Satoshi Kurihara

Is the volume of the parathyroid gland a predictor of Maxacalcitol response in advanced secondary hyperparathyroidism

Abstract:  We evaluated the relationship between the volume of parathyroid glands estimated by ultrasonography (US) and response of 22‐oxa calcitriol (Maxacalcitol, OCT) in patients with secondary hyperparathyroidism (2HPT) to evaluate whether the volume can be a predictor of the OCT response. Eleven institutes participated in this study. Ninety‐four patients with advanced 2HPT were enrolled. The volume of the parathyroid glands were estimated by US before and 6 months after OCT treatment. The response of OCT treatment was classified into three groups (Group A: i‐PTH < 300 pg/mL; Group B: 300 pg/mL ≤ i‐PTH < 500 pg/mL; Group C: i‐PTH ≥ 500 pg/mL). Forty‐eight patients were in Group A, 28 patients in Group B, and 18 patients in Group C. The PTH levels at the beginning and 6 months were 458.3–199.1 pg/mL (P < 0.0001) in Group A, 524.6–403.2 pg/mL (P = 0.007) in Group B and 736.7–613.6 pg/mL (ns) in Group C, respectively. The volume of the largest gland in Group B was significantly larger than that in Group A (96.2 vs. 343.2 mm3: P < 0.001). Clinical factors affecting response of OCT was evaluated by logistic regression analysis and only the volume of the largest gland was a significant factor. In the patients whose volume was less than 300 mm3, the OCT response was significantly effective. We conclude that the glandular volume of the largest parathyroid gland estimated by US can be a useful factor to predict the OCT response in patients with moderate or severe renal HPT.

Removal of digoxin by column for specific adsorption of β2‐microglobulin: A potential use for digoxin intoxication

A β2‐microglobulin adsorption column used for the treatment of dialysis‐related amyloidosis removes serum β2‐microglobulin by recognition of lipophilic residue in the protein. No data are available for the adsorption of the highly lipophilic drug digoxin.

Survey of the Effects of a Column for Adsorption of β2-Microglobulin in Patients With Dialysis-Related Amyloidosis in Japan

Dialysis‐related amyloidosis is a serious complication of long‐term hemodialysis. Its pathogenic mechanism involves accumulation of β2‐microglobulin in the blood, which then forms amyloid fibrils and is deposited in tissues, leading to inflammation and activation of osteoclasts. Lixelle, a direct hemoperfusion column for adsorption of β2‐microglobulin, has been available since 1996 to treat dialysis‐related amyloidosis in Japan. However, previous studies showing the therapeutic efficacy of Lixelle were conducted in small numbers of patients with specific dialysis methods. Here, we report the results of a nationwide questionnaire survey on the therapeutic effects of Lixelle. Questionnaires to patients and their attending physicians on changes in symptoms of dialysis‐related amyloidosis by Lixelle treatment were sent to 928 institutions that had used Lixelle, and fully completed questionnaires were returned from 345 patients at 138 institutions. The patients included 161 males and 184 females 62.9 ± 7.7 years age, who had undergone dialysis for 25.9 ± 6.2 years and Lixelle treatment for 3.5 ± 2.7 years. Based on self‐evaluation by patients, worsening of symptoms was inhibited in 84.9–96.5% of patients. Of the patients, 91.3% felt that worsening of their overall symptoms had been inhibited, while attending physicians evaluated the treatment as effective or partially effective for 72.8% of patients. Our survey showed that Lixelle treatment improved symptoms or prevented the progression of dialysis‐related amyloidosis in most patients.

Parathyroid Interventions for Secondary Hyperparathyroidism in Hemodialyzed Patients

