Epidemiology of Fabry disease in patients in hemodialysis in the Madrid community.

This study screened for Fabry disease (FD) in patients in hemodialysis (HD) in the region of Madrid (CAM) with a cross-sectional design to evaluate HD-prevalent patients, followed by a three-year period prospective design to analyze HD-incident patients. INCLUSION CRITERIA: patients older than 18 years on HD in the CAM, excluding patients diagnosed with any other hereditary disease with renal involvement different from FD, that sign the Informed Consent (IC). EXCLUSION CRITERIA: underaged patients or not agreeing or not being capable of signing the IC. RESULTS: 3470 patients were included, 63% males and with an average age of 67.9±9.7 years. 2357 were HD-prevalent patients and 1113 HD-incident patients. For HD-prevalent patients, average time in HD was 45.2 months (SD 51.3), in HD-incident patients proteinuria was present in 28.4%. There were no statistical differences in plasmatic alpha-galactosidase A (α-GAL-A) activity or Lyso-GL-3 values when comparing HD-prevalent and HD-incident populations and neither between males and females. A genetic study was performed in 87 patients (2.5% of patients): 60 male patients with decreased enzymatic activity and 27 female patients either with a decreased GLA activity, increased Lyso-Gl3 levels or both. The genetic variants identified were: p.Asp313Tyr (4 patients), p.Arg220Gln (3 patients) and M290I (1 patient). None of the identified variants is pathogenic. CONCLUSIONS: 76% of HD Centers of the CAM participated in the study. This is the first publication to describe the prevalence of FD in the HD-population of a region of Spain as well as its average α-GAL-A-activity and plasmatic Lyso-Gl3 levels. It is also the first study that combines a cross-sectional design with a prospective follow-up design. This study has not identified any FD patient.

Persistent pruritus as a rare and potentially serious manifestation of liver involvement in autosomal dominant polycystic kidney disease.

Polycystic liver disease (PCLD) is the most frequent extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD), usually asymptomatic. We present a patient with ADPKD who developed cholestatic pruritus due to bile duct compression of multiple liver cysts. Because of severity of pruritus she received treatment with lanreotide to reduce liver volume and she was studied to be included in the liver transplant waiting list. She evolved favourably with medical treatment and she is now asymptomatic. In conclusion, persistent pruritus is a rare but potentially serious manifestation of PCLD, so it should be taken into account in patients with ADPKD.

Comparison of urea recirculation and thermodilution for monitoring of vascular access in patients undergoing hemodialysis.

Introduction It is important to monitor vascular access in patients with stage 5 chronic kidney disease receiving hemodialysis. Access recirculation can help to detect a need for intervention. OBJECTIVES: To compare urea recirculation with recirculation by thermodilution using blood temperature monitoring to predict a need for intervention of vascular access over a 6-month period. METHODS: We analyzed urea recirculation and blood temperature monitoring simultaneously in 61 patients undergoing hemodialysis. During the 6-month follow-up, we recorded all cases of angioplasty or surgery (thrombectomy or reanastomosis). In line with previous studies, we considered a value to be positive when urea recirculation was >10% and blood temperature monitoring >15%. Receiver operating characteristic curves were constructed. RESULTS: Mean urea recirculation was 9.5% ± 6.6% and mean blood temperature monitoring 12.9% ± 4.3% (p = 0.001). Urea recirculation >10% had a sensitivity of 80% and specificity of 78%. Blood temperature monitoring >15% had a sensitivity of 33% and specificity of 85%. During follow-up, 25% of patients developed need for intervention of vascular access. We found an association between vascular access dysfunction and urea recirculation. The Kaplan-Meier analysis confirmed an association between urea recirculation and risk of vascular access dysfunction (log rank = 17.2; p = 0.001). We were unable to confirm this association with blood temperature monitoring (log rank = 0.879; p = 0.656). CONCLUSION: Urea recirculation is better predictor of vascular access dysfunction than thermodilution.

Is High-Volume Online Hemodiafiltration Associated With Malnutrition?

