The risks associated with percutaneous native kidney biopsies: a prospective study.

BACKGROUND: The known risks and benefits of native kidney biopsies are mainly based on the findings of retrospective studies. The aim of this multicentre prospective study was to evaluate the safety of percutaneous renal biopsies and quantify biopsy-related complication rates in Italy. METHODS: The study examined the results of native kidney biopsies performed in 54 Italian nephrology centres between 2012 and 2020. The primary outcome was the rate of major complications 1 day after the procedure, or for longer if it was necessary to evaluate the evolution of a complication. Centre and patient risk predictors were analysed using multivariate logistic regression. RESULTS: Analysis of 5304 biopsies of patients with a median age of 53.2 years revealed 400 major complication events in 273 patients (5.1%): the most frequent was a ≥2 g/dL decrease in haemoglobin levels (2.2%), followed by macrohaematuria (1.2%), blood transfusion (1.1%), gross haematoma (0.9%), artero-venous fistula (0.7%), invasive intervention (0.5%), pain (0.5%), symptomatic hypotension (0.3%), a rapid increase in serum creatinine levels (0.1%) and death (0.02%). The risk factors for major complications were higher plasma creatinine levels [odds ratio (OR) 1.12 for each mg/dL increase, 95% confidence interval (95% CI) 1.08-1.17], liver disease (OR 2.27, 95% CI 1.21-4.25) and a higher number of needle passes (OR for each pass 1.22, 95% CI 1.07-1.39), whereas higher proteinuria levels (OR for each g/day increase 0.95, 95% CI 0.92-0.99) were protective. CONCLUSIONS: This is the first multicentre prospective study showing that percutaneous native kidney biopsies are associated with a 5% risk of a major post-biopsy complication. Predictors of increased risk include higher plasma creatinine levels, liver disease and a higher number of needle passes.

What volume to choose to assess online Kt/V?

INTRODUCTION: Urea distribution volume (V) can be assessed in different ways, among them the anthropometric Watson Volume (VW). However, many studies have shown that VW does not coincide with V and that the latter can be more accurately estimated with other methods. The present multicentre study was designed to answer the question: what V to choose to assess online Kt/V? MATERIALS AND METHODS: Pre- and postdialysis blood urea nitrogen concentrations and the usual input data set for urea kinetic modelling were obtained for a single dialysis session in 201 Caucasian patients treated in 9 Italian dialysis units. Only dialysis machines measuring ionic dialysance (ID) were utilized. ID reflects very accurately the mean effective dialyser urea clearance (Kd). Six different V values were obtained: the first one was VW; the second one was computed from the equation established by the HEMO Study to predict the single pool-adjusted modelled V from VW (VH) (Daugirdas JT et al. KI 64: 1108, 2003); the others were estimated kinetically as: 1. V_ID, in which ID is direct input in the in the double pool variable volume (dpVV) calculation by means of the Solute-solver software; 2. V_Kd, in which the estimated Kd is direct input in the dpVV calculation by means of the Solute-solver software; 3. V_KTV, in which V is calculated by means of the second generation Daugirdas equation; 4. V_SPEEDY, in which ID is direct input in the dpVV calculation by means of the SPEEDY software able to provide results quite similar to those provided by Solute-solver. RESULTS: Mean± SD of the main data are reported: measured ID was 190.6 ± 29.6 mL/min, estimated Kd was 211.6 ± 29.0 mL/min. The relationship between paired data was poor (R2 = 0.34) and their difference at the Bland-Altman plot was large (21 ± 27 mL/min). VW was 35.3 ± 6.3 L, VH 29.5 ± 5.5, V_ID 28.99 ± 7.6 L, V_SPEEDY 29.4 ± 7.6 L, V_KTV 29.7 ± 7.0 L. The mean ratio VW/V_ID was 1.22, (i.e. VW overestimated V_ID by about 22%). The mean ratio VH/V_ID was 1.02 (i.e. VH overestimated V_ID by only 2%). The relationship between paired data of V_ID and VW was poor (R2 = 0.48) and their mean difference at the Bland-Altman plot was very large (- 6.39 ± 5.59 L). The relationship between paired data of V_ID and VH was poor (R2 = 47) and their mean difference was small but with a large SD (- 0.59 ± 5.53 L). The relationship between paired data of V_ID and V_SPEEDY was excellent (R2 = 0.993) and their mean difference at the Bland-Altman plot was very small (- 0.54 ± 0.64 L). The relationship between paired data of V_ID and V_KTV was excellent (R2 = 0.985) and their mean difference at the Bland-Altman plot was small (- 0.85 ± 1.06 L). CONCLUSIONS: V_ID can be considered the reference method to estimate the modelled V and then the first choice to assess Kt/V. V_SPEEDY is a valuable alternative to V_ID. V_KTV can be utilized in the daily practice, taking also into account its simple way of calculation. VW is not advisable because it leads to underestimation of Kt/V by about 20%.

