Trace Elements and Chronic Kidney Disease: A Cross-Sectional Study from Jamaica

Background: Several environmental studies have reported that low-level exposure to nephrotoxic elements increases the risk of chronic kidney disease (CKD). In developing countries, finite resources can limit epidemiological studies and environmental risk assessment; however, the unique soil profile in Jamaica has raised some concerns for the potential exposure to populations who are of high risk. Method: This study investigated the potential for using trace element profiling in CKD, by analysing blood concentration levels of vanadium, chromium, iron, cobalt, copper, zinc, selenium, strontium (Sr), arsenic, barium, cadmium, mercury, and lead. Trace element analysis was conducted using inductively coupled plasma mass spectrometry. Results: One hundred and fifty-eight individuals were included and were predominantly of African descent (98%) and their ages ranged from 21 to 90 years old. Three main correlation clusters were evident: firstly, vanadium, chromium, copper, silicon, and selenium, with mercury and barium more distantly related; secondly, lead, arsenic, nickel, and Sr; and thirdly, iron and zinc. Cadmium was an outlier. Blood Sr was strongly associated with estimated glomerular filtration rate (r = -0.83; p<0.001) and strong linear progression models (r2=0.96; p<0.001). Algorithmic models placed Sr as the highest-ranking trace element biomarker (area under the curve: 95.6%; p<0.001). Discussion: The decline in kidney function may result in the retention of non-essential trace elements. Strong corresponding trends between kidney function and blood Sr concentration indicate biomarker potential for a trace element with a unique profile in patients with CKD. Other significant relationships may also be unveiled as CKD biomarkers as trace element profiling is explored in the region.

Blood Volume Monitoring: A Clinical Tool to Guide Ultrafiltration in Volume Control and Optimisation of Intradialytic Blood Pressure

The importance of extracellular volume control and avoidance of volume overload has been well documented in relation to the management of patients with chronic haemodialysis. Chronic volume overload results in poorly controlled hypertension, increased cardiovascular events, and increased all-cause mortality. Traditional methods of dry weight assessment have relied on clinical assessment to guide volume status. The challenge of achieving the balance between dry weights and preventing intradialytic complications is a formidable one. In order to achieve this, reproducible and sensitive methods are desirable to aid objective quantification of volume status. One such method is by the use of blood volume monitoring, which is achieved by real-time calculation of changes in relative blood volume via a cuvette placed in the arterial blood-line, which can be used to guide ultrafiltration targets during the haemodialysis session. This review article examines the use of blood volume monitoring as a tool to guide ultrafiltration during dialysis and to examine the current evidence to supports its use in assessing dry weight and in preventing intradialytic hypotension events.

The Role of Dexmedetomidine for the Prevention of Acute Kidney Injury in Critical Care

Acute kidney injury (AKI) occurs in up to 50% of patients admitted to the intensive care unit and is associated with increased mortality. Currently, there is no effective pharmacotherapy for prevention or treatment of AKI. In animal models of sepsis and ischaemia-reperfusion, α2-agonists like dexmedetomidine (DEX) exhibit anti-inflammatory properties and experimental data indicate a potential protective effect of DEX on renal function. However, clinical trials have yielded inconsistent results in critically ill patients. This review discusses the pathophysiological mechanisms involved in AKI, the renal effects of DEX in various intensive care unit-related conditions, and summarises the available literature addressing the use of DEX for the prevention of AKI.

Causes of Hypermagnesaemia: A Literature Review

Magnesium is one of the commonly overlooked electrolytes, yet it plays a vital role in many of the processes in the human body. The balance of magnesium can translate into subtle changes in a person’s daily life, causing fatigue and confusion, to extreme cases that can end up causing central nervous system depression, respiratory failure, or cardiac arrhythmias. It is vital to be familiar with the physiology of magnesium regulation and knowledgeable regarding the causes that can lead to its toxicity to ensure the prevention of the possibly fatal condition. Magnesium balance can be summarised as the difference between magnesium intake and its excretion. Any factor overwhelming either of the two factors can cause pathological levels of the electrolyte. In addition to learning preventive measures to help patients against effects of magnesium toxicity, it is also important that the medical community trains to be able to treat cases of hypermagnesaemia. This review assesses the latest advancements in knowledge of magnesium metabolism, examines the case reports of hypermagnesaemia in an attempt to list the causes of magnesium toxicity, and enumerates management advances for the condition.

The Non-coding MicroRNA-223 is a Promising Biomarker of Chronic Kidney Disease

Renal diseases are consecutive to a deregulation of gene expression regulated by non-coding RNAs. These non-coding RNAs were discovered at the turn of the 21st century when it was established that post-transcriptional regulation was performed through small non-coding RNAs, known as microRNAs (miRNAs). Up to 3,000 miRNAs are expressed by human cells. They are small, single-stranded nucleic acids, which trigger translational repression of mRNA by base-pairing with the 3′ untranslated region of their mRNA targets. In addition to miRNA regulation, it was also demonstrated that 60,000 long non-coding RNAs are expressed in the human cell and that they are able to regulate gene expression at all levels. The roles of these various RNA families are just beginning to be understood in the field of nephrology. In the past decade, the authors and various others have published that several miRNAs are deregulated during the onset of chronic kidney disease (CKD) and are associated with cardiovascular damage. This review focuses on miRNA-223 (miR-223) as its expression is increased in vivo in the large vessels of a mouse model of CKD, whereas it is diminished in the serum of both mice and human patients with CKD. In patients, miR-223 expression was correlated with all-cause mortality, as well as cardiovascular and renal events. Molecular clues were given by a multi-omics approach, indicating that miR-223 modulates gene regulation at all levels including mRNA expression, protein amounts, and metabolic molecule accumulation. miR-223 is thus a potential target to prevent or treat complications of CKD pathogenesis.

