Case Discussion < Case presentation >      The patient was a 38-year-old man who had hepatitis B and C virus-related liver cirrhosis, Child class B and type 2 diabetes mellitus under oral hypoglycemic agent control for five years. On April 13, 2003, he noted that his urine became dark-colored and contained whitish debris. This was accompanied by a sudden onset of low back pain and followed by anuria. He suffered from fever, chills, and general myalgia three days later.      In our emergency department on April 21, his consciousness was clear. His temperature was 36.8oC, pulse rate was 88 beats/min, respiration rate was 20/min, and blood pressure was 160/108 mmHg.. Renal sonography showed bilateral enlarged kidneys and hydronephrosis, air in renal parenchyma, and hyperechoic foci in the medullary pyramids (Fig 1 ). Abdominal MRI revealed enlargement of both kidneys and loss of the corticomedullary junctions. The renal calyces and bilateral ureters were dilated down to the uretero-vesicular junction level, which was obstructed by debris. Coronary T2W image demonstrated ring shadows in the midportion of medullary pyramids and classic filling of clefts originating from fornices of the superior caliceal group, which suggested papillary necrosis in situ. Some air pockets in the right renal pelvis were also noted. < Course and Treatment >      The blood cultures on April 17 and April 21, and urine culture on April 21 all yielded Candida tropicalis. Fluconazole 200 mg/day was instituted starting on April 22. However, anuria followed by fever and chills developed on April 25, 2003. Renal sonography showed outflow obstruction by debris and bilateral hydronephrosis. Therefore, he received bilateral percutaneous nephrostomy (PCN). The urine output recovered later up to 3000 mL /day.      He was afebrile after the fifth hospitalization day. The hemogram revealed a leukocyte count of 8,530 (/μL). The BUN and creatinine also returned to 23.2 mg/dL and 1.21 mg/dL, respectively which were within normal ranges. Fluconazole was increased to 400 mg/day. One month later, anterograde pyelography showed improvement of hydronephrosis, and PCN was removed on June 6 smoothly, and urine output was adequate thereafter. Intravenous fluconazole had been administered for four weeks and then shifted to the oral form for another week. He was followed up regularly with adequate urine output and stable renal function. < Laboratory and Image Study > 1. CBC/DC Date WBC RBC  Hb Hct MCV MCHC Plt    /ul M/ul g/dl %  fL  %  K/ul Apr. 21 14620  2.96  8.5 25.3 85.5 33.6 128 Date Seg Eos Baso Mono Lym Apr 21 80.5 2.3 0.8 6.8  9.6  2. Biochemistry BUN Cre UA Na  K  Cl Ca P Mg  Glu  Mg/dL Mg/dL Mg/dL mM mM mM Mg/dL mM mM Mg/dL 55.1 7.97 10.39 129.8 3.9  103 1.82 3.44 0.81 438  Alb Glo AST ALT  T-bil CK ALP GGT LDH g/dL g/dL U/L  U/L Mg/dL U/L U/L U/L U/L 2.1 4.8  29 10 0.6 25 900 459 718 3. Urinalysis App. pH Pro Glu Ket OB Urobi     Mg/dL Mg/dL      EU/dL  Y/T 6.0  - 100 - 2+ 0.1   Bil WBC RBC Epi Cast Crystal Others - 22-28 15-20 (morphology negative) 3-6 -  - Yeast (1+)           < Analysis >              C. tropicalis infection has been most often seen in persons with cancer and diabetes mellitus [1]. It appears to be more virulent than C. albicans in patients with hematological malignancies, and disseminated infection is associated with higher mortality rates than infection with C. albicans and C. parapsilosis [2].      Fungal infiltration at the tips of the renal papillae may also cause papillary necrosis [3]. Like in our patient, less resistant individuals with severe fungal infection develop microabscesses in the renal parenchyma.[3] The coexistence of liver cirrhosis and diabetes mellitus supports the contention, at least partly, for the severity coexistence of bilateral EPN and RPN.      The diagnosis of papillary necrosis usually relies on destructive changes involving the tips of the pyramids shown on excretory urography (IVP) [4]. To avoid the contrast related nephropathy in this patient with acute renal failure, we looked for “ring signs” consistent with papillary necrosis in MRI.      In our patent, infection was controlled, and renal function preserved after PCN drainage and fluconazole treatment. As in our patient, it was reported that the presence of loculated gas pattern and presence of exudates in EPN or the presence of gas in the collecting system reflect a better prognosis than mottled gas pattern.[5] We suggest that if appropriate diagnostic studies demonstrate evidence of urinary obstruction in bilateral EPN and RPN, intensive medical treatment and surgical drainage is necessary.      In conclusion, disseminated candidiasis could result in severe bilateral EPN and RPN, especially in diabetic and cirrhotic patients. Treatment should attempt to eradicate the fungus and relieve the obstruction by surgical drainage of the lesions.[6]     < Legends to Figures >     Fig 1.      