The 370 Da inhibitor of the sodium pump in the plasma of haemodialysis patients

Background: Previous studies have shown that a molecule of mass 370 Da that inhibits the sodium pump can be extracted from human placentas and from the concentrated plasma or ultrafiltrate of volume-expanded patients. Aim: To study the abundance of the 370 Da molecule and its changes across dialysis in a population of patients with renal failure treated by haemodialysis. Methods: 4 mL pre- and post-dialysis blood samples (2 mL plasma) were taken from patients receiving intermittent haemodialysis and analysed by high performance liquid chromatography (HPLC) coupled to high sensitivity mass spectrometry. Results: In over half the study population, the 370 Da molecule was present in an abundance that exceeded the limit of quantitation. Most patients experienced a marked fall in the abundance of the molecule over a haemodiafiltration (HDF) session, though exceptions were seen in two individuals both of whom showed clear evidence for the presence of two structural isomers of the 370 Da molecule. Conclusions: Advanced renal failure is frequently accompanied by an increased abundance of a 370 Da inhibitor of the sodium pump and that abundance is strongly impacted by haemodialysis. The technique described here could readily be applied to other clinical situations where sodium pump inhibition might be anticipated, such as hypertension, pregnancy and fetal medicine and thereby lead to a better understanding of the physiology and patho-physiology of these conditions.

Management and outcome assessment of pregnancy-related acute kidney injury in Western India: a single centred, prospective, observational study

Background: Pregnancy-related acute kidney injury (PRAKI) remains a large public health problem, with decreasing incidences in developing countries like India. However, some single centred studies from United States and Canada revealed an increasing incidence of PRAKI. This increase could be due to higher rates of hypertensive disorders of pregnancy.Methods: To assess the management and outcome of PRAKI. In this prospective, observational study, total 1021 cases of acute renal failure were observed.Results: 96 (9.4%) were of obstetric origin and enrolled as per inclusion criteria. Regarding management of PRAKI, 78 out of 96 (81.25%) required haemodialysis. 67 (69.79%) among them were managed with intermittent haemodialysis (IHD) while 10 (10.41%) who had hypotension at presentation were dialysed with slow, low efficiency dialysis (SLED). Continuous renal replacement therapy (CRRT) was done in 1 (10.4%) patient. Maternal mortality in this PRAKI study was 19 of 96 patients (19.79%). Sepsis accounted for 52.63% of deaths. Foetal death was observed in 58 out of 96 patients (60.41%) comprising of intrauterine death in 55 (55.29%) and abortion in 3 (3.13%) patients. 38 of 96 (39.58%) patients gave birth to live born child out of which 27 were at full term and 11 were preterm.Conclusions: In order to avoid further increase in PRAKI in India, treating obstetrician should remain aware of management and outcome of PRAKI. The better awareness of diagnosis and management protocols will ultimately lead to further reduction in prevalence of PRAKI in our country.

Managing valproic acid toxicity-related hyperammonaemia: an unpredicted course

A 20-year-old woman presented following an intentional overdose of valproic acid. Use of valproic acid, either acute or chronic, can result in hyperammonaemia. Mild hyperammonaemia with chronic use is mostly asymptomatic but can also present with concern for encephalopathy. Acute valproic acid toxicity results in significant hyperammonaemia, which can contribute to encephalopathy. Levocarnitine is the treatment of choice in valproic acid toxicity-related hyperammonaemia. For severe cases of encephalopathy, intermittent haemodialysis can also be considered. To our knowledge, this is the first case report to clearly show symptom relapse and hyperammonaemia after discontinuing levocarnitine. We recommend levocarnitine therapy for at least 72 hours, followed by an additional 24 hours of monitoring for symptom relapse and hyperammonaemia after levocarnitine discontinuation.

Kinetics of Plasma Cytokines During and After Two Different Modalities of Extracorporeal Blood Purification in Critically Ill COVID-19 Patients

Cytokine storm syndrome (CSS) has been documented in coronavirus disease 2019 (COVID-19) since the first reports of this disease. In the absence of vaccines or direct therapy for COVID-19, extracorporeal blood treatment (EBT) could represent an option for the removal of cytokines and may be beneficial to improve the clinical outcome of critically ill patients. Intermittent haemodialysis (IHD), using high flux (HF) or high cut-off membranes, and continuous renal replacement therapy (CRRT) could be used for blood purification in COVID-19 patients with CSS. To the best of our knowledge, cytokine kinetics during and after different types of EBT on COVID-19 patients have never been studied. In this study, we describe cytokine variation and removal during and after IHD and CRRT in COVID-19 patients with acute kidney injury (AKI). Methods: Patients with COVID-19-related AKI according to Kidney Disease Improving Global Outcomes (KDIGO) criteria and admitted at Intensive Care Unit (ICU) were studied. Blood samples were collected at the start and end of both IHD using HF membranes (10 patients) and continuous venovenous haemodiafiltration (CVVHDF: 10 patients) in two sessions for measuring 13 different plasma interleukins and calculating the cytokine removal rate. Results: We evaluated cytokine removal in patients with COVID-19-related AKI undergoing either prolonged IHD (10 patients) or CRRT (CVVHDF: 10 patients). There was no difference between the IHD and CVVHDF groups regarding mechanical ventilation, vasoactive drug use, age or prognostic scores. Patients treated by CRRT presented higher levels of IL-2 and IL-8 than patients treated by prolonged IHD at the start of dialysis. Cytokine removal ranged from 9–78%. Patients treated by CRRT presented higher cytokine removal rates than those treated by prolonged IHD for IL-2, IL-6 IL-8, IP-10 and TNF. The removal rates of IL-4, IL-10, IL-1β, IL-17A, IFN, MCP-1 and free active TGF-B1 were similar in the two groups. After one session of CVVHDF (24 h) the IL-2 and IL-1β levels did not vary significantly, whereas IL-4, IL-6, IL-8, IL-10, IL-17A, TNF, IFN, IP-10, MCP-1, IL-12p70 and free active TGF-B1 decreased by 33.8–76%, and this decrease was maintained over the next 24 h. In the prolonged IHD groups, IL-2, IL-6, TNF, IP-10 and IL-1β levels did not decrease significantly whereas IL-4, IL-8, IL-10, IL-17A, IFN, MCP-1, IL-12p70 and free active TGF-B1 decreased by 21.8–72%. However, all cytokine levels returned to their initial values after 24 h, despite their removal. Conclusions: Cytokine removal is lower using prolonged IHD with HF membranes than by using CVVHDF, and IHD allows a transient and selective decrease in cytokines that can be correlated with mortality during CSS-related COVID-19.

