Transcatheter Mitral Valve Repair Using MitraClip in Patients With Renal Transplantation.

OBJECTIVES: To evaluate the renal function in patients with renal transplantation 1 month after treatment of their severe symptomatic mitral regurgitation using transcatheter mitral valve repair (TMVRep) using MitraClip (Abbott Cardiovascular). METHODS: We enrolled 22 patients with previous history of end-stage renal disease and kidney transplant with severe symptomatic mitral regurgitation (MR) in this study. Each patient was evaluated by the structural heart team and underwent transesophageal echocardiographic evaluation for MR etiology, severity, and location of the MR jet, as well as to rule out left atrial appendage clot formation. Serum creatinine and estimated glomerular filtration rate using the Modification of Diet in Renal Disease formula were measured at baseline and at 1-month follow-up. RESULTS: Fourteen patients (64%) were male and mean age of the study group was 50.4 ± 11.0 years. Mean ejection fraction was 29.0 ± 5.6%. The majority (86%) of the MRs treated were classified as functional MR. Follow-up creatinine values were significantly lower after treatment of their symptomatic MR with TMVRep compared with baseline creatinine values (baseline, 3.2 ± 0.49 mg/dL; follow-up, 1.99 ± 0.31 mg/dL; P<.05). CONCLUSIONS: TMVRep in patients with renal transplantation was associated with lower serum creatinine values at 1-month follow-up and represents an alternative to surgery in this high-risk group of patients. Further studies are needed to confirm our findings and to find the best treatment option for these patients.

Update on the Management of Urological Problems Following Kidney Transplantation.

Urological problems in kidney transplant recipients are not limited only to posttransplantation urological complications. These problems are a cause of significant patient mortality and morbidity that have wide-ranging effects on graft survival throughout the entire life of the graft. Ultimately, the transplant comprises a major portion of the urinary system; therefore, the transplant team should be prepared for foreseeable and unforeseeable urological problems in the short and long terms. These mainly include postoperative urological complications (urine leakage, ureteral stenosis, and vesicoureteral reflux), bladder outlet obstruction, and graft urolithiasis. In recent years, significant advances have been made in the management of urological complications, especially due to advances in endourologic interventions. The aim of this review is to summarize the management of urological problems after kidney transplantation in the context of the current literature.

Perioperative Anesthetic Management and Clinical Outcomes in Patients Undergoing Coronary Artery Bypass Grafting and Kidney Transplant in the Same Session.

BACKGROUND: Cardiovascular disease is commonly seen in patients with end-stage renal disease (ESRD) and is a major cause of graft failure and death in patients undergoing kidney transplant. METHODS: The retrospective study included 77 patients with ESRD who underwent combined coronary artery bypass grafting (CABG) and kidney transplant between May 2010 and September 2017. RESULTS: The patients included 65 (84.4%) men and 12 (15.6%) women. Diabetes mellitus (DM) and hypertension (HT) were present in 71.4% and 90.9% of the patients, respectively. Mean postoperative intensive care unit (ICU) stay was 3.4 ± 1.6 days, mean time to extubation was 12.1 ± 3.7 hours, and mean hospital stay was 11.6 ± 3.5 days. In the small group with graft rejection, EF was 41.1 ± 12.3. Two patients underwent second kidney transplant, and 1 patient underwent a third kidney transplant. Mean amount of red blood cells (RBC) and fresh-frozen plasma (FFP) transfusion was 2.6 ± 0.7 and 2.1 ± 0.7 units, respectively. CONCLUSION: The study showed that CABG and kidney transplant can be performed in a combined approach in the same session and that this combined approach is likely to have a more favorable effect on mortality and morbidity compared to the administration of these 2 surgeries in separate sessions.

Use of Tacrolimus During Pregnancy After Kidney Transplantaion.

