Clinical use of computational modeling for surgical planning of arteriovenous fistula for hemodialysis.

BACKGROUND: Autogenous arteriovenous fistula (AVF) is the best vascular access (VA) for hemodialysis, but its creation is still a critical procedure. Physical examination, vascular mapping and doppler ultrasound (DUS) evaluation are recommended for AVF planning, but they can not provide direct indication on AVF outcome. We recently developed and validated in a clinical trial a patient-specific computational model to predict pre-operatively the blood flow volume (BFV) in AVF for different surgical configuration on the basis of demographic, clinical and DUS data. In the present investigation we tested power of prediction and usability of the computational model in routine clinical setting. METHODS: We developed a web-based system (AVF.SIM) that integrates the computational model in a single procedure, including data collection and transfer, simulation management and data storage. A usability test on observational data was designed to compare predicted vs. measured BFV and evaluate the acceptance of the system in the clinical setting. Six Italian nephrology units were involved in the evaluation for a 6-month period that included all incident dialysis patients with indication for AVF surgery. RESULTS: Out of the 74 patients, complete data from 60 patients were included in the final dataset. Predicted brachial BFV at 40 days after surgery showed a good correlation with measured values (in average 787 ± 306 vs. 751 ± 267 mL/min, R = 0.81, p < 0.001). For distal AVFs the mean difference (±SD) between predicted vs. measured BFV was -2.0 ± 20.9%, with 50% of predicted values in the range of 86-121% of measured BFV. Feedbacks provided by clinicians indicate that AVF.SIM is easy to use and well accepted in clinical routine, with limited additional workload. CONCLUSIONS: Clinical use of computational modeling for AVF surgical planning can help the surgeon to select the best surgical strategy, reducing AVF early failures and complications. This approach allows individualization of VA care, with the aim to reduce the costs associated with VA dysfunction, and to improve AVF clinical outcome.

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.

The key role of color Doppler ultrasound in the work-up of hemodialysis vascular access.

Vascular access (VA) is the lifeline for the hemodialysis patient and the native arterio-venous fistula (AVF) is the first-choice access. Among the different tests used in the VA domain, color Doppler ultrasound (CD-US) plays a key role in the clinical work-up. At the present time, three are the main fields of CD-US application: (i) evaluation of forearm arteries and veins in surgical planning; (ii) testing of AVF maturation; (iii) VA complications. Specifically, during the AVF maturation, CD-US allows to measure the diameter and flow volume in the brachial artery and calculate the peak systolic velocity (PSV) of the arterial axis, anastomosis and efferent vein, to detect critical stenosis. The borderline stenosis, revealed by the discrepancies between access flow rate and PSV, should be followed up with subsequent tests to detect progression of stenosis; the cases with significant changes in brachial flow should be referred to angiography. In conclusion, clinical monitoring remains the backbone of any VA program. CD-US is of utmost importance in a patient-centered VA evaluation, because it allows the appropriate management of all aspects of VA care. These are the main reasons why we strongly advocate the adoption of a VA surveillance program based on CD-US.

Efficacy and Safety of a New Technique of Conversion from Temporary to Tunneled Central Venous Catheters.

The usually applied conversion technique from temporary to tunneled central venous catheters (CVCs) using the same venous insertion site requires a peel-away sheath. We propose a conversion technique without peel-away sheath: a guide wire is advanced through the existing temporary CVC; then, a subcutaneous tunnel is created from the exit to the venotomy site. After removing the temporary CVC, the tunneled one is advanced along the guide wire. The study group included all patients requiring a catheter conversion from January 2012 to June 2014; the control group included incident patients who had received de novo placement of tunneled CVCs from January 2010 to December 2011. The main outcome measures were technical success and immediate complications. Seventy-two tunneled catheters (40 with our conversion technique and 32 with the traditional one) were placed in 72 patients. The technical success was 95% in the study group and 75% in the controls (p = 0.019). The immediate complications were one bleeding in the study group (2.5%) and one air embolism, one pneumothorax, and four bleedings (18.7%) in the controls (p = 0.039). Conversion from temporary to tunneled CVC using a guide wire and without a peel-away sheath is an effective and safe procedure.

