ESPN 54th Annual Meeting

ESPN 2022


 
EGFR EQUATIONS IN PEDIATRIC ADPKD PATIENTS: ONE OR THE OTHER?
Schellekens Pieter 1 Marcelien Verjans 1 Dachy Angélique 2 Peter Janssens 3 De Rechter Stéphanie 1 Breysem Luc 1 Allegaert Karel 1 Bammens Bert 1 Vennekens Rudi 4 Vermeersch Pieter 1 Pottel Hans 4 Mekahli Djalila 1

1- KU Leuven/ UZ Leuven
2- KU Leuven / CHU Liège
3- VUB
4- KU Leuven
 
Introduction:

Pediatric ADPKD could benefit from novel disease altering therapies. However, the lack of sensitive and validated endpoints in this population renders clinical trials very challenging. We aimed to evaluate methods for the estimated glomerular filtration rate (eGFR) in order to identify the most accurate method for this population.

 

Material and methods:

Serum creatinine (SCr) and serum Cystatin C (SCysC)  were measured in a large cohort of genotyped ADPKD children with long-term follow-up. Commonly used equations for eGFR were compared  for their relative performance, using the reference intervals for healthy children.

 

Results:

We included 68 genetically confirmed ADPKD children (sex ratio 1:1) with a mean age of 10.2 years (min-max: 0-23 years) and with a mean time of follow-up of 3.6 years (1-8 years). SCr was mostly within the reference interval, regardless age and sex. The revised Schwartz formula (CKiD) showed a highly significant and clinically important decline in eGFR with aging (-3.31ml/min/1.73m2/year,  p<0.0001). The recently updated equation by the Schwartz group (CKiDU25) showed a smaller (-0.90 mL/min/1.73m²/year) but significant (p=0.001) decline in eGFR with aging and also showed a significant unexplainable sex difference  (p<0.0001). SCr normalized for Q and the related FAS-SCr did not show a clear age or sex dependency (table 1). Finally, CysC based and combined equations were independent of age and sex in this paediatric ADPKD cohort.

 

Conclusions:

The CKiD equation, the most widely used method to calculate eGFR in children, and the CKiDU25 were associated with unexpected age and sex differences in the young ADPKD population. In contrast, FAS-SCr, FAS-CysC and the combined FAS equation which are all normalized by Q, showed an age and sex independency and might therefore be more reliable to monitor kidney function in this population. This finding could help future design of the upcoming clinical trials.

 

Table 1. Comparison of the different eGFR equations and SCr & SCysC normalized by Q. A p-value of < 0.0023 was considered significant to account for multiple testing

Equation

Gender effect
mean value F/M (p-value)

Age effect
(mL/min/1.73m²/year)

133.9 < Fr < 160.1 (mL/min/1.73m²)

Fr > 160.1 (mL/min/1.73m²)

CKiD

124.9 / 127.4 (NS)

-3.31 (p < 0.0001)

23.6%

12.0%

CKiDU25

110.0 / 124.7 (< 0.0001)

-0.90 (p = 0.0011)

14.6%

5.5%

FAS-Age

119.7 / 125.5 (p = 0.0275)

-0.61 (p = 0.0266)

17.5%

6.6%

FAS-Height

122.2 / 131.7 (p = 0.0020)

-0.98 (p = 0.0005)

20.4%

9.1%

EKFC

107.2 / 111.6 (p = 0.0008)

-0.27 (p = 0.0004)

1.1%

0.0%

LMR18

101.9 / 107.4 (p = 0.0002)

-0.45 (p = 0.0004)

0.4%

0.0%

CKDEPI40

105.3 / 112.0 (p = 0.0001)

-0.08 (NS)

0.4%

0.0%

FAS-CysC

104.7 / 101.7 (NS)

0.096 (NS)

1.8%

0.4%

Fas-Combined

112.3 / 114.0 (NS)

-0.2872 (NS)

6.18%

1.09%

Equation

Gender effect
mean F/M (p-value)

Age effect
(mL/min/1.73m²/year)

Fr < 0.80

(mg/dL/year)

Fr < 0.67

(mg/dL/year)

SCr/Q

0.93 / 0.88 (p = 0.0068)

+0.0044 (p = 0.0296)

17.1%

6.9%

Equation

Gender effect
mean F/M (p-value)

Age effect
(mL/min/1.73m²/year)

Fr < 0.80

(mg/L/year)

Fr < 0.67

(mg/L/year)

CysC/Q’

1.06 / 1.07 (NS)

-0.001 (NS)

1.8%

1.5%

 F: female, M: male, Fr: fraction, NS: not statistically significant.