Tuck Y. Yong

Circulating microRNA expression is reduced in chronic kidney disease

BACKGROUND MicroRNAs (miRNAs) are important regulators of gene expression, which have roles in renal development and disease. They exist in biological fluids including blood and urine and may have signalling roles and potential as disease biomarkers. METHODS We measured the levels of miRNAs in patients with different stages of chronic kidney failure including those receiving maintenance haemodialysis treatment. RESULTS In patients with severe chronic renal failure, circulating levels of total and specific miRNAs are reduced in comparison to patients with mild renal impairment or normal renal function. A strong correlation exists between detected circulating miRNAs and estimated glomerular filtration rate, and less strong correlations with other features of chronic kidney disease, such as anaemia and hyperparathyroidism. CONCLUSION These findings have important implications for the use of circulating miRNAs as biomarkers in individuals with renal impairment and for the pathogenesis of uraemia.

Review: The role of microRNAs in kidney disease.

MicroRNAs (miRNAs) are short non‐coding RNAs that modulate physiological and pathological processes by inhibiting target gene expression via blockade of protein translation or by inducing mRNA degradation. These miRNAs potentially regulate the expression of thousands of proteins. As a result, miRNAs have emerged rapidly as a major new area of biomedical research with relevance to kidney disease. MiRNA expression has been shown to differ between the kidney and other organs as well as between different kidney regions. Furthermore, miRNAs have been found to be functionally important in models of podocyte development, diabetic nephropathy and polycystic kidney disease. Of particular interest, podocyte‐specific deletion of Dicer, a key enzyme in the biogenesis of miRNA, results in proteinuria and severe renal impairment in mice. One miRNA (miR‐192) can also act as an effector of transforming growth factor‐β activity in the high‐glucose environment of diabetic nephropathy. Differential expression of miRNAs has been reported in kidney allograft rejection. It is anticipated that future studies involving miRNAs will generate new insights into the complex pathophysiology underlying various kidney diseases, generate diagnostic biomarkers and might be of value as therapeutic targets for progressive kidney diseases. The purpose of this review is to highlight key miRNA developments in kidney diseases and how this might influence the diagnosis and management of patients with kidney disease in the future.

The role of microRNAs in kidney disease

MicroRNAs (miRNAs) are short non‐coding RNAs that modulate physiological and pathological processes by inhibiting target gene expression via blockade of protein translation or by inducing mRNA degradation. These miRNAs potentially regulate the expression of thousands of proteins. As a result, miRNAs have emerged rapidly as a major new area of biomedical research with relevance to kidney disease. MiRNA expression has been shown to differ between the kidney and other organs as well as between different kidney regions. Furthermore, miRNAs have been found to be functionally important in models of podocyte development, diabetic nephropathy and polycystic kidney disease. Of particular interest, podocyte‐specific deletion of Dicer, a key enzyme in the biogenesis of miRNA, results in proteinuria and severe renal impairment in mice. One miRNA (miR‐192) can also act as an effector of transforming growth factor‐β activity in the high‐glucose environment of diabetic nephropathy. Differential expression of miRNAs has been reported in kidney allograft rejection. It is anticipated that future studies involving miRNAs will generate new insights into the complex pathophysiology underlying various kidney diseases, generate diagnostic biomarkers and might be of value as therapeutic targets for progressive kidney diseases. The purpose of this review is to highlight key miRNA developments in kidney diseases and how this might influence the diagnosis and management of patients with kidney disease in the future.

Successful control of Scedosporium prolificans septic arthritis and probable osteomyelitis without radical surgery in a long-term renal transplant recipient

Abstract: Scedosporium species are increasingly isolated from immunocompromised and immunocompetent patients. Scedosporium infections are generally resistant to multiple antifungals, and Scedosporium prolificans is particularly resistant to all single antifungal agents currently in use with in vitro testing. We report here a long‐term renal transplant recipient who developed isolated S. prolificans septic monoarthritis and probable osteomyelitis. The infection was successfully treated with a combination of voriconazole and terbinafine in addition to joint washout but did not require radical surgery. This combination has been shown to have synergistic in vitro effect, and anecdotal in vivo success has also been reported recently. We also review the clinical presentation, treatment, and outcome of S. prolificans infection in patients with solid organ transplantation.

Bilateral basal ganglia lesions in patients with end-stage diabetic nephropathy.

