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Review
. 2024 Jun 11;13(12):3427.
doi: 10.3390/jcm13123427.

Granulomatous Tubulointerstitial Nephritis in a Kidney Allograft: Treatment with Interleukin-6 Receptor Antagonist Stabilises Kidney Function

Gabriel T Doctor  1 , Caroline Dudreuilh  1 , Ranmith Perera  1 , Anthony Dorling  1
Affiliations
Review

Granulomatous Tubulointerstitial Nephritis in a Kidney Allograft: Treatment with Interleukin-6 Receptor Antagonist Stabilises Kidney Function

Gabriel T Doctor et al. J Clin Med. .

Abstract

Granulomatous tubulointerstitial nephritis (GTIN) attributed to early onset sarcoidosis is an ultrarare finding in an allograft kidney biopsy. We present the case of a young man with allograft dysfunction who had GTIN upon biopsy. We performed a thorough case review based on recovered records from early childhood and reassessed genetic testing results. We revised his underlying diagnosis from cryopyrin-associated periodic syndrome to early-onset sarcoidosis with wild-type NOD2 and established a rationale to use the interleukin-6 (IL-6) receptor blocker tocilizumab (TCZ). This suppressed his inflammatory disease and stabilised kidney function. We performed a literature review related to the emerging role of IL-6 pathway blockade in kidney transplantation. We identified 18 reports with 417 unique patients treated with TCZ for indications including HLA-desensitisation, transplant immunosuppression induction, treatment of chronic antibody-mediated rejection, and treatment of subclinical rejection. Both TCZ and the direct IL-6 inhibitor clazakizumab are being studied in ongoing randomised control trials.

Keywords: antibody-mediated rejection; clazakizumab; cryopyrin-associated periodic syndrome; early-onset sarcoidosis; granulomatous tubulointerstitial nephritis; interleukin-6 antagonist; kidney allograft; tocilizumab.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Histology from the second allograft biopsy performed 18 months post-transplantation: (A) ×20 magnification of renal cortex stained with haematoxylin and eosin. Illustrates widespread lymphocytic interstitial infiltrate with several granulomata. (B) ×40 magnification stained with periodic acid methenamine silver. Demonstrates a granuloma with multinucleated giant cells. (C) ×40 magnification stained with anti-C4d antibody immunohistochemistry (IHC), showing diffuse staining (C4d3) along the peritubular capillaries.
Figure 2
Figure 2
Renal function (serum creatinine) and CRP post-transplantation. Annotations illustrate the timing of the three allograft biopsies, with histological diagnoses, and the point at which anti-IL-6 treatment was re-started. (Conversion factor serum creatinine in mg/dL to μmol/L, ×88.4).
See this image and copyright information in PMC

References

    1. Roufosse C., Simmonds N., Clahsen-van Groningen M., Haas M., Henriksen K.J., Horsfield C., Loupy A., Mengel M., Perkowska-Ptasińska A., Rabant M., et al. A 2018 Reference Guide to the Banff Classification of Renal Allograft Pathology. Transplantation. 2018;102:1795–1814. doi: 10.1097/TP.0000000000002366. - DOI - PMC - PubMed
    1. Lane T., Williams R., Rowczenio D., Youngstein T., Trojer H., Pepper R., Brogan P., Hawkins P., Lachmann H. A Decade of Anti-IL-1 Therapy in CAPS—A Spectrum of Efficacy in This Spectrum of Diseases. Pediatr. Rheumatol. 2015;13:O65. doi: 10.1186/1546-0096-13-S1-O65. - DOI
    1. Shen S.Y., Hall-Craggs M., Posner J.N., Shabazz B. Recurrent Sarcoid Granulomatous Nephritis and Reactive Tuberculin Skin Test in a Renal Transplant Recipient. Am. J. Med. 1986;80:699–702. doi: 10.1016/0002-9343(86)90828-4. - DOI - PubMed
    1. Vargas F., Gedalia A., Craver R.D., Vehaskari V.M. Recurrence of Granulomatous Interstitial Nephritis in Transplanted Kidney. Pediatr. Transplant. 2010;14:e54–e57. doi: 10.1111/j.1399-3046.2009.01173.x. - DOI - PubMed
    1. Gedalia A., Khan T.A., Shetty A.K., Dimitriades V.R., Espinoza L.R. Childhood Sarcoidosis: Louisiana Experience. Clin. Rheumatol. 2016;35:1879–1884. doi: 10.1007/s10067-015-2870-9. - DOI - PubMed