PURPOSE: Motherhood is the greatest privilege that nature gives to women. Although pregnancy is a physiological event for women, every pregnancy is a risky pregnancy. During a normal pregnancy, the health of mother and baby are monitored. In post-transplantation pregnancies, the function of the transplanted organ, along with the mother and the infant, must be monitored, since the continuation of pregnancy depends on both the maternal and infant health and an organ functioning within normal limits. The desire is for every baby to be born in due time and at normal weight, but this is not always possible in pregnancies after transplants. Publications about the pharmocokinetics of tacrolimus are very limited. In this study, we wanted to share our experiences with pregnancy in our clinic. MATERIAL AND METHOD: Patients who used tacrolimus during their pregnancies after renal transplantation (RT) at Antalya Medicapark Organ Transplantation Unit, during November 2008 to July 2018 were included in the study. Patient's gestational age, pregnancy, drug levels, is charge, and labor creatinine clearances were examined. FINDINGS: Four thousand six hundred thirty-five RT occurred between November 2008 to July 2018; 786 of the patients were female between the ages 18 and 45. Thirty-one pregnancies went full term. Twenty-six pregnant women, who used tacrolimus after RT, were included in the study. Five patients had pre-eclampsia, 1 patient had abortus immines, 2 patients had hypertansion due to pregnancy, and 1 patient had aplated placenta. There was a breech presentation in 1 patient with preeclampsia. Acute rejection developed in 3 postpartum patients, but renal values normalized with medical treatment. All the babies were born alive and healthy; postpartum graft loss was not observed. CONCLUSION: If planning to become pregnant after RT,our center recommends waiting at least 2 years after the RT, when graft function should be normal and without any signs of HT and proteinuria. Our recommendation regarding the level of tacrolimus after RT is 4.5 to 7 µg.

Results of minimally invasive surgical treatment of allograft lithiasis in live-donor renal transplant recipients: a single-center experience of 3758 renal transplantations.

Allograft lithiasis is a rare urologic complication of renal transplantation (RT). Our aim is to present our experience with minimally invasive surgical treatment of allograft lithiasis in our series of live-donor renal transplant recipients. In a retrospective analysis of 3758 consecutive live-donor RTs performed in our center between November 2009 and January 2017, the results of minimally invasive surgery for the treatment of renal graft lithiasis diagnosed at follow-up were evaluated. Twenty-two (0.58%) patients underwent minimally invasive surgery for renal graft lithiasis. The mean age was 41.6 years, and duration between RT and surgical intervention was 27.3 months (range 3-67). The mean stone size was 11.6 mm (range 4-29). Stones were located in the urethra in 1, bladder in 2, ureter in 9, renal pelvis in 7 and calices in 3 patients. Surgical treatment included percutaneous nephrolithotomy in 1, cystoscopic lithotripsy in 3, flexible ureteroscopic lithotripsy in 6 and rigid ureteroscopic lithotripsy in 12 patients. No major complications were observed. One patient (4.5%) who underwent flexible ureteroscopy developed postoperative urinary tract infection. All patients were stone-free except two (9%) patients who required a second-look procedure after flexible ureteroscopic lithotripsy for residual stones. Stone recurrence was not observed in any patient during a mean follow-up duration of 30.2 months (range 8-84). Renal transplant lithiasis is uncommon and minimally invasive surgical treatment is rarely performed for its treatment. Endourological surgery may be performed safely, effectively and with a high success rate in these patients.

Ex vivo stone surgery in donor kidneys at renal transplantation.

OBJECTIVE: To report our experience on the outcomes of ex vivo ureteroscopy and ex vivo pyelolithotomy carried out on the donor kidney before living donor renal transplantation. METHODS: Between 2009 and 2016, 13 stone-bearing donor kidneys underwent ex vivo bench surgery after donor nephrectomy. Of these, six patients underwent ex vivo ureteroscopy and seven patients underwent ex vivo pyelolithotomy. Data were analyzed for technical feasibility, intraoperative and postoperative complications, stone clearance, and stone recurrence. RESULTS: The mean stone burden was 9.1 mm (range 5-15 mm). Renal collecting system access and stone extraction were successfully achieved, and a stone-free status was accomplished with both techniques. The mean duration of ex vivo ureteroscopy was 12.5 min (range 9-20 min), and the mean duration of ex vivo pyelolithotomy was 3.1 min (range 1-8 min). One patient in the pyelolithotomy group developed urinary leakage and underwent surgical repair on the third postoperative day. The mean long-term follow-up duration was 49.6 months (range 14-101 months). None of the 13 patients included in the study suffered from stone recurrence. CONCLUSIONS: Our experience suggests that both ex vivo ureteroscopy and ex vivo pyelolithotomy procedures can safely and effectively be carried out in stone-bearing living donor kidneys, without compromising renal allograft function.

