Renal, Electrolyte, and Hypertension Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
J Am Soc Nephrol. 2021 Nov;32(11):2863-2876. doi: 10.1681/ASN.2021010044. Epub 2021 Aug 4.
Patients with diabetic or hypertensive kidney disease rarely undergo kidney biopsy because nephrologists commonly believe that biopsy-related risk outweighs the potential benefits of obtaining histologic information to guide clinical decisions. Although kidney function is acutely regulated, histologic changes such as interstitial fibrosis, tubular atrophy, and glomerulosclerosis may represent chronic kidney damage, and thus might provide additional information about disease severity. However, whether histologic analysis provides information complementary to clinically used kidney function measurements, such as eGFR and proteinuria, is unclear.
We performed a standardized semiquantitative histologic analysis of 859 nephrectomies obtained from individuals with or without diabetes mellitus or hypertension and varying degrees of kidney dysfunction. Changes in glomeruli, tubules, interstitium, and the vasculature were scored using 17 descriptive parameters in a standardized manner. We used multivariable linear and logistic regression analyses and unbiased, hierarchical clustering to assess associations between histologic alterations and clinical variables.
At CKD stages 3-5, eGFR correlates reasonably well with the degree of glomerulosclerosis and interstitial fibrosis and tubular atrophy (IFTA). In patients with CKD stages 1-2, the degree of histologic damage was highly variable and eGFR poorly estimated the degree of damage. Individuals with diabetes mellitus, hypertension, or Black race had significantly more glomerulosclerosis and IFTA, at the same eGFR level. Inclusion of glomerulosclerosis improved the kidney function decline estimation, even at early disease stages.
Histologic analysis is an important complementary method for kidney disease evaluation, especially at early disease stages. Some individuals present with relatively severe structural damage despite preserved eGFR.
患有糖尿病或高血压肾病的患者很少进行肾活检,因为肾病学家通常认为活检相关的风险大于获得组织学信息以指导临床决策的潜在益处。尽管肾功能是急性调节的,但间质纤维化、肾小管萎缩和肾小球硬化等组织学变化可能代表慢性肾脏损伤,因此可能提供有关疾病严重程度的额外信息。然而,组织学分析是否提供与临床使用的肾功能测量(如 eGFR 和蛋白尿)互补的信息尚不清楚。
我们对 859 例来自患有或不患有糖尿病或高血压以及不同程度肾功能障碍的个体的肾切除术进行了标准化半定量组织学分析。使用 17 个描述性参数以标准化方式对肾小球、肾小管、间质和脉管系统的变化进行评分。我们使用多变量线性和逻辑回归分析以及无偏、分层聚类来评估组织学改变与临床变量之间的关联。
在 CKD 3-5 期,eGFR 与肾小球硬化和间质纤维化和肾小管萎缩(IFTA)的程度相当相关。在 CKD 1-2 期的患者中,组织学损伤的程度变化很大,eGFR 对损伤程度的估计很差。在相同的 eGFR 水平下,患有糖尿病、高血压或黑人种族的个体有明显更多的肾小球硬化和 IFTA。包括肾小球硬化在内的分析改善了肾功能下降的估计,即使在早期疾病阶段也是如此。
组织学分析是肾脏疾病评估的重要补充方法,特别是在早期疾病阶段。尽管 eGFR 保持不变,但一些个体仍存在相对严重的结构损伤。