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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2014  |  Volume : 25  |  Issue : 4  |  Page : 858-863
Treatment of severe henoch-schonlein purpura nephritis with mycophenolate mofetil

Urmia University School of Medicine, Urmia, Iran

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Date of Web Publication24-Jun-2014


Henoch-Schonlein purpura (HSP) is the most common childhood vasculitis. Renal involvement in HSP is one of the major causes of chronic renal failure in children. It is important to start effective and relatively safe medication to prevent end-stage renal disease (ESRD). Mycophenolate mofetil (MMF) appears to be a promising therapeutic agent in many autoimmune diseases such as lupus nephritis and vasculitis. Herein, we describe the treatment with MMF of three patients with HSP nephritis. In two cases with rapidly progressive glomerulonephritis without response to steroid, after treatment with MMF, significant improvement in kidney function and proteinuria were observed. In another patient with HSP nephritic-nephrotic syn­drome who showed resistance to steroid, MMF offered a favorable effect. MMF seems to be a promising therapeutic agent in the treatment of the severe HSP nephritis.

How to cite this article:
Nikibakhsh AA, Mahmoodzadeh H, Karamyyar M, Hejazi S, Noroozi M, Macooie AA. Treatment of severe henoch-schonlein purpura nephritis with mycophenolate mofetil. Saudi J Kidney Dis Transpl 2014;25:858-63

How to cite this URL:
Nikibakhsh AA, Mahmoodzadeh H, Karamyyar M, Hejazi S, Noroozi M, Macooie AA. Treatment of severe henoch-schonlein purpura nephritis with mycophenolate mofetil. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2021 Dec 3];25:858-63. Available from: https://www.sjkdt.org/text.asp?2014/25/4/858/135182

   Introduction Top

Patients with Henoch-Schonlein purpura (HSP) are reported to have renal involvement in 20- 60% of the cases. [1],[2] Although HSP is generally considered a self-limiting disease, the long-term prognosis depends on the severity of renal involvement. [3] Morbidity is higher among those with severe renal disease, and several studies have reported the relationship between clinical presentations at onset and prognosis. [4],[5],[6],[7]

Risk factors that may result in renal failure in­clude old age, hypertension, elevated serum creatinine, nephrotic and mixed nephritic- nephrotic syndrome at the onset of disease. [7],[8],[9],[10]

In 50% of patients with mixed nephritic- nephrotic syndrome, chronic renal failure may develop, and, in such conditions, the risk of end-stage renal disease (ESRD) is also high. [8] Therefore it is important to start effective and relatively safe medications to prevent ESRD. In patients with severe renal involvement, such as rapidly progressive glomerulonephritis (RPGN), the recommended medications in­clude corticosteroids, intravenous immunoglo-bulin (IVIG), cyclosporin, cyclophosphamide, plasma exchange and a combination of immu-nosuppressive therapy, [11],[12],[13],[14],[15],[16] but yet the treat­ment of HSP nephritis remains controversial.

Mycophenolate mofetil (MMF), an immuno­suppressive agent, has been widely used in organ transplantation including pediatric renal transplantation, [17] and also appears to be a pro­mising therapeutic agent in many autoimmune diseases such as lupus nephritis and vasculitis. In this case study, we report the effect of a combination therapy with MMF with steroid in the treatment of patients with HSP nephritis.

   Case Reports Top

Case 1

A 6-year-old girl was referred to our center with the classic clinical symptoms and signs of HSP, including purpuric rash, abdominal pain, arthralgia, hematuria and lower gastrointestinal bleeding. Because of these complications, oral prednisolone (2 mg/kg/day) was prescribed. Gastrointestinal bleeding improved on the second day and abdominal pain, arthralgia and purpuric rash improved on the fourth day. On the day of admission, laboratory tests were as follows: Hb 12g/dL; Hct 36.2%; ESR 78 mm/h; leukocytosis (WBC 13,200/µL); BUN 16 mg/dL; serum creatinine 0.6 mg/dL; urina­lysis, macroscopic hematuria and proteinuria 2 g/day; CRP 6.6 mg/dL; antistreptolysin O (ASO) titrate 123IU/L; C3 125 mg/dL; C4 11 mg/dL; ANA negative; C-ANCA 0.1 units; P-ANCA 0.1 units; and stool for occult blood positive.

Despite the improvement of the extrarenal involvements from the third day, BUN and serum creatinine increased and urine volume decreased down to 160 mL/day. On the sixth day, the patient developed generalized edema and hypertension (160/100 mm Hg), with urine output 110 mL/day, and the serum albumin reduced to 2.4 g/dL, serum lipids increased to cholesterol 320 mg/dL and triglyceride 290 mg/dL, BUN increased to 90 mg/dL and crea­tinine increased to 6 mg/dL.

