Advances in chronic kidney disease

Publisher: National Kidney Foundation


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    Advances in chronic kidney disease (Online), Advances in chronic kidney disease
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    Document, Periodical, Internet resource
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    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publications in this journal

  • Advances in chronic kidney disease 05/2014; 21(3):256-259.
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    ABSTRACT: Diabetes mellitus with its attendant complications is a significant cause of morbidity and mortality with diabetic nephropathy being the leading cause of end stage renal disease in the Western world. Characteristic structural and functional changes in the kidney early in the course of diabetes have been shown to have enduring effects on the progression of disease. A better understanding of the mechanisms underlying these changes is imperative to the development of new therapeutic strategies. Renal hypertrophy and hyperfiltration along with proximal tubular hyperreabsorption are among the distinctive features of early diabetic nephropathy. Additionally, there are particular alterations in the sensitivity of the glomerular and tubular function to dietary salt intake in early diabetes. Herein, we focus on these early physiologic changes and discuss some of the primary and secondary mechanisms discovered in recent years which lead to these alterations in kidney function.
    Advances in chronic kidney disease 05/2014; 21(3):297-303.
  • Advances in chronic kidney disease 05/2014; 21(3):251-255.
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    ABSTRACT: The nature of CKD in diabetes is changing. Diabetic glomerulosclerosis remains the cause of CKD in most type 1 diabetic individuals. However, the rate of progression of diabetic nephropathy has slowed because of improving glucose and blood pressure control. Most individuals with type 2 diabetes and 5% to 30% of those with type 1 diabetes with progressive CKD have normal urine albumin excretion or low-level microalbuminuria (albumin-to-creatinine ratio approximately <100 mg/g), which does not progress despite the decline in glomerular filtration. People with progressive CKD but normal albuminuria have predominantly interstitial or vascular changes with much less glomerular changes. It seems likely that these histological abnormalities relate to blood pressure, aging, obesity, and intrarenal vascular disease. Initial studies suggested that 85% to 100% of diabetic individuals with microalbuminuria (Kidney Disease Improving Global Outcomes [KDIGO] CKD albuminuria A2) progressed to proteinuria (KDIGO CKD albuminuria A3). Recent data demonstrate that even after 2 to 3 years of persistent microalbuminuria, most will revert to normal albumin excretion (KDIGO CKD albuminuria A1). Regression is more likely at lower levels of microalbuminuria and with improved glucose, blood pressure, and lipid control. Thus, low levels of microalbuminuria cannot be considered as established diabetic nephropathy.
    Advances in chronic kidney disease 05/2014; 21(3):267-272.
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    ABSTRACT: Diabetes continues to cast a long shadow over the lives of many people. It is now clear that even transient hyper- or hypoglycemia or increased glycemic variability around healthy mean glucose levels can have long-lasting and long-term effects on the development and progression of diabetic complications, including cardiovascular disease, kidney disease, retinopathy, and neuropathy. Even after glycemic control has been achieved and maintained for many years, it appears hard to undo the changes that are instilled, including epigenetic programming, compositional changes, post-translational modifications, or simply lead time toward an inevitable fate. This phenomenon has become known as "metabolic memory" or the "legacy effect," but it may be better characterized as "metabolic karma," in which the intent and actions of an individual (with respect to metabolic control) influence the future health of that individual. This "bad karma" has been used to explain many clinical observations surrounding diabetes and its management, including the lack of benefits in many short- and intermediate-term trials, and the potential utility of early intensive glycemic control. Further understanding the molecular basis of a metabolic legacy in diabetes will certainly provide new targets for intervention.
    Advances in chronic kidney disease 05/2014; 21(3):311-317.
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    ABSTRACT: Diabetic nephropathy is the most common cause of CKD and represents a large and ominous public health problem. Patients with diabetic kidney disease have exceptionally high rates of cardiovascular morbidity and mortality. In fact, the excess mortality among patients with diabetes appears to be largely limited to the subgroup with kidney disease and explained by their high burden of cardiovascular disease. The mechanisms underlying the strong association between diabetic kidney disease and various forms of cardiovascular disease are poorly understood. Traditional risk factors for cardiovascular disease, although prevalent among those with diabetes, do not fully account for the heightened risk observed. Despite their susceptibility to cardiovascular disease, patients with CKD are less likely to receive appropriate risk factor modification than the general population. Moreover, because patients with CKD have commonly been excluded from major cardiovascular trials, the evidence for potential treatments remains limited. The mainstays of treatment for diabetic kidney disease currently include blockade of the renin-angiotensin-aldosterone system and control of hypertension, hyperglycemia, and dyslipidemia. Increased awareness of the vulnerability of this patient population and more timely interventions are likely to improve outcomes while large evidence gaps are filled with newer studies.
