Long-term impact of immediate versus deferred antiretroviral therapy on kidney health in people with HIV.

People with human immunodeficiency virus (HIV) are at risk for chronic kidney disease (CKD) due to HIV and antiretroviral therapy (ART) nephrotoxicity. Immediate ART initiation reduces mortality and is now the standard of care, but the long-term impact of prolonged ART exposure on CKD is unknown. To evaluate this, the Strategic Timing of Antiretroviral Treatment (START) trial randomized 4,684 ART-naïve adults with CD4 cell count under 500 cells/mm3 to immediate versus deferred ART. We previously reported a small but statistically significantly greater decline in estimated glomerular filtration rate (eGFR) over a median of 2.1 years in participants randomized to deferred versus immediate ART. Here, we compare the incidence of CKD events and changes in eGFR and urine albumin/creatinine ratio (UACR) in participants randomized to immediate versus deferred ART during extended follow-up. Over a median of 9.3 years, eight participants experienced kidney failure or kidney-related death, three in the immediate and five in the deferred ART arms, respectively. Over a median of five years of more comprehensive follow-up, the annual rate of eGFR decline was 1.19 mL/min/1.73m2/year, with no significant difference between treatment arms (difference deferred - immediate arm 0.055; 95% confidence interval -0.106, 0.217 mL/min/1.73m2). Results were similar in models adjusted for baseline covariates associated with CKD, including UACR and APOL1 genotype. Similarly, there was no significant difference between treatment arms in incidence of confirmed UACR 30 mg/g or more (odds ratio 1.13; 95% confidence interval 0.85, 1.51). Thus, our findings provide the most definitive evidence to date in support of the long-term safety of early ART with respect to kidney health.

Association of HIV and viral suppression status with hospital acute kidney injury in the era of antiretroviral therapy.

In the modern era, it is unknown if people that are virally suppressed with HIV (PWH) are at increased risk for acute kidney injury (AKI) compared to people without HIV and no studies have compared the risk of AKI by viral suppression status. Here, we determined the associations of HIV status and AKI among PWH with and without viral suppression compared to people without HIV. An observational cohort study of PWH and people without HIV hospitalized in a large New York City health system between 2010-2019 was conducted. Multivariable Cox proportional hazards models were used to determine associations between HIV status and risk of AKI, severe AKI and development of chronic kidney disease (CKD). Among 173,884 hospitalized patients, 4,718 had HIV; 2,532 (53.7%) were virally suppressed and 2,186 (46.3%) were not suppressed. Compared to people without HIV, PWH with and without viral suppression were at increased risk of AKI (adjusted hazard ratio 1.27, 95% confidence interval 1.15, 1.40 and 1.73, 1.58, 1.90, respectively) and AKI requiring kidney replacement therapy (1.89, 1.27, 2.84 and 1.87, 1.23, 2.84, respectively). Incremental, graded associations were observed between HIV status and Stage 2 or 3 AKI, and among AKI survivors, and incident CKD. The elevated risk of AKI across ages of PWH was similar in magnitude to older people without HIV. Thus, regardless of virologic control, HIV is an independent risk factor for AKI among hospitalized patients. Future studies should determine the mechanisms by which HIV increases susceptibility to AKI and identify strategies to prevent AKI in PWH.

Association of marijuana, tobacco and alcohol use with estimated glomerular filtration rate in women living with HIV and women without HIV.