Outcomes of Conservative Management of Asymptomatic Live Donor Kidney Stones.

OBJECTIVE: To evaluate the long-term outcomes of asymptomatic stones ≤4 mm that are left in situ during renal transplantation (RT). MATERIALS AND METHODS: Between 2009 and 2017, 31 patients who received stone-bearing (≤4 mm) kidneys were analyzed. At their last follow-up, the patients were evaluated with computerized tomography (CT) imaging and the results were compared to the initial CT findings obtained during donor evaluation. RESULTS: The mean stone size was 2.9 mm (range 1-4.3). The mean follow-up period after RT was 43.1 months (range 12-97). According to the CT findings of the last follow-up, the stone had passed spontaneously in 26 patients (83.9%). Three patients (9.6%) with a stone size of 4 mm required surgical intervention because the stone became symptomatic within the first year after transplantation. In the remaining 2 patients (6.4%), the stone remained in situ, without a change in its size. In terms of spontaneous passage rate, there was no significant difference between lower and midupper pole stones (P = .948). De novo stone formation was observed in 2 patients (6.4%). CONCLUSION: Asymptomatic stones <4 mm that are detected on donor evaluation may safely be left in situ during RT. Regardless of their localization in the kidney, these stones have high spontaneous passage rates after RT, and the long-term recurrence rates are also considerably low.

Prevalence of Sexually Transmitted Diseases in Asymptomatic Renal Transplant Recipients.

OBJECTIVES: Sexually transmitted diseases, which may be asymptomatic, have the potential to cause serious health problems in renal transplant recipients. The aim of this study was to determine the prevalence of sexually transmitted diseases in sexually active asymptomatic renal transplant patients by using real-time multiplex polymerase chain reaction assays. MATERIALS AND METHODS: This prospective controlled study was conducted between November 2016 and January 2017 in our hospital. Our study group included 80 consecutive, sexually active asymptomatic patients (40 men and 40 women) who had undergone renal transplant in our hospital and who presented to our outpatient clinic for routine follow-up. We also included a control group of 80 consecutive, sexually active nontransplant patients (40 men and 40 women). All patient samples were tested for Gardnerella vaginalis and obligate anaerobes (Prevotella bivia, Porphyromonas species), Candida species, Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma species, Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, herpes simplex virus 1 and 2, and Cytomegalovirus by real-time multiplex polymerase chain reaction. RESULTS: The prevalences of infection with Gardnerella vaginalis and obligate anaerobes (P = .043), Ureaplasma species (P = .02), and Cytomegalovirus (P = .016) were found to be significantly higher in the study group versus the control group. However, there was no difference between the 2 groups regarding the prevalence of Mycoplasma infection (P = .70). CONCLUSIONS: Sexually transmitted diseases may occur more frequently in sexually active asymptomatic renal transplant recipients than in nontransplanted individuals. Real-time multiplex polymerase chain reaction analysis may be a suitable method for determining these pathogens.

Comparative Results of Transurethral Incision with Transurethral Resection of The Prostate in Renal Transplant Recipients with Benign Prostate Hyperplasia.

