Moxonidine normalizes sympathetic hyperactivity in patients with eprosartan-treated chronic renal failure

Enalapril and losartan reduce but not normalize sympathetic hyperactivity in patients with hypertensive chronic renal failure (CRF). This study assessed the effect of chronic eprosartan on BP and sympathetic activity, and assessed the effect of moxonidine during chronic eprosartan treatment. In 11 stable patients with CRF (creatinine clearance 47 +/- 10 ml/min), muscle sympathetic nerve activity (MSNA; peroneal nerve), BP, and baroreceptor sensitivity were measured in the absence of antihypertensive drugs (except diuretics) during chronic eprosartan therapy (600 mg for 6 wk) and in 9 patients after moxonidine (0.2 mg for 6 wk) was added. Normovolemia was controlled by diuretics and confirmed by extracellular fluid volume measurements. BP, heart rate, and MSNA were higher in patients than in 22 controls. During eprosartan therapy, mean arterial pressure (111 +/- 9 to 98 +/- 7 mmHg, P < 0.001), heart rate (71 +/- 10 to 65 +/- 8 bpm, P < 0.001), and MSNA (35 +/- 10 to 27 +/- 8 bursts/min, P < 0.001) decreased. After the addition of moxonidine (n = 9), a further reduction of mean arterial pressure to 89 +/- 7 mmHg (P < 0.05) and of MSNA to 20 +/- 10 bursts/min (P < 0.05) occurred. Sympathetic activity in patients with CRF can be normalized, and angiotensin II-independent sympathetic hyperactivity contributes to the pathogenesis of renal hypertension. Sympathetic hyperactivity is associated with poor cardiovascular outcomes, implying that reduction might be beneficial to the patients. The addition of moxonidine to angiotensin II antagonist treatment might be appropriate.     

Zinc in patients with chronic renal failure

In order to assess zinc status in patients with chronic renal failure (CRF) plasma and erythrocyte zinc levels were determined in 13 patients undergoing regular haemodialysis. Additional determinations of plasma copper, plasma and erythrocyte magnesium and potassium were also performed. The mean plasma zinc level was slightly less than normal, but the difference was not statistically significant. The erythrocyte zinc content, however, as well as erythrocyte magnesium and potassium levels were significantly increased (p<0.001). This increase may be partly related to haemolysis in uraemia. Plasma copper concentration in CRF patients did not differ significantly from the control level. The almost normal plasma zinc concentration, elevated erythrocyte zinc, and normocupraemia do not indicate zinc deficiency in CRF patients.     

慢性肾功能衰竭患者的高同型半胱氨酸血症

目的 研究慢性肾功能衰竭（ＣＲＦ）患者血浆同型半胱氨酸（Ｈｃｙ）水平、影响因素以及与心、脑血管疾病的关系。方法 采用荧光偏振免疫分析法测定１６０例ＣＲＦ患者血浆总同型半胱氨酸（ｔＨｃｙ）水平，以３１例冠心病患者和４５例正常人为对照。结果 以正常组血浆ｔＨｃｙｘ±２ｓ为９５％可信度上限，ＣＲＦ患者高同型半胱氨酸血症的发生率为８２．５０％，明显高于冠心病组（２２．５８％）（Ｐ＜０．０１）；血液透析（ＨＤ）组血浆ｔＨｅｙ水平［（２４．１３±１２．６８）μｍｏｌ／Ｌ，ｎ＝７３］明显高于持续性非卧床腹膜透析（ＣＡＰＤ）组［（１６．４３ ±５．５８）μｍｏｌ／Ｌ，ｎ＝１９］、冠心病组［（１１．１３±４．９７）μｍｏｌ／Ｌ，ｎ＝３１］以及正常组（７．９７±２．６５）μｍｏｌ／Ｌ，ｎ＝４５，Ｐ均＜０．０１。９２例透析治疗的ＣＲＦ患者中有明确心、脑血管病者的血浆ｔＨｃｙ水平［（２７．１２±１５．９４）μｍｏｌ／Ｌ，ｎ＝３０］明显高于无此类病史的患者［（２０．１７±８．７１）μｍｏｌ／Ｌ，ｎ＝６２］。未经透析的 ＣＲＦ患者血浆 ｔＨｃｙ水平与内生肌酐清除率呈负相关（ｒ＝－０．３７４，Ｐ＜０．０１），与患者年龄、血葡萄糖、血脂及血浆白     

