Elsevier

Journal of Diabetes and its Complications

Volume 28, Issue 5, September–October 2014, Pages 667-673
Journal of Diabetes and its Complications

A practical method to measure GFR in people with type 1 diabetes

https://doi.org/10.1016/j.jdiacomp.2014.06.001Get rights and content

Abstract

Aims

Improved early diagnostic methods are needed to identify risk for kidney disease in people with type 1 diabetes. We hypothesized that glomerular filtration rate (GFR) measured by iohexol clearance in dried blood spots (DBS) on filter paper would be comparable to plasma (gold-standard) and superior to estimated GFR (eGFR) and, second, that adjustment for ambient blood glucose would improve accuracy and precision of GFR measurement.

Methods

GFR was measured by iohexol clearance in plasma, DBS, and as estimated by the CKD-Epidemiology Collaboration equations in 15 adults with type 1 diabetes at two visits, one euglycemic and one hyperglycemic.

Results

GFR measured by DBS was more comparable and less biased than GFR cystatin C, serum creatinine, and both combined. GFR was higher during hyperglycemia. Correction for between visit glycemia statistically significantly reduced bias and mean squared error for GFR measured by DBS as compared to gold-standard during euglycemia.

Conclusions

Iohexol clearance measured with DBS performed better than eGFR methods. Correction for ambient blood glucose improved precision and accuracy of GFR measurement. This method is more convenient than the gold-standard GFR method and may improve screening and diagnostic capabilities in people with type 1 diabetes, especially when GFR is > 60 ml/min/1.73 m2.

Introduction

Although effective treatment exists to prevent or slow decline in renal function (de Boer, Sun, et al., 2011, Marshall, 2012), diabetic kidney disease continues to cause morbidity and mortality in type 1 diabetes (de Boer, Rue, et al., 2011, Maahs and Rewers, 2006, Rosolowsky et al., 2011). Improved early diagnostic methods are needed to better identify those at risk to progress to diabetic nephropathy (Cherney and Maahs, 2013, Maahs, 2012). One barrier in renal research is a clinically easy and accurate method to assess glomerular filtration rate (GFR), especially when GFR is > 60 ml/min/1.73 m2 (Hsu, Chertow, & Curhan, 2002) and estimating equations are inaccurate (Stevens, Coresh, Greene, & Levey, 2006). A recent DCCT-EDIC paper states that changes in eGFR over a clinically relevant period may not reflect changes in measured GFR (de Boer et al., 2014). Improved methods should be less cumbersome than current methods to measure GFR and provide more accurate and precise assessment of GFR than estimates from equations (eGFR), especially when GFR is > 60 ml/min/1.73 m2. Ideally, such a method could be applied to detect early change in GFR when therapeutic intervention could have the greatest impact (Bjornstad, Cherney and Maahs, 2014, Maahs et al., 2013).

Multiple factors can influence GFR measurements. In people with type 1 diabetes, an additional challenge in measuring GFR is the acute effect of blood glucose. Hyperglycemia is known to affect renal hemodynamics and increase GFR by up to 20 ml/min/1.73 m2 (Cherney et al., 2010, Christiansen et al., 1981, De et al., 1993, Dullaart et al., 1990, Jones et al., 1992, Skott et al., 1991, Wiseman et al., 1985, Wiseman et al., 1987). However, the effect of blood glucose is not generally accounted for when measuring GFR in people with type 1 diabetes (Amin et al., 2005, Caramori et al., 1999, Chiarelli et al., 1995, Dahlquist et al., 2001, Lervang et al., 1988, Lervang et al., 1992, Magee et al., 2009, Mogensen, 1986, Steinke et al., 2005, Yip et al., 1996, Zerbini et al., 2006). Potentially, failure to maintain euglycemia, or possibly account for hyperglycemia, could result in differential misclassification and bias in measurement (and estimation) of GFR hindering the ability to determine early changes in GFR within an individual (Bjornstad, McQueen, et al., 2014, Cherney and Maahs, 2013, Maahs, 2012).

In this study, we adapt a simple approach to measure GFR, requiring an injection of iohexol with samples obtained by finger prick (Mafham et al., 2007, Niculescu-Duvaz et al., 2006). We compare measures of GFR by iohexol clearance using dried blood spots (DBS) on filter paper to plasma (gold-standard) in adults with type 1 diabetes. We hypothesized that GFR measured by iohexol clearance using DBS would be comparable to plasma and superior to GFR estimated by serum creatinine and cystatin C based GFR equations (eGFR) (Inker et al., 2012). Second, we hypothesized that accounting for hyperglycemia would improve precision and accuracy of GFR measurement (when compared to GFR measured during euglycemia) by iohexol clearance in plasma and DBS and as estimated by the CKD-EPI equations.

Section snippets

Materials and methods

Inclusion criteria were age 18–60 years, provider diagnosis of type 1 diabetes, ability to fast for the study and follow dietary advice. Exclusion criteria were non type 1 diabetes, a history of eGFR < 60 ml/min/1.73 m2 or microalbuminuria or greater, allergies to seafood or iodine, hypertension (defined as use of BP lowering medications [including renin angiotensin aldosterone system blockers] or BP > 130/80 mmHg), smoking, and caffeine intake < 8 h prior to study. Fifteen participants completed two

Results

Characteristics of participants were as follows: age 29 ± 12 years, 53% male, 93% non-Hispanic White, diabetes duration 19 ± 9 years, HbA1c = 7.6 ± 1.8%, BP = 116/73 mmHg, ACR 52 ± 85 mg/g. Blood glucose was similarly stabilized during the first 3 h of the study (Supplemental Fig. 1, 8 AM–11 AM) for V1 compared to V2 (median and IQR: 97 (85–130 mg/dl) v. 97 (82–120 mg/dl), p = 0.35) and hours 1 through 3 (Supplemental Fig. 1, 9 AM–11 AM, 92 [79–118 mg/dl] v. 90 [76–109 mg/dl], p = 0.27). In contrast, blood glucose was

Discussion

GFR measured in DBS is comparable to the gold standard method of GFR plasma iohexol and more accurate, precise and less biased than eGFR measures. A major barrier in diabetic kidney disease research is a clinically easy means to accurately and precisely assess GFR, especially when GFR is > 60 ml/min/1.73 m2 and estimating equations are inaccurate (Stevens et al., 2006). By that point half of renal function may already be lost (Maahs, 2012). GFR-DBS offers a more convenient approach to quantify GFR

Author contributions

DMM researched, wrote, contributed to discussion, and reviewed/edited the manuscript; LB researched, contributed to discussion, and reviewed/edited the manuscript; BK researched, contributed to discussion, and reviewed/edited the manuscript; SE researched, contributed to discussion, and reviewed/edited the manuscript; LP researched, contributed to discussion, and reviewed/edited the manuscript; KM researched, contributed to discussion, and reviewed/edited the manuscript; AB researched,

Acknowledgments

Support for this study was provided by an Innovative Grant from the Juvenile Diabetes Research Foundation5-2013-122.

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    Disclosure: The authors have no conflicts of interest to disclose.

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