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.     

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.     

Dialysis in the treatment of renal failure in patients with liver disease

The value and effects of treating renal failure by dialysis are analyzed in a series of 84 patients with various types of liver disease. Although none of the 25 patients with cirrhosis survived, six of 50 with fulminant hepatic failure recovered completely as did seven of nine patients with renal failure secondary to extrahepatic biliary tract obstruction or with liver and renal damage following episodes of severe hypotension. Dialysis was required for seven weeks before diuresis occurred in one patient in the latter group. Both peritoneal and hemodialysis satisfactorily controlled plasma urea and creatinine levels, except in patients with fulminant hepatic failure in whom this was only achieved by hemodialysis. Complications of dialysis were most common in patients with cirrhosis and fulminant hepatic failure and included hypotension, gastrointestinal bleeding, and intraperitoneal sepsis. Overall, the results show that dialysis is only worth attempting in those patients in whom recovery of the underlying liver lesion is possible, and even then treatment for prolonged periods may be necessary.     

Major determinants of hyperhomocysteinemia in peritoneal dialysis patients

The mechanisms leading to elevated total homocysteine concentrations in peritoneal dialysis patients are only partially understood. We show that a common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T transition) results in increased total homocysteine levels in peritoneal dialysis patients compared to age- and sex-matched healthy individuals. The allelic frequency of the C677T transition in the MTHFR gene in peritoneal dialysis patients (0.29) was comparable to the frequency in healthy individuals (0.34). Separate comparison of the total homocysteine plasma levels between non-carriers of the MTHFR polymorphism (C/C), heterozygous (C/T) and homozygous (T/T) subjects was performed by analysis of covariance in the patient and the control group. In the patient group the mean total homocysteine level was 61.7 +/- 40.1 mumol/liter in individuals with the (T/T) genotype, which was significantly higher than the total homocysteine concentration of 23.1 +/- 15.8 mumol/liter in (C/T) patients and 22.2 +/- 11.1 mumol/liter for non-carriers (P = 0.0001). Vitamin B12 (P = 0.0001), folate (P = 0.0005), serum creatinine (P = 0.016), albumin (P = 0.0157) and dialysis center (P = 0.0173) significantly influenced total homocysteine plasma levels in peritoneal dialysis patients, whereas this was not the case for age, gender, weekly Kt/V, weekly creatinine clearance, residual renal function, duration of dialysis, mode of peritoneal dialysis and vitamin intake. Folate levels in peritoneal dialysis patients were significantly affected by the MTHFR genotype (P = 0.016). Elevated total homocysteine levels in diabetic patients with cardiovascular disease were associated with increased cardiovascular morbidity. In summary, the present study provides evidence that homozygosity for the C677T transition in the MTHFR gene, low vitamin B12 and low folate levels result in elevated total homocysteine levels in peritoneal dialysis patients.     

Pharmacokinetics of gentamicin during peritoneal dialysis in children

The pharmacokinetics of gentamicin were examined on two occasions using intravenous and intraperitoneal routes in five children undergoing intermittent peritoneal dialysis for chronic renal failure. Serum, urine and dialysis fluid (DF) were assayed microbiologically for gentamicin and the data were subjected to computer analysis using equations evolved for a two-compartment model which considered the bi-directional flux of the drug. Following i.v. injection of 1 mg/kg of gentamicin, the apparent volume of distribution averaged 23% (range, 13 to 36%) of body wt (similar to normal), the mean half-life was 21 hr (range 9 to 37 hr; normal, 2 hr) and the peritoneal clearance averaged 4.0 ml/min/m2 (range, 1.2 to 7.0 ml/min/m2). During peritoneal administration of gentamicin (15 mg/liter of DF, 0.7 liters/m2 administered in each cycle over 9 to 12 cycles), serum concentrations increased towards extrapolated steady-state levels which averaged 42% (range, 25 to 68%) of DF concentrations. The mean renal clearance of gentamicin was only 1.6 ml/min/m2 while total body clearance ranged from 2.3 to 8.0 ml/min/m2 mostly occurring by a variable degree of dialysance. Peritoneal clearances and half-lives of gentamicin were similar in each patient following either treatment mode. The appreciable variability in gentamicin pharmacokinetics among adolescent patients with renal insufficiency necessitates dosage adjustments based on measurements of serum concentrations.     

