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.

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.

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.

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.

Successful treatment of calcific uremic arteriolopathy with sodium thiosulfate in a renal transplant recipient.

Abstract Calcific uremic arteriolopathy (CUA) is a rare but life-threatening disorder of arteriolar calcification. It frequently leads to severe ischemia, intense pain, and tissue necrosis with non-healing skin ulcerations. CUA usually occurs in patients with chronic kidney disease (CKD), especially those on dialysis, and its occurrence is rare in kidney transplant recipients. The treatment of this disorder is not clearly defined, and no randomized prospective trials are available. Treatment has focused on optimizing dialysis treatment, control of bone mineral parameters, wound care, experimental anticalcification therapies-using bisphosphonates, cinacalcet, parathyroidectomy, and hyperbaric oxygen. Such treatments are based on the pathophysiological considerations and evidences from case reports or series. Recently, several cases have reported about the emerging benefits of intravenous sodium thiosulfate (STS) in the treatment of CUA. STS has resulted in rapid pain relief, wound healing, and prevention of death. We report a case of CUA in a 63-year-old Caucasian man with a functioning renal allograft. In this patient, intravenous STS was administered for 8 months, which was the principal therapy, which resulted in complete resolution of the CUA and skin healing.

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.

The selection of acute medical admissions for a short-stay unit.

Objective of this study is to evaluate the selection of patients to be admitted to a hospital medical short-stay unit (SSU) where acute medical admissions with a predicted length of stay of between 24 and 72 h are managed. This is a retrospective observational study evaluating outcomes of all admissions to the medical SSU between January 2005 and December 2008. Factors that influence inappropriate allocation of patients to the SSU or alternative longer stay medical units were evaluated. Length of stay (LOS), mortality, Charlson score, admission to intensive care unit (ICU) (from the SSU), discharge diagnosis, and 7-day readmission rate were analysed. Over 4 years, 45% of the general medical inpatient take, 9,125 admission episodes, were managed by the medical SSU. On an average, 72% of these admissions to the SSU stayed fewer than 72 h. After excluding in-hospital deaths, there were 8,381 admissions to the general medical unit discharged within 72 h, and 77% of these were managed by the SSU during the study period. Inappropriate admissions to the SSU (LOS more than 72 h) tended to be older patients with more complex medical comorbidities. Other factors contributing to prolonged stay in the SSU included weekend admissions, and transfers to the ICU. The 7-day readmission rate was low at 3%; the all-cause hospital mortality for patients admitted to the medical SSU was 2% despite a 32% increase in workload in the medical SSU over these 4 years. In the context of fixed resources and a steeply increasing patient workload, a large proportion of general medical patients can be managed in a medical SSU with the majority being discharged home within 72 h while keeping all-cause in-hospital mortality and readmission rates low. More accurate identification of appropriate patients on admission by using a physiological clinical score and addressing operational issues particularly on weekends could lead to a more efficient SSU.

Malignant pleural mesothelioma with associated minimal change disease and acute renal failure.

Paraneoplastic manifestations in malignant pleural mesothelioma are rare. We report a case of malignant pleural mesothelioma associated with minimal change disease (MCD). A 58-year-old man with occupational exposure to asbestos presented with severe peripheral edema, heavy proteinuria, and acute renal failure shortly after the diagnosis of mesothelioma had been confirmed. The renal biopsy demonstrated MCD. The underlying pathogenesis of this association remains unknown.

Outcomes of establishing an acute assessment unit in the general medical service of a tertiary teaching hospital.

OBJECTIVE: To evaluate the impact of an acute assessment unit (AAU) on length of hospital stay (LOS), emergency department (ED) waiting times, direct discharge rate, unplanned readmission rate and all-cause hospital mortality of general medical patients. DESIGN AND SETTING: Retrospective comparison of data for general medical patients admitted to a tertiary teaching hospital in Adelaide, South Australia, before and after the establishment of an AAU (reference years, 2003 [before] and 2006 [after]). MAIN OUTCOME MEASURES: Mean LOS, ED waiting times and all-cause hospital mortality during calendar years 2003 (pre-establishment) and 2006 (post-establishment). RESULTS: Following the establishment of an AAU, the mean LOS shortened (from 6.8 days in 2003 to 5.7 days in 2006; P < 0.001) despite a 50.5% increase in the number of admissions (from 2652 to 3992). The number of admitted patients waiting in the ED more than 8 hours for a hospital bed decreased (from 28.7% to 17.9%; P < 0.001), as did the number waiting more than 12 hours (from 20.2% to 10.4%; P < 0.001). The rates of unplanned readmission within 7 and 28 days did not change. The all-cause hospital mortality for general medical admissions was 4.6% in 2003 v 3.7% in 2006 (P = 0.056). CONCLUSION: The establishment of an AAU within the general medical service coincided with decreases in both LOS and ED waiting times, despite a 50% increase in admissions. This structural reform in the process of acute medical care may have contributed to the improvement in these key health care performance indices without compromising the quality of patient care.

Mediastinal parathyroid carcinoma presenting with severe skeletal manifestations.

Parathyroid carcinoma is a rare malignancy, accounting for about 1% of primary hyperparathyroidism. We report the case of a 23-year-old man who presented with poorly united mid-shaft fracture of the left femur with severe hypercalcaemia in the setting of 99 mTc sestamibi-avid lesions in the mediastinal and thoracic vertebrae. The patient underwent surgery, and histopathology revealed a low-grade parathyroid carcinoma. After surgery, the patient developed severe hungry bone syndrome requiring intensive calcium, magnesium and active vitamin D supplementation. A review of the literature was undertaken with regards to mediastinal parathyroid carcinoma, management of refractory hypercalcaemia in this setting and hungry bone syndrome.