Kenji Yuasa

Serum levels of soluble secreted α-Klotho are decreased in the early stages of chronic kidney disease, making it a probable novel biomarker for early diagnosis.

Backgroundα-Klotho was first identified as an aging gene and was later shown to be a regulator of phosphate metabolism. Fibroblast growth factor 23 (FGF23) is the key regulator of phosphate metabolism. Serum levels of soluble α-Klotho in chronic kidney disease (CKD) patients have not previously been determined, especially in relation with FGF23 and creatinine levels. This study was designed to investigate whether serum soluble α-Klotho levels are modulated by renal function, age, and FGF23 level in CKD patients. This study is the first report on the utility of measuring soluble α-Klotho levels in human CKD.MethodsA total of 292 CKD patients were enrolled. Serum samples were collected, and FGF23 and soluble α-Klotho levels were measured using enzyme-linked immunosorbent assay kits. In addition, serum creatinine, hemoglobin, albumin, calcium, and phosphate levels were measured.ResultsSerum soluble α-Klotho levels were associated positively with estimated glomerular filtration rate (eGFR) (Pxa0<xa00.0001) and inversely with serum creatinine level (Pxa0<xa00.01). Interestingly, α-Klotho levels were significantly decreased in stage 2 CKD compared with stage 1 (Pxa0=xa00.0001). Serum FGF23 levels were associated positively with serum creatinine and negatively with eGFR. FGF23 levels were significantly increased in stage 5 compared with stage 1 CKD. Soluble α-Klotho was associated inversely with log-transformed FGF23 level (Pxa0<xa00.01).ConclusionOur data indicate that soluble α-Klotho levels are significantly decreased in stage 2 CKD compared to stage 1, and not only in the advanced stages of the disease. Soluble α-Klotho may thus represent a new biomarker for the diagnosis of CKD, especially in the early stage.

Serum level of soluble (pro)renin receptor is modulated in chronic kidney disease

BackgroundProrenin, the precursor of renin, binds to the (pro)renin receptor [(P)RR] and triggers intracellular signaling. The ligand binding sites of (P)RR are disconnected and are present in the soluble form of the receptor in serum. Given that the clinical significance of serum prorenin and soluble (P)RR in chronic kidney disease (CKD) is unclear, we investigated the relationship between serum prorenin, soluble (P)RR, and various clinical parameters in patients with CKD.MethodsA total of 374 patients with CKD were enrolled. Serum samples were collected, and the levels of soluble (P)RR and prorenin were measured using ELISA kits. Serum creatinine (Cr), blood urea nitrogen (BUN), uric acid (UA), hemoglobin (Hb), soluble secreted α-Klotho, and the urine protein/Cr ratio were also measured. Similarly, clinical parameters were also evaluated using serum and urine sample collected after 1xa0year (nxa0=xa0204).ResultsSoluble (P)RR levels were positively associated with serum Cr (Pxa0<xa00.0001, rxa0=xa00.263), BUN (Pxa0<xa00.0001, rxa0=xa00.267), UA (Pxa0<xa00.005, rxa0=xa00.168) levels, CKD stage (Pxa0<xa00.0001, rxa0=xa00.311) and urine protein/Cr ratio (Pxa0<xa00.01, rxa0=xa00.157), and inversely with estimated glomerular infiltration rate (eGFR) (Pxa0<xa00.0001, rxa0=xa0−0.275) and Hb (Pxa0<xa00.005, rxa0=xa0−0.156). Soluble (P)RR levels were inversely associated with α-Klotho levels (Pxa0<xa00.001, rxa0=xa0−0.174) but did not correlate with prorenin levels. With respect to antihypertensive drugs, soluble (P)RR levels were significantly lower in patients treated with an angiotensin II receptor blocker (ARB) than in those without ARB therapy (Pxa0<xa00.005). Soluble (P)RR levels were significantly lower in CKD patients with diabetes mellitus or primary hypertension than in those without these conditions (Pxa0<xa00.05). In contrast, serum levels of prorenin did not correlate with parameters related to renal function. Serum prorenin levels were significantly higher in CKD patients with diabetes mellitus than in nondiabetic patients (Pxa0<xa00.05), but not in CKD patients with hypertension (Pxa0=xa00.09). Finally, with respect to the relationship between basal soluble (P)RR levels and the progression rates of renal function, soluble (P)RR levels were positively associated with ΔCr (Pxa0<xa00.05, rxa0=xa00.159) and inversely associated with ΔeGFR (Pxa0<xa00.05, rxa0=xa0−0.148).ConclusionSerum levels of soluble (P)RR correlated with the stage of CKD. Our findings suggest that soluble (P)RR may be involved in renal injury and influence the progression of CKD.

Study of recombinant human erthropoietin administration for anemia in hemodialysis patients. Clinical study of dose determination.

目的: 腎性貧血に対するリコンビナント・ヒト・エリスロポエチン (r-HuEPO) の至適投与量を明らかにするため多施設共同試験を実施した. 対象と方法: 慢性腎不全血液透析患者でHt値25%以下の症例273例を対象とした. 初期投与を3群 (1,500IU×3/W, 1,500IU×2/W, 3,000×2/W) に分類し, Ht値が27-33%に達した時点より維持投与に移行し, Ht値を30%前後に維持するように投与量を変更もしくは休薬した. 結果: 初期投与では投与後4週後のHt値は3群とも有意な上昇を示し, 3群間では3,000×2/Wが有意に高値であり, その効果は用量依存性であった. 12週目では3群間に差がなく, 貧血改善を緩徐に行うためには1,500IU×2/Wで十分であった. 維持投与量は, 低用量に移行し, 4,500IU/W以下が約80%を占めた. しかしながらHt値30%を維持するためには25%の症例で6,000IU/Wの投与が必要であった. 副作用は34例 (12.5%) に認められ, 主要な副作用は血圧上昇で, 投与量が増えるに従い, その発生頻度が増加した. 6,000IU/W投与する場合, 血圧の上昇を懸念する必要があると思われた.