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1.
J Diabetes Complications ; 37(6): 108478, 2023 06.
Article in English | MEDLINE | ID: covidwho-2323019

ABSTRACT

BACKGROUND: Diabetic kidney disease (DKD) increases the risk of cardiovascular (CV) complications, kidney disease progression, and mortality. We aimed to determine the incidence and risk of these outcomes according to DKD phenotype among the Jordanian population. METHODS: A total of 1172 type 2 diabetes mellitus patients with estimated glomerular filtration rates (eGFRs) of >30 ml/min/1.73 m2 were followed-up from 2019 to 2022. At baseline, patients were classified according to the presence of albuminuria (>30 mg/g creatinine) and reduced eGFR (<60 ml/min/1.73 m2) into four phenotypes: non-DKD (reference category), albuminuric DKD without decreased eGFR, non-albuminuric DKD with decreased eGFR, and albuminuric DKD with decreased eGFR. RESULTS: Mean follow-up was 2.9 ± 0.4 years. Overall, 147 patients (12.5 %) experienced CV events, while 61 (5.2 %) demonstrated kidney disease progression (eGFR: <30 ml/min/1.73 m2). The mortality rate was 4.0 %. Multivariable-adjusted risk for CV events and mortality was greatest for the albuminuric DKD with decreased eGFR group (hazard ratio [HR]: 1.45, 95 % confidence interval [CI]: 1.02-2.33 and HR: 6.36, 95 % CI: 2.98-13.59, respectively), with the risk increasing when adjusted for prior CV history (HR: 1.47, 95 % CI: 1.06-3.42 and HR: 6.70, 95 % CI: 2.70-16.60, respectively). Risk of a ≥40 % decline in eGFR was greatest for the albuminuric DKD with decreased eGFR group (HR: 3.45, 95 % CI: 1.74-6.85), followed by the albuminuric DKD without decreased eGFR group (HR: 1.6, 95 % CI: 1.06-2.75). CONCLUSION: Thus, patients with albuminuric DKD and decreased eGFR were at greater risk for poor CV, renal, and mortality outcomes compared to other phenotypes.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Cohort Studies , Jordan/epidemiology , Diabetic Nephropathies/etiology , Albuminuria/complications , Albuminuria/epidemiology , Disease Progression , Glomerular Filtration Rate
2.
Diabetes Obes Metab ; 25(6): 1758-1768, 2023 06.
Article in English | MEDLINE | ID: covidwho-2326828

ABSTRACT

AIM: To evaluate the albuminuria-lowering effect of dapagliflozin, exenatide, and the combination of dapagliflozin and exenatide in patients with type 2 diabetes and microalbuminuria or macroalbuminuria. METHODS: Participants with type 2 diabetes, an estimated glomerular filtration rate (eGFR) of more than 30 ml/min/1.73m2 and an urinary albumin: creatinine ratio (UACR) of more than 3.5 mg/mmol and 100 mg/mmol or less completed three 6-week treatment periods, during which dapagliflozin 10 mg/d, exenatide 2 mg/wk and both drugs combined were given in random order. The primary outcome was the percentage change in UACR. Secondary outcomes included blood pressure, HbA1c, body weight, extracellular volume, fractional lithium excretion and renal haemodynamic variables as determined by magnetic resonance imaging. RESULTS: We enrolled 20 patients, who completed 53 treatment periods in total. Mean percentage change in UACR from baseline was -21.9% (95% CI: -34.8% to -6.4%) during dapagliflozin versus -7.7% (95% CI: -23.5% to 11.2%) during exenatide and -26.0% (95% CI: -38.4% to -11.0%) during dapagliflozin-exenatide treatment. No correlation was observed in albuminuria responses between the different treatments. Numerically greater reductions in systolic blood pressure, body weight and eGFR were observed during dapagliflozin-exenatide treatment compared with dapagliflozin or exenatide alone. Renal blood flow and effective renal plasma flow (ERPF) did not significantly change with either treatment regimen. However, all but four and two patients in the dapagliflozin and dapagliflozin-exenatide groups, respectively, showed reductions in ERPF. The filtration fraction did not change during treatment with dapagliflozin or exenatide, and decreased during dapagliflozin-exenatide treatment (-1.6% [95% CI: -3.2% to -0.01%]; P = .048). CONCLUSIONS: In participants with type 2 diabetes and albuminuria, treatment with dapagliflozin, exenatide and dapagliflozin-exenatide reduced albuminuria, with a numerically larger reduction in the combined dapagliflozin-exenatide treatment group.


