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

The acute encephalopathy occurring in children in Muzaffarpur, India, also recognised in other litchi-cultivating areas of India, Bangladesh, Vietnam and China, had previously been linked to litchi consumption. Recently, it has been identified as hypoglycaemic encephalopathy of an unusual aetiology with three key factors: undernutrition, prolonged fasting and litchi consumption. A second set of investigators has independently reconfirmed the diagnosis and the three-factor aetiology. Skipping the evening meal with an intake of large amounts of litchi in undernourished children is causative. Early-morning hypoglycaemia with an inadequate glycogen store leads to initiation of gluconeogenesis and fatty acid β-oxidation, but methylene cyclopropyl alanine and glycine present in the litchi aril block the fatty acid β-oxidation cycle. The outcomes are uncorrected hypoglycaemia and encephalopathy due to the entry of metabolic intermediates that cross the blood-brain barrier and affect neuronal function. Suggested measures include early 10% dextrose infusion. Awareness about the disease is of prime importance. The diagnosis and aetiopathogenesis are still under question from a part of the scientific community. This review was undertaken to present a comprehensive view of hypoglycaemic encephalopathy and to remove some of the lingering doubts.