Summary:  Acute movement disorder associated with reversible bilateral basal ganglia lesions is an increasingly recognized syndrome in patients with end‐stage renal disease, especially in the setting of concurrent diabetes mellitus. We report an elderly man with end‐stage diabetic nephropathy treated by daily automated peritoneal dialysis who developed subacute symptoms of gait disturbance, dysarthria, dysphagia and lethargy. Computed tomography and magnetic resonance imaging of the head revealed bilateral symmetrical basal ganglia lesions. Repeat imaging 3 weeks later showed that these lesions had regressed spontaneously. However, his neurological symptoms improved slowly. These findings were similar to 23 other cases in the literature. Review of these cases shows that clinical features were predominantly bradykinesia, gait disturbance and concurrent metabolic acidosis (observed in 90% of cases). The pathogenesis of this condition has not been clearly defined, but uraemia may be an aggravating factor in predisposed patients, particularly in the presence of diabetic microvascular disease. There is no specific treatment for this condition; supportive measures are the mainstay of management. In the majority of patients, neurological improvement lags behind regression of basal ganglia lesions seen with neuroimaging, and the long‐term outcome is variable.

Atypical femoral fracture in a patient treated with denosumab

Atypical fractures of the femur (AFF) have been reported in the literature at an increasing rate over the past decade, especially in patients who have been on prolonged courses of bisphosphonates. However, there have only been a few reported cases of AFF in those treated with other antiresorptive medications. In this case report, a 72-year-old woman with chronic obstructive pulmonary disease and osteoporosis presented with an atraumatic right femoral fracture in the setting of denosumab use. In contrast with other reports, this patient had received bisphosphonate therapy for a short duration before the switch to denosumab. While causality between the fracture and denosumab use cannot be established in this case, there is a growing number of reports of a similar association. Ongoing vigilance is required to determine whether denosumab is associated with or potentially a cause of AFF.

Characteristics and outcomes of discharges against medical advice among hospitalised patients

Discharge against medical advice (DAMA) occurs when an in‐patient chooses to leave the hospital before discharge is recommended by the treating clinicians. The long‐term outcomes of patients who DAMA are not well documented.

Medication prescription among elderly patients admitted through an acute assessment unit

Aim:  This study assessed medication use patterns and polypharmacy in patients who were admitted through an acute assessment unit (AAU) and stratified results according to patient age. This study also examined risk factors associated with polypharmacy and consequences of polypharmacy, namely prescription writing errors, drug–drug interaction and geriatric syndrome.

MicroRNAs: are they the missing link between hypoxia and pre-eclampsia?

Pre-eclampsia is a multisystem disorder that occurs in the second half of pregnancy affecting 5% of pregnancies. It remains the leading cause of maternal and perinatal mortality and morbidity worldwide. Impaired placental implantation, hypoxia, endothelial dysfunction and systemic inflammation are thought to have a role in the pathogenesis of pre-eclampsia. MicroRNAs (miRNAs) are short non-coding RNAs. They are important regulators of gene expression and have been found to affect cell development, proliferation, differentiation and function. Specific patterns of miRNAs have been detected in the placenta and there is altered miRNA expression in the placenta of patients with pre-eclampsia to but their role in the pathogenesis remains unclear. Furthermore, deregulated miRNAs have also been reported in human villous trophoblasts during hypoxic stress. One of the more consistently elevated miRNAs by hypoxia and in the placenta of patients with pre-eclampsia is miR-210. Whether such miRNAs are bystander markers of hypoxia, or are directly involved in the pathogenesis of pre-eclampsia, needs to be clarified. There is potential for miRNAs to be used as predictors, markers or therapy in pre-eclampsia. This review provides current knowledge about miRNAs, particularly hypoxia-related miRNAs and the interaction of hypoxia, miRNAs and placenta in pre-eclampsia.

Identifying risk factors and patterns for unplanned readmission to a general medical service.

OBJECTIVE To identify factors and patterns associated with 7- and 28-day readmission for general medicine patients at a tertiary public hospital. METHODS A retrospective observational study was conducted using an administrative database at a general medicine service in a tertiary public hospital between 1 January 2007 and 31 December 2011. Demographic and clinical factors, as well as readmission patterns, were evaluated for the association with 7- and 28-day readmission. RESULTS The study cohort included 13 802 patients and the 28-day readmission rate was 10.9%. In multivariate analysis, longer hospital stay of the index admission (adjusted relative risk (ARR) 1.34), Charlson index ≥ 3 (ARR 1.28), discharge against medical advice (ARR 1.87), active malignancy (ARR 1.83), cardiac failure (ARR 1.48) and incomplete discharge summaries (ARR 1.61) were independently associated with increased risk of 28-day readmission. Patients with diseases of the respiratory system, neurological or genitourinary disease, injury and unclassifiable conditions were likely to be readmitted within 7 days. Patients with circulatory and respiratory disease were likely to be readmitted with the same system diagnosis. CONCLUSION Readmission of general medicine patients within 28 days is relatively common and is associated with clinical factors and patterns. Identification of these risk factors and patterns will enable the interventions to reduce potentially preventable readmissions.