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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2020  |  Volume : 31  |  Issue : 2  |  Page : 521-523
Successful treatment of a patient with posttransplant IgA nephropathy with targeted release formulation of budesonide

1 Department of Nephrology, Institute of Nephro-urology, Bengaluru, Karnataka, India
2 Department of Nephropathology, Manipal Hospitals, Bengaluru, Karnataka, India

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Date of Submission09-May-2019
Date of Decision28-Jun-2019
Date of Acceptance08-Jul-2019
Date of Web Publication09-May-2020


Recurrence of glomerulonephritis is the third-leading cause of allograft loss. Graft loss due to IgA nephropathy occurs in 10% at 10-year follow-up. The NEFIGAN trial demonstrated that Target Release Formulation (TRF) of budesonide is a specific treatment for IgA nephropathy targeting intestinal mucosal immunity upstream of disease manifestation with favorable safety profile. We are reporting a case of successful treatment of a patient with posttransplant IgA nephropathy with TRF of budesonide.

How to cite this article:
Lingaraj U, Aralapuram K, Chikkanayakanhalli S, Vishwanathan A, Vankalakunti M. Successful treatment of a patient with posttransplant IgA nephropathy with targeted release formulation of budesonide. Saudi J Kidney Dis Transpl 2020;31:521-3

How to cite this URL:
Lingaraj U, Aralapuram K, Chikkanayakanhalli S, Vishwanathan A, Vankalakunti M. Successful treatment of a patient with posttransplant IgA nephropathy with targeted release formulation of budesonide. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2022 Nov 29];31:521-3. Available from: https://www.sjkdt.org/text.asp?2020/31/2/521/284029

   Introduction Top

Recurrence of glomerulonephritis is the third leading cause of allograft loss.[1] IgA nephropathy recurs posttransplant in 58% of patients in the protocol biopsy series and 25% in indicated biopsy series.[2],[3] Graft loss due to IgA nephropathy occurs in 10% at 10-year follow- up.[1] The NEFIGAN trial demonstrated that Target Release Formulation (TRF) of budesonide is a specific treatment for IgA nephropathy, targeting intestinal mucosal immunity up-stream of disease manifestation with favorable safety profile.[4] We are reporting a case of successful treatment of a patient with

   Case Report Top

Informed consent was obtained from the patient before publishing the case.

Mr. P., a 34-year-old male patient, was a recipient of a living related renal allograft, the donor being his mother. The native kidney disease was presumed to be chronic glome- rulonephritis. The patient was on standard triple-drug immunosuppressive therapy post- transplant. He had stable graft function with nadir serum creatinine (SCr) being 1 mg/dL. Two years posttransplant, the patient presented with swelling of lower limbs for two days with decreased urine output. On evaluation, he had bilateral pitting pedal edema; urine exami- ation revealed 3+ proteinuria with active urinary sediment and 24-h urine protein quantification being 3 g. The patient also had acute graft dysfunction, and SCr increased to 2.5 mg/dL from 1.1 mg/dL. He underwent an allograft biopsy to evaluate the cause of his symptoms.

Renal biopsy comprised 10 glomeruli. There was a focal increase in the mesangial matrix segmentally, besides mild mesangial cell proliferation. Glomerular capillaries were patent without any luminal thrombus. Basement membranes were single contoured. There was no evidence of glomerulitis/necrotizing lesion/crescent formation. Tubulointerstitial compartment revealed a mild degree of acute tubular injury. No signs of tubulitis/interstitial inflammation were noticed. Similarly, the vascular compartment did not reveal any foci of peritubular capillaritis or endarteritis [Figure 1].
Figure 1: Light microscopic image (PAS stain).

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Immunoperoxidase stain for complement- C4d was negative in the peritubular capillaries [Figure 2]. Direct immunofluorescence on the renal tissue revealed four viable glomeruli. They showed diffuse and global granular deposits with IgA (3+) and C3 (1+) in the mesangium. Others, including IgG, IgM, and C1q, were negative. Kappa and Lambda light chain stains did not show restriction. There were no extra-glomerular deposits. Since the biopsy findings were suggestive of IgA nephropathy with MEST-C score of 0, the patient was treated with TRF budesonide 9 mg/day, omega three fatty acids, and ramipril 2.5 mg/day. The dose of ramipril was subsequently increased to 5 mg/d to target blood pressure <125/75 mm Hg. Maintenance immunosuppressive therapy was continued as earlier except for the reduction of prednisolone dose to 5 mg/day. Three months posttherapy, patient’s SCr was 1.1 mg/dL, and the urine routine showed traces of albumin with the disappearance of microhematuria. 24-h quantification of urine protein was 240 mg/day. The patient attained complete remission at the end of three months. The same treatment was continued for three more months following which TRF budesonide was reduced to 3 mg/d and continued. During his last outpatient follow-up, the patient was in sustained clinical remission with his SCr of 1.1 mg/dL, and urine examination was normal. No therapy- related adverse effects were noted during the study period.
Figure 2: C4d Immunoperoxidase staining.