Subject(s)
Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Exenatide/therapeutic use , Exenatide/pharmacology , Albuminuria/urine , Benzhydryl Compounds/adverse effects , Glomerular Filtration Rate , Body Weight
3.
Scand J Clin Lab Invest ; 83(4): 251-257, 2023 07.
Article in English | MEDLINE | ID: covidwho-2319393

ABSTRACT

Acute kidney injury (AKI) is common in COVID-19 and is diagnosed using relative serum creatinine increase. Estimated GFR (eGFR) is a more accurate measure of glomerular filtration due to compensation for age and sex. Serum Cystatin-C, less affected by non-renal factors than creatinine, may further improve renal function estimation and add prognostic information. Our aim is to investigate the importance of a calculated eGFR in relation to creatinine as well as the value of Cystatin-C in patients with severe COVID-19. This study is a retrospective cohort study investigating levels and trends of routine laboratory parameters combined with clinical data from 286 consecutive patients with severe COVID-19 from Karolinska University Hospital. AKI developed in 38% of the patients and 15% were treated with hemodialysis. Mortality in the AKI group was 42% compared to 5% in the non-AKI group. At admission, eGFR, but not creatinine, was significantly associated with AKI development, need of intubation and mortality. Moreover, discrepant results between eGFR creatinine (eGFRCR) and eGFR Cystatin-C (eGFRCYS) was common in the ICU patients compared to non-ICU patients and related to outcome. In addition, we found that daily median Cystatin-C levels during the hospital stay were correlated to neutrophil count. eGFRCR was found to be an overall better prognostic marker than creatinine regarding AKI development and prognosis in severe COVID-19. Fulfillment of Shrunken pore syndrome criteria indicated a higher mortality risk. Cystatin-C may be related to neutrophil count, which could be a clue to the discrepant eGFR results.


Subject(s)
Acute Kidney Injury , COVID-19 , Renal Insufficiency, Chronic , Humans , Prognosis , Creatinine , Retrospective Studies , Cystatin C , Glomerular Filtration Rate , Acute Kidney Injury/diagnosis , Hospitals , Biomarkers
4.
Sci Rep ; 13(1): 5831, 2023 04 10.
Article in English | MEDLINE | ID: covidwho-2306192

ABSTRACT

Little is known about the prevalence of chronic kidney disease (CKD) during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to investigate the long-term trends in CKD prevalence from South Korea including the early pandemic. We used data from 108,152 Korean adults from 2007 to 2020 obtained from a representative longitudinal serial study. We defined CKD as a condition when the participant's estimated glomerular filtration rate was < 60 mL/min/1.73 m2, or one-time spot proteinuria was ≥ 1 +, and then examined the overall trends in the prevalence of CKD. Among the included adults (n = 80,010), the overall national prevalence of CKD was 6.2%. The trend slope gradually increased from 2007 to 2019, however, there was a sudden decrease in 2020 (2007-2010, 5.1% [95% confidence interval (CI) 4.7-5.5]; 2017-2019, 7.1% [95% CI 6.6-7.6]; pandemic period, 6.5% [95% CI 5.7-7.3]; and ßdiff, - 0.19; 95% CI - 0.24 to - 0.13). The prevalence of CKD among younger adults and those with poor medical utilization significantly decreased during the early pandemic. This study was the first large-scale study to investigate the longitudinal prevalence of CKD from 2007 to 2020. Further research is needed to fully understand the exact causes for this decline and to identify healthcare policy strategies for preventing and managing CKD.


Subject(s)
COVID-19 , Renal Insufficiency, Chronic , Adult , Humans , Prevalence , COVID-19/epidemiology , Renal Insufficiency, Chronic/epidemiology , Glomerular Filtration Rate , Republic of Korea/epidemiology , Risk Factors
5.
Eur Rev Med Pharmacol Sci ; 27(6): 2706-2714, 2023 03.
Article in English | MEDLINE | ID: covidwho-2267809

ABSTRACT

OBJECTIVE: In this study, we aimed to evaluate the kidney involvement assessed by estimated glomerular filtration rate (eGFR), the associations with specific clinical disease variables and laboratory findings, and the predictive role of eGFR on clinical outcomes of patients admitted with COVID-19 in Internal Medicine ward in the first wave. PATIENTS AND METHODS: Clinical data of 162 consecutive patients hospitalized in the University Hospital Policlinico Umberto I in Rome, Italy, between December 2020 to May 2021 were collected and retrospectively analyzed. RESULTS: The median eGFR was significantly lower in patients with worse outcomes than in patients with favorable outcomes [56.64 ml/min/1.73 m2 (IQR 32.27-89.73) vs. 83.39 ml/min/1.73 m2 (IQR 69.59-97.08), p<0.001]. Patients with eGFR < 60 ml/min/1.73 m2 (n=38) were significantly older compared to patients with normal eGFR [82 years (IQR 74-90) vs. 61 years (IQR 53-74), p<0.001] and they had fever less frequently [39.5% vs. 64.2%, p<0.01]. Kaplan-Meier curves demonstrated that overall survival was significantly shorter in patients with eGFR < 60 ml/min/1.73 m2 (p<0.001). In multivariate analysis, only eGFR < 60 ml/min/1.73 m2 [HR=2.915 (95% CI=1.110-7.659), p<0.05] and platelet to lymphocyte ratio [HR=1.004 (95% CI=1.002-1.007), p<0.01] showed a significant predictive value for death or transfer to intensive care unit (ICU). CONCLUSIONS: Kidney involvement on admission was an independent predictor for death or transfer to ICU among hospitalized COVID-19 patients. The presence of chronic kidney disease could be regarded as a relevant factor in risk stratification for COVID-19.


