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BMC Infectious Diseases Sep 2023In immunocompromised populations, such as patients with AIDS and recipients of solid organ and hematopoietic stem cell transplants, BK polyomavirus (BKPyV) can... (Review)
Review
BACKGROUND
In immunocompromised populations, such as patients with AIDS and recipients of solid organ and hematopoietic stem cell transplants, BK polyomavirus (BKPyV) can reactivate and cause several diseases, which can lead to death in their severe forms. Unlike hemorrhagic cystitis and BKPyV-associated nephropathy, BKPyV-associated pneumonia is rare, with only seven known cases worldwide. However, the disease can rapidly progress with extremely high mortality.
CASE PRESENTATION
Herein, we report two cases of BKPyV-associated pneumonia following hematopoietic stem cell transplantation. Both patients had consistent infectious pneumonia and graft-versus-host disease after stem cell transplantation. The diagnosis of BKPyV-associated pneumonia was confirmed by metagenomic next-generation sequencing and polymerase chain reaction after the sudden worsening of the pulmonary infection signs and symptoms concomitant with renal dysfunction and systemic immune weakening. Both patients eventually died of systemic multi-organ failure caused by severe pneumonia.
CONCLUSIONS
Currently, BKPyV reactivation cannot be effectively prevented. Immunocompromised patients must actively manage their primary lung infections, pay close attention to pulmonary signs and imaging changes. Especially during and after steroid pulse therapy or immunosuppressive therapy for graft versus host diseases, BKPyV load in blood/urine needs to be regularly measured, and the immunosuppressive intensity should be adjusted properly after the BKPyV reactivation diagnosis. Clinical trials of new antiviral drugs and therapies for BKPyV are urgently needed.
Topics: Humans; BK Virus; Pneumonia; Antiviral Agents; Cystitis; Heart Rate
PubMed: 37697264
DOI: 10.1186/s12879-023-08577-2 -
American Journal of Physiology. Renal... Aug 2020Human immunodeficiency virus (HIV) infection of kidney cells can lead to HIV-associated nephropathy (HIVAN) and aggravate the progression of other chronic kidney...
Human immunodeficiency virus (HIV) infection of kidney cells can lead to HIV-associated nephropathy (HIVAN) and aggravate the progression of other chronic kidney diseases. Thus, a better understanding of the mechanisms of HIV-induced kidney cell injury is needed for effective therapy against HIV-induced kidney disease progression. We have previously shown that the acetylation and activation of key inflammatory regulators, NF-κB p65 and STAT3, were increased in HIVAN kidneys. Here, we demonstrate the key role of sirtuin 1 (SIRT1) deacetylase in the regulation of NF-κB and STAT3 activity in HIVAN. We found that SIRT1 expression was reduced in the glomeruli of human and mouse HIVAN kidneys and that HIV-1 gene expression was associated with reduced SIRT1 expression and increased acetylation of NF-κB p65 and STAT3 in cultured podocytes. Interestingly, SIRT1 overexpression, in turn, reduced the expression of negative regulatory factor in podocytes stably expressing HIV-1 proviral genes, which was associated with inactivation of NF-κB p65 and a reduction in HIV-1 long terminal repeat promoter activity. In vivo, the administration of the small-molecule SIRT1 agonist BF175 or inducible overexpression of SIRT1 specifically in podocytes markedly attenuated albuminuria, kidney lesions, and expression of inflammatory markers in Tg26 mice. Finally, we showed that the reduction in SIRT1 expression by HIV-1 is in part mediated through miR-34a expression. Together, our data provide a new mechanism of SIRT1 regulation and its downstream effects in HIV-1-infected kidney cells and indicate that SIRT1/miR-34a are potential drug targets to treat HIV-related kidney disease.
Topics: AIDS-Associated Nephropathy; Animals; Humans; Kidney; Kidney Glomerulus; Mice; Podocytes; Renal Insufficiency, Chronic; Sirtuin 1; Transcription Factor RelA
PubMed: 32657157
DOI: 10.1152/ajprenal.00140.2020 -
HIV Medicine Mar 2022HIV-associated kidney disease is common but data on the pathology spectrum of kidney biopsy in China is lacking. This study aimed to illustrate the clinical...
OBJECTIVES
HIV-associated kidney disease is common but data on the pathology spectrum of kidney biopsy in China is lacking. This study aimed to illustrate the clinical presentation, laboratory findings and pathological spectrum of different subtypes of HIV-associated kidney disease in China.
