Search

Nonalcoholic fatty liver disease is a rapidly rising problem in the 21st century and is a leading cause of chronic liver disease that can lead to end-stage liver diseases, including cirrhosis and hepatocellular cancer. Despite this rising epidemic, no pharmacological treatment has yet been established to treat this disease. The rapidly increasing prevalence of nonalcoholic fatty liver disease and its aggressive form, nonalcoholic steatohepatitis (NASH), requires novel therapeutic approaches to prevent disease progression. Alterations in microbiome dynamics and dysbiosis play an important role in liver disease and may represent targetable pathways to treat liver disorders. Improving microbiome properties or restoring normal bile acid metabolism may prevent or slow the progression of liver diseases such as NASH. Importantly, aberrant systemic circulation of bile acids can greatly disrupt metabolic homeostasis. Bile acid sequestrants are orally administered polymers that bind bile acids in the intestine, forming nonabsorbable complexes. Bile acid sequestrants interrupt intestinal reabsorption of bile acids, decreasing their circulating levels. We determined that treatment with the bile acid sequestrant sevelamer reversed the liver injury and prevented the progression of NASH, including steatosis, inflammation, and fibrosis in a Western diet-induced NASH mouse model. Metabolomics and microbiome analysis revealed that this beneficial effect is associated with changes in the microbiota population and bile acid composition, including reversing microbiota complexity in cecum by increasing Lactobacillus and decreased Desulfovibrio The net effect of these changes was improvement in liver function and markers of liver injury and the positive effects of reversal of insulin resistance.

BackgroundPhosphate binders are commonly used in the treatment of patients with hyperphosphatemia. While phosphate binders are used to lower phosphate, the effects of specific phosphate binder types on vitamin D metabolism are unknown.MethodsWe performed a secondary analysis of the Phosphate Normalization Trial in which patients with moderate to advanced chronic kidney disease were randomized to receive either placebo, sevelamer carbonate, lanthanum carbonate or calcium acetate for 9 months. We evaluated changes in serum concentrations of vitamin D metabolites including 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the ratio of 24,25(OH)2D3 to 25-hydroxyvitamin D [the vitamin D metabolite ratio (VMR)] and the ratio of serum 1,25(OH)2D to 25-hydroxyvitamin D.ResultsCompared with placebo, randomization to the calcium acetate arm was associated with a 0.6 ng/mL (95% CI 0.2, 1) and 13.5 pg/ng (95% CI 5.5, 21.5) increase in 24,25(OH)2D and VMR, respectively, and a 5.2 pg/mL (95% CI 1.1, 9.4) reduction in 1,25(OH)2D. Randomization to sevelamer carbonate was associated with a 0.5 ng/mL (95% CI -0.9, -0.1) and 11.8 pg/ng (95% CI -20, -3.5) reduction in 24,25(OH)2D3 and VMR, respectively. There was no association of the sevelamer arm with the change in 1,25(OH)2D3, and randomization to lanthanum carbonate was not associated with a change in any of the vitamin D metabolites.ConclusionAdministration of different phosphate binders to patients with moderate to severe CKD results in unique changes in vitamin D metabolism.

Aims: Sevelamer has been reported to have anti-oxidative and anti-inflammatory effects as well as effects on glycaemic control and plasma lipids. The aim of this study was to determine the effects of one-week treatment with sevelamer on oxidative nucleic acid modifications and inflammation markers. Methods: Two double-blinded studies including 30 patients with type 2 diabetes (T2D) and 20 healthy individuals were conducted. Participants were randomised to one week of treatment with sevelamer (1600 mg three times daily) or placebo. RNA and DNA oxidation, measured by urinary excretion of 8-oxo-7,8-dihydroguanosine(8-oxoGuo) and (8-oxo-7,8-dihydro-2′-deoxyguanosine(8-oxodG), and markers of inflammation were determined before and after the intervention. Results: In patients with T2D there was no significant placebo-corrected reduction in 8-oxoGuo or 8-oxodG. However, a reduction in 8-oxoGuo was observed within the group treated with sevelamer (∆8-oxoGuo/creatinine (median[IQR]): −0.04 [−0.24; 0.01] nmol/mmol, p = 0.02). A sevelamer-mediated reduction in interleukin-2 (p = 0.04) and a trend towards reduction in interleukin-6 (p = 0.053) were found in patients with T2D. Conclusions: This study reveals a potential effect of sevelamer treatment on inflammation and possible oxidative RNA modifications. The potential protective effects of sevelamer in terms of cardiovascular disease in patients with T2D need further investigation.

