Elvira Fernández

Treatment with Sevelamer Decreases Bicarbonate Levels in Hemodialysis Patients

Accessible online at: www.karger.com/journals/nef Dear Sir, Until now, hyperparathyroidism has been among the most difficult chronic renal failure-associated conditions to treat. Hyperphosphatemia plays a key role in the development of hyperparathyroidism in hemodialysis patients. Although new membranes and high-flux dialyzers have improved hemodialysis quality in recent years, phosphate balance remains positive regardless of the type of hemodialysis [1]. Slow nocturnal daily hemodialysis is effective but is not applicable in most hemodialysis facilities [2]. The use of calcium-based salts is useful to bind phosphate but often results in hypercalcemia and increase of the calcium ! phosphate product, thus limiting the use of calcitriol and increasing soft-tissue calcifications [3]. Aluminum-based salts carry a risk of intoxication which also limits their use. Sevelamer is a new aluminum and calcium free molecule which has proven to be effective in lowering phosphate without raising calcium levels and consequently, decreasing the calcium ! phosphate product [4, 5]. However, although some studies have shown a decrease of bicarbonate levels during the first weeks of treatment with sevelamer [6, 7], this aspect has not been given much attention by investigators. We investigated the effects of sevelamer on bicarbonate levels in 18 stable chronic hemodialysis patients who were followed-up for 3 months. They were previously treated with calcium carbonate/acetate or alumiFig. 1. Ca ! P product (a) and bicarbonate (b) levels at baseline, 15 days and 3 months after the introduction of sevelamer.

Predicting cardiovascular disease morbidity and mortality in chronic kidney disease in Spain. The rationale and design of NEFRONA: a prospective, multicenter, observational cohort study

BackgroundCardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Cardiovascular risk assessment in this population is hampered by the failure of traditional risk factors to fully account for the elevated CVD risk (reverse epidemiology effect) and the presence of emerging risk factors specifically related to kidney failure. Therefore, diagnostic tools capable of improving cardiovascular risk assessment beyond traditional risk factors are currently warranted. We present the protocol of a 4-year prospective study aimed to assess the predictive value of non-invasive imaging techniques and biomarkers for CVD events and mortality in patients with CKD.MethodsFrom November 2009 to October 2010, 4137 asymptomatic adult patients with stages 2 to 5 CKD will be recruited from nephrology services and dialysis units throughout Spain. During the same period, 843 participants without CKD (control group) will be recruited from lists of primary care physicians, only at baseline. During the follow-up, CVD events and mortality will be recorded from all CKD patients. Clinical and laboratory characteristics will be collected in a medical documentation sheet. Three trained itinerant teams will carry out a carotid ultrasound to assess intima-media thickness and presence of plaques. A composite atherosclerosis score will be constructed based on carotid ultrasound data and measurement of ankle-brachial index. In CKD patients, presence and type of calcifications will be assessed in the wall of carotid, femoral and brachial arteries, and in cardiac valves, by ultrasound. From all participants, blood samples will be collected and stored in a biobank to study novel biomarkers.ConclusionsThe NEFRONA study is the first large, prospective study to examine the predictive value of several non-invasive imaging techniques and novel biomarkers in CKD patients throughout Spain. Hereby, we present the protocol of this study aimed to explore the most effective way in which these tests can be integrated with traditional risk factors to maximize CVD detection in this population.

Association of serum phosphorus with subclinical atherosclerosis in chronic kidney disease. Sex makes a difference

BACKGROUND Cardiovascular disease is the leading cause of mortality in chronic kidney disease (CKD). Serum phosphate has been associated to cardiovascular disease in the general population and this effect seems to be different according to sex. In the present study we analyze the effect of phosphate on subclinical atherosclerosis in the NEFRONA population and its effect depending on sex. DESIGN Carotid ultrasound assessing the presence of plaques was performed by an itinerant team in 1687 CKD patients not in dialysis without previous cardiovascular events. Standard blood test and anthropometrical parameters were also recorded. RESULTS Multivariate linear regression to model phosphate levels in patients with CKD showed an interaction of sex with age. Thus, among men, serum phosphate levels declined significantly with age almost linearly. Serum phosphate levels in women under the age of 40-45 years overlapped with those in men and then stayed above, showing and overall constant relationship. Multivariate logistic regression analysis showed that higher phosphate levels associated with a higher risk of presenting atheromatous plaque. This risk however was different according to sex. In men, phosphate levels within the normal range associated with an increased risk of subclinical atheromatosis whereas in women this risk only increased with serum levels over the normal range. CONCLUSIONS This study demonstrates that phosphate levels are associated with the presence of subclinical atheromatosis in a large CKD population. This effect of phosphate on subclinical atheromatosis was different according to sex, suggesting that a recommended serum phosphate levels could be different for male than for female CKD patients.