METHODS
Eighteen HIV patients with renal biopsy indications at the Peking Union Medical College Hospital from January 2002 to October 2021 were retrospectively enrolled. All had CD4 counts and HIV viral load measurements. Renal biopsies were examined with light microscopy, immunofluorescence, and electron microscopy. Shapiro-Wilk test was used to test whether the data was normally distributed. The data is presented as medians (interquartile range), number (%), or means (±SD) according to their distribution.
RESULTS
Seventeen patients had glomerular disease, and one patient had interstitial nephritis. Membranous nephropathy was present in eight patients (47.1%), and IgA nephropathy in four patients (23.5%). The difference in urine protein and serum albumin before and after treatment was statistically significant and no deaths or dialysis were observed to the end of follow-up.
CONCLUSION
This study found that classic HIV-associated nephropathy (HIVAN) was uncommon in Chinese HIV patients. HIV immune complex kidney (HIVICK) disease, such as membranous or IgA nephropathy, was more common, and associated with better prognosis. Antiretroviral therapy, ACE inhibitors, and angiotensin II receptor blockers were effective in decreasing proteinuria and preserving renal function. The use of corticosteroids and immunosuppressive agents seems safe. However, the nephrotoxic effect of antiretroviral agents and other medications should be carefully monitored.
Topics: AIDS-Associated Nephropathy; Biopsy; Female; Glomerulonephritis, IGA; HIV Infections; Humans; Kidney; Male; Retrospective Studies
PubMed: 35293105
DOI: 10.1111/hiv.13246 -
Cureus Mar 2023Human immunodeficiency virus (HIV) is a viral infection which progressively leads to acquired immunodeficiency syndrome (AIDS) in the absence of treatment. This happens... (Review)
Review
Human immunodeficiency virus (HIV) is a viral infection which progressively leads to acquired immunodeficiency syndrome (AIDS) in the absence of treatment. This happens through the destruction of crucial cells in the immune system, such as the helper T cells, dendritic cells, and macrophages. Since the first case was isolated in the 20th century, the disease has spread rapidly among humans, with significant renal, cardiovascular, respiratory, and neurological complications. It is predominantly sexually transmitted but non-sexual transmission. A relationship between HIV and renal diseases has been suggested for a long time, but only a few systematic studies have centered on this association. This systematic review aims to analyze the possible association between HIV and renal diseases as well as the range and pathogenesis of these renal diseases. HIV remains a critical infectious disease globally, inciting substantial morbidity and mortality. Studies have shown that people living with HIV (PLWH) are at increased risk of acute and chronic kidney disease. This review is based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Google Scholar, and Cochrane databases were searched exhaustively using the inclusion criteria of free full-text English papers that have exclusively studied humans in the last 20 years. Sixteen articles were selected including a systematic review, observational studies, and comprehensive narrative reviews on the role of HIV in the etiology of renal diseases, and were systemically reviewed and analyzed to elicit the wide range of possible renal complications resulting from HIV infection.
PubMed: 37123789
DOI: 10.7759/cureus.36755 -
Revista Da Associacao Medica Brasileira... Jan 2020The scenario of infection by the human immunodeficiency virus (HIV) has been undergoing changes in recent years, both in relation to the understanding of HIV infection... (Review)
Review
The scenario of infection by the human immunodeficiency virus (HIV) has been undergoing changes in recent years, both in relation to the understanding of HIV infection and regarding the treatments available. As a result, the disease, which before was associated with high morbidity and mortality, is now seen as a chronic disease that can be controlled, regarding both transmission and symptoms. However, even when the virus replication is well controlled, the infected patient remains at high risk of developing renal involvement, either by acute kidney injury not associated with HIV, nephrotoxicity due to antiretroviral drugs, chronic diseases associated with increased survival, or glomerular disease associated to HIV. This review will cover the main aspects of kidney failure associated with HIV.
