Journal of Urology and Renal Diseases (ISSN: 2575-7903)

case report

  PDF Download

Recurrent Iga Nephropathy in A Kidney Transplant Patient: A Case Report

Amna Jousaf Hashmi1, László Bidiga2, Csilla Markóth3, Ibolya File3, József Balla3, Réka P. Szabó3*

1Faculty of Medicine, University of Debrecen, H-4032, Nagyerdei krt. 98, Debrecen, Hungary

2Institute of Pathology, Faculty of Medicine, University of Debrecen, H-4032, Nagyerdei krt. 98, Debrecen, Hungary

3Department of Nephrology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032, Nagyerdei krt. 98, Debrecen, Hungary

*Corresponding author Réka P. Szabó, Institute of Internal Medicine, University of Debrecen, H-4032, Nagyerdei krt. 98, Debrecen, Hungary

Received Date: 11 January, 2022

Accepted Date: 20 January 2023

Published Date: 23 January 2023

Citation: Hashmi AJ, Bidiga L, Markóth C, File I, Balla J, et al. (2023) Recurrent Iga Nephropathy in A Kidney Transplant Patient: A Case Report. J Urol Ren Dis 08: 1302. DOI: https://doi.org/10.29011/2575-7903.001302.

Abstract

There are no universally accepted guidelines for the treatment of recurrent IgA nephropathy. The clinical course of this condition is variable due to the fact that it can be diagnosed in asymptomatic patients on a protocol biopsy, in patients with mild hematuria or proteinuria, or in patients with a rapidly deteriorating kidney function. Our aim was to present the case of a kidney transplant patient with biopsy proven IgA nephropathy. Our findings show that glomerular filtration pressure can be successfully decreased with combined antihypertensive treatment and SGLT2 inhibitor treatment. Refill with personalized immunosuppressive regimen helped us achieve partial remission.

Keywords: Kidney transplantation; Recurrent IgA nephropathy; SGLT2-inhibitor

Introduction

It is common in patients receiving kidney transplantation for kidney failure due to IgA nephropathy that IgA deposits recur in the transplanted kidney. The clinical course of recurrent IgA nephropathy is variable as the condition may be diagnosed in asymptomatic patients on a protocol biopsy,, in patients with mild hematuria or proteinuria, or in patients with a rapidly deteriorating kidney function. As a result, reported rates of recurrence vary significantly between 9% and 61%, mainly due to diverse biopsy protocols and differences in follow-up [1]. Recent studies have shown that recurrence of IgA nephropathy usually manifests a couple of years after transplantation, and longer follow-up studies showed lower survival rates after 5-10 years [2]. A number of risk factors for IgA nephropathy recurrence have been described, including younger age at transplant, transplant without an induction agent, higher HLA-mismatch, and early steroid withdrawal immunosuppressive regimens [4-13]. Biopsies often reveal crescents and fibrinoid necrosis that are also predictors for poor graft outcome. Data from Eurotransplant Registry with 1200 IgA nephropathy subjects found strong association with HLA-B8 and HLA-DR3 [14-17].

Case History

We report the case of a 67-year-old man with biopsy proven IgA nephropathy. According to his history, he had had hypertension since the age of 27, 6 months of hemodialysis, and received a transplant at the age of 43. He had stable kidney graft function, and his main immunosuppression treatment included cyclosporin A and mycophenolate mofetil. He had no preformed or de novo donor specific antibodies at all. He had diabetes, for which metformin was started. In 2020 the patient was diagnosed with microscopic hematuria, accompanied by proteinuria with a range of 2 g-1500 mg /24 hours. We recommended graft biopsy and checked his immune laboratory parameters. Serum electrophoresis did not show monoclonality, and cryoglobulin was also negative (Table 1). Histology showed IgA nephropathy in graft kidney, as shown in Figure 1. We increased immunosuppression in order to achieve a higher cyclosporin level, and increased mycophenolate mofetil for 3 months. An SGLT2 inhibitor (dapagliflozin) was also administered in addition to ARB’s. The patient was followed up by our team. There were no significant reductions in eGFR before or after dapagliflozin administration, and no dehydration or urogenital infections were observed during the treatment course; proteinuria (ACR: albumin creatinine ratio) decreased. Table 1 summarises our patients’ clinical data.

