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1.
J Am Soc Nephrol ; 32(11): 2851-2862, 2021 11.
Article in English | MEDLINE | ID: covidwho-1690622

ABSTRACT

BACKGROUND: COVID-19 is associated with increased risk of post-acute sequelae involving pulmonary and extrapulmonary organ systems-referred to as long COVID. However, a detailed assessment of kidney outcomes in long COVID is not yet available. METHODS: We built a cohort of 1,726,683 US Veterans identified from March 1, 2020 to March 15, 2021, including 89,216 patients who were 30-day survivors of COVID-19 and 1,637,467 non-infected controls. We examined risks of AKI, eGFR decline, ESKD, and major adverse kidney events (MAKE). MAKE was defined as eGFR decline ≥50%, ESKD, or all-cause mortality. We used inverse probability-weighted survival regression, adjusting for predefined demographic and health characteristics, and algorithmically selected high-dimensional covariates, including diagnoses, medications, and laboratory tests. Linear mixed models characterized intra-individual eGFR trajectory. RESULTS: Beyond the acute illness, 30-day survivors of COVID-19 exhibited a higher risk of AKI (aHR, 1.94; 95% CI, 1.86 to 2.04), eGFR decline ≥30% (aHR, 1.25; 95% CI, 1.14 to 1.37), eGFR decline ≥40% (aHR, 1.44; 95% CI, 1.37 to 1.51), eGFR decline ≥50% (aHR, 1.62; 95% CI, 1.51 to 1.74), ESKD (aHR, 2.96; 95% CI, 2.49 to 3.51), and MAKE (aHR, 1.66; 95% CI, 1.58 to 1.74). Increase in risks of post-acute kidney outcomes was graded according to the severity of the acute infection (whether patients were non-hospitalized, hospitalized, or admitted to intensive care). Compared with non-infected controls, 30-day survivors of COVID-19 exhibited excess eGFR decline (95% CI) of -3.26 (-3.58 to -2.94), -5.20 (-6.24 to -4.16), and -7.69 (-8.27 to -7.12) ml/min per 1.73 m2 per year, respectively, in non-hospitalized, hospitalized, and those admitted to intensive care during the acute phase of COVID-19 infection. CONCLUSIONS: Patients who survived COVID-19 exhibited increased risk of kidney outcomes in the post-acute phase of the disease. Post-acute COVID-19 care should include attention to kidney disease.


Subject(s)
COVID-19/complications , Kidney Diseases/epidemiology , Kidney Diseases/virology , Veterans/statistics & numerical data , Aged , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , Case-Control Studies , Cohort Studies , Critical Care , Female , Glomerular Filtration Rate , Hospitalization , Humans , Kidney Diseases/diagnosis , Male , Middle Aged , United States
2.
BMC Geriatr ; 22(1): 119, 2022 02 12.
Article in English | MEDLINE | ID: covidwho-1690963

ABSTRACT

BACKGROUND: The reduced renal function has prognostic significance in COVID-19 and it has been linked to mortality in the general population. Reduced renal function is prevalent in older age and thus we set out to better understand its effect on mortality. METHODS: Patient clinical and demographic data was taken from the COVID-19 in Older People (COPE) study during two periods (February-June 2020 and October 2020-March 2021, respectively). Kidney function on admission was measured using estimated glomerular filtration rate (eGFR). The primary outcomes were time to mortality and 28-day mortality. Secondary outcome was length of hospital stay. Data were analysed with multilevel Cox proportional hazards regression, and multilevel logistic regression and adjusted for individual patient clinical and demographic characteristics. RESULTS: One thousand eight hundred two patients (55.0% male; median [IQR] 80 [73-86] years) were included in the study. 28-day mortality was 42.3% (n = 742). 48% (n = 801) had evidence of renal impairment on admission. Using a time-to-event analysis, reduced renal function was associated with increased in-hospital mortality (compared to eGFR ≥ 60 [Stage 1&2]): eGFR 45-59 [Stage 3a] aHR = 1.26 (95%CI 1.02-1.55); eGFR 30-44 [Stage 3b] aHR = 1.41 (95%CI 1.14-1.73); eGFR 1-29 [Stage 4&5] aHR = 1.42 (95%CI 1.13-1.80). In the co-primary outcome of 28-day mortality, mortality was associated with: Stage 3a adjusted odds ratio (aOR) = 1.18 (95%CI 0.88-1.58), Stage 3b aOR = 1.40 (95%CI 1.03-1.89); and Stage 4&5 aOR = 1.65 (95%CI 1.16-2.35). CONCLUSION: eGFR on admission is a good independent predictor of mortality in hospitalised older patients with COVID-19 population. We found evidence of a dose-response between reduced renal function and increased mortality.


Subject(s)
COVID-19 , Renal Insufficiency, Chronic , Aged , Cohort Studies , Female , Glomerular Filtration Rate , Humans , Male , Prognosis , Renal Insufficiency, Chronic/diagnosis , SARS-CoV-2
3.
EBioMedicine ; 76: 103817, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1632870

