Case Of Acute Interstitial Nephritis Research Articles

#1795 Diverse histological findings of kidney injury in cancer patients on immunotherapy- impact on clinical management

Abstract Background and Aims Immune checkpoint inhibitors (CPIs) are becoming rapidly more used to treat various types of cancer. Acute interstitial nephritis (AIN) is considered the most common pattern of kidney injury in these patients, however other distinct histological lesions are increasingly reported. The aim of this study is to assess the histological findings and the value of kidney biopsy in the management of patients with CPI-associated nephrotoxicity. Method All records from patients treated with CPIs and kidney injury that underwent a kidney biopsy during the last 4 years were retrospectively assessed. Results We included 16 biopsied patients treated with CPIs and kidney injury, 8 males and 8 females. The mean age at the time of renal biopsy was 68 (± 8.2) years and the median follow up time was 11.5 (8-29) months. The most common primary malignancy was non-small cell lung cancer (n = 8), followed by melanoma (n = 3), endometrial cancer (n = 2), renal cell carcinoma (n = 1), breast cancer (n = 1) and hepatocellular carcinoma (n = 1). At the time of kidney biopsy eleven patients were treated with pembrolizumab, three patients with ipilimumab and nivolumab combination, one patient with ipilimumab and one patient with atezolizumab. Eleven patients were on immune-chemo combined therapy. Twelve patients presented with acute kidney injury (AKI), two with nephrotic syndrome, one with nephrotic range proteinuria and one with acute onset of hypertension and subnephrotic proteinuria [Urine Protein (UPr): 3 g/24 h]. The median time to developing kidney injury from CPI initiation was 9 (4.25-21.5) months. The prevalent histologic lesion was AIN (n = 5), followed by three cases of mixed AIN with acute tubular injury (ATI), and two cases of pure ATI. We recorded three cases of CPI-associated glomerulonephritis including membranous nephropathy (MN) with a lupus-like pattern on immunofluorescence, AA amyloidosis and Focal Segmental Glomerulosclerosis (FSGS) cellular variant. Two patients had diabetic nephropathy (DN) with ATI and one patient had thrombotic microangiopathy (TMA) with ATI. Immunotherapy was temporarily withheld in all patients at the time of kidney biopsy. After the establishment of the histological diagnosis: we continued treatment with corticosteroids in nine patients (five cases with AIN, one case with mixed AIN/ATI, one case with MN, one case with FSGS and one case with TMA/ATI). Withdrawal of corticosteroids was decided in five cases (two patients with diabetic nephropathy, two patients with mixed ATI/AIN and one with ATI). The patient with AA amyloidosis was treated with colchicine and cortisone with partial remission of nephrotic syndrome (UPr: 1.2 g/24 h). In one case with pure ATI, corticosteroids, and the concomitant chemotherapeutic agent (pemetrexed) were withdrawn with complete response of AKI. Partial remission of proteinuria occurred in the patient with FSGS (UPr: 1.3 g/24 h). At the end of follow up, kidney recovery occurred in all 12 patients with AKI (among them one patient who required renal replacement therapy at the time of biopsy). Rechallenge with a CPI was attempted in 8 patients. After rechallenging, one patient experienced relapse of nephrotic syndrome (MN) and immunotherapy was withdrawn. The other seven patients continued CPI treatment without recurrence of kidney injury. The overall patient survival was 62.5%. Conclusion AIN is only one of the possible causes of nephrotoxicity in patients receiving CPIs. Kidney biopsy establishes the accurate diagnosis of CPI-associated AKI. In selected cases it allows the continuation of immunotherapy and can prevent the unnecessary use of corticosteroids.

17 A mysterious case of Acute interstitial Nephritis

17 A mysterious case of Acute interstitial Nephritis

A case of acute interstitial nephritis superimposed on rhabdomyolysis in a refugee patient.

A case of acute interstitial nephritis superimposed on rhabdomyolysis in a refugee patient.

