Introduction:
Hyperphosphatemia is one of the major factors associated with the development of vascular calcification in patients with chronic kidney disease (CKD). Since phosphate is retained in ...such patients, pharmacological treatment and other measures are necessary to control hyperphosphatemia. Several phosphate binders (calcium salts, magnesium salts, non-calcium-based binders and aluminium) are available for the treatment of hyperphosphatemia. Nevertheless, none of the above mentioned agents has shown an overall superiority over others, while potency and side effects are quite variable among them creating difficulties in choosing the optimal drug for each patient.
Areas covered:
The authors discuss the disturbed phosphate metabolism, the available phosphate binders, as well as the general therapeutic principles of treating hyperphosphatemia in CKD patients. The literature used for this review had been retrieved from PubMed and covers a large number of original and retrospective studies as well as prospective cohort studies, meta-analyses and international clinical guidelines.
Expert opinion:
Lowering serum phosphate levels in CKD patients may potentially have a positive impact on cardiovascular morbidity and mortality. Factors that should be taken into consideration when selecting a specific drug include CKD stage, cardiovascular disease, severity of secondary hyperparathyroidism, concomitant medications, life expectancy and patient compliance. Therefore, when selecting a specific phosphate binder, individualisation is mandatory.
Purpose
Cardiac valve calcification (CVC) is a significant risk factor for cardiovascular morbidity and mortality in patients with chronic kidney disease on maintenance hemodialysis. The aim of this ...study was to investigate the association of several risk factors and particularly of malnutrition on CVC.
Methods
In this cross-sectional cohort study, we included stable adult patients on maintenance hemodialysis. Calcification of cardiac valves was evaluated using two-dimensional echocardiography. Nutritional assessment and body composition measurements were performed using the MQSGA clinical tool and bioelectrical impedance analysis, respectively. Biochemical parameters such as serum calcium, phosphorus, iPTH, 1.25 hydroxy-vitamin-D, triglycerides, total cholesterol, HDL-C, LDL-C, total proteins, albumin, creatinine and CRP were assessed as potentially risk factors. The receiver operating characteristic (ROC) curve analysis was used to evaluate the prognostic ability of the aforementioned variables on severe degree CVC. Binary logistic regression analysis was also performed to identify independent variables of severe CVC.
Results
Overall, 42 patients were included in the study with half of them exhibiting mitral calcification, 38% aortic valve calcification, and 16.7% calcification in both valves. ROC analysis indicated that aging (
p
= 0.011), increased CRP (
p
= 0.038) and decreased value of serum albumin to total proteins ratio (
p
= 0.012) were positive prognostic factors for moderate to severe degree cardiac valve calcification. Low phase angle was also associated with CVC, although with moderate specificity.
Conclusion
Aging, inflammation, low serum albumin to total proteins ratio and low phase angle values as indicators of malnutrition are predictors of severe CVC in end-stage renal disease patients on hemodialysis.
Systemic inflammation in chronic kidney disease (CKD) is associated (as a cause or effect) with intestinal barrier dysfunction and increased gut permeability, with mechanisms not yet fully ...understood. This study investigated different parameters of the intestinal barrier in CKD patients, especially tight junction (TJ) proteins and their possible association with systemic endotoxemia and inflammation.
Thirty-three patients with stage I-IV CKD (n = 17) or end-stage kidney disease (ESKD) (n = 16) and 11 healthy controls underwent duodenal biopsy. Samples were examined histologically, the presence of CD3+ T-lymphocytes and the expression of occludin and claudin-1 in the intestinal epithelium was evaluated by means of immunohistochemistry, circulating endotoxin concentrations were determined by means of ELISA and the concentrations of the cytokines IL-1β, IL-6, IL-8, IL-10 and TNF-α in serum were measured using flow cytometry.
Patients with stage I-IV CKD or ESKD had significantly higher serum endotoxin, IL-6, IL-8 and IL-10 levels compared to controls. Intestinal occludin and claudin-1 were significantly decreased, and their expression was inversely correlated with systemic endotoxemia. Regarding occludin, a specific expression pattern was observed, with a gradually increasing loss of its expression from the crypt to the tip of the villi.
The expression of occludin and claudin-1 in enterocytes is significantly reduced in patients with CKD, contributing to systemic endotoxemia and inflammatory responses in these patients.
Immunoglobulin A nephropathy (IgAN) is among the commonest glomerulonephritides in Greece and an important cause of end-stage kidney disease (ESKD) with an insidious chronic course. Thus, the ...recently published International IgAN prediction tool could potentially provide valuable risk stratification and guide the appropriate treatment module. This study aimed to externally validate this prediction tool using a patient cohort from the IgAN registry of the Greek Society of Nephrology.