Bakgrund: Det finns läkemedel som ger ökad risk för vitamin D-brist. En kartläggningsstudie av hur patientgrupper med olika riskläkemedel hanteras i Landstinget i Kalmar län har inte gjorts tidigare. En sådan studie är önskvärd, för att få en nulägesanalys och öka medvetenheten bland hälso-och sjukvårdspersonal om hur läkemedel påverkar D-vitaminstatus. Syfte: Syftet var att undersöka omfattningen av ordinerade riskläkemedel hos samtliga patienter, samt hos patientgruppen ≥75år och hur dessa handläggs avseende ordination av supplementering (samtidig behandling med läkemedel innehållande vitamin D3 / kalcium och vitamin D3,), provtagning och analysresultat avseende kalcidiol i serum. Metod: Riskläkemedel för vitamin D-brist identifierades. Inklusionskriterier för studien var patienter med de fördefinierade riskläkemedlen med ordinationer under 2012 och/eller 2013. Populationen som ingick i studien var patienter i Landstinget i Kalmar län. Data hämtades från patientdatasystemet Cambio Cosmic. Utifrån dessa data analyserades förekomst av supplementering, provtagning för S-25(OH)D kalcidiol och analyssvar. Materialet strukturerades efter respektive läkemedel avseende kön och ålder (≥75 år.) Resultat: 9118 individer ordinerades något av riskläkemedelen orlistat, sevelamer, kolestyramin, kolestipol, efavirenz, prednison, prednisolon, fenytoin, fenobarbital eller karbamazepin. 31% av patienterna som ordinerats riskläkemedel var ≥75 år. Totalt behandlades 22% med supplementationspreparat av de som ordinerats riskläkemedel. I åldersgruppen ≥75 år behandlades 43% med supplement. 61% av de supplementerade patienterna var ≥75 år. Totalt provtogs enbart 4,1% avseende kalcidiol av de som ordinerats riskläkemedel. Av dessa hade 37% av de provtagna en bristnivå av S-25(OH)D (≤50 nmol/L) vid första provtillfället. 57% av de som visade brist supplementerades. Endast 8,3% av de som hade en brist följdes upp med ytterligare en eller flera provtagningar. Av patienterna ≥75 år provtogs 4, Introduction: Some drugs increase the risk for vitamin D deficiency. To date, no survey has been performed in Kalmar County about how patients medicated with risk pharmaceuticals are handled. Such a survey would be desirable in order to increase knowledge among healthcare workers about how substances interfere with vitamin D status. Aim: The aim was to examine the extent to which risk pharmaceuticals are prescribed among all patients and among patients aged ≥75, and to investigate how these patients are treated with respect to supplementation (drugs containing vitamin D3 / Calcuim and vitamin D3), blood sampling and analysis of serum calcidiol levels. Method: Drugs interfering with vitamin D were identified. Inclusion criteria for the survey were patients that had been prescribed the pre-defined risk pharmaceuticals during 2012 and/ or 2013. The surveyed population was residents in Kalmar County. Data were collected from the patient database Cambio Cosmic. From these data analyzes were made about the occurrence of: supplementation, sampling of S-25(OH)D calcidiol and test results. The collected data were arranged by substance, gender and age (elderly aged ≥75). Results: 9118 patients were prescribed at least one of the risk pharmaceuticals; orlistat, sevelamer, cholestyramine, colestipol, efavirenz, prednisol, prednison, phenytoin, phenobarbital or carbamazepine. 31% of these were aged ≥75. Overall, 22% of the patients were prescribed supplements. Out of these, 61% were elderly. Among the patients that had been prescribed risk pharmaceuticals a minority, 4,1% of the patients were sampled for calcidiol. 37% of these had deficiency in S-25(OH)D (≤50 nmol/L). 8.3% of patients with a vitamin D deficiency were sampled more than once. Out of the patients with deficiency 57% were treated with supplements. Out of the elderly patients prescribed risk pharmaceuticals, 4.1% of the patients were tested for calcidiol. This means that 31% of the tested patients were aged ≥75 and, Betydelsen av bra D-vitaminstatus för äldres hälsa – Hur stor är förekomsten av D-vitaminbrist hos äldre i Kalmar län och hur påverkar läkemedel D-vitaminstatus