Subject(s)
COVID-19 , Renal Insufficiency, Chronic , Humans , Retrospective Studies , Risk Factors , Glomerular Filtration Rate , Kidney
6.
Blood Purif ; 52(2): 114-121, 2023.
Article in English | MEDLINE | ID: covidwho-2282468

ABSTRACT

INTRODUCTION: Cell-based therapies potentially delay the trajectory toward end-stage kidney disease (ESKD) in late stage 4 diabetic chronic kidney disease (DKD). We describe the trial design, baseline patient characteristics, and early results of an IRB-approved phase II multicenter clinical trial, utilizing Renal Autologous Cell Therapy (REACT) in adults with pre-ESKD due to type 2 DKD. The trial objectives were safety and tolerability of REACT by assessment of the procedure, product administration, and renal-specific adverse events in addition to evaluate the impact on renal function following injection. METHODS: Ten adults with an eGFR of 14-20 mL/min/1.73 m2 were enrolled in a single-arm open-label trial. Following a percutaneous kidney biopsy, an ex vivo expansion of selected renal cells that form the REACT was injected into the cortex of the biopsied kidney with CT image guidance. Each participant received two doses of the REACT product at 6-month intervals. A 6-month observation pre-trial was required to establish patients' "own" baseline and rate of DKD progression. RESULTS: Five men and 5 women underwent 19 REACT injections (1 participant received only one injection). Their baseline characteristics were as follows: 3 Hispanic/Latino, 7 non-Hispanic, 7 white; mean (SD) age: 58.9 years (5.22), BMI 35.8 (8.2), eGFR (sCR) 15.5 (2.72), eGFR (sCR + Cys-C) 17.7 (3.67) mL/min/1.73 m2, sCr 3.6 mg/mL (0.73), Cys-C 2.6 mg/mL (0.52), and log random UACR 7.9 mg/g (1.01). The pre- and post-injection eGFR slope was -6.5 mL/min/1.73 m2 and -3.9 mL/min/1.73 m2. No cell-related adverse events occurred, and two procedure-related hematomas required observation without transfusion or angiographic interventions. Dialysis was delayed a mean of 16 months (range 6-28 months). At 15 months, 2 patients (20%) have eGFR slope stability and have not commenced renal replacement therapy. CONCLUSION: Trials that include patients with an eGFR of <20 mL/min/1.73 m2 are uncommon, and none to date involve autologous homologous cell-based treatments. REACT has the potential to stabilize or delay dialysis in high-risk late stage 4 DKD.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Kidney Failure, Chronic , Renal Insufficiency, Chronic , Adult , Female , Humans , Male , Middle Aged , Diabetes Mellitus, Type 2/drug therapy , Glomerular Filtration Rate , Kidney/physiology , Renal Dialysis
7.
Trials ; 23(1): 1042, 2022 Dec 22.
Article in English | MEDLINE | ID: covidwho-2274174

ABSTRACT

BACKGROUND: Chronic active antibody-mediated rejection (AMR) is a major cause of graft loss with no approved drugs for its treatment. Currently, off-label regimens are used, reflecting the high unmet need for effective therapies based on well-controlled trials. Clazakizumab is a high-affinity, humanized monoclonal antibody that binds interleukin-6 and decreases donor-specific antibody (DSA) production and inflammation. Phase 2 pilot studies of clazakizumab in kidney transplant recipients with chronic active AMR suggest modulation of DSA, stabilization of glomerular filtration rate (GFR), and a manageable safety profile. We report the design of the Phase 3 IMAGINE study (NCT03744910) to evaluate the safety and efficacy of clazakizumab for the treatment of chronic active AMR. METHODS: IMAGINE is a multicenter, double-blind trial of approximately 350 kidney transplant recipients with chronic active AMR (Banff chronic glomerulopathy [cg] >0 with concurrent positive human leukocyte antigen DSA) randomized 1:1 to receive clazakizumab or placebo (12.5 mg subcutaneous once every 4 weeks). The event-driven trial design will follow patients until 221 occurrences of all-cause graft loss are observed, defined as return to dialysis, graft nephrectomy, re-transplantation, estimated GFR (eGFR) <15 mL/min/1.73m2, or death from any cause. A surrogate for graft loss (eGFR slope) will be assessed at 1 year based on prior modeling validation. Secondary endpoints will include measures of pharmacokinetics/pharmacodynamics. Recruitment is ongoing across North America, Europe, Asia, and Australia. DISCUSSION: IMAGINE represents the first Phase 3 clinical trial investigating the safety and efficacy of clazakizumab in kidney transplant recipients with chronic active AMR, and the largest placebo-controlled trial in this patient population. This trial includes prognostic biomarker enrichment and uniquely utilizes the eGFR slope at 1 year as a surrogate endpoint for graft loss, which may accelerate the approval of a novel therapy for patients at risk of graft loss. The findings of this study will be fundamental in helping to address the unmet need for novel therapies for chronic active AMR. TRIAL REGISTRATION: ClinicalTrials.gov NCT03744910 . Registered on November 19, 2018.


