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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2019  |  Volume : 30  |  Issue : 1  |  Page : 235-238
IgM nephropathy – Successful treatment with rituximab

1 Hospitalist Department, OSF Saint Anthony Medical Centre, Rockford, Illinois, USA
2 Division of Nephrology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA

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Date of Submission24-Jan-2018
Date of Decision08-Mar-2018
Date of Acceptance12-Mar-2018
Date of Web Publication26-Feb-2019


Immunoglobulin M nephropathy (IgMN) is a primary glomerulonephritis which is characterized by variable degrees of morphological features ranging from minimal glomerular involvement to segmental or global sclerosis. No specific treatment is known to date for this disease because of uncertainties in etiopathogenesis. The mainstay treatment for this disease has been corticosteroids, which has varying degrees of resistance ranging from 0% to 50%. We present the case of a 59-year-old Caucasian male who was referred to the outpatient nephrology clinic for the evaluation of proteinuria and was diagnosed with IgMN. We successfully treated the patient with rituximab with resolution of his proteinuria.

How to cite this article:
Ahmed FA, El-Meanawy A. IgM nephropathy – Successful treatment with rituximab. Saudi J Kidney Dis Transpl 2019;30:235-8

How to cite this URL:
Ahmed FA, El-Meanawy A. IgM nephropathy – Successful treatment with rituximab. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2021 Sep 28];30:235-8. Available from: https://www.sjkdt.org/text.asp?2019/30/1/235/252917

   Introduction Top

Immunoglobin M nephropathy (IgMN) is a primary glomerulonephritis (GN) characterized by varying degrees of morphological features with minimal glomerular involvement to segmental or global sclerosis.[1] There have been no well-established studies to determine the incidence or prevalence of this disease. Therefore, most of the epidemiological data for IgMN were derived from the renal biopsies.[2] IgMN most commonly affects children and young adults. It can have varied clinical presentation. There have been no randomized controlled trials to date to address the treatment of IgMN in adults. There has been one case report of recurrent IgMN after renal transplantation which was successfully treated with rituximab.[3] The most common complications reported are renal insufficiency and hypertension.[1]

   Case Report Top

We present the case of a 59-year-old Caucasian male with proteinuria. His medical history was significant for hypertension, idiopathic throm-bocytopenic purpura (ITP), prostate cancer, chronic obstructive pulmonary disease, and atrial fibrillation. His only symptom was urinary frequency, which has been chronic, secondary to bladder contractility problem.

He had multiple surgeries in the past (splenectomy for ITP, partial prostatectomy, and few orthopedic surgeries). His medications included amlodipine, metoprolol, oxybutynin, tramadol, aspirin, omeprazole, and inhaler. He denied using any over-the-counter medications or herbal medicines. Social history was negative for any recent tobacco, alcohol, illicit, or intravenous drug usage. His family history was negative for any kidney diseases, hypertension, diabetes, or malignancies. His sexual history was negative for same sex contacts or multiple partners.

On physical examination, the patient had a body mass index of 35.2 and normal vitals except for mildly elevated blood pressure of 132/90 mm Hg. He had 2+ pitting edema extending to the knees bilaterally. The remainder physical examination was unremarkable.

Laboratory investigations showed normal basic metabolic panel and blood picture. His urinalysis was positive for 4+ protein, moderate blood, and 6–25 red blood cells per high-power field. His urine protein-to-creatinine ratio was 2800 mg/g. Antinuclear antibody, antineutrophil cytoplasmic antibodies, complement levels, antistreptolysin O titers, HIV, hepatitis screen, and anti-glomerular basement membrane antibodies were negative or within the normal range. His serum electrophoresis revealed small amount of IgM-lambda and IgG-lambda. Urine electrophoresis was positive for IgG-lambda and free lambda. His kappa-to-lambda ratio was 0.41.

Subsequently, he underwent a percutaneous renal biopsy. Light microscopy showed increased mesangial cellularity and matrix and mild interstitial fibrosis without any basement membrane alteration as shown in [Figure 1]. Immunofluorescence was positive for mesan-gial staining with IgM in diffuse global pattern as shown in [Figure 2]. Electron microscopy (EM) showed severe effacement of podocyte foot processes with normal basement membrane as shown in [Figure 3]. Kidney biopsy diagnosis was IgM nephropathy with minimal focal segmental glomerular sclerosis. The patient was treated with rituximab 1 g for two months and started on lisinopril. Follow-up urine protein-to-creatinine ratio was <0.2 mg/g without any worsening for more than two years.
Figure 1: Light microscopy showing increased mesangial cellularity and matrix (a) hematoxylin and eosin stain; (b) Periodic acid–Schiff stain; (c) trichrome stain; (d) silver stain.

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Figure 2: Immunofluorescence staining with IgM.

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Figure 3: Electron microscopy showing severe effacement of podocyte foot processes with normal basement membrane.

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   Discussion Top

IgMN is a primary GN, which was first described by two different researchers Cohen et al[4] and Bhasin et al[5] in patients who presented with heavy proteinuria. There is no well-defined or universally acceptable definition for this disease.[2] The prevalence of the disease has been reported primarily based on the renal biopsy diagnosis of IgMN. The frequency of IgMN has been reported between 2% and 18.5% based on a literature review.[4],[5],[6]

The etiology of this primary GN remains unclear. The glomerular IgM deposits can be seen in other autoimmune and systemic diseases.[7],[8] Therefore, these diseases must be excluded before making a diagnosis of IgMN.