UnlabelledAbnormal levels of inflammation are associated with cardiovascular disease and mortality in human immunodeficiency virus (HIV)-infected patients. Microbial translocation, which may cause inflammation, is decreased by sevelamer in patients undergoing hemodialysis. In this single-arm study, we evaluated the effects of 8 weeks of sevelamer therapy on 36 HIV-infected subjects who were not receiving antiretroviral therapy. Sevelamer did not significantly change markers of microbial translocation, inflammation, or T-cell activation. During sevelamer treatment, however, levels of soluble tissue factor, low-density lipoprotein (LDL) cholesterol, and oxidized LDL cholesterol decreased significantly, whereas D-dimer levels increased. Thus, in this study population, sevelamer did not reduce microbial translocation but may have yielded cardiovascular benefits.Clinical trials registrationNCT 01543958.

Bakgrund: Det finns läkemedel som ger ökad risk för vitamin D-brist. En kartläggningsstudie av hur patientgrupper med olika riskläkemedel hanteras i Landstinget i Kalmar län har inte gjorts tidigare. En sådan studie är önskvärd, för att få en nulägesanalys och öka medvetenheten bland hälso-och sjukvårdspersonal om hur läkemedel påverkar D-vitaminstatus. Syfte: Syftet var att undersöka omfattningen av ordinerade riskläkemedel hos samtliga patienter, samt hos patientgruppen ≥75år och hur dessa handläggs avseende ordination av supplementering (samtidig behandling med läkemedel innehållande vitamin D3 / kalcium och vitamin D3,), provtagning och analysresultat avseende kalcidiol i serum. Metod: Riskläkemedel för vitamin D-brist identifierades. Inklusionskriterier för studien var patienter med de fördefinierade riskläkemedlen med ordinationer under 2012 och/eller 2013. Populationen som ingick i studien var patienter i Landstinget i Kalmar län. Data hämtades från patientdatasystemet Cambio Cosmic. Utifrån dessa data analyserades förekomst av supplementering, provtagning för S-25(OH)D kalcidiol och analyssvar. Materialet strukturerades efter respektive läkemedel avseende kön och ålder (≥75 år.) Resultat: 9118 individer ordinerades något av riskläkemedelen orlistat, sevelamer, kolestyramin, kolestipol, efavirenz, prednison, prednisolon, fenytoin, fenobarbital eller karbamazepin. 31% av patienterna som ordinerats riskläkemedel var ≥75 år. Totalt behandlades 22% med supplementationspreparat av de som ordinerats riskläkemedel. I åldersgruppen ≥75 år behandlades 43% med supplement. 61% av de supplementerade patienterna var ≥75 år. Totalt provtogs enbart 4,1% avseende kalcidiol av de som ordinerats riskläkemedel. Av dessa hade 37% av de provtagna en bristnivå av S-25(OH)D (≤50 nmol/L) vid första provtillfället. 57% av de som visade brist supplementerades. Endast 8,3% av de som hade en brist följdes upp med ytterligare en eller flera provtagningar. Av patienterna ≥75 år provtogs 4, Introduction: Some drugs increase the risk for vitamin D deficiency. To date, no survey has been performed in Kalmar County about how patients medicated with risk pharmaceuticals are handled. Such a survey would be desirable in order to increase knowledge among healthcare workers about how substances interfere with vitamin D status. Aim: The aim was to examine the extent to which risk pharmaceuticals are prescribed among all patients and among patients aged ≥75, and to investigate how these patients are treated with respect to supplementation (drugs containing vitamin D3 / Calcuim and vitamin D3), blood sampling and analysis of serum calcidiol levels. Method: Drugs interfering with vitamin D were identified. Inclusion criteria for the survey were patients that had been prescribed the pre-defined risk pharmaceuticals during 2012 and/ or 2013. The surveyed population was residents in Kalmar County. Data were collected from the patient database Cambio Cosmic. From these data analyzes were made about the occurrence of: supplementation, sampling of S-25(OH)D calcidiol and test results. The collected data were arranged by substance, gender and age (elderly aged ≥75). Results: 9118 patients were prescribed at least one of the risk pharmaceuticals; orlistat, sevelamer, cholestyramine, colestipol, efavirenz, prednisol, prednison, phenytoin, phenobarbital or carbamazepine. 31% of these were aged ≥75. Overall, 22% of the patients were prescribed supplements. Out of these, 61% were elderly. Among the patients that had been prescribed risk pharmaceuticals a minority, 4,1% of the patients were sampled for calcidiol. 37% of these had deficiency in S-25(OH)D (≤50 nmol/L). 8.3% of patients with a vitamin D deficiency were sampled more than once. Out of the patients with deficiency 57% were treated with supplements. Out of the elderly patients prescribed risk pharmaceuticals, 4.1% of the patients were tested for calcidiol. This means that 31% of the tested patients were aged ≥75 and, Betydelsen av bra D-vitaminstatus för äldres hälsa – Hur stor är förekomsten av D-vitaminbrist hos äldre i Kalmar län och hur påverkar läkemedel D-vitaminstatus

