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malignities&#44; auto-immune and auto-inflammatory diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#44;3</span></a> Treatment is needed for cumbersome symptom of pruritis and life-threatening medical emergency of angioedema&#46; Omalizumab&#44; which is recombinant humanized monoclonal antibody for immunoglobulin &#40;Ig&#41; E is advised for treatment of CIU as the third or fourth line of therapy after histamine receptor type 1 &#40;H<span class="elsevierStyleInf">1</span>&#41; antihistamines and leukotriene receptor antagonists are unsuccessful&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A 53-year-old female patient with diabetes mellitus&#44; hysterectomy and CIU had symptoms of nausea and fatigue&#46; In her medical history&#44; she has been taking bilastine &#40;20<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; for 1 year&#44; methylprednisolone was prescribed to the patient due to angioedema which affected tongue and larynx for 30 days until 5 months ago&#44; diclofenac was given for pain relief after hysterectomy&#44; she had taken dexketoprofen &#40;25<span class="elsevierStyleHsp" style=""></span>mg&#47;every 3 day&#41; for 3 months until 2 months ago and she was injected the fifth monthly dose of 150<span class="elsevierStyleHsp" style=""></span>mg omalizumab 15 days ago&#46; Laboratory evaluation revealed increased serum creatinine level &#40;1&#46;64<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; with respect to basal levels &#40;0&#46;65<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; of 6 months earlier&#44; decreased glomerular filtration rate &#40;GFR&#41; &#40;estimated GFR using Chronic Kidney Disease Epidemiology Collaboration&#44; CKD-EPI equation was 34<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#44; 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Presence of high amount of low molecular weight proteins &#40;beta-2 microglobulin&#41; in her urine analysis indicated tubular type consisting majority of proteinuria&#46; Kidney biopsy showed acute interstitial nephritis accompanied with chronic interstitial injury related findings without immune deposition &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; In addition&#44; early stage of diabetic nephropathy was observed due to diffuse basal membrane thickening&#46; Oral methylprednisolone was given to the patient at the dose of 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d for treatment of AIN&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Dose was slowly tapered to 5<span class="elsevierStyleHsp" style=""></span>mg&#47;day after a month and prescribed for another 3 months&#46; Her serum creatinine level was decreased from 2&#46;24<span class="elsevierStyleHsp" style=""></span>mg&#47;dL to 1&#46;58<span class="elsevierStyleHsp" style=""></span>mg&#47;dL in 10 days of treatment&#44; and after 4 months her serum creatinine level was 0&#46;82<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The cause of AIN in majority of the patients was known as hypersensitivity towards drugs &#40;75&#37; of the cases&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> Practically&#44; every drug may have a potential for causing AIN&#44; yet mostly reported drugs are antibiotics&#44; NSAID&#44; proton pump inhibitors and allupurinol&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> The time interval between drug intake and onset of AIN can vary from 1 week to 9 months &#40;10&#8211;11 weeks being the commonest&#41; among the patients&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> The most possible offending agent for AIN of the patient was thought as diclofenac since absence of any report regarding the other medications that our patient had taken &#40;methylprednisolone&#44; dexketoprofen&#44; gliclazide&#44; metformin&#44; bilastine&#44; and omalizumab&#41;&#46; It is known that NSAID induced AIN does not generally response to glucocorticoid therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Conflicting with this information&#44; our patient responded well to corticosteroid treatment which made us suspect some other drug she used might have led to AIN other than NSAID&#46; The association of CIU with AIN has not been reported yet&#46; It might be possible but needs to be clarified that AIN of our patient may result from one of the hypersensitivity reaction and manifestation of CIU&#46; However&#44; her itching symptoms completely abolished by omalizumab and this AIN developed during omalizumab treatment of 5 months duration&#46; Omalizumab has been shown to decrease serum eosinophil levels and effective in treatment of CIU through its functions against eosinophils&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> In theory&#44; omalizumab might have been protective for development of AIN via these eosinophil depleting effects&#46; However&#44; even though 5 months of omalizumab treatment&#44; our patient had AIN which was treated successfully with methylprednisolone&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In conclusion&#44; AIN of our case most probably was secondary to diclofenac intake 5 months earlier even though presence of response to glucocorticoids&#46; Whether presence of CIU increase the tendency of patients to development of AIN secondary to offending drugs has not been known yet&#46; Renal functions especially tubular proteinuria should be evaluated and searched thoroughly in order to diagnose early and treat appropriately for AIN among individuals with CIU before and during prescription of any drug&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Authors&#8217; contributions</span><p id="par0025" class="elsevierStylePara elsevierViewall">Kubra Kaynar&#58; Conception&#44; design&#44; drafting the article&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Nejla K&#252;&#231;&#252;k&#58; Drafting the article&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Sevdeg&#252;l Mungan&#58; Drafting the pathological data of the case&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Beyhan G&#252;vercin&#58; Drafting the article&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">&#350;&#252;kr&#252; Ulusoy&#58; Drafting the article&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gender&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nausea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Blood pressure &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">120&#47;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serum creatinine level &#40;mg&#47;dL&#41;6 months earlier&#47;at admission&#47;during AKI&#47;last visit&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;65&#47;1&#46;64&#47;2&#46;21&#47;0&#46;82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Proteinuria level &#40;g&#47;d&#41;At admission&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Albuminuria &#40;mg&#47;d&#41;At admission&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Beta-2 microglobulinuria level &#40;&#956;g&#47;L&#41;At admission&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">21&#44;300&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Past drug history for the last 6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Methylprednisolone&#44; diclofenac&#44; dexketoprofen&#44; and omalizumab&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serum ANA&#44; anti dsDNA&#44; and ANCA test results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Present drug history&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Gliclazide&#44; metformin&#44; bilastine&#44; and omalizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis based on&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Clinical and histopathological data&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Comorbid diseases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Diabetes mellitus&#44; chronic idiopathic urticaria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Renal pathology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acute interstitial nephritis accompanied with chronic interstitial injury and early stage of diabetic nephropathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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Vol. 42. Núm. 1.enero - febrero 2022
Páginas 1-112
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Vol. 42. Núm. 1.enero - febrero 2022
Páginas 1-112
Letter to the Editor
Open Access
Acute interstitial nephritis in a patient with chronic idiopathic urticaria
Nefritis intersticial aguda en un paciente con urticaria crónica idiopática
Visitas
5048
Kubra Kaynara,
Autor para correspondencia
kkaynar@yahoo.com

