Urine-to-Plasma Urea Ratio: Disentangling Tubular Concentrating Ability From GFR.
Urine-to-Plasma Urea Ratio: Disentangling Tubular Concentrating Ability From GFR.
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尿液与血浆尿素比率：将肾小管浓缩能力与 GFR 分开。
DOI：
10.1053/j.ajkd.2022.10.006
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Ix,JoachimH
中科院分区：
文献类型：
--
作者：
Ascher,SimonB;Garimella,PranavS;Ix,JoachimH
肾小管构成了肾脏皮质结构的绝大多数，消耗了肾脏所使用的大部分能量，并在各种基本的生物功能中发挥着核心作用。然而，慢性肾脏疾病(CKD)的诊断、分期和预后仍然依赖于估计的肾小球滤过率(EGFR)和蛋白尿，这主要反映了肾小球的健康状况，并不能完全反映肾小管病变。1活检证实的间质纤维化和肾小管萎缩几乎见于所有形式的CKD，其严重程度与肾功能衰竭的预后密切相关。1、2最近的研究评估了反映CKD患者肾小管损伤和功能障碍的非侵入性生物标志物的临床意义，进一步强化了这样一种观点，即对肾脏健康进行更广泛的评估--超越EGFR和蛋白尿--可以提供有关肾脏健康和一系列下游不良后果的额外信息。3肾小管的一个重要功能是通过尿液稀释和浓缩来维持体内水分平衡。先前关于尿液渗透压与不良肾脏结局的研究结果相互矛盾。尿液渗透压是后叶加压素刺激和尿液浓缩能力的指标。几项大型多中心慢性肾脏病队列研究表明，尿液渗透压较低与EGFR下降较快相关，并与独立于EGFR和蛋白尿的CKD进展风险相关。4、5、6此外，对常染色体显性遗传性多囊肾病(ADPKD)和EGFR基本保留的个体的分析表明，基线尿渗透压较低与EGFR下降较快相关。7相比之下，对患有和不患有ADPKD的患者进行的较小规模的研究报告称，尿液渗透压较高，而不是较低，与不良肾脏结局有关。8、9最近，一项针对ADPKD患者的研究评估了尿素的尿浆比([U/P]尿素)--据称是衡量尿液浓缩能力的指标--发现较低的[U/P]尿素与隔夜禁食后的尿液渗透压降低密切相关，并与EGFR的快速下降独立相关。10
The kidney tubules make up the vast majority of the kidney’s cortical structure, expend most of the energy used by the kidneys, and play a central role in a variety of essential biological functions. However, chronic kidney disease (CKD) diagnosis, staging, and prognosis remain anchored to estimated glomerular filtration rate (eGFR) and albuminuria, which primarily reflect glomerular health and do not fully capture tubular pathology. 1 Biopsy-proven interstitial fibrosis and tubular atrophy is found in nearly all forms of CKD, and its severity is strongly prognostic of kidney failure. 1, 2 Recent studies evaluating the clinical significance of noninvasive biomarkers reflecting tubule injury and dysfunction in individuals with CKD have further strengthened the argument that a broader assessment of kidney health—beyond eGFR and albuminuria—can provide additional information about the health of the kidney and an array of downstream adverse consequences. 3A critical function of the kidney tubules is maintaining body water homeostasis through urinary dilution and concentration. Previous studies examining associations of urine osmolality, an indicator of vasopressin stimulation and urine concentrating ability, with adverse kidney outcomes have yielded conflicting results. Several large multicenter CKD cohort studies have demonstrated that lower urine osmolality is associated with faster decline in eGFR and subsequent risk of CKD progression independent of eGFR and albuminuria. 4, 5, 6 In addition, an analysis of individuals with autosomal dominant polycystic kidney disease (ADPKD) and largely preserved eGFR showed that lower baseline urine osmolality was associated with faster decline in eGFR. 7 In contrast, smaller studies of individuals with and without ADPKD reported that higher, rather than lower, urine osmolality was associated with adverse kidney outcomes. 8, 9 More recently, a study of individuals with ADPKD evaluated urine-to-plasma ratio of urea ([U/P] urea)—a purported surrogate for urine concentrating ability—and found that lower [U/P] urea is strongly correlated with lower urine osmolality after an overnight fast, and is independently associated with faster decline in eGFR. 10