Pharmacokinetics of cefamandole in patients undergoing hemodialysis and peritoneal dialysis

The pharmacokinetics of cefamandole nafate, a new parenteral cephalosporin derivative, were evaluated in 11 patients with chronic renal failure (creatinine clearance less than 5 ml/min), including five patients during hemodialysis, four patients during routine peritoneal dialysis, and two patients during the interdialytic period. Peak serum levels of cefamandole were comparable to those observed in patients with normal renal function. Clearance of the drug during the interdialytic period and during hemodialysis and peritoneal dialysis was minimal, with a resultant significant prolongation of serum half-life. The nondialyzability of cefamandole is in contrast with reported studies of cephalothin, where significant reduction of the serum half-life was achieved during hemodialysis but not peritoneal dialysis. The concentration of cefamandole in the peritoneal dialysate after parenteral administration was observed to be bactericidal for many gram-negative pathogens and, with the exception of Streptococcus faecalis, most gram-positive organisms found in bacterial peritonitis in patients with severe renal failure. The present data suggest that if stable bactericidal serum levels of cefamandole are to be maintained during hemodialysis and peritoneal dialysis, a parenteral loading dose must be administered followed by one-half the loading dose every half-life.     

A comparative study of the outcome of renal transplantation in peritoneal dialysis and hemodialysis patients

Fifty-four cases of renal transplantation performed in peritoneal dialysis (PD) patients were compared with 48 cases in hemodialysis (HD) patients. Three immunosuppressive treatments were used: prednisolone, azathioprine and cyclosporine. Methylprednisolone was used to treat rejection, and polyclonal Atgem or monoclonal OKT3 antibodies were used if there was no response. There was no difference in sex, age, donor source, immunosuppressive regime, duration of dialysis before transplantation, or duration of follow-up between the two groups. Following transplantation, there was no significant difference in patient mortality and survival or graft survival between the groups. The incidences of infections were also similar in the two groups. PD is commonly used in developing countries as an alternative to hemodialysis for the treatment of chronic renal failure. This study has shown that renal transplantation can be successfully performed in patients treated by this method.     

Stability of the peritoneal membrane in long-term peritoneal dialysis patients

It is now well established that the formation of free radicals and oxidative stress-induced neuronal cell death can be involved in various neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. The pineal hormone melatonin has been suggested to be a neuroprotective antioxidant. To better understand the molecular mechanism of this activity, we compared the ability of melatonin and its precursor, N-acetyl-serotonin (normelatonin), to protect human neuroblastoma SK-N-MC cells and primary cerebellar granular neurons against oxidative stress. We found that normelatonin and melatonin have differential neuroprotective effects depending on the neuronal cell type. Normelatonin was more protective against hydrogen peroxide (H2O2) and glutamate-induced cell death in SK-N-MC cells compared to melatonin which was more effective to protect primary cerebellar granular neurons against the toxicity of H2O2, glutamate and N-methyl-D-aspartate when compared to normelatonin. At the molecular level, we tested the capacity of normelatonin and melatonin to inhibit the oxidative stress-induced NF-kappaB activation in both neuronal systems. Whereas normelatonin was more potent in the suppression of the activation of NF-kappaB by H2O2 in SK-N-MC cells compared to melatonin, no apparent differences in the extent of suppression could be detected in primary neurons. Normelatonin's and melatonin's neuroprotective activity in SK-N-MC neuroblastoma cells may be mediated by the suppression of NF-kappaB activation.     

Pathophysiology of peritoneal fluid eosinophilia in peritoneal dialysis patients

This study deals with the stress distribution in concrete deck slabs on composite steel beams used with integral abutment bridges. The applied loading is composed of one or more side-by-side HS20-44 trucks. The finite-element method is used to analyze two bridge structures with different numbers of beams, beam spacings, and supporting piles. The transverse and longitudinal slab stresses in the deck slab are investigated in the positive and negative bending regions near and away from the integral abutment. The slab stresses in the integral abutment bridges are compared with the corresponding stresses induced in the slab of equivalent jointed bridges. The results indicate that integral abutment bridges distribute the loads in the deck slab more uniformly than their jointed counterparts. The maximum stresses in the transverse direction of the slab can be 25–50% lower in the integral bridges than in their corresponding simply supported ones.     