Subject(s)
Kidney Transplantation , Humans , Kidney Transplantation/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Double-Blind Method , Glomerular Filtration Rate , Graft Rejection/drug therapy , Graft Rejection/prevention & control , Isoantibodies , Graft Survival
8.
Curr Med Res Opin ; 39(4): 505-516, 2023 04.
Article in English | MEDLINE | ID: covidwho-2231242

ABSTRACT

OBJECTIVE: Type 2 diabetes mellitus (T2DM) and impaired kidney function are associated with a higher risk of poor outcomes of coronavirus disease 2019 (COVID-19). We conducted a retrospective study in hospitalized T2DM patients with COVID-19 to assess the association between in-hospital mortality and admission values of different hematological/biochemical parameters, including estimated glomerular filtration rate (eGFR), plasma glucose and C-peptide (the latter serving as a marker of beta-cell function). METHODS: The study included T2DM patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who were consecutively admitted to our Institution between 1 October 2020 and 1 April 2021. RESULTS: Patients (n = 74) were categorized into survivors (n = 55) and non-survivors (n = 19). Non-survivors exhibited significantly higher median white blood cell (WBC) count, D-dimer, neutrophil-to-lymphocyte ratio, high-sensitivity C-reactive protein (hsCRP), and procalcitonin levels, as well as significantly lower median serum 25-hydroxyvitamin D [25(OH)D] levels compared to survivors. Non-survivors exhibited significantly higher median admission plasma glucose (APG) values compared to survivors (210 vs. 166 mg/dL; p = .026). There was no statistically significant difference in median values of (random) plasma C-peptide between non-survivors and survivors (3.55 vs. 3.24 ng/mL; p = .906). A significantly higher percentage of patients with an eGFR < 60 mL/min/1.73 m2 was observed in the non-survivor group as compared to the survivor group (57.9% vs. 23.6%; p = .006). A multivariate analysis performed by a logistic regression model after adjusting for major confounders (age, sex, body mass index, major comorbidities) showed a significant inverse association between admission eGFR values and risk of in-hospital mortality (OR, 0.956; 95% CI, 0.931-0.983; p = .001). We also found a significant positive association between admission WBC count and risk of in-hospital mortality (OR, 1.210; 95% CI, 1.043-1.404; p = .011). CONCLUSIONS: Admission eGFR and WBC count predict in-hospital COVID-19 mortality among T2DM patients, independently of traditional risk factors, APG and random plasma C-peptide. Hospitalized patients with COVID-19 and comorbid T2DM associated with impaired kidney function at admission should be considered at high risk for adverse outcomes and death.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Humans , COVID-19/complications , SARS-CoV-2 , Diabetes Mellitus, Type 2/complications , C-Peptide , Retrospective Studies , Glomerular Filtration Rate , Hospital Mortality , Blood Glucose
9.
J Med Virol ; 95(2): e28477, 2023 02.
Article in English | MEDLINE | ID: covidwho-2173235

ABSTRACT

To analyze the dynamic changes of renal function longitudinally and investigate the cytokine profiles at 6 months in patients with Omicron COVID-19. Forty-seven patients with a proven diagnosis of Omicron COVID-19 from January to February 2022 attended a 6-month follow-up after discharge at Tianjin First Central Hospital. The demographic parameters, clinical features, and laboratory indexes were collected during hospitalization and 6 months after discharge. The serum cytokine levels at 6 months were also assessed. Patients were grouped according to with or without kidney involvement at admission. The levels of serum creatinine and estimated glomerular filtration rate (eGFR) were all normal both in the hospital and at follow-up. Whereas, compared with renal function in the hospital, serum creatinine levels at 6 months increased remarkably; meanwhile, eGFR decreased significantly in all patients. The serum levels of interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, and TNF-α and IFN-γ significantly decreased and TGF-ß remarkably increased in the kidney involvement group. The serum levels of IL-2 and IL-5 were positively correlated with age; contrarily, TGF-ß showed a negative correlation with aging. The younger was an independent risk factor of the higher TGF-ß levels. Omicron patients showed a decline in renal function at follow-up, reflecting the trend of CKD. Serum cytokine profiles were characterized with the majority of cytokines decreased and TGF-ß increased in the kidney involvement group; the latter may be used as a sign of CKD. The tendency of CKD is one of the manifestations of long COVID and deserves attention.


