Leptospirosis: An Ignored Cause of Acute Renal Failure in Taiwan Chih-Wei Yang, MD, Ming-Jeng Pan, PhD, Mai-Szu Wu, MD, Yu-Ming Chen, MD, Yu-Tang Tsen, MD, Chun-Liang Lin, MD, Cheng-Hung Wu, MD, and Chiu-Ching Huang, MD 0 Leptospirosis, caused by a spirochete, is the most common zoonosis in domestic or wild animals. Animals excrete infected urine in soil or water and may cause human infections through abrased wound, mucosa, conjunc- tiva, or by swallowing contaminated water. Clinical presentations of leptospirosis are mostly subclinical. Five to ten percent of leptospirosis are fatal, causing fever, hemorrhage, jaundice, and acute renal failure @Veil’s syndrome). Leptospirosis has been ignored as a cause of acute renal failure in Taiwan. We report two patients with lep- tospirosis who presented with high fever, abdominal pain, jaundice, and acute renal failure. Patient 1 died on day 12 of admission of multiple organ failure associated with pancytopenia, hypogammaglobulinemia, and reactive hemophagocytosis. Leptospirosis was recognized after death. Patient 2 was admitted with similar presentations 2 weeks later. Penicillin and doxycycline were given early in the course, and azotemia, jaundice, respiratory failure, and aseptic meningitis gradually improved. Renal biopsy showed interstitial nephritis. Several tubular clearance tests showed proximal tubular defect with severe bicarbonate wasting (FeHCO,- 20.9%) and incomplete type II renal tubular acidosis without affecting the distal nephron. After 80 days of treatment, this patient was discharged with recovery of conscious level and renal function. This is the first leptospirosis patient with detailed tubular functional and morphological studies of the kidney. Diagnosis of leptospirosis was made by microscopic agglutina- tion test (MAT) for antibody to leptospira and by polymerase chain reaction (PCR) for leptospira DNA in blood and urine (interrogans serogroup australis in case 1 and Leptospira borgpetersenii serogroup ballum in case 2). Because active surveillance has resulted in 13 cases diagnosed as leptospirosis islandwide thereafter, underesti- mation and ignorance of leptospirosis as a cause of acute renal failure may occur in Taiwan. Therefore, an area with a low leptospirosis incidence may actually have a very high incidence. Leptospirosis should be suspected in febrile patients with jaundice and renal failure when pathogens cannot be identified by traditional culture for microorganisms. 0 1997 by the National Kidney Foundation, Inc. INDEX WORDS: Leptospirosis; acute renal failure; interstitial nephritis. EPTOSPIROSIS is considered to be the most L widespread spirochetal zoonosis in the world, infecting humans particularly in regions with humid climates. It causes a broad spectrum of clinical manifestations in humans when trans- mitted from animals. The clinical syndromes vary from subclinical infection, self-limited anic- teric febrile illness, to severe and potentially fatal disease. Well’s syndrome, a most severe form of the infection, consists of febrile illness with hemorrhagic tendency, hepatic dysfunction, and acute renal failure. l-3 Risk factors of the infection include occupational exposures, recreational ac- tivities, and household environment with close contacts with animals. Its diagnosis depends on serologic methods, polymerase chain reaction (PCR), and culture of organism from patient’s From the Division of Nephrology, Chang Gung Memorial Hospital, Department of Veterinary Medicine, National Tai- wan University, Taipei, Taiwan, Republic of China. Received February 8, 1997; accepted in revisedform May 23, 1997. Address reprint requests to Chih- Wei Yang, MD, Associate Professor, Division of Nephrology, Chang Gung Memorial Hospital, 199, Tun-Hwa North Rd, Taipei, 105, Taiwan. E- mail: cwyang@msl.hinet.net 0 1997 by the National Kidney Foundation, Inc. 0272.6386/97/3006-0017$3.00/O blood, urine, or body fluid. Penicillin is the drug of choice for moderate to severe leptospirosis. Oral doxycycline can be used for mild cases.? The kidney is the major target organ, and renal involvement is very common in both icteric and anicteric leptospirosis, but the symptoms are seen only in patients with icterus. Azotemia, oliguria, and anuria commonly occur during the second week of the illness but may appear as early as 3 to 4 days after the onset.3 Despite adequate ther- apy, the cured patients may become carriers or shedders of the pathogens from their urine for several months.’ Both oliguric or nonoliguric forms of acute renal failure have been reported to be associated with high frequencies of hypoka- lemia.4 The cause of hypokalemia is thought to be attributable to the proximal tubular lesion, leading to the decrease in sodium and water reab- sorption. The increase in distal sodium and water delivery may enhance potassium secretion.4*5 In Taiwan, leptospirosis has not been thought of as a common infectious disease, although the first cases were reported 20 years ago.6 The rea- son for the absence of diagnostic cases for the last 20 years was that the diagnostic facilities had not been established for human study. Recently, we have encountered two patients infected by leptospira presented by acute renal failure, which 840 American Journal of Kidney Diseases, Vol 30, No 6 (December), 1&7: pp 640-845