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.

Patients with human immunodeficiency virus infection do not have inferior outcomes after dialysis access creation.

OBJECTIVE: Despite improvements in treating human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), the risk of end-stage renal disease and need for long-term arteriovenous (AV) access for hemodialysis remain high in HIV-infected patients. Associations of HIV/AIDS with AV access creation complications have been conflicting. Our goal was to clarify short- and long-term outcomes of patients with HIV/AIDS undergoing AV access creation. METHODS: The Vascular Quality Initiative registry was queried from 2011 to 2018 for all patients undergoing AV access creation. Documentation of HIV infection status with or without AIDS was recorded. Data were propensity score matched (4:1) between non-HIV-infected patients and HIV/AIDS patients. Subsequent multivariable analysis and Kaplan-Meier analysis were performed for short- and long-term outcomes. RESULTS: There were 25,711 upper extremity AV access creations identified: 25,186 without HIV infection (98%), 424 (1.6%) with HIV infection, and 101 (.4%) with AIDS. Mean age was 61.8 years, and 55.8% were male. Patients with HIV/AIDS were more often younger, male, nonwhite, nonobese, and current smokers; they were more often on Medicaid and more likely to have a history of intravenous drug use, and they were less often diabetic and less likely to have cardiac comorbidities (P < .05 for all). There was no significant difference in autogenous or prosthetic access used in these cohorts. Wound infection requiring incision and drainage or explantation within 90 days was low for all groups (0.6% vs 1.9 vs 0%; P = .11) of non-HIV-infected patients vs HIV-infected patients vs AIDS patients. Kaplan-Meier analysis showed no significant difference in 1-year freedom from primary patency loss (43.9% vs 46.3%; P =.6), 1-year freedom from reintervention (61% vs 60.7%,; P = .81), or 3-year survival (83% vs 83.8%; P = .57) for those with and without HIV/AIDS, respectively. Multivariable analysis demonstrated that patients with HIV/AIDS were not at significantly higher risk for access reintervention (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.76-1.24; P = .81), occlusion (HR, 1.06; 95% CI, 0.86-1.29; P = .6), or mortality (HR, 1.08; 95% CI, 0.83-1.43; P = .57). CONCLUSIONS: Patients with HIV/AIDS undergoing AV access creation have outcomes similar to those of patients without HIV infection, including long-term survival. Patients with HIV/AIDS had fewer traditional end-stage renal disease risk factors compared with non-HIV-infected patients. Our findings show that the contemporary approach for creation and management of AV access in patients with HIV/AIDS should be continued; however, further research is needed to identify risk factors in this population.

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.

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.

Predictors of HIV-associated nephropathy.

Renal disease accounts for significant morbidity and mortality in patients with HIV-1 infection. HIV-associated nephropathy (HIVAN) is an important cause of end stage renal disease in this population. Although multiple genetic, clinical, and laboratory characteristics such as Apolipoproetin-1 genetic polymorphism, high viral load, low CD-4 count, nephrotic range proteinuria, and increased renal echogenicity on ultrasound are predictive of HIVAN, kidney biopsy remains the gold standard to make the definitive diagnosis. Current treatment options for HIVAN include initiation of combined active antiretroviral therapy, blockade of the renin-angiotensin system, and steroids. In patients with progression of HIVAN, renal transplant should be pursued as long as their systemic HIV infection is controlled.

[Case of serious HIV-associated nephropathy resulting in the introduction of hemodialysis].

A previously healthy 46-year-old black man visited the other hospital because of fever, appetite loss and nausea. Renal dysfunction, liver injury, and a highly markedly elevated LDH level were found. Abdominal CT demonstrated enlarged liver, spleen, kidney and lymph nodes. Human immunodeficiency virus (HIV) was serologically positive. His serum BUN, creatinine and potassium were 74.9 mg/dL, 11.78 mg/dL, and 5.6 mEq/L, respectively. After admission, anuria persisted and the progression of renal failure continued despite various treatment methods, necessitating the introduction of maintenance hemodialysis(HD). A kidney biopsy was performed to confirm classical HIV-associated nephropathy (HIVAN). Antiretroviral therapy (ART) was started. Although urine was transiently excreted, HD could not be discontinued. It has been reported that HIVAN is too difficult to treat and that kidney dysfunction seldom recovers. HIVAN is well-known to occur frequently in black HIV-infected patients. However, in Japan, there have been only a few reports describing patients with serious HIVAN and renal failure necessitating HD. We present here a very rare case with HIVAN, with reference to some recent findings.

