B-type natriuretic peptide and severe heart failure at baseline predict overall mortality in incident dialysis patients.

AIMS: The B-type natriuretic peptide (BNP) has become increasingly important as a diagnostic and prognostic method for cardiovascular disease or death. To our knowledge no prospective studies exist to evaluate the value of baseline BNP and baseline heart failure as predictors of overall death in incident rather than prevalent hemodialysis patients with end-stage renal disease (ESRD). METHODS: 255 ESRD patients were included in our observational study with a median observation period of 1.11 years. A Kaplan-Meier survival curve was stratified by BNP concentration (< 340 pg/ml and > or = 340 pg/ml) to estimate the impact on the overall mortality rate. Univariate and multiple Cox regression models were fitted for a variety of covariables including severe heart failure (graded according to the New York Heart Association) to evaluate the independent predictors of death. Association between BNP and four explanatory variables was described in a multiple linear regression model. RESULTS: Survival analysis demonstrated a significantly higher mortality rate in patients with higher BNP values at baseline. The independent predictive value of high BNP concentration at baseline could be statistically confirmed by multiple Cox regression analysis. However, when including the covariates hemoglobin and severe heart failure, significantly associated with BNP, in the same model, severe heart failure rather than BNP becomes a significant predictor of overall death. CONCLUSIONS: A higher BNP level at baseline may be confirmed as an independent predictor of death in the incident dialysis population. However, severe heart failure may affect the impact of BNP on the overall survival rate and thus be a stronger predictor of death than BNP.

Successful off-label use of cinacalcet HCl after standard therapy failure in a young man with pseudohypoparathyroidism Type 1b and vitamin D intoxication sequelae.

We describe the case of a young man with pseudohypoparathyroidism Type 1b--a rare genetic disorder characterized by end-organ resistance to parathormone (PTH)--and vitamin D intoxication sequelae due to inappropriate and poorly monitored calcitriol treatment in his adolescence, who could no longer be successfully treated by standard vitamin D treatment alone. Off-label administration of cinacalcet HCl, a calcimimetic approved for the treatment of secondary hyperparathyroidism, together with the vitamin D analog dihydrotachysterol, however, proved successful in controlling parathormone (PAH), bone-specific alkaline phosphatase (BAP), serum calcium, and phosphate levels.

Ezetimibe for the treatment of uncontrolled hypercholesterolemia in patients with high-dose statin therapy after renal transplantation.

We investigated prospectively the efficacy of ezetimibe in addition to statin therapy in stable renal transplant patients in whom hypercholesterolemia was not sufficiently treated. Eighteen renal transplant patients received 10 mg ezetimibe once daily in addition to high-dose statin therapy for uncontrolled hypercholesterolemia. Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, Tacrolimus (Tac)- and Cyclosporine A (CsA) blood levels, creatinine, urea, liver enzymes, electrolytes and creatinkinase (CK) were measured before initiation of ezetimibe therapy, after 7 days, 6 weeks and 3 months. Cholesterol concentrations decreased significantly (p < 0.005) from 264 +/- 46 mg/dL at baseline to 205 +/- 48 mg/dL after 1 week to 202 +/- 48 mg/dL after 6 weeks and 212 +/- 40 mg/dL after 3 months (reduction after 3 months 21 +/- 10%). LDL-concentrations decreased significantly (p < 0.005) from 178 +/- 41 mg/dL at baseline to 129 +/- 35 mg/dL after 1 week to 123 +/- 25 after 6 weeks and to 117 +/- 40 mg/dL after 3 months (reduction after 3 months 37 +/- 14%). Two patients stopped ezetimibe therapy due to nausea and muscle pain without CK elevation. Significant changes of CsA and Tac blood levels, liver and muscle enzymes were not observed. Ezetimibe seems to be an effective therapy for uncontrolled hypercholesterolemia in renal transplant patients when combined with high-dose statin therapy.

Impact of febrile infections on the long-term function of kidney allografts.