Aim: To establish if PD patients experience more gastrointestinal (GI) symptoms than haemodialysis (HD) patients and whether this impacts on food intake. Background(s): Malnutrition is a frequent finding amongst dialysis patients. Many studies have reported gastrointestinal (GI) disorders in the peritoneal dialysis (PD) population. Nurses working with this group of patients at our hospital reported frequent complaints about gastric symptoms such as nausea, vomiting, early satiety, poor appetite and constipation. Method(s): Experienced renal dietitians surveyed 122 PD patients and 172 HD patients regarding the prevalence and impact of gastrointestinal symptoms. Result(s): Those on PD reported significantly greater incidence of nausea, vomiting, bloating, early satiety, diarrhoea, heartburn and fatigue than those on HD. Eighty-five percent of patients on PD reported at least one GI symptom, compared to 51% of HD patients. When weight loss and fatigue were considered, 91% of PD and 60% of HD patients reported at least one symptom. Those on PD were also significantly more likely to report that the symptoms were related to the onset of dialysis. More patients on PD had noted a change in food intake and attempted dietary changes to alleviate symptoms. Serum albumin levels were significantly lower for those on PD. This group had lower body mass indexes at commencement of dialysis but this difference was not significant for current weight. Those on PD had dialysed for less average time than the group on HD. There was no difference in numbers of diabetics or those taking cinacalcet or sevelamer between the groups. Conclusion(s): PD patients report a significantly greater number and frequency of GI symptoms than HD patients, and that these symptoms result in decreased food intake.

Aim: To establish if PD patients experience more gastrointestinal (GI) symptoms than haemodialysis (HD) patients and whether this impacts on food intake. Background(s): Malnutrition is a frequent finding amongst dialysis patients. Many studies have reported gastrointestinal (GI) disorders in the peritoneal dialysis (PD) population. Nurses working with this group of patients at our hospital reported frequent complaints about gastric symptoms such as nausea, vomiting, early satiety, poor appetite and constipation. Method(s): Experienced renal dietitians surveyed 122 PD patients and 172 HD patients regarding the prevalence and impact of gastrointestinal symptoms. Result(s): Those on PD reported significantly greater incidence of nausea, vomiting, bloating, early satiety, diarrhoea, heartburn and fatigue than those on HD. Eighty-five percent of patients on PD reported at least one GI symptom, compared to 51% of HD patients. When weight loss and fatigue were considered, 91% of PD and 60% of HD patients reported at least one symptom. Those on PD were also significantly more likely to report that the symptoms were related to the onset of dialysis. More patients on PD had noted a change in food intake and attempted dietary changes to alleviate symptoms. Serum albumin levels were significantly lower for those on PD. This group had lower body mass indexes at commencement of dialysis but this difference was not significant for current weight. Those on PD had dialysed for less average time than the group on HD. There was no difference in numbers of diabetics or those taking cinacalcet or sevelamer between the groups. Conclusion(s): PD patients report a significantly greater number and frequency of GI symptoms than HD patients, and that these symptoms result in decreased food intake.

