Combined extracorporeal CO2 removal and renal replacement therapy in a pregnant patient with COVID-19: a case report.

Background. Pregnant women are at high risk of Coronavirus disease 2019 (COVID-19) complications, including acute respiratory distress syndrome. Currently, one of the cornerstones in the treatment of this condition is lung-protective ventilation (LPV) with low tidal volumes. However, the occurrence of hypercapnia may limit this ventilatory strategy. So, different extracorporeal CO2 removal (ECCO2R) procedures have been developed. ECCO2R comprises a variety of techniques, including low-flow and high-flow systems, that may be performed with dedicated devices or combined with continuous renal replacement therapy (CRRT). Case description. Here, we report a unique case of a pregnant patient affected by COVID-19 who required extracorporeal support for multiorgan failure. While on LPV, because of the concomitant hypercapnia and acute kidney injury, the patient was treated with an ECCO2R membrane inserted in series after a hemofilter in a CRRT platform. This combined treatment reducing hypercapnia allowed LPV maintenance at the same time while providing kidney replacement and ensuring maternal and fetal hemodynamic stability. Adverse effects consisted of minor bleeding episodes due to the anticoagulation required to maintain the extracorporeal circuit patency. The patient's pulmonary and kidney function progressively recovered, permitting the withdrawal of any extracorporeal treatment. At the 25th gestational week, the patient underwent spontaneous premature vaginal delivery because of placental abruption. She gave birth to an 800-gram female baby, who three days later died because of multiorgan failure related to extreme prematurity. Conclusions. This case supports using ECCO2R-CRRT combined treatment as a suitable approach in the management of complex conditions, such as pregnancy, even in the case of severe COVID-19.

Kidney Transplantation in a Patient Affected by Sickle Cell Trait: A Case Report and State-of-the-Art Review.

Chronic kidney disease (CKD) is a common feature of sickle cell disease (SCD). The awareness of the clinical presentation and renal involvement in patients affected by hemoglobinopathies is greatly needed. Patient management is particularly complex, especially with kidney transplantation. We, therefore, report the case of a 56-year-old patient affected by sickle cell trait who underwent kidney transplantation. This case will underline all the various challenges the nephrologist must face in this clinical setting and their management.

Extracorporeal Carbon Dioxide Removal: From Pathophysiology to Clinical Applications; Focus on Combined Continuous Renal Replacement Therapy.

Lung-protective ventilation (LPV) with low tidal volumes can significantly increase the survival of patients with acute respiratory distress syndrome (ARDS) by limiting ventilator-induced lung injuries. However, one of the main concerns regarding the use of LPV is the risk of developing hypercapnia and respiratory acidosis, which may limit the clinical application of this strategy. This is the reason why different extracorporeal CO2 removal (ECCO2R) techniques and devices have been developed. They include low-flow or high-flow systems that may be performed with dedicated platforms or, alternatively, combined with continuous renal replacement therapy (CRRT). ECCO2R has demonstrated effectiveness in controlling PaCO2 levels, thus allowing LPV in patients with ARDS from different causes, including those affected by Coronavirus disease 2019 (COVID-19). Similarly, the suitability and safety of combined ECCO2R and CRRT (ECCO2R-CRRT), which provides CO2 removal and kidney support simultaneously, have been reported in both retrospective and prospective studies. However, due to the complexity of ARDS patients and the limitations of current evidence, the actual impact of ECCO2R on patient outcome still remains to be defined. In this review, we discuss the main principles of ECCO2R and its clinical application in ARDS patients, in particular looking at clinical experiences of combined ECCO2R-CRRT treatments.

Longitudinal Cluster Analysis of Hemodialysis Patients with COVID-19 in the Pre-Vaccination Era.

