
Introduction
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Protein glycation adducts, early glycation adducts, such as N∊-fructosyl-lysine, and advanced glycation end products (AGEs) are uremic toxins. Glycation adducts are found in plasma and tissue proteins (glycation adduct residues), in peptides (glycation adduct peptide residues), and glycated amino acids (glycation free adducts). The latter two analyte groups arise from proteolysis of glycated proteins and glycation of peptides and amino acids. Quantitation of glycation adducts in uremia is difficult because of the presence of many different AGEs at low concentrations in different forms in the presence of many potential interferences. Application of liquid chromatography with tandem mass spectrometric (LC-MS/MS) detection to plasma, urine, and dialysate samples of uremic patients has provided a comprehensive and quantitative analysis of glycation adducts in uremia. Glycation free adducts accumulate markedly in the plasma of uremic patients and are eliminated in the peritoneal dialysate. Multiple glycation adducts, and also protein oxidation and nitration adducts, may be quantified concurrently. Glycation free adducts are the major form of glycation adduct eliminated in dialysate. LC-MS/MS may now be used to quantify concentrations, extents of protein modification, clearances, and excretion rates of glycation adducts in uremia.





Continuous ambulatory peritoneal dialysis (CAPD) is an effective form of treatment for patients with end-stage renal disease. Open insertion of peritoneal dialysis (PD) catheters is the standard surgical technique, but it is associated with a relatively high incidence of catheter-related problems. To overcome these problems, different laparoscopic techniques have been presented, being preferable to the open and percutaneous methods.
To introduce and evaluate the efficiency of laparoscopic omental fixation and extraperitoneal placement of the cuff–coil part (the straight portion) of the catheter to prevent catheter tip migration, pericatheter leakage, severe abdominal pain, and the obstruction caused by omental wrapping.
The study was carried out in the General Surgery Department, Akdeniz University Medical School, in Turkey.
Between November 2001 and March 2005, the technique was applied in 44 consecutive patients (mean age 51.6 years, range 18 – 67 years) with end-stage renal disease. During this laparoscopic technique, the omentum was first fixed onto the parietal peritoneum, and then the catheter was introduced through the subumbilical trocar site into the posterior rectus compartment and advanced toward the symphysis pubis. The catheter was then inserted into the abdominal cavity, passing the peritoneal opening, which was prepared before catheter insertion. The straight portion of the catheter was located into the extraperitoneal area of the anterior abdominal wall. The curled end, which contains the side-holes of the catheter, was placed into the true pelvis. Catheter position and patency were verified under direct vision using a 2 mm telescope.
All procedures were completed laparoscopically. Operating time ranged between 40 and 100 minutes (median 52 minutes). There was no intraoperative complication or surgical mortality. Peritoneal dialysis was initiated within 15 – 24 hours after catheter implantation. After a median follow-up period of 17.4 months (range 1 – 38 months), early exit-site infection occurred in 1 of 44 patients. All catheters functioned well postoperatively. There was no pain during CAPD.
This new laparoscopic technique using an extraperitoneal approach with omentopexy for PD catheter placement could prove extremely useful for preventing catheter malfunction caused by catheter tip migration, pericatheter leakage, omental wrapping, and periodic catheter movement that causes abdominal pain in CAPD.
The ideal method for inserting continuous ambulatory peritoneal dialysis (PD) catheters remains debatable. Minimally invasive techniques are becoming more popular. The routine recommendation for starting PD is 4 – 6 weeks after catheter insertion. We planned a prospective study to evaluate whether this waiting period is necessary. From January 2003 to July 2004, 42 double-cuff Tenckhoff CAPD catheters were inserted into 41 patients. Percutaneous technique was used and PD was started on the sixth day. Only 2 pericatheter leakages (4.8%) were detected. This procedure is comparatively safe, simple, and less costly than surgical and peritoneoscopic placement. The rate of early pericatheter leakage may be lowered with this technique and PD may be started earlier.
Patients on continuous ambulatory peritoneal dialysis (CAPD) with
We retrospectively reviewed the short- and long-term outcomes of all CAPD patients who had undergone simultaneous removal and reinsertion of their PDC for the treatment of refractory
Over a 10-year period, 37 CAPD patients underwent the operation. Mean age of the patients was 59.5 ± 10.9 years. The interval between the diagnosis of ESI and the operation was 16.7 ± 6.9 weeks. The patients received 7.6 ± 2.5 weeks of antibiotic treatment before the procedure. Early postoperative complications were uncommon. None of the patients developed ESI within 4 weeks after the operation. At 1 year after the operation, 3 patients (8%) had developed recurrence of
We conclude that simultaneous removal and reinsertion of the PDC is feasible in eradicating refractory ESI due to
Although subcutaneous administration of recombinant human erythropoietin (rHuEPO) in continuous ambulatory peritoneal dialysis (CAPD) patients is a widely accepted recommendation, the lowest possible frequency of an efficient dosing regimen remains controversial. Darbepoetin alpha, a new erythropoiesis-stimulating protein with a threefold longer serum half-life compared with rHuEPO, has greater
In this single-center, prospective cohort study, 11 stable CAPD patients (5 males, 6 females; mean age 68.8 ± 14.1 years; mean duration on peritoneal dialysis 31.6 ± 13 months) maintained average hemoglobin and hematocrit levels of 12.09 ± 1.29 g/dL and 37.29% ± 3.58%, respectively, while receiving a mean weekly maintenance dose of epoetin alfa of 129 IU/kg. These same patients were assigned to receive the equivalent weekly darbepoetin dose once monthly for 24 consecutive weeks. Hematological response, iron status (transferrin saturation, serum ferritin levels), C-reactive protein (CRP), and the patients’ biochemical profiles were evaluated monthly.