We validated the predictive performance of the two full models (with or without race) derived from the International IgAN Prediction Tool study in the Greek Society of Nephrology registry of patients with IgAN using external validation of survival prediction models (Royston and Altman). The discrimination and calibration of the models were tested using the C-statistics and stratified analysis, coefficient of determination (
) for model fit, and the regression coefficient of the linear predictor (β
), respectively.
The study included 264 patients with a median age of 39 (30-51) years where 65.2% are men. All patients were of Caucasian origin. The 5-year risk of the primary outcome (50% reduction in estimated glomerular filtration rate or ESKD) was 8%. The
for the full models with and without race when applied to our cohort was 39 and 35%, respectively, and both were higher than the reported
for the models applied to the original validation cohorts (26.3, 25.3, and 35.3%, respectively). Harrel's C statistic for the full model with race was 0.71, and for the model without race was 0.70. Renal survival curves in the subgroups (<16th, ~16 to <50th, ~50 to <84th, and >84th percentiles of linear predictor) showed adequate separation. However, the calibration proved not to be acceptable for both the models, and the risk probability was overestimated by the model.
The two full models with or without race were shown to accurately distinguish the highest and higher risk patients from patients with low and intermediate risk for disease progression in the Greek registry of IgAN.
The effect of a functioning arteriovenous fistula on cardiac function in kidney transplant recipients has not been thoroughly investigated.
We retrospectively evaluated cardiac function in 99 renal ...transplant recipients using transthoracic echocardiography, with available follow-up at baseline and 2 and 5 years posttransplant. Patients were divided into 2 groups: a control group (n = 47) with no functioning arteriovenous fistula immediately after transplant and an arteriovenous fistula group (n = 52) with a functioning arteriovenous fistula for at least 5 years after transplant. Left ventricular ejection fraction, diastolic thickness of the interventricular septum, and left ventricular end-diastolic diameter were assessed.
In our study, patients (62.6% men, 7.1% with diabetes, mean age of 55.6 ± 11.5 years), we observed no significant differences with respect to baseline left ventricular ejection fraction and interventricular septum; however, in the arteriovenous fistula group, baseline left ventricular end-diastolic diameter was marginally higher than that shown in the control group (50.6 ± 5.4 vs 48.6 ± 4.4 mm; P = .054). In multivariate analysis, functioning fistula and peripheral arterial disease were negatively associated with left ventricular ejection fraction at 5 years posttransplant, whereas baseline left ventricular ejection fraction had a minimal positive effect: B (95% confidence interval) of -2.186 (-4.312 to -0.061) (P = .044), -5.304 (-9.686 to -0.922) (P = .018), and 0.247 (0.047 to 0.446) (P = .016), respectively. Functioning fistula also emerged as associated with larger left ventricular end-diastolic diameter at 2 and 5 years posttransplant: B (95% confidence interval) of 3.047 (1.470-4.625) (P < .001) and 2.122 (0.406-3.838) (P = .016), respectively.
Maintenance of a functioning fistula in kidney transplant recipients may be associated with adverse long-term effects on left ventricular ejection fraction and left ventricular end-diastolic diameter.
Circulating autoantibodies against phospholipase A2 receptor (anti-PLA2R) are recognized as key elements in the pathogenesis of idiopathic membranous nephropathy. In current clinical practice, they ...are increasingly gaining attention as novel tools for diagnosis and disease monitoring. We investigated the diagnostic and prognostic utility of anti-PLA2R antibody measurements in Greek patients with biopsy-proven membranous nephropathy.
Anti-PLA2R levels were measured in serum samples from 33 patients at diagnosis using ELISA and were associated with treatment outcome. Moreover, serial anti-PLA2R measurements were performed in 15 patients under different clinical conditions and level alterations were correlated with disease activity.
Positive anti-PLA2R antibodies at diagnosis were found in 16 of 33 patients (48.5%). Anti-PLA2R levels were independently associated with the achievement of complete remission of nephrotic syndrome after immunosuppressive treatment compared to partial remission (p = 0.02, R2 = 0.265, 95%CI -0.019 to -0.0003). Higher detectable antibody levels at diagnosis were correlated with higher proteinuria levels (r = 0.813, p = 0.0001, 95%CI 0.532 to 0.933) and lower eGFR at the end of follow-up (r = -0.634, p = 0.0083, 95%CI -0.86 to -0.202). Serial antibody measurements during follow-up showed that anti-PLA2R titers were significantly reduced at the end of treatment after complete remission was achieved, remained low under sustained clinical remission, and increased during relapse.
