Néstor Fontseré

Bioimpedance-Guided Fluid Management in Hemodialysis Patients

BACKGROUND AND OBJECTIVES Achieving and maintaining optimal fluid status remains a major challenge in hemodialysis therapy. The aim of this interventional study was to assess the feasibility and clinical consequences of active fluid management guided by bioimpedance spectroscopy in chronic hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Fluid status was optimized prospectively in 55 chronic hemodialysis patients over 3 months (November 2011 to February 2012). Predialysis fluid overload was measured weekly using the Fresenius Body Composition Monitor. Time-averaged fluid overload was calculated as the average between pre- and postdialysis fluid overload. The study aimed to bring the time-averaged fluid overload of all patients into a target range of 0.5 ± 0.75 L within the first month and maintain optimal fluid status until study end. Postweight was adjusted weekly according to a predefined protocol. RESULTS Time-averaged fluid overload in the complete study cohort was 0.9 ± 1.6 L at baseline and 0.6 ± 1.1 L at study end. Time-averaged fluid overload decreased by -1.20 ± 1.32 L (P<0.01) in the fluid-overloaded group (n=17), remained unchanged in the normovolemic group (n=26, P=0.59), and increased by 0.59 ± 0.76 L (P=0.02) in the dehydrated group (n=12). Every 1 L change in fluid overload was accompanied by a 9.9 mmHg/L change in predialysis systolic BP (r=0.55, P<0.001). At study end, 76% of all patients were either on time-averaged fluid overload target or at least closer to target than at study start. The number of intradialytic symptoms did not change significantly in any of the subgroups. CONCLUSIONS Active fluid management guided by bioimpedance spectroscopy was associated with an improvement in overall fluid status and BP.

Adiponectin and risk of new-onset diabetes mellitus after kidney transplantation.

Background. New-onset diabetes mellitus after transplantation (NODAT) is a severe complication of kidney transplantation (KTx) with negative effects upon patient and graft survival. Several risk factors for NODAT have been described; however, the search for an early predictive marker is ongoing. It has recently been demonstrated that high concentrations of adiponectin (APN), which is an adipocyte-derived peptide with antiinflammatory and insulin-sensitizing properties, protect against future development of type 2 diabetes in healthy individuals. The purpose of this report was to study pretransplant insulin resistance and analyze pretransplant serum leptin and APN levels as independent risk factors for the development of NODAT. Methods. A total of 68 KTx patients were studied [mean age, 48±11 years; 70% males; body mass index (BMI), 25±3 kg/m2]; 31 KTx patients with NODAT and 37 KTx patients without NODAT (non-NODAT) with similar age, sex, BMI, immunosuppression, and posttransplant time were studied. All patients received prednisone and calcineurin inhibitors (75% tacrolimus and 25% cyclosporine A), and 76% of patients received mycophenolate mofetil. Family history of diabetes mellitus was recorded. Pretransplant homeostasis model assessment for insulin resistance (HOMA-IR) index was calculated from fasting plasma glucose and insulin. Pretransplant serum leptin and APN levels were determined by radioimmunoassay. Results. NODAT patients showed higher pretransplant plasma insulin concentrations [NODAT, 13.4 (11–22.7) &mgr;IU/mL; non-NODAT, 10.05 (7.45–18.4) &mgr;IU/mL; P=0.049], HOMA-IR index [NODAT, 4.18 (2.49–5.75); non-NODAT, 2.63 (1.52–4.68); P=0.043], and lower pretransplant serum APN concentration [NODAT, 8.78 (7.2–11.38) &mgr;g/mL; non-NODAT, 11.4 (8.56–15.27) &mgr;g/mL, P=0.012]. Inverse correlations between APN and BMI (r=−0.33; P=0.014) and APN and HOMA-IR index (r=−0.39; P=0.002) and between APN and NODAT (r=−0.31; P=0.011) were observed. Multiple logistic regression analysis showed the patients with lower pretransplant APN concentrations to be those at greater risk of developing NODAT [Odds Ratio=0.832 (0.71–0.96); P=0.01]. Conclusion. Pretransplant serum APN concentration is an independent predictive factor for NODAT development in kidney-transplanted patients.