Coronavirus disease 2019 (COVID-19) in hemodialysis patients (HD) is characterized by heterogeneity of clinical presentation and outcomes. To stratify patients, we collected clinical and laboratory data in two cohorts of HD patients at COVID-19 diagnosis and during the following 4 weeks. Baseline and longitudinal values were used to build a linear mixed effect model (LME) and define different clusters. The development of the LME model in the derivation cohort of 17 HD patients (66.7 ± 12.3 years, eight males) allowed the characterization of two clusters (cl1 and cl2). Patients in cl1 presented a prevalence of females, higher lymphocyte count, and lower levels of lactate dehydrogenase, C-reactive protein, and CD8 + T memory stem cells as a possible result of a milder inflammation. Then, this model was tested in an independent validation cohort of 30 HD patients (73.3 ± 16.3 years, 16 males) assigned to cl1 or cl2 (16 and 14 patients, respectively). The cluster comparison confirmed that cl1 presented a milder form of COVID-19 associated with reduced disease activity, hospitalization, mortality rate, and oxygen requirement. Clustering analysis on longitudinal data allowed patient stratification and identification of the patients at high risk of complications. This strategy could be suitable in different clinical settings.

The Evolving Scenario of COVID-19 in Hemodialysis Patients.

Coronavirus disease 2019 (COVID-19) is a rapidly changing disease. Therefore, in this study, to evaluate the evolution of COVID-19 in hemodialysis patients, we retrospectively compared patients affected by COVID-19 during the first pandemic waves of 2020 (from March to December 2020-Group 1) with patients with COVID-19 from September 2021 to February 2022 (Group 2) after the full completion of vaccination. Group 1 was constituted of 44 patients (69.3 ± 14.6 years), and Group 2 of 55 patients (67.4 ± 15.3 years). Among Group 2, 52 patients (95%) were vaccinated. Patients of Group 2, compared with Group 1, were more often asymptomatic (38 vs. 10%, p = 0.002) and reported less frequent fever and pulmonary involvement. At diagnosis, Group 2 showed a significantly higher number of lymphocytes and lower levels of circulating IL-6 (16 ± 13.3 vs. 41 ± 39.4 pg/mL, p = 0.002). Moreover, in Group 2, inflammatory parameters significantly improved after a few days from diagnosis. Patients of Group 2 presented a lower hospitalization rate (12.7 vs. 38%, p = 0.004), illness duration (18.8 ± 7.7 vs. 29.2 ± 19.5 days, p = 0.005), and mortality rate (5.4 vs. 25%, p = 0.008). Finally, responders to the vaccination (80% of vaccinated patients) compared with nonresponders showed a reduction in infection duration and hospitalization (5 vs. 40%, p = 0.018). In conclusion, we found that COVID-19 presentation and course in hemodialysis patients have improved over time after the implementation of vaccine campaigns. However, due to the evolving nature of the disease, active surveillance is necessary.

Impact of COVID-19 Pandemic on In-Hospital Acute Kidney Injury Epidemiology and Outcomes: A Retrospective Cohort Study

BACKGROUND AND AIMS Acute kidney injury (AKI) is a common complication in patients affected by coronavirus disease-19 (COVID-19) and its development is associated with high mortality [1]. However, it is also clear that the COVID-19 pandemic has effects on the management of diseases not directly related to COVID-19 [2]. In this study, we investigated the impact of the COVID-19 pandemic on general intrahospital AKI incidence and outcomes. METHOD We performed a retrospective cohort study comparing data on AKI epidemiology and outcomes of patients hospitalized from January 2016 to December 2019 (pre-COVID-19 period) and from January to December 2020 (COVID-19 period, including both SARS-CoV-2 negative and positive patients). AKI was defined and classified by evaluating the kinetics of intra-hospital creatinine (comparing the peak to the minimum serum creatinine level, considered as the basal value) [3]. The prevalence of chronic kidney disease (CKD) (i.e. eGFR < 60 mL/min) was calculated in patients with previous creatinine values available. Patients with CKD stage 4–5 (i.e. eGFR < 30 mL/min/1.73 m2) and with a length of hospital stay > 30 days were excluded. RESULTS A total of 51 681 patients during the pre-COVID-19 period and 10 ,062 during the COVID-19 period (9026 SARS-CoV-2 negative and 1036 SARS-CoV-2 positive patients) were analysed. Patients admitted in the COVID-19 period were significantly older, with a higher prevalence of males and a reduced prevalence of chronic conditions. In-hospital AKI incidence was 31.7% during the COVID-19 period (30.5% in SARS-CoV-2 negative patients and 42.2% in SARS-CoV-2 positive ones) as compared with 25.9% during the pre-COVID-19 period (P < .0001) (Fig. 1). Similarly, the COVID-19 period showed an increase in AKI stage 2–3 incidence both for AKI on CKD and for ‘de novo AKI’. In multivariate analysis, demographic characteristics, length of hospital stay, ICU admission, main comorbidities, basal sCr, admission period (pre-COVID-19 or COVID-19) and SARS-CoV-2 infection were significantly associated with the risk of AKI. In particular, the admission in the COVID-19 period increased the risk of AKI [OR 1.18, 95% confidence interval (95% CI) 1.12–2.25] regardless of SARS-CoV-2 infection. Moreover, we found that in the COVID-19 period, there was an increased number of patients admitted to ICU, accompanied by a significant increase in the length of hospital stay and intrahospital mortality. In the multivariate analysis, development of AKI, admission in the COVID-19 period and active SARS-CoV-2 infection remained significantly and independently associated with mortality risk (Fig. 2).Figure 1: Incidence and staging of in-hospital AKI. Comparison of AKI incidence and stages between patients hospitalized in the pre-COVID-19 period (2016–2019) versus COVID-19 period (2020). *P < 0.0001 versus pre-COVID-19;§ P < .0001 versus pre-COVID-19 and SARS-CoV-2 negative.Figure 2: Cox regression analyses for intra-hospital mortality in hospitalized patients between 2016 and 2020. CONCLUSION Overall, we found that AKI was more common and severe in the COVID-19 period, regardless of SARS-CoV-2 infection, when compared with patients admitted to the same hospital during the four years before the pandemic. So, we provide evidence that the COVID-19 pandemic has changed general in-hospital AKI epidemiology. These findings call attention to the need to adapt the resources dedicated to the prevention and management of the intra-hospital AKI in response to health emergencies.

