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Epidemiological, clinical, and laboratory factors associated with chronic kidney disease in Mexican HIV-infected patients

ABSTRACT

Aim:

To determine the prevalence of chronic kidney disease (CKD) and the epidemiological, clinical, and laboratory factors associated with CKD in Mexican HIV-infected patients.

Methods:

Cross-sectional study. We included 274 patients with HIV/AIDS. CKD was defined by the estimated glomerular filtration rate (eGFR < 60 mL/min/1.73 m2 assessed by CKD-EPI) and albuminuria criteria from KDIGO guidelines. Clinical, epidemiological, and laboratory characteristics were compared between patients with and without CKD. The factors associated with CKD were assessed by logistic regression analysis.

Results:

The mean age was 41±11 years, and 72.3% of the patients were men. The global prevalence of CKD was 11.7% (n = 32); 7.2% (n = 20) were defined by eGFR criterion; 7.6% (n = 21), by the albuminuria criterion; and 3.2% (n = 9), by both CKD criteria. The most frequently observed stages of CKD were KDIGO G3A1 stage with 4.7% (n = 13), KDIGO G1A2 stage with 3.6% (n = 10) and KDIGO G3A2 stage with 1.7% (n = 5). The factors associated with CKD were use of abacavir/lamivudine (OR 3.2; 95% CI 1.1-8.9; p = 0.03), a CD4 lymphocyte count < 400 cells/µL (OR 2.6; 95% 1.03-6.4, p = 0.04), age (OR 1.1; 95% CI 1.04-1.2, p = 0.001) and albuminuria (OR 19.98; 95% CI: 5.5-72.2; p < 0.001).

Conclusions:

CKD was a frequent complication in HIV-infected patients. These findings confirm the importance of screening and the early detection of CKD, as well as the importance of identifying and treating traditional and non-traditional risk factors associated with CKD.

Keywords:
Renal Insufficiency, Chronic; HIV; Renal Insufficiency

RESUMO

Objetivo:

Determinar a prevalência de doença renal crônica (DRC) e os fatores epidemiológicos, clínicos e laboratoriais associados à DRC em pacientes mexicanos infectados pelo HIV.

Métodos:

Estudo transversal. Incluímos 274 pacientes com HIV/AIDS. A DRC foi definida pela taxa de filtração glomerular estimada (TFGe < 60 mL/min/1,73 m2, avaliada pelo CKD-EPI) e pelos critérios de albuminúria das diretrizes do KDIGO. As características clínicas, epidemiológicas e laboratoriais foram comparadas entre pacientes com e sem DRC. Os fatores associados à DRC foram avaliados por análise de regressão logística.

Resultados:

A média da idade foi de 41 ± 11 anos e 72,3% dos pacientes eram homens. A prevalência global de DRC foi de 11,7% (n = 32); 7,2% (n = 20) foram definidos pelo critério TFGe; 7,6% (n = 21), pelo critério da albuminúria; e 3,2% (n = 9), pelos dois critérios para DRC. Os estágios mais frequentemente observados da DRC foram o estágio KDIGO G3A1 com 4,7% (n = 13); estágio KDIGO G1A2 com 3,6% (n = 10) e estágio KDIGO G3A2 com 1,7% (n = 5). Os fatores associados à DRC foram o uso de abacavir/lamivudina (OR 3,2; IC95% 1,1-8,9; p = 0,03), contagem de linfócitos CD4 < 400 células/µL (OR 2,6; 95% 1,03-6,4, p = 0,04), idade (OR 1,1; IC95% 1,04-1,2, p = 0,001) e albuminúria (OR 19,98; IC95%: 5,5-72,2; p < 0,001).

Conclusões:

A DRC foi uma complicação frequente em pacientes infectados pelo HIV. Esses achados confirmam a importância do rastreamento e da detecção precoce da DRC, bem como a importância de identificar e tratar os fatores de risco tradicionais e não tradicionais associados à DRC.