Elimination of large uremic toxins by a dialyzer specifically designed for high-volume convective therapies.

Background: Unlike conventional hemodialysis treatments, which rely almost solely on diffusion-related mechanisms for solute removal, hemodiafiltration (HDF) allows more efficient removal of higher molecular weight toxins due to convective transport mechanisms. To facilitate the removal of these toxins in HDF treatment modalities, dialyzers with highly efficient high-flux membranes are necessary. This study assessed the large uremic toxin removal ability of a high-flux dialyzer (FX CorDiax 60) specifically designed to facilitate convective therapies compared with a standard high-flux dialyzer (FX 60). Methods: In an open, randomized, cross-over, single-center, controlled, prospective clinical study, 30 adult chronic hemodialysis patients were treated by post-dilution online HDF with the FX 60 or the FX CorDiax 60 dialyzer. All other dialysis parameters were kept constant in both study arms. The reduction rate (RR) of blood urea nitrogen, phosphate, β2-microglobulin (β2-m), myoglobin, prolactin, α1-microglobulin, α1-acid glycoprotein, albumin and total protein as well as the elimination into dialysate was intraindividually compared for the two dialyzer types. Results: For FX CorDiax 60 versus FX 60, the RR was significantly higher for blood urea nitrogen (86.23 ± 4.14 vs. 84.89 ± 4.59%, p = 0.015), β2-m (84.67 ± 3.79 vs. 81.30 ± 4.82%, p < 0.0001), myoglobin (75.23 ± 10.48 vs. 58.60 ± 12.1%, p < 0.0001), prolactin (72.96 ± 9.68 vs. 56.91 ± 13.01%, p < 0.0001) and α1-microglobulin (20.89 ± 18.27 vs. 13.60 ± 12.50%, p = 0.016). There were no significant differences in the RR for phosphate, α1-acid glycoprotein, albumin and total protein. Mass removal was significantly higher with the FX CorDiax 60 than with the FX 60 for β2-m (0.26 ± 0.09 vs. 0.24 ± 0.09 g, p = 0.0006), myoglobin (1.83 ± 0.89 vs. 1.51 ± 0.76 mg, p = 0.0017), prolactin (0.17 ± 0.13 vs. 0.14 ± 0.08 mg, p = 0.02) and albumin (4.25 ± 3.49 vs. 3.01 ± 2.37 g, p = 0.03). Conclusions: This study demonstrates that treating patients with an FX CorDiax 60 instead of an FX 60 dialyzer in post-dilution HDF mode significantly increases the elimination of middle molecules.

Nocturnal, every-other-day, online haemodiafiltration: an effective therapeutic alternative

BACKGROUND Longer and more frequent dialysis sessions have demonstrated excellent survival and clinical advantages, while online haemodiafiltration (OL-HDF) provides the most efficient form of dialysis treatment. The aim of this study was to evaluate the beneficial effects of a longer (nocturnal) and more frequent (every-other-day) dialysis schedule with OL-HDF at the same or the highest convective volume. METHODS This prospective, in-centre crossover study was carried out in 26 patients, 18 males and 8 females, 49.2±14 years old, on 4-5 h thrice-weekly post-dilution OL-HDF, switched to nocturnal every-other-day OL-HDF. Patient inclusion criteria consisted of stable patients with good vascular access and with good prospects for improved occupational, psychological and social rehabilitation. Patients were randomly assigned into two groups: Group A received the same convective volume as previously for 6 months followed by a higher convective volume for a further 6 months, while Group B received the same schedule in reverse order. RESULTS Nocturnal every-other-day OL-HDF was well tolerated and 56% of patients who were working during the baseline period continued to work throughout the study with practically no absenteeism. The convective volume was 26.7±2 L at baseline, 27.5±2 with the unchanged volume and 42.9±4 L with the higher volume. eKt/V increased from 1.75±0.4 to 3.37±0.9. Bicarbonate, blood urea nitrogen (BUN) and creatinine values decreased, while phosphate levels fell markedly with a 90% reduction in phosphate binders. Blood pressure and left ventricular hypertrophy (LVH) improved and the use of anti-hypertensive drugs decreased. In both groups, BUN, creatinine and β2-microglobulin reduction ratios improved. Different removal patterns were observed for myoglobin, prolactin and α1-acid glycoprotein. CONCLUSIONS Nocturnal every-other-day OL-HDF could be an excellent therapeutic alternative since good tolerance and occupational rehabilitation, marked improvement in dialysis dose, nutritional status, LVH, phosphate and hypertension control and a substantial reduction in drug requirements were observed. In this crossover study, different removal patterns of large solutes were identified.

