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Cystatin C is a more Reliable Predictor of Chronic Kidney Disease Compared to Serum Creatinine in Patients with Cloacal and Anorectal Malformation
Brian A. VanderBrink, MD, Lori Hazelwood, RN, Pramod Reddy, MD, Shumyle Alam, MD.
Cincinnati Childrens Hospital Medical Center, Cincinnati, OH, USA.

BACKGROUND:
Chronic kidney disease (CKD) has been reported in a significant number of patients with anorectal malformation (ARM) with some patients progressing to end stage renal disease. Early diagnosis of CKD is important to minimize its effect and prevent progression. Accepted methods of assessing renal function include measurement of serum creatinine and using the Schwartz equation to calculate glomerular filtration rate (GFR). One limitation of using serum creatinine is that creatinine is not a constant and therefore may overestimate renal function. Cystatin C has been reported as an alternative method of calculating GFR because it is a product of nucleated cells, independent of muscle mass and may be more sensitive assessment tool. The purpose of this study was to determine how reliable calculated GFR using creatinine and the Schwartz Formula (sGFR) or Cystatin C (cGFR) are to measured nuclear GFR in a pediatric ARM population.
METHODS: A retrospective review of 110 patients with ARM and cloacal malformations seen at our institution with nuclear GFR measurement (nGFR) utilizing (99m)Tc- diethylenetriaminepentaacetic acid was performed. The nGFR result was compared to calculated GFR using the Schwartz equation (sGFR = [0.41 × Height] / Serum creatinine) and Cystatin C calculated GFR (cGFR) to determine the blood tests ability to predict nGFR and CKD Staging. Statistical differences between the two measures to predict nGFR was measured with Fisher's exact test.
RESULTS: A total of 128 nGFR measurements were available in the cohort. Median age of patietns was 7 years. Twenty patients (18%) had a solitary kidney. Median nGFR was 105 mL/min/1.73 m2(range 44-211). Classifying the nGFR measurements according to CKD staging criteria resulted in CKD Stage 1 (n=64), Stage 2 (n=39) and Stage 3 (n=9). Glomerular hyperfiltration (nGFR <150 mL/min/1.73 m2) was seen in 13% (n=16) of measurements. Comparison of the ability of either cGFR or sGFR to predict CKD staging by nGFR is shown below:
CKD Stage derived from cGFR vs nGFR n=93
Cyst C predicted same CKD stage compared to nGFRCyst C overpredicted CKD stage compared to nGFRCyst C underpredicted CKD stage compared to nGFR
All stages of CKD59% (n=55)*30% (n=28)11% (n=10)
CKD Stage ≥249% (n=24)#37% (n=18)14% (n=7)

Comparison of CKD Staging derived from sGFR vs nGFR n=95
sGFR predicted same CKD stage compared to nGFRsGFR overpredicted CKD stage compared to nGFRsGFR underpredicted CKD stage compared to nGFR
All stages of CKD49% (n=47)14% (n=13)37% (n=35)
CKD Stage ≥226% (n=11)16% (n=7)58% (n=25)

* - Comparison between cGFR and eGFR’s ability to predict equivalent nGFR
* (p=0.19)
# (p=0.03)
Using the Bland and Altman analysis to test agreement between the sGFR and nGFR showed considerable bias, with a mean difference of +22%. In contrast, the Bland and Altman analysis applied on the cGFR showed less bias with a mean difference to be -6%.
CONCLUSIONS: CKD Stage 2 or higher was prevelant in 27% of the patients in our ARM cohort based upon nGFR assessment. In our series, cGFR had greater correlation with nGFR measurement compared to sGFR in patients with greater degrees of renal dysfunction. We recommend Cystatin C as adjunct to the care of ARM patients as a method to identify renal injury prior to onset of clinical or radiographic signs.


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