Microalbuminuria and urinary retinol binding protein as markers of subtle renal injury in visceral leishmaniasis: sensitivity, specificity and predictive values of the immunoturbidimetric technique

Leishmania donovani-related visceral leishmaniasis (VL) is endemic over large areas of Sudan. It is a serious febrile illness and is characterized by fever, hepatosplenomegaly, lymph adenopathy, pancytopenia, and renal injury. Microalbuminuria (MA) and urinary retinol binding protein (urRBP) are useful markers for glomerular and tubular dysfunctions, respectively. Paromomycin (R), an amino glycoside antibiotic that is under assessment as an alternative treatment for VL, is known to be nephrotoxic. The nephrotoxicity is dose related. We report the frequency of subtle renal affection of VL and Paromomycin treatment in 46 parasitologicaly-confirmed VL patients enrolled for random treatment with different Paromomycin doses (15 mg/kg/day for 28 days or 20 mg/kg/day for 21 days) in a prospective, hospital-based and comparative study. We introduce the turbidimetric measurement for MA as a simple and field-based technique. Blood and urine were collected before and after treatment for hematological, biochemical profiles in addition to MA and urRBP measurement using competitive solid-phase, sandwich enzyme-linked immune sorbent assay (ELISA), and immunoturbidimetry. All patients (46/46; 100%) had normal serum urea and creatinine levels. More than 50% of patients had pretreatment MA detected by ELISA, whereas 54% were reactive with turbidimetry. Of the 46 patients, 4.3% had pre-urRBP detected by ELISA. Post-treatment MA was seen in more than 80% of patients who were treated with 20 mg/kg/day for 21 days Paromomycin while all of the patients who were treated with 15 mg/kg/day lost their pre-treatment reactivity. The sensitivity, specificity, positive and negative predictive values for MA using the turbidimetric technique were calculated as 100%, 86%, 85% and 100%, respectively. In conclusion, subtle renal injury in VL is mainly glomerular. Use of the 20 mg/kg/day Paromomycin should be critically investigated before implementation in routine use. Turbidimetry for MA measurement is a simple inexpensive, sensitive, and specific technique with high predictive values.