Home About us Current issue Ahead of Print Back issues Submission Instructions Advertise Contact Login   

Search Article 
Advanced search 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 3737 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 

Table of Contents   
Year : 2014  |  Volume : 25  |  Issue : 4  |  Page : 864-868
Low-dose corticosteroid and gallium-67 scintigraphy and acute interstitial nephritis

Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan

Click here for correspondence address and email

Date of Web Publication24-Jun-2014


We describe a 19-year-old male who developed diclofenac-induced acute inters­titial nephritis (AIN). Diffuse mononuclear cell infiltration was confirmed by renal biopsy and a Gallium (Ga)-67 scintigraphy revealed diffuse uptake of the isotope in both kidneys. His renal function had gradually and promptly recovered after initiation of low-dose prednisolone (0.5 mg/kg/day). There are no established criteria for the administration of corticosteroids in the treatment of drug-induced AIN. Moreover, no clear recommendations regarding the optimal dose and duration of steroid administration in the treatment for drug-induced AIN has been established. In addition, we discuss the clinical benefit of steroid treatment and the diagnostic impact of Ga scanning on the management of drug-induced AIN.

How to cite this article:
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

How to cite this URL:
Akimoto T, Horikoshi R, Muto S, Kusano E. Low-dose corticosteroid and gallium-67 scintigraphy and acute interstitial nephritis. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2022 Jan 17];25:864-8. Available from: https://www.sjkdt.org/text.asp?2014/25/4/864/135184

   Introduction Top

The optimal management of drug-induced acute interstitial nephritis (AIN) remains to be delineated. [1],[2] However, several reports have demonstrated a better outcome of drug-induced AIN in patients who receive corticosteroids, although there were considerable variations in their dose and duration thus suggesting that they may help to avoid subsequent interstitial fibrosis and an incomplete recovery of renal function. [3],[4],[ [5]

In this report, we describe a case of drug-induced AIN in which the deteriorated renal function was successfully recovered following administration of low-dose oral prednisolone (PSL). The use of Gallium-67 (Ga-67) scinti-gram seemed to be of assistance in evaluating and monitoring disease activity and response to treatment.

   Case Report Top

A 19-year-old male was referred and admitted to our hospital in October 2006 with com­plaints of appetite loss, low-grade fever and progressive renal failure. Three weeks prior to admission, he had lumbar tenderness and pain, dysuria and a fever of 38°C. Urinalysis re­vealed pyuria with occasional red blood cells. A presumptive diagnosis of a urinary tract in­fection was made and, accordingly, he received oral cephalosporin cefcapene pivoxil hydro-chloride hydrate (CFPN) (300 mg/day) and diclofenac (75 mg/day). A few days later, he felt less tired and the subsequent laboratory tests showed improvement of his urinalysis; however, his serum creatinine (SCr) gradually increased from 1.7 mg/ dL up to 2.55 mg/dL. He had no apparent past history of renal disease. Both drugs were discontinued two weeks prior to admission.

A physical examination upon admission re­vealed a well-nourished man with periorbital and leg edema. His blood pressure was 122/74 mm Hg, pulse rate was 72 beats/min, respira­tory rate was 12/min and temperature was 37.1°C. His lungs were clear and heart sounds were normal. There was no rash, lymphade-nopathy or swelling of his joints. Renal sono-graphy showed the right and left kidneys to measure 11.1 cm and 11.0 cm, respectively, with normal cortex echogenicity. A laboratory evaluation revealed white blood cells 11,800/ mm [3] , polymorphonuclear leukocytes 75.9%, eosinophils 0.4%, lymphocytes 13.1% and monocytes 6.4%; hemoglobin 12.6 g/dL; hema­tocrit 37.7%; platelet count 52.1 × 10 [4] /mm [3] ; blood urea nitrogen 25 mg/dL; SCr 2.48 mg/ dL; and C-reactive protein (CRP) 2.68 mg/dL. No abnormalities were observed in his electro­lyte levels or liver functions. Anti-glomerular basement membrane antibodies, myeloperoxi­dase anti-neutrophil cytoplasmic antibodies and proteinase 3 anti-neutrophil cytoplasmic antibodies were negative and complement le­vels were within the normal limits.

Urinalysis revealed active sediments with 11-12 epithelial casts per low-power field and less than two red blood cells per high-power field. Protein in a 24-h specimen was 0.51 g. The fraction of excretion of sodium (FE Na ) was 0.37. The urinary excretion of β2-microglo-bulin (β2MG) and jV-acetyl-beta-D-glucosami-nidase (NAG) were 10,981 g/L and 16.6 U/L, respectively.

