Renal parenchymal malacoplakia: a rare cause of ARF with a review of recent literature

CASE REPORT

Renal Parenchymal Malacoplakia: A Rare Cause of ARF With a Review of Recent Literature Vincent K.K. Tam, FACP, W.H. Kung, FRCS, Robert Li, FRACR, and K.W. Chan, FRCPath ● Renal parenchymal malacoplakia is a rare cause of acute renal failure. Traditionally, it was associated with a high mortality rate and commonly resulted in renal failure requiring renal replacement therapy. The authors report on a 70-year-old woman who presented with acute renal failure caused by renal parenchymal malacoplakia. Her renal function recovered after levofloxacin treatment. All cases reported in the English-language literature since 1990, when fluoroquinolone was first used to treat malacoplakia, were reviewed. Although some patients still had renal failure, with renal biopsy and fluoroquinolone treatment, the patient mortality rate from renal parenchymal malacoplakia is remarkably low. Am J Kidney Dis 41:E21. © 2003 by the National Kidney Foundation, Inc. INDEX WORDS: Renal parenchymal malacoplakia; malacoplakia; acute renal insufficiency; fluoroquinolones; Michaelis-Gutman bodies.

M

ALACOPLAKIA is a rare chronic inflammatory disease with a predilection for the urinary tract, principally the urinary bladder. It may affect the kidneys causing renal parenchymal disease. Conventionally, the latter carried a high mortality rate and commonly resulted in renal failure requiring renal replacement therapy.1 We report on a 70-year-old patient with renal parenchymal malacoplakia who presented initially with anemia and acute renal failure. Her renal function recovered after levofloxacin treatment. A MEDLINE search was performed, and all the cases reported in the English-language literature since 1990 were reviewed. CASE REPORT A 70-year-old Chinese woman was hospitalized in January 2002 because of progressive weakness and poor appetite for several weeks. She had history of long-standing hypertension, chronic atrial fibrillation, and hyperuricemia. Medications included digoxin, 0.1 mg daily; amilodipine, 5 mg daily; allopurinol, 100 mg daily; and a tablet of combination of dihydralazine, 10 mg, reserpine, 0.1 mg, and hydrochlorothiazide, 10 mg daily. Two months before this admission, her blood tests showed normal white blood cell (WBC) count, serum creatinine level of 1.45 mg/dL (128 ␮mol/L), and blood urea nitrogen (BUN) value of 28 mg/dL (9.99 mmol/L). Vital signs on admission were blood pressure, 170/70 mm Hg; heart rate, 82 beats per minute; respiratory rate, 22 breaths per minute; and temperature, 98.6°F. Body weight was 44 kg, and body height was 148 cm. Significant physical findings included pallor and mild shortness of breath. Mild pitting edema of the lower limbs was present. There was no lymphadenopathy. No significant loin tenderness was elicited. Urinalysis results showed specific gravity of 1.010, pH of 6.0, 340 WBCs, 40 red blood cells (RBCs), and trace amount

of protein. Other laboratory findings included serum sodium, 133 mEq/L (133 mmol/L); potassium, 3.7 mEq/L (3.7 mmol/L); BUN, 60 mg/dL (21.42 mmol/L); creatinine, 2.94 mg/dL (260 ␮mol/L); serum calcium, 8.84 mg/dL (2.21 mmol/L); serum albumin, 2.66 g/dL (26.6 g/L); total protein, 6.42 g/dL (64.2 g/L); serum globulin, 3.76 g/dL (37.6 g/L); and alkaline phosphatase, 195 units/L (195 U/L). White blood cell count was 13,800/␮L (13.8 ⫻ 109/L) with 90% neutrophils. Hemoglobin level was 6.1 g/dL (61 g/L), and platelet count was 353,000/␮L (353 ⫻ 109/L). Spot urine osmolality was 278 mOsmol/kg, and spot urine sodium was 91 mEq/L (91 mmol/L). Twenty-four–hour urine collection disclosed creatinine clearance of 10.8 mL/min (0.18 mL/s), and she passed 1.3 g of protein into her urine every day. Abdominal ultrasound scan showed her right kidney of 11.9 cm in diameter and left kidney of 13.1 cm in diameter. There was diffusely increased echogenicity in the renal parenchyma. A simple cyst of 1.9 cm in diameter was noted in her right kidney, and several tiny simple cysts were noted in her left kidney. Serology was negative for antinuclear antibody (ANA), rheumatoid factor, and antineutrophil cytoplasmic antibody (ANCA). Further laboratory workup included erythrocyte sedimentation rate (ESR), 77 mm/h; complement C3, 1.0 (normal, 0.9 to 1.8) g/L; complement C4, 0.25 (normal, 0.10 to 0.40) g/L; and serum protein electrophoresis showed hypoalbuminemia. She was transfused with 3 units of packed red blood cells, and her hemoglobin increased to 12.2 g/dL