SARS-CoV-2-Associated Nephropathy: Direct Renal Infection and Damage

Acute kidney injury is a frequent complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), principally because of hypotension and decreased kidney perfusion secondary to haemodynamic or haemostatic factors, drug-induced nephrotoxicity, and cytokine storm syndrome related to sepsis. Additionally, several factors support the existence of SARS-CoV-2-associated nephropathy, such as early, new-onset proteinuria and haematuria in many patients, the identification of SARS-CoV-2 viral load in precisely defined kidney compartments, ultrastructural and immunohistochemical evidence of direct viral infection of the kidneys, and, most importantly, morphological alterations associated with cytopathic action induced by the virus. In addition, collapsing glomerulopathy that has been reported in patients of African American descent with underlying apolipoprotein L1 (APOL1) kidney risk alleles and SARS-CoV-2 infection is evidence of a distinct form of SARS-CoV-2-associated nephropathy, the APOL1-SARS-CoV2-associated nephropathy.

Diabetic Kidney Disease in Childhood and Adolescence: Conventional and Novel Renoprotective Strategies

Diabetic kidney disease (DKD) is defined as a clinical syndrome consisting of persistent macroalbuminuria, progressive decline in glomerular filtration rate (GFR), hypertension, increased cardiovascular disease events, and the associated mortality of these conditions. The disease evolves from the microvascular complications of poorly controlled Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM). The pathogenic pathways comprise renal haemodynamic changes, ischaemia and inflammation, and overactive renin–angiotensin–aldosterone system (RAAS), through which several events cascade down from hyperglycaemia to renal fibrosis. Conventional and novel renoprotective strategies target modifiable DKD risk factors and specific stages of the pathogenic pathways, respectively. Although these strategies may slow DKD progression to end-stage kidney disease (ESKD), novel drugs are still undergoing trials for validation in human participants. This narrative review appraises these renoprotective strategies and highlights the current clinical staging and pathogenesis of the disease.

New Aspects of Pathogenesis and Treatment of Membranous Glomerulopathy After the MENTOR Study

Membranous nephropathy (MN) is the major cause of nephrotic syndrome in adults, accounting for 20% of cases with an annual incidence of 1 per 100,000 population. In the past 10 years, the role of podocytes has been identified. Environmental triggers in genetically predisposed patients can activate podocytes to exhibit antigenic epitopes, including PLA2R, THBS1, and NELL1, which become targets of specific autoantibodies with subsequent complement activation. The discovery of these mechanisms has opened a new horizon in the treatment of MN, and novel drugs are available with more specific mechanisms of action. Rituximab, a monoclonal antibody directed against CD20 expressed on B lymphocytes, has been used in several trials and appears to induce remission of nephrotic syndrome in 60% of patients (GEMRITUX trial). The recently published results of the MENTOR trial documented the superior efficacy of rituximab in patients observed for up to 24 months. In MN, the concept of targeting disease control has introduced novel therapies with specific blocking mechanisms, such as belimumab; nonspecific blocking mechanisms, such as those against adrenocorticotropic hormone; and new therapeutic options, such as ofatumumab, bortezomib, and eculizumab, which have recognised the pathological processes involved in the glomerular diseases.

Acute Kidney Injury: Risk Factors and Management Challenges in Low- and Middle-Income Countries

Acute kidney injury (AKI) is a major global health problem, occurring in >13 million people and responsible for >2.3 million deaths every year, 85% of which are in developing countries. Although the International Society of Nephrology (ISN) set a goal of eliminating preventable deaths by AKI by 2025, implementation of this program in developing countries presents major challenges for several reasons: there are few data on the epidemiology and causes of AKI in low- and middle-income countries (LMIC); health care resources to diagnose, manage, and treat AKI are often limited; and governments, institutions, and global health initiatives have not focussed sufficiently on the AKI problems. Thus, developing and implementing effective strategies to eliminate preventable deaths from AKI in LMIC have required efforts to better understand how to increase the awareness of AKI by health care workers and institutions.

Pharmacokinetics of Amoxicillin and Cefepime During Prolonged Intermittent Renal Replacement Therapy: A Case Report

Prolonged intermittent renal replacement therapy (PIRRT) is an emerging form of renal replacement therapy in critically ill patients, but dosing data for antibiotics such as amoxicillin and cefepime are scarce and limited. This case report describes the effect of PIRRT on the plasma pharmacokinetics of amoxicillin and cefepime in a 69-year-old, critically ill patient with a polymicrobial intra-abdominal infection. Blood samples taken over 2 days, including a 7-hour PIRRT session, were analysed and a two-compartment model was used to describe cefepime and amoxicillin clearance and dosing requirements during PIRRT and off-PIRRT in this patient. Based on these data, an off-PIRRT dose of 1 g amoxicillin 12-hourly and cefepime 2 g daily with an on-PIRRT dose of 1 g amoxicillin 8-hourly and cefepime 2 g 12-hourly was deemed appropriate.