The impact of haemodialysis arteriovenous fistula on haemodynamic parameters of the cardiovascular system.

BACKGROUND: Satisfactory vascular access flow (Qa) of an arteriovenous fistula (AVF) is necessary for haemodialysis (HD) adequacy. The aim of the present study was to further our understanding of haemodynamic modifications of the cardiovascular system of HD patients associated with an AVF. The main objective was to calculate using real data in what way an AVF influences the load of the left ventricle (LLV). METHODS: All HD patients treated in our dialysis unit and bearing an AVF were enrolled into the present observational cross-sectional study. Fifty-six patients bore a lower arm AVF and 30 an upper arm AVF. Qa and cardiac output (CO) were measured by means of the ultrasound dilution Transonic Hemodialysis Monitor HD02. Mean arterial pressure (MAP) was calculated; total peripheral vascular resistance (TPVR) was calculated as MAP/CO; resistance of AVF (AR) and systemic vascular resistance (SVR) are connected in parallel and were respectively calculated as AR = MAP/Qa and SVR = MAP/(CO - Qa). LLV was calculated on the principle of a simple physical model: LLV (watt) = TPVR·CO(2). The latter was computationally divided into the part spent to run Qa through the AVF (LLVAVF) and that part ensuring the flow (CO - Qa) through the vascular system. The data from the 86 AVFs were analysed by categorizing them into lower and upper arm AVFs. RESULTS: Mean Qa, CO, MAP, TPVR, LLV and LLVAVF of the 86 AVFs were, respectively, 1.3 (0.6 SD) L/min, 6.3 (1.3) L/min, 92.7 (13.9) mmHg, 14.9 (3.9) mmHg·min/L, 1.3 (0.6) watt and 19.7 (3.1)% of LLV. A statistically significant increase of Qa, CO, LLV and LLVAVF and a statistically significant decrease of TPVR, AR and SVR of upper arm AVFs compared with lower arm AVFs was shown. A third-order polynomial regression model best fitted the relationship between Qa and LLV for the entire cohort (R (2) = 0.546; P < 0.0001) and for both lower (R (2) = 0.181; P < 0.01) and upper arm AVFs (R (2) = 0.663; P < 0.0001). LLVAVF calculated as % of LLV rose with increasing Qa according to a quadratic polynomial regression model, but only in lower arm AVFs. On the contrary, no statistically significant relationship was found between the two parameters in upper arm AVFs, even if mean LLVAVF was statistically significantly higher in upper arm AVFs (P < 0.0001). CONCLUSIONS: Our observational cross-sectional study describes statistically significant haemodynamic modifications of the CV system associated to an AVF. Moreover, a quadratic polynomial regression model best fits the relationship between LLVAVF and Qa, but only in lower arm AVFs.

Pregnancy in end-stage renal disease patients on dialysis: how to achieve a successful delivery.

