PDF(Pubmed)
Abstract：
Autosomal polycystic kidney disease (ADPKD) is the most common genetic form of kidney failure, reflecting unmet needs in management. Prescription of the only approved treatment (tolvaptan) is limited to persons with rapidly progressing ADPKD. Rapid progression may be diagnosed by assessing glomerular filtration rate (GFR) decline, usually estimated (eGFR) from equations based on serum creatinine (eGFRcr) or cystatin-C (eGFRcys). We have assessed the concordance between eGFR decline and identification of rapid progression (rapid eGFR loss), and measured GFR (mGFR) declines (rapid mGFR loss) using iohexol clearance in 140 adults with ADPKD with ≥3 mGFR and eGFRcr assessments, of which 97 also had eGFRcys assessments. The agreement between mGFR and eGFR decline was poor: mean concordance correlation coefficients (CCCs) between the method declines were low (0.661, range 0.628 to 0.713), and Bland and Altman limits of agreement between eGFR and mGFR declines were wide. CCC was lower for eGFRcys. From a practical point of view, creatinine-based formulas failed to detect rapid mGFR loss (-3 mL/min/y or faster) in around 37% of the cases. Moreover, formulas falsely indicated around 40% of the cases with moderate or stable decline as rapid progressors. The reliability of formulas in detecting real mGFR decline was lower in the non-rapid-progressors group with respect to that in rapid-progressor patients. The performance of eGFRcys and eGFRcr-cys equations was even worse. In conclusion, eGFR decline may misrepresent mGFR decline in ADPKD in a significant percentage of patients, potentially misclassifying them as progressors or non-progressors and impacting decisions of initiation of tolvaptan therapy.
摘要：
常染色体多囊肾病（ADPKD）是肾衰竭最常见的遗传形式，反映管理中未满足的需求。唯一批准的治疗（托伐普坦）的处方仅限于进展迅速的ADPKD患者。快速进展可以通过评估肾小球滤过率（GFR）下降来诊断。通常从基于血清肌酐（eGFRcr）或胱抑素C（eGFRcys）的方程中估计（eGFR）。我们已经评估了eGFR下降和快速进展（快速eGFR损失）之间的一致性。和测量的GFR（mGFR）下降（快速mGFR损失）使用碘海醇清除率在140名成人ADPKD与≥3mGFR和eGFR评估，其中97人也进行了eGFRcys评估。mGFR和eGFR下降之间的一致性较差：方法下降之间的平均一致性相关系数（CC）较低（0.661，范围0.628至0.713），Bland和Altman在eGFR和mGFR下降之间的协议界限很宽。eGFRcys的CCC较低。从实践的角度来看,在约37%的病例中,基于肌酐的公式未能检测到快速mGFR丢失(-3mL/min/y或更快).此外，公式错误地表明，大约40％的中度或稳定下降的病例为快速进展者。与快速进展患者相比，非快速进展患者组检测真实mGFR下降的公式可靠性较低。eGFRcys和eGFRcr-cys方程的性能更差。总之,eGFR下降可能在相当比例的患者中歪曲ADPKD的mGFR下降，可能将其错误分类为进展者或非进展者，并影响开始托伐普坦治疗的决定。