ABSTRACT

BACKGROUND: Kidney damage in COVID-19 patients has been of special concern. The association of acute kidney injury (AKI) with post-acute kidney function among COVID-19 survivors was not sufficiently elucidated. METHODS: An ambidirectional cohort study was conducted with enrollment of COVID-19 survivors discharged from hospital between Jan 7, and May 29, 2020. Study participants were invited to follow-up visits at 6 and 12 months after symptom onset. The primary outcome was percentage of estimated glomerular filtration rate (eGFR) decreased from acute phase (between symptom onset and hospital discharge) to follow-up, and secondary outcome was reduced renal function at follow-up. FINDINGS: In total, 1,734 study participants were included in this study. Median follow-up duration was 342.0 days (IQR, 223.0-358.0) after symptom onset. After multivariable adjustment, percentage of eGFR decreased from acute phase to follow-up was 8.30% (95% CI, 5.99-10.61) higher among AKI participants than those without AKI at acute phase. Participants with AKI had an odds ratio (OR) of 4.60 (95% CI, 2.10-10.08) for reduced renal function at follow-up. The percentage of eGFR decreased for participants with AKI stage 1, stage 2, and stage 3 was 6.02% (95% CI, 3.48-8.57), 15.99% (95% CI, 10.77-21.22), and 17.79% (95% CI, 9.14-26.43) higher compared with those without AKI, respectively. INTERPRETATION: AKI at acute phase of COVID-19 was closely related to the longitudinal decline and post-acute status of kidney function at nearly one-year after symptom onset. Earlier and more intense follow-up strategies on kidney function management could be beneficial to COVID-19 survivors. FUNDING: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS 2020-I2M-CoV19-005, 2018-I2M-1-003, and 2020-I2M-2-013); National Natural Science Foundation of China (82041011); National Key Research and Development Program of China (2018YFC1200102); Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis (2020ZX09201001).


Subject(s)
Acute Kidney Injury/diagnosis , COVID-19/pathology , Kidney/physiology , Acute Kidney Injury/etiology , Aged , COVID-19/complications , COVID-19/virology , Cohort Studies , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Male , Middle Aged , Odds Ratio , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index , Survivors
4.
Saudi J Kidney Dis Transpl ; 32(2): 377-386, 2021.
Article in English | MEDLINE | ID: covidwho-1622688

ABSTRACT

Coronavirus disease-2019 (COVID-19) is a global pandemic, also affecting Pakistan with its first case reported on February 26, 2020. Since then, it has been declared a pandemic by the World Health Organization. Our study aimed to evaluate the renal derangements associated with COVID-19 infection in our population. A retrospective, observational study was conducted to include all the admitted patients having COVID-19 positive, and evaluated those for derangements of renal function (n = 362). Out of the 362 patients, 229were admitted in the ward, 133 were in intensive care unit (ICU), 258 of them recovered, while 104 deaths reported. At admission, the renal profile was deranged in almost one-half of ICU admissions and mortalities which increased to two-third during the hospital stay, with around 80% of deaths reported with increased urea and creatinine levels. Among the deceased patients, around one-third of the mortalities developed renal profile derangements during the hospital stay although they were admitted with a normal renal profile. An estimated glomerular filtration rate showed a mean increase of 13.37 mL/min/1.73 m2 during the hospital stay of surviving patients, while a decline of 19.92 in nonsurviving patients. A hazard ratio of 3.293 (P <0.001) for admitting serum urea and 3.795 (P = 0.009) at discharge and for serum creatinine at 5.392 (P <0.001) on discharge was associated significantly with mortality. Kaplan-Meier plot showed a significant decline in days of survival with deranged urea and creatinine (P <0.001). The deranged renal function in COVID-19 patients is associated with an increased number of ICU admissions as well as mortalities.


Subject(s)
Acute Kidney Injury/etiology , COVID-19/complications , Hospital Mortality , Intensive Care Units/statistics & numerical data , SARS-CoV-2 , Acute Kidney Injury/mortality , Acute Kidney Injury/therapy , COVID-19/mortality , COVID-19 Nucleic Acid Testing , Creatinine/blood , Glomerular Filtration Rate , Humans , Incidence , Kidney Function Tests , Pakistan/epidemiology , Renal Dialysis , Retrospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Tertiary Healthcare , Urea/blood
5.
CPT Pharmacometrics Syst Pharmacol ; 11(1): 94-103, 2022 01.
Article in English | MEDLINE | ID: covidwho-1520276

ABSTRACT

Remdesivir, a prodrug of the nucleoside analog GS-441524, plays a key role in the treatment of coronavirus disease 2019 (COVID-19). However, owing to limited information on clinical trials and inexperienced clinical use, there is a lack of pharmacokinetic (PK) data in patients with COVID-19 with special characteristics. In this study, we aimed to measure serum GS-441524 concentrations and develop a population PK (PopPK) model. Remdesivir was administered at a 200 mg loading dose on the first day followed by 100 mg from day 2, based on the package insert, in patients with an estimated glomerular filtration rate (eGFR) greater than or equal to 30 ml/min. In total, 190 concentrations from 37 Japanese patients were used in the analysis. The GS-441524 trough concentrations were significantly higher in the eGFR less than 60 ml/min group than in the eGFR greater than or equal to 60 ml/min group. Extracorporeal membrane oxygenation in four patients hardly affected the total body clearance (CL) and volume of distribution (Vd ) of GS-441524. A one-compartment model described serum GS-441524 concentration data. The CL and Vd of GS-441524 were significantly affected by eGFR readjusted by individual body surface area and age, respectively. Simulations proposed a dose regimen of 200 mg on day 1 followed by 100 mg once every 2 days from day 2 in patients with an eGFR of 30 ml/min or less. In conclusion, we successfully established a PopPK model of GS-441524 using retrospectively obtained serum GS-441524 concentrations in Japanese patients with COVID-19, which would be helpful for optimal individualized therapy of remdesivir.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Adenosine/analogs & derivatives , Alanine/analogs & derivatives , COVID-19/drug therapy , Kidney Diseases/blood , Adenosine/blood , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/pharmacokinetics , Aged , Aged, 80 and over , Alanine/administration & dosage , Alanine/pharmacokinetics , Body Surface Area , COVID-19/blood , Drug Administration Schedule , Extracorporeal Membrane Oxygenation , Female , Glomerular Filtration Rate , Humans , Japan , Male , Middle Aged , Monte Carlo Method , Precision Medicine , Retrospective Studies
6.
BMC Nephrol ; 22(1): 381, 2021 11 13.
Article in English | MEDLINE | ID: covidwho-1515439

