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The assessment of renal function in HIV-positive patients before the introduction of antiretroviral therapy
volume 9 • number 2 • 2010
pages: 45–47
hiv & aids r e v i e w
title
The assessment of renal function in HIV-positive patients before the introduction of antiretroviral therapy
authors Elżbieta Jabłonowska • Ewa Małolepsza • Kamila Wójcik Department of Infectious Diseases and Hepatology, Medical University of Lodz
summary Background: A wide clinical spectrum of kidney diseases has been recognized in individuals with HIV (human immunodeficiency virus). The aim of this retrospective study was to assess renal function in HIV patients before the introduction of combined a ntiretroviral therapy (cART). Material and methods: The study group consisted of 106 HIV-positive patients (72 males, 34 females).The level of serum creatinine and creatinine clearance using the Cockcroft-Gault formula were assessed. Urine analysis for proteinuria was performed. The relationship between HIV infection including CD4 cells count, CD4 nadir and renal function was determined. Results: The correlation between the creatinine clearance and CD4 nadir and CD4 cells count before the introduction of cART was found (p = 0.037, p = 0.036). Conclusion: The kidney dysfunction measured with the creatinine clearance before the introduction of cART was associated with the immunodeficiency.
key words renal dysfunction, antiretroviral therapy, immunodeficiency
address Elżbieta Jabłonowska Wojewódzki Specjalistyczny Szpital im. Wł. Biegańskiego Kniaziewicza 1/5 Str. • 91–347 Łódź • Poland e-mail: [email protected] 45
HIV&AIDS REVIEW
Background
Results
The chronic kidney disease is characterized by the pres We studied 106 HIV-positive patients (72 males, 34 ence of an abnormal urinalysis, usually in the form of profemales) of whom 29 patients were infected by sexual conteinuria, and/or an estimated creatinine clearance using tact and 75 individuals were intravenous drug users. In two the Cockcroft-Gault formula (GFR) <90 mL/min/1.73 m2 patients the route of HIV transmission was unknown. of at least 3 months duration (1). The mean age at the time of the introduction of cART was A wide spectrum of kidney diseases not associated with 31.8 years. HIV (human immunodeficiency virus) infection has been The mean CD4+ cells count nadir in study group was diagnosed in with HIV-positive individuals, including 143.4 cells/mm3. The mean CD4+ cells count before the inimembranous nephropathy, focal segmental glomeruloscletiation of cART were 175.7 cells/mm3 (table 1). rosis and thrombotic microangiopathy. There are also The mean serum creatinie level at the time of the introspecific syndromes related to the HIV infection, such as duction of cART was 0.79 mg/dl. HIVAN (HIV associated ephropathy), HIV immune complex The mean estimated GFR at the moment of the initiaglomerulonephritis and antiretroviral-associated nephrotion of cART was 119.31 ml/min/1.73 m2. In 20.8% of toxicity (2, 3). patients before the initiation of cART proteinuria was In HIV-positive individuals, proteinuria and impaired observed. kidney function are associated with faster progression to Renal impairment with the decreased GFR (<90 mL/ the immunodeficiency syndrome and death (4, 5). The inmin/1.73 m2) was observed in 15 (14.1%) patients before fluence of chronic kidney diseases on mortality in HIVthe initiation of cART. The renal parameters present tables infected individuals increases with deteriorated renal func2, 3 and 4. tion. HIV-infected persons with estimated GFR <15 mL/min/1.73 m2 are nearly 6 times more likely to die as compared with those Table 1. The mean age and CD4 cells count before the cART introduction with estimated GFR> 60 mL/min/1.73 m2 (2, 6, 7). at the moment of cART initiation
Material and methods The aim of this retrospective study was to assess renal function in HIV-positive patients of Caucasian race before the initiation of combined antiretroviral therapy (cART). Patients with hypertension and diabetes diagnosed before the initiation of cART were excluded from the study. The level of serum creatinine and creatinine clearance using the Cockcroft-Gault formula were assessed as well as urine analysis for proteinuria was performed. The affect of HIV infection including CD4 cells count, CD4 nadir on renal function was determined. Proteinuria was defined by the protein concentration above 30 mg/dl in urine sample using the turbidimetric method. The influence of some epidemic factors as sex, age, route of HIV transmission on renal function was investigated. The mean values, median and standard deviation of quantitative traits were calculated, and the minimal and maximal values were noted. The mean values of quantitative features were compared according to the Manna-Whitney test. We used Chi-square test to compare how frequently certain categories of quantitative traits occur red in individual groups. Multivariante regression modeling was used to identify independent predictors of renal dysfunction in univariante analysis. Correlation between variables was analyzed by using Spearman`s correlation coefficient.