Chronic malnutrition is a common problem in patients with end-stage renal disease on hemodialysis. Some studies have reported albumin loss into dialysis fluid during postdilution online hemodiafiltration (OL-HDF). The aim of the study was to assess the nutritional status of patients on high-volume OL-HDF and to demonstrate that higher convective clearances are not associated with malnutrition due to possible loss of nutrients with ultrafiltration. Demographic and clinical data, corporal composition with bioimpedance spectroscopy, dialysis features, albumin loss into dialysis fluid and laboratory parameters were collected in twenty-eight patients with ESRD undergoing postdilution OL-HDF with stable convective volumes over 28 L/session. Convective volume (CV) in the last six months was 32.51 ± 3.52 L per session. Cross-sectional analysis of dialysis features showed 32.7 ± 3.34 L of CV and high reduction rates of beta-2-microglobulin (84.2 ± 3.8%) and cystatin-C (81.6 ± 3.47%). Beta-2-microglobulin reduction showed a positive correlation with prealbumin levels (P = 0.048). CV was only correlated with cystatin-C reduction (P = 0.025). Estimated albumin loss into dialysis fluid (1.82 ± 1.05 g/session) was not related to laboratory or bioimpedance nutritional parameters, or to CV. Among patients with higher CV, serum albumin levels maintained more stability during the observational period. High volume OL-HDF results in better convective clearances and is not associated with malnutrition. Albumin and nutrients loss into dialysis fluid should not be a limiting factor of the substitution volume.

New expectations in the treatment of anemia in chronic kidney disease. / Nuevas expectativas en el tratamiento de la anemia en la enfermedad renal crónica.

The new drugs developed for the treatment of anemia in chronic kidney disease patients, together with their mechanisms of action are reviewed. At present, many of them are already in advanced stages of clinical trials and is expected to be incorporated into the therapeutic arsenal in the coming years. The potential benefits and possible limitations are also described.

The impact of access blood flow surveillance on reduction of thrombosis in native arteriovenous fistula: a randomized clinical trial.

PURPOSE: The usefulness of access blood flow (QA) measurement is an ongoing controversy. Although all vascular access (VA) clinical guidelines recommend monitoring and surveillance protocols to prevent VA thrombosis, randomized clinical trials (RCTs) have failed to consistently show the benefits of QA-based surveillance protocols. We present a 3-year follow-up multicenter, prospective, open-label, controlled RCT, to evaluate the usefulness of QA measurement using Doppler ultrasound (DU) and ultrasound dilution method (UDM), in a prevalent hemodialysis population with native arteriovenous fistula (AVF). METHODS: Classical monitoring and surveillance methods are applied in all patients, the control group (n = 98) and the QA group (n = 98). Besides this, DU and UDM are performed in the QA group every three months. When QA is under 500 ml/min or there is a >25% decrease in QA the patient goes for fistulography, surgery or close clinical/surveillance observation. Thrombosis rate, assisted primary patency rate, primary patency rate and secondary patency rate are measured. RESULTS: After one-year follow-up we found a significant reduction in thrombosis rate (0.022 thrombosis/patient/year at risk in the QA group compared to 0.099 thrombosis/patient/year at risk in the control group [p = 0.030]). Assisted primary patency rate was significantly higher in the QA group than in control AVF (hazard ratio [HR] 0.23, 95% confidence interval [CI] 0.05-0.99; p = 0.030). In the QA group, the numbers unddergoing angioplasty and surgery were higher but with no significant difference in non-assisted primary patency rate (HR 1.41, 95% CI 0.72-2.84; p = 0.293). There was a non-significant improvement in secondary patency rate in the QA group (HR 0.510, 95% CI 0.17-1.50; p = 0.207). CONCLUSIONS: The measurement of QA combining DU and UDM shows a reduction in thrombosis rate and an increased assisted primary patency rate in AVF after one-year follow-up. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02111655.

Body composition affects the response to erythropoiesis-stimulating agents in patients with chronic kidney disease in dialysis.

