Carolina Gracia-Iguacel

Vitamin D Deficiency in Dialysis Patients: Effect of Dialysis Modality and Implications on Outcome

OBJECTIVE Vitamin D deficiency has been linked to cardiovascular disease and mortality in hemodialysis (HD) patients. The purpose of the present cross-sectional study was to analyze the Vitamin D status of dialysis patients from a single center, study determinants of Vitamin D deficiency, and assess its implications on outcome. METHODS A prospective observational study of 115 prevalent dialysis patients was carried out, in which clinical and dialysis-related characteristics including routine biochemistry were studied in relation to levels of 25-hydroxyvitamin-D (25[OH]D, chemiluminescence). Survival was assessed after a median follow-up period of 413 days. RESULTS 25(OH)D deficiency and insufficiency was present in 51% and 42% of the patients, respectively. Only 7% of the patients showed normal 25(OH)D levels. Peritoneal dialysis patients presented the lowest 25(OH)D levels. Also, a significant difference was found between on-line hemodiafiltration (OL-HDF) and conventional HD (11 [6 to 16] versus 19 [13 to 27] ng/mL; P < 0.001; 25th to 75th percentiles, conventional HD versus OL-HDF respectively). In multinomial logistic regression analysis, patients on conventional HD had 8.35 greater odds (95% CI [2.04 to 34.20]) of 25(OH)D deficiency than OL-HDF even after adjustment for sex, parathyroid hormone, pH, and Charlson comorbidity index. During the follow-up period, 18 patients died. Both crude and adjusted (hazard ratio, 6.96; 95% CI [1.44 to 33.64]) Cox analysis identified 25(OH)D deficiency as a mortality risk factor. CONCLUSION This observational study underlines the high prevalence of hypovitaminosis D in dialysis patients and its strong implications on outcome. Furthermore, our results suggest that OL-HDF was associated with a better preservation of the vitamin D status as compared with conventional HD.

Phosphorus and Nutrition in Chronic Kidney Disease

Patients with renal impairment progressively lose the ability to excrete phosphorus. Decreased glomerular filtration of phosphorus is initially compensated by decreased tubular reabsorption, regulated by PTH and FGF23, maintaining normal serum phosphorus concentrations. There is a close relationship between protein and phosphorus intake. In chronic renal disease, a low dietary protein content slows the progression of kidney disease, especially in patients with proteinuria and decreases the supply of phosphorus, which has been directly related with progression of kidney disease and with patient survival. However, not all animal proteins and vegetables have the same proportion of phosphorus in their composition. Adequate labeling of food requires showing the phosphorus-to-protein ratio. The diet in patients with advanced-stage CKD has been controversial, because a diet with too low protein content can favor malnutrition and increase morbidity and mortality. Phosphorus binders lower serum phosphorus and also FGF23 levels, without decreasing diet protein content. But the interaction between intestinal dysbacteriosis in dialysis patients, phosphate binder efficacy, and patient tolerance to the binder could reduce their efficiency.

Subclinical versus overt obesity in dialysis patients: more than meets the eye

BACKGROUND Obesity is an important problem in the epidemic of chronic kidney disease (CKD). Obesity is usually diagnosed by body mass index (BMI), but this metric has limitations as a measure of adiposity in CKD patients. Simple anthropometric tools, like skinfold thickness measurements, have been shown to be a better test to classify obesity among those with CKD. METHODS The prevalence of obesity was estimated by BMI (>30 kg/m(2)) and by skinfold thickness-estimated body fat (>25% in men and 35% in women) in two cohorts comprising 284 incident dialysis and 209 prevalent haemodialysis (HD) patients from Sweden. Patient characteristics were compared among individuals with differing diagnosis. RESULTS BMI obesity cut-offs misdiagnosed many patients (>50%) with excess adiposity. Obesity, estimated by BMI, was present in 9 and 10% of incident and prevalent dialysis patients, respectively. When estimated by percentage of body fat, the prevalence of obesity rose to 64 and 65%. In both cohorts, a large proportion of patients (55%) were obese in the context of a normal BMI (termed as subclinical obesity). These individuals were older, presented more co-morbidity and lower surrogates of muscle mass [handgrip strength, arm muscle circumference or insulin-growth factor (IGF)-1 levels] than those diagnosed by both methods (termed overt obesity). CONCLUSION A BMI of <30 kg/m(2) does not exclude the presence of excess adiposity. Subclinical obesity is a frequent condition in dialysis patients, and the clinical consequences of this finding deserve further consideration.

