Renal transplants increase in size and function in keeping with compensatory renal hypertrophy.

AIM: To evaluate changes in allograft kidney length in renal transplant recipients and the relationship with estimated glomerular filtration rate (eGFR). METHODS: This single-centre retrospective study of renal transplant recipients was conducted at Flinders Medical Centre (FMC) from January 2007 to June 2020. Donor and recipient details, renal allograft length from transplant ultrasounds at 0, 1, 3, 6 and 12 months were collected. The association between compensatory renal hypertrophy (CRH) and eGFR and its magnitude was analysed using multivariate multilevel mixed-effects linear regression models. RESULTS: A total of 183 renal transplant recipients were studied. 100 of 175 recipients (62.9%) demonstrated an increase in renal length defined as any increase in maximal longitudinal diameter on serial ultrasounds. Twenty-three recipients (13.1%) had no change in transplant length and 42 recipients (24%) had a decrease in length. The mean increase in kidney length over the first 12 months was 0.57 cm. Ninety of 156 (57.7%) recipients with a renal ultrasound within a month post-transplant demonstrated a mean increase kidney length of 0.3 cm. Multivariate analysis demonstrated that eGFR increased by 2.5 mL/min/1.73 m2 (95% CI 0.72- 4.4; p = .006) with every 1 cm increase in kidney length. Absolute changes in kidney length did not demonstrate any statistically significant correlation with eGFR in both complete case and multiple imputation analysis. CONCLUSION: An increase in transplant kidney length is common in renal transplant recipients and is associated with enhanced eGFR. However, further studies need to be performed to study the association of absolute change in kidney length and eGFR.

Renal disease is not associated with delays in hyperacute stroke management in South Australia.

OBJECTIVE: The aims of the present study were to determine how renal disease is associated with the time to receive hyperacute stroke care. METHODS: The present study involved a 5-year cohort of all patients admitted to stroke units in South Australia. RESULTS: In those with pre-existing renal disease there were no significant differences in the time taken to receive a scan, thrombolysis or endovascular thrombectomy. CONCLUSIONS: The present study shows that in protocolised settings there were no significant delays in hyperacute stroke management for patients with renal disease.

SARS-CoV-2 produces a microRNA CoV2-miR-O8 in patients with COVID-19 infection.

Many viruses produce microRNAs (miRNAs), termed viral miRNAs (v-miRNAs), with the capacity to target host gene expression. Bioinformatic and cell culture studies suggest that SARS-CoV-2 can also generate v-miRNAs. This patient-based study defines the SARS-CoV-2 encoded small RNAs present in nasopharyngeal swabs of patients with COVID-19 infection using small RNA-seq. A specific conserved sequence (CoV2-miR-O8) is defined that is not expressed in other coronaviruses but is preserved in all SARS-CoV-2 variants. CoV2-miR-O8 is highly represented in nasopharyngeal samples from patients with COVID-19 infection, is detected by RT-PCR assays in patients, has features consistent with Dicer and Drosha generation as well as interaction with Argonaute and targets specific human microRNAs.

Protocol for the Flinders Kidney Health Registry: patient outcomes of kidney cancers and nephrectomies.

BACKGROUND: Kidney cancer accounts for 2% of new cancers diagnosed in Australia annually. Partial and radical nephrectomy are the treatment of choice for kidney cancer. Nephrectomy is also performed for living donor kidney transplantation. Nephrectomy is a risk factor for new-onset chronic kidney disease (CKD) or deterioration of pre-existing CKD. Understanding the risk factors for new-onset or deterioration of existing CKD after nephrectomy is important in developing preventive measures to provide better care for these patients. There is also a need to understand the incidence, natural history, management trends, and sequelae of radiofrequency ablation as well as surveillance of small renal cancers or small renal masses (SRMs). Clinical registries are critical in providing excellent patient-centre care and clinical research as well as basic science research. Registries evaluate current practice and guide future practice. The Flinders Kidney Health Registry will provide the key information needed to assess various treatment outcomes of patients with kidney cancer and patients who underwent nephrectomy for other reasons. The registry aims to provide clinical decision makers with longitudinal data on patient outcomes, health systems performance, and the effect of evolving clinical practice. The registry will also provide a platform for large-scale prospective clinical studies and research. METHODS: Patients above the age of 18 undergoing nephrectomy or radiofrequency ablation for any indication and patients with SRMs will be included in the registry. Demographic, clinical and quality of life data will be collected from hospital information systems and directly from the patient and/or caregiver. DISCUSSION: The Registry will report a summary of patient characteristics including indication for treatment, clinical risk profiles, surgical and oncological outcomes, the proportion of patients who progress to CKD and end stage kidney disease, quality of life post treatment as well as other relevant outcomes for all patients who have undergone nephrectomy for any indication, ablation or surveillance for SRMs. The registry will record the follow-up practice after nephrectomy and patient on active surveillance, which will help to develop and enhance a best practice protocol. The collected prospective data will provide a platform for ongoing patient-orientated research and improve patient-centred healthcare delivery.

