Renal dysfunction in leprosy: a historical cohort of 923 patients in Brazil

Introduction

Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae, which had a global prevalence of 224,717 cases at the beginning of 2007. ¹ Renal dysfunction in leprosy has been described in the medical literature but the exact pathogenesis of this complication remains uncertain. ^2,3 Renal lesions such as glomerulonephritis, tubulo-interstitial diseases and nephrosclerosis were reported in autopsy studies. ^4,5 Chronic kidney disease can also occur and is mainly due to amyloidosis. ⁶

A retrospective study was conducted which included patients with a confirmed diagnosis of leprosy followed at tertiary hospitals in Fortaleza City, northeastern Brazil, between January 1976 and October 2007. Patients were excluded if they had any co-morbidity which could cause renal dysfunction. The patients were classified according to the recommendations of the World Health Organization. ¹ Patients showing negative smears at all sites were grouped as having paucibacillary leprosy (PB), while those showing positive smears at any site were grouped as having multibacillary leprosy (MB). Parameters such as gender, age, length of disease, leprosy classification, reaction episodes, treatment and outcome were analysed. Laboratory data included an assessment of serum urea, creatinine, sodium, potassium, aspartate amino transaminase (AST), alanine amino transaminase (ALT), direct bilirubin, indirect bilirubin, total cholesterol, high density lipoprotein, low density lipoprotein, triglycerides and urinalysis. Renal dysfunction was considered as serum level of creatinine higher than 1.4 mg/dL. The study protocol was reviewed and approved by the Ethical Committee of the institutions.

A total of 923 patients were included with a mean age of 41.5 ± 19.1 years and 53.3% were male. The mean length of disease was 20.9 ± 35.5 months and the mean length of treatment was 13.4 ± 14.1 months. Patients were classified as PB (65%) and MB (35%). A comparison between PB and MB patients can be seen in Tables 1 and 2. A predominance of male gender among MB patients was observed (P < 0.001). Renal dysfunction, reaction episode and treatment were also more frequent in multibacillary ones (P < 0.001, P < 0.001 and P = 0.001, respectively). The comparison of laboratory data between the two groups showed higher levels of creatinine, AST and ALT among multibacillary patients (P < 0.001, P = 0.01 and P = 0.02, respectively).

The mean serum urea and creatinine of the 923 patients was 30.5 ± 24.7 mg/dL and 0.9 ± 1.3 mg/dL, respectively. Renal dysfunction was found in 35 cases (3.8%). Among these patients, there were 23 (65.7%) lepromatous, three (8.6%) tuberculoid, five (14.3%) indeterminate and four (11.4%) borderline. Urinary abnormalities were found in all clinical presentations of leprosy. Proteinuria was found in 44 cases (4.8%), haematuria in 63 (6.8%) and leukocyturia in 96 (10.4%).

The following factors were associated with renal dysfunction by the univariate analysis: reaction episode (OR = 5.7, 95% confidence interval [CI] = 2.1–15.2, P = 0.001), multibacillary classification (OR = 4.6, 95% CI = 2.1–15.2, P < 0.001), male gender (OR = 4.0, 95% CI = 1.7–8.9, P < 0.001), duration of disease (OR = 1.01, 95% CI = 1.00–1.01, P < 0.001) and advanced age (49 ± 19.1 years; OR = 1.02, 95% CI = 1.00–1.04, P = 0.009). Independent risk factors for renal dysfunction were: reaction episode (OR = 3.9, 95% CI = 1.07–14.4, P = 0.03), multibacillary classification (OR = 3.5, 95% CI = 1.17–10.8, P = 0.02) and age (OR = 1.04, 95% CI = 1.01–1.08, P = 0.01). Four patients died (0.4%) due to septic shock (2), acute kidney injury (1) and pulmonary embolism (1).

Our investigation of renal dysfunction was undertaken with the largest cohort of leprosy patients studied to date. Our findings suggest that the reaction episode, multibacillary classification and age are risk factors for renal function impairment in leprosy.

Important renal abnormalities were found. Leprosy patients with renal dysfunction have a large spectrum of clinical manifestations, which range from asymptomatic disease to classical nephrotic syndrome. ² In this study, high levels of serum creatinine were seen in 4% of the patients. Most (71.4%) had MB leprosy, which suggests that this form of disease has an association with renal damage (P < 0.001). The patients had no other disease besides leprosy. The amount of bacilli seems to play an important role in the pathogenesis of renal dysfunction as MB patients presented more significant abnormalities. They also have a lower glomerular filtration rate (GFR) with a higher frequency of glomerular dysfunction when compared with the PB and control group. ⁷

In previous studies, the prevalence of renal damage in lepromatous leprosy patients was 56.5% and 52.4% in non-lepromatous. ⁸ High levels of proteinuria (50.9% versus 2.7%), haematuria (25.1% versus 0%) and nephrotic syndrome (6.6% versus 5.4%) were found in lepromatous leprosy compared with tuberculoid leprosy patients. We found significant urine abnormalities among our patients, including proteinuria (4.8%), haematuria (6.8%) and leukocyturia (10.4%). All these abnormalities could be caused by the leprosy itself, as glomerulonephritis has already been described in leprosy patients.

Proteinuria in leprosy has been reported before, ⁷ and its frequency is variable among the different studies. Kirsztajn et al., ³ analysing 96 patients, found proteinuria levels higher than 0.1 g/dL in 2.1% of cases, with none of them presenting with nephrotic proteinuria. Shwe and Woodruff, ⁹ analysing 221 leprosy patients, found a significantly higher frequency of proteinuria in lepromatous leprosy patients, especially in those with a high bacterial index and those in reaction episodes. Proteinuria has been reported in the absence of a reaction episode but it is commonly associated with erythema nodosum leprosum and reversal reaction.

Haematuria has been more frequently associated with lepromatous leprosy patients in the presence of reaction episodes. Oliveira et al. ⁷ found haematuria in 27% of his patients without reaction episodes or leukocyturia in 13 (22%). In the present study, haematuria was found in 63 (6.8%) cases and leukocyturia in 96 (10.4%) cases.

Factors associated with renal dysfunction were: reaction episode; multibacillary classification; male gender; age; and time of disease. Renal dysfunction seems to be common in patients with erythema nodosum leprosum, ¹⁰ which is classically associated with the deposition of immune complexes in the glomeruli, leading to proliferative glomerulonephritis and reduced GFR. Oliveira et al. ⁷ found that leprosy patients with no erythema nodosum leprosum have lower GFR and altered tubular function compared with the controls, which suggest an independent mechanism for GFR decrease other than immune complexes deposits.

Conclusion

In summary, leprosy can cause important renal abnormalities. Old age, reaction episode and multibacillary are risk factors for renal dysfunction in leprosy.