Glomerular tip lesion in minimal change nephropathy: a study of autopsies before 1950

The clinical significance of the glomerular tip lesion, characterized by podocyte prominence, capsular adhesion, and/or intracapillary foam cells at or adjacent to the urinary pole, remains unclear. It has been postulated that this lesion simply represents a response to heavy proteinuria, and cases of nephrotic syndrome with tip lesions, but no other histological abnormalities, may represent a form of minimal change nephropathy (MCN). However, others have reported that such lesions have a clinical course similar to that of primary focal segmental glomerulosclerosis (FSGS), and the tip lesion often is included among histological variants of FSGS. To determine whether tip lesions may be seen in MCN, we examined histological slides of kidneys from pre-1950 autopsies of patients with a diagnosis of lipoid nephrosis, a term that at that time comprised MCN and FSGS. Before the introduction of antibiotics and corticosteroid therapy, patients with nephrotic syndrome frequently died of sepsis. Eight such cases, with autopsies performed from 1924 to 1943, were identified in which no glomeruli had changes typical of classic FSGS or membranous nephropathy. More than 400 glomeruli were present in each case. Patient ages ranged from 3 to 45 years (six patients <11 years), all had marked edema (duration, 2 weeks to 21 months) and heavy proteinuria, and each died of sepsis and/or pneumonia (pneumococcal in six patients). Glomerular tip lesions were found in five of these eight cases (range, 3 to 26 lesions per case; 0.3% to 4.4% of total glomeruli present), with no predilection for the deep, middle, or superficial cortex. No tip lesions were seen in kidneys from autopsies of age-matched patients without a history of glomerular disease. These findings suggest that the glomerular tip lesion can occur in MCN and most likely represents a response to heavy proteinuria that is not disease specific.