At this time, we started peritoneal dialysis. After controlling the blood pressure, oral pred­nisolone was switched to intravenous methyl-prednisolone pulses (20 mg/kg/day) for three days and then continued with oral prednisolone (2 mg/kg/day). At end of the second week after admission to the hospital, the patient still had oliguria and high BUN and serum creatinine. At this time, MMF 30 mg/kg/day was added and oral prednisolone was tapered to 1.5 mg/ kg and changed to every other day, and discon­tinued one month later. Renal biopsy revealed extensive mesangial proliferation, variable intra­luminal leukocytes and up to 60% crescents (Grade IV) by light microscopy [Figure 1], [Figure 2], [Figure 3] and predominant deposition of IgA in the mesangial matrix and basement membrane of the glomerulus. One week after adding MMF to the previous steroid treatment, the urine out­put began to increase but the patient still had a nephrotic level of proteinuria (above 3 g/day) with microscopic hematuria. Two weeks later, the BUN decreased to 41 mg/dL and serum creatinine to 1.7/dL, and peritoneal dialysis was discontinued.
Figure 1: Light microscopy of renal biopsy showing extensive mesangial proliferation, variable intraluminal leukocytosis and up to 60% crescents (Grade IV classification).

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Figure 2: Light microscopy of renal biopsy showing extensive mesangial proliferation, variable intraluminal leukocytes and up to 60% crescents (Grade IV classification).

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Figure 3: Light microscopy of renal biopsy showing circumferential cellular crescents seen in more than 60% of the glomeruli. In this case, there is a marked compression of the tuft (Grade IV classification).

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After one month of treatment with MMF, the blood urea and serum creatinine became nor­mal and proteinuria regressed to 130 mg/day, but hematuria was still present until the 5 th month. MMF was discontinued at the end of the 6 th month, and the patient was free of disease symptoms ten months after the discon­tinuation of MMF.

Case 2

A 5-year-old boy was admitted to the hospital with purpuric rash, macroscopic hematuria, arthralgia, severe abdominal pain and lower gastrointestinal bleeding. On the second day after hospitalization, he had generalized edema with normal blood pressure (100/60 mm Hg) and normal BUN and serum creatinine. Other laboratory tests showed leukocytosis (WBC: 11,400/µL); Hb 11 g/dL; Hct 33.1; urinalysis, macroscopic hematuria and proteinuria 3 g/day; ESR 68 mm/h; CRP 7.6 mg/dL; antistrep­tolysin O titer 133 IU/L; C3 119 mg/dL (normal); C4 13 mg/dL (normal); serum albu­min 2.1 g/dL; cholesterol 340 mg/dL; trigly­ceride 270 mg/dL; ANA negative; c-ANCA less than 0.1 units; p-ANCA less than 0.1 units (normal); and stool for occult blood positive.

Oral prednisolone (2 mg/kg/day) was started from the second day and rapid improvement in purpuric rash, arthralgia, abdominal pain and lower gastrointestinal bleeding was seen du­ring the first week but generalized edema, hematuria and proteinuria were continuing. On the 6 th day, BUN increased to 35 mg/dL and serum creatinine to 1.9 mg/dL, and urine output began to decrease (200 mL/day). Three doses of (20 mg/kg/day) intravenous methyl-prednisolone were added, but proteinuria, edema and hypo-albuminemia did not improve and BUN and serum creatinine continued to rise. On the 16th day after hospitalization, laboratory tests showed leukocytosis (WBC: 13,600/µL); Hb 9  g/dL; Hct 27.1; ESR 54  mm/h; urine volume 450/day; microscopic hematuria; proteinuria 3 g/day; CRP 5.6  mg/ dL; serum albumin 2 g/dL; cholesterol 360 mg/ dL; triglyceride 250 mg/dL; BUN 74 mg/dL; and serum creatinine 5 mg/dL. Although hypertension has been controlled by nifedipine and furosemide, clinically, the patient had mild edema, cushingoid face and considerable hyper-activity. MMF 30 mg/kg/day was added and prednisolone was tapered (1.5 mg/kg every other day) and was discontinued 30 days later. At this time, kidney biopsy was recommended but, unfortunately, the parents refused to take kidney biopsy.

A few days after tapering of prednisolone, the hyperactivity got reduced considerably and 1 week after starting MMF, the urine output in­creased (750 mL/day) and BUN and serum creatinine began to decrease and became nor­mal two weeks later. After one month of treat­ment with MMF, proteinuria regressed to 140 mg/day, but hematuria continued up to the 4 th month.

Case 3

A 7-year-old boy with no previous health problems was admitted due to abdominal pain and lower gastrointestinal bleeding. The patient was thought to have gastrointestinal bleeding (GIB) and underwent complete work-up du­ring the 12 days of admission. While the pa­tient was admitted, he developed erythematous rash on the buttocks and thigh, which were palpable, followed by hematuria. The patient was diagnosed as a case of HSP and predni-solone 2 mg/kg/day was started by the rheu-matologist. Despite six weeks of corticosteroid therapy, the patient still had significant protei-nuria with intermittent hematuria and was referred to our center for further work-up. Laboratory examination found cholesterol 340 mg/dL; triglyceride 270 mg/dL; BUN 18 mg/ dL; serum creatinine 0.5 mg/dL; proteinuria and hematuria, 24-h urine protein 1534 mg/24 h, urine volume 750 mL/24 h; urine creatinine 325 mg/24 h; urine analysis (UA), WBC 1-2, RBC 30-50 and two granular casts; serum total protein 5.17; and albumin 2.23.