PURPOSE: We prospectively determined the impact of febrile infectious disease on long-term renal graft function compared with a matched control group. MATERIALS AND METHODS: Included in our study were 39 patients who presented with episodes of febrile infection with body temperature greater than 38C on 2 consecutive occasions, necessitating hospitalization. In addition, 39 controls without febrile infection requiring hospitalization within 2 months were chosen from the complete data pool of all renal transplant recipients followed at our transplant clinic using the matched pair technique. Renal function was estimated by serum creatinine and calculated creatinine clearance. RESULTS: Of the 39 patients with infection 15 had urinary tract infection and 24 had other, mostly bacterial infection, including pneumonia/severe bronchitis in 12, oral/dental infection in 2, gastroenteritis in 2, shunt sepsis in 1, herpes zoster in 1, cytomegalovirus in 1 and other in 5. Mean estimated creatinine clearance plus or minus standard deviation was similar in the infection and control groups at the beginning of the study (51 +/- 22 and 51 +/- 23 ml. per minute, respectively). During the infectious episode mean creatinine clearance significantly decreased to 38 +/- 17 ml. per minute in the infection group. After infection resolved creatinine clearance returned to an almost baseline mean value of 50 +/- 23 ml. per minute. However, after 2 years of followup there was a significant difference in mean creatinine clearance in the infection group versus controls (45 +/- 25 versus 52 +/- 25 ml. per minute, p = 0.022). CONCLUSIONS: To our knowledge we have shown for the first time in a prospective controlled study that febrile infectious episodes correlate with poor long-term renal graft function.

The nitric oxide synthase inhibitor L-NMMA potentiates noradrenaline-induced vasoconstriction: effects of the alpha2-receptor antagonist yohimbine.

OBJECTIVE: Alpha2-adrenoceptors can be found both on vascular smooth muscle cells and on the endothelium, where they exert opposing effects on vascular tone. In vitro, the stimulation of alpha2-adrenoceptors on endothelial cells leads to the release of vasodilating substances like nitric oxide (NO) and prostanoids. Little is known of this mechanism in vivo. DESIGN AND METHODS: We investigated the effects of the NO-synthase inhibitor L-NMMA (10(-6) mol) and the alpha2-adrenoceptor antagonist yohimbine (YO, 10(-10)-10(-6) mol) on noradrenaline (NA, 10(-12)-10(-8) mol)-induced vasoconstriction in the forearm skin microcirculation of 16 healthy volunteers using double injection technique and laser Doppler flowmetry. Results are expressed in perfusion units (PU) as differences from baseline and control in mean +/- SEM; the area under the time-response-curve was calculated (AUC). RESULTS: NA (10(-8)- 10(-12) mol) caused a marked, dose-dependent reduction in blood flow (mean effect -745 +/- 84 AUC PU; P< 0.001 versus saline). NA-induced vasoconstriction was enhanced by L-NMMA (mean effect -916 +/- 72 AUC PU; P< 0.001 versus NA). YO (10(-6)-10(-10) mol) induced a significant, dose-dependent vasodilation (mean effect +/- 446 +/- 110 AUC PU; P < 0.05 versus control); high doses of YO (10(-6) mol) inhibited NA constriction (P < 0.001 versus NA), whereas lower doses of YO (10(-8)/10(-10) mol) had no effect or even increased NA-induced constriction. In the presence of L-NMMA, YO (10(-8) and 10(-10) mol) further potentiated NA-induced vasoconstriction (mean effect -1165 +/- 108 AUC PU; NS versus NA). CONCLUSION: These data demonstrate, that in humans in vivo, endogenous NO attenuates noradrenergic constriction. The effects of YO suggest that endothelial alpha2-adrenoceptors are involved in the release of NO and other vasodilating substances. Furthermore, there is an additive NO-independent vasodilation, which can be unmasked by L-NMMA.

Conversion from cyclosporine A to tacrolimus after kidney transplantation due to hyperlipidemia.

