Teruhiko Maeba

Spherical Carbon Adsorbent (AST-120) Protects Deterioration of Renal Function in Chronic Kidney Disease Rats through Inhibition of Reactive Oxygen Species Production from Mitochondria and Reduction of Serum Lipid Peroxidation

Background/Aim: An imbalance in renal redox status contributes to progression of renal dysfunction. We investigated the effects of an oral charcoal adsorbent (AST-120) on renal redox status, superoxide production from renal mitochondria, and serum lipid peroxidation using chronic kidney disease (CKD) model rats. Methods: CKD was induced by 5/6 nephrectomy. CKD rats were divided into 2 groups: controls, and those treated with AST-120 for 20 weeks. We evaluated: (1) renal redox status by in vivo low-frequency electron spin resonance imaging (EPRI); (2) renal superoxide scavenging activity (SSA); (3) superoxide production from renal mitochondria; (4) immunostaining for Cu-Zn superoxide dismutase (SOD), and (5) oxidative stress markers including LDL-negative charge (LDL-CMF), serum lipid peroxide (LPO) and urinary hexanoyl-lysine (HEL). The effect of indoxyl sulfate, a uremic toxin, on mitochondrial superoxide production was also investigated. Results: AST-120 treatment improved renal function, renal SSA, renal mitochondrial superoxide production, renal SOD expression, renal redox status by EPRI, and oxidative stress profiles by LDL-CMF, LPO and urinary HEL. Addition of indoxyl sulfate increased mitochondrial superoxide production and AST-120 also decreased this. Conclusions: Improvements in the redox status and lipid peroxidation induced by AST-120 may delay the progression of CKD.

D-Lactate Metabolism in Patients with Chronic Renal Failure Undergoing CAPD

To clarify the D-lactate metabolism in patients with chronic renal failure undergoing CAPD, plasma levels, loaded doses and urinary excretion of D-lactate were measured. In addition, D-2-hydroxy acid dehydrogenase activities in resected and autopsied specimens were measured. The daily loaded dose of D-lactate by CAPD was 88.9 +/- 1.29 mmol and urinary excretion was negligible. There was no tendency for the plasma D-lactate to accumulate. The enzyme activity was detected in the liver, kidney and pancreas tissues both in the resected and autopsied specimens. The above findings indicate that the loaded D-lactate is catabolized in patients with chronic renal failure undergoing CAPD, and D-2-hydroxy acid dehydrogenase is responsible for the metabolism of D-lactate in humans.

Carpal Tunnel Syndrome in Patients Undergoing CAPD: A Collaborative Study in 143 Centers

Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) who developed carpal tunnel syndrome (CTS) were retrospectively studied in 143 centers in Japan. Among the total 5,050 patients undergoing CAPD between 1980 and 1993 only 7 patients (0.14%) given CAPD developed CTS. Five of these 7 patients treated solely with CAPD developed CTS 12-108 months after starting CAPD. The remaining 2 patients who were initially treated with HD for 7-9 years and then switched to CAPD developed this complication 9 years after starting CAPD. All 7 patients were women, ranging in age from 32 to 70 (average 52) years. We detected the presence of amyloid deposits in 2 of 5 specimens and beta 2-microglobulin in 2 of 4 specimens from these patients. It was concluded that CAPD minimizes the emergence of CTS although constant surveillance is necessary to detect CTS in patients during CAPD.

Role of nitric oxide synthase activity in experimental ischemic acute renal failure in rats

To determine the role of nitric oxide (NO) in acute renal failure (ARF), we have studied the time course change activities to activity of nitric oxide synthase (NOS) isoform activities, both calcium dependent and independent NOS, in experimental ischemic ARF. We have also analyzed change activities to activity of the NOS activities in both renal cortex and medulla. Male SD rats (n = 5) were inducted to ARF by ischemia-reperfusion injury and divided into the following groups; Control group (sham operation), Day 0 group, (measurement performed on that day of operation), Day 1 group, (measurement performed one day after induction of ARF), Day 3 group and Day 7 group. Measurement of NOS activity was based on the following principles; NO is synthesized from arginine by nitric oxide synthase (NOS) and NO is converted to NO2−/NO3− (NOx) by oxidation. Detection of the final metabolite of NO, NOx was done using flow injection method (Griess reaction). The results were, (1) calcium dependent NOS activity in the cortex and medulla decreased, however it increased in the recovery period in the renal cortex (Cortex; Control, 0.941 ± 0.765, D0, 0.382 ± 0.271, D1, 0.118 ± 0.353, D3, 2.030 ± 0.235, D7, 3.588 ± 2.706, Medulla; Control, 1.469 ± 0.531, D0, 0.766 ± 0.156, D1, 0.828 ± 0.187, D3, 2.078 ± 0.094, D7, 1.289 ± 0.313 μmol NOx produced/mg protein/30 min). (2) On the other hand, iNOS activity increased in the early phase of ARF, both in the cortex and medulla, but returned to control values during the recovery phase in cortex and was maintained at higher levels in the medulla (Cortex; Control, 0.333 ± 0.250, D0, 0.583 ± 0.428, D1, 1.167 ± 0.262, D3, 0.250 ± 0.077, D7, 0.452 ± 0.292, Medulla; Control, 0.139 ± 0.169, D0, 0.279 ± 0.070, D1, 1.140 ± 0.226, D3, 0.452 ± 0.048, D7, 0.625 ± 0.048 μmol NOx produced/mg protein/30 min). These findings suggest that the role of NOS in ARF are different for the different NOS isoforms and have anatomic heterogeneity.

