Comparative hospitalization of hemodialysis and peritoneal dialysis patients in Canada.

BACKGROUND: Most comparisons of hemodialysis (HD) and peritoneal dialysis (PD) have used mortality as an outcome. Relatively few studies have directly compared the hospitalization rates, an outcome of perhaps equal importance, of patients using these different dialysis modalities. METHODS: Eight hundred twenty-two consecutive patients at 11 Canadian institutions with irreversible renal failure had an extensive assessment of comorbid illness and initial mode of dialysis collected prospectively immediately prior to starting dialysis therapy. The cohort was assembled between March 1993 and November 1994. The mean follow-up was 24 months. Admission data were used to compare hospitalization rates in HD and PD. RESULTS: Thirty-four percent of patients at baseline and 50% at three months used PD. Twenty-five percent of HD and 32% of PD patients switched dialysis modality at least once after their first treatment (P = NS). Nine percent of HD patients and 30% of PD patients switched modality after three months (P < 0. 001). Total comorbidity was higher in HD patients at baseline (P < 0. 001) and at three months (P = 0.001). The overall hospitalization rate was 40.2 days per 1000 patient days after baseline and 38.0 days per 1000 patient days after three months. When an adjustment was made for baseline comorbid conditions, patients on PD had a lower rate of hospitalization in intention-to-treat analysis according to the type of dialysis in use at baseline (RR 0.85, 95% CI, 0.82 to 0.87, P < 0.001), but a higher rate according to the type of dialysis in use three months after study entry (RR 1.31, 95% CI, 1.27 to 1.34, P < 0.001). In analyses based on the amount of time actually spent on each treatment modality, PD was associated with a higher rate of hospitalization when analyzed according to the type of dialysis in use at baseline (RR 1.10, 95% CI, 1.07 to 1.13, P < 0.001) and according to the type of dialysis in use three months after study entry (RR 1.26, 95% CI, 1.23 to 1.30, P < 0.001). CONCLUSIONS: Conclusions regarding comparative hospitalization rates are heavily dependent on the analytic starting point and on whether intention-to-treat or treatment-received analyses are used. When early treatment switches are accounted for, HD is associated with a lower rate of hospitalization than PD, but the effect is modest.

Comparative mortality of hemodialysis and peritoneal dialysis in Canada.

BACKGROUND: Comparisons of mortality rates in patients on hemodialysis versus those on peritoneal dialysis have been inconsistent. We hypothesized that comorbidity has an important effect on differential survival in these two groups of patients. METHODS: Eight hundred twenty-two consecutive patients at 11 Canadian institutions with irreversible renal failure had an extensive assessment of comorbid illness collected prospectively, immediately prior to starting dialysis therapy. The cohort was assembled between March 1993 and November 1994; vital status was ascertained as of January 1, 1998. RESULTS: The mean follow-up was 24 months. Thirty-four percent of patients at baseline, 50% at three months, and 51% at six months used peritoneal dialysis. Values for a previously validated comorbidity score were higher for patients on hemodialysis at baseline (4.0 vs. 3.1, P < 0.001), three months (3.7 vs. 3.2, P = 0.001), and six months (3.6 vs. 3.2, P = 0.005). The overall mortality was 41%. The unadjusted peritoneal dialysis/hemodialysis mortality hazard ratios were 0.65 (95% CI, 0. 51 to 0.83, P = 0.0005), 0.84 (95% CI, 0.66 to 1.06, P = NS), and 0. 83 (95% CI, 0.64 to 1.08, P = NS) based on the modality of dialysis in use at baseline, three months, and six months, respectively. When adjusted for age, sex, diabetes, cardiac failure, myocardial infarction, peripheral vascular disease, malignancy, and acuity of renal failure, the corresponding hazard ratios were 0.79 (95% CI, 0. 62 to 1.01, P = NS), 1.00 (95% CI, 0.78 to 1.28, P = NS), and 0.95 (95% CI, 0.73 to 1.24, P = NS). Adjustment for a previously validated comorbidity score resulted in hazard ratios of 0.74 (95% CI, 0.58 to 0.94, P = 0.01), 0.94 (95% CI, 0.74 to 1.19, P = NS), and 0.88 (95% CI, 0.68 to 1.13, P = NS) at baseline, three months, and six months. There was no survival advantage for either modality in any of the major subgroups defined by age, sex, or diabetic status. CONCLUSIONS: The apparent survival advantage of peritoneal dialysis in Canada is due to lower comorbidity and a lower burden of acute onset end-stage renal disease at the inception of dialysis therapy. Hemodialysis and peritoneal dialysis, as practiced in Canada in the 1990s, are associated with similar overall survival rates.