46
mean
standard deviation
CD4 [cells/mm3]
175.7
±118
2
989
CD4 nadir [cells/mm3]
143.4
97.16
2.0
786.0
age [years]
31.8
±8,7
17
65
min
max.
Table 2. The creatinine clearance before the cART introduction creatinine clearance ml/min/1.73 m2 at the moment of initiation of cART (n = 106)
<60
60–80
80–89
≥90
1(0.9%)
7 (6.6%)
7 (6.6%)
91 (85.9%)
Table 3. The kidney parameters before the cART introduction at the moment of cART initiation
serum creatinine level [mg/dl] creatinine clearance [ml/min/1.73 m2]
mean
standard deviation
min
max.
0.79
±0.19
0.42
1.58
119.31
±36.2
40.00
256.16
Table 4. The presence of proteiuria before the cART introduction before the cART introduction
proteinuria
n (%)
present
22 (20.8%)
absent
84 (79.2%)
volume 9 • number 2 • 2010
HIV&AIDS REVIEW The correlation between creatinine clearance and CD4 nadir and CD4 cells count before the initiation of cART was noted (p = 0.03795, p = 0.03662) (table 5).
Table 5. Correlation analysis of renal and HIV-infection parameters before the cART introduction correlation coefficient
significance
CD4 nadir vs creatinine clearance
0.204
p = 0.03795
CD4 cells count vs creatinine clearance
0.205
p = 0.03662
Discussion Kidney diseases are a significant cause of morbidity and mortality among HIV-infected patients. In this group of patients elevated serum creatinine level and lower GFR occur frequently. Gallant showed that 30% patients had or developed GFR <90 ml/min/1.73 m2 (8). Other investigators reported GFR <60 ml/min/1.73 m2 in 2.4–10% of their patients (9, 10, 11). In our analysis, decreased creatinine clearence and elevated serum creatinine level were observed less commonly. Creatinine clearance <60 ml/min/1,73 m2 was noted namely in 0.9% patients before the introduction of antiretroviral therapy. Alongside with the disturbances of creatinine level and GFR, proteinuria is also frequently observed in HIV-infected patients. Fabian et al. described microalbuminuria/ proteinuria in 44% HIV-infected population (12). Gupta reported proteinuria in up to 30% HIV-infected individuals (13). Szczech et al demonstrated microalbuminuria in 15% of black and in 7% of white HIV-infected patients compared to 2% in non HIV-infected control (14). In our study, proteinuria was observed in 20.8% of patients before the initiation of cART. Our analysis, similarly to others, showed that the renal dysfunction before the introduction of cART was associated with a low CD4 cells count. We observed that lower clearence creatinine correlates with lower CD4 and CD4 nadir count whilst in Janakiraman`s study proteinuria was proved to have a negative correlation with CD4 count (15). Not only do renal diseases frequently occur in HIV-infected patients but they are also regarded as independent predictors of poor outcome. Proteinuria and elevated serum creatinine level are associated with faster progression to Acquired Immune Deficiency Syndrome (AIDS) (7). Renal dysfunction increases 2,5 times the risk of death (16). The screening for kidney disease including the assessment of serum creatinine, glomerular filtration rate and standard urine analysis for proteinuria is highly recommended in HIV-infected patients (17). According to our study its conduct is particularly important in patients with lower CD4 cells count.