PURPOSE: The aim of this study is to compare the results of transurethral incision of the prostate (TUIP) and transurethral resection of the prostate (TURP) for the surgical treatment of benign prostate hyperplasia (BPH) in patients with renal transplantation. MATERIALS AND METHODS: Between April 2009 and May 2016, BPH patients with renal transplants whose prostate volumes were less than 30 cm3 were treated surgically. Forty-seven patients received TURP and 32 received TUIP. The patients' age, duration of dialysis, duration between transplant and TURP/TUIP, preoperative and postoperative serum creatinine (SCr), International Prostate Symptom Score (IPSS), maximum flow rate (Qmax) and postvoidresidual volume (PVR) were recorded. At 1-,6- and 12-month follow-up, early and long-term complications were assessed. Results were evaluated retrospectively. RESULTS: In both groups, SCr, PVR and IPSS decreased significantly after the operation, while Qmax increased significantly (P < .001). There was no difference between the two groups in terms of increase in Qmax and decrease in IPSS, SCr and PVR (P = .89, P = .27, P = .08, and P = .27). Among postoperative complications, urinary tract infection (UTIs) and retrograde ejaculation (RE) rates were higher in the TURP group than the TUIP group (12.7% versus 6.2% and 68.1% versus 25%,respectively), whereas urethral strictures were more prevalent in the TUIP group (12.5% versus 6.3%). CONCLUSION: For the treatment of BPH in renal transplant patients with a prostate volume less than 30 cm3, bothTUIP and TURP are safe and effective.

Results of transurethral resection of the prostate in renal transplant recipients: a single center experience.

OBJECTIVES: The aim of this study was to retrospectively evaluate the early and long-term results of renal transplantation (RT) patients undergoing transurethral resection of the prostate (TURP) due to benign prostate hyperplasia (BPH). MATERIALS AND METHODS: Eighty-nine patients with RT performed in our hospital underwent TURP between November 2008 and March 2016. Results were evaluated along with early and long-term complications. Patients were followed up for a minimum of 12 months. RESULTS: The mean age of the patients was 61.4 ± 7.4 years. The median duration of dialysis was 28 (0-180) months. The median duration between transplantation and TURP was 13 (0-84) months. Before TURP, the mean serum creatinine (sCr) was 1.99 ± 0.83 mg/dL and the mean prostate volume was 33.3 ± 14.6 cm3. The mean Q max, Q ave and PVR values were 9.5 ± 3.7, 5.2 ± 2.2 ml/s and 85(5-480) mL, respectively. None of the patients developed perioperative and postoperative major complications. Twelve patients (13.4%) developed urinary tract infections in the postoperative period. The sCr, IPSS and PVR values significantly decreased, while Q max and Q ave significantly increased at the 1-month follow-up. At the 6-month follow-up, 63 (70.8%) patients had retrograde ejaculation. Patients were followed up for a median of 42 (12-96) months. Three patients (3.3%) were re-operated for bladder neck contracture and eight (8.9%) patients were re-operated for urethral stricture. CONCLUSION: TURP can be safely and successfully applied for the treatment of BPH after RT. LUTS and renal functions significantly improve after the operation. Patients should be followed up for UTIs in the short term and for urethral stricture in the long term.

Clinical SYNTAX Score Can Predict Acute Kidney Injury following On-Pump but Not Off-Pump Coronary Artery Bypass Surgery.

BACKGROUND: The complexity of coronary artery disease is usually a neglected factor in risk stratification systems. We aimed to analyze the discriminative ability of the clinical SYNTAX score (CSS) for acute kidney injury (AKI) following on- and off-pump coronary artery surgery. METHODS: A total of 193 patients were reviewed in this study. Patients were divided into two groups according to the surgical procedure (group I: off-pump coronary artery bypass grafting, n = 89; group II: on-pump coronary artery bypass grafting, n = 104). Preoperative demographic data, the CSS and postoperative renal functions were evaluated. The postoperative AKI classification was made using the RIFLE (Risk, Injury, Failure, Loss of function, and End-stage renal disease) criteria. RESULTS: Postoperative AKI occurred in 14 of 89 patients (15.7%) in group I and in 29 of 104 patients in group II (27.8%; p = 0.046). The CSS did not vary much between the groups (31.52 ± 13.08 vs. 29.89 ± 15.70; p = 0.638). In group I, the CSS was not different between patients with AKI and those without AKI (30.167 ± 3.93 vs. 31.91± 14.75; p = 0.78). In group II, the CSS was 36.85 ± 18.33 in patients with AKI and 28.02 ± 12.32 in those without, and the difference was significant (p = 0.02). The discriminative ability of the CSS for postoperative AKI using the AUC analysis was 0.500 in group I and 0.840 in group II. CONCLUSION: The CSS may be a simple and successful means of risk prediction of postoperative AKI in on-pump coronary artery surgery.