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.

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.

How to manage catheter-related right atrial thrombosis: Our conservative approach.

BACKGROUND: Catheter-related right atrial thrombosis is an underestimated, severe, and life-threatening complication of any type of central venous catheters. No clear-cut epidemiological data are available. Catheter-related right atrial thrombosis is often asymptomatic; however, it can lead to serious complications and death. CASE SERIES: We report seven catheter-related right atrial thrombosis events occurred in five hemodialysis patients; two recurrences following primary treatment are included in the report, all of them managed with a conservative approach without catheter removal. Systemic anticoagulation (vitamin K antagonists), having a well-defined target of International Normalized Ratio of 2.5-3.0, combined with urokinase as a locking solution at the end of each hemodialysis session were the therapeutic strategy used in all patients. After the first month, the anticoagulation target was reduced to an International Normalized Ratio value of 1.5-2.0 and urokinase to a weekly administration. After sixth months, when no thrombus was identified at transthoracic echocardiographic examinations, the treatment was stopped. No bleeding complications were reported. CONCLUSION: The combination therapy here described is safe, quick, and effective, achieving the goal of not removing catheters.

Vitamin D treatment in hemodialysis patients with low serum levels of parathyroid hormone: which is the best choice?

BACKGROUND: This short-term prospective study aimed to assess the effects of treatment with calcidiol (25-hydroxycholecalciferol) or calcitriol in the subset of hemodialysis patients characterized by stable low serum levels of parathyroid hormone (PTH) or affected by hypoparathyroidism after total parathyroidectomy (PTx). METHODS: Two groups were created according to baseline serum levels of 25-hydroxyvitamin D (25(OH)D): group A (12 patients): <15 ng/mL; group B (12 patients): >15 ng/mL. They underwent a 6-month treatment with oral calcidiol (group A) or oral calcitriol (group B). RESULTS: Group A showed a statistically significant increase in the serum levels of calcium corrected for serum albumin (cCa), phosphorus (P), total alkaline phosphatases (ALP), PTH and 25(OH)D. Group B showed a statistically significant increase in serum levels of cCa and P. A statistically significant decrease in serum levels of ALP and 25(OH)D was observed. Baseline serum 25(OH)D levels were 12.6 + 3.8 ng/mL in group A and 23.0 + 5.0 ng/mL in group B (p<0.0001). After 6 months, they increased to 38.3 + 21.0 ng/mL in group A (p<0.01) and decreased to 16.9 + 5.8 ng/mL in group B (p<0.01). CONCLUSIONS: Treatment with oral calcitriol was associated with a decrease in the serum levels of ALP and 25(OH)D; treatment with oral calcidiol was associated with more physiological serum levels of 25(OH)D and with an increase in the serum levels of ALP and PTH: whether the statistically significant differences in the biochemical parameters achieved with the 2 treatments have a clinical relevance, remains a matter of debate.

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.

Autogenous side-to-side brachial-basilic fistulas without vein transposition: a valuable option?

