Home About us Current issue Back issues Submission Instructions Advertise Contact Login   

Search Article 
  
Advanced search 
 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 30 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 
 


 
CASE REPORT Table of Contents   
Year : 2009  |  Volume : 20  |  Issue : 2  |  Page : 266-269
Late de novo minimal change disease in a renal allograft


1 Renal Unit, Taranaki District Health Board, New Plymouth, NewZealand
2 Anatomical Pathology, Medlab Central, Palmerston North, NewZealand

Click here for correspondence address and email
 

   Abstract 

Among the causes of the nephrotic syndrome in renal allografts, minimal change disease is a rarity with only few cases described in the medical literature. Most cases described have occurred early in the post-transplant course. There is no established treatment for the condition but prognosis is favorable. We describe a case of minimal change disease that developed 8 years after a successful transplantation of a renal allograft in a middle-aged woman. The nephrotic syndrome was accompanied by deterioration of allograft function. Treatment with mycophenolate mofetil was successful in inducing remission and stabilizing allograft function.

Keywords: Kidney Allograft, Transplantation, Nephrotic Syndrome, De novo Minimal change Disease

How to cite this article:
Madhan KK, Temple-Camp CR. Late de novo minimal change disease in a renal allograft. Saudi J Kidney Dis Transpl 2009;20:266-9

How to cite this URL:
Madhan KK, Temple-Camp CR. Late de novo minimal change disease in a renal allograft. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2014 Sep 24];20:266-9. Available from: http://www.sjkdt.org/text.asp?2009/20/2/266/45576

   Introduction Top


De Novo Minimal Change Disease (MCD) in renal allografts is an uncommon condition; Newstead has called it "an occasional curio­sity". [1] There are only a few case descriptions in published literature even though the neph­rotic syndrome posttransplantation is not a rarity among the several thousand transplants performed each year in the world. [2],[3],[4],[5],[6],[7] Zafarmand et al have reported five cases out of 67 patients with the post-transplant nephrotic syndrome over a period of 12 years. [8] Four of the 5 cases of de novo MCD occurred within 4 months of transplantation and one did so at 24 months. Markowitz et al reported one patient who de­veloped MCD at 2 ½ years post-transplantation. [5]

We report a case of de novo MCD that de­veloped in a woman aged 56 years, 8 ½ years following successful kidney transplantation for kidney failure due to chronic tubulointerstitial disease.


   Case Report Top


The patient had received a deceased donor re­nal allograft in August 1997. Four years prior, in November 1993, she had reached end-stage kidney failure secondary to chronic tubuloin­terstitial disease and was treated with hemodia­lysis. After transplantation, she was managed with a triple drug regimen of cyclosporine mic­roemulsion (Neoral), azathioprine and predni­sone. There were no complications in the immediate post-transplant period and there were no episodes of acute rejection. The pa­tient maintained good allograft function for several years and her serum creatinine re­mained in the range of 100 to 120 µmol/L until August 2004. At this stage, her urine dipstick was negative for protein or blood, and micros­copy showed no cellular elements.

Through late 2004 and 2005, her serum crea­tinine fluctuated between 130-150 µmol/L. Uri­nalysis remained benign and there were no other mitigating factors. Chronic allograft neph­ropathy was assumed to be the cause of decline in allograft function. Cyclosporine dose was lowered to maintain a 12-hour trough level of 80-100 µg/L.

In January 2006, a routine urine examination detected 1+ proteinuria with dipstick, which in­creased to 3+ in April 2006 and was accom­panied by mild microscopic hematuria. Protei­nuria was 3.8 grams/day. The patient developed clinical appearance of the nephrotic syndrome with generalized edema, increased blood pre­ssure, hypoalbuminemia, and hypercholeste­rolemia. Serum creatinine increased to 180 µmol/L. There was no clinical evidence of a connective tissue or vasculitic disorder. In par­ticular, there was no suggestion of a lympho­proliferative malignancy on careful clinical exa­mination and imaging for abdomino-thoracic lymphadenopathy.

A kidney biopsy was performed and revealed normal glomeruli by light microscopy [Figure 1]. There was no interstitial infiltrate or evi­dence of cyclosporine toxicity. Immunofluore­scence studies were negative. Electron micros­copy showed extensive podocyte foot process fusion [Figure 2].

Prednisone was increased to 1 mg/kg/day. Sodium and fluid restriction along with a loop diuretic was initiated. Blood pressure was con­trolled with additional antihypertensive medi­cation including an angiotensin converting en­zyme inhibitor. The patient developed signifi­cant general ill health including cushingoid features and proximal myopathy within 8 weeks. Proteinuria continued to increase and reached 5.8 g/24 hours. Creatinine increased further to 210 µmol/L. Mycophenolate mofetil, 1 g twice daily, was begun at this stage and prednisone was tapered to a low maintenance dose. Soon after starting mycophenolate, clini­cal improvement with resolution of edematous state became evident. Creatinine stabilized at 180 µmol/L, and proteinuria abated to less than 2 grams/day within 4 weeks and further to 0.6 gram/day over 4 months. The patient main­tained stable renal function with minimal pro­teinuria one year after the initial diagnosis.


   Discussion Top


This case presents some unique features of de novo MCD in renal allografts including the very late appearance after transplantation, deterioration of renal function, and rapid res­ponse to mycophenolate mofetil therapy. The longest period for its occurrence previously reported has been 24 months after transplan­tation. In fact, Zafarmand et al reported that most cases occur with-in the first 4 months and argued that nephrotic syndrome developing more than 1 year following transplantation is probably not because of MCD. [8] There is no doubt whatsoever that this case shows all the histological features of MCD. The normal light microscopic appearance, negative immunofluo­rescence, and wide-spread foot process efface­ment without evidence of immune deposits or other inclusions is highly supportive.