Prevalence, characteristics and risk factors of frequently readmitted patients to an internal medicine service.

BACKGROUND: Unplanned hospital readmissions (HRA), which have been used as key performance index of healthcare quality, are becoming more prevalent. They are associated with substantial financial burden to hospital systems and considerable impacts on patients' physical and mental health. Patients with frequent readmissions are not well studied. AIMS: To determine the prevalence, characteristics and risk factors associated with frequent readmissions (FRA) to an internal medicine service at a tertiary public hospital. METHOD: A retrospective observational study was conducted at an internal medicine service in a tertiary teaching hospital between 1 January 2010 and 30 June 2016. FRA was defined as four or more readmissions within 12 months of discharge from the index admission (IA). Demographic and clinical characteristics and potential risk factors were evaluated. RESULTS: A total of 50 515 patients was included; 1657 (3.3%) had FRA and were associated with nearly 2.5 times higher in 12-month mortality rates. They were older, had higher rates of indigenous Australians (3.2%), more disadvantaged status (index of relative socio-economic disadvantage decile of 5.3) and more comorbidities (mean Charlson comorbidity index 1.4) in comparison, to infrequent readmission group. The mean length of hospital stay during the IA was 6 days for FRA group (21.4% staying more than 7 days) with higher incidence of discharge against medical advice (2.0% higher). Intensive care unit admission rate was 6.6% for FRA group compared with 3.9% for infrequent readmission group. Multivariate analysis showed mental disease and disorders, neoplastic, alcohol/drug use and alcohol/drug-induced organic mental disorders are associated with FRA. CONCLUSION: The risk factors associated with FRA were older age, indigenous status, being socially disadvantaged, having higher comorbidities and discharging against medical advice. Conditions that lead to FRA were mental disorders, alcohol/drug use and alcohol/drug-induced organic mental disorders and neoplastic disorders.

Mycoplasma hominis bursitis in a simultaneous pancreas-kidney transplant recipient: case report and literature review.

Mycoplasma hominis can be isolated frequently from the genitourinary tract of some healthy individuals. On rare occasions, it acts as a pathogen in immunocompromised patients such as transplant recipients. Here, we describe the case of a 39-year-old man with end-stage kidney disease secondary to diabetic nephropathy who received a simultaneous pancreas-kidney transplant. He developed pancreatitis and arterial thrombosis 2 weeks post-transplant and required a pancreatectomy. His kidney allograft function remained normal. He developed severe left hip pain 2 weeks post-transplant with a trochanteric bursal effusion detected on magnetic resonance imaging. The effusion grew M. hominis. The patient was treated with 100 mg of doxycycline twice daily for 9 months with full resolution of the effusion at 4 months post-treatment. We also review all previously reported M. hominis infections in transplant recipients.

Compensatory renal hypertrophy following nephrectomy: When and how?

Following surgical removal of one kidney, the other enlarges and increases its function. The mechanism for the sensing of this change and the growth is incompletely understood but begins within days and compensatory renal hypertrophy (CRH) is the dominant contributor to the growth. In many individuals undergoing nephrectomy for cancer or kidney donation this produces a substantial and helpful increase in renal function. Two main mechanisms have been proposed, one in which increased activity by the remaining kidney leads to hypertrophy, the second in which there is release of a kidney specific factor in response to a unilateral nephrectomy that initiates CRH. Whilst multiple growth factors and pathways such as the mTORC pathway have been implicated in experimental studies, their roles and the precise mechanism of CRH are not defined. Unrestrained hypoxia inducible factor activation in renal cancer promotes growth and may play an important role in driving CRH.

Atypical Haemolytic Uraemic Syndrome Associated with Clostridium difficile Infection Successfully Treated with Eculizumab.

Clostridium difficile infection is a rare precipitant of atypical haemolytic uraemic syndrome (aHUS). A 46-year-old man presented with watery diarrhoea following an ileocaecal resection. He developed an acute kidney injury with anaemia, thrombocytopaenia, raised lactate dehydrogenase, low haptoglobin, and red cell fragments. Stool sample was positive for C. difficile toxin B. He became dialysis-dependent as his renal function continued to worsen despite treatment with empiric antibiotics and plasma exchange. The ADAMTS13 level was normal consistent with a diagnosis of aHUS. The commencement of eculizumab led to the resolution of haemolysis and stabilisation of haemoglobin and platelets with an improvement in renal function.