Serum levels of matrix metalloproteinase-10 are associated with the severity of atherosclerosis in patients with chronic kidney disease.

Cardiovascular disease is the leading cause of mortality in chronic kidney disease (CKD). As matrix metalloproteinases have a major role in atherosclerosis, we hypothesized that alterations in metalloproteinases-8, -10 and their tissue inhibitor-1 can be associated with the severity of atherosclerosis in patients with kidney disease. This was evaluated in a cross-sectional, observational study of 111 patients with stages I-V kidney disease, 217 patients on dialysis and 50 healthy controls. The severity of atherosclerosis was estimated with the atherosclerosis score (AS), combining the results of ankle-brachial index and carotid ultrasound. Serum levels of the two metalloproteinases and tissue inhibitor-1 were measured by enzyme-linked immunosorbent assay and were significantly increased in patients with kidney disease compared with the healthy controls, and higher in patients on dialysis than in earlier stages of CKD. The severity of the AS was also more prevalent in the dialysis group, in which serum levels of both metalloproteinases and tissue inhibitor-1 were significantly higher. After multivariate analysis, metalloproteinase-10, dialysis, C-reactive protein, age, and male gender were associated with increased risk of atherosclerosis. Thus, patients with CKD exhibit elevated levels of circulating metalloproteinase-10, and this was independently associated with the severity of atherosclerosis and may represent a new biomarker of atherosclerotic diseases.

A low fractional excretion of Phosphate/Fgf23 ratio is associated with severe abdominal Aortic calcification in stage 3 and 4 kidney disease patients

BackgroundVascular calcification (VC) contributes to high mortality rates in chronic kidney disease (CKD). High serum phosphate and FGF23 levels and impaired phosphaturic response to FGF23 may affect VC. Therefore, their relative contribution to abdominal aortic calcification (AAC) was examined in patients CKD stages 3–4.MethodsPotential risk factors for AAC, measured by the Kauppila Index (KI), were studied in 178 patients.ResultsIn multivariate linear analysis, AAC associated positively with age, male gender, CKD-stage, presence of carotid plaques (CP) and also with FGF23, but negatively with fractional excretion of phosphate (FEP). Intriguingly, FEP increased with similar slopes with elevations in PTH, with reductions in GFR, and also with elevations in FGF23 but the latter only in patients with none (KI = 0) or mild (KI = 1-5) AAC. Lack of a FEP-FGF23 correlation in patients with severe AAC (KI > 5) suggested a role for an impaired phosphaturic response to FGF23 but not to PTH in AAC. Logistic and zero-inflated analysis confirmed the independent association of age, CKD stage, male gender and CP with AAC, and also identified a threshold FEP/FGF23 ratio of 1/3.9, below which the chances for a patient of presenting severe AAC increased by 3-fold. Accordingly, KI remained unchanged as FEP/FGF23 ratios decreased from 1/1 to 1/3.9 but markedly increased in parallel with further reductions in FEP/FGF23 < 1/3.9.ConclusionsIn CKD 3–4, an impaired phosphaturic response to FGF23 with FEP/FGF23 < 1/3.9 associates with severe AAC independently of age, gender or CP.

Vitamin D receptor levels in colorectal cancer Possible role of BsmI polymorphism

A high expression of vitamin D receptor (VDR) in colorectal cancer (CRC) tumoral tissue has been related to a good prognosis and it has been proposed that it could be a good biological marker of CRC progression. Nevertheless, there are no previous studies that compare the VDR expression in tumoral towards normal tissue of the same CRC patient in relation to VDR BsmI genotype. We collected normal and tumoral tissue samples, as well as blood samples, from CRC patients (n=170) and controls (n=122). VDR genotyping was performed and BsmI homozygous patients were selected (CRC=50, Cont=32). VDR mRNA and protein levels were analyzed. We also measured 25-Hydroxyvitamin D serum levels. We found no differences in the polymorphism distribution in tumoral versus normal tissue (control: BB=15.7%, bb=41.3%, Bb=43%; CRC: BB=14.2%, bb=41.9%, Bb=43.9%). Furthermore, VDR levels decreased in colonic cancer tissue (mean: 3.03) versus normal mucosa (11.62) from the same patient (p<0.001), but this decrease was similar in both genotypes. There were differences in 25-Hydroxyvitamin D(3) levels between the CRC and the control group (CRC=8.65 ng/ml, Cont=18.15 ng/ml). In conclusion, we found a decrease in VDR levels in tumoral compared with normal mucosa from the same patient. This difference is independent of the BsmI polymorphism.

