APOL1-G0 protects podocytes in a mouse model of HIV-associated nephropathy.

African polymorphisms in the gene for Apolipoprotein L1 (APOL1) confer a survival advantage against lethal trypanosomiasis but also an increased risk for several chronic kidney diseases (CKD) including HIV-associated nephropathy (HIVAN). APOL1 is expressed in renal cells, however, the pathogenic events that lead to renal cell damage and kidney disease are not fully understood. The podocyte function of APOL1-G0 versus APOL1-G2 in the setting of a known disease stressor was assessed using transgenic mouse models. Transgene expression, survival, renal pathology and function, and podocyte density were assessed in an intercross of a mouse model of HIVAN (Tg26) with two mouse models that express either APOL1-G0 or APOL1-G2 in podocytes. Mice that expressed HIV genes developed heavy proteinuria and glomerulosclerosis, and had significant losses in podocyte numbers and reductions in podocyte densities. Mice that co-expressed APOL1-G0 and HIV had preserved podocyte numbers and densities, with fewer morphologic manifestations typical of HIVAN pathology. Podocyte losses and pathology in mice co-expressing APOL1-G2 and HIV were not significantly different from mice expressing only HIV. Podocyte hypertrophy, a known compensatory event to stress, was increased in the mice co-expressing HIV and APOL1-G0, but absent in the mice co-expressing HIV and APOL1-G2. Mortality and renal function tests were not significantly different between groups. APOL1-G0 expressed in podocytes may have a protective function against podocyte loss or injury when exposed to an environmental stressor. This was absent with APOL1-G2 expression, suggesting APOL1-G2 may have lost this protective function.

Effects of aging, baseline renal function and stage of HIV infection on post-treatment changes in renal function among HIV-infected patients: a retrospective cohort study.

OBJECTIVES: The use of combination antiretroviral therapy (cART) increases clinical uncertainty about changes in renal function. Specifically, little is known regarding the interaction of the effects of aging, baseline renal impairment, and stages of HIV infection on post-treatment changes in renal function. METHODS: This analysis included 5533 HIV-infected patients on cART in 2004-2016. Progression to chronic kidney disease (CKD) was defined as either two consecutive estimated glomerular filtration rate (eGFR) measurements < 60 mL/min/1.73 m2 for baseline eGFR ≥ 60 mL/min/1.73 m2 (mild renal impairment or normal renal function) or a 25% decline for baseline eGFR < 60 mL/min/1.73 m2 (moderate renal impairment). RESULTS: During follow-up (median 4.8 years), 130 (2.3%) of the patients progressed to CKD. A total of 20.1% of patients with baseline normal renal function progressed to mild renal impairment, while 74.0% of patients with baseline mild or moderate renal impairment improved to normal renal function. In multivariable analysis, a significant positive baseline-eGFR-by-World Health Organization (WHO)-stage interaction effect on progression to CKD in all patients was identified, indicating a cross-over effect from a reduced risk to an increased risk. A significant negative baseline-age-by-WHO-stage interaction effect on progression to mild renal impairment in patients with baseline normal renal function was identified, with adjusted hazard ratios progressively lower at older ages. In addition, there were significant associations with older age, lower baseline eGFR, Dai ethnic minority, and anaemia for both outcomes, hyperglycaemia for CKD only, and higher CD4 count, tenofovir and ritonavir-boosted lopinavir use for mild renal impairment only. CONCLUSIONS: Our data suggest a complex pattern of renal function dynamics in patients on cART, which requires precise management with systematic monitoring of the interaction of the effects of sociodemographic, nephrological and HIV-specific clinical characteristics.

HIV Associated Neurodegenerative Disorders: A New Perspective on the Role of Lipid Rafts in Gp120-Mediated Neurotoxicity.

The implementation of combination antiretroviral therapy (cART) as the primary means of treatment for HIV infection has achieved a dramatic decline in deaths attributed to AIDS and the reduced incidence of severe forms of HIV-associated neurocognitive disorders (HAND) in infected individuals. Despite these advances, milder forms of HAND persist and prevalence of these forms of neurocognitive impairment are rising with the aging population of HIV infected individuals. HIV enters the CNS early in the pathophysiology establishing persistent infection in resident macrophages and glial cells. These infected cells, in turn, secrete neurotoxic viral proteins, inflammatory cytokines, and small metabolites thought to contribute to neurodegenerative processes. The viral envelope protein gp120 has been identified as a potent neurotoxin affecting neurodegeneration via indirect and direct mechanisms involving interactions with chemokine co-receptors CCR5 and CXCR4. This short review focuses on gp120 neurotropism and associated mechanisms of neurotoxicity linked to chemokine receptors CCR5 and CXCR4 with a new perspective on plasma membrane lipid rafts as an active participant in gp120-mediated neurodegeneration underlying HIV induced CNS pathology.