From the Departments of Medicine, Surgery, and Radiology, St. Paul’s Hospital, and the Departments of Pathology and Physiology, Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Received November 25, 2002; accepted in revised form February 5, 2003. Address reprint requests to Dr. Vincent K. K. Tam, FACP, Room 1402, Lane Crawford House, 70 Queen’s Road Central, Hong Kong, China. E-mail: [email protected] © 2003 by the National Kidney Foundation, Inc. 1523-6838/03/4106-0025$30.00/0 doi:10.1016/S0272-6386(03)00368-8

American Journal of Kidney Diseases, Vol 41, No 6 (June), 2003: E21

1

2

TAM ET AL

(122 g/L). However, her serum creatinine level rose to 3.68 mg/dL (325.4 ␮mol/L) on the fifth hospital day. Percutaneous renal biopsy was performed. The initial conclusion drawn at the examination of a frozen section of the renal biopsy was acute interstitial nephritis. Methylprednisolone sodium succinate, 500 mg, was started intravenously for 3 days to treat presumably acute inflammation of the kidneys. The definitive renal biopsy diagnosis of malacoplakia was made the following day, after the paraffin sections had been examined. Urine and blood were collected repeatedly for culture. Antibiotics treatment with ceftriaxone was commenced. Only one urine culture grew Escherichia coli. All other urine and blood culture results were negative. Later on, cefuroxime and levofloxacin were also introduced according to the antibiotic sensitivity of the bacteria. Despite full doses of antibiotics, patient’s serum creatinine level continued to rise and peaked on the tenth hospital day at 4.1 mg/dL (362.4 ␮mol/L). Ascorbic acid, 100 mg, 3 times a day was added. It was the 17th hospital day (ie, the 12th day on combination of antibiotics) that her serum creatinine level started to show a significant rate of decline. The patient’s appetite and general condition improved. She was discharged on the 22nd hospital day on continuous oral levofloxacin therapy. On discharge, her serum creatinine level was 2.48 mg/dL (219 ␮mol/L).

KIDNEY BIOPSY FINDINGS

The renal biopsy was processed routinely. It was divided into 3 parts for paraffin, frozen, and ultrastructural sections. The paraffin sections showed 7 glomeruli with one glomerulus globally sclerotic and the others showing no significant abnormalities. There was extensive interstitial inflammation with an infiltrate of neutrophils and other mononuclear inflammatory cells including plasma cells. Focal microabscess formation was evident. In the medulla region, there was a solid infiltrate of histiocytic cells with abundant eosinphilic foamy cytoplasm. Many of them contained basophilic inclusions, the so-called Michaelis-Gutman bodies, which were strongly periodic acid-Schiff (PAS) positive (Fig 1). The arterial vessels showed mild hyaline change. Immunofluorescence studies showed no immune deposits in the glomeruli. The diagnosis was renal parenchymal malakoplakia. DISCUSSION

Malacoplakia is a rare chronic inflammatory disease. It is characterized by large polygonalshaped macrophages with foamy eosinophilic cytoplasm (von Hansemann cells) and the pathognomonic PAS-positive granules called Michaelis-Gutmann bodies.2 Michaelis-Gutmann bodies

Fig 1. The interstitium of the renal medulla is densely infiltrated by histiocytic cells containing the MichaelisGutman bodies, which are strongly PAS positive and frequently show a targetoid appearance. (PAS stain, original magnification x 400).

