Plasma biomarkers improve prediction of diabetic kidney disease in adults with type 1 diabetes over a 12-year follow-up: CACTI study

Bjornstad, Petter; Pyle, Laura; Cherney, David Z.I.; Johnson, Richard J.; Sippl, Rachel; Wong, Randy; Rewers, Marian; Snell‐Bergeon, Janet K.

doi:10.1093/ndt/gfx255

Cited by 20 publications

(24 citation statements)

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“…Similar associations have also been demonstrated with plasma OPN and B2M . In a prior study of patients with T1D, elevations in UMOD conferred a protective effect in the development of DKD, whereas in our study patients with DKD did have lower UMOD concentrations as compared to controls, although UMOD levels were statistically similar among DKD resistors and participants with DKD.…”

Section: Discussionsupporting

confidence: 85%

“…Plasma NGAL has been shown to be elevated in DKD related to both type 1 and type 2 diabetes and has been associated with the development of elevated albumin excretion, rapid decline in GFR and, in some studies, with progression of DKD . Similar associations have also been demonstrated with plasma OPN and B2M . In a prior study of patients with T1D, elevations in UMOD conferred a protective effect in the development of DKD, whereas in our study patients with DKD did have lower UMOD concentrations as compared to controls, although UMOD levels were statistically similar among DKD resistors and participants with DKD.…”

Section: Discussionsupporting

confidence: 66%

“…We and others have demonstrated that these kidney injury biomarkers relate to acute and chronic tubular and glomerular injury in patients with diabetes . In fact, we demonstrated that elevated NGAL confers greater odds of elevated albumin excretion and impaired GFR over 12 years in adults with T1D . While diabetic tubulopathy is thought to precede glomerulopathy, the interplay between tubular and glomerular disease in T1D remains poorly understood …”

Section: Introductionmentioning

confidence: 76%

“…Average intra‐ and inter‐assay precision for the biomarkers was 3% and 8%, respectively. These kits were originally designed by MSD to monitor drug‐induced kidney toxicity; however, they have since been successfully applied to predict DKD and non‐DKD …”

Section: Methodsmentioning

confidence: 99%

“…5 In fact, we demonstrated that elevated NGAL confers greater odds of elevated albumin excretion and impaired GFR over 12 years in adults with T1D. 6 While diabetic tubulopathy is thought to precede glomerulopathy, the interplay between tubular and glomerular disease in T1D remains poorly understood. 7,8 Epidemiologic studies, however, are limited by estimations of glomerular filtration rate (GFR) and are without data on other parameters of intrarenal haemodynamic function, including effective renal plasma flow (ERPF), renal blood flow (RBF), renal vascular resistance (RVR), filtration fraction (FF), glomerular pressure (P GLO ), afferent (R A ) and efferent (R E ) arteriolar resistances.…”

mentioning

confidence: 90%

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The relationships between markers of tubular injury and intrarenal haemodynamic function in adults with and without type 1 diabetes: Results from the Canadian Study of Longevity in Type 1 Diabetes