Heart Rate Variability and Electrocardiographic Parameters Predictive of Arrhythmias in Dogs with Stage IV Chronic Kidney Disease Undergoing Intermittent Haemodialysis

Intermittent haemodialysis (IHD) is used in dogs with chronic kidney disease (CKD) to reduce azotaemia. Monitoring the cardiovascular system plays an important role in this treatment to detect cardiovascular repercussions. Heart rate variability (HRV) and dispersions of the QT interval and P wave are important markers for mortality risk in humans. This study aimed to describe the time-domain and frequency-domain heart rate variability indexes, P and QT dispersions and electrocardiographic alterations observed in dogs with Stage IV CKD undergoing IHD. Thirty dogs of both sexes, of varying ages and breeds, and weighing between 15 and 30 kg were used. Animals were divided into three groups, control (10 healthy dogs), clinical treatment (10 dogs with CKD IV submitted to clinical treatment twice a week) and IHD (10 dogs with CKD IV submitted to clinical treatment and to dialysis treatment with intermittent haemodialysis twice a week). Clinical, laboratory, HRV indexes and electrocardiographic parameters, as well as QT and P-wave dispersions, were assessed in both CKD groups, prior to and after the end of each clinical treatment/IHD session during the first three sessions. Dogs with CKD IV undergoing IHD had clinically important electrolyte imbalances, primarily hypokalaemia, and pertinent electrocardiographic findings, such as the occurrence of supraventricular arrhythmias and increases in possible predictive parameters for arrhythmias. In spite of these observations, HRV indexes were better in animals undergoing haemodialysis and, in addition, IHD was more effective at reducing levels of creatinine, urea and phosphorus compared to intravenous fluid therapy treatment.

Vancomycin for Dialytic Therapy in Critically Ill Patients: Analysis of Its Reduction and the Factors Associated with Subtherapeutic Concentrations

This study aimed to evaluate the reduction in vancomycin through intermittent haemodialysis (IHD) and prolonged haemodialysis (PHD) in acute kidney injury (AKI) patients with sepsis and to identify the variables associated with subtherapeutic concentrations. A prospective study was performed in patients admitted at an intensive care unit (ICU) of a Brazilian hospital. Blood samples were collected at the start of dialytic therapy, after 2 and 4 h of treatment and at the end of therapy to determine the serum concentration of vancomycin and thus perform pharmacokinetic evaluation and PK/PD modelling. Twenty-seven patients treated with IHD, 17 treated with PHD for 6 h and 11 treated with PHD for 10 h were included. The reduction in serum concentrations of vancomycin after 2 h of therapy was 26.65 ± 12.64% and at the end of dialysis was 45.78 ± 12.79%, higher in the 10-h PHD group, 57.70% (40, 48–64, 30%) (p = 0.037). The ratio of the area under the curve to minimal inhibitory concentration (AUC/MIC) at 24 h in the PHD group was significantly smaller than at 10 h (p = 0.047). In the logistic regression, PHD was a risk factor for an AUC/MIC ratio less than 400 (OR = 11.59, p = 0.033), while a higher serum concentration of vancomycin at T0 was a protective factor (OR = 0.791, p = 0.009). In conclusion, subtherapeutic concentrations of vancomycin in acute kidney injury (AKI) patients in dialysis were elevated and may be related to a higher risk of bacterial resistance and mortality, besides pointing out the necessity of additional doses of vancomycin during dialytic therapy, mainly in PHD.

Metformin-associated lactic acidosis: reinforcing learning points

Metformin-associated lactic acidosis (MALA) carries a high mortality rate. It is seen in patients with type 2 diabetes on metformin or patients who attempt suicide with metformin overdose. We present the case of a man in his early 20s with type 2 diabetes, hypertension and hypothyroidism who presented with agitation, abdominal pain and vomiting after ingesting 50–60 g of metformin; he developed severe lactic acidosis (blood pH 6.93, bicarbonate 7.8 mEq/L, lactate 28.0 mEq/L). He was managed with intravenous 8.4% bicarbonate infusion and continuous venovenous haemodiafiltration. He also developed acute renal failure (ARF) requiring intermittent haemodialysis and continuous haemodiafiltration. MALA is uncommon and causes changes in different vital organs and even death. The primary goals of therapy are restoration of acid-base status and removal of metformin. Early renal replacement therapy for ARF can result in rapid reversal of the acidosis and good recovery, even with levels of lactate normally considered to be incompatible with survival.