Proximal Tubule Secretory Clearance, Injury, and Kidney Viability in Cirrhosis.

IF 3 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Clinical and Translational Gastroenterology Pub Date : 2024-10-07 DOI:10.14309/ctg.0000000000000775
Michael L Granda, Eric Luitweiler, David K Prince, Andrew S Allegretti, Cary Paine, Raimund Pichler, Lena Sibulesky, Scott W Biggins, Bryan Kestenbaum
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Abstract

Introduction: Cirrhosis affects all structures of the kidney, in particular the tubules, which are responsible for secretion of protein-bound metabolites and electrolyte/water homeostasis. Yet, prevailing assessments of kidney function focus solely on glomerular filtration rate (GFR), which may incompletely reflect these processes. We sought to characterize markers of tubular function, injury, and viability in patients with and without cirrhosis.

Methods: We recruited outpatients undergoing liver transplantation evaluation for a collection of plasma and 24-hour urine, matching by GFR to control participants without cirrhosis. We measured urinary kidney injury molecule-1, a marker of proximal tubular injury, as well as epidermal growth factor (EGF), a marker of viability necessary for tubular epithelial cell proliferation after injury. We also estimated secretory clearance by measuring several highly secreted endogenous metabolites in urine and plasma.

Results: We recruited 39 patients with cirrhosis (mean model for end-stage liver disease 17 ± 4, Child-Pugh 8 ± 2, estimated glomerular filtration rate 66 ± 20 mL/min/1.73 m 2 ) and 58 GFR-matched controls without cirrhosis (estimated glomerular filtration rate 66 ± 21 mL/min/1.73 m 2 ). Urinary kidney injury molecule-1 was 4.4-fold higher than controls (95% confidence interval: 2.9-6.5), and EGF averaged 7.41-fold higher than controls (95% confidence interval: 2.15-25.53). We found that of 8 solutes, 5 had significantly greater kidney clearance in cirrhosis (1.3-2.1-fold higher): indoxyl sulfate, p-cresol sulfate, pyridoxic acid, tiglylglycine, and xanthosine.

Discussion: Cirrhosis was characterized by molecular signs of tubular injury in stable outpatients without acute kidney injury, accompanied by largely preserved tubular secretory clearance and greater signs of tubular viability. Within the limitations of the study, this suggests a phenotype of chronic ischemic injury but with initial preservation of tubular function in cirrhosis.

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肝硬化患者近端小管分泌物清除率、损伤和肾脏活力
目的:肝硬化会影响肾脏的所有结构,尤其是肾小管,因为肾小管负责分泌与蛋白质结合的代谢产物和维持电解质/水的平衡。然而,目前对肾功能的评估仅关注肾小球滤过率(GFR),这可能无法完全反映这些过程。我们试图描述肝硬化和非肝硬化患者肾小管功能、损伤和存活能力的标志物:我们招募了正在接受肝移植评估的门诊患者,收集他们的血浆和 24 小时尿液,并通过 GFR 与未患肝硬化的对照参与者进行比对。我们测量了尿液中的肾损伤分子-1(KIM-1)和表皮生长因子(EGF),前者是近端肾小管损伤的标志物,后者是损伤后肾小管上皮细胞增殖所必需的活力标志物。我们还通过测量尿液和血浆中几种高度分泌的内源性代谢物来估计分泌清除率:我们招募了 39 名肝硬化患者(平均 MELD-Na 17±4,Child-Pugh 8±2,eGFR 66±20 ml/min/1.73m2)和 58 名无肝硬化的 GFR 匹配对照组(eGFR 66±21 ml/min/1.73m2)。尿 KIM-1 比对照组高 4.4 倍(95% CI:2.9-6.5),EGF 平均比对照组高 7.41 倍(95% CI:2.15-25.53)。我们发现,在 8 种溶质中,有 5 种物质在肝硬化时的肾脏清除率明显增高(高出 1.3-2.1 倍):硫酸吲哚啉、硫酸对甲酚、吡哆醇酸、替甘氨酸和黄嘌呤:肝硬化的特点是,在病情稳定的门诊患者中,肾小管损伤的分子标志没有急性肾损伤,同时肾小管分泌清除率基本保持不变,肾小管活力的标志较强。在研究的局限性范围内,这表明肝硬化患者存在慢性缺血性损伤的表型,但肾小管功能最初仍得以保留。
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来源期刊
Clinical and Translational Gastroenterology
Clinical and Translational Gastroenterology GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
7.00
自引率
0.00%
发文量
114
审稿时长
16 weeks
期刊介绍: Clinical and Translational Gastroenterology (CTG), published on behalf of the American College of Gastroenterology (ACG), is a peer-reviewed open access online journal dedicated to innovative clinical work in the field of gastroenterology and hepatology. CTG hopes to fulfill an unmet need for clinicians and scientists by welcoming novel cohort studies, early-phase clinical trials, qualitative and quantitative epidemiologic research, hypothesis-generating research, studies of novel mechanisms and methodologies including public health interventions, and integration of approaches across organs and disciplines. CTG also welcomes hypothesis-generating small studies, methods papers, and translational research with clear applications to human physiology or disease. Colon and small bowel Endoscopy and novel diagnostics Esophagus Functional GI disorders Immunology of the GI tract Microbiology of the GI tract Inflammatory bowel disease Pancreas and biliary tract Liver Pathology Pediatrics Preventative medicine Nutrition/obesity Stomach.
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