A Scoring Tool to Predict Pulmonary Complications in Severe Leptospirosis with Kidney Failure

Rapid identification of patients likely to develop pulmonary complications in severe leptospirosis is crucial to prompt aggressive management and improve survival. The following article is a cohort study of leptospirosis patients admitted at the National Kidney and Transplant Institute (NKTI). Logistic regression was used to predict pulmonary complications and obtain a scoring tool. The Kaplan–Meir method was used to describe survival rates. Among 380 patients with severe leptospirosis and kidney failure, the overall mortality was 14%, with pulmonary hemorrhage as the most common cause. In total, there were 85 (22.4%) individuals who developed pulmonary complications, the majority (95.3%) were observed within three days of admission. Among the patients with pulmonary complications, 56.5% died. Patients placed on mechanical ventilation had an 82.1% mortality rate. Multivariate analyses showed that dyspnea (OR = 28.76, p < 0.0001), hemoptysis (OR = 20.73, p < 0.0001), diabetes (OR = 10.21, p < 0.0001), renal replacement therapy (RRT) requirement (OR = 6.25, p < 0.0001), thrombocytopenia (OR = 3.54, p < 0.0029), and oliguria/anuria (OR = 3.15, p < 0.0108) were significantly associated with pulmonary complications. A scoring index was developed termed THe-RADS score (Thrombocytopenia, Hemoptysis, RRT, Anuria, Diabetes, Shortness of breath). The odds of developing pulmonary complications were 13.90 times higher among patients with a score >2 (63% sensitivity, 88% specificity). Pulmonary complications in severe leptospirosis with kidney failure have high mortality and warrant timely and aggressive management.

Longitudinal genome-wide DNA methylation changes in response to kidney failure replacement therapy

Chronic kidney disease (CKD) is an emerging public health priority associated with high mortality rates and demanding treatment regimens, including life-style changes, medications or even dialysis or renal transplantation. Unavoidably, the uremic milieu disturbs homeostatic processes such as DNA methylation and other vital gene regulatory mechanisms. Here, we aimed to investigate how dialysis or kidney transplantation modifies the epigenome-wide methylation signature over 12 months of treatment. We used the Infinium HumanMethylation450 BeadChip on whole blood samples from CKD-patients undergoing either dialysis (n = 11) or kidney transplantation (n = 12) and 24 age- and sex-matched population-based controls. At baseline, comparison between patients and controls identified several significant (PFDR < 0.01) CpG methylation differences in genes with functions relevant to inflammation, cellular ageing and vascular calcification. Following 12 months, the global DNA methylation pattern of patients approached that seen in the control group. Notably, 413 CpG sites remained differentially methylated at follow-up in both treatment groups compared to controls. Together, these data indicate that the uremic milieu drives genome-wide methylation changes that are partially reversed with kidney failure replacement therapy. Differentially methylated CpG sites unaffected by treatment may be of particular interest as they could highlight candidate genes for kidney disease per se.

The impact of vaccination on incidence and outcomes of SARS-CoV-2 infection in patients with kidney failure in Scotland

Background Patients with kidney failure requiring kidney replacement therapy (KRT) are at high risk of complications and death following SARS-CoV-2 infection with variable antibody responses to vaccination reported. We investigated the effects of COVID-19 vaccination on incidence of infection, hospitalization and death of COVID-19 infection. Methods Study design was an observational data linkage cohort study. Multiple healthcare datasets were linked to ascertain all SARS-CoV-2 testing, vaccination, hospitalization, and mortality data for all patients treated with KRT in Scotland, from the start of the pandemic over a period of 20 months. Descriptive statistics, survival analyses and vaccine effectiveness were calculated. Results As of 19th September 2021, 93% (n=5281) of the established KRT population in Scotland had received two doses of an approved SARS-CoV-2 vaccine. Over the study period, there were 814 cases of SARS-CoV-2 infection (15.1% of the KRT population). Vaccine effectiveness against infection and hospitalization was 33% (95% CI 0-52) and 38% (95% CI 0-57) respectively. 9.2% of fully vaccinated individuals died within 28 days of a SARS-CoV-2 positive PCR test (7% dialysis patients and 10% kidney transplant recipients). This compares to <0.1% of the vaccinated Scottish population being admitted to hospital or dying death due to COVID19 during that period. Conclusions These data demonstrate a primary vaccine course of two doses has limited impact on COVID-19 infection and its complications in patients treated with KRT. Adjunctive strategies to reduce risk of both COVID-19 infection and its complications in this population are urgently required.

Cannabinoids for Symptom Management in Patients with Kidney Failure

People with kidney failure can experience a range of symptoms that lead to suffering and poor quality of life. Available therapies are limited, and evidence for new treatment options is sparse, often resulting in incomplete relief of symptoms. There is growing interest in the potential for cannabinoids, including cannabidiol and tetrahydrocannabinol, to treat symptoms across a wide range of chronic diseases. As legal prohibitions are withdrawn or minimized in many jurisdictions, patients are increasingly able to access these agents. Cannabinoid receptors, CB1 and CB2, are widely expressed in the body, including within the nervous and immune systems, and exogenous cannabinoids can have anxiolytic, anti-emetic, analgesic and anti-inflammatory effects. Considering their known physiological actions and successful studies in other patient populations, cannabinoids may be viewed as potential therapies for a variety of common symptoms affecting those with kidney failure, including pruritus, nausea, insomnia, chronic neuropathic pain, anorexia, and restless legs syndrome. In this review, we summarize the pharmacology and pharmacokinetics of cannabinoids, along with what is known about the use of cannabinoids for symptom relief in those with kidney disease, and the evidence available concerning their role in management of common symptoms. Presently, while these agents show varying efficacy with a reasonable safety profile in other patient populations, evidence-based prescribing of cannabinoids for people with symptomatic kidney failure is not possible. Given the symptom burden experienced by individuals with kidney failure, there is an urgent need to understand the tolerability and safety of these agents in this population, which must ultimately be followed by robust, randomized controlled trials to determine if they are effective for symptom relief.