Hiroaki Muramoto

Correlation between serum carnitine levels and erythrocyte osmotic fragility in hemodialysis patients.

The relationship between serum carnitine levels and erythrocyte osmotic fragility was investigated in 26 chronic hemodialysis patients (10 males and 16 females, mean age: 57.3 +/- 13.5 years). Serum total-carnitine (TC), free-carnitine (FC) and acyl-carnitine (AC) levels were determined by a spectrophotometric method. Erythrocyte osmotic fragility was measured with a coil planet centrifuge. Serum TC levels were 39.9 +/- 13.4 mumol/l (mean +/- SD), FC levels were 21.8 +/- 7.8 mumol/l and AC levels were 18.0 +/- 9.6 mumol/l. The mean hemolysis end point (HEP) was 67.4 +/- 5.4 mOsM, the hemolysis maximum point (HMP) was 86.3 +/- 5.4 mOsM and the hemolysis start point (HSP) was 101.2 +/- 4.4 mOsM. Each hemolysis point in hemodialysis patients was elevated in comparison with the normal range. There were no significant differences in hemolysis points between a recombinant human erythropoietin (rhEPO)-treated group and nontreated group. HEP correlated with serum TC (r = -0.56, p < 0.01) and AC levels (r = -0.58, p < 0.01). HMP correlated with serum TC (r = -0.42, p < 0.05) and FC levels (r = -0.41, p < 0.05). Dose requirement of rhEPO maintaining target hematocrit correlated with serum TC (r = 0.54, p < 0.05) and FC levels (r = 0.50, p < 0.05). These data support that low serum carnitine levels accelerate erythrocyte osmotic fragility. Carnitine may contribute to the metabolism of erythrocyte membrane and have an impact on the efficacy of rhEPO in correcting renal anemia.

Telmisartan Treatment Decreases Visceral Fat Accumulation and Improves Serum Levels of Adiponectin and Vascular Inflammation Markers in Japanese Hypertensive Patients

Hypertension contributes to the occurrence and progression of cardiovascular diseases. The angiotensin II type 1 receptor blocker telmisartan is reported to activate the peroxisome proliferator–activated receptor γ and improve insulin sensitivity. We investigated the effects of telmisartan treatment on visceral fat, serum adiponectin and vascular inflammation markers in Japanese hypertensive patients. This was an open-label, non-controlled study. Twenty-eight essential hypertensive patients (22 men and 6 women; age 60.6±1.9 years; body mass index [BMI] 25.5±0.6 kg/m2) participated. Fat area was assessed with computerized tomography. All the subjects were started on telmisartan 40 mg/day, which was increased to 80 mg/day to achieve the blood pressure target of less than 130/80 mmHg. We assessed the visceral and subcutaneous fat areas, serum adiponectin levels, and vascular inflammation markers at baseline and 24 weeks of telmisartan treatment. There were significant reductions in visceral fat area (from 103.1±7.9 to 93.3±8.4 cm2, p<0.01) and pulse wave velocity (from 1,706±52 to 1,587±51 cm/s, p<0.01) at 24 weeks. In contrast, significant increases in serum high-density lipoprotein cholesterol (from 5.06±0.15 to 5.32±0.13 mmol/L, p<0.05) and adiponectin levels (from 8.27±0.76 to 9.13±0.81 μg/mL, p<0.05) were observed. Also, there were reductions in the interleukin-6 level (from 2.26±0.27 to 1.60±0.14 pg/mL, p<0.01). We also conducted these investigations in male subjects alone and similar findings were obtained for all of these parameters. In conclusion, telmisartan treatment was associated with an improvement of vascular inflammation, reductions in visceral fat and increases in serum adiponectin.