are thought to derive from the phagolysosomes containing incompletely destroyed bacteria with abnormal deposition of calcium and iron.2 The underlying cellular defect is believed to be the impaired intracellular killing of bacteria.3,4 Coliforms are the bacteria most frequently associated with malacoplakia.3 About 70% to 75% of the coliforms are E coli.2 The common presenting features of renal parenchymal malacoplakia are high fever, loin tenderness, and palpable mass in association with history of urinary tract infection.3 The kidneys are usually enlarged. In fact, malacoplakia is not infrequently diagnosed as cancer before pathology results show the true identity of the problem.5 Our patient presented with acute renal failure. She had low-grade fever and only minimal loin discomfort. These make the diagnosis of malacoplakia very difficult without resorting to renal biopsy and pathologic examination. Because the defect of malacoplakia is believed to lie inside the cell, benethacol and ascorbic acid, which raise the ratio of intracellular cyclic guanosine monophosphate to cyclic adenosine monophosphate and may improve the intracellular killing defect, were suggested as treatment in the past.2 Antimicrobials capable of intracellular penetration such as trimethoprim-sulfamethoxazole were advocated.2 From 1990, there were cases of malacoplakia successfully treated by ciprofloxacin.6-8 Norfloxacin also was used successfully in one reported case.9 Our patient was

RENAL PARENCHYMAL MALACOPLAKIA Table 1.

Study (Case No.)

3

Summary of Patients of Renal Parenchymal Malacoplakia Reported After 1990 (Only Those With Outcome Recorded Were Included) Age/Sex

Bacteria Identified

Treatment

Curran et al6 (1) Hurwitz et al5 (2)

49/F 49/F

E coli No bacteria identified

Mikrzycki et al7 (3) Cozar et al12 (4) Saleem et al13 (5)

61/M 53/M 8-wk

E coli No culture result reported E coli

al-Sulaiman14 (6)

25/F

E coli

Dobyan et al3 (7)

56/F

No bacteria identified

Mitchell et al15 (8) McKenzie et al16 (9)

64/F 29/F

Mark et al17 (10)

42/F

Ozkurkcugil et al18 (11)

44/F

Hayes et al19 (12) van der Voort et al20 (13) Albitar et al9 (14)

79/F 68/F 69/M

E coli Transplant allograft, lactose-fermenting bacilli Unilateral with eye infection, E coli Unilateral with lung shadow, no culture result reported E coli E coli E coli

Honjo et al21 (15)

4-wk

E coli

Kapasi et al22 (16) Evans et al23 (17) Evans et al23 (18) Evans et al23 (19) Houston et al24 (20)

67/M 67/F 82/F 73/F 50/F

No bacteria identified E coli E coli E coli E coli

Van Crevel et al4 (21) Hong et al25 (22)

63/F 47/F

E coli E coli

Immunosuppressant methylprednisolone followed with TMP-SMZ TMP-SMZ Ciprofloxacin Conservative Drained and ciprofloxacin Ciprofloxacin, rifampin, ascorbic acid Ciprofloxacin Ceftizoxime, gentamicin

Yang et al26 (23)

62/F

E coli

Ciprofloxacin

Vankatesh et al27 (24)

26/F

E coli

Hill et al28 (25)

39/F

E coli

Left nephrectomy and TMP-SMZ Rifampin, ascorbic acid, bethanechol antibiotics

Ciprofloxacin Right nephrectomy and cephalosporin Ciprofloxacin Surgery Prednisolone, azathioprine Cephalosporin and TMP-SMZ TMP-SMZ, ascorbic acid, bethanecol Ciprofloxacin, bethanecol Medical (not specified)

Outcome

Survival; Cr, 1.5 mg/dL Survival Survival Death Survival Survival; Cr, 1.3 mg/dL, Cr Cl, 40 mL/min Survival; Cr, normal

Nephrectomy

Survival; Cr, 1 mg/dL Survival; Cr, 3.98–4.55 mg/dL Survival

Surgery and TMP-SMZ

Survival

Surgery Ciprofloxacin Norfloxacin

Survival Survival Survival; Cr, 3.18 mg/dL Hemodialysis 3 years later Survival

Survival Survival Survival Death Survival; Cr ⬍ 2.0 mg/dL Survival; Cr, Normal Survival; on chronic hemodialysis Survival; Cr, 7.3 mg/dL after 12 months Survival Survival; Cr, 1.8 mg/dL

