Background: We aimed to examine associations among serum 25-hydroxyvitamin D (25OHD) levels, 1,25-dihyroxyvitamin D (1,25OHD) levels, vitamin D receptor (VDR) polymorphisms, and renal function based on estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.Methods: In a cross-sectional study of 410 patients, chronic kidney disease (CKD) stage assessed by eGFR was compared with 25OHD, 1,25OHD, and VDR FokI (rs10735810) polymorphisms by an ordered logistic regression model adjusted for the following confounders: disease duration, calendar month, use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers or statins, and serum calcium, phosphate, and intact parathyroid hormone levels.Results: 1,25OHD levels, rather than 25OHD levels, showed seasonal oscillations; peak levels were seen from May to October and the lowest levels were seen from December to February. These findings were evident in patients with CKD stage 3 similar to 5 but not stage 1 similar to 2. eGFR was in direct proportion to both 25OHD and 1,25OHD levels (P<0.0001), but it had stronger linearity with 1,25OHD (r = 0.73) than 25OHD (r = 0.22) levels. Using multivariate analysis, 1,25OHD levels (P<0.001), but not 25OHD levels, were negatively associated with CKD stage. Although FokI polymorphisms by themselves showed no significant associations with CKD stage, a significant interaction between 1,25OHD and FokITT was observed (P = 0.008). The positive association between 1,25OHD and eGFR was steeper in Fok/CT and CC polymorphisms (r = 0.74) than Fok/TT polymorphisms (r = 0.65).Conclusions: These results suggest that higher 1,25OHD levels may be associated with better CKD stages in patients with type 2 diabetes and that this association was modified by FokI polymorphisms.

BACKGROUND:We investigated the influence of cinacalcet on serum Ca and P in hemodialyzed patients with or without a high PTH level, according to K/DOQI guideline, to control serum Ca and P levels.METHODS:We recruited 130 patients in this prospective cohort study and classified them into Group A (iPTH > 300 pg/ml), Group B (iPTH = 181 - 300 pg/ml), and Group C (iPTH ≤ 180 pg/ml). After 24 weeks on cinacalcet, serum Ca, P and iPTH were measured.RESULTS:The achievement rate of the target iPTH level in JSDT guideline was significantly higher in Group B compared with Group A. The achievement rate of serum Ca and P target levels in the Japanese Society for Dialysis Therapy (JSDT) guideline was higher in Group C. In Group A and Group C, the simultaneous achievement rates (Ca, P, and iPTH) in KDOQI guideline increased after treatment with cinacalcet (p < 0.01). There was no difference in the reduction of Ca and P among the groups, while the iPTH reduction was significantly lower in groups B and C compared with that in A.CONCLUSION:Administration of cinacalcet to patients with or without high PTH levels, according to the K/DOQI guideline, facilitates the control of Ca and P levels.

Background Hypertension is a leading cause of cardiovascular (CV) disease in the general population. Although hypertension is very common in maintenance hemodialysis (HD) patients, adequate blood pressure (BP) values and measurement timing have not been defined. Methods A total of 49 hypertensive HD patients were recruited. Average age was 63 ± 11 years, and duration of dialysis therapy was 6.2 ± 4.2 years. Dialysis unit BPs and various types of home BPs were separately measured, and which BPs were the most critical markers in evaluating the effect of hypertension on left ventricular hypertrophy and CV events was investigated. Results Predialysis systolic BPs were not correlated with any home BPs. Left ventricular mass index (LVMI) had a significant positive correlation with home BPs, especially morning systolic BPs on HD days ( P < 0.01) and non-HD days ( P < 0.05), on univariate and multivariate analysis. In contrast, predialysis BPs did not correlate with LVMI. During the follow-up period (47 ± 18 months), it was demonstrated that diabetes and home BPs, especially systolic BPs on the morning of HD days, were significant predictors of CV events on multivariate Cox regression analysis. A 10 mmHg increase in BP had a significantly elevated relative risk for CV events. Conclusions Home BP, especially systolic BPs in the morning on HD days, can provide pivotal information for management of HD patients.

