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Early Glomerular Filtration Rate Loss as a Marker of Diabetic Nephropathy


Table 1: Comparison of Formulas for Estimating Glomerular Filtration Rate MDRD Study Formula


GFR Parameter


Adjusts for Age, Gender, Race Accuracy:


GFR <60 ml/min/1.73 m2 GFR >60 ml/min/1.73 m2


Creatinine* Yes


CKD-EPI Formula Creatinine*


Yes Satisfactory Accurate Underestimates GFR27 Generally more accurate than the


MDRD formula, except in the elderly or those with extremes of body mass28 May not exhibit better performance than the MDRD formula in diabetes30


GFR gradient


Underestimates GFR gradient if initial eGFR >90 ml/min/1.73 m2


Current evidence suggests that it will Accurately reflects early iGFR underestimate GFR gradient if initial eGFR >90 ml/min/1.73 m2


gradients in type 1 diabetes39


Underestimates GFR in obesity Influenced by extra-renal factors Assays require standardisation


CKD-EPI = Chronic Kidney Disease Epidemiology; GFR = glomerular filtration rate; eGFR = estimated GFR; iGFR = isotopic GFR; MDRD = Modification of Diet in Renal Disease. * eGFR derived from creatinine-based formulas can be influenced by variations in muscle mass, renal tubular creatinine secretion, meat intake and ethnicity.


Figure 3: Glomerular Filtration Rate Decline in Hyperfiltering and Normofiltering Patients with Type 1 Diabetes Group A


100 110 120 130 140 150 160 170 180


80 90


70


Mean baseline and final glomerular filtration rate (GFR) in hyperfiltration (red symbols) and normofiltration (blue symbols) subgroups from 12 observational studies of GFR trajectory over 3–18 years in type 1 diabetes patients. Baseline GFR is joined to final GFR by a solid line to form a ‘dumb-bell’ symbol for both hyperfiltration and normofiltration groups. Group A = prospective studies; group B = retrospective studies. The six studies in group B show data categorised retrospectively according to progression or non-progression of albumin excretion rate (AER) to at least microalbuminuria. Note that GFR was not shown to decline below 60 ml/min/1.73 m2 al, 2010.35


References.40–50


glucose control arm showed a lower rate of developing serum creatinine >2.0 mg/dl (0.7 % in the intensive arm versus 2.8 % in the control arm).24


all participants, and is therefore useful not only in clinical trials but also in individual subjects at a clinical level.


A more recent study from the DCCT/EDIC research group has shown that the long-term risk of developing an eGFR <60 ml/min/1.73 m2 over a median follow-up period of 22 years was lower with early intensive glucose control compared with conventional glucose control.25


Glomerular Filtration Rate Slopes in Early Diabetic Nephropathy


There are two main ways of assessing GFR loss in DN. The first is by assessing the proportion of subjects progressing to a predefined endpoint, such as the doubling of serum creatinine (equivalent to the halving of GFR), or reaching a specific stage, such as eGFR <60 ml/min/1.73 m2. While these endpoints are useful in established nephropathy, they focus on fast trackers and do not allow the assessment of early GFR loss in the study group as a whole. By contrast, the assessment of eGFR gradients allows monitoring of GFR profiles in


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As shown in Table 1, the Modification of Diet in Renal Disease (MDRD) study and the Chronic Kidney Disease Epidemiology (CKD-EPI)26 formulas both provide satisfactory estimates of GFR at low GFR levels. However, the MDRD formula seriously underestimates GFR in the normal range in subjects with type 2 diabetes.27,28


It follows that


the MDRD formula will underestimate GFR gradients during long-term assessment of individuals with an initial GFR >90 ml/min/1.73 m2. Because of the above considerations, the CKD-EPI formula has been proposed as a more sensitive method of assessing early GFR loss in diabetes. However, both formulas underestimate GFR in the hyperfiltration range (>130 ml/min/1.73 m2). Furthermore, there is increasing evidence showing that the CKD-EPI equation is less accurate in patients with type 2 diabetes than in healthy individuals, and does not exhibit better performance than the MDRD formula for estimating GFR in diabetes.29,30


29 Group B


100 110 120 130 140 150 160 170 180


70 80 90


Cystatin C-Based Formula Cystatin C


No Accurate More accurate than the MDRD formula


in any of the studies. Source: reproduced with permission from Jerums et


GFR (ml/min/1.73m2)


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