Specialized chronic care for dialysis patients--a five-year study.

BACKGROUND: At least 40% of those starting onto renal dialysis at the present time are aged over 65 years old. With old age comes increased comorbidity and decreased functional status. The long term management of older patients is limited by the need for rehabilitation and by placement concerns. We describe a 5-year experience of a pilot program, created in 1991 on the recommendation of the Metropolitan Toronto District Health Council, to rehabilitate and care for elderly and disabled patients on either hemodialysis or peritoneal dialysis. METHODS AND RESULTS: This retrospective, observational study reports on a total of 185 patients admitted over a 5-year period to the Riverdale Chronic Dialysis Unit for chronic care or rehabilitation. The mean age of patients admitted was 67 years (quartiles 61 and 75 years). Eighty-five percent of patients had 2 or more severe comorbidities, while 60% had 3 or more active medical issues. The most commonly used dialysis modality was hemodialysis (80%). Of the 185 patients followed 34% were discharged home, 35% died and 13% were still resident at the time of completion of the study. The most common acute medical problems seen in these patients related to their vascular access and necessitated temporary transfer to an acute nephrology center. A total of 4.7 transfers were recorded for each patient-year of follow up. CONCLUSIONS: This study describes the adaptation of facilities already present in our area, to allow better management and placement of older dialysis patients. Transfer of patients from a high level acute care facility to a chronic care facility makes economic and practical sense and may allow better long term health care planning as well as more stability for the family or care-givers.

Venous stenosis and thrombosis associated with the use of internal jugular vein catheters for hemodialysis.

Previous studies have demonstrated venous stenosis and thrombosis in hemodialysis patients who had repeated or prolonged cannulation of the subclavian vein. Early reports, however suggested that patients with catheters placed in the internal jugular vein were not at risk of such complications. We conducted a retrospective case series to determine if this was correct. We report a series of seven patients who were found to have stenosis of the upper neck veins despite having never had subclavian vein cannulation. We suggest that previous reports suggesting a superior safety profile with internal jugular catheters may have been misleading and propose that all measures be taken to encourage wider use of arteriovenous grafts and fistulae.

Autosomal dominant polycystic kidney disease in Toronto.

This study describes the Toronto, Ontario experience with autosomal dominant polycystic kidney disease (ADPKD). Patients were divided into three groups: Group 1, 19 families studied with genetic markers; Group 2, 80 pre-dialysis ADPKD patients followed by Toronto nephrologists in whom the incidence of non-renal complications and the mean age of onset of symptomatology is documented; Group 3, 4,449 individuals who entered end-stage renal failure (ESRF) in the Toronto region between the years 1981 and 1992, 320 with ADPKD and 4129 with other diseases. In this third group age of onset of ESRF, frequency, age and cause of death is compared between ADPKD and non-ADPKD. ADPKD caused by a gene different from that linked to chromosome 16 short-arm probes occurred at a frequency of between 8 and 17%. Incidence of hepatic cysts in ADPKD was similar to that of previous series, other organ involvement was underdiagnosed without deliberate screening, and incidence of symptomatic intracranial aneurysm was 1.25%. A 5% excess of patients with ADPKD died of cerebro-vascular accident. Years of survival after ESRF measured by life table analysis was significantly greater for ADPKD patients than for non-ADPKD patients. A high frequency of death due to infection still exists in ADPKD despite the reduction of invasive procedures in diagnosis and treatment, and despite the presumably improved recent methods of managing infection. The average age of onset of ESRF has been delayed by over six years, and average age of death of ADPKD patients at 63.9 years-old by 12.4 years since 1960.

Linkage exclusion between the autosomal dominant polycystic kidney disease locus and chromosome 16 markers in a new family.

