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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2017  |  Volume : 28  |  Issue : 1  |  Page : 95-101
Visceral leishmaniasis in adults with nephropathy


1 Department of Medicine A, Charles Nicolle Hospital; Faculty of Medicine, Tunis El Manar University, Tunis, Tunisia
2 Department of Nephrology, La Rabta Hospital; Faculty of Medicine, Tunis El Manar University, Tunis, Tunisia
3 Department of Parasitology, Charles Nicolle Hospital; Faculty of Medicine, Tunis El Manar University, Tunis, Tunisia
4 Laboratory of Renal Pathology LR00SP01, Charles Nicolle Hospital; Faculty of Medicine, Tunis El Manar University, Tunis, Tunisia

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Date of Web Publication12-Jan-2017
 

   Abstract 

The aim of this study is to evaluate the features of visceral leishmaniasis (VL) in adults with nephropathy, who were not infected with the human immunodeficiency virus. This is a retrospective study of 14 adults hospitalized between 2000 and 2014, with VL and renal involvement. Clinical, biological, and therapeutic data were collected from the patients' medical files. Eleven women and three men, most of whom were from the North of the country, with a mean age of 40.5 years were studied. Lupus was present in five cases, the Sicca syndrome in three cases, diabetes in one case, renal failure on dialysis in two cases, and there were three renal transplant recipients. Major clinical symptoms were fever and weakness in all cases. Enlargement of the spleen was present in eight cases and hepatomegaly in six cases. Biologic inflammatory syndrome and anemia were present in all cases, and pancytopenia was present in seven cases. Renal insufficiency was noted in all cases. Diagnosis of VL was confirmed by bone marrow examination or serology. Treatment consisted of antimoniate in 10 cases and amphotericin B in four cases. Seven deaths were recorded. Clinical symptoms of VL are atypical in patients with nephropathy and therefore, the diagnosis should be suspected in such patients because VL is still endemic in our country.

How to cite this article:
El Jeri H K, Harzallah A, Barbouch S, Bacha M M, Kheder R, Turki S, Trabelsi S, Abderrahim E, Hamida F B, Abdallah T B. Visceral leishmaniasis in adults with nephropathy. Saudi J Kidney Dis Transpl 2017;28:95-101

How to cite this URL:
El Jeri H K, Harzallah A, Barbouch S, Bacha M M, Kheder R, Turki S, Trabelsi S, Abderrahim E, Hamida F B, Abdallah T B. Visceral leishmaniasis in adults with nephropathy. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2017 Nov 23];28:95-101. Available from: http://www.sjkdt.org/text.asp?2017/28/1/95/198159

   Introduction Top


Visceral Leishmaniasis (VL) is endemic in Tunisia, where it occurs in its Mediterranean infant form, usually caused by L. infantum. It is now described more particularly in immunocompromised adults than in children.[1] ,[2] ,[3] ,[4] This new epidemiological situation is probably related to increased prevalence of immunosuppression that can be due to infections such as acquired immunodeficiency syndrome, iatrogenic or induced by immunosuppressive treatment, or secondary to an underlying disease. Thus, the association of VL to diseases or conditions responsible for disturbances of the immune system is being increasingly reported.[5] ,[6] ,[7] ,[8] ,[9] ,[10] The aim of our study was to evaluate the clinical, biological, therapeutic, and evolutionary features of VL in adults with chronic kidney disease (CKD) who were not infected with the human immunodeficiency virus (HIV).


   Patients and Methods Top


This is a retrospective study of 14 patients aged over 18 years, hospitalized in our department between 2000 and 2014, with renal impairment and VL.

The diagnosis of leishmaniasis was made either by the detection of amastigote form of Leishmania in bone marrow smears and/or on serology performed by indirect immunofluorescence (IIF) or by ELISA. The use of these different tools was according to the evolution of diagnostic techniques over years in our center. The inclusion criteria of our patients were fever (body temperature >37.8°C) and/or hepatosplenomegaly associated with hematological abnormalities [anemia (hemoglobin <12 g/dL)] and/or leukopenia (white blood cell count <4000/mm3 ) and/or thrombocytopenia (platelet count <150,000/mm3 ) with positive serological tests and/or positive bone marrow aspirate and/or detection of the parasite DNA on peripheral blood or marrow by polymerase chain reaction (PCR).

Renal involvement was defined by the presence of CKD, which was defined as abnormalities of kidney structure or function, present for more than three months and was classified according to the Kidney Disease Improving Global Outcomes classification. Renal function was evaluated by the modification of diet in renal disease formula. We did not include patients infected with the HIV. The clinical and laboratory data were collected from the medical records.

