Context: Tetanus is a disease caused by Clostridium tetani . Acute renal failure (ARF) can occur in patients with tetanus and a number of mechanisms may contribute to this, including rhabdomyolysis and autonomic nervous system overactivity. Aims: To investigate the occurrence of ARF and other clinical features in patients with tetanus in Brazil. Settings and Design: Retrospective study of patients with tetanus admitted to Sao Jose Infectious Diseases Hospital, in Fortaleza City, Brazil. Materials and Methods: All patients admitted from January 1999 to December 2003 were included, except those with previously diagnosed renal insufficiency, diabetes mellitus, systemic arterial hypertension, systemic lupus erythematosous, or any other factors not associated with tetanus that could lead to renal dysfunction. We compared survivors with non survivor patients in order to investigate the differences in clinical manifestations and laboratory tests. Statistical Analysis Used: Statistical analysis was performed using SPSS 10.0 for Windows® . Results: A total of 85 patients were included. The mean age was 52 ± 16 years and 82% were male. The main symptoms and signs presented at admission were trismus (68.2%), dysfagia (50.6%), and neck stiffness (41.2%). AFR was found in 10 patients (11.8%). Death occurred in 8 cases (9.4%). Hyperglicemia (OR = 1.014, p = 0.03), hyperkalemia (OR = 3.2, p = 0.04), and thrombocytopenia (OR = 1.000, p = 0.03) were associated with increased mortality. ARF was not associated with death (p>0.5). Conclusions: ARF is an important complication of tetanus, which was not associated with death. Hyperglicemia, hyperkalemia, and thrombocytopenia seem to increase mortality.
Keywords: Acute renal failure, infectious diseases, prognosis, symptoms, tetanus
|How to cite this article:
Moura Filho FR, Mendonca PR, Lima EB, Silva JS, Pinho ML, Mota RM, Silva GB, Daher EF. Acute renal failure and other clinical features in tetanus patients from northeastern Brazil. Ann Trop Med Public Health 2008;1:52-5
|How to cite this URL:
Moura Filho FR, Mendonca PR, Lima EB, Silva JS, Pinho ML, Mota RM, Silva GB, Daher EF. Acute renal failure and other clinical features in tetanus patients from northeastern Brazil. Ann Trop Med Public Health [serial online] 2008 [cited 2020 Aug 9];1:52-5. Available from: https://www.atmph.org/text.asp?2008/1/2/52/50684
Tetanus is a nervous system disorder characterized by severe muscle spasms caused by the neurotoxin tetanospasmin produced by Clostridium tetani , a Gram-positive bacillus spore-forming obligate anaerobe whose natural habit is soil. , This toxin is usually acquired through the contamination of wounds with soil, manure, or rusty metal. 
Tetanospasmin has a predominant effect on inhibitory neurons inhibiting the release of glycine and gamma aminobutyric acid (GABA). ,, Uncontrolled disinhibited efferent discharge from motor neurones in the cord and brainstem lead to intense muscular rigidity and spasm, which may mimic convulsions. Disinhibited autonomic discharge leads to disturbances in autonomic control, with sympathetic overactivity and excessive plasma catecholamine levels.  Neuronal binding of toxins is thought to be irreversible. Recovery requires the growth of new nerve terminals, which explains the prolonged duration of tetanus. , The incubation period varies from 3-21 days, with an average of 8 days. 
In the most common form of tetanus, the first sign is spasm of the jaw muscles, followed by stiffness of the neck, difficulty in swallowing, and stiffness of the abdominal muscles. ,, Other signs include fever, sweating, hypertension, and tachycardia. Laryngospasm is a complication that can lead to interference with breathing and asphyxia.  Patients can also break their spine or long bones due to convulsions.  Other possible complications include hypotension, arrhythmias, and secondary infections, which are common because of a prolonged hospital stay. ,, In addition, altered renal physiology may be seen. 
Acute renal failure (ARF) can occur with tetanus and a number of mechanisms may contribute to this, including rhabdomyolysis and autonomic nervous system overactivity. ,,,, ARF due to tetanus is high in certain countries such as Brazil, where some studies have reported ARF in 34% of the cases.  Studies have already shown that up to 50% of patients with tetanus have a glomerular filtration rate (GFR) lower than 50 mL/min in the first or second week of hospitalization. This finding seems to be related to autonomic nervous system (ANS) overactivity, characterized by intense variations in systolic and diastolic blood pressure, increased heart rate, and elevated urinary metanephrine excretion. In some patients, blood pressure varies widely and terminal patients may develop hypotension and cold periphery. Renal glycosuria in euglycemic tetanus patients was also found and is probably related to tenospasmin. Tetanus-induced ARF is usually mild, non oliguric, has early onset, and is not related to the severity of the disease. 
In Brazil, approximately 1,500 cases are reported each year, and case mortality occurs at a rate of 1.6 cases per 100,000 inhabitants.  In developed countries, the incidence is as low as 50 to 70 cases each year. ,,
As tetanus still has a high incidence and mortality rate (around 30% in Brazil),  it is important to identify its complications in order to manage them as soon as possible and prevent unfavorable outcomes. ,,
The aim of this study was to describe the occurrence of ARF in tetanus and to investigate the factors associated with death.
|Materials and Methods|
This is a retrospective study including all patients with tetanus admitted to Sao Jose Infectious Diseases Hospital, in Fortaleza City, Brazil from January 1999 to December 2003. Clinical and laboratory features during the hospital stay were analyzed. A standardized case investigation form was used to complete demographical, epidemiological, clinical, and laboratory data. Serum concentration of urea, creatinine, potassium, sodium, and complete blood count were recorded at admission. ARF was defined as an increase of serum creatinine concentration by more than 50% or greater than 0.5 mg/dL above baseline. A comparison between survivors and non survivors was performed.
