Maski Manish R, Thomas Robert J, Karumanchi S Ananth, Parikh Samir M
Division of Nephrology/ Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America.
Division of Pulmonary, Critical Care, & Sleep Medicine/ Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS One. 2016 May 5;11(5):e0154503. doi: 10.1371/journal.pone.0154503. eCollection 2016.
Obstructive sleep apnea (OSA) is a well-established risk factor for hypertension and cardiovascular morbidity and mortality. More recently, OSA has been implicated as an independent risk factor for chronic kidney disease. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is a well-accepted early biomarker of subclinical kidney tubular injury, preceding an increase in serum creatinine. The goal of this study was to determine if an association exists between OSA and increased urinary NGAL levels.
We prospectively enrolled adult patients from the sleep clinic of an academic medical center. Each underwent polysomnography and submitted a urine specimen upon enrollment. We measured NGAL and creatinine levels on all urine samples before participants received treatment with continuous positive airway pressure (CPAP), and, in a subset of OSA patients, after CPAP therapy. We compared the urinary NGAL/creatinine ratio between untreated participants with and without OSA, and within a subset of 11 OSA patients also after CPAP therapy.
A total of 49 subjects were enrolled: 16 controls based on an apnea-hypopnea index (events with at least 4% oxygen desaturation; AHI-4%) <5 events/hour (mean AHI-4% = 0.59 +/- 0.60); 33 OSA patients based on an AHI-4% >5 events/hour (mean AHI-4% = 43.3 +/- 28.1). OSA patients had a higher mean body-mass index than the control group (36.58 +/- 11.02 kg/m2 vs. 26.81 +/- 6.55 kg/m2, respectively; p = 0.0005) and were more likely to be treated for hypertension (54.5% vs. 6.25% of group members, respectively; p = 0.0014). The groups were otherwise similar in demographics, and there was no difference in the number of diabetic subjects or in the mean serum creatinine concentration (control = 0.86 +/- 0.15 mg/dl, OSA = 0.87 +/- 0.19 mg/dl; p = 0.7956). We found no difference between the urinary NGAL-to-creatinine ratios among untreated OSA patients versus control subjects (median NGAL/creatinine = 6.34 ng/mg vs. 6.41 ng/mg, respectively; p = 0.4148). Furthermore, CPAP therapy did not affect the urinary NGAL-to-creatinine ratio (p = 0.7758 for two-tailed, paired t-test).
In this prospective case-control study comparing patients with severe, hypoxic OSA to control subjects, all with normal serum creatinine, we found no difference between urinary levels of NGAL. Furthermore, CPAP therapy did not change these levels pre- and post-treatment.
阻塞性睡眠呼吸暂停（OSA）是高血压以及心血管疾病发病和死亡的公认危险因素。最近，OSA被认为是慢性肾脏病的独立危险因素。尿中性粒细胞明胶酶相关脂质运载蛋白（NGAL）是公认的亚临床肾小管损伤的早期生物标志物，出现在血清肌酐升高之前。本研究的目的是确定OSA与尿NGAL水平升高之间是否存在关联。
我们前瞻性地纳入了一家学术医疗中心睡眠诊所的成年患者。每位患者均接受多导睡眠图检查，并在入组时提交一份尿液标本。在参与者接受持续气道正压通气（CPAP）治疗之前，我们测量了所有尿液样本中的NGAL和肌酐水平，并且在一部分OSA患者中，在CPAP治疗后也进行了测量。我们比较了未治疗的有和没有OSA的参与者之间以及11名OSA患者亚组在CPAP治疗后的尿NGAL/肌酐比值。
共纳入49名受试者：16名对照者，基于呼吸暂停低通气指数（至少4%氧饱和度下降的事件；AHI-4%）<5次/小时（平均AHI-4% = 0.59±0.60）；33名OSA患者，基于AHI-4%>5次/小时（平均AHI-4% = 43.3±28.1）。OSA患者的平均体重指数高于对照组（分别为36.58±11.02kg/m²和26.81±6.55kg/m²；p = 0.0005），并且更有可能接受高血压治疗（分别为组内成员的54.5%和6.25%；p = 0.0014）。两组在人口统计学方面其他方面相似，糖尿病患者数量或平均血清肌酐浓度没有差异（对照组 = 0.86±0.15mg/dl，OSA组 = 0.87±0.19mg/dl；p = 0.7956）。我们发现未治疗的OSA患者与对照受试者之间的尿NGAL与肌酐比值没有差异（中位数NGAL/肌酐分别为6.34ng/mg和6.41ng/mg；p = 0.4148）。此外，CPAP治疗并未影响尿NGAL与肌酐比值（双侧配对t检验，p = 0.7758）。
在这项将重度、低氧性OSA患者与对照受试者进行比较的前瞻性病例对照研究中，所有患者血清肌酐均正常，我们发现尿NGAL水平没有差异。此外，CPAP治疗在治疗前后并未改变这些水平。
