Treatment of hyperphosphatemia in hemodialysis patients: The Calcium Acetate Renagel Evaluation (CARE Study)

Treatment of hyperphosphatemia in hemodialysis patients: The Calcium Acetate Renagel Evaluation (CARE Study).BackgroundHyperphosphatemia underlies development of hyperparathyroidism, osteodystrophy, extraosseous calcification, and is associated with increased mortality in hemodialysis patients.MethodsTo determine whether calcium acetate or sevelamer hydrochloride best achieves recently recommended treatment goals of phosphorus ≤5.5mg/dL and Ca × P product ≤55mg2/dL2, we conducted an 8-week randomized, double-blind study in 100 hemodialysis patients.ResultsComparisons of time-averaged concentrations (weeks 1 to 8) demonstrated that calcium acetate recipients had lower serum phosphorus (1.08mg/dL difference, P = 0.0006), higher serum calcium (0.63mg/dL difference, P < 0.0001), and lower Ca × P (6.1mg2/dL2 difference, P = 0.022) than sevelamer recipients. At each week, calcium acetate recipients were 20% to 24% more likely to attain goal phosphorus [odds ratio (OR) 2.37, 95% CI 1.28–4.37, P = 0.0058], and 15% to 20% more likely to attain goal Ca × P (OR 2.16, 95% CI 1.20–3.86, P = 0.0097). Transient hypercalcemia occurred in 8 of 48 (16.7%) calcium acetate recipients, all of whom received concomitant intravenous vitamin D. By regression analysis hypercalcemia was more likely with calcium acetate (OR 6.1, 95% CI 2.8–13.3, P < 0.0001). Week 8 intact PTH levels were not significantly different. Serum bicarbonate levels were significantly lower with sevelamer hydrochloride treatment (P < 0.0001).ConclusionCalcium acetate controls serum phosphorus and calcium-phosphate product more effectively than sevelamer hydrochloride. Cost-benefit analysis indicates that in the absence of hypercalcemia, calcium acetate should remain the treatment of choice for hyperphosphatemia in hemodialysis patients

Risk of Kaposi's sarcoma and of other cancers in Italian renal transplant patients

A follow-up study of 1844 renal transplant patients in Italy showed a 113-fold increased risk for Kaposi's sarcoma. Kaposi's sarcoma risk was higher in persons born in southern than in northern Italy. Significant increases were also observed for cancers of the lip, liver, kidney and for non-Hodgkin's lymphoma

Chronic Kidney Disease and Coronary Artery Disease: JACC State-of-the-Art Review

Chronic kidney disease (CKD) is a major risk factor for coronary artery disease (CAD). As well as their high prevalence of traditional CAD risk factors, such as diabetes and hypertension, persons with CKD are also exposed to other nontraditional, uremia-related cardiovascular disease risk factors, including inflammation, oxidative stress, and abnormal calcium-phosphorus metabolism. CKD and end-stage kidney disease not only increase the risk of CAD, but they also modify its clinical presentation and cardinal symptoms. Management of CAD is complicated in CKD patients, due to their\ua0likelihood of comorbid conditions and potential for side effects during interventions. This summary of the Kidney\ua0Disease: Improving Global Outcomes (KDIGO) Controversies Conference on CAD and CKD (including end-stage\ua0kidney disease and\ua0transplant recipients) seeks to improve understanding of the epidemiology, pathophysiology, diagnosis, and\ua0treatment of CAD in CKD and to identify knowledge gaps, areas of controversy, and\ua0priorities for research

K13 blocks KSHV lytic replication and deregulates vIL6 nad hIL6 expression: A model of lytic replication induced clonal selection in viral oncogenesis

Background. Accumulating evidence suggests that dysregulated expression of lytic genes plays an important role in KSHV (Kaposi's sarcoma associated herpesvirus) tumorigenesis. However, the molecular events leading to the dysregulation of KSHV lytic gene expression program are incompletely understood. Methodoloxy/Principal Findings. We have studied the effect of KSHV-encoded latent protein vFLIP K13, a potent activator of the NF-κB pathway, on lytic reactivation of the virus. We demonstrate that K13 antagonizes RTA, the KSHV lytic-regulator, and effectively blocks the expression of lytic proteins, production of infectious virions and death of the infected cells. Induction of lytic replication selects for clones with increased K13 expression and NF-κB activity, while siRNA-mediated silencing of K13 induces the expression of lytic genes. However, the suppressive effect of K13 on RTA-induced lytic genes is not uniform and it falls to block RTA-induced viral IL6 secretion and cooperates with RTA to enhance cellular IL-6 production, thereby dysregulating the lytic gene expression program. Conclusions/Significance. Our results support a model in which ongoing KSHV, lytic replication selects for clones with progressively higher levels of K13 expression and NF-κB activity, which in turn drive KSHV tumorigenesis by not only directly stimulating cellular survival and proliferation, but also indirectly by dysregulating the viral lytic gene program and allowing non-lytic production of growth-promoting viral and cellular genes. Lytic Replication-Induced Clonal Selection (LyRICS) may represent a general mechanism in viral oncogenesis. 2007 Zhao et al

