate dialysate has shown beneficial effects in reducing the morbidity associated with dialysis, but a small amount of acetate in bicarbonate dialysate may evoke hypotension or malaise. Acetate-free citrate hemodialysis (AFHD) may avoid these problems. In 44 hemodialysis patients bicarbonate hemodialysis (BHD) was conducted for three months, followed by a switch to AFHD for three months, and a further switch to bicarbonate hemodialysis (ReBHD). In BHD, AFHD and ReBHD, intra-dialysis hypotension and post-dialysis malaise were determined (hypotension: intra-dialysis systolic blood pressure (SBP) was expressed as a percentage of SBP at the start of hemodialysis, malaise was assessed by a self-reported 0 to 3 scale, 0: absence of malaise, 3: unbearable malaise). Compared with BHD, AFHD patients complained of less malaise but the intra-dialysis blood pressure change did not differ significantly (malaise: BHD 0.73 ± 0.76 vs. AFHD 0.32 ± 0.47, P

Although antiplatelet medication is used in various situations, including for the prevention of ischemic and thrombotic complications, long-term antiplatelet therapy in hemodialysis patients who are at high risk of bleeding may result in a harmful bleeding tendency. We investigated bleeding events that required the cessation of the use of heparin for hemodialysis in all the hemodialysis patients treated in our clinic. This analysis revealed 111 patients, of whom 52 had been treated with antiplatelet agents (female/male, 15/37; age, 70.4 ± 11.3 years; number of days of hemodialysis treatment in our clinic, 1073 ± 696 [31–2144] days; diabetes mellitus [DM]/non-DM, 29/23), and 59 had not been treated with them (female/male, 17/42; age, 66.7 ± 14.0 years; number of days of hemodialysis treatment in our clinic, 917 ± 605 [26–2102] days; DM/non-DM, 21/38). During treatment in our clinic, 21 of the 52 patients undergoing antiplatelet therapy experienced a bleeding event (gastrointestinal bleeding 16, brain stem hemorrhage 2, others 3), while 7 of the 59 patients not receiving them had a bleeding event (gastrointestinal bleeding 7) (P

内シャント穿刺に伴う疼痛は，血液透析を施行する上で，頻繁に認められる問題である．われわれは，11名の血液透析患者で，内シャント穿刺に伴う疼痛を，穿刺局所を20度に冷却した場合（cool down：CD），リドカイン貼付を使用した場合（lidocaine patch：LP），何もしなかった場合（control：C）で比較した．各々の血液透析患者で，CD，LP，Cによる血液透析を3回ずつ施行した．穿刺時の疼痛は，疼痛スコア（0：lack of pain, 10：unbearable pain）を使用し，各々の患者で，CD，LP，Cそれぞれの3回の穿刺時痛を合計して比較した．穿刺局所の温度は，CDで21.0±2.3℃，LPで34.7±0.7℃，Cで34.9±1.4℃であった．3回の穿刺痛の合計は，CD：9.8±4.7，LP：9.3±6.8，C：15.3±6.4であった（CD vs. LP：p＝n. s., CD vs. C：p＝0.0012, LP vs. C：p＝0.0002）．LPの使用では，局所の発赤，掻痒が時折みられたが，CDでは，副作用はみられなかった．穿刺局所の冷却は，血液透析患者の内シャント穿刺時の痛み軽減に有効な方法と考えられた．

Although cardiovascular disease (CVD) is an important cause of death in patients on hemodialysis, evidence of a beneficial effect of percutaneous intervention (PCI) on stable heart disease is scarce. We investigated the cardiovascular outcomes of hemodialysis patients under our policy of encouraging coronary artery screening tests to the extent possible. A total of 147 hemodialysis patients have been treated in our clinic so far. In 98 of them, coronary artery screening tests were performed, three in unstable and 95 in asymptomatic patients. Significant coronary artery stenosis was detected in 29 at the first tests and in 11 during subsequent tests (40/98, 40.8%), and PCI or coronary artery bypass grafting (CABG) was performed. Multiple PCIs were needed in 21 patients. In the other 49 patients, coronary artery screening tests were not undertaken based on the nephrologist's decision or patient refusal. At the end of the study, 73 (74.5%) patients with tests, and 14 (28.6%) without tests were still outpatients (P0.01). Of 40 patients transferred to other hospitals for medical reasons or who died before transfer, there was cerebrovascular accident in eight, malignancy in six, congestive heart failure without CVD in four, infection in three, sudden cardiac death in one, and others 18. No patient with tests died of CVD and the only patient who died of sudden cardiac death probably due to myocardial infarction was a patient who had declined the screening tests. Coronary artery screening tests, intervention and subsequent periodic tests for asymptomatic hemodialysis patients can reduce the occurrence of cardiovascular events in this population.