Peritoneal dialysis (PD) is recommended as the first line of treatment for end-stage renal disease patients in terms of integrated renal replacement therapy (RRT), since PD can preserve residual renal function and fluid homeostasis. However, few analyses have been studied regarding the risk factors for death among patients, including cases transferred from PD. This study retrospectively examined 98 patients (63-years-old, male/female ratio: 59/39, non-DM/DM: 57/41) who started PD for their first RRT between Jan. 1999 and Dec. 2003 in a single center. The risk factors for patient death were evaluated During the average observational period of 28 months, 35 cases (35.7%) were withdrawn from PD, and among these, 24 patients (24.5%) died (including 7 cases after transferal to HD). The leading causes of death were cardiovascular disease (CVD) and infectious disease in 8, respectively (33.3% each) and no cases were found who developed encapsulating peritoneal sclerosis. As compared to living patients, the group of patients who died was significantly older and had a high frequency of CVD history. Their serum albumin (Alb) level was significantly lower, whereas the D/P (dialysate/plasma) creatinine (Creat) ratio as well as diastolic blood pressure was higher. In the Cox Hazard model, D/P Creat ratio >0.65 (category high/high average), DM nephropathy and history of CVD were independent predictors of death (hazard ratio (HR): 1.78, 95% CI: 1.10-2.94, HR: 1.81, 95% CI: 1.11-3.11, HR: 2.23, 95% CI: 1.37-3.73). These results suggest that DM nephropathy, history of CVD and higher peritoneal permeability at PD initiation are independent risk factors of death in patients starting PD for their first RRT. Hence, a strict follow-up is needed in these patients.

長期CAPD患者の腹膜生検によるperitoneal mesothelial cell layer (PMCL) の有無と生検時より2か月以内に施行したperitoneal equilibration test (PET) およびcharge selectivity index (CSI) について検討した. 生検を実施した40例を対象とし, 組織所見にしたがい, 正常群9例, PF (M+) 群: 腹膜線維症でPMCLが存在する群14例, PF (M-) 群: PMCLがない群11例, PS群: 腹膜硬化症群6例に分類した. PETに準じて, 2.5%透析液2Lを4時間腹腔内に貯留し中間点で採血し, 血中 (P) と排液中 (D) のglutamine (Gln), glutamate (Glu), lysine (Lys), creatinine (Cr) を測定しD/P比を求め, さらに, D/D0 glucose ratio (D/D0) およびCSI {CSI (Glu/Gln): GluのD/P比÷GlnのD/P比, CSI (Lys/Gln): LysのD/P比÷Gln D/P比} を算出した. 透析期間は, 正常群6.7±6.6, PF (M+) 群23.8±21.9, PF (M-) 群40.9±22.8, PS群95.3±23.7 (月) で, 正常とPF (M+) 群およびPF (M-) とPS群に有意差を認めた. D/P (Cr) は, 正常群0.537±0.138, PF (M+) 群0.595±0.116, PF (M-) 群0.650±0.084, PS群0.825±0.082. D/D0では, 正常群0.456±0.106, PF (M+) 群0.417±0.074, PF (M-) 群0.348±0.052, PS群0.251±0.051. CSI (Glu/Gln) では, 正常群0.571±0.112, PF (M+) 群0.529±0.161, PF (M-) 群0.765±0.084, PS群0.957±0.069. CSI (Lys/Gln) では, 正常群0.813±0.070, PF (M+) 群0.814±0.069, PF (M-) 群0.886±0.054, PS群0.981±0.048で, PETおよびCSIともにPF (M+) とPF (M-) 群およびPF (M-) とPS群に有意差があり, 正常群とPF (M+) 群には有意な差はなかった. PMCLはCSI (Glu/Gln) が0.633以下で全例に存在し, 0.735以上では存在せず, D/D0が0.447以上で全例に存在し, 0.330以下では存在しなかった. PMCLの有無は, PETおよびCSIに影響することが示された.