The treatment consisted of either meglumine antimoniate or amphotericin B. Clinical and laboratory monitoring was conducted to look for signs of intolerance to treatment.

Criteria of positive response to medication included disappearance of clinical signs with apyrexia, correction of biochemical abnormalities, and negative of immunoassays.


   Results Top


There were 11 women and three men with a mean age of 40.5 years (range: 18-62 years). Our patients were from Northern Tunisia in nine cases and from the Northwest in five.

The clinical characteristics of the patients are summarized in [Table 1].
Table 1. General characteristics of the study patients.

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Five patients had systemic lupus erythematosus (SLE), three patients had the Sicca syndrome, two patients were in end-stage renal disease (ESRD) treated by hemodialysis for two and five years, respectively, one patient was diabetic and three patients had undergone renal transplantation from cadaveric kidney in one case and from a living donor in two cases. At diagnosis of VL, 10 patients were on corticosteroids and/or immunosuppressive therapy for an average duration of 10 years. VL occurred concomitantly with SLE in two cases and occurred as a complication of this disease in three other cases.

All patients had fever and impaired general condition, with gastrointestinal symptoms in four cases. The clinical and laboratory parameters are summarized in [Table 2] and [Table 3].
Table 2. Clinical and biological signs in the study patients.

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Table 3. Laboratory parameters in the study patients.

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Hypergammaglobulinemia was present in 11 cases. Pancytopenia was noted in seven cases and bicytopenia in three cases. Renal failure was present in all cases; it was chronic in seven cases with three having ESRD and acute in the other seven cases. Obstructive nephropathy was found in one case related to bilateral ureteral compression by lymphadenopathy.

Detection of anti-Leishmania antibodies was performed by IIF in 11 patients with a positive test in 10 patients and by ELISA in two cases with a positive test in both cases. Bone marrow study was performed in 13 cases, which detected Leishmania by direct identification in 11 cases. The detection of parasite DNA by positive PCR was noted in one case.

The treatment consisted of antimony meglumine (Glucantime®) at the average dose of 20 mg/kg/day intramuscularly in eight cases followed by amphotericin B in two cases because of occurrence of adverse effects, and with sodium stibogluconate (Pentostam®) in one case at a dose of 10 mg/kg/day intravenously, because of the presence of coagulation disorders. Amphotericin B (Fungizone®) was used from the start in four cases at dose of 0.3 to 1 mg/kg every 48 h, intravenously. Side effects of treatment with antimonials are summarized in [Table 4]. However, there was a good clinical and biological tolerance with amphotericin B except for occurrence of thrombophlebitis and abscess at the injection site in one case.
Table 4. Adverse effects of treatment by meglumine antimoniate seen in our study patients.

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The subsequent evolution was favorable with recovery in seven cases. Death occurred in seven cases after an average period of 25 days (0-90 days) from the beginning of treatment ([Table 1]). After a mean follow-up of two years, a relapse was observed in only one case.


   Discussion Top


The incidence of VL has increased in our country probably due to some ecological changes creating favorable microclimates to sand flies. Besides these factors, acquired or iatrogenic immunosuppression plays an important role. Thus, recent years have seen forms of VL essentially described in immunocompromised adults, especially with HIV coinfection.[7] Other conditions are also described especially chronic renal failure, organ transplantation, and even pregnancy.[5] ,[6] ,[7] ,[8] ,[9] ,[10] ,[11] ,[12] Our cases showed features of VL occurring in patients with CKD and not infected with HIV. Our series is characterized also by the high frequency of association between SLE and VL, seen in five cases. We reported too, the first case published of the association between VL and the Sicca syndrome.[10]

This study highlights the difficulties one can face in the diagnosis of VL in patients with CKD with associated SLE and those with organ transplantation. Indeed, reported clinical and laboratory abnormalities are not specific for VL and may be related to the underlying disease. This could lead to failure to recognize leishmaniasis resulting in delayed diagnosis and compromising the prognosis of these patients. Our study population is characterized by a clear female predominance, probably explained by the high incidence of systemic diseases in our patients which usually affect females more frequently. The geographical origin in our study shows a predominance of patients from the north of Tunisia, and this is comparable to the data from different Tunisian epidemiological studies.[1] ,[3] The course of the disease is usually progressive, resulting in a deterioration of the general condition with irregular fever. Furthermore, gastrointestinal symptoms may be present.[13] ,[14] ,[15] All our patients presented with fever and deterioration of the general condition, with digestive symptoms in only four cases. Lymph node enlargement is also a common feature of VL.[14] ,[15] In our series, deep lymph nodes were responsible for obstructive acute renal failure by bilateral ureteral compression, in one case. Pancytopenia is frequently observed. It was present in our study in seven cases and bicytopenia in three cases. Inflammatory biological syndrome is of great diagnostic value and is an important parameter that needs to be monitored. Hypergammaglobulinemia may be absent in the beginning, particularly in adults treated with long-term corticosteroids.[16] All these clinical and laboratory abnormalities could be related to the underlying disease, particularly in SLE or the Sicca syndrome.[16] ,[17] ,[18] ,[19] ,[20] . Similarly, in organ transplant recipients, hematological abnormalities may be a side effect of the immunosuppressive treatment.