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

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.

HIV infection-induced transcriptional program in renal tubular epithelial cells activates a CXCR2-driven CD4+ T-cell chemotactic response.

OBJECTIVE: Viral replication and interstitial inflammation play important roles in the pathogenesis of HIV-associated nephropathy. Cell-cell interactions between renal tubule epithelial cells (RTECs) and HIV-infected T cells can trigger efficient virus internalization and viral gene expression by RTEC. To understand how HIV replication initiates HIV-associated nephropathy, we studied the cellular response of RTECs to HIV, examining the transcriptional profiles of primary RTECs exposed to cell-free HIV or HIV-infected T cells. METHODS: HIV-induced gene expression in hRTECs was examined in vitro by Illumina RNA deep sequencing and revealed an innate response to HIV, which was subclassified by gene ontology biological process terms. Chemokine responses were examined by CD4 T-cell chemotaxis assays. RESULTS: As compared with cell-free virus infection, exposure to HIV-infected T cells elicited a stronger upregulation of inflammatory and immune response genes. A major category of upregulated genes are chemokine/cytokine families involved in inflammation and immune response, including inflammatory cytokines CCL20, IL6 and IL8-related chemokines: IL8, CXCL1, CXCL2, CXCL3, CXCL5 and CXCL6. Supernatants from virus-exposed RTECs contained strong chemoattractant activity on primary CD4 T cells, which was potently blocked by a CXCR2 antagonist that antagonizes IL8-related chemokines. We observed a preferential migration of CXCR2-expressing, central memory CD4 T cells in response to HIV infection of RTECs. CONCLUSION: Interactions between primary RTECs and HIV-infected T cells result in potent induction of inflammatory response genes and release of cytokines/chemokines from RTECs that can attract additional T cells. Activation of these genes reflects an innate response to HIV by nonimmune cells.

Association of urine α1-microglobulin with kidney function decline and mortality in HIV-infected women.

BACKGROUND AND OBJECTIVES: Despite advances in therapy, HIV-infected individuals remain at higher risk for kidney dysfunction than uninfected individuals. It was hypothesized that urine levels of α1-microglobulin, a biomarker of proximal tubular dysfunction, would predict kidney function decline and mortality risk in HIV-infected and uninfected women. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In the Women's Interagency HIV Study, urine α1-microglobulin and creatinine concentrations were measured in 903 HIV-infected and 287 uninfected women using stored urine from 1999 to 2000, when prevalence of tenofovir use was <1%. Participants were categorized into three categories by level of α1-microglobulin-to-creatinine ratio, and associations with kidney decline and all-cause mortality over 8 years were evaluated. RESULTS: Urine α1-microglobulin was detectable in 60% of HIV-infected and 40% of uninfected women (P<0.001). Among HIV-infected women, there were 177 (22%), 61 (7%), and 128 (14%) patients with incident CKD, with 10% annual eGFR decline, and who died, respectively. Compared with HIV-infected women in the lowest α1-microglobulin category, HIV-infected women in the highest α1-microglobulin category had a 2.1-fold risk of incident CKD (95% confidence interval, 1.3 to 3.4), 2.7-fold risk of 10% annual eGFR decline (95% confidence interval, 1.2 to 5.9), and 1.6-fold mortality risk (95% confidence interval, 1.0 to 2.6) in models adjusting for kidney risk factors, baseline eGFR, and albuminuria. Among uninfected women, the highest α1-microglobulin category was associated with 3% (relative risk, 2.2; 95% confidence interval, 1.4 to 3.5) and 5% (relative risk, 2.2; 95% confidence interval, 1.1 to 4.3) annual eGFR decline relative to the lowest α1-microglobulin category. CONCLUSIONS: Proximal tubular dysfunction, indicated by urine α1-microglobulin, was independently associated with kidney function decline in HIV-infected and uninfected women and mortality risk among HIV-infected women.

The association of adiposity with kidney function decline among HIV-infected adults: findings from the Fat Redistribution and Metabolic Changes in HIV Infection (FRAM) study.

