Depression, alexithymia and long-term mortality in chronic hemodialysis patients.

BACKGROUND: Depression increases the risk of mortality in hemodialysis patients. Alexithymia, a disorder of affect regulation, has also been reported to be associated with mortality risk in the general population. We conducted a prospective study to estimate the independent impact of depression and alexithymia on long-term mortality. METHODS: A total of 230 hemodialysis outpatients, with a mean age of 56.3 +/- 9.6 years, completed a batch of self-report measures including the Beck Depression Inventory-II (BDI-II), the 20-item Toronto Alexithymia Scale (TAS-20) and the 36-item Short Form Health Survey (SF-36). Survival status was confirmed every 6 months for up to 5 years. The presence of depression and alexithymia was defined by a BDI-II score of > or =14 and a TAS-20 score of > or =61, respectively. RESULTS: During the follow-up period, 27 deaths were confirmed. Both depression and alexithymia were associated with an increased risk for all-cause mortality; the age- and sex-adjusted hazard ratio for depression was 2.36 (95% CI: 1.08-5.15; p = 0.03) and that for alexithymia was 4.29 (95% CI: 1.95-9.42; p < 0.001). Depression lost its statistical significance after controlling for alexithymia, whereas alexithymia remained significant even after adjusting for the baseline depression, health status (the summary scores of the SF-36), marital status and clinical covariates (multivariate adjusted hazard ratio = 3.62; 95% CI: 1.32-9.93; p = 0.01). CONCLUSIONS: Alexithymia is a strong independent risk factor for all-cause mortality in hemodialysis patients.

Loss of fractal heart rate dynamics in depressive hemodialysis patients.

OBJECTIVE: To assess the relationship between depression, reduced heart rate (HR) variability, and altered HR dynamics among patients with end-stage renal disease who are receiving hemodialysis (HD) therapy. METHODS: We analyzed the 24-hour electrocardiograms of 119 outpatients receiving chronic HD. HR variability was quantified with the standard deviation of normal-to-normal R-R intervals, the triangular index, and the powers of the high- (HF), low- (LF), very-low (VLF), and ultra-low frequency (ULF) components. Nonlinear HR dynamics was assessed with the short-term (alpha(1)) and long-term (alpha(2)) scaling exponents of the detrended fluctuation analysis and approximate entropy. The depression level was assessed using the Beck Depression Inventory, Second Edition (BDI-II). HR variability and dynamics measurements were compared by gender, diabetes, and depression with adjustment for age and serum albumin concentration. RESULTS: Most indices of HR variability and dynamics were negatively correlated with age, serum albumin concentration, depression score, and were lower in women and patients with diabetes. The alpha(2) was inversely associated with these variables. Depressed men had significantly lower HF, LF, VLF, and marginally lower ULF than nondepressed persons after adjustment for diabetes and other covariates; no difference in depression was observed in women. The alpha(2) showed marginally significant difference in depression independent from gender and diabetes. CONCLUSIONS: Among the patients who received HD, depression is associated with reduced HR variability and loss of fractal HR dynamics. However, the influence of depression on HR variability may vary by gender and physiological backgrounds. Further prospective studies are necessary to confirm their association with poor prognosis.

Independent associations of alexithymia and social support with depression in hemodialysis patients.

OBJECTIVE: The influences of alexithymia and social support on depression among chronically ill patients were examined prospectively. METHODS: The study population was 230 outpatients receiving chronic hemodialysis (HD) therapy. The Beck Depression Inventory-II (BDI-II), the 20-item Toronto Alexithymia Scale (TAS-20), and two subscales of the Social Support Questionnaire were given to the subjects. The BDI-II was readministered after a 6-month interval, and subjects who showed deterioration in their depression score above the level predicted from their baseline score were identified. Multivariate logistic analysis adjusted for age, gender, cause of dialysis, and psychosocial variables were performed. RESULTS: Baseline depression was significantly and independently associated with alexithymia and low satisfaction with available support. Deterioration of depression after 6 months was predicted by alexithymia and poor available support. CONCLUSIONS: Alexithymia and reduced social support might have independent associations with the presence and the prognosis of depression among HD patients.

Effects of combination treatment with losartan and trandolapril on office and ambulatory blood pressures in non-diabetic renal disease: a COOPERATE-ABP substudy.

BACKGROUND: In the COOPERATE trial, the combination treatment of the angiotensin-II receptor blocker losartan and the angiotensin-converting-enzyme inhibitor trandolapril significantly retarded progression of non-diabetic kidney disease compared with each monotherapy. The benefit could be greatly attributable to the potent reduction of proteinuria, because the three treatment groups showed the same reductions of office blood pressure (OBP). Ambulatory blood pressure (ABP) is reported to be better than OBP in predicting progression of kidney disease. METHODS: Ninety-two patients enrolled in the COOPERATE trial underwent 24-hour ABP monitoring at randomization and at month 6, year 1, year 2 and year 3 on randomized treatment. RESULTS: Both OBP and ABP were similarly reduced among the three groups at all measurement points (p = NS) and throughout the whole study period (p = NS). No significant correlation between the change in 24-hour ABP and the change in proteinuria was seen (p = NS). A Cox-multivariable analysis showed that covariates affecting the renal outcomes (a doubling serum-Cr level and/or end-stage renal failure) were the change in proteinuria (hazard ratio 0.49, 95% CI 0.34-0.78, p = 0.01) and treatments (0.58, 0.45-0.99, 0.03), but not 24-hour ABP (0.98, 0.89-2.01, 0.17). CONCLUSION: The better renoprotective effect of the combination treatment is attributed to BP-independent mechanisms by more complete renin-angiotensin system blockade.

