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Usefulness of gallium-67 scintigraphy for evaluating the histopathological activity in interstitial nephritis

Clinical and Experimental Nephrology volume 27, pages 251–261 (2023)Cite this article

Abstract

Background

Interstitial nephritis is a common cause of renal failure. Gallium-67 scintigraphy is reportedly useful for diagnosing interstitial nephritis; however, its ability to assess disease activity remains unknown. We aimed to analyze the relationship between the renal uptake of gallium-67 and the disease activity in interstitial nephritis.

Methods

We retrospectively analyzed the data of patients who underwent gallium-67 scintigraphy at a hospital in Tokyo. The renal uptake adjusted for the soft tissues beneath the kidneys was semi-quantitatively evaluated. We compared the renal uptake levels between patients clinically diagnosed with and without interstitial nephritis. Among those undergoing renal biopsy, we evaluated the predictive ability of gallium-67 scintigraphy and analyzed the renal uptake levels regarding the disease activity through a histopathological analysis.

Results

We included 143 patients; among them, 30, 17, and 96 patients were clinically diagnosed with interstitial nephritis, other kidney diseases, and non-kidney diseases, respectively. The renal uptake of gallium-67 was the highest among patients with interstitial nephritis. Among the 25 patients who underwent renal biopsy, 15 were pathologically diagnosed with interstitial nephritis. The renal uptake levels showed a high discriminative ability (C-statistic: 0.83). Furthermore, net reclassification improvement with the addition of gallium-67 scintigraphy to N-acetyl-β-D-glucosaminidase for the prediction of interstitial nephritis was 1.14. Histopathological analysis revealed a positive correlation between renal uptake and inflammation in the cortex and peritubular capillaries.

Conclusions

This study confirmed the diagnostic value and potential usefulness of gallium-67 scintigraphy for evaluating interstitial nephritis.

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Data availability

The data underlying this article may be available on reasonable request to the corresponding author.

References

  1. Kodner CM, Kudrimoti A. Diagnosis and management of acute interstitial nephritis. Am Fam Physician. 2003;67:2527–34.

    PubMed  Google Scholar 

  2. Fogazzi GB, Ferrari B, Garigali G, Simonini P, Consonni D. Urinary sediment findings in acute interstitial nephritis. Am J Kidney Dis. 2012;60:330–2.

    Article  PubMed  Google Scholar 

  3. Perazella MA. Diagnosing drug-induced AIN in the hospitalized patient: a challenge for the clinician. Clin Nephrol. 2014;81:381–8.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Shi Y, Su T, Qu L, Wang C, Li X, Yang L. Evaluation of urinary biomarkers for the prognosis of drug-associated chronic tubulointerstitial nephritis. Am J Med Sci. 2013;346:283–8.

    Article  PubMed  Google Scholar 

  5. Toto RD. Acute tubulointerstitial nephritis. Am J Med Sci. 1990;299:392–410.

    Article  CAS  PubMed  Google Scholar 

  6. Rossert J. Drug-induced acute interstitial nephritis. Kidney Int. 2001;60:804–17.

    Article  CAS  PubMed  Google Scholar 

  7. Linton AL, Richmond JM, Clark WF, Lindsay RM, Driedger AA, Lamki LM. Gallium67 scintigraphy in the diagnosis of acute renal disease. Clin Nephrol. 1985;24:84–7.

    CAS  PubMed  Google Scholar 

  8. Koselj M, Kveder R, Bren AF, Rott T. Acute renal failure in patients with drug-induced acute interstitial nephritis. Ren Fail. 1993;15:69–72.

    Article  CAS  PubMed  Google Scholar 

  9. Graham F, Lord M, Froment D, Cardinal H, Bollée G. The use of gallium-67 scintigraphy in the diagnosis of acute interstitial nephritis. Clin Kidney J. 2016;9:76–81.

    Article  CAS  PubMed  Google Scholar 

  10. Graham GD, Lundy MM, Moreno AJ. Failure of Gallium-67 scintigraphy to identify reliably noninfectious interstitial nephritis: concise communication. J Nucl Med. 1983;24:568–70.

    CAS  PubMed  Google Scholar 

  11. Ohkubo Y, Sasayama A, Takegahara I, Katoh S, Abe K, Kohno H, Kubodera A. 67Ga in transferrin-unbound form is taken up by inflamed liver of mouse treated with CCl4. Ann Nucl Med. 1990;4:89–93.

    Article  CAS  PubMed  Google Scholar 

  12. Akimoto T, Horikoshi R, Muto S, Kusano E. Low-dose corticosteroid and gallium-67 scintigraphy and acute interstitial nephritis. Saudi J Kidney Dis Transpl. 2014;25:864–8.

    Article  PubMed  Google Scholar 

  13. Helms E, Servilla KS, Hartshorne MF, Harris A, Nichols MJ, Tzamaloukas AH. Tubulointerstitial nephritis and uveitis syndrome: use of gallium scintigraphy in its diagnosis and treatment. Int Urol Nephrol. 2005;37:119–22.