Effects of ivabradine on 6-minute walk test and quality of life in patients with previously implanted CRT-D.

BACKGROUND: We aimed to evaluate clinical effects of additional heart rate control by ivabradine on life quality score and 6-minute walking test in patients with previously implanted biventricular cardiac resynchronization therapy defibrillator (CRT-D) with ischemic heart failure under regular treatment. METHODS: Fifteen men and 14 women with a median age of 63 years (range, 48-79 years) were studied. Twenty-one patients were in New York Heart Association class II (8 patients were in class III), CRT-D implanted previously, and with resting heart rates greater than 70 beats per minute with sinus rhythm despite conventional medication. Patients were given 2.5- to 7.5-mg ivabradine orally twice a day, and drug dosage was titrated to decrease the patients' average heart rate to 70 beats per minute. Before and 3 months after ivabradine treatment, all patients underwent extensive clinical, echocardiographic, and laboratory evaluation. RESULTS: Ivabradine treatment produced dose-dependent reductions in heart rate at rest and at peak exercise (91.9 ± 6.3 to 71.7 ± 4.8 and 114.4 ± 7.6 to 96.8 ± 4.8; P = 0.001 and P = 0.001, respectively). There were also significant improvements in life quality score (52.4 ± 9.5 to 37.9±7.8; P = 0.001) and 6-minute walking distance (278.7 ± 85.8 to 373.3 ± 94.0; P = 0.001) of patients. All patients with New York Heart Association class III became class II after 3 months of ivabradine treatment. CONCLUSION: Heart rate reduction in a short-term period by ivabradine produced significant improvements in exercise capacity and life quality in patients with CRT-D and conventional therapy.

Use of peritoneal ultrafiltration in the elderly refractory congestive heart failure patients.

BACKGROUND: Refractory congestive heart failure (RCHF), due to its high mortality and hospitalization rates, is a growing health problem. In this study, as an alternative and/or supportive treatment to conventional medical therapies, we have evaluated the clinical value of peritoneal ultrafiltration, performed as a single daily exchange with icodextrin or conventional dextrose-based peritoneal dialysis solutions, in elderly patients with RCHF. METHODS: This was an observational study of 6 elderly patients with RCHF and non-terminal chronic kidney disease (CKD). Their mean age was 72.8 ± 4.9 years. Four of the six patients had NYHA class 4 and two had NYHA class 3 RCHF and a medical history of 18.6 ± 14.9 days/year hospitalization on average, due to decompensated congestive heart failure (CHF). Their baseline glomerular filtration rate, as calculated by the MDRD formula was 49.4 ± 14.6 mL/min/1.73 m(2). During hospitalization, patients were initially treated with several sessions of continuous veno-venous hemofiltration and, following the achievement of hemodynamic stabilization, peritoneal ultrafiltration was initiated as the maintenance ultrafiltration modality. Patients were followed up monthly in terms of their clinical status, hospitalization rates, weight changes, serum sodium levels, and renal function. Echocardiographic changes were also evaluated every 3 months. RESULTS: All patients tolerated peritoneal ultrafiltration well, their functional status improved by 1 or 2 NYHA classes to reach a mean of NYHA class 2 CHF status. During the follow-up period, with a mean daily ultrafiltration rate of 850 ± 176 mL, no hospitalization for decompensated CHF or acute renal failure was required. The patients' renal function was well preserved, with a mean GFR of 49 ± 14.6 mL/min/1.73 m(2) at baseline and 51.6 ± 22.9 mL/min/1.73 m(2) at the 6th month of the study. Additionally, their mean serum sodium levels increased from 128 ± 5.7 mEq/L to 138 ± 5 mEq/L. Echocardiographic evaluation did not show any significant changes during the observation period. No peritonitis or other non-infectious complication of chronic peritoneal dialysis was seen in any of the patients. CONCLUSIONS: Peritoneal ultrafiltration seems to be an efficient and safe procedure and a treatment of choice in elderly patients with RCHF without non-terminal CKD. Peritoneal ultrafiltration improves the quality of life and the effort capacity, and reduces hospitalization rates due to decompensated heart failure and acute renal failure.