Pregnancy in women with chronic kidney disease has always been considered as a challenging event both for the mother and the fetus. Over the years, several improvements have been achieved in the outcome of pregnant chronic renal patients with increasing rates of successful deliveries. To date, evidence suggests that the stage of renal failure is the main predictive factor of worsening residual kidney function and complications in pregnant women. Moreover, the possibility of success of the pregnancy depends on adequate depurative and pharmacological strategies in patients with end-stage renal disease. In this paper, we propose a review of the current literature about this topic presenting our experience as well.

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.

Sodium setpoint and gradient in bicarbonate hemodialysis.

BACKGROUND: The demonstration of an individual osmolar setpoint in hemodialysis (HD) is crucial to individualize dialysate sodium concentrations. Furthermore, the diffusive gradient between plasma and dialysate sodium is important in the "fine tuning" of the intradialytic sodium mass balance (MB). METHODS: The design of this study included part A: a retrospective analysis of predialysis plasma sodium concentrations extracted from a 6-year database in our HD population (147 prevalent white anuric patients); and part B: study of intradialytic sodium kinetics in 48 patients undergoing one 4-hour bicarbonate HD session. Direct potentiometry with an ion-selective electrode was used for sodium measurements. RESULTS: Study part A: the mean number of plasma sodium measurements per patient was 16.06 ± 14.03 over a mean follow-up of 3.55 ± 1.76 years. The mean of the averaged plasma sodium concentrations was 136.7 ± 2.1 mmol/L, with a low mean intraindividual coefficient of variation (1.39 ± 0.4). Study part B: mean predialysis and postdialysis plasma sodium concentrations were 135.8 ± 0.9 and 138.0 ± 0.9 mmol/L (p<0.001). Mean inlet dialyzer sodium concentration was 138.7 ± 1.1 mmol/L; the hourly diffusion concentration gradients showed a statistically significant transfer from dialysate to plasma (Wilks ? <0.0001). A statistically significant relationship was found between sodium MB and diffusion gradient (p<0.02), and between sodium MB and ultrafiltration volume (p<0.01). CONCLUSIONS: A relatively "fixed" and individual osmolar setpoint in HD patients was shown for the first time in a long-term follow-up. A dialysate sodium concentration of 140 mmol/L determined a dialysate to plasma sodium gradient.

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.

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.

Bioimpedance and the duration of the hemodialysis session.

Bioelectrical impedance analysis (BIA) is composed of resistance (R) and reactance (Xc). The aim of this study was to investigate whether BIA may be influenced by the duration of hemodialysis (HD) sessions. Eleven uremic patients underwent one 4-hour and one 8-hour bicarbonate HD session. Volume of blood and dialysate processed, volume of ultrafiltration (V(UF)), and dialysate electrolyte concentrations were prescribed to be the same. R and Xc were determined at the start and the end of each session, injecting 800 µA at 50 kHz alternating sinusoidal current (BIA 101; Akern, Italy). Mean pre- and postdialysis body weights and V(UF) were not significantly different in the 4-hour and 8-hour treatments. Postdialysis R, ΔR (the difference between post- and predialysis R values), and percent increase of R values were significantly higher in the 8-hour sessions, when compared with the corresponding values of the 4-hour sessions (p < 0.0001, 0.02, and 0.02, respectively). In conclusion, this study shows that 8-hour HD sessions were associated with postdialysis R, ΔR, and percent increase of R values significantly higher than the corresponding ones of 4-hour sessions. If higher R values may represent a proxy of a correct dry body weight, it remains a matter of future research.

Calcium mass balances during standard bicarbonate hemodialysis and long-hour slow-flow bicarbonate hemodialysis.