Topics: AIDS-Associated Nephropathy; Acute Kidney Injury; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Chronic Disease; HIV Infections; Humans; Kidney; Risk Factors; Tenofovir
PubMed: 31939539
DOI: 10.1590/1806-9282.66.S1.75 -
Clinical Kidney Journal Jan 2024Diabetic nephropathy (DN) and non-diabetic renal diseases (NDRD) represent intricate challenges in diagnosis and treatment within the context of the global diabetes... (Review)
Review
Diabetic nephropathy (DN) and non-diabetic renal diseases (NDRD) represent intricate challenges in diagnosis and treatment within the context of the global diabetes epidemic. As the prevalence of diabetes continues to escalate, effective management of renal complications becomes paramount. Recent advancements in comprehending the multifaceted nature of renal damage, fueled by insights from histopathological investigations, offer unprecedented prospects for refining diagnostic strategies and customizing therapeutic interventions. Renal biopsies have emerged as indispensable tools for unraveling the diverse phenotypes of renal damage in diabetes. The pioneering study by Mazzucco identified three classes of renal damage in type 2 diabetes patients: classical diabetic glomerulosclerosis (DN), vascular and ischemic glomerular changes (NDRD), and other glomerulonephritides in the presence (DN + NDRD, mixed forms) or absence of DN (NDRD). The prevalence of these classes varies widely in published studies, influenced by factors such as ethnicity, geography and selection criteria for renal biopsy. Moreover, the international Renal Pathology Society consensus classification system has stratified the classical diabetic nephropathy into progressive categories of renal impairment, a breakthrough that aids in prognostication. Histopathological scrutiny, particularly the intricate correlation between glomerular and tubulointerstitial lesions, contributes profoundly to enhancing our grasp of the phenotype's heterogeneity. This amplified comprehension holds the potential to steer personalized treatment strategies. Cutting-edge interventions, encompassing sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists and anti-endothelin receptor agents, are broadening the arsenal against renal injury in diabetes. When combined with the profound insights garnered from histopathological, omics, imaging and clinical data, these therapeutic avenues promise a transformative shift towards precision-driven care paradigms. Collaborative efforts uniting researchers, clinicians and patients are indispensable for propelling our knowledge of diabetic renal damage and ameliorating patient outcomes. The fusion of histopathological, omics and imaging findings into clinical decision-making harbors the potential to customize interventions and optimize care for individuals grappling with diabetes-associated renal complications. Furthermore, groundbreaking initiatives like the iBeat Study within the BEAt-DKD (Biomarker Enterprise to Attack Diabetic Kidney Disease) project (https://www.beat-dkd.eu/), elucidating distinct phenotypes of renal damage within diabetes, underscore the imperative necessity of integrating histopathological data into the broader framework of diabetic renal management.
PubMed: 38186902
DOI: 10.1093/ckj/sfad266 -
AIDS Research and Therapy Mar 2020Chronic kidney disease (CKD) is a comorbidity of major clinical significance amongst people living with HIV (PLWHIV) and is associated with significant morbidity and... (Review)
Review
Chronic kidney disease (CKD) is a comorbidity of major clinical significance amongst people living with HIV (PLWHIV) and is associated with significant morbidity and mortality. The prevalence of CKD is rising, despite the widespread use of antiretroviral therapy (ART) and is increasingly related to prevalent non-infectious comorbidities (NICMs) and antiretroviral toxicity. There are great disparities evident, with the highest prevalence of CKD among PLWHIV seen in the African continent. The aetiology of kidney disease amongst PLWHIV includes HIV-related diseases, such as classic HIV-associated nephropathy or immune complex disease, CKD related to NICMs and CKD from antiretroviral toxicity. CKD, once established, is often relentlessly progressive and can lead to end-stage renal disease (ESRD). Identifying patients with risk factors for CKD, and appropriate screening for the early detection of CKD are vital to improve patient outcomes. Adherence to screening guidelines is variable, and often poor. The progression of CKD may be slowed with certain clinical interventions; however, data derived from studies involving PLWHIV with CKD are sparse and this represent an important area for future research. The control of blood pressure using angiotensin converting enzyme inhibitors and angiotensin receptor blockers, in particular, in the setting of proteinuria, likely slows the progression of CKD among PLWHIV. The cohort of PLWHIV is facing new challenges in regards to polypharmacy, drug-drug interactions and adverse drug reactions. The potential nephrotoxicity of ART is important, particularly as cumulative ART exposure increases as the cohort of PLWHIV ages. The number of PLWHIV with ESRD is increasing. PLWHIV should not be denied access to renal replacement therapy, either dialysis or kidney transplantation, based on their HIV status. Kidney transplantation amongst PLWHIV is successful and associated with an improved prognosis compared to remaining on dialysis. As the cohort of PLWHIV ages, comorbidity increases and CKD becomes more prevalent; models of care need to evolve to meet the new and changing chronic healthcare needs of these patients.
