Vascular access: past, present, and future.

Vascular access is the Achilles' heel of hemodialysis. Current vascular access approaches for hemodialysis include arteriovenous (AV) fistula, AV graft, and central venous catheter. Strengths and weaknesses of each access type are described. New technology and procedures in introducing an access, monitoring access function, and salvaging a non-functioning access are also described.

High-intensity hemodialysis: the wave of the future?

Various modalities of high-intensity hemodialysis are gathering increasing popularity. Some of the advantages of these new dialysis regimens are presented. Time and the increasing use of these novel approaches will ultimately determine their role in the overall management of patients with endstage renal disease.

Nitric oxide synthase in circulating vs. extravasated polymorphonuclear leukocytes.

It is becoming increasingly apparent that certain forms of acute and chronic inflammation are associated with enhanced production of nitric oxide (NO). Although substantial information has been obtained describing the regulation of NO synthase (NOS) in macrophages, little information is available regarding the biochemistry and molecular biology of NOS in circulating vs. extravasated polymorphonuclear leukocytes (PMNs). The objective of this study was to characterize the molecular and biochemical properties of the inducible NO synthase (iNOS) in circulating vs. extravasated rat and human PMNs. Circulating rat and human PMNs were purified from peripheral blood and extravasated PMNs were elicited in rats by intraperitoneal injection of 1% oyster glycogen or in humans by peritoneal dialysis of patients with peritonitis. Inducible NOS mRNA from circulating and elicited PMNs was quantified using slot blot hybridization analysis with a cDNA probe specific for iNOS. iNOS protein was identified using Western immunoblot analysis, and NOS activity was quantified by measuring the NG-monomethyl-L-arginine (L-NMMA)-inhibitable conversion of 14C-labeled L-arginine to L-[14C]citrulline. In a separate series of experiments, circulating or extravasated PMNs were cultured for 4 h and the accumulation of L-NMMA-inhibitable nitrite (NO2-) in the supernatant was determined and used as a measure of NO production in vitro. We found that circulating PMNs (rat or human) contained no iNOS mRNA, protein, or enzymatic activity. Furthermore, circulating rat or human PMNs (2 x 10(6) cells/well) were unable to generate significant amounts of NO2- when cultured for 4 h in vitro. In contrast, iNOS mRNA levels in 4- and 6-h elicited rat PMNs increased 21- and 42-fold, respectively, when compared with circulating cells. Western blot analysis revealed the presence of iNOS protein in the elicited rat PMNs and iNOS enzymatic activity increased from normally undetectable levels in circulating rat PMNs to 81 and 285 pmol/min/mg for the 4- and 6-h elicited rat PMNs, respectively. Approximately 20-30% of the total iNOS activity was Ca(2+)-dependent. Nitrite formation by elicited rat PMNs in the absence of any exogenous stimuli increased from normally undetectable amounts for circulating PMNs to approximately 8 and 11 microM/10(6) cells for the 4- and 6-h elicited PMNs, respectively. Highly enriched preparations of extravasated human PMNs contained neither message, protein nor iNOS enzymatic activity. Taken together our data demonstrate that inflammation-induced extravasation of rat PMNs upregulates the transcription and translation of iNOS in a time-dependent fashion and that 20-30% of the total inducible NOS is Ca(2+)-dependent. In contrast, neither circulating nor extravasated human PMNs contained iNOS message, protein, or enzymatic activity. These data suggest that the human PMN iNOS gene is under very different regulation than is the rat gene.

Transdermal clonidine in mild hypertension. A randomized, double-blind, placebo-controlled trial.

In 30 patients with mild essential hypertension, clonidine hydrochloride was delivered from a skin patch reservoir designed to release medication at a constant rate for seven days. After a four-week washout period, patients were randomized (double-blind) into a clonidine- or a placebo-treated group. Clonidine or placebo was then given for five weeks, followed by a two-week washout period to assess withdrawal from treatment. Blood pressure was controlled in 11 of 15 clonidine-treated patients but in only four of 15 placebo-treated patients. The clonidine-treated group evidenced larger decreases in both systolic and diastolic blood pressures. In the clonidine-treated group, blood pressures and plasma clonidine levels were stable throughout a representative seven-day period. Besides mild skin irritation with both clonidine and placebo patches, few side effects were observed. After discontinuation of clonidine administration, plasma levels declined in a non-log linear manner. There was no rebound hypertension. The results suggest that clonidine delivered transdermally is safe and effective for control of mild essential hypertension.

Spurious hyperphosphatemia due to hyperlipidemia.

