HIV-1 infection of renal epithelial cells: 30 years of evidence from transgenic animal models, human studies and in vitro experiments.

Although antiretroviral therapy (ART) has increased life expectancy in people with HIV-1 (PWH), acute and chronic kidney disease remain common in this population and are associated with poor outcomes. A broad spectrum of kidney disorders can be observed in PWH, some of which are directly related to intrarenal HIV infection and gene expression. HIV-associated nephropathy (HIVAN) was the most common kidney disease in PWH before ART became available. Animal models and human biopsy studies established the causal relationships between direct HIV-1 infection of renal epithelial cells and HIVAN, expression of viral genes in renal epithelial cells, and dysregulation of host genes involved in cell differentiation and cell cycle. In this review, we provide a summary of the body of work demonstrating HIV-1 infection of epithelial cells in the kidney and recent advancements in the understanding of viral entry mechanisms and consequences of HIV-1 gene expression in those cells.

High risk APOL1 genotypes and kidney disease among treatment naïve HIV patients at Kano, Nigeria.

INTRODUCTION: Racial disparities are known in the occurrence of kidney disease with excess risks found among people of African descent. Apolipoprotein L1 (APOL1) gene variants G1 and G2 are associated with kidney disease among HIV infected individuals of African descent in the USA as well as among black population in South Africa. We set out to investigate the prevalence of these high-risk variants and their effects on kidney disease among HIV infected patients in Northern Nigeria with hitherto limited information despite earlier reports of high population frequencies of these alleles from the Southern part of the country. METHODS: DNA samples obtained from the whole blood of 142 participants were genotyped for APOL1 G1 and G2 variants after initial baseline investigations including assessment of kidney function. Participants comprised 50 HIV positive patients with no evidence of kidney disease, 52 HIV negative individuals with no kidney disease and 40 HIV positive patients with chronic kidney disease (CKD) evidenced by persistent proteinuria and/or reduced eGFR, who also had a kidney biopsy. All the HIV positive patients were newly diagnosed and treatment naïve. RESULTS: The distribution of the APOL1 genotypes among the study participants revealed that 24.6% had a G1 risk allele and 19.0% a G2. The frequency of the High Risk Genotype (HRG) was 12.5% among those with CKD compared to 5.8% in the HIV negative group and zero in the HIV positive no CKD group. Having the HRG was associated with a higher odds for developing HIV Associated Nephropathy (HIVAN) (2 vs 0 risk alleles: OR 10.83, 95% CI 1.38-84.52; P = 0.023; 2 vs 0 or 1 risk alleles: OR 5.5, 95% CI 0.83-36.29; P = 0.07). The HRG was also associated with higher odds for Focal Segmental Glomerulosclerosis (FSGS) (2 vs 0 risk alleles: OR 13.0, 95% CI 2.06-81.91; P = 0.006 and 2 vs 0 or 1 risk alleles: OR 9.0, 95%CI 1.62-50.12; P = 0.01) when compared to the control group. CONCLUSION: This study showed a high population frequency of the individual risk alleles of the APOL1 gene with higher frequencies noted among HIV positive patients with kidney disease. There is high association with the presence of kidney disease and especially FSGS and HIVAN among treatment naive HIV patients carrying two copies of the HRG.

HIV at 40: kidney disease in HIV treatment, prevention, and cure.

Four decades after the first cases of HIV were reported, kidney disease remains an important comorbidity in people with HIV (PWH). Both HIV-associated nephropathy and immune complex kidney disease were recognized as complications of HIV infection in the early years before treatment was available. Although the introduction of effective antiretroviral therapy in the late 1990s resulted in dramatic improvements in survival and health in PWH, several commonly used antiretroviral agents have been associated with kidney injury. HIV infection and treatment may also promote the progression of comorbid chronic kidney disease due to traditional risk factors such as diabetes, and HIV is one of the strongest "second hits" for the high-risk APOL1 genotype. Unique considerations in the management of chronic kidney disease in PWH are largely related to the need for lifelong antiretroviral therapy, with potential for toxicity, drug-drug interactions, and polypharmacy. PWH who develop progressive chronic kidney disease are candidates for all modalities of kidney replacement therapy, including kidney transplantation, and at some centers, PWH may be candidates to serve as donors for recipients with HIV. Transplantation of kidney allografts from donors with HIV also offers a unique opportunity to study viral dynamics in the kidney, with implications for kidney health and for research toward HIV cure. In addition, HIV-transgenic animal models have provided important insights into kidney disease pathogenesis beyond HIV, and experience with HIV and HIV-related kidney disease has provided important lessons for future pandemics.

