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Chronic kidney disease in Australian Human Immunodeficiency Virus-infected patients: Analysis of the Australian HIV Observational Database.

ABSTRACT: AIM:The aim of the present study was to examine data from the Australian HIV Observational Database (AHOD), and firstly, to describe the incidence of chronic kidney disease (CKD) and the rate of loss of renal function in HIV-infected individuals living in Australia, and then to examine the risk factors contributing to CKD in this population. METHODS:AHOD patients over 18 years of age were eligible if they had at least two serum creatinine measurements from 1 April 2008 until 31 March 2016 and an initial estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m3 . Cox proportional hazards models were used to assess risk factors for CKD, which included key patient demographic data and antiretroviral therapy (ART) exposure. RESULTS:Of 1924 patients included in the analysis between April 2008 and March 2016, 81 (4.2%) developed CKD (confirmed eGFR of less than 60 mL/min per 1.73 m3 through two consecutive eGFR measurements at least 3 months apart). Of the examined risk factors, baseline age, baseline eGFR, and the route of HIV acquisition were statistically significant predictors of development of CKD. ART exposure, viral hepatitis co-infection, high viral load and low CD4 lymphocyte count were not found to be significant risk factors for CKD. CONCLUSION:This is the first study to investigate the risk factors for development of CKD among Australian HIV-infected patients using cohort data. It highlights the need for awareness of renal risk factors, particularly among older patients or in those with pre-existing renal dysfunction. Further research is required to explore the discrepancy between patients who have acquired HIV through different means of exposure.

SUBMITTER: Cheung J

PROVIDER: S-EPMC5799037 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Chronic kidney disease in Australian Human Immunodeficiency Virus-infected patients: Analysis of the Australian HIV Observational Database.

Cheung Jason J Puhr Rainer R Petoumenos Kathy K Cooper David A DA Woolley Ian I Gunathilake Manoji M Raymond Nigel N Varma Rick R O'Connor Catherine C CC Gracey David M DM

Nephrology (Carlton, Vic.) 20180801 8

<h4>Aim</h4>The aim of the present study was to examine data from the Australian HIV Observational Database (AHOD), and firstly, to describe the incidence of chronic kidney disease (CKD) and the rate of loss of renal function in HIV-infected individuals living in Australia, and then to examine the risk factors contributing to CKD in this population.<h4>Methods</h4>AHOD patients over 18 years of age were eligible if they had at least two serum creatinine measurements from 1 April 2008 until 31 Ma ...[more]

PMID: 28703924

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Project description:Background and objectivesHIV-infected patients are at risk for developing chronic kidney disease (CKD), defined by estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2. Our purpose was to understand the genesis of CKD in HIV patients from a large urban clinic in Houston, Texas, USA, and to characterize progression of CKD in the cohort.Design, setting, participants and measurementsA retrospective cohort study (2012-2016) was conducted in all HIV-infected patients seen in a federally qualified community health center in Houston, Texas. CKD prevalence and its association with HIV viral load and CD4 count were determined. The association of the change in eGFR over time and comorbidities was assessed using linear mixed models.ResultsOf 3714 HIV-infected patients analyzed, 153 (4.1%) had CKD. The prevalence of CKD in the different racial groups was 5.4% White, 4.0% African American, 2.8% Hispanic/Latino and 3.2% Asian. There was no difference in the rate of decline in kidney function in White vs. African American HIV infected patients with CKD. Compared with non-CKD patients, CKD patients were older, had lived longer with HIV infection, had lower CD4 cell counts, higher proportions of hypertension, hyperlipidemia, and cerebrovascular disease, and had significantly higher rates of eGFR deterioration represented by a median decrease of 26.5% from first to last follow-up eGFR (versus 0% change). Linear mixed modeling identified older age, male gender, White race, longer time with HIV infection, hypertension, history of kidney stones, cerebrovascular disease, autoimmune disease, increased potassium and total cholesterol levels, and being treated with combination ART as associated with a worsening eGFR over time.ConclusionThis study demonstrates a prevalence of CKD in HIV-infected patients of 4.1% and points to an important role for HIV medications and other common comorbidities in the genesis and progression of kidney disease. Importantly, CKD was not more prevalent in African Americans than in Whites, perhaps due to a low prevalence of IV drug abuse as inferred from the lower prevalence of HCV infection in this cohort.