A patient had hyperlipidemia associated with apparent hyperphosphatemia. Further tests on his serum and on the lipemic sera from 15 additional patients revealed a method-dependent overestimation of inorganic phosphorus values. The degree of overestimation was found to correlate positively with the serum triglyceride concentration. Unexplained elevation of the serum phosphorus level should alert the physician to the possibility of spurious hyperphosphatemia due to hyperlipidemia.

Subxiphoid pericardiostomy for hemodialysis-associated pericardial effusion.

Sixteen patients receiving maintenance hemodialysis in whom moderate-to-large pericardial effusions developed were treated with short-term drainage via a large-bore tube implanted into the pericardial sac. Drainage tubes were implanted using a subxiphoid approach (subxiphoid pericardiostomy) while the patient was under local anesthesia. In seven patients, triamcinolone hexacetonide was instilled into the pericardial sac through the drainage tube at regular intervals. In all patients, a drainage period of two to four days, with or without instillation of nonabsorbable steroids, was associated with resolution of the pericardial effusion. Only one recurrence of effusion was demonstrable over a follow-up period extending from three months to eight years (median, 4.2 years). Complications of subxiphoid pericardiostomy were minor (incisional hernia, wound infection, and small pneumothorax) and easily treatable. Our results suggest that short-term drainage via a surgically implanted drainage tube is an effective and safe treatment of moderate-to-large hemodialysis-associated pericardial effusion.

Sclerotic thickening of the peritoneal membrane in maintenance peritoneal dialysis patients.

Five patients receiving maintenance peritoneal dialysis (duration, three months to four years) required surgical exploration of the abdomen for various reasons. Four had a prior history of bacterial peritonitis, and four of aseptic peritonitis. At laparotomy, the peritoneal membrane was found to be markedly thickened and sclerotic in all patients, and loops of bowel were bound together in a dense, opaque casing. On microscopic examination, an increase in fibroconnective tissue in the peritoneum was observed.

Peritoneal fluid eosinophilia in patients undergoing maintenance peritoneal dialysis.

In ten patients undergoing maintenance peritoneal dialysis, large numbers of eosinophils were found in the peritoneal fluid. A few of the affected patients complained of episodic abdominal pains, but there was no correlation between abdominal symptoms and the number of peritoneal fluid eosinophils. Microorganisms failed to grow on cultures of the peritoneal fluids, and results of tests for endotoxin were negative. The cause of eosinophilia could not be determined. Peritoneal fluid eosinophil counts were noted to be elevated soon after catheter insertion and initiation of peritoneal dialysis. In some patients, peritoneal fluid eosinophil counts spontaneously returned to normal despite continued peritoneal dialysis.

Asymptomatic, nonketotic, severe hyperglycemia with hyponatremia.

We describe five patients with asymptomatic, nonketotic, severe hyperglycemia (serum glucose concentrations between 45.8 and 92 mmol/L) in the face of renal insufficiency are described. As opposed to most of the previously described patients with hyperglycemic, nonketotic, hyperosmolar coma, our patients were hyponatremic. The lack of symptoms in our patients may be related to the absence of cerebral cellular dehydration. Aggressive treatment of hyperglycemia in such patients is unnecessary. Attention to the serum sodium level as well as to the serum glucose concentration will allow recognition of this clinical entity.

Severe anaphylactoid reactions to cuprammonium cellulose hemodialyzers.

Twenty-one severe reactions to hemodialysis occurred in approximately 260,000 dialysis treatments at three centers within a 10 1/2-year period. Reactions typically appeared within minutes of initiating dialysis, and were characterized by cardiopulmonary, mucocutaneous, and/or gastrointestinal tract symptoms highly suggestive of anaphylaxis. Four respiratory arrests and one death resulted. Analysis of dialyzer use patterns and of each patient's dialyzer exposure history strongly implicated hollow-fiber dialyzers made of cuprammonium cellulose (CC) as a cause of these reactions. No obvious factors could be found to identify predisposed patients. Less than optimal rinsing of the CC hollow-fiber dialyzers prior to use may have been responsible for some, but not all, of these reactions.

Blood eosinophilia in patients undergoing maintenance peritoneal dialysis.

To determine the prevalence of blood eosinophilia in patients receiving maintenance peritoneal dialysis, routine peripheral WBC counts of 49 such patients were reviewed. In 29 patients, blood eosinophilia was noted. Elevations in blood eosinophil counts tended to be mild and episodic. They were often associated with concomitant elevation of peritoneal fluid eosinophil counts. Possible predisposing factors included recent peritoneal catheter insertion and antibiotic therapy for peritonitis.

Phosphorus-enriched hemodialysis for the treatment of patients with severe methanol intoxication.