ABSTRACT

BACKGROUND: Kidney dysfunction occurs in severe COVID-19, and is a predictor of COVID-19 mortality. Whether kidney dysfunction causes severe COVID-19, and hence is a target of intervention, or whether it is a symptom, is unclear because conventional observational studies are open to confounding. To obtain unconfounded estimates, we used Mendelian randomization to examine the role of kidney function in severe COVID-19. METHODS: We used genome-wide significant, uncorrelated genetic variants to predict kidney function, in terms of estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), and then assessed whether people with genetically instrumented higher eGFR or lower UACR, an indication of better kidney function, had a lower risk of severe COVID-19 (8779 cases, 1,001,875 controls), using the largest available cohorts with extensive genotyping. For comprehensiveness, we also examined their role in COVID-19 hospitalization (24,274 cases, 2,061,529 controls) and all COVID-19 (1,12,612 cases, 2,474,079 controls). RESULTS: Genetically instrumented higher eGFR was associated with lower risk of severe COVID-19 (odds ratio (OR) 0.90, 95% confidence interval (CI) 0.83, 0.98) but not related to COVID-19 hospitalization or infection. Genetically instrumented UACR was not related to COVID-19. CONCLUSIONS: Kidney function appears to be one of the key targets for severe COVID-19 treatment. Use of available medications to improve kidney function, such as antihypertensives, might be beneficial for COVID-19 treatment, with relevance to drug repositioning.


Subject(s)
COVID-19/complications , COVID-19/genetics , Glomerular Filtration Rate/genetics , Kidney/physiopathology , Patient Acuity , Albuminuria/urine , Case-Control Studies , Creatinine/urine , Genetic Variation , Genome-Wide Association Study , Hospitalization , Humans , Mendelian Randomization Analysis , Risk Factors , SARS-CoV-2 , /genetics
7.
Inflammopharmacology ; 29(6): 1795-1805, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1505910

ABSTRACT

Hydroxychloroquine has attracted attention in the treatment of COVID-19. Many conflicting findings have been reported regarding the efficacy and safety of this drug, which has been used safely in the rheumatological diseases for years. However, these studies lacked measurement methods that allow accurate assessment of hydroxychloroquine and its metabolite levels. The aim of this study was to measure hydroxychloroquine and its metabolite levels in whole blood samples of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's syndrome (SS) and scleroderma (Scl) by a robust, simple and accurate validated tandem mass spectrometric method, and to investigate the relationship between these levels with drug-related adverse effects and disease activity scores. The validated LC-MS/MS method was applied to measure blood hydroxychloroquine and its metabolite levels of patients with RA, SLE, SS, Scl. Various haematological and biochemical parameters were measured with Beckman-Coulter AU 5800 and Beckman Coulter LH 780 analyzers, respectively. QTc intervals were calculated with Bazett's formula, and the patients were followed up by clinicians in terms of clinical findings and adverse effects. Hydroxychloroquine levels of patients were similar to previous studies. There was a negative correlation between disease activity scores and hydroxychloroquine levels, while the highest correlation was between QTc interval, creatinine and GFR levels with desethylchloroquine. Bidetylchloroquine had the highest correlation with RBC count and liver function tests. Our findings showed that hydroxychloroquine and its metabolite levels were associated with disease activity scores, renal, hepatic function, QTc prolongation, and hematological parameters.


Subject(s)
Antimalarials/adverse effects , Antimalarials/blood , COVID-19/complications , Connective Tissue Diseases/complications , Hydroxychloroquine/adverse effects , Hydroxychloroquine/blood , Adult , Aged , Chromatography, High Pressure Liquid , Creatinine/blood , Electrocardiography , Erythrocyte Count , Female , Glomerular Filtration Rate/drug effects , Humans , Kidney Function Tests , Liver Function Tests , Long QT Syndrome/chemically induced , Male , Middle Aged , Tandem Mass Spectrometry , Young Adult
8.
J Am Soc Nephrol ; 32(11): 2948-2957, 2021 11.
Article in English | MEDLINE | ID: covidwho-1496700

ABSTRACT

BACKGROUND: The COVID-19 pandemic caused major disruptions to care for patients with advanced CKD. METHODS: We investigated the incidence of documented ESKD, ESKD treatment modalities, changes in eGFR at dialysis initiation, and use of incident central venous catheters (CVCs) by epidemiologic week during the first half of 2020 compared with 2017-2019 historical trends, using Centers for Medicare and Medicaid Services data. We used Poisson and logistic regression for analyses of incidence and binary outcomes, respectively. RESULTS: Incidence of documented ESKD dropped dramatically in 2020 compared with the expected incidence, particularly during epidemiologic weeks 15-18 (April, incidence rate ratio [IRR], 0.75; 95% CI, 0.73 to 0.78). The decrease was most pronounced for individuals aged ≥75 years (IRR, 0.69; 95% CI, 0.66 to 0.73). Pre-emptive kidney transplantation decreased markedly during weeks 15-18 (IRR, 0.56; 95% CI, 0.46 to 0.67). Mean eGFR at dialysis initiation decreased by 0.33 ml/min per 1.73 m2 in weeks 19-22; non-Hispanic Black patients exhibited the largest decrease, at 0.61 ml/min per 1.73 m2. The odds of initiating dialysis with eGFR <10 ml/min per 1.73 m2 were highest during weeks 19-22 (May, OR, 1.14; 95% CI, 1.05 to 1.17), corresponding to an absolute increase of 2.9%. The odds of initiating peritoneal dialysis (versus hemodialysis) were 24% higher (OR, 1.24; 95% CI, 1.14 to 1.34) in weeks 11-14, an absolute increase of 2.3%. Initiation with a CVC increased by 3.3% (OR, 1.30; 95% CI, 1.20 to 1.41). CONCLUSIONS: During the first wave of the COVID-19 pandemic, the number of patients starting treatment for ESKD fell to a level not observed since 2011. Changes in documented ESKD incidence and other aspects of ESKD-related care may reflect differential access to care early in the pandemic.