Prevalence and risk factors of chronic kidney disease in an HIV positive Mexican cohort.

BACKGROUND: HIV subjects have several kidney pathologies, like HIV-associated nephropathy or antiretroviral therapy injury, among others. The global prevalence of Chronic Kidney Disease (CKD) is 8-16%; however, in HIV subjects, the prevalence varies between geographic regions (2-38%). The aim was to determine the prevalence of CKD and identify the associated risk factors. METHODS: A longitudinal descriptive study was carried out at the 'Hospital Civil de Guadalajara' Feb'18 - Jan'19. Basal clinical, demographic, opportunistic infections (OI), and laboratory data were obtained at months 0 and 3; inclusion criteria were ≥ 18 years old, naïve HIV + , urine albumin/creatinine ratio, serum creatinine & urine test, and signed informed consent. Descriptive and multiple logistic regression statistical analyses were made. RESULTS: One hundred twenty subjects were included; 92.5% were male, 33 ± 9.5 years, 60% consumed tobacco, 73% alcohol, and 59% some type of drug. The CKD prevalence was 15.8%. CKD patients had a higher risk of hepatitis C virus coinfection, Relative Risk (RR):5.9; HCV infection, RR:4.3; ≥ 30 years old, RR:3.9; C clinical-stage, RR:3.5; CD4+ T cells count < 200 cells/µL, RR: 2.4; and HIV-1 viral load ≥ 100,000 cop/mL, RR: 2.7. CONCLUSIONS: Our study showed a higher CKD prevalence in patients with HIV; higher CKD development with coinfections as Hepatitis C Virus and Mycobacterium tuberculosis. The identification and prompt management of CKD and coinfections should be considered to avoid the progression and to delay renal replacement therapy as long as possible.

The spectrum of kidney biopsy findings in HIV-infected patients in the modern era.

HIV-associated kidney disease is evolving rapidly. Few North American studies have addressed modern trends and none has applied the 2018 Kidney Disease Improving Global Outcomes (KDIGO) pathologic classification. Therefore we performed a retrospective clinical-pathologic analysis of all HIV-positive patients with kidney biopsy interpreted at Columbia University from 2010-2018 using the KDIGO classification. The biopsy cohort of 437 HIV-positive patients had median age 53 years, including 66% males, 80% on anti-retroviral therapy, 57% with hypertension, 31% with diabetes, 27% with hepatitis C and 6% with hepatitis B co-infections. Race, known in 308 patients, included 58% black, 25% white and 17% Hispanic. Pathologic diagnoses were surprisingly diverse. Immune complex glomerulonephritis (ICGN) and diabetic nephropathy each outnumbered HIV-associated nephropathy, followed by tenofovir nephrotoxicity, FSGS- not otherwise specified (NOS) and global sclerosis (NOS). HIV-associated nephropathy was the most common disease in patients not on anti-retroviral therapy, and 94% were black. The association of FSGS (NOS) with black race (68%) and anti-retroviral therapy use (77%) suggests some cases may represent attenuated HIV-associated nephropathy. The most common ICGNs were IgA nephropathy and membranous glomerulopathy, both associating with anti-retroviral therapy (over 90%), followed by hepatitis C-associated proliferative ICGN. Among the 16 cases of uncharacterized ICGN lacking identifiable etiology, 69% were not on anti-retroviral therapy, possibly representing true HIV-associated immune complex kidney disease. Dual diseases occurred in 17% of patients, underscoring lesion complexity. Thus, anti-retroviral therapy has shifted the landscape of HIV-associated kidney disease toward diverse ICGN, diabetic nephropathy, and non-collapsing glomerulosclerosis, but has not eradicated HIV-associated nephropathy.

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.

The effects of add-on corticosteroids on renal outcomes in patients with biopsy proven HIV associated nephropathy: a single centre study from South Africa.