Acute interstitial nephritis secondary to sarcoid-like reaction after autologous bone marrow transplantation: Case report

Sarcoid-Like Reaction is a systemic inflammatory granulomatous condition that does not meet the criteria for systemic Sarcoidosis—it is triggered by a known underlying factor, such as immunosuppression. Here we report a case of acute interstitial nephritis without granuloma in the context of a Sarcoid-Like systemic disease in the three-year period after an autologous stem cell transplant. The patient presented with a suspected relapse, associated with hemolytic anemia and an increase of serum creatinine. The investigation showed non-caseating epithelioid cell granuloma in a chest lymph node and in bone marrow, associated with combined hypogammaglobulinemia. Evaluation of the kidney tissue demonstrated acute interstitial nephritis.

New-Onset Acute Interstitial Nephritis Post-SARS-CoV-2 Infection and COVID-19 Vaccination: A Panoramic Review.

The 2019 coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has posed a considerable challenge to global healthcare. Acute interstitial nephritis (AIN) post SARS-CoV-2 infection and vaccination has been reported, but its clinical features and pathogenesis remained unclear. We reviewed so far the largest 22 cases of AIN post SARS-CoV-2 infection and 36 cases of AIN following COVID-19 vaccination. The onset of AIN was mainly related to messenger RNA vaccines (52.8%). Apart from fever, proteinuria (45.5%) was the main manifestation of AIN post SARS-CoV-2 infection, left acute kidney injury (AKI, 63.9%) in patients post COVID-19 vaccination. The potential mechanism of vaccination induced AIN was conjugating vaccines with proteins to form a hapten, which activated dendritic cells and promoted a cascade immunological reaction leading to AIN.

#6045 TWO-YEAR INPATIENT ACTIVITY OF A DEDICATED ONCONEPHROLOGY DEPARTMENT

Abstract Background and Aims Onconephrology is a rapidly evolving nephrology subspecialty that focuses on the interaction between cancer and the kidney. Our aim was to describe the clinical activity of a Nephrology Department in a cancer care center, in a 2-year period. Method We retrospectively analyzed the patients observed by the Nephrology Department at our center between 2021 and 2022. Demographic, clinical and laboratory data were collected. The statistical analysis was performed with SPSS software. Results During the 2-year period, there were 26,015 admissions, 636 of which required a Nephrology observation. Sixty-two per cent were female; the mean age was 68 years (SD ±12.4) with a median Charlson Comorbidity Index of 7. Most cancers were from gastrointestinal (24.1%, n = 153) or urologic origins (22.3%, n = 142), 37% had metastatic disease. Hematologic malignancies accounted for 12.1% of patients (n = 77). Nearly 44.5% of patients (n = 283) had chronic kidney disease (CKD), 20.8% (n = 59) of which were on hemodialysis (HD). Urinary tract obstruction (23.3%), cardiovascular risk factors (17.3%) and nephron loss (10.6%) were the most common causes of CKD. The main reasons for admission were renal dysfunction (23.7%; n = 151), infectious complications (23.3%, n = 148) and elective surgery (20.3%; n = 129). Of the patients observed, 40.7% (n = 259) had acute kidney injury (AKI), 23.3% (n = 148) acute-on-chronic kidney disease and 11.8% (n = 75) hydro-electrolytic disorders. Ten patients (1.6%) were evaluated for nephrotic syndrome (NS) or rapidly progressive renal failure (RPRF). Among AKI patients, intrinsic causes were the most prevalent (48.7% of all cases), with sepsis and ischemic and toxic acute tubular necrosis being the most frequent. Pre-renal and post-renal etiologies occurred in 29.7% and 21.6% of cases, respectively. Gynaecological and prostate tumours were the main neoplastic cause of post-renal AKI. There were 5 TMA cases in allogenic stem cell transplanted patients or treated with gemcitabine and six cases of acute interstitial nephritis, the majority immune check-point inhibitors-related. Over 54% (n = 142) of patients presented with AKI stage 3. About 13% (n = 34) needed renal replacement therapy (RRT), mainly continuous or hybrid techniques (58.8%; n = 20), and only 38% (n = 13) recovered renal function. The group of acute-on-chronic CKD patients included mostly stage 3b and 4 CKD. Most of them (54.1%; n = 80) had an intrinsic cause for kidney dysfunction. There was an equal distribution between stages of AKI severity. About 5% (n = 8) needed RRT and only two of those recovered. Hyponatremia was the most common electrolyte disturbance (56%; n = 42), followed by hypercalcemia (17.3%; n = 13). Over 40% of all cases of hyponatremia occurred in patients with metastatic lung cancer, probably related with the high prevalence of SIADH in this population. All but two patients with NS or RPRF underwent kidney biopsy. Among the patients with NS, its etiologies were: focal and segmental glomerulosclerosis secondary to pamidronate (n = 2), podocytopathy related to pazopanib (n = 1), paraneoplastic membranous nephropathy (n = 1), AL amyloidosis (n = 1) and TMA secondary to gemcitabine (n = 1). The causes of RPRF were ANCA-negative small vessel vasculitis, crescentic glomerulonephritis (GN) related to pembrolizumab and TMA. We also followed two patients with acute kidney disease, one with ATN secondary to bisphosphonates therapy and other with paraneoplastic fibrillary glomerulopathy. The median duration of hospitalization was 10 days (IQR 7.0 – 20.8), with median Nephrology follow-up time of 5.5 days (IQR 3.0 – 9.0). The overall mortality rate was 21.5%, and it was even higher on the subgroup with AKI (27.4%; p = 0.03). About 44% (n = 219) of patients were referred to outpatient Nephrology follow-up, at discharge. Conclusion Our data provides a picture of the rich inward activity developed at our cancer center by the nephrology team. The complexity of these patients highlights the importance of a multidisciplinary approach in their management. No surprisingly, there was a high mortality rate, which was even higher in the AKI-patients subset.