Subject(s)
COVID-19/epidemiology , Kidney Failure, Chronic/epidemiology , Adolescent , Adult , Aged , Catheterization, Central Venous/statistics & numerical data , Glomerular Filtration Rate , Humans , Incidence , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/therapy , Kidney Transplantation/statistics & numerical data , Logistic Models , Middle Aged , Odds Ratio , Procedures and Techniques Utilization , Renal Dialysis/statistics & numerical data , United States , Young Adult
10.
J Am Soc Nephrol ; 32(3): 677-685, 2021 03.
Article in English | MEDLINE | ID: covidwho-1496676

ABSTRACT

BACKGROUND: Patients may accrue wait time for kidney transplantation when their eGFR is ≤20 ml/min. However, Black patients have faster progression of their kidney disease compared with White patients, which may lead to disparities in accruable time on the kidney transplant waitlist before dialysis initiation. METHODS: We compared differences in accruable wait time and transplant preparation by CKD-EPI estimating equations in Chronic Renal Insufficiency Cohort participants, on the basis of estimates of kidney function by creatinine (eGFRcr), cystatin C (eGFRcys), or both (eGFRcr-cys). We used Weibull accelerated failure time models to determine the association between race (non-Hispanic Black or non-Hispanic White) and time to ESKD from an eGFR of ≤20 ml/min per 1.73 m2. We then estimated how much higher the eGFR threshold for waitlisting would be required to achieve equity in accruable preemptive wait time for the two groups. RESULTS: By eGFRcr, 444 CRIC participants were eligible for waitlist registration, but the potential time between eGFR ≤20 ml/min per 1.73 m2 and ESKD was 32% shorter for Blacks versus Whites. By eGFRcys, 435 participants were eligible, and Blacks had 35% shorter potential wait time compared with Whites. By the eGFRcr-cys equation, 461 participants were eligible, and Blacks had a 31% shorter potential wait time than Whites. We estimated that registering Blacks on the waitlist as early as an eGFR of 24-25 ml/min per 1.73 m2 might improve racial equity in accruable wait time before ESKD onset. CONCLUSIONS: Policies allowing for waitlist registration at higher GFR levels for Black patients compared with White patients could theoretically attenuate disparities in accruable wait time and improve racial equity in transplant access.


Subject(s)
Glomerular Filtration Rate , Healthcare Disparities , Kidney Transplantation , Racism , Renal Insufficiency, Chronic/physiopathology , Renal Insufficiency, Chronic/surgery , Waiting Lists , African Americans , Aged , Cohort Studies , Disease Progression , Female , Health Policy , Healthcare Disparities/statistics & numerical data , Humans , Kidney Failure, Chronic/physiopathology , Kidney Failure, Chronic/surgery , Male , Middle Aged , Models, Statistical , Racism/statistics & numerical data , Time Factors , United States
11.
J Am Soc Nephrol ; 32(3): 708-722, 2021 03.
Article in English | MEDLINE | ID: covidwho-1496675

ABSTRACT

BACKGROUND: Late antibody-mediated rejection (ABMR) is a leading cause of transplant failure. Blocking IL-6 has been proposed as a promising therapeutic strategy. METHODS: We performed a phase 2 randomized pilot trial to evaluate the safety (primary endpoint) and efficacy (secondary endpoint analysis) of the anti-IL-6 antibody clazakizumab in late ABMR. The trial included 20 kidney transplant recipients with donor-specific, antibody-positive ABMR ≥365 days post-transplantation. Patients were randomized 1:1 to receive 25 mg clazakizumab or placebo (4-weekly subcutaneous injections) for 12 weeks (part A), followed by a 40-week open-label extension (part B), during which time all participants received clazakizumab. RESULTS: Five (25%) patients under active treatment developed serious infectious events, and two (10%) developed diverticular disease complications, leading to trial withdrawal. Those receiving clazakizumab displayed significantly decreased donor-specific antibodies and, on prolonged treatment, modulated rejection-related gene-expression patterns. In 18 patients, allograft biopsies after 51 weeks revealed a negative molecular ABMR score in seven (38.9%), disappearance of capillary C4d deposits in five (27.8%), and resolution of morphologic ABMR activity in four (22.2%). Although proteinuria remained stable, the mean eGFR decline during part A was slower with clazakizumab compared with placebo (-0.96; 95% confidence interval [95% CI], -1.96 to 0.03 versus -2.43; 95% CI, -3.40 to -1.46 ml/min per 1.73 m2 per month, respectively, P=0.04). During part B, the slope of eGFR decline for patients who were switched from placebo to clazakizumab improved and no longer differed significantly from patients initially allocated to clazakizumab. CONCLUSIONS: Although safety data indicate the need for careful patient selection and monitoring, our preliminary efficacy results suggest a potentially beneficial effect of clazakizumab on ABMR activity and progression.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Graft Rejection/therapy , Interleukin-6/antagonists & inhibitors , Kidney Transplantation/adverse effects , Adult , Allografts , Antibodies, Monoclonal, Humanized/adverse effects , Double-Blind Method , Female , Glomerular Filtration Rate , Graft Rejection/immunology , Graft Rejection/physiopathology , Humans , Infections/etiology , Interleukin-6/immunology , Isoantibodies/blood , Male , Middle Aged , Tissue Donors , Treatment Outcome , Young Adult
12.
J Am Soc Nephrol ; 32(2): 448-458, 2021 02.
Article in English | MEDLINE | ID: covidwho-1496669

