Urinary pH in HIV-infected adults in Ivory Coast and in France
Mortier, Emmanuela; Toure, Siakab; Seyler, Catherineb; Bloch, Martinea; Anglaret, Xavierb,c
aDepartment of Internal Medicine, Hospital Louis Mourier, AP-HP, Colombes, France; bProgramme Pac-ci, Abidjan, Côte d'Ivoire; and cUnité INSERM 593, Université Victor Segalen Bordeaux 2, Bordeaux, France.
Received: 13 March 2003; revised: 10 April 2003; accepted: 7 May 2003.
In industrialized countries, indinavir-related side-effects include urinary stones in 4–12% of patients . Recent data suggest that urinary stones may occur less frequently in sub-Saharan patients taking indinavir [2–4]. The risk of urinary stones increases with urinary pH. In water, indinavir solubility is 100 mg per milliliter at pH 3.5 and 0.03 mg per milliliter at pH 6.0, and immediate precipitation occurs at pH above 6.5 whatever the concentration . Whereas urinary pH from adults living in industrialized countries has long been shown to be usually acid , data on urinary pH in sub-Saharan African adults are scarce. We made a preliminary study to compare the urinary pH between HIV-infected adults living in Abidjan, Ivory Coast and in Paris, France.
In June 2002, consecutive adults consulting in two HIV outpatient clinics in Abidjan and in Paris were asked to participate in the study. Exclusion criteria were diuretic treatment, pregnancy, and ongoing symptoms, including diarrhoea, vomiting, urogenital symptoms, diabetes mellitus, and fever. Age, sex, geographical origin, last available CD4 cell count, drugs taken within the past week, body weight, body height and date of menstruation in women were recorded through standardized questionnaires. Urine samples were collected to measure pH, leukocytes, albumin, erythrocytes, nitrite and urine density using a reagent urinary strip (Multistix 8 SG; Bayer Corporation, USA).
A total of 189 patients were included in the study (Abidjan: 91, Paris: 98). All patients in Abidjan were of sub-Saharan African origin. In Paris 52, 11 and 37% of patients were of sub-Saharan African, north-African, and European origin, respectively. Overall, there were statistical differences between Abidjan and Paris in terms of the percentage of men (30 versus 61%, P < 0.001), mean body mass index (21.8 versus 23.4 kg/m2, P < 0.001), mean time from last available CD4 cell count (117 versus 76 days, P < 0.001), last available CD4 cell percentage (18.0 versus 22.3%, P = 0.005), and the percentage of patients receiving antiretroviral multitherapy (34 versus 66%, P < 0.001) or cotrimoxazole (70 versus 30%, P < 0.001). The difference was not statistically significant for the following variables: mean age (35.9 versus 38.1 years, P = 0.07), last available CD4 cell count (352 versus 410 cells/mm3, P = 0.13), and percentage of patients receiving indinavir (10 versus 5%, P = 0.21). In patients receiving antiretroviral treatment in Abidjan, 58% received a two nucleoside reverse transcriptase inhibitors (NRTI) plus one protease inhibitor regimen, 26% a two NRTI plus one non-nucleoside reverse transcriptase inhibitor regimen, 0% a three NRTI regimen, and 16% other regimens (versus 55, 31, 5 and 9% in Paris, respectively).
Overall, the mean urinary pH was 6.32 [standard deviation (SD) 0.66] in Abidjan and 5.91 (SD 0.94) in Paris (P < 0.001). There was no significant difference in terms of urine density (1.020 versus 1.019, P = 0.63), the presence of nitrite (2 versus 0%, P = 0.23) and the presence of erythrocytes (5 versus 9%, P = 0.67). There were significantly more samples with leucocyturia (16 versus 1%, P = 0.003) and albuminuria (26 versus 5%, P < 0.001) in Abidjan than in Paris. As shown in Table 1, the variables associated with a urinary pH less than 6 in univariate analyses were the city (Paris), sex (male), older age, origin other than sub-Saharan Africa, higher body mass index, higher CD4 cell count, the absence of cotrimoxazole treatment, and the absence of albuminuria. In multivariate analysis, the only variable that remained associated with the urinary pH was the city.
When considering only patients of sub-Saharan African origin, the mean urinary pH was 6.32 for those living in Abidjan and 5.92 for those living in Paris (P < 0.001). When considering only patients living in Paris, the mean urinary pH was not significantly different bt between patients of sub-Saharan (5.92) and European origin (6.0) (P = 0.70).
Further studies should confirm these findings, and explore whether they could be caused by dietary or genetic differences. In our study, patients from sub-Saharan and European origin living in Paris had similar urinary pH, reinforcing the dietary hypothesis. In an old report of urinary pH values in women living in Uganda, the mean pH was significantly higher in women of Ugandan origin than in women of European origin, which could be consistent with both hypotheses .
In all cases, a higher urinary pH in African adults living in sub-Saharan Africa is not likely to explain the lower frequency of indinavir-related urinary stones in subsub-Saharan Africa. Apart from a high urinary pH, the other mechanism causing urinary stones is the concentration of the drug or its metabolites in urine . Genetic differences in the metabolism of indinavir could be hypothesized to be associated with the different frequency of indinavir-associated urinary stones, as suggested by a recent study showing an increasing risk of urinary stones in Caucasian patients in a cohort of HIV-infected adults in the USA .
1. Kopp JB, Miller KD, Mican JAM, Feuerstein IM, Vaughan E, Baker C, et al
. Crystalluria and urinary tract abnormalities associated with indinavir. Ann Intern Med
2. Bouchaud O, Ralaimazava P, Longuet C, Aumaitre H, Matheron S, Coulaud JP. Tolerance of indinavir in 87 African patients living in France compared to European controls.
In: XIth International Conference on AIDS and STDs in Africa
. Luzaka, 1999 [Abstract 15PT56-10].
3. Seyler C, Dakoury-Dogbo N, Danel C, et al
. Mortality of HIV-infected adults receiving antiretroviral therapy in the ANRS 1203 cohort study, Abidjan, Côte d'Ivoire.
In: XIIth International Conference on AIDS and STD in Africa
. Ouagadougou, Burkina Faso, 9–13 December 2001 [Abstract 10DT3-1].
4. Laurent C, Diakhaté N, Ngom Gueye NF, Touré MA, Sow PS, Faye MA, et al. The Senegalese government's highly active antiretroviral therapy initiative: an 18-month follow-up study. AIDS
5. Salahuddin S, Hsu YS, Buchholz NP, Dieleman JP, Gyssens IC, Kok DJ. Is indinavir crystalluria an indicator for indinavir stone formation? AIDS
6. Ziegler JD, Brice AT. Reaction and specific gravity of urine in relation to nephritis. Ann Intern Med
7. Wing AJ, Gunstone RF, Njema D, Shani HGP. Urinary pH values in African, Asian and European subjects in Kampala. African J Med Sci
8. Dworkin MS, Wan PCT. Indinavir, zidovudine, lamivudine: 3-year follow-up
. Ann Intern Med
© 2003 Lippincott Williams & Wilkins, Inc.