Kidney Biopsy Findings Among Allogenic Hematopoietic Stem Cell Transplant Recipients With Kidney Injury: A Case Series

The incidence of kidney disease is high in patients after allogeneic hematopoietic cell transplantation (aHCT). Although rarely performed, kidney biopsy may be useful to make a precise diagnosis because several mechanisms and risk factors can be involved, and to adjust the treatment accordingly. This case series aimed to report the spectrum of biopsy findings from patients with kidney injury after aHCT. Single-center retrospective case series. All individuals who underwent a native kidney biopsy, among all adult patients who received aHCT in a tertiary hospital in Montreal (Canada) from January 1, 2010, to December 31, 2020, were identified, and the clinical data were extracted from their medical records. A total of 17 patients were included. Indications for biopsy included acute kidney injury (n=6), chronic kidney disease (n=5), nephrotic syndrome (n=4), and subnephrotic proteinuria (n=2). Pathologic findings from the kidney biopsy were heterogenous: 10 patients showed evidence of thrombotic microangiopathy (TMA), 5 of acute tubular injury, and 4 of membranous nephropathy. Cases of acute interstitial nephritis, BK virus nephropathy, immune complex nephropathy, focal and segmental glomerulosclerosis, minimal change disease, and karyomegalic-like interstitial nephritis were also described. There was no systematic kidney biopsy performed for all patients with kidney injury after aHCT. Only a small proportion of patients with kidney damage underwent biopsy, making the results less generalizable. Kidney biopsy is useful in patients with kidney disease after aHCT to make a precise diagnosis and tailor therapy accordingly. This series is one of the few published studies describing pathologic findings of biopsies performed after aHCT in the context of acute kidney injury and chronic kidney disease. TMA was widely present on biopsy even when there was no clinical suspicion of such a diagnosis, suggesting that the current clinical criteria for a diagnosis of TMA are not sensitive enough for kidney-limited TMA.

403 Curious Case of Acute Interstitial Nephritis in Kidney Transplant: Association With Red Meat Allergy?

403 Curious Case of Acute Interstitial Nephritis in Kidney Transplant: Association With Red Meat Allergy?

Changing Tides of Acute Interstitial Nephritis: A Retrospective Observational Study from South India.