ABSTRACT

BACKGROUND: Fine particulate matter (PM2.5) is an important environmental risk factor for cardiopulmonary diseases. However, the association between PM2.5 and risk of CKD remains under-recognized, especially in regions with high levels of PM2.5, such as China. METHODS: To explore the association between long-term exposure to ambient PM2.5 and CKD prevalence in China, we used data from the China National Survey of CKD, which included a representative sample of 47,204 adults. We estimated annual exposure to PM2.5 before the survey date at each participant's address, using a validated, satellite-based, spatiotemporal model with a 10 km×10 km resolution. Participants with eGFR <60 ml/min per 1.73 m2 or albuminuria were defined as having CKD. We used a logistic regression model to estimate the association and analyzed the influence of potential modifiers. RESULTS: The 2-year mean PM2.5 concentration was 57.4 µg/m3, with a range from 31.3 to 87.5 µg/m3. An increase of 10 µg/m3 in PM2.5 was positively associated with CKD prevalence (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.22 to 1.35) and albuminuria (OR, 1.39; 95% CI, 1.32 to 1.47). Effect modification indicated these associations were significantly stronger in urban areas compared with rural areas, in males compared with females, in participants aged <65 years compared with participants aged ≥65 years, and in participants without comorbid diseases compared with those with comorbidities. CONCLUSIONS: These findings regarding the relationship between long-term exposure to high ambient PM2.5 levels and CKD in the general Chinese population provide important evidence for policy makers and public health practices to reduce the CKD risk posed by this pollutant.


Subject(s)
Air Pollution/adverse effects , Albuminuria/epidemiology , Environmental Exposure/adverse effects , Particulate Matter/adverse effects , Renal Insufficiency, Chronic/epidemiology , Adult , Aged , Albuminuria/diagnosis , China , Female , Glomerular Filtration Rate , Humans , Logistic Models , Male , Middle Aged , Prevalence , Renal Insufficiency, Chronic/diagnosis , Risk Factors , Surveys and Questionnaires , Time Factors
13.
J Am Soc Nephrol ; 32(1): 115-126, 2021 01.
Article in English | MEDLINE | ID: covidwho-1496665

ABSTRACT

BACKGROUND: Although diabetic kidney disease is the leading cause of ESKD in the United States, identifying those patients who progress to ESKD is difficult. Efforts are under way to determine if plasma biomarkers can help identify these high-risk individuals. METHODS: In our case-cohort study of 894 Chronic Renal Insufficiency Cohort Study participants with diabetes and an eGFR of <60 ml/min per 1.73 m2 at baseline, participants were randomly selected for the subcohort; cases were those patients who developed progressive diabetic kidney disease (ESKD or 40% eGFR decline). Using a multiplex system, we assayed plasma biomarkers related to tubular injury, inflammation, and fibrosis (KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40). Weighted Cox regression models related biomarkers to progression of diabetic kidney disease, and mixed-effects models estimated biomarker relationships with rate of eGFR change. RESULTS: Median follow-up was 8.7 years. Higher concentrations of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were each associated with a greater risk of progression of diabetic kidney disease, even after adjustment for established clinical risk factors. After accounting for competing biomarkers, KIM-1, TNFR-2, and YKL-40 remained associated with progression of diabetic kidney disease; TNFR-2 had the highest risk (adjusted hazard ratio, 1.61; 95% CI, 1.15 to 2.26). KIM-1, TNFR-1, TNFR-2, and YKL-40 were associated with rate of eGFR decline. CONCLUSIONS: Higher plasma levels of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were associated with increased risk of progression of diabetic kidney disease; TNFR-2 had the highest risk after accounting for the other biomarkers. These findings validate previous literature on TNFR-1, TNFR-2, and KIM-1 in patients with prevalent CKD and provide new insights into the influence of suPAR and YKL-40 as plasma biomarkers that require validation.


Subject(s)
Biomarkers/blood , Diabetic Nephropathies/genetics , Kidney Failure, Chronic/genetics , Renal Insufficiency, Chronic/genetics , Adult , Aged , Chemokine CCL2/blood , Chitinase-3-Like Protein 1/blood , Cohort Studies , Diabetic Nephropathies/blood , Disease Progression , Female , Glomerular Filtration Rate , Hepatitis A Virus Cellular Receptor 1/blood , Humans , Kidney Failure, Chronic/blood , Male , Middle Aged , Phenotype , Prevalence , Receptors, Tumor Necrosis Factor, Type I/blood , Receptors, Tumor Necrosis Factor, Type II/blood , Receptors, Urokinase Plasminogen Activator/blood , Renal Insufficiency, Chronic/blood , Risk , Young Adult
14.
Biochim Biophys Acta Mol Basis Dis ; 1868(1): 166289, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1466061

