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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
CASE REPORT  
Year : 2017  |  Volume : 28  |  Issue : 3  |  Page : 621-624
Primary focal segmental glomerulosclerosis recurring rapidly as collapsing glomerulopathy in a renal allograft recipient


1 Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

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Date of Web Publication18-May-2017
 

   Abstract 

Recurrent focal segmental glomerulosclerosis (FSGS) develops in about 30%-40% of patients of FSGS undergoing renal transplantation. We report a patient who received a live- related renal transplant for end-stage renal disease due to a primary FSGS (not otherwise specified) in the native kidney and presented with graft dysfunction in the immediate posttransplant period. The first and the second biopsy showed no evidence of rejection or glomerular lesion. A repeat biopsy done on the 30th day revealed recurrent FSGS morphologically presenting as collapsing variant. The patient was found to have massive proteinuria. Electron microscopy done retrospectively showed glomerular foot process effacement even in the first biopsy. This case highlights the presence of an early minimal change disease-like phase in recurrent FSGS and the necessity of evaluation for proteinuria even in immediate and early posttransplant period. It also shows that different variants of FSGS may represent a spectrum of the same disease and suggests a likely role of a pathogenic circulating factor even in collapsing FSGS requiring further evaluation.

How to cite this article:
Agrawal V, Prasad N, Singh P. Primary focal segmental glomerulosclerosis recurring rapidly as collapsing glomerulopathy in a renal allograft recipient. Saudi J Kidney Dis Transpl 2017;28:621-4

How to cite this URL:
Agrawal V, Prasad N, Singh P. Primary focal segmental glomerulosclerosis recurring rapidly as collapsing glomerulopathy in a renal allograft recipient. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2019 Sep 21];28:621-4. Available from: http://www.sjkdt.org/text.asp?2017/28/3/621/206465

   Introduction Top


Recurrence of focal segmental glomerulo- sclerosis (FSGS) is seen in about 30%-40% of patients with primary FSGS who undergo renal transplantation.[1] Recurrent FSGS occurs within the 1st year of transplant in about 80% of patients and may even manifest within hours after transplantation.[2],[3] A true recurrence, characterized by an early recurrence of pro- teinuria within days or a few weeks after renal transplant, is thought to be due to the presence of pathogenic circulating factor.[4]

We report an unusual case of early onset recurrent FSGS morphologically presenting as collapsing variant in a patient with a primary diagnosis of FSGS [not otherwise specified- (NOS)].

FSGS is histologically classified according to the Columbia classification into five mutually exclusive morphological variants. The previous reports suggest that 80% of recurrent FSGS in renal allografts is of the same morphological type as in the native kidney.[5] This case highlights the many faces of recurrent FSGS and that clinical suspicion early in posttransplant period is required for timely diagnosis.


   Case Report Top


A 36-year-male with nephrotic syndrome was diagnosed as FSGS-NOS. He was on maintenance dialysis for three years. Four years after the primary disease was diagnosed, he underwent live related renal transplant. The donor was his mother. He was on triple drug immunosuppression - cyclophosphamide, tacro- limus, and prednisolone.

On day 2 of the transplant, the serum creatinine was 2.2 mg%, and the urine output was 260 mL/day. Graft biopsy was performed which showed isolated vascular lesion with presence of endothelialitis in one vessel. There was no tubulitis or interstitial inflammation (v2/t0/i0). C4d was negative on immunofluo- rescence. The patient received intravenous antithymocyte globulin and five sessions of plasmapheresis. However, the patient remained dialysis dependent with a urine output of 500700 mL/day and serum creatinine of 5 mg%. A repeat renal biopsy on day 14 showed acute tubular necrosis with no evidence of rejection. C4d was negative on immunofluorescence. The hematological investigations showed a normal platelet count. The patient did not respond to the supportive treatment, and a repeat biopsy was performed on day 30. This biopsy showed evidence of collapsing FSGS in one glome- rulus [Figure 1].
Figure 1: Renal allograft biopsy on day-30 posttransplant in a patient of primary focal segmental glomerulosclerosis showing collapsing glomerulopathy with collapse of part of the glomerular tuft accompanied by proliferation of visceral epithelial cells and presence of prominent resorption droplets (A – PAS, ×400; B – PSM, ×400).

