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.

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.

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.

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.

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.

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.

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.

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 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.

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.

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.

Sestamibi scintigraphy, topography, and histopathology of parathyroid glands in secondary hyperparathyroidism.

BACKGROUND: Several imaging techniques presently are available to assess the location of hyperplastic parathyroid glands. The purpose of the present study is to assess the place of dual-phase technetium Tc 99m-sestamibi (MIBI) scintigraphy in the preoperative localization of hyperplastic parathyroid glands in patients with severe secondary hyperparathyroidism (SHPT). METHODS: We studied 35 consecutive adult white hemodialysis patients undergoing a first parathyroidectomy after performing MIBI scintigraphy. Hyperplasia of the parathyroid glands was classified as diffuse (DH) or nodular (NH). Statistical analysis was conducted by comparing patients with MIBI-negative (no focal area of increased uptake) with MIBI-positive (> or = 1 focal area of increased uptake) results and stratifying parathyroid glands according to location (superior and inferior). RESULTS: MIBI scintigraphy showed focal areas of increased uptake in at least 1 gland in 25 patients (71.4%). Total number of focal areas of increased uptake was 42 of 121 glands removed (sensitivity, 34.7%; specificity, 100%). One hundred one glands showed NH and 20 glands showed DH. The 25 patients with MIBI-positive results had 85 pathological glands removed, and the 10 patients with MIBI-negative results had 36 pathological glands removed: in the former, most glands showed NH (77 of 85 glands; 90.6%), and in the latter, 24 of 36 glands showed NH (66.7%; P = 0.004 at chi-square test). The sensitivity of MIBI scintigraphy for distinguishing specific subtypes of hyperplasia was 37.6% (38 of 101 glands) for NH and 20.0% (4 of 20 glands) for DH (P = 0.0005). The following values were significantly greater in inferior compared with superior glands: (1) estimated weight (2.1 +/- 0.8 versus 1.6 +/- 1.2 g; P = 0.04), (2) percentage of MIBI positivity (34 of 42 inferior glands [80.9%] versus 8 of 42 superior glands [19.1%]; P = 0.0001), and (3) percentage of localization permitted by MIBI scintigraphy (34 of 63 inferior glands [54.0%] versus 8 of 58 superior glands [13.8%]; P = 0.0001). Thus, NH, although equally distributed between inferior (53 of 63 glands) and superior (48 of 58 glands) glands, showed a percentage of MIBI positivity significantly greater in inferior (34 of 53 glands [64.1%]) compared with superior glands (8 of 48 glands [16.7%]; P = 0.0001). CONCLUSION: MIBI scintigraphy did not show high sensitivity in identifying hyperplastic glands, although it was able to identify those with NH better than those with DH. Thus, MIBI scintigraphy has limited value preoperatively for patients with SHPT. Estimated weight, percentage of MIBI positivity, and percentage of localization permitted by MIBI scintigraphy were significantly greater in inferior glands.

Post-parathyroidectomy serum phosphate kinetics is peculiar to female hemodialysis patients with a high body mass index.

BACKGROUND: Persistent hyperphosphatemia is one of the most important factors in the development of secondary hyperparathyroidism (sHPTH). Recently, we demonstrated that a higher body mass index (BMI) and female gender could predispose to a larger phosphate (P) body burden, thereby influencing the severity of sHPTH. METHODS: This prospective study aimed to verify if these two risk factors, i.e. BMI and female gender, also influenced calcium (Ca) and P kinetics in the immediate post-parathyroidectomy (PTx) period in 42 consecutive adult Caucasian anuric hemodialysis (HD) patients referred for first PTx. Serum Ca and P were measured pre-PTx and on the 5 consecutive post-PTx days; serum immunoreactive parathyroid hormone (iPTH) and alkaline phosphatase (ALP) levels were measured pre-PTx and 3 days post-PTx. RESULTS: Ablation of parathyroid tissue determined a significant reduction in serum iPTH, ALP, Ca and P (p = 0.001). The stratification of the cohort into four groups according to the cut-off value of BMI = 25 kg/m(2) and according to gender showed the following: males and females with BMI >25 kg/m(2) (analyzed both separately and as a subgroup including males and females) had significantly higher pre-PTx serum P levels, when compared with the respective sub-groups with BMI <25 kg/m(2) (p < 0.01); a significantly higher mean area under the concentration curve (AUC) of serum P was observed in the high BMI group (males and females), when compared with the low/normal BMI group (p = 0.03); the serum P kinetics in the 5 post-PTx days did not differ between the two groups of male patients (low/normal BMI males vs. high BMI males), whereas a significantly higher mean serum P AUC was observed in the high BMI female patients, when compared with the low/normal BMI female patients (p = 0.003); finally, the serum P kinetics in the 5 post-PTx days did not differ between the two groups of low/normal male and female patients, whereas a significantly higher mean serum P AUC was observed in the high BMI female patients, when compared with the high BMI male patients (p = 0.006). A linear multiple regression analysis with the serum P AUC of each patient as a dependent variable and BMI, gender, age and dialysis duration as independent variables showed that BMI (p = 0.0001) and female gender (p = 0.001) were independent predictors of the serum P AUC. CONCLUSIONS: High BMI and female gender are associated with peculiar serum P kinetics in the immediate post-PTx period, suggesting the existence of a larger P body burden in high BMI female HD patients. The existence of a larger P pool exclusively based on serum P kinetics prompts the need for further studies to better understand such intriguing aspects of bone pathophysiology in response to parathyroid gland removal in chronically uremic patients.