Project description:Background and objectivesThe cytokine midkine (MK) is pathologically implicated in progressive chronic kidney disease (CKD) and its systemic consequences and has potential as both a biomarker and therapeutic target. To date, there are no published data on MK levels in patients with different stages of CKD. This study aims to quantify MK levels in patients with CKD and to identify any correlation with CKD stage, cause, progression, comorbid disease or prescribed medication.MethodsIn this observational, single-centre study, demographic data were collected, and serum and urine assayed from 197 patients with CKD and 19 healthy volunteers in an outpatient setting.ResultsThe median serum and urine MK level in volunteers was 754 pg/mL (IQR: 554-1025) and 239 pg/mL (IQR: 154-568), respectively. Compared with serum MK in stage 1 CKD (660 pg/mL, IQR: 417-893), serum MK increased in stage 3 (1878 pg/mL, IQR: 1188-2756; p<0.001), 4 (2768 pg/mL, IQR: 2065-4735; p<0.001) and 5 (4816 pg/mL, IQ: 37477807; p<0.001). Urine MK levels increased from stage 1 CKD (343 pg/mL, IQR: 147-437) to stage 3 (1007 pg/mL, IQR: 465-2766; p=0.07), 4 (2961 pg/mL, IQR: 1368-5686; p=0.005) and 5 (6722 pg/mL, IQR: 3796-10 060; p=0.001). Fractional MK excretion (FeMK) increased from stage 1 CKD (0.159, IQR: 0.145-0.299) to stage 3 (1.024, IQR: 0.451-1.886, p=0.047), 4 (3.39, IQR: 2.10-5.82, p=0.004) and 5 (11.95, IQR: 5.36-24.41, p<0.001). When adjusted for estimated glomerular filtration rate, neither serum nor urine MK correlated with primary CKD diagnosis or CKD progression (small sample). There was a positive correlation between protein:creatinine ratio and FeMK (p=0.003). Angiotensin blockade (adjusted for proteinuria) was associated with lower urine MK (p=0.018) and FeMK (p=0.025).ConclusionMK levels sequentially rise with CKD stage beyond stage 2, and our data support existing animal evidence for an MK/renin angiotensin-system/proteinuria relationship. To what extent this is related to renal clearance versus pathology, or the consequences of chronically elevated MK levels requires further exploration.