Palavras-chave:
Insuficiência Renal Crônica; HIV; Insuficiência Renal

INTRODUCTION

Significant advances in antiretroviral therapy have deceased the progression of disease and improved survival of HIV-infected patients. In fact, chronic kidney disease (CKD) has arisen as one of the leading noninfectious conditions affecting HIV-infected persons.11 Estrella MM, Fine DM. Screening for chronic kidney disease in HIV-infected patients. Adv Chronic Kidney Dis 2010;17:26-35. The reported prevalence of CKD in patients infected with HIV in North America and Europe ranges from 4.7% to 9.7%, and higher rates have been reported when CKD is defined by either estimated glomerular filtration rate (eGFR) or proteinuria.22 Choi AI, Rodriguez RA, Bacchetti P, Bertenthal D, Volberding PA, O'Hare AM. Racial differences in end-stage renal disease rates in HIV infection versus diabetes. J Am Soc Nephrol 2007;18:2968-74.

3 Fernando SK, Finkelstein FO, Moore BA, Weissman S. Prevalence of chronic kidney disease in an urban HIV infected population. Am J Med Sci 2008;335:89-94.
-44 Baekken M, Os I, Sandvik L, Oektedalen O. Microalbuminuria associated with indicators of inflammatory activity in an HIV-positive population. Nephrol Dial Transplant 2008;23:3130-7. HIV infection is a well-established risk factor for CKD and end-stage renal disease (ESRD).

The majority of CKD cases in HIV infection are due to HIV-associated nephropathy (HIV-AN). However, up to 50% of kidney diseases in HIV-infected persons result from a wide array of non-HIVAN pathology.55 Estrella M, Fine DM, Gallant JE, Rahman MH, Nagajothi N, Racusen LC, et al. HIV type 1 RNA level as a clinical indicator of renal pathology in HIV-infected patients. Clin Infect Dis 2006;43:377-80. These patients may develop multiple glomerular nephropathies (IgA nephropathy, lupus-like glomerulonephritis, focal and segmental glomerulosclerosis, membranoproliferative glomerulonephritis with cryoglobulinemia, and membranous glomerulopathy) and vascular (thrombotic microangiopathy), tubulointerstitial (tubular nephropathy by drugs, tubulointerstitial immunoallergic nephritis, and Fanconi syndrome), and obstructive nephropathies (nephropathy due to crystal deposition) related to the virus itself, the drugs administered or the coinfections.66 Kopp JB, Naicker S. Human Immunodeficiency Virus Infection and the Kidney. In: Floege J, Johnson R, Feehally J, eds. Comprehensive Clinical Nephrology. 4th ed. Saint Louis: Elsevier Saunders; 2010. p. 675-83. On the other hand, traditional risk factors for CKD are becoming increasingly prevalent in HIV-infected populations, including aging, diabetes mellitus, hypertension, cardiovascular disease, previous AKI and race/ethnicity.77 Achhra AC, Mocroft A, Ross MJ, Ryom L, Lucas GM, Furrer H, et al.; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group. Kidney disease in antiretroviral-naïve HIV-positive adults with high CD4 counts: prevalence and predictors of kidney disease at enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med 2015;16:55-63. This has caused the risk factors for CKD in HIV-infected persons to be a combination of traditional and HIV-related factors, including low CD4 counts, high viral load, intravenous drug use, hepatitis C virus (HCV) coinfection, and use of specific antiretroviral drugs.88 Kalayjian RC, Franceschini N, Gupta SK, Szczech LA, Mupere E, Bosch RJ, et al. Suppression of HIV-1 replication by antiretroviral therapy improves renal function in persons with low CD4 cell counts and chronic kidney disease. AIDS 2008;22:481-7.

9 Gupta SK, Smurzynski M, Franceschini N, Bosch RJ, Szczech LA, Kalayjian RC, et al.; AIDS Clinical Trials Group Longitudinal Linked Randomized Trials Study Team. The effects of HIV type-1 viral suppression and non-viral factors on quantitative proteinuria in the highly active antiretroviral therapy era. Antivir Ther 2009;14:543-9.

10 Lucas GM, Lau B, Atta MG, Fine DM, Keruly J, Moore RD. Chronic kidney disease incidence, and progression to end-stage renal disease, in HIV-infected individuals: a tale of two races. J Infect Dis 2008;197:1548-57.