BACKGROUND: Dialysate calcium (Ca) concentration should be viewed as part of the integrated therapeutic regimen to control renal osteodystrophy and maintain normal mineral metabolism. Thus, a correct ionized calcium mass balance (Ca++MB) during hemodialysis (HD) is crucial in the treatment of renal osteodystrophy. The GENIUS single-pass batch dialysis system (Fresenius Medical Care, Germany) consists of a closed dialysate tank of 90 L; it offers the 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 2 bicarbonate HD sessions, 1 of 4 hours (4h) and the other of 8 hours (8h) in a random sequence, always at the same interdialytic interval, at least 1 week apart. The GENIUS system and high-flux FX80 dialyzers (Fresenius Medical Care, Germany) were used. The volume of blood and dialysate processed, volume of ultrafiltration and dialysate Ca concentrations (1.50 mmol/L) were prescribed to be the same. Trends of plasma Ca++, blood pH and bicarbonates during dialysis, as well as Ca++MBs were determined. Plasma parathyroid hormone (PTH) levels at the start and end of the 2 treatments were measured. RESULTS: Ca++MBs (mean ± SD) were +284.6 ± 137.4 mg and +297.7 ± 131.6 mg (p=0.307) in the 4h and 8h treatments, respectively. No single session out of the 22 had a negative Ca++MB for the patient. Mean plasma Ca++, blood pH and bicarbonate levels were not statistically significantly different when comparing the start and end of the sessions of the 2 treatments. Mean plasma Ca++, blood pH and bicarbonate levels increased significantly along the time points in both 4h and 8h HD sessions (repeated measures ANOVA: p<0.0001). Mean plasma PTH levels were not statistically significantly different when comparing the start and end of the sessions of the 2 treatments. The differences between predialysis and postdialysis plasma PTH levels were not statistically significantly different either in 4h or 8h sessions (Wilcoxon's test: p=NS), even though a trend toward lower postdialysis plasma PTH levels was observed in both 4h and 8h treatments. CONCLUSIONS: Our data show incontrovertibly that, when dialyzing with a dialysate Ca concentration of 1.50 mmol/L, 4h standard bicarbonate HD and 8h slow-flow bicarbonate HD always achieve a quite similar positive Ca++MB for the patients.

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: ß(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 ß(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 ß(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 ß(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.

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.

A new index of hemodialysis adequacy: clearance x dialysis time / bioelectrical resistance.

BACKGROUND: Kt/V urea was established as an index of hemodialysis (HD) adequacy. The use of V urea (as derived by the Watson et al formulae) 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 and liver size (LV) have been proposed (respective HD adequacy indices: Kt/W 0.67, Kt/BSA, Kt/REE, Kt/HMRO and Kt/LV). METHODS: The present study aimed to calculate the 6 previously described normalizing factors (all obtained utilizing anthropometric variables) and to measure bioelectrical resistance (R), an independent and directly achievable biological parameter, in 481 white, disease-free individuals and 270 white prevalent HD patients, pair-matched by age, body weight and height, after stratification by sex. Further, we aimed to evaluate the effect of substituting BSA, W 0.67, REE, HMRO, LV and R for V urea as denominator in Kt/V urea on the distribution of target dialysis dose in a cohort of 1,058 white prevalent HD patients. All individuals underwent 1 single-frequency bioelectrical impedance measurement, on the nondominant side of the body, injecting 800 µA at 50 kHz alternating sinusoidal current with a standard tetrapolar technique. RESULTS: When comparing pair-matched disease-free men and women with HD men and women, respectively, only R was statistically significantly different (p<0.0001 and p<0.02, respectively). As expected, V urea, BSA, W 0.67, REE, HMRO and LV were not significantly different in both comparisons. Furthermore, equivalent Kt/R for a range of prescribed Kt/V urea was able to give a more clearcut differentiation among sexes and body sizes, when compared with the other methods for scaling dialysis dose. CONCLUSIONS: BSA, W 0.67, REE, HMRO and LV, as well as V urea are derived by means of calculations which utilize anthropometric variables. In contrast, R is a biological parameter which can be directly measured in the clinical setting by means of a simple, low-cost, fast and repeatable procedure. Even though Kt/R is probably the most appropriate method for scaling dialysis dose among those evaluated in the present study, further work is required to develop these concepts and translate them into rigorous outcome-based adequacy targets suitable for clinical usage.

Serum parathyroid hormone and phosphate influence the levels of circulating CD34+ cells in uremia.