Uremic small artery disease: calciphylaxis with penis involvement.

Two male patients with chronic renal failure maintained on hemodialysis developed progressive clinical features of ischemic necrosis (so called calciphylaxis) of their extremities and penis. Both patients died. In one patient, penectomy provided tissue for histopathologic examination and there were changes of small artery calcification. A role of iron overload on the production of calciphylaxis is reviewed. This report is perhaps the first in nephrology literature on the occurrence of calciphylaxis involving penis and prepuce.

Patterns of compliance with once versus twice daily antihypertensive drug therapy in primary care: a randomized clinical trial using electronic monitoring.

OBJECTIVE: To evaluate patterns of compliance with once versus twice daily administration of antihypertensive therapy (primary-outcome measure) and relevance of partial compliance for blood pressure control (secondary outcome measure). DESIGN: Multicentre, nonblinded, parallel group randomized design. SETTING: Nonacademic primary care practices across Canada. STUDY POPULATION: Patients with mild essential hypertension (diastolic blood pressure 95 to 110 mmHg) of either sex (40% women), age 18 to 80 years (average 55 years). One hundred and ninety-eight patients were randomized to active treatment; 14 patients discontinued the study because of side effects. INTERVENTIONS: After a four-week placebo run-in period, patients were randomized to amlodipine 5 mg once-a-day or diltiazem slow release formulation (SR) 90 mg twice daily. Doses were increased to 10 mg and 180 mg to achieve sitting diastolic blood pressure of 90 mmHg or less. OUTCOME MEASURE: During 20 weeks on active treatment, compliance was assessed by pill counts and medication event monitoring system (MEMS), assessing percentage of prescribed doses taken, percentage days correct doses taken, percentage prescribed doses taken on time and blood pressure control as determined by office blood pressure measurement. RESULTS: The percentage prescribed doses taken (by either pill count of MEMS) showed a high degree of compliance, similar for the two treatments. However, other parameters of compliance were significantly better with once versus twice daily therapy. Partial compliance (less than 80% by pill count) led to less blood pressure control with the short acting diltiazem, but did not affect blood pressure control for the long acting amlodipine. Side effects profiles did not differ between the two treatments. CONCLUSIONS: Within the constraints of a clinical trial, hypertensive patients in primary care show a high degree of overall compliance with once or twice daily pill-taking, but patterns of pill-taking are more erratic with twice versus once daily medication, particularly in men. The results suggest that the negative consequences of partial compliance for blood pressure control can be offset by choosing agents with a duration of action well beyond the dosing interval.

Prediction of early death in end-stage renal disease patients starting dialysis.