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, Nejla Küçükb, Sevdegül Munganc, Beyhan Güvercina, Şükrü Ulusoya
a Department of Nephrology, Karadeniz Technical University, Faculty of Medicine, Trabzon, Turkey
b Department of Internal Medicine, Karadeniz Technical University, Faculty of Medicine, Trabzon, Turkey
c Department of Pathology, Karadeniz Technical University, Faculty of Medicine, Trabzon, Turkey
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Acute interstitial nephritis (AIN) which is characterized as inflammation and oedema around renal tubuli mostly due to hypersensitivity to drugs, has been reported to be underlying aetiology among 5–27% of acute kidney injury cases in hospitalized patients.1 Chronic idiopathic urticaria (CIU), is an intrinsic immunological abnormality independent of external causes without a triggering stimulus like stress, physical factor, drug and food. It usually affects females with a prevalence of 1% and mostly begins at the age of 30–50 years.2 Diagnosis mostly depend on chronic recurrent itching persisting at least six weeks with exclusion of diseases like infections, malignities, auto-immune and auto-inflammatory diseases.2,3 Treatment is needed for cumbersome symptom of pruritis and life-threatening medical emergency of angioedema. Omalizumab, which is recombinant humanized monoclonal antibody for immunoglobulin (Ig) E is advised for treatment of CIU as the third or fourth line of therapy after histamine receptor type 1 (H1) antihistamines and leukotriene receptor antagonists are unsuccessful.3,4

