SARS-CoV-2 Infection: A Forerunner or Precursor in Anti-neutrophil Cytoplasmic Antibody-Associated Vasculitis With Kidney Injury.

COVID-19 disease and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis are both multi-systemic conditions. It is postulated there is a causal relationship between both conditions and this is supported by some case reports. The symptoms of COVID-19 can mimic those of vasculitis especially when the respiratory system is affected.

Obesity and CKD in Sub-Saharan Africa: A Narrative Review.

Obesity is a major public health problem in the developed world, where it has reached an epidemic status over the last few decades. In parallel with this, the prevalence of chronic kidney disease (CKD) has increased. Although obesity is a risk factor for hypertension and diabetes, it is also independently associated with the development and progression of CKD.

Sodium-glucose co-transporter 2 inhibitors: game changers when handled with care?

Recent years have seen a paradigm shift in the management of patients with diabetes mellitus. Rather than good glycaemic control being the sole primary aim, the therapeutic focus has broadened to consider potential additional cardiovascular and renal benefits. Sodium-glucose co-transporter 2 inhibitors, such as empagliflozin, canagliflozin and dapagliflozin, have gained increasing prominence, with evidence suggesting significant improvement in outcomes in patients with established cardiovascular and renal disease.

Thrombotic microangiopathy with renal injury: an approach for the general physician.

Thrombotic microangiopathy with renal dysfunction is a haematological and renal emergency warranting urgent diagnosis and intervention. As the potential underlying causes may be complex, assessment and management can be challenging for treating clinicians, and a timely and collaborative approach between general physicians, haematologists and nephrologists may be extremely helpful in order to optimise clinical outcomes. This paper will aim to build an understanding of different potential presentations of thrombotic microangiopathies and provide a practical framework for diagnosis and management, using a case-based discussion format, for acute and general physicians.

Retroperitoneal fibrosis: a rare disease for frontline clinicians.

Retroperitoneal fibrosis is a rare cause of renal dysfunction, typically presenting with obstructive uropathy (sometimes with extra-renal manifestations). Given its insidious and subtle presentation, reaching the diagnosis can be challenging. We report the case of a 65-year-old female presenting with a 6-month history of unexplained constitutional symptoms, weight loss and mild renal impairment.

Multiple Faces of Chronic Lymphocytic Leukaemia: A Patient with Renal, Cardiac, and Skeletal Complications.

We describe a patient who had chronic lymphocytic leukaemia (CLL) Binet stage A at presentation with further evidence of disease at multiple sites but who initially required no treatment. However, several years later, her peripheral blood lymphocyte count started to increase, and soon after that she suffered an acute myocardial infarct (in the absence of coronary atheroma) together with proteinuric renal failure due to membranoproliferative glomerulonephritis. Her renal function improved markedly following anti-CLL chemotherapy.

Hepatitis E infection in solid organ transplant recipients: An overlooked diagnosis? .

Hepatitis E virus (HEV) is gaining recognition as an important but under-recognized pathogen, particularly in immunocompromised individuals. It should be considered as a potential differential diagnosis in such patients presenting with acute hepatitis. We report a case of a kidney-pancreas transplant recipient who developed acute liver dysfunction; this was found to be due to HEV infection acquired through consumption of undercooked pork.

A Catastrophic Consequence of Cramp.

Quinine has long been used for the treatment of conditions such as malaria and leg cramps, and is also present at low levels in some beverages; however, it can cause serious side effects. We describe a patient who developed severe haemolysis, thrombocytopaenia, and acute kidney injury following the ingestion of a single dose of quinine. This case demonstrates the importance of awareness of such potentially life-threatening consequences of exposure to this agent.

Lesson of the month 1: Diabetic ketoacidosis in established renal failure.

Diabetic ketoacidosis (DKA) is a common medical emergency. The pathophysiology of DKA in patients with advanced chronic kidney disease differs significantly from patients with preserved renal function. We describe a patient with pre-dialysis renal failure who presented with DKA.

Hypertension and hydronephrosis: rapid resolution of high blood pressure following relief of bilateral ureteric obstruction.

Hypertension secondary to hydronephrosis is not commonly reported in the medical literature. Tubuloglomerular feedback and the renin-angiotensin-aldosterone axis are thought to mediate this process. We describe a patient presenting with acute kidney injury and bilateral hydronephrosis secondary to pelvic malignancy in which peripheral venous renin and aldosterone were elevated.

Pulmonary fibrosis-an uncommon manifestation of anti-myeloperoxidase-positive systemic vasculitis?

Small vessel vasculitides such as microscopic polyangiitis and Wegener's granulomatosis commonly involve the kidney and lung, with alveolar haemorrhage being the commonest manifestation of pulmonary involvement. Here we describe a patient who developed acute renal failure and pulmonary haemorrhage with positive autoantibodies against myeloperoxidase 1 year after a diagnosis of usual interstitial pneumonia had been made and we discuss the uncommon association of pulmonary fibrosis and anti-myeloperoxidase positive vasculitis.

