Fevzi Ersoy

Laparoscopic omental fixation technique versus open surgical placement of peritoneal dialysis catheters.

Background: 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 outflow obstruction and dialysis leak. Omental wrapping is the most common cause of mechanical problems. The purpose of this study was to determine the efficacy of the laparoscopic omental fixation technique to prevent the obstruction caused by omental wrapping and also to compare this laparoscopic technique with open peritoneal dialysis catheter insertion with respect to postoperative discomfort, complication rates, and catheter survival. Methods: Between March 1998 and October 2001, 42 double-cuff, curled-end CAPD catheters were placed in 42 patients. The outcomes of the 21 patients in whom the PD catheters were placed laparoscopically with omental fixation technique were compared with those of the 21 patients in whom the catheters were placed with open surgical technique. Recorded data included patient demographics, catheter implantation method, early and late complications, catheter survival, and catheter outcome. Results: Early peritonitis episodes occurred in 8 of 21 patients (38.0%) in the open surgical group (OSG) versus 2 of 21 patients (9.5%) in the laparoscopic omental fixation group (LOFG) (p < 0.05); late peritonitis episodes occurred in 3 of 21 patients (14.2%) in the OSG versus 1 of 21 patients (4.7%) in the LOFG (p < 0.05). Early exit site infection occurred in 8 of 21 patients (38.0%) in the OSG versus 4 of 21 patients (19.0%) in the LOFG (p < 0.05), with many catheter-related problems in the conventional surgical group. There was no outflow obstruction in the LOFG. The conventional procedure was faster than the laparoscopic omental fixation technique. Analgesic requirements and hospital stay were less in the laparoscopic group. Laparoscopic surgery also enabled diagnosis of intraabdominal pathologies and treatment of the accompanying surgical problems during the same operation. Occult inguinal hernia was diagnosed in 2 patients, inguinal hernioplasty was performed in 4 patients, adhesiolysis was performed in 8 patients who had previous abdominal surgery, and liver biopsy was taken in 2 patients. Ovarian cystectomy was performed in another patient during laparoscopic CAPD catheter placement. Conclusion: The laparoscopic omental fixation technique (described by Öğünç and published in 1999) is a highly effective and successful method for preventing obstruction due to omental wrapping with a better catheter survival. Laparoscopic surgery also allows the diagnosis and treatment of the accompanying surgical pathologies during the same operation.

Osteoporosis in the elderly with chronic kidney disease.

Considering the aging dialysis population of today, increasing our knowledge about the nature, diagnosis and the treatment of bone mineral density (BMD) problems in end-stage renal disease (ESRD) patients deserves more attention. Osteoporosis is basicly defined as a decrease in bone mass. Large epidemiological studies in general population have identified several risk factors for osteoporosis including advancing age, female gender, white race, decreased calcium intake, gastric acid suppression therapy, sedentary lifestyle, premature loss of gonadal function, decreased estrogen secretion, thin body habitus, decreased physical activity, cigarette smoking, alcohol abuse, excess glucocorticoid exposure, and possibly some genetic factors. Osteoporosis in ESRD patients is only a part of a wider spectrum of metabolic bone problems, namely uremic osteodystrophy. Therefore, its diagnosis, management and follow-up may differ from the general population and an individualization of diagnosis and definition for dialysis population may be necessary. However, standard diagnostic tools such as dual energy X-ray absorptiometry (DEXA) have been widely used for the assesment of bone mineral deficiency status in ESRD patients. Regardless of the methods, most of the studies are in concordance with a reduced BMD in HD and PD patients. Dialysis patients are known to be at increased risk for low-trauma fractures. Thinning of cortical bone, which is responsible for the largest contribution toward reduced bone mineral content in chronic renal failure results in increased fracture risk. In either normal population and dialysis patients, fracture risk is increased with age. But in dialysis patients, besides age, several other factors may also affect the degree of bone mineral deficiency, and age-BMD relationship may be blunted. Female sex, in hemodialysis patients is negatively associated with total hip BMD. While several studies have been unable to demonstrate any association between BMD and PTH levels, larger body size has been shown to have a significant positive effect on BMD in both hemodialysis and peritoneal dialysis patients. Although they have been used in small groups of chronic kidney disease (CKD) and ESRD patients, because of their potential nephrotoxicity and hypocalcemic effects, use of biphosphonates in renal patients is questionable. Currently, bone biopsy, in order to exclude adynamic bone disease is recommended before beginning treatment with bisphosphonates in chronic kidney disease and dialysis patients.

Advanced oxidative protein products are independently associated with endothelial function in peritoneal dialysis patients

Aim:  Oxidative stress (OS) and asymmetric dimethylarginine (ADMA) are accepted as non‐classical cardiovascular risk factors in end‐stage renal disease patients. To clarify the role of these factors in the atherosclerotic process, we investigated if OS and ADMA are associated with endothelial function (EF) in peritoneal dialysis (PD) patients.