Augmenting solute clearance in peritoneal dialysis

BACKGROUND: The removal of low molecular weight solutes by peritoneal dialysis is less than by hemodialysis. The targets for Kt/Vurea and creatinine clearance formulated in the Dialysis Outcome Quality Initiative are unlikely to be achieved in a substantial portion of peritoneal dialysis patients. Possibilities to increase small solute clearances have therefore been subject to many investigations. METHODS: A review of the literature and of recent new data on determinants of solute removal, such as residual renal function, the role of drained dialysate volume and manipulation of the diffusive capacity of the peritoneum are presented. RESULTS: The contribution of residual GFR is more important for the clearance of creatinine than for Kt/Vurea. It is even more important for the removal of organic acids that are removed from the body by tubular secretion. High dosages of furosemide increase the urinary volume and the fractional Na+ excretion, but have no effect on the magnitude of residual GFR, renal creatinine clearance, renal urea clearance, and peritoneal transport characteristics. The drained dialysate volume per day is the main determinant of the peritoneal removal of urea. Its effect decreases the higher the molecular weight of a solute. It can be augmented by using large instillation volumes, by the application of more exchanges, and by increasing peritoneal ultrafiltration. A large exchange volume is especially effective in patients with an average transport state, but in those with high solute transport rates, Kt/Vurea is especially influenced by the number of exchanges. Possibilities to increase ultrafiltration are discussed. The diffusive capacity of the peritoneum can be augmented by using low dosages of intraperitoneally administered nitroprusside. This increases solute transport most markedly when it is applied in combination with icodextrin as osmotic agent. CONCLUSIONS: Small solutes clearances cannot be increased by furosemide. Increasing the instilled volume of dialysis fluid and the number of exchanges both affect solute clearance. Studies are necessary on long-term effects of manipulation of the peritoneal membrane with nitroprusside.     

Management of malnutrition in peritoneal dialysis

Peritoneal dialysis is associated with nutritional abnormalities due to peritoneal glucose absorption and protein or amino acid losses into the dialysate. Nutritional assessment, every four months, is essential, based on body composition, anthropometric measurements, clinical characteristics, biochemical parameters and dietary survey. Thus 1.2 g to 1.3 protein/kg/day and 30 to 35 kcal/kg/day energy intake may be required. Oral, parenteral or intraperitoneal amino acids supplementation can improve the nutritional status in peritoneal dialysis patients.     

Group work with patients on peritoneal dialysis

The patient in end-stage renal failure, whose life depends on an artificial kidney machine, must make major emotional and physical adjustments. The author describes how in-hospital group treatment can help these patients cope with their new life situation.     

Pharmacokinetics of gadodiamide injection in patients with severe renal insufficiency and patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis

RATIONALE AND OBJECTIVES: The authors performed this study to evaluate the pharmacokinetics, dialysability, and safety of gadodiamide injection in patients with severely reduced renal function not treated with renal replacement therapy and patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis. MATERIALS AND METHODS: Twenty-seven patients--nine with severely reduced renal function (glomerular filtration rate, 2-10 mL/min), nine undergoing hemodialysis, and nine undergoing continuous ambulatory peritoneal dialysis--were followed up for 5, 8, and 22 days, respectively, after receiving gadodiamide injection (0.1 mmol per kilogram body weight). RESULTS: Gadodiamide injection caused no changes in renal function. In patients with severely reduced renal function, the elimination half-life of gadodiamide injection was prolonged (34.3 hours +/- 22.9) compared with data in healthy volunteers (1.3 hours +/- 0.25). An average of 65% of the gadodiamide injected was eliminated during a hemodialysis session. After 22 days of continuous ambulatory peritoneal dialysis, 69% of the total amount of gadodiamide was excreted; this reflects the low peritoneal clearance. In all patients, no metabolism or transmetallation of gadodiamide was found. There were no contrast material-related adverse events. CONCLUSION: Gadodiamide is dialysable and can safely be used in patients with severely impaired renal function or those undergoing hemodialysis or continuous ambulatory peritoneal dialysis. No precautions to increase the elimination are necessary.     

Peritoneal dialysis. An adjunct to pediatric postcardiotomy fluid management

The need for structural grafting in rhinoplasty arises when the nasal skeletal framework is weakened, malpositioned, or both. This review will be limited to structural grafting of the cartilaginous nasal skeleton. Current techniques will be reviewed and a technique introduced that addresses the common deformity of a superiorly rotated and deprojected nasal tip complex while simultaneously correcting nasal valve collapse. This technique is referred to as the Dynamic Adjustable Rotational Tip (DART) technique. The operative technique of the DART, as well as the basic philosophy regarding the tensile nature of the cartilaginous nasal skeleton will be described.     