BACKGROUND: The response to erythropoiesis-stimulating agents (ESA) in patients with chronic kidney disease (CKD) is variable. The body mass index (BMI) variations can modify the response to ESA. The objective was to assess the effect of body composition on the response to ESA in dialysis patients. METHODS: This is an observational cross-sectional study. Prevalent hemodialysis and peritoneal dialysis (PD) patients were selected. In the same day, a single blood test, a body composition analysis using bioimpedance spectroscopy and anthropometric measurements were performed. We collected ESA doses. We analyzed erythropoietin resistance index (ERI). The ERI was calculated dividing the weekly weight-adjusted (kg) dose of ESA (IU) by the hemoglobin level (g/dL). RESULTS: The study was comprised of 218 patients (58% men; age 65 (16) years old; 80% hemodialysis, 20% PD). There was an inverse correlation between ERI and BMI (p=0.01), fat tissue index (FTI) (p=0.01) and prealbumin (p=0.04). We found an independent association between higher ERI levels and lower FTI and prealbumin values. CONCLUSION: Response to ESA is influenced by body composition. Fat tissue favors the body's response to ESA.

Evaluation of methods based on creatinine and cystatin C to estimate glomerular filtration rate in chronic kidney disease.

PURPOSE: Estimated glomerular filtration rate (GFR) is a useful tool for the detection of chronic kidney disease (CKD). Several methods have been proposed, but findings can vary in specific groups such as patients with diabetes, elderly and high and low body mass index and, also, with the stage of CKD. The objective of this study was comparing the accuracy of the currently used equations for estimating GFR with that of the gold standard technetium-(99m)-diethylene triamine pentaacetic acid (99mTc-DTPA). METHODS: We performed a cross-sectional study of 129 patients with all five CKD stages. GFR was estimated using the following: 24-h urine creatinine clearance, Cockcroft-Gault equation, MDRD equation, CKD-EPI equation, Hoek's cystatin C equation, and isotopic 99mTc-DTPA (as gold standard). We evaluated agreement in the whole study population and according to age, sex, weight, and diabetes. RESULTS: All methods had good agreement. The best agreement was observed with the cystatin C [intraclass coefficient correlation (ICC) 95 % confidence interval (95 % CI), 0.87 (0.82-0.91)], followed by CKD-EPI [ICC 0.83 (0.77-0.88)]. Twenty-four-hour urine creatinine clearance showed the worst agreement in patients older than 65 years [ICC 0.70 (0.56-0.79)]. The Cockcroft-Gault equation showed the worst agreement in younger than 65 years [ICC 0.64 (0.42-0.79)]. The best agreement for classification in the correct CKD stage was with the cystatin C equation [κ = 0.80 (0.74-0.87)]. GFR was overestimated with all methods in CKD stages 4 and 5. CONCLUSIONS: The methods used in clinical practice are adequate for classification of CKD. Cystatin C is the most accurate method, followed by CKD-EPI. The Cockcroft-Gault equation is not accurate in young patients. Twenty-four-hour urine creatinine clearance loses accuracy in patients aged older than 65 years.

Detection of patients at high risk for non-occlusive mesenteric ischemia in hemodialysis.

BACKGROUND: Nonocclusive mesenteric ischemia (NOMI) is an emerging condition in hemodialysis (HD) patients not widely studied. MATERIALS AND METHODS: A retrospective study was conducted between 2003 and 2011. NOMI cases were recorded, and demographic, clinical, biochemical, and HD parameters were collected. This group was compared with a control group (n = 93). Risk factors, prognosis, and survival were analyzed. RESULTS: There were 57 episodes of NOMI (incidence, 2.29 episodes per 100 patients/y). Cecum was the most frequently affected segment. Nineteen patients (33%) underwent surgery. Twenty-six patients (59%) did not survive the acute episode. Cecal damage was the only protective factor associated with mortality (relative risk [RR], 0.712; P = 0.044). The incidence of NOMI was related to erythropoietin resistance index, diabetes mellitus, and longer time on HD compared with control group (RR, 6.92, P = 0.009; RR, 9.98, P = 0.005; and RR, 1.017, P < 0.001, respectively). Mortality in survival NOMI patients was higher at 4-y follow-up compared with that in the control group (log-rank, 15.5; P < 0.0001). CONCLUSIONS: NOMI is associated with erythropoietin resistance index, diabetes mellitus, and longer time on HD. Hypotension must be avoided in these high-risk patients to prevent NOMI.

Factors related to the absence of anemia in hemodialysis patients.