11 Mocroft A, Kirk O, Reiss P, De Wit S, Sedlacek D, Beniowski M, et al.; EuroSIDA Study Group. Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients. AIDS 2010;24:1667-78.
-1212 Orlando G, Meraviglia P, Cordier L, Meroni L, Landonio S, Giorgi R, et al. Antiretroviral treatment and age-related comorbidities in a cohort of older HIV-infected patients. HIV Med 2006;7:549-57. Finally, as in the general population, albuminuria and decreased kidney function in HIV-positive individuals have been associated with worse outcomes such as a progression to AIDS and death.1313 Szczech LA, Hoover DR, Feldman JG, Cohen MH, Gange SJ, Goozé L, et al. Association between renal disease and outcomes among HIV-infected women receiving or not receiving antiretroviral therapy. Clin Infect Dis 2004;39:1199-206.,1414 Gardner LI, Holmberg SD, Williamson JM, Szczech LA, Carpenter CC, Rompalo AM, et al.; HIV Epidemiology Research Study Group. Development of proteinuria or elevated serum creatinine and mortality in HIV-infected women. J Acquir Immune Defic Syndr 2003;32:203-9.

The aim of our study was to assess the prevalence of CKD and to determine epidemiological, clinical, and laboratory factors associated with CKD in Mexican HIV-infected patients.

METHODS

A cross-sectional study was performed with patients evaluated from November 2015 to September 2016. The protocol was reviewed and approved by the Institutional Research and Ethics Committee. We included patients with HIV/AIDS from the Outpatient Center for AIDS and Sexual Transmission Infections Care (CAPASITS) in Sinaloa, Mexico.

Clinical (age, sex, smoking, drug use, medications, HCV coinfection, hepatitis B virus (HBV) coinfection, hypertension, and diabetes mellitus diagnosis), laboratory (serum creatinine, urea, hemoglobin, leukocytes, platelets, albuminuria, and estimated glomerular filtration rate) and HIV-infection variables (CD4 lymphocyte count, viral load, clinical stage of HIV-infection, antiretroviral medications) were collected and compared between patients with and without CKD.

The diagnosis of CKD was documented if the patient had two consecutive determinations, measured with a 3-month interval or more, of a GFR < 60 mL/min/1.73 m2 estimated with the equation CKD-EPI (GFR = 141 * min (Scr/κ,1) α * max ( Scr/κ, 1) -1.209 * 0.993Age * 1.018 [if female] * 1.159 [if black]) and/or albuminuria in the dipstick or 24-hour urine collection. The stage of CKD was determined by the eGFR rate (stage 1: eGFR > 90 mL/min/1.73 m2; stage 2: eGFR 60-89 mL/min/1.73 m2; stage 3a: eGFR 45-59 mL/min/1.73 m2; stage 3b: eGFR 30-44 mL/min/1.73 m2; stage 4: eGFR 15-29 mL/min/1.73 m2; stage 5: eGFR < 15 mL/min/1.73 m2) and albuminuria (A1: albuminuria < 30 mg/g; A2: albuminuria 30- 299 mg/g; A3: albuminuria > 300 mg/g), according to the diagnostic and classification criteria for CKD of the Kidney Disease Improving Global Outcomes (KDIGO) foundation.1515 Group KDIGOKCW. KDIGO clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013;3:19-62.,1616 Lucas GM, Ross MJ, Stock PG, Shlipak MG, Wyatt CM, Gupta SK, et al.; HIV Medicine Association of the Infectious Diseases Society of America. Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2014;59:e96-138. Staging of HIV infection was done according to clinical categories (category A1: asymptomatic infection, acute infection, persistent generalized lymphadenopathy; category B: symptomatic infection, not A or C; category C: defining conditions of AIDS) and immunological categories (category 1: lymphocyte count > 500 cells/µL; category 2: lymphocyte count of 200-499 cells/µL; category 3: lymphocyte count < 200 cells /µL) of the revised classification system of HIV infection of the Centers for Disease Control.1717 From the Centers for Disease Control and prevention. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. JAMA 1993;269:460.

Descriptive statistics with means and standard deviations were used to describe continuous variables; frequencies and proportions were used to describe categorical variables. Comparisons between groups were performed using Student's t-test and one-way ANOVA for continuous variables and the χ2 test for categorical variables. The study of factors associated with CKD was performed by multivariate logistic regression. Variables with p < 0.05 in the univariate analysis and those that have been consistently associated with CKD in the medical literature were included in the multivariate analysis. A value of p < 0.05 was considered statistically significant.

RESULTS

1. GENERAL POPULATION CHARACTERISTICS

We included 274 patients with an average age of 41 ± 11 years; of these patients, 72.3% (n = 198) were males. The most frequently observed comorbidities were smoking in 28.5% (n = 78), drug abuse in 14.6% (n = 40), hypertension in 7.7% (n = 21), and diabetes mellitus in 6.9% (n = 19) of the patients. The main viral coinfection in our population was HCV in 2.9% (n = 8) of the patients.