A family segregating for autosomal dominant polycystic kidney disease (ADPKD) is reported. The clinical picture was typical for ADPKD in some family members, although others showed mild involvement. DNA from family members was probed with seven chromosome 16 single-copy DNA sequences that mapped to the telomere of the short arm of the chromosome. The most likely order of six of the probes from the telomere is palpha3'HVR.64 at the designated locus D16S85, CRI-0327 at D16S63, CRI-090 at D16S45, CRI-0129 at D16S56, CRI-0133 at D16S58, and CRI-0136 at D16S60, with the PKD1 locus for ADPKD between D16S85 and D16S63. The seventh probe 24-1 at D16S80 had not been ordered in relation to the other sequences, but PKD1 had been mapped between it and D16S85. The three probes that were informative in our family, palpha3'HVR.64, CRI-090, and CRI-0136 had been linked to the disease locus at recombination frequencies of 4% and approximately 6 and 12%, respectively. Linkage was excluded between the ADPKD locus in our family and palpha3'HVR.64 at a recombination value of up to 6%. Linkage was also excluded between CRI-090 and the disease locus at a recombination value of up to 5%. The data for linkage between CRI-0136 and the ADPKD locus in our family were inconclusive. Multipoint analysis excluded the possibility that the disease in this family lies between the flanking genetic markers that have previously been used to define the genetic interval in which the most common form of polycystic kidney disease, PKD1, lies. We have not made a positive assignment of the ADPKD mutation in this family.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative cost-analysis of two different chronic care facilities for end-stage renal disease patients.

OBJECTIVE: To investigate the cost and quality of life associated with the first specialized chronic care facility for disabled dialysis patients. DESIGN: A case controlled study in dialysis patients admitted to a specialized chronic dialysis unit (RCDU). SETTING: The study compares the cost of care in a specialized chronic care facility with that of a tertiary hospital. PATIENTS: All dialysis patients with severe chronic disability, resident in Greater Toronto, who were unable to be discharged into the community and who were admitted to the RCDU in the first year of the program. INTERVENTIONS: Chronic care and rehabilitation services in a specialized dialysis unit. OUTCOME MEASURES: Costs are expressed as $Cdn per patient year. Quality of life scores were measured using SIP and SF-36 questionnaires. RESULTS: The data show a saving of $37,022 Cdn over the 618 day study period with care in the RCDU compared with that of a tertiary hospital. Quality of life measures show no difference in scores. CONCLUSIONS: We conclude that this preliminary report confirms a cost benefit of a specialized chronic care dialysis unit.

Hyperglycemia-induced hyponatremia: metabolic considerations in calculation of serum sodium depression.

Hyperglycemia is associated with a decrease in serum sodium concentration. Previous methods of estimating the degree of decrease have not considered the fact that glucose will enter certain cells despite relative insulin deficiency; thus, glucose will not contribute directly to the osmotic gradient responsible for water shifts into or out of these tissues. The expected decrease in serum sodium concentration is 1.35 meg/l for every 100mg/dl increase in blood glucose concentration - the metabolic correction factor. Although the numerical difference between this factor and that calculated by others is small, the metabolic implications could be critical. In the hyperglycemic state the water content of tissues not requiring insulin for glucose transport could increase, and where tissue swelling is physically restricted (for example, in the brain) this expansion could seriously affect organ function.

Effect of amphotercin B on urine acidification in rats: implications for the pathogenesis of distal renal tubular acidosis.

It has been proposed that distal renal tubular acidosis is a gradient-limited disorder an that the low urine Pco2 observed in this condition is caused by back diffusion of carbonic acid. This study was designed to examine this hypothesis using the amphotericin B model of gradient-limited distal renal tubular acidosis in rats. After induction of acute metabolic acidosis the minimum urine pH in 12 of 24 amphotericin B-treated rats exceeded 5.63 (mean 5.76 +/- 0.04), whereas it was 5.41 +/-0.04 in control rats. These animals with impaired urine acidification were presumed to have a gradient lesion and were studied in bicarbonate-loading experiments. The urine minus blood Pco2 gradient in these rats was 24.9 +/- 1.5 mm. Hg, a value similar to that of the control rats (26.7 +/- 2.1 mm. Hg). The presence of a normal urine minus blood Pco2 value in this experimentally induced gradient-limited type of acidification lesion indicates that a permeability defect for hydrogen ions was not associated with a similar defect for carbonic acid and that the urine minus blood Pco2 gradient is a valid index of distal nephron hydrogen ion secretion in amphotericin B-like gradient-type lesions.

Purification of an equine apotransferrin variant (thyromedin) essential for thyroid hormone dependent growth of GH1 rat pituitary tumor cells in chemically defined culture.