BACKGROUND: The aim of this study was to assess, the efficacy and safety of add-on corticosteroids to antiretroviral therapy [ART] in patients with biopsy proven HIV associated nephropathy. METHODS: All included patients had histological evidence of either collapsing or non-collapsing focal segmental glomerulosclerosis (FSGS) or podocyte and/or parietal cell hypertrophy or hyperplasia. All patients had evidence of tubulointerstitial inflammation with microcysts. Patients were randomized to ART with the addition of 1 mg/kg of corticosteroids [ART+C] or remained in the group [ART Alone] and followed for 2 years. A repeat biopsy was performed at 6 months. RESULTS: Twenty-one patients were randomized to [ART+C] and 17 to [ART Alone]. The baseline estimated glomerular filtration rate (eGFR) was significantly lower in the [ART+C] vs. [ART Alone] group [35mls/min/1.73m2 vs. 47 mls/min/1.73m2, p = 0.015]. The [ART+C] cohort had a statistically significant improvement in median (eGFR) from baseline to last follow up compared with [ART Alone] i.e. [Δ = 25mls/min (IQR: 15;51) vs 9 mls/min (IQR: 0-24), p = 0.008]. There were no statistically significant differences between the groups when proteinuria and histology were analyzed. There were 8 deaths during the trial period, 7 from [ART+C] (Log rank p = 0.071). CONCLUSIONS: In the [ART+C] cohort there was a significant improvement in eGFR over 2-years with increased mortality. Routine corticosteroid use cannot currently be recommended. Further investigation to define which subgroup of this cohort would safely benefit from the positive effects is required. TRIAL REGISTRATION: ISRCTN study ID ( 56112439 ] was retrospectively registered on the 5 September 2018.

Association of HIV Suppression With Kidney Disease Progression Among HIV-Positive African Americans With Biopsy-Proven Classic FSGS.

BACKGROUND: In the era of combined antiretroviral therapy, classic focal segmental glomerulosclerosis (FSGS) is the most common histopathological finding in African American HIV-positive patients with kidney disease. We sought to determine whether HIV suppression is associated with lower risk of progression to end-stage renal disease (ESRD) among HIV-positive African Americans with biopsy-confirmed classic FSGS. METHODS: HIV-positive African Americans who underwent kidney biopsies at a single tertiary hospital between January 1996 and June 2011 were confirmed as having classic FSGS by the presence of segmental glomerulosclerosis without features of HIV-associated nephropathy. Multivariable Cox proportional hazards models were used to examine the independent association of viral suppression (HIV-RNA < 400 copies per milliliter at biopsy) with time to progression to ESRD. RESULTS: Of the 55 HIV-positive African Americans with classic FSGS, 26 had suppressed viral loads at the time of biopsy. Compared to viremic patients, those who were virally suppressed had a significantly higher mean CD4 cell count (452 vs. 260 cell/mm, respectively; P = 0.02) and median estimated glomerular filtration rate (53.5 vs 35.5 mL/min/1.73 m, respectively; P = 0.002). Adjusting for sex and baseline CD4 cell count, estimated glomerular filtration rate, and proteinuria, those with HIV-RNA levels <400 copies per milliliter at baseline had a 75% lower risk of progressing to ESRD (hazard ratio = 0.25; 95% CI: 0.07 to 0.88) during a median follow-up time of 2.70 years (interquartile range: 0.80-5.15 years). CONCLUSIONS: HIV suppression is associated with significantly lower risk of progression to ESRD among HIV-infected African Americans with classic FSGS, supporting the potential role of combined antiretroviral therapy for this histopathology in addition to HIV-associated nephropathy among HIV-positive individuals.

Kidney disease in the setting of HIV infection: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

HIV-positive individuals are at increased risk for kidney disease, including HIV-associated nephropathy, noncollapsing focal segmental glomerulosclerosis, immune-complex kidney disease, and comorbid kidney disease, as well as kidney injury resulting from prolonged exposure to antiretroviral therapy or from opportunistic infections. Clinical guidelines for kidney disease prevention and treatment in HIV-positive individuals are largely extrapolated from studies in the general population, and do not fully incorporate existing knowledge of the unique HIV-related pathways and genetic factors that contribute to the risk of kidney disease in this population. We convened an international panel of experts in nephrology, renal pathology, and infectious diseases to define the pathology of kidney disease in the setting of HIV infection; describe the role of genetics in the natural history, diagnosis, and treatment of kidney disease in HIV-positive individuals; characterize the renal risk-benefit of antiretroviral therapy for HIV treatment and prevention; and define best practices for the prevention and management of kidney disease in HIV-positive individuals.

Immunomodulatory Role of Complement Proteins in the Neuropathology Associated with Opiate Abuse and HIV-1 Co-Morbidity.

