Renal Biopsy

Nephrocor

Specimen Type:

Kidney

History:

At the time of biopsy, this patient was a 9 year-old female 6-weeks post renal transplantation from a cadaveric donor who had developed end stage renal disease in her native kidney due to focal segmental glomerulosclerosis. Within 48 hr after transplantation she had massive proteinuria with a 50 gm protein/gm creatinine. After 4 weeks of treatment which included plasmapheresis, proteinuria had decreased to about 12 – 14 gm/gm. At the time of biopsy, she had 7 gm/gm proteinuria and serum creatinine was 3.6 mg/dl.

Pathologic Features:

Light Microscopy

The specimen was core that consisted entirely of renal cortex. Approximately 36 glomeruli were examined. About 25% of the glomeruli had mild to severe segmental sclerosis with collapsed capillaries and expanded mesangial matrix. One glomerulus appeared to be globally sclerotic. The rest of the glomeruli appeared normal. The tubulointerstitium was essentially normal with no significant edema, fibrosis, or atrophy and only a small focus of intense chronic inflammation consisting almost exclusively of lymphocytes. Tubulitis was not seen. There was very focal ectasia of the proximal tubules with mild attenuation of the brush borders. There were three interlobular arteries that were normal without inflammation or necrosis. Arterioles were also normal.

Immunofluorescence

Tubulointerstitial capillaries were negative for C4d. There was diffuse staining of the glomerular mesangium, but positive staining glomeruli are frequently observed in the absence of rejection. Positive control tissue for antibody-mediated rejection showed intense linear staining of tubulointerstitial capillary walls as expected.

Electron Microscopy

One glomerulus was examined. Basement membranes were normal thickness with normal structure. Podocytes foot processes had occasional segmental areas of effacement. Segmental sclerosis was not seen in this glomerulus. No electron-dense deposits are seen. Tubulointerstitial capillaries had a single layer of basement membrane material.

Differential Diagnosis:

Not applicable for this case, please continue to the Diagnosis.

Diagnosis:

Kidney, transplant, needle biopsy

  • Consistent with recurrent focal segmental glomerulosclerosis
  • Focal acute tubular injury
  • No evidence of rejection

This biopsy shows pathological findings consistent with recurrence of the patient’s original native renal disease: focal segmental glomerulosclerosis (FSGS). FSGS is frequently cited as recurring in approximately 30% of patients after transplantation (1, 2) although the reported range is as great as 20 – 80% (3). The recurrence rate is higher in younger patients (2). It is generally heralded by proteinuria, often within the first few days and is accompanied by foot process effacement in biopsies performed 2 – 7 days after recurrence (4). Biopsy-proven recurrence had a mean of 7.5 months with a range from 0.5 months to 44 months in one study (5). Non-hereditary FSGS recurs more frequently than hereditary FSGS, although recurrences have been reported in the latter as well, even in some cases where the donors were unrelated to the patients (2). There has been much interest in the role of glomerular permeability factors, but their identities remain undetermined. Nevertheless the possibility that they may play a pathogenic role provides much of the rationale behind the use of plasmapheresis in the therapeutic regimen (1). Indeed, remission has been reported in over 50% of patients (1). Complete or partial remission of proteinuria is associated with prolonged graft survival (6).

Given the rapid reappearance in this case of segmental, sclerotic lesions so quickly after transplantation, one must consider the possibility of donor-disease; however, the glomerular lesions appear relatively fresh without hard collagenization or hyalinosis. Furthermore there were no significant chronic tubulointerstitial changes in the biopsy such as fibrosis or atrophy. Therefore to evoke donor disease as the source of the lesions, one would necessarily hypothesize that the donor had him/herself developed FSGS very slightly before his/her demise. Thus, it is more plausible in this case to accept that these lesions developed acutely during the 6-week period following transplantation.

References:

  1. Vincenti, F., and Ghiggeri, G.M. 2005. New insights into the pathogenesis and the therapy of recurrent focal glomerulosclerosis. Am J Transplant 5:1179-1185.
  2. Weber, S., and Tonshoff, B. 2005. Recurrence of focal-segmental glomerulosclerosis in children after renal transplantation: clinical and genetic aspects. Transplantation 80:S128-134.
  3. Pardon, A., Audard, V., Caillard, S., Moulin, B., Desvaux, D., Bentaarit, B., Remy, P., Sahali, D., Roudot-Thoraval, F., Lang, P., et al. 2006. Risk factors and outcome of focal and segmental glomerulosclerosis recurrence in adult renal transplant recipients. Nephrol Dial Transplant 21:1053-1059.
  4. Cheong, H.I., Han, H.W., Park, H.W., Ha, I.S., Han, K.S., Lee, H.S., Kim, S.J., and Choi, Y. 2000. Early recurrent nephrotic syndrome after renal transplantation in children with focal segmental glomerulosclerosis. Nephrol Dial Transplant 15:78-81.
  5. Artero, M., Biava, C., Amend, W., Tomlanovich, S., and Vincenti, F. 1992. Recurrent focal glomerulosclerosis: natural history and response to therapy. Am J Med 92:375-383.
  6. Gipson, D.S., Chin, H., Presler, T.P., Jennette, C., Ferris, M.E., Massengill, S., Gibson, K., and Thomas, D.B. 2006. Differential risk of remission and ESRD in childhood FSGS. Pediatr Nephrol 21:344-349.