Conclusions The kidney dysfunction measured with the creatinine clearance before the introduction of cART was associated with the immunodeficiency.
References 1. Rachakonda AK, Kimmel PL. CKD in HIV-infected patients other than HIV-associated nephropathy. Adv Chronic Kidney Dis. 2010; 17(1): 83–93. 2. Atta MG. Diagnosis and natural history of HIV-associated nephropathy. Adv Chronic Kidney Dis. 2010 ;17(1): 52–58. 3. Bruggeman LA, Bark C, Kalayjian RC. HIV and the Kidney. Infect Dis Rep. 2009; 11(6): 479–485. 4. Fabian J, Naicker S. HIV and kidney disease in sub-Saharan Africa. Nat Rev Nephrol. 2009 ; 5(10): 591–598. 5. Franey C, Knott D, Barnighausen T, Dedicoat M, Adam A, Lessells RJ, Newell ML, Cooke GS. Renal impairment in a rural African antiretroviral programme. BMC Infect Dis. 2009;28;9:143. 6. Gupta SK, Komarow L, Gulick RM, Pollard RB, Robbins GK, Franceschini N, Szczech LA, Koletar SL, Kalayjian RC. Proteinuria, creatinine clearance, and immune activation in antiretroviral-naive HIV-infected subjects. J Infect Dis. 2009 ;15;200(4): 614–618. 7. Szczech LA. Renal disease: the effects of HIV and antiretroviral therapy and the implications for early antiretroviral therapy initiation. Curr Opin HIV AIDS. 2009; 4(3): 167–170. 8. Gallant JE, Staszewski S, Pozniak AL et al. 903 Study Group. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3–year randomized trial. JAMA 2004; 292: 191–201. 9. Jones CY, Jones CA, Wilson IB, et al: Cystatin C and creatinine in an HIV cohort: The nutrition for healthy living study. Am J Kidney Dis 2008; 51: 914–924. 10. Overton ET, Nurutdinova D, Freeman J, et al: Factors associated with renal dysfunction within an Urban HIV-infected cohort in the era of highly active antiretroviral therapy. HIV Med 2009; 10: 343–350. 11. Fernando SK, Finkelstein FO, Moore BA, et al. Prevalence of chronic kidney disease in an urban HIV infected population. Am J Med Sci 2008; 355: 89–94. 12. Fabian J, Naicker S, Venter WD, Baker L, Naidoo S, Paget G, Wadee S. Urinary screening abnormalities in antiretroviralnaive HIV-infected outpatients and implications for management – a single-center study in South Africa. Ethn Dis. 2009;19(1 Suppl 1): 80–85. 13. Gupta SK, Komarow L, Gulick RM, Pollard RB, Robbins GK, Franceschini N, Szczech LA, Koletar SL, Kalayjian RC. Proteinuria, creatinine clearance, and immune activation in antiretroviral-naive HIV-infected subjects. J Infect Dis. 2009; 15;200(4): 614–618. 14. Szczech LA, Hoover DR, Feldman JG et al. Association between renal disease and outcomes among HIV-infected women receiving or not receiving antiretroviral therapy. Clin Infect Dis. 2004;39(8): 1199–1206. 15. Janakiraman H, Abraham G, Matthew M, Kuruvilla S, Pani kar V, Solomon S, Kumaraswamy, Seshan SV, Lesley N. Correlation of CD4 counts with renal disease in HIV positive patients.Saudi J Kidney Dis Transpl. 2008;19(4): 603–607. 16. Gardner LI, Holmberg SD, Williamson JM, Szczech LA, Carpenter CC, Rompalo AM, Schuman P, Klein RS. Development of proteinuria or elevated serum creatinine and mortality in HIV-infected women. HIV. Epidemiology Research Study Group. Acquir Immune Defic Syndr. 2003; 1;32(2): 203–209. 17. Campbell LJ, Ibrahim F, Fisher M, Holt SG, Hendry BM, Post FA. Spectrum of chronic kidney disease in HIV-infected patients. HIV Med. 2009; 10(6): 329–336.