Bacteremia complicating peritonitis in peritoneal dialysis patients

Bacteremia is a rare complication of peritonitis in end-stage renal failure (ESRF) patients treated by peritoneal dialysis. Three of our ESRF patients on peritoneal dialysis developed bacteremia during a peritonitis episode (1/19 peritonitis episodes). In 2 cases, the responsible organism was Escherichia coli and peritonitis was most likely associated with infection of the biliary tract. The 3rd patient had a perforation of the colon and Klebsiella spp. was the infective organism. Only the last patient survived but had to be transferred to hemodialysis. Bacteremia during peritonitis is infrequent in peritoneal dialysis patients and it appears to be related to other intra-abdominal events.     

Peritonitis influences mortality in peritoneal dialysis patients

Mortality remains high in peritoneal dialysis (PD) patients. Known risk factors for mortality include age, diabetes, race, initial albumin level, and cardiovascular disease. Peritonitis is reported to cause death in 1 to 6% of PD patients but has not been well studied as a risk factor for mortality. This study examined 516 adults with a total of 896 yr on PD at one center to determine if peritonitis influenced mortality. Time at risk began on Day 1 of training and ended at death, transplant, or 60 days after transfer to hemodialysis or intermittent peritoneal dialysis. The overall mortality rate was 17.4/100 patient yr. Survival was lower for whites, men, diabetic patients, and older patients. Independent risk factors for mortality (by Cox proportional hazards) were race, diabetes, increased age, and increased peritonitis rate. Use of the Y-set was not associated with decreased mortality. Peritonitis was a risk factor only in whites, nondiabetic patients, and those patients over the age of 60. For every 0.5/yr increase in the peritonitis rate, the risk of death increased 10% in whites, 11% in those patients who were over the age of 60, and 4% for nondiabetic patients. Mortality rates did not decrease over time (1979 to 1995), although peritonitis rates fell significantly (P < 0.001). Rates of Gram-negative and fungal peritonitis showed no trend over time. Peritonitis contributed to 25 of 158 (15.8%) of deaths. Gram-negative/fungal peritonitis accounted for 14 deaths (9.5% of all Gram-negative/fungal episodes) whereas Staphylococcus epidermidis accounted for only 1 death (0.5% of all S. epidermidis episodes) (P < 0.001). Cardiovascular disease was more common in those patients whose deaths were unrelated to peritonitis (P < 0.01), whereas an infectious cause was more common in those patients whose deaths were peritonitis-related (P < 0.001). In this study, peritonitis was a risk factor for death in whites, nondiabetic patients, and older patients. However, the Y-set did not improve survival, perhaps because it does not decrease Gram-negative/fungal peritonitis. To have an impact on survival, efforts are needed to reduce the peritonitis that results from these more serious pathogens.     

Acid-base balance in chronic peritoneal dialysis patients

Endogenous acid production has never been measured directly in dialysis patients and an empiric formula is used to estimate acid production from their protein catabolic rate. We have studied acid-base balance in 19 stable CAPD patients attending the peritoneal dialysis clinic of Mount Sinai Hospital. They obtained a 24 hour collection of peritoneal dialysis fluid and urine while consuming their usual diet and performing their usual activities. Total alkali gain was calculated from net GI alkali absorption plus urinary net acid excretion plus alkali gain from dialysate, while total acid production was measured directly from the urinary and dialysate excretions of sulfate and organic anions. Net GI alkali absorption was estimated from the difference between cations (Na + K+Ca + Mg) and anions (Cl + 1.8P) in the 24 hour dialysate and urine collections minus the daily total amount of lactate infused. All of our patients had a normal or high serum bicarbonate concentration, which was stable with time. Total alkali gain was virtually identical to total acid production (54.2 vs. 52.4 mEq/day) which suggests that these patients were in neutral acid-base balance. Net GI alkali absorption (22.7 mEq/day) was one of the same range as that of chronic renal failure patients not on dialysis and represented almost one half of the total daily alkali gain. The daily acid production of 52.4 mEq/day was numerically equal to 84% of the protein catabolic rate expressed as g/day, which is similar to the predicted value of 77% of PCR reported in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevention of renal osteodystrophy in peritoneal dialysis

