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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
CASE REPORT  
Year : 2016  |  Volume : 27  |  Issue : 6  |  Page : 1260-1264
Unconventional strategies in the battle of focal and segmental glomerulosclerosis


1 Department of Nephrology, Armed Forces Medical College and Command Hospital, Pune, Maharashtra, India
2 Department of Pathology and Laboratory Sciences, Armed Forces Medical College and Command Hospital, Pune, Maharashtra, India
3 Department of Radiodiagnosis and Imaging, Armed Forces Medical College and Command Hospital, Pune, Maharashtra, India
4 Department of Medicine, Armed Forces Medical College and Command Hospital, Pune, Maharashtra, India

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Date of Web Publication28-Nov-2016
 

   Abstract 

A 24-year-old male presented with classic features of the nephrotic syndrome. An initial renal biopsy revealed minimal change disease and thereafter, a second biopsy showed features of focal and segmental glomerulosclerosis. There was no response to conventional immunosuppression, and the patient had to be given rituximab; in spite of this, he went on to develop end-stage renal disease. He continued to have heavy proteinuria leading to severe hypoalbuminemia, thrombosis, infections, and malnutrition, placing the patient in a life-threatening situation. Bilateral renal ablation with embolization of both kidneys with coiling was done at one setting, which finally resolved the proteinuria in the patient. He then underwent a living-related renal transplant, developing recurrence immediately post-transplant. He was again given rituximab along with tacrolimus, mycophenolate mofetil, and prednisolone. There was no response to rituximab, and the patient underwent plasmapheresis, which leads to complete remission. An arteriovenous fistula was created post-transplant to facilitate regular plasmapheresis.

How to cite this article:
Mendonca S, Kumar R, Gupta D, Gupta P, Barki S, Sharma M L. Unconventional strategies in the battle of focal and segmental glomerulosclerosis. Saudi J Kidney Dis Transpl 2016;27:1260-4

How to cite this URL:
Mendonca S, Kumar R, Gupta D, Gupta P, Barki S, Sharma M L. Unconventional strategies in the battle of focal and segmental glomerulosclerosis. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2020 Aug 9];27:1260-4. Available from: http://www.sjkdt.org/text.asp?2016/27/6/1260/194684

   Introduction Top


Focal and segmental glomerulosclerosis (FSGS) is one of the leading causes of the nephrotic syndrome in adults and frequently diagnosed as minimal change disease (MCD) on renal biopsy, due to its focal character. [1] The pathogenesis of FSGS is an immune dysregulation with the involvement and cross talk between Tand B-cells, secreting a glomerular permeability factor leading to proteinuria. [2] Rituximab is a chimeric monoclonal antibody against CD20, thus depleting the B-cells. The experience of rituximab in FSGS is limited with variable results, and a good response is seen if the patient is young with a normal serum albumin. [3] Our patient did not respond to this drug and developed end-stage renal disease (ESRD); however, in spite of renal failure, he continued to have heavy proteinuria leading to severe hypoalbuminemia, thrombosis, infections, and malnutrition, placing the patient in a life-threatening situation. We had to resort to embolization of his kidneys to reduce the proteinuria. The patient subsequently underwent a living-related donor renal transplantation. He developed recurrence of proteinuria immediately post-transplant which was not unexpected.

The recurrence was treated with rituximab, to which, the patient did not respond. He was subsequently given plasmapheresis to which he responded.


   Case Report Top


A 24-year-old male presented with complaints of swelling of the feet and face of one month's duration. Evaluation revealed that he had anasarca, hypertension, normal renal functions, and nephrotic range proteinuria; 24-h urinary protein was 5200 mg/24 h. Urine showed 3+ proteins and no red blood cells, serum albumin was 2.1 g/dL (normal levels 3.5-5.5 g/dL), and serum cholesterol was 335 mg/dL (normal level <200 mg/dL). Serological investigations in the form of anti-nuclear antibody and anti-neutrophil cytoplasmic antibody were negative, C3 and C4 levels were normal, and he was negative for hepatitis B and C and human immunodeficiency virus serology. There was no past or family history of any such illness. No history of any drug or toxin intake was elicited. A clinical diagnosis of primary glomerulonephritis with possible FSGS was made on the basis of nephrotic range proteinuria and hypertension. A renal biopsy was performed which revealed features of MCD [Figure 1].
Figure 1: H- and E-stained section of kidney biopsy showing normal glomeruli, tubules, and blood vessels suggesting minimal change disease (×100).

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The patient was started on prednisolone 1 mg/kg body weight, along with angiotensinconverting enzyme inhibitors (ACEI) in the optimal dose, and diuretics. Over the next three weeks, his proteinuria worsened increasing to 7200 mg/24 h and the serum creatinine rose to 2.4 mg/dL. A possibility of bilateral renal vein thrombosis was considered; Doppler of renal vessels was normal. The second possibility of diuretic-induced acute tubular necrosis (ATN) was thought of and his diuretics were stopped, and he was put on 100 mL 20% albumin infusions twice a day, to prevent intravascular volume depletion. Oral prednisolone was stopped, and he was given three doses of 750 mg pulse methyl prednisolone over three days followed by oral prednisolone and mycophenolate mofetil (MMF) were added, 1000 mg twice daily.

