Urinary Vacuolar Casts Are a Unique Type of Casts in Advanced Proteinuric Glomerulopathies

Abstract

Key Points Vacuolar casts are a distinct type of casts identifiable by urinary sediment microscopy.Identification of urinary vacuolar casts is associated with the presence of an advanced and severe form of a proteinuric glomerular disease. Background Identification of casts by urinary sediment microscopy is a valuable diagnostic clinical tool for the evaluation of kidney disease. Vacuolar casts are an unrecognized unique type of casts characterized by the presence of nonpolarizable, clear vesicles of various sizes contained within a cast matrix, different from lipid casts, erythrocyte casts, or any other casts. We aimed to gain better understanding of the clinical relevance of these casts by establishing a multinational collaborative group to search for cases in which vacuolar casts were identified. Methods Leveraging an educational social media platform, we conducted a multinational observational study extracting cases of patients who presented with urinary vacuolar casts during evaluation for impaired kidney function. Parameters assessed included degree of proteinuria and kidney dysfunction, clinical and histopathological diagnosis, and severity of renal parenchymal scarring on biopsy. A control group of patients without vacuolar casts was included for comparison. Results Forty-six patients with urinary vacuolar casts were compiled from six countries. Nephrotic range proteinuria (82%), glomerular etiology (98%), and advanced CKD stage (62% 3B-5) were salient features. Histopathological diagnosis was available in 26 (57%) patients. Combining clinical and pathological diagnoses, diabetic nephropathy (48%), arterionephrosclerosis (30%), podocytopathies (15%), and proliferative glomerulonephritides (15%) accounted for most patients. Vacuolization of tubules or podocytes was present in 61% of the specimens. When compared with patients with histopathological diagnoses in which vacuolar casts were not found (n=186), patients with vacuolar casts more frequently had a glomerular etiology (100% versus 71%, P = 0.002), had greater proteinuria (median urine protein-to-creatinine 10.3 versus 2.2 g/g, P < 0.001), and had greater proportion of patients with ≥30% glomerular obsolescence (46% versus 20%, P = 0.003). Conclusions Thus, urinary vacuolar casts are strongly associated with advanced glomerulopathies with severe proteinuria. Future studies should examine their origin, composition, and prognostic value. Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/K360/2024_01_26_KID0000000000000346.mp3