-
Clinical Journal of the American... Feb 2021Rates of many types of severe kidney disease are much higher in Black individuals than most other ethnic groups. Much of this disparity can now be attributed to genetic... (Review)
Review
Rates of many types of severe kidney disease are much higher in Black individuals than most other ethnic groups. Much of this disparity can now be attributed to genetic variants in the apoL1 (APOL1) gene found only in individuals with recent African ancestry. These variants greatly increase rates of hypertension-associated ESKD, FSGS, HIV-associated nephropathy, and other forms of nondiabetic kidney disease. We discuss the population genetics of APOL1 risk variants and the clinical spectrum of APOL1 nephropathy. We then consider clinical issues that arise for the practicing nephrologist caring for the patient who may have APOL1 kidney disease.
Topics: AIDS-Associated Nephropathy; Africa; Alleles; Apolipoprotein L1; Black People; Diabetic Nephropathies; Genetic Variation; Glomerulosclerosis, Focal Segmental; Humans; Hypertension; Kidney Diseases; Kidney Failure, Chronic; Kidney Transplantation; Risk Factors
PubMed: 32616495
DOI: 10.2215/CJN.15161219 -
BMC Nephrology May 2020Glomerulonephritides (GN) are relatively rare kidney diseases with substantial morbidity and mortality. They are often difficult to treat, sometimes with no cure, and...
BACKGROUND
Glomerulonephritides (GN) are relatively rare kidney diseases with substantial morbidity and mortality. They are often difficult to treat, sometimes with no cure, and can lead to chronic kidney disease (CKD) and end stage kidney disease (ESKD). Kidney biopsy is the diagnostic procedure of choice with variable indications from center to center. It helps in identifying the exact specific diagnosis, assessing the level of disease activity and severity, and hence aids in proper therapy and helps predicting prognosis. There is a global change of pattern of glomerular disease over the last five decades.
METHODS
Retrospective analysis of all kidney biopsies (545 cases) that were done in patients over 12 year-old over last six years in four major hospitals in Kuwait. The indications for kidney biopsy were categorized into six clinical syndromes: nephrotic syndrome, sub-nephrotic proteinuria, nephrotic syndrome plus acute kidney injury (AKI), sub-nephrotic proteinuria plus AKI, isolated hematuria, and Unexplained renal impairment. We calculated the incidence of each type of kidney disease and indication of biopsy.
RESULTS
most common indication of kidney biopsy was sub-nephrotic proteinuria associated with AKI in 179 cases (32.8%). Primary Glomerulonephritis was the main diagnosis that was reported in 356 cases (65.3%). Immunoglobulin A Nephropathy (IgAN) was the commonest lesion in primary glomerulonephritis in 85 (23.9%) cases. Secondary Glomerulonephritis was diagnosed in 134 cases (24.6%), 56 (41.8%) of them were reported as lupus nephritis cases. In young adults (below 18 years of age) there were 31 cases reviews, 35.5% were found to have minimal change disease (MCD).
CONCLUSION
IgAN is the commonest glomerulonephritis in primary nephrotic syndromes in Kuwait over the past six years. Lupus nephritis is the leading secondary glomerulonephritis diagnosis.
Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Child; Diabetic Nephropathies; Female; Glomerulonephritis; Glomerulonephritis, IGA; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Hematuria; Humans; Kuwait; Lupus Nephritis; Male; Middle Aged; Nephritis, Interstitial; Nephrosis, Lipoid; Nephrotic Syndrome; Proteinuria; Thrombotic Microangiopathies; Time Factors; Young Adult
PubMed: 32423387
DOI: 10.1186/s12882-020-01836-3 -
Kidney International Mar 2018HIV-positive individuals are at increased risk for kidney disease, including HIV-associated nephropathy, noncollapsing focal segmental glomerulosclerosis, immune-complex...
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.
Topics: AIDS-Associated Nephropathy; Anti-HIV Agents; Comorbidity; Diagnosis, Differential; Evidence-Based Medicine; Genetic Predisposition to Disease; HIV; Host-Pathogen Interactions; Humans; Kidney; Nephrology; Predictive Value of Tests; Renal Insufficiency, Chronic; Risk Factors; Treatment Outcome
PubMed: 29398134
DOI: 10.1016/j.kint.2017.11.007 -
HIV/AIDS (Auckland, N.Z.) 2018Despite the decreased incidence of human immunodeficiency virus (HIV)-associated nephropathy due to the widespread use of combined active antiretroviral therapy, it... (Review)
Review
Despite the decreased incidence of human immunodeficiency virus (HIV)-associated nephropathy due to the widespread use of combined active antiretroviral therapy, it remains one of the leading causes of end-stage renal disease (ESRD) in HIV-1 seropositive patients. Patients usually present with low CD4 count, high viral load and heavy proteinuria, with the pathologic findings of collapsing focal segmental glomerulosclerosis. Increased susceptibility exists in individuals with African descent, largely due to polymorphism in gene. Other clinical risk factors include high viral load and low CD4 count. Advanced kidney disease and nephrotic range proteinuria have been associated with progression to ESRD. Improvement in kidney function has been observed after initiation of combined active antiretroviral therapy. Other treatment options, when clinically indicated, are inhibition of the renin-angiotensin system and corticosteroids. Further routine management approaches for patients with chronic kidney disease should be implemented. In patients with progression to ESRD, kidney transplant should be pursued, provided that viral load control is adequate. Screening for the presence of kidney disease upon detection of HIV-1 seropositivity in high-risk populations is recommended.