Subject(s)
COVID-19 , Renal Insufficiency, Chronic , Humans , Cytokines , Creatinine , Post-Acute COVID-19 Syndrome , Interleukin-5 , Transforming Growth Factor beta , Glomerular Filtration Rate , Kidney/physiology
10.
Int J Mol Sci ; 23(24)2022 Dec 10.
Article in English | MEDLINE | ID: covidwho-2155137

ABSTRACT

A selective decrease in the renal filtration of larger molecules is attributed to the shrinkage of glomerular pores, a condition termed Shrunken Pore Syndrome (SPS). SPS is associated with poor long-term prognosis. We studied SPS as a risk marker in a cohort of patients with COVID-19 treated in an intensive care unit. SPS was defined as a ratio < 0.7 when the estimated glomerular filtration rate (eGFR), determined by cystatin C, calculated by the Cystatin C Caucasian-Asian-Pediatric-Adult equation (CAPA), was divided by the eGFR determined by creatinine, calculated by the revised Lund−Malmö creatinine equation (LMR). Clinical data were prospectively collected. In total, SPS was present in 86 (24%) of 352 patients with COVID-19 on ICU admission. Patients with SPS had a higher BMI, Simplified Physiology Score (SAPS3), and had diabetes and/or hypertension more frequently than patients without SPS. Ninety-nine patients in the total cohort were women, 50 of whom had SPS. In dexamethasone-naïve patients, C-reactive protein (CRP ), TNF-alpha, and interleukin-6 did not differ between SPS and non-SPS patients. Demographic factors (gender, BMI) and illness severity (SAPS3) were independent predictors of SPS. Age and dexamethasone treatment did not affect the frequency of SPS after adjustments for age, sex, BMI, and acute severity. SPS is frequent in severely ill COVID-19 patients. Female gender was associated with a higher proportion of SPS. Demographic factors and illness severity were independent predictors of SPS.


Subject(s)
COVID-19 , Kidney , Female , Humans , Male , COVID-19/complications , Creatinine , Cystatin C , Dexamethasone/therapeutic use , Glomerular Filtration Rate/physiology , Syndrome , Kidney/physiopathology
11.
J Am Soc Nephrol ; 33(2): 442-453, 2022 02.
Article in English | MEDLINE | ID: covidwho-2141040

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) is highly prevalent in CKD and is associated with worse cardiovascular and kidney outcomes. Limited data exist on use of AF pharmacotherapies and AF-related procedures by CKD status. We examined a large "real-world" contemporary population with incident AF to study the association of CKD with management of AF. METHODS: We identified patients with newly diagnosed AF between 2010 and 2017 from two large, integrated health care delivery systems. eGFR (≥60, 45-59, 30-44, 15-29, <15 ml/min per 1.73 m2) was calculated from a minimum of two ambulatory serum creatinine measures separated by ≥90 days. AF medications and procedures were identified from electronic health records. We performed multivariable Fine-Gray subdistribution hazards regression to test the association of CKD severity with receipt of targeted AF therapies. RESULTS: Among 115,564 patients with incident AF, 34% had baseline CKD. In multivariable models, compared with those with eGFR >60 ml/min per 1.73 m2, patients with eGFR 30-44 (adjusted hazard ratio [aHR] 0.91; 95% CI, 0.99 to 0.93), 15-29 (aHR, 0.78; 95% CI, 0.75 to 0.82), and <15 ml/min per 1.73 m2 (aHR, 0.64; 95% CI, 0.58-0.70) had lower use of any AF therapy. Patients with eGFR 15-29 ml/min per 1.73 m2 had lower adjusted use of rate control agents (aHR, 0.61; 95% CI, 0.56 to 0.67), warfarin (aHR, 0.89; 95% CI, 0.84 to 0.94), and DOACs (aHR, 0.23; 95% CI, 0.19 to 0.27) compared with patients with eGFR >60 ml/min per 1.73 m2. These associations were even stronger for eGFR <15 ml/min per 1.73 m2. There was also a graded association between CKD severity and receipt of AF-related procedures (vs eGFR >60 ml/min per 1.73 m2): eGFR 30-44 ml/min per 1.73 (aHR, 0.78; 95% CI, 0.70 to 0.87), eGFR 15-29 ml/min per 1.73 m2 (aHR, 0.73; 95% CI, 0.61 to 0.88), and eGFR <15 ml/min per 1.73 m2 (aHR, 0.48; 95% CI, 0.31 to 0.74). CONCLUSIONS: In adults with newly diagnosed AF, CKD severity was associated with lower receipt of rate control agents, anticoagulation, and AF procedures. Additional data on efficacy and safety of AF therapies in CKD populations are needed to inform management strategies.


Subject(s)
Atrial Fibrillation/complications , Atrial Fibrillation/therapy , Renal Insufficiency, Chronic/complications , Adult , Aged , Aged, 80 and over , Anti-Arrhythmia Agents/therapeutic use , Anticoagulants/therapeutic use , Atrial Fibrillation/drug therapy , Cohort Studies , Female , Glomerular Filtration Rate , Humans , Male , Middle Aged , Multivariate Analysis , Renal Insufficiency, Chronic/physiopathology , Severity of Illness Index , Warfarin/therapeutic use
12.
Toxins (Basel) ; 14(10)2022 09 28.
Article in English | MEDLINE | ID: covidwho-2066492