Over the next week, his renal functions deteriorated and the blood urea rose to 242 mg/dL and serum creatinine to 8.2 mg/dL, and he became oliguric. He was initiated on hemodialysis (HD) through a double lumen jugular catheter.

In view of rapidly worsening renal functions, a trial of injection rituximab, 1000 mg, was given with a plan to repeat the next dose after two weeks. A repeat renal biopsy was performed which showed features of FSGS associated with ATN [Figure 2]. His immunosuppression was continued along with HD and albumin infusions. He continued to remain oliguric and a second dose of rituximab 1000 mg was given.
Figure 2: H and E stained section of kidney biopsy revealed mesangial hypercellularity, segmental tuft sclerosis, and tubular casts suggestive of focal and segmental glomerulosclerosis (×400).

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He then developed right-sided lobar pneumonia and sepsis, for which he was started on antibiotics, MMF was stopped, and prednisolone was reduced.

After being on dialysis for four weeks, he continued to be oliguric but was having heavy proteinuria 15,200 mg/24 h. The serum albumin had decreased to 1.4 g/dL, and serum cholesterol had risen to 435 mg/dL. The anasarca was worsening, and in between, he also developed spontaneous bacterial peritonitis of the ascitic fluid, and an episode of cellulitis of the right lower limb again leading to sepsis.

He was deteriorating as time went by with repeated infections, malnutrition, and inadequate dialysis as he was developing hypotension during dialysis due to which adequate ultrafiltration could not be achieved. A left radial arteriovenous fistula (AVF) was created which got thrombosed after a week and another left brachial AVF was made which also got thrombosed. This was most likely due to his procoagulant state and very low serum albumin with intravascular volume depletion. Finally, a right permacath was inserted for dialysis access.

In view of his worsening general condition, a decision for bilateral renal embolization was undertaken. Since medical renal ablation in the form of high-dose diuretics, non-steroidal antiinflammatory drugs (NSAIDs), and ACEI would not be tolerated by the patient, he was scheduled for bilateral coiling of the renal vessels. Coiling was done with 500-700 μ vinyl alcohol particles placed in both the renal arteries through the femoral route [Figure 3] and [Figure 4].
Figure 3: Flush aortography before embolization showing both the kidneys.

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Figure 4: Flush aortography after embolization. Note the absence of renal perfusion after embolization and the visible coils indicating successful renal ablation.

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Post-embolization, he developed accelerated hypertension and pulmonary edema for which he had to be placed on ventilatory support. His urine output had decreased to 30 mL which was also a sign of successful coiling. He was initiated on continuous venovenous HD, which was continued for three days and 12,500 mL of ultrafiltrate was removed. He was then taken off ventilatory support.

The patient was then placed on regular maintenance HD. Over a period of two months, his serum albumin increased to 4.2 g/ dL and the lipid profile was normalized. He was vaccinated for pneumococcus and influenza and was worked up for renal transplant with his mother as the prospective kidney donor.

He underwent the transplantation and immunosuppression included tacrolimus, MMF, and prednisolone. The immediate posttransplant period was uneventful. However, he developed proteinuria on the 2 nd day of transplant with the 24-h urinary proteins being 8.6 g/24 h. A graft biopsy performed after one week was normal with no features of FSGS. He was again treated with rituximab 1000 mg weekly for four weeks, but there was no response. He was initiated on twice weekly plasmapheresis, and a right radial AVF was made to facilitate plasmapheresis as the patient did not have a vascular access and there was an anticipation of prolonged sessions of plasmapheresis. Presently, he is in complete remission with 24-h urinary proteins reduced to 300 mg/24 h. The blood pressure is well controlled, and he has a stable renal function with a serum creatinine of 1.4 mg/dL. However, he requires once a fortnight plasmapheresis to prevent the recurrence of proteinuria.


   Discussion Top


FSGS is one of the leading causes of the nephrotic syndrome in adults and frequently diagnosed as MCD on renal biopsy, due to its focal character. [1] However, MCD associated with hypertension, hematuria, steroid dependence, or resistance is usually a pointer toward FSGS. Our patient was diagnosed initially as having MCD on renal biopsy; however, he had a progressive renal dysfunction with hypertension and a repeat biopsy revealed FSGS. The patient rapidly progressed to ESRD indicating the severity of the disease. A trial of rituximab was given, without any response. The pathogenesis of FSGS is an immune dysregulation with the involvement of Tand Bcells, secreting a glomerular permeability factor leading to proteinuria. [2] Rituximab is a chimeric monoclonal antibody against CD20 which helps in depleting the B-cells. The experience of rituximab in FSGS is limited with variable results, and a good response is seen if the patient is young with a normal serum albumin. [3]