The inclusion criteria were patients above 18 years of age with a diagnosis of tetanus admitted during the time period mentioned above. The exclusion criteria were patients who had been previously diagnosed with renal insufficiency, diabetes mellitus, systemic arterial hypertension, systemic lupus erythematosous, as well as those who either were taking any nephotoxic drug or had any other factors not associated with tetanus that could lead to renal dysfunction. The study was approved by the Ethics Committee of Sao Jose Infectious Diseases Hospital.
The statistical analysis consisted of univariate and multivariate analyses of clinical and laboratory data performed using SPSS 10.0 for Windows® (SPSS Inc. Chicago, IL, USA). Groups were compared by using student’s t-test and Mann-Whitney. test when appropriated.The analysis of association between death and the categorized risk factors was done through the Fischer’s exact test, Pearson’s chi square test, and verisimilitude ratio test. A logistic regression model was used for quantitative variables. Adjusted odds ratio and 95% confidence interval were calculated. The descriptive values below 5% (p value < 0.05) were considered statistically significant.
A total of 85 patients were included. ARF was found in 10 cases (11.8%). The distribution of tetanus cases and ARF is summarized in [Table 1]. The mean age was 52 ± 16 years and over 82% were male.
The main symptoms and signs at admission were trismus (68.2%), dysfagia (50.6%), neck stiffness (41.2%), fever (23.5%), and abdominal pain (21.2%). Oliguria was found in 2 cases (2.4%) as summarized in [Table 2].
The mean laboratory values at admission were: serum creatinine 1.0 ± 0.6 mg/dL, blood urea nitrogen (BUN) 38 ± 26 mg/dL, sodium 137 ± 13 mEq/L, potassium 3.8 ± 0.6 mEq/L, hemoglobin 12 ± 1.9 g/dL, hematocrit 35 ± 5.4%, white blood cells 9,725 ± 3,919/mm 3 , platelets 267,879 ± 121,650/mm 3 , AST 81 ± 120 IU/L, ALT 62 ± 98 IU/L.
The mean of maximum and minimum systolic blood pressure was 146 ± 23 mmHg and 101 ± 19 mmHg, respectively. The maximum and minimum diastolic blood pressure was 93 ± 14 mmHg and 61 ± 11 mmHg, respectively. The maximum and minimum heart rate was 103 ± 17 bpm and 66 ± 13 bpm.
Among the 10 patients with ARF in our study, serum creatinine ranged from 1.5 to 6.2 (2.56 ± 1.78 mg/dL) and BUN ranged from 39 to 136 (80.3 ± 33.7 mg/dL). The BUN/creatinine ratio ranged from 25 to 78 (38.7 ± 14.8). None of these patients had oliguria. Tachycardia and fluctuations in blood pressure were observed in these patients. Heart rate was 108 ± 15 bpm. The variation in systolic blood pressure was 59 ± 25 mmHg (30-100) and diastolic blood pressure was 36 ± 19 mmHg (20-80).
Death occurred in 8 cases (9.4%). Hyperglicemia (OR = 1.014, CI = 1.001-1.028, p = 0.03), hyperkalemia (OR = 3.2, CI = 1.0-10.4, p = 0.04), and thrombocytopenia (OR = 1.000, CI = 1.000-1.000, p = 0.03) were associated with increased mortality. ARF was not associated with an increased risk of death (p>0.5). [Table 3] shows a comparison between survivors and non survivor patients.
Tetanus is an infectious disease that is preventable through vaccination but is still endemic in our region.  Neck stiffness and difficulty opening the mouth are usually early symptoms. Trismus is caused by a masseter spasm. A spasm progressively extends to other muscles, such as those of swallowing leading to dysphagia. , These common clinical signs and symptoms were also seen in over half of the patients in this study.
We found that hyperglycemia is associated with a greater risk of death. ARF was a complication found in almost 12% of patients, but did not show significant association with increased risk of death.
Among the patients who died (n=8), only one, a 23-year-old male, had ARF. His serum creatinine was 1.7 mg/dL and BUN was 75 mg/dl on admission. He also had sepsis with leukocytosis (12.700/mm 3 ), tachycardia (120 bpm), tachypnea (40 irmp), and a temperature of 39°C. He died 24 hours after admission. Thus, septicemia played an important role in the pathogenesis of renal dysfunction in this case. On the other hand, all patients who died had raised serum glucose, ranging from 105 to 259 mg/dL. As for lower values of serum sodium found in those who died, raised glucose may have contributed to that; serum sodium decreases by 1.9 mg/dL for every 100 mg/dL increase in glucose above normal.
Hypotension due to dehydration was not the cause of the acute renal failure, since adequate hydration was maintained in all patients. In the same way, nephrotoxic drugs and rhabdomyolysis were not observed to be involved with acute renal failure.in those patients.
Studies have shown that in severe tetanus impaired renal tubular function and decrease in glomerular filtration rate can occur. Sespis, dehydration, rhabdomyolysis, and alterations in renal blood flow due to catecholamines can contribute to renal failure. Clinically important renal impairment is associated with adrenergic overactivity and renal histology frequnetly shows acute tubular necrosis. ,,,
In summary, mortality was not high among the studied patients. Acute renal failure is an important complication of tetanus, but was not associated with death and this maybe due to prompt specific treatment. Hyperglicemia, hyperkalemia, and thrombocytopenia seem to increase mortality. Autonomic dysfunction seems to be an important pathophysiologic mechanism by which acute renal failure develops.
We are very grateful to the team of attending physicians, residents, medical students, and nurses from the Sao Jose Infectious Diseases Hospital for the assistance provided to the patients and for the technical support provided for the development of this research.
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Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2], [Table 3]