2. CLINICAL AND IMMUNOLOGICAL STAGES OF HIV-INFECTION

The most common clinical category was category B with 39.8% (n = 109), followed by category C with 31.4% (n = 86), and category A with 28.8% (n = 79) of the patients. The most common immunologic category was category 2 with 43.5% (n = 119), followed by category 3 with 40.1% (n = 110), and category 1 with 16.4% (n = 45) of the patients. Based on these categories, the most frequently observed clinical stages of HIV in our population were stage C3 (22.6%, n = 62), stage B2 (21.2%, n = 58), and stage A2 (15%, n = 41).

On the other hand, the initial viral load (pretreatment) was 89.220 + 244.945 copies/mL and the CD4 lymphocyte count was 369 + 276 cells/µL. Coinfection was observed in 8.3% (n = 23) of the HIV patients, of which 0.7% (n = 2) corresponded to coinfection with HBV; 2.9% (n = 8), to coinfection with HCV; and 4.7% (n = 13), to concomitant infection with Treponema Pallidum.

3. PREVALENCE OF CHRONIC KIDNEY DISEASE

The global prevalence of CKD in our HIV-infected population was 11.7% (n = 32); 7.2% (n = 20) were diagnosed by the eGFR criterion, 7.6% (n = 21) were diagnosed by the albuminuria criterion, and 3.2% (n = 9) by both CKD criteria. Of the patients with CKD, 34.3% (n = 11) were fulfilled with the eGFR < 60 mL/min criterion, 37.5% (n = 12) fulfilled the albuminuria criterion, and 28.1% (n = 9) with both CKD criteria.

The most frequent stages of CKD in our population were KDIGO G3A1 stage with 4.7% (n = 13), KDIGO G1A2 stage with 3.6% (n = 10), and KDIGO G3A2 stage with 1.7% (n = 5) of the cases (Table 1).

Table 1
Prevalence of CKD in Mexican HIV-infected patients

4. COMPARISON OF CLINICAL, LABORATORY, TREATMENT, AND HIV-INFECTION CHARACTERISTICS BETWEEN PATIENTS WITH AND WITHOUT CKD

When comparing the general characteristics between CKD patients vs non-CKD patients, we observed that patients with albuminuria-CKD criterion were younger than patients with eGFR-CKD criterion (35 vs. 51 years, p = 0.001), eGFR + albuminuria CKD criteria (35 vs. 49, p = 0.001), and non-CKD patients (35 vs 40, p = 0.001). No statistically significant difference was observed in the other general characteristics shown in Table 2.

Table 2
Comparison of clinical, laboratory and HIV-infection characteristics between patients with and without CKD

Comparing medical prescriptions between groups, we observed that the use of angiotensin II receptor antagonism (ARA) (11.1%, n = 1 vs. 0.8%, n = 2; p < 0.01) and antiretroviral treatment with saquinavir/ritonavir (22.2%, n = 2 vs. 3.3%, n = 8; p = 0.03) were more frequent in patients with CKD by eGFR and /or albuminuria criteria than in patients without CKD. No statistically significant difference was found for the remaining medications shown in Table 3.

Table 3
Comparison of medications used between patients with and without CKD

5. FACTORS ASSOCIATED WITH CKD

In the multivariate logistic regression analysis, the factors associated with CKD defined by the eGFR and/or albuminuria in our HIV population were abacavir /lamivudine treatment, with an OR of 3.2 (95% CI of 1.1-8.9; p=0.03), and a CD4 lymphocyte count < 400 cells/µL, with an OR of 2.6 (95% CI of 1.03-6.4, p = 0.04). On the other hand, the factors associated with CKD defined only by the eGFR were age, with OR of 1.1 (95% of CI 1.04-1.2, p = 0.001); and albuminuria, with an OR of 19.98 (95% of CI: 5.5-72.2; p = 0.00). In our HIV population, we did not observe factors associated with CKD defined by albuminuria (Table 4).