OBJECTIVES: The aim of the study was to investigate the association of adiposity with longitudinal kidney function change in 544 HIV-infected persons in the Study of Fat Redistribution and Metabolic Change in HIV infection (FRAM) cohort over 5 years of follow-up. METHODS: The regional distribution of muscle and adipose tissue was quantified by whole-body magnetic resonance imaging (MRI), and total adiponectin and leptin levels were measured in serum. Kidney function was assessed using the estimated glomerular filtration rate from serum cystatin C (eGFRCys), obtained at baseline and follow-up. Rapid kidney function decline was defined as annual loss of eGFRCys ≥ 3 mL/min/1.73 m(2) , and incident chronic kidney disease (CKD) was defined as eGFRCys <60 mL/min/1.73 m(2) . Multivariate regression analysis was adjusted for age, race, gender, glucose, antihypertensive use, serum albumin, baseline and change in HIV viral load. RESULTS: At baseline, mean age was 43 years, mean eGFRCys was 86 mL/min/1.73 m(2) , and 21% of patients had albuminuria. The mean (± standard deviation) eGFRCys decline was -0.11 ± 4.87 mL/min/1.73 m(2) per year; 23% of participants had rapid kidney function decline, and 10% developed incident CKD. The lowest tertile of visceral adipose tissue and the highest tertile of adiponectin were both marginally associated with annual kidney function decline of -0.5 mL/min/1.73 m(2) each, but these associations were not statistically significant after adjustment. We found no statistically significant associations of MRI-measured regional adiposity or serum adipokines with rapid kidney function decline or incident CKD (all P-values>0.1 in adjusted models). CONCLUSIONS: Contrary to findings in the general population, adiposity did not have a substantial association with longitudinal change in kidney function among HIV-infected persons.

Pain, sleep disturbances, and functional limitations in people living with HIV/AIDS-associated distal sensory peripheral neuropathy.

BACKGROUND: Pain, sleep, and functional disturbances are a common occurrence in people living with HIV/AIDS-related distal sensory peripheral neuropathy (PLWHA-DSPN) yet lack group classification and quantification. METHODS: A total of 46 PLWHA-DSPN were recruited, as part of a 2-group intervention study, to complete the Neuropathic Pain Scale and the Pittsburgh Sleep Quality Index (PSQI) questionnaires. The participant's performance during a forward reach task and walking distance in 6 minutes was recorded as a measure of function. RESULTS: The pain (60.77 +/- 17.85) and sleep (14.62 +/- 4.28) scores denote marked pain and sleep disturbances, compared to seronegative, age-matched individuals. The ambulation distance was limited (243.99 +/- 141.04 m) and inversely associated with the PSQI-sleep efficiency subscale (rs = -.35, P < .05). The average reaching distances measured (36.07 +/- 7.37 cm) were similar to seronegative, age-matched individuals. Pain, sleep, and functional measures exhibited significant associations. CONCLUSIONS: The data collected suggest that PLWHA-DSPN report moderate-to-severe pain and significant sleep disturbances and exhibit limited ambulation distances.

Serum albumin and kidney function decline in HIV-infected women.

BACKGROUND: Serum albumin concentrations are a strong predictor of mortality and cardiovascular disease in human immunodeficiency virus (HIV)-infected individuals. We studied the longitudinal associations between serum albumin levels and kidney function decline in a population of HIV-infected women. STUDY DESIGN: Retrospective cohort analysis. SETTING & PARTICIPANTS: Study participants were recruited from the Women's Interagency HIV Study (WIHS), a large observational study designed to understand risk factors for the progression of HIV infection in women living in urban communities. 908 participants had baseline assessment of kidney function and 2 follow-up measurements over an average of 8 years. PREDICTOR: The primary predictor was serum albumin concentration. OUTCOMES: We examined annual change in kidney function. Secondary outcomes included rapid kidney function decline and incident reduced estimated glomerular filtration rate (eGFR). MEASUREMENTS: Kidney function decline was determined by cystatin C-based (eGFR(cys)) and creatinine-based eGFR (eGFR(cr)) at baseline and follow-up. Each model was adjusted for kidney disease and HIV-related risk factors using linear and relative risk regression. RESULTS: After multivariate adjustment, each 0.5-g/dL decrement in baseline serum albumin concentration was associated with a 0.56-mL/min faster annual decline in eGFR(cys) (P < 0.001), which was attenuated only slightly to 0.55 mL/min/1.73 m(2) after adjustment for albuminuria. Results were similar whether using eGFR(cys) or eGFR(cr). In adjusted analyses, each 0.5-g/dL lower baseline serum albumin level was associated with a 1.71-fold greater risk of rapid kidney function decline (P < 0.001) and a 1.72-fold greater risk of incident reduced eGFR (P < 0.001). LIMITATIONS: The cohort is composed of only female participants from urban communities within the United States. CONCLUSIONS: Lower serum albumin levels were associated strongly with kidney function decline and incident reduced eGFRs in HIV-infected women independent of HIV disease status, body mass index, and albuminuria.