Demand for dialysis for patients with end-stage renal disease is growing, as is the comorbidity of dialysis patients. Accurate prediction of those destined to die quickly despite dialysis could be useful to patients, providers, and society in making decisions about starting dialysis. To determine whether age and comorbidity accurately predict death within 6 months of first dialysis for end-stage renal disease, a prospective cohort study of 822 patients starting dialysis at one of 11 Canadian centers was performed. Patient characteristics were recorded at first dialysis. Follow-up continued until death or study end (at least 6 months after enrollment). One hundred thirteen of 822 (13.7%) patients died within 6 months. Although an existing scoring system predicted prognosis, adverse scores greater than 9 were found in only 9.7% of those who died; only 52% of those who scored higher than 9 died within 6 months. No score cutoff point combined high true-positive and low false-positive rates for predicting early death. Age, severity of heart failure or peripheral vascular disease, arrhythmias, malnutrition, malignancy, or myeloma were independent prognostic factors identified in multivariate models. However, the best fit discriminant and logistic models were also unable to accurately predict death within 6 months. Clinicians were very accurate in assigning patients to prognostic groups up to a 50% risk of death by 6 months, above which they tended to overestimate risk. However, clinicians were only marginally better than the predictive models in determining whether a given high-risk patient would die. The inability of a scoring system or clinical intuition to accurately predict death soon after starting dialysis for end-stage renal disease suggests that limiting access to dialysis on the basis of likely short survival may be inappropriate in Canada.

24 hour blood pressure control with once-daily versus twice-daily formulations of diltiazem.

The antihypertensive effects of once-daily diltiazem CD over a 24 hour period were compared with twice-daily diltiazem SR in 95 patients with mild to moderate hypertension using ambulatory blood pressure monitoring. This trial was designed as a multicenter, double-blind, parallel-group study. Following a 2 to 4 week placebo run-in period, diltiazem was administered as once-daily CD or twice-daily SR, starting with 180 mg daily and increasing to a maximum of 360 mg daily, to achieve a seated diastolic blood pressure goal of < or = 90 mmHg as measured by cuff between 08:00 and 10:00 in the morning. Following drug titration, patients received a maintenance dose of diltiazem for an additional 6 week follow-up phase. Twenty-four hour ambulatory blood pressure monitoring recordings were obtained at the end of the placebo, titration, and maintenance phases. Both diltiazem CD and diltiazem SR significantly reduced both systolic and diastolic blood pressure over the 24 hour day and maintained a normal circadian pattern. As well, treatment with once-a-day diltiazem CD significantly decreased the slope of the early morning rise of diastolic and mean blood pressure. Thus, diltiazem CD is as effective as diltiazem SR in lowering diastolic blood pressure over a 24 hour period and has the advantage of a once-daily formulation.

Comparison of the efficacy and safety of once-daily versus twice-daily formulations of diltiazem in the treatment of systemic hypertension. The Canadian Multicenter Diltiazem-CD Hypertension Trial Group.

The efficacy and safety of optimally titrated once-daily (CD) and twice-daily (SR) diltiazem were compared in 111 patients with mild to moderate systemic hypertension [seated diastolic blood pressure (DBP) > or = 95 mmHg and < or = 114 mmHg] in a multicenter, randomized, double-blind, placebo run-in, parallel-group trial. Following a 4 week washout and placebo-controlled run-in period, patients were randomized to receive diltiazem CD 180 mg and matching placebo (n = 54), or diltiazem SR 90 mg bid (n = 57). Total daily doses were titrated from 180 mg to 360 mg to achieve a goal of seated DBP < 90 mmHg during a 6 week titration period. The patients continued to receive their optimal dose for a 6 week follow-up period. Ninety-six (96) patients (diltiazem CD: 47, diltiazem SR: 49) completed the study protocol, with 60% of the diltiazem CD and 55% of the diltiazem SR patients achieving the goal of seated DBP of < 90 mmHg (p = 0.685). Although significant decreases occurred in seated and standing measurements of diastolic and systolic BP and heart rate with treatment in both groups, there were no significant differences between treatment groups. Both medications were well tolerated, with a similar frequency of adverse effects [diltiazem CD: 24/54 (37%) patients; diltiazem SR: 24/57 (42.1%) patients] with the most frequently reported adverse effects being headache and edema.

The relationship of plasma norepinephrine levels and aortic distensibility in elderly with isolated systolic hypertension.