Our findings confirm the usefulness of anti-PLA2R measurements in the diagnosis of idiopathic membranous nephropathy. Low levels of anti-PLA2R antibodies at diagnosis are predictive of complete remission of nephrotic syndrome following immunosuppressive treatment. Serial anti-PLA2R measurements correlate well with clinical status throughout the follow-up period and could be used routinely for monitoring of disease activity and treatment planning.
Lupus nephritis in the context of Systemic Lupus Erythematosus (SLE) is characterized by an unpredicted course with remissions and flare-ups. Among others, it remains a significant cause of end-stage ...kidney disease (ESKD) in relatively young patients. Therapeutic regimens with newer immunosuppressive agents have been introduced in order to control SLE clinical manifestations more efficiently and limit organ damage induced by immune complex formation and sustained inflammation. Treatment is usually long-term, and the cumulative impact of immunosuppression is expressed through the increased frequency of infections and neoplasms. However, if the observed immunity dysregulation is secondary and pharmaceutically induced or there is a pre-existing, primary immunodeficiency that shares common pathogenetic pathways with SLE's autoimmunity is not always clear. Herein, we present the case of a 39-year-old woman, that reached ESKD due to lupus nephritis. After an upper respiratory cytomegalovirus (CMV) infection and concomitant CMV reactivations the investigation revealed significant immunodeficiency. Not long after the initiation of intravenous immunoglobulin (IVIG) administration, patient received a cadaveric kidney transplant. IVIG was continued along with standard immunosuppression so that both recurrent infections and allograft rejection are avoided. Patient is closely monitored, and her post-transplant course is remarkably satisfying so far. ESKD patients with immunodeficiency syndromes should not be excluded by definition from kidney transplantation.
Inflammation plays a crucial role in diabetes and obesity through macrophage activation. Macrophage chemoattractant protein-1 (MCP-1), activin-A, and clusterin are chemokines with known roles in ...diabetes and obesity. The aim of this study is to investigate their possible diagnostic and/or early prognostic values in children and adolescents with obesity and type-1 diabetes mellitus (T1DM).
We obtained serum samples from children and adolescents with a history of T1DM or obesity, in order to measure and compare MCP-1, activin-A, and clusterin concentrations.
Forty-three subjects were included in each of the three groups (controls, T1DM, and obesity). MCP-1 values were positively correlated to BMI z-score. Activin-A was increased in children with obesity compared to the control group. A trend for higher values was detected in children with T1DM. MCP-1 and activin-A levels were positively correlated. Clusterin levels showed a trend towards lower values in children with T1DM or obesity compared to the control group and were negatively correlated to renal function.
The inflammation markers MCP-1, activin-A, and clusterin are not altered in children with T1DM. Conversely, obesity in children is positively correlated to serum MCP-1 values and characterized by higher activin-A levels, which may reflect an already established systematic inflammation with obesity since childhood.
Renal Replacement Therapy in Patients with Heart and Kidney Failure Goumenos, Dimitrios S; Papachristou, Evangelos; Papasotiriou, Marios
Prilozi (Makedonska akademija na naukite i umetnostite. Oddelenie za medicinski nauki),
11/2016, Letnik:
37, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The incidence of chronic kidney disease (CKD) in patients with chronic heart failure (CHF) is high as CKD and CHF share underlying risk factors such as arterial hypertension, diabetes mellitus and ...atherosclerosis. Cardiac failure leads to renal hypoperfusion and dysfunction and then fluid overload and need for aggressive diuretic therapy. However, development of diuretic resistance represents a significant problem in the management of these patients.
The role of Renal Replacement Therapy (RRT) is important for patients who do not response to conservative management of fluid overload facilitating the failing heart to restore function. According to the guidelines, venovenous isolated Ultrafiltration (UF) is indicated for patients with refractory congestion not responding to medical therapy with loop diuretics and infusion of dopamine. A systematic review of randomized controlled trials on the effect of UF vs. IV furosemide for decompensated heart failure showed a benefit of UF on total body weight loss and on readmissions due to heart failure in patients with decompensated heart failure and CKD. Peritoneal dialysis (PD) can provide efficient ultrafiltration and sodium extraction in volume overloaded patients followed by decline of hospitalization days, decrease of body weight and improvement of LVEF in patients with refractory heart failure. The continuous draw of ultrafiltrate is followed by a lesser risk of abrupt hypotension and better preservation of the residual kidney function. This represents a significant advantage of PD over intermittent UF by dialysis.
In conclusion, application of UF by dialysis and PD is followed by significant total body weight loss, reduced need for hospital readmissions and better quality of life. PD has a higher probability of preservation of residual kidney function and can be used by patients at home.
PDF
