CASE REPORT Nephrology http://dx.doi.org/10.3346/jkms.2015.30.1.110 • J Korean Med Sci 2015; 30: 110-114 Megalocytic Interstitial Nephritis Following Acute Pyelonephritis with Escherichia coli Bacteremia: A Case Report Hee Jin Kwon,1 Kwai Han Yoo,1 Megalocytic interstitial nephritis is a rare form of kidney disease caused by chronic In Young Kim,1 Seulkee Lee,1 inflammation. We report a case of megalocytic interstitial nephritis occurring in a 45-yr- Hye Ryoun Jang,2 and Ghee Young Kwon3 old woman who presented with oliguric acute kidney injury and acute pyelonephritis accompanied by Escherichia coli bacteremia. Her renal function was not recovered despite 1Department of Medicine, 2Division of Nephrology, Department of Medicine, and 3Department of adequate duration of susceptible antibiotic treatment, accompanied by negative Pathology, Samsung Medical Center, Sungkyunkwan conversion of bacteremia and bacteriuria. Kidney biopsy revealed an infiltration of University School of Medicine, Seoul, Korea numerous histiocytes without Michaelis-Gutmann bodies. The patient’s renal function was markedly improved after short-term treatment with high-dose steroid. Received: 24 April 2014 Accepted: 27 August 2014 Keywords: Acute Kidney Injury; Megalocytic Interstitial Nephritis; Interstitial Nephritis Address for Correspondence: Hye Ryoun Jang, MD Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Korea Tel: +82.2-3410-0782, Fax: +82.2-3410-3849 E-mail: [email protected] INTRODUCTION serum creatinine level of 6.80 mg/dL, high C-reactive protein level of 24.61 mg/dL, and high procalcitonin level of 39.05 ng/ Megalocytic interstitial nephritis is a rare form of chronic renal mL. Liver function test showed abnormalities including low al- inflammatory disease associated with defect in intracellular bumin level of 2.9 g/dL, high aspartate aminotransferase level destruction of invading foreign organisms by macrophages (1). of 139 U/L, but alanine aminotransferase of 31 U/L. Coagula- These unusual inflammatory disorders are often associated tion time was prolonged to a PT INR of 1.46. Urinary findings with chronic urinary tract infection by Gram-negative bacteria showed hematuria and pyuria. Physical examinations and lab- (2). Although the pathogeneses of these diseases are unclear, oratory results suggested urosepsis with underlying alcoholic macrophage bactericidal dysfunction has been presumed as a liver cirrhosis. possible pathogenic mechanism (3). We report an extraordinary A computed tomographic (CT) scan of the abdomen reveal- case of a 45-yr-old woman who had oliguric acute kidney injury ed diffuse swelling of both kidneys with perinephric infiltration, (AKI) and acute pyelonephritis with Escherichia coli (E. coli) suggestive of acute pyelonephritis. Additionally, hepatic nodu- bacteremia, accompanied by megalocytic interstitial nephritis. larity and atrophic change as features of liver cirrhosis were ob- served. CASE DESCRIPTION The patient was diagnosed with acute pyelonephritis (APN) accompanied by oliguric AKI. Antibiotic treatment using cefo- A 45-yr-old woman was hospitalized for abdominal pain, wa- taxime (third-generation cephalosporin) and azithromycin was tery diarrhea, and jaundice of one-week duration on October administered for a presumed diagnosis of APN, Weil’s disease, 28, 2013. One day before admission, she noticed a marked re- and rickettsial infection. Continuous renal replacement therapy duction in her urine output. Her past medical history was unre- (CRRT) was initiated for septic shock with oliguric AKI. After re- markable except for a two-year history of alcoholism. covering from septic shock, the patient was switched to con- At the time of admission, her blood pressure was 134/84 mmHg, ventional hemodialysis for the treatment of AKI. Later, E. coli and heart rate was 93 beats per minute. Her respiratory rate and susceptible to all feasible antibiotics were isolated from initial body temperature were 20 breaths/min and 36.5°C, respective- urine and blood cultures. Azithromycin administration was ly. The patient was icteric and confused. She was unable to state discontinued because there was no evidence of elevation of her precise complaints. Physical examination was unremark- tsutsugamushi and leptospira antibodies. able except distended abdomen. Although there was no microorganism in subsequent blood Laboratory findings included leukocytosis of 24,300/μL, high and urine cultures with improving parameters of infection such © 2015 The Korean Academy of Medical Sciences. pISSN 1011-8934 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. eISSN 