The role of albuminuria in the follow-up of HIV-infected pediatric patients.

BACKGROUND: In HIV-infected adults, elevated albumin has been associated with increased inflammatory activity, HIV-related nephropathy, and type 2 diabetes. Data on albuminuria in HIV-infected children are very scarce, and guidelines do not include routine determination of urinary albumin/creatinine ratio in this population. METHODS: We performed a cross-sectional study in a cohort of HIV-infected pediatric patients. Urinary protein/creatinine and albumin/creatinine ratios and hematuria were determined from at least three morning urine samples, and glomerular filtration rate (GFR) was estimated from creatinine levels. Persistent renal damage was defined according to the presence of at least two sequentially abnormal values in one of the parameters. The relationship between renal damage, HIV-related variables, and metabolic comorbidities (dyslipidemia, fat redistribution, glucose intolerance, hypertension) was investigated. RESULTS: Symptom-free renal damage was observed in 13 of 68 patients (19.1%) and mainly consisted of persistent proteinuria (17.6%); glomerular proteinuria was twice as prevalent as tubular proteinuria. GFR were normal in all cases. No relationship between renal markers and HIV-related variables or metabolic comorbidities was observed. CONCLUSIONS: Mild proteinuria affected approximately one fifth of patients in our cohort. The determination of albuminuria allowed the differentiation between glomerular and tubular proteinuria, although no relationship with metabolic comorbidities was observed.

The validity of the modification of diet in renal disease formula in HIV-infected patients: a systematic review.

RATIONALE, AIMS AND OBJECTIVES: Renal dysfunction is highly prevalent in HIV-infected patients and may require dose adjustment of renally excreted antiretroviral drugs. The Modification of Diet in Renal Disease (MDRD)-4 formula is frequently used in daily practice to estimate patients' renal function. The aim of this systematic review was to assess the validity of the MDRD-4 formula in HIV-infected patients. METHOD: A systematic search in Pubmed and EMBASE was done to identify studies which compared MDRD-4 with measured glomerular filtration rate (mGFR) in HIV-infected patients. RESULTS: Five studies were included, which provided data from 464 HIV-infected patients with mean mGFR ranging from 87 to 118 ml/min/1.73 m(2). In all studies, results from the MDRD-4 gave an underestimation of the mGFR. Mean bias ((MDRD-4) - mGFR) ranged from -6 to -11 ml/min/1.73 m(2) across studies. The accuracy expressed in terms of P 30 ranged from 64 to 89 %. CONCLUSIONS: The MDRD-4 formula is as valid in HIV-positive as in HIV-negative patients. Because the available studies comprised mainly HIV-infected patients with mildly impaired to good renal function (GFR ≥ 60 ml/min/1.73 m(2)), more research is needed to validate the MDRD-4 formula in HIV-infected patients with moderate to severe renal impairment.

Classification of human immunodeficiency virus-infected patients with chronic kidney disease using a combination of proteinuria and estimated glomerular filtration rate.

BACKGROUND: In 2012, the Kidney Disease: Improving Global Outcomes (KDIGO) updated the 2002 Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guideline for chronic kidney disease (CKD). The 2012 KDIGO guideline elaborated the identification and prognosis of CKD by combining albuminuria with estimated glomerular filtration rate (eGFR). Identification of CKD with a high risk for a poor prognosis was investigated in human immunodeficiency virus (HIV)-infected individuals by applying the new guideline. METHODS: A total of 1,447 HIV-infected patients (1,351 male, 96 female; mean age 44.4 ± 11.5 years) were classified using a combination of eGFR and dipstick proteinuria, as a convenient alternative to albuminuria. Proteinuria was classified into 3 grades-(A1) - and +/- , (A2) 1+ and 2+ , and (A3) 3+ and 4+. eGFR was classified into 6 grades-(G1) ≤90, (G2) 60-89, (G3a) 45-59, (G3b) 30-44, (G4) 15-29, and (G5) <15 mL/min/1.73 m(2). RESULTS: Mean CD4 cell count was 487 ± 214 /µL, with 80.7 % of patients having an undetectable HIV-RNA level. The prevalence of CKD stage ≤2 and stage ≥3 classified according to KDOQI staging was 93.4 and 6.6 %, respectively. Using the new KDIGO classification, the prevalence of CKD with either a low (green) or moderately increased (yellow) risk was 96.9 %, while the prevalence for a high (orange) and very high (red) risk was 3.1 %. CONCLUSION: The use of the new KDIGO classification may reduce the prevalence of HIV-infected CKD individuals who are at high risk for a poor prognosis by nearly a half.