Pituitary tumor cells require thyroid hormones for growth in vivo [Sorrentino, J. M., Kirkland, W. L., & Sirbasku, D. A. (1976) J. Natl. Cancer Inst. 56, 1155-1158]. In vitro, GH1 rat pituitary tumor cells were studied in a serum-free defined medium (PCM-10) formulated with Ham's F12 and Dulbecco's modified Eagle's media (1:1, v/v) supplemented with 2.2 g/L sodium bicarbonate, 15 mM 4-(2-hydroxy-ethyl)-1-piperazineethanesulfonic acid (pH 7.2), 10 micrograms/mL human transferrin, 50 microM ethanolamine, 10 micrograms/mL insulin, 10 ng/mL selenous acid, 0.1 nM 3,5,3'-triiodothyronine (T3) and 500 micrograms/mL bovine serum albumin and in the same medium without T3 (PCM-0). The cells only grew in PCM-10 when low concentrations of horse serum were added. Attempts to replace the serum factor requirement with known growth factors and adhesion proteins were unsuccessful. The Mr 65,000-72,000 serum factor regulating T3-induced growth (thyromedin) was purified to homogeneity and identified as equine transferrin R and/or D by amino acid sequencing. The ED50 in PCM-10 was 17-40 micrograms/mL (260-620 nM) while in PCM-0 half-maximum growth was not achieved at 200 micrograms/mL. Concentrations of 75 micrograms/mL in PCM-10 caused 80% of serum-stimulated growth rate. Removal of iron from thyromedin, and assay in iron salts reduced PCM-10, increased the specific activity 110-270-fold to ED50 150 ng/mL (2.3 nM); at 1.0 micrograms/mL, growth in PCM-10 was 16-fold greater than in PCM-0. Iron saturation of thyromedin caused total loss of biological activity. We conclude that the horse transferrin variant isolated in this report is active as apotransferrin.

Lithium-induced impairment of urine acidification.

The purpose of this study was to clarify the means by which lithium induced a disorder of urine acidification. Rats infused with hydrochloric acid (1 mEq/kg) developed acute metabolic acidosis (blood Ph = 7.32; bicarbonate, 18 mEq/liter) with a urine pH of approximately 5.85. The addition of lithium chloride (4 mEq/kg i.p) caused an increase in the urine pH (6.38) and a further decrease in blood bicarbonate (11.0 mEq/liter). During bicarbonate loading, lithium caused the urine PCO2 to fall significantly (urine minus blood PCO2 decreased from 25.3 +/-2.8 To 14.4 +/- 2.3 mm Hg) These changes were not seen following equimolar i.p. administration of sodium chloride. Similarly, lithium administration depressed bicarbonate reabsorption by 11.1% (from 30.6 to 27.2muEq/ml of GFR) during alkali infusion, while saline caused only a 5% decrease (30.0 to 28.5muEq/ml of GFR). The combination of an increase in urine PCO2 in alkaline urine indicates that lithium produced a defect in distal nephron hydrogen ion secretion. The fall in bicarbonate reabsorption following lithium administration oculd be due to a mild hydrogen ion secretory defect located in the proximal tubule or a severe defect in the distal nephron.

Results of a controlled drug trial in membranoproliferative glomerulonephritis.

A prospective randomized drug trial was carried out on 59 patients with confirmed membranoproliferative glomerulonephritis (MPGN). The treatment group (27 patients) received cyclophosphamide, coumadin, and dipyridamole for 18 months, and the control group (32 patients) received no specific therapy. Complications of the renal disease such as hypertension and fluid retention were treated similarly in both groups. Entrance criteria included confirmed renal pathology demonstrating either types I or II MPGN, a corrected creatinine clearance (CCr) of less than 80 ml/min/1.73 m2, and/or proteinuria greater than 2 g/day. Actuarial survival was not different between the treatment and the control groups in either MPGN type and was 85% in type I and 90% in type II at 2 years. The change in renal function, as measured by both the slope of CCr and the plasma creatinine reciprocal (1/Cr) at 6, 12, and 18 months was not significantly different between treatment and control groups in either types I or II when tested by both parametric and nonparametric analysis. The age, sex, and initial level of CCr did not influence the rate of decline. Control and treatment group proteinuria was not different at any time point in either types I or II MPGN. The small numbers of type II MPGN cases do not give sufficient power to allow conclusions regarding this therapy in type II. We can conclude that this treatment is ineffective in altering the natural history of type I MPGN.