Sympathetic hyperactivity in chronic renal failure: a wake-up call

Sympathetic hyperactivity plays an important and distinct role in hypertension associated with chronic renal failure (CRF). Renal ischemia, elevated angiotensin II, and suppressed brain nitric oxide (NO) all stimulate sympathetic activity. Evidence is accumulating for a role of sympathetic hyperactivity in renal and cardiac damage in patients with CRF. Decreased NO availability and increased oxidative stress, characteristic in CRF patients, seem to sensitize target organs for damaging actions of sympathetic hyperactivity. Fortunately, sympatholytic agents can slow down progression of renal and cardiac dysfunction. Angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists suppress sympathetic activity, but complete elimination of the effect of sympathetic hyperactivity can be obtained only with specific adrenergic blockers. However, this important therapeutic option is grossly neglected, painfully illustrated by the unwillingness to treat CRF patients with beta-blockers, even if they have had a myocardial infarction. After discussion of mechanisms and effects of the sympathetic hyperactivity, a case is made for increased application of specific adrenergic blockers in patients with CRF.     

Hip arthroplasty in patients with chronic renal failure

Patients with chronic renal failure who underwent total hip arthroplasty were retrospectively evaluated. Thirty hips in patients with renal transplants and 16 hips in patients on chronic renal dialysis were reviewed. The average follow-up period was 54 months. The renal transplant patients exhibited generally satisfactory results. Their postoperative course was comparable to that of patients with avascular necrosis undergoing hip reconstruction without underlying renal disease. However, patients undergoing hip arthroplasty while on chronic renal dialysis had poor results (81%), including a deep infection rate of 19%. It was concluded that total hip arthroplasty be reserved for patients who are expecting a renal transplant or preferably for those who have already received a successful transplant.     

Calcitriol metabolism in patients with chronic renal failure

We studied calcitriol metabolism in white patients with chronic renal failure and in age- and sex-matched normal subjects. The plasma levels of calcitriol (21.9 +/- 1.6 pg/mL, n = 7, v control, 37.4 +/- 2.9 pg/mL, P less than 0.001), metabolic clearance rate (MCR) of calcitriol (0.45 +/- .01 mL/min/kg v control, 0.58 +/- .02 mL/min/kg, P less than 0.001), and production rate (PR) of calcitriol (14.2 +/- 1.0 ng/kg/d v control, 31.8 +/- 3.2 ng/kg/d, P less than 0.001) were significantly lower in patients with moderate renal failure (average creatinine clearance, 0.59 +/- 0.01 mL/s [35.1 +/- 6.1 mL/min]) when compared with the respective values of normal control subjects. The MCR of calcitriol was determined again in patients with renal failure after they received calcitriol, 1 microgram/d, for 1 week. The MCR remained unchanged (0.46 +/- .04 mL/min/kg, n = 7) and plasma levels of calcitriol were increased to 34.6 +/- 2.77 pg/mL. The mechanism by which the MCR of calcitriol decreases in renal failure is partly due to the presence of inhibitory factors of degradation enzymes in uremic plasma. When the ultrafiltrates of uremic plasma obtained from hemodialysis patients were infused to normal Sprague-Dawley rats, the MCRs of calcitriol (0.20 +/- .01 mL/min/kg, n = 6) were markedly suppressed in comparison to those of rats infused with the ultrafiltrates of normal plasma (0.37 +/- .01 mL/min/kg, n = 6, P less than 0.001). The uremic plasma also contained factors that inhibit the synthesis of calcitriol. We conclude that metabolic degradation of calcitriol is decreased in patients with renal failure, and uremic plasma contains inhibitory factors that suppress the synthesis and degradation of calcitriol.     