volume 9 • number 2 • 2010
47
pages: 45–47
hiv & aids r e v i e w
title
The assessment of renal function in HIV-positive patients before the introduction of antiretroviral therapy
authors Elżbieta Jabłonowska • Ewa Małolepsza • Kamila Wójcik Department of Infectious Diseases and Hepatology, Medical University of Lodz
summary Background: A wide clinical spectrum of kidney diseases has been recognized in individuals with HIV (human immunodeficiency virus). The aim of this retrospective study was to assess renal function in HIV patients before the introduction of combined a ntiretroviral therapy (cART). Material and methods: The study group consisted of 106 HIV-positive patients (72 males, 34 females).The level of serum creatinine and creatinine clearance using the Cockcroft-Gault formula were assessed. Urine analysis for proteinuria was performed. The relationship between HIV infection including CD4 cells count, CD4 nadir and renal function was determined. Results: The correlation between the creatinine clearance and CD4 nadir and CD4 cells count before the introduction of cART was found (p = 0.037, p = 0.036). Conclusion: The kidney dysfunction measured with the creatinine clearance before the introduction of cART was associated with the immunodeficiency.
key words renal dysfunction, antiretroviral therapy, immunodeficiency
address Elżbieta Jabłonowska Wojewódzki Specjalistyczny Szpital im. Wł. Biegańskiego Kniaziewicza 1/5 Str. • 91–347 Łódź • Poland e-mail: [email protected] 45
HIV&AIDS REVIEW
Background
Results
The chronic kidney disease is characterized by the pres We studied 106 HIV-positive patients (72 males, 34 ence of an abnormal urinalysis, usually in the form of profemales) of whom 29 patients were infected by sexual conteinuria, and/or an estimated creatinine clearance using tact and 75 individuals were intravenous drug users. In two the Cockcroft-Gault formula (GFR) <90 mL/min/1.73 m2 patients the route of HIV transmission was unknown. of at least 3 months duration (1). The mean age at the time of the introduction of cART was A wide spectrum of kidney diseases not associated with 31.8 years. HIV (human immunodeficiency virus) infection has been The mean CD4+ cells count nadir in study group was diagnosed in with HIV-positive individuals, including 143.4 cells/mm3. The mean CD4+ cells count before the inimembranous nephropathy, focal segmental glomeruloscletiation of cART were 175.7 cells/mm3 (table 1). rosis and thrombotic microangiopathy. There are also The mean serum creatinie level at the time of the introspecific syndromes related to the HIV infection, such as duction of cART was 0.79 mg/dl. HIVAN (HIV associated ephropathy), HIV immune complex The mean estimated GFR at the moment of the initiaglomerulonephritis and antiretroviral-associated nephrotion of cART was 119.31 ml/min/1.73 m2. In 20.8% of toxicity (2, 3). patients before the initiation of cART proteinuria was In HIV-positive individuals, proteinuria and impaired observed. kidney function are associated with faster progression to Renal impairment with the decreased GFR (<90 mL/ the immunodeficiency syndrome and death (4, 5). The inmin/1.73 m2) was observed in 15 (14.1%) patients before fluence of chronic kidney diseases on mortality in HIVthe initiation of cART. The renal parameters present tables infected individuals increases with deteriorated renal func2, 3 and 4. tion. HIV-infected persons with estimated GFR <15 mL/min/1.73 m2 are nearly 6 times more likely to die as compared with those Table 1. The mean age and CD4 cells count before the cART introduction with estimated GFR> 60 mL/min/1.73 m2 (2, 6, 7). at the moment of cART initiation
Material and methods The aim of this retrospective study was to assess renal function in HIV-positive patients of Caucasian race before the initiation of combined antiretroviral therapy (cART). Patients with hypertension and diabetes diagnosed before the initiation of cART were excluded from the study. The level of serum creatinine and creatinine clearance using the Cockcroft-Gault formula were assessed as well as urine analysis for proteinuria was performed. The affect of HIV infection including CD4 cells count, CD4 nadir on renal function was determined. Proteinuria was defined by the protein concentration above 30 mg/dl in urine sample using the turbidimetric method. The influence of some epidemic factors as sex, age, route of HIV transmission on renal function was investigated. The mean values, median and standard deviation of quantitative traits were calculated, and the minimal and maximal values were noted. The mean values of quantitative features were compared according to the Manna-Whitney test. We used Chi-square test to compare how frequently certain categories of quantitative traits occur red in individual groups. Multivariante regression modeling was used to identify independent predictors of renal dysfunction in univariante analysis. Correlation between variables was analyzed by using Spearman`s correlation coefficient.
