Acute leg pain and weakness in pregnancy: A new diagnosis of myotonic dystrophy.

We present a unique case of a 44-year-old woman who presented at 29 weeks' gestation with proximal limb pain and elevated creatine kinase. This occurred in the background of premature cataracts, atrial fibrillation and abnormal liver function. Clinical, pathological and neurodiagnostic findings supported a diagnosis of myotonic dystrophy, confirmed by genetic testing which revealed dystrophia myotonica protein kinase gene expansion.

Expression of NEDD4L and ENaC in Urinary Extracellular Vesicles in Pre-eclampsia.

Objective: To assess changes in expression of renal epithelial sodium channel (ENaC) and NEDD4L, a ubiquitin ligase, in urinary extracellular vesicles (UEV) of pre-eclamptic women compared to normal pregnant controls.

Methods: Urine was collected from pre-eclamptic women (PE,  = 20) or during normal pregnancy (NP,  = 20). UEV were separated by differential ultracentrifugation.

Management of chronic rheumatic diseases in women 18-45 years of age in Asia Pacific: insights from patient and clinician surveys.

Objective: Perspectives of women aged 18-45 years with chronic rheumatic diseases (CRD), and clinicians, in the Asia-Pacific (APAC) region are reported.

Methods: Online surveys were completed by women, pregnant in the past 2-5 years, with moderate to severe rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), and rheumatologists, obstetricians, orthopaedic surgeons who medically manage CRDs.

Results: Among 210 (RA 122, PsA 48, axSpA 40) patients, 52% (n = 109/210) delayed their decision to have children, most commonly due to concerns of passing on disease to offspring.

Successful Implementation of an Increased Viral Risk Donor Waiting List for Preconsented Kidney Transplant Candidates in Victoria, Australia.

Unlabelled: Increased viral risk donors (IVRDs) with increased risk behaviors for blood-borne virus infection and negative nucleic acid testing have a low absolute risk of "window period" infection. Utilization and allocation of IVRD organs differ between jurisdictions.

Methods: We examined the characteristics and utilization of deceased donor IVRD kidneys and recipient outcomes within a 2-y period (July 31, 2018-July 31, 2020) postimplementation of a new opt-in allocation pathway for preconsented recipients in Victoria, Australia.

Dialysis and driving: an anonymous survey of patients receiving dialysis for end-stage kidney disease.

Background: Driving is a complex task requiring multiple cognitive domains and the musculoskeletal system. Cognitive dysfunction is associated with driving impairment. Dialysis patients are known to have a high prevalence of cognitive impairment and other comorbidities, and may be at risk of driving impairment.

Management of thrombotic microangiopathy in pregnancy and postpartum: report from an international working group.

Pregnancy and postpartum are high-risk periods for different forms of thrombotic microangiopathy (TMA). However, the management of pregnancy-associated TMA remains ill defined. This report, by an international multidisciplinary working group of obstetricians, nephrologists, hematologists, intensivists, neonatologists, and complement biologists, summarizes the current knowledge of these potentially severe disorders and proposes a practical clinical approach to diagnose and manage an episode of pregnancy-associated TMA.

A case of ANCA-associated vasculitis presenting de novo in pregnancy, successfully treated with rituximab.

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are rare small vessel vasculitides of unknown cause. The pathogenic role of MPO-ANCA in the vasculitides has been supported using various animal models, with B-cells playing a role in the disease pathogenesis. Pregnancy in the presence of an autoimmune disease such as vasculitis is often associated with significant morbidity.

Ganciclovir-resistant post-transplant cytomegalovirus infection due to combined deletion mutation at codons 595-596 of the UL97 gene.

The development of antiviral-resistant cytomegalovirus (CMV) infection complicates the management of transplant recipients. We describe the case of a 65-year-old male who developed CMV disease on valganciclovir prophylaxis (donor CMV IgG positive, recipient CMV IgG indeterminate) 30 days after combined liver-kidney transplantation for alcoholic cirrhosis and hepato-renal syndrome. After an initial complete response to treatment dose oral valganciclovir, he developed recurrent CMV viraemia.

Immunomodulatory drugs in pregnancy and lactation.

Pregnancy presents challenges for women with autoimmune diseases. It is associated with significant physiological, hormonal and immunomodulatory changes which are complex and vary according to the stage of pregnancy Pregnancy planning and counselling should be offered Autoimmune diseases such as rheumatoid arthritis tend to improve in pregnancy while systemic lupus erythematosus may increase in activity During pregnancy the chosen regimen should control or prevent underlying disease activity and minimise risk to the fetus. Ideally, women should be on a stable regimen before conception Poorly controlled disease is associated with poor outcomes for both mother and fetus, such as higher risks of pre-eclampsia, early delivery and growth restriction of the fetus Postpartum, there is a sudden fall in hormone concentrations, and a switch to a pro-inflammatory state.