Major surgery in patients with chronic renal failure

To determine the risks of performing major surgical procedures on patients with chronic renal failure, the charts of twenty-nine hemodialysis patients who underwent thirty-eight elective and nine emergency operations were reviewed. Preoperative preparation included adequate hemodialysis of the patients, 88 per cent of whom were dialyzed within 24 hours of surgery. Azotemia was well controlled prior to administration of anesthesia. The average preoperative hematocrit was 26 per cent, and only one patient was hyperkalemic preoperatively. There were no intraoperative complications attributable to the patients' impaired renal function. Postoperative complications were frequent and are discussed in detail. Hemodialysis was done immediately postoperatively in five patients and on the first postoperative day in twenty-three additional patients with no problems. There were only two deaths (4.3 per cent) in the series. With careful monitoring during the perioperative period, major surgical procedures can safely be performed on patients with chronic renal failure.     

Adrenal function in patients with chronic renal failure

Previous studies have reported divergent findings on the function of the hypothalamic-pituitary-adrenal axis in patients with chronic renal failure (CRF). The low-dose adrenocorticotropin (ACTH) test offers the possibility of unmasking adrenal dysfunction, which might remain undiscovered using the ACTH test with the standard 250-microg dose. Furthermore, the choice of renal replacement therapy (either hemodialysis or continuous ambulatory peritoneal dialysis [CAPD]) might have an impact on adrenal function. To investigate these possibilities, ACTH tests were performed with three different doses (ie, 1, 5, and 250 microg) in 14 CRF patients and in seven healthy controls. Seven of the CRF patients were receiving chronic hemodialysis and seven were receiving CAPD. Basal plasma concentrations of cortisol were comparable in the three groups tested (5.3+/-0.4 microg/dL in the controls, 6.6+/-0.7 microg/dL in the hemodialysis patients, and 7.9+/-1.0 microg/dL in the CAPD patients), whereas basal ACTH concentrations were significantly elevated in the CRF patients (28.5+/-3.8 pg/mL in the hemodialysis patients and 33.0+/-6.0 pg/mL in the CAPD patients) when compared with normal controls (17.0+/-1.4 pg/mL; P < 0.05). All three doses of ACTH resulted in a rapid increase of plasma cortisol concentrations that was comparable in all three groups. In the hemodialysis patients, a trend toward a diminished response to the lowest dose of 1 microg was noticed. We conclude, therefore, that adrenal response to ACTH in various doses is unaffected in CRF independent of whether hemodialysis or CAPD is chosen for renal replacement therapy.     

Energy expenditure in patients with chronic renal failure

Although nondialyzed, chronically uremic patients and patients undergoing maintenance hemodialysis often show evidence for wasting and calorie malnutrition and have low dietary energy intakes, their energy expenditure has never been systematically evaluated. It is possible that low energy intakes are an adaptive response to reduced energy needs; alternatively, energy expenditure could be normal or high and the low energy intakes would be inappropriate. Energy expenditure was therefore measured by indirect calorimetry in 12 normal individuals, 10 nondialyzed patients with chronic renal failure, and 16 patients undergoing maintenance hemodialysis. Energy expenditure was measured in the resting state, during quiet sitting, during controlled exercise on an exercise bicycle, and for four hours after ingestion of a test meal. Resting energy expenditure (kcal/min/1.73 m2) in the normal subjects, chronically uremic patients and hemodialysis patients was, respectively, 0.94 +/- 0.24 (SD), 0.91 +/- 0.20, and 0.97 +/- 0.10. There was also no difference among the three groups in