During the monthly administration of darbepoetin, mean serum levels of Hb and Hct were 12.17 ± 1.28 g/dL and 37.1% ± 1.19% respectively. No statistically significant difference was apparent between the previous and monthly dosing values (12.09 ± 1.29 vs 12.17 ± 1.28 g/dL,
These results indicate that darbepoetin alfa can be effectively given subcutaneously at monthly intervals for the treatment of anemia in stable CAPD patients. However, more studies are needed to validate the long-term efficacy of this monthly subcutaneous administration.
It is well known that injection of calcitriol (CT) or maxacalcitol (OCT) is very effective in hemodialysis patients with secondary hyperparathyroidism (2HPT). However, it is difficult to use these drugs with peritoneal dialysis (PD) patients with 2HPT because these drugs must be injected two or three times per week. The objective of the present study was to evaluate the stability of physiological activities of CT and OCT in PD bags and to determine the CT or OCT dosage for intraperitoneal (IP) administration.
We added CT 1.5 μg or OCT 10 μg to Dianeal PD-2 (approximate pH = 5.0, calcium = 0.87 mmol/L; Baxter, Tokyo, Japan), Midpeliq 250 (approximate pH = 7.0, Ca = 1.0 mmol/L; Terumo Corporation, Tokyo, Japan), and Peritoliq 250 (approximate pH = 5.5, Ca = 1.0 mmol/L; Terumo Corp.). Dialysis solutions were collected from the PD bags at 0, 1, 4, 8, 12, 24, 48, and 72 hours after addition of CT and OCT. The activities of CT and OCT in the dialysis effluent were measured by radioimmunoassay. The levels of serum and effluent OCT after a single IP administration of 10 μg OCT were examined in 4 PD patients with advanced 2HPT.
Although the levels of CT and OCT in PD bags made of polyvinyl resins decreased by 70% – 75% immediately after injection, levels in PD bags made of polypropylene resins decreased only slightly. The concentration of CT mixed into the acidic solution in glass containers was stable; the decreased concentration of CT in the PD solution might be due to adsorption onto polyvinyl resins. The maximum serum concentration after IP administration of 10 μg OCT was 750 pg/mL after 5 minutes, and remained at 500 pg/mL at 60 minutes. These results show good peritoneal transport of OCT but not rapid disappearance, unlike intravenous administration.
If peritoneal administration of vitamin D derivatives is contemplated, it is important to select the composition of PD bag resins, type of vitamin D analog, and time lag to use when deciding the dosage of injectable vitamin D preparations, such as OCT or CT, for IP administration to PD patients. It appears that IP administration in overnight dwells might be useful for PD patients as a complementary vitamin D preparation.
Several intraperitoneally administered drugs have been shown to modify transport of peritoneal solute and fluid. Fewer studies, however, have evaluated the effect of orally administered drugs. The present study was performed to evaluate the effects of oral losartan, prazosin, and verapamil on peritoneal membrane transport during a peritoneal equilibration test (PET), as well as the effects on creatinine clearance (CrCl), Kt/V urea, 24-hour protein in drained dialysate, and drained volume.
This was an open, controlled, crossover clinical trial performed in 20 patients on continuous ambulatory peritoneal dialysis. All subjects used four 2-L 1.5% glucose dialysis exchanges per day. After a 7-day washout period (without antihypertensives), they had a baseline standard PET and dialysis adequacy assessment performed. Subsequently, they were randomly allocated to receive the first of three study drugs (losartan, prazosin, and verapamil), which were administered orally for a 7-day period. Immediately after each drug period, patients had a new 3-day washout and subsequently started the next drug, until they had received each of the three drugs. On the last day of administration of each drug, patients were subjected to a new PET and adequacy of dialysis evaluation.
None of the studied drugs significantly modified the peritoneal transport of creatinine, glucose, urea, sodium, potassium, or total protein as evaluated by PET. Verapamil significantly increased peritoneal CrCl [51.3 (44.3 – 53.3) vs baseline 45.8 (41.4 – 50.5) L/week/1.73 m2,
Oral administration of losartan, prazosin, and verapamil did not modify the peritoneal transport of solutes during a 4-hour PET. Oral verapamil significantly increased CrCl, Kt/V urea, and 24-hour drained dialysate volume. It is most likely that verapamil increases peritoneal (hydraulic) conductivity, and then net ultrafiltration volume and convective transport of urea, creatinine, and protein. Verapamil could be considered as an alternative in patients requiring increased dialysis dose and/or ultrafiltration.