    Article  PubMed  Google Scholar 

  14. Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A, Collaborators developing the Japanese equation for estimated GFR. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.

    Article  CAS  PubMed  Google Scholar 

  15. Lucio CG, Vincenzo C, Antonio R, Oscar T, Antonio R, Luigi M. Neurological applications for myocardial MIBG scintigraphy. Nucl Med Rev Cent East Eur. 2013;16:35–41.

    Article  PubMed  Google Scholar 

  16. Muriithi AK, Leung N, Valeri AM, Cornell LD, Sethi S, Fidler ME, Nasr SH. Biopsy-proven acute interstitial nephritis, 1993–2011: a case series. Am J Kidney Dis. 2014;64:558–66.

    Article  PubMed  Google Scholar 

  17. Nolan CM, Abernathy RS. Nephropathy associated with methicillin therapy. Prevalence and determinants in patients with staphylococcal bacteremia. Arch Intern Med. 1977;137:997–1000.

    Article  CAS  PubMed  Google Scholar 

  18. Roufosse C, Simmonds N, Clahsen-van Groningen M, Haas M, Henriksen KJ, Horsfield C, Loupy A, Mengel M, Perkowska-Ptasińska A, Rabant M, Racusen LC, Solez K, Becker JU. A 2018 reference guide to the banff classification of renal allograft pathology. Transplantation. 2018;102:1795–814.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Yamaguchi Y, Kanetsuna Y, Honda K, et al. Characteristic tubulointerstitial nephritis in IgG4-related disease. Hum Pathol. 2012;43(4):536–49.

    Article  PubMed  Google Scholar 

  20. Schisterman EF, Perkins NJ, Liu A, Bondell H. Optimal cut-point and its corresponding Youden Index to discriminate individuals using pooled blood samples. Epidemiology. 2005;16:73–81.

    Article  PubMed  Google Scholar 

  21. Leening MJ, Vedder MM, Witteman JC, Pencina MJ, Steyerberg EW. Net reclassification improvement: computation, interpretation, and controversies: a literature review and clinician’s guide. Ann Intern Med. 2014;160:122–31.

    Article  PubMed  Google Scholar 

  22. Mikami S, Hamano T, Fujii N, Nagasawa Y, Isaka Y, Moriyama T, Matsuhisa M, Ito T, Imai E, Hori M. Serum osteoprotegerin as a screening tool for coronary artery calcification score in diabetic pre-dialysis patients. Hypertens Res. 2008;31:1163–70.

    Article  CAS  PubMed  Google Scholar 

  23. Ito Y, Okuyama S, Sato K, Takahashi K, Sato T, Kanno I. 67Ga tumor scanning and its mechanisms studied in rabbits. Radiology. 1971;100:357–62.

    Article  CAS  PubMed  Google Scholar 

  24. Tsan MF, Chen WY, Scheffel U, Wagner HN Jr. Studies on gallium accumulation in inflammatory lesions: I. Gallium uptake by human polymorphonuclear leukocytes. J Nucl Med. 1978;19:36–43.

    CAS  PubMed  Google Scholar 

  25. Hoffer PB, Huberty J, Khayam-Bashi H. The association of Ga-67 and lactoferrin. J Nucl Med. 1977;18:713–7.

    CAS  PubMed  Google Scholar 

  26. Bombardieri E, Aktolun C, Baum RP, Bishof-Delaloye A, Buscombe J, Chatal JF, Maffioli L, Moncayo R, Mortelmans L, Reske SN. 67Ga scintigraphy: procedure guidelines for tumour imaging. Eur J Nucl Med Mol Imaging. 2003;30:BP125-31.

    PubMed  Google Scholar 

  27. Menon S, Wagner HN Jr, Tsan MF. Studies on gallium accumulation in inflammatory lesions: II. uptake by Staphylococcus aureus: concise communication. J Nucl Med. 1978;19:44–7.

    CAS  PubMed  Google Scholar 

  28. Ando A, Nitta K, Ando I, Sanada S, Katsuda S, Tonami N, Hiraki T, Hisada K, Ogawa H. Mechanism of gallium 67 accumulation in inflammatory tissue. Eur J Nucl Med. 1990;17:21–7.

    Article  CAS  PubMed  Google Scholar 

  29. Fernandez-Juarez G, Perez JV, Caravaca-Fontán F, Quintana L, Shabaka A, Rodriguez E, Gadola L, de Lorenzo A, Cobo MA, Oliet A, Sierra M, Cobelo C, Iglesias E, Blasco M, Galeano C, Cordon A, Oliva J, Praga M, Spanish Group for the Study of Glomerular Diseases (GLOSEN). Duration of treatment with corticosteroids and recovery of kidney function in acute interstitial nephritis. Clin J Am Soc Nephrol. 2018;13:1851–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Rankin AJ, Cannon E, Gillis K, Crosby J, Mark PB, Geddes CC, Fox JG, Mackinnon B, McQuarrie EP, Kipgen D. Predicting outcome in acute interstitial nephritis: a case–series examining the importance of histological parameters. Histopathology. 2020;76:698–706.