Nutrients Turned into Toxins: Microbiota Modulation of Nutrient Properties in Chronic Kidney Disease

In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of death. Some uremic toxins are ingested with the diet, such as phosphate and star fruit-derived caramboxin. Others result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves. These nutrients include l-carnitine, choline/phosphatidylcholine, tryptophan and tyrosine, which are also sold over-the-counter as nutritional supplements. Physicians and patients alike should be aware that, in CKD patients, the use of these supplements may lead to potentially toxic effects. Unfortunately, most patients with CKD are not aware of their condition. Some of the dietary components may modify the gut microbiota, increasing the number of bacteria that process them to yield uremic toxins, such as trimethylamine N-Oxide (TMAO), p-cresyl sulfate, indoxyl sulfate and indole-3 acetic acid. Circulating levels of nutrient-derived uremic toxins are associated to increased risk of death and cardiovascular disease and there is evidence that this association may be causal. Future developments may include maneuvers to modify gut processing or absorption of these nutrients or derivatives to improve CKD patient outcomes.

Eculizumab in secondary atypical haemolytic uraemic syndrome

Background. Complement dysregulation occurs in thrombotic microangiopathies (TMAs) other than primary atypical haemolytic uraemic syndrome (aHUS). A few of these patients have been reported previously to be successfully treated with eculizumab. Methods. We identified 29 patients with so‐called secondary aHUS who had received eculizumab at 11 Spanish nephrology centres. Primary outcome was TMA resolution, defined by a normalization of platelet count (>150 × 109/L) and haemoglobin, disappearance of all the markers of microangiopathic haemolytic anaemia (MAHA), and improvement of renal function, with a ≥25% reduction of serum creatinine from the onset of eculizumab administration. Results. Twenty‐nine patients with secondary aHUS (15 drug‐induced, 8 associated with systemic diseases, 2 with postpartum, 2 with cancer‐related, 1 associated with acute humoral rejection and 1 with intestinal lymphangiectasia) were included in this study. The reason to initiate eculizumab treatment was worsening of renal function and persistence of TMA despite treatment of the TMA cause and plasmapheresis. All patients showed severe MAHA and renal function impairment (14 requiring dialysis) prior to eculizumab treatment and 11 presented severe extrarenal manifestations. A rapid resolution of the TMA was observed in 20 patients (68%), 15 of them showing a ≥50% serum creatinine reduction at the last follow‐up. Comprehensive genetic and molecular studies in 22 patients identified complement pathogenic variants in only 2 patients. With these two exceptions, eculizumab was discontinued, after a median of 8 weeks of treatment, without the occurrence of aHUS relapses. Conclusion. Short treatment with eculizumab can result in a rapid improvement of patients with secondary aHUS in whom TMA has persisted and renal function worsened despite treatment of the TMA‐inducing condition.