As more than 90% of renal grafts retain their function 1 year after renal transplantation, side effects of immunosuppressive therapy gain more and more importance. In a randomised prospective study, we investigated the effects of conversion from cyclosporine A to tacrolimus due to hyperlipidemia in recipients of renal allografts. Fifty-seven patients with stable graft function treated with cyclosporine were randomly assigned to conversion to tacrolimus or continuation of their current therapy and followed for 1 year. Twenty-seven patients were switched and 30 patients remained on cyclosporine A. Cholesterol levels decreased significantly in the tacrolimus group as compared to controls in the intent to treat analysis. When only those patients were evaluated who received cyclosporine or tacrolimus during the whole study, statistical significance was even more pronounced. Triglyceride levels decreased in the tacrolimus group, whereas they increased in controls. Creatinine levels remained stable and no acute rejection was observed. A switch to tacrolimus is a safe alternative in cases of hyperlipidemia after renal transplantation.

Quality of life in patients before and after kidney transplantation.

Abstract The aim of the present study was to differentially determine quality of life (QOL) in patients with end-stage renal disease (ESRD) after successful kidney transplantation (RT, Group A) compared with ESRD patients on a waiting list for RT (Group B). and with healthy controls (Group C) because opinions vary as to which treatment modality can best assure ESRD patients a high QOL. Groups A, B and C each consisted of 149 persons, matched for age and gender. The Munich Quality of Life Dimensions List (MLDL) was used to measure global aspects of QOL. Distinct aspects of QOL were investigated by the Brief Symptom Inventory (BSI) and the Questionnaire for Social Support (K-22). Groups A and C reported similar QOL. Which was significantly higher than in group B (p < .0001). This was particularly true for the physical and psychological status and daily activities, but not for the social situation. Groups A and B reported similar social support, which was significantly, lower than in group C (p < 006). Both ESRD groups reported higher satisfaction with social support than healthy controls (p < .0001). Successful RT nor only improved distinct aspects of QOL in patients with ESRD, but even put them on par with healthy controls regarding physical and psychological QOL. Lower social support and higher satisfaction with social support in both groups of ESRD patients should be evaluated further. From a clinical viewpoint. the improvement of physical and psychological aspects of QOL in RT patients is impressive; but more attention should be paid to constantly low social support in this group of patients. International multi center longitudinal studies to investigate QOL in ESRD patients under different treatments am necessary.

Quality of life in end-stage renal disease patients after successful kidney transplantation: development of the ESRD symptom checklist - transplantation module.

The End-Stage Renal Disease Symptom Checklist - Transplantation Module (ESRD-SCL((R))) was developed to assess the specific physical and psychological quality of life of renal transplant recipients, with a special focus on side effects of immune system suppression therapy. A list of potentially relevant items was administered to 458 transplant recipients. The symptoms present in >20% of patients were chosen, and factor analysis was used to create the final questionnaire which consists of 43 items in six dimensions: (1) limited physical capacity (10 items; internal consistency: Cronbach's alpha = 0.85); (2) limited cognitive capacity (8 items, alpha = 0.82); (3) cardiac and renal dysfunction (7 items, alpha = 0. 76); (4) side effects of corticosteroids (5 items, alpha = 0.77); (5) increased growth of gum and hair (5 items, alpha = 0.78), and (6) transplantation-associated psychological distress (8 items, alpha = 0.80). All questions are scored on a five-point Likert scale. Validity was demonstrated in correlation with corresponding SF-36 scales and in a stepwise hierarchical regression model predicting the subscales of the ESRD-SCL by sociodemographic and medical data. The ESRD-SCL was found to have adequate reliability, test-retest correlations in a subsample of 88 stable patients after 1 year, and construct validity.

[Quality of life following transplantation. The impact ofa new immunosuppressive substance]. / Lebensqualität nach Nierentransplantation. Einfluss neuer immunsuppressiver Substanzen.

