Figure 4.

Cost analysis. (A) Modeled diagnostic trajectories for patients with suspected genetic kidney diseases based on clinical categories. In the late WES model, the patient undergoes investigations included in tiers 1, 2, and 3 until reaching a final diagnosis. The diagnostic workup is based on current guidelines, available literature, and local clinical practice for each clinical category. Tier 1 includes baseline investigations that allow clinicians to suspect inherited nephropathies as belonging to broad clinical categories (podocytopathies, collagenopathies, tubulopathies, ciliopathies, syndromic CKD, metabolic kidney disorders). Tier 2 and 3 include increasingly complex and/or expensive investigations. Tier 3 includes first-choice genetic testing for each clinical category, excluding WES. Genomic investigations were modeled according to literature, current guidelines, and the genetic architecture of each clinical category of kidney diseases. In the late WES model, if the diagnostic workup (including genomic and nongenomic investigations of tiers 2 and 3) turns out negative, the patient undergoes WES. In the early WES model, the patient goes through only tier 1 and then directly to WES. In both models, patients are selected with the clinical criteria adopted in this study. (B) Comparison between mean costs per diagnosis of the late WES model versus the early WES model in the study population. We excluded patients belonging to the CKDu category because of the lack of guidelines allowing us to model the diagnostic trajectory for this clinical condition. (C) Strategy applied for real-life costs analysis and comparison with the early WES model. Real-life diagnostic pathway included all the real costs retrieved from the clinical history of a subgroup of patients (n=66) with all available clinical information and recorded data in the administrative database. The clinical categories (podocytopathies, collagenopathies, tubulopathies, ciliopathies, syndromic CKD, metabolic kidney disorders) were equally represented. Costs of the real-life diagnostic pathway were compared with those derived from the hypothetical application of the early WES model to the same patients. (D) Comparison between mean costs per diagnosis of the real-life diagnostic pathway versus the early WES model in 66 patients. Icons included in Panels A and C are from the website Noun Project (thenounproject.com) and the credits go to their creators. CKDu, CKD of unknown origin; CAKUT, congenital anomalies of the kidney and urinary tract; WES, whole-exome sequencing.