Zoccali Carmine, Mallamaci Francesca, De Caterina Raffaele
Renal Research Institute, New York, NY, USA.
Institute of Molecular Biology and Genetics (Biogem), Ariano Irpino, Italy.
Clin Kidney J. 2023 Apr 10;16(10):1580-1586. doi: 10.1093/ckj/sfad079. eCollection 2023 Oct.
In chronic kidney disease (CKD) patients, hypofiltration may lead to the accumulation of drugs that are cleared mainly by the kidney and, vice versa, hyperfiltration may cause augmented renal excretion of the same drugs. In this review we mainly focus on the issue of whether hyperfiltration significantly impacts the renal clearance of drugs and whether the same alteration may demand an up-titration of the doses applied in clinical practice. About half of severely ill, septic patients and patients with burns show glomerular hyperfiltration and this may lead to enhanced removal of drugs such as hydrophilic antibiotics and a higher risk of antibiotic treatment failure. In general, hyperfiltering obese individuals show higher absolute drug clearances than non-obese control subjects, but this depends on the body size descriptor adopted to adjust for fat excess. Several mechanisms influence pharmacokinetics in type 2 diabetes, including renal hyperfiltration, reduced tubular reabsorption and augmented tubular excretion. However, no consistent pharmacokinetic alteration has been identified in hyperfiltering obese subjects and type 2 diabetics. Non-vitamin K antagonist oral anticoagulants (NOACs) have exhibited lower plasma concentrations in hyperfiltering patients in some studies in patients with atrial fibrillation, but a recent systematic review failed to document any excess risk for stroke and systemic embolism in these patients. Hyperfiltration is common among severely ill patients in intensive care units and drug levels should be measured whenever possible in these high-risk patients to prevent underdosing and treatment failure. Hyperfiltration is also common in patients with obesity or type 2 diabetes, but no consistent pharmacokinetic alteration has been described in these patients. No NOAC dose adjustment is indicated in patients with atrial fibrillation being treated with these drugs.
在慢性肾脏病（CKD）患者中，滤过减少可能导致主要经肾脏清除的药物蓄积，反之，滤过增加可能导致相同药物的肾脏排泄增加。在本综述中，我们主要关注滤过增加是否会显著影响药物的肾脏清除率，以及同样的改变是否需要在临床实践中上调用药剂量。约一半的重症脓毒症患者和烧伤患者存在肾小球滤过增加，这可能导致亲水性抗生素等药物清除增加，以及抗生素治疗失败风险升高。一般来说，滤过增加的肥胖个体比非肥胖对照者的药物绝对清除率更高，但这取决于用于校正脂肪过多的身体大小描述指标。有几种机制影响2型糖尿病患者的药代动力学，包括滤过增加、肾小管重吸收减少和肾小管排泄增加。然而，在滤过增加的肥胖受试者和2型糖尿病患者中，尚未发现一致的药代动力学改变。在一些针对心房颤动患者的研究中，非维生素K拮抗剂口服抗凝药（NOACs）在滤过增加的患者中血浆浓度较低，但最近一项系统评价未能证明这些患者有任何额外的中风和全身性栓塞风险。滤过增加在重症监护病房的重症患者中很常见，对于这些高危患者，应尽可能测量药物水平，以防止用药不足和治疗失败。滤过增加在肥胖或2型糖尿病患者中也很常见，但这些患者中尚未描述一致的药代动力学改变。接受这些药物治疗的心房颤动患者无需调整NOAC剂量。
