Voskaridou E, Terpos E, Michail S, Hantzi E, Anagnostopoulos A, Margeli A, Simirloglou D, Loukopoulos D, Papassotiriou I
Thalassemia Center, Laikon General Hospital, Athens, Greece.
Kidney Int. 2006 Jun;69(11):2037-42. doi: 10.1038/sj.ki.5000248.
Progressive renal failure is one of the main complications in HbS/beta-thalassemia (HbS/beta-thal). Early identification of patients at high risk of developing renal failure is of great importance as it may allow specific measures to delay the progression of renal damage and thus reduce the incidence of end-stage renal failure and mortality. Early predictors of renal impairment in HbS/beta-thal remain to explore. Within this context, we studied 87 compound HbS/beta-thal patients (36 males/51 females; median age 39 years) and 30 healthy controls. In addition to conventional renal biochemistries we measured serum cystatin-C (Cys-C), urine N-acetyl-beta-D-glucosaminidase (NAG) excretion and serum and urinary beta(2)-microglobulin (beta(2)-M). Cystatin-C, NAG and serum beta(2)-M levels were higher in patients than controls. The incidence of patients with high levels of Cys-C, NAG, and beta(2)-M was 32.1, 74.7, and 70.1% respectively, while only 6.8% of patients had increased serum creatinine levels. Cystatin-C and serum beta(2)-M showed a strong correlation with creatinine clearance and age, while NAG positively correlated with proteinuria. An inverse correlation was also shown between hemoglobin and beta(2)-M, NAG, and Cys-C levels. Seven patients with proteinuria received therapy with angiotensin-converting enzyme (ACE) inhibitors. Changes of poteinuria positively correlated with NAG levels. These results indicate that Cys-C is an accurate marker of renal dysfunction, and urinary NAG excretion can be considered as a reliable index of the tubular toxicity, and possible predictor of proteinuria and eventual renal impairment in HbS/beta-thal patients. Furthermore, NAG measurement may be used for monitoring ACE-inhibitors therapy in HbS/beta-thal patients with proteinuria.
进行性肾衰竭是镰状细胞血红蛋白/β地中海贫血（HbS/β地贫）的主要并发症之一。早期识别有发生肾衰竭高风险的患者非常重要，因为这可能使采取特定措施延缓肾损害进展，从而降低终末期肾衰竭的发生率和死亡率。HbS/β地贫患者肾损害的早期预测指标仍有待探索。在此背景下，我们研究了87例复合型HbS/β地贫患者（36例男性/51例女性；中位年龄39岁）和30名健康对照者。除了常规的肾脏生化指标外，我们还检测了血清胱抑素C（Cys-C）、尿N-乙酰-β-D-氨基葡萄糖苷酶（NAG）排泄量以及血清和尿β2微球蛋白（β2-M）。患者的Cys-C、NAG和血清β2-M水平高于对照者。Cys-C、NAG和β2-M水平升高的患者发生率分别为32.1%、74.7%和70.1%，而仅有6.8%的患者血清肌酐水平升高。Cys-C和血清β2-M与肌酐清除率和年龄呈强相关，而NAG与蛋白尿呈正相关。血红蛋白与β2-M、NAG和Cys-C水平之间也呈负相关。7例蛋白尿患者接受了血管紧张素转换酶（ACE）抑制剂治疗。蛋白尿的变化与NAG水平呈正相关。这些结果表明，Cys-C是肾功能不全的准确标志物，尿NAG排泄可被视为肾小管毒性的可靠指标，以及HbS/β地贫患者蛋白尿和最终肾损害的可能预测指标。此外，NAG检测可用于监测HbS/β地贫蛋白尿患者的ACE抑制剂治疗。