    Advances in chronic kidney disease 05/2014; 21(3):273-280.
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    ABSTRACT: Diabetes is increasing at daunting rates worldwide, and approximately 40% of affected individuals will develop kidney complications. Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease, and there are significant healthcare costs providing appropriate renal replacement therapies to affected individuals. For several decades, investigators have sought to discover inherited risk factors and biomarkers for DKD. In recent years, advances in high-throughput laboratory techniques and computational analyses, coupled with the establishment of multicenter consortia, have helped to identify genetic loci that are replicated across multiple populations. Several genome-wide association studies (GWAS) have been conducted for DKD with further meta-analysis of GWAS and comprehensive "single gene" meta-analyses now published. Despite these efforts, much of the inherited predisposition to DKD remains unexplained. Meta-analyses and integrated-omics pathway studies are being used to help elucidate underlying genetic risks. Epigenetic phenomena are increasingly recognized as important drivers of disease risk, and several epigenome-wide association studies have now been completed. This review describes key findings and ongoing genetic and epigenetic initiatives for DKD.
    Advances in chronic kidney disease 05/2014; 21(3):287-296.
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    ABSTRACT: Alterations and injury to glomerular podocytes play a key role in the initiation and progression of diabetic kidney disease (DKD). Multiple factors in diabetes cause abnormalities in podocyte signaling that lead to podocyte foot process effacement, hypertrophy, detachment, loss, and death. Alterations in insulin action and mammalian target of rapamycin activation have been well documented to lead to pathology. Reduced insulin action directly leads to albuminuria, increased glomerular matrix accumulation, thickening of the glomerular basement membrane, podocyte apoptosis, and glomerulosclerosis. In addition, podocytes generate factors that alter signaling in other glomerular cells. Prominent among these is vascular endothelial growth factor-A, which maintains glomerular endothelium viability but causes endothelial cell pathology when generated at too high a level. Finally, circulating vascular factors (eg, activated protein C) have a profound effect on podocyte stability and survival. This cytoprotective factor is critical for podocyte health, and its deficiency promotes podocyte injury and apoptosis. Thus, the podocyte sits in the center of a network of paracrine and hormonal signaling systems that in health keep the podocyte adaptable and viable, but in diabetes they can lead to pathologic changes, detachment, and death.
    Advances in chronic kidney disease 05/2014; 21(3):304-310.
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    ABSTRACT: Prevalence rates of diabetic kidney disease (DKD) are increasing in parallel with the incidence rates of diabetes mellitus. DKD has already become a significant health problem worldwide. Without radical improvements in prevention and treatment, DKD prevalence will continue to climb. The pathogenesis of DKD is complex and multifactorial, with genetic and environmental factors involved. Several nonmodifiable risk factors contribute to DKD, including genetics, sex, age, age at onset, and duration of diabetes. However, there are also several modifiable risk factors that have a strong effect on the risk of DKD. Traditional modifiable factors include glycemic control, blood pressure, lipids, and smoking. Other recently discovered modifiable risk factors include chronic low-grade inflammation, advanced glycation end products, and lack of physical activity. Efficient management of these modifiable risk factors may improve the prognosis of diabetic patients at risk of DKD.
    Advances in chronic kidney disease 05/2014; 21(3):260-266.
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    ABSTRACT: Glomerular diseases are major contributors to the global burden of end-stage kidney disease. The clinical course and outcome of these disorders are extremely variable and difficult to predict. The clinical trajectories range from a benign and spontaneously remitting condition to a symptomatic and rapidly progressive disease. The diagnosis is based entirely on the evaluation of kidney biopsy, but this invasive procedure carries multiple risks and often fails to predict the clinical course or responsiveness to treatment. However, more recent advances in genetics and molecular biology have facilitated elucidation of novel pathogenic mechanisms of these disorders. These discoveries fuel the development of novel biomarkers and offer prospects of noninvasive diagnosis and improved prognostication. Our review focuses on the most promising novel biomarkers that have recently emerged for the major types of glomerular diseases, including immunoglobulin A nephropathy, membranous nephropathy, focal segmental glomerulosclerosis, and membranoproliferative glomerulonephritis.
    Advances in chronic kidney disease 03/2014; 21(2):205-216.
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    ABSTRACT: Hypertension is a common problem among patients with glomerular disease and CKD. Optimal blood pressure targets for these patients have been the source of much debate. Careful review of the available data supports a blood pressure target of less than 140/90 mmHg. Consideration for a lower goal of less than 130/80 mmHg should be given for patients with heavy proteinuria. Renin-angiotensin system inhibitors should be used as the cornerstone of therapy for all patients with glomerular disease and CKD.