BACKGROUND: Parathyroid hormone (PTH) is an active stimulator of bone marrow osteoblasts; it is involved in the niche organization, ie the bone marrow microenvironment which controls the turnover and the fate of endothelial progenitor cells (EPCs). PTH stimulates EPC production; this action can be measured by counting the number of circulating CD34+ cells. METHODS: This observational cross-sectional study aimed to verify this effect in 3 groups of hemodialysis patients with different serum PTH levels. The first group consisted of 11 patients affected by secondary hyperparathyroidism (SHPTH group, serum PTH levels >500 pg/ml); the second group consisted of 10 patients with serum PTH levels between 150 and 500 pg/ml (TargetPTH group); the third group consisted of 10 patients with serum PTH levels below the treatment target after parathyroidectomy (PTx group, serum PTH levels <150 pg/ml). Serum PTH, calcium (Ca), phosphorus (P), alkaline phosphatases (ALP), urea nitrogen, albumin and hemoglobin were measured. Flow cytofluorimetry with CD45+ sequential gating was effected; therefore, CD34+ cells could be analyzed. RESULTS: The SHPTH group showed significantly higher values of serum PTH, P and ALP (respectively, p<0.0001, p<0.033 and p<0.0001), and significantly lower values of circulating CD34+ cells (both in absolute and percent terms) in the SHPTH and in the TargetPTH groups (for both, p<0.0001). Two models of multiple regression analysis built with circulating CD34+ cells (expressed as percentage in the first one and as absolute values in the second one) as dependent variables showed that only serum PTH and P values were inversely associated with both. CONCLUSIONS: Our data suggest that an inverse relationship exists in uremic patients among circulating CD34+ cells and serum P and PTH levels. The count of circulating CD34+ cells might represent a novel biomarker for the assessment of the cardiovascular risk for dialysis patients.

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.

The Mediterranean diet: a matter of history, tradition, culture and health.

We can state that unhealthy diets are among the top 10 causes of mortality in Western countries. The Mediterranean diet is gaining popularity because it encourages weight loss, improving the quality of life by offering a variety of healthy and palatable foods. Moreover, it ensures adequate intake of fruits, vegetables, nuts, fish, fibers, legumes, cereals and olive oil, which have been associated with a longer lifespan of people thanks to their anti-inflammatory and antioxidant properties. Thus the Mediterranean diet could act as therapy in inflammatory diseases including cardiovascular disease, obesity, type 2 diabetes, metabolic syndrome and chronic renal failure.

Does vitamin D receptor and calcium receptor activation therapy play a role in the histopathologic alterations of parathyroid glands in refractory uremic hyperparathyroidism?

BACKGROUND AND OBJECTIVES: Vitamin D receptor activation by vitamin D sterols and calcium-sensing receptor stimulation by cinacalcet are the most powerful treatments of secondary hyperparathyroidism. This study was aimed to assess a possible association between histopathologic changes of parathyroid tissue and treatment modality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Studies were performed on 82 parathyroids of 22 adult white hemodialysis patients undergoing first parathyroidectomy. The type of hyperplasia and the distribution of chief and oxyphil cells, expressed as oxyphil/chief cell ratio, were assessed. Three groups could be studied according to treatment modality: group A consisted of 6 patients who were treated with cinacalcet, intravenous calcitriol, and phosphate binders; group B consisted of 6 patients who were treated with intravenous calcitriol and phosphate binders, and group C consisted of 10 patients who were treated with phosphate binders alone. RESULTS: Sixty-eight (82.9%) out of 82 glands removed showed nodular hyperplasia. It was more frequent in groups A and B than in group C. A stepwise forward logistic regression model showed that the probability of nodular hyperplasia was higher in patients who were on calcitriol and/or cinacalcet therapy, in female gender and in patients with a higher body mass index. Oxyphil/chief cell ratio also was significantly different among the three groups. Cinacalcet treatment was the only predictor of this ratio. CONCLUSIONS: An association was found between calcitriol and/or cinacalcet therapy and a high prevalence of nodular hyperplasia, and between cinacalcet therapy and high oxyphil/chief cell ratio. The meaning of the observed associations remains uncertain.

