Annalisa Teutonico

Removal of uraemic retention solutes in standard bicarbonate haemodialysis and long-hour slow-flow bicarbonate haemodialysis

BACKGROUND Several studies already stressed the importance of haemodialysis (HD) time in the removal of uraemic toxins. In those studies, however, also the amount of dialysate and/or processed blood was altered. The present study aimed to investigate the isolated effect of the factor time t (by processing the same total blood and dialysate volume in two different time schedules) on the removal and kinetic behaviour of some small, middle and protein-bound molecules. METHODS The present study had a crossover design: 11 stable anuric HD patients underwent two bicarbonate HD sessions (~ 4 and ~ 8 h) in a random sequence, at least 1 week apart. The GENIUS single-pass batch dialysis system and the high-flux FX80 dialysers (Fresenius Medical Care, Bad Homburg, Germany) were used. The volume of blood and dialysate processed, volume of ultrafiltration, and dialysate composition were prescribed to be the same. For each patient, blood was sampled from the arterial line at 0, 60, 120, 180 and 240 min (all sessions), and at 360 and 480 min (8-h sessions). Dialysate was sampled at the end of HD from the dialysate tank. The following solutes were investigated: (i) small molecules: urea, creatinine, phosphorus and uric acid; (ii) middle molecule: β(2)M; and (iii) protein-bound molecules: homocysteine, hippuric acid, indole-3-acetic acid and indoxyl sulphate. Total solute removals (solute concentration in the spent dialysate of each analyte × 90 L - the volume of dialysate) (TSR), clearances (TSR of a solute/area under the plasma water concentration time curve of the solute) (K), total cleared volumes (K × dialysis time) (TCV), and dialyser extraction ratios (K/blood flow rate) (ER) were determined. The percent differences of TSR, K, TCV and ER between 4- and 8-h dialyses were calculated. Single-pool Kt/Vurea, and post-dialysis percent rebounds of urea, creatinine and β(2)M were computed. RESULTS TSR, TCV and ER were statistically significantly larger during prolonged HD for all small and middle molecules (at least, P < 0.01). Specifically, the percent increases of TSR (8 h vs 4 h) were: for urea 22.6.0% (P < 0.003), for creatinine 24.8% (P < 0.002), for phosphorus 26.6% (P < 0.001), and for β(2)M 39.2% (P < 0.005). No statistically significant difference was observed for protein-bound solutes in any of the parameters being studied. Single-pool Kt/Vurea was 1.41 ± 0.19 for the 4-h dialysis sessions and 1.80 ± 0.29 for the 8-h ones. The difference was statistically significant (P < 0.0001). Post-dialysis percent rebounds of urea, creatinine and β(2)M were statistically significantly greater in the 4-h dialysis sessions (at least, P < 0.0002). CONCLUSIONS The present controlled study using a crossover design indicates that small and middle molecules are removed more adequately from the deeper compartments when performing a prolonged HD, even if blood and dialysate volumes are kept constant. Hence, factor time t is very important for these retention solutes. The kinetic behaviour of protein-bound solutes is completely different from that of small and middle molecules, mainly because of the strength of their protein binding.

Effect of Dialysate Calcium Concentrations on Parathyroid Hormone and Calcium Balance During a Single Dialysis Session Using Bicarbonate Hemodialysis: A Crossover Clinical Trial