The complement system which is a critical mediator of innate immunity plays diverse roles in the neuropathogenesis of HIV-1 infection such as clearing HIV-1 and promoting productive HIV-1 replication. In the development of HIV-1 associated neurological disorders (HAND), there may be an imbalance between complement activation and regulation, which may contribute to the neuronal damage as a consequence of HIV-1 infection. It is well recognized that opiate abuse exacerbates HIV-1 neuropathology, however, little is known about the role of complement proteins in opiate induced neuromodulation, specifically in the presence of co-morbidity such as HIV-1 infection. Complement levels are significantly increased in the HIV-1-infected brain, thus HIV-induced complement synthesis may represent an important mechanism for the pathogenesis of AIDS in the brain, but remains underexplored. Anti-HIV-1 antibodies are able to initiate complement activation in HIV-1 infected CNS cells such as microglia and astrocytes during the course of disease progression; however, this complement activation fails to clear and eradicate HIV-1 from infected cells. In addition, the antiretroviral agents used for HIV therapy cause dysregulation of lipid metabolism, endothelial, and adipocyte cell function, and activation of pro-inflammatory cytokines. We speculate that both HIV-1 and opiates trigger a cytokine-mediated pro-inflammatory stimulus that modulates the complement cascade to exacerbate the virus-induced neurological damage. We examined the expression levels of C1q, SC5b-9, C5L2, C5aR, C3aR, and C9 key members of the complement cascade both in vivo in post mortem brain frontal cortex tissue from patients with HAND who used/did not use heroin, and in vitro using human microglial cultures treated with HIV tat and/or heroin. We observed significant expression of C1q and SC5b-9 by immunofluorescence staining in both the brain cortical and hippocampal region in HAND patients who abused heroin. Additionally, we observed increased gene expression of C5aR, C3aR, and C9 in the brain tissue of both HIV-1 infected patients with HAND who abused and did not abuse heroin, as compared to HIV negative controls. Our results show a significant increase in the expression of complement proteins C9, C5L2, C5aR, and C3aR in HIV transfected microglia and an additional increase in the levels of these complement proteins in heroin-treated HIV transfected microglia. This study highlights the a) potential roles of complement proteins in the pathogenesis of HIV-1-related neurodegenerative disorders; b) the combined effect of an opiate, like heroin, and HIV viral protein like HIV tat on complement proteins in normal human microglial cells and HIV transfected microglial cells. In the context of HAND, targeting selective steps in the complement cascade could help ameliorating the HIV burden in the CNS, thus investigations of complement-related therapeutic approaches for the treatment of HAND are warranted.

Screening and management practices for renal disease in the HIV-positive patient population of an inner metropolitan sexual health service.

Renal disease is an important and commonly encountered co-morbidity in HIV infection. Despite this, few data are available concerning renal disease in this patient group. A retrospective review was conducted of all HIV-positive patients of an inner metropolitan sexual health service who attended from 1 August 2013 to 31 July 2014 for HIV management. One hundred eighty-eight HIV-positive patients attended the clinic during the study period. The majority were male (96%), Caucasian (70%) and 30-39 years of age (37%). There was a high prevalence of renal risk factors in the population, including potentially nephrotoxic antiretroviral therapy (61%), smoking (38%), hypertension (12%), dyslipidemia (11%) and hepatitis C co-infection (7%). In the previous year, measurements of estimated glomerular filtration rate were performed in all patients, but measurements of lipid profiles, urinary protein and serum phosphate were performed within the last year in only 48%, 33% and 30% of patients, respectively. These are the first comprehensive data regarding renal disease, associated risk factors and screening and management practices in the HIV-positive patient population of a specialized sexual health service in Australia. This patient population demonstrates a particularly high prevalence of risk factors for renal disease. Despite this, screening investigations were not performed as recommended. This represents a potential area to improve patient care.

Viral-Associated GN: Hepatitis C and HIV.

Viruses are capable of inducing a wide spectrum of glomerular disorders that can be categorized on the basis of the duration of active viremia: acute, subacute, or chronic. The variable responses of the adaptive immune system to each time period of viral infection results mechanistically in different histologic forms of glomerular injury. The unique presence of a chronic viremic carrier state with either hepatitis C (HCV) or HIV has led to the opportunity to study in detail various pathogenic mechanisms of viral-induced glomerular injury, including direct viral infection of renal tissue and the development of circulating immune complexes composed of viral antigens that deposit along the glomerular basement membrane. Epidemiologic data show that approximately 25%-30% of all HIV patients are coinfected with HCV and 5%-10% of all HCV patients are coinfected with HIV. This situation can often lead to a challenging differential diagnosis when glomerular disease occurs in this dual-infected population and requires the clinician to be familiar with the clinical presentation, laboratory workup, and pathophysiology behind the development of renal disease for both HCV and HIV. Both of these viruses can be categorized under the new classification of infection-associated GN as opposed to being listed as causes of postinfectious GN as has previously been applied to them. Neither of these viruses lead to renal injury after a latent period of controlled and inactive viremia. The geneses of HCV- and HIV-associated glomerular diseases share a total dependence on the presence of active viral replication to sustain renal injury so the renal disease cannot be listed under "postinfectious" GN. With the new availability of direct-acting antivirals for HCV and more effective combined antiretroviral therapy for HIV, successful remission and even regression of glomerular lesions can be achieved if initiated at an early stage.