HIV-associated nephropathy (HIVAN): a short review of different authors.

Human immunodeficiency virus associated nephropathy (HIVAN) is clinically and morphologically a distinctive type of renal parenchymal disorder. It is presented in an HIV-seropositive individual by proteinuria and progressive renal insufficiency, usually without oedema or hypertension. Renal biopsy most commonly reveals a collapsing form of focal segmental glomerulosclerosis with marked proliferation of glomerular podocytes and tubular microcystic dilatation. These characteristic changes are attributed to incorporation of DNA and mRNA of human immunodeficiency virus type 1 into the renal parenchymal cells. Newly introduced highly active anti-retroviral therapy (HAART) has significantly reduced the incidence of HIVAN in the recent years. The HAART has been found to retard and revert the progression of renal insufficiency towards end-stage renal disease, and to increase survival of the patient. Therefore a renal biopsy should be performed in all suspected patients for definitive diagnosis of HIVAN and better patient management.

[HIV infection and associated kidney disease]. / Virus HIV e nefropatie correlate.

A wide spectrum of kidney diseases is observed in patients with HIV infection and renal involvement. After the introduction of highly active antiretroviral treatment (ART), the survival of patients has increased and the pattern of chronic kidney diseases changed. There has been a reduction in the prevalence of diseases more strictly related to HIV infection and an increase in comorbid conditions like diabetic nephropathy, nephroangiosclerosis, HCV hepatitis and drug-related tubulointerstitial nephritis, in particular related to antiretroviral drugs. Among the glomerular diseases four groups can be identified: 1) HIV-associated nephropathy (HIVAN), a severe collapsing glomerulosclerosis; 2) immune-complex glomerulonephritis (ICGN), including many varieties; 3) various non-HIVAN, non-ICGN glomerular diseases; 4) thrombotic microangiopathy. Moreover, acute and chronic tubulointerstitial nephritis has been found to occur. The pathogenesis of HIVAN is due to direct infection of cells, in particular podocytes, by HIV or its viral products. Genetic predisposition plays an important role in HIVAN. The treatment of HIV-related glomerulonephritis is mainly based on prolonged use of ART associated with ACE inhibitors. We have studied a series of 93 patients with HIV infection and kidney disease who underwent renal biopsy in a single nephrology center. Eighty-seven patients had glomerular diseases, among which six cases of thrombotic microangiopathy. Coinfection with HCV was present in 60% of patients with glomerulonephritis. Moreover, we observed six cases of tubulointerstitial nephritis. Dialysis and transplantation can be safely performed in uremic HIV patients without any major complications. ART is used to improve their survival.

The kidney in HIV infection: beyond HIV-associated nephropathy.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are more common in HIV-infected persons than in the general population. AKI is associated with poor health outcomes, including increased risk of heart failure, cardiovascular events, end-stage renal disease (ESRD), and mortality. The most common causes of AKI in HIV-infected persons are systemic infections and adverse drug effects. The prevalence of CKD is rising in the HIV-infected population and CKD is increasingly likely to be caused by comorbid conditions, such as diabetes and hypertension, that frequently cause CKD in the general population. Guidelines for CKD screening in HIV-infected patients are being revised. It is currently recommended that all patients be screened for creatinine-based estimates of glomerular filtration rate and for urine protein at the time of HIV diagnosis. Annual screening is recommended for high-risk patients. Hemodialysis, peritoneal dialysis, and kidney transplantation are all options for treating ESRD in HIV-infected patients. Hemodialysis and peritoneal dialysis offer similar survival in HIV-infected patients with ESRD. In selected patients with well-controlled HIV infection, kidney transplantation is associated with survival intermediate between that in the overall transplant population and that among transplant recipients older than 65 years. This article summarizes a presentation by Christina M. Wyatt, MD, at the IAS-USA continuing medical education program held in Chicago in May 2012, describing AKI and CKD using case illustrations.

Outcomes of rationing dialysis therapy in biopsy-proven end-stage renal disease in South Africa.