Exhaustive differentiation of alloreactive CD8+ T cells: critical for determination of graft acceptance or rejection.

Background: The precise role that CD8+ T cells play in the rejection and acceptance of different types of allograft is unclear and has been shown to vary between donor-recipient combinations.

Methods: The response of adoptively transferred CD8+ T cells reactive to the donor alloantigen H2Kb was examined after transplantation of H2Kb liver, kidney, and heart grafts in mice.

Results: After transfer of 6 x 10(6) alloreactive CD8+ T cells to T-cell depleted syngeneic mice spontaneous long-term acceptance of liver grafts was observed, whereas kidney and heart grafts were acutely rejected.

CD25+CD4+ regulatory T cells develop in mice not only during spontaneous acceptance of liver allografts but also after acute allograft rejection.

Background: Liver grafts transplanted across a major histocompatibility barrier are accepted spontaneously and induce donor specific tolerance in some species. Here, we investigated whether liver allograft acceptance is characterized by, and depends upon, the presence of donor reactive CD25CD4 regulatory T cells.

Methods: CD25 and CD25CD4 T cells, isolated from CBA.

IFN-gamma production by alloantigen-reactive regulatory T cells is important for their regulatory function in vivo.

The significance of cytokine production by CD4(+) regulatory T (T reg) cells after antigen exposure in vivo and its impact on their regulatory activity remains unclear. Pretreatment with donor alloantigen under the cover of anti-CD4 therapy generates alloantigen reactive T reg cells that can prevent rejection of donor-specific skin grafts that are mediated by naive CD45RB(high)CD4(+) T cells. To examine the kinetics and importance of cytokine gene transcription by such alloantigen-reactive T reg cells, pretreated mice were rechallenged with donor alloantigen in vivo.

CD25+CD4+ regulatory T cells generated by exposure to a model protein antigen prevent allograft rejection: antigen-specific reactivation in vivo is critical for bystander regulation.

The importance of CD25(+)CD4(+) regulatory T (Treg) cells in the control of immune responses is established, but their antigen specificity in vivo remains unclear. Understanding Treg-cell specificity requirements will be important if their potential is to be developed for immunotherapy. Pretreatment of recipient mice with donor alloantigen plus anti-CD4 antibody generates CD25(+)CD4(+) Treg cells with the capacity to prevent skin allograft rejection in adoptive transfer recipients.

A simple method to cure established tumors by inflammatory killing of normal cells.

We describe a simple technology used to cure an established metastatic disease. Intradermal injection of plasmid DNA encoding a transcriptionally targeted cytotoxic gene, along with hsp70, not only promoted tissue-specific, inflammatory killing of normal melanocytes, but also induced a CD8(+) T-cell-dependent, antigen-specific response in mice that eradicated systemically established B16 tumors. This CD8(+) T cell response was subsequently suppressed in vivo within a few days.

Alloantigen-induced CD25+CD4+ regulatory T cells can develop in vivo from CD25-CD4+ precursors in a thymus-independent process.

The capacity of naturally occurring autoreactive CD25+CD4+ regulatory T cells (Treg) to control immune responses both in vivo and in vitro is now well established. It has been demonstrated that these cells undergo positive selection within the thymus and appear to enter the periphery as committed CD25+CD4+ Treg. We have shown previously that CD25+CD4+ Treg with the capacity to prevent skin allograft rejection can be generated by pretreatment with donor alloantigen under the cover of anti-CD4 therapy.

Regulatory cells in transplantation.

Regulatory T cells can play an important role in both the induction and maintenance of tolerance to donor alloantigens in vivo. Regulatory activity specific for donor alloantingens is enriched amongst CD4+CD25+ T cells in some settings and can be induced by manipulating the immune system before transplantation. Donor alloantigen-specific CD4+CD25+ regulatory T cells can control aggressive CD4+ as well as CD8+ T cells thereby preventing rejection and can mediate linked unresponsiveness.

Pretransplant blood transfusion without additional immunotherapy generates CD25+CD4+ regulatory T cells: a potential explanation for the blood-transfusion effect.

Background: Preoperative blood transfusion has had a significant historic impact on graft outcome in clinical kidney transplantation, and the effect has been widely replicated in many experimental transplant models. Although the mechanisms underlying the blood-transfusion effect are poorly understood, one possibility is that preexposure to alloantigen results in the induction of regulatory cells with the capacity to control the effector arm of the immune response.

Methods: Recent studies in autoimmune models have shown that T cells with regulatory function can be isolated from unmanipulated animals on the basis of CD25 expression, and we have recently shown that pretreatment of recipient mice with donor alloantigen combined with anti-CD4 antibody therapy generates CD25+CD4+ T cells that can prevent graft rejection.