The decision of renal ablation with embolization was a desperate measure which had to be taken, in view of the dire consequences of malnutrition, muscle wasting, prothrombotic risk, and infections to save the life of the patient rather than the kidney. Surgical nephrectomy is associated with a high mortality of 11% and morbidity reaching 87% and hence, medical nephrectomy is a preferable option. [4] The use of diuretics, high-dose ACEI, and NSAIDs is usually not well tolerated by the patients, and hence trans-femoral artery cathetermediated polyvinyl alcohol particle ablation of the kidneys is the best option. Previously, coiling has been performed for renal neoplasms and heavy proteinuric diseases such as amyloidosis, but its use for FSGS has been documented recently. [5]

The patient developed recurrence of proteinuria immediately post-transplant which was expected. The risk factors for recurrence include early age of onset of disease, rapid progression to ESRD, black race, patients with mesangial proliferation in the native kidneys, patients who receive the kidney from a living donor, and those who have undergone pretransplant bilateral nephrectomy. [6] Recurrence of FSGS post-transplant is seen in 30%-40% of patients and is an adverse risk factor for long-term survival of the graft. [7] FSGS due to a genetic defect of the glomerular filtration barrier has a very low incidence of recurrence. This implied that our patient most likely had an FSGS due to immune dysregulation and a permeability factor.

The patient was administered rituximab twice; however, in spite of four doses of rituximab, there was no response and proteinuria persisted. There are no prospective studies on the use of rituximab in post-transplant FSGS other than case series and reports. Overall, the data show that response to rituximab is variable and less effective in post-transplant FSGS. [8]

The role of plasmapheresis in post-transplant FSGS is well known. [9] The concept of plasmapheresis in FSGS is the basis of the circulating permeability factor which is filtered. Our patient had complete remission with plasmapheresis; however, as the effect of plasmapheresis waned he again developed heavy proteinuria thus cementing the fact that the glomerular permeability factor circulating in the plasma is responsible for FSGS. The patient was placed on weekly plasmapheresis for three months and is presently on plasmapheresis once a fortnight. He is on triple immunosuppression with tacrolimus, MMF, and prednisolone and remains in complete remission with normal renal function.

The creation of an AVF post-transplant for vascular access to facilitate plasmapheresis is till date, undocumented.

Finally, this case has many learning points in the form of differentiating MCD from FSGS, the variable response to rituximab, the fact that the permeability factor is responsible for FSGS, the importance of vascular access in patients with FSGS even post-transplant, and the aggressive management of FSGS with heavy proteinuria may be lifesaving.

Conflict of interest: None declared.

 
   References Top

1.
Garin EH, Mu W, Arthur JM, et al. Urinary CD80 is elevated in minimal change disease but not in focal segmental glomerulosclerosis. Kidney Int 2010;78:296-302.  Back to cited text no. 1
    
2.
Wei B, El Hindi S, Li J, et al. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat Med 2011;17: 952-60.  Back to cited text no. 2
    
3.
Sinha A, Bagga A. Rituximab therapy in nephrotic syndrome: implications for patients' management. Nat Rev Nephrol 2013;9:154-69.  Back to cited text no. 3
    
4.
Keller FS, Coyle M, Rosch J, Dotter CT. Percutaneous renal ablation in patients with end-stage renal disease: alternative to surgical nephrectomy. Radiology 1986;159:447-51.  Back to cited text no. 4
    
5.
Tikkakoski T, Leppänen M, Turunen J, Anderson S, Södervik H. Percutaneous transcatheter renal embolization with absolute ethanol for uncontrolled nephrotic syndrome. Case reports. Acta Radiol 2001;42:80-3.  Back to cited text no. 5
    
6.
Van Stralen KJ, Verrina E, Belingheri M, et al. Impact of graft loss among kidney diseases with a high risk of post-transplant recurrence in the paediatric population. Nephrol Dial Transplant 2013;28:1031-8.  Back to cited text no. 6
    
7.
Hickson LJ, Gera M, Amer H, et al. Kidney transplantation for primary focal segmental glomerulosclerosis: outcomes and response to therapy for recurrence. Transplantation 2009; 87:1232-9.  Back to cited text no. 7
    
8.
Kumar J, Shatat IF, Skversky AL, et al. Rituximab in post-transplant pediatric recurrent focal segmental glomerulosclerosis. Pediatr Nephrol 2013;28:333-8.  Back to cited text no. 8
    
9.
Straatmann C, Kallash M, Killackey M, et al. Success with plasmapheresis treatment for recurrent focal segmental glomerulosclerosis in pediatric renal transplant recipients. Pediatr Transplant 2014;18:29-34.  Back to cited text no. 9
    

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Correspondence Address:
Satish Mendonca
Department of Nephrology, Armed Forces Medical College and Command Hospital, Pune - 411 040, Maharashtra
India
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DOI: 10.4103/1319-2442.194684

PMID: 27900977

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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    Abstract
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