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Diagnosis: Focal and segmental glomerulosclerosis
First native kidney biopsy (2000): Tip lesion
Second native kidney biopsy (2002): NOS variant
Kidney allograft biopsy (2004): NOS variant

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. 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.

Howie AJ, et al (Kidney Int, 2005 [PubMed link]) reported that the earliest lesions in patients with FSGS were probably all at the tubular origin, equivalent to the tip variant of FSGS. In some patients, lesions remained at this site, but progression to renal failure was accompanied by morphologic progression, with development of lesions at various sites, equivalent to FSGS, not otherwise specified (NOS). Progression was more likely if there were large lesions, abnormal mesangium, and extensive acute tubular damage. Patients with lesions at the tubular origin at presentation had a shorter duration of symptoms and less chronic renal damage than those with multiple lesions, were more likely to have a complete response of the nephrotic syndrome, and were less likely to progress to renal failure.

Glomerular tip lesion and its relation to different glomerular diseases is a subject of controversy. The therapeutic and prognostic clinical implications of glomerular tip lesions are ambiguous. According to Stokes MB, et al (Kidney Int, 2004 [PubMed link]) "glomerular tip lesion is a distinctive and prognostically favorable clinical-pathologic entity whose presenting features and outcome more closely approximate those of minimal change disease". In a study by Thomas DB, et al (Kidney Int 2006 [PubMed link]) better renal function and less severe tubulointerstitial injury were observed in patients with tip variant; these patients were more likely to receive steroids and more often achieved complete remission (50%).

Chun MJ et al (JASN 2004 [PubMed link] [Free Full text]) reported that the clinical features at biopsy were similar among patients with NOS, collapsing, and tip variants, with the exception that patients with the tip lesion were older and patients with the collapsing lesion had more severe proteinuria. Over the course of follow-up, 63% of patients treated attained remission and the response to steroid therapy was similar among the groups (NOS 53% versus collapsing lesion 64% versus tip lesion 78%; P = 0.45). They conclude: "the remission rate after treatment is similar among patients with the histologic variants, response to therapy cannot be predicted on the basis of histology alone. Thus, nephrotic patients with primary FSGS should receive a trial of therapy irrespective of the histologic lesion when not contraindicated".

Our case is very interesting due to the agressive course, rapid evolution to end-stage renal disease, and early post-transplant recurrence. So, tip variant do not indicate a favorable prognosis, and we considerate this morphologic lesion diverse to minimal change disease.

See the chapter [Focal and segmental glomerulosclerosis] (Text and atlas. Only in spanish).

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Bibliography

• Thomas DB, Franceschini N, Hogan SL, Ten Holder S, Jennette CE, Falk RJ, Jennette JC. Clinical and pathologic characteristics of focal segmental glomerulosclerosis pathologic variants. Kidney Int. 2006;69:920-6. [PubMed link]
• Chun MJ, Korbet SM, Schwartz MM, Lewis EJ. Focal segmental glomerulosclerosis in nephrotic adults: presentation, prognosis, and response to therapy of the histologic variants. J Am Soc Nephrol. 2004;15:2169-77. [PubMed link] [Free Full text]
• Howie AJ, Pankhurst T, Sarioglu S, Turhan N, Adu D. Evolution of nephrotic-associated focal segmental glomerulosclerosis and relation to the glomerular tip lesion.
  Kidney Int. 2005;67:1188-9. [PubMed link]
• Stokes MB, Markowitz GS, Lin J, Valeri AM, D'Agati VD. Glomerular tip lesion: a distinct entity within the minimal change disease/focal segmental glomerulosclerosis spectrum. Kidney Int. 2004;65:1690-702.[PubMed link]
  

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