Comparison of risk factors and outcomes in HIV immune complex kidney disease and HIV-associated nephropathy.

BACKGROUND AND OBJECTIVES: HIV-associated nephropathy (HIVAN) is well described, but the clinical features of a group of renal pathologies characterized by Ig or immune complex depositions referred to as HIV-associated immune complex kidney disease (HIVICK) have not been well established. The objective of this study is to assess risk factors for HIVICK compared with contemporaneous control participants. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A nested case-control study of 751 HIV-infected patients followed from January 1996 to June 2010 was conducted. Groups were compared using the chi-squared test or rank-sum analysis. Conditional logistic regression was used to estimate odds ratios (ORs) for HIVICK. Incidences of overall ESRD and with/without combined antiretroviral therapy (cART) exposure were calculated. RESULTS: HIVICK patients were predominantly African American (92%). Compared with matched controls, patients with HIVICK were more likely to have HIV RNA >400 copies/ml (OR, 2.5; 95% confidence interval [95% CI], 1.2 to 5.2), diabetes (OR, 2.8; 95% CI, 1.1 to 6.8), and hypertension (OR, 2.3; 95% CI, 1.2 to 4.5). Compared with HIVAN, patients with HIVICK had more antiretroviral therapy exposure, lower HIV viral loads, and higher CD4 and estimated GFR. ESRD was less common in the HIVICK versus the HIVAN group (30% versus 82%; P<0.001), and the use of cART was not associated with ESRD in HIVICK patients (25% versus 26; P=0.39). CONCLUSIONS: HIVICK was predominantly observed in African-American patients and associated with advanced HIV disease. ESRD incidence is lower in HIVICK patients compared with those with HIVAN. Unlike HIVAN, cART use was not associated with the incidence of ESRD in HIVICK.

Determinants of incident chronic kidney disease and progression in a cohort of HIV-infected persons with unrestricted access to health care.

OBJECTIVES: As socioeconomic factors may impact the risk of chronic kidney disease (CKD), we evaluated the incidence and risk factors of incident CKD among an HIV-infected cohort with universal access to health care and minimal injecting drug use (IDU). METHODS: Incident CKD was defined as an estimated glomerular filteration rate (eGFR) <60 ml/min/1.73 m(2) for ≥ 90 days. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Rates were calculated per 1000 person-years (PY). Associations with outcomes were assessed using two separate Cox proportional hazard models, adjusting for baseline and time-updated covariates. RESULTS: Among 3360 participants [median age 29 years; 92% male; 44% African American (AA)] contributing 23,091 PY of follow-up, 116 developed incident CKD [5.0/1000 PY; 95% confidence interval (CI) 4.2-6.0/1000 PY]. The median first eGFR value was 97.0 mL/min/1.73 m(2) [interquartile range (IQR) 85.3-110.1 mL/min/1.73 m(2)]. Baseline factors associated with CKD included older age, lower CD4 count at HIV diagnosis [compared with CD4 count ≥ 500 cells/µL, hazard ratio (HR) 2.1 (95% CI 1.2-3.8) for CD4 count 350-499 cells/µL; HR 3.6 (95% CI 2.0-6.3) for CD4 count 201-349 cells/µL; HR 4.3 (95% CI 2.0-9.4) for CD4 count ≤ 200 cells/µL], and HIV diagnosis in the pre-highly active antiretroviral therapy (HAART) era. In the time-updated model, low nadir CD4 counts, diabetes, hepatitis B, hypertension and less HAART use were also associated with CKD. AA ethnicity was not associated with incident CKD in either model. CONCLUSIONS: The low incidence of CKD and the lack of association with ethnicity observed in this study may in part be attributable to unique features of our cohort such as younger age, early HIV diagnosis, minimal IDU, and unrestricted access to care. Lower baseline CD4 counts were significantly associated with incident CKD, suggesting early HIV diagnosis and timely introduction of HAART may reduce the burden of CKD.

Polyneuropathy induced by HIV disease and antiretroviral therapy.

