Prognostic Value of Tubulointerstitial Lesions, Urinary N-Acetyl-β-D-Glucosaminidase, and Urinary β2-Microglobulin in Patients with Type 2 Diabetes and Biopsy–Proven Diabetic Nephropathy

Mise, Kazuyuki; Hoshino, Junichi; Ueno, Toshiharu; Hazue, Ryo; Hasegawa, Jumpei; Sekine, Akinari; Sumida, Keiichi; Hiramatsu, Rikako; Hasegawa, Eiko; Yamanouchi, Masayuki; Hayami, Noriko; Suwabe, Tatsuya; Sawa, Naoki; Fujii, Takeshi; Hara, Shigeko; Ohashi, Kenichi; Takaichi, Kenmei; Ubara, Yoshifumi

doi:10.2215/cjn.04980515

Cited by 100 publications

(93 citation statements)

References 41 publications

(44 reference statements)

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“…The Lee [28] and Oxford [6] classifications were used to score all-round pathological severity in IgA nephropathy. Glomerular sclerosis index [29][30][31] and interstitial fibrosis and tubular atrophy (IFTA) score [32,33] were used to determine glomerular and tubulointerstitial scarring. Parameters for specific lesions included mesangial proliferation, segment damage, glomerular sclerosis, inflammatory cell infiltration, interstitial fibrosis, tubular atrophy, vessel wall thickening, and hyaline degeneration and were semi-quantified using the Katafuchi's scoring system [34].…”

Section: Pathological Scoringmentioning

confidence: 99%

Serum miR-192 Is Related to Tubulointerstitial Lesion and Short-Term Disease Progression in IgA Nephropathy

Fan

Zhu

et al. 2019

Nephron

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Background/Aims: Clinical manifestation and renal histology serve as the current “gold standard” for evaluation of renal lesions in IgA nephropathy. MiR-192 is regarded as a potential noninvasive biomarker for kidney disease. We sought to elucidate a relationship between intrarenal, serum, and urinary exosomal miR-192 with renal lesions and disease progression in IgA nephropathy. Methods: Serum and urinary exosomal miR-192 were detected and correlated with clinical and pathological parameters from consecutive IgA nephropathy patients (n = 50) and healthy control patients (n = 25). Patients then received a follow-up of 24 months after biopsy. Disease progression was defined as a 40% reduction in estimated glomerular filtration rate. Expression of miR-192 was quantified by Taqman RT-PCR. Intrarenal miR-192 was detected in 8 IgA nephropathy patients and 4 matched patients receiving kidney nephrectomy as controls via in situ hybridization. TGF-β1 and E-cadherin expression in renal tissue was evaluated using immunohistochemistry. Results: Intrarenal miR-192 was correlated with serum miR-192 (r = 0.690, p = 0.013). Both intrarenal and serum miR-192 decreased in IgA nephropathy patients and were correlated with estimated glomerular filtration ratio. Patients with lower intrarenal and serum miR-192 levels had a higher interstitial fibrosis and tubular atrophy score, more severe lesions in tubular atrophy, and interstitial inflammation. Renal E-cadherin expression was correlated (r = 0.484, p = 0.004) and TGF-β1 was inversely correlated (r = –0.527, p < 0.001) with serum miR-192 in IgA. Patients with higher serum miR-192 had a lower disease progression rate over the course of 2 years (0 vs. 16%, p = 0.028). No correlation was found in urinary exosomal miR-192 with the clinical and pathological parameters mentioned earlier. Conclusions: Lower serum miR-192 in IgA nephropathy patients indicates lower intrarenal miR-192 expression, more severe tubular atrophy, interstitial inflammation, and fibrotic tendency (with higher TGF-β and E-cadherin in renal miR-192). IgA nephropathy patients with higher serum miR-192 are less likely to have renal function decline over the course of 2 years.

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Section: Pathological Scoringmentioning

confidence: 99%

Serum miR-192 Is Related to Tubulointerstitial Lesion and Short-Term Disease Progression in IgA Nephropathy

Fan

Zhu

et al. 2019

Nephron

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“…90 Interestingly, tubular biomarkers have shown that tubular dysfunction can be present early in DN, occasionally preceding glomerular injury. This observation underscores the fact that tubular biomarkers are early predictors of DN compared to microalbuminuria and other glomerular biomarkers.…”