Treatment of Refractory Hyperparathyroidism in Patients on Hemodialysis by Intermittent Oral Administration of 1,25(OH)2Vitamin D3

Intermittent oral administration of high dose 1,25(OH)2vitamin D3 was conducted in 7 patients associated with treatment-resistant secondary hyperparathyroidism (2nd HPT) on hemodialysis (HD) therapy. Each patient had a long history of HD therapy (range: 101-181 months, 145 +/- 29 months). Although serum calcium levels were maintained under the upper limit of the normal range with the appropriate dose of 1 alpha(OH)vitamin D3 every day before the present therapy, 2nd HPT could not have been controlled. The dose of 2-3 micrograms of 1,25(OH)2vitamin D3 3 times a week could successfully suppress serum levels of parathyroid hormone (iPTH) in all 7 patients after 20-32 weeks. The vitamin was given in the evening before each HD session and the dose and frequency of administration were dependent of the serum calcium level in each patient. After 20 weeks the iPTH-C and iPTH-intact levels decreased significantly from 35.0 +/- 15.8 to 18.6 +/- 11.7 ng/ml and from 533.2 +/- 200.0 to 249.5 +/- 136.2 pg/ml, respectively. The frequency of harmful elevations of serum calcium levels was not significantly increased in comparison with that in the previous period of the study, because serum calcium levels were strictly monitored with frequent checks. In conclusion, we could safely obtain an effect similar to the intravenous administration of the vitamin through the intermittent administration of a high oral dose 1,25(OH)2vitamin D3 in the treatment of refractory 2nd HPT in patients on HD therapy.

Severe gastrointestinal complications of dialysis-related amyloidosis in two patients on long-term hemodialysis

Two patients undergoing long-term hemodialysis developed severe gastrointestinal complications due to dialysis-related amyloidosis (DRA). Case 1, a 68-year-old male on hemodialysis for 18 years developed marked gastric dilatation and severe paralytic ileus. Five years later he died of peritonitis. Autopsy showed extensive amyloid deposits in the muscle layers and blood vessels throughout the gastrointestinal tract. Case 2, a 56-year-old male on hemodialysis for 19 years, developed panperitonitis due to perforation of the sigmoid colon. The resected colon showed massive amyloid deposits in the muscle layers. In both cases, immunological studies revealed positive staining for antihuman beta2-microglobulin antibody. In long-term hemodialysis patients with gastrointestinal symptoms, gastrointestinal complications of DRA should be considered.

Absence of CD69 expression on peripheral eosinophils in episodic angioedema and eosinophilia.

A 45‐year‐old woman with episodic angioedema and eosinophilia is presented. CD69, which is one of the surface antigens of activated eosinophils, was not expressed on the peripheral eosinophils in this patient, in contrast to hypereosinophilic syndrome. This suggests that CD69, which is not dependent on eosinophil density, may be another useful activation marker of eosinophils to distinguish episodic angioedema and eosinophilia from hypereosinophilic syndrome.

Impaired Metabolism of Guanidinoacetic Acid in Uremia

In order to investigate the guanidinoacetic acid (GAA) metabolism in uremia, we have measured serum guanidino compounds in patients with chronic renal failure (CRF) in comparison with normal subjects, and the renal content of GAA and glycine amidinotransferase (GAT) activity in the kidney of experimental CRF rabbits. Serum concentrations of guanidinosuccinic acid (GSA) and methylguanidine (MG) in the patients with CRF were higher than those in the normal subjects, as well as serum urea nitrogen (BUN) and creatinine (Cr) levels. The serum GAA levels were however, significantly lower and showed a tendency to decrease inversely with the elevation of BUN in the patients with CRF under conservative therapy. On the contrary, in the patients under maintenance hemodialysis (MHD) therapy, the serum GAA level did not decrease in spite of the elevation of BUN. Four anephric patients under MHD therapy showed a level of serum GAA similar to the other MHD patients. In the CRF rabbits, the renal GAA content was significantly lower than in the sham-operated rabbits and showed an inverse correlation with BUN. Renal GAT activity was also significantly lower in the CRF rabbits, showing a positive correlation with serum GAA concentration and an inverse correlation with BUN. These results indicate that renal GAT activity decreases as the BUN level rises in the course of renal damage, resulting in lower concentration of serum GAA in the uremic state; in a more advanced stage of renal failure, the inability of the kidney to synthesize GAA may be compensated by other organ(s). Some dialyzable substances which might inhibit renal GAT activity may also be present.