The present study evaluated the relationship of plasma norepinephrine (NE) and aortic distensibility (AOD) in a group of elderly patients with isolated systolic hypertension. Aortic distensibility was calculated as AOD = 2 x (delta aortic diameter)/diastolic aortic diameter) x (delta aortic pressure). Results indicate that the aortic diameters were significantly increased while the diastolic blood pressure and heart rate were decreased, in response to combined alpha- and beta-receptor blockade (labetalol). However, we found that AOD was not significantly related to plasma NE. We therefore conclude that AOD can be increased in elderly hypertensives by alpha-beta-blockade, as has been found in younger patients, but plasma NE is not a useful marker for AOD in this population.

Effectiveness and tolerability of once versus twice daily nitrendipine in the treatment of mild to moderate hypertension. The Canadian Nitrendipine Study Group.

Improved measurement of plasma concentrations of nitrendipine demonstrates a plasma half-life of 17 to 21 h allowing once daily dosing for antihypertensive treatment. To determine the effectiveness and tolerability of nitrendipine given once versus twice daily, 78 patients with mild to moderate essential hypertension were randomized in a double-blind fashion to 12 weeks of treatment with either nitrendipine 20 mg once daily (n = 39) or nitrendipine 10 mg bid (n = 39). Blood pressures measured at the end of the dosing interval were similar on 20 mg once daily and 10 mg bid. Adverse events considered to be drug related (flushing and headaches) occurred mostly at the beginning of active treatment and more frequently on the once daily dosing, resulting in a greater number of patients being withdrawn from the once daily treatment group. Thus, nitrendipine 20 mg once daily lowered blood pressure as effectively as 10 mg bid but was associated with a higher incidence of adverse events. These could be minimized by starting at nitrendipine 10 mg once daily and increasing to 20 mg once daily after two to four weeks.

Once- vs. twice-daily nitrendipine in the treatment of mild to moderate hypertension, Canadian Nitrendipine Study Group.

Improved measurement of the plasma concentration of nitrendipine demonstrated a plasma half-life of 17-21 h, allowing once-daily (o.d.) instead of currently twice-daily (b.i.d.) dosing. To determine the effectiveness of nitrendipine given o.d. vs. b.i.d., 78 hypertensive patients, [supine diastolic blood pressure (DBP) of 95-114 mm Hg] were randomized in a double-blind fashion to 12 weeks of treatment with either nitrendipine 10 mg b.i.d. (n = 39) or nitrendipine 20 mg o.d. (n = 39) after a 2-week placebo baseline period. Blood pressures (BPs) were measured in the morning at the end of the dosing interval. Mean +/- SD reduction in supine systolic BP (SBP) and DBP in patients evaluable for efficacy (greater than or equal to 14 days treatment) were 7.2 +/- 16.5 and 7.7 +/- 10.3 mm Hg, respectively, after nitrendipine b.i.d. (n = 38) and 9.4 +/- 15.1 and 9.5 +/- 7.0 mm Hg, respectively, after nitrendipine o.d. (n = 36). Similar falls in BP were found for both regimens in patients completing the full 12 weeks of treatment period (n: o.d. = 28, b.i.d. = 32). Discontinuation due to adverse experiences (AEs) occurred in three patients on b.i.d. and eight patients on o.d., the latter mostly in the first 2 weeks of therapy. Overall, AEs were higher in the o.d. group (% AEs at least possibly related to study medication: o.d. = 44%, b.i.d. = 33%). Most frequent AEs were headache and flushing.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood pressure profile in two adult male populations.