    Advances in chronic kidney disease 03/2014; 21(2):200-204.
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    ABSTRACT: A major shift in our understanding of glomerular diseases is the focus on which components of the complement pathway are involved in mediating kidney injury. For example, the membranoproliferative glomerulonephritis lesion is no longer classified solely by ultrastructural findings on biopsy and is now divided into immune-complex-mediated lesions vs complement-mediated lesions. In turn, this emphasis on complement leads to interest in therapies that target complement as potential disease-modifying agents. Eculizumab, the first available anti-complement therapy, blocks at the level of C5 and has revolutionized the treatment of atypical hemolytic uremic syndrome. Whether this agent will work equally well for the far more heterogeneous entities of C3 glomerulonephritis and dense deposit disease remains unclear. Instead, newer agents that target C3 may turn out to be the most effective and specific therapy for these C3 glomerulopathies.
    Advances in chronic kidney disease 03/2014; 21(2):152-158.
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    ABSTRACT: Membranous nephropathy, focal segmental glomerulosclerosis (FSGS), and minimal change disease (MCD) are the most common causes of idiopathic nephrotic syndrome. For many years prednisone, alkylating agents, and calcineurin inhibitors have been the standard of therapy for these patients. More effective or better tolerated treatment modalities are needed. B cell targeted therapy was recently introduced in clinical practice. In this review, we briefly summarize the current standard therapy and discuss the efficacy of B cell targeted therapy in primary glomerular diseases. Observational, short-term studies suggest that rituximab is effective and comparable to standard therapy in maintaining remissions in patients with frequently relapsing or steroid-dependent MCD or FSGS. In contrast, response is limited in patients with steroid-resistant nephrotic syndrome. Rituximab also induces remissions in patients with membranous nephropathy. Controlled clinical trials on kidney endpoints are urgently needed to position B cell targeted therapy in clinical practice.
    Advances in chronic kidney disease 03/2014; 21(2):166-181.
  • Advances in chronic kidney disease 03/2014; 21(2):119-20.
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    ABSTRACT: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small-vessel vasculitis that primarily comprises 2 clinical syndromes: granulomatosis with polyangiitis and microscopic polyangiitis. Cyclophosphamide and glucocorticoids have traditionally been used for induction of remission. However, more recent studies have shown that rituximab is as effective as cyclophosphamide for induction therapy in patients with newly diagnosed severe AAV and superior for patients with relapsing AAV. There is also accumulating evidence indicating a potential role of rituximab for maintenance therapy in AAV. In this article, we will review the evidence supporting the various treatment choices for patients with AAV.
    Advances in chronic kidney disease 03/2014; 21(2):182-193.
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    ABSTRACT: Glomerular diseases are common in elderly patients and are a major cause of kidney failure. Most glomerular diseases in the elderly are caused by chronic systemic diseases, including arterial hypertension, diabetes, and atherosclerotic vascular diseases, although acute systemic vasculitis, especially anti-neutrophil-cytoplamic-antibody-mediated vasculitis, and membranous nephropathy related to malignancy, drug toxicity, and idiopathic form also occur often. Complex age-related changes and sensitivity to drug toxicity can render diagnosis and treatment for elderly patients challenging. As the general population is aging and the rate of CKD rising, updating knowledge on managing these patients is critical for care providers. We provide a comprehensive review and update of the diagnosis and treatment of glomerular diseases in the elderly.
    Advances in chronic kidney disease 03/2014; 21(2):228-246.
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    ABSTRACT: Soon after the emergence of the renin-angiotensin-aldosterone system (RAAS) blocking treatment as the cornerstone of renoprotective treatment in the prevention and treatment of diabetic and nondiabetic CKD, it was investigated if a higher degree of achievable RAAS blockade by combining more than one compound is feasible and advantageous. Regardless of the benefits from using monotherapy for diabetic kidney disease, there is still much improvement to wish for in terms of kidney prognosis in these populations. A great deal of research has gone into evaluating combinations of the RAAS blocking treatments in different populations and with different drugs and doses. Studies have mostly been short-term and use surrogate endpoints such as albuminuria. Side effects have been well known and expected in terms of increasing potassium levels and hypotension, but to an acceptable extent. With recent disappointing results from major hard endpoint trials using dual RAAS blockade the concept is now under scrutiny. In this review we will discuss the pros and cons of dual RAAS blockade, with facts and findings from smaller studies, endpoint trials, and meta-analyses.
    Advances in chronic kidney disease 03/2014; 21(2):159-165.