An autogenous brachial-basilic arteriovenous fistula (BBAVF) in the upper arm must be considered before placing prosthetic grafts in hemodialysis patients with multiple failures of forearm AVFs. The aim of this observational study was to compare technical and clinical outcomes of a new construction technique for BBAVF (n-BBAVF) with that of the standard one-stage side-artery to end-vein transposed BBAVF (t-BBAVF). A n-BBAVF is constructed in the following way: basilic vein and brachial artery are isolated. Patency of the proximal and distal vein is verified by injecting warmed (37 degrees C) saline solution. A venotomy and an arterotomy of 4-5 mm are performed. The two vessels are prepared for a side-to-side anastomosis without transposition of the vein. The latter allows both an antegrade and retrograde flow along the basilic vein, both proximally and distally to the anastomosis with more sites available for the venipunctures of the dialysis. Thirty BBAVFs were constructed as the secondary or tertiary vascular access in 30 patients over a 4-year period: 17 patients with adequate forearm basilic vein underwent the construction of a n-BBAVF; 13 underwent the construction of a t-BBAVF. The construction of a n-BBAVF requires a significantly lesser surgical time (55.0 +/- 9.0 minutes vs. 115.0 +/- 18.0, p < 0.0001), has fewer surgical complications (5.9% vs. 46.2%, p < 0.0001), and a reduced time to first use (24.5 +/- 6.3 vs. 37.7 +/- 9.1 days, p < 0.0001) than that of a t-BBAVF. n-BBAVFs showed a relatively low rate of thrombosis per patient-year at risk (0.067 at 1 year and 0.099 at 2 years). The latter was significantly lower at 1 year when compared with t-BBAVFs (0.067 vs. 0.285; p < 0.004). Our policy of "all AVFs should be autogenous" led us to the construction of a vascular access which is based on a side-to-side anastomosis between the brachial artery and the basilic vein without transposition of the vein allowing both antegrade and retrograde flow into the basilic vein. The results of this surgical technique appear satisfactory.

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.

[Membranoproliferative glomerulonephritis with relapsing episodes of acute kidney injury in the Schnitzler syndrome].

The Schnitzler syndrome (SS) is a rare and underdiagnosed entity that associates a chronic urticarial rash, monoclonal IgM (or sometimes IgG) gammopathy and signs and symptoms of systemic inflammation. During the past 45 years the SS has evolved from an elusive, little-known disorder to the paradigm of a late-onset auto-inflammatory acquired syndrome. Though there is no definite proof of its precise pathogenesis, it should be considered as an acquired disease involving abnormal stimulation of the innate immune system, which can be reversed by the interleukin 1 (IL-1) receptor antagonist anakinra. Here we describe the case of a 56-year-old male Caucasian patient affected by SS and hospitalized several times in our unit because of relapsing episodes of acute kidney injury. He underwent an ultrasound-guided percutaneous kidney biopsy in September 2012, which showed the histologic picture of type I membranoproliferative glomerulonephritis. He has undergone conventional therapies, including nonsteroidal anti-inflammatory drugs, steroids and immunosuppressive drugs; more recently, the IL-1 receptor antagonist anakinra has been prescribed, with striking clinical improvement. Although the literature regarding kidney involvement in the SS is lacking, it can however be so severe, as in the case reported here, to lead us to recommend the systematic search of nephropathy markers in the SS.

Kidney involvement in the Schnitzler syndrome, a rare disease.

The Schnitzler syndrome (SS) is a rare and underdiagnosed entity that associates a chronic urticarial rash, monoclonal IgM (or sometimes IgG) gammopathy and signs and symptoms of systemic inflammation. During the past 45 years, the SS has evolved from an elusive little-known disorder to the paradigm of a late-onset acquired auto-inflammatory syndrome. Though there is no definite proof of its precise pathogenesis, it should be considered as an acquired disease involving abnormal stimulation of the innate immune system, which can be reversed by the interleukin-1 receptor antagonist anakinra. It clearly expands our view of this group of rare genetic diseases and makes the concept of auto-inflammation relevant in polygenic acquired diseases as well. Increasing numbers of dermatologists, rheumatologists, allergologists, haematologists and, more recently, nephrologists, recognize the SS. The aim of this review is to focus on kidney involvement in the SS. Although the literature regarding kidney involvement in the SS is very poor it can be severe, as in our own case here reported, leading us to recommend the systematic search for nephropathy markers in the SS.

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.

Female hemodialysis patients have an increased risk of nodular hyperplasia of parathyroid glands.