Lack of appropriate investigations in making a diagnosis of syndrome of inappropriate antidiuretic hormone.

The syndrome of inappropriate antidiuretic hormone (SIADH) is reported as the most common cause of hyponatraemia. This retrospective cross-sectional study evaluated the diagnosis of SIADH in 110 hospitalised patients in an Australian tertiary hospital with reference to recently published clinical guidelines. Investigation of SIADH was incomplete in all but 20% of cases. Adrenal insufficiency and hypothyroidism were not excluded in a significant number of cases.

Diagnosing an atypical site of giant cell arteritis with magnetic resonance angiography: a case report.

BACKGROUND: Giant cell arteritis typically involves the temporal arteries, but can involve other cranial arteries. Temporal artery biopsy is the mainstay for the diagnosis of giant cell arteritis; however, biopsy may be problematic if giant cell arteritis involves other cranial arteries that are inaccessible for sampling. In these situations, magnetic resonance angiography is a useful, non-invasive adjunctive method in the diagnosis of giant cell arteritis. In this case report, we describe a case of giant cell arteritis involving only the occipital artery which was revealed by magnetic resonance angiography. CASE PRESENTATION: A 67-year-old Caucasian man was admitted to our hospital with a 4-week history of malaise, fever, and mild occipital headaches. There were no other positive findings on physical examination. Laboratory studies were remarkable for normocytic anemia, raised inflammatory markers, and mildly deranged liver function tests. To exclude intracranial pathology, he underwent a cranial magnetic resonance imaging with gadolinium, which demonstrated a thickened wall and mural enhancement of his right occipital artery, consistent with giant cell arteritis. His temporal arteries were normal. His occipital arteries were not accessible for biopsy and he was commenced on high-dose prednisolone (60 mg daily). His symptoms resolved completely after a week of glucocorticoid steroid treatment and he was well on 5 mg of prednisolone once a day on follow-up. CONCLUSION: While magnetic resonance angiography may not replace the need for biopsy, it may have a diagnostic role in suspected giant cell arteritis, such as when the involved arteries are inaccessible for biopsy.

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.

Human cytomegalovirus encoded microRNAs: hitting targets.

Human cytomegalovirus (HCMV) infection is of particular concern in immunodeficient individuals notably transplant recipients, leading to increased morbidity and mortality. HCMV is predicted to encode multiple microRNAs (miRNAs) and several have been characterized in vitro. Furthermore, these miRNAs have been shown to target human and viral mRNAs. Pathways involved in human cellular targets have key roles in vesicle trafficking, immune evasion and cell cycle control. This demonstration of viral miRNA targets provides novel insights into viral pathogenesis. This review details the evidence for the existence of HCMV-encoded miRNA and their targets. HCMV miRNA in blood and other tissues is a potential diagnostic tool and blocking the effects of specific HCMV-encoded miRNA with sequence specific antagomirs is a potential new therapy.

Predicting admission of patients by their presentation to the emergency department.

OBJECTIVE: The present study aims to determine the importance of certain factors in predicting the need of hospital admission for a patient in the ED. METHODS: This is a retrospective observational cohort study between January 2010 and March 2012. The characteristics, including blood test results, of 100,123 patients who presented to the ED of a tertiary referral urban hospital, were incorporated into models using logistic regression in an attempt to predict the likelihood of patients' disposition on leaving the ED. These models were compared with triage nurses' prediction of patient disposition. RESULTS: Patient age, their initial presenting symptoms or diagnosis, Australasian Triage Scale category, mode of arrival, existence of any outside referral, triage time of day and day of the week were significant predictors of the patient's disposition (P < 0.001). The ordering of blood tests for any patient and the extent of abnormality of those tests increased the likelihood of admission. The accuracy of triage nurses' admission prediction was similar to that offered by a model that used the patients' presentation characteristics. The addition of blood tests to that model resulted in only 3% greater accuracy in prediction of patient disposition. CONCLUSIONS: Certain characteristics of patients as they present to hospital predict their admission. The accuracy of the triage nurses' prediction for disposition of patients is the same as that afforded by a model constructed from these characteristics. Blood test results improve disposition accuracy only slightly so admission decisions should not always wait for these results.

Dipping your feet in the water: podocytes in urine.

Podocyte injury and loss plays an important role in the pathogenesis and progression of many kidney diseases. Studies have shown that podocyte-related markers and products can be detected in the urine of patients with glomerular diseases such as focal segmental glomerulosclerosis, IgA nephropathy, lupus nephritis, diabetic nephropathy and pre-eclampsia. Therefore, detecting the loss of podocytes in the urine provides a useful noninvasive technique of gathering information about the disease type and/or activity of glomerular diseases. Currently, urine podocyte-related protein markers, mRNA, microRNA and exosomes have been used with varying degrees of success to study glomerular diseases. The determination of urinary podocyte loss may become an important noninvasive tool in the evaluation of glomerular diseases.

