Altered kidney function induced by SARS-CoV-2 infection and acute kidney damage markers predict survival outcomes of COVID-19 patients: a prospective pilot study.

BACKGROUND: Literature with regard to coronavirus disease 2019 (COVID-19) associated morbidities and the risk factors for death are still emerging. In this study, we investigated the presence of kidney damage markers and their predictive value for survival among hospitalized subjects with COVID-19. METHODS: Forty-seven participants was included and grouped as: 'COVID-19 patients before treatment', 'COVID-19 patients after treatment', 'COVID-19 patients under treatment in intensive care unit (ICU)', and 'controls'. Kidney function tests and several kidney injury biomarkers were compared between the groups. Cumulative rates of death from COVID-19 were determined using the Kaplan-Meier method. The associations between covariates including kidney injury markers and death from COVID-19 were examined, as well. RESULTS: Serum creatinine and cystatin C levels, urine Kidney Injury Molecule-1 (KIM-1)/creatinine ratio, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), CKD-EPI cystatin C, and CKD-EPI creatinine-cystatin C levels demonstrated significant difference among the groups. The most significant difference was noted between the groups 'COVID-19 patients before treatment' and 'COVID-19 patients under treatment in ICU'. Advancing age, proteinuria, elevated serum cystatin C, and urine KIM-1/creatinine ratio were all significant univariate correlates of death (p < 0.05, for all). However, only elevated urine KIM-1/creatinine ratio retained significance in an age, sex, and comorbidities adjusted multivariable Cox regression (OR 6.11; 95% CI: 1.22-30.53; p = 0.02), whereas serum cystatin C showing only a statistically non-significant trend (OR 1.42; 95% CI: 0.00-2.52; p = 0.09). CONCLUSIONS: Our findings clearly demonstrated the acute kidney injury related to COVID-19. Moreover, urine KIM-1/creatinine ratio was associated with COVID-19 specific death.

Cystatin C, COVID-19 severity and mortality: a systematic review and meta-analysis.

BACKGROUND: Combined markers of renal dysfunction and inflammation, e.g., cystatin C, might assist with risk stratification and clinical decisions in patients with coronavirus disease 19 (COVID-19). We conducted a systematic review and meta-analysis with meta-regression of serum cystatin C in COVID-19. METHODS: We searched PubMed, Web of Science and Scopus, between January 2020 and February 2021, for studies reporting serum cystatin C concentrations, measures of clinical severity and survival outcomes in hospitalized COVID-19 patients (PROSPERO registration number: CRD42021245295). RESULTS: Thirteen studies in 2510 COVID-19 patients, 1972 with low severity or survivor status and 538 with high severity or non-survivor status during follow up, were included in the meta-analysis. The pooled results showed that serum cystatin C concentrations were higher in patients with high disease severity or non-survivor status (standard mean deviation, SMD, 1.71, 95% CI 0.95 to 2.46, p < 0.001). Extreme between-study heterogeneity was observed (I2 = 97.5%, p < 0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not substantially modified. The Begg's and Egger's t tests did not show publication bias. In meta-regression, the SMD of serum cystatin C was not associated with age, proportion of males, C-reactive protein, neutrophils, lymphocytes, aspartate aminotransferase, alanine aminotransferase, albumin, creatinine, creatine kinase-MB, lactate dehydrogenase, and proportion of patients with diabetes or hypertension. CONCLUSIONS: Higher concentrations of serum cystatin C were associated with higher COVID-19 severity and mortality.

Divergence between serum creatine and cystatin C in estimating glomerular filtration rate of critically ill COVID-19 patients.

BACKGROUND: The clinical use of serum creatine (sCr) and cystatin C (CysC) in kidney function evaluation of critically ill patients has been in continuous discussion. The difference between estimated glomerular filtration rate calculated by sCr (eGFRcr) and CysC (eGFRcysc) of critically ill COVID-19 patients were investigated in this study. METHODS: This is a retrospective, single-center study of critically ill patients with COVID-19 admitted in intensive care unit (ICU) at Wuhan, China. Control cases were moderate COVID-19 patients matched in age and sex at a ratio of 1:1. The eGFRcr and eGFRcysc were compared. The association between eGFR and death were analyzed in critically ill cases. The potential factors influencing the divergence between eGFRcr and eGFRcysc were explored. RESULTS: A total of 76 critically ill COVID-19 patients were concluded. The mean age was 64.5 ± 9.3 years. The eGFRcr (85.45 (IQR 60.58-99.23) ml/min/1.73m2) were much higher than eGFRcysc (60.6 (IQR 34.75-79.06) ml/min/1.73m2) at ICU admission. About 50 % of them showed eGFRcysc < 60 ml/min/1.73 m2 while 25% showed eGFRcr < 60 ml/min/1.73 m2 (χ2 = 10.133, p = 0.001). This divergence was not observed in moderate group. The potential factors influencing the divergence included serum interleukin-6 (IL-6), tumor necrosis factor (TNF-α) level as well as APACHEII, SOFA scores. Reduced eGFRcr (<60 mL/min/1.73 m2) was associated with death (HR = 1.939, 95%CI 1.078-3.489, p = 0.027). CONCLUSIONS: The eGFRcr was generally higher than eGFRcysc in critically ill COVID-19 cases with severe inflammatory state. The divergence might be affected by inflammatory condition and illness severity. Reduced eGFRcr predicted in-hospital death. In these patients, we advocate for caution when using eGFRcysc.