ABSTRACT

Chronic kidney disease (CKD) patients are more susceptible to infections compared to the general population. SARS-CoV-2 virus pathology is characterized by a cytokine storm responsible for the systemic inflammation typical of the COVID-19 disease. Since CKD patients have a reduced renal clearance, we decided to investigate whether they accumulate harmful mediators during the COVID-19 disease. We conducted a retrospective study on 77 COVID-19 hospitalized subjects in the acute phase of the illness. Thirteen different cytokines were assessed in plasma collected upon hospitalization. The patients were divided into three groups according to their estimated glomerular filtration rate, eGFR &lt; 30 (n = 23), 30 &lt; eGFR &lt; 60 (n = 33), eGFR &gt; 60 mL/min (n = 21). We found that Tumor Necrosis Factor α and its receptors I and II, Interleukin-7, Leukemia Inhibitory Factor, FAS receptor, Chitinase 3-like I, and the Vascular Endothelial Growth Factor showed an increased accumulation that negatively correlate with eGFR. Moreover, non-survivor patients with an impaired kidney function have significantly more elevated levels of the same mediators. In conclusion, there is a tendency in COVID-19 ESRD patients to accumulate harmful cytokines. The accumulation seems to associate with mortality outcomes and may be due to reduced clearance but also to increased biosynthesis in most severe cases.


Subject(s)
COVID-19 , Chitinases , Renal Insufficiency, Chronic , Renal Insufficiency , Humans , Chemokines , fas Receptor , Glomerular Filtration Rate/physiology , Interleukin-7 , Leukemia Inhibitory Factor , Retrospective Studies , SARS-CoV-2 , Tumor Necrosis Factor-alpha , Vascular Endothelial Growth Factor A , Cytokines/immunology
13.
Nutrients ; 14(19)2022 Sep 29.
Article in English | MEDLINE | ID: covidwho-2066297

ABSTRACT

Several studies provide evidence that obesity is a significant risk factor for adverse outcomes in coronavirus disease 2019 (COVID-19). Altered renal function and disturbances in magnesium levels have been reported to play important pathophysiological roles in COVID-19. However, the relationship between obesity, renal function, circulating magnesium levels, and mortality in patients with COVID-19 remains unclear. In this retrospective cohort study, we characterized 390 hospitalized patients with COVID-19 that were categorized according to their body mass index (BMI). Patients were clinically characterized and biochemical parameters, renal function, and electrolyte markers measured upon admission. We found that in patients who died, BMI was associated with reduced estimated glomerular filtration rate (eGFR, Rho: -0.251, p = 0.001) and serum magnesium levels (Rho: -0.308, p < 0.0001). Multiple linear regression analyses showed that death was significantly associated with obesity (p = 0.001). The Cox model for obese patients showed that magnesium levels were associated with increased risk of death (hazard ratio: 0.213, 95% confidence interval: 0.077 to 0.586, p = 0.003). Thus, reduced renal function and lower magnesium levels were associated with increased mortality in obese COVID-19 patients. These results suggest that assessment of kidney function, including magnesium levels, may assist in developing effective treatment strategies to reduce mortality among obese COVID-19 patients.


Subject(s)
COVID-19 , Renal Insufficiency , COVID-19/complications , Glomerular Filtration Rate/physiology , Humans , Kidney/physiology , Magnesium , Obesity/complications , Renal Insufficiency/complications , Retrospective Studies , Risk Factors
14.
Curr Opin Crit Care ; 28(6): 630-637, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2051669

ABSTRACT

PURPOSE OF REVIEW: While it is now widely established acute kidney injury (AKI) is a common and important complication of coronavirus disease (COVID-19) disease, there is marked variability in its reported incidence and outcomes. This narrative review provides a mid-2022 summary of the latest epidemiological evidence on AKI in COVID-19. RECENT FINDINGS: Large observational studies and meta-analyses report an AKI incidence of 28-34% in all inpatients and 46-77% in intensive care unit (ICU). The incidence of more severe AKI requiring renal replacement therapy (RRT) in ICU appears to have declined over time, in data from England and Wales RRT use declined from 26% at the start of the pandemic to 14% in 2022. The majority of survivors apparently recover their kidney function by hospital discharge; however, these individuals appear to remain at increased risk of future AKI, estimated glomerular filtration rate (eGFR) decline and chronic kidney disease. Importantly even in the absence of overt AKI a significant proportion of survivors of COVID-19 hospitalisation had reduced eGFR on follow-up. SUMMARY: This review summarises the epidemiology, risk factors, outcomes and treatment of COVID-19-associated AKI across the global pandemic. In particular the long-term impact of COVID-19 disease on kidney health is uncertain and requires further characterisation.


Subject(s)
Acute Kidney Injury , COVID-19 , Humans , COVID-19/complications , Renal Replacement Therapy , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Intensive Care Units , Glomerular Filtration Rate , Risk Factors , Retrospective Studies
15.
BMC Nephrol ; 23(1): 304, 2022 09 05.
Article in English | MEDLINE | ID: covidwho-2038672