Increased expression and phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoforms in urinary exosomes in pre-eclampsia.

Background: Glycolysis is altered in various kidney diseases, but little is known about glycolysis in pre-eclampsia, a multi-system disorder with major pathological effects on the kidney. Urinary exosomes provide a non-invasive alternative for studying changes in kidney metabolism. This study aims to characterise the expression and phosphorylation of isozymes of the key glycolytic regulatory protein, 6-phosphofructokinase-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2), in urinary exosomes of subjects with pre-eclampsia (PE), compared to normotensive non-pregnant (NC) and normotensive pregnant (NP) controls.

Pre-eclampsia is associated with altered expression of the renal sodium transporters NKCC2, NCC and ENaC in urinary extracellular vesicles.

Pre-eclampsia is a hypertensive disorder of pregnancy characterised by hypertension and sodium retention by the kidneys. To identify changes in sodium uptake proteins in the tubules of the distal nephron, we studied their expression in urinary extracellular vesicles or exosomes (uEVs). Urine was collected from women with pre-eclampsia or during normal pregnancy, and from healthy non-pregnant controls.

A rare cause of hypertension in pregnancy: Phaeochromocytoma.

A 26-year-old primigravida at 35 weeks' gestation was transferred to our institution from a regional hospital for management of presumed preeclampsia. Due to the labile nature of her hypertension, further investigation was undertaken which revealed a right-sided phaeochromocytoma. Alpha blockade was commenced, and an uncomplicated elective caesarean delivery was performed at 38 weeks' gestation under spinal anaesthetic.

Suspected atypical haemolytic uraemic syndrome in two post-partum patients with foetal-death in utero responding to eculizumab.

Background: Atypical haemolytic uraemic syndrome (aHUS) is a rare condition with the triad of microangiopathic haemolytic anaemia, thrombocytopenia and acute kidney injury. Other conditions that present in a similar manner peri-partum include thrombotic thrombocytopaenic purpura, and pregnancy associated conditions including HELLP syndrome (haemolysis, elevated liver enzymes and low platelets), severe pre-eclampsia and less commonly acute fatty liver of pregnancy.

Case Reports: We describe two cases of suspected aHUS, who presented post-partum with foetal death-in-utero at 33 and 37 weeks respectively.

Corticosteroids worsen proteinuria and increase intraglomerular signaling by NF-ĸB in a model of membranous glomerulonephritis.

Background/aims: Passive Heymann nephritis (PHN) is a model of human membranous glomerulonephritis characterized by heavy proteinuria. We have recently demonstrated activation of NF-κB by podocytes in this model. In this study, therefore, we have determined whether dexamethasone (DEX) and pyrrolidine dithiocarbamate (PDTC), therapies that inhibit NF-κB, influence proteinuria.

A pilot, randomized, double-blind, cross-over study of high cut-off versus high-flux dialysis membranes.

Background: High cut-off (HCO) membranes may increase beta(2)-microglobulin (beta2M) removal compared to standard high-flux membranes.

Methods: Eight stable haemodialysis patients were enrolled in a prospective, randomized, double-blind, cross-over study and treated with HCO and high-flux membranes for 2 weeks each, between a 1-week washout period. Primary end point was serum beta2M removal.

Induction of passive Heymann nephritis in complement component 6-deficient PVG rats.

Passive Heymann nephritis (PHN), a model of human membranous nephritis, is induced in susceptible rat strains by injection of heterologous antisera to rat renal tubular Ag extract. PHN is currently considered the archetypal complement-dependent form of nephritis, with the proteinuria resulting from sublytic glomerular epithelial cell injury induced by the complement membrane attack complex (MAC) of C5b-9. This study examined whether C6 and MAC are essential to the development of proteinuria in PHN by comparing the effect of injection of anti-Fx1A antisera into PVG rats deficient in C6 (PVG/C6(-)) and normal PVG rats (PVG/c).

Results of an Aboriginal community-based renal disease management program incorporating point of care testing for urine albumin:creatinine ratio.

Introduction: There has been a significant increase in the burden of renal disease among Aboriginal Australians over the past 15 years. Urine albumin:creatinine ratio (ACR) is a well-established marker of microalbuminuria and can be conveniently performed on the DCA 2000 point-of-care testing (POCT) analyser (Bayer Australia; Melbourne, VIC, Australia) with an on-site result available in 7 min. The application of the urine ACR POCT for renal disease risk assessment was pioneered by our group in the Umoona Kidney Project.

