COMPARATIVE STUDY
JOURNAL ARTICLE

Glomerular tip lesion: a distinct entity within the minimal change disease/focal segmental glomerulosclerosis spectrum

M Barry Stokes, Glen S Markowitz, Julie Lin, Anthony M Valeri, Vivette D D'Agati
Kidney International 2004, 65 (5): 1690-702
15086908

BACKGROUND: The glomerular tip lesion (GTL) is a distinctive but controversial histopathologic lesion occurring in patients with idiopathic nephrotic syndrome. The relationship of GTL to minimal change disease (MCD) and idiopathic focal segmental glomerulosclerosis (FSGS) has been disputed.

METHODS: In order to define the clinical features and natural history of GTL, we retrospectively reviewed the presenting clinical features, biopsy findings and outcome of 47 cases. Presenting clinical features of GTL were compared to those of controls with MCD (N= 61) or idiopathic FSGS (N= 50).

RESULTS: The cohort of GTL consisted of 45 adults and two children (mean age 47.5 years; range 12 to 79 years), including 76.6% Caucasians and 53% males. At presentation, 93.6% of patients had edema, 89.1% had nephrotic syndrome (mean urine protein 8.31 g, mean serum albumin 2.27 g/dL, and mean cholesterol 340.6 mg/dL), and 34.8% had renal insufficiency. Mean time from onset of renal disease to biopsy was 2.4 months. At biopsy, glomerular segmental lesions included GTL alone in 26%, GTL and peripheral lesions in 6%, GTL and indeterminate lesions in 36%, and GTL with peripheral and indeterminate lesions in 32%. No initial biopsy contained perihilar sclerosis and most (81%) segmental lesions were cellular. Follow-up data were available in 29 patients, of whom 21 received steroids alone and eight received sequential therapy with steroids and a cytotoxic agent. At a mean follow-up of 21.5 months, 58.6% of patients achieved complete remission of nephrotic syndrome, 13.8% had partial remission, and 27.6% had persistent nephrotic proteinuria. Only one patient progressed to end-stage renal disease (ESRD). Predictors of nonremission included severity of proteinuria at presentation and % peripheral lesions. When compared to controls with MCD and idiopathic FSGS, GTL more closely resembled MCD with respect to high incidence of nephrotic syndrome (P < 0.001), severity of proteinuria (P < 0.05), short duration from onset to biopsy (P < 0.001), and absence of chronic tubulointerstitial disease (P < 0.0054).

CONCLUSION: Within the MCD/FSGS spectrum, GTL is a distinctive and prognostically favorable clinical-pathologic entity whose presenting features and outcome more closely approximate those of MCD.

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