BACKGROUND In bicarbonate-based hemodialysis, dialysate total calcium (tCa) concentration may have effects on mineral metabolism. STUDY DESIGN Randomized crossover trial of 3 dialysate tCa concentrations (2.5, 2.75, and 3.0 mEq/L). SETTING & PARTICIPANTS 22 stable anuric uremic patients underwent three 4-hour bicarbonate hemodialysis sessions with the 3 different dialysate tCa concentrations using a single-pass batch dialysis system. OUTCOMES Hourly measurements of plasma water ionized calcium (iCa) and plasma parathyroid hormone (PTH) concentrations. tCa mass balances were measured from the dialysate side. RESULTS Hourly plasma water iCa concentrations were higher with a dialysate tCa concentration of 3.0 compared with 2.75 and 2.5 mEq/L (P < 0.05), as were iCa concentrations at the end of dialysis sessions (2.66 ± 0.1, 2.56 ± 0.12, and 2.4 ± 0.08 mEq/L, respectively; P < 0.001). Mean tCa mass balance values (diffusion gradient from the dialysate to the patient) were positive with all dialysate tCa concentrations and increased progressively with dialysate tCa concentration (75 ± 122, 182 ± 125, and 293 ± 228 mg, respectively; P < 0.001). Plasma PTH levels increased during dialysis using dialysate tCa concentration of 2.5 mEq/L (mean increase, 225 ± 312 pg/mL) and decreased with dialysate tCa concentrations of 2.75 and 3.0 mEq/L (mean decreases, 68 ± 325 and 99 ± 432 pg/mL, respectively). LIMITATIONS Small sample size and lack of measurement of total-body calcium mass balances. CONCLUSIONS A dialysate tCa concentration of 2.75 mEq/L might be preferable to 2.5 or 3.0 mEq/L because it is associated with mildly positive tCa mass balance values, plasma water iCa levels in the reference range, and stable PTH levels during dialysis.

Comparison of alternative methods for scaling dialysis dose

BACKGROUND Kt/Vurea was established as an index of haemodialysis (HD) adequacy. The use of Vurea as a normalizing factor has been questioned, and alternative parameters such as body weight(0.67) (W(0.67)), body surface area (BSA), resting energy expenditure (REE), high metabolic rate organ (HMRO) mass, liver size (LV) and more recently, bioelectrical resistance (R), an independent and directly measurable biological parameter, were proposed as alternative methods for scaling dialysis dose. METHODS The present study aimed to prospectively evaluate the predictive power of some demographic, anthropometric, bioelectrical (BIA) and biochemical parameters, of seven scaling parameters, namely Vurea, as derived from the Watson et al. formulae, W(0.67), BSA, REE, HMRO, LV and R and of eight HD adequacy indices [single-pool variable-volume Kt/Vurea, computed using the Daugirdas equation, its rescaled equivalents (Kt/W(0.67), Kt/BSA, Kt/REE, Kt/HMRO, Kt/LV and Kt/R) and Kt] on long-term survival of a cohort of 328 incident white HD patients. All individuals underwent periodical (every 3 months) biochemical evaluations and single-frequency BIA measurements, injecting 800 microA at 50 kHz alternating sinusoidal current with a standard tetrapolar technique. RESULTS A first Cox regression analysis, testing the predictive power of some demographic, anthropometric, BIA and biochemical parameters, and of the eight HD adequacy indices on long-term survival of the patients, showed that only higher serum creatinine (Scr) levels (P < 0.0001) and lower Kt/R values (P < 0.04) were significant outcome predictors. As Kt was shown not to be an outcome predictor, a second Cox regression analysis, testing the predictive power of the same demographic, anthropometric, BIA and biochemical parameters, and of the seven scaling parameters on long-term survival of the patients, was built. It showed that only higher Scr levels (P < 0.0001) and higher R values (P < 0.04) were significant outcome predictors. Kaplan-Meier survival analyses of the patients stratified into two groups, respectively, according to the first quartile of R values (0.0-467.8 Ohm), the fourth quartile of Kt/R values (98-106 ml/Ohm) and the first quartile of Scr levels (0.0-11.6 mg/dl) showed a significantly higher long-term survival in the groups of patients having R values above the first quartile (P < 0.04), Kt/R values below the fourth quartile (P < 0.03) and Scr levels above the first quartile (P < 0.0001). CONCLUSIONS Kt/R, R and Scr were independent significant predictors of long-term-survival in incident HD patients: R is related to the fluid status, whereas Scr, which reflects the lean body mass, seems to suggest that body composition is more important than body weight and/or body mass index. Further work is required to develop these concepts and to translate them into rigorous outcome-based adequacy targets suitable for clinical usage.

