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Sr Editor: La nefritis tubulointerticial fue descrita por Councilman1 en 1898. Es una entidad clínico-patológica poco frecuente , se estima una incidencia de 8-14%, en los pacientes biopsiados por Insuficiencia Renal Aguda de causa no aclarada2. Las causas desencadenantes de esta enfermedad son las neoplasias, los fármacos y las infecciones. Presentamos el caso clínico de un paciente que debutó con nefritis tubulointerticial aguda y nefromegalia, secundario a levofloxacino.
To the editor: Tubulointerstitial nephritis was first described by Councilman1 in 1898. It is an infrequent clinical-pathological entity with an estimated incidence of 8-14% among patients subjected to biopsy for acute renal failure of indeterminate origin.2 The triggering factors of this disease comprise neoplasms, drugs and infections. We present the case of a patient who manifested with acute tubulointerstitial nephritis and a large kidney (nephromegaly) secondary to levofloxacin.
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To the editor: Tubulointerstitial nephritis was first described by Councilman1 in 1898. It is an infrequent clinical-pathological entity with an estimated incidence of 8-14% among patients subjected to biopsy for acute renal failure of indeterminate origin.2 The triggering factors of this disease comprise neoplasms, drugs and infections. We present the case of a patient who manifested with acute tubulointerstitial nephritis and a large kidney (nephromegaly) secondary to levofloxacin.
CLINICAL CASE
The clinical case corresponds to a 67-year-old male. His personal history included allergy to nicotinamide, ischemic
heart disease (requiring three coronary stents, with follow-up comprising 6 catheterizations ¿ the last performed one year before admission) and dilated myocardiopathy secondary to the latter. His usual treatment consisted
of pantoprazole 40 mg/24 h, carvedilol 25 mg/12 h, aspirin 100 mg/24 h, amlodipine 5 mg/24 h, isosorbide
dinitrate 20 mg/8 h, and simvastatin 20 mg/24 h.
The patient reported to the Emergency Service with right-flank abdominal pain irradiating to the hypogastrium,
and accompanied by vomiting and fever. Physical examination revealed positive right-side fist-percussion as
sole significant finding. The emergency complementary tests showed creatinine 4 mg/dl, leukocytosis (16,000/μl) and urine sediment with leukocyturia. The chest and abdominal X-rays showed no anomalies. The study was completed with abdominal ultrasound, which revealed an enlarged right (15 cm) (fig. 1) and left kidney (14.5 cm) ¿ the latter organ also showing two cortical cysts. Based on the above data, admission to the Nephrology ward was decided, and a more complete evaluation with laboratory tests was made ¿ the immune and tumor marker parameters proving negative. The blood and urine cultures were also negative. Fluid therapy and broad-spectrum antibiotic treatment was prescribed, resulting in clinical and analytical improvement (creatinine 1.6 mg/dl); hospital discharge was thus decided. The patient was posteriorly readmitted with this same clinical presentation on two further occasions, with the clinical diagnosis of acute pyelonephritis refractory to medical treatment. During the admissions, the study was completed with blood cultures, urine cultures, and gallium gammagraphy. In view of the persistence of the bilateral nephromegaly, the possibility of amyloidosis was discarded by a rectal and abdominal adipose tissue biopsy, which proved negative. Tuberculosis was likewise ruled out by negative Mantoux tests and specific cultures. A bone marrow aspirate to evaluate possible myeloma was also negative. Thus, due to the suspicion of disease circumscribed to the kidneys, a renal biopsy was performed, revealing a diffuse interstitial inflammatory infiltrate composed of T lymphocytes, numerous plasma cells and few β lymphocytes. These findings were compatible with acute tubulointerstitial nephritis, as a result of which treatment with prednisone was started.
DISCUSSION
The quinolones are broad spectrum antibiotics that are easy to use and which possess absorption and bioavailability
characteristics that make them one of the most widely used antibiotic groups. In this group it has been shown that ciprofloxacin3 is able to cause acute tubulointerstitial nephritis, and there are also isolated reports implicating the rest of the drugs belonging to this same group. Levofloxacin is a third-generation quinolone with a broad spectrum
of action and with the same side effects as the rest of the quinolones. Its association to acute tubulointerstitial nephritis is very infrequent; a Medline search spanning the period between 1998 and March 2008 revealed only four
cases of renal failure induced by levofloxacin4- 7, and none of them were accompanied by nephromegaly.