Clinical Characteristics, Management and Outcomes of Critically ill COVID-19 Patients Undergoing CRRT: Comparison Between the First Two Pandemic Waves

BACKGROUND AND AIMS Acute kidney injury (AKI) is a common complication of coronavirus disease-19 (COVID-19), which, particularly in critically ill patients requiring continuous renal replacement therapy (CRRT), is associated with an elevated mortality risk [1, 2]. However, knowledge about COVID-19 pathogenesis and management is evolving, and clinical practice is changing rapidly. Here, we evaluated if this process had an impact on the management and outcome of AKI patients. METHODS We performed a retrospective observational study on critically ill adult COVID-19 patients who received CRRT in the intensive care unit (ICU) during the first two pandemic waves before the availability of COVID-19 vaccines: the first one from March to August 2020 (first) and the second one (second) from September to December 2020. RESULTS Overall, we considered 63 patients, aged 65 (60–69) years, 76.2% males. The main comorbidities were diabetes (DM), cardiovascular disease (CVD) and chronic kidney disease (CKD). Among them, 28 (44%) were in the first group and 35 (66%) in the second group. There were no significant differences in general characteristics, such as in comorbidities, except for a higher prevalence of CVD in the first group (Fig. 1). Lab examinations at ICU admission, including serum creatinine level (sCr), were not different between the two groups. While all patients required respiratory support, non-invasive ventilation was more prevalent in the second wave. Notably, during this period, decapneization combined with CRRT was introduced. Regarding drugs, we found that in the second group, hydroxychloroquine was abandoned, tocilizumab use was reduced and heparin administration significantly increased. The AKI time course was similar between the patients of the two waves (Fig. 2). There were no significant differences in CRRT techniques. However, in the second, the use of additional CRRT-devices, in particular adsorption-based filters, significantly increased. In most cases, citrate anticoagulation was used in both groups. Looking at the outcomes, we found no significant difference between the two waves. Indeed, 17 (60.2%) and 22 (62.8%) patients died in the ICU in the first and second groups, respectively. The length of ICU hospitalization, days on CRRT, invasive ventilation and DM were significantly related to overall mortality;time of ICU hospitalization was the only remaining significant at multivariate Cox regression. Overall, 21 (33%) patients survived hospitalization. At the 6 months after the discharge, 3 of them died, 3 were on HD and 15 were dialysis-free, even if 6 of them presented CKD.FIGURE 1: Clinical characteristics and ICU management of critically ill COVID-19 patients undergoing CRRT.FIGURE 2: Kidney function and management of critically ill COVID-19 patients undergoing CRRT. CONCLUSION Our data confirm the high complexity and mortality of COVID-19 patients undergoing CRRT. Comparing the first two pandemic waves, we found that the patients also presented similar characteristics in terms of renal function and AKI time course. Regarding treatments, we observed some significant modifications in the management of ventilation, drug administration and dialysis membranes, mainly because of the results of ongoing clinical trials. However, these changes did not impact patients’ outcomes. These data support the view that only game-change strategies, such as vaccination or infection-specific drugs, may impact the presentation and outcome of COVID-19 patients undergoing CRRT. Finally, patients surviving this condition deserve special attention in the follow-up.

