Year : 2009 | Volume
: 20 | Issue : 2 | Page : 266--269
Late de novo minimal change disease in a renal allograft
Krishan K Madhan1, Cynric R.E Temple-Camp2,
1 Renal Unit, Taranaki District Health Board, New Plymouth, NewZealand
2 Anatomical Pathology, Medlab Central, Palmerston North, NewZealand
Krishan K Madhan
Renal Unit, Taranaki District Health Board, Private Bag 2016, New Plymouth 4321
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.
|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;20:266-269
|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 2023 Feb 4 ];20:266-269
Available from: https://www.sjkdt.org/text.asp?2009/20/2/266/45576
De Novo Minimal Change Disease (MCD) in renal allografts is an uncommon condition; Newstead has called it "an occasional curiosity".  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. ,,,,, Zafarmand et al have reported five cases out of 67 patients with the post-transplant nephrotic syndrome over a period of 12 years.  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. 
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.
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.
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.  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.  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.  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.  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.
|1||Newstead CG. Recurrent disease in renal transplants. Nephrol Dial Transplant 2003;18:vi6874.|
|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.|
|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.|
|4||Markowitz GS, Stemmer CL, Croker BP, D'Agati VD. De novo minimal change disease. Am J Kidney Dis 1998;32:508-13.|
|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.|
|6||McLeish KR, Gohara AF, Shapiro RS. Massive post-transplant proteinuria with minimal histological changes. Transplantation 1980;29:392-6.|
|7||Shapiro RS, Deshmukh A, Kropp K. Massive post-transplant proteinuria. Biopsy proven nil disease. Transplantation 1976;22:489-92.|
|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.|
|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.|
|10||Choi MJ, Eustace JA, Gimenez LF, et al. Mycophenolate mofetil treatment for primary glomerular diseases. Kidney Int 2002;61:1098-114.|
|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.|