Dual blockade of the renin-angiotensin system in chronic renal disease: to do or not to do.

The renin-angiotensin-aldosterone system has an important role in the progression of both diabetic and nondiabetic nephropathy. Angiotensin-converting enzyme inhibitors and angiotensin-II receptor blocker can effectively retard or halt this progression. However, their renoprotective effect is not enough, because approximately 20% of patients have a progressive course to endstage renal disease. There is now clear evidence that combination therapy of two agents is more antiproteinuric and, likely renoprotective, than each agent alone. However, several critical issues should be addressed before recommending it as standard treatment in chronic renal disease.

Elimination kinetics of quinaprilat and perindoprilat in hypertensive patients with renal failure on haemodialysis.

Objective of the present study was to investigate the elimination kinetics of quinaprilat and perindoprilat, the active metabolites of angiotensin-converting enzyme (ACE) inhibitors quinapril and perindopril, in hypertensive patients with renal failure under haemodialysis to evaluate the appropriate duration of off-dose of these drugs before starting of low-density lipoprotein (LDL) apheresis. The informed consent was received from 12 hypertensive patients with renal failure, who were under haemodialysis (42 to 62 years). The patients received oral administration of quinapril (10 mg) or perindopril (2 mg) once a day for four weeks. First, to evaluate the dialyzability of each metabolite, blood samples were collected before and after haemodialysis one week after the repeated doses. Second, to evaluate the elimination kinetics of quinaprilat or perindoprilat, blood samples were collected at 24, 72, 120, 192 and 240 h after the final administration. Plasma concentrations of quinaprilat and perindoprilat were measured by high-performance liquid chromatography (HPLC) and radioimmunoassay, respectively. Pharmacokinetic parameters were determined by a model-dependent method. Values of haemodialysis clearance (CL(HD)) and extraction ratio (ER) were 51.5+/-30.2 ml/min and 0.35+/-0.21 for quinaprilat and 108.1+/-5.9 ml/min and 0.75+/-0.04 for perindoprilat, respectively. The terminal elimination half-lives of quinaprilat and perindoprilat were 60.7+/-2.1 and 79.9+/-14.0 h, respectively. The dialyzability of perindoprilat was much higher than that of quinaprilat probably due to low protein binding potency. The present study suggests that hypertensive patients receiving chronic therapy with quinapril or perindopril on haemodialysis should be withdrawn for at least 2 to 3 weeks before LDL apheresis.

[An efficacy study of a TPN kit with multivitamin addictive in the HPN].

When home parenteral nutrition (HPN) is instituted, one should aim at reducing the risk of infections, simplifying the operation, and improving the patient's QOL, while considering the differences between the hospital and home. As for simplification of the operation, the problem is who and when to prepare the TPN while paying attention to the stability of multivitamins. Recently, a TPN kit that includes multivitamins and does not need a syringe or an injection needle to add vitamins to the TPN preparation was launched. Accordingly, we conducted a study to examine the simplicity of the procedure and usefulness of the product on the basis of time required to add other components to the TPN preparation, as assessed by questionnaire. The subjects of the study were medical care providers as well as patients on HPN and their families. The time required for TPN admixtures was significantly shorter compared with the conventional method. According to the questionnaire, the storability and easiness of the procedure were particularly highly appreciated. This product has the advantage that sterility can be maintained at home, that contamination with foreign bodies can be reduced, and that it can be stored at room temperature. Since it can be preserved in preparation for natural disasters and can be carried around during travel, it is expected to improve the QOL of patients on HPN and their families.

[An efficacy study of a TPN kit with multivitamin additive in the HPN].

When home parenteral nutrition (HPN) is instituted, one should aim at reducing the risk of infections, simplifying the operation, and improving the patient's QOL, while considering the differences between the hospital and home. As for simplification of the operation, the problem is who and when to prepare the TPN while paying attention to the stability of multivitamins. Recently, a TPN kit that includes multivitamins and does not need a syringe or an injection needle to add vitamins to the TPN preparation was launched. Accordingly, we conducted a study to examine the simplicity of the procedure and usefulness of the product on the basis of time required to add other components to the TPN preparation, as assessed by questionnaire. The subjects of the study were medical care providers as well as patients on HPN and their families. The time required for TPN admixtures was significantly shorter compared with the conventional method. According to the questionnaire, the storability and easiness of the procedure were particularly highly appreciated. This product has the advantage that sterility can be maintained at home, that contamination with foreign bodies can be reduced, and that it can be stored at room temperature. Since it can be preserved in preparation for natural disasters and can be carried around during travel, it is expected to improve the QOL of patients on HPN and their families.