Because of an elevated serum phosphate level, patients who suffer from chronic kidney failure frequently tend to have cardiovascular calcification and are therefore exposed to a higher probability of a fatal event. Phosphate binders are able to reduce these negative effects. Currently, there are primarily two groups of phosphate binders (calcium-containing and calcium-free phosphate binders) which are considered to be almost equally effective in terms of binding of free phosphate. There are, however, a few disadvantages of the two groups. While the calcium-containing binders are associated with an increased risk of hypercalcaemia, which is dose dependent, calcium-free binders have been criticized as being too expensive. As the expenditure for patients suffering from chronic kidney failure increases from year to year, as a result of increasing prevalence, there is a growing need for an alternative to existing phosphate binders. The study presented here therefore summarizes available information for the novel combination preparation OsvaRen® (calcium acetate/magnesium carbonate) as an alternative therapy to the calcium-free phosphate binder Renagel® (sevelamer-hydrochloride) and to calcium-containing preparations. The results of this systematic review showed that OsvaRen® is at least equally effective in the regulation of serum phosphate level as Renagel®. In particular, OsvaRen® shows no clinically relevant difference in terms of the control of the serum calcium levels compared to Renagel® and thereby does not increase the risk of a hypercalcaemia, in contrast to pure calcium-based phosphate binders. On the other hand, Renagel® therapy is much more frequently associated with gastrointestinal side-effects, a tendency to result in higher tablet burden for patients and high medication costs. The CALMAG study showed that OsvaRen® was at least as effective and safe in terms of controlling serum phosphate and serum calcium levels as Renagel® while, at the same time, result

Many traditional and nontraditional risk factors contribute to vascular calcification among maintenance hemodialysis (MHD) patients. It is not clear whether coronary artery calcification (CAC) delineates a higher mortality risk independent of known risk factors. We examined 6-year (10/2001-9/2007) survival of 166 MHD patients, aged 53 +/- 13 years, with baseline CAC scores. Patients were grouped into four CAC groups: 0, 1-100, 101-400, and 400+. The 101-400 and 400+ groups were associated with a significantly higher adjusted risk of death than CAC 0 with hazard ratios (HR) 8.5 (95% CI: 1.1-48.1, p = 0.02) and 13.3 (95% CI: 1.3-65.1, p = 0.01), respectively, independent of demographics, comorbidity, lipids and other cardiovascular risks, surrogates of bone disease, nutritional and inflammatory markers and dialysis dose. Total CAC [HR 6.7 (1.1-21.5, p = 0.03)] followed by the presence of CAC in the left main [4.6 (2.2-9.8, p = 0.001)] and left anterior descending artery [4.3 (2.1-14.2, p = 0.001)] were strong independent predictors of mortality even after adjusting for above covariates. Total and vessel-specific CAC predict mortality in MHD patients independent of traditional and nontraditional risk factors.

AimsIn individuals with chronic kidney disease (CKD), including those undergoing maintenance hemodialysis (MHD), coronary artery calcification (CAC) is common. We hypothesized that, in MHD patients, intake of the calcium-free phosphate binder sevelamer is associated with lower CAC compared to calcium-based phosphate binders (CBPB).Material and methodsThis is a cross-sectional study of MHD patients, who underwent computerized tomography to assess coronary artery calcium scores (CACS). Patients were stratified into two mutually exclusive groups based on taking only a CBPB vs. sevelamer. Logistic regression was used to calculate adjusted odds ratio (OR) of CACS > or = 400, CACS 100 < or =; CACS < 400, 10 < or =; CACS < 100 vs. CACS < 10.Results117 MHD patients were either on a CBPB alone (n = 60) or sevelamer alone (n = 57). Despite increased prevalence of DM in the sevelamer group (58%) as compared to the CBPB group (35%), CACS was significantly lower with sevelamer use (283 + or - 83 vs. 494 + or - 94, p = 0.02). The OR of significant CACS > or =; 400 vs. CAC < 10 was 4.35 (95% confidence interval: 1.5 - 9.9, p = 0.008) for CBPB compared with sevelamer, after controlling for case-mix, cholesterol-lowering medication, DM, and inflammatory markers.ConclusionIn our cohort, significant CAC was significantly more prevalent among MHD patients taking CBPB as compared to sevelamer monotherapy.