BACKGROUND: Due to poverty, many countries of sub-Saharan Africa suffer a severe burden of end-stage renal disease (ESRD), the cause of which is often unidentified. We sought to identify biopsy-proven causes of ESRD in Cape Town, South Africa, and to determine the outcome of these patients. METHODS: Records of biopsies reported as ESRD over a 10-year period were selected for analysis. The demographic, clinical and biochemical characteristics of the patients at the time of biopsy were documented. The decision of the committee that assesses the eligibility of patients for long-term renal replacement therapy (RRT) was documented, and if a patient was not accepted the reasons for the rejection were noted. RESULTS: Chronic glomerulonephritis (CGN) was the most frequent cause of ESRD (31.2%); human immunodeficiency virus-associated nephropathy (HIVAN) accounted for 12.5% of ESRD cases. Sixty-six patients (45.8%) were never reviewed by the assessment committee for placement in the dialysis program. Of the remaining 78 patients (54.2%) reviewed for RRT, only 48/78 (61.5%) were selected. A higher frequency of patients with HIVAN were not accepted for RRT (17.7%) than patients with HIVAN who were accepted (2.1%) (p=0.008). Social factors such as lack of housing, alcohol abuse, illicit drug abuse, lack of transportation and lack of family/social support accounted for 56.7% of patients not being accepted for RRT. CONCLUSION: There needs to be a development of programs amongst Africans to provide effective solutions that tackle the burden of ESRD, especially related to the increasing prevalence of HIVAN.

Evolución de un paciente infectado por el VIH-SIDA en hemodiálisis: experiencia en el centro asistencial / Evolution of a patientinfected by VIH-SIDA in hemodialysis: experience in the assistencial center

La afectación renal en el SIDA es un tema poco abordado a pesar de su frecuencia, la misma depende de la acción directa e indirecta del virus, así como de las complicaciones y del tratamiento. La más frecuente de las complicaciones es la Insuficiencia Renal Aguda. La forma más típica de nefropatía asociada al virus de la inmunodeficiencia humana se caracteriza por alto grado de proteinuria con progresión rápida a Insuficiencia Renal Terminal. En el SIDA se presentan diversas formas de glomerulopatías cuya expresión clínica va desde el Síndrome Nefrítico hasta el Síndrome Nefrótico. Se presenta la experiencia de un caso infectado por el VIH-SIDA con 5 años de evolución, en tratamiento hemodialítico donde se mostró una alta morbilidad en el proceder.

Renal involvement in AIDS is an issue not too much spoken In spite of its frequency, this condition depends on direct and indirect virus action, just as the complications and treatment. The most frecuent complication is the acute renal insufficiency. The most typic way of aids-associated nephropathy is characterized by high level of proteinuria with faster progresión to chronic kidney failure. Different forms of glomerulopathies are presented in aids, clinic expression of which goes from nephritic syndrome to nephrotic syndrome. Following an experience case infected by HIV-AIDS with five years progressing in hemodialitic treatment is presented where it showed a high morbidity.

Renal disease in patients with HIV infection: epidemiology, pathogenesis and management.

With the introduction of highly active antiretroviral therapy, we have witnessed prolonged survival with the potential for normal life expectancy in HIV-infected individuals. With improved survival and increasing age, HIV-infected patients are increasingly likely to experience co-morbidities that affect the general population, 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, cigarette smoking and injection drug use. Furthermore, they have exposures unique to this population, including antiretrovirals and other medications. Therefore, the differential diagnosis is vast. Early identification (through efficient screening) and definitive diagnosis (by kidney biopsy when indicated) of kidney disease in HIV-infected individuals are critical to optimal management. Earlier interventions with disease-specific therapy, often with the help of a nephrologist, are likely to lead to better outcomes. In those with chronic kidney disease, interventions, such as aggressive blood pressure control with the use of ACE inhibitors or angiotensin receptor antagonists where tolerated, tight blood glucose control in those with diabetes, and avoidance of potentially nephrotoxic medications, can slow progression and prevent end-stage renal disease. Only with greater awareness of kidney-disease manifestations and their implications in this particularly vulnerable population will we be able to achieve success in confronting this growing problem.

Antiretroviral therapy in the treatment of HIV-associated nephropathy.

BACKGROUND: The effect of antiretroviral therapy (ART) on the clinical course of patients with human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is not well-established. This study was undertaken to further elucidate the potential benefit of ART in HIV-infected patients with documented HIVAN. METHODS: A cohort of 263 consecutive HIV-infected patients referred to the Johns Hopkins renal clinic from 1995 to 2004 was examined. Patients were included if they had biopsy-proven HIVAN and did not require dialysis within 1 month of their kidney biopsy. The cumulative probability of renal survival was calculated using the Kaplan-Meier method. Multivariate analysis was performed using the Cox regression method. RESULTS: Fifty-three patients among 152 biopsied patients had HIVAN. Among 36 patients who met the inclusion criteria, 26 were treated with ART (group I) and 10 patients were not (group II). Except for age, baseline demographics and clinical characteristics were similar in the two groups. Renal survival was significantly better in the group receiving ART by both univariate (P = 0.025) and multivariate analysis (overall adjusted hazard ratio = 0.30; 95% confidence interval 0.09-0.98; P < 0.05) for ART compared with no treatment. CONCLUSIONS: Patients with biopsy-proven HIVAN treated with ART had better renal survival compared with patients who did not receive ART. HIVAN should be considered as an indication to initiate ART.