ABSTRACT

To explore the recovery of renal function in severely ill coronavirus disease (COVID-19) survivors and determine the plasma metabolomic profile of patients with different renal outcomes 3 months after discharge, we included 89 severe COVID-19 survivors who had been discharged from Wuhan Union Hospital for 3 months. All patients had no underlying kidney disease before admission. At patient recruitment, renal function assessment, laboratory examination, chest computed tomography (CT) were performed. Liquid chromatography-mass spectrometry was used to detect metabolites in the plasma. We analyzed the longitudinally change in the estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin-c levels using the CKD-EPI equation and explored the metabolomic differences in patients with different eGFR change patterns from hospitalization to 3 months after discharge. Lung CT showed good recovery; however, the median eGFR significantly decreased at the 3-month follow-up. Among the 89 severely ill COVID-19 patients, 69 (77.5%) showed abnormal eGFR (<90 mL/min per 1.73 m2) at 3 months after discharge. Age (odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.08-1.47, p = 0.003), body mass index (OR = 1.97, 95% CI = 1.20-3.22, p = 0.007), and cystatin-c level (OR = 1.22, 95% CI = 1.07-1.39, p = 0.003) at discharge were independent risk factors for post-discharge abnormal eGFR. Plasma metabolomics at the 3-months follow-up revealed that ß-pseudouridine, uridine, and 2-(dimethylamino) guanosine levels gradually increased with an abnormal degree of eGFR. Moreover, the kynurenine pathway in tryptophan metabolism, vitamin B6 metabolism, cysteine and methionine metabolism, and arginine biosynthesis were also perturbed in survivors with abnormal eGFR.


Subject(s)
COVID-19/complications , COVID-19/virology , Energy Metabolism , Glomerular Filtration Rate , Kidney Diseases/etiology , Kidney Diseases/metabolism , SARS-CoV-2 , Aged , COVID-19/diagnosis , Comorbidity , Female , Humans , Kidney Diseases/diagnosis , Kidney Function Tests , Male , Metabolic Networks and Pathways , Metabolome , Metabolomics/methods , Middle Aged , Odds Ratio , Patient Discharge , Severity of Illness Index , Symptom Assessment
15.
Int J Clin Pract ; 75(12): e14938, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1450550

ABSTRACT

OBJECTIVE: The safety profile of favipiravir in patients with severe renal impairment has not been investigated and available data are insufficient. The study aimed to compare the incidence of favipiravir-associated adverse events amongst patients with varying renal function statuses. METHODS: Records of 921 patients who were hospitalised for COVID-19 and had received at least 5 days of favipiravir treatment were retrospectively evaluated and 228 patients were included in the study. Patients' age, sex, comorbidities, estimated glomerular filtration rate (eGFR) and haematological and biochemical values were recorded. The incidence of adverse events was compared with the age, sex, comorbidities and eGFR of the patients. RESULTS: The mean age of the patients was 59.3 ± 15.6 years, and 38.2% of the patients were women. One hundred and thirty-one (57.5%) patients had experienced adverse events. These adverse effects consisted of ALT elevation (35.5%), AST elevation (21.5%), anaemia (16.2%), hyperuricaemia (10.5%), hepatocellular injury (9.2%), neutropenia (3.5%) and thrombocytopenia (2.6%). The incidence of adverse events was not significantly different when patients had eGFR >60 mL/min/1.73 m2 or eGFR 30-60 mL/min/1.73 m2 (P > .05), but significantly increased when the eGFR dropped to <30 (P < .05). The differences seen with hyperuricaemia and anaemia were significant (P < .05). CONCLUSION: Even though favipiravir appeared to be well tolerated in the individuals with renal failure in this study, its use in this population remains a challenge that requires more research and analysis.


Subject(s)
Amides/therapeutic use , COVID-19 , Pyrazines/therapeutic use , Renal Insufficiency , Adult , Aged , Amides/adverse effects , COVID-19/drug therapy , Female , Glomerular Filtration Rate , Humans , Male , Middle Aged , Pyrazines/adverse effects , Retrospective Studies
16.
J Am Soc Nephrol ; 32(11): 2948-2957, 2021 11.
Article in English | MEDLINE | ID: covidwho-1430594

ABSTRACT

BACKGROUND: The COVID-19 pandemic caused major disruptions to care for patients with advanced CKD. METHODS: We investigated the incidence of documented ESKD, ESKD treatment modalities, changes in eGFR at dialysis initiation, and use of incident central venous catheters (CVCs) by epidemiologic week during the first half of 2020 compared with 2017-2019 historical trends, using Centers for Medicare and Medicaid Services data. We used Poisson and logistic regression for analyses of incidence and binary outcomes, respectively. RESULTS: Incidence of documented ESKD dropped dramatically in 2020 compared with the expected incidence, particularly during epidemiologic weeks 15-18 (April, incidence rate ratio [IRR], 0.75; 95% CI, 0.73 to 0.78). The decrease was most pronounced for individuals aged ≥75 years (IRR, 0.69; 95% CI, 0.66 to 0.73). Pre-emptive kidney transplantation decreased markedly during weeks 15-18 (IRR, 0.56; 95% CI, 0.46 to 0.67). Mean eGFR at dialysis initiation decreased by 0.33 ml/min per 1.73 m2 in weeks 19-22; non-Hispanic Black patients exhibited the largest decrease, at 0.61 ml/min per 1.73 m2. The odds of initiating dialysis with eGFR <10 ml/min per 1.73 m2 were highest during weeks 19-22 (May, OR, 1.14; 95% CI, 1.05 to 1.17), corresponding to an absolute increase of 2.9%. The odds of initiating peritoneal dialysis (versus hemodialysis) were 24% higher (OR, 1.24; 95% CI, 1.14 to 1.34) in weeks 11-14, an absolute increase of 2.3%. Initiation with a CVC increased by 3.3% (OR, 1.30; 95% CI, 1.20 to 1.41). CONCLUSIONS: During the first wave of the COVID-19 pandemic, the number of patients starting treatment for ESKD fell to a level not observed since 2011. Changes in documented ESKD incidence and other aspects of ESKD-related care may reflect differential access to care early in the pandemic.