We started MMF 30 mg/kg/day and tapered prednisolone to 2 mg/kg every other day and discontinued one month later. Kidney biopsy showed diffuse mesangial cell proliferation with mesangial expansion without crescent formation (light microscope). The patient was asymptomatic one month later and investi­gations showed urine protein 122 mg/24 h; urine volume 900 mL/24 h; urine creatinine 310 mg/24 h; UA, WBC 1-2, RBC many; and the complete blood count and lipid profile were normal; serum total protein was 6.17; and albumin was 4.23. Treatment with MMF was continued for three months and, after a six-month follow-up, there was no clinical and laboratory abnormality except mild micros­copic hematuria.

   Discussion Top

Studies have reported the use of medications including high-dose corticosteroid, IVIG, cyclos-porine, azathioprine, methotrexate, cyclophos-phamide, rituximab and plasmapheresis in ca­ses with complicated HSP nephritis. [11],[13],[14],[18],[19]

Currently, MMF is being used in the treatment of autoimmune disorders such as lupus nephritis, vasculitis, necrotizing glomerulonephritis and corticosteroid-resistant glomerulonephritis. MMF suppresses lymphocyte proliferation and decreases antibody production in the kidney diseases. [20] Studies have suggested that myco-phenolic acid, the active metabolite of MMF, can significantly inhibit the adhesion of leuko­cytes to endothelial cells, which is a key pro­cess in the development of ANCA-associated vasculitis. [21] Several studies indicate that MMF is an effective agent in the treatment and management of lupus nephritis, particularly in refractory lupus nephritis. [22],[23] It has been shown that MMF has effects beyond the inhibition of lymphocyte proliferation, such as inhibition of mesangial cell proliferation, and these other effects may also contribute to the beneficial influence of MMF on improvement in glome-rular cellularity and extracellular matrix depo­sition and decrease in proteinuria. [24],[25]

However, the available evidence to support the use of MMF in HSP is limited to a few case study reports. A case of HSP that mani­fested after pantoprazole ingestion has been reported by Muzaffar. [26] In this patient, the ra­pidly progressive glomerulonephritis was ini­tially unresponsive to intravenous pulse ste­roids, whereas his renal function recovered after treatment with MMF. In a study, the clin­ical courses of six patients (four boys and two girls with a mean age of 13.2 years) with HSP and nephrotic syndrome (resistant to oral pred-nisolone) were reviewed. In this study, the treatment protocols included cyclosporine A, cyclophosphamide, MMF or tacrolimus. They suggested that an early aggressive immuno-suppressive approach improves long-term re­nal outcome in corticoid resistance HSP pa­tients with nephrotic syndrome. [27]

Herein, we report the beneficial effect of MMF combination with steroid in the treatment of severe HSP nephritis. In case 1 with rapid progressive glomerulonephritis and nephritic- nephrotic syndrome without response to ste­roid, significant improvement in kidney func­tion and proteinuria was observed by MMF. In case 2 with nephritic-nephrotic syndrome and acute renal failure, despite early tapering of prednisolone, MMF had a significant effect on control of HSP nephritis. Unfortunately, in this case, we do not have a histological finding due to parents denying renal biopsy. In case 3, ano­ther patient with HSP nephritc-nephrotic syn­drome who showed resistance to steroid, MMF, offered a favorable effect in the control of pro-teinuria.

There was no significant side-effects, except mild anemia and diarrhea in case  1 (not re­quiring any intervention) and abdominal pain and diarrhea in case  2, which was relieved by changing MMF to four divided doses.

Although we cannot overlook the possible effect of steroid therapy on the nephritis of these patients, it is important to note that MMF had a significant role in the treatment. This is consistent with the reported benefits of MMF in the other form of autoimmune disorders such as lupus nephritis, vasculitis, necrotizing glomerulonephritis, corticosteroid-resistant glo-merulonephritis and non-renal complicated HSP. [21],[22],[23],[24],[25],[26],[27],[28],[29],[30] Considering favorable experiences with MMF in the treatment of many immuno-logically mediated renal diseases, the anti-fibrotic and antiproliferative effects of this medication in the corticosteroid-resistant glo-merulonephritis, very small incidence of bone marrow suppression and considerably less ad­verse effects compared with other immuno-suppressives such as cyclophosphamide, [29],[30] it is suggested that MMF can be especially va­luable in the treatment of complicated HSP.

   Conclusion Top

The results of this case report suggest that MMF is a promising therapeutic agent in the treatment of the severe HSP nephritis.

   References Top

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Correspondence Address:
Ahmad Ali Nikibakhsh
Nephrology-Urology and Transplantation Research Center, Urmia University School of Medicine, Urmia
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DOI: 10.4103/1319-2442.135182

PMID: 24969202

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  [Figure 1], [Figure 2], [Figure 3]

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