Chronic kidney disease and valvular heart disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies conference

Chronic kidney disease (CKD) is a major risk factor for valvular heart disease (VHD). Mitral annular and aortic valve calcifications are highly prevalent in CKD patients and commonly lead to valvular stenosis and regurgitation, as well as complications including conduction system abnormalities and endocarditis. VHD, especially mitral regurgitation and aortic stenosis, is associated with significantly reduced survival among CKD patients. Knowledge related to VHD in the general population is not always applicable to CKD patients because the pathophysiology may be different, and CKD patients have a high prevalence of comorbid conditions and elevated risk for periprocedural complications and mortality. This Kidney Disease: Improving Global Outcomes (KDIGO) review of CKD and VHD seeks to improve understanding of the epidemiology, pathophysiology, diagnosis, and treatment of VHD in CKD by summarizing knowledge gaps, areas of controversy, and priorities for research

Kaposi's Sarcoma Associated with Previous Human Herpesvirus 8 Infection in Kidney Transplant Recipients

This study investigates the prevalence of human herpesvirus 8 (HHV-8) infection in kidney transplant patients, evaluating the risk of HHV-8 transmission via transplantation and the association between pre- and posttransplantation HHV-8 infection and the subsequent development of Kaposi's sarcoma (KS). Immunofluorescence and an enzyme immunoassay were used to determine HHV-8 seroprevalence in 175 patients awaiting kidney transplantation and 215 controls who were attending our clinic for other reasons. All patients in the study came from central or southern Italy. Seroprevalence was similar in both groups (14.8 versus 14.9%), with no significant difference between the rates for male and female patients. Of the 175 patients, 100 were tested for anti-HHV-8 antibodies at various times during follow-up. During follow-up, seroprevalence increased from 12% on the date of transplantation to 26%. This increase was paralleled by an age-related increase in seroprevalence in the control group. During follow-up from 3 months to 10 years after transplantation, KS was diagnosed in seven patients (4.0%). Six of these patients were positive for HHV-8 prior to transplantation. Overall, 23.0% of patients who were HHV-8 positive before transplantation developed KS, whereas only 0.7% of seronegative patients developed the disease (relative risk, 34.4; 95% confidence interval, 4.31 to 274.0). This finding suggests that the key risk factor for KS is infection prior to transplantation and that antibody detection in patients awaiting transplantation could be useful in identifying patients at high risk for KS. In patients from geographic areas with a high prevalence of HHV-8, serological tests on donors may be less important

Membranous Nephropathy and Kimura\u27s Disease Manifesting a Hip Mass. A Case Report with Literature Review

We report a case of Kimura\u27s disease with membranous nephropathy. A 15-year-old Japanese boy was referred to our hospital with proteinuria and a subcutaneous mass in the hip. Renal biopsy demonstrated secondary membranous nephropathy (MN) with mild mesangial proliferation and some electron-dense deposits in the mesangium. Laboratory tests revealed eosinophilia and a high level of serum IgE, which are common findings in Kimura\u27s disease. A biopsy of the mass in the hip was performed and Kimura\u27s disease was diagnosed. Treatment with oral prednisolone resulted in a decrease of proteinuria and regression of the subcutaneous mass. Kimura\u27s disease should be included in the differential diagnosis of secondary MN

Chronic kidney disease and valvular heart disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Chronic kidney disease (CKD) is a major risk factor for valvular heart disease (VHD). Mitral annular and aortic valve calcifications are highly prevalent in CKD patients and commonly lead to valvular stenosis and regurgitation, as well as complications including conduction system abnormalities and endocarditis. VHD, especially mitral regurgitation and aortic stenosis, is associated with significantly reduced survival among CKD patients. Knowledge related to VHD in the general population is not always applicable to CKD patients because the pathophysiology may be different, and CKD patients have a high prevalence of comorbid conditions and elevated risk for periprocedural complications and mortality. This Kidney Disease: Improving Global Outcomes (KDIGO) review of CKD and VHD seeks to improve understanding of the epidemiology, pathophysiology, diagnosis, and treatment of VHD in CKD by summarizing knowledge gaps, areas of controversy, and priorities for research