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.

Comorbid conditions and gender impact the primary survival of distal radio-cephalic arteriovenous fistula inpatients on long-term hemodialysis.

BACKGROUND: Vascular access failure complicates the clinical picture of patients on long-term hemodialysis, increasing the number of hospitalizations and the respective costs. In these patients we analyzed the possible meaningful relationship between comorbidities and primary survival of the autologous distal radio-cephalic arteriovenous fistula (dAVF), pointing out the influence of other variables on that relationship. METHODS: We evaluated the dAVF placed in our unit between January 1, 1995, and December 31, 2003, on 105 patients (55 males) 63.8 +/- 14.1 (average +/- SD) years old. The dAVF creation date was the starting point while the dAVF failures due to either thrombosis or malfunction (KT/V < 1.2) were the study end-point. Death, conversion to peritoneal dialysis, transfer to other units and renal transplantation were assumed as censure criteria. ICED score, single comorbidities, use of temporary catheter at the hemodialysis initiation, serum lipids and CRP levels, hematocrit, blood platelet count and coagulative parameters (at the time of the dAVF creation) were considered as covariates. The Kaplan-Meier method and Cox's proportional hazards regression were used in the dAVF survival analysis. RESULTS: During the study we recorded 38 dAVF failures (median primary survival of the dAVF 487.3 days, with a failure rate of 0.645 per patient-year). Age, lab variables, single comorbidities, and use of temporary catheters did not impact the dAVF primary survival. Conversely ICED score > 1 (P = 0.014; hazard ratio = 1.648; 95% CI = 1.106-2.454) as well as feminine gender (P = 0.018; hazard ratio = 1.640; 95% CI = 1.024-2.256) increased the risk of dAVF failure. CONCLUSIONS: In our cohort of patients on long-term hemodialysis neither the single comorbidities nor the temporary catheterization influence the lifespan of the vascular access. However our data demonstrated the meaningful inverse relationship between dAVF primary survival and a composite comorbidity index reflecting not only the type of the diseases but also their associations and severities. This relationship was not influenced by other covariates although the feminine gender was significantly associated with worse survival of the vascular access.

Are low plasma levels of 25-(OH)vitamin D a major risk factor for hyperparathyroidism independent of calcitriol in renal transplant patients?

