Sorbonne Université, Inserm UMR_S 1155, Paris, France; Unit of Renal Physiology, AP-HP Hôpital Tenon, Paris, France.
CESP, Inserm U1018, Univ Paris-Saclay, Univ Paris-Sud, UVSQ, Villejuif, France; FCRIN INI-CRCT, France.
Am J Kidney Dis. 2019 May;73(5):596-604. doi: 10.1053/j.ajkd.2018.12.024. Epub 2019 Feb 15.
RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) characterized by decreased glomerular filtration rate (GFR) is often accompanied by various degrees of impaired tubular function in the cortex and medulla. Assessment of tubular function may therefore be useful in establishing the severity of kidney disease and identifying those at greater risk for CKD progression. We explored reductions in urinary concentrating ability, a well-known feature of CKD, as a risk factor for GFR decline and end-stage renal disease (ESRD).
Prospective longitudinal cohort study.
SETTING & PARTICIPANTS: 2,084 adult patients with CKD stages 1 to 4 from the French NephroTest Cohort Study.
Fasting urinary osmolality measured using delta cryoscopy.
ESRD, mortality before ESRD, and measured GFR (mGFR) assessed using Cr-EDTA renal clearance.
Cause-specific hazards models were fit to estimate crude and adjusted associations of urinary osmolality with ESRD and death before ESRD. Linear mixed models with random intercepts were fit to evaluate the association of urinary osmolality with slope of decline in mGFR.
At baseline, mean age was 58.7±15.2 (SD) years with a median mGFR of 40.2 (IQR, 29.1-54.5) mL/min/1.73m and a median fasting urinary osmolality of 502.7±151.7mOsm/kg HO. Baseline fasting urinary osmolality was strongly associated with mGFR (R=0.54; P < 0.001). 380 ESRD events and 225 deaths before ESRD occurred during a median follow-up of 5.9 (IQR, 3.8-8.2) years. Patients with lower baseline fasting urinary osmolality had higher adjusted risk for ESRD but not for mortality (HRs of 1.97 [95% CI, 1.26-3.08] and 0.99 [95% CI, 0.68-1.44], respectively, for the lowest vs highest tertile). Based on a mixed linear model adjusted for baseline mGFR and clinical characteristics, patients in the lowest tertile of baseline urinary osmolality had a steeper decline in kidney function (-4.9% ± 0.9% per year; P < 0.001) compared with patients in the highest tertile.
Fasting was self-reported.
Fasting urinary osmolality may be a useful tool, in addition to GFR and albuminuria, for assessing nonglomerular damage in patients with CKD who are at higher risk for CKD progression.
慢性肾脏病（CKD）的特征是肾小球滤过率（GFR）下降，常伴有皮质和髓质肾小管功能的不同程度损害。因此，评估肾小管功能可能有助于确定肾脏疾病的严重程度，并识别那些更有可能进展为 CKD 的患者。我们探讨了尿浓缩能力的降低，这是 CKD 的一个众所周知的特征，作为 GFR 下降和终末期肾病（ESRD）的危险因素。
前瞻性纵向队列研究。
来自法国 NephroTest 队列研究的 2084 名 CKD 1 至 4 期的成年患者。
使用差示冰点测定法测量空腹尿渗透压。
ESRD、ESRD 前死亡和使用 Cr-EDTA 肾清除率评估的估计肾小球滤过率（mGFR）。
采用因果风险模型估计尿渗透压与 ESRD 和 ESRD 前死亡的粗关联和调整关联。采用具有随机截距的线性混合模型评估尿渗透压与 mGFR 下降斜率的关联。
基线时，平均年龄为 58.7±15.2（SD）岁，中位 mGFR 为 40.2（IQR，29.1-54.5）mL/min/1.73m，中位空腹尿渗透压为 502.7±151.7mOsm/kgHO。基线空腹尿渗透压与 mGFR 呈强相关（R=0.54；P<0.001）。在中位随访 5.9（IQR，3.8-8.2）年期间，发生了 380 例 ESRD 事件和 225 例 ESRD 前死亡。基线空腹尿渗透压较低的患者调整后的 ESRD 风险较高，但死亡率无差异（最低与最高三分位组的风险比分别为 1.97（95%CI，1.26-3.08）和 0.99（95%CI，0.68-1.44））。基于调整基线 mGFR 和临床特征的混合线性模型，基线尿渗透压最低三分位的患者肾功能下降更陡峭（每年-4.9%±0.9%；P<0.001）与最高三分位组相比。
空腹状态为自我报告。
除了 GFR 和白蛋白尿外，空腹尿渗透压可能是一种有用的工具，用于评估肾小球滤过率下降和蛋白尿患者的非肾小球损伤，这些患者更有可能进展为 CKD。