Causal blood pressure measurements were recorded in two groups of men aged 40 to 64 years; of the 7024 men in metropolitan Saint John, NB, and the 4044 men in seven suburbs of Quebec who were asked, 5840 (83.1%) and 3097 (76.6%) respectively agreed to participate. Of the Saint John group 9.0% were taking antihypertensive drugs, as compared with only 3.3% of the Quebec group (p less than 0.0001). Among the treated subjects 33% in Saint John and 53% in Quebec still had a diastolic pressure greater than 95 mm Hg (p less than 0.01). Among the participants not taking antihypertensive drugs the systolic blood pressure increased with age, but the diastolic blood pressure increased only slightly up to 55 years of age and then decreased. On average the subjects in Saint John who were not being treated had a systolic pressure 6.2 mm Hg lower and a diastolic blood pressure 3.6 mm Hg lower than their Quebec counterparts (p less than 0.0001). This difference was observed in all the age groups and was not the result of the treatment of a greater proportion of the Saint John cohort. Despite the higher blood pressures and the smaller number receiving adequate treatment in the Quebec group, the rate of death due to coronary artery disease was 10% lower than that in the Saint John group. A bias in the data from Quebec may have influenced the magnitude of the differences between the two samples, but if present it should have underestimated the blood pressures in the Quebec group and therefore not have changed the outcome.

Drug-induced acute interstitial nephritis: report of 10 cases.

Between January 1979 and June 1985, 10 patients with acute allergic interstitial nephritis were seen in a clinical nephrology service at a large regional hospital. The onset of renal failure was temporally related to the use of a drug: a nonsteroidal anti-inflammatory agent (NSAID) (in four patients), cimetidine (in three), antibiotics (in two) or allopurinol (in one). The onset of renal failure was acute in three patients and insidious in seven. Two patients also exhibited marked proteinuria. Clinical features such as fever, rash, hematuria, pyuria with or without eosinophiluria, and mild to marked proteinuria had led to suspicion of the disease. The diagnosis was confirmed by renal biopsy findings of inflammatory cells, predominantly lymphocytes, plasma cells and eosinophils. Three patients required hemodialysis; two of them received steroids as well. Steroid therapy was also used in two patients with NSAID-induced proteinuria. Renal function improved in nine patients by 35 days, but one patient continued to have slow but progressive deterioration of renal function. Acute interstitial nephritis can be distinguished from other forms of acute renal failure by heavy renal uptake of gallium 67, maximal 48 hours or more after injection. The improvement in renal function after discontinuation of the implicated drug, the characteristic histopathological findings of allergic interstitial nephritis, and the presence of eosinophils and sometimes IgE in the blood suggest a hypersensitivity reaction.

Blood pressure: distribution in students of junior and senior high schools in Saint John, NB.

Blood pressures were recorded for 8950 students (82.4% of the total student population) of the junior high and high schools of Saint John, NB. Among the boys the mean systolic pressure rose from 104 mm Hg at age 12 to 117 mm Hg at age 18; among the girls the rise was from 105 to 110 mm Hg. The mean diastolic pressure also rose, from 61 to 67 mm Hg, in both sexes. These data are similar to those found in epidemiologic studies in Montreal and Bogalusa, Louisiana. However, the mean systolic values are lower by 10 mm Hg than those in an Edmonton study and the norms published by a United States task force. Recording methods could explain some of the observed differences, but population differences may also contribute. The discrepancies suggest that the current standards for children and adolescents need to be reassessed.

A large regional hospital's experience with treatment of end-stage renal disease.

During the first 10 years of the treatment program for end-stage renal disease at the Saint John (New Brunswick) Regional Hospital 164 adults were treated by hemodialysis (with or without renal transplantation, performed outside of the province) or peritoneal dialysis. The primary causes of renal disease were not significantly different in men and women except for glomerulonephritis, which was twice as common in men as in women. Life-table analysis showed that the younger transplant recipients had the highest survival rate, but that the prognosis was almost as good among the much older patients who received continuous ambulatory peritoneal dialysis. Probably because they tended to be younger and their renal disease was caused by less threatening conditions, men survived longer than women. The survival rates were significantly related to the primary cause of the renal disease; patients with diabetes or systemic disease had the worst prognosis. Overall, these results compare well with those obtained in major university centres.