The improvement of quality of life is one of the major goals in the treatment of patients after renal transplantation. While immunosuppressive therapy is present in almost all of these patients, little is known about the effects of newer immunosuppressive agents. We therefore investigated the impact of tacrolimus on life quality. From November 1997 to January 1998, a questionnaire was handed out which focussed on physical and mental problems as well as sexual capacity and the attitudes towards graft, donor and transplant related side effects. 50 kidney graft recipients treated with tacrolimus were matched to 50 patients with a cyclosporine-based immunosuppression (= controls). Values are given as mean +/- standard deviation. Tacrolimus treated patients had a mean creatinine of 1.8 +/- 0.8 mg/dl, as compared to 1.6 +/- 0.7 mg/dl in controls. The overall status of health was assessed to be good in 82% of the tacrolimus group (controls: 80%). 38% were working full-time (controls: 20%). Only 14% of patients described their physical condition as poor (16% in controls). Sexual function was good in 66% (controls: 74%) and poor in 10% (controls: 12%). Mental function was assessed to be good in 92% (controls: 82%). The majority of patients felt comfortable with their physical, sexual and mental capabilities. This was independent from the immunosuppressive regimen.

Prevalence of diverticulosis and incidence of bowel perforation after kidney transplantation in patients with polycystic kidney disease.

Sigmoid perforation due to diverticulitis is a life-threatening complication in the postoperative course of allogenic kidney transplantation. The incidence of diverticulosis is especially high among patients with autosomal dominant polycystic kidney disease (ADPKD). Thus, those who undergo allogenic kidney transplantation represent a high-risk group. The aim of this study was to evaluate the prevalence of diverticulosis in ADPKD patients awaiting renal transplantation and the incidence of bowel perforation following allogenic kidney transplantation due to ADPKD. Within the group of 1128 patients who underwent transplantation between January 1974 and January 1990, there were 46 patients (4.07%) whose indication for transplantation was ADPKD. There was one patient who developed a sigmoid perforation under postoperative immunosuppression. Surgical treatment was a discontinuity resection of the sigmoid (Hartmann's procedure). The postoperative course was favorable, the bowel continuity has already been restored, and the graft is still functioning well. Fifteen of the 28 (53.5%) ADPKD patients awaiting transplantation had colon diverticulosis (12 male and 3 female patients). No case of bowel perforation has thus far been observed in 15 of these patients who have undergone transplantation. A sigmoid resection was necessary in one patient due to diverticulitis without perforation. We did not find a higher prevalence of diverticulosis in patients with ADPKD, nor did we see a higher incidence of sigmoid perforation during post-transplant immunosuppression in this study.

Metabolic factors have a major impact on kidney allograft survival.

BACKGROUND: At the present time, late graft loss is the major cause of kidney failure after transplantation. However, the influence of metabolic factors on this process is ill-defined. METHODS: To identify the impact of lipid metabolism, glucose metabolism, and blood pressure and their prognostic value for graft survival, data for all recipients of a kidney allograft with a potential graft survival of >15 years and a minimum graft survival of 1 month were analyzed retrospectively. Recipients of kidney grafts functioning more than 15 years (n=32) were compared with those with a graft function of less than 10 years (n=152, controls) and evaluated in a multivariate analysis. RESULTS: Low levels of serum cholesterol, triglycerides, and glucose, before and after transplantation, were accompanied by a prolonged graft survival. Prognostic factors for early graft failure included serum triglycerides >300 mg/dl, cholesterol >250 mg/dl before transplantation, serum creatinine >4.0 mg/dl 1 month after transplantation, and donor age above 45 or less than 10 years. Additionally, systolic and, particularly, diastolic blood pressure was lower in the group with a prolonged graft function as compared with controls immediately before and after transplantation. In addition, the incidence of primary graft function was lower and the incidence of acute rejection episodes higher in controls. Cold and warm ischemic time, body mass index, recipient age, and gender did not differ significantly. CONCLUSIONS: Our data suggest that metabolic parameters play an important role in the process of late graft loss after kidney transplantation.

Effect of exercise on propranolol pharmacokinetics.

The effect of submaximal exercise on the pharmacokinetics of low dose intravenous propranolol was studied in 15 healthy human subjects. There was a wide individual variation in the results for each subject and a large difference in the degree of changes with exercise. The effect of exercise on the pharmacokinetics of propranolol, a flow limited drug, is marked but variable. This phenomenon may have profound effects on patients taking the drug regularly who exercise intermittently and drug doses may have to be adjusted.