Hints to the diagnosis of uromodulin kidney disease

Abstract Background Uromodulin kidney disease (UKD) is an inherited kidney disease caused by a uromodulin (UMOD) gene mutation. The UMOD gene encodes the Tamm–Horsfall protein (THP), which is the most abundant protein in healthy human urine. Because of its rarity, the incidence of UKD has not been fully elucidated. The purpose of the present study is to clarify the frequency of UKD among patients who underwent renal biopsy. Methods Immunostaining for THP was performed for patients <50 years of age with renal insufficiency and hyperuricemia without overt urinalysis abnormality from renal biopsy databases. Serum and urinary THP concentrations were evaluated in available individuals. Results Fifteen patients were selected for immunostaining from a total of 3787 patients. In three independent patients, abnormal THP accumulation in renal tubular cells was observed. A novel missense A247P UMOD mutation was detected in two of the three patients, including one having a typical family history of familial juvenile hyperuricemic nephropathy. Serum and urinary THP concentrations of all available patients with UMOD A247P mutation were significantly lower than those of controls. Conclusions In the present study, UKD was detected in <1 in 1000 subjects who underwent renal biopsies. However, in subjects meeting all of the above criteria, abnormal THP accumulation was detected in 20% (3/15), suggesting that renal biopsy with immunostaining for THP is a good tool for diagnosing UKD. Also, low serum THP concentration detected in the present subjects might be a good diagnostic marker or important in understanding the pathogenesis of UKD.

A case of autoimmune hepatitis combined with ventricular tachycardia.

症例は62歳の女性. 急性肝炎と心室性頻拍の診断にて入院. 各種自己抗体 (抗平滑筋抗体, 抗核抗体, 抗RNP抗体) と肝生検所見により自己免疫性肝炎と診断された. ステロイド投与により, 自己免疫性肝炎のみならず心室性頻拍も改善した. また, 急性期に認められていた123I-BMIPP心筋シンチグラフィーの前側壁および後下壁の集積低下は, 肝炎とともに改善した. 以上の臨床経過より, 本症例の心室性頻拍も自己免疫性機序により引き起こされた可能性が示唆された.不整脈を合併した自己免疫性肝炎の報告はなく, その両者の発症に自己免疫の関与が考えられ, 極めて興味深い症例と考えられた. また, 自己免疫性の心筋障害において123I-BMIPP心筋シンチグラフィーは, 潜在性の心筋障害をも反映し得る有用な検査と考えられた.

Measurement of Creatine and Phosphocreatine in Muscle Tissue Using HPLC

Most uremic subjects usually show muscle weakness and a decreased activity of daily living. Since the ability of the kidney to synthesize guanidinoacetic acid (GAA) decreases in uremia, the impaired metabolism of GAA may affect muscle energy metabolism, because creatine (CTN), an energy source of muscle, is a metabolite of GAA. CTN is produced from GAA in the liver, transfered to muscle tissue for energy storage, and stored as phospho-creatine (PC). In order to evaluate CTN metabolism in uremia, it is necessary to evaluate the muscle content of CTN and PC as well as that in blood. The usual method to measure CTN is an enzymatic spectrophotometric method and the sensitivity is not high enough to apply to muscular content. We investigated a more reliable method to measure CTN and PC in muscle tissue using HPLC.

Amelioration of Guanidinoacetic Acid Metabolism in Streptozotocin-Induced Diabetic Rats by Insulin Treatment

We have already reported1 that in diabetic patients serum guanidino- acefcic acid (GAA) is lower than in normal subjects in spite of the absence of renal dysfunction and the pancreatic glycine amidinotransferase (GAT) activity decreases in the experimental diabetic rats, although the effect of insulin on pancreatic GAT activity was yet under investigation. Funahashi et al.2 reported that in the perfusion experiments on isolated kidney, GAT activity was significantly diminished in diabetic rats, and was not restored to the control level by insulin administration. From this point of view, we measured serum concentration of GAA and the renal and pancreatic GAT activities in controls, streptozotocin (STZ)-induced diabetic, and insulin-treated diabetic rats.