Bjornstad

Singh

Snell‐Bergeon

et al. 2018

Diabetes Obesity Metabolism

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Objective Our aim was to define the relationships between plasma biomarkers of kidney injury and intrarenal haemodynamic function (glomerular filtration rate [GFR], effective renal plasma flow [ERPF], renal vascular resistance [RVR]) in adults with type 1 diabetes (T1D). Methods The study sample comprised patients with longstanding T1D (duration ≥50 years), among whom 44 were diabetic kidney disease (DKD) resistors (eGFR >60 mL/min/1.73 m2 and <30 mg/d urine albumin excretion) and 22 had DKD, in addition to 73 control participants. GFRINULIN and ERPFPAH were measured, RVR was calculated, and afferent (RA)/efferent (RE) areteriolar resistances were derived from Gomez equations. Plasma neutrophil gelatinase‐associated lipocalin (NGAL), β2 microglobulin (B2M), osteopontin (OPN) and uromodulin (UMOD) were measured using immunoassay kits from Meso Scale Discovery. Results Plasma NGAL, B2M and OPN were higher and UMOD was lower in DKD patients vs DKD resistors and non‐diabetic controls. In participants with T1D, plasma NGAL inversely correlated with GFR (r = −0.33; P = 0.006) and ERPF (r = −0.34; P = 0.006), and correlated positively with RA (r = 0.26; P = 0.03) and RVR (r = 0.31; P = 0.01). In participants without T1D, NGAL and B2M inversely correlated with GFR (NGAL r = −0.18; P = 0.13 and B2M r = −0.49; P < 0.0001) and with ERPF (NGAL r = −0.19; P = 0.1 and B2M r = −0.42; P = 0.0003), and correlated positively with RA (NGAL r = 0.19; P = 0.10 and B2M r = 0.3; P = 0.01) and with RVR (NGAL r = 0.20; P = 0.09 and B2M r = 0.34; P = 0.003). Differences were significant after adjusting for age, sex, HbA1c, SBP and LDL. There were statistical interactions between T1D status, B2M and intrarenal haemodynamic function (P < 0.05). Conclusions Elevated NGAL relates to intrarenal haemodynamic dysfunction in T1D, whereas elevated NGAL and B2M relate to intrarenal haemodynamic dysfunction in adults without T1D. These data may define a diabetes‐specific interplay between tubular injury and intrarenal haemodynamic dysfunction.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 76%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 90%

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The relationships between markers of tubular injury and intrarenal haemodynamic function in adults with and without type 1 diabetes: Results from the Canadian Study of Longevity in Type 1 Diabetes

Bjornstad

Singh

Snell‐Bergeon

et al. 2018

Diabetes Obesity Metabolism

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Review of potential biomarkers of inflammation and kidney injury in diabetic kidney disease

Khanijou

Zafari

Coughlan

et al. 2022

Diabetes Metabolism Res

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Diabetic kidney disease is expected to increase rapidly over the coming decades with rising prevalence of diabetes worldwide. Current measures of kidney function based on albuminuria and estimated glomerular filtration rate do not accurately stratify and predict individuals at risk of declining kidney function in diabetes. As a result, recent attention has turned towards identifying and assessing the utility of biomarkers in diabetic kidney disease. This review explores the current literature on biomarkers of inflammation and kidney injury focussing on studies of single or multiple biomarkers between January 2014 and February 2020. Multiple serum and urine biomarkers of inflammation and kidney injury have demonstrated significant association with the development and progression of diabetic kidney disease. Of the inflammatory biomarkers, tumour necrosis factor receptor-1 and -2 were frequently studied and appear to hold most promise as markers of diabetic kidney disease.With regards to kidney injury biomarkers, studies have largely targeted markers of tubular injury of which kidney injury molecule-1, beta-2-microglobulin and neutrophil gelatinase-associated lipocalin emerged as potential candidates. Finally, the use of a small panel of selective biomarkers appears to perform just as well as a panel of multiple biomarkers for predicting kidney function decline.

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Screening, Early Diagnosis, Genetic Markers and Predictors of Progression

Tuazon

Cho

2022

Diabetes and Kidney Disease

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Plasma biomarkers improve prediction of diabetic kidney disease in adults with type 1 diabetes over a 12-year follow-up: CACTI study

Abstract: Plasma kidney injury biomarkers can help predict development of DKD in T1D.

Cited by 20 publications

References 37 publications

The relationships between markers of tubular injury and intrarenal haemodynamic function in adults with and without type 1 diabetes: Results from the Canadian Study of Longevity in Type 1 Diabetes

The relationships between markers of tubular injury and intrarenal haemodynamic function in adults with and without type 1 diabetes: Results from the Canadian Study of Longevity in Type 1 Diabetes

Review of potential biomarkers of inflammation and kidney injury in diabetic kidney disease

Screening, Early Diagnosis, Genetic Markers and Predictors of Progression

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