Haemodynamic stability in standard bicarbonate haemodialysis and long-hour slow-flow bicarbonate haemodialysis

BACKGROUND The interplay of correct solute mass balances, such as that of sodium (Na+) and potassium (K+) (respectively, Na+MB and K+MB) with adequate ultrafiltration volumes (V(UF)), is crucial in order to achieve haemodynamic stability during haemodialysis (HD). The GENIUS single-pass batch dialysis system (Fresenius Medical Care, Germany) consists of a closed dialysate tank of 90 L; it offers the unique opportunity of effecting mass balances of any solute in a very precise way. METHODS The present study has a crossover design: 11 stable anuric HD patients underwent two bicarbonate HD sessions, one of 4 h and the other of 8 h in a random sequence, always at the same interdialytic interval, at least 1 week apart. The GENIUS system and high-flux FX80 dialysers (Fresenius Medical Care, Germany) were used. The volume of blood and dialysate processed, V(UF) and dialysate Na+ and K+ concentrations were prescribed to be the same. Plasma water Na+ and K+ trends during dialysis as well as Na+MBs and K+MBs were determined. At the same time, systolic blood pressure (SBP) and diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate trends during dialysis were analysed. Plasma volume (PV) changes were computed from plasma total protein concentrations and their trends analysed. RESULTS Plasma water Na+ and K+ levels were not significantly different when comparing the start and the end of the sessions of the two treatments. Both the increase of plasma water Na+ levels and the decrease of plasma water K+ levels in the first 4 h were significantly slower during the 8-h sessions when compared with the 4-h ones (P < 0.048 and P < 0.006, respectively). Dialysis sessions were uneventful. SBP decreased significantly during the 4-h sessions, whereas it remained stable during the 8-h ones (P < 0.0001 and P = NS, respectively). Statistically significantly lower intradialysis decreases of SBP (-4.5 ± 16.2 vs -20.0 ± 15.0 mmHg, P < 0.02) and MAP (-1.4 ± 11.7 vs -8.6 ± 11.0 mmHg, P < 0.04) were achieved in the 8-h sessions with respect to the 4-h sessions, in spite of no significant difference for mean V(UF) (2.9 ± 0.9 vs 2.9 ± 0.8 L; P = NS) and mean Na+MBs (-298.1 ± 142.2 vs -286.2 ± 150.7 mmol; P = NS). The decrease of PV levels in the first 4 h was significantly slower during the 8-h sessions when compared with the 4-h ones (P < 0.0001). PV decrease was significantly higher at the end of the 4-h HD sessions than at the end of the 8-h HD sessions (P < 0.043). CONCLUSIONS The present highly controlled experiments using a crossover design and precise Na+MB and K+MB controls showed that better haemodynamic stability was achieved in the 8-h sessions with respect to the 4-h sessions, in spite of no difference for mean V(UF) and Na+MBs. Thus, other pathophysiological mechanisms, namely, a better PV preservation, must be advocated in order to explain the better haemodynamic stability peculiar to long-hour slow-flow nocturnal HD treatments.

Is there a link between the late occurrence of a brachial artery aneurysm and the ligation of an arteriovenous fistula

Arteriomegaly and aneurysms proximal to long‐standing posttraumatic arteriovenous fistulas (AVF) have been described. Much fewer are the reports of the late occurrence of brachial artery aneurysms following the closure of a hemodialysis AVF. Here, we report the case of a 55‐year‐old male patient. He had received a cadaver donor kidney transplant in 1996; his distal radiocephalic (RC) wrist AVF in the left arm had been ligated in 2001; he developed an aneurysm of the left brachial artery 9 years after the ligation of the AVF (2009). He underwent the surgical intervention of aneurysmectomy at the level of the left brachial artery with construction of a bypass with autologous saphenous vein. In conclusion, the development of a RC wrist AVF is an intrinsically dynamic process characterized by the increase in both blood flow rate and internal diameter of the brachial artery; the latter might be associated with enhanced fracture of the elastic fibers with the consequent risk of the development of an aneurysm. Thus, arteriomegaly and aneurysm of the brachial artery proximal to long‐standing AVFs might be seen as a “continuum” of these morphologic modifications.