A Comparison of Prediction Equations for Estimating Glomerular Filtration Rate in Adult Patients with Chronic Kidney Disease Stages 4–5

Background: The accuracy of prediction equations has not been validated in adult patients with chronic kidney disease (CKD) stages 4–5 in extreme situations of nutritional status and age. Objective and Methods: The significance of nutritional status, calculated with the creatinine production (CP) formula, and age (≤64 years and >64 years) in the application of different prediction equations – modification of diet in renal disease (MDRD), simplified MDRD (sMDRD), Cockcroft-Gault (CG) – and the mean of urea and creatinine clearance (Cr-Ur) compared with the isotopic glomerular filtration rate (GFR) estimation calculated by 51Cr-EDTA was studied in 87 Caucasian adults with CKD stages 4–5 (GFR: 30–8 ml/min/1.73 m2). The Bland-Altman method and Lin’s concordance coefficient (Rc) were used to study accuracy (bias) and precision. Results: The GFR calculated with 51Cr-EDTA in the study group was 22.2 ± 6.9 ml/min/1.73 m2 (range: 8–30). CG and sMDRD were the best prediction equations with bias of –1.1 and –3.8 ml/min/1.73 m2 and Rc of 0.52–0.50. In this situation, the mean Cr-Ur proved the most inaccurate equation compared with the isotopic technique with bias of –5.4 ml/min/1.73 m2 and Rc of 0.32. In the analysis of patients with higher CP (> 0.90; n = 44), CG and sMDRD obtained the best bias of 1.2 and –2.7 ml/min/1.73 m2 and Rc of 0.54–0.53. In patients aged ≤64 (n = 44), these equations obtained a bias of 1.1 and –3.6 ml/min/1.73 m2 and Rc 0.50–0.49. Both in lower CP (≤0.90; n = 43) and older age (>64 years; n = 43), all the equations underestimated the value obtained with isotopic GFR. In these situations, the results obtained with CG had a bias of –2.2 and –3.6 ml/min/1.73 m2 (Rc 0.29–0.56) and with sMDRD –4.0 and –4.1 ml/min/1.73 m2 (Rc 0.39–0.51). In these circumstances, Cr-Ur was the most inaccurate equation, obtaining a bias of –10.1 and –13.2 ml/min/1.73 m2 (Rc 0.14–0.16). Conclusions: In the group with higher CP and age ≤64 years, results of the presented data yielded no evidence for superiority of the MDRD equation over CG formula in patients with advanced renal failure. On the basis of our results, we do not recommend the use of the Cr-Ur adjusted to 1.73 m2 of body surface area, which was the most imprecise equation. Application of all the equations proved inaccurate in lower CP patients with or without advanced age, implying the premature start of substitution renal treatment. In these circumstances, ambulatory GFR determination by isotopic techniques would be indicated.

Influence of the ionic dialysance monitor on Kt measurement in hemodialysis.