A Ga-67 scintigraphy study revealed diffuse 4+ uptake of the isotope in both kidneys [Figure 1]A.
Figure 1: (A) A posterior 48-h Ga-67 scan performed in October 2006 showed increased gallium uptake in both kidneys. (B) A posterior 48-h Ga-67 scan 5 months after the previous scintigram demonstrated no abnormal gallium uptake in either kidney. (C and D) The renal biopsy sections showed normal-appearing glomeruli with sporadic eosinophils (arrows) (C) and mononuclear infiltrates associated with interstitial edema (D). Periodic acid-Schiff stain, the scale bar is indicated in each panel.

Click here to view

A renal biopsy specimen obtained four days after admission consisted of three cores of renal parenchyma with 16 glomeruli, and showed no significant histological changes [Figure 1]C. There was marked diffuse infiltra­tion with lymphocytes and eosinophils accom­panied by partial destruction of tubular struc­tures [Figure 1]D. Interstitial edema and mild tubular atrophy were also observed. Immuno-histochemistry failed to reveal any immune complex deposits among the observed glo-meruli. Electron microscopy disclosed focal fusions of the foot processes of the glomerular visceral epithelial cells.

The CFPN was negative for the drug lym­phocyte stimulation test (DLST) determined by a commercially based clinical diagnostic testing service (SRL. Inc., Tokyo, Japan), while the patient showed a specific high stimulation index (SI) score for diclofenac of 182% (the cutoff value for positivity is 180%). Finally, the patient was diagnosed to have diclofenac-associated AIN. Because elevation of SCr persisted despite the discontinuation of the offending agent, oral PSL at a dose of 30 mg/day (0.5 mg/kg/day) was initiated on Day 15, and the following laboratory analysis revealed gradual improvement in his renal function [Figure 2]. In January 2007, his SCr had decreased to 1.13 mg/dL despite gradual tapering of the dose of PSL to 5 mg/day. Two months later, the disappearance of renal Ga-67 uptake was confirmed by the iterative scinti-gram [Figure 1]B, and oral administration of PSL was discontinued. Thereafter, his clinical course was uneventful and his SCr was finally decreased to 0.99 mg/dL in November 2007.
Figure 2: Changes in the SCr, β2MG and NAG.. Note the insufficient decreases in both the urinary excretion of β2MG and NAG at the time when the second Ga-67 scan was performed.

Click here to view

   Discussion Top

There are no established criteria for the admi­nistration of corticosteroids in the treatment of drug-induced AIN, while the common regimen for the treatment of drug-induced AIN consists of an initial dose equivalent to 1 mg/kg/day or 60 mg/day of PSL in patients with no infec-tion. [1],[5] In our case, the interval between drug withdrawal and the onset of steroid treatment was approximately four weeks. Therefore, one may argue that the spontaneous remission played a role in the renal recovery and that the effect of the steroid was marginal. [2],[5] However, the prompt improvements in his renal function after the initiation of steroid treatment led us to conclude that the discontinuation of the causative agents administered prior to admis­sion was insufficient and that even the rela­tively low dose of PSL of 0.5 mg/kg/day had a clinical benefit on his deteriorated renal function, similar to our previous experiences. [3],[4]

Ga-67 scanning has been widely used for many years in the study of numerous renal inflammatory disorders. [6],[7],[8] The renal Ga-67 up­take is not necessarily positive in some pa­tients with chronic interstitial nephritis, [9] while such uptake may be observed in some subjects with no evidence of renal disease. [10] Therefore, the diagnostic impact and the clinical signi­ficance of Ga-67 scanning in the overall management of patients with renal interstitial injuries should be evaluated more carefully. Nevertheless, the fact that there were no ad­verse changes in the present patient's renal characteristics after cessation of steroid treat­ment, when there was negative renal Ga-67 uptake, but insufficient recovery of the urinary β2MG and NAG supports the concept that Ga-67 scanning may be useful for evaluating the disease activity and the therapeutic response of certain subsets of patients with renal disorders, including AIN, [11],[12],[13],[14] and may also be of assis­tance in determining the duration of the steroid administration and the appropriate point for the cessation of steroid treatment. Obviously, the validity of these concepts needs to be evaluated in greater depth in further studies.

The DLST has been considered to be a useful diagnostic procedure for various kinds of drug hypersensitivity, including drug-induced AIN, although it may sometimes give a negative result when the number of sensitized lympho­cytes in the peripheral blood is low or the stage of AIN is advanced. [15],[16],[17] In our present patient, the CFPN was negative in the DLST, while he showed a specific high SI score for diclofenac. AIN due to CFPN has not pre­viously been reported in the literature; how­ever, this does not mean that this agent may offer an improved renal safety profile com­pared with other cephalosporin derivatives. [1] Nonetheless, we feel it is reasonable to con­sider that the administration of diclofenac, rather than CFPN, played a role in the deve­lopment of AIN associated with renal dysfunc­tion, as was reported anecdotally. [4],[18],[19] Consis­tently, our patient had an FE Na of below 1% just after admission, suggesting the presence of reduced renal perfusion due to a presumable decrease in prostaglandin vasodilators induced by diclofenac. [4],[20]