Hemophagocytic syndrome in kidney transplant recipients: report of four cases from a single center.

BACKGROUND: The prognosis of hemophagocytic syndrome (HPS) in kidney transplant recipients is reported to be poor, however the optimal therapeutic approach is still unclear. PATIENTS AND METHODS: The clinical and follow-up data of the 4 patients with HPS (3 male, 1 female; age 39.7 +/- 11.3 years) among 368 kidney transplant recipients during a 5-year period were retrospectively analyzed. RESULTS: HPS developed 35-61 days in the post-transplant period. All 4 patients presented with fever. Hepatosplenomegaly and lymphadenopathy were observed only in the first patient. Laboratory tests revealed pancytopenia and hyperferritinemia in all patients, but elevated liver enzymes were observed in 3. Two patients had cytomegalovirus infection, and 1 had Epstein-Barr virus infection. Three patients died despite aggressive supportive therapy, however the fourth case survived after graft nephrectomy. CONCLUSION: HPS pathogenesis in kidney transplants appears to be related with the graft itself. Graft nephrectomy may be the preferable therapeutic approach for kidney transplant recipients with HPS resistant to standard supportive therapy.

Effect of renal transplantation on endothelial function in haemodialysis patients.

BACKGROUND: Haemodialysis patients (HD) have been characterized by a high incidence and prevalence of atherosclerotic cardiovascular disease. Based on the traditional cardiovascular risk factors in this population, we cannot explain this high incidence and prevalence. One of the mechanisms contributing to cardiovascular risk in HD patients may be to uraemic toxins. Cardiovascular risk factors and uraemic toxins themselves may cause endothelial dysfunction, which may play a pivotal role in the development and progression of atherosclerosis in this population. We hypothesized that elimination of uraemic toxins in response to renal transplantation (RTx) can improve endothelial function as assessed by flow-mediated dilatation of brachial artery in haemodialysis (HD) patients. METHODS: Endothelial function measured by flow-mediated dilatation of the brachial artery (FMD) and glyceryltrinitrate-induced dilatation of the brachial artery (NMD) were assessed twice, during haemodialysis treatment and after RTx in 30 chronic haemodialysis patients. All patients were characterized by absence of known atherosclerotic disease and traditional cardiovascular risk factors. We also studied age- and gender-matched 20 normotensive healthy controls. RESULTS: FMD values significantly improved after RTx (6.69+/-3.1% vs 10.50+/-3.0%, P<0.001) in HD patients. FMD of patients both during haemodialysis and after RTx was lower than in healthy controls (6.69+/-3.1%, 10.50+/-3.0% vs 14.02+/-2.3%, P<0.001 and P<0.01, respectively). There was no change in NMD values after RTx in HD patients (16.27+/-1.9% vs 16.30+/-1.8%, P>0.05). Also, NMD values in all patients were similar to healthy control values. CONCLUSIONS: There is an improvement of endothelial function as assessed by FMD of the brachial artery after RTx in HD patients. This may be attributed to the elimination of uraemic toxins by successful RTx.

Uremic toxins: a new focus on an old subject.

The uremic syndrome is characterized by an accumulation of uremic toxins due to inadequate kidney function. The European Uremic Toxin (EUTox) Work Group has listed 90 compounds considered to be uremic toxins. Sixty-eight have a molecular weight less than 500 Da, 12 exceed 12,000 Da, and 10 have a molecular weight between 500 and 12,000 Da. Twenty-five solutes (28%) are protein bound. The kinetics of urea removal is not representative of other molecules such as protein-bound solutes or the middle molecules, making Kt/V misleading. Clearances of urea, even in well-dialyzed patients, amount to only one-sixth of physiological clearance. In contrast to native kidney function, the removal of uremic toxins in dialysis is achieved by a one-step membrane-based process and is intermittent. The resulting sawtooth plasma concentrations of uremic toxins contrast with the continuous function of native kidneys, which provides constant solute clearances and mass removal rates. Our increasing knowledge of uremic toxins will help guide future treatment strategies to remove them.