Severe methanol poisoning requires treatment with prolonged and intensive hemodialytic therapy. Such treatment can engender either the de novo development of hypophosphatemia or the worsening of pre-existing hypophosphatemia. Phosphorus-enriched hemodialysis therapy can prevent the occurrence of this complication. We report three patients with severe methanol poisoning who were treated with phosphorus-enriched hemodialysis. Prevention or treatment of hypophosphatemia was successfully achieved with this dialytic technique.

Serum potassium and acid-base parameters in severe dialysis-associated hyperglycemia treated with insulin therapy.

We analyzed the changes in serum potassium concentration ([K]) and acid-base parameters in 43 episodes of dialysis-associated hyperglycemia (serum glucose level > 33.3 mmol/L), 22 of which were characterized as diabetic ketoacidosis (DKA) and the remaining 21 as nonketotic hyperglycemia (NKH). All episodes were treated with insulin therapy only. Age, gender, initial and final serum values of glucose, sodium, chloride, tonicity and osmolality did not differ between DKA and NKH. At presentation, serum values of [K] (DKA 6.2 +/- 1.3 mmol/L; NKH 5.2 +/- 1.5 mmol/L) and anion gap [AG] (DKA 27.2 +/- 6.4 mEq/L; NKH 15.4 +/- 3.5 mEq/L) were higher in DKA, whereas serum total carbon dioxide content [TCO2 ] (DKA 12.0 +/- 4.6 mmol/L; NKH 22.5 +/- 3.1 mmol/L), arterial blood pH (DKA 7.15 +/- 0.09; NKH 7.43 +/- 0.07) and arterial blood PaCO2 (DKA 26.2 +/- 12.3 mm Hg; NKH 34.5 +/- 6.7 mm Hg) were higher in NKH. At the end of insulin treatment, serum values of [K] (DKA 4.0 +/- 0.7 mmol/L, NKH 4.0 +/- 0.5 mmol/L), [AG] (DKA 16.3 +/- 5.4 mEq/L, NKH 14.9 +/- 3.0 mEq/L), [TCO2 ] (DKA 23.5 +/- 5.0 mmol/L, NKH 24.1 +/- 4.2 mmol/L), arterial blood pH (DKA 7.42 +/- 0.09, NKH 7.51 +/- 0.14) and arterial blood PaCO2 (DKA 31.8 +/- 6.7 mm Hg, NKH 34.2 +/- 8.3 mm Hg) did not differ between the two groups. Linear regression of the decrease in serum [K] value during treatment, (Delta[K]), on the presenting serum [K] concentration,([K]2 ), was: DKA, Delta[K] = 2.78 - 0.81 x [K]2 , r = -0.85, p < 0.001; NKH, Delta[K] = 2.44 - 0.71 x [K]2 , r = -0.90, p < 0.001. The slopes of the regressions were not significantly different. Stepwise logistic regression including both DKA and NKH cases identified the presenting serum [K] level and the change in serum [TCO2 ] value during treatment as the predictors of Delta[K] (R2 = 0.81). Hyperkalemia is a feature of severe hyperglycemia (DKA or NKH) occurring in patients on dialysis. Insulin administration brings about correction of DKA and return of serum [K] concentration to the normal range in the majority of the hyperglycemic episodes without the need for other measures. The initial serum [K] value and the change in serum [TCO2 ] level during treatment influence the decrease in serum [K] value during treatment of dialysis-associated hyperglycemia with insulin.

Protein-calorie malnutrition and cutaneous anergy in hemodialysis maintained patients.

In 52 unselected patients maintained in intermittent hemodialysis, protein calorie malnutrition was present in 10 patients (19%). Complete cutaneous anergy to four intradermal skin antigens. (Candida, tuberculin, Streptokinase-dornase, and mumps) and failure to respond to contact sensitization to dinitrochlorobenzene was present in 60% of the patients. No correlation between cutaneous anergy and protein calorie malnutrition could be demonstrated.

Cerebrospinal fluid changes in experimental cardiopulmonary bypass using hemodilution with glucose water.

Cardiopulmonary bypass using hemodilution with isotonic glucose water was performed on seven dogs. Intense systemic metabolic acidosis, hyponatremia, hypochloremia, and hyperglycemia were accompanied by only comparatively small changes in the corresponding cerebrospinal fluid values. The data suggested that in the present study, cardiopulmonary bypass was not associated with gross disruptions of the barriers for bicarbonate, sodium, chloride, and glucose between blood and cerebrospinal fluid.

Fanconi syndrome associated with a non-ossifying fibroma of bone.

A 20-year-old man presenting with osteomalacia was found to have the Fanconi syndrome, as evidenced by hypophosphatemia with hyperphosphaturia, glycosuria in the presence of normoglycemia, and generalized aminoaciduria. After removal of a non-ossifying fibroma of the left tibia, the renal tubular abnormalities promptly resolved with subsequent healing of the osteomalacia. A humoral factor released from the tumor may have caused the disorder in proximal renal tubular cell transport.