Many traditional and nontraditional risk factors contribute to vascular calcification among maintenance hemodialysis (MHD) patients. It is not clear whether coronary artery calcification (CAC) delineates a higher mortality risk independent of known risk factors. We examined 6-year (10/2001-9/2007) survival of 166 MHD patients, aged 53 +/- 13 years, with baseline CAC scores. Patients were grouped into four CAC groups: 0, 1-100, 101-400, and 400+. The 101-400 and 400+ groups were associated with a significantly higher adjusted risk of death than CAC 0 with hazard ratios (HR) 8.5 (95% CI: 1.1-48.1, p = 0.02) and 13.3 (95% CI: 1.3-65.1, p = 0.01), respectively, independent of demographics, comorbidity, lipids and other cardiovascular risks, surrogates of bone disease, nutritional and inflammatory markers and dialysis dose. Total CAC [HR 6.7 (1.1-21.5, p = 0.03)] followed by the presence of CAC in the left main [4.6 (2.2-9.8, p = 0.001)] and left anterior descending artery [4.3 (2.1-14.2, p = 0.001)] were strong independent predictors of mortality even after adjusting for above covariates. Total and vessel-specific CAC predict mortality in MHD patients independent of traditional and nontraditional risk factors.

AimsIn individuals with chronic kidney disease (CKD), including those undergoing maintenance hemodialysis (MHD), coronary artery calcification (CAC) is common. We hypothesized that, in MHD patients, intake of the calcium-free phosphate binder sevelamer is associated with lower CAC compared to calcium-based phosphate binders (CBPB).Material and methodsThis is a cross-sectional study of MHD patients, who underwent computerized tomography to assess coronary artery calcium scores (CACS). Patients were stratified into two mutually exclusive groups based on taking only a CBPB vs. sevelamer. Logistic regression was used to calculate adjusted odds ratio (OR) of CACS > or = 400, CACS 100 < or =; CACS < 400, 10 < or =; CACS < 100 vs. CACS < 10.Results117 MHD patients were either on a CBPB alone (n = 60) or sevelamer alone (n = 57). Despite increased prevalence of DM in the sevelamer group (58%) as compared to the CBPB group (35%), CACS was significantly lower with sevelamer use (283 + or - 83 vs. 494 + or - 94, p = 0.02). The OR of significant CACS > or =; 400 vs. CAC < 10 was 4.35 (95% confidence interval: 1.5 - 9.9, p = 0.008) for CBPB compared with sevelamer, after controlling for case-mix, cholesterol-lowering medication, DM, and inflammatory markers.ConclusionIn our cohort, significant CAC was significantly more prevalent among MHD patients taking CBPB as compared to sevelamer monotherapy.

Amino-terminally truncated parathyroid hormone (PTH) fragments are detected to differing degrees by first- and second-generation immunometric PTH assays (PTH-IMAs), and acute changes in serum calcium affect the proportion of these fragments in circulation. However, the effect of chronic calcium changes and different vitamin D doses on these PTH measurements remains to be defined. In this study, 60 pediatric dialysis patients, aged 13.9 ± 0.7 years, with secondary hyperparathyroidism were randomized to 8 months of therapy with oral vitamin D combined with either calcium carbonate (CaCO3) or sevelamer. Serum phosphorus levels did not differ between groups. Serum calcium levels rose from 9.3 ± 0.1 to 9.7 ± 0.1 mg/dl during CaCO3 therapy (p < 0.01 from baseline) but remained unchanged during sevelamer therapy. In the CaCO3 and sevelamer groups, baseline serum PTH levels (1st PTH-IMA; Nichols Institute Diagnostics, San Clemente, CA) were 964 ± 75 and 932 ± 89 pg/ml, and levels declined to 491 ± 55 and 543 ± 59 pg/ml, respectively (nonsignificant between groups). Patients treated with sevelamer received higher doses of vitamin D than those treated with CaCO3. The PTH values obtained by first- and second-generation PTH-IMAs correlated closely throughout therapy and the response of PTH was similar to both PTH-IMAs, despite differences in serum calcium levels.