Table 4
Factors asociated with CKD in Mexican HIV-infected patients

DISCUSSION

The global prevalence of CKD in our HIV population was 11.7% (n = 32); 7.2% (n = 20) of the patients were diagnosed by the eGFR criterion, and 7.6% (n = 21) of the patients were diagnosed by the albuminuria criterion. These findings are in line with previous reports by other researchers worldwide, ranging from 7.2% (USA) to 13.7% (China) applying the albuminuria criterion and from 3.5% (Europe) to 9.7% (USA) considering the eGFR criterion < 60 mL/min. On the other hand, the global prevalence of CKD (eGFR and /or albuminuria) in our population was less than that reported in Japan (15.5%) and USA (23.7%), although globally, this varies from 2 to 30%.1818 Winston JA. HIV and CKD epidemiology. Adv Chronic Kidney Dis 2010;17:19-25.

Coinfection with HCV was 2.9% (n = 8), which was lower than previous reports (30%, with a range between 3-70%).1919 Vallet-Pichard A, Pol S. Natural history and predictors of severity of chronic hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection. J Hepatol 2006;44:S28-34. On the other hand, HBV coinfection was 0.7% (n = 2) in our population, which is below the prevalence described by other authors. 2020 Alter MJ. Epidemiology of viral hepatitis and HIV co-infection. J Hepatol 2006;44:S6-9.,2121 World Health Organization (WHO). Guidelines for the Prevention, Care and Treatment of Persons with Chronic Hepatitis B Infection. Geneva: WHO; 2015. Raboni et al. conducted a cross-sectional study in southern Brazil in which the authors documented hepatitis/HIV coinfection in 6.6% of HIV-infected patients. The HCV/HIV coinfection was confirmed in 4.0% and HBV/HIV coinfection in 1.3% of HIV-infected patients.2222 Raboni SM, Tuon FF, Beloto NC, Demeneck H, Oliveira A, Largura D, et al. Human immunodeficiency virus and hepatitis C virus/hepatitis B virus co-infection in Southern Brazil: clinical and epidemiological evaluation. Braz J Infect Dis 2014;18:664-8.

Previous clinical studies have described multiple traditional risk factors (age, hypertension, diabetes, proteinuria, etc.) and non-traditional risk factors specific to HIV patients (elevated viral load, low CD4 cell count, coinfection with HBV and HCV, drugs, etc.) associated with the development of CKD.77 Achhra AC, Mocroft A, Ross MJ, Ryom L, Lucas GM, Furrer H, et al.; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group. Kidney disease in antiretroviral-naïve HIV-positive adults with high CD4 counts: prevalence and predictors of kidney disease at enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med 2015;16:55-63.

8 Kalayjian RC, Franceschini N, Gupta SK, Szczech LA, Mupere E, Bosch RJ, et al. Suppression of HIV-1 replication by antiretroviral therapy improves renal function in persons with low CD4 cell counts and chronic kidney disease. AIDS 2008;22:481-7.

9 Gupta SK, Smurzynski M, Franceschini N, Bosch RJ, Szczech LA, Kalayjian RC, et al.; AIDS Clinical Trials Group Longitudinal Linked Randomized Trials Study Team. The effects of HIV type-1 viral suppression and non-viral factors on quantitative proteinuria in the highly active antiretroviral therapy era. Antivir Ther 2009;14:543-9.

10 Lucas GM, Lau B, Atta MG, Fine DM, Keruly J, Moore RD. Chronic kidney disease incidence, and progression to end-stage renal disease, in HIV-infected individuals: a tale of two races. J Infect Dis 2008;197:1548-57.
-1111 Mocroft A, Kirk O, Reiss P, De Wit S, Sedlacek D, Beniowski M, et al.; EuroSIDA Study Group. Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients. AIDS 2010;24:1667-78.

Age was a factor associated with CKD in our population. This finding is similar to those reported by other studies, being that the relative risk increase for CKD (defined as eGFR or albuminuria) for every 10 years of age is from 1.5 to 5.5. When age was analyzed as a dichotomous variable by other authors, patients > 50 years presented a relative risk of 2.0 for progression to ESRD or an eGFR < 15 mL/min compared to patients < 30 years.1616 Lucas GM, Ross MJ, Stock PG, Shlipak MG, Wyatt CM, Gupta SK, et al.; HIV Medicine Association of the Infectious Diseases Society of America. Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2014;59:e96-138.