PubMed: 29872351
DOI: 10.2147/HIV.S141978 -
Expert Opinion on Pharmacotherapy Jan 2018Human immunodeficiency virus (HIV) remains a worldwide disease with significant mortality and morbidity. There are a multitude of HIV-related kidney diseases including... (Review)
Review
INTRODUCTION
Human immunodeficiency virus (HIV) remains a worldwide disease with significant mortality and morbidity. There are a multitude of HIV-related kidney diseases including HIV-associated nephropathy (HIVAN) most prominently. The risk of developing HIVAN increases with decreasing CD4 count, higher viral load, and based on genetic factors. The mortality rate for those with HIVAN-end stage renal disease (ESRD) remains 2.5-3 times higher than ESRD patients without HIVAN.
AREAS COVERED
The epidemiology of HIVAN, particularly risk assessment, will be explored in this review. Further, the pathogenesis of HIVAN, from viral-specific renal expression to the role of genetics as well as characteristic renal pathology will be described. Diagnosis and management of HIVAN will be addressed, with an emphasis on various treatment strategies including medication, dialysis, and kidney transplantation.
EXPERT OPINION
HIVAN is associated with a high risk for progression to ESRD and increased mortality. The backbone of HIVAN therapy remains combined anti-retroviral therapy (cART), while adjunctive therapies including RAAS blockade and prednisone, should be considered. In those who progress to ESRD, dialysis remains the mainstay of management, though increasing evidence has demonstrated that kidney transplantation can be effective in those with controlled HIV disease.
Topics: AIDS-Associated Nephropathy; CD4 Lymphocyte Count; Disease Progression; HIV Infections; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Renal Dialysis; Viral Load
PubMed: 29224373
DOI: 10.1080/14656566.2017.1416099 -
Pediatric Nephrology (Berlin, Germany) Aug 2021HIV-associated nephropathy (HIVAN) predominantly affects people of African ancestry living with HIV who do not receive appropriate antiretroviral therapy (ART).... (Review)
Review
HIV-associated nephropathy (HIVAN) predominantly affects people of African ancestry living with HIV who do not receive appropriate antiretroviral therapy (ART). Childhood HIVAN is characterized by heavy proteinuria and decreased kidney function. Kidney histology shows mesangial expansion, classic or collapsing glomerulosclerosis, and microcystic renal tubular dilatation leading to kidney enlargement. The pathogenesis of HIVAN involves the kidney recruitment of inflammatory cells and the infection of kidney epithelial cells. In addition, both viral and genetic factors play key roles in this disease. Modern ART has improved the outcome and decreased the prevalence of childhood HIVAN. However, physicians have had modest success providing chronic ART to children and adolescents, and we continue to see children with HIVAN all over the world. This article discusses the progress made during the last decade in our understanding of the pathogenesis and treatment of childhood HIVAN, placing particular emphasis on the mechanisms that mediate the infection of kidney epithelial cells, and the roles of cytokines, the HIV-Tat gene, and the Apolipoprotein-1 (APOL1) gene risk variants in this disease. In view of the large number of children living with HIV at risk of developing HIVAN, better prevention and treatment programs are needed to eradicate this disease.
Topics: AIDS-Associated Nephropathy; Adolescent; Apolipoprotein L1; HIV Infections; HIV-1; Humans; Kidney
PubMed: 33044676
DOI: 10.1007/s00467-020-04756-4 -
Current Opinion in Nephrology and... May 2011HIV-associated nephropathy (HIVAN) is characterized histologically by a collapsing form of focal segmental glomerulosclerosis (FSGS), microcystic tubular dilation,... (Review)
Review
PURPOSE OF REVIEW
HIV-associated nephropathy (HIVAN) is characterized histologically by a collapsing form of focal segmental glomerulosclerosis (FSGS), microcystic tubular dilation, interstitial inflammation and fibrosis. In this review, we provide a summary of the current state of knowledge about the mechanisms involved in the pathogenesis of HIVAN.