Section: Tubular Biomarkersmentioning

confidence: 99%

The role of novel biomarkers in predicting diabetic nephropathy: a review

Uwaezuoke

2017

IJNRD

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Diabetic nephropathy (DN) is one of the microvascular complications of the kidney arising commonly from type 1 diabetes mellitus (T1DM), and occasionally from type 2 diabetes mellitus (T2DM). Microalbuminuria serves as an early indicator of DN risk and a predictor of its progression as well as cardiovascular disease risk in both T1DM and T2DM. Although microalbuminuria remains the gold standard for early detection of DN, it is not a sufficiently accurate predictor of DN risk due to some limitations. Thus, there is a paradigm shift to novel biomarkers which would help to predict DN risk early enough and possibly prevent the occurrence of end-stage kidney disease. These new biomarkers have been broadly classified into glomerular biomarkers, tubular biomarkers, biomarkers of inflammation, biomarkers of oxidative stress, and miscellaneous biomarkers which also include podocyte biomarkers, some of which are also considered as tubular and glomerular biomarkers. Although they are potentially useful for the evaluation of DN, current data still preclude the routine clinical use of majority of them. However, their validation using high-quality and large longitudinal studies is of paramount importance, as well as the subsequent development of a biomarker panel which can reliably predict and evaluate this renal microvascular disease. This paper aims to review the predictive role of these biomarkers in the evaluation of DN.

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“…Specifically, in our analysis of the prognostic value of KIM-1 and NAG for ESRD, the study sample was comprised of patients with diabetic kidney disease (DKD) and a general community-based population which may not have been sufficiently representative of CKD. There was also a notable variation in the measurement of kidney function among studies, including: the use of GFR measured by non-radioactive iothalamate in one study[13]; and use of the eGFR calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation in three studies[12, 16, 17]and using the Modification of Diet in Renal Disease (MDRD) study equation in six. It is important to note that of the three studies evaluating the incidence of CKD stage 3, none used the CKD-EPI equation whose accuracy has been shown to be superior to that of the MDRD equation in patients with early CKD stages[1].…”

Section: Discussionmentioning

confidence: 99%

“…It is also noteworthy that three different definitions of CKD stage 3 were used, either with or without restriction of minimal decline. Moreover, two studies having a shorter follow-up period, used ‘halving of the eGFR as a surrogate endpoint for the incidence of ESRD in their analysis[14, 16]. The validity of the surrogate endpoint has recently come under scrutiny.…”

Section: Discussionmentioning

confidence: 99%

Are Urinary Tubular Injury Markers Useful in Chronic Kidney Disease? A Systematic Review and Meta Analysis

Zhou

Pan

et al. 2016

PLoS ONE

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BackgroundAdverse outcome of chronic kidney disease, such as end stage renal disease, is a significant burden on personal health and healthcare costs. Urinary tubular injury markers, such as NGAL, KIM-1 and NAG, could provide useful prognostic value for the early identification of high-risk patients. However, discrepancies between recent large prospective studies have resulted in controversy regarding the potential clinical value of these markers. Therefore, we conducted the first meta-analysis to provide a more persuasive argument to this debate.MethodsIn the current meta-analysis, based on ten prospective studies involving 29366 participants, we evaluated the role of urinary tubular injury markers (NGAL, KIM-1 and NAG) in predicting clinical outcomes including CKD stage 3, end stage renal disease and mortality. The prognostic values of these biomarkers were estimated using relative risks and 95% confidence interval in adjusted models. All risk estimates were normalized to those of 1 standard deviation increase in log-scale concentrations to minimize heterogeneity. Fixed-effects models were adopted to combine risk estimates. The quality of the research and between-study heterogeneity were evaluated. The level of research evidence was identified according to the GRADE profiler.ResultsuNGAL was identified as an independent risk predictor of ESRD (pooled adjusted relative risk: 1.40[1.21 to 1.61], p<0.001) and of overall mortality (pooled adjusted relative risk: 1.10[1.03 to 1.18], p = 0.001) in patients with chronic kidney disease. A borderline significance of uKIM-1 in predicting CKD stage 3 independently in the community-based population was observed (pooled adjusted relative risk: 1.13[1.00 to 1.27], p = 0.057). Only the prognostic value of uNGAL for ESRD was supported by a grade B level of evidence.ConclusionThe concentration of uNGAL can be used in practice as an independent predictor of end stage renal disease among patients with chronic kidney disease, but it may be not useful in predicting disease progression to CKD stage 3 among community-based population.

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Prognostic Value of Tubulointerstitial Lesions, Urinary N-Acetyl-β-D-Glucosaminidase, and Urinary β2-Microglobulin in Patients with Type 2 Diabetes and Biopsy–Proven Diabetic Nephropathy

Cited by 100 publications

References 41 publications

Serum miR-192 Is Related to Tubulointerstitial Lesion and Short-Term Disease Progression in IgA Nephropathy

Serum miR-192 Is Related to Tubulointerstitial Lesion and Short-Term Disease Progression in IgA Nephropathy

The role of novel biomarkers in predicting diabetic nephropathy: a review

Are Urinary Tubular Injury Markers Useful in Chronic Kidney Disease? A Systematic Review and Meta Analysis

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