OBJECTIVE: Marijuana, tobacco and alcohol use are prevalent among people with HIV and may adversely affect kidney function in this population. We determined the association of use of these substances with estimated glomerular filtration rate (eGFR) among women with HIV (WWH) and women without HIV. DESIGN: We undertook a repeated measures study of 1043 WWH and 469 women without HIV within the United States Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-seropositive and HIV-seronegative women. METHODS: We quantified substance exposures using semi-annual questionnaires. Using pooled eGFR data from 2009 to 2019, we used linear regression models with multivariable generalized estimating equations to ascertain associations between current and cumulative substance use exposures with eGFR, adjusting for sociodemographics, chronic kidney disease risk factors and HIV-related factors. RESULTS: Marijuana use of 1-14 days/month versus 0 days/month was associated with 3.34 ml/min per 1.73 m 2 [95% confidence interval (CI) -6.63, -0.06] lower eGFR and marijuana use of >0.02-1.6 marijuana-years versus 0-0.2 marijuana-years was associated with 3.61 ml/min per 1.73 m 2 (95% CI -5.97, -1.24) lower eGFR. Tobacco use was not independently associated with eGFR. Alcohol use of seven or more drinks/week versus no drinks/week was associated with 5.41 ml/min per 1.73 m 2 (95% CI 2.34, 8.48) higher eGFR and alcohol use of >0.7-4.27 drink-years and >4.27 drink-years versus 0-0.7 drink-years were associated with 2.85 ml/min per 1.73 m 2 (95% CI 0.55, 5.15) and 2.26 ml/min per 1.73 m 2 (95% CI 0.33, 4.20) higher eGFR, respectively. CONCLUSION: Among a large cohort of WWH and women without HIV, marijuana use was associated with a lower eGFR while alcohol use was associated with a higher eGFR.

Outcomes of PD for AKI treatment during COVID-19 in New York City: A multicenter study.

BACKGROUND: The high incidence of acute kidney injury (AKI) requiring dialysis associated with COVID-19 led to the use of peritoneal dialysis (PD) for the treatment of AKI. This study aims to compare in-hospital all-cause mortality and kidney recovery between patients with AKI who received acute PD versus extracorporeal dialysis (intermittent haemodialysis and continuous kidney replacement therapy). METHODS: In a retrospective observational study of 259 patients with AKI requiring dialysis during the COVID-19 surge during Spring 2020 in New York City, we compared 30-day all-cause mortality and kidney recovery between 93 patients who received acute PD at any time point and 166 patients who only received extracorporeal dialysis. Kaplan-Meier curves, log-rank test and Cox regression were used to compare survival and logistic regression was used to compare kidney recovery. RESULTS: The mean age was 61 ± 11 years; 31% were women; 96% had confirmed COVID-19 with median follow-up of 21 days. After adjusting for demographics, comorbidities, oxygenation and laboratory values prior to starting dialysis, the use of PD was associated with a lower mortality rate compared to extracorporeal dialysis with a hazard ratio of 0.48 (95% confidence interval: 0.27-0.82, p = 0.008). At discharge or on day 30 of hospitalisation, there was no association between dialysis modality and kidney recovery (p = 0.48). CONCLUSIONS: The use of PD for the treatment of AKI was not associated with worse clinical outcomes when compared to extracorporeal dialysis during the height of the COVID-19 pandemic in New York City. Given the inherent selection biases and residual confounding in our observational study, research with a larger cohort of patients in a more controlled setting is needed to confirm our findings.

COVID-19 and Kidney Disease.

COVID-19 can cause acute kidney injury and may cause or exacerbate chronic kidney diseases, including glomerular diseases. SARS-CoV-2 infection of kidney cells has been reported, but it remains unclear if viral infection of kidney cells causes disease. The most important causes of kidney injury in patients with COVID-19 include impaired renal perfusion and immune dysregulation. Chronic kidney disease, especially kidney failure with kidney replacement therapy and kidney transplant, is associated with markedly increased COVID-19 mortality. Persons with severe kidney disease have been excluded from most clinical trials of COVID-19 therapies, so therapeutic approaches must be extrapolated from studies of patients without kidney disease. Some medications used to treat COVID-19 should be avoided or used at reduced dosages in patients with severe kidney disease and in kidney transplant recipients. Additional research is needed to determine the optimal strategies to prevent and treat COVID-19 in patients with kidney disease.

The Impact of Chronic Kidney Disease on Outcomes of Patients with COVID-19 Admitted to the Intensive Care Unit.