Medical and social outcome in adolescents with end-stage renal failure.

Clinical information was collected on 118 adolescents who developed ESRF at age 143 months or older and were treated between 1966 and 1986 at the Toronto Hospital for Sick Children. The cumulative survival rate in transplanted patients (N = 109) was 80.1% after 15 years. Survival rates after four years were 93.9% in transplanted and 46.9% in nontransplanted patients (P less than 0.001). No patient receiving dialysis alone (N = 9) was followed longer than four years. Nine patients received three transplants and had an 89% survival rate. Six of these had a functioning graft at end of the follow-up. The cumulative survival of the entire group was 76.4% at eighteen years. Forty-two (35.6%) patients had a height below the third percentile. Functional status obtained by a structure telephone interview with a member of the present treating nephrology service was good (G) or excellent (E) for 66.7% of all patients (73.5% of transplant patients (N = 68) and 45% of dialysis patients (N = 20). Hemodialysis patients functioned less well [25% G/E (N = 12)] than peritoneal dialysis patients [75% G/E (N = 8)]. Most patients achieved an appropriate level of formal education although more slowly than normal adolescents. Only 11 patients were neither enrolled in an educational institution nor employed. We conclude that aggressive treatment for adolescents with ESRF is an appropriate application of health care resources.

Clinical practice guidelines: prevention of cytomegalovirus disease after renal transplantation.

OBJECTIVE: To develop a set of comprehensive, standardized, evidence-based guidelines for the use of antiviral therapy to prevent cytomegalovirus disease in adult patients having undergone renal transplantation. OPTIONS: The use of medication, at the time of induction therapy or at the earliest sign of viremia. Treatments were evaluated by patient and donor serologic groups and the induction regimen used. OUTCOMES: The control of symptoms and features of cytomegalovirus disease over the first 6 mo to 1 yr after transplantation. EVIDENCE: Articles, compiled using a MEDLINE search from 1976 to July 1997, were reviewed by representatives of nephrology, microbiology, pharmacy, and epidemiology. Additional information was obtained from recent review articles and conference abstracts, and from experts in the field. VALUES: The evidence-based methods and values of the Canadian Task Force on the Periodic Health Examinations were used. High value was placed on studies with a randomized controlled design and blinded outcome observers. Study quality was classified as poor when cointervention was present (especially with regard to immunosuppressive regimens), when more than 20% of patients were lost to follow-up, and when intention to treat analysis was not performed. Recommendations were made with a graded system (grades A and B: Use of the intervention advised, based on high or fair quality evidence, respectively; grades D and E: Use of the intervention not advised, based on high or fair quality evidence, respectively: grade C: No recommendation made because of insufficient or conflicting evidence). RECOMMENDATIONS: (1) Seropositive recipient; donor seropositive or seronegative; immunosuppression with antilymphocyte products. Prophylaxis with antiviral therapy recommended (grade A recommendation). (2) Seronegative recipient; seropositive donor; immunosuppression with antilymphocyte products. Prophylaxis with antiviral therapy recommended (grade A recommendation) (3) Seronegative recipient; seropositive donor; conventional immunosuppression. Prophylaxis with antiviral therapy recommended (grade B recommendation). (4) Seronegative recipient; seronegative donor; any immunosuppressive regimen. No prophylaxis with antiviral therapy required (grade D/E recommendation). (5) Seropositive recipient: donor seropositive or seronegative; conventional immunosuppression. Prophylaxis left to the discrimination of the physician in charge (grade C recommendation).

The design of phenylglycine containing benzamidine carboxamides as potent and selective inhibitors of factor Xa.

Factor Xa, a critical serine protease in the blood coagulation cascade, has become a target for inhibition as a strategy for the invention of novel anti-thrombotic agents. Here we describe the development of phenylglycine containing benzamidine carboxamides as novel, potent and selective inhibitors of factor Xa.