Maurel Stéphane, Stankovic Stojanovic Katia, Avellino Virginie, Girshovich Alexey, Letavernier Emmanuel, Grateau Gilles, Baud Laurent, Girot Robert, Lionnet Francois, Haymann Jean-Philippe
Service d'Explorations Fonctionnelles,, †Sickle Cell Centre, and, ‡Internal Medicine Service, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Paris, France;, §Institut National de la Santé et de la Recherche Médicale, UMR_S 1155, Paris, France, ‖Sorbonne Universités, UPMC Univ Paris 06, DHUI2B, Paris, France.
Clin J Am Soc Nephrol. 2014 Apr;9(4):648-53. doi: 10.2215/CJN.09790913. Epub 2014 Jan 23.
Very few studies report acid base disorders in homozygous patients with sickle cell anemia (SCA) and describe incomplete renal acidosis rather than true metabolic acidosis, the prevalence of which is unknown and presumably low. This study aimed to assess the prevalence of metabolic acidosis and to identify its risk factors and mechanisms.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study retrospectively analyzed 411 homozygous patients with SCA with a GFR ≥ 60 ml/min per 1.73 m(2), referred in a single center between 2007 and 2012. Acidosis and nonacidosis groups were compared for clinical and biologic data including SCA complications and hemolytic parameters. A subgroup of 65 patients with SCA, referred for a measured GFR evaluation in the setting of sickle cell-associated nephropathy, was further analyzed in order to better characterize metabolic acidosis.
Metabolic acidosis was encountered in 42% of patients with SCA, with a higher prevalence in women (52% versus 27% in men; P<0.001). Several hemolytic biomarkers, such as lactate dehydrogenase, were different between the acidosis and nonacidosis groups (P=0.02 and P=0.03 in men and women, respectively), suggesting higher hemolytic activity in the former group. To note, fasting urine osmolality was low in the whole study population and was significantly lower in men with SCA in the acidosis group (392 versus 427 mOsm/kg; P=0.01). SCA subgroup analysis confirmed metabolic acidosis with a normal anion gap in 14 patients, characterized by a lower urinary pH (P<0.02) and no increase in urinary ammonium. Serum potassium, plasma renin, and aldosterone were similar between the two groups and thus could not explain impaired urinary ammonium excretion.
These results suggest that the prevalence of metabolic acidosis in patients with SCA is underestimated and related to impaired ammonium availability possibly due to an altered corticopapillary gradient. Future studies should evaluate whether chronic metabolic acidosis correction may be beneficial in this population, especially in bone remodeling.
极少有研究报道纯合子型镰状细胞贫血（SCA）患者的酸碱紊乱情况，且这些研究描述的是不完全性肾小管酸中毒而非真正的代谢性酸中毒，其患病率未知且可能较低。本研究旨在评估代谢性酸中毒的患病率，并确定其危险因素及机制。
设计、地点、参与者与测量方法：本研究回顾性分析了2007年至2012年间在单一中心就诊的411例GFR≥60 ml/（min·1.73 m²）的纯合子型SCA患者。对酸中毒组和非酸中毒组的临床及生物学数据进行比较，包括SCA并发症和溶血参数。对65例因镰状细胞相关性肾病进行GFR测量评估而转诊的SCA患者亚组进行进一步分析，以更好地描述代谢性酸中毒。
42%的SCA患者存在代谢性酸中毒，女性患病率更高（52%对男性的27%；P<0.001）。酸中毒组和非酸中毒组的几种溶血生物标志物，如乳酸脱氢酶，存在差异（男性和女性分别为P=0.02和P=0.03），提示前一组溶血活性更高。值得注意的是，整个研究人群的空腹尿渗透压较低，酸中毒组的男性SCA患者显著更低（392对427 mOsm/kg；P=0.01）。SCA亚组分析证实14例患者存在正常阴离子间隙的代谢性酸中毒，其特征为尿pH值较低（P<0.02）且尿铵无增加。两组间血清钾、血浆肾素和醛固酮相似，因此无法解释尿铵排泄受损的情况。
这些结果表明，SCA患者代谢性酸中毒的患病率被低估，且可能与由于皮质-髓质梯度改变导致的铵可用性受损有关。未来的研究应评估慢性代谢性酸中毒的纠正是否对该人群有益，尤其是在骨重塑方面。