HIV-associated renal disease - an overview.

The cause of the human immunodeficiency virus (HIV) epidemic in South Africa (SA) was worsened by the denial by key political players that HIV causes acquired immunodeficiency syndrome (AIDS). South Africa continues to have the highest rate of HIV world-wide, which has had a huge impact on the development of both chronic kidney disease and acute kidney injury. Fortunately, there is now an effective antiretroviral therapy (ART) roll-out program. SA is also dealing with a collision of epidemics of HIV, tuberculosis, and non-communicable disease, particularly hypertension and diabetes. This has been evidenced by recent data seen in the reinstated SA renal registry. There is also an unacceptably high rate of tuberculosis in regions of SA, this has led to high rates of granulomatous interstitial nephritis (GIN) and case reports of TB-GIN immune reconstitution inflammatory syndrome (IRIS). HIV-associated nephropathy (HIVAN) remains common in SA and responds well to ART. The definitive diagnosis requires a renal biopsy, which is often not possible in many regions of sub-Saharan Africa. Unfortunately, there is still a high rate of HIVAN in SA due to late presentation and lack of effective screening for renal disease in HIV-positive patients. Transplantation for HIV-positive donors to positive recipients offers a unique and encouraging way forward for these patients.

Renal tubular disease in the era of combination antiretroviral therapy.

OBJECTIVES: To describe the spectrum of renal tubular disease (RTD) in HIV-positive patients and its association with exposure to antiretroviral therapy (ART). DESIGN: Review of 265 consecutive renal biopsies from HIV-positive patients attending eight clinics in the United Kingdom between 2000 and 2012. METHODS: We described the clinical characteristics of patients with RTD and compared current/recent exposure (at the time of, or up to 3 months prior to the date of biopsy) to potentially nephrotoxic ART [tenofovir (TDF), atazanavir (ATV), indinavir (IDV) and lopinavir/ritonavir (LPV/r)]. We also analysed the incidence of RTD in the UK CHIC cohort. Kruskall-Wallis, analysis of variance and Fisher's exact tests were used to evaluate between-group differences. RESULTS: Of the 60 RTD cases, 54 (90%) were included in the analyses. RTD comprised of three distinct patterns: acute tubular injury (ATI, n = 22), tubulo-interstitial nephritis (TIN, n = 20) and interstitial fibrosis and tubular atrophy (IFTA, n = 12). Compared with TIN and IFTA, ATI cases were less likely to be of black ethnicity (10 vs. 42-55%; P = 0.006), more likely to be on ART (100 vs. 55-68%; P = 0.001), with HIV-RNA below 200 copies/ml (100 vs. 54-58%; P < 0.001), and more likely to have current/recent exposure to TDF (P < 0.001). We did not find evidence for an association between exposure to TDF, ATV/r or LPV/r and either TIN or IFTA. CONCLUSION: RTD was present in approximately 20% of renal biopsies and comprised three distinct injury patterns with considerable clinical overlap. ATI was associated with TDF exposure, although the overall incidence of biopsy-defined ATI was low.

HIV and noncommunicable diseases: the Asian perspective.

Asia is seeing a rise in noncommunicable diseases in their general population and among people living with HIV. Many Asians have low body weight, which can lead to higher plasma concentrations of antiretrovirals and, as a result, their toxicities. Examples are metabolic complications from protease inhibitors, chronic kidney disease from tenofovir, and hepatotoxicity from nevirapine. Asia has not only the highest burden of hepatitis B viral infection than any other continent but also a predominance of genotypes B and C, the latter associated with higher risk for hepatocellular carcinoma. HIV-associated neurocognitive disorders are equally common among Asians as other populations. Diastolic dysfunction and asymptomatic myocardial ischemia are not infrequent. Non-Hodgkin lymphoma is the most common AIDS-related cancer, whereas Kaposi sarcoma is relatively infrequent. Emerging data show high prevalence of human papillomavirus-associated anal dysplasia in men who have sex with men. Resource-limited countries in Asia suffer from lack of resources for national screening programs of noncommunicable diseases, which, in turn, limits the epidemiologic data that exist to guide the use of national health resources.