Subject(s)
COVID-19/epidemiology , Kidney Failure, Chronic/epidemiology , Adolescent , Adult , Aged , Catheterization, Central Venous/statistics & numerical data , Glomerular Filtration Rate , Humans , Incidence , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/therapy , Kidney Transplantation/statistics & numerical data , Logistic Models , Middle Aged , Odds Ratio , Procedures and Techniques Utilization , Renal Dialysis/statistics & numerical data , United States , Young Adult
17.
J Am Soc Nephrol ; 32(11): 2851-2862, 2021 11.
Article in English | MEDLINE | ID: covidwho-1394649

ABSTRACT

BACKGROUND: COVID-19 is associated with increased risk of post-acute sequelae involving pulmonary and extrapulmonary organ systems-referred to as long COVID. However, a detailed assessment of kidney outcomes in long COVID is not yet available. METHODS: We built a cohort of 1,726,683 US Veterans identified from March 1, 2020 to March 15, 2021, including 89,216 patients who were 30-day survivors of COVID-19 and 1,637,467 non-infected controls. We examined risks of AKI, eGFR decline, ESKD, and major adverse kidney events (MAKE). MAKE was defined as eGFR decline ≥50%, ESKD, or all-cause mortality. We used inverse probability-weighted survival regression, adjusting for predefined demographic and health characteristics, and algorithmically selected high-dimensional covariates, including diagnoses, medications, and laboratory tests. Linear mixed models characterized intra-individual eGFR trajectory. RESULTS: Beyond the acute illness, 30-day survivors of COVID-19 exhibited a higher risk of AKI (aHR, 1.94; 95% CI, 1.86 to 2.04), eGFR decline ≥30% (aHR, 1.25; 95% CI, 1.14 to 1.37), eGFR decline ≥40% (aHR, 1.44; 95% CI, 1.37 to 1.51), eGFR decline ≥50% (aHR, 1.62; 95% CI, 1.51 to 1.74), ESKD (aHR, 2.96; 95% CI, 2.49 to 3.51), and MAKE (aHR, 1.66; 95% CI, 1.58 to 1.74). Increase in risks of post-acute kidney outcomes was graded according to the severity of the acute infection (whether patients were non-hospitalized, hospitalized, or admitted to intensive care). Compared with non-infected controls, 30-day survivors of COVID-19 exhibited excess eGFR decline (95% CI) of -3.26 (-3.58 to -2.94), -5.20 (-6.24 to -4.16), and -7.69 (-8.27 to -7.12) ml/min per 1.73 m2 per year, respectively, in non-hospitalized, hospitalized, and those admitted to intensive care during the acute phase of COVID-19 infection. CONCLUSIONS: Patients who survived COVID-19 exhibited increased risk of kidney outcomes in the post-acute phase of the disease. Post-acute COVID-19 care should include attention to kidney disease.


Subject(s)
COVID-19/complications , Kidney Diseases/epidemiology , Kidney Diseases/virology , Veterans/statistics & numerical data , Aged , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , Case-Control Studies , Cohort Studies , Critical Care , Female , Glomerular Filtration Rate , Hospitalization , Humans , Kidney Diseases/diagnosis , Male , Middle Aged , United States
18.
BMC Nephrol ; 22(1): 297, 2021 08 31.
Article in English | MEDLINE | ID: covidwho-1381255

ABSTRACT

BACKGROUND: Kidney disease and renal failure are associated with hospital deaths in patients with COVID - 19. We aimed to test if contrast enhancement affects short-term renal function in hospitalized COVID - 19 patients. METHODS: Plasma creatinine (P-creatinine) was measured on the day of computed tomography (CT) and 24 h, 48 h, and 4-10 days after CT. Contrast-enhanced (n = 142) and unenhanced (n = 24) groups were subdivided, based on estimated glomerular filtration rates (eGFR), > 60 and ≤ 60 ml/min/1.73 m2. Contrast-induced acute renal failure (CI-AKI) was defined as ≥27 µmol/L increase or a > 50% rise in P-creatinine from CT or initiation of renal replacement therapy during follow-up. Patients with renal replacement therapy were studied separately. We evaluated factors associated with a > 50% rise in P-creatinine at 48 h and at 4-10 days after contrast-enhanced CT. RESULTS: Median P-creatinine at 24-48 h and days 4-10 post-CT in patients with eGFR> 60 and eGFR≥30-60 in contrast-enhanced and unenhanced groups did not differ from basal values. CI-AKI was observed at 48 h and at 4-10 days post contrast administration in 24 and 36% (n = 5/14) of patients with eGFR≥30-60. Corresponding figures in the eGFR> 60 contrast-enhanced CT group were 5 and 5% respectively, (p < 0.037 and p < 0.001, Pearson χ2 test). In the former group, four of the five patients died within 30 days. Odds ratio analysis showed that an eGFR≥30-60 and 30-day mortality were associated with CK-AKI both at 48 h and 4-10 days after contrast-enhanced CT. CONCLUSION: Patients with COVID - 19 and eGFR≥30-60 had a high frequency of CK-AKI at 48 h and at 4-10 days after contrast administration, which was associated with increased 30-day mortality. For patients with eGFR≥30-60, we recommend strict indications are practiced for contrast-enhanced CT. Contrast-enhanced CT had a modest effect in patients with eGFR> 60.