Reviews: 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.

Oxidative Stress and Asymmetric Dimethylarginine Is Independently Associated with Carotid Intima Media Thickness in Peritoneal Dialysis Patients

Backgrounds: Oxidative stress (OS) and asymmetric dimethylarginine (ADMA) are accepted as nonclassical cardiovascular risk factors in end-stage renal disease patients. To clarify the role of these factors in the atherosclerotic process, we investigated if OS and ADMA are associated with common carotid artery intima media thickness (CIMT) in peritoneal dialysis (PD) patients. Methods: Thirty PD patients without known atherosclerotic disease and classical cardiovascular risk factors as well as age- and gender-matched 30 healthy individuals were included. We measured serum thiobarbituric acid-reactive substances (TBARS), malondialdehyde (MDA), advanced glycation end product (AGE), pentosidine, advanced oxidation protein products (AOPP), ADMA and CIMT in each subjects. Results: TBARS, MDA, AOPP, AGE, pentosidine and ADMA levels were significantly higher in PD patients than in controls (p < 0.001). CIMT in patients was higher than in the control group (0.83 ± 0.09 vs. 0.77 ± 0.06 mm; p < 0.01). CIMT was independently correlated with TBARS (β = 0.33, p < 0.01), MDA (β = 0.27, p < 0.01), AOPP (β = 0.22, p < 0.02), AGE (β = 0.45, p < 0.01), pentosidine (β = 0.56, p < 0.01) and ADMA (β = 0.54, p < 0.01). Conclusions: OS markers and serum ADMA levels independently predict the CIMT level in PD patients.

Phosphorus control in peritoneal dialysis patients

Hyperphosphatemia is independently associated with an increased risk of death among dialysis patients. In this study, we have assessed the status of phosphate control and its clinical and laboratory associations in a large international group of patients on chronic peritoneal dialysis (PD) treatment. This cross-sectional multicenter study was carried out in 24 centers in three different countries (Canada, Greece, and Turkey) among 530 PD patients (235 women, 295 men) with a mean+/-s.d. age of 55+/-16 years and mean duration of PD of 33+/-25 months. Serum calcium (Ca(2+)), ionized Ca(2+), phosphate, intact parathyroid hormone (iPTH), 25-hydroxy vitamin D(3), 1,25-dihydroxy vitamin D(3), total alkaline phosphatase, and bone alkaline phosphatase concentrations were investigated, along with adequacy parameters such as Kt/V, weekly creatinine clearance, and daily urine output. Mean Kt/V was 2.3+/-0.65, weekly creatinine clearance 78.5+/-76.6 l, and daily urine output 550+/-603 ml day(-1). Fifty-five percent of patients had a urine volume of <400 ml day(-1). Mean serum phosphorus level was 4.9+/-1.3 mg per 100 ml, serum Ca(2+) 9.4+/-1.07 mg per 100 ml, iPTH 267+/-356 pg ml(-1), ionized Ca(2+) 1.08+/-0.32 mg per 100 ml, calcium phosphorus (Ca x P) product 39+/-19 mg(2)dl(-2), 25(OH)D(3) 8.3+/-9.3 ng ml(-1), 1,25(OH)(2)D(3) 9.7+/-6.7 pg ml(-1), total alkaline phosphatase 170+/-178 U l(-1), and bone alkaline phosphatase 71+/-108 U l(-1). While 14% of patients were hypophosphatemic, with a serum phosphorus level lower than 3.5 mg per 100 ml, most patients (307 patients, 58%) had a serum phosphate level between 3.5 and 5.5 mg per 100 ml. Serum phosphorus level was 5.5 mg per 100 ml or greater in 28% (149) of patients. Serum Ca(2+) level was > or =9.5 mg per 100 ml in 250 patients (49%), between 8.5 and 9.5 mg per 100 ml in 214 patients (40%), and lower than 8.5 mg per 100 ml in 66 patients (12%). Ca x P product was >55 mg(2)dl(-2) in 136 patients (26%) and lower than 55 mg(2)dl(-2) in 394 patients (74%). Serum phosphorus levels were positively correlated with serum albumin (P<0.027) and iPTH (P=0.001), and negatively correlated with age (P<0.033). Serum phosphorus was also statistically different (P = 0.013) in the older age group (>65 years) compared to younger patients; mean levels were 5.1+/-1.4 and 4.5+/-1.1 mg per 100 ml, respectively, in the two groups. In our study, among 530 PD patients, accepted uremic-normal limits of serum phosphorus control was achieved in 58%, Ca x P in 73%, serum Ca(2+) in 53%, and iPTH levels in 24% of subjects. Our results show that chronic PD, when combined with dietary measures and use of phosphate binders, is associated with satisfactory serum phosphorus control in the majority of patients.