Topics: Anti-HIV Agents; Clinical Trials as Topic; Comorbidity; Disease Progression; HIV Infections; Humans; Prevalence; Renal Insufficiency; Renal Insufficiency, Chronic; Risk Factors
PubMed: 32178687
DOI: 10.1186/s12981-020-00266-3 -
Kidney International Oct 2022Four 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... (Review)
Review
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.
Topics: AIDS-Associated Nephropathy; Animals; Anti-Retroviral Agents; Antigen-Antibody Complex; Apolipoprotein L1; HIV Infections; Humans; Renal Insufficiency, Chronic
PubMed: 35850290
DOI: 10.1016/j.kint.2022.06.021 -
Frontiers in Medicine 2021Variants in the () gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an...
Variants in the () gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an increased risk of non-diabetic chronic kidney disease (CKD) and in particular of HIV associated nephropathy (HIVAN). In light of the significantly increased risk of HIVAN in carriers of two risk alleles, a role in HIV infectivity has been postulated in the mechanism of associated kidney disease. Herein, we aim to explore the association between HIV viremia and genotype. In addition, we investigated interaction between BK and JC viruria, CKD and HIV viremia. A total of 199 persons living with HIV/AIDS (comprising 82 CKD cases and 117 controls) from among the participants in the ongoing Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network case control study have been recruited. The two renal risk alleles (RRA) genotypes were associated with a higher risk of CKD (OR 12.6, 95% CI 3.89-40.8, < 0.0001). Even a single APOL1 RRA was associated with CKD risk (OR 4.42, 95% CI 1.49-13.15, = 0.007). The 2 APOL1 RRA genotypes were associated with an increased probability of having HIV viremia (OR 2.37 95% CI 1.0-5.63, = 0.05). HIV viremia was associated with increased CKD risk (OR 7.45, 95% CI 1.66-33.35, = 0.009) and with a significant reduction of JC virus urine shedding (OR 0.35, 95% CI 0.12-0.98, = 0.046). In contrast to prior studies, JC viruria was not associated with CKD but was restricted in patients with HIV viremia, regardless of CKD status. These findings suggest a role of variants in HIV infectivity and emphasize that JC viruria can serve as biomarker for innate immune system activation.
PubMed: 34513880
DOI: 10.3389/fmed.2021.718300 -
American Journal of Nephrology 2020Impaired mobility is associated with functional dependence, frailty, and mortality in prevalent patients undergoing dialysis. We investigated risk factors for mobility... (Observational Study)
Observational Study
BACKGROUND
Impaired mobility is associated with functional dependence, frailty, and mortality in prevalent patients undergoing dialysis. We investigated risk factors for mobility impairment, (poor gait speed) in patients incident to dialysis, and changes in gait speed over time in a 2-year longitudinal study.
METHODS
One hundred eighty-three patients enrolled within 6 months of dialysis initiation were followed up 6, 12, and 24 months later. Grip strength, health-related quality of life, and comorbidities were assessed at baseline. Outcomes were (a) baseline gait speed and (b) change in gait speed over time. Gait speed was assessed by 4-meter walk. Multivariate linear regression was used to identify risk factors for low gait speed at baseline. For longitudinal analyses, linear mixed effects modeling with gait speed modeled over time was used as the outcome.
RESULTS
Participants were 54.7 ± 12.8 years old, 52.5% men, 73.9% black with mean dialysis vintage of 100.1 ± 46.9 days and median gait speed 0.78 (0.64-0.094) m/s. Lower health utility and grip strength, diabetic nephropathy, and walking aids were associated with lower baseline gait speed. Loss of 0.1 m/s gait speed occurred in 24% of subjects at 1 year. In multivariate mixed effects models, only age, walking aid use, lower health utility, and lower handgrip strength were significantly associated with gait speed loss.
CONCLUSIONS
In our cohort of incident dialysis patients, overall gait speed is very low and 54.2% of the subjects continue to lose gait speed over 2 years. Older age, lower handgrip strength, and quality of life are risk factors for slowness. Patients at highest risk of poor gait speed can be identified at dialysis initiation to allow targeted implementation of therapeutic options.
Topics: Adult; Age Factors; Aged; Disease Progression; Female; Follow-Up Studies; Frailty; Hand Strength; Humans; Longitudinal Studies; Male; Middle Aged; Quality of Life; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Walking Speed
PubMed: 32781443
DOI: 10.1159/000509225