我々は維持透析の経過中に脊髄硬膜外血腫を合併した一例を報告する. 症例は63歳男性で, 糖尿病性腎症にて週3回の血液透析を施行していた. 10日ほど前より肩こり, 後頸部痛が出現しており狭心症の疑いにて入院となった. 入院後後頸部の激痛を訴え, 急速に四肢麻痺が出現した. 知覚はC4以下で全知覚消失となった. このためMRIを施行したところ頸髄硬膜外にC2-C6にかけてT1 low intensity, T2 iso~high intensityのmassを認め頸髄の硬膜外血腫と診断し完全四肢麻痺出現後30時間で血腫除去および椎弓形成手術を施行した. 術後上肢に神経症状の改善をみたが, それ以上の改善は認めず死亡した. 透析患者の脊髄硬膜外血腫は稀であり, また脳血管障害の予後は良くないが, 症状の改善が見込まれるのであれば診断がつき次第できるだけ早く手術を施行すべきであると思われた.

腹膜機能の指標として, 分子量が同等で等電点の異なる中性のglutamine (Gln) と酸性のglutamate (Glu) および塩基性のlysine (Lys) を用いた腹膜のcharge selectivity index (CSI) と物質透過性に関するthree pore modelの理論より開発された腹膜機能検査法であるpersonal dialysis capacity (PDC) 検査の諸因子と比較検討した. 検討実施前1年以上腹膜炎の既往がないCAPD38例 (男性24例, 女性14例, 平均年齢は57.8±11.4歳, 平均CAPD期間は46.9±33.2月) を対象とした.2.5%透析液2Lを4時間腹腔内に貯留し中間点採血し, 血中 (P) と排液 (D) のGln, Glu, Lysを測定しD/P比を求め, CSI【CSI (Glu, Lys): (Glu, Lys) D/P比÷Gln D/P比】を算出し, 同時に, PDC検査を施行し, Area, Plasma loss, AbsorptionおよびAreaを構成するcell pore, small pore, large poreの面積について検討した. その結果, CSI (Glu, Lys) ともに, Area, small poreおよびcell poreと良い正相関を示し, Plasma loss, Absorption, large poreとは相関を認めなかった. 腹膜のcharge selectivityの減少は腹膜の透析面積の増加を意味するが, この理由としてsmall poreおよびcell poreの面積の増加に依存している可能性が示唆された.

【目的】 腹膜透析を長期に継続した時に, 腹膜の機能変化とパラメータについては明確なものは未だ確立されていない. 今回は, 従来より検討されているperitoneal equilibration test (PET) の諸因子だけではなく, 新たに示された腹膜機能検査の排液中のIL-6値およびcharge selectivity index (CSI) についても, 平均18か月間の経時的変化を測定した.【対象および方法】 腹膜透析患者30例を対象とし, PET標準法に準じて, 2.5%透析液2Lを4時間腹腔内に貯留し中間点採血し, 排液中のIL-6値および血中 (P) と排液中 (D) のglutamate (Glu), glutamine (Gln), lysine (Lys), creatinine (Cr), β2-microglobulin (β2-MG), albumin (Alb) を測定し, Cr, β2-MG, AlbのD/P比を求め, さらにD/D0 glucose比およびCSI【CSI (Glu): Glu D/P比÷Gln D/P比, CSI (Lys): Lys D/P比÷Gln D/P比】 を算出し, 平均観察期間18か月の経時的変化を求めた.【結果】 (1) 血清のCr値, β2-MG値およびAlb値に変化はなく, また, β2-MG, AlbのD/P比にも変化はなかった. (2) CrのD/P比, 排液中のIL-6値, CSI (Glu) およびCSI (Lys) は有意に上昇し, D/D0 glucose比は有意に下降した. (3) CrのD/P比, D/D0 glucose比,排液中のIL-6値, CSI (Glu) およびCSI (Lys) の変化率では, 排液中のIL-6値が最も鋭敏に変化した.【結論】 CrのD/P比, 排液中のIL-6値, CSI (Glu), CSI (Lys) およびD/D0 glucose比は経時的な変化を示した. 以上の指標のなかでも排液中のIL-6値が最も鋭敏に腹膜機能の劣化を反映するものと考えられた.