CONTEXT: Coronavirus disease 2019 (COVID-19) disproportionately impacts patients with chronic kidney disease (CKD), especially those with kidney failure requiring replacement therapy (KFRT). Patients with KFRT have increased risk of developing COVID-19, and though initial reports suggested that mortality of these patients in the intensive care unit (ICU) setting is prohibitively high, those studies suffered from significant limitations. Subject of Review: The Study of the Treatment and Outcomes in Critically Ill Patients With COVID-19 (STOP-COVID) is a multicenter cohort study that enrolled adults with COVID-19 admitted to ICUs in 68 medical centers across the USA. STOP-COVID investigators compared characteristics at the time of ICU admission and clinical outcomes in 143 patients with KFRT, 521 with nondialysis-dependent CKD (ND-CKD), and 3,600 patients without CKD. Patients with KFRT were less likely to have typical COVID-19 symptoms but more likely to have altered mental status at the time of ICU admission and were less likely to require mechanical ventilation during hospitalization than those without kidney disease. Approximately, 50% of patients with KFRT and ND-CKD died within 28 days of ICU admission, and in fully adjusted models, patients with KFRT and ND-CKD had 1.41- and 1.25-fold higher risk of 28-day mortality than those without CKD. Patients with KFRT and ND-CKD were also less likely to receive emerging therapies for COVID-19 than those without CKD. Second Opinion: This study provides important new data demonstrating differences in clinical presentation in patients with KFRT and ND-CKD with COVID-19. Alhough patients with severe CKD had higher mortality than those without CKD, approximately half survived after 28 days, demonstrating that patients with COVID-19 and severe CKD can benefit from ICU care. The markedly lower use of emerging COVID-19 treatments in patients with severe CKD highlights the need to include these patients in clinical trials of new COVID-19 therapies and for clinicians to ensure equal access to care in patients with severe CKD and COVID-19.

Brief Report: Acute Kidney Injury in People Living With HIV Hospitalized With Coronavirus Disease 2019: Clinical Characteristics and Outcomes.

BACKGROUND: Data on clinical characteristics and outcomes of people living with HIV (PLWH) hospitalized with coronavirus disease 2019 (COVID-19) who develop acute kidney injury (AKI) are limited. SETTING: Large tertiary health care system in the Bronx, NY. METHODS: We performed a retrospective cohort study of 83 PLWH and 4151 patients without HIV hospitalized with COVID-19 from March 10, 2020, to May 11, 2020. We compared the clinical characteristics and outcomes associated with AKI by HIV serostatus and evaluated HIV-related factors for AKI among PLWH. AKI was defined and staged using Kidney Disease Improving Global Outcomes criteria. RESULTS: The incidence of AKI in hospitalized patients with COVID-19 did not differ significantly by HIV serostatus (54.2% in PLWH vs 49.5% in patients without HIV, P = 0.6). Despite a higher incidence of stage 3 AKI (28.9% vs 17.1% P = 0.05) in PLWH compared with those without HIV, there was no significant difference in the need for renal replacement therapy (22.2% vs 13.4% P = 0.12), renal recovery (76.9% vs 82.5% P = 0.61), or dependence on renal replacement therapy (7.7% vs 3.8% P = 0.27). CD4 T-cell count, HIV-1 RNA viral suppression, and antiretroviral therapy use were not associated with AKI. AKI was associated with increased need for invasive ventilation and in-hospital death, but HIV was not an independent risk factor of in-hospital death after AKI [adjusted hazard ratio 1.01 (95% CI: 0.59 to 1.72), P = 0.98]. CONCLUSIONS: HIV-related factors were not associated with increased risk of AKI in PLWH hospitalized with COVID-19. PLWH hospitalized with COVID-19 had more stage 3 AKI, but outcomes after AKI were similar to those without HIV.

Use of peritoneal dialysis for acute kidney injury during the COVID-19 pandemic in New York City: a multicenter observational study.

