Kidney International. Supplement

Fibrosis of the kidney is caused by the prolonged injury and deregulation of normal wound healing and repair processes, and by an excess deposition of extracellular matrices. Despite intensive research, our current understanding of the precise mechanism of fibrosis is limited. There is a connection between fibrotic events involving inflammatory and non-inflammatory glomerulonephritis, inflammatory cell infiltration, and podocyte loss. The current review will discuss the inflammatory response after renal injury that leads to fibrosis in relation to non-inflammatory mechanisms...

Solid organ transplantation is the standard treatment to improve both the quality of life and survival in patients with various end-stage organ diseases. The primary barrier against successful transplantation is recipient alloimmunity and the need to be maintained on immunosuppressive therapies with associated side effects. Despite such treatments in renal transplantation, after death with a functioning graft, chronic allograft dysfunction (CAD) is the most common cause of late allograft loss. Recipient recognition of donor histocompatibility antigens, via direct, indirect, and semidirect pathways, is critically dependent on the antigen-presenting cell (APC) and elicits effector responses dominated by recipient T cells...

The development of immunosuppressive drugs to control adaptive immune responses has led to the success of heart transplantation as a therapy for end-stage heart failure. However, these agents are largely ineffective in suppressing components of the innate immune system. This distinction has gained clinical significance as mounting evidence now indicates that innate immune responses have important roles in the acute and chronic rejection of cardiac allografts including cardiac allograft vasculopathy (CAV). Whereas clinical interest in natural killer (NK) cells was once largely confined to the field of bone marrow transplantation, recent findings suggest that these cells can also participate in the acute rejection of cardiac allografts and in the development of CAV...

B cells have many possible mechanisms by which they can affect allograft survival, including antigen presentation, cytokine production, immune regulation, and differentiation into alloantibody-producing plasma cells. This report reviews the last mechanism, which the authors regard as most critical for the long-term survival of allografts, namely, the promotion of chronic rejection by alloantibodies. Chronic humoral rejection characteristically arises late after transplantation and causes transplant glomerulopathy, multilamination of peritubular capillary basement membranes, and C4d deposition in PTCs and glomeruli...

No abstract text is available yet for this article.

The metabolic syndrome is a constellation of defined cardiovascular risk factors occurring simultaneously in a single individual. The result of dysregulated glucose and vascular metabolism, the syndrome has been identified as a significant risk factor for cardiovascular morbidity in the general population. More recently, a relatively high prevalence of the metabolic syndrome has been recognized among kidney transplant recipients. The prevalence, risk factors, pathophysiology, and potential consequences of the metabolic syndrome in the general population and in kidney transplant recipients are reviewed...

Currently used immunosuppressants exacerbate cardiovascular risk. However, attempts to limit the use of these agents increase the risk of allograft rejection. Immunosuppressants targeting signal 2 and signal 3 lymphocyte activation pathways are under clinical development. Clinical data from trials of the Janus family protein tyrosine kinase-3 inhibitor tasocitinib and the costimulation blocker belatacept are presented. Additional pipeline agents are described. Results from two phase III clinical trials of belatacept revealed efficacy that is not inferior to that provided by cyclosporine (CsA)...

Modern immunosuppression has expanded access to kidney transplantation by limiting the risk of rejection. However, cardiovascular disease (CVD) remains the principal cause of death with a functioning graft, threatening the long-term survival of transplant recipients. The article reviews the leading risk factors for cardiovascular morbidity both before and after kidney transplantation. Evidence linking poor renal function to CVD is discussed. The function of immunosuppression in exacerbating the risk of both nephrotoxicity and CVD is explored through means of a clinical case study...

Diabetes is the most common cause of end-stage renal disease and an important risk factor for morbidity and mortality in dialysis patients. Glycemic control, utilizing serial measurement of glycosylated hemoglobin (HbA1c), is generally recommended to limit end-organ damage, including cardiovascular morbidity and mortality. We, along with others, have previously suggested that HbA1c may not be a reliable measure of glycemic control in dialysis patients, and have therefore explored the use of serum fructosamine (SF) as an alternative marker...

Malnutrition is a strong predictor of mortality in peritoneal dialysis (PD) patients. Extracellular mass (ECM) contains all the metabolically inactive, whereas body cell mass (BCM) contains all the metabolically active, tissues of the body. ECM/BCM ratio is a highly sensitive index of malnutrition. The objective of this study was to explore the relationship between ECM/BCM ratio and survival in PD patients. We enrolled 62 patients from November 2000 to July 2008. On enrollment, demographic, clinical, and biochemical data were recorded...

Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease. The management of SHPT commonly involves vitamin D, either calcitriol or newer analogs (paricalcitol or doxercalciferol), along with dietary phosphorus restriction and phosphate binding agents. Published reports have suggested that treatment with paricalcitol in hemodialyzed (HD) patients offers a morbidity or mortality advantage in comparison with treatment with calcitriol. We have recently reported that switching from calcitriol to paricalcitol resulted in a lower serum calcium and calcium-phosphorus product (Ca x P product), as well as lower parathyroid hormone (PTH) and alkaline phosphatase during 6 months of serial treatment...

Anemia is one of the most common and morbid complications of chronic kidney disease, causing unpleasant symptoms and reducing the quality of life. The availability of recombinant human erythropoietin (rHuEPO) in 1989 has been one of the most important developments in the care of this population in the past several decades. Treatment with erythropoiesis-stimulating agents (ESAs) has improved patients' lives, but recent studies have found that higher hemoglobin (Hgb) targets cause harm, resulting in more cautious treatment...

The objectives of this review are to introduce and explore the following representative ethical problems generated by modern renal replacement therapy: (1) reviewing the historical origin of medical ethics with specific reference to nephrology; (2) recognizing the complex stresses surrounding assignment of a deceased donor renal transplant to a geriatric patient while young patients continue waiting for a donor kidney; and (3) appreciating the concept of futility and support for a uremic patient opting for death rather than further uremia therapy as the best in choice in coping with renal failure...

Recent evidence suggests that the traditional syndromes known as renal osteodystrophy, secondary hyperparathyroidism, and vitamin D deficiency are related to mortality in persons with moderate to advanced chronic kidney disease (CKD). The so-called 'kidney bone disease', also known as 'mineral and bone disorders', is defined to include bone disorders, mineral disarrays, and vascular calcification. We have identified 14 common and clinically relevant conditions of contemporary nature that are related to the kidney bone disease, including calcitriol (active vitamin D) deficiency, 25(OH)-vitamin D deficiency, biochemical hyperparathyroidism, relatively low parathyroid hormone (PTH) level, increased serum alkaline phosphatase (hyperphosphatasemia), elevated fibroblast growth factor (FGF)-23, high turnover bone disease, adynamic bone disease, uremic osteoporosis, vascular calcification, hyper- and hypophosphatemia, and hyper- and hypocalcemia...

No abstract text is available yet for this article.

The pilot program Kidney Evaluation for You (KEY) was conducted in Australia to screen for chronic kidney disease (CKD). Targeting people at high risk (those with diabetes, hypertension, a first-degree relative with kidney failure, or age >50 years), KEY aimed to establish community-based screening protocols, assess efficacy in promoting changes in risk-factor management, and explore participant CKD awareness. KEY offered free cardiovascular and kidney checks using point-of-care testing for on-site pathology measurements (estimated glomerular filtration rate, hemoglobin A1c, cholesterol, hemoglobin, albuminuria), lifestyle assessment, and exit interviews...

The National Kidney Foundation Kidney Early Evaluation Program (KEEP) is a free community screening program aimed at early detection of kidney disease among high-risk individuals. A pilot phase of KEEP México began in 2008 in México City and Jalisco State. Adults with diabetes, hypertension, or family history of diabetes, hypertension, or chronic kidney disease (CKD) were invited to participate through advertising campaigns. All participants completed a questionnaire. Blood pressure, weight, and height were measured; blood and urine tests included albuminuria and serum creatinine to estimate glomerular filtration rate using the Modification of Diet in Renal Disease Study equation...

The International Kidney Evaluation Association Japan evaluated chronic kidney disease (CKD) in Japan, using a Japanese version of the US National Kidney Foundation's Kidney Early Evaluation Program (KEEP). The screening criteria for the first 1065 participants were presence of diabetes or hypertension, or family history of diabetes, hypertension, or kidney disease. Mean age was 59.7+/-16.1 years; 501 participants were men, 564 women. Of participants, 26.9% had diabetes, 59.2% had hypertension (with an additional 21...

No abstract text is available yet for this article.

At present, solid organ transplantation relies on chronic immunosuppression. Calcineurin inhibitors (CNIs) still remain one of the most important components in current immunosuppressive regimens. However, life-long immunosuppression of transplant recipients is associated with high costs for the individual, health-care systems, and society. Hence, there is an urgent need of generic drugs that have the potential to exert equivalent therapeutic efficacy at a lower cost. Here, we report our findings of the conversion of 59 stable long-term kidney graft recipients from cyclosporine A (CsA) Neoral to CsA Neoimmun/Equoral...