当院腎臓内科外来通院中のクレアチニン3mg/dL以上の慢性腎不全患者, 血液透析通院患者それぞれに対し, 腎移植の適応, 肉親からの生体腎提供の有無について, 調査した. 慢性腎不全患者39人中15人が将来腎移植適応と考えられ, 全員が透析よりも腎移植を希望し, うち9人に肉親からの生体腎提供が可能であった. 血液透析患者86人中31人が腎移植適応と考えられ, うち11人が腎移植を希望したが, 全員肉親から腎提供を得ることはできなかった. 透析導入前の患者に比べ透析導入後の患者は, 腎移植希望の傾向が弱かったが, 肉親からの生体腎提供に対する遠慮とも考えられた. 1997年以降12例の末期腎不全, 透析患者に対し生体腎移植が施行され, その経過は現在まで良好である. 生体腎移植は倫理的問題もあるが, 死体腎提供が極端に少ない現時点では, 末期腎不全患者に対する重要な治療法であり, 十分に情報を与えればより多くの症例を得ることが可能と考えられた.

A 66-year-old man with an abdominal aneurysm who developed renal failure and had blue toes after coronary angiography was transferred to our hospital, and cholesterol crystal embolism was diagnosed by renal and skin biopsies. After the initiation of low-density lipoprotein apheresis (LDL-A) following short-term corticosteroid therapy, in pain and the blueness in the toes disappeared rapidly, and inflammation decreased, but after the discontinuance of these therapies renal function and inflammation worsened again. Following the re-administration of corticosteroid, the inflammation disappeared and renal function gradually recovered. Although LDL-A is an effective treatment for the control of pain due to blue toes, its effect is additive. However, corticosteroid is a possible treatment for cholesterol crystal embolism, particularly in patients with severe inflammatory reaction, which suggests the possible participation of inflammatory or immunological factors in the progression of cholesterol crystal embolism.

Background Refractory ascites is recognized in patients with various conditions. Although intravenous reinjection of ascitic fluid after its filtration and concentration (IRA) is an effective method of treating this condition, many associated side-effects have been reported. We performed extracorporeal ultrafiltration of ascitic fluid (EUA) to demonstrate the efficacy and advantages of this method of treating refractory ascites. Methods EUA was performed in seven patients with hepatic cirrhosis (3 cases), lupus nephritis, diabetic nephropathy, and carcinomatous peritonitis (2 cases) for a total of 122 sessions. IRA was performed in three of these seven patients for a total of 12 sessions. Results The average volumes of ascitic fluid removed by EUA and IRA were 3.94+/-1.45 litres and 2.87+/-0.69 litres (mean+/-SD) respectively. Although chills and acute renal failure were recognized as complications of IRA in five and one sessions respectively, the only complication of EUA was severe intra-abdominal haemorrhage, which resolved spontaneously. In spite of rapid and massive removal of ascitic fluid (maximum 2.0 litres per 15 min), significant changes in blood pressure were not noted during EUA. In three patients (hepatic cirrhosis, lupus nephritis, and diabetic nephropathy), de novo production of ascitic fluid disappeared. In one patient with hepatic cirrhosis and chronic renal failure on haemodialysis, 67 sessions of EUA have been performed under stable conditions. Three patients (one case of hepatic cirrhosis and two cases of carcinomatous peritonitis) died of their primary diseases. Conclusions We conclude that EUA is a useful method for the treatment of massive refractory ascites.

A 50-year-old woman was referred to our hospital because of skin purpura, anemia, high fever, and acute renal insufficiency. Five years ago, she had been diagnosed as having ventricular septal defect without any complications. A blood culture drawn during the hospitalization grew Streptococcus viridans. She was diagnosed as having infective endocarditis-induced crescentic glomerulonephritis (GN) according to echocardiography and renal biopsy results. Although antibiotic treatment alone showed no apparent efficacy, after the initiation of plasmapheresis, the high fever and acute renal insufficiency were dramatically improved. After clinical stability was achieved, closure of the ventricular septal defect was performed. This result suggests that plasmapheresis may be beneficial in the treatment of infective endocarditis-induced crescentic GN. The possible mechanisms of this therapy are discussed. (Am J Kidney Dis 1998 Aug;32(2):309-13)

Propylthiouracil, which is used as an antithyroid drug, is associated with many side effects. Vasculitis is a rare complication of this drug. Recently, antineutrophil cytoplasmic antibodies (ANCA) have been described in association with vasculitic disorders, including rapidly progressive glomerulo-nephritis. We report a case of ANCA-positive rapidly progressive glomerulonephritis caused by propylthiouracil administration. Although renal function was improved by discontinuation of the drug and initiation of steroid therapy, assay results for ANCA to myeloperoxidase remained positive throughout the clinical period.