Association Between the Concentration and Rangeability of Cystatin C and Mortality of COVID-19 Patients With or Without Type 2 Diabetes Mellitus: A Retrospective Analysis.

Background: We investigated if the concentration and "rangeability" of cystatin C (CysC) influenced the prognosis of coronavirus disease 2019 (COVID-19) in patients suffering from, or not suffering from, type 2 diabetes mellitus (T2DM). Methods: A total of 675 T2DM patients and 572 non-T2DM patients were divided into "low" and "high" CysC groups and low and high CysC-rangeability groups according to serum CysC level and range of change of CysC level, respectively. Demographic characteristics, clinical data, and laboratory results of the four groups were analyzed. Results: COVID-19 patients with a high level and rangeability of CysC had more organ damage and a higher risk of death compared with those with a low level or low rangeability of CysC. Patients with a higher level and rangeability of CysC had more blood lymphocytes and higher levels of C-reactive protein, alanine aminotransferase, and aspartate aminotransferase. After adjustment for possible confounders, multivariate analysis revealed that CysC >0.93 mg/dL was significantly associated with the risk of heart failure (OR = 2.231, 95% CI: 1.125-5.312) and all-cause death (2.694, 1.161-6.252). CysC rangeability >0 was significantly associated with all-cause death (OR = 4.217, 95% CI: 1.953-9.106). These associations were stronger in patients suffering from T2DM than in those not suffering from T2DM. Conclusions: The level and rangeability of CysC may influence the prognosis of COVID-19. Special care and appropriate intervention should be undertaken in COVID-19 patients with an increased CysC level during hospitalization and follow-up, especially for those with T2DM.

Could urinary kidney injury molecule-1 be a good marker in subclinical acute kidney injury in mild to moderate COVID-19 infection?

PURPOSE: To evaluate urinary kidney injury molecule-1 (uKIM-1), which is a proximal tubule injury biomarker in subclinical acute kidney injury (AKI) that may occur in COVID-19 infection. METHODS: The study included proteinuric (n = 30) and non-proteinuric (n = 30) patients diagnosed with mild/moderate COVID-19 infection between March and September 2020 and healthy individuals as a control group (n = 20). The uKIM-1, serum creatinine, cystatin C, spot urine protein, creatinine, and albumin levels of the patients were evaluated again after an average of 21 days. RESULTS: The median (interquartile range) uKIM-1 level at the time of presentation was 246 (141-347) pg/mL in the proteinuric group, 83 (29-217) pg/mL in the non-proteinuric group, and 55 (21-123) pg/mL in the control group and significantly high in the proteinuric group than the others (p < 0.001). Creatinine and cystatin C were significantly higher in the proteinuric group than in the group without proteinuria, but none of the patients met the KDIGO-AKI criteria. uKIM-1 had a positive correlation with PCR, non-albumin proteinuria, creatinine, cystatin C, CRP, fibrinogen, LDH, and ferritin, and a negative correlation with eGFR and albumin (p < 0.05). In the multivariate regression analysis, non-albumin proteinuria (p = 0.048) and BUN (p = 0.034) were identified as independent factors predicting a high uKIM-1 level. After 21 ± 4 days, proteinuria regressed to normal levels in 20 (67%) patients in the proteinuric group. In addition, the uKIM-1 level, albuminuria, non-albumin proteinuria, and CRP significantly decreased. CONCLUSIONS: Our findings support that the kidney is one of the target organs of the COVID-19 and it may cause proximal tubule injury even in patients that do not present with AKI or critical/severe COVID-19 infection.

Neurological and psychiatric presentations associated with COVID-19.