    Article  PubMed  Google Scholar 

  31. Wendt R, Schliecker J, Beige J. Inflammatory leucocyte infiltrates are associated with recovery in biopsy-proven acute interstitial nephritis: a 20-year registry-based case series. Clin Kidney J. 2019;12:814–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Joaquim AI, Mendes GE, Ribeiro PF, Baptista MA, Burdmann EA. Ga-67 scintigraphy in the differential diagnosis between acute interstitial nephritis and acute tubular necrosis: an experimental study. Nephrol Dial Transplant. 2010;25:3277–82.

    Article  CAS  PubMed  Google Scholar 

  33. Linton AL, Clark WF, Driedger AA, Turnbull DI, Lindsay RM. Acute interstitial nephritis due to drugs: review of the literature with a report of nine cases. Ann Intern Med. 1980;93:735–41.

    Article  CAS  PubMed  Google Scholar 

  34. Lin WY, Hsieh JF, Tsai SC, Lan JL, Cheng KY, Wang SJ. Semi-quantitative evaluation of gallium-67 scintigraphy in lupus nephritis. Eur J Nucl Med. 2000;27:1626–31.

    Article  CAS  PubMed  Google Scholar 

  35. Skálová S. The diagnostic role of urinary N-acetyl-beta-D-glucosaminidase (NAG) activity in the detection of renal tubular impairment. Acta Medica (Hradec Kralove). 2005;48:75–80.

    Article  PubMed  Google Scholar 

  36. Obert LA, Elmore SA, Ennulat D, Frazier KS. A review of specific biomarkers of chronic renal injury and their potential application in nonclinical safety assessment studies. Toxicol Pathol. 2021;49:996–1023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Trof RJ, Di Maggio F, Leemreis J, Groeneveld AB. Biomarkers of acute renal injury and renal failure. Shock. 2006;26:245–53.

    Article  CAS  PubMed  Google Scholar 

  38. Wu Y, Yang L, Su T, Wang C, Liu G, Li XM. Pathological significance of a panel of urinary biomarkers in patients with drug-induced tubulointerstitial nephritis. Clin J Am Soc Nephrol. 2010;5:1954–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Hettinga YM, Scheerlinck LM, Lilien MR, Rothova A, de Boer JH. The value of measuring urinary β2-microglobulin and serum creatinine for detecting tubulointerstitial nephritis and uveitis syndrome in young patients with uveitis. JAMA Ophthalmol. 2015;133:140–5.

    Article  PubMed  Google Scholar 

  40. Tsai SC, Hsieh TY, Huang PW, Lin WY. Absolute quantitative evaluation of 67Ga scintigraphy in lupus nephritis. Clin Nucl Med. 2016;41:442–6.

    Article  PubMed  Google Scholar 

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Acknowledgements

We would like to thank the hospital and laboratory staff for supporting this study. This study was not funded by any commercial, private, or not-for-profit sectors.

Funding

The authors did not receive support from any organization for the submitted work.

Author information

Authors and Affiliations

  1. Department of Nephrology, Tokyo Teishin Hospital, 2-14-23 Fujimi, Chiyoda-Ku, Tokyo, Japan

    Mimiko Matsumura, Mariko Sekiguchi & Hideki Takano

  2. Division of Nephrology and Endocrinology, Graduate School of Medicine Faculty of Medicine, The University of Tokyo, Tokyo, Japan

    Mimiko Matsumura, Akira Okada, Tetsuhiro Tanaka & Masaomi Nangaku

  3. Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine Faculty of Medicine, The University of Tokyo, Tokyo, Japan

    Akira Okada

  4. Department of Radiology, Tokyo Teishin Hospital, Tokyo, Japan

    Hiroaki Yokoyama

  5. Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan

    Akira Shimizu

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  1. Mimiko Matsumura
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Contributions

MM, AO, HY, MS, AS, and HT developed the study concept and design. MM, HY, and MS participated in data acquisition. MM, HY, and AO performed the statistical analysis. MM, AO, and AS interpreted the data. MM and AO drafted the manuscript. AS, TT, MN, and HT critically revised the work for important intellectual content. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Mimiko Matsumura.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee at which the studies were conducted (IRB approval number 1124) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Matsumura, M., Okada, A., Yokoyama, H. et al. Usefulness of gallium-67 scintigraphy for evaluating the histopathological activity in interstitial nephritis. Clin Exp Nephrol 27, 251–261 (2023). https://doi.org/10.1007/s10157-022-02302-0

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