BACKGROUND Ionic dialysance can provide accurate monitoring of dialysis dose during each hemodialysis session. Increasingly, hemodialysis machines incorporate devices that measure ionic dialysance, allowing the dialysis dose to be determined noninvasively in real time and in each session. Because Kt product was proposed as a measure of hemodialysis dose to avoid the reverse J-shaped curve between urea reduction ratio or Kt/V and mortality, we investigated whether ionic dialysance values and Kt measurements are affected by different ionic dialysance monitors (Diascan and online clearance monitoring [OCM]) and dialysis machines. STUDY DESIGN Four-period crossover. SETTING & PARTICIPANTS 31 adult long-term hemodialysis patients using 2 different ionic dialysance monitors in 4 dialysis machines: Diascan in Hospal Integra and Gambro AK-200 machines and OCM in Fresenius 4008S and 5008 machines. PREDICTORS Ionic dialysance monitor and machine used in 4 hemodialysis sessions for each participant. OUTCOMES Kt and Kt/V measured by using ionic dialysance and serum urea nitrogen. RESULTS Mean values for initial and final ionic dialysance were similar for Integra and AK-200 machines, both measured by using Diascan, and for the 4008S and 5008 machines, both measured by using OCM; however, OCM values tended to be greater in the 4008S and 5008 machines. Kt measured in the 4008S and 5008 machines was greater (59.6 +/- 12 and 58.6 +/- 11 L, respectively) than with the Integra and AK-200 machines (53.4 +/- 11 and 53.8 +/- 11 L). Mean urea reduction ratio and Kt/V were 78.0% +/- 8% and 1.89 +/- 0.43 for Diascan monitors and 79.6% +/- 8% and 1.99 +/- 0.44 for OCM monitors, respectively (P < 0.01). Differences between monitors in Kt determination were caused in part by a real difference in dialysis effectiveness (6%) and in part by an intermethod difference (4%). Kt adjusted by Kt/V differences was recalculated, and because of good correlation between Diascan and OCM, we were able to apply a formula (Kt(OCM) = 1.08 Kt(Diascan) - 2; r =0.95) that allowed both Kt quantification methods to be compared. LIMITATIONS Nonblinded nonrandomized small sample. CONCLUSIONS Kt is a valid method for judging dialysis dose in real time by using ionic dialysance measurements. Adjustments to correct intermethod differences may be necessary to ensure generalizability among ionic dialysance monitors.

Mid-Dilution Hemodiafiltration: A Comparison with Pre- and Postdilution Modes Using the Same Polyphenylene Membrane

As a change from Diapes to polyphenylene membrane in the mid-dilution filter has recently been developed, the aim of this study was to compare mid-dilution using this new dialyzer versus pre- and postdilution. The prospective study included 20 patients who underwent 4 hemodiafiltration (HDF) sessions: 1.7 m2 polyphenylene and predilution infusion flow (Qi) 200 ml/min, 1.7 m2 and postdilution Qi 100 ml/min, 1.9 and 2.2 m2 mid-dilution both with Qi 200 ml/ min. The urea and creatinine reduction ratios were slightly higher in postdilution. The β2-microglobulin (85.8%), myoglobin (73.6%), prolactin (67.8%) and retinol-binding protein (29.2%) reduction ratios with 1.9 m2 mid-dilution, which was similar to 2.2 m2 mid-dilution, were significantly higher than with the post- and predilution modes. Mid-dilution appears to be a good HDF alternative that allows a better removal of larger molecules than postdilution and, mainly, predilution. Mid-dilution using 1.9 or 2.2 m2 dialyzers, at the same convective volume, showed a similar removal.

Aneurysmal Degeneration of the Inflow Artery after Arteriovenous Access for Hemodialysis

OBJECTIVES After arteriovenous fistula creation, the arterial flow increase can lead to aneurysmal degeneration, even increased after fistula ligation or renal transplant immunosuppression. The aim of this study is to describe the therapeutic options and outcomes of true aneurysms of the inflow artery after arteriovenous fistula for hemodialysis. METHODS Prospectively collected data of patients with true aneurysmal degeneration of the inflow artery after fistula creation (excluding pseudoaneuryms, anastomotic or infected aneurysms, or surgical complications), surgically repaired between January 2010 and February 2014 (cohort study) have been included. Patient demographics and access characteristics, symptoms, treatment, and follow-up have been reviewed. RESULTS 12 patients (75% men, median age 63 years) were treated for aneurysmal degeneration of the axillary (1), brachial (6), or radial (5) artery. They had had a previous distal arteriovenous fistula (7 radiocephalic, 3 brachiocephalic, 2 brachiobasilic) created 15.6 years before (range 9.9-28.5) and the majority of them were currently ligated or thrombosed. Most patients were symptomatic (pain [6], distal embolization [1]). They were treated by means of a bypass (using the cephalic [3], basilic [4], or saphenous vein [2]), direct ligature (2), or excision with end-to-end reconstruction (1). No major complications or ischemic symptoms occurred before discharge. After a median follow-up of 8.6 months (3.1-36.5), one patient needed re-operation for new proximal brachial aneurysmal degeneration, and another presented with an asymptomatic post-traumatic thrombosis of the proximal axillary artery and brachial bypass. No other complications, bypass dilatation or ischemic symptoms occurred during follow-up. CONCLUSIONS Inflow artery aneurysmal degeneration can occur after long-term arteriovenous access. Surgical treatment by autogenous bypass exclusion in most cases (or ligation or end-to-end reconstructions in selected cases) is a safe and effective option.