ABSTRACT

BACKGROUND: There is a growing literature on guidelines regarding Ramadan fasting for chronic kidney disease (CKD) patients. However, most studies only consider the impact of fasting on renal function. This study additionally aims to assess factors influencing Ramadan fasting in patients with CKD. METHOD: This is a prospective before and after cohort study. CKD patients were counseled regarding fasting and followed-up post-Ramadan for renal function status, actual fasting behavior, and other relevant outcomes. RESULTS: Of the 360 patients who attended the pre-Ramadan consultation, 306 were reachable after Ramadan of whom 55.3% were female. Of these 306 67.1% reported that they had fasted, 4.9% had attempted to fast but stopped, and 28% did not fast at all. Of these 74 has a post-fasting kidney test. Of the patients, 68.1% had stage 3A CKD, 21.7% had stage 3B, 7.9% stage 4, and only 2% stage 5. Of those who fasted, 11.1% had a drop in Glomerular Filtration Rate (eGFR) of 20% or more. Those who did not fast (16.7%) presented a similar drop. Conversely, among the few who attempted to fast and had to stop, half showed a drop in eGFR of more than 20%. In linear regression, fasting was not associated with post-Ramadan eGFR, when controlling for age and baseline eGRF. There were 17 (5.6%) significant events, including one death. More significant events occurred among the group who fasted some of Ramadan days, 26.7% of the subjects experienced an adverse event-while 4.7% of the group who did not fast had a significant adverse event compared to 4.4% among those who fasted all Ramadan. CONCLUSION: Fasting was not a significant determining factor in renal function deterioration in the study's population, nor did it have any significant association with adverse events.


Subject(s)
Diabetes Mellitus, Type 2 , Renal Insufficiency, Chronic , Cohort Studies , Diabetes Mellitus, Type 2/complications , Female , Glomerular Filtration Rate , Humans , Islam , Male , Prospective Studies
17.
PLoS One ; 17(3): e0266317, 2022.
Article in English | MEDLINE | ID: covidwho-1974296

ABSTRACT

BACKGROUND: The association between renal function and all-cause mortality in patients with hypertensive crisis remains unclear. We aimed to identify the impact of estimated glomerular filtration rate (eGFR) on all-cause mortality in patients with hypertensive crisis visiting the emergency department (ED). METHODS: This retrospective study included patients aged ≥18 years admitted to the ED between 2016 and 2019 for hypertensive crisis (systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg). They were classified into four groups according to the eGFR at admission to the ED: ≥90, 60-89, 30-59, and <30 mL/min/1.73 m2. RESULTS: Among the 4,821 patients, 46.7% and 5.8% had an eGFR of ≥90 and <30 mL/min/1.73 m2, respectively. Patients with lower eGFR were older and more likely to have comorbidities. The 3-year all-cause mortality rates were 7.7% and 41.9% in those with an eGFR ≥90 and <30 mL/min/1.73 m2, respectively. After adjusting for confounding variables, those with an eGFR of 30-59 (hazard ratio [HR], 1.93; 95% confidence interval [CI], 1.47-2.54) and <30 mL/min/1.73 m2 (HR, 2.35; 95% CI, 1.71-3.24) had significantly higher 3-year all-cause mortality risks than those with an eGFR of ≥90 mL/min/1.73 m2. Patients with an eGFR of 60-89 mL/min/1.73 m2 had a higher mortality (21.1%) than those with an eGFR of ≥90 mL/min/1.73 m2 (7.7%); however, the difference was not significant (HR, 1.21; 95% CI, 0.94-1.56). CONCLUSIONS: Renal impairment is common in patients with hypertensive crisis who visit the ED. A strong independent association was observed between decreased eGFR and all-cause mortality in these patients. eGFR provides useful prognostic information and permits the early identification of patients with hypertensive crisis with an increased mortality risk. Intensive treatment and follow-up strategies are needed for patients with a decreased eGFR who visit the ED.


Subject(s)
Emergency Service, Hospital , Adolescent , Adult , Blood Pressure , Glomerular Filtration Rate/physiology , Humans , Retrospective Studies , Risk Assessment
18.
Biomed Pharmacother ; 153: 113454, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1936097

ABSTRACT

BACKGROUND: Analysis of autopsy tissues obtained from patients who died from COVID-19 showed kidney tropism for SARS-COV-2, with COVID-19-related renal dysfunction representing an overlooked problem even in patients lacking previous history of chronic kidney disease. This study aimed to corroborate in a substantial sample of consecutive acutely ill COVID-19 hospitalized patients the efficacy of estimated GFR (eGFR), assessed at hospital admission, to identify acute renal function derangement and the predictive role of its association with in-hospital death and need for mechanical ventilation and admission to intensive care unit (ICU). METHODS: We retrospectively analyzed charts of 764 patients firstly admitted to regular medical wards (Division of Internal Medicine) for symptomatic COVID-19 between March 6th and May 30th, 2020 and between October 1st, 2020 and March 15th, 2021. eGFR values were calculated with the 2021 CKD-EPI formula and assessed at hospital admission and discharge. Baseline creatinine and GFR values were assessed by chart review of patients' medical records from hospital admittance data in the previous year. The primary outcome was in-hospital mortality, while ARDS development and need for non-invasive ventilation (NIV) and invasive mechanical ventilation (IMV) were the secondary outcomes. RESULTS: SARS-COV-2 infection was diagnosed in 764 patients admitted with COVID-19 symptoms. A total of 682 patients (age range 23-100 years) were considered for statistical analysis, 310 needed mechanical ventilation and 137 died. An eGFR value <60 mL/min/1.73 m2 was found in 208 patients, 181 met KDIGO AKI criteria; eGFR values at hospital admission were significantly lower with respect to both hospital discharge and baseline values (p < 0.001). In multivariate analysis, an eGFR value <60 mL/min/1.73 m2 was significantly associated with in-hospital mortality (OR 2.6, 1.7-4.8, p = 0.003); no association was found with both ARDS and need for mechanical ventilation. eGFR was non-inferior to both IL-6 serum levels and CALL Score in predicting in-hospital death (AUC 0.71, 0.68-0.74, p = 0.55). CONCLUSIONS: eGFR calculated at hospital admission correlated well with COVID-19-related kidney injury and eGFR values < 60 mL/min/1,73 m2 were independently associated with in-hospital mortality, but not with both ARDS or need for mechanical ventilation.


