Kung Vanderlene L, Giannini Gabriel, Nast Cynthia C
Department of Pathology and Laboratory Medicine, Oregon Health and Science University, Portland, OR, USA.
Department of Pathology, Yosemite Pathology Medical Group, Modesto, CA, USA.
Glomerular Dis. 2024 Mar 15;4(1):74-83. doi: 10.1159/000537977. eCollection 2024 Jan-Dec.
Type 2 diabetes mellitus (DM) and diabetic kidney disease are increasing. Hepatitis C infection (HCV) occurs in 1% of the world population and can induce several kidney diseases. DM prevalence is increased in individuals with HCV; however, kidney diseases in those with both DM and HCV have not been assessed. Direct-acting antiviral agents (DAAs) became available for HCV treatment in 2014; it is unknown if DAAs altered the spectrum of kidney disease in patients with DM and HCV.
Case review identifying patients with kidney biopsy and clinical history of DM and HCV between 2009-2013 (pre-DAA) and 2016-2020 (post-DAA), excluding kidney transplant, hepatitis B, HIV, and inadequate biopsy, identified 245 biopsies. Biopsies were evaluated for diabetic glomerulosclerosis (DGS) class, global and focal segmental glomerulosclerosis (FSGS), other glomerular diseases, interstitial fibrosis/tubular atrophy (IFTA), interstitial nephritis, acute tubular injury and degree of arterial and arteriolar sclerosis. Kidney disease differences in pre-DAA versus post-DAA eras and in mild versus severe DGS were assessed by χ and Fisher's exact tests.
The most common non-DGS lesions were non-collapsing FSGS (41%), HCV-related IgM dominant immune complex glomerulonephritis (IgM-ICGN, 18%), IgA nephropathy (9%), and membranoproliferative glomerulonephritis (MPGN, 7%). Collapsing FSGS was more common pre-DAA versus post-DAA (8% vs. 1%, = 0.03). Biopsies from patients with HCV and DM were reduced in post-DAA (0.7%) versus pre-DAA (1.3%) ( < 0.0001). Post-DAA there were less MPGN (2% vs. 10%, = 0.02) and more advanced DGS (85% vs. 61%, = 0.0002), non-collapsing FSGS (57% vs. 31%, < 0.0001), IFTA (2.0 vs. 1.6, = 0.0002), and vascular sclerosis (2.1 vs. 1.6, < 0.0001).
Post-DAA there were reduced biopsies and MPGN, with more severe DGS class, non-collapsing FSGS, IFTA, and chronic vascular changes. This suggests a modulating effect of DAAs on HCV-related kidney pathology with DM and chronic changes driving indications for kidney biopsy.
2型糖尿病（DM）和糖尿病肾病的发病率正在上升。丙型肝炎病毒（HCV）感染在全球1%的人口中出现，可引发多种肾脏疾病。HCV感染者中DM患病率增加；然而，同时患有DM和HCV者的肾脏疾病尚未得到评估。直接抗病毒药物（DAAs）于2014年开始用于HCV治疗；尚不清楚DAAs是否改变了DM和HCV患者的肾脏疾病谱。
病例回顾确定了2009 - 2013年（DAAs应用前）和2016 - 2020年（DAAs应用后）期间有肾脏活检及DM和HCV临床病史的患者，排除肾移植、乙型肝炎、HIV及活检不充分者，共确定245例活检病例。对活检组织进行糖尿病性肾小球硬化（DGS）分级、全球性和局灶节段性肾小球硬化（FSGS）、其他肾小球疾病、间质纤维化/肾小管萎缩（IFTA）、间质性肾炎、急性肾小管损伤以及动脉和小动脉硬化程度的评估。通过χ检验和Fisher精确检验评估DAAs应用前与应用后时代以及轻度与重度DGS患者的肾脏疾病差异。
最常见的非DGS病变为非塌陷性FSGS（41%）、HCV相关IgM为主的免疫复合物性肾小球肾炎（IgM - ICGN，18%）、IgA肾病（9%）和膜增生性肾小球肾炎（MPGN，7%）。塌陷性FSGS在DAAs应用前比应用后更常见（8%对1%，P = 0.03）。HCV和DM患者的活检病例在DAAs应用后（0.7%）比应用前（1.3%）减少（P < 0.0001）。DAAs应用后MPGN较少（2%对10%，P = 0.02），而更严重的DGS（85%对61%，P = 0.0002）、非塌陷性FSGS（57%对31%，P < 0.0001）以及IFTA（2.0对1.6，P = 0.0002）和血管硬化（2.1对1.6，P < 0.0001）增多。
DAAs应用后活检病例和MPGN减少，DGS分级更严重，非塌陷性FSGS、IFTA及慢性血管改变增多。这表明DAAs对DM合并HCV相关肾脏病理有调节作用，且DM和慢性改变促使了肾脏活检的指征。