Noninvasive diagnosis of VL is with serology with good specificity of the different techniques used.[21] ,[22] ,[23] ,[24] ,[25] Where possible, the detection of parasite DNA by PCR is an excellent tool for the diagnosis and monitoring of leishmaniasis.[26] ,[27] It was carried out in only one of our study patients since this technique has only been introduced only recently in our center.

The definitive diagnosis of VL remains however parasitological and is based on the identification of the parasite in the reticulohistiocytic cells sought mainly in the bone marrow, on smears stained with May-GrunwaldGiemsa. Nevertheless, this test can show false negative results because of the very small number of Leishmania that exist in the bone marrow or hemodiluted sample. Thus, culture of the bone marrow aspirate improves the sensitivity of the detection of parasites.[18] ,[19] ,[20] ,[21] The diagnosis of VL was confirmed in our patients mainly by identification of Leishmania in bone marrow aspirate. Typing of Leishmania was not performed in our study because it is generally L. infantum which is prevalent in our country.[2]

Therapeutically, most of our patients were treated with antimonials. The usual recommended dose is 60 mg/kg/day for antimony meglumine (Glucantime®) and 20 mg/kg/day for sodium stibogluconate (Pentostam®).[28] ,[29] In immunocompromised patients with normal renal function, the regimen is the same as in immunocompetent patients; this is because of nephrotoxicity of these products due to which, their doses have to be reduced in renal failure. There is no well-established treatment regimen available, but from the published cases the dose in renal failure ranges from 5 to 30 mg/kg/day.[28] ,[29] In our patients, antimony meglumine was used at a mean dose of 20 mg/kg/day. However, this treatment is characterized by a number of adverse effects including intolerance, which occurs after the first injection and poisoning, which depends on the cumulative dose used. The latter is more common in patients with impaired renal function. It results in cardiac, hepatic, pancreatic, renal, and neurological toxicity. In our study, adverse events were mainly pancreatitis and renal toxicity causing acute renal failure. It seems that glomerular filtration rate plays a role in the occurrence of such toxicity and this would explain the frequency of such events in our patients, all of whom had renal impairment. Amphotericin B is one of the most active anti-Leishmania drugs.[29] ,[30] However, because of its toxicity and the difficulty of handling, it is considered as a second-line treatment. In our study, we did not observe any signs of intolerance. According to the latest recommendations, liposomal amphotericin B (Ambisome) is recommended for firstline treatment of VL due to its excellent efficacy with less toxicity[31] ,[32] ,[33]

The natural course of VL is fatal in few months with cachexia, sometimes aggravated by hemorrhagic accident or infection. The survival rate varies from 76% to 97% in immunocompetent individuals and seems lower in immunosuppressed individuals.[3] ,[4] ,[5] ,[21] Thus, recovery was observed in only 50% of our patients. The high mortality seen in our study is probably due to poor immunity because the majority were on immunosuppressive treatment, and it can also be due to delayed diagnosis, since most of our patients died soon after starting treatment. Relapses are possible, seen in 8%-42% of cases.[4] ,[18] Among our patients, after a mean follow-up of two years, only one case of recurrence was reported. To prevent these relapses, some authors have proposed chemoprophylaxis with pentamidine.[34]


   Conclusion Top


VL in immunocompromised patients not infected with the HIV and having nephropathy is characterized by an atypical presentation, leading to diagnostic delay. Antimonials are difficult to handle in these patients because of their nephrotoxicity. The liposomal amphotericin B is currently the treatment of choice.

Conflict of interest: None declared.

 
   References Top

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Correspondence Address:
A Harzallah
Department of Medicine A, Charles Nicolle Hospital, Tunis
Tunisia
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DOI: 10.4103/1319-2442.198159

PMID: 28098109

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