To demonstrate feasibility of acute peritoneal dialysis (PD) for acute kidney injury during the coronavirus disease 2019 (COVID-19) pandemic, we performed a multicenter, retrospective, observational study of 94 patients who received acute PD in New York City in the spring of 2020. Patient comorbidities, severity of disease, laboratory values, kidney replacement therapy, and patient outcomes were recorded. The mean age was 61 ± 11 years; 34% were women; 94% had confirmed COVID-19; 32% required mechanical ventilation on admission. Compared to the levels prior to initiation of kidney replacement therapy, the mean serum potassium level decreased from 5.1 ± 0.9 to 4.5 ± 0.7 mEq/L on PD day 3 and 4.2 ± 0.6 mEq/L on day 7 (P < 0.001 for both); mean serum bicarbonate increased from 20 ± 4 to 21 ± 4 mEq/L on PD day 3 (P = 0.002) and 24 ± 4 mEq/L on day 7 (P < 0.001). After a median follow-up of 30 days, 46% of patients died and 22% had renal recovery. Male sex and mechanical ventilation on admission were significant predictors of mortality. The rapid implementation of an acute PD program was feasible despite resource constraints and can be lifesaving during crises such as the COVID-19 pandemic.

The Role of Glomerular Epithelial Injury in Kidney Function Decline in Patients With Diabetic Kidney Disease in the TRIDENT Cohort.

INTRODUCTION: Although diabetic kidney disease (DKD) is responsible for more than half of all chronic and end-stage kidney disease (ESKD), the association of light (LM) and electron microscopic (EM) structural changes with clinical parameters and prognosis in DKD is incompletely understood. METHODS: This is an interim analysis of 62 patients diagnosed with biopsy-confirmed DKD from the multicenter TRIDENT (Transformative Research in Diabetic Nephropathy) study. Twelve LM and 8 EM descriptors, representing changes in glomeruli, tubulointerstitium, and vasculature were analyzed for their relationship with clinical measures of renal function. Patients were followed every 6 months. RESULTS: Multivariable linear regression analysis revealed that estimated glomerular filtration rate (eGFR) upon enrollment correlated the best with interstitial fibrosis. On the other hand, the rate of kidney function decline (eGFR slope) correlated the most with glomerular lesions including global glomerulosclerosis and mesangiolysis. Unbiased clustering analysis based on histopathologic data identified 3 subgroups. The first cluster, encompassing subjects with the mildest histologic lesions, had the most preserved kidney function. The second and third clusters had similar degrees of kidney dysfunction and structural damage, but differed in the degree of glomerular epithelial cell and podocyte injury (podocytopathy DKD subtype). Cox proportional hazard analysis showed that subjects in cluster 2 had the highest risk to reach ESKD (hazard ratio: 17.89; 95% confidence interval: 2.13-149.79). Glomerular epithelial hyperplasia and interstitial fibrosis were significant predictors of ESKD in the multivariate model. CONCLUSION: The study highlights the association between fibrosis and kidney function and identifies the role of glomerular epithelial changes and kidney function decline.

Effect of Systemic Glucocorticoids on Mortality or Mechanical Ventilation in Patients With COVID-19.

The efficacy of glucocorticoids in COVID-19 is unclear. This study was designed to determine whether systemic glucocorticoid treatment in COVID-19 patients is associated with reduced mortality or mechanical ventilation. This observational study included 1,806 hospitalized COVID-19 patients; 140 were treated with glucocorticoids within 48 hours of admission. Early use of glucocorticoids was not associated with mortality or mechanical ventilation. However, glucocorticoid treatment of patients with initial C-reactive protein (CRP) ≥20 mg/dL was associated with significantly reduced risk of mortality or mechanical ventilation (odds ratio, 0.23; 95% CI, 0.08-0.70), while glucocorticoid treatment of patients with CRP <10 mg/dL was associated with significantly increased risk of mortality or mechanical ventilation (OR, 2.64; 95% CI, 1.39-5.03). Whether glucocorticoid treatment is associated with changes in mortality or mechanical ventilation in patients with high or low CRP needs study in prospective, randomized clinical trials.

Publisher Correction: The HIV protease inhibitor darunavir prevents kidney injury via HIV-independent mechanisms.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Characteristics, Outcomes and 60-Day Hospital Mortality of ICU Patients with COVID-19 and Acute Kidney Injury.