Combined therapy with peritoneal dialysis and hemodialysis: a multicenter retrospective observational cohort study in Japan.

Background/Aims: Combining peritoneal dialysis (PD) and hemodialysis (HD) has been common treatment option in Japan. Methods: In this retrospective, multicenter, observational study, the clinical characteristics and outcomes of 104 patients (57 w 11 years, males 72%) who had switched from PD alone to combined therapy with PD and HD were studied. Clinical parameters were measured at baseline and after 3 months of combined therapy. Results: At baseline, urine volume, dialysate-to-plasma ratio of creatinine (D/P Cr), and total Kt/V were 150 ml/day (range: 0-2,000 ml/day), 0.67 w 0.11, and 1.8 w 0.4, respectively. During the first 3 months of combined therapy, body weight, urine volume, serum creatinine level, and D/P Cr decreased, whereas hemoglobin levels increased. Conclusions: In patients where PD does not result in acceptable outcomes, combined therapy with PD and HD may have potential benefits in terms of dialysis adequacy and hydration status. Video Journal Club “Cappuccino with Claudio Ronco” at http://www.karger.com/?doi=368389 i 2014 S. Karger AG, Basel

Imbalance between production and scavenging of hydroxyl radicals in patients maintained on hemodialysis

BackgroundReactive oxygen species are as being related to the pathophysiology of endstage renal disease (ESRD). We measured the plasma hydroxyl radical (·OH)-producing ability and ·OH-scavenging activity in patients with ESRD to clarify the pathophysiological states involved.MethodsWe used electron spin resonance to measure plasma N-t-butyl-α-phenylnitron radical spin adduct (pPBN rsa) as ·OH-producing ability and plasma 3,3,5,5-tetramethyl-1-pyrroline-N-oxide radical spin adduct (pM4PO rsa) as ·OH-scavenging activity. Oxidative injuries were evaluated by determining oxidised low-density lipoprotein (Ox-LDL).ResultsThe pPBN rsa of the ESRD patients was lower than that of the controls (1.83 vs 2.94 µmol/g protein). The pM4PO rsa of the ESRD patients was higher than that of the controls (3.85 vs 3.15 mmol l-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl hydrogen phosphate] potassium salt (EPC-K1)/g protein). The pPBN rsa and pM4PO rsa were correlated, both in the ESRD patients and in the controls (r = 0.47 and r = 0.53). Ox-LDL was correlated with hemodialysis (HD) duration (r = 0.49) and was negatively correlated with pPBN rsa (r = −0.54), which indicates that oxidative stress was increased as HD therapy was prolonged and suppressed pPBN rsa.ConclusionsThere was an imbalance between ·OH-producing ability and ·OH-scavenging activity, in the ESRD patients, and this may be responsible for compromising the health of ESRD patients.

Alteration of energy production by the heart in CRF patients undergoing peritoneal dialysis

Cardiovascular disease is commonly observed in patients with chronic renal failure and this is a leading cause of death in patients with end-stage renal disease undergoing maintenance dialysis. Myocardial energy production is a very crucial aspect of cardiac function. Therefore, to evaluate energy metabolism of myocardial muscle in peritoneal dialysis (PD) patients, we carried out the following study using Magnetic resonance spectroscopy (MRS).

Optimal route of administration and dosage of recombinant human erythropoietin in CAPD patients.

CAPD患者に対するrecombinant human erythropoietin (EPO) の皮下注投与は実用的な投与経路として注目されている. 今回我々は, CAPD患者に対しEPOの皮下注投与を行い, その臨床効果, 投与量, 投与間隔, 安全性について検討し, 同時に静注投与との比較も行った.対象は安定したCAPD患者16名 (男性9名, 女性7名, 平均年齢45歳) で, 4名は静注投与で開始し維持投与の段階で皮下注投与に変更, 他の12名は皮下注投与のみを行った.週1回の静注投与で維持されている3名を同量の皮下注投与に変更した結果, 静注投与と同量または半量でヘモグロビン (Hb) 濃度を長期に維持することができた. 週2回の6,000U静注と週1回の6,000U皮下注投与で初期投与10週までの週当りのHb上昇度を検討した結果, 皮下注投与は静注投与と同様の効果が認められた. 皮下注の初期投与 (12週まで) として4群に分けて検討した結果, 週当たりのHb上昇度は週1回6,000U (n=5) で0.30g/dl, 2週に1回9,000U (n=3) で0.22g/dl, 2週に1回6,000U (n=3) で0.18g/dl, 4週に1回9,000U (n=1) で0.08g/dlと, 2週に1回の皮下注投与で十分な効果が認められた. 皮下注の維持投与は平均27.5週観察した結果, 16名中14名が2週に1回1,500-9,000U, 他は1名が週1回6,000U, もう1名が4週に1回9,000Uで目標のHb濃度 (9g/dl) を長期に維持することができた. 皮下注投与によるCAPD患者のEPO維持量は静注投与によるHD患者に比べ少ない傾向が認められた.CAPD患者に対するEPO皮下注投与は静注投与同様に安全な投与経路であり, 2週に1回の投与で十分な効果が得られ, その結果通院回数を減らすことができた.