Changes of Acute Kidney Injury Epidemiology during the COVID-19 Pandemic: A Retrospective Cohort Study.

To evaluate the impact of the Coronavirus Disease-19 (COVID-19) pandemic on the epidemiology of acute kidney injury (AKI) in hospitalized patients, we performed a retrospective cohort study comparing data of patients hospitalized from January 2016 to December 2019 (pre-COVID-19 period) and from January to December 2020 (COVID-19 period, including both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative and positive patients). AKI was classified by evaluating the kinetics of creatinine levels. A total of 51,681 patients during the pre-COVID-19 period and 10,062 during the COVID-19 period (9026 SARS-CoV-2-negative and 1036 SARS-CoV-2-positive) were analyzed. Patients admitted in the COVID-19 period were significantly older, with a higher prevalence of males. In-hospital AKI incidence was 31.7% during the COVID-19 period (30.5% in SARS-CoV-2-negative patients and 42.2% in SARS-CoV-2-positive ones) as compared to 25.9% during the pre-COVID-19 period (p < 0.0001). In the multivariate analysis, AKI development was independently associated with both SARS-CoV-2 infection and admission period. Moreover, evaluating the pre-admission estimated glomerular filtration rate (eGFR) we found that during the COVID-19 period, there was an increase in AKI stage 2-3 incidence both in patients with pre-admission eGFR < 60 mL/min/1.73 m2 and in those with eGFR ≥ 60 mL/min/1.73 m2 ("de novo" AKI). Similarly, clinical outcomes evaluated as intensive care unit admission, length of hospital stay, and mortality were significantly worse in patients admitted in the COVID-19 period. Additionally, in this case, the mortality was independently correlated with the admission during the COVID-19 period and SARS-CoV-2 infection. In conclusion, we found that during the COVID-19 pandemic, in-hospital AKI epidemiology has changed, not only for patients affected by COVID-19. These modifications underline the necessity to rethink AKI management during health emergencies.

Copy Number Variant Analysis and Genome-wide Association Study Identify Loci with Large Effect for Vesicoureteral Reflux.

BACKGROUND: Vesicoureteral reflux (VUR) is a common, familial genitourinary disorder, and a major cause of pediatric urinary tract infection (UTI) and kidney failure. The genetic basis of VUR is not well understood. METHODS: A diagnostic analysis sought rare, pathogenic copy number variant (CNV) disorders among 1737 patients with VUR. A GWAS was performed in 1395 patients and 5366 controls, of European ancestry. RESULTS: Altogether, 3% of VUR patients harbored an undiagnosed rare CNV disorder, such as the 1q21.1, 16p11.2, 22q11.21, and triple X syndromes ((OR, 3.12; 95% CI, 2.10 to 4.54; P=6.35×10-8) The GWAS identified three study-wide significant and five suggestive loci with large effects (ORs, 1.41-6.9), containing canonical developmental genes expressed in the developing urinary tract (WDPCP, OTX1, BMP5, VANGL1, and WNT5A). In particular, 3.3% of VUR patients were homozygous for an intronic variant in WDPCP (rs13013890; OR, 3.65; 95% CI, 2.39 to 5.56; P=1.86×10-9). This locus was associated with multiple genitourinary phenotypes in the UK Biobank and eMERGE studies. Analysis of Wnt5a mutant mice confirmed the role of Wnt5a signaling in bladder and ureteric morphogenesis. CONCLUSIONS: These data demonstrate the genetic heterogeneity of VUR. Altogether, 6% of patients with VUR harbored a rare CNV or a common variant genotype conferring an OR >3. Identification of these genetic risk factors has multiple implications for clinical care and for analysis of outcomes in VUR.

Volume Balance in Chronic Kidney Disease: Evaluation Methodologies and Innovation Opportunities.