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C4d was negative on immunofluorescence. Investigation for urine protein showed markedly elevated levels in the nephrotic range with a urine protein to creatinine ratio of 4.3.

He subsequently received ten sessions of plasmapheresis. Tacrolimus was replaced by mycophenolate mofetil and cyclosporine was added. However, the serum creatinine remained high, and he was discharged on request with serum creatinine of 4.3 mg%. One month later, the urine output was 2300 mL, and investigations revealed serum creatinine of 3.9 mg% and proteinuria of 16.5 g/day.

Electron microscopy was performed on formalin-fixed, paraffin-embedded tissue of the first and the third graft biopsies. Glomeruli in both the graft biopsies displayed diffuse visceral epithelial cell foot process effacement [Figure 2].
Figure 2: Electron microscopy of the renal allograft biopsy on day-2 posttransplant showing effacement of glomerular podocyte foot processes diagnostic of minimal change disease with no evidence of segmental sclerosis (lead citrate and uranyl acetate, ×11000).

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On follow-up of eight months, the patient remained dialysis dependent.


   Discussion Top


We report a case of recurrent FSGS. A patient with known native kidney FSGS-NOS, had a recurrence as collapsing FSGS within the 1st month of live-related renal transplantation. The histological diagnosis on the third graft biopsy prompted an investigation for urine protein which was markedly elevated. The early glomerular lesion of minimal change disease (MCD), revealed on retrospective electron microscopy, was initially missed. The patient did not respond to therapy and remained dialysis dependent with graft failure.

Recurrent FSGS is one of the common recurrent glomerular diseases in the renal allograft; with a recurrence rate of 30%-50% and presents a major therapeutic challenge.[6],[7] A national registry (1999 United States Renal Data System) of 101,808 renal transplant recipients showed that recurrent FSGS accounted for graft loss in 18.7% of live donor and 7.8% of cadaveric recipients.[8] It also reported that a live donor was associated with superior overall graft survival in recurrent FSGS. Factors associated with graft loss resulting from recurrent FSGS were white recipient, donor African-American kidney in white recipient, younger recipient age, and treatment for rejection.[8] Recurrent FSGS in the first allograft has been shown to have a very high risk of recurrence in subsequent allografts.[9]

Although recurrent FSGS can develop any time after transplantation, it usually occurs early after transplantation (within hours or days) and is associated with proteinuria.[6] The early marker of disease recurrence is often nephrotic-range proteinuria that can appear two to three days after transplantation.[10] In kidney transplant recipients with FSGS in native kidneys, MCD has been reported to be the most frequent histological pattern at the time of recurrence of proteinuria after trans- plantation.[11] However, in patients with persistent proteinuria, the incidence of MCD decreases progressively while FSGS is increasingly observed after three months of transplanta- tion.[11] In our patient, the retrospective electron microscopy of the renal graft biopsies shows that the diagnosis was missed during the initial posttransplant period due to normal appearing glomeruli on histology. Urinary protein estimation after correcting for low urine output could have been useful to detect the disease early.

In 1996, Savin et al described a circulating glomerular permeability factor in the serum strongly associated with recurrence of FSGS after renal transplantation.[12] Higher serum soluble urokinase receptor (suPAR) levels pre- transplant have been observed in subjects with FSGS who later developed recurrent FSGS after transplantation.[13] The role of a circulating factor in recurrent FSGS is further supported by the beneficial effects of plasmapheresis in some patients. However, the usefulness of plasmapheresis has not been tested in large randomized trials. Some studies have doubted the usefulness of suPAR levels for the diagnosis of FSGS and for prediction of recurrence.[6],[14]

Canaud et al have shown that there is no distinctive pathologic subtype of FSGS more likely to recur than the other subtypes.[11] In their series of 42 patients with recurrent FSGS, less than 10% showed the same morphological pattern of FSGS according to the Columbia classification, as in the initial biopsy.[11] Although there are studies showing up to 80% correlation in morphological type between primary FSGS and recurrent FSGS, most studies show that histologic classification for FSGS in native kidney does not correlate with the risk and type of recurrence in renal transplants.[5],[11]

Collapsing FSGS is known to be associated with an immature deregulated phenotype of the podocyte and in comparison to other variants, it is thought to represent a distinct category with more pronounced proteinuria and rapid decline in renal function.[15] Our case highlights that different variants of FSGS may represent a spectrum of the same disease and also suggests the possible role of circulating factors even in collapsing FSGS. Early detection of recurrent FSGS before the development of morphological lesions requires estimation of urinary protein as a routine investigation in renal allograft recipients.