Project description:IntroductionAIDS-related deaths in people living with HIV/AIDS have been decreasing in number since the introduction of combination antiretroviral treatment (cART). However, data on recent causes of death in the Asia-Pacific region are limited. Hence, we analysed and compared AIDS-related and non-AIDS-related mortality in high- and low-income settings in the region.MethodsPatients from the TREAT Asia HIV Observational Database (TAHOD) and Australian HIV Observational Database (AHOD) receiving cART between 1999 and 2017 were included. Causes of death verification were based on review of the standardized Cause of Death (CoDe) form designed by the D:A:D group. Cohorts were grouped as AHOD (all high-income sites), TAHOD-high (high/upper-middle income countries) and TAHOD-low (lower-middle income countries). TAHOD sites were split into high/upper-middle income and lower-middle income country settings based on World Bank classifications. Competing risk regression was used to analyse factors associated with AIDS and non-AIDS-related mortality.ResultsOf 10,386 patients, 522 died; 187 from AIDS-related and 335 from non-AIDS-related causes. The overall incidence rate of deaths during follow-up was 0.28 per 100 person-years (/100 PYS) for AIDS and 0.51/100 PYS for non-AIDS. Analysis indicated that the incidence rate of non-AIDS mortality decreased from 0.78/100 PYS to 0.37/100 PYS from year groups 2003 to 2007 to 2013 to 2017 (p < 0.001). Similarly, incidence rates of AIDS-related deaths decreased from 0.51/100 PYS to 0.09/100 PYS from year groups 2003 to 2007 to 2013 to 2017 (p < 0.001). More recent years of follow-up were associated with reduced hazard for non-AIDS mortality (2008 to 2012: aSHR (adjusted sub-hazard ratio) 0.72, 95% confidence interval (CI) 0.54 to 0.96, p = 0.027; 2013 to 2017: aSHR 0.64, 95% CI 0.47 to 0.87, p = 0.004) compared to years 2003 to 2007. The AHOD cohort had almost twice the hazard of non-AIDS mortality compared to TAHOD-low (lower-middle income sites) (aSHR 1.72, 95% CI, 1.20 to 2.46, p = 0.003); there were no differences between cohorts for AIDS-related mortality (p = 0.834).ConclusionAIDS and non-AIDS-related mortality rates have decreased over the past years in the Asia-Pacific region. There is a greater risk for non-AIDS-associated deaths in the AHOD cohort compared to lower-middle income settings in TAHOD.

Project description:Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are both associated with chronic kidney disease (CKD), a major complication after orthotopic liver transplantation (OLT). The aim of this study was to assess predictors of post-OLT CKD in HIV/HCV-coinfected recipients versus HIV-infected recipients without HCV (HIV/non-HCV recipients). Data from a National Institutes of Health study of 116 OLT recipients (35 HIV/non-HCV recipients and 81 HIV/HCV-coinfected recipients) from 2003 to 2010 (Solid Organ Transplantation in HIV: Multi-Site Study) were analyzed for the pretransplant CKD prevalence [estimated glomerular filtration rate (eGFR)?<?60 mL/minute for ?3 months] and the incidence of CKD up to 3 years posttransplant. Proportional hazards models were performed to assess predictors of posttransplant CKD. A contemporaneous cohort of HCV-monoinfected transplant recipients from the Scientific Registry of Transplant Recipients database was also analyzed. The median age at transplant was 48 years, the median serum creatinine level was 1.1 mg/dL, and the median eGFR was 77 mL/minute. Thirty-four patients were suspected to have pretransplant CKD; 20 of these patients (59%) had posttransplant CKD. Among the 82 patients without pretransplant CKD (26 HIV/non-HCV patients and 56 HIV/HCV-coinfected patients), the incidence of stage 3 CKD 3 years after OLT was 62% (55% of HIV/non-HCV patients and 65% of HIV/HCV-coinfected patients), and the incidence of stage 4/5 CKD was 8% (0% of HIV/non-HCV patients and 12% of HIV/HCV-coinfected patients). In a multivariate analysis, older age [[hazard ratio (HR)?=?1.05 per year, P?=?0.03] and the CD4 count (HR?=?0.90 per 50 cells/?L, P?=?0.01) were significant predictors of CKD. HCV coinfection was significantly associated with stage 4/5 CKD (HR?=?10.8, P?=?0.03) after adjustments for age. The cumulative incidence of stage 4/5 CKD was significantly higher for HIV/HCV-coinfected patients versus HIV/non-HCV transplant recipients and HCV-monoinfected transplant recipients (P?=?0.001). In conclusion, CKD occurs frequently in HIV-infected transplant recipients. Predictors of posttransplant CKD include older age and a lower posttransplant CD4 count. HCV coinfection is associated with a higher incidence of stage 4/5 CKD.

Dataset Information

Chronic kidney disease in Australian Human Immunodeficiency Virus-infected patients: Analysis of the Australian HIV Observational Database.

Publications

Chronic kidney disease in Australian Human Immunodeficiency Virus-infected patients: Analysis of the Australian HIV Observational Database.

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