Deterioration of kidney function is not a fea­ture of MCD, when it occurs in native kidneys. In a transplant recipient, the most common etiology for deteriorating kidney function, in absence of specific other disease, would be chronic allograft nephropathy or calcineurin toxicity, both of which were not found on biopsy. While it is tempting to speculate that deterioration of kidney function was related to MCD, it may be a non-specific consequence of the nephrotic state.

Treatment of de novo MCD remains a matter of conjecture. Patients with renal transplan­tation are usually on immunosuppressive regi­mens with the usual agents used for treatment of MCD in native kidneys. Furthermore, as Zafarmand et al have shown in their review of the available literature, prognosis appears to be good in most cases with complete remission being achieved in most cases in response to a variety of immunosuppressive therapies. Myco­phenolate appears to have been successful in inducing an almost complete remission of pro­teinuria as well as improvement in renal function although spontaneous resolution could have also taken place. The rationale for use of mycophenolate in idiopathic glomerulopathies is empirical and is based on clinical observations. Certainly, the exact role of immuno­logical mechanisms in MCD is uncertain even though the disease is highly responsive to im­munosuppressive agents such as corticoste­ roids, cyclophosphamide and cyclosporine. The pathogenesis of MCD may nevertheless be linked to alterations in cellular immunity. [9] My­cophenolate has been shown to be effective in treatment of both steroid sensitive and steroid resistant nephrotic syndrome in adult patients including patients with MCD in native kid­neys. [10] Day et al report experience with mycophenolate treatment in patients with steroid re­sistant nephrotic syndrome due to MCD or focal segmental glomerulosclerosis with 6 of 7 patients achieving complete remission. [11] There­fore, the empiric use of mycophenolate in the nephrotic syndrome appears to be a reasonable option for idiopathic glomerulopathies in ge­neral and perhaps in transplant patients as shown in our case.

 
   References Top

1.Newstead CG. Recurrent disease in renal trans­plants. Nephrol Dial Transplant 2003;18:vi68­74.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Cheigh JS, Mouradian J, Susin M, et al. Kidney transplant nephrotic syndrome: Relationship between allograft histopathology and natural course. Kidney Int 1980;18:358-65.  Back to cited text no. 2  [PUBMED]  
3.Gephardt GN, Tubbs RR, Braun WE, Novick AC, McMahon JT, Steinmuller DR. Nephrotic range proteinuria with "minimal change glo­merulopathy" in human renal allografts: Re­port of four cases. Am J Kidney Dis 1988; 12:51-61.  Back to cited text no. 3  [PUBMED]  
4.Markowitz GS, Stemmer CL, Croker BP, D'Agati VD. De novo minimal change disease. Am J Kidney Dis 1998;32:508-13.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Mauer SM, Hellerstein S, Cohn RA, Sibley RK, Vernier RL. Recurrence of steroid-respon­sive nephrotic syndrome after renal transpla­tation. J Pediatr 1979;95:261-4.  Back to cited text no. 5  [PUBMED]  
6.McLeish KR, Gohara AF, Shapiro RS. Massive post-transplant proteinuria with minimal histo­logical changes. Transplantation 1980;29:392-6.  Back to cited text no. 6  [PUBMED]  
7.Shapiro RS, Deshmukh A, Kropp K. Massive post-transplant proteinuria. Biopsy proven nil disease. Transplantation 1976;22:489-92.  Back to cited text no. 7    
8.Zafarmand AA, Baranowska-Daca E, Ly PD, et al. De novo minimal change disease asso­ciated with reversible post-transplant nephrotic syndrome. A report of five cases and review of literature. Clin Transplant 2002;16:350-61.  Back to cited text no. 8    
9.Grimbert P, Audard V, Remy P, Lang P, Sahali D. Recent approaches to the patho­genesis of minimal-change nephrotic syndrome. Nephrol Dial Transplant 2003;18:245-8.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Choi MJ, Eustace JA, Gimenez LF, et al. Mycophenolate mofetil treatment for primary glomerular diseases. Kidney Int 2002;61:1098-114.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]
11.Day CJ, Cockwell P, Lipkin GW, Savage CO, Howie AJ, Adu D. Mycophenolate mofetil in the treatment of resistant idiopathic nephrotic syndrome. Nephrol Dial Transplant 2002;17: 2011-3.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]

Top
Correspondence Address:
Krishan K Madhan
Renal Unit, Taranaki District Health Board, Private Bag 2016, New Plymouth 4321
NewZealand
Login to access the Email id


PMID: 19237816

Get Permissions



    Figures

  [Figure 1], [Figure 2]

This article has been cited by
1 De novo minimal change disease after ABO-incompatible kidney transplantation
Mochizuki, Y. and Iwata, T. and Nishikido, M. and Uramatsu, T. and Sakai, H. and Taguchi, T.
Clinical Transplantation. 2012; 26(SUPPL.24): 81-85
[Pubmed]
2 Expression of the Integrin-Linked Kinase in a Rat Kidney Model of Chronic Allograft Nephropathy
Han, C. and Zou, H. and Li, Q. and Wang, Y. and Shi, Y. and Lv, T. and Chen, L. and Zhou, W.
Cell Biochemistry and Biophysics. 2011; 61(1): 73-81
[Pubmed]



 

Top
 
 
    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
  Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  
 


 
    Abstract
    Introduction
    Case Report
    Discussion
    References
    Article Figures
 

 Article Access Statistics
    Viewed1164    
    Printed64    
    Emailed0    
    PDF Downloaded232    
    Comments [Add]    
    Cited by others 2    

Recommend this journal