里中 弘志

A 79-year-old male patient with type 2 diabetic nephropathy and hypertension was admitted to our hospital because of acute kidney injury with significantly elevated serum creatinine (8.12 mg/dL) and urinary β2-microglobulin (β2MG, 31,748 μg/L) levels. α-Glucosidase inhibitor (α-GI) miglitol, started two weeks prior to presentation, was discontinued because drug-induced acute interstitial nephritis (AIN) was suspected. Renal biopsy revealed AIN and diabetic nephropathy. The drug-induced lymphocyte stimulation test for miglitol was also positive. After the discontinuation of miglitol, the urinary β2MG levels decreased to the normal range. This case raises the possibility that α-GI miglitol can worsen the renal function in patients with underlying renal dysfunction.

高血圧治療ガイドラインでは,診察室血圧(OBP)は1-2分間隔で測定を繰り返し,安定した2回の測定値の平均で評価することとされているが,数多い高血圧患者の実地診療において測定を繰り返すことは難しく,1回の測定で評価される場合も多い.本研究では診察室血圧が高値を呈する高血圧患者において,深呼吸後に測定を繰り返すことによる血圧の変化を検討した.外来を受診した高血圧患者で,診察室の収縮期血圧(SBP)140mmHg以上を呈した160名を対象とした.1回目の測定の後,深呼吸を繰り返し1-2分後に2回目の測定を行い,血圧の変化に関係する因子を検討した.1回目のOBPは147/84mmHgであったが,2回目は136/82mmHgと平均11/2mmHg低下し,69%が非高血圧となった.SBPが10mmHg以上低下したR群(91名)と10mmHg未満のN群(69名)の比較では,R群の方が血清クレアチニン(sCr)が低く(1.03 vs 1.36mg/dL,p=0.018)血中ヘモグロビン(Hb)が高値(13.9 vs 13.1g/dL,p=0.012)で,SBPの低下とHbの間には負の相関が認められた(r=-0.157,p=0.046).SBPが140未満に低下した110例ではしなかった50例に比べ,家庭血圧で夜のSBPが低く,HbやeGFR(62.3 vs 52.1mL/分/1.73m2,p=0.021)が高値で,sCrやアルブミン尿(124 vs 425mg/gCr,p=0.025)が低値であった.外来加療中の高血圧患者で診察室血圧が高値である場合,特に腎機能低下や蛋白尿がなければ,多くは深呼吸を繰り返すことにより正常化するため,治療方針を決める際に考慮するべきであると思われる.(著者抄録)

In minimal change nephrotic syndrome, podocyte vesicle transport is enhanced. Adenomatous polyposis coli (APC) anchors microtubules to cell membranes and plays an important role in vesicle transport. To clarify the role of APC in vesicle transport in podocytes, nephrotic syndrome was induced by puromycin amino nucleoside (PAN) injection in mice expressing APC1638T lacking the C-terminal of microtubule-binding site (APC1638T mouse); this was examined in renal tissue changes. The kidney size and glomerular area of APC1638T mice were reduced (p = 0.014); however, the number of podocytes was same between wild-type (WT) mice and APC1638T mice. The ultrastructure of podocyte foot process was normal by electron microscopy. When nephrotic syndrome was induced, the kidneys of WT+PAN mice became swollen with many hyaline casts, whereas these changes were inhibited in the kidneys of APC1638T+PAN mice. Electron microscopy showed foot process effacement in both groups; however, APC1638T+PAN mice had fewer vesicles in the basal area of podocytes than WT+PAN mice. Cytoplasmic dynein-1, a motor protein for vesicle transport, and α-tubulin were significantly reduced in APC1638T+PAN mice associated with suppressed urinary albumin excretion compared to WT+PAN mice. In conclusion, APC1638T mice showed reduced albuminuria associated with suppressed podocyte vesicle transport when minimal change nephrotic syndrome was induced.

<title>Abstract</title><sec> <title>Background</title> Though treatment of anemia in chronic kidney disease (CKD) patients has been improved remarkably by erythropoiesis-stimulating agents (ESA), hypo-responsiveness to ESA poses a persistent problem in a subgroup of CKD patients, especially those on dialysis, with deteriorated mortality or cardiovascular risks. Pathomechanism of this condition including cardiovascular implications has not been sufficiently investigated. </sec><sec> <title>Methods</title> Clinical parameters of 101 chronic hemodialysis patients which included those hospitalized in our university hospital were examined cross-sectionally. As a marker estimating ESA hypo-responsiveness, erythropoietin resistance index (ERI) was calculated. Numbers of circulating endothelial progenitor cells (EPC) were measured by flow cytometry. Associations among values were analyzed by methods including multiple linear regression. </sec><sec> <title>Results</title> Majority (93%) of the subjects were hospitalized patients with various comorbidities. ERI (18.4 [7.2–33.0] IU/week/kg/g/dL) and ESA dose (161.6 [75.0–320.9] IU/week/kg) of all the subjects were relatively high. Factors negatively correlated with EPC included age, HD vintage, CRP, pulse rate, ESA dose and ERI, while male sex and systolic blood pressure were positively correlated. By multiple linear regression analysis, age, sex and ERI (standardized coefficient beta − 0.202, <italic>p</italic> = 0.039) remained as the independently predicting factors of EPC (log CD133/Flk1+ EPC). Darbepoetin alpha was used in 65 patients, especially predominant when requiring higher ESA doses, but by correlation or multivariable analyses, this did not substantially modify the negative association between ERI and EPC. </sec><sec> <title>Conclusions</title> ERI was independently associated with EPC paucity in a cohort with various comorbidities. This may suggest a link which connects ESA hypo-responsiveness to compromised cardiovascular prognosis of dialysis patients. </sec>