Ranking of factors determining potassium mass balance in bicarbonate haemodialysis

BACKGROUND One of the most important pathogenetic factors involved in the onset of intradialysis arrhytmias is the alteration in electrolyte concentration, particularly potassium (K(+)). METHODS Two studies were performed: Study A was designed to investigate above all the isolated effect of the factor time t on intradialysis K(+) mass balance (K(+)MB): 11 stable prevalent Caucasian anuric patients underwent one standard (∼4 h) and one long-hour (∼8 h) bicarbonate haemodialysis (HD) session. The latter were pair-matched as far as the dialysate and blood volume processed (90 L) and volume of ultrafiltration are concerned. Study B was designed to identify and rank the other factors determining intradialysis K(+)MB: 63 stable prevalent Caucasian anuric patients underwent one 4-h standard bicarbonate HD session. Dialysate K(+) concentration was 2.0 mmol/L in both studies. Blood samples were obtained from the inlet blood tubing immediately before the onset of dialysis and at t60, t120, t180 min and at end of the 4- and 8-h sessions for the measurement of plasma K(+), blood bicarbonates and blood pH. Additional blood samples were obtained at t360 min for the 8 h sessions. Direct dialysate quantification was utilized for K(+)MBs. Direct potentiometry with an ion-selective electrode was used for K(+) measurements. RESULTS Study A: mean K(+)MBs were significantly higher in the 8-h sessions (4 h: -88.4 ± 23.2 SD mmol versus 8 h: -101.9 ± 32.2 mmol; P = 0.02). Bivariate linear regression analyses showed that only mean plasma K(+), area under the curve (AUC) of the hourly inlet dialyser diffusion concentration gradient of K(+) (hcgAUCK(+)) and AUC of blood bicarbonates and mean blood bicarbonates were significantly related to K(+)MB in both 4- and 8-h sessions. A multiple linear regression output with K(+)MB as dependent variable showed that only mean plasma K(+), hcgAUCK(+) and duration of HD sessions per se remained statistically significant. Study B: mean K(+)MBs were -86.7 ± 22.6 mmol. Bivariate linear regression analyses showed that only mean plasma K(+), hcgAUCK(+) and mean blood bicarbonates were significantly related to K(+)MB. Again, only mean plasma K(+) and hcgAUCK(+) predicted K(+)MB at the multiple linear regression analysis. CONCLUSIONS Our studies enabled to establish the ranking of factors determining intradialysis K(+)MB: plasma K(+) → dialysate K(+) gradient is the main determinant; acid-base balance plays a much less important role. The duration of HD session per se is an independent determinant of K(+)MB.

A study on glucose metabolism in a small cohort of children and adolescents with kidney transplant

Post-transplant diabetes mellitus (PTDM) and impaired glucose tolerance are now considered among the major adverse events following organ transplantation. The present study was aimed at investigating the regulation of glucose metabolism in pediatric recipients of a kidney transplant (KT), receiving tacrolimus or cyclosporine A-based immunosuppression. Twelve subjects, eight males and four females, aged 12.1±3.8 yr, and with a mean time from KT of 45.6 months were enrolled in the study. All patients had a basal evaluation of fasting glucose (GF), fasting insulin (IF), C-peptide and glycated hemoglobin (HbA1c) levels. They then underwent oral glucose tolerance test (OGTT), with measurement of blood glucose and insulin concentration. Two children had impaired GF, associated with supernormal HbA1c levels, one patient showed impaired glucose tolerance, none had PTDM. Peripheral insulin resistance, as measured by quantitative insulin sensitivity check index (QUICKI) and homeostasis model assessment estimate of insulin sensitivity (HOMA-IR) index, was enhanced in 3 patients. Subsequently, GF significantly increased with time from transplant (p=0.01), while fasting C-peptide and the area under the curve of insulin correlated with creatinine clearance. In conclusion, our results, although generated in a small sample size, would suggest that long-term follow-up of children receiving a KT should extend to explore the response to oral glucose load and at least the basal measure of insulin response.