Is the New Mayo Clinic Quadratic Equation Useful for the Estimation of Glomerular Filtration Rate in Type 2 Diabetic Patients

OBJECTIVE—To test the Mayo Clinic Quadratic (MCQ) equation against isotopic glomerular filtration rate, compared with the Modification of Diet in Renal Disease (MDRD) and the Cockcroft-Gault formulas, in type 2 diabetes. RESEARCH DESIGN AND METHODS—Based on values obtained with iothalamate, 118 type 2 diabetic patients were divided into three groups according to renal function: hyperfiltration (26), normal function (56), or chronic kidney disease (CKD) stages 3–4 (36). ANOVA, the Bland-Altman procedure, and Lins coefficient (Rc) were performed to study accuracy. RESULTS—In the hyperfiltration and normal function groups, all prediction equations significantly underestimated the value obtained with isotopic glomerular filtration rate (P < 0.05). In the CKD group, all equations also presented significant differences with the isotopic method. However, MDRD had a bias of −5.3 (Rc 0.452), Cockcroft-Gault formula −0.2 (Rc 0.471), and the MCQ −4.5 (Rc 0.526). CONCLUSIONS—The MCQ and prediction equations proved inaccurate (excessive underestimation) in type 2 diabetic patients with hyperfiltration or normal renal function. With regard to CKD, the results obtained provided no evidence of superiority of the MCQ over the MDRD or the Cockcroft-Gault formula.

Valoración de la superficie del dializador en la hemodiafiltración on-line. Elección objetiva de la superficie del dializador

INTRODUCTION Online hemodiafiltration (OL-HDF) is currently the most effective technique. Several randomized studies and meta-analyses have observed a reduction in mortality as well as a direct association with convective volume. Currently, it has not been well established whether a larger dialyzer surface area could provide better results in terms of convective and depurative effectiveness. The aim of this study was to assess the effect of larger dialyzer surface areas on convective volume and filtration capacity. MATERIAL AND METHODS A total of 37 patients were studied, including 31 men and 6 women, who were in the OL-HDF program using a 5008 Cordiax monitor with auto-substitution. Each patient was analyzed in 3 sessions in which only the dialyzer surface area varied (1.0, 1.4 or 1.8 m(2)). The concentrations of urea (60 Da), creatinine (113 Da), β2-microglobulin (11800 Da), myoglobin (17200 Da) and α1-microglobulin (33000 Da) were determined in serum at the beginning and end of each session in order to calculate the percent reduction of these solutes. RESULTS The convective volume reached was 29.8 ± 3.0 with 1.0 m(2), 32.7 ± 3.1 (an increase of 6%) with 1.4 m(2), and 34.7 ± 3.3 L (an increase of 16%) with 1.8 m(2) (p<.001). The increased surface of the dialyzer showed an increase in the dialysis dose as well as urea and creatinine filtration. The percentage of β2m reduction increased from 80.0 ± 5.6 with 1.0 m(2) to 83.2 ± 4.2 with 1.4 m(2) and to 84.3 ± 4.0% with 1.8 m(2). As for myoglobin and a1-microglobulin, significant differences were observed between smaller surface area (1.0 m(2)) 65.6 ± 11 and 20.1 ± 9.3 and the other two surface areas, which were 70.0 ± 8.1 and 24.1 ± 7.1 (1.4 m(2)) and 72.3 ± 8.7 and 28.6 ± 12 (1.8 m(2)). CONCLUSION The 40% and 80% increases in surface area led to increased convective volumes of 6 and 16% respectively, while showing minimal differences in both the convective volume as well as the filtration capacity when the CUF was higher than 45 ml/h/mmHg. It is recommended to optimize the performance of dialyzers with the minimal surface area possible when adjusting the treatment prescription.