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. Early diagnosis and treatment of ANCA-vasculitis cannot be overemphasized as this reduces the risk of severe organ damage. We report a 64-year-old lady with SARS-CoV-2 infection who developed ANCA-vasculitis with acute kidney injury and we reviewed the literature on this plausible association. We performed an electronic search of the MEDLINE, EMBASE, CINAHL, and EMCARE databases for research studies and case series and reports published in the English language between April 2020 and February 2022. Our review suggests that patients with COVID-19 infection who had proteinase 3-ANCA positive vasculitis with diffuse alveolar haemorrhage had fatal outcomes. We also noticed an increased incidence of active urine sediments. We emphasize the importance of a high index of suspicion for diagnosis and early treatment of vasculitis to ensure an improved outcome.

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. Two-third of patients with CKD worldwide will be residents of developing countries by the year 2030. Risk factors for CKD are prevalent in the sub-Saharan Africa region; this review discusses the available data regarding the relationship between obesity and CKD. The prevalence of CKD appears to correlate with increasing adiposity in sub-Saharan Africa; however, limited data are currently available, and the analysis of this association is further complicated by a variety of parameters used to define obesity. (eg, body mass index vs waist circumference). Longer, large-scale studies are needed to inform the prevalence and kidney implications of obesity in sub-Saharan Africa.

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. Here, we discuss the benefits and relative risks of these novel agents and highlight important clinical issues of relevance to general physicians.

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. Some aspects of subsequent specialist management are also discussed.

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. Abdominal imaging revealed bilateral ureteric obstruction due to retroperitoneal fibrosis and so she underwent urgent ureteric stent insertion. Subsequent treatment with oral corticosteroids led to resolution of her symptoms and regression of the retroperitoneal mass.

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. We postulate that her cardiac and renal disease were both complications of her CLL. In patients with CLL who develop new clinical signs or symptoms (even if apparently unrelated), consideration should be given as to whether these may be disease complications as this may serve as an indication to commence anti-CLL therapy; close liaison between different specialties is vital.

Hepatitis E infection in solid organ transplant recipients: An overlooked diagnosis?
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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. His immunosuppression was cautiously reduced, and his liver biochemistry and viral PCR gradually normalized without the need for additional antiviral therapy.
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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. This case highlights the importance of tailoring the established management guidelines appropriately.

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. Her blood pressure improved rapidly following insertion of bilateral nephrostomies. The speed of resolution of hypertension following relief of obstruction suggests that humorally mediated vasoconstriction can play an important role in the mechanism by which hydronephrosis causes hypertension. We also discuss other causes of renal parenchymal compression that may lead to the development of hypertension.

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. Within 5 days of liver transplantation, we found that the entire H2Kb-reactive T-cell pool was stimulated to proliferate and differentiate into memory or effector cells that were detectable within lymphoid tissues as well as the liver graft itself. However, despite the generation of effector or memory T cells, liver allografts were accepted, which correlated with the exhaustion or deletion of such cells. In contrast, although activation and proliferation of H2Kb-reactive CD8+ T cells was observed after transplantation of heart or kidney grafts, unactivated, H2Kb-reactive CD8+ T cells were still present in the spleen even long term. Interestingly, differences in the effector function of liver and kidney graft infiltrating donor-reactive CD8+ T cells were not detected after adoptive transfer into immunodeficient mice, despite a reduction in Th1-type cytokines within liver grafts. CONCLUSIONS: The rapid and extensive initial activation and differentiation of donor-reactive CD8+ T cells that occurs after liver transplantation leads to clonal exhaustion or deletion of the alloreactive CD8+ T-cell repertoire resulting in spontaneous tolerance induction.

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. Ca (H2) recipients of C57BL/10 (B10; H2) liver and heart allografts 10 days after transplantation, were transferred into CBA. Rag1 mice to investigate their influence on skin allograft rejection mediated by CD45RBCD4 effector T Cells. RESULTS: Fully allogeneic B10 liver allografts were spontaneously accepted by naive CBA.Ca recipient mice, whereas B10 cardiac allografts were acutely rejected (mean survival time=7 days). Strikingly, however, CD25CD4 T cells isolated from both liver and cardiac allograft recipients were able to prevent skin allograft rejection in this adoptive transfer model. Interestingly, CD25CD4 T cells isolated from liver graft recipients also showed suppressive potency upon adoptive transfer. Furthermore, depletion of CD25CD4 T cells in primary liver allograft recipients did not prevent the acceptance of a secondary donor-specific skin graft. CONCLUSIONS: Our data provide evidence that the presence of CD25CD4 regulatory T cells is not a unique feature of allograft acceptance and is more likely the result of sustained exposure to donor alloantigens in vivo.

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(+) T cells, but not CD25(-)CD4(+) T cells, showed a fivefold increase in IFN-gamma mRNA expression within 24 h of re-encountering alloantigen in vivo. This expression kinetic was highly antigen-specific and was of functional significance. Neutralizing IFN-gamma at the time of cotransfer of alloantigen reactive T reg cells, together with CD45RB(high)CD4(+) effector T cells into Rag(-/-) skin graft recipients, resulted in skin graft necrosis in all recipients; the generation and function of alloantigen-reactive T reg cells was impaired dramatically in IFN-gamma-deficient mice. These data support a unique role for IFN-gamma in the functional activity of alloantigen-reactive T reg cells during the development of operational tolerance to donor alloantigens 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. Here we demonstrate that, although this regulation can be antigen-specific, reactivation with the original tolerizing alloantigen allows the Treg cells to suppress rejection of third-party allografts. Aware of the limitations of alloantigen pretreatment, we asked whether graft-protective Treg cells could be generated against unrelated, nongraft antigens. We demonstrate that bystander regulation also extends to CD25(+)CD4(+) Treg cells generated in vivo by exposure to nominal antigens under anti-CD4 antibody cover. Providing these Treg cells are reexposed to the tolerizing antigens before adoptive transfer, they prevent the rejection of fully allogeneic skin grafts. That this might form the basis of a clinically relevant tolerance induction strategy is demonstrated by the fact that, when combined with subtherapeutic anti-CD8 antibody, Treg cells generated in response to nongraft antigens facilitate the acceptance of cardiac allografts in primary recipients.