NOTE. To convert serum creatinine in mg/dL to ␮mol/L, multiply by 88.4. Abbreviations: TMP-SMX, trimethoprim-sulfamethoxazole; Cr, serum creatinine level.

the first one treated with levofloxacin who had recovery of renal function. The treatment success of malacoplakia with fluoroquinolones may very well be a class effect of the drugs because of their high intracellular concentration.10,11 Renal parenchymal malacoplakia has traditionally been associated with substantial mortality rate (⬃70%) and poor recovery of renal function (⬃10%).1 We performed a MEDLINE search

and reviewed all the cases reported in the Englishlanguage literature since 1990, when fluoroquinolone was first reported to treat malacoplakia successfully. Only those cases with outcome reported were analyzed and listed in Table 1. It should be noted that only 7 of the 25 patients had some form of surgical treatment. More than 70% of them had medical treatment only. The patient survival rate was very good (⬎90%). Only 2

4

TAM ET AL

mortalities were reported (case 412 and case 1923). The patient reported by Evans et al23 definitely suffered from multiple medical problems in addition to renal parenchymal malacoplakia. Six of the 25 patients had significant impairment of renal function. Among the 6, 3 ultimately required renal replacement therapy. It should be noted that 2 of the 3 patients requiring dialysis later had partial recovery of their kidney function and did not have renal failure until 3 years after their initial presentation. This would lend support to the theory that interstitial nephritis precedes the renal parenchymal malacoplakia, which is then followed by interstitial fibrosis.3 Once the interstitium is destroyed beyond a critical point, even if fluoroquinolone is very effective in clearing the bacteria, it may not be able to reverse the damage to the kidney that has already been done. The patient may progress to renal failure despite clearing of the bacteria. This underlies the importance of early diagnosis of malacoplakia to successfully salvage as much viable kidney tissue as possible. Prompt and prolonged use of appropriate antibiotics like fluoroquinolone, which can penetrate the cell well, may have a higher chance of arresting the disease and reversing the interstitial process. Because the disease can only be diagnosed by microscopic examination, the importance of timely renal biopsy can not be overemphasized. Renal parenchymal malacoplakia is no longer frequently fatal in the new millenium. The morbidity rate is still high. With time, a considerable number of patients will progress to renal failure. To improve the renal survival rate, renal biopsy early in the course of disease and prompt initiation of appropriate antibiotics therapy for prolonged period of time are of paramount importance. With the advent of antibiotics and better imaging techniques, surgery is only seldom utilized. Renal parenchymal malacoplakia should be considered in the differential diagnosis of acute renal failure. REFERENCES 1. Ling BN, Delaney VB, Campbell WG Jr: Acute renal failure due to bilateral renal parenchymal malacoplakia. Am J Kidney Dis 13:430-433, 1989 2. Stanton MJ, Maxted W: Malacoplakia: A study of the literature and current concepts of pathogenesis, diagnosis and treatment. J Urol 125:139-141, 1981 3. Dobyan DC, Truong LD, Eknoyan G: Renal malacoplakia reappraised. Am J Kidney Dis 22:243-252, 1993