46
mean
standard deviation
CD4 [cells/mm3]
175.7
±118
2
989
CD4 nadir [cells/mm3]
143.4
97.16
2.0
786.0
age [years]
31.8
±8,7
17
65
min
max.
Table 2. The creatinine clearance before the cART introduction creatinine clearance ml/min/1.73 m2 at the moment of initiation of cART (n = 106)
<60
60–80
80–89
≥90
1(0.9%)
7 (6.6%)
7 (6.6%)
91 (85.9%)
Table 3. The kidney parameters before the cART introduction at the moment of cART initiation
serum creatinine level [mg/dl] creatinine clearance [ml/min/1.73 m2]
mean
standard deviation
min
max.
0.79
±0.19
0.42
1.58
119.31
±36.2
40.00
256.16
Table 4. The presence of proteiuria before the cART introduction before the cART introduction
proteinuria
n (%)
present
22 (20.8%)
absent
84 (79.2%)
volume 9 • number 2 • 2010
HIV&AIDS REVIEW The correlation between creatinine clearance and CD4 nadir and CD4 cells count before the initiation of cART was noted (p = 0.03795, p = 0.03662) (table 5).
Table 5. Correlation analysis of renal and HIV-infection parameters before the cART introduction correlation coefficient
significance
CD4 nadir vs creatinine clearance
0.204
p = 0.03795
CD4 cells count vs creatinine clearance
0.205
p = 0.03662
Discussion Kidney diseases are a significant cause of morbidity and mortality among HIV-infected patients. In this group of patients elevated serum creatinine level and lower GFR occur frequently. Gallant showed that 30% patients had or developed GFR <90 ml/min/1.73 m2 (8). Other investigators reported GFR <60 ml/min/1.73 m2 in 2.4–10% of their patients (9, 10, 11). In our analysis, decreased creatinine clearence and elevated serum creatinine level were observed less commonly. Creatinine clearance <60 ml/min/1,73 m2 was noted namely in 0.9% patients before the introduction of antiretroviral therapy. Alongside with the disturbances of creatinine level and GFR, proteinuria is also frequently observed in HIV-infected patients. Fabian et al. described microalbuminuria/ proteinuria in 44% HIV-infected population (12). Gupta reported proteinuria in up to 30% HIV-infected individuals (13). Szczech et al demonstrated microalbuminuria in 15% of black and in 7% of white HIV-infected patients compared to 2% in non HIV-infected control (14). In our study, proteinuria was observed in 20.8% of patients before the initiation of cART. Our analysis, similarly to others, showed that the renal dysfunction before the introduction of cART was associated with a low CD4 cells count. We observed that lower clearence creatinine correlates with lower CD4 and CD4 nadir count whilst in Janakiraman`s study proteinuria was proved to have a negative correlation with CD4 count (15). Not only do renal diseases frequently occur in HIV-infected patients but they are also regarded as independent predictors of poor outcome. Proteinuria and elevated serum creatinine level are associated with faster progression to Acquired Immune Deficiency Syndrome (AIDS) (7). Renal dysfunction increases 2,5 times the risk of death (16). The screening for kidney disease including the assessment of serum creatinine, glomerular filtration rate and standard urine analysis for proteinuria is highly recommended in HIV-infected patients (17). According to our study its conduct is particularly important in patients with lower CD4 cells count.
Conclusions The kidney dysfunction measured with the creatinine clearance before the introduction of cART was associated with the immunodeficiency.