Gender                                                     Male

 

Age (years)

67

 

 

 

 

 

after treatment

Primary renal disease

IgA nephropathy

 

 

Period         after      transplantation

(years)

23

 

 

Waist circumference (cm)

93

 

87

Immunosuppressant

CyA, MPA

 

 

Concomitant drugs

dapagliflozin,        metformin,               telmisartan, fluvastatin

ezetimibe,

dapagliflozin, metformin, telmisartan, ezetimibe, fluvastatin

Complications

Fatty liver dyslipidemia, hypothyreosis

 

 

Family history

DM (-) Renal disease (-)

 

 

Past history

HT

 

 

Laboratory

 

 

 

IgA

elevated

 

 

ANCA

negative

 

 

cryoglobulin

negative

 

 

DSA (MFI)

negative

 

 

ACR (mg/mmol)

>70

 

15>

creatinine (µmol/L)

124

 

134

eGFR (ml/min/1,73 m2)

51

 

46

HgbA1 C (%)

6.7

 

6.1

hgb (g/L)

126

 

118

LDL-C (mmol/L)

4.93

 

3.1

HDL-C (mmol/L)

1.01

 

1.03

Abbreviations: ACR: Albumin Creatinine Ratio; Cya: Cyclosporin A; DM: Diabetes Mellitus; HT: Hypertension; Igan: Iga Nephropathy; EGFR: Estimated Glomerular Filtration Rate; MMF: Mycophenolate Mofetil

Table 1: Clinical profile of the patient.

 

Figure 1: 1a. immunostaining confirms mesangial IgA deposits and IgA positivity in the glomerular mesangium with typical tree branch pattern 1b. electronmicroscopy: mesangial deposits near the paramesangial glomerular basal membrane, electron-dense deposition in mesangium, podocyte fusion in 30-40%.

Discussion

There are no universally accepted guidelines for the treatment of recurrent IgA nephropathy. Management of recurrent IgA deposits focused mainly on starting or increasing ACEi or ARB treatment. Additional therapies, such as pulse steroids or intravenous cyclophosphamide, lack strong evidence in literature. Nonetheless, in 25% of patients, one of these treatments was used [18,19]. As the DAPA-CKD trial included more patients with immunoglobulin A nephropathy (IgAN) than any of the previous IgAN trials, dual renin-angiotensin/SGLT2 inhibition may become the new standard. In differential diagnosis we need to take into consideration postinfectious glomerulonephritis, shunt nephritis, endocarditis related glomerulonephritis, and IgA dominant infection related GN [20-23].

Conclusion

To conclude, we presented a recurrent IgA np case after kidney transplantation. There were no significant reductions in eGFR before or after dapagliflozin administration, and no dehydration or urogenital infections were observed during the treatment course. Glomerular filtration pressure can be successfully decreased with combined antihypertensive and SGLT2 inhibitor treatment. After refill with individualized immunosuppressive regimen and dual RAAS blockade with SGLT2 inhibitors we could achieve partial remission. This case report has several limitations. First, this report is a single-center study including only one case; but as there are a few reports worldwide, we do hope that this presentation will trigger further research.