OBJECTIVE: To investigate the underlying mechanisms of polyneuropathy induced by HIV infection or antiretroviral drugs. METHODS: We tested 100 HIV patients (59 with AIDS). Ninety-three patients received antiretroviral drugs. Forty-four were treated with neurotoxic compounds (ddI, ddC, d4T). Nerve conduction velocities and the sympathetic skin response (SSR) in palms and soles were measured in all patients. In skin biopsies (ankle and thigh), the intraepidermal nerve fiber density (IENFD) and the number of epidermal fibers without contact to the basal membrane (fragments) were quantified using PGP9.5 staining. RESULTS: Severity of the disease (CD4 +count) correlated to conduction velocities of peroneal (p < 0.01, Spearmans rank correlation), sural (p < 0.01) and median nerves (p < 0.05/p < 0.001, sensory/motor). In contrast, the duration of neurotoxic treatment did not impair conduction velocities (p > 0.3) but correlated to reduced IENFD in the ankle (r = -0.24, p < 0.05). Despite their reduced IENFD, patients with long neurotoxic treatment had a high number of fragments irrespective of their CD4 +count. CONCLUSIONS: Neurotoxic treatment appears to primarily impair thin fiber conduction, whereas HIV neuropathy is linked to large fiber impairment and reduction of fragments of nerve fibers. SIGNIFICANCE: These findings emphasize the differential pattern of polyneuropathy in HIV patients caused by the infection or induced by antiretroviral treatment.

Urinary markers of kidney injury and kidney function decline in HIV-infected women.

OBJECTIVE: HIV-infected persons have substantially higher risk of kidney failure than persons without HIV, but serum creatinine levels are insensitive for detecting declining kidney function. We hypothesized that urine markers of kidney injury would be associated with declining kidney function among HIV-infected women. METHODS: In the Women's Interagency HIV Study, we measured concentrations of albumin-to-creatinine ratio, interleukin-18 (IL-18), kidney injury marker-1 (KIM-1), and neutrophil gelatinase-associated lipocalin from stored urine among 908 HIV-infected and 289 HIV-uninfected participants. Primary analyses used cystatin C-based estimated glomerular filtration rate (CKD-EPI eGFRcys) as the outcome, measured at baseline and 2 follow-up visits over 8 years; secondary analyses used creatinine (CKD-EPI eGFRcr). Each urine biomarker was categorized into tertiles, and kidney decline was modeled with both continuous and dichotomized outcomes. RESULTS: Compared with the lowest tertiles, the highest tertiles of albumin-to-creatinine ratio (-0.15 mL/min per 1.73 m, P < 0.0001), IL-18 (-0.09 mL/min per 1.73 m, P < 0.0001) and KIM-1 (-0.06 mL/min per 1.73 m, P < 0.001) were independently associated with faster eGFRcys decline after multivariate adjustment including all 3 biomarkers among HIV-infected women. Among these biomarkers, only IL-18 was associated with each dichotomized eGFRcys outcome: ≥3% (relative risk = 1.40; 95% confidence interval: 1.04 to 1.89); ≥5% (1.88; 1.30 to 2.71); and ≥10% (2.16; 1.20 to 3.88) for the highest versus lowest tertile. In alternative models using eGFRcr, the high tertile of KIM-1 had independent associations with 5% (1.71; 1.25 to 2.33) and 10% (1.78; 1.07 to 2.96) decline, and the high IL-18 tertile with 10% decline (1.97; 1.00 to 3.87). CONCLUSIONS: Among HIV-infected women in the Women's Interagency HIV Study cohort, novel urine markers of kidney injury detect risk for subsequent declines in kidney function.

Renal dysfunction in the setting of HIV/AIDS.

Antiretroviral therapy has been immensely successful in reducing the incidence of opportunistic infections and death after HIV infection. This has resulted in heightened interest in noninfectious comorbidities including kidney disease. Although HIV-associated nephropathy, the most ominous kidney disease related to the direct effects of HIV, may be prevented and treated with antiretrovirals, kidney disease remains an important issue in this population. In addition to the common risk factors for kidney disease of diabetes mellitus and hypertension, HIV-infected individuals have a high prevalence of other risk factors, including hepatitis C and exposure to antiretrovirals and other medications. Therefore, the differential diagnosis is vast. Early identification (through efficient screening) and prompt treatment of kidney disease in HIV-infected individuals are critical to lead to better outcomes. This review focuses on clinical and epidemiological issues, treatment strategies (including dialysis and kidney transplantation), and recent advances among kidney disease in the HIV population.