Yasumichi Kinoshita

Randomized crossover study of the efficacy and safety of sevelamer hydrochloride and lanthanum carbonate in Japanese patients undergoing hemodialysis.

Insufficient control of serum calcium and phosphate levels in patients undergoing hemodialysis is associated with increased mortality. As commonly used calcium‐containing phosphate binders can cause arterial calcification, newly developed calcium‐free phosphate binders, such as sevelamer hydrochloride (SH) and lanthanum carbonate (LC), have received much attention. We assessed the efficacy and safety of SH and LC treatment in Japanese patients undergoing hemodialysis in a prospective randomized open blinded endpoint (PROBE) crossover study. Forty‐two patients were randomized to receive SH or LC for 13 weeks, with the dosages adjusted every 2 weeks, followed by treatment with the other drug for another 13 weeks. The average daily doses of SH and LC were 2971 ± 1464 mg and 945 ± 449 mg, respectively. The mean dosage ratio of SH to LC was 3.05, which was maintained throughout the treatment period. SH and LC were similarly effective at controlling serum calcium and phosphate levels in the majority of patients (78–93%). A few serious adverse events (AEs) involving the biliary system occurred during the LC treatment period, but they were not considered to be treatment‐induced. Although the incidence of constipation, the most common treatment‐related AE, was higher during the SH period (27% vs. 5%; P < 0.05), no difference was observed in total treatment‐related AEs. This study demonstrates that SH and LC are comparable treatments for controlling serum phosphate and calcium levels, and that both compounds are safe and well‐tolerated in Japanese patients undergoing hemodialysis.

Quantitation of C3 nephritic factor of alternative complement pathway by an enzyme-linked immunosorbent assay.

We have developed an enzyme-linked immunosorbent assay (ELISA) for the quantitation of C3 nephritic factor of the alternative pathway of complement (NeFA). Incubation of the NeFA-positive serum (patient KS serum) with normal human serum (NHS) in Mg-EGTA resulted in the formation of C3-B-IgG complex. No complex was formed in EDTA. At first this was detected as three types of complexes: C3-IgG, B-IgG and B-C3, by the combination of antibodies. The reaction mixture in Mg-EGTA was filtered through an ACA 22 column, from which the complexes were eluted in the same part as the first protein peak. When IgG purified from KS serum was incubated with NHS in Mg-EGTA, B-C3 complex increased in proportion to the dose of IgG. These results indicated that only one kind of complex consisting of IgG, C3 and B (IgG-C3-B) was generated by the addition of NeFA to NHS. Serum NeFA could be quantified as the titer of B-C3 complex formed after its incubation with NHS in Mg-EGTA. Using the ELISA method, NeFA was positive in five out of six patients with membranoproliferative glomerulonephritis (MPGN) type II and in only one of 17 with MPGN type I. Titers obtained by the new method were in good accordance with those by C3 conversion and C3bBb stabilization assays for NeFA, and the new method was more exact and simple than the conventional methods.

Quantitation of C4 nephritic factor by an enzyme-linked immunosorbent assay

We have developed an enzyme-linked immunosorbent assay (ELISA) for the quantitation of C4 nephritic factor (C4NeF). Incubation of the C4NeF-positive serum from patient M.I. with normal human serum (NHS) in the presence of human aggregated IgG (AHG) resulted in the formation of stable C4-C2 complex. No complex was formed in EDTA or under the condition free of AHG. The reaction mixture was filtered through an ACA 22 column, from which the C4-C2 complex was eluted at the first protein peak. When IgG purified from M.I. serum was incubated with NHS and AHG, C4-C2 complex also increased in proportion to dose of the purified M.I. IgG. These results show that C4NeF in M.I. serum stabilizes C4b2a convertase of the classical complement pathway, and is quantified by the ELISA. C4NeF activity was measured, using the ELISA method, in patients with various glomerular diseases, and found elevated in three of 24 patients with membranoproliferative glomerulonephritis (MPGN) type I and slightly but distinctly positive in seven of 24. No C4NeF was detected in two C3 nephritic factor-positive patients with MPGN type II and six with active systemic lupus erythematosus. The new method was more simple and quantitative than C4b2a stabilization assay for C4NeF.

Hemosiderosis secondary to parenteral iron therapy in chronic hemodialysis patients

目的: 慢性透析患者の貧血に対し鉄剤投与や輸血が行われる事が多い. この際の合併症であるヘモジデローシスは従来早期診断が困難であり, 血清鉄値, UIBC, 血清フェリチン値, 臨床経過等により総合的に推定されるのみであった. しかしCTの出現により, 鉄の肝臓への異常蓄積が早期にかつ直接的に診断できるようになった. このような観点から我々は鉄剤投与および輸血を受けた透析患者25名に肝CTを施行した.結果: 血清フェリチン値と鉄投与量の相関 (r=0.491, 0.01<p<0.02) に比べ, 肝CT値と鉄投与量の間には良い相関が得られた (r=0.714, p<0.001). もともと肝機能障害のある3例を除く22例中10例に一過性のトランスアミナーゼ値 (以下Tra.) の上昇がみられ, 残り12例は経過中Traは正常であった. Traの上昇のあった群はTraの正常な群に比べて有意に鉄投与量が多く, また有意に肝CT値が高かったので, 鉄剤投与の結果肝ヘモジデローシスがおきTraが上昇したものと考えられる. これに対し, 血清フェリチン値とTraの上昇の間には相関はみられなかった. また輸血によっても肝CT値は上昇する傾向がみられた. 肝CT値の上昇とともに脾CT値もわずかながら上昇した. 鉄剤投与を中止して6ヵ月後にCTを再検してみると, 肝CT値はほとんど変化せず, 鉄の肝臓への沈着は不可逆的である事が示唆された.以上の結果により, 肝CT値は血清フェリチン値よりも正確にヘモジデローシスを反映しており, その早期診断に有用と思われる. 鉄剤投与または輸血の施行されている透析患者には経過を追って肝CTを施行し, 止むを得ない場合でも肝CT値80 H. U. を越えないようにすべきである. ただし肝CTには鉄欠乏に関する情報はなく, 従来通り血清フェリチンも併せて参考にすべきであろう.