Omega-3 polyunsaturated fatty acids and proxies of cardiovascular disease in hemodialysis: a prospective cohort study.

BACKGROUND: Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have antithrombotic, lipid-lowering and antiinflammatory properties. The aim of this study was to verify if dietary supplementation with omega-3 PUFAs is able to induce changes of blood pressure, nutritional and coagulative profile, inflammation and blood cell counts in patients on hemodialysis (HD). METHODS: We designed a 12-month, prospective, single-blind, sequential intervention, cohort study. All of the HD patients undergoing HD in our unit were eligible for the study. Patients on HD for at least 6 months with an autologous vascular access were enrolled. No thresholds for blood pressure or lab parameters were considered. Patients taking nonsteroidal antiinflammatory drugs, steroids or statins or those with catheters, grafts, liver diseases, malignancies, malnutrition or sepsis were excluded. After the baseline evaluations the patients underwent 3 consecutive 4-month study periods taking the following supplements: A (olive oil: 2 g/day), B (omega-3 PUFA: 2 g/day), C (olive oil: 2 g/day). RESULTS: Twenty-four patients met the inclusion criteria. All patients completed the follow-up. Fibrinogen, hemoglobin, platelet, red and white blood cell counts, parathormone (PTH), partial thromboplastin time (PTT), serum total cholesterol, triglycerides, apolipoprotein A and B, C-reactive protein (CRP) and albumin levels did not change significantly during the study. On the contrary, systolic (mean +/- SD) (A: 131 +/- 17.8 mm Hg; B: 122 +/- 12.8 mm Hg; C: 129 +/- 13.2 mm Hg), diastolic (A: 83 +/- 16.3 mm Hg; B: 72 +/- 14.8 mm Hg; C: 79 +/- 6.5 mm Hg) and mean blood pressure (A: 99 +/- 16.8 mm Hg; B: 88 +/- 14.1 mm Hg; C: 96 +/- 8.7 mm Hg) were significantly lower at the end of study period B (repeated measures ANOVA and Tukey's post hoc test: p<0.05). CONCLUSIONS: In our experience, blood pressure was the only parameter influenced by omega-3 PUFA supplementation in patients on long-term HD.

Total body water in health and disease: Have anthropometric equations any meaning?

BACKGROUND: The accurate measurement of total body water (TBW) requires isotopic dilution techniques that are not easily applicable to the clinical setting. Therefore, indirect methods of estimating TBW are commonly employed, such as bioelectrical impedance analysis (BIA) and anthropometry. In the human body, >90% of the measured impedance is composed of resistance (R). METHODS: The aim of the present study was to compare TBW estimated by means of two anthropometric equations (by Watson and Hume) with TBW obtained by BIA (equations proposed by Sun et al.) in a group of white disease-free individuals (n = 3625, 1860 men and 1765 women) and white haemodialysis (HD) patients (n = 688, 443 men and 245 women). They underwent one single-frequency BIA measurement, on the nondominant side of the body, injecting an 800-muA and 50-kHz alternating sinusoidal current with a standard tetrapolar technique. The BIA variable measured was R. RESULTS: Among them, a selection of disease-free individuals (n = 481) and HD patients (n = 270), pair-matched by age, body weight and height, after stratification by gender, was made. When comparing the four pair-matched groups, it was found that (1) TBW was not different (disease-free men versus HD men; disease-free women versus HD women) when using anthropometric equations, which utilize quite identical parameters (age, body weight and height); (2) R was statistically significantly different in the four groups (511 +/- 58 SD Omega in disease-free men versus 558 +/- 80 in HD men, P < 0.0001; 593 +/- 70 Omega in disease-free women versus 615 +/- 100 in HD women, P < 0.02) and (3) therefore, TBW was statistically significantly different only when applying BIA equations (P < 0.0001 and 0.05, respectively). CONCLUSIONS: The present study demonstrates that anthropometric equations for the estimation of TBW can be used only within a specific population in order to assess individual differences; they cannot be used in order to compare two different populations.