Thyroid dysfunction in uremia: evidence for thyroid and hypophyseal abnormalities

Disturbances in thyroid function and a high prevalence of goiter develop in patients on chronic hemodialysis. This study shows that in patients on dialysis, mean serum thyroxine and triiodothyronine levels are lower than normal. Patients with chronic renal failure not on dialysis, have mean serum thyroxine levels similar to normal subjects and low mean serum triiodothyronine levels. However, both serum thyroxine and triiodothyronine concentrations decrease as the renal failure worsens. In addition, both groups of patients with renal failure have a decreased serum thyroxine response to oxogenous thyrotrophin and a diminished serum thyrotrophin response to thyrotrophin-releasing hormone. These data suggest the presence of an intrathyroidal and an hypophyseal defect in uremic patients. Although serum iodide concentrations are elevated, there is no correlation between the level of serum iodide and the degree of renal failure. Therefore, we have no direct evidence that iodide excess is responsible for the abnormalities observed.     

The pathogenesis and consequences of AGE formation in uraemia and its treatment

Advanced glycation endproducts (AGEs) accumulate in uraemia as a consequence of diminished clearance of low molecular weight forms which retain their reactivity and may subsequently combine with circulating and tissue macromolecules. Successful renal transplantation is the only form of renal replacement therapy which effectively clears these circulating AGEs; both haemodialysis and peritoneal dialysis are comparatively ineffective although high-flux haemodialysis confers some benefits. De novo AGE formation may be accelerated in uraemia due to carbonyl and oxidative stress leading to further accumulation. The consequences for the patient with chronic renal failure may be acceleration of vascular disease, renal failure progression and dialysis-related amyloidosis. Accelerated peritoneal AGE formation as a consequence of treatment with peritoneal dialysis fluids may be detrimental to peritoneal membrane function but does not appear to contribute to systemic elevation of AGEs.     

Estrogen-stimulated neurophysin in chronic renal failure

Estrogen-stimulated neurophysin (ESN) was determined by radioimmunoassay in three groups of patients with chronic renal failure: predialysis patients, patients on hemodialysis and patients on continuous ambulatory peritoneal dialysis. ESN levels were significantly elevated in all patients. ESN of these patients is undistinguishable from highly purified pituitary ESN. Immunological and physicochemical analyses of ESN in patients with renal failure suggest that the elevated plasma level is due to a failure of renal clearance. In addition, heterogeneity of urinary ESN, revealed by multiple immunoreactive peaks after gel filtration, indicates altered renal metabolism.     

Improvement of host response to sepsis by photobiomodulation

OBJECTIVE: To evaluate the correlation between predialysis glycemic control and clinical outcomes for type II diabetic patients on continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Sixty type II diabetic patients on CAPD were classified into 2 groups according to the status of glycemic control. In group G (good glycemic control), more than 50% of blood glucose determinations were within 3.3-11 mmol/L and the glycosylated hemoglobin (HbA1C) level was within 5-10% at all times. In group P (poor glycemic control), fewer than 50% of blood glucose determinations were within 3.3-11 mmol/L or HbA1C level was above 10% at least once during the follow-up duration. In addition to glycemic control status, predialysis serum albumin, cholesterol levels, residual renal function, peritoneal membrane function, and the modes of glycemic control were also recorded. SETTING: Dialysis Unit, Department of Nephrology of a single university hospital. PATIENTS: From February 1988 to October 1995, 60 type II diabetic patients receiving CAPD for at least 3 months were enrolled. MAIN OUTCOME MEASURES: Morbidities before and during the dialysis period, patient survival, and causes of mortality. RESULTS: The patients with good glycemic control had significantly better survival than patients with poor glycemic control (p < 0.01). There was no significant difference in predialysis morbidity between the two groups. No significant differences were observed in patient survival between the patients with serum albumin greater than 30 g/L and those with less than 30 g/L (p = 0.77), with cholesterol levels greater or less than 5.18 mmol/L (p = 0.73), and with different peritoneal membrane solute transport characteristics evaluated by peritoneal equilibration test (p = 0.12). Furthermore, there was no significant difference in survival whether the patients controlled blood sugar by diet or with insulin (p = 0.33). Cardiovascular disease and infection were the major causes of death in both groups. Although good glycemic control predicts better survival, it does not change the pattern of mortality in diabetics maintained on CAPD. CONCLUSIONS: Glycemic control before starting dialysis is a predictor of survival for type II diabetics on CAPD. Patients with poor glycemic control predialysis are associated with increased morbidity and shortened survival.     

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.     