Our case represented a diagnostic challenge due to the suspicion of acute pyelonephritis during the entire clinical
course. Only in the light of the torpid evolution of events did we attempt to rule out other possible etiologies characterized by large kidney, renal failure and fever. Thus, having discarded hereditary causes of nephromegaly, we evaluated non-hereditary disorders such as amyloidosis, Gaucher¿s disease, mycoses, tuberculosis, AIDS, renal oncocytomatosis, angiofollicular ganglionic hyperplasia, myeloma, primary renal lymphoma, secondary renal lymphoma and acute leukemia.8 After ruling out some of these etiologies from the start, we examined the more plausible possibilities such as lymphoma, leukemia, myeloma, tuberculosis and amyloidosis. Since positive results were not obtained, a renal biopsy was decided, which revealed the above mentioned alterations. After corticoid
therapy with initial doses of 60 mg/kg of prednisone followed by slow withdrawal, kidney function was seen to normalize, with a reduction in kidney size (right 12.6 cm and left 13 cm), on occasion of the last ultrasound control (fig. 1).
CLINICAL CASE
The clinical case corresponds to a 67-year-old male. His personal history included allergy to nicotinamide, ischemic
heart disease (requiring three coronary stents, with follow-up comprising 6 catheterizations ¿ the last performed one year before admission) and dilated myocardiopathy secondary to the latter. His usual treatment consisted
of pantoprazole 40 mg/24 h, carvedilol 25 mg/12 h, aspirin 100 mg/24 h, amlodipine 5 mg/24 h, isosorbide
dinitrate 20 mg/8 h, and simvastatin 20 mg/24 h.
The patient reported to the Emergency Service with right-flank abdominal pain irradiating to the hypogastrium,
and accompanied by vomiting and fever. Physical examination revealed positive right-side fist-percussion as
sole significant finding. The emergency complementary tests showed creatinine 4 mg/dl, leukocytosis (16,000/μl) and urine sediment with leukocyturia. The chest and abdominal X-rays showed no anomalies. The study was completed with abdominal ultrasound, which revealed an enlarged right (15 cm) (fig. 1) and left kidney (14.5 cm) ¿ the latter organ also showing two cortical cysts. Based on the above data, admission to the Nephrology ward was decided, and a more complete evaluation with laboratory tests was made ¿ the immune and tumor marker parameters proving negative. The blood and urine cultures were also negative. Fluid therapy and broad-spectrum antibiotic treatment was prescribed, resulting in clinical and analytical improvement (creatinine 1.6 mg/dl); hospital discharge was thus decided. The patient was posteriorly readmitted with this same clinical presentation on two further occasions, with the clinical diagnosis of acute pyelonephritis refractory to medical treatment. During the admissions, the study was completed with blood cultures, urine cultures, and gallium gammagraphy. In view of the persistence of the bilateral nephromegaly, the possibility of amyloidosis was discarded by a rectal and abdominal adipose tissue biopsy, which proved negative. Tuberculosis was likewise ruled out by negative Mantoux tests and specific cultures. A bone marrow aspirate to evaluate possible myeloma was also negative. Thus, due to the suspicion of disease circumscribed to the kidneys, a renal biopsy was performed, revealing a diffuse interstitial inflammatory infiltrate composed of T lymphocytes, numerous plasma cells and few β lymphocytes. These findings were compatible with acute tubulointerstitial nephritis, as a result of which treatment with prednisone was started.
DISCUSSION
The quinolones are broad spectrum antibiotics that are easy to use and which possess absorption and bioavailability
characteristics that make them one of the most widely used antibiotic groups. In this group it has been shown that ciprofloxacin3 is able to cause acute tubulointerstitial nephritis, and there are also isolated reports implicating the rest of the drugs belonging to this same group. Levofloxacin is a third-generation quinolone with a broad spectrum
of action and with the same side effects as the rest of the quinolones. Its association to acute tubulointerstitial nephritis is very infrequent; a Medline search spanning the period between 1998 and March 2008 revealed only four
cases of renal failure induced by levofloxacin4- 7, and none of them were accompanied by nephromegaly.
Our case represented a diagnostic challenge due to the suspicion of acute pyelonephritis during the entire clinical
course. Only in the light of the torpid evolution of events did we attempt to rule out other possible etiologies characterized by large kidney, renal failure and fever. Thus, having discarded hereditary causes of nephromegaly, we evaluated non-hereditary disorders such as amyloidosis, Gaucher¿s disease, mycoses, tuberculosis, AIDS, renal oncocytomatosis, angiofollicular ganglionic hyperplasia, myeloma, primary renal lymphoma, secondary renal lymphoma and acute leukemia.8 After ruling out some of these etiologies from the start, we examined the more plausible possibilities such as lymphoma, leukemia, myeloma, tuberculosis and amyloidosis. Since positive results were not obtained, a renal biopsy was decided, which revealed the above mentioned alterations. After corticoid
therapy with initial doses of 60 mg/kg of prednisone followed by slow withdrawal, kidney function was seen to normalize, with a reduction in kidney size (right 12.6 cm and left 13 cm), on occasion of the last ultrasound control (fig. 1).