Amino-terminally truncated parathyroid hormone (PTH) fragments are detected to differing degrees by first- and second-generation immunometric PTH assays (PTH-IMAs), and acute changes in serum calcium affect the proportion of these fragments in circulation. However, the effect of chronic calcium changes and different vitamin D doses on these PTH measurements remains to be defined. In this study, 60 pediatric dialysis patients, aged 13.9 ± 0.7 years, with secondary hyperparathyroidism were randomized to 8 months of therapy with oral vitamin D combined with either calcium carbonate (CaCO3) or sevelamer. Serum phosphorus levels did not differ between groups. Serum calcium levels rose from 9.3 ± 0.1 to 9.7 ± 0.1 mg/dl during CaCO3 therapy (p < 0.01 from baseline) but remained unchanged during sevelamer therapy. In the CaCO3 and sevelamer groups, baseline serum PTH levels (1st PTH-IMA; Nichols Institute Diagnostics, San Clemente, CA) were 964 ± 75 and 932 ± 89 pg/ml, and levels declined to 491 ± 55 and 543 ± 59 pg/ml, respectively (nonsignificant between groups). Patients treated with sevelamer received higher doses of vitamin D than those treated with CaCO3. The PTH values obtained by first- and second-generation PTH-IMAs correlated closely throughout therapy and the response of PTH was similar to both PTH-IMAs, despite differences in serum calcium levels.

IntroductionCardiovascular disease accounts for almost half of all deaths in individuals with chronic kidney disease stage 5 despite advances in both dialysis treatment and cardiology. A combination of lipid-lowering and anti-inflammatory effects along with avoidance of hypercalcemia should be taken into account when choosing phosphorus binders for maintenance hemodialysis (MHD) patients.MethodsWe examined the association of sevelamer versus calcium-based phosphorus binders with lipid profile, inflammatory markers including C-reactive protein (CRP), and mineral metabolism in MHD patients who participated in the Nutritional and Inflammatory Evaluation of Dialysis Patients (NIED) study from October 2001 to July 2005.ResultsOf the 787 MHD patients in the NIED study, 697 were on either sevelamer, a calcium-based binder, or both and eligible for this study. We compared the groups based on taking sevelamer monotherapy (n = 283) or calcium binder monotherapy (n = 266) for serum phosphate control. There were no differences between the groups on dialysis vintage. There were significant differences in age, serum calcium and phosphorus levels, as well as intact parathyroid hormone levels. Using a logistic regression models, the sevelamer group had a higher odds of serum CRP <10 mg/l [odds ratio (OR): 1.06, 95% CI: 1.02-1.11] and LDL cholesterol <70 mg/dl (OR: 1.33, 95% CI: 1.19-1.47) when compared to the calcium binder group independent of age, vintage, body mass index, statin use or other variables.ConclusionThe improvements in multiple surrogate markers of inflammation and lipids in the NIED study make sevelamer a promising therapy for treatment in MHD patients with high risk of cardiovascular disease and mortality.