Grover’s disease in patients with chronic renal failure receiving hemodialysis: Clinicopathologic review of 4 cases

In 4 patients undergoing hemodialysis for chronic renal failure, a transient or persistent, papular and keratotic eruption developed on the trunk and arms. Histologic examination disclosed focal acantholysis with dyskeratosis. The lesions were clinically and histologically indistinguishable from those of Grovers disease. A possible association with Grovers disease and chronic renal failure and/or hemodialysis is postulated. Possible implicated pathogenic mechanisms are discussed. We suggest that Grovers disease should be included in the differential diagnosis of cutaneous eruptions in patients with chronic renal failure.

The Role of Carotid Ultrasound in Assessing Carotid Atherosclerosis in Individuals at Low-to-intermediate Cardiovascular Risk

INTRODUCTION AND OBJECTIVES Detection of carotid atherosclerosis might help to better identify individuals susceptible to cardiovascular events. We aimed to quantify the number of participants with carotid atherosclerosis and low-to-intermediate cardiovascular risk according to the traditional risk factor scoring, and therefore with an elevated risk of cardiovascular events. METHODS Cross-sectional, observational study performed during a cardiovascular screening program. From a total of 3778 volunteers, low-to-intermediate cardiovascular risk individuals (N=2354) were identified and studied. Physical examination, blood test, and carotid ultrasound followed standard procedures. Common, bulb, and internal carotid arteries were examined and common carotid intima-media thickness was measured. SCORE risk value was calculated for all participants. Univariate and multivariate statistical analysis was performed. RESULTS Mean age of participants was 58.9 (15) years, 43.8% were men, 23.7% had hypertension, and 20.5% had hypercholesterolemia. The mean SCORE value was 1.47 (1.4). Both carotid intima-media thickness and the prevalence of carotid plaques increased steadily and significantly (P<.005) as advanced decades of life were analyzed. Variables significantly related with the presence of carotid atherosclerosis were age, male sex, and systolic blood pressure. Interestingly, 592 (25.1%) individuals were reclassified to a higher risk due to the presence of carotid atherosclerosis. CONCLUSIONS There was a clear dissociation between cardiovascular risk scoring and the presence of atherosclerosis, because 1 of 4 study participants at low-to-intermediate cardiovascular risk had carotid atherosclerosis.

Factors influencing pathological ankle-brachial index values along the chronic kidney disease spectrum: the NEFRONA study

Background: The ankle‐brachial index (ABI) is widely used to diagnose subclinical peripheral artery disease (PAD) in the general population, but data assessing its prevalence and related factors in different chronic kidney disease (CKD) stages are scarce. The aim of this study is to evaluate the prevalence and associated factors of pathological ABI values in CKD patients. Methods: NEFRONA is a multicentre prospective project that included 2445 CKD patients from 81 centres and 559 non‐CKD subjects from 9 primary care centres across Spain. A trained team collected clinical and laboratory data, performed vascular ultrasounds and measured the ABI. Results: PAD prevalence was higher in CKD than in controls (28.0 versus 12.3%, P < 0.001). Prevalence increased in more advanced CKD stages, due to more patients with an ABI ≥1.4, rather than ≤0.9. Diabetes was the only factor predicting both pathological values in all CKD stages. Age, female sex, carotid plaques, higher carotid intima‐media thickness, higher high‐sensitivity C‐reactive protein (hsCRP) and triglycerides, and lower 25‐hydroxi‐vitamin D were independently associated with an ABI ≤0.9. Higher phosphate and hsCRP, lower low‐density lipoprotein (LDL)‐cholesterol and dialysis were associated with an ABI ≥1.4. A stratified analysis showed different associated factors in each CKD stage, with phosphate being especially important in earlier CKD, and LDL‐cholesterol being an independent predictor only in Sage 5D CKD. Conclusions: Asymptomatic PAD is very prevalent in all CKD stages, but factors related to a low or high pathological ABI differ, revealing different pathogenic pathways. Diabetes, dyslipidaemia, inflammation and mineral‐bone disorders play a role in the appearance of PAD in CKD.

Diálisis peritoneal incremental: resultados clínicos y preservación de la función renal residual

INTRODUCTION Initiation of peritoneal dialysis (PD) with 3 exchanges has become common practice in recent years, despite the lack of published clinical data. OBJECTIVE To describe experience with incremental peritoneal dialysis (IPD) at a single site. MATERIAL AND METHODS A total of 46 IPD patients undergoing 2-year clinical, laboratory, treatment and progression follow-up. RESULTS To 25% of patients were trasplanted on IPD. Mean time on IPD before transfer to conventional PD of 24 months, half of the patients because of fluid balance. Good clinical and biochemical results with a peritonitis rate of one episode per 99 months. There was an improvement in the loss of residual kidney function compared to the pre-dialysis period (-7.06 vs. -1.58ml/min/year; P=.0001). CONCLUSIONS IPD with 3 peritoneal exchanges offers good results. Most patients remain stable during the first 2 years and there is an improvement in the loss of residual kidney function compared to the pre-dialysis period.