Effects of Different Dialysis Modalities on Cardiac Autonomic Dysfunctions in End-Stage Renal Disease Patients: One Year Prospective Study

Cardiac autonomic dysfunction (CAD) is a common problem in patients with end‐stage renal disease (ESRD) and may contribute to the risk of cardiac mortality. Long‐term effects of dialysis modalities on CAD in ESRD patients are not clear. In this one‐year prospective study, we studied the effects of different dialysis modalities on CAD in ESRD patients. The study consisted of 20 ESRD patients who had the indications for initiating dialysis therapy (13 hemodialysis and 7 CAPD patients) and 15 healthy controls (M/F: 5/10; age 30 ± 4). In all the subjects, first at the beginning of study (in patient groups just before initiating dialysis therapy) and then after 12 months, we studied 24 hours ECG‐Holter monitoring and heart rate variability parameters (time and frequency domain analysis parameters; SDNN: standard deviations of nn intervals, rMSSD: square root of the median of standard deviation, HRVI: heart rate variability index, LF/HF: low frequency/high frequency). In ESRD patients, before dialysis therapy, all the parameters of time domain analysis were significantly lower compared to control group (p = 0.001). In patient groups, after dialysis therapy (on the 12th month), significant improvement was observed in time domain analysis parameters (p = 0.001). When dialysis modalities were compared, the increase in the time domain analysis parameters was significantly greater in the CAPD group compared to hemodialysis (HD) group. Our findings suggest that CAD is frequent in ESRD patients, a dialysis therapy of 12 months can cause significant improvement on CAD and the ameliorative effect of CAPD is better than HD.

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.

The cost effectiveness of mycophenolate mofetil in the first year after living related renal transplantation.

REJECTION of transplanted organs results from the ability of lymphocytes to proliferate for the destruction of foreign tissue. Like all human somatic cells, lymphocytes proliferate by mitotic division and need purine and pyrimidine nucleotides for DNA synthesis. There are two major pathways in purine nucleotide synthesis: the de novo pathway and the salvage pathway. Most of human cell types can use salvage pathway for the proliferation if de novo synthesis is blocked; whereas, T and B lymphocytes depend mainly on de novo pathway. Mycophenolate Mofetil (MMF) selectively inhibits the proliferation of T and B lymphocytes because it acts as a reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), a rate limiting enzyme in the de novo pathway of guanosine nucleotide synthesis. Depletion of guanosine nucleotides with MMF results in impaired DNA synthesis and exerts antiproliferative effect. Since lymphocytes rely on de novo purine synthesis, this antiproliferative effect is selectively on lymphocytes. It is different from azathioprine because of its selective antiproliferative effect on lymphocytes. MMF has also two other effects on immune response: It suppresses antibody formation by B lymphocytes and inhibits the glycosylation of lymphocyte and monocyte glycoproteins. In some studies, MMF, in combination with corticosteroids and cyclosporine, reduced the incidence of renal allograft rejection within the first 6 months after transplantation when compared with triple drug protocols with azathioprine (AZA). In this study, we assessed the cost effectiveness of triple immunosuppressive regimen including MMF in the first year after living related renal transplantation.

Impact of chronic renal failure and peritoneal dialysis fluids on advanced glycation end product and iNOS levels in penile tissue: an experimental study

OBJECTIVES To investigate the impact of chronic renal failure (CRF) on advanced glycation end product and inducible nitric oxide synthase (iNOS) in penile tissue, we examined the advanced glycation end product 5-hydroxy methyl furfural (5-HMF) content and iNOS expression in rats in which uremia had been produced by greater than 85% nephrectomy. In addition, the contribution of peritoneal dialysis (PD) fluids to the elevation of penile tissue 5-HMF levels and iNOS staining scores has been investigated. METHODS Adult male Wistar rats, aged between 10 and 12 weeks and weighing 200 to 330 g, were divided into five groups that each included 6 animals. The first group served as a control group. In the second group, CRF was induced and a peritoneal catheter was implanted, but PD was not performed. In group 3, CRF was induced and PD was performed using dialysis fluids containing 1.36% glucose and icodextrin. In group 4, CRF was also induced and PD was performed using 3.86% glucose and icodextrin. Finally, in group 5, without CRF, an indwelling catheter was implanted, and the PD procedure was performed using dialysis fluids containing 3.86% glucose and icodextrin. RESULTS The elevation in 5-HMF levels and iNOS staining scores in penile tissue from groups 2, 3, 4, and 5 was significant compared with group 1 (P <0.05). The elevation in 5-HMF levels and iNOS staining scores was also significant between groups 2 and 3, 2 and 4, 3 and 4, 3 and 5, and 4 and 5 (P <0.05). Moreover, the correlation between the 5-HMF levels and iNOS staining scores was statistically significant (r = 0.525, P = 0.003). CONCLUSIONS In the present experimental study, we found that 5-HMF levels and iNOS staining scores were significantly elevated in rat penile tissue in which uremia had been produced compared with the groups without CRF. Additionally, PD fluids containing glucose had an effect on the elevation of penile tissue 5-HMF levels and iNOS staining scores.