   References Top

1.Rossert J. Drug-induced acute interstitial nephritis. Kidney Int 2001;60:804-817.  Back to cited text no. 1
2.Clarkson MR, Giblin L, O'Connell FP, et al. Acute interstitial nephritis: Clinical features and response to corticosteroid therapy. Nephrol Dial Transplant 2004;19:2778-83.  Back to cited text no. 2
3.Onishi A, Yamamoto H, Akimoto T, et al. Reversible acute renal failure associated with clomipramine-induced interstitial nephritis. Clin Exp Nephrol 2007;11:241-3.  Back to cited text no. 3
4.Inoue M, Akimoto T, Saito O, Ando Y, Muto S, Kusano E. Successful relatively low-dose corticosteroid therapy for diclofenac-induced acute interstitial nephritis with severe renal failure. Clin Exp Nephrol 2008;12:296-9.  Back to cited text no. 4
5.González E, Gutiérrez E, Galeano C, et al. Early steroid treatment improves the recovery of renal function in patients with drug-induced acute interstitial nephritis. Kidney Int 2008; 73:940-6.  Back to cited text no. 5
6.Lin DS, Sanders JA, Patel BR. Delayed renal localization of Ga-67: Concise communication. J Nucl Med 1983;24:894-7.  Back to cited text no. 6
7.Wood BC, Sharma JN, Germann DR, Wood WG, Crouch TT. Gallium citrate Ga 67 imaging in noninfectious interstitial nephritis. Arch Intern Med 1978;138:1665-6.  Back to cited text no. 7
8.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.  Back to cited text no. 8
9.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.  Back to cited text no. 9
10.Garcia JE, Van Nostrand D, Howard WH 3rd, Kyle RW. The spectrum of gallium-67 renal activity in patients with no evidence of renal disease. J Nucl Med 1984;25:575-80.  Back to cited text no. 10
11.Lin WY, Cheng KY, Wang SJ. Ga-67 scintigraphy in lupus nephritis. Clin Nucl Med 1998;23:517-20.  Back to cited text no. 11
12.Yen TC, Tzen KY, Chen WP, Lin CY. The value of Ga-67 renal SPECT in diagnosing and monitoring complete and incomplete treatment in children with acute pyelonephritis. Clin Nucl Med 1999;24:669-73.  Back to cited text no. 12
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.  Back to cited text no. 13
14.Masuda T, Akimoto T, Ando Y, et al. Changes in the urinary excretion of beta2-microglobulin (beta 2MG) and N-acetyl-beta-D-glucosami-nidase (NAG) during treatment for lupus nephritis. Intern Med 2008;47:287-90.  Back to cited text no. 14
15.Joh K, Aizawa S, Yamaguchi Y, et al. Drug-induced hepersensitivity nephritis: Lympho­cyte stimulation testing and renal biopsy in 10 cases. Am J Nephrol 1990;10:222-30.  Back to cited text no. 15
16.Pichler WJ, Tilch J. The lymphocyte transformation test in the diagnosis of drug hyper-sensitivity. Allergy 2004;59:809-20.  Back to cited text no. 16
17.Suzuki Y, Miwa S, Shirai M, et al. Drug lymphocyte stimulation test in the diagnosis of adverse reactions to antituberculosis drugs. Chest 2008;134:1027-32.  Back to cited text no. 17
18.Wolters J, van Breda Vriesman PJ. Minimal change nephropathy and interstitial nephritis associated with diclofenac. Neth J Med 1985; 28:311-4.  Back to cited text no. 18
19.Revai T, Harmos G. Nephrotic syndrome and acute interstitial nephritis associated with the use of diclofenac. Wien Klin Wochenschr 1999;111:523-4.  Back to cited text no. 19
20.Brown MA, Trew PA, Smart RC. A simple aid to the differential diagnosis of oliguria. Aust NZ J Med 1983;13:608-12.  Back to cited text no. 20

Correspondence Address:
Tetsu Akimoto
Division of Nephrology, Department of Internal Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-Shi, Tochigi 329-0498
Login to access the Email id

DOI: 10.4103/1319-2442.135184

PMID: 24969203

Rights and Permissions


  [Figure 1], [Figure 2]

This article has been cited by
1 Tubulointerstitial nephritis and uveitis syndrome following meningitis and systemic lymphadenopathy with persistent Toxoplasma immunoglobulin M: a case report
Yoshihiro Oya, Hidekazu Futami, Takuya Nakazawa, Kazuyuki Ishijima, Keiko Umemiya, Fumiyoshi Takizawa, Naoki Imai, Hiroshi Kitamura, Ryutaro Matsumura
Journal of Medical Case Reports. 2021; 15(1)
[Pubmed] | [DOI]


    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  

   Case Report
    Article Figures

 Article Access Statistics
    PDF Downloaded463    
    Comments [Add]    
    Cited by others 1    

Recommend this journal