Reference

  1. Marinaki S, Lionaki S, Boletis JN (2013) Glomerular disease recurrence in the renal allograft: A hurdle but not a barrier for successful kidney Transplant Proc 45: 3-9.
  2. Wyld ML, Chadban SJ (2016) Recurrent IgA nephropathy after kidney Transplantation 100: 1827-1832.
  3. Floege J (2004) Recurrent IgA nephropathy after renal transplantation. Semin Nephrol 24: 287-291.
  4. Ponticelli C, Traversi L, Feliciani A, Cesana BM, Banfi G, et al. (2001) Kidney transplantation in patients with IgA mesangial Kidney Int 60: 1948-1954.
  5. Berthoux F, El Deeb S, Mariat C, Diconne E, Laurent B, et al. (2008) Antithymocyte globulin (ATG)induction therapy and disease recurrence in renal transplant recipients with primary IgA nephropathy. Transplantation 85: 1505-1507.
  6. Han SS, Huh W, Park SK, Ahn C, Han JS, et al. (2010) Impact ofrecurrent disease and chronic allograft nephropathy on the long-term allograft outcome in patients with IgA nephropathy. Transpl Int 23: 169
  7. Ortiz F, Gelpi R, Koskinen P, Manonelles A, Carrera M, et al. (2012) IgA nephropathy recurs early in the graft when assessed by protocol Nephrol Dial Transplant 27: 2553-2558.
  8. Moroni G, Longhi S, Quaglini S, Gallelli B, Banfi G, et al. (2013) The long-term outcome of renal transplantation of IgA nephropathy and the impact of recurrence on graft survival. Nephrol Dial Transplant 28: 1305-1314.
  9. Sato Y, Ishida H, Shimizu T, Tanabe K (2014) Evaluation of tonsillectomy before kidney transplantation in patients with IgA nephropathy. Transpl Immunol 30: 12-17.
  10. Von Visger JR, Gunay Y, Andreoni KA, Bhatt UY, Nori US, et al. (2014) The risk of recurrent IgA nephropathy in a steroid-free protocol and other modifying immunosuppression. Clin Transplant 28: 845-8
  11. Nijim S, Vujjini V, Alasfar S, Luo X, Orandi B, et al. (2016) Recurrent IgA nephropathy after kidney Transplant Proc 48: 2689-2694.
  12. Avasare RS, Rosenstiel PE, Zaky ZS, Tsapepas DS, Appel GB, et al.(2017) Predicting posttransplant recurrence of IgA nephropathy: The importance of crescents. Am J Nephrol 45: 99-106.
  13. Di Vico MC, Messina M, Fop F, Barreca A, Segoloni GP, et al. (2018)Recurrent IgA nephropathy after renal transplantation and steroid Clin Transplant 32: e13207.
  14. Uffing A, Perez-Saez MJ, La Manna G, Comai G, Fischman C, et (2018) A large, international study on post-transplant glomerular diseases: The TANGO project. BMC Nephrol 19: 229.
  15. Cochat (2009) Disease recurrance in pediatric renal transplantation. Nephrol 24: 2097-2108.
  16. Tzang (2008) Recurrent or de nove IgA nephropathy with crescent formation after renal transpalntation . Ren fail 30: 611-616.
  17. Coppo (2007) Serological and genetic factors in early recurrance ogfIgA nephropathy after renal Clin Transplant 21: 42837.
  18. Moroni G (2013) The long-term outcome of renal transplantation of IgA nephropathy and the impact ofrecurrance on graft survival. Nephrol Transplant 28: 1305-1314.
  19. Oritz F (2012) IgA nephropathy recurs early in the graft when assessed by protocol biopsy. nephrol Dial Transplant 27: 2553-2558.
  20. Anders H, Peired AJ, Romagnani P (2022) SGLT2 inhibition requires reconsideration of fundamental paradigms in chronic kidney disease, ‘diabetic nephropathy’, IgA nephropathy and podocytopathies with FSGS lesions. Nephrology Dialysis Transplantation 37: 1609-1615.
  21. Kanduri SR, Kovvuru K, Hansrivijit P, Thongprayoon C, Vallabhajosyula S, et al. (2020) SGLT2 Inhibitors and Kidney Outcomes in Patients with Chronic Kidney Disease, J. Clin. Med 24: 2723.
  22. Evans M, Morgan AR, Whyte MB, Hanif W, Bain SC, et al. (2022) NewTherapeutic Horizons in Chronic Kidney Disease: The Role of SGLT2 Inhibitors in Clinical Practice Strain Drugs 82: 97-108.
  23. Kovesdy C, Schmedt N, Folkerts K, Bowrin K, Raad H, et al. (2022) Predictors of cardio-kidney complications and treatment failure in patients with chronic kidney disease and type 2 diabetes treated with SGLT2 inhibitors. BMC Medicine 20: 2.

Copyright and Licensing: This is an Open Access Journal Article Published Under Attribution-Share Alike CC BY-SA: Creative Commons Attribution-Share Alike 4.0 International License. With this license readers can share, distribute, download, even commercially, as long as the original source is properly cited. Read More.

   

share article