title: Renal tubular dysfunction in patients with American cutaneous leishmaniasis.
abstract: Renal dysfunction seen in patients with American cutaneous leishmaniasis (ACL) has been attributed to the use of antimonials for treatment. To determine whether ACL itself causes tubular dysfunction, we measured renal function in 37 patients with ACL prior to their treatment and compared results to that in 10 healthy volunteers of similar mean age. None of the patients presented with glomerular dysfunction; however, 27 had a urinary concentrating defect. There was no statistical difference between groups in the pre- and post-desmopressin test of urine osmolality, but the post-test urine osmolality of the controls was significantly higher. Urinary AQP2 levels, determined by western blot of isolated exosomes, were found to be significantly lower in patients than in controls, whereas that of the cotransporter (NKCC2) was significantly higher. A urinary acidification defect (post-test pH greater than 5.50 following calcium chloride) was found in 15 patients. Pretest plasma bicarbonate was below normal in 12 patients as was the pretest plasma pH in 14. Expression of the Na/H exchanger (NHE3), H(+)-ATPase, and pendrin were all significantly higher in patients with ACL than in controls. A combined urinary concentration and acidification defect was found in 12 patients. Thus, the urinary concentrating defect of ACL may be caused by decreased AQP2, with increased NKCC2 compensatory. Pendrin upregulation may be related to the urinary acidification defect with increased NHE3 and H(+)-ATPase also compensatory. Hence, ACL can cause asymptomatic renal tubular dysfunction.
authors.affiliation: Department of Internal Medicine, School of Medicine, Federal University of Ceará, Cariri Campus, Barbalha, Brazil. rodrigoalves@ufc.br
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Oliveira
authors.forename: Lúcyo F B
authors.initials: LF
authors.lastname: Diniz
authors.forename: Leonardo O
authors.initials: LO
authors.lastname: Teotônio
authors.forename: Cláudio G
authors.initials: CG
authors.lastname: Lima
authors.forename: Rosa M S
authors.initials: RM
authors.lastname: Mota
authors.forename: Alice
authors.initials: A
authors.lastname: Martins
authors.forename: Talita R
authors.initials: TR
authors.lastname: Sanches
authors.forename: Antônio C
authors.initials: AC
authors.lastname: Seguro
authors.forename: Lúcia
authors.initials: L
authors.lastname: Andrade
authors.forename: Geraldo B
authors.initials: GB
authors.lastname: Silva
authors.forename: Alexandre B
authors.initials: AB
authors.lastname: Libório
authors.forename: Elizabeth F
authors.initials: EF
authors.lastname: Daher
mesh_terms: D000328:Adult; D051399:Aquaporin 2 / Q000652:urine; D001639:Bicarbonates / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015153:Blotting, Western; D001938:Brazil; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007671:Kidney Concentrating Ability; D007674:Kidney Diseases / Q000469:parasitology* / Q000503:physiopathology / Q000652:urine; D007684:Kidney Tubules / Q000378:metabolism / Q000469:parasitology* / Q000503:physiopathology; D016773:Leishmaniasis, Cutaneous / Q000150:complications / Q000469:parasitology*; D008297:Male; D026901:Membrane Transport Proteins / Q000652:urine; D008875:Middle Aged; D009994:Osmolar Concentration; D011446:Prospective Studies; D006180:Proton-Translocating ATPases / Q000652:urine; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000652:urine; D028021:Sodium-Potassium-Chloride Symporters / Q000652:urine; D064466:Solute Carrier Family 12, Member 1; D000076988:Sulfate Transporters; D055815:Young Adult
chemical_list: C496023:AQP2 protein, human; D051399:Aquaporin 2; D001639:Bicarbonates; D015415:Biomarkers; D026901:Membrane Transport Proteins; C578714:SLC12A1 protein, human; C085609:SLC26A4 protein, human; C000613385:SLC9A3 protein, human; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D000076988:Sulfate Transporters; D006180:Proton-Translocating ATPases