The incidence of acute interstitial nephritis (AIN) has been increasing in recent years. The causes and outcomes of AIN have been changing with time and vary widely based on geographical region. A retrospective observational study was conducted in a tertiary care center. All (n = 6234) native kidney biopsies were reviewed from January 2016 to December 2021. All biopsy-proven AIN cases were included in the study. AIN associated with systemic diseases (such as SLE, Sjogren's, sarcoidosis, plasma cell dyscrasias), proliferative glomerulonephritis, and allograft biopsies were excluded. Among 6234 biopsies analyzed, there were 156 biopsy-proven AIN cases. The majority were in the 6th decade of life (24.4%) and males (80.8%). 50% of the patients had a history of drug intake, the most common being tenofovir (12.3%) followed by alternate forms of medications (10.3%). The majority (96.2%) presented with acute kidney injury (AKI). At the end of six months, 79.5% recovered completely, 19.2% progressed to chronic kidney disease. The presence of nephrotic range proteinuria at presentation was associated with progression to chronic kidney disease. AIN is an important cause of AKI, especially in the elderly population. Drugs are the most common cause, especially HAART follwed by alternate forms of medication. The presence of nephrotic range proteinuria was associated with increased risk of progression to chronic kidney disease.

Tertiary lymphoid structure signatures are associated with immune checkpoint inhibitor related acute interstitial nephritis.

Tertiary lymphoid structures (TLSs) are associated with anti-tumor response following immune checkpoint inhibitor (ICI) therapy, but a commensurate observation of TLS is absent for immune related adverse events (irAEs) i.e. acute interstitial nephritis (AIN). We hypothesized that TLS-associated inflammatory gene signatures are present in AIN and performed NanoString-based gene expression and multiplex 12-chemokine profiling on paired kidney tissue, urine and plasma specimens of 36 participants who developed acute kidney injury (AKI) on ICI therapy: AIN (18), acute tubular necrosis (9), or HTN nephrosclerosis (9). Increased T and B cell scores, a Th1-CD8+ T cell axis accompanied by interferon-g and TNF superfamily signatures were detected in the ICI-AIN group. TLS signatures were significantly increased in AIN cases and supported by histopathological identification. Furthermore, urinary TLS signature scores correlated with ICI-AIN diagnosis but not paired plasma. Urinary CXCL9 correlated best to tissue CXCL9 expression (rho 0.75, p < 0.001) and the ability to discriminate AIN vs. non-AIN (AUC 0.781, p-value 0.003). For the first time, we report the presence of TLS signatures in irAEs, define distinctive immune signatures, identify chemokine markers distinguishing ICI-AIN from common AKI etiologies and demonstrate that urine chemokine markers may be used as a surrogate for ICI-AIN diagnoses.

S3707 A Cautionary Side of the Widely Prescribed: A Case of PPI-Induced AIN

Introduction: Proton pump inhibitors (PPIs) are widely prescribed for the treatment of gastric acid-related disorders. While generally well-tolerated, PPIs are not without side effects, including acute kidney injury. Here we highlight a rare case of biopsy proven PPI-induced acute interstitial nephritis (AIN). Case Description/Methods: A 54-year-old male with history of rheumatoid arthritis presented with one week history of fever, fatigue, arthralgias, and weight loss. One month prior he was admitted with upper GI bleeding due to NSAID induced peptic ulcer disease and promptly stopped NSAIDs with strict adherence to PPI therapy. He took no additional medications or supplements. On admission labs were notable for recurrent anemia without melena and new acute kidney injury, creatinine 2.32 mg/dL from baseline of 1. Given recent GI bleed patient underwent repeat EGD which showed a clean based healing antral ulcer. Recurrent anemia was attributed to renal dysfunction, which continued to worsen despite supportive care with peak creatinine 3.8 mg/dL. Urine studies were unrevealing without evidence of obstruction on imaging, but incidentally noted narrowing of the celiac artery was concerning for vasculitis related nephropathy given history of autoimmune disease. Confirmatory contrast enhanced imaging however was negative for evidence of vasculitis with negative serologies. Renal biopsy was performed which showed interstitial inflammation and tubulitis consistent with AIN. Ultimate diagnosis of PPI-induced AIN was made as he took no alternative medications which could be implicated. Patient was started on steroids with notable improvement in renal function. He was switched to an H2 receptor blocker to complete treatment of gastric ulcer and discharged on a steroid taper with complete renal recovery (Figure 1). Discussion: Initially described in 1992, PPI-induced AIN is a well-recognized albeit rare complication. It is thought to arise due to a hypersensitivity reaction, which may explain the classic presenting triad of fever, rash, and eosinophilia. However, studies have shown that this clinical triad is only present in 10% of cases thereby highlighting the difficulties of diagnosing AIN, which may ultimately require renal biopsy for definitive diagnosis. Treatment requires removal of the offending agent as well as initiation of steroids. Even with treatment, 30-70% of patients may develop chronic kidney disease. As such, it is important for clinicians to be cognizant of this potentially life altering complication of PPI.Figure 1.: Kidney biopsy showing inflammatory changes predominantly in the interstitium.