BACKGROUND: An association between female gender and more aggressive patterns of secondary hyper-parathyroidism (sHPTH) has been suggested: an increased incidence of refractory sHPTH seems evident in females; therefore, necessitating parathyroidectomy (PTx). METHODS: This study aimed to verify the existence of such an association and secondly to evaluate the impact of female gen-der on parathyroid gland histology. Therefore, a retrospective study was conducted on 67 patients who underwent first PTx (either total or subtotal) in our hospital from 1999-2003. Out of these patients, we selected 55 (28 males, 27 females, mean age 50.8 +/- 14.7 SD yrs, dialysis duration 109.2 +/- 62.4 months) in whom all four parathyroid glands were identified and removed. Serum levels of immunoreactive intact parathyroid hormone (iPTH), alkaline phosphatase, calcium and phosphate were determined at the PTx time point. The same pathologist performed the histological studies of the parathyroid glands on seven serial sections of the glands. Gland hyperplasia was classified as (1) exclusively diffuse (EDH) when only diffuse hyperplasia was found in the four glands; (2) exclusively nodular (ENH) when only nodular hyper-plasia was found in the four glands; (3) diffuse/nodular (D/NH), in which the four glands showed varying degrees of evolution towards both nodular and diffuse hyperplasia. RESULTS: EDH was found in 13 patients with a prevalence of males (11/13; 84.6%); ENH was found in 23 patients with a prevalence of females (15/23; 65.2%); D/NH was found in 19 patients with a similar prevalence between females and males (10 females and 9 males). The difference in the male/female prevalence among the three groups was statistically significant (chi2 test, p=0.015). Serum calcium was significantly higher in the ENH group (one-way analysis of variance, p=0.009). No difference was found among the three groups as far as age, dialysis duration, serum levels of iPTH, alkaline phosphatase and phosphate were concerned. CONCLUSIONS: Female gender is associated with more aggressive histological sHPTH patterns; this association seems to suggest that female gender predisposes to monoclonal proliferation of parathyroid glands in chronic uremia.

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.

End-stage renal disease in leprosy.

BACKGROUND: Leprosy or Hansen's disease (HAD) undoubtedly remains an emergency in certain countries. It is an ancient deforming disease caused by Mycobacterium leprae. The countries with the highest endemic leprosy rate in 2000 were Brazil, India and Madagascar. In Italy, the old epidemic has been defeated and there are approximately 400 patients under constant monitoring with three to four new cases per year involving Italian residents. The kidney is one of the target organs during the splanchnic localization of leprosy. The histopathological renal lesion spectrum includes glomerulonephritis (GN), renal amyloidosis (RA) and interstitial nephritis (IN). Both proteinuria and chronic renal failure are the main clinical expressions of renal damage in leprosy. To the best of our knowledge, very little is reported concerning end-stage renal disease (ESRD) in leprosy patients both in the most important national and international renal registries and in the available literature. This study aimed to report the long-term experience of our department in this field. METHODS: To achieve this, we analyzed retrospectively the HAD Center (Gioia del Colle) database at ourhospital. RESULTS: Eight leprosy patients were dialyzed from 1980 to June 2003 (six males and two females), with a mean age of 61.0+/-8.9 SD yrs (range: 51-76) and a mean HAD duration of 36.1+/-5.1 yrs. The first clinical nephropathymanifestations were non-nephrotic proteinuria associated with chronic renal failure in four patients, and nephrotic proteinuria in four patients. Kidney biopsies performed in three patients showed two had RA, and one had IN. Two patients were treated initially by peritoneal dialysis; they were then switched to hemodialysis (HD) after 3 and 10 months because of recurrent peritonitis. HD treatment lasted 40.6+/-31.4 months (range: 9-101). Six patients died, one due to hyperkalemia, one because of a technical dialysis accident, and the remainder due to causes unrelated to the dialysis treatment. Two patients are still alive, treated with HD for 17 and 44 months. CONCLUSIONS: Uremia represents a late complication of leprosy and has a multifactorial genesis, although RA is among the most frequent causes, conventional bicarbonate HD appears to offer good results in the treatment of uremia in leprosy patients.