Estimated GFR in autosomal dominant polycystic kidney disease: errors of an unpredictable method

Abstract

Background Autosomal dominant polycystic kidney disease (ADPKD) causes about 10% of cases of end stage renal disease. Disease progression rate is heterogeneous. Tolvaptan is presently the only specific therapeutic option to slow kidney function decline in adults at risk of rapidly progressing ADPKD with chronic kidney disease (CKD) stages 1–4. Thus, a reliable evaluation of kidney function in patients with ADPKD is needed. Methods We evaluated the agreement between measured (mGFR) and estimated glomerular filtration rate (eGFR) by 61 formulas based on creatinine and/or cystatin-C (eGFR) in 226 ADPKD patients with diverse GFR values, from predialysis to glomerular hyperfiltration. Also, we evaluated whether incorrect categorization of CKD using eGFR may interfere with the indication and/or reimbursement of Tolvaptan treatment. Results No formula showed acceptable agreement with mGFR. Total Deviation Index averaged about 50% for eGFR based on creatinine and/or cystatin-C, indicating that 90% of the estimations of GFR showed bounds of error of 50% when compared with mGFR. In 1 out of 4 cases with mGFR < 30 ml/min, eGFR provided estimations above this threshold. Also, in half of the cases with mGFR between 30 and 40 ml/min, formulas estimated values < 30 ml/min. Conclusions The evaluation of renal function with formulas in ADPKD patients is unreliable. Extreme deviation from real renal function is quite frequent. The consequences of this error deserve attention, especially in rapid progressors who may benefit from starting treatment with tolvaptan and in whom specific GFR thresholds are needed for the indication or reimbursement. Whenever possible, mGFR is recommended. Graphic abstract

The error of estimated GFR in predialysis care

“…All these factors determine the known low correlation between these biomarkers and mGFR 36 which could be as large as 200% 13 . Unfortunately, this error has not been solved by the creation of formulas, since the correlation between eGFR and mGFR is as wide as that of the single markers and mGFR 16 , 36 , 37 (Fig. 1 ).…”

“…The lack of precision and accuracy of eGFR has been shown in different settings, such as CKD 15 , polycystic kidney disease 16 , renal transplantation 17 , living kidney donors 51 , children with CKD 52 etc. However, few studies analyzed the reliability of formulas in predialysis care.…”

Clinical Characteristics and Kidney Outcomes in Chinese Patients with Autosomal Dominant Polycystic Kidney Disease

“…Thus, a study with larger size and a longer follow-up would be required to assess 40% decline in eGFR among the different subclasses. Efforts have been done to assess the validity of various eGFR estimating equations to determine differences in the natural history of disease progression in ADPKD, 35 which we have not investigated in our study with a Chinese cohort. However, the evaluation of renal function with these formulas in patients with ADPKD is currently unreliable, and certainly none of these equations have been validated in Chinese.…”

Octreotide Lar in Patients with Autosomal Dominant Polycystic Kidney Disease: From Bench to A Novel Perspective of Therapy

“…30 The sample size however, was not adequately increased to obviate to this limitation that unavoidably increased random data fluctuations because of the large imprecision and inaccuracy of serum-creatinine-based GFR estimations; 52 a limitation that has been found to specifically apply also to patients with ADPKD. 53,54 Thus, DIPAK1 was underpowered (only 309 participants included as compared to the 1,455 of the Tolvaptan trial) for any considered outcome variable: 1. As for the detection of renal events, including the one pre-defined by the Authors, because the trial excluded per protocol specifically those patients who were at highest risk of events because of more severe renal insufficiency to start with.…”