POS-134 ACUTE INTERSTITIAL NEPHRITIS AS A PRIMARY PRESENTATION OF CANDIDA INFECTIVE ENDOCARDITIS

Acute Interstitial Nephritis (AIN) is an important cause of Acute Kidney Injury (AKI) , and infections are the second most common etiology, after the drugs. However, AIN following fungal infections is rare. We describe two cases of AIN, which on the investigation turn out to be candidemia following fungal infective endocarditis.

Une cause originale d’insuffisance rénale aiguë au cours du myélome multiple : néphrite interstitielle aiguë induite par le lénalidomide

IntroductionLenalidomide is an immunomodulatory drug widely used in the treatment of multiple myeloma. Several cases of nephrotoxicity have been reported, but few have been documented histologically. Case presentationWe report a case of acute interstitial nephritis to lenalidomide in a 62-year-old patient with multiple myeloma after administration of the second course of chemotherapy according to the protocol combining bortezomib, lenalidomide and dexamethasone. The outcome was quickly favorable after stopping lenalidomide, with corticosteroid therapy. ConclusionLenalidomide may be responsible for acute interstitial nephritis. When acute kidney injury occurs in myeloma, the nephrotoxicity of therapeutic agents should be considered in addition to the common causes of kidney failure. The chronology of events and the histological data are essential and guide the specific management.

Clinicopathological Characteristics of Drug-Induced Acute Interstitial Nephritis and Role of Steroids in Management: A Single-Center Observational Study

Background: Acute interstitial nephritis (AIN) is a potentially reversible, but underdiagnosed cause of acute kidney injury. The role of steroids in the management of drug-induced AIN is debatable. There is scarcity of data on clinical characteristics of drug-induced AIN, management approach and effect of steroids on renal outcomes from the low-middle-income countries. Methods: We performed a retrospective study of patients with biopsy-proven AIN over a period of 12 years. The main outcomes were recovery of renal function (early (? 3 weeks) or late (&gt; 3 weeks)) and hemodialysis (HD) dependence at 12 weeks. Results: A total of 48 (4.9%) AIN cases were found among 978 renal biopsies. Mean age was 47.6 ± 12.1 years and 56.3% were males. The offending agent could be identified in half of the patients (non-steroidal anti-inflammatory drugs (NSAIDs) most commonly followed by antibiotics, diuretics and proton pump inhibitor (PPI)). Three quarters of patients presented with estimated glomerular filtration rate (eGFR) &lt; 15 mL/min/1.73 m 2 (n = 36), out of which 58.3% (n = 21) required HD. Thirty-nine (81.3%) patients ended up receiving steroids. Mean dose of prednisone was 0.8 ± 0.2 mg/kg per day. Early use of steroids (? 11 days) was significantly associated with earlier (? 21 days) onset of recovery (P = 0.003) as compared to late use of steroids (&gt; 11 days). Conclusion: Our data showed the benefit of earlier use of steroids in achieving rapid and complete renal recovery in drug-induced AIN in a low-middle-income country with frequent use of over-the-counter drugs. Late steroid use (? 3 weeks) was not associated with any further recovery at an additional risk of exposing patients to undue adverse effects. World J Nephrol Urol. 2022;11(1):24-30 doi: https://doi.org/10.14740/wjnu427

Clinical and pathological characteristics of patients with acute kidney injury in Japan in whom kidney biopsy was performed: a cross-sectional analysis of the Japan Renal Biopsy Registry (J‑RBR).

