White blood cell fractions correlate with lesions of diabetic kidney disease and predict loss of kidney function in Type 2 diabetes

Wheelock, Kevin M.; Saulnier, Pierre Jean; Tanamas, Stephanie K.; Vijayakumar, Pavithra; Weil, E. Jennifer; Looker, Helen C.; Hanson, Robert L.; Lemley, Kevin V.; Yee, Berne; Knowler, William C.; Hadjadj, Samy; Najafian, Behzad; Mauer, Michael; Nelson, Robert G.

doi:10.1093/ndt/gfx231

Cited by 24 publications

(30 citation statements)

References 45 publications

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“…The association of NLR with decreased eGFR might reflect the relationship of IFTA severity with worse damage. However, the level of NLR was dissociated from the glomerular lesions, which is consistent with the results of Wheelock et al 18 investigating the associations of NLR with morphometric parameters in 108 Pima Indians with DN. It is noteworthy that the median of eGFR at baseline in this study was 56.53 mL/min per 1.73 m 2 , and 86.7% (214) kidney biopsy reports showed scores of IFTA were 1-2, suggesting that the pathologic changes in DN was highly heterogeneous.…”

Section: Discussionsupporting

confidence: 91%

“…Additionally, a recent study in 2017 has shown that NLR was inversely correlated with percentage of normally fenestrated endothelial cells and could predict the renal function loss in 108 Pima Indians and 941 Europeans with T2DM. 18 In our study, the NLR was significantly associated with IFTA and renal dysfunction. These findings suggested that the differences in NLR levels might reflect the inflammatory condition and result in the underlying renal injury, which finally leaded to the decline of e-GFR in DN.…”

Section: Discussionsupporting

confidence: 54%

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Effects of neutrophil–lymphocyte ratio on renal function and histologic lesions in patients with diabetic nephropathy

Zhang

Wang

et al. 2019

Nephrology

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Aim Chronic low‐grade inflammation related to diabetic nephropathy (DN) may affect the serum neutrophil–lymphocyte ratio (NLR). We aimed to examine the cross‐sectional relationships of NLR with renal function and structural lesions of DN in patients with type 2 diabetes mellitus (T2DM). Methods The study retrospectively included 247 patients with T2DM and biopsy‐proven DN. The severity of different pathological lesions was evaluated based on the criteria of Renal Pathology Society. The patients were divided into two groups based on the median (2.42) of NLR level, group 1: NLR < 2.42 (n = 122) and group 2: NLR ≥ 2.42 (n = 125). Renal dysfunction was defined by estimated glomerular filtration rate less than 60 mL/min per 1.73 m2. The influence of NLR on renal dysfunction was evaluated using logistic regression analysis. Results The spearman's rank‐correlation test indicted that NLR was positively correlated with interstitial fibrosis and tubular atrophy (r = 0.170, P = 0.007) and serum fibrinogen (r = 0.261, P < 0.001), whereas negatively related with estimated glomerular filtration rate (r = −0.233, P < 0.001). However, the NLR level demonstrated no association with glomerular lesions, interstitial inflammation and arteriolar hyalinosis. A multivariate logistic regression analysis showed that higher level of NLR (≥2.42) was significantly associated with renal dysfunction when adjusting for some important baseline clinical and pathological variables (odds ratio, 2.46; 95% confidence interval, 1.21–4.97; P = 0.012). Conclusion Increased NLR affects renal function and histologic lesions in patients with T2DM and may be an important factor for the progression of DN.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 54%

Effects of neutrophil–lymphocyte ratio on renal function and histologic lesions in patients with diabetic nephropathy

Zhang

Wang

et al. 2019

Nephrology

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“…These activated cells in turn produce pro-inflammatory cytokines that promote local tissue damage 67–69 . A recent study in Pima Indians with type 2 diabetes found that lower lymphocyte and higher eosinophil and neutrophil fractions are also associated with early kidney structural damage, including increased GBM width and loss of glomerular endothelial cell fenestrations 66 . Examination of the kidney tissue revealed a higher proportion of WBC’s in the peripheral glomerular capillaries of participants with more advanced structural lesions, with frequent projections from the white cells touching endothelial cells within the glomerular capillary, suggesting signaling between these cells (Figure 3).…”

Section: Biomarkers Of Kidney Structurementioning

confidence: 98%

“…White blood cell counts and fractions are biomarkers of inflammation, which are linked to diabetes and its vascular complications 63–65 , including a greater risk of ≥40% loss of GFR in a European type 2 diabetes cohort 66 . These findings are thought to be related, at least in part, to activation of white cells by advanced glycation end-products.…”

Section: Biomarkers Of Kidney Structurementioning

confidence: 99%

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Role of Kidney Biopsies for Biomarker Discovery in Diabetic Kidney Disease

Looker

Mauer

Nelson

2018

Advances in Chronic Kidney Disease

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Although estimated glomerular filtration rate and albuminuria are well-established biomarkers of diabetic kidney disease (DKD), additional biomarkers are needed, especially for the early stages of the disease when both albuminuria and estimated glomerular filtration rate may still be in the normal range and are less helpful for identifying those at risk of progression. Traditional biomarker studies for early DKD are challenging because of a lack of good early clinical end points, and most rely on changes in existing imprecise biomarkers to assess the value of new biomarkers. There are well-characterized changes in kidney structure, however, that are highly correlated with kidney function, always precede the clinical findings of DKD and, at preclinical stages, predict DKD progression. These structural parameters may thus serve as clinically useful end points for identifying new biomarkers of early DKD. In addition, investigators are analyzing tissue transcriptomic data to identify pathways involved in early DKD which may have associated candidate biomarkers measurable in blood or urine, and differentially expressed microRNAs and epigenetic modifications in kidney tissue are beginning to yield important observations which may be useful in identifying new clinically useful biomarkers. This review examines the emerging literature on the use of kidney tissue in biomarker discovery in DKD.

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Screening of Diabetic Nephropathy Progression-Related Genes Based on Weighted Gene Co-expression Network Analysis

Tao

2022

Biochem Genet

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White blood cell fractions correlate with lesions of diabetic kidney disease and predict loss of kidney function in Type 2 diabetes

Abstract: WBC fractions associate with morphometric lesions of DKD and predict RFL in individuals with Type 2 diabetes.

Cited by 24 publications

References 45 publications

Effects of neutrophil–lymphocyte ratio on renal function and histologic lesions in patients with diabetic nephropathy

Effects of neutrophil–lymphocyte ratio on renal function and histologic lesions in patients with diabetic nephropathy

Role of Kidney Biopsies for Biomarker Discovery in Diabetic Kidney Disease

Screening of Diabetic Nephropathy Progression-Related Genes Based on Weighted Gene Co-expression Network Analysis

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