Asymptomatic elevation of creatine kinase in patients with hyponatremia.

Elevated creatine kinase (hyper-CKemia) has been observed in small number of patients with hyponatremia. This study evaluated the features and outcomes of patients admitted with hyponatremia complicated by hyper-CKemia. Patients admitted with hyponatremia and concurrently found to have elevated creatine kinase (CK) of above 375 IU/L (male) or 225 IU/L (female), over a 5-year period were retrospectively reviewed. Those with myocardial injury (elevated CK-MB isoenzyme [CK-MB/CK percentage of >2.5%] or Troponin T [>0.02 µg/L]), traumatic or ischemic muscle damage, primary myopathic disorder, seizures prior to CK measurement or those taking medications which can cause myopathy, were excluded. Thirty-two patients with hyponatremia and hyper-CKemia were identified. All patients had no muscular symptoms or weakness. The commonest cause of hyponatremia in this cohort was related to diuretics (50%). The mean sodium level on presentation was 116.0 ± 6.9 mmol/L and the median peak CK was 895.5 (interquartile range: 610.8-1691.8) IU/L. Six (18%) patients developed acute kidney injury (AKI). The length of hospital admission of the entire cohort was 8.0 ± 5.8 days. Patients with hyper-CKemia in the setting of diuretic-associated hyponatremia were older and had longer hospital length of stay compared with primary-polydipsia-associated. Asymptomatic hyper-CKemia is an uncommon association with hyponatremia of various etiologies. Hyponatremia-associated hyper-CKemia can be complicated by AKI.

Minimal change disease associated with newly diagnosed mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a rare but aggressive form of non-Hodgkin's lymphoma. Involvement of the kidney is an infrequent occurrence in patients with MCL and can be the result of direct infiltration or paraneoplastic glomerulopathy. Proliferative glomerulonephritis, membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis have previously been reported in association with MCL. We report a 55-year-old woman who developed nephrotic syndrome due to biopsy proven minimal change disease (MCD) in association with MCL. Proteinuria decreased with prednisolone treatment and MCD remains in remission without any immunosuppressant after the treatment of the underlying MCL.

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.

Timeliness in discharge summary dissemination is associated with patients' clinical outcomes.

RATIONALE, AIMS AND OBJECTIVES: To determine the relation of the readmission rate of general medical patients to either the existence of a discharge summary or the timeliness of its dispatch. METHODS: This was a retrospective study on discharge summaries of all discharges from the general medical service at a tertiary referral teaching hospital from January 2005 to December 2009. The main outcome measures were readmission rate to hospital within 7 or 28 days of discharge RESULTS: A total of 16 496 patient admissions were included in the analysis. Of these discharges, 3397 (20.6%) patients did not have a summary completed within a week of discharge. There were significant linear trends between patients' readmission rates within 7 (P < 0.001) or 28 days (P < 0.001) and categories reflecting the delay in dispatch of their discharge summaries. The absence of a discharge summary was associated with a 79% increase in the rate of readmission within 7 days [95% confidence interval (CI) 42 to 124% increase; P < 0.001] and a 37% increased rate of readmission within 28 days (95% CI 17 to 61% increase; P < 0.001). If aged less than 80 years, the absence of a discharge summary was associated with a 127% increase in readmission rate within 7 days (95% CI 72 to 202% increase; P < 0.001) and a 55% increase within 28 days (95% CI 25 to 91% increase; P < 0.001) after discharge. CONCLUSIONS: Delayed transmission or absence of a discharge summary is associated with readmission of the patient; more so in patients less than 80 years old. If no summary is generated by 7 days after discharge, the rate of readmission within 7 or 28 days after discharge is indistinguishable from no summary being written at all.

Azathioprine hypersensitivity presenting as cardiogenic shock and Sweet's syndrome in a patient with microscopic polyangiitis.

Azathioprine hypersensitivity is a clinical syndrome which may manifest from isolated fever and rash to multi-organ failure. This rare condition is usually self-limiting following the discontinuation of azathioprine. Therefore, it is important to maintain a high index of clinical suspicion for hypersensitivity reactions with azathioprine therapy. We report a case of azathioprine hypersensitivity in a 69-year-old woman who developed cardiogenic shock and Sweet's syndrome following the initiation of azathioprine for her underlying autoantibodies to neutrophil cytoplasmic antigens (ANCA) associated microscopic polyangiitis.