Measuring the economic impact of ambulatory dialysis: the case of continuous ambulatory peritoneal dialysis

BACKGROUND: As concerns the treatment of terminal renal failure (TRF), France is characterized by a minimal use of peritoneal dialysis, even though this technique is as effective and less expensive than others and that authorities precognize to switch patients to out-of-centre techniques, like peritoneal dialysis. The purpose of the article is to estimate benefits for the Social Security induced by an incitative program leading the current structure of TRF treatment to the existing government standards defined in 1984. METHODS: We computed treatment cost differences, on the basis of an incident case of TRF followed during 7 years, between three different situations: the current French structure of TRF treatment (29.5% of patients treated by out-of-center techniques); two reference situations A and B (respectively 45% and 37% of patients treated by out-of-center techniques). We performed a sensitivity analysis on the rate of use of continuous ambulatory peritoneal dialysis (CAPD). We made assumptions on the cost of techniques, the cost of complications and the rate of CAPD treatment failure. RESULTS: Results stress the existence of benefits induced by increased use of out-of-centre techniques on the basis of a 7-year follow-up of an incident TRF patient: around 65,000 FF in situation A with a 20% rate of use of CAPD; around 5,000 FF in situation B with a 15% rate of use of CAPD. Assumptions concerning CAPD treatment lead to an underestimation of the true benefits. CONCLUSION: The study highlights the therapeutic and economic interest to transfer some patients from hemodialysis to peritoneal dialysis.     

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)     

The use of an indwelling peritoneal catheter in the treatment of chronic renal failure

Thirty-seven patients with end-stage renal failure were treated by dialysis by the peritoneal route, with a Tenckoff catheter. The basic regime was 30 2-litre exchanges twice a week. Two patients died while receiving peritoneal therapy, and 7 patients were transferred to haemodialysis because of catheter failure. Four patients received transplants directly from peritoneal dialysis, 22 were transferred electively to haemodialysis, and 2 are still being treated by peritoneal dialysis. Fourteen (1-2%) of the 1,161 dialyses were complicated by peritoneal infection. This was controlled in 13 instances by the addition of gentamicin to the dialysate, but removal of the catheter was required in one case. The mean duration of peritoneal dialysis was 14-4 weeks; 4 patients underwent this type of therapy for 78, 63, 41 and 40 weeks respectively.     

Peritoneal dialysis. Current status

Peritoneal dialysis has a definite role in the treatment of acute or chronic renal failure and certain fluid and electrolyte disturbances. Its major advantages are simplicity and availability. On the other hand, it is less effective and causes more patient discomfort than hemodialysis. Many factors enter into the decision to use one method of dialysis or the other, and the two should be considered complementary. The numerous complications that may occur during peritoneal dialysis can be avoided by careful attention to technical details. With the recent development of indwelling catheters and automatic cycling devices, long-term peritoneal dialysis is being used increasingly and successfully in the home, particularly in patients for whom home hemodialysis is difficult or inappropriate.     

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.     

Perspectives of end stage renal failure therapy in Singapore

Haemodialysis in Singapore started in 1961 when a patient with kidney failure was dialysed using the twin coil artificial kidney. Over the years, we have seen various new techniques like rapid high efficiency dialysis, haemodiafiltration (HDF) and rapid high flux HDF introduced. Dialysers with newer membranes have improved solute transport, biocompatibility and water removal. Mini heparinisation and heparin-free dialysis have circumvented problems of bleeding in high risk patients. Technological advances in haemodialysis will continue with more new modalities introduced. Newer forms of vascular access through the subclavian and internal jugular veins have phased out the use of chronic arterio-venous (AV) shunts. Continuous ambulatory peritoneal dialysis (CAPD) was introduced in 1980. This has been a boon for cardiac and diabetic patients. The initial problems with peritonitis are now manageable with our current rate of 24.1 patient months compared to 13.2 patient months in 1983. This has been achieved through the use of ultraviolet (UV) germicidal exchange device and transfer tube changes by trained nursing personnel as well as better patient training and education. New techniques have included the "O" disconnect set, the use of 2.5 litre dialysate, low calcium dialysate and the introduction of continuous cycling peritoneal dialysis (CCPD). Future focus will be on the problems of nutrition and protein loss. Renal transplantation remains the ideal renal replacement therapy. Cadaveric renal transplantation was initiated in 1970 and living related donor transplant in 1976. From 1970-1985, immunotherapy was azathioprine-based and from 1985, cyclosporin A (CyA) was introduced. CyA has abrogated many immunological risk factors. Preformed cytotoxic antibodies are still important.(ABSTRACT TRUNCATED AT 400 WORDS)     