A CD4 lymphocyte count < 400 cells/µL was another factor associated with CKD (defined by GFR or albuminuria) in our population. This has been consistently demonstrated by other investigators, reporting a relative risk range for CKD (defined by GFR or albuminuria) from 1.1 to 1.25 for each decrease of 100 cells/µL or from 1.4 to 2.2 for patients with CD4 < 200 vs. > 201 cells/µL. On the other hand, the CD4 count has also been associated with the progression to ESRD or a GFR < 15 mL/min, with a relative risk of 1.7 per 100 cells/µL decrease and 1.4 to 2.7-fold increased risk for patients with CD4 < 200 vs. > 201 cells/µL.1616 Lucas GM, Ross MJ, Stock PG, Shlipak MG, Wyatt CM, Gupta SK, et al.; HIV Medicine Association of the Infectious Diseases Society of America. Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2014;59:e96-138. Another study documented a decreased CKD risk in association with CD4 cell restoration and plasma viral load suppression during treatment with HAART.2323 Kalayjian RC, Lau B, Mechekano RN, Crane HM, Rodriguez B, Salata RA, et al. Risk factors for chronic kidney disease in a large cohort of HIV-1 infected individuals initiating antiretroviral therapy in routine care. AIDS 2012;26:1907-15.

In our HIV population, the presence of albuminuria was the main factor associated with CKD (defined by the eGFR criterion). The presence of albuminuria is frequent and is observed in up to a third of patients infected with HIV. Multiple observational studies in the general population and cohorts of HIV-infected patients demonstrate a strong and consistent association between the presence of albuminuria and clinical outcomes in these patients, such as progression to ESRD, cardiovascular disease, AIDS, and death.1414 Gardner LI, Holmberg SD, Williamson JM, Szczech LA, Carpenter CC, Rompalo AM, et al.; HIV Epidemiology Research Study Group. Development of proteinuria or elevated serum creatinine and mortality in HIV-infected women. J Acquir Immune Defic Syndr 2003;32:203-9.,2424 Wyatt CM, Hoover DR, Shi Q, Seaberg E, Wei C, Tien PC, et al. Microalbuminuria is associated with all-cause and AIDS mortality in women with HIV infection. J Acquir Immune Defic Syndr 2010;55:73-7.

25 Choi AI, Li Y, Deeks SG, Grunfeld C, Volberding PA, Shlipak MG. Association between kidney function and albuminuria with cardiovascular events in HIV-infected persons. Circulation 2010;121:651-8.

26 Gravemann S, Brinkkoetter PT, Vehreschild JJ, Franke B, Ehren K, Bünemann E, et al. Low-grade proteinuria is highly prevalent in HIV-positive patients on antiretroviral treatment. AIDS 2014;28:1783-9.
-2727 Gupta SK, Mamlin BW, Johnson CS, Dollins MD, Topf JM, Dubé MP. Prevalence of proteinuria and the development of chronic kidney disease in HIV-infected patients. Clin Nephrol 2004;61:1-6.

Treatment with abacavir/lamivudine was another factor associated with CKD in our population. Although abacavir and lamivudine have shown a low nephrotoxicity in some clinical studies, abacavir has been associated with tubular nephrotoxicity and acute tubulointerstitial nephritis and lamivudine with Fanconi syndrome and nephrogenic diabetes insipidus.2828 Nelson M, Azwa A, Sokwala A, Harania RS, Stebbing J. Fanconi syndrome and lactic acidosis associated with stavudine and lamivudine therapy. AIDS 2008;22:1374-6.,2929 Kalyesubula R, Perazella MA. Nephrotoxicity of HAART. AIDS Res Treat 2011;2011:562790. Takeshi Nishijima et al. compared the deterioration of eGFR (a 25% decrease in baseline renal function) between HIV-infected patients treated with an antiretroviral regimen based on a tenofovir- vs. an abacavir-based regimen in a cohort of 503 Japanese patients. Although impairment of renal function was greater in patients under the tenofovir regimen (22.1%), impairment of renal function was also observed in patients under the abacavir regimen (13.5%).3030 Nishijima T, Gatanaga H, Komatsu H, Tsukada K, Shimbo T, Aoki T, et al. Renal function declines more in tenofovir- than abacavir-based antiretroviral therapy in low-body weight treatment-naïve patients with HIV infection. PLoS One 2012;7:e29977. In the AIDS Clinical Trials Group Study 5202 (ACTG), the frequency of Fanconi syndrome, toxic nephropathy, proteinuria, and renal failure was similar between patients treated with tenofovir/emtricitabine and those treated with abacavir/lamivudine.3131 Sax PE, Tierney C, Collier AC, Daar ES, Mollan K, Budhathoki C, et al.; AIDS Clinical Trials Group Study A5202 Team. Abacavir/lamivudine versus tenofovir DF/emtricitabine as part of combination regimens for initial treatment of HIV: final results. J Infect Dis 2011;204:1191-201. These findings confirm that although abacavir has a lower nephrotoxicity profile, it is still a nephrotoxic antiretroviral drug.