The pathogenesis of this disease remains largely unknown. An immune complex disease with complement activation via the classical pathway was suggested by Hsu et al[9] in their study of 41 patients. It was also hypothesized that there may be abnormalities of T-cell function or alteration. Elevated serum IgM or IgM immune complex concentrations have also been reported in studies in patients with IgMN.[9],[10]

IgMN can affect any age group, but most commonly involves the pediatric and young adult groups. The study done in Finland by Myllymäki et al[1] showed that nephrotic syndrome was the most common clinical finding in the pediatric age group, whereas asymptomatic proteinuria and hematuria were common in adults and women, respectively. There was a prevalence of renal insufficiency in 15% and hypertension in 35% of cases.[1]

Diagnosis of IgMN relies primarily on the pathology. In light microscopy, morphological alterations can be seen in different areas with variable degrees of involvement of each area. In the study done by Myllymäki et al,[1] the most common finding was minimal or mild mesangial cell proliferation and/or mild mesangial sclerosis. Focal and segmental sclerosis was demonstrated in four out of the 41 cases of IgMN in the study done by Hsu et al.[9] Other morphological changes include tubular atrophy, interstitial fibrosis, interstitial inflammation, and arteriolar hyalosclerosis.[1] Immunofluorescence is critical in the diagnosis of IgMN, and the characteristic pattern is a diffuse and global mesangial positivity of IgM with intensity of plus 1 and greater.[1],[11] Sixty-nine cases of 110 patients studied by Myllymäki et al[1] had positive staining for C3 in arterioles. Majority of the studies made the diagnosis without EM. The reported EM changes are variable degree of foot process effacement and low-volume, low-density, electron-dense deposits.[2]

The most important complications reported are renal insufficiency with progression to end-stage renal disease (ESRD) and hypertension. In the study done by Myllymäki et al,[1] 23% of the patients who were followed up for 15 years or more and 5% of the patients who were followed up for <15 years developed ESRD. The prevalence of hypertension at the time of biopsy was 35%, which increased to 45% by the end of follow-up.[1]

No specific treatment is known to date for this disease because of uncertainties in etiopathogenesis. The mainstay treatment for this disease has been corticosteroids, which has varying degrees of resistance ranging from 0% to 50%.[12] In the Finland study, one-third of the patients were steroid resistant and more than half were steroid dependent.[1] This indicates that the steroid response rate of IgMN is worse than minimal change disease. There is not much data on the effectiveness of immunosup-pressive agents. There have been two case reports of recurrent IgMN in renal transplant patients, which have used rituximab with success.[3],[13]

Conflict of interest:

None declared.

   References Top

Myllymäki J, Saha H, Mustonen J, Helin H, Pasternack A. IgM nephropathy: Clinical picture and long-term prognosis. Am J Kidney Dis 2003;41:343-50.  Back to cited text no. 1
Mubarak M, Kazi JI. IgM nephropathy revisited. Nephrourol Mon 2012;4:603-8.  Back to cited text no. 2
Betjes MG, Roodnat JI. Resolution of IgM nephropathy after rituximab treatment. Am J Kidney Dis 2009;53:1059-62.  Back to cited text no. 3
Cohen AH, Border WA, Glassock RJ. Nephrotic syndrome with glomerular mesan-gial IgM deposits. Lab Invest 1978;38:610-9.  Back to cited text no. 4
Bhasin HK, Abuelo JG, Nayak R, Esparza AR. Mesangial proliferative glomerulonephritis. Lab Invest 1978;39:21-9.  Back to cited text no. 5
Singhai AM, Vanikar AV, Goplani KR, et al. Immunoglobulin M nephropathy nephropathy in adults and adolescents in India: A single-center study of natural history. Indian J Pathol Microbiol 2011;54:3-6.  Back to cited text no. 6
[PUBMED]  [Full text]  
Mokhtar GA. IgM nephropathy: Clinical picture and pathological findings in 36 patients. Saudi J Kidney Dis Transpl 2011;22: 969-75.  Back to cited text no. 7
[PUBMED]  [Full text]  
Salmon AH, Kamel D, Mathieson PW. Recurrence of IgM nephropathy in a renal allograft. Nephrol Dial Transplant 2004;19: 2650-2.  Back to cited text no. 8
Hsu HC, Chen WY, Lin GJ, et al. Clinical and immunopathologic study of mesangial IgM nephropathy: Report of 41 cases. Histopathology 1984;8:435-46.  Back to cited text no. 9
Disciullo SO, Abuelo JG, Moalli K, Pezzullo JC. Circulating heavy IgM in IgM nephropathy. Clin Exp Immunol 1988;73:395-400.  Back to cited text no. 10
Mubarak M, Kazi JI, Shakeel S, Lanewala A, Hashmi S, Akhter F. Clinicopathologic characteristics and steroid response of IgM nephropathy in children presenting with idiopathic nephrotic syndrome. APMIS 2011; 119:180-6.  Back to cited text no. 11
Border WA. Distinguishing minimal-change disease from mesangial disorders. Kidney Int 1988;34:419-34.  Back to cited text no. 12
Westphal S, Hansson S, Mjörnstedt L, Mölne J, Swerkersson S, Friman S. Early recurrence of nephrotic syndrome (immunoglobulin m nephropathy) after renal transplantation successfully treated with combinations of plasma exchanges, immunoglobulin, and rituximab. Transplant Proc 2006;38:2659-60.  Back to cited text no. 13

Correspondence Address:
Faheemuddin Azher Ahmed
Hospitalist Department, OSF Saint Anthony Medical Center, Rockford, Illinois
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DOI: 10.4103/1319-2442.252917

PMID: 30804288

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