BACKGROUND: Patients affected by chronic kidney disease are at a risk of cardiovascular morbidity and mortality. Body fluids unbalance is one of the main characteristics of this condition, as fluid overload is highly prevalent in patients affected by the cardiorenal syndrome. SUMMARY: We describe the state of the art and new insights into body volume evaluation. The mechanisms behind fluid balance are often complex, mainly because of the interplay of multiple regulatory systems. Consequently, its management may be challenging in clinical practice and even more so out-of-hospital. Availability of novel technologies offer new opportunities to improve the quality of care and patients' outcome. Development and validation of new technologies could provide new tools to reduce costs for the healthcare system, promote personalized medicine, and boost home care. Due to the current COVID-19 pandemic, a proper monitoring of chronic patients suffering from fluid unbalances is extremely relevant. Key Message: We discuss the main mechanisms responsible for fluid overload in different clinical contexts, including hemodialysis, peritoneal dialysis, and heart failure, emphasizing the potential impact provided by the implementation of the new technologies.

Effects of Different Dialysis Strategies on Inflammatory Cytokine Profile in Maintenance Hemodialysis Patients with COVID-19: A Randomized Trial.

Uncontrolled inflammation plays a relevant role in the pathogenesis of coronavirus disease-19 (COVID-19). Here, we studied the time trend of inflammatory markers in a population of hemodialysis (HD) patients affected by COVID-19, undergoing two different dialysis approaches. In a prospective study, thirty-one maintenance HD patients with COVID-19 were randomized to expanded HD (HDx), performed using a medium cut-off membrane, or standard treatment using a protein-leaking dialyzer (PLD). Circulating levels of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), soluble TLR4 (sTLR4), and interferon-gamma (IFN-γ), were collected at diagnosis, and one and two weeks after. Compared with 14 non-infected HD patients, COVID-19 patients showed lymphopenia and higher ferritin and lactate dehydrogenase levels. Moreover, COVID-19 patients had higher levels of IL-10 (15.2 (12.5) vs. 1.2 (1.4) pg/mL, p = 0.02). Twenty-nine patients were randomized to HDx (n = 15) or PLD (n = 14). After a single treatment, IL-8 showed a significant reduction in both groups, whereas IL-10 decreased only in HDx. All over the study, there were no significant modifications in circulating cytokine levels between the two groups, except for a parallel increase of IL-8 and IL-10 at one week control in the HDx group. No correlations were found between cytokine levels and clinical outcomes. In maintenance HD patients, COVID-19 is not related to a sustained inflammatory response. Therefore, modulation of inflammation seems not to be a suitable therapeutic target in this specific population.

Kidney disease and all-cause mortality in patients with COVID-19 hospitalized in Genoa, Northern Italy.

BACKGROUND: The prevalence of kidney involvement during SARS-CoV-2 infection has been reported to be high. Nevertheless, data are lacking about the determinants of acute kidney injury (AKI) and the combined effect of chronic kidney disease (CKD) and AKI in COVID-19 patients. METHODS: We collected data on patient demographics, comorbidities, chronic medications, vital signs, baseline laboratory test results and in-hospital treatment in patients with COVID-19 consecutively admitted to our Institution. Chronic kidney disease was defined as eGFR < 60 mL/min per 1.73 m2 or proteinuria at urinalysis within 180 days prior to hospital admission. AKI was defined according to KDIGO criteria. The primary and secondary outcomes were the development of AKI and death. RESULTS: Of 777 patients eligible for the study, acute kidney injury developed in 176 (22.6%). Of these, 79 (45%) showed an acute worsening of a preexisting CKD, and 21 (12%) required kidney replacement therapy. Independent associates of AKI were chronic kidney disease, C-reactive protein (CRP) and ventilation support. Among patients with acute kidney injury, 111 died (63%) and its occurrence increased the risk of death by 60% (HR 1.60 [95% IC 1.21-2.49] p = 0.002) independently of potential confounding factors including hypertension, preexisting kidney damage, and comorbidities. Patients with AKI showed a significantly higher rate of deaths attributed to bleeding compared to CKD and the whole population (7.5 vs 1.5 vs 3.5%, respectively). CONCLUSION: Awareness of kidney function, both preexisting CKD and development of acute kidney injury, may help to identify those patients at increased risk of death.