血管收縮素受體阻斷劑對糖尿病或高血壓病人尿中 D-乳酸濃度之影
響
The Effect of AngiotensinⅡType 1 Receptor Blocker on Urinary
D-Lactate Concentrations in Diabetic or Hypertensive Patients
中文摘要
根據我們之前的動物實驗結果，尿中 D-乳酸濃度（μM/mM creatinine）可能可以作為偵測早 期腎臟損傷之指標；人體實驗結果，糖尿病與高血壓病患尿中 D-乳酸濃度在腎臟損傷之生化指 標微白蛋白尿（microalbuminuria）尚未出現前，即顯著高於正常人（P＜0.05）。因此，本 研究進一步探討：糖尿病與高血壓病患服用具有腎保護功能及降低蛋白尿之 Angiotensin Ⅱ receptor blocker—valsartan，對病患尿中 D-乳酸、N-acetyl-β-D-glucosaminidase （NAG）及 microalbumin 濃度之影響，以及尿中 D-乳酸與腎臟病變之相關性。
本試驗採收 39 位健康成年人之尿液做為對照組，並且將糖尿病（n = 74）與高血壓（n = 81） 患者分別分為三組：未服用 valsartan，服用 valsartan 12 週，以及服用 valsartan 24 週。 患者服用 valsartan 之劑量依照醫師之診斷，其範圍為 40-120 mg/day。結果顯示，未服用 valsartan 之糖尿病患者尿中 D-乳酸濃度（31.69 ± 8.83 μM/mM cr）皆顯著高於服用 valsartan12 週（9.08 ± 2.12 μM/mM cr）或服用 valsartan 24 週（4.03 ± 0.90 μM/mM cr）之患者；未服用 valsartan 之高血壓患者尿中 D-乳酸濃度（12.57 ± 3.85 μM/mM cr） 皆顯著高於服用 valsartan12 週（8.85 ± 1.50 μM/mM cr）或服用 valsartan 24 週（3.73 ± 1.11 μM/mM cr）之患者。值得注意的是，糖尿病或高血壓患者尿中 D-乳酸、NAG 及 microalbumin 濃度下降之趨勢與病患服用 valsartan 週數有明顯正相關性，而且服用 valsartan 24 週之糖尿病或高血壓患者，其尿中 D-乳酸、NAG 及 microalbumin 濃度與正常 人比較皆無統計之差異。
綜合上述，糖尿病患者尿中 D-乳酸與微白蛋白尿具有相同之特性—確實會因患者服用
valsartan 之影響而下降，而且在微白蛋白尿出現之前，尿中 D-乳酸濃度即顯著升高。因此， 我們建議可以偵測尿中 D-乳酸濃度作為早期腎臟損傷之指標。
英文摘要
According to our previous research, there was a significant increase in urine levels of D-lactate (μM/mM creatinine) in diabetic rats compared to normal rats (P < 0.01). We further demonstrated the urine levels of D-lactate in diabetic or hypertensive patients were prominently elevated before the appearance of microalbuminuria (P < 0.05). In this study, we investigated an angiotensin II receptor blocker, valsartan, with proven effect on microalbuminuria on the clinical effects of urinary D-lactate concentrations in diabetic or hypertensive patients.
We studied three groups in diabetic or hypertensive patients who were not receiving valsartan, receiving 12-week, and 24-week valsartan. Valsartan dosage ranged from 40-120 mg/day according to doctor’s diagnosis. Urine levels of D-lactate, NAG (N-acetyl-β-D-glucosaminidase), and microalbumin were measured in 74 diabetic patients, 81 hypertensive patients, and 39 healthy subjects as controls.
In diabetic patients, the levels of urinary D-lactate were significantly lower in patients receiving either 24-week (4.03 ± 0.90 μM/mM cr) or 12-week (9.08 ± 2.12 μM/mM cr) valsartan compared with those not receiving valsartan (31.69 ± 8.83 μM/mM cr). In hypertensive patients, the levels of urinary D-lactate were significantly lower in patients receiving either 24-week (3.73 ± 1.11 μM/mM cr) or 12-week (8.85 ± 1.50 μM/mM cr) valsartan compared with those not receiving valsartan (12.57 ± 3.85 μM/mM cr). The descending tendency of urinary D-lactate, NAG, and microalbumin all had a positive relationship with the duration of patients receiving valsartan. Notably, there were no difference in urine levels of D-lactate, NAG, and
microalbumin between 24-week valsartan group of diabetic or hypertensive patients and healthy subjects.
In conclusion, the significant reduction of urinary D-lactate was similar with the proven effect on microalbuminuria by valsartan in diabetic or hypertensive patients. We suggest that urinary D-lactate may be a useful indicator for early diagnosis of diabetic or hypertensive nephropathy, serving in the assessment of therapeutic effects.