Phosphate kinetics during different dialysis modalities.

BACKGROUND: An abnormal serum phosphate concentration is common in acute renal failure patients, with a reported incidence of 65-80%. Phosphate removal and kinetics during intermittent hemodialysis (IHD) have been investigated, but there is no information on its kinetics during slow low-efficiency dialysis (SLED) and continuous renal replacement therapy (CRRT). METHODS: Eight IHD, 8 SLED, and 10 continuous venovenous hemofiltration (CVVH) patients with a residual renal clearance of <4.0 ml/min were studied during a single treatment to evaluate phosphate removal and kinetics. CVVH was studied the first 24 h after initiation. Dialysis/replacement fluid contained no phosphate. Kt/V, clearance of urea (Ku), inorganic phosphate (Kp) and solute removal was determined by direct dialysate quantification (DDQ). RESULTS: Kp recorded with the three techniques were: IHD, 126.9 +/- 18.4 ml/min; SLED, 58.0 +/- 15.8 ml/min, and CVVH, 31.5 +/- 6.0 ml/min. However, in shorter dialysis treatment the total removal of phosphate was significantly lower than in longer dialysis (IHD, 29.9 +/- 7.7 mmol; SLED, 37.6 +/- 9.6 mmol; CVVH, 66.7 +/- 18.9 mmol, p = 0.001). The duration of treatment is the only factor determining phosphate removal (r = 0.7, p < 0.0001 by linear correlation model). Like IHD, phosphate kinetics during SLED could not be explained by the two-pool kinetic model, and the rebound of phosphate extended beyond 1 h after dialysis. Rebound, however, is less marked than in short dialysis. CONCLUSION: These results are reliable evidence about amount of phosphate removal and behavior of intradialytic phosphate kinetics in renal failure patients undergoing different dialysis modalities. These data will help clinicians plan phosphate supplementation and treatment intensity.

Protective effect of urate oxidase on uric acid induced-monocyte apoptosis.

Uremic patients have a higher risk of infection and malignancy than normal subjects. Previous studies have deomonstrated that monocytes isolated from uremic patients display an increased apoptosis rate compared to normal subjects; furthermore uremic plasma can increase apoptosis rates on U937, a human monocytic cell line. In several pathological conditions, precipitation of uric acid crystals can lead to renal insufficiency or acute renal failure by different mechanisms. In recent studies uric acid has been shown to induce inflammatory response from monocytes and it has been suggested to be involved in cell dysfunction. Rasburicase is a new recombinant urate oxidase developed to prevent and treat hyperuricaemia in patients with cancer or renal failure; it degrades uric acid to allantoin, a less toxic and more soluble product. In the present study, we aimed at determining whether uric acid may be a factor affecting U937 apoptosis, and whether urate oxidase may reduces or even prevent uric acid induced cell apoptosis. Hoechst staining and internucleosome ledder fragmentation of DNA showed that uric acid increased the percentage of apoptotic cells comparing to the control and that when the U937 cells were incubated with uric acid and urate oxidase the percentage of apoptosis significantly decreased (from 43+/-7% to 19+/- 3%, p<0.05). Also, the activity of caspase-8 and caspase-3 showed the same trend (caspase 3: from 2.7+/-0.53 to 1.6+/-0.42; caspase-8: from 2.2+/-0.43 to 1.3+/-0.57). A reduction of intracellular reduced glutathione (GSH) concentration was found in uric acid treated cells while the addition of urate oxidase in the uric acid incubated cells decreased the GSH extrusion. The concentration of TNF-alpha was increased in the sample incubated with uric acid comparing to the control. Uric acid is an inducer of apoptosis on U937 cell line, and therefore it may be a component of the mosaic of uremic toxins both in acute and chronic renal disease. We can hypothesize that uric acid might be directly involved in the apoptotic process trough the activation of both death receptor and mitochondrial-mediated pathways. We have, also, demonstrated that urate oxidase is able to prevent at least in part, the effect of uric acid on U937 apoptosis. This effect might be a result of different mechanisms of action.