4. van Crevel R, Curfs J, van der Ven AJ, Assmann K, Meis JF, van der Meer JW: Functional and morphological monocyte abnormalities in a patient with malakoplakia. Am J Med 105:74-77, 1998 5. Hurwitz G, Reimund E, Moparty KR, Hellstrom WJ: Bilateral renal parenchymal malacoplakia: A case report. J Urol 147:115-117, 1992 6. Curran KA, Peterson JC, Croker BP, Drane WE, Tisher CC: Gallium scan in the diagnosis and treatment of renal malacoplakia. Am J Nephrol 10:416-421, 1990 7. Mokrzycki MH, Yamase H, Kohn OF: Renal malacoplakia with papillary necrosis and renal failure. Am J Kidney Dis 19:587-591, 1992 8. van Furth R, van’t Wout JW, Wertheimer PA, Zwartendijk J: Ciprofloxacin for treatment of malakoplakia. Lancet 339:148-149, 1992 9. Albitar S, Genin R, Fen-Chong M, et al: The febrile patient presenting with acute renal failure and enlarged kidneys—another mode of presentation of malakoplakia. Nephrol Dial Transplant 12:1724-1726, 1997 10. Garcia I, Pascual A, Ballesta S, Perea EJ: Uptake and intracellular activity of ofloxacin isomers in human phagocytic and non-phagocytic cells. Int J Antimicrob Agents 15:201-205, 2000 11. Trampuz A, Wenk M, Rajacic Z, Zimmerli W: Pharmacokinetics and pharmacodynamics of levofloxacin against Streptococcus pneumoniae and Staphylococcus aureus in human skin blister fluid. Antimicrob Agents Chemother 44:1352-1355, 2000 12. Cozar Olmo JM, Carcamo P, Gaston de Iriarte E, Jimenez F, Martinez-Pineiro L, Martinez-Pineiro JA: Genitourinary malakoplakia. Br J Urol 72:6-12, 1993 13. Saleem MA, Milford DV, Raafat F, White RH: Renal parenchymal malakoplakia–a case report and review of the literature. Pediatr Nephrol 7:256-258, 1993 14. al-Sulaiman MH, al-Khader AA, Mousa DH, alSwailem RY, Dhar J, Haleem A: Renal parenchymal malacoplakia and megalocytic interstitial nephritis: Clinical and histological features. Report of two cases and review of the literature. Am J Nephrol 13:483-488, 1993 15. Mitchell MA, Markovitz DM, Killen PD, Braun DK: Bilateral renal parenchymal malacoplakia presenting as fever of unknown origin: Case report and review. Clin Infect Dis 18:704-718, 1994 16. McKenzie KJ, More IA: Non-progressive malakoplakia in a live donor renal allograft. Histopathology 28:274276, 1996 17. Mark IR, Westlake W, Montgomery BS, Tiptaft RC, Pambakian H: Escherichia coli endophthalmitis: A rare presentation of renal parenchymal malakoplakia. Br J Urol 76:401-402, 1995 18. Ozkurkcugil C, Duzcan E, Gultekin Y, Gokalp A: A case of renal parenchymal malacoplakia with bilateral pulmonary lesions. Br J Urol 77:159-160, 1996 19. Hayes MC, Bateman AC, Ratan P, Ramsay AD, Smart CJ: Ruptured kidney–An unusual presentation of renal malakoplakia. Br J Urol 77:753-754, 1996 20. van der Voort HJ, ten Velden JA, Wassenaar RP, Silberbusch J: Malacoplakia. Two case reports and a comparison of treatment modalities based on a literature review. Arch Intern Med 156:577-583, 1996

RENAL PARENCHYMAL MALACOPLAKIA

21. Honjo K, Sato T, Matsuo M, Miyazaki S, Tomiyoshi Y: Renal parenchymal malakoplakia in a four-week-old infant. Clin Nephrol 47:341-344, 1997 22. Kapasi H, Robertson S, Futter N: Diagnosis of renal malacoplakia by fine needle aspiration cytology. A case report. Acta Cytol 42:1419-1423, 1998 23. Evans NL, French J, Rose MB: Renal malacoplakia: An important consideration in the differential diagnosis of renal masses in the presence of Escherichia coli infection. Br J Radiol 71:1083-1085, 1998 24. Houston TK 2nd, Peacock JE Jr, Appel RG, Cowan RJ: Gallium-67-citrate scanning of renal parenchymal malacoplakia. J Nucl Med 39:1454-1457, 1998

5

25. Hong JJ, Liao PL, Lin JL, Hsueh S, Huang CC: Bilateral renal parenchymal malakoplakia presenting as haemolytic-uraemic syndrome. Nephrol Dial Transplant 14:2206-2209, 1999 26. Yang AH, Tarng DC, Chen JY, Lu SH: Post-infectious glomerulonephritis in a patient with vesicorenal malacoplakia–coincidence or causal relationship? Nephrol Dial Transplant 15:1060-1062, 2000 27. Venkatesh SK, Mehrotra N, Gujral RB: Sonographic findings in renal parenchymal malacoplakia. J Clin Ultrasound 28:353-357, 2000 28. Hill GS, Droz D, Nochy D: The woman who loved well but not too wisely, or the vicissitudes of immunosuppression. Am J Kidney Dis 37:1324-1329, 2001