References 1. Rachakonda AK, Kimmel PL. CKD in HIV-infected patients other than HIV-associated nephropathy. Adv Chronic Kidney Dis. 2010; 17(1): 83–93. 2. Atta MG. Diagnosis and natural history of HIV-associated nephropathy. Adv Chronic Kidney Dis. 2010 ;17(1): 52–58. 3. Bruggeman LA, Bark C, Kalayjian RC. HIV and the Kidney. Infect Dis Rep. 2009; 11(6): 479–485. 4. Fabian J, Naicker S. HIV and kidney disease in sub-Saharan Africa. Nat Rev Nephrol. 2009 ; 5(10): 591–598. 5. Franey C, Knott D, Barnighausen T, Dedicoat M, Adam A, Lessells RJ, Newell ML, Cooke GS. Renal impairment in a rural African antiretroviral programme. BMC Infect Dis. 2009;28;9:143. 6. Gupta SK, Komarow L, Gulick RM, Pollard RB, Robbins GK, Franceschini N, Szczech LA, Koletar SL, Kalayjian RC. Proteinuria, creatinine clearance, and immune activation in antiretroviral-naive HIV-infected subjects. J Infect Dis. 2009 ;15;200(4): 614–618. 7. Szczech LA. Renal disease: the effects of HIV and antiretroviral therapy and the implications for early antiretroviral therapy initiation. Curr Opin HIV AIDS. 2009; 4(3): 167–170. 8. Gallant JE, Staszewski S, Pozniak AL et al. 903 Study Group. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3–year randomized trial. JAMA 2004; 292: 191–201. 9. Jones CY, Jones CA, Wilson IB, et al: Cystatin C and creatinine in an HIV cohort: The nutrition for healthy living study. Am J Kidney Dis 2008; 51: 914–924. 10. Overton ET, Nurutdinova D, Freeman J, et al: Factors associated with renal dysfunction within an Urban HIV-infected cohort in the era of highly active antiretroviral therapy. HIV Med 2009; 10: 343–350. 11. Fernando SK, Finkelstein FO, Moore BA, et al. Prevalence of chronic kidney disease in an urban HIV infected population. Am J Med Sci 2008; 355: 89–94. 12. Fabian J, Naicker S, Venter WD, Baker L, Naidoo S, Paget G, Wadee S. Urinary screening abnormalities in antiretroviralnaive HIV-infected outpatients and implications for management – a single-center study in South Africa. Ethn Dis. 2009;19(1 Suppl 1): 80–85. 13. Gupta SK, Komarow L, Gulick RM, Pollard RB, Robbins GK, Franceschini N, Szczech LA, Koletar SL, Kalayjian RC. Proteinuria, creatinine clearance, and immune activation in antiretroviral-naive HIV-infected subjects. J Infect Dis. 2009; 15;200(4): 614–618. 14. Szczech LA, Hoover DR, Feldman JG et al. Association between renal disease and outcomes among HIV-infected women receiving or not receiving antiretroviral therapy. Clin Infect Dis. 2004;39(8): 1199–1206. 15. Janakiraman H, Abraham G, Matthew M, Kuruvilla S, Pani kar V, Solomon S, Kumaraswamy, Seshan SV, Lesley N. Correlation of CD4 counts with renal disease in HIV positive patients.Saudi J Kidney Dis Transpl. 2008;19(4): 603–607. 16. Gardner LI, Holmberg SD, Williamson JM, Szczech LA, Carpenter CC, Rompalo AM, Schuman P, Klein RS. Development of proteinuria or elevated serum creatinine and mortality in HIV-infected women. HIV. Epidemiology Research Study Group. Acquir Immune Defic Syndr. 2003; 1;32(2): 203–209. 17. Campbell LJ, Ibrahim F, Fisher M, Holt SG, Hendry BM, Post FA. Spectrum of chronic kidney disease in HIV-infected patients. HIV Med. 2009; 10(6): 329–336.
volume 9 • number 2 • 2010
47