Nephron. Clinical Practice

BACKGROUND: Acute kidney injury (AKI) is common in hospitalised patients and is associated with adverse long-term consequences. There is an urgent need to understand these sequelae in general hospitalised patients utilising a prospective cohort-based approach. We aimed to test the feasibility of study methodology prior to commencing a large-scale study and investigate the effects of AKI on chronic kidney disease (CKD) progression and proteinuria. METHODS: Pilot study testing novel methodology for remote patient recruitment within a prospective case-control design...

BACKGROUND/AIMS: Lower serum sodium levels have been associated with increased mortality among patients with chronic kidney disease (CKD). Our aim was to analyze the independent factors associated with lower sodium levels among nondialysis patients with advanced CKD and to evaluate the evolution of these patients in comparison to those with higher plasma sodium over a 1-year period. METHODS: We included 72 patients with CKD stages 4 and 5 without clinically evident cardiopathy or liver disease...

Treatment options for systemic lupus erythematosus (SLE) and lupus nephritis (LN) have high associated morbidity and mortality. Side effects, particularly from long-term corticosteroid usage, limit patient adherence, with subsequent impacts on treatment efficacy. In addition, a subset of patients with SLE/LN fails to respond to current standard immunotherapy. There is an urgent need to develop steroid-sparing treatment regimens as well as novel therapies for the management of refractory disease. Rituximab is a chimeric mouse/human monoclonal antibody directed against the B cell CD20 receptor...

The ideal treatment of patients with primary membranous nephropathy (MN) and persistent nephrotic syndrome (NS) is still a matter of debate. This is a major issue since these patients may progress to end-stage kidney disease (ESKD) in 5-10 years. Steroids, alkylating agents, and calcineurin inhibitors have been suggested to achieve NS remission and prevent ESKD in this population. Treatment benefits, however, are uncertain and are often offset by serious adverse events (SAEs). Evidence that B cells play a crucial role in the pathogenesis of the disease, both as precursors of autoantibody-producing cells and as antigen-presenting cells, provided the background for explorative studies testing the role of B cell-depletion therapy with the monoclonal antibody rituximab...

The complement pathway is a central part of the innate immune system and also modulates adaptive immunity. It is implicated in the pathogenesis of glomerular disease by a number of clinical findings. These include the presence of complement components in renal biopsy samples, decreases in circulating levels indicating consumption, the presence of autoantibodies to complement proteins and the association of genetic mutations with disease either in individuals or within families. Further support and mechanistic insights comes from animal models...

Introduction of the standard immunosuppressive treatment has dramatically changed the outcome of patients with both ANCA-associated vasculitis and lupus nephritis, transforming them from incurable diseases with very high short-term mortality to chronic debilitating diseases with much lower short-term, but still relatively high long-term, morbidity/mortality. Long-term morbidity with damage accumulating partly due to the adverse events of the available treatment (namely gonadal toxicity, malignancy, bone disease, cataracts, diabetes, and thromboembolic and cardiovascular disease) has become a major concern...

BACKGROUND: Heat shock proteins (HSPs) are expressed by cells in response to various environmental stresses. A single-nucleotide polymorphism A+1267G of the HSPA1B gene affects the expression of HSP70-2, with the A allele being protective against inflammatory conditions. We investigated the relation between the HSP A+1267G polymorphism and the clinical outcomes of Chinese peritoneal dialysis (PD) patients. METHODS: We studied 347 new PD cases (181 males, age 56...

BACKGROUND: Acute kidney injury (AKI) is common in hospitalized patients. Despite the progress that has been made in the last decade, early identification of AKI cases remains a challenge. In recent years, electronic AKI alert (e-AKI alert) systems have been tested and are usually based on changes in serum creatinine (Cr) values. However, these methods do not include one of the common scenarios, i.e. when there is no available preadmission Cr value available for a patient to compare and hence an e-AKI alert cannot be issued...

Fibroblast growth factor-23 (FGF23) is a bone-derived hormone that regulates phosphate and 1,25-hydroxyvitamin D [1,25(OH)2D] metabolism. FGF23 binds to FGF receptor 1 with its coreceptor Klotho and maintains serum phosphate levels within the normal range by increasing renal phosphate excretion. In addition, FGF23 reduces the synthesis and accelerates the degradation of 1,25(OH)2D to reduce intestinal phosphate absorption. Moreover, FGF23 acts at the parathyroid gland to decrease parathyroid hormone synthesis and secretion...