Conflict of interest: None declared.

 
   References Top

1.
D’Agati VD, Kaskel FJ, Falk RJ. Focal segmental glomerulosclerosis. N Engl J Med 2011;365:2398-411.  Back to cited text no. 1
    
2.
Baum MA, Stablein DM, Panzarino VM, Tejani A, Harmon WE, Alexander SR. Loss of living donor renal allograft survival advantage in children with focal segmental glomerulo- sclerosis. Kidney Int 2001;59:328-33.  Back to cited text no. 2
    
3.
Briggs JD, Jones E. Recurrence of glomerulo- nephritis following renal transplantation. Scientific Advisory Board of the ERA-EDTA Registry. European Renal Association- European Dialysis and Transplant Association. Nephrol Dial Transplant 1999;14:564-5.  Back to cited text no. 3
    
4.
Gohh RY, Yango AF, Morrissey PE, et al. Preemptive plasmapheresis and recurrence of FSGS in high-risk renal transplant recipients. Am J Transplant 2005;5:2907-12.  Back to cited text no. 4
    
5.
IJpelaar DH, Farris AB, Goemaere N, et al. Fidelity and evolution of recurrent FSGS in renal allografts. J Am Soc Nephrol 2008;19: 2219-24.  Back to cited text no. 5
    
6.
Sprangers B, Kuypers DR. Recurrence of glomerulonephritis after renal transplantation. Transplant Rev (Orlando, Fla) 2013;27(4):126- 34.  Back to cited text no. 6
    
7.
Vincenti F, Ghiggeri GM. New insights into the pathogenesis and the therapy of recurrent focal glomerulosclerosis. Am J Transplant 2005;5:1179-85.  Back to cited text no. 7
    
8.
Abbott KC, Sawyers ES, Oliver JD 3rd, et al. Graft loss due to recurrent focal segmental glomerulosclerosis in renal transplant recipients in the United States. Am J Kidney Dis 2001;37:366-73.  Back to cited text no. 8
    
9.
Newstead CG. Recurrent disease in renal transplants. Nephrol Dial Transplant 2003;18 Suppl 6:vi68-74.  Back to cited text no. 9
    
10.
Vinai M, Waber P, Seikaly MG. Recurrence of focal segmental glomerulosclerosis in renal allograft: An in-depth review. Pediatr Transplant 2010;14:314-25.  Back to cited text no. 10
    
11.
Canaud G, Dion D, Zuber J, et al. Recurrence of nephrotic syndrome after transplantation in a mixed population of children and adults: Course of glomerular lesions and value of the Columbia classification of histological variants of focal and segmental glomerulosclerosis. Nephrol Dial Transplant 2010;25: 1321-8.  Back to cited text no. 11
    
12.
Savin VJ, Sharma R, Sharma M, et al. Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis. N Engl J Med 1996;334:878-83.  Back to cited text no. 12
    
13.
Wei C, El Hindi S, Li J, et al. Circulating uro- kinase receptor as a cause of focal segmental glomerulosclerosis. Nat Med 2011; 17:952-60.  Back to cited text no. 13
    
14.
Maas RJ, Wetzels JF, Deegens JK. Serum- soluble urokinase receptor concentration in primary FSGS. Kidney Int 2012;81:1043-4.  Back to cited text no. 14
    
15.
Barisoni L, Kriz W, Mundel P, D’Agati V. The dysregulated podocyte phenotype: A novel concept in the pathogenesis of collapsing idiopathic focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol 1999;10:51-61.  Back to cited text no. 15
    

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Correspondence Address:
Vinita Agrawal
Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh
India
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DOI: 10.4103/1319-2442.206465

PMID: 28540902

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    Abstract
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