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   Discussion Top

To our knowledge, to date, the use of TRF budesonide for the treatment of posttransplant IgA nephropathy has not been published in the literature. A dysregulated mucosal immune system with defective immune tolerance to commonly encountered pathogens or alimentary components is likely to be the key factor in triggering IgA nephropathy.[5] In healthy individuals, dendritic cells could process and present microbiota or dietary antigens to T- cells in Peyer patches that activate B cells, which produce secretory IgA.[5] In genetically predisposed individuals with IgA nephropathy, there is the unchecked presence of TNF ligand superfamily member 13, also called as A Proliferation Inducing Ligand (APRIL), TNF ligand superfamily member 13B also called as B cell Activating Factor (BAFF), and Transforming Growth Factor p, which enhances survival of activated B cells, resulting in excessive production of galactose- deficient IgA.[5] Because Peyer patches are supposed to be primed to produce galactose- deficient IgA1, the initial step in the patho- genesis of IgA nephropathy, focusing on a drug targeted to the mucosal B lymphocytes in Peyer patches seems to be a promising treatment closer to the source.[5],[6] Based on these observations, the Swedish group performed a pilot study, which demonstrated a 40% reduction in proteinuria in patients with IgA nephropathy with enteric budesonide, which is designed to release the drug at the ileocecal junction.[7] The recent double-blind, randomized, controlled clinical trial, the NEFIGAN Study, was designed to evaluate the effectiveness and safety of Nefecon (TRF budesonide). The study showed that Nefecon significantly decreased the level of proteinuria and maintained stable kidney function in patients with IgA nephropathy with a safety profile comparable with placebo.[4] Unpublished data from our institution in patients with native kidney IgA nephropathy showed favorable results with a good safety profile. Based on this proof of concept and favorable data, we used TRF budesonide in a posttransplant patient with IgA nephropathy successfully along with ACEi and omega-three fatty acids. Limitations of our study include the absence of an electron microscopy study of the biopsy specimen. Other limitations included the presence of other medications that could favorably affect therapy outcomes, observer’s subjectivity, retrospective in nature, resulting in recall bias and nongeneralizability.

   Conclusions Top

With the improvement of early outcomes of renal transplant, recurrence of GN is increasingly being identified as a leading cause of late graft dysfunction, which poses a therapeutic challenge. Targeted release of corticosteroids for IgA nephropathy seems to be a promising treatment that targets relevant pathophysiology. In future, multi-center and multinational studies are necessary to confirm these results and evaluate the long-term effect on allograft function.

Conflict of interest: None declared.

   References Top

Briganti EM, Russ GR, McNeil JJ, Atkins RC, Chadban SJ. Risk of renal allograft loss from recurrent glomerulonephritis. N Engl J Med 2002;347:103-9  Back to cited text no. 1
Odum J, Peh CA, Clarkson AR, et al. Recurrent mesangial IgA nephritis following renal transplantation. Nephrol Dial Transplant 1994; 9:309-12  Back to cited text no. 2
Ohmacht C, Kliem V, Burg M, et al. Recurrent immunoglobulin A nephropathy after renal transplantation: A significant contributor to graft loss. Transplantation 1997;64:1493-6  Back to cited text no. 3
Fellstrom BC, Barratt J, Cook H, et al. Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): A double-blind, randomised, placebo-controlled phase 2b trial. Lancet 2017;389:2117-27  Back to cited text no. 4
Coppo R. The intestine-renal connection in IgA nephropathy. Nephrol Dial Transplant 2015;30: 360-6  Back to cited text no. 5
Coppo R. The gut-kidney axis in IgA nephro- pathy: Role of microbiota and diet on genetic predisposition. Pediatr Nephrol 2018; 33:53-61  Back to cited text no. 6
Smerud HK, Barany P, Lindstrom K, et al. New treatment for IgA nephropathy: Enteric budesonide targeted to the ileocecal region ameliorates proteinuria. Nephrol Dial Transplant 2011;26:3237-42.  Back to cited text no. 7

Correspondence Address:
Umesh Lingaraj
Department of Nephrology, Institute of Nephro-urology, Victoria Hospital Campus, Bengaluru - 560 002, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.284029

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