Acute kidney injury (AKI) is a worldwide concern and it leads to a poor prognosis or end-stage kidney disease. The purpose of this study was to clarify the characteristics of patients with AKI in whom kidney biopsy was performed using data of the Japan Renal Biopsy Registry (J-RBR). We screened 38,351 cases that were registered in the J-RBR from 2007 to 2018. We obtained data for 383 patients with AKI based on clinical diagnosis for analysis 1 and data for 714 patients with acute interstitial nephritis (AIN) or acute tubular necrosis (ATN) based on pathological diagnosis for analysis 2. Of the cases screened, 383 patients with AKI (1.0%) were included in analysis 1. The main pathological diagnoses of AKI were AIN, ATN, chronic interstitial nephritis, nephro-sclerosis and crescentic glomerulonephritis. Of the cases screened, 589 patients with AIN (1.5%) and 110 patients with ATN (0.3%) were included in analysis 2. The main clinical diagnoses of AIN were AKI, rapidly progressive glomerulonephritis (RPGN), chronic nephritic syndrome (CNS) and drug-induced nephropathy (DIN), whereas those of ATN were AKI, RPGN, DIN and CNS. ATN patients had a higher serum creatinine level than that of AIN patients. Our results revealed that cases in the J-RBR included 1.0% of AKI cases based on clinical diagnosis and 1.5% and 0.3% of AIN and ATN cases, respectively, based on pathological diagnosis. In patients with suspected intrinsic AKI, kidney biopsy should be performed for diagnosis of the precise etiology and selection of appropriate treatment.

Development and external validation of a diagnostic model for biopsy-proven acute interstitial nephritis using electronic health record data.

Patients with acute interstitial nephritis (AIN) can present without typical clinical features, leading to a delay in diagnosis and treatment. We therefore developed and validated a diagnostic model to identify patients at risk of AIN using variables from the electronic health record. In patients who underwent a kidney biopsy at Yale University between 2013 and 2018, we tested the association of &gt;150 variables with AIN, including demographics, comorbidities, vital signs and laboratory tests (training set 70%). We used least absolute shrinkage and selection operator methodology to select prebiopsy features associated with AIN. We performed area under the receiver operating characteristics curve (AUC) analysis with internal (held-out test set 30%) and external validation (Biopsy Biobank Cohort of Indiana). We tested the change in model performance after the addition of urine biomarkers in the Yale AIN study. We included 393 patients (AIN 22%) in the training set, 158 patients (AIN 27%) in the test set, 1118 patients (AIN 11%) in the validation set and 265 patients (AIN 11%) in the Yale AIN study. Variables in the selected model included serum creatinine {adjusted odds ratio [aOR] 2.31 [95% confidence interval (CI) 1.42-3.76]}, blood urea nitrogen:creatinine ratio [aOR 0.40 (95% CI 0.20-0.78)] and urine dipstick specific gravity [aOR 0.95 (95% CI 0.91-0.99)] and protein [aOR 0.39 (95% CI 0.23-0.68)]. This model showed an AUC of 0.73 (95% CI 0.64-0.81) in the test set, which was similar to the AUC in the external validation cohort [0.74 (95% CI 0.69-0.79)]. The AUC improved to 0.84 (95% CI 0.76-0.91) upon the addition of urine interleukin-9 and tumor necrosis factor-α. We developed and validated a statistical model that showed a modest AUC for AIN diagnosis, which improved upon the addition of urine biomarkers. Future studies could evaluate this model and biomarkers to identify unrecognized cases of AIN.