The objective is to investigate coronavirus disease 2019 (COVID-19)-associated neurological and psychiatric effects and explore possible pathogenic mechanisms. This study included 77 patients with laboratory-confirmed COVID-19 in Wuhan, China. Neurological manifestations were evaluated by well-trained neurologists, psychologists, psychiatric presentations and biochemical changes were evaluated using the Generalized Anxiety Disorder 7-item scale, Patient Health Questionnaire-9, Brief Psychiatric Rating Scale, and electronic medical records. Eighteen (23.4%) patients presented with neurological symptoms. Patients with neurological presentations had higher urea nitrogen, cystatin C, and high-sensitivity C-reactive protein levels and lower basophil counts. Among them, patients with muscle involvement had higher urea nitrogen and cystatin C levels but lower basophil counts. In addition, patients with psychiatric presentations were older and had higher interleukin (IL)-6 and IL-10 levels and higher alkaline phosphatase, R-glutamate transferase, and urea nitrogen levels. Moreover, patients with anxiety had higher IL-6 and IL-10 levels than those without, and patients with moderate depression had higher CD8 + T cell counts and lower CD4 + /CD8 + ratios than other patients. This study indicates that the central nervous system may be influenced in patients with COVID-19, and the pathological mechanisms may be related to direct virus invasion of the central nervous system, infection-mediated overreaction of the immune system, and aberrant serum pro-inflammatory factors. In addition, basophils and cystatin C may also play important roles during these pathological processes. Our findings suggest that neurological and psychiatric presentations should be evaluated and managed in patients with COVID-19. Further studies are needed to investigate the underlying mechanisms.

Early predictors of acute kidney injury in COVID-19 patients.

AIM: This study aims to determine the frequency of COVID-19 related AKI and to identify the early predictors of AKI. METHODS: This study is a single-center, retrospective, observational study. Hospitalized COVID-19 patients between 24/03/2020 and 31/05/2020 were included in the study. All patients were evaluated for renal dysfunctions with urine dipstick, protein/creatinine ratio, albumin/creatinine ratio in spot urine, serum cystatin C, serum creatinine level on hospital admission, and 28th day of hospital admission. To assess the utility of these parameters to predict AKI, a receiver-operating characteristic curve was generated and the area under the curve (AUC) was calculated. RESULTS: 348 patients were included. The average incidence of AKI was 4.9% (n = 17). The incidence of AKI in mild, moderate and severe COVID-19 cases was 1.3% (n = 4), 9.0% (n = 3) and 76.9% (n = 10), respectively. Proteinuria was detected in 7.8% (n = 27) of patients with a urine dipstick test. In spot urine analysis, proteinuria was found in 20.1% (n = 70) of patients. The frequency of persistent proteinuria was 5.2% (n = 18). The AUC alue of serum cystatin C, D-dimer and albumin/creatinine ratio to predict COVID-19 related AKI were 0.96 (0.90 to 1.0), 0.94 (0.89-0.98), and 0.95 (0.91-0.98). CONCLUSION: In COVID-19 patients with normal serum creatinine levels on hospital admission, albuminuria, serum cystatin C and D-dimer levels may be an early predictor of COVID-19 related AKI and these patients should be monitored closely for AKI. Since the sample size in the AKI group was small, our study results should be confirmed with larger cohort studies.

Serum Cystatin C and Coronavirus Disease 2019: A Potential Inflammatory Biomarker in Predicting Critical Illness and Mortality for Adult Patients.

This study aimed at determining the relationship between baseline cystatin C levels and coronavirus disease 2019 (COVID-19) and investigating the potential prognostic value of serum cystatin C in adult patients with COVID-19. 481 patients with COVID-19 were consecutively included in this study from January 2, 2020, and followed up to April 15, 2020. All clinical and laboratory data of COVID-19 patients with definite outcomes were reviewed. For every measure, COVID-19 patients were grouped into quartiles according to the baseline levels of serum cystatin C. The highest cystatin C level was significantly related to more severe inflammatory conditions, worse organ dysfunction, and worse outcomes among patients with COVID-19 (P values < 0.05). In the adjusted logistic regression analyses, the highest cystatin C level and ln-transformed cystatin C levels were independently associated with the risks of developing critically ill COVID-19 and all-cause death either in overall patients or in patients without chronic kidney disease (P values < 0.05). As a potential inflammatory marker, increasing baseline levels of serum cystatin C might independently predict adverse outcomes for COVID-19 patients. Serum cystatin C could be routinely monitored during hospitalization, which showed clinical importance in prognosticating for adult patients with COVID-19.