IntroductionCardiovascular disease accounts for almost half of all deaths in individuals with chronic kidney disease stage 5 despite advances in both dialysis treatment and cardiology. A combination of lipid-lowering and anti-inflammatory effects along with avoidance of hypercalcemia should be taken into account when choosing phosphorus binders for maintenance hemodialysis (MHD) patients.MethodsWe examined the association of sevelamer versus calcium-based phosphorus binders with lipid profile, inflammatory markers including C-reactive protein (CRP), and mineral metabolism in MHD patients who participated in the Nutritional and Inflammatory Evaluation of Dialysis Patients (NIED) study from October 2001 to July 2005.ResultsOf the 787 MHD patients in the NIED study, 697 were on either sevelamer, a calcium-based binder, or both and eligible for this study. We compared the groups based on taking sevelamer monotherapy (n = 283) or calcium binder monotherapy (n = 266) for serum phosphate control. There were no differences between the groups on dialysis vintage. There were significant differences in age, serum calcium and phosphorus levels, as well as intact parathyroid hormone levels. Using a logistic regression models, the sevelamer group had a higher odds of serum CRP <10 mg/l [odds ratio (OR): 1.06, 95% CI: 1.02-1.11] and LDL cholesterol <70 mg/dl (OR: 1.33, 95% CI: 1.19-1.47) when compared to the calcium binder group independent of age, vintage, body mass index, statin use or other variables.ConclusionThe improvements in multiple surrogate markers of inflammation and lipids in the NIED study make sevelamer a promising therapy for treatment in MHD patients with high risk of cardiovascular disease and mortality.

Metabolic acidosis, a common condition in patients with renal failure, may be linked to protein-energy malnutrition (PEM) and inflammation, together also known as malnutrition-inflammation complex syndrome (MICS). Methods of serum bicarbonate measurement may misrepresent the true bicarbonate level, since the total serum carbon dioxide measurement usually overestimates the serum bicarbonate concentration. Moreover, the air transportation of blood samples to distant laboratories may lead to erroneous readings. In patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD), a significant number of endocrine, musculoskeletal, and metabolic abnormalities are believed to result from acidemia. Metabolic acidosis may be related to PEM and MICS due to an increased protein catabolism, decreased protein synthesis, endocrine abnormalities including insulin resistance, decreased serum leptin level, and inflammation among individuals with renal failure. Evidence suggests that the catabolic effects of metabolic acidosis may result from an increased activity of the adenosine triphosphate (ATP)-dependent ubiquitin-proteasome and branched-chain keto acid dehydrogenase. In contrast to the metabolic studies, many epidemiologic studies in maintenance dialysis patients have indicated a paradoxically inverse association between mildly decreased serum bicarbonate and improved markers of protein-energy nutritional state. Hence metabolic acidosis may be considered as yet another element of the reverse epidemiology in ESRD patients. Interventional studies have yielded inconsistent results in CKD and ESRD patients, although in peritoneal dialysis patients, mitigating acidemia appears to more consistently improve nutritional status and reduce hospitalizations. Large-scale, prospective randomized interventional studies are needed to ascertain the potential benefits of correcting acidemia in malnourished and/or inflamed CKD and maintenance hemodialysis patients. Until then, all a

Metabolic acidosis, a common condition in patients with renal failure, may be linked to protein-energy malnutrition (PEM) and inflammation, together also known as malnutrition-inflammation complex syndrome (MICS). Methods of serum bicarbonate measurement may misrepresent the true bicarbonate level, since the total serum carbon dioxide measurement usually overestimates the serum bicarbonate concentration. Moreover, the air transportation of blood samples to distant laboratories may lead to erroneous readings. In patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD), a significant number of endocrine, musculoskeletal, and metabolic abnormalities are believed to result from acidemia. Metabolic acidosis may be related to PEM and MICS due to an increased protein catabolism, decreased protein synthesis, endocrine abnormalities including insulin resistance, decreased serum leptin level, and inflammation among individuals with renal failure. Evidence suggests that the catabolic effects of metabolic acidosis may result from an increased activity of the adenosine triphosphate (ATP)-dependent ubiquitin-proteasome and branched-chain keto acid dehydrogenase. In contrast to the metabolic studies, many epidemiologic studies in maintenance dialysis patients have indicated a paradoxically inverse association between mildly decreased serum bicarbonate and improved markers of protein-energy nutritional state. Hence metabolic acidosis may be considered as yet another element of the reverse epidemiology in ESRD patients. Interventional studies have yielded inconsistent results in CKD and ESRD patients, although in peritoneal dialysis patients, mitigating acidemia appears to more consistently improve nutritional status and reduce hospitalizations. Large-scale, prospective randomized interventional studies are needed to ascertain the potential benefits of correcting acidemia in malnourished and/or inflamed CKD and maintenance hemodialysis patients. Until then, all a