Use of sevelamer in chronic kidney disease: beyond phosphorus control

espanolEl sevelamer es un captor no calcico de fosforo que se utiliza en la ERC avanzada y en dialisis para el control de la hiperfosforemia. Varios estudios experimentales, observacionales y ensayos clinicos han mostrado que el sevelamer tiene efectos pleiotropicos, mas alla del control de la hiperfosforemia, incluyendo acciones sobre la inflamacion, el estres oxidativo, el perfil lipidico y la aterogenesis, la calcificacion vascular, la disfuncion endotelial y la disminucion de diversas toxinas uremicas, todo lo cual seria la base biologica de su efecto global sobre la morbilidad y la mortalidad cardiovascular en pacientes con enfermedad renal cronica. En esta revision, se hace enfasis en estas acciones pleiotropicas del sevelamer y su impacto en la salud cardiovascular, con la experiencia publicada despues de mas de 10 anos de experiencia clinica EnglishSevelamer is a calcium-free phosphate binder used in advanced chronic kidney disease (CKD) and in dialysis to control hyperphosphatemia. Several experimental and observational studies and clinical trials have shown that sevelamer has pleiotropic effects that go beyond controlling hyperphosphatemia; these pleiotropic effects include acting on inflammation, oxidative stress, lipid profile and atherogenesis, vascular calcification, endothelial dysfunction and decreasing various uremic toxins. All of these represent the biological basis for the global effect of sevelamer on cardiovascular morbidity and mortality in patients with CKD. In this review, we emphasis these pleiotropic actions of sevelamer and their impact on cardiovascular health, with the experience published after more than 10 years of clinical experience.Sevelamer is a non-calcium phosphate binder used in advanced chronic kidney disease (CKD) and in dialysis for hyperphosphataemia control. Several experimental, observational studies and clinical trials have shown that sevelamer has pleiotropic effects, beyond hyperphosphataemia control, including actions on inflammation, oxidative stress, lipid profile and atherogenesis, vascular calcification, endothelial dysfunction and the reduction of several uremic toxins. This is the biological basis for its global effect on cardiovascular morbidity and mortality in patients with chronic kidney disease. This review focuses on these pleiotropic actions of sevelamer and their impact on cardiovascular health, with the experience published after more than ten years of clinical expertise.

Cortisol levels are associated with mortality risk in hemodialysis patients.

BACKGROUND End-stage renal disease (ESRD) conveys high mortality risk by complex mechanisms not fully elucidated but possibly linked to hormonal abnormalities, including cortisol. Whereas a high serum cortisol level has recently been linked with increased mortality in the general population, there is scarce information on the clinical associates and prognostic value of cortisol levels in ESRD. PATIENTS AND METHODS Prospective study of prevalent hemodialysis patients (n = 75), mostly non-diabetic (76%), where cortisol levels were assessed and patients were afterwards followed for a median of 20 (interquartile range (IQR) 8 - 31) months. RESULTS Cortisol levels were negatively correlated with plasma sodium (Rho = -0.26. p < 0.025) and positively correlated with C-reactive protein (CRP; Rho = 0.26, p = 0.027). The association with CRP remained independent of multiple confounders. Baseline cortisol levels of those who died were higher than of those who survived (19.8 ± 6.9 vs. 15.3 ± 5.7 mcg/dL, p = 0.0083). Kaplan-Meier analysis showed that patients with cortisol levels within the highest tertile (≥ 18 mcg/dL) were at increased risk of death. Cortisol was associated with risk of death both in crude and adjusted Cox proportional hazards models (HR 1.09 (1.021 - 1.167) p = 0.011; and 1.16 (1.027 - 1.309), p = 0.01, respectively)). CONCLUSIONS High serum concentrations of cortisol were associated with a state of inflammation and independently identified a subgroup of chronic hemodialysis patients at a high mortality risk.

A decrease in intact parathyroid hormone (iPTH) levels is associated with higher mortality in prevalent hemodialysis patients

