Low agreement between various eGFR formulae in pediatric and young adult ADPKD patients

Schellekens, Pieter; Verjans, Marcelien; Janssens, Peter; Dachy, Angélique; Rechter, Stéphanie De; Breysem, Luc; Allegaert, Karel; Bammens, Bert; Vennekens, Rudi; Vermeersch, Pieter; Pottel, Hans; Mekahli, Djalila

doi:10.1007/s00467-023-05926-w

Cited by 6 publications

(2 citation statements)

References 38 publications

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“…Decreased kidney function is a strong indicator of rapidly progressive disease, but in most pediatric patients, function is preserved, which limits the predictive utility of this risk factor [ 38 ]. Further, the applicability of the most commonly used equation for estimating eGFR in children (CKiD) has been questioned for the ADPKD population [ 39 ]. Although PKD1 truncating and nontruncating variants are known to be associated with greater risk of rapidly progressive ADPKD, genetic determinants are too complex to accurately predict disease course [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Estimating risk of rapid disease progression in pediatric patients with autosomal dominant polycystic kidney disease: a randomized trial of tolvaptan

Mekahli,

Guay-Woodford,

Cadnapaphornchai

et al. 2023

Pediatr Nephrol

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Background Tolvaptan preserves kidney function in adults with autosomal dominant polycystic kidney disease (ADPKD) at elevated risk of rapid progression. A trial (NCT02964273) evaluated tolvaptan safety and pharmacodynamics in children (5–17 years). However, progression risk was not part of study eligibility criteria due to lack of validated criteria for risk assessment in children. As risk estimation is important to guide clinical management, baseline characteristics of the study participants were retrospectively evaluated to determine whether risk of rapid disease progression in pediatric ADPKD can be assessed and to identify parameters relevant for risk estimation. Methods Four academic pediatric nephrologists reviewed baseline data and rated participant risk from 1 (lowest) to 5 (highest) based on clinical judgement and the literature. Three primary reviewers independently scored all cases, with each case reviewed by two primary reviewers. For cases with discordant ratings (≥ 2-point difference), the fourth reviewer provided a secondary rating blinded to the primary evaluations. Study participants with discordant ratings and/or for whom data were lacking were later discussed to clarify parameters relevant to risk estimation. Results Of 90 evaluable subjects, primary reviews of 69 (77%) were concordant. The proportion considered at risk of rapid progression (final mean rating ≥ 3.5) by age group was: 15–17 years, 27/34 (79%); 12– < 15, 9/32 (28%); 4– < 12, 8/24 (33%). The panelists agreed on characteristics important for risk determination: age, kidney imaging, kidney function, blood pressure, urine protein, and genetics. Conclusions High ratings concordance and agreement among reviewers on relevant clinical characteristics support the feasibility of pediatric risk assessment. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

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Section: Discussionmentioning

confidence: 99%

Estimating risk of rapid disease progression in pediatric patients with autosomal dominant polycystic kidney disease: a randomized trial of tolvaptan

Mekahli,

Guay-Woodford,

Cadnapaphornchai

et al. 2023

Pediatr Nephrol

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“…[5,8,9] Low agreement between the pediatric and adult formulae has also been shown in patients with autosomal dominant polycystic kidney disease. [10] One of the reasons for the poor performance of the CKD-Epi formula in people younger than 30 years of age, is the fact that less than 30 of the 3,995 people from three areas of the world were in that age group. Sharma et al demonstrated that the diagnostic performance of any eGFR formula is always best in the GFR range where most of the patients were included.…”

Section: Introductionmentioning

confidence: 99%

Limitations of U25 CKiD and CKD-EPI eGFR formulae in patients 2-20 years of age with measured GFR>60 mL/min/1.73 m2 – A cross-sectional study

Filler

Ahmad

Bhayana

et al. 2023

Preprint

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Background: When applying Pierce U25 formula for estimating glomerular filtration rate (eGFR), we observed a higher proportion of eGFR<90 mL/min/1.73 m2 (chronic kidney disease=CKD stage 2). We compared agreement and accuracy of the Pierce U25 (ages 2-25), Pottel (ages 2-100), and CKD-EPI (ages 18-100) formulae to GFR measurements. Methods: Post-hoc analysis of the three eGFRs compared to 367 99m technetium-diethylene-triamine penta-acetic acid (99Tc DTPA) GFR measurements (240 patients) using 3 sampling points and Brockner/Mørtensen correction (body surface area calculation based on ideal weight) on simultaneous serum creatinine and cystatin C measurements. Results: Overall, the U25 formula performed well with a Spearman r of 0.8102 (95% confidence interval 0.7706 to 0.8435, p<0.0001) while diagnostic accuracy was low in patients with normal mGFR. The U25 formula reclassified 29.5% of patients with normal mGFR as CKD stage 2; whereas the average of the modified Schwartz formula based on serum creatinine and the Filler formula based on cystatin C, only over diagnosed CKD stage 2 in 8.5%, 24.5% within 10% and 62.7% within 30%. We therefore combined both. The average Schwartz/Filler eGFR had 36.5% of results within 10%, 84.7% within 30%, and normal mGFR accuracy was 26.8%, 63.9% for 10% and 30%, respectively, outperforming the CKD-EPI and Pottel formulae. Interpretation: The Pierce U25 formula results correlated well with mGFR<75 mL/min/1.73m2. Over the entire GFR range, accuracy was better for patients with a higher mGFR, when averaging the combined Schwartz/Filler formulae. More work is needed to prospectively confirm our findings in other centers.

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Limitations of U25 CKiD and CKD-EPI eGFR formulae in patients 2–20 years of age with measured GFR > 60 mL/min/1.73 m2—a cross-sectional study

Filler,

Ahmad,

Bhayana

et al. 2023

Pediatr Nephrol

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Low agreement between various eGFR formulae in pediatric and young adult ADPKD patients

Cited by 6 publications

References 38 publications

Estimating risk of rapid disease progression in pediatric patients with autosomal dominant polycystic kidney disease: a randomized trial of tolvaptan

Estimating risk of rapid disease progression in pediatric patients with autosomal dominant polycystic kidney disease: a randomized trial of tolvaptan

Limitations of U25 CKiD and CKD-EPI eGFR formulae in patients 2-20 years of age with measured GFR>60 mL/min/1.73 m2 – A cross-sectional study

Limitations of U25 CKiD and CKD-EPI eGFR formulae in patients 2–20 years of age with measured GFR > 60 mL/min/1.73 m2—a cross-sectional study

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Low agreement between various eGFR formulae in pediatric and young adult ADPKD patients

Cited by 6 publications

References 38 publications

Estimating risk of rapid disease progression in pediatric patients with autosomal dominant polycystic kidney disease: a randomized trial of tolvaptan

Estimating risk of rapid disease progression in pediatric patients with autosomal dominant polycystic kidney disease: a randomized trial of tolvaptan

Limitations of U25 CKiD and CKD-EPI eGFR formulae in patients 2-20 years of age with measured GFR&gt;60 mL/min/1.73 m2 – A cross-sectional study

Limitations of U25 CKiD and CKD-EPI eGFR formulae in patients 2–20 years of age with measured GFR > 60 mL/min/1.73 m2—a cross-sectional study

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Limitations of U25 CKiD and CKD-EPI eGFR formulae in patients 2-20 years of age with measured GFR>60 mL/min/1.73 m2 – A cross-sectional study