1598-6357 Kwon HJ, et al. • Megalocytic Interstitial Nephritis with Bacteremia as fever, CRP, and procalcitonin, there were persistent severe (for calcium) negativity, and Prussian blue (for iron) negativity. leukocytosis with atypical lymphocytes and high level of lactate Additionally, C1q staining and electron dense deposits were dehydrogenase over 1,000 IU/L. Serum protein electrophoresis shown in mesangial matrix without clinical and serological evi- (PEP) revealed increased gamma-globulin (34.5%), and serum dence of systemic lupus erythematosus. The final pathologic immunofixation (IF) showed an abnormal band against anti- diagnosis was megalocytic interstitial nephritis accompanied immunoglobulin G (IgG) and anti-lambda. To evaluate hepato- by C1q nephropathy (Fig. 1). splenomegaly and blood cell abnormalities including leukocy- Intravenous administration of methylprednisolone 1 mg/kg tosis, thrombocytopenia, and monoclonal gammopathy (< 3 g/ was initiated for megalocytic interstitial nephritis and severe dL), bone marrow examination was performed. Bone marrow infection-related hemophagocytic lymphohistiocytosis that was examination showed hemophagocytic histiocytes and increased seen in the histological examination of the patient’s kidney and plasma cells (below 10%). These results suggested the possibili- bone marrow, respectively. High-dose steroid treatment was ty of monoclonal gammopathy of undetermined significance performed for one week, and steroid was halved every 3 days because there was no evidence of bone lesion and hypercalce- for 2 weeks. Both oliguric AKI and severe leukocytosis were dra- mia. After one month, kidney biopsy was performed to clarify matically improved after steroid treatment (Fig. 2). the cause of persistent oliguric AKI despite adequate conserva- After using steroids for 12 days, her kidney function had im- tive treatment. Light microscopic examination showed exten- proved enough to stop dialysis. On the day of discharge, her se- sive interstitial inflammation with a massive infiltration of his- rum creatinine level was 2.48 mg/dL. Her renal function had tiocytic cells without Michaelis-Gutmann bodies. Special stain- improved further by her first visit to the outpatient clinic; the ing showed CD68 positivity in infiltrated histiocytes, Von Kossa serum creatinine level was 1.95 mg/dL. A B C D Fig. 1. Features of the renal biopsy. (A) Under light microscopy (×200), the mesangial matrix was mildly increased and the interstitium was multifocally infiltrated by histiocytic collection. (B) Tubules revealed diffuse acute damage and minimal atrophy accompanied by mild interstitial fibrosis. Immunohistochemistry studies showed CD68 positivity in infiltrated histiocytes. But stain for iron and calcium were negative. C( ) Using immunofluorescence microscopy (×400), mesangial staining was positive for C1q (2+). D( ) Elec- tron microscopy showed moderate effacement of epithelial foot processes. The mesangial matrix is moderately increased with a few electron dense deposits. http://dx.doi.org/10.3346/jkms.2015.30.1.110 http://jkms.org 111 Kwon HJ, et al. • Megalocytic Interstitial Nephritis with Bacteremia 8 7 6 5 4 BM biopsy Kidney biopsy 3 Creatinine (mg/dL) S-M 2 1 mg/kg Rapid tapering Renal replacement therapy 1 0 1 2 3 4 5 8 10 12 15 17 20 22 26 29 32 36 39 41 44 47 50 52 54 57 59 Hospital day (HD) A 50 45 40 L) μ / 35 3 30 25 S-M Rapid tapering 20 1 mg/kg BM biopsy Kidney biopsy WBC count (×10 15 10 5 Renal replacement therapy 0 1 2 3 4 5 8 10 12 15 17 20 22 26 29 32 36 39 41 44 47 50 52 54 57 59 Hospital day (HD) B Fig. 2. Change in serum creatinine level (A), WBC count (B), and clinical course during hospitalization. After administration of methylprednisolone 1 mg/kg for megalocytic inter- stitial nephritis and severe HLH on the 38th hospital day, both oliguric AKI and severe leukocytosis were dramatically improved. S-M, Solu-Medrol® (methylprednisolone sodium succinate); BM, bone marrow. DISCUSSION other risk factor of this disease. Göttz et al. (8) previously report- ed an alcoholic patient with E. coli bacteremia and biopsy-prov- Megalocytic interstitial nephritis is an uncommon form of in- en megalocytic interstitial nephritis. In that paper, chronic alco- terstitial nephritis affecting mainly the renal cortex in an other- hol consumption was reported to cause immune system dam- wise normal kidney. This disease was first described by Zollinger age and subsequently facilitate the development of the disease. in 1945 (4). The diagnosis of megalocytic interstitial nephritis There is no clear