During heat sterilization and during prolonged storage, glucose in peritoneal dialysis fluids (PDF) degrades to carbonyl compounds commonly known as glucose degradation products (GDPs). Of these, 3,4-dideoxyglucosone-3-ene (3,4-DGE) is the most cytotoxic. It is an intermediate in degradation between 3-deoxyglucosone (3-DG) and 5-hydroxymethyl-2-furaldehyde (5-HMF). We have earlier reported that there seems to be equilibrium between these GDPs in PDF. The aim of the present study was to investigate details of this equilibrium.
Aqueous solutions of pure 3-DG, 3,4-DGE, and 5-HMF were incubated at 40°C for 40 days. Conventional and low-GDP fluids were incubated at various temperatures for up to 3 weeks. Formaldehyde, acetaldehyde, glyoxal, methylglyoxal, 3-DG, 3,4-DGE, and 5-HMF were analyzed using high performance liquid chromatography.
Incubation of 100 μmol/L 3,4-DGE resulted in the production of 36 μmol/L 3-DG, 4 μmol/L 5-HMF, and 40 μmol/L unidentified substances. With the same incubation, 200 μmol/L 3-DG was converted to 9 μmol/L 3,4-DGE, 6 μmol/L 5-HMF, and 14 μmol/L unidentified substances. By contrast, 100 μmol/L 5-HMF was uninfluenced by incubation. In a conventional PDF incubated at 60°C for 1 day, the 3,4-DGE concentration increased from 14 to a maximum of 49 μmol/L. When the fluids were returned to room temperature, the concentration decreased but did not reach original values until after 40 days. In a low GDP fluid, 3,4-DGE increased and decreased in the same manner as in the conventional fluid but reached a maximum of only 0.8 μmol/L.
Considerable amounts of 3,4-DGE may be recruited by increases in temperature in conventional PDFs. Lowering the temperature will again reduce the concentration but much more time will be needed. Precursors for 3,4-DGE recruitment are most probably 3-DG and the enol 3-deoxyaldose-2-ene, but not 5-HMF. Considering the ease at which 3,4-DGE is recruited from its pool of precursors and the difficulty of getting rid of it again, one should be extremely careful with the temperatures conventional PDFs are exposed to.
Standard peritoneal glucose solutions may induce the formation of advanced glycation end products (AGEs). Preliminary data suggest that AGE formation may be less with the use of polyglucose solutions (icodextrin). Therefore, we investigated whether the use of icodextrin for the long dwell would result in a reduction in plasma and dialysate levels of the AGE products N∊-(carboxymethyl) lysine (CML) and N∊-(carboxyethyl)lysine (CEL).
40 patients were randomized to treatment with standard glucose solutions (1.36%) and icodextrin for the long dwell during a 4-month study period; 32 patients completed the study. CML was assessed by stable isotope dilution/tandem mass spectrometry.
CML levels in plasma increased significantly in patients treated with icodextrin (0.146 ± 0.056 at start vs 0.188 ± 0.069 μmol/mmol Lys at the end of the study,
Contrary to the hypothesis, plasma and dialysate levels of CML increased in patients treated using icodextrin for the long dwell.
The aim of this study was to evaluate hepatic subcapsular steatosis (HSS) and its association with clinical parameters in nondiabetic continuous ambulatory peritoneal dialysis (CAPD) patients and in diabetic CAPD patients receiving intraperitoneal (IP) or subcutaneous (SC) insulin.
Cross-sectional study.
A tertiary-care university hospital.
28 CAPD patients (17 males and 11 females; mean age 53.5 ± 14 years; mean CAPD duration 22.8 ± 9 months) were included in the study. 14 patients had type II diabetes mellitus and 14 were nondiabetics. In the diabetic group, 8 patients were receiving IP insulin and 6 were receiving SC insulin.
HSS was diagnosed on computed tomography without contrast administration. Other data collected were body mass index (BMI), weekly Kt/V, peritoneal equilibration test (PET) results, daily insulin dosage, duration of diabetes mellitus, duration of insulin treatment, dialysate glucose load, and serum findings for alanine aminotransferase, aspartate aminotransferase, albumin, and lipid profiles.
HSS was detected in 5 of the 8 diabetics who were receiving IP insulin. None of the diabetics receiving SC insulin and none of the nondiabetic patients exhibited HSS. Daily insulin dosage [108 (95 – 108.5) vs 54 (36 – 72) U/day,
Our results suggest that IP insulin plays a more important role in the pathogenesis of HSS than glucose levels in diabetic CAPD patients. They also indicate that HSS is associated with higher daily insulin requirement, obesity, hypertriglyceridemia, and high peritoneal transport rate in diabetic CAPD patients receiving IP insulin.