腹膜機能検査の一つとして期待される排液中のIL-6値とperitoneal equilibration testの諸因子との関係について検討した. 1年以上腹膜炎の既往のない腹膜透析患者40例を対象とした. 2.5%透析液2Lを4時間腹腔内に貯留し, 中間点で採血した. 血中 (P) と排液中 (D) のIL-6, Cr, β2-MG, Albを測定した. Cr, β2-MG, AlbのD/P比を求め, さらにD/D0 glucose比を算出し, 排液中のIL-6値との関連を比較した. (1) 排液中のIL-6値は54.43±38.02 pg/mlであった. (2) 排液中のIL-6値と各指標との相関は, D/D0 glucose比ではR=-0.803 (p.<0.001), CrのD/P比ではR=0.773 (p.<0.001), β2-MGのD/P比ではR=0.594 (p.<0.01), AlbのD/P比ではR=0.468 (p.<0.05) と, とくにD/D0 glucose比との間に良い相関を示した. (3) CAPD施行期間と排液中のIL-6値では, R=0.797 (p.<0.001) と良い相関が認められた. 4時間停滞の腹膜透析排液中のIL-6値は新しい腹膜機能の指標となりうる可能性が示唆された.

今回, 我々はCrow-Fukase症候群 (CFS) の難治性胸腹水, 浮腫に対し腹水濾過濃縮再静注療法が奏功した1例を経験したので報告する.症例: 71歳男性. 主訴: 胸腹水, 浮腫, 腎機能障害. 現病歴: 1989年に色素沈着, 浮腫, 女性化乳房, 多発性神経炎を認めCrow-Fukase症候群と診断. 96年10月より下肢の浮腫, 胸腹水の増加による呼吸困難, 腹部膨満感, 腎機能障害の進行を認め12月車椅子で入院. 入院時現症: 全身に茶褐色の色素沈着, 皮膚硬化, 浮腫, 女性化乳房, 左下肺で呼吸音減弱, 腹部膨満, 四肢の深部腱反射消失, 振動覚低下を認めた. 検査所見では貧血, 低蛋白血症, 腎機能低下, 内分泌異常を認めた. 画像上胸腹水, 心嚢水を認めたがM蛋白は認めず, 血液, 尿の免疫電気泳動でも異常は認めず骨髄は軽度の低形成のみで形質細胞の増生は認めず. 入院後経過: 薬物療法では胸腹水は難治性であり, 対症的に腹水を穿刺排液した. 低蛋白血症の進行のため, 腹水濾過濃縮再静注療法を併用した. 外来通院可能とするためテンコフカテーテル挿入し, CAPDシステムを使用し簡単に腹水採取でき, それを濾過濃縮再静注することで腹水コントロール可能となり退院. 同療法開始後次第に胸水, 心嚢水もコントロールされ約10日間隔で車椅子で外来通院中. 本治療法は対症療法ではあるものの安全にしかも容易に行えることから今後このような症例に式みられる-治療法であると考えられた.

CAPD症例におけるアミノ酸の腹膜透析動態は, 不明な点が多い. 今回は, 血液中と排液中の中性アミノ酸, 特にFischer比について検討した. 外来管理中で, 観察期間中に腹膜炎の経験のない糖尿病性腎不全 (DM) 6例, および非DM 9例の合計15例 (男14/女1, 年齢49±9歳) を対象とした. 2.5%ダイアニール®2lを, 注入終了より排液開始まで4時間正確に腹腔内に貯留し, 血中および排液中のアミノ酸を測定し, Fischer比 (Val+Leu+Ile/Phe+Tyr) を算出した. 1) CAPD 15例の中性アミノ酸の分子量 (log MW) とD/P比の平均値は, 良い相関を示した (Y=1-0.137X, R=-0.986). 2) Fischer比は血中2.72, 排液中3.09で, 排液中において高値を示した (p<0.01). 3) DM例と非DM例の血中および排液中のFischer比には有意差はなかった.以上より, CAPD症例では, 中性アミノ酸のD/P比は, 分子量の大きさに従い, アミノ酸Fischer比は, 血中に比較して排液中において有意に高値を示した.