Skin necrosis and protein C deficiency associated with vitamin K depletion in a patient with renal failure.

Skin necrosis similar to that induced by warfarin was seen in a patient who had never received the drug but who was vitamin K-deficient due to malnutrition and prolonged treatment with broad-spectrum antibiotics. He also had end-stage renal failure and was receiving prophylactic subcutaneous heparin therapy because of immobilization. His plasma protein C antigen level and, disproportionately, his plasma protein C functional activity were decreased. Both protein C values improved after vitamin K therapy, discontinuation of heparin, and initiation of hemodialysis. We surmise that skin necrosis occurred as a result of protein C deficiency caused by vitamin K depletion. Production of abnormal (descarboxy) protein C/protein S due to vitamin K deficiency and increased protein C inhibitory activity associated with renal failure and/or heparin administration may have contributed to the clinical picture. This rare but serious complication of a relatively common disorder, viz., vitamin K deficiency, reinforces the importance of vitamin K supplementation in malnourished patients who receive long-term antibiotic maintenance therapy.

Variation in blood sample collection for determination of hemodialysis adequacy. Council on Renal Nutrition National Research Question Collaborative Study Group.

Inadequate dialysis has been associated with high morbidity and mortality in end-stage renal disease (ESRD) patients receiving maintenance hemodialysis. The accurate estimation of dialysis adequacy, measured either as a calculated urea kinetics (Kt/V) or a simple urea reduction ratio (URR) is dependent on the proper collection of blood samples for predialysis and postdialysis blood urea nitrogen (BUN) determination. Because no established protocol exists for blood sampling, we surveyed the study cohort of dialysis centers participating in the National Kidney Foundation Council on Renal Nutrition National Research Question Collaborative Study to determine the comparability of BUN data that were collected to calculate URR to determine adequacy of dialysis. Surveys were completed by 100% of the 202 units participating: 195 in the United States (from 43 states) and seven from Canada, treating approximately 15,000 hemodialysis patients in total. The distribution of the sample by the type of facility mirrored that of 1996 United States Renal Data System (USRDS) Annual Report facilities data. Results showed a 5.0% error in predialysis blood draw and an 8.4% to 41.6% error in the postdialysis counterpart. There was a large variability in the observed postdialysis methods in general. Dilution of predialysis sample with either heparin or saline will falsely underestimate Kt/V and URR. The presence of access-derived, recirculated blood in the postdialysis sample will falsely overestimate Kt/V and URR. Excessive delay in drawing postdialysis sample will reduce Kt/V and URR because of urea rebound. Adoption by all dialysis providers of a uniform blood sample draw procedure will result in a consistency necessary to allow reliable and valid comparison of adequacy of dialysis parameters within and between ESRD patients, units, and clinical trials.

Management of hypophosphatemia induced by high-flux hemodiafiltration for the treatment of vancomycin toxicity: intravenous phosphorus therapy versus use of a phosphorus-enriched dialysate.

Intensive high-flux hemodiafiltration is often used in the management of vancomycin toxicity. We describe two patients who developed hypophosphatemia as a consequence of this form of therapy. The first patient was treated with an intravenous phosphorus infusion. For the second patient, hypophosphatemia was corrected, during hemodiafiltration, with the use of a phosphorus-enriched dialysate. The latter dialysate was prepared by adding sodium phosphate salts to the "base concentrate" of a dual-concentrate, bicarbonate-based dialysate delivery system. This simple method was more efficient than intravenous therapy in ameliorating the hypophosphatemia secondary to aggressive hemodiafiltration treatment.

Determination of the solute removal index for urea by using a partial spent dialysate collection method.

In 22 hemodialysis patients, during a dialysis session, the solute removal index (SRI) for urea obtained from the use of a partial spent dialysate collection method was compared with that derived from the use of a total spent dialysate collection technique. The partial spent dialysate collection method was used to harvest a small representative sample of the total spent dialysate. The volumes of spent dialysate collected by the partial and the total spent dialysate collection methods were 1.7 +/- 0.4 L and 129.6 +/- 15.3 L, respectively. The total amount of urea nitrogen removed by dialysis as estimated by the partial spent dialysate collection method was similar to that determined by the total spent dialysate collection approach. As a result, the SRI value for urea obtained by the partial spent dialysate collection method (namely, 63% +/- 8%) correlated very well (r = 0.95, P < 0.001) with that derived by the total spent dialysate collection technique (namely, 62% +/- 8%). Our data suggest that it is feasible to use a simple partial spent dialysate collection method to obtain SRI results in patients treated with hemodialysis.