Potential relationship between eGFR(cystatin C) /eGFR(creatinine) -ratio and glomerular basement membrane thickness in diabetic kidney disease.
Potential relationship between eGFR(cystatin C) /eGFR(creatinine) -ratio and glomerular basement membrane thickness in diabetic kidney disease.
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DOI：
10.14814/phy2.14939
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发表时间：
2021-07
影响因子：
2.5
通讯作者：
Christensson A
中科院分区：
文献类型：
--
作者：
Öberg CM;Lindström M;Grubb A;Christensson A
糖尿病肾病(DKD)是全球终末期肾脏疾病和肾脏替代治疗的主要原因。DKD的一个病理生理特征是肾小球基底膜(GBM)增厚，而微小病变病(MCD)则不存在这一特征。根据基本的运输生理学原理，较厚的基底膜将阻碍胱抑素C等中间分子的扩散，潜在地导致胱抑素C的GFR(EGFR)低于肌酐的GFR。在这里，我们测试了肾小球滤器增厚导致胱抑素C扩散长度增加和清除量降低的假设。29名肾活检诊断为DKD(n=17)或MCD(n=12)的患者被回顾性纳入研究。在活检标本的20个不同位置测量基底膜厚度，并从健康记录中检索血浆胱抑素C和肌酐水平。一个改进的双孔模型被用来模拟较厚的基底膜对肾小球水分和溶质运输的影响。患者的平均年龄为52岁，其中38%是女性。DKD组eGFRcystatin C/eGFRcreatinine-比值平均为74%，而MCD组为98%(P<0.001)。平均基底膜厚度与eGFRcystatin C/eGFRcreatinine比值呈显著负相关(Pearson‘s r=−0.61，p<0.01)。双孔模型预测DKD患者的eGFRcystatin C/eGFRcreatinine比率为78%。我们提供的临床和理论证据表明，在DKD中，肾小球滤器增厚，增加cystatin C的扩散长度，降低eGFRcystatin C/eGFRcreatinine比率。糖尿病和慢性肾脏疾病在全球范围内迅速增加。在糖尿病肾病中，我们发现eGFRcystatin C/eGFRcreatinine比值与肾小球基底膜厚度之间存在相关性。提示eGFRcystatin C/eGFRcreatinine/eGFRcystatin C/eGFR肌酐比值降低可能是糖尿病肾病的生物标志物。
Diabetic kidney disease (DKD) is a leading cause of end‐stage renal disease and renal replacement therapy worldwide. A pathophysiological hallmark of DKD is glomerular basal membrane (GBM) thickening, whereas this feature is absent in minimal change disease (MCD). According to fundamental transport physiological principles, a thicker GBM will impede the diffusion of middle‐molecules such as cystatin C, potentially leading to a lower estimated GFR (eGFR) from cystatin C compared to that of creatinine. Here we test the hypothesis that thickening of the glomerular filter leads to an increased diffusion length, and lower clearance, of cystatin C. Twenty‐nine patients with a kidney biopsy diagnosis of either DKD (n = 17) or MCD (n = 12) were retrospectively included in the study. GBM thickness was measured at 20 separate locations in the biopsy specimen and plasma levels of cystatin C and creatinine were retrieved from health records. A modified two‐pore model was used to simulate the effects of a thicker GBM on glomerular water and solute transport. The mean age of the patients was 52 years, and 38% were women. The mean eGFRcystatin C/eGFRcreatinine‐ratio was 74% in DKD compared to 98% in MCD (p < 0.001). Average GBM thickness was strongly inversely correlated to the eGFRcystatin C/eGFRcreatinine‐ratio (Pearson's r = −0.61, p < 0.01). Two‐pore modeling predicted a eGFRcystatin C/eGFRcreatinine‐ratio of 78% in DKD. We provide clinical and theoretical evidence suggesting that thickening of the glomerular filter, increasing the diffusion length of cystatin C, lowers the eGFRcystatin C/eGFRcreatinine‐ratio in DKD. Diabetes and chronic kidney disease is rapidly increasing globally. Here we found a correlation between eGFRcystatin C/eGFRcreatinine‐ratio and glomerular basement membrane thickness in diabetic kidney disease. The results imply that a reduced eGFRcystatin C/eGFRcreatinine‐ratio could be a possible biomarker for diabetic nephropathy.
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DOI：
10.1152/ajprenal.00313.2016
发表时间：
2016-11-01
期刊：
American journal of physiology. Renal physiology
影响因子：
--
作者：
Marshall CB
通讯作者：
Marshall CB
影响因子：
6.8
作者：
Nyman, Ulf;Grubb, Anders;Bjork, Jonas
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影响因子：
5.5
作者：
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Norden, Anthony G. W.
影响因子：
13.2
作者：
Dharnidharka, VR;Kwon, C;Stevens, G
通讯作者：
Stevens, G
影响因子：
2.5
作者：
Lubbad L;Öberg CM;Dhanasekaran S;Nemmar A;Hammad F;Pathan JY;Rippe B;Bakoush O
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Bakoush O