Alex Ryan, Press Ella, Sanchez Lorin, Whitson Jeremy, Marder Brad, Tumlin James Alan
From the NephroNet Clinical Trials Consortium, Atlanta, GA.
Horizon Therapeutics, Deerfield, IL.
J Clin Rheumatol. 2024 Apr 1;30(3):110-116. doi: 10.1097/RHU.0000000000002068. Epub 2024 Feb 14.
The association between hyperuricemia and development of progressive chronic kidney disease has received increasing attention in recent years. Recent preclinical studies have shown that non-crystalline uric acid can induce renal-specific arteriolopathy, leading to renal injury and tubulointerstitial inflammation.
We conducted a open-label cross-sectional study of 25 patients with chronic kidney disease stage III (estimated glomerular filtration rate [eGFR], 7.0 mg/dL) levels of serum uric acid. To determine the correlation between hyperuricemia on urinary protein levels and renal disease progression, we retrospectively compared urine protein and eGFR data between the 2 groups.
Eleven patients with normal uric acid levels and 14 with hyperuricemia were enrolled. Urinary levels of both kidney injury molecule-1 (KIM-1) and monocyte chemoattractant protein-1 (MCP-1) were significantly higher in patients with hyperuricemia. Among the normouricemic White and African American (AA) subgroups, there was no difference in KIM-1 or MCP-1 levels, whereas KIM-1 levels were significantly higher among hyperuricemic AA patients with hyperuricemia. Urinary protein was significantly higher between Whites and AA patients with serum uric acid level >7.0 mg/dL as well as patients with urinary KIM-1 levels >1000 pg/mg Cr. A trend toward a more rapid decline in eGFR was noted among hyperuricemic AAs; however, this trend was not statistically significant.
Patients with type 2 diabetic nephropathy and persistently elevated serum uric acid levels express higher levels of both KIM-1 and MCP-1 reflective of on-going renal injury and inflammation.
近年来,高尿酸血症与进行性慢性肾脏病发展之间的关联受到越来越多的关注。最近的临床前研究表明,非结晶尿酸可诱发肾脏特异性小动脉病变,导致肾损伤和肾小管间质炎症。
我们对25例慢性肾脏病Ⅲ期(估计肾小球滤过率[eGFR],7.0mg/dL)患者进行了一项开放标签的横断面研究,检测血清尿酸水平。为了确定高尿酸血症与尿蛋白水平及肾脏疾病进展之间的相关性,我们回顾性比较了两组患者的尿蛋白和eGFR数据。
纳入11例尿酸水平正常的患者和14例高尿酸血症患者。高尿酸血症患者的肾损伤分子-1(KIM-1)和单核细胞趋化蛋白-1(MCP-1)尿水平均显著升高。在尿酸正常的白人和非裔美国人(AA)亚组中,KIM-1或MCP-1水平无差异,而高尿酸血症AA患者的KIM-1水平显著更高。血清尿酸水平>7.0mg/dL的白人和AA患者以及尿KIM-1水平>1000pg/mg Cr的患者尿蛋白显著更高。在高尿酸血症的AA患者中观察到eGFR有更快下降的趋势;然而,这一趋势无统计学意义。
2型糖尿病肾病且血清尿酸水平持续升高的患者表达更高水平的KIM-1和MCP-1,这反映了持续的肾损伤和炎症。