47-Year-Old Woman With Bilateral Flank Pain

47-Year-Old Woman With Bilateral Flank Pain

Acute interstitial nephritis associated with ingestion of Achyranthes japonica extract: a case report

BackgroundThe Japanese chaff flower, Achyranthes japonica, is used as complementary medicine to control degenerative arthritis. Although commonly used in South Korea, there has been no report of side effects. We report the first case of acute interstitial nephritis (AIN) that occurred in a woman who ingested A. japonica extract for 4 months.Case presentationA 56-year-old Korean woman was admitted for deterioration of renal function. She had general weakness and nausea for 1 month. Her initial blood urea nitrogen and serum creatinine levels were 26.3 mg/dL and 3.2 mg/dL, respectively. She acknowledged ingesting A. japonica extract for the past 4 months. Renal histology demonstrated AIN represented by immune cell infiltration into the interstitium, tubulitis, and tubular atrophy, but the glomeruli were intact. A. japonica was discontinued immediately and conservative management was started. Renal function was nearly restored to the baseline level without medication after 13 months.ConclusionThis is a rare case report of AIN associated with a pure A. japonica extract. In the case of unknown etiology of AIN, physicians should ask about the use of herbal medicines, nutraceuticals, and traditional folk medicines including A. japonica.

Acute interstitial nephritis and nephrogenic diabetes insipidus following treatment with sulfamethoxazole‐trimethoprim and temozolomide

We report a case of acute interstitial nephritis with associated nephrogenic diabetes insipidus in a patient treated with temozolomide and sulfamethoxazole-trimethoprim for glioblastoma multiforme. Kidney biopsy demonstrated focal tubulointerstitial change with tubular dilatation, epithelial change and interstitial inflammation. The patient's kidney function improved with cessation of sulfamethoxazole-trimethoprim and treatment with hydrochlorothiazide for nephrogenic diabetes insipidus. Recommencement of temozolomide did not result in further deterioration in kidney function. In this case report, we discuss the novel association between sulfamethoxazole-trimethoprim-induced acute interstitial nephritis and nephrogenic diabetes insipidus, and suggest possible mechanisms involved.

TUBULO-INTERSTITIAL NEPHRITIS IN GRAFT KIDNEY TRANSPLANT POST AZATHIOPRINE INTRODUCTION

Kidney Transplant is the gold standard of care for end-stage kidney disease (ESKD). Immunosuppression has a central role to maintain the graft function and its survival. Despite newer agents, still, old agents such as azathioprine are still used by many clinicians at various places worldwide. However, hypersensitivity reactions, such as tubulointerstitial nephritis, can occur after starting these medications. There can be many causes of tubulointerstitial nephritis; drugs, infections and autoimmune diseases e.g.: sarcoidosis, systemic lupus erythematosus and Sjogren’s syndrome. We report a case of acute interstitial nephritis after the introduction of azathioprine in a kidney transplant recipient. A young female with a living related kidney transplant on triple immunosuppression medication consisting of prednisolone, tacrolimus and mycophenolate mofetil, expressed her desire to conceive eight months after her wedding. Accordingly, mycophenolate mofetil was replaced by azathioprine. In subsequent visits, it was observed that her graft kidney function was deteriorating progressively. All possible causes which could contribute to graft function deterioration were evaluated and a graft biopsy was performed. The biopsy showed moderate interstitial inflammatory infiltrate rich in eosinophils with no evidence of cellular or antibody-mediated rejection.It was successfully treated by stopping azathioprine and starting high dose oral prednisolone.Deterioration of kidney function in kidney transplant patients, who are put on azathioprine, should raise the suspicion of tubulointerstitial nephritis as a differential diagnosis. To the best of our knowledge, this is the first report of a kidney transplant recipient in whom graft kidney function deteriorated upon introduction of azathioprine. Kidney biopsy revealed moderate interstitial inflammatory infiltrate rich in eosinophils with no evidence of cellular or antibody-mediated rejection. The graft kidney function improved after the cessation of azathioprine and increasing the dose of steroids.