A composite of urinary biomarkers for differentiating between tubulointerstitial inflammation and interstitial fibrosis/tubular atrophy in kidney allografts

Abstract

Backgrounds/AimsCompared with a single urinary biomarker, a composite of multiple urinary biomarkers may be more helpful for differentiating tubulointerstitial inflammation from interstitial fibrosis/tubular atrophy (IFTA) in kidney allografts.MethodsIn this cross-sectional cohort study, we collected urine samples from 115 patients with for-cause biopsy, 53 patients with stable allografts, and 50 living kidney donors. We measured the urinary levels of transglutaminase 2 (TG2), syndecan-4 (SDC4), alpha 1 microglobulin (A1M), interferon-inducible protein 10 (IP-10), interleukin 6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1).ResultsThe for-cause biopsy group showed significantly higher levels of logeTG2/Cr, logeA1M/Cr, logeIL-6/Cr, and logeMCP-1/Cr compared with other groups. In the for-cause biopsy group, logeTG2/Cr level was positively correlated with the severity of IFTA. After adjusting for age, sex, body mass index, diabetes, hypertension, cardiovascular disease, and the interval between kidney transplant and biopsy, TG2 and the interval between transplant and biopsy were significantly correlated variables for the severity of IFTA. Regarding tubulointerstitial inflammation, Body mass index, TG2, SDC4, and IP-10 were positively-correlated variables, and MCP-1 and the interval between transplant and biopsy were negatively-correlated variables.ConclusionsOur results show that post-transplant urinary levels of TG2, SDC4, MCP-1 and IP-10 may be a useful biomarker for tubulointerstitial inflammation and IFTA.

Urinary transglutaminase 2 as a potent biomarker to predict interstitial fibrosis and tubular atrophy of kidney allograft during early posttransplant period in deceased donor kidney transplantation

“…Richardson et al [27] analyzed HSPG localization in corneal fibroblasts and revealed that the nuclear localization of HSPG core proteins was greater in fibronectin cells and proposed that fibronectin-mediated nuclear localization of HSPG might play an important role in inducing biological responses and regulating nuclear function. We have previously reported composition of urinary TG2, SDC4, IP-10, and MCP-1 as potent biomarkers to distinguish IFTA from tubulointerstitial inflammation in kidney transplant recipients [28]. To our knowledge, this is the first study to verify the value of urinary TG2 as a biomarker for allograft fibrosis and IFTA in deceased donor kidney transplant patients.…”

Tubular biomarkers and histology in lupus nephritis

“…The aim of our study was to identify indicators of tubular damage in stable LN patients and to correlate them with kidney biopsy findings. We selected a panel of tubular biomarkers that have been correlated with interstitial fibrosis and cortical interstitial inflammation in different CKD populations: α1‐mcg, β2‐mcg, UMOD, NGAL, KIM‐1, MCP‐1, and uDKK3 19–24 …”

“…We selected a panel of tubular biomarkers that have been correlated with interstitial fibrosis and cortical interstitial inflammation in different CKD populations: α1-mcg, β2-mcg, UMOD, NGAL, KIM-1, MCP-1, and uDKK3. [19][20][21][22][23][24] 2 | ME THODS…”

An Indole-2-Carboxamide Derivative, LG4, Alleviates Diabetic Kidney Disease Through Inhibiting MAPK-Mediated Inflammatory Responses

“…[2][3][4] Meanwhile, glomerular dysfunction and morphological changes that lead to subsequent development of glomerulosclerosis and nephron dropout will be seen with or without tubular atrophy, tubulointerstitial fibrosis and renal arteriolar hyalinosis. [5][6][7][8] Although the progression of DKD could be slowed with tight glycemic control and antihypertensive/lipid-lowering therapies, these interventions do not prevent the progress of DKD to end stage of renal disease (ESRD) or renal failure. 9 Chronic inflammation in the kidney plays a key role in the development and progression of DKD.…”