BACKGROUND: Recently, some studies have emphasized the role of plasma 25-(OH)vitamin D (25OHD) levels in mineral metabolism dysregulation in chronic kidney diseases (CKDs). However, to date little attention has been paid to 25OHD metabolism abnormalities after renal transplantation (Tx). This cross-sectional study aimed to focus on its role in mineral metabolism dysregulation in functioning Tx. METHODS: Twenty-eight out of 75 Caucasian Tx patients were selected following strict inclusion and exclusion criteria. Two blood samples were effected at the end of the winter for the measurements of plasma 25OHD and calcitriol levels. Serum creatinine (Cr), alkaline phosphatase (SAP), immunoreactive intact parathyroid hormone (PTH), electrolytes and 24-hr proteinuria were also determined. The Kolmogorov-Smirnov test was used to evaluate the data distribution: serum Cr, Cr clearance, dialysis duration and PTH levels were non-normally distributed and were log-transformed. Values of p<=0.01 were assumed as statistically significant. RESULTS: Median serum Cr and PTH levels were, respectively, 1.0 mg/dL and 90.0 pg/mL (range 27-420; normal range 10-65); most of our Tx patients (78.5%) had serum PTH levels above the upper limit of normal values. Mean plasma 25OHD concentration was 19.6 +/- 8.9 SD ng/mL (range: 6-36). None had levels <5 ng/mL (severe deficiency); 10 patients (35.7%) had mild deficiency (5-15 ng/mL); 14 patients (50%) had vitamin D insufficiency (16-30 ng/mL); and only four patients (14.3%) had target levels (>30 ng/mL). Mean plasma calcitriol levels were 69.7 +/- 19.0 pg/mL (range 47-105; normal range 35-85). They were not significantly correlated to plasma 25OHD levels. Proteinuria (292.6 +/- 147.0 mg/24 hr) inversely correlated to plasma 25OHD levels (r=-0.480; p<0.01). The bivariate correlation analysis between logPTH and the other parameters showed a significant correlation for SAP (r=0.494; p=0.008), plasma 25OHD levels (r=-0.442; p=0.01), proteinuria (r=0.452; p=0.01), log serum Cr (r=0.551; p=0.002) and log Cr clearance (r=-0.534; p=0.003). The other parameters did not correlate significantly with logPTH, notably plasma calcitriol and serum phosphate levels. Only the parameters significantly correlated to logPTH in the bivariate correlation analysis were included in the back stepwise multiple linear regression analysis as independent variables (model: p<0.0001; R2=0.54): among them, only plasma 25OHD levels (Beta=-0.486; p=0.001) and log serum Cr levels (Beta=0.589; p=0.0002) were the dependent variable logPTH predictors. CONCLUSIONS: This cross-sectional study demonstrated that plasma calcitriol levels in a highly selected group of Tx patients were normal and not significantly correlated to either plasma 25OHD or serum PTH levels. Most patients (85.7%) had plasma 25OHD levels below the target value of 30 ng/mL; the latter were inversely correlated with serum PTH levels. Therefore, our study strengthens the suggestion that low plasma 25OHD levels are a major risk factor for secondary hyperparathyroidism (sHPTH) in Tx patients and stresses the importance of monitoring these patients.

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.

Does atorvastatin influence serum C-reactive protein levels in patients on long-term hemodialysis?

BACKGROUND: The increase in serum C-reactive protein (CRP) levels is an independent determinant of cardiovascular events in long-term hemodialysis (HD) patients. Recently, statins have shown anti-inflammatory properties in addition to their lipid-lowering effect. METHODS: We designed a 6-month, prospective, randomized, controlled study to assess the safety and efficacy of atorvastatin in reducing serum CRP levels in long-term HD patients. Patients on HD therapy for at least 6 months, with autologous vascular access, were included. Patients presenting with illnesses and/or use of drugs that may affect CRP levels were excluded. After randomization, group A included 16 patients treated with atorvastatin (10 mg/d orally), and group B included 17 patients treated with placebo. Body mass index, Kt/V, normalized protein catabolic rate, mean blood pressure, and levels of hemoglobin, serum CRP, albumin, creatinine, lipids, and enzymes were recorded at baseline and after 6 months. RESULTS: Qualitative/quantitative parameters were homogeneous between the groups at baseline. In group A, median serum CRP levels decreased from 9 mg/L (range, 5 to 22 mg/L) at baseline to 5 mg/L (range, 3 to 16 mg/L) after 6 months (P = 0.004). In group B, values were 8 mg/L (range, 4 to 14 mg/L) at baseline and 7 mg/L (range, 3 to 17 mg/L) after 6 months (P = 0.98). Serum CRP levels were lower in group A than group B at month-4 (5 mg/L; range, 3 to 11 mg/L versus 7 mg/L; range, 3 to 10 mg/L, respectively; P = 0.054) and month-6 evaluations (5 mg/L; range, 3 to 16 mg/L versus 7 mg/L; range, 3 to 17 mg/L, respectively; P = 0.060). After 6 months, only in group A was there a significant decrease in serum cholesterol levels (P = 0.041) and a significant increase in serum albumin levels (P = 0.004). Enzyme levels were stable during the study in both groups. CONCLUSION: Administration of atorvastatin is safe in patients on long-term HD therapy and, in addition to its beneficial effects on lipid levels, induces a significant decrease in serum CRP levels, with a consequential increase in serum albumin levels.