Guidelines for nonspecific bronchial provocation tests

This study evaluated the effects of a predialysis patient education programme on functioning and well-being in 28 uraemic patients. The programme consisted of four group sessions with the following themes: renal disease and dietary restriction, active renal replacement therapy, physical exercise, and the impact of chronic renal failure on economy, family and social life. Three to 9 months after having started dialysis the patients were evaluated regarding symptoms, perceived health (Health Index), functional (SIP) and emotional (STAI) status. Twenty-eight patients already on dialysis treatment informed according to conventional routines constituted the comparison group. There were no significant differences between the groups regarding age, sex, educational or social background, duration of kidney disease, choice of dialysis treatment, cause of renal disease and laboratory tests except for s-urea. The patients who participated in the education programme scored significantly better mood, less mobility problems (HI), less functional disabilities (SIP) and lower levels of anxiety (STAI) compared to the comparison group. There were no significant differences between the two groups regarding symptoms and overall health. The differences between the groups prevailed during the first 6 months on dialysis treatment, after which the differences disappeared. In the comparison group age correlated significantly to anxiety and overall SIP, which was not the case in the experimental group. In conclusion, the experimental group that participated in a predialysis patient education programme, showed better functional and emotional well-being than the non-educated comparison group. The positive effects of participating in an education programme prevailed during the first 6 months of dialysis treatment. Moreover, the younger patients seemed especially to benefit from participation in a predialysis patient education programme. It is suggested that patient education should be ongoing for patients with end-stage renal failure initiated during the predialysis stage and continued after maintenance dialysis has been established.     

Switching of the great vessels (arterial switch surgery) in transpositio vasorum

Since April 1992 the arterial switch operation (ASO) has been the treatment of neonates with transposition of the great arteries (TGA) at Rigshospitalet, Copenhagen. Thirteen mature neonates with TGA underwent ASO. Ten patients had simple TGA, two had TGA associated with a ventricular septal defect (VSD), and one had TGA with VSD and in addition moderate right ventricular hypoplasia. All patients survived the operation and are still alive. Perioperative bleeding was a problem in three cases. Eleven patients had an uncomplicated postoperative course. One patient had peri- and postoperative left ventricular failure and was reoperated after three months for a residual VSD. One child developed renal failure and needed peritoneal dialysis. The patients have been followed for 5.5 (range 0-12) months, they are all in good condition and thriving well. The presented early results after ASO justify continued recommendation of ASO as the operation of choice for TGA in neonates at Rigshospitalet.     

Small patients--big costs: the economic aspects of treating young children with renal failure

Since 1985, 20 children have been followed with early onset of chronic renal failure (plasma creatinine > 120 mumol/l in first year of life). So far, 10 and 7 patients underwent peritoneal dialysis and renal transplantation, respectively. The aim of this study was to assess the overall costs. The recorded costs comprised both the direct costs of dialysis and transplantation, and the costs of all medical and psychosocial measures. The annual median costs of conservative treatment, peritoneal dialysis, the year of transplantation, and follow-up after transplantation amounted to 30,000, 93,000, 130,000 and 28,000 Swiss francs, respectively. The youngest patients caused the highest expenses. The active treatment permitted not only survival, but--in most patients--also a normal cognitive and psychosocial development.     

Dialysis adequacy and nutrition determine prognosis in continuous ambulatory peritoneal dialysis patients

Peritoneal membrane function was assessed in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) using parameters derived from urea kinetic modeling and the peritoneal equilibration test (PET). Their relationships with other nutritional markers and overall morbidity were determined. Data regarding the patients' nutritional status as determined by total body nitrogen (TBN) measurements, hospital admissions, and infectious complications within the last 12 months were reviewed. Total dialysate clearance (Kt/V) delivered was highly dependent on residual renal function (P < 0.0001). Kt/V derived from peritoneal clearance diminished with increasing age (P < 0.05). A higher delivered total Kt/V was associated with higher normalized protein catabolic rates (P < 0.002), which in turn were associated with improved TBN (P < 0.05). Hospital admissions decreased with improved normalized protein catabolic rates (P < 0.05), and higher serum albumin and total protein levels (P < 0.01 and P < 0.002, respectively). Infectious complications correlated positively with time on dialysis (P < 0.01), and correlated negatively with TBN measurements (P = 0.05). No correlations were found between infectious complications and serum albumin level or peritoneal protein loss. However, the total duration of hospitalization was shortened with higher serum albumin and total protein levels (P < 0.0001 and P < 0.002, respectively). Although Kt/V determinations did not correlate with clearances determined by the PET, the PET-determined creatinine transport rate correlated with TBN (P < 0.05) but not with infectious complications. In conclusion, nutritional parameters correlate with outcome on continuous ambulatory peritoneal dialysis. An integral relationship exists between nutritional status and dialysis delivery, which is best assessed by urea kinetic modeling.