Is dialysis modality a factor in survival of patients with ESRD and HIV-associated nephropathy?

BACKGROUND: Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN), characterized by a fulminant form of focal segmental glomerulosclerosis, has become the third leading cause of end-stage renal disease (ESRD) in young African Americans. There is a theoretical possibility that hemodialysis (HD) therapy in these patients may enhance HIV replication through the activation of white blood cells and release of such cytokines as tumor necrosis factor-alpha, interleukin-1, and interleukin-6, which have been found to increase HIV replication in vitro. We therefore determined whether dialysis modality is a factor in the survival of patients with HIVAN and ESRD. METHODS: Information regarding dialysis modality was available for 6,053 of 6,166 patients with ESRD and HIVAN who started dialysis therapy in the United States from December 1995 to December 1999 by using the US Renal Data System database. RESULTS: Eighty-nine percent were black. Eighty-eight percent underwent HD, and 12%, peritoneal dialysis (PD). On Cox-proportional hazard analysis, after adjusting for demographic variables and year of dialysis therapy initiation, there was no difference in survival between the different modalities (PD versus HD: hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.13). In addition, on censoring patients at the time of first dialysis modality switch, no difference in survival was found between PD and HD. CONCLUSION: We conclude that patients with HIVAN and ESRD should be given an option to choose dialysis modality because it is not a factor in predicting survival.

Spontaneous improvement of the renal function in a patient with HIV-associated focal glomerulosclerosis.

Collapsing glomerulopathy is a pattern of renal injury that is seen in association with human immunodeficiency virus (HIV) infection. Patients with this HIV-associated nephropathy (HIVAN) present nephrotic syndrome and rapid deterioration of the renal function. There is no proven effective therapy for HIVAN, and the majority of the patients become dialysis dependent. We report a case of biopsy-proven HIVAN that showed spontaneous improvement of the renal function.

Doença renal na infecçäo pelo vírus da imunodeficiência humana / Renal disease in human immunodeficiency virus infection

O presente artigo visa a discussão da nefropatia relacionada à infecção pelo vírus da imunodeficiência adquirida (HIV) em seus aspectos epidemiológicos, clínicos e histopatológicos, ressaltando a importância e necessidade de seu melhor conhecimento e do aprofundamento do diagnóstico e terapêutica, com o objetivo de alcançar a diminuição da morbiletalidade relacionada à doença

Infections of the nervous system: an update on recent developments.

The past decade has seen major changes in the field of infectious diseases. In particular, many new infections of the nervous system have been recognised, including the lethal infections of Enterovirus 71, and the Nipah and West Nile viruses. Increased interest in prion diseases has occurred, following the recognition of animal-to-human transmission in Europe. Familiar bacteria such as the pneumococcus continue to cause problems due to increasing resistance to multiple antibiotics. Furthermore, human immunodeficiency virus-infected and other immunocompromised patients are under the constant threat of opportunistic infections, many of which are targeted towards the brain and spinal cord. This paper reviews the changing world of nervous system infections, highlighting some of the most significant recent developments.

Human immunodeficiency virus-associated nephropathy.

Human immunodeficiency virus-associated nephropathy (HIVAN) is a clinicopathological entity characterised by proteinuria, rapidly developing azotemia and histologically by collapsig variant of focal and segmental glomerulosclerosis with acute tubular necrosis and mild interstitial inflammation. Untreated, it may result in end stage renal disease (ESRD) in as little as four months. The incidence of HIVAN continues to increase and is the single most common cause of chronic renal disease in HIV-1 seropositive patients. It affects predominantly black individuals. Exact pathogenesis is still not clear but a great deal of progress has been made in the recent past by studies on transgenic mouse model, renal cell cultures and from study of human biopsy material. Current considerations revolve around the role of HIV or protein in renal epithelium and the effects of cytokines, including transforming growth factor-beta and basic fibroblast growth factor on renal structures. Different modalities of treatment with corticosteroids, zidovudine or angiotensin converting enzyme inhibitors have been tried with modest success.