Abstract:  Although parathyroidectomy (PTX) is the ultimate treatment for secondary hyperparathyroidism (SHPT) that is resistant to medical treatment, recent advances in ultrasonographic techniques have increased the treatment options in Japan. Percutaneous ethanol injection therapy (PEIT) of the parathyroid was approved under the national health insurance system in 2004, and there have been trials of direct injection of vitamin D (VD) preparations. We followed 30 patients for at least 1 year who had undergone PEIT at the same institution. The overall mean concentration of intact parathyroid hormone (PTH) fell from 865.3 ± 388.4 pg/mL to 291.9 ± 277.8 pg/mL, or 34% of the pretreatment value. The effect was even more pronounced for one or two glands, with 68.4% reaching the target of intact PTH ≤ 300 pg/mL recommended in the K/DOQI guidelines, in comparison with 36.4% of cases of hypertrophy of three or four glands. The average time taken to achieve the target PTH concentration was 4 months. No correlation was found between the response to PEIT and the total parathyroid volume, or the volume of glands with suspected nodular hyperplasia. Cases in which PTH does not fall sufficiently after five or more injections should be considered refractory to PEIT and evaluated for PTX. Following PEIT, PTH falls relatively slowly, whereas after total PTX with forearm autograft the PTH concentration falls immediately and may still be less than 60 pg/mL 4 or 5 years later. Bone biopsies performed 1 year after total PTX with autograft showed a change from an osteitis fibrosa pattern to an adynamic bone disease pattern. In some cases of hypertrophy of three to four glands, markers of bone metabolism kept decreasing more than did PTH, corresponding to marked improvement in the patients’ quality of life. Important considerations for treatment selection include: (i) ultrasonography of the cervical region as screening; (ii) earlier recognition of the limits of medical therapy; and (iii) the number of affected glands, the age of the patient, and the likely course postintervention.

Collagen type Iα1 gene polymorphism may be associated with the rate of bone mineral density decrease in female hemodialyzed patients

AbstractBackground. Polymorphism of the collagen type Iα1 gene (COLIA1) has been shown to be involved in bone density in the general population. However, the significance of this polymorphism has not been examined in patients with chronic renal failure. Methods. We first determined the COLIA1 Bal I restriction fragment length polymorphism (RFLP) at the Sp 1 binding site, and, next, we measured biochemical bone markers and the bone mineral density (BMD) of the lumbar spine (L2–L4) and radius (distal one-third) in 181 hemodialyzed patients. Results. Distributions of the Bal I RFLP were: SS, 62%; Ss, 32%; and ss, 6%. The Z scores for the BMD and for the serum levels of Ca, P, alkaline phosphatase, intact-parathyroid hormone (PTH), osteocalcin, and tartrate-resistant acid phosphatase were not significantly different among the three genotype groups. The slope of the regression line in the age-BMD relationship, a measure of the rate of BMD decrease, was similar among the three genotypes in men, but was significantly (P < 0.05) larger in the ss group than in the SS and Ss groups in women. Conclusions. The COLIA1 polymorphism may be associated with the bone loss seen in female patients on hemodialysis.

Long-term effect of parathyroidectomy on renal osteodystrophy of hemodialysis patients.

透析患者の腎性骨異栄養症 (ROD) に対する副甲状腺摘出術 (PTX) の効果についての報告は, PTX後2年以内の比較的短期間のものが多く, これ以上長期に経過したPTX後の骨所見に関する報告は少ない. 今回我々は, PTXの長期的効果を明らかにするため, PTXおよび前腕への自家移植術を施行後43-56か月 (平均50か月) の患者8名において骨の生化学的指標と骨塩量を測定し, 対照群18名および二次性副甲状腺機能亢進症 (2°HPT) 群14名と比較検討するという横断的検索を行った.オステオカルシン, C-PTH, Intact-PTHは対照群とPTX群の間で有意な差がなかったが, 2°HPT群ではこれらの2群より明らかに高かった. Ca, P, AI-P, カルシトニン, 酒石酸抵抗性Ac-P, アルミニウムは3群で有意差が認められなかった. Dual-energy X-ray absorptiometry法にて測定したLean body massに対する全身骨塩量の比 (%) は, 2°HPT群が対照群より有意に低かった. その他, 全身, 頭部, 腰椎, 体幹, 左・右上肢, 下肢の骨塩量も2°HPT群では対照群と比べて同様ないしは低値を示した. 一方, PTX群と2°HPT群の間では, 骨塩量比・骨塩量の値に一定の傾向はなく, 有意差が認められなかった.以上より, 透析患者の2°HPTを伴ったRODでは, PTX後に骨の生化学的指標は正常化するが, PTX後50か月の時点でみると骨塩量は必ずしも増加していない可能性が示唆された. 今後は縦断的検索も加えた検討が必要と考えられる.