With earlier institution of antiretroviral therapy, kidney diseases other than HIV-associated nephropathy (HIVAN) predominate in HIV-infected persons. Outcomes for these diseases are typically worse among those infected with HIV, but the reasons for this are not clear. Here, we examined the role of APOL1 risk variants in predicting renal histopathology and progression to ESRD in 98 HIV-infected African Americans with non-HIVAN kidney disease on biopsy. We used survival analysis to determine time to ESRD associated with APOL1 genotype. Among the 29 patients with two APOL1 risk alleles, the majority (76%) had FSGS and 10% had hypertensive nephrosclerosis. In contrast, among the 54 patients with one APOL1 risk allele, 47% had immune-complex GN as the predominant lesion and only 23% had FSGS. Among the 25 patients with no APOL1 risk allele, 40% had immune-complex GN and 12% had FSGS. In 310 person-years of observation, 29 patients progressed to ESRD. In adjusted analyses, individuals with two APOL1 risk alleles had a nearly three-fold higher risk for ESRD compared with those with one or zero risk alleles (P=0.03). In summary, these data demonstrate an association between APOL1 variants and renal outcomes in non-HIVAN kidney disease, suggesting a possible use for APOL1 genotyping to help guide the care of HIV-infected patients.
IgA nephropathy remains the most common primary glomerular disease worldwide. It affects children and adults of all ages, and is a leading cause of end-stage kidney disease, making it a considerable public health issue in many countries. Despite being initially described over 50 years ago, there are still no disease specific treatments, with current management for most patients being focused on lifestyle measures and renin-angiotensin-aldosterone system blockade. However, significant advances in the understanding of its pathogenesis have been made particularly over the past decade, leading to great interest in developing new therapeutic strategies, and a significant rise in the number of interventional clinical trials being performed. In this review, we will summarise the current state of management of IgAN, and then describe major areas of interest where new therapies are at their most advanced stages of development, that include the gut mucosal immune system, B cell signalling, the complement system and non-immune modulators. Finally, we describe clinical trials that are taking place in each area and explore future directions for translational research.
Almost 40 years ago, Legionella pneumophila was initially recognized as the cause of a major respiratory outbreak. Since the first description of Legionnaires' disease, surveillance schemes have been implemented worldwide; however, legionellosis is still an underdiagnosed and underreported entity. Legionella pneumophila causes a severe inflammatory pneumonia that primarily affects susceptible patients as a result of advanced age, underlying debilitating conditions, and immunosuppression. Organ-specific and extrapulmonary manifestations have also been described. Cooling towers and water systems in buildings and hospitals have been reported to be environmental reservoirs that commonly harbor this pathogen. Numerous prevention guidelines vary in scope, and effective surveillance and detection systems are required for early clinical intervention. Various diagnostic tests are available, but they do not offer the desired sensitivity. To date, urinary antigen testing is still the most rapid and inexpensive method used in the diagnosis of Legionella infection. Culture and isolation of L. pneumophila from clinical specimens are not as costeffective as other diagnostic methods, but they continue to be the criterion standard for the diagnosis of Legionnaires' disease. The newer macrolides and respiratory tract fluoroquinolones are highly effective in the treatment of Legionella infection. Current understanding of Legionnaires' disease is crucial in the identification and management of major outbreaks.
BackgroundPrimary myelofibrosis (PMF) is a type of myeloproliferative neoplasm (MPN) characterized by the predominant proliferation of megakaryocytes and granulocytes in the bone marrow, leading to the deposition of fibrous tissue, and by a propensity toward extramedullary hematopoiesis. Renal involvement in PMF is rare, but kidney tissue samples from these patients reveal MPN-related glomerulopathy, a recently discovered condition, in the late stages of the disease.Case presentationWe present the first case described in the medical literature of a patient with early renal glomerular involvement in PMF/MPN. A 60-year-old man with stage 4 chronic kidney disease and a recent diagnosis of PMF (within 4 weeks of presentation at our renal division) presented with generalized body swelling, acute kidney injury, and massive nephrotic-range proteinuria. Kidney biopsy was performed to determine the etiology of the patient’s renal dysfunction and revealed early renal glomerular involvement that was histologically characteristic of MPN-related glomerulopathy. Early diagnosis and prompt medical management returned the patient’s kidney functionality to the levels seen on initial presentation at our hospital.ConclusionLarge studies with long follow-up durations are necessary to identify and categorize the risk factors for the development of MPN-related glomerulopathy, to standardize therapeutic regimens, and to determine whether aggressive management of the myelofibrosis slows the progression of kidney disease.
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