血液透析患者において, 糖尿病性ケトアシドーシス (DKA) を発症した稀な1例を経験したので報告する. 症例は46歳, 男性. 25歳時より糖尿病を指摘され, 1987年, インスリン依存性糖尿病 (IDDM) を診断されていた. 1994年8月, 糖尿病性腎症を原疾患として血液透析を導入. 1995年10月, 上気道炎症状の増悪に伴い経口摂取不能となったがインスリン投与を自己判断にて中止したところ, 血糖値1467mg/dlと著明な高血糖, アシドーシス, 高ケトン血症を呈し, DKAを発症した. 血清Na値は118mEq/lと低値を示した. 意識レベルはGlasgow Coma Scaleにて14点で, 意識障害は非常に軽度であった. インスリン大量投与では, 血糖の低下は認められず, 血液透析療法施行にて速やかに血糖値, アシドーシスの改善を認めた. 透析患者のDKAは, 高血糖および高尿素窒素濃度のため高浸透圧血症を認めるが, 浸透圧利尿をきたさないため脳細胞の脱水をきたしにくく, 意識障害が軽度であることが特徴と考えられた. また, インスリン投与の効果が著しく弱く, 血液透析療法以外では改善は困難と思われた.

Compared with acetate dialysate, bicarbonate dialysate has shown beneficial effects in reducing the morbidity associated with dialysis, but a small amount of acetate in bicarbonate dialysate may evoke hypotension or malaise. Acetate-free citrate hemodialysis (AFHD) may avoid these problems. In 44 hemodialysis patients bicarbonate hemodialysis (BHD) was conducted for three months, followed by a switch to AFHD for three months, and a further switch to bicarbonate hemodialysis (ReBHD). In BHD, AFHD and ReBHD, intra-dialysis hypotension and post-dialysis malaise were determined (hypotension: intra-dialysis systolic blood pressure (SBP) was expressed as a percentage of SBP at the start of hemodialysis, malaise was assessed by a self-reported 0 to 3 scale, 0: absence of malaise, 3: unbearable malaise). Compared with BHD, AFHD patients complained of less malaise but the intra-dialysis blood pressure change did not differ significantly (malaise: BHD 0.73 ± 0.76 vs. AFHD 0.32 ± 0.47, P 0.0001, end hemodialysis SBP: BHD 93.6 ± 8.9 vs. AFHD 93.8 ± 10.1, P = NS). After switching to ReBHD from AFHD, the malaise score increased (AFHD 0.32 ± 0.47 vs. ReBHD 0.77 ± 0.89, P 0.0001) and the intra-dialysis blood pressure dropped markedly (end hemodialysis SBP: AFHD 93.8 ± 10.1 vs. ReBHD 87.3 ± 10.5, P 0.0001). Malaise was very severe in five patients who could not continue ReBHD. After ten days under ReBHD, ReBHD was changed to AFHD again in all patients. Although the exact mechanisms are not known, AFHD may be preferable to BHD to prevent hemodialysis-induced hypotension and malaise.

A lack of deceased kidney donors in Japan has led to dependence on living donors in as many as 80% of cases. At the same time, indications for living-donor kidney donation have been expanding in terms of donor medical status as well as HLA matching and ABO compatibility, thus emphasizing the donor shortage. To facilitate final medical decision-making for living kidney donation, we attempted kidney biopsy in six donor candidates who had problems such as mild diabetes and slight proteinuria. The biopsy specimens showed various degrees of tissue injury ranging from partial glomerular sclerosis to arteriole hyalinization. On the basis of the biopsy findings, kidney donation was subsequently performed in three of the six cases with full informed consent, and not done in the remaining three cases. Longer-term studies will be needed to clarify the outcome in both the donors and recipients in these cases.

Erythropoietin deficiency is the major cause of anemia in hemodialysis patients. Although continuous erythropoietin receptor activator (CERA) has a long half-life and once-monthly administration is recommended, the optimal interval to achieve the greatest efficacy is not known. In 44 hemodialysis patients, CERA was administered at an interval of once every 2 weeks (Q2W) and 4 weeks (Q4W) consecutively and reticulocyte counts and hemoglobin levels were compared prospectively. In six patients with CERA 100 μg/4 weeks, CERA intervals were further changed to 1 week (Q1W). Mean reticulocyte counts were higher during Q2W than Q4W (41.5 ± 10.7 and 36.4 ± 8.8 × 103/μL, respectively, p