Albuminuria in a remote South Australian Aboriginal community: results of a community-based screening program for renal disease.

Introduction: The poverty, poor environmental living conditions and poor health standards experienced by Aboriginal Australians in some communities in rural and remote Australia have been described recently as 'fourth world'. For more than a century Aboriginal people have suffered the effects of dispossession of their land; destruction of their traditional culture and values; and exposure to infectious diseases, alcohol and the Western diet that is high in fat and sugar. Collectively these factors have contributed to the prevalence of chronic disease that afflicts Aboriginal people.

Targeting gene expression to endothelium in transgenic animals: a comparison of the human ICAM-2, PECAM-1 and endoglin promoters.

It is highly likely that successful pig-to-human xenotransplantation of vascularized organs will require genetic modification of the donor pig, and in particular of donor vascular endothelium. Promoters are generally tested in transgenic mice before generating transgenic pigs. Several promoters have been used to drive endothelial cell-specific expression in mice but none have yet been tested in pigs.

Renal ischemia-reperfusion increases endothelial VEGFR-2 without increasing VEGF or VEGFR-1 expression.

Background: Hypoxia is a potent stimulus to angiogenesis. Expression of the angiogenic growth factor vascular endothelial growth factor (VEGF) and its receptors (VEGFR-1 and VEGFR-2) is up-regulated by hypoxia in a variety of organs and cell lines. We have previously reported that VEGF expression is not increased in renal ischemia-reperfusion injury, although tubular cells concentrate VEGF at their basolateral surface.

Activation of nuclear factor-kappa B by podocytes in the autologous phase of passive Heymann nephritis.

Background: The present study examined whether activation of nuclear factor-kappa B (NF-kappa B) occurs within podocytes in passive Heymann nephritis (PHN) and contributes to the pathogenesis of proteinuria.

Methods: Electrophoretic mobility shift assays (EMSAs) were used to detect NF-kappa B activation, and supershift assays were used to determine the subunits involved. Localization of the activated NF-kappa B subunit p50 was performed by immunohistochemistry.

Inhibition of heparin-binding epidermal growth factor-like growth factor increases albuminuria in puromycin aminonucleoside nephrosis.

Background: Our previous work in the acute puromycin aminonucleoside nephrosis (PAN) model has demonstrated up-regulation of heparin-binding epidermal growth factor-like growth factor (HB-EGF) mRNA and protein within glomerular epithelial cells (GECs) prior to the onset of proteinuria.

Methods: To determine whether increased HB-EGF expression in the acute PAN model contributes to the pathogenesis of proteinuria, a monoclonal antibody (DE10) was produced against recombinant human HB-EGF.

Results: The specificity of DE10 for human HB-EGF was confirmed by enzyme-linked immunosorbent assay, immunohistochemical staining, and flow cytometry of transfected cells expressing human and rat HB-EGF, and inhibition of cell proliferation.

Heparin-binding epidermal growth factor-like growth factor is expressed in the adhesive lesions of experimental focal glomerular sclerosis.

Background: In this study, we attempted to determine whether heparin-binding epidermal growth factor-like growth factor (HB-EGF) was up-regulated in two chronic models of proteinuria.

Methods: Chronic passive Heymann nephritis (PHN) and puromycin aminonucleoside (PAN) models were induced in Sprague-Dawley rats. HB-EGF expression was studied by Northern blotting, in situ hybridization, and immunohistochemistry.

Heparin-binding EGF-like growth factor mRNA is upregulated in the peri-infarct region of the remnant kidney model: in vitro evidence suggests a regulatory role in myofibroblast transformation.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a potent fibroblast and epithelial cell mitogen that may be important in wound healing. The aim of this study was to determine its distribution and possible function in segmental renal infarction. At day 1 postinfarction, in situ hybridization showed that HB-EGF mRNA was markedly increased by tubular epithelial cells bordering the infarcted zone.

Heparin-binding epidermal growth factor-like growth factor in experimental models of membranous and minimal change nephropathy.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a recently described member of the epidermal growth factor (EGF) family. It binds to heparan sulfate proteoglycans via a cationic domain and is a potent mitogen for epithelial cells, fibroblasts and vascular smooth muscle cells. In the present study we have attempted to identify changes in quantity and distribution of HB-EGF in two models of acute glomerular epithelial cell injury, using Western blotting, immunohistochemistry and in situ hybridization.