Effects of different dialysate calcium concentrations on intradialysis hemodynamic stability

BACKGROUND The interplay of correct solute mass balances, such as those of sodium (Na+), potassium (K+) and total calcium (tCa) (Na+MB, K+MB and tCaMB, respectively) with adequate ultrafiltration volumes (VUF) is crucial to achieving hemodynamic stability during hemodialysis (HD). METHODS Twenty-two stable anuric uremic patients underwent three 4-hour bicarbonate HD sessions, each with a different dialysate tCa concentration (1.25, 1.375 and 1.50 mmol/L). The GENIUS dialysis system (Fresenius Medical Care, Germany) was used. Volumes of blood and dialysate processed, VUF and dialysate Na+ and K+ concentrations were prescribed to be the same. Hourly measurements of plasma water ionized Ca (Ca++), Na+ and K+ were made, and their trends analyzed. tCaMBs, Na+MBs and K+MBs were determined. Systolic (SBP), diastolic (DBP) blood pressure, mean arterial pressure (MAP) and heart rate (HR) trends during dialysis were analyzed. RESULTS Mean hourly plasma water Ca++ concentrations were statistically significantly higher with a dialysate tCa concentration of 1.50 mmol/L. Mean tCaMBs were positive (diffusion gradient from the dialysate to the patient), increasing with increasing dialysate tCa concentrations (+75 ± 122 mg, +182 ± 125 mg, +293 ± 228 mg, respectively). Their difference was statistically significant (p<0.0005). Mean Na+MBs and K+MBs were not statistically significantly different. SBP, DBP, MAP and HR were not statistically significantly different among the 3 treatments. CONCLUSIONS These highly controlled experiments showed that hemodynamic stability does not appear to be statistically significantly influenced by any specific dialysate tCa concentration in this peculiar subset of patients.

The systemic capillary leak syndrome: a scarcely known nephrological entity.

The idiopathic systemic capillary leak syndrome (SCLS) is a rare life-threatening disorder characterized by periodic episodes of hypovolemic shock, due to plasma leakage from the intravascular to the interstitial space, as reflected by accompanying hypoalbuminemia, hemoconcentration and edema. Here we report the case of a 65-year-old woman affected by SCLS who required aggressive resuscitation with norepinephrine, steroids, albumin and crystalloids. Then, a long-term prophylaxis with a ß(2)-adrenergic receptor agonist and theophylline was started. In conclusion, though SCLS is a rare entity, the associated morbidity and mortality require the physicians awareness to provide timely therapy. Underrecognition in the medical community and rarity of this syndrome have precluded analysis by rational clinical trial designs that are necessary to determine more targeted and adequate therapy. This report is meant to enhance awareness of SCLS in the nephrology community.

Is the removal of a central venous catheter always necessary in the context of catheter-related right atrial thrombosis?:

Catheter-related right atrial thrombosis is a severe and life-threatening complication of central venous catheters in both adult and young patients. Catheter-related right atrial thrombosis can occur with any type of central venous catheters, utilized either for hemodialysis or infusion. Up to 30% of patients with central venous catheter are estimated to be affected by catheter-related right atrial thrombosis; however, neither precise epidemiological data nor guidelines regarding medical or surgical treatment are available. This complication seems to be closely associated with positioning of the catheter tip in the atrium, whereas it is unlikely with a tip located within superior vena cava. Herein, we report the case of a patient affected by catheter-related right atrial thrombosis, who showed a quick resolution of thrombosis with a new therapeutic scheme combining loco-regional thrombolytic therapy (urokinase as a locking solution) and systemic anticoagulation therapy (vitamin K antagonists), thus avoiding catheter removal. Neither complications of the combination therapy were reported, nor recurrence of catheter-related right atrial thrombosis occurred. In conclusion, the combination therapy here described was safe, quick and effective, achieving the goal of not removing the catheter.