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.

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.

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.

High Temperature Effects during High Energy Laser Strikes on Embedded Fiber Bragg Grating Sensors.

As the applications of fiber Bragg gratings (FBGs) continue to grow and become more advanced, it becomes necessary to understand their behavior when exposed to high temperatures in unique situations. In these experiments, uniform 1530-nm fiber Bragg gratings and Type K Cr-Al thermocouples were embedded in three-ply carbon fiber composites. A 100 W high energy laser (HEL) heated the composites to high temperatures over timespans less than one second, and FBG spectral data and thermocouple temperature data were collected during each HEL heating test. The data from three high energy laser tests that represent different levels of damage to the FBG are analyzed to explore the spectral response and thermal decay of embedded FBG sensors when exposed to high temperatures over short timespans. Results are compared to a previously proposed power-law model describing the decay of FBGs in bare fiber when held at constant temperatures over much longer timespans.

Using CRISPR to inactivate endogenous retroviruses in pigs: an important step toward safe xenotransplantation?

Xenotransplantation could theoretically provide an unlimited supply of organs for patients living with end-stage kidney disease and other end-stage organ failure, but severe rejection and concerns about possible transmission of zoonotic infections remain important obstacles. In a recent study, investigators used CRISPR-cas9 to generate genetically modified pigs in which all endogenous retroviruses were inactivated. This approach may address one important barrier to the feasibility of clinical trials of xenotransplantation.

Evaluating the Athlete with Suspected Exercise-Induced Asthma or Bronchospasm.

Exercise-induced asthma (EIA) and exercise-induced bronchospasm (EIB)/bronchoconstriction (EIC) describes two clinical entities by which exercise triggers bronchial hyperresponsiveness. Exercise is a common trigger of bronchospasm in the asthmatic (EIA), as well as athletes without the underlying inflammation associated with asthma (EIC/EIB). Approximately 10% to 20% of the general population have EIA or EIB (). The approach to the diagnosis and subsequent management relies on the clinician's ability to recognize clinical signs and symptoms, then selecting the correct diagnostic test. A baseline spirometry/pulmonary function test is recommended for all athletes to evaluate for underlying asthma. Subsequent direct or indirect bronchial provocation testing is recommended to correctly diagnose EIA or EIB (). Athletes should not be treated empirically with bronchodilators based on symptoms alone without confirmatory spirometry and provocative testing.

ACE2 as therapy for glomerular disease: the devil is in the detail.

Angiotensin-converting enzyme 2 cleaves angiotensin (Ang) II to Ang(1-7), which antagonizes the deleterious effects of Ang II. In this issue, 2 groups administered angiotensin-converting enzyme 2 in murine models of kidney disease. Angiotensin-converting enzyme 2 did not improve glomerular injury in 2 models of mild diabetic nephropathy but was partially protective in an Alport syndrome model. These discrepant findings may be explained by the inability of angiotensin-converting enzyme 2 to reach the urinary space in the absence of severe proteinuria.

Recycling to discover something new: the role of autophagy in kidney disease.

This year, the Nobel Prize in Physiology or Medicine was awarded to Yoshinori Ohsumi for his groundbreaking work in dissecting the mechanisms of autophagy, a cellular process resulting in the organized degradation of cytoplasmic components. Ohsumi's work paved the way for subsequent studies that demonstrated critical roles for autophagy in modulating both acute and chronic kidney injury. This work may lead to future therapeutic approaches that target the autophagy system to prevent or treat kidney diseases.

APOL1: a case in point for replacing race with genetics.

Ethnicity-specific differences in apolipoprotein L1 (APOL1) polymorphisms are associated with racial disparities in kidney transplantation outcomes. APOL1 genotyping may better help define graft outcome risk pre-transplantation; however, more research is needed.

Telenephrology: current perspectives and future directions.

There is increasing interest in telemedicine among physicians and patients; however, the evidence regarding the quality of care delivered by telemedicine, and telenephrology in particular, compared with in-person care is limited. In this review, different electronic modalities used to deliver nephrology care are reviewed and critiqued, with a focused analysis from the Australian and United States perspectives. Both countries are geographically expansive with significant rural populations where access to nephrology care is limited. However, their health care systems are organized differently. The Australian health care system is a mostly nonprofit, single-payer system, whereas the United States system is more fractured with a greater proportion of patients covered by for-profit private insurance or no insurance coverage. Videoconferencing is widely used in Australia to manage kidney disease including chronic kidney disease, dialysis, pediatric nephrology, and post-kidney transplantation care. In contrast, the United States telenephrology experience is limited, with most reports originating from the Veterans Health Administration, a single-payer system providing care for nearly 9 million veterans, ∼3 million of whom reside in rural communities. Preliminary reports from the Veterans Health Administration suggest that that delivery of nephrology care via videoconferencing results in clinical outcomes that are at least equivalent to in-person care and improved patient adherence to scheduled appointments. Nevertheless, large, adequately controlled studies are needed to identify patient populations that are most likely to benefit from telenephrology and to determine the optimal systems for the delivery of telenephrology care.

Epithelial-to-mesenchymal transition of tubular epithelial cells in renal fibrosis: a new twist on an old tale.

Recent publications have questioned whether epithelial-to-mesenchymal transition of tubular epithelial cells is an important contributor to renal fibrosis. Two recent publications describe an intratubular epithelial-to-mesenchymal transition-like program of epithelial cell dedifferentiation that may contribute to the recruitment or proliferation of interstitial myofibroblasts after kidney injury.

LAPping up dead cells to prevent lupus nephritis: a novel role for noncanonical autophagy in autoimmunity.

The mechanisms underlying the development of systemic lupus erythematosus and lupus nephritis remain poorly understood. A recent study demonstrates that deficiencies in the immune system's ability to degrade scavenged dead cells via noncanonical autophagy is sufficient to break immune tolerance and produce features commonly seen in lupus, including circulating autoantibodies, inflammatory cytokines, and nephritis. This work provides a possible mechanism for the association of polymorphisms in autophagy genes with the risk of lupus.

Improving the Nephrology Match: the Path Forward.

The Fellowship Match process was designed to provide applicants and program directors with an opportunity to consider all their options before making decisions about post-residency training. In a Match, applicants can choose the programs that best suit their career goals, and program directors can consider all candidates before preparing a rank order list. The Match is a contract, requiring obligations of both programs and applicants to achieve success, ensure uniformity, and standardize participation.

Hepatitis C virus infection and kidney transplantation: newer options and a brighter future ahead?

Recent studies including the current article by Sawinski et al. demonstrate that hepatitis C virus (HCV) infection is associated with worse outcomes in kidney transplant recipients with and without HIV infection. We comment on the significance of these findings in the context of newer options for the treatment of HCV infection that have improved efficacy and fewer side effects when administered in both kidney transplant candidates and recipients.

Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.