Subject(s)
Acute Kidney Injury , COVID-19 , Respiratory Distress Syndrome , Acute Kidney Injury/diagnosis , Acute Kidney Injury/therapy , Adult , Aged , Aged, 80 and over , COVID-19/therapy , Glomerular Filtration Rate , Hospital Mortality , Hospitals , Humans , Middle Aged , Retrospective Studies , Risk Factors , SARS-CoV-2 , Young Adult
19.
J Comput Assist Tomogr ; 46(5): 701-706, 2022.
Article in English | MEDLINE | ID: covidwho-1891220

ABSTRACT

PURPOSE: COVID-19 infection poses a significant risk of both renal injury and pulmonary embolism, producing a clinical challenge, as the criterion standard examination for pulmonary embolism, computed tomography angiography (CTA), requires the use of nephrotoxic iodinated contrast agents.Our investigation evaluated whether symptomatic COVID-19-positive patients without laboratory evidence of renal impairment are at increased risk for developing contrast-associated acute kidney injury (CA-AKI). METHOD: All COVID-19-positive patients undergoing noncontrast chest computed tomography and CTA at an apex tertiary medical center between March 1 and December 10, 2020, were retrospectively evaluated. A total of 258 renal-competent (estimated glomerular filtration rate >30) patients with baseline and 48- to 72-hour postexamination creatinine measurements were identified and analyzed for incidence of acute kidney injury (AKI) meeting the criteria for CA-AKI. RESULTS: Twenty-five of 191 patients undergoing CTA (13.1%) and 9 of the 67 undergoing noncontrast computed tomography (13.4%) experienced creatinine increases meeting the criteria for CA-AKI. Univariate and multivariate analyses accounting for known AKI risk factors revealed no correlation between iodinated contrast administration and the incidence AKI meeting the criteria for CA-AKI (univariable odds ratio, 0.97 [95% confidence interval, 0.43-2.20]; multivariable odds ratio, 0.97 [95% confidence interval, 0.40-2.36]). CONCLUSIONS: Renal-competent COVID-19 patients undergoing chest CTA may not have an increased risk of AKI. Additional studies are needed to confirm this preliminary finding.


Subject(s)
Acute Kidney Injury , COVID-19 , Pulmonary Embolism , Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , Angiography , Contrast Media/adverse effects , Creatinine , Glomerular Filtration Rate , Humans , Incidence , Kidney/diagnostic imaging , Retrospective Studies , Risk Factors
20.
Sci Rep ; 12(1): 8650, 2022 05 23.
Article in English | MEDLINE | ID: covidwho-1860396

ABSTRACT

COVID-19 is strongly influenced by age and comorbidities. Acute kidney injury (AKI) is a frequent finding in COVID-19 patients and seems to be associated to mortality and severity. On the other hand, the role of kidney dysfunction in COVID-19 is still debated. We performed a retrospective study in a cohort of 174 hospitalized COVID-19 patients in Italy from March 3rd to May 21st 2020, to investigate the role of kidney dysfunction on COVID-19 severity and mortality. Moreover, we examined in depth the relationship between kidney function, age, and progression of COVID-19, also using different equations to estimate the glomerular filtration rate (GFR). We performed logistic regressions, while a predictive analysis was made through a machine learning approach. AKI and death occurred respectively in 10.2% and 19.5%, in our population. The major risk factors for mortality in our cohort were age [adjusted HR, 6.2; 95% confidence interval (CI) 1.8-21.4] and AKI [3.36 (1.44-7.87)], while, in these relationships, GFR at baseline mitigated the role of age. The occurrence of AKI was influenced by baseline kidney function, D-dimer, procalcitonin and hypertension. Our predictive analysis for AKI and mortality reached an accuracy of ≥ 94% and ≥ 91%, respectively. Our study scales down the role of kidney function impairment on hospital admission , especially in elderly patients. BIS-1 formula demonstrated a worse performance to predict the outcomes in COVID-19 patients when compared with MDRD and CKD-EPI.


Subject(s)
Acute Kidney Injury , COVID-19 , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Aged , COVID-19/complications , Glomerular Filtration Rate , Humans , Kidney , Retrospective Studies , Risk Factors , SARS-CoV-2
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