The gold standard for the assessment of diabetic nephropathy in children is still the quantitative analysis of microalbumin through 24-hr urine collection. However, many factors such as exercise, hypertension, hyperglycemia can influence daily urinary albumin excretion (12
). Day-to-day variation according to the volume of collected urine can hinder the diagnosis of diabetic nephropathy (4
). Discovery of microalbuminuria through 24-hr urine collection can also be erroneous because of improper collection, which commonly happens with children and adolescents. Therefore, a test using timed urine collection has been suggested to be repeated three times to confirm microalbuminuria, but this is very hard to apply to children.
Recent studies have demonstrated good correlation between spot urine ACR and 24-hr urinary albumin excretion (6
). Spot urine ACR was thought to be more accurate because it eliminates the possibility of improper collection. The method using spot urine samples may ensure better compliance than timed urine test, especially in childhood patients. Furthermore, the spot urine ACR has the advantage of being less affected by urine volume because it is a ratio of two measured substances (14
Nevertheless, few studies have reported the efficacy and effectiveness of spot urine ACR compared with creatinine clearance through 24-hr urine collection in childhood patients with diabetes. The present study showed that spot urine ACR was closely correlated with 24-hr urine albumin excretion and creatinine clearance in children and adolescents with diabetes. However, we can not definitively support that spot urine ACR should be used in place of 24-hr urine collected miacroalbumin due to the small study population. We do, however, feel that spot urine ACR would be useful as a screening tool when timed urine collection is diffcult to obtain in out-patient settings.
The use of endogenous markers to evaluate renal function is also important in the evaluation of diabetic nephropathy. Various low molecular proteins, such as cysC, β2
-microglobulin, and collagen type IV, instead of serum creatinine have been suggested as useful endogenous markers for evaluating renal function (8
). Among these, previous studies have demonstrated that cysC might be a more sensitive indicator of GFR than serum creatinine, but there have been few studies on cysC as an endogenous marker reflecting GFR in children with diabetic nephropathy (15
In the present study, the level of serum cysC, but not serum creatinine, was significantly different between the normoalbuminuria group and the microalbuminuria group. Estimated GFR according to the Schwartz and MDRD II formulas did not demonstrate any difference between the two groups, although creatinine clearance was significantly lower in the microalbuminuria group. It is thought that serum creatinine is unable to reflect the early signs of decreased renal function in childhood diabetic patients, while serum cysC can. However, we cannot say that serum cysC might be surrogate marker of diabetic nephropathy, because diabetic patients have the increased possibility of decreased renal function due to causes other than diabetic nephropathy. Nevertheless, cysC based GFR is suggested to be a useful method for estimating renal function (18
). Recently, Schwartz et al. proposed an updated Schwartz formula using cysC (19
). We can estimate that cysC based GFR may be a better method than creatinine based GFR on the findings in this study.
Our studies have some limitations in that we did not perform the measurement of exogenous substances such as insulin, 51Cr
-diethylenetriaminepentaacetic acid, iohexol (20
) or DTPA renogram, which has been suggested as the most accurate method to evaluate renal function. However, DTPA renogram or other accurate measurements based on the measurement of exogenous substances are hard to perform, especially in childhood diabetic patients. More studies with a large sample population are needed to confirm that spot urine ACR can replace 24-hr urine microalbumin in childhood diabetes.
There was a discrepancy between eGFR and creatinine clearance through 24-hr urine collection in this study. For this we considered two possibilities. First, the discrepancy may implicate that urine collection is inaccurate. Second, the MDRD formula within the normal range of creatinine might not reflect accurate renal function.
Nevertheless, to the best of our knowledge, the present study is the first to simultaneously check both serum cysC and spot urine ACR in children and adolescents with diabetes, and our study demonstrated that spot urine ACR might be a more accurate, convenient, and effective indicator for the detection of microalbuminuria instead of 24-hr urine microalbumin in diabetic children. CysC based GFR may be a more accurate method than creatinine based GFR to evaluate renal function.