药物相关肾实质性急性肾衰竭患者的贫血特征、红细胞生成素水平及其与肾损害的关系

目的:回顾性分析药物相关的不同原因急性肾衰竭(acute renal failure, ARF)患者的临床病理特点及血清学指标,探讨其贫血特征、红细胞生成素(erythropoietin, EPO)水平及与肾小管间质损害的关系.方法:选择近5年的药物相关肾实质性ARF住院患者16例,包括急性肾小管坏死(acute tubular necrosis, ATN)组和急性肾小管间质肾病(acute tubular-interstitial nephropathy, ATIN)组]以及健康志愿者(正常对照组,8例)为观察对象,回顾性分析其肾活检时的贫血相关指标、血清EPO、肌酐水平和肾小管功能.对ARF各组患者的肾小管功能和肾病理改变进行半定量评分.对血红蛋白(hemoglobin, Hb)、EPO水平与肾功能和肾病理损伤指数进行相关分析.结果:(1)药物相关肾实质性急性肾衰竭各组患者血清肌酐(serum creatinine, Scr)水平均较对照组明显增高(P<0.05),肾小管功能损伤指数和肾小管间质病理损伤指数较对照组有所增高,以ATIN组为最高(P<0.01).(2)ATIN组患者Hb、红细胞压积(haematocrit, Hct)、红细胞(red blood cell, RBC)的水平较对照组明显降低(P<0.01).(3)ATN组、ATIN组EPO水平较对照组分别明显下降84.8%和70.7%(P<0.01).(4)肾实质性ARF患者的Hb与EPO呈正相关(r=0.589,P<0.01);而EPO则与Scr、肾小管功能损伤指数及肾小管、间质病理损伤指数之间均呈负相关(P<0.05).结论:ATIN是药物相关急性肾衰竭伴贫血患者的主要原因之一,该组患者贫血的机制可能与急性肾小管间质损伤导致内源性EPO分泌不足、进而引起红细胞生成减少有关.

Relationship among the characteristics of anemia, serum level of erythropoietin and the renal tubulointerstitial injury in drug-associated renal parenchymal acute renal failure patients

OBJECTIVE: To recognize the characteristics of anemia in patients with drug-associated renal parenchymal ARF and to investigate the possible relations among Hb, serum level of EPO and the renal tubulointerstitial injury. METHODS: Sixteen in-patients with drug-associated renal parenchymal ARF (including ATN and ATIN groups) for the last five years and 8 healthy volunteers (control group) were assessed in this study. The general information of these patients was analyzed retrospectively. Anemia related laboratory parameters, serum EPO, serum creatinine (Scr) and the renal tubular function from the samples on the time of renal biopsy in each group were compared. For pathological comparison of renal tubulointerstitial pathological changes, renal biopsy specimens from 5 patients with mild non-IgA mesangial proliferative glomerulonephritis were used as negative controls. The pathological changes in renal tubules and interstitial area were semi-quantitive scored by a computer imaging system. The correlations between Hb and EPO levels, as well as EPO level and renal function or pathological injury index were analyzed, respectively. RESULTS: There was no significant difference among the ages, genders and the time intervals both from the administration to the onset of the disease and from the onset to the kidney biopsy among ATN and ATIN groups. Scr level was all higher than that in the control group (P<0.05). The renal tubular function injury index and the tubular interstitial pathologic injury index in the two groups were relatively elevated, in which the ATIN group had the highest indexes compared to the others (P<0.01). There were more anemia patients in ATIN group. It showed much lower levels of Hb, Hct and RBC than those in the control group (P<0.01). ATN group possessed fewer anemia patients and the levels of Hb, Hct and RBC remained in the normal range. The remarkable decline of EPO levels was found as 84.8% and 70.7% in the ATN and ATIN groups, respectively (P<0.01). In all patients with renal parenchyma ARF, the levels of Hb and EPO showed an obvious positive correlation (r=0.589, P<0.01), but the negative correlations existed between EPO and Scr, the renal tubular function injury index and renal tubular interstitial pathological injury index, respectively (P<0.05). CONCLUSION: The mechanism of the anemia in the drug-associated parenchymal ARF patients may be due to the lack of intrinsic EPO secretion, mainly induced by acute renal tubular interstitial injury, which contributes to the decreased genesis of red blood cells.