Background The mortality of dialysis patients is 10- to 100-fold higher than in the general population. Baseline serum PTH levels, and more recently, changes in serum PTH levels (ΔPTH) over time, have been associated to mortality in dialysis patients. Methods We explored the relationship between ΔPTH over 1 year with mortality over the next year in a prospective cohort of 115 prevalent hemodialysis patients from a single center that had median baseline iPTH levels within guideline recommendations. Results Median baseline iPTH levels were 205 (116.5, 400) pg/ml. ΔiPTH between baseline and 1 year was 85.2 ± 57.1 pg/ml. During the second year of follow-up, 27 patients died. ΔiPTH was significantly higher in patients who survived (+157.30 ± 25.82 pg/ml) than in those who died (+39.03 ± 60.95 pg/ml), while baseline iPTH values were not significantly different. The highest mortality (48%) was observed in patients with a decrease in ΔiPTH (ΔiPTH quartile 1, negative ΔiPTH) and the lowest (12%) mortality in quartile 3 ΔiPTH (ΔiPTH increase 101–300 pg/ml). In a logistic regression model, ΔiPTH was associated with mortality with an odds ratio (OR) of 0.998 (95% CI 0.996–0999, p = 0.038). In multivariable analysis, mortality risk was 73% and 88% lower for patients with ΔiPTH 0–100 pg/ml and 101–300 pg/ml, respectively, than for those with a decrease in ΔiPTH. In patients with a decrease in ΔiPTH, the OR for death was 4.131 (1.515–11.27)(p = 0.006). Conclusions In prevalent hemodialysis patients with median baseline iPTH values within the guideline recommended range, a decrease in ΔiPTH was associated with higher mortality. Further studies are required to understand the mechanisms and therapeutic implications of this observation that challenges current clinical practice.

Impact of Altered Intestinal Microbiota on Chronic Kidney Disease Progression

In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of CKD progression. Some uremic toxins result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves, such as trimethylamine N-Oxide (TMAO), p-cresyl sulphate, indoxyl sulphate and indole-3 acetic acid. Increased intake of some nutrients may modify the gut microbiota, increasing the number of bacteria that process them to yield uremic toxins. Circulating levels of nutrient-derived uremic toxins are associated to increased risk of CKD progression. This offers the opportunity for therapeutic intervention by either modifying the diet, modifying the microbiota, decreasing uremic toxin production by microbiota, increasing toxin excretion or targeting specific uremic toxins. We now review the link between nutrients, microbiota and uremic toxin with CKD progression. Specific focus will be placed on the generation specific uremic toxins with nephrotoxic potential, the decreased availability of bacteria-derived metabolites with nephroprotective potential, such as vitamin K and butyrate and the cellular and molecular mechanisms linking these toxins and protective factors to kidney diseases. This information provides a conceptual framework that allows the development of novel therapeutic approaches.

MP721A DECREASE IN INTACT PARATHYROID HORMONE (iPTH) LEVELS IS ASSOCIATED WITH HIGHER MORTALITY

Seroconversion rates were compared between the two vaccines using chi squared test. RESULTS: ENG patients (N = 24,677) were older (63. 9 vs. 63.1 years), had a higher eKt/V (1.6 vs. 1.5), a higher proportion of diabetics (61.5% vs. 54.9%), fewer patients with congestion heart failure (12.3% vs. 16.1%), lower dialysis vintage (0.8 vs. 1.1 years) and lower hemoglobin (11.2 vs. 11.5 g/dL) compared to REC patients (N = 1,320) (Table 1). Seroconversion rates were significantly higher with ENG compared to REC (1st series: 73.7% vs. 64.3%, D=9.4% 95% CI: 6.7 % to 12.1%); 1st and 2nd series combined: 78.5% vs. 64.6%, D=13.9%, 95% CI: 11.2% to 16.5%) (Figure 1). CONCLUSIONS: When administering full vaccination courses as outlined above, Engerix-B yields substantially higher primary seroconversion rates than RecombivaxHB. The same is true when looking at cumulative response rates for the 1 and 2 series combined. These results hold true even after adjusting for differences in population characteristics. Reference 1)Rustgi VK., Comparative study of the immunogenicity and safety of Engerix-B administered at 0, 1, 2 and 12 months and Recombivax HB administered at 0, 1, and 6 months in healthy adults. Vaccine. 1995 Dec; 13(17):1665-8. 2) Rault R., Efficacy of different hepatitis B vaccination strategies in patients receiving hemodialysis. ASAIO J. 1995 Jul-Sep;41(3):M717-9. 3)Lacson E., Antibody response to Engerix-B and Recombivax-HB hepatitis B vaccination in end-stage renal disease. Hemodial Int. 2005 Oct;9(4):367-75.