Background: AKI has been reported in patients with COVID-19 pneumonia and it is associated with higher mortality. The aim of our study is to describe characteristics, outcomes, and 60-day hospital mortality of patients with COVID-19 pneumonia and AKI in the intensive care unit (ICU). Methods: We conducted a retrospective study in which all adult patients with confirmed COVID-19 who were admitted to ICUs of Montefiore Medical Center and developing AKI were included. The study period ranged from March 10 to April 11, 2020. The 60-day follow-up data through June 11, 2020 were obtained. Results: Of 300 adults admitted to the ICUs with COVID-19 pneumonia, 224 patients (75%) presented with AKI or developed AKI subsequent to admission. A total of 218 (97%) patients required invasive mechanical ventilation for moderate to severe acute respiratory distress syndrome (ARDS). A total of 113 (50%) patients had AKI on day 1 of ICU admission. The peak AKI stages observed were stage 1 in 49 (22%), stage 2 in 35 (16%), and stage 3 in 140 (63%) patients, respectively. Among patients with AKI, 114 patients (51%) required RRT. The mortality rate of patients requiring RRT was 70%. Of the 34 patients who were survivors, 25 (74%) were able to be weaned off RRT completely before hospital discharge. Nonsurvivors were older and had significantly higher admission and peak creatinine levels, admission hemoglobin, and peak phosphate levels compared with survivors. The 60-day hospital mortality was 67%. Conclusions: COVID-19 requiring ICU admission is associated with high incidence of severe AKI, necessitating RRT in approximately half of such patients. The majority of patients with COVID-19 and AKI in ICU developed moderate to severe ARDS, requiring invasive mechanical ventilation. Timing or severity of AKI did not affect outcomes. The 60-day hospital mortality is high (67%). Patients with AKI requiring RRT have high mortality, but survivors have good rates of RRT recovery. Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/K360/2020_12_31_KID0004282020.mp3.

The HIV protease inhibitor darunavir prevents kidney injury via HIV-independent mechanisms.

HIV-associated nephropathy (HIVAN) is a rapidly progressive kidney disease that is caused by HIV infection of renal epithelial cells with subsequent expression of viral genes, including vpr. Antiretroviral therapy ameliorates HIVAN without eradicating HIV from the kidneys and the mechanism by which it protects kidneys is poorly understood. Since HIV protease inhibitors have "off target" cellular effects, we studied whether darunavir, the most commonly prescribed protease inhibitor, protects kidneys from HIV-induced injury via mechanisms independent of HIV protease and viral replication. Renal epithelial cells were transduced with lentiviruses encoding HIV (lacking protease and reverse transcriptase), Vpr, or vector control. Darunavir attenuated HIV and Vpr-induced activation of Stat3, Src, Erk, and cytokines, which are critical for HIVAN pathogenesis. We then studied HIV-transgenic mice, which develop HIVAN in the absence of HIV protease or reverse transcriptase. Mice were treated with darunavir, zidovudine, darunavir + zidovudine, or control. Darunavir and darunavir + zidovudine reduced albuminuria and histologic kidney injury and normalized expression of dysregulated proteins. RNA-seq analyses demonstrated that darunavir suppressed HIV-induced upregulation of immune response genes in human kidney cells. These data demonstrate that darunavir protects against HIV-induced renal injury via mechanisms that are independent of inhibition of HIV protease.

Sleep and Health Among Collegiate Student Athletes.

Although the link between sleep, health, and performance has been well documented, research on this link in collegiate student athletes is still in its infancy. A large body of evidence indicates that collegiate student athletes are not obtaining enough sleep, but less is known about their sleep quality, patterns, and the impact on health and performance. Consequently, short sleep negatively affects physical and mental health, as well as several domains of performance (ie, aerobic, anaerobic, sport-specific, cognitive). The majority of studies examining the links between short sleep, health, and performance have been conducted with healthy adults or noncollegiate athlete samples; however, collegiate student athletes have demands unlike those of their nonathlete or noncollegiate athlete counterparts. Poor sleep health and sleep disorders are of increasing concern among the college athlete population and have recently been recognized by national and international sports governing bodies. The purpose of this review is to summarize the available literature on sleep and its impact on health and performance among athletes, specifically addressing gaps where little to no data is available on collegiate student athletes. Consideration is also given to evidence-based sleep interventions that have been utilized with athletes, as well as recommendations for future research and intervention development.