Ring signs consistent with papillary necrosis. Longitudinal sonogram of the left kidney showed an enlarged kidney (13.9cm). Echogenic papillae (arrows) in a medullary pyramid and hydrocalyces were noted. Surrounding the echogenic region were echolucent rims, consistent with fluid dissection into and around necrotic papillae.  < Reference >    Kao, A.S., M.E. Brandt, W.R. Pruitt, et al. The epidemiology of candidemia in two United States cities: results of a population-based active surveillance. Clin Infect Dis 1999; 29: 1164-70. Leung, A.Y., C.S. Chim, P.L. Ho, et al. Candida tropicalis fungaemia in adult patients with haematological malignancies: clinical features and risk factors. J Hosp Infect 2002; 50: 316-9. Kale, H., R.S. Narlawar, and K. Rathod. Renal fungal ball: an unusual sonographic finding. J Clin Ultrasound 2002; 30: 178-80. Tomashefski, J.F., Jr. and C.R. Abramowsky. Candida-associated renal papillary necrosis. Am J Clin Pathol 1981; 75: 190-4. Wan, Y.L., S.K. Lo, M.J. Bullard, et al. Predictors of outcome in emphysematous pyelonephritis. J Urol 1998; 159: 369-73. Wu, V.C., C.C. Fang, W.Y. Li, et al. Candida tropicalis-associated bilateral renal papillary necrosis and emphysematous pyelonephritis. Clin Nephrol 2004; 62: 473-5.        繼續教育考題 1. (C)  Renal papillary necrosis 常發生的部位是：請看圖2作答 A  cortex B  renal pelvis C  medulla D  ureteropelvic junction(upj) E  ureter 2. (A)  那一種candidaemia最常見 A  C. albicans B  C. parapsilosis C  C. tropicalis D  Candida krusei 3. (E)  renal papillary necrosis 在下列疾病的病人最不常發生 A  Liver cirrhosis B  Diabetes mellitus C  Obstructive uropathy D  Analgesic abuse E  Thalathemia 4. (B)  Renal papillary necorsis 的常見表現何者為非? A  Microscopic haematuria B  Glucosuria C  Sterile pyuria D  Proteinuria ( <2 g/24hr) 5. (D)  在 Pyography中 renal papillary necorsis 的表現何者為非? A  ring-shaped filling defects (sloughed papilla) B  Ring signs C  Ball in the cup D  triangle E  Moth eaten calyces 6. (D)  處理renal papillary necorsis 又有obstructive nephropthy最好的方式  是? A  Surgical relief obstruciton B  Metabolic control C  Infection control D  All of above 7. (E)  Renal papillary necorsis 的臨床表現何者為非? A  Gloden brown lipofuchsin –like pigment in tubular cells B  Focal glomerular sclerosis and hyalinosis C  Obliteration of vasa recta with medullary necrosis and fibrosis D  The most common presentation is painless macroscopic hematuria. E  Non of above 8. (C)  以下何者非 breakthrough candidaemia的危險因子 A  mucositis B  use of broad-spectrum antibiotics C  isolation of Candida from blood D  invasive medical procedures 9. (A)  Outpatient-acquired candidaemia.的最常見的危險因子 A  chronic renal failure B  gastrointestinal bleeding C  use of proton pump inhibitors D  invasive medical procedures 10. (C)  阻塞引起的hydronephrosis不包括： A  infection stones B  renal papillary necrosis C  vesicoureteral reflux D  indwelling catheters

答案解說 ( C )The diagnosis of papillary necrosis usually relies on destructive changes involving the tips of the pyramids shown on excretory urography (IVP) ( A ) ：Patients with C. albicans (55%) had the highest fatality rate and frequently received immunosuppressive therapy, while patients with Candida parapsilosis (16%) had the lowest fatality and complication rates. Candida tropicalis (16%) was associated with youth, severe neutropenia, acute leukaemia or bone marrow transplantation, Candida glabrata (10%) was associated with old age and chronic disease, and Candida krusei (2%) was associated with prior fluconazole therapy (Hosp Infect. 2005 Oct;61(2):146-54) ( E ) Interstitial nephritides, such as pyelonephritis and nephritis due to obstructive uropathy, diabetes mellitus, or analgesic abuse, that are associated with papillary necrosis were ruled out. . Papillary necrosis due to ischemic damage to the papillae is a well-known complication of sickle cell syndromes but is uncommon at presentation. (N Engl J Med. 2005 Mar 24;352(12):1237) ( B ) Renal papillary necrosis can be nearly asymptomatic and follow a more indolent course with aboutrs of urinary infecitno and / or renal colic. ( D ) ( D ) ( E ) ( C ) Breakthrough candidaemia was defined as the occurrence of candidaemia in a patient receiving at least 3 days of systemic anti-fungal therapy. Common risk factors included mucositis, isolation of Candida from sites other than blood, use of broad-spectrum antibiotics, and invasive medical procedures. ( A ) Compared with patients with nosocomial candidaemia, chronic renal failure was more frequent in the outpatient group, who were also more commonly exposed to haemodialysis. Ileus, gastrointestinal bleeding, previous bacteraemia, use of proton pump inhibitors, previous stay in the intensive care unit and requirement for antibiotics, blood transfusion, vasopressors and invasive medical procedures were more frequent in the nosocomial group. Candidaemia must be considered as a potential cause of sepsis in the community, and it is associated with a high mortality rate. (J Hosp Infect. 2005 Jun;60(2):129-34.) ( C )