Treatment with saquinavir/ritonavir (OR 3.3, 95% CI 0.8-13.3, p = 0.09) and tenofovir/emtricitabine (OR 2.2, 95% CI 0.9-5.6, p = 0.09) showed a statistical trend for CKD risk defined by eGFR and albuminuria. These findings have been confirmed by Mocroft et al., who studied the cumulative nephrotoxic effect of the major antiretroviral drugs used in a cohort of 23,005 HIV-infected patients in the United States, Europe, and Australia. The authors documented an increase in the risk of CKD (defined by eGFR < 60 mL/min) of 14, 20, and 11% for each year of exposure only for tenofovir, ritonavir/atazanavir and ritonavir/lopinavir, respectively. The increase in the incidence of CKD with chronic exposure to these antiretrovirals over the 6-year follow-up, indicates a cumulative nephrotoxic effect of tenofovir, ritonavir/atazinovir, and ritonavir/lopinavir.3232 Mocroft A, Lundgren JD, Ross M, Fux CA, Reiss P, Moranne O, et al.; Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) Study. Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study. Lancet HIV 2016;3:e23-32. However, saquinavir has been shown to be a safe antiretroviral drug from the point of view of nephrotoxicity, so the risk of CKD of the saquinavir/ritonavir combination observed in our population is probably due to ritonavir. 3333 Valle R, Haragsim L. Nephrotoxicity as a complication of antiretroviral therapy. Adv Chronic Kidney Dis 2006;13:314-9.

Regarding the weaknesses of our work, the retrospective nature of the study stands out with all the limitations that this entails for obtaining clinical, laboratory, and antiretroviral treatment information. It was not possible to assess the effect of coinfection with HBV and HCV in the logistic regression model due to the small number of patients coinfected with these viruses in our population. It was also not possible to assess the effect of other nephrotoxic drugs frequently used by HIV-infected patients, such as trimetropim/sulfamethoxazole, acyclovir, amphotericin B, and NSAIDs.

CONCLUSIONS

CKD was a frequent complication in the studied Mexican HIV-infected patients. The presence of albuminuria, age, CD4+ lymphocyte count, and abacavir/lamivudine treatment were the factors associated with CKD in our population. These findings confirm the importance of screening and early detection of CKD, as well as the identification and treatment of traditional and non-traditional risk factors associated with CKD. This could prevent or slow further decline in kidney function and improve outcomes in HIV-infected patients.

REFERENCES

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    Estrella MM, Fine DM. Screening for chronic kidney disease in HIV-infected patients. Adv Chronic Kidney Dis 2010;17:26-35.
  • 2
    Choi AI, Rodriguez RA, Bacchetti P, Bertenthal D, Volberding PA, O'Hare AM. Racial differences in end-stage renal disease rates in HIV infection versus diabetes. J Am Soc Nephrol 2007;18:2968-74.
  • 3
    Fernando SK, Finkelstein FO, Moore BA, Weissman S. Prevalence of chronic kidney disease in an urban HIV infected population. Am J Med Sci 2008;335:89-94.
  • 4
    Baekken M, Os I, Sandvik L, Oektedalen O. Microalbuminuria associated with indicators of inflammatory activity in an HIV-positive population. Nephrol Dial Transplant 2008;23:3130-7.
  • 5
    Estrella M, Fine DM, Gallant JE, Rahman MH, Nagajothi N, Racusen LC, et al. HIV type 1 RNA level as a clinical indicator of renal pathology in HIV-infected patients. Clin Infect Dis 2006;43:377-80.
  • 6
    Kopp JB, Naicker S. Human Immunodeficiency Virus Infection and the Kidney. In: Floege J, Johnson R, Feehally J, eds. Comprehensive Clinical Nephrology. 4th ed. Saint Louis: Elsevier Saunders; 2010. p. 675-83.
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Publication Dates

  • Publication in this collection
    10 July 2018
  • Date of issue
    Jan-Mar 2019

History

  • Received
    10 Jan 2018
  • Accepted
    03 May 2018
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