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.

HIV and the aging kidney.

PURPOSE OF REVIEW: To review unique considerations in the epidemiology, diagnosis, and management of kidney disease in older adults with HIV. RECENT FINDINGS: HIV infection may accelerate the course of kidney disease associated with traditional risk factors, such as diabetes, which are more common in older adults. The risks of acute and chronic kidney disease are increased both with HIV infection and with older age. Although the prevalence of chronic kidney disease is higher among HIV-infected adults than among HIV-negative adults, the mean age at diagnosis of end-stage renal disease is similar. Recent studies have supported the use of newer creatinine-based kidney function estimates in HIV-infected adults, although data in older adults are limited. These estimates are susceptible to artifact in the setting of newer medications that interfere with the secretion of creatinine, including cobicistat and dolutegravir. The management of kidney disease in older adults with HIV infection may be complicated by polypharmacy and increased risk for medication toxicity. SUMMARY: With aging of the HIV-infected population, age-related comorbid conditions such as kidney disease are increasingly important causes of morbidity and mortality. Although recent data do not support premature aging of HIV-infected individuals with respect to kidney disease, the risk of acute and chronic kidney disease is increased by HIV infection and its treatment.

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.

[Changing spectrum of renal disease in HIV infection]. / Veränderungen im Spektrum der Nierenerkrankungen bei HIV-Infektion.

BACKGROUND AND OBJECTIVE: Renal disease is a common complication in HIV-infected patients. The causes and spectrum of kidney disease among these patients is extensive, including HIV-related and HIV unrelated causes. Our objective was to assess the changes in distribution of renal disease under antiretroviral therapy (ART). PATIENTS AND METHODS: Retrospective analysis of all patients from the Frankfurt HIV Cohort (FHC) who underwent renal biopsy because of chronic, progressive renal disease between 1989 and 2012. Two time periods were defined: 1989-2001 (early period) and 2000-2012 (late period). RESULTS: 69 HIV-infected patients, mostly Caucasian and male, underwent renal biopsy (early period: 22 patients, late period: 47 patients). During the total observation time immuncomplex-mediated glomerulonephritis (26.1 %), hypertensive (20.3 %) and diabetic nephropathy (20.3 %) were the most frequent causes of chronic renal disease. HIV-associated renal diseases were predominant in the first period, whereas hypertensive and diabetic kidney disease accounted for almost 50 % of cases diagnosed in the late period. Other types of renal disease frequently encountered during the late period include renal AA-amyloidosis and tenofovir-related kidney disease. CONCLUSION: The underlying pathology of renal disease in HIV-infected patients is highly variable and evolving. Since the introduction of HAART, renal disease not directly related to HIV has become the predominant cause, reflecting the growing burden of co-morbidities in this aging population.

The changing pattern of glomerular disease in HIV and hepatitis C co-infected patients in the era of HAART.

Previous reports have suggested a poor renal prognosis in patients with HIV and HCV co-infection with a preponderance of immune complex mediated glomerular disease on biopsy. Although the benefits of HAART on HIVAN are known, its impact on co-infected patients is unclear. We describe the renal biopsy findings and renal outcome in 29 co-infected patients in the HAART era and compare them to findings in 14 historical controls reported from our institution in the pre-HAART era. Our present cohort was predominantly male and Black with the majority reporting a history of intravenous (i.v.) drug use. Renal biopsy findings included 16 patients with immune complex mediated glomerular disease and 14 patients with FSGS, of which only 3 had collapsing features and/or tubular microcysts typical of HIVAN. Five patients had other biopsy diagnoses not directly related to viral infection. Median renal survival in our cohort was 15.6 months - significantly better than the 1.7 months seen our pre-HAART cohort. The modern cohort's improved renal outcome occurred despite older patients, longer HIV infection and similar levels of renal insufficiency. Our data indicate a changing epidemiology and natural history of renal disease in the HAART era with less immune complex mediated glomerular disease and more non-collapsing FSGS of the usual type. The marked improvement is likely to be multifactorial, including use of antiretroviral and anti-HCV therapies, RAAS antagonists, earlier nephrology referral and generally improved medical care.