BACKGROUND: Renal osteodystrophy (ROD) is still one of the major long-term complications in end-stage renal disease leading to considerable morbidity. Despite some progress in understanding the pathogenesis of secondary hyperparathyroidism (sHPT) during recent years, prevention and treatment of ROD is still suboptimal, requiring surgical parathyroidectomy in 6 to 10% of all patients on dialysis after 10 years. In addition, the spectrum of bone lesions has changed, with non-aluminum-related adynamic bone disease (ABD) found in up to 43% of peritoneal dialysis (PD) patients. METHODS: Current recommendations concerning prevention of ROD in PD based on the literature and personal recent data were reviewed. The focus is on (i) the importance of early prophylactic intervention to prevent parathyroid gland hyperplasia, (ii) the pathogenesis of ABD, and (iii) the role of metabolic acidosis in ROD. RESULTS: There is ample evidence that sHPT starts early during the course of renal failure and results from both hypersecretion of PTH by parathyroid cells and glandular hyperplasia. As shown by experimental and clinical studies, established parathyroid cell hyperplasia is hardly reversible by pharmacological means, and therefore prevention of parathyroid cell proliferation needs to start early. Recent data from randomized trials document the efficacy and safety of low dose active vitamin D (0.125 to 0.25 microgram/day) and/or an oral calcium substitute to prevent progression of sHPT in patients with mild to moderate renal failure. Since little is known about the pathogenesis, natural course and clinical impact of ABD in PD, specific therapeutic concepts have not yet been generated. Diabetes and advanced age are established risk factors, whereas the role of calcium and vitamin D overtreatment or the type of dialysis (PD vs. HD) are still controversial. Currently no evidence for different functional behavior of the parathyroids in ABD and sHPT has been found. The role of circulating or local factors such as cytokines, growth factors or the presence of advanced glycation end-product (AGE)-modified matrix proteins for the pathogenesis of either type of ROD deserves further investigation. Avoiding oversuppression of parathyroid gland and the use of low calcium dialysate may help prevent ABD. There is growing evidence that a correction of metabolic acidosis will influence ROD by both direct effects on the bone and on parathyroid cell function. New dialysate composition for CAPD with a high HCO3 concentration will allow normalization of acid-based metabolism in PD patients. Their effects on ROD under long term conditions remain to be determined. CONCLUSION: Therapeutic efforts should aim to prevent the development of parathyroid gland hyperplasia and sHPT early during the course of renal failure, and should include the use of low dose vitamin D therapy and oral calcium substitution as well as correction of metabolic acidosis. Concerning ABD, more information is needed regarding the causes and consequences of this type of bone lesion to develop a more specific therapy.     

Biocompatibility and buffers: effect of bicarbonate-buffered peritoneal dialysis fluids on peritoneal cell function

BACKGROUND: Conventional peritoneal dialysis fluids (PDF) have been shown to compromise the function of both leukocytes and human peritoneal mesothelial cells (HPMC). Various in vitro studies have identified the low initial pH in combination with high lactate content, as well as the hyperosmolality and high glucose concentration present in currently used solutions as the primary determinants of their bioincompatibility. Bicarbonate buffered PDF (at neutral pH) display improved in vitro biocompatibility as compared to conventional, lactate buffered PDF. However, little information is currently available regarding the potential impact of PDF on the function of human peritoneal fibroblasts (HPFB), the major cell population present in peritoneal interstitium. METHODS: The current study compares the effect of bicarbonate and lactate buffered PDF in a model system of resting peritoneal mesothelial cells and fibroblasts cultured from human omentum. Interleukin-1 beta-stimulated IL-6 release from HPMC and HPFB was used as the cell functional parameter. RESULTS: While short (30 min) pre-exposure to lactate buffered PDF significantly reduced the IL-1 beta-stimulated IL-6 release from HPMC during a subsequent recovery period (24 hr), a significant decrease in HPMC IL-6 secretion with bicarbonate buffered PDF was only observed after prolonged (> or = 60 min) exposure. In contrast, no significant IL-6 inhibition was detected with HPFB pre-exposed to PDF for up to 90 minutes. A significant suppression of HPFB IL-6 secretion was only observed in coincubation experiments (24 hr) with dilutions of both types of PDF. CONCLUSIONS: These results indicate that (i) bicarbonate buffered PDF are less inhibitory to peritoneal cell function as compared to conventional, lactate buffered PDF; and (ii) HPFB may be more resistant than HPMC to bioincompatible PDF.