BACKGROUND: A small number of hemodialysis (HD) patients have normal hemoglobin (Hb) levels without the need for erythropoiesis-stimulating agents (ESAs). The factors associated with this condition have been little studied. The objective of this prospective study was to determine these factors in a prevalent population of HD patients. MATERIALS AND METHODS: All patients who had normal Hb levels and who had not received ESAs in the last 6 months (non-ESA group) were included. Epidemiological and laboratory data were collected and we performed an abdominal ultrasound to assess hepatic and renal cysts. This group was compared to a control group of 205 prevalent HD patients on ESA therapy (control group). RESULTS: We included 45 patients (16% from the whole group) in the non-ESA group. In this group, there was a higher proportion of men (76.5 vs. 61%), patients were younger (61.1 ± 14.7 vs. 67.5 ± 15.2 years), had a longer duration of renal replacement therapy (RRT) (9.4 ± 8.3 vs. 5.3 ± 5.8 years) and had a higher prevalence of adult polycystic kidney disease (APKD) and hepatitis C virus (HCV) liver disease (42.2 vs. 10.2%), p < 0.01. In the non-ESA group, HCV+ patients had a lower prevalence of APKD (2.2 vs. 38.4%) and hepatic cysts (2.2 vs. 19.2%), but significantly higher endogenous erythropoietin levels (55.8 ± 37.1 vs. 30.9 ± 38.4 mU/ml). No significant differences in anemia, iron metabolism, insulin, IGF-1 and renin were found between non-ESA and control groups. Non-ESA patients had a significantly higher number of renal (90.6 vs. 36.5%) and hepatic cysts (12.5 vs. 3.4%), and these were also larger in size (3.3 ± 2.4 vs. 1.5 ± 0.8 cm). In the multivariate Cox analysis, independent predictor factors for absence of anemia in HD patients were number of renal cysts >10 cysts (95% CI 1.058-1.405; p = 0.00), HCV+ liver disease (95% CI 1.147-1.511; p = 0.05) and time on RRT (95% CI 1.002-1.121; p = 0.05). CONCLUSIONS: The absence of anemia in HD patients is not infrequent. Its frequency is higher in men and younger patients with long-term RRT, in patients with HCV+ liver disease and in APKD. It is associated with increased endogenous erythropoietin production and the presence of renal and hepatic cysts.

Effects of atorvastatin on inflammatory and fibrinolytic parameters in patients with chronic kidney disease.

Although substantial evidence suggests that treatment of dyslipidemia with statins reduces mortality and morbidity that are associated with cardiovascular disease, only a few studies have examined the efficacy of statins on inflammatory and fibrinolytic status in patients with chronic kidney disease (CKD). A 6-mo, prospective, randomized study was designed to assess the efficacy of atorvastatin in reducing circulating inflammatory and fibrinolytic parameters in patients with CKD. Sixty-six patients with CKD (stages 2, 3, and 4) and LDL cholesterol levels > or =100 mg/dl were randomly assigned (2:1) to receive 20 mg/d atorvastatin (n = 44) or nonatorvastatin therapy (n = 22). Lipid profile, renal function, fibrinolytic balance (tissue plasminogen activator [t-PA] and plasminogen activator inhibitor-1), and inflammatory markers (C-reactive protein [CRP], IL-1 beta, IL-6, and TNF-alpha) were measured before and 6 mo after atorvastatin was added to the treatment. Twenty-five age-matched individuals with normal renal function (estimated GFR >90 ml/min) were used as healthy control subjects. Patients with CKD had higher CRP, IL-1 beta, TNF-alpha, and IL-6 levels than age-matched population with normal renal function. t-PA concentration was higher in patients with CKD (P = 0.000). Plasminogen activator inhibitor-1 values were comparable in all patients. Total cholesterol and LDL cholesterol were significantly reduced only in patients who received atorvastatin. In addition to the hypolipidemic effect, atorvastatin treatment significantly reduced inflammatory parameters: CRP (median 4.1 to 2.9; P = 0.015), TNF-alpha (6.0 +/- 2.7 to 4.7 +/- 2.4; P = 0.046), and IL-1 beta levels (1.9 +/- 0.7 to 1.2 +/- 0.7; P = 0.001). These parameters remained unchanged in patients who were not treated with atorvastatin. Fibrinolytic parameters were not modified by atorvastatin treatment. Patients with CKD showed higher levels of inflammatory parameters and t-PA levels than age-matched healthy control subjects. Atorvastatin treatment, in addition to its beneficial effect on cholesterol levels, improved the inflammatory state of these patients without modifying fibrinolytic balance.