BACKGROUND/AIMS: There is disagreement regarding the performance of conventional optical microscopy to assess the origin of hematuria. The aim of this study was to determine the optimal cutoff point for dysmorphic cells in order to detect glomerular hematuria by optical and phase-contrast microscopy. METHODS: In total, 131 urine samples (66 from patients with glomerulopathies and 65 from nephrolithiasis patients) were evaluated in a blinded fashion. The percentages of doughnut cells and acanthocytes were verified by optical and phase-contrast microscopy...

BACKGROUND: Bioimpedance analysis (BIA) is well established to assess body composition. Agreements between single- and multi-frequency bioimpedance (SF-BIA, MF-BIS) measurements in subjects undergoing 6 or 3 times/week hemodialysis (HD) were analyzed. METHODS: Total body water (TBW) and intra- and extracellular fluid (ICF, ECF) of subjects enrolled in the Frequent Hemodialysis Network (FHN) Daily Trial (www.clinicaltrials.gov No. NCT00264758) were measured with a Hydra 4200 at baseline (BL) and at 5 months (M5)...

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BACKGROUND: Leukocytosis is a powerful predictor of incident chronic kidney disease (CKD) and related outcomes. However, the association between periodontitis measures and increased leukocytosis in the context of CKD has not been well described. We sought to identify which individual measures of periodontal disease may best associate with reduced estimated glomerular filtration rate (eGFR) and albuminuria, and to test if these measures were associated with increased leukocytosis in subjects with established CKD...

The major advances achieved in immunology and cellular biology have led to the development of biotherapies that specifically target different mediators and pathways involved in the physiopathology of renal diseases. After the major breakthroughs obtained with B-cell depletion in autoantibody-mediated glomerulopathies, several other immunomodulation strategies are being tested in autoimmune glomerulonephritides, such as blockade of B-cell costimulation and activation, inhibition of complement pathways or modification of the T-B-lymphocyte crosstalk...

A major shift in our understanding of the membranoproliferative glomerulonephritis (MPGN) lesion is the focus on which components of the complement pathway are involved in mediating renal injury. Hence, MPGN is no longer classified solely by ultrastructural findings on biopsy but instead divided into immune complex-mediated lesions versus complement-mediated lesions. This emphasis on complement, in turn, leads to interest in therapies that target complement as potential disease-modifying agents. Eculizumab, the first available anticomplement therapy, blocks at the level of C5 and has revolutionized the treatment of complement-mediated diseases such as paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome...

Treatment of nephrotic syndrome due to minimal change disease and focal segmental glomerulosclerosis remains a challenge since steroid dependence, steroid resistance and a relapsing disease course exhibits a high cumulative steroid dosage. The necessity of using alternative steroid-sparing immunosuppressive agents with potential toxic side effects also restricts their long-term use. Rituximab, a monoclonal antibody targeting CD20, has been increasingly used in the therapy of difficult-to-treat nephrotic syndrome...

Since the early 2000s, considerable advances have been achieved in the understanding of molecular pathomechanisms of human membranous nephropathy (MN), inspired by studies of Heymann nephritis, a faithful experimental model. These studies led to the identification of neutral endopeptidase, the type-M phospholipase A2 receptor (PLA2R), and cationic bovine serum albumin as target antigens of circulating and deposited antibodies in neonatal alloimmune, adult 'idiopathic', and early childhood MN, respectively. A genome-wide association study further showed a highly significant association of the PLA2R1 and the HLA-DQA1 loci with idiopathic MN in patients of white ancestry...

BACKGROUND/AIMS: Endotoxaemia, a driver of systemic inflammation, appears to be driven by dialysis-induced circulatory stress in haemodialysis (HD) patients. More frequent HD regimens are associated with lower ultrafiltration requirements, improved haemodynamic stability and lower systemic inflammation. This study investigated the hypothesis that more frequently dialysed patients, with reduced exposure to dialysis-induced haemodynamic perturbation, would have lower circulating endotoxin (ET) levels...

This position paper critically analyzes the available controlled data regarding biologic therapy in lupus nephritis (LN). Rather than an exhaustive review of all published evidence, the stress is put on the unmet medical needs in LN, the design of trials aimed at testing the effect of a biologic in LN, the possible reasons for LN trial failures and the future of biological therapy in LN.

BACKGROUND/AIMS: Lupus nephritis is an organ manifestation of systemic autoimmunity. Current treatment algorithms are still based on unselective immunosuppressive drugs. There is hope that highly selective biological drugs could be as or even more effective but less toxic. A profound understanding of the pathogenesis of lupus nephritis is necessary to identify the optimal molecular targets. METHODS: PubMed and www.clincialtrials.gov were searched using 'lupus nephritis' as the key word...