Subject(s)
Acute Kidney Injury/chemically induced , COVID-19/complications , Contrast Media/adverse effects , Creatinine/blood , Iodine/adverse effects , Kidney/drug effects , Acute Kidney Injury/blood , Acute Kidney Injury/mortality , Acute Kidney Injury/therapy , Aged , COVID-19/blood , COVID-19/mortality , COVID-19/physiopathology , Female , Glomerular Filtration Rate , Humans , Kidney/diagnostic imaging , Kidney/physiopathology , Male , Middle Aged , Odds Ratio , Regression Analysis , Renal Replacement Therapy , Retrospective Studies , Time Factors , Tomography, X-Ray Computed
19.
Diabetes Metab Syndr ; 15(5): 102240, 2021.
Article in English | MEDLINE | ID: covidwho-1347578

ABSTRACT

AIMS: To evaluate calculated total plasma osmolality as a marker of outcome prediction, fluid and metabolic balance, thrombotic risk in severe COVID-19 patients. METHODS: Retrospective data of RT-PCR confirmed hospitalized severe COVID-19 patients (total: n = 175 patients, including diabetic subset: n = 102) were analyzed. Clinically applicable cut-offs were derived using receiver operating characteristic (ROC) curve analysis for calculated total osmolality, eGFR, and D-dimer, and their correlations were studied. RESULTS: Among 175 severe COVID-19 patients, a significant association with mortality was seen with respect to calculated total osmolality (p < 0.001), eGFR (p < 0.001), and D-dimer (p < 0.001). In the total cohort, applicable cut-offs based on ROC curve in predicting outcome were, for total osmolality 299 mosm/kg (area under the curve (AUC)-0.773, odds ratio (OR)-1.09), eGFR 61.5 ml/min/m2 (AUC-0.789, OR-0.96), D-dimer 5.13 (AUC-0.814, OR-2.65) respectively. In diabetic subset, the cut-offs for total osmolality were 298 mosm/kg (AUC-0.794, OR-1.12), eGFR 44.9 ml/min/m2 (AUC-0.774, OR-0.96) and D-dimer 1.59 (AUC-0.769, OR-1.52) respectively. CONCLUSIONS: Applicable cut-offs for calculated total plasma osmolality, eGFR, and D-dimer predicts clinical outcome in severe COVID-19 with and without diabetes. Correlation studies validated calculated total osmolality as a marker of the combined effect of fluid and metabolic imbalance, compromised renal function and hypercoagulability.


Subject(s)
COVID-19/diagnosis , Glomerular Filtration Rate/physiology , Plasma/chemistry , Biomarkers/blood , Blood Coagulation/physiology , COVID-19/blood , COVID-19/physiopathology , COVID-19/therapy , Cohort Studies , Diabetes Complications/blood , Diabetes Complications/diagnosis , Diabetes Complications/physiopathology , Diabetes Complications/therapy , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrin Fibrinogen Degradation Products/metabolism , Humans , India , Male , Middle Aged , Osmolar Concentration , Patient Admission/statistics & numerical data , Prognosis , Retrospective Studies , Risk Factors , Severity of Illness Index , Thrombosis/blood , Thrombosis/diagnosis , Thrombosis/etiology , Thrombosis/physiopathology , Water-Electrolyte Balance/physiology
20.
Nephrol Dial Transplant ; 36(1): 87-94, 2021 01 01.
Article in English | MEDLINE | ID: covidwho-1327386

ABSTRACT

Diabetes, hypertension and cardiovascular disease have been listed as risk factors for severe coronavirus disease 2019 (COVID-19) since the first report of the disease in January 2020. However, this report did not mention chronic kidney disease (CKD) nor did it provide information on the relevance of estimated glomerular filtration rate (eGFR) or albuminuria. As the disease spread across the globe, information on larger populations with greater granularity on risk factors emerged. The recently published OpenSAFELY project analysed factors associated with COVID-19 death in 17 million patients. The picture that arose differs significantly from initial reports. For example, hypertension is not an independent risk factor for COVID-19 death [adjusted hazard ratio (aHR) 0.89], but renal disease very much is. Dialysis (aHR 3.69), organ transplantation (aHR 3.53) and CKD (aHR 2.52 for patients with eGFR <30 mL/min/1.73 m2) represent three of the four comorbidities associated with the highest mortality risk from COVID-19. The risk associated with CKD Stages 4 and 5 is higher than the risk associated with diabetes mellitus (aHR range 1.31-1.95, depending upon glycaemic control) or chronic heart disease (aHR 1.17). In another recent publication, the Global Burden of Disease collaboration identified that worldwide, CKD is the most prevalent risk factor for severe COVID-19. Moreover, the distribution of risk factors for COVID-19 mortality appears to be different in patients with CKD when compared with the general population. The high prevalence of CKD in combination with the elevated risk of mortality from COVID-19 in CKD necessitates urgent action for this group of patients. This article defines essential action points (summarized in Box 1), among which is advocating the inclusion of CKD patients in clinical trials testing the efficacy of drugs and vaccines to prevent severe COVID-19.


Subject(s)
COVID-19/complications , COVID-19/epidemiology , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Albuminuria/epidemiology , Cardiovascular Diseases/mortality , Comorbidity , Critical Care , Diabetes Mellitus/epidemiology , Europe , Female , Glomerular Filtration Rate , Humans , Hypertension/complications , Male , Prevalence , Proportional Hazards Models , Registries , Renal Dialysis , Risk Factors , Societies, Medical
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