RECENT FINDINGS
Two variants in the ApoL1 gene have been identified as the susceptibility alleles that account for a majority of the increased risk of FSGS and nondiabetic end-stage renal disease in blacks. HIVAN1 and HIVAN2 are the other host susceptibility genes that have been identified in animal models for HIVAN. HIV infects renal tubular epithelial cells likely through direct cell-cell transmission. Both in-vivo and in-vitro evidence suggests that Nef and Vpr are the key viral genes mediating HIVAN. Nef induces podocyte dysfunction, whereas Vpr induces renal tubular epithelial cell apoptosis.
SUMMARY
HIVAN results from direct infection by HIV-1 and expression of viral genes, especially Nef and Vpr, in renal epithelial cells in a genetically susceptible host. The infected renal epithelium acts as a separate viral compartment from the blood and facilitates evolution of strains distant from blood. Dysregulation of several host cellular pathways, including those involved in cell cycle and apoptosis, ultimately results in the unique histopathological syndrome of HIVAN.
Topics: AIDS-Associated Nephropathy; Animals; Apolipoprotein L1; Apolipoproteins; Cell Differentiation; Cell Proliferation; Humans; Lipoproteins, HDL; Molecular Motor Proteins; Myosin Heavy Chains; Nephritis, Interstitial; Podocytes
PubMed: 21358326
DOI: 10.1097/MNH.0b013e328345359a -
Topics in Antiviral Medicine 2017The risk of acute and chronic kidney disease remains higher in HIV-infected persons than in the general population, and kidney disease in HIV-infected persons is... (Review)
Review
The risk of acute and chronic kidney disease remains higher in HIV-infected persons than in the general population, and kidney disease in HIV-infected persons is associated with poor outcomes, including increased mortality. HIV-associated nephropathy occurs less frequently in the era of antiretroviral therapy. HIV immune complex kidney disease is being diagnosed more frequently, but the term is currently used to refer to a heterogeneous group of kidney diseases. Comorbid chronic kidney disease poses a growing burden in HIV-infected persons due to an overrepresentation of risk factors such as black race, diabetes, hypertension, and coinfection with hepatitis C virus. Drug-induced kidney toxicity also remains a concern. This article summarizes a presentation by Christina M. Wyatt, MD, at the Ryan White HIV/AIDS Program Clinical Care Conference held in New Orleans, Louisiana, in December 2015.
Topics: Comorbidity; HIV Infections; Humans; Kidney Diseases; Prevalence
PubMed: 28402929
DOI: No ID Found -
The Cochrane Database of Systematic... Jan 2013Human immunodeficiency virus-associated nephropathy (HIVAN) is the most common cause of end stage kidney disease (ESKD) in human immunodeficiency virus-1 (HIV-1)... (Review)
Review
BACKGROUND
Human immunodeficiency virus-associated nephropathy (HIVAN) is the most common cause of end stage kidney disease (ESKD) in human immunodeficiency virus-1 (HIV-1) serotype patients and it mostly affects patients of African descent. It rapidly progresses to ESKD if untreated. The goal of treatment is directed toward reducing HIV-1 replication and/or slowing the progression of chronic kidney disease. The following pharmacological agents have been used for the treatment of HIVAN: antiretroviral therapy, angiotensin-converting enzyme inhibitors (ACEi), steroids and recently cyclosporin. Despite this, the effect of each intervention is yet to be evaluated.
OBJECTIVES
To evaluate the benefits and harms of adjunctive therapies in the management of HIVAN and its effects on symptom severity and all-cause mortality.
SEARCH METHODS
In January 2012 we searched the Cochrane Renal Group's Specialised Register, AIDS Education Global Information System (AEGIS database), ClinicalTrial.gov, the WHO International Clinical Trials Registry Portal, and reference lists of retrieved articles without language restrictions. In our original review we searched CENTRAL, MEDLINE, EMBASE, and AIDSearch, in addition to contacting individual researchers, research organisations and pharmaceutical companies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs of any therapy used in the treatment of HIVAN.
DATA COLLECTION AND ANALYSIS
We independently screened the search outputs for relevant studies and to retrieve full articles when necessary. For dichotomous outcomes results were to be expressed as risk ratios with 95% confidence intervals, and for continuous scales of measurement the mean difference was to be used.
MAIN RESULTS
We identified four relevant ongoing studies: one is still ongoing; two have completed recruitment but are yet to be published; and the fourth study was suspended for unspecified reasons. No completed RCTs or quasi-RCTs were identified. We summarised and tabulated the data from the observational studies, however no formal analyses were performed.
AUTHORS' CONCLUSIONS
There is currently no RCT-based evidence upon which to base guidelines for the treatment of HIVAN, however three ongoing studies have been identified. Data from observational studies suggest steroids and angiotensin-converting enzyme inhibitors appear to improve kidney function in patients with HIVAN, however no formal analyses were performed in this review. This review highlights the need for good quality RCTs to address the effects of interventions for treating this group.
Topics: AIDS-Associated Nephropathy; Angiotensin-Converting Enzyme Inhibitors; Humans; Steroids
PubMed: 23440812
DOI: 10.1002/14651858.CD007183.pub3