A 53-year-old female patient with diabetes mellitus, hysterectomy and CIU had symptoms of nausea and fatigue. In her medical history, she has been taking bilastine (20mg/day) for 1 year, methylprednisolone was prescribed to the patient due to angioedema which affected tongue and larynx for 30 days until 5 months ago, diclofenac was given for pain relief after hysterectomy, she had taken dexketoprofen (25mg/every 3 day) for 3 months until 2 months ago and she was injected the fifth monthly dose of 150mg omalizumab 15 days ago. Laboratory evaluation revealed increased serum creatinine level (1.64mg/dL) with respect to basal levels (0.65mg/dL) of 6 months earlier, decreased glomerular filtration rate (GFR) (estimated GFR using Chronic Kidney Disease Epidemiology Collaboration, CKD-EPI equation was 34mL/min/1.73m2, creatinine clearance using 24-h urine collection was 37.4mL/min), microalbuminuria (98mg/d), increased proteinuria (1.3g/d), and increased beta-2 microglobulinuria (21,300μg/L, normal value <300μg/L5). Her urinary beta-2 microglobulin: creatinine ratio was 76071 (μg/g) (normal<300μg/g6). Biochemically her serum creatinine level was increased to 2.21mg/dL within 8 days (Table 1). Presence of high amount of low molecular weight proteins (beta-2 microglobulin) in her urine analysis indicated tubular type consisting majority of proteinuria. Kidney biopsy showed acute interstitial nephritis accompanied with chronic interstitial injury related findings without immune deposition (Fig. 1). In addition, early stage of diabetic nephropathy was observed due to diffuse basal membrane thickening. Oral methylprednisolone was given to the patient at the dose of 1mg/kg/d for treatment of AIN.7 Dose was slowly tapered to 5mg/day after a month and prescribed for another 3 months. Her serum creatinine level was decreased from 2.24mg/dL to 1.58mg/dL in 10 days of treatment, and after 4 months her serum creatinine level was 0.82mg/dL.

Table 1.

Clinical and laboratory findings of the patient.

Parameter  Patient 
Age (years)  53 
Gender  Female 
Complain  Nausea 
Blood pressure (mmHg)  120/80 
Serum creatinine level (mg/dL)6 months earlier/at admission/during AKI/last visit  0.65/1.64/2.21/0.82 
Proteinuria level (g/d)At admission  1.3 
Albuminuria (mg/d)At admission  98 
Beta-2 microglobulinuria level (μg/L)At admission  21,300 
Past drug history for the last 6 months  Methylprednisolone, diclofenac, dexketoprofen, and omalizumab 
Serum ANA, anti dsDNA, and ANCA test results  Negative 
Present drug history  Gliclazide, metformin, bilastine, and omalizumab 
Diagnosis based on  Clinical and histopathological data 
Comorbid diseases  Diabetes mellitus, chronic idiopathic urticaria 
Renal pathology  Acute interstitial nephritis accompanied with chronic interstitial injury and early stage of diabetic nephropathy 
Fig. 1.

Severe interstitial lymphocytic (including eosinophylic lymphocytes, plasma cells and mostly mononuclear leukocytes) infiltration affected 60% of cortical area, and interstitial fibrosis with tubular atrophy involved 30% of the tissue, H.E. 100×.

(0.08MB).

The cause of AIN in majority of the patients was known as hypersensitivity towards drugs (75% of the cases).8 Practically, every drug may have a potential for causing AIN, yet mostly reported drugs are antibiotics, NSAID, proton pump inhibitors and allupurinol.9 The time interval between drug intake and onset of AIN can vary from 1 week to 9 months (10–11 weeks being the commonest) among the patients.9 The most possible offending agent for AIN of the patient was thought as diclofenac since absence of any report regarding the other medications that our patient had taken (methylprednisolone, dexketoprofen, gliclazide, metformin, bilastine, and omalizumab). It is known that NSAID induced AIN does not generally response to glucocorticoid therapy.7 Conflicting with this information, our patient responded well to corticosteroid treatment which made us suspect some other drug she used might have led to AIN other than NSAID. The association of CIU with AIN has not been reported yet. It might be possible but needs to be clarified that AIN of our patient may result from one of the hypersensitivity reaction and manifestation of CIU. However, her itching symptoms completely abolished by omalizumab and this AIN developed during omalizumab treatment of 5 months duration. Omalizumab has been shown to decrease serum eosinophil levels and effective in treatment of CIU through its functions against eosinophils.10 In theory, omalizumab might have been protective for development of AIN via these eosinophil depleting effects. However, even though 5 months of omalizumab treatment, our patient had AIN which was treated successfully with methylprednisolone.

In conclusion, AIN of our case most probably was secondary to diclofenac intake 5 months earlier even though presence of response to glucocorticoids. Whether presence of CIU increase the tendency of patients to development of AIN secondary to offending drugs has not been known yet. Renal functions especially tubular proteinuria should be evaluated and searched thoroughly in order to diagnose early and treat appropriately for AIN among individuals with CIU before and during prescription of any drug.

Authors’ contributions

Kubra Kaynar: Conception, design, drafting the article.

Nejla Küçük: Drafting the article.

Sevdegül Mungan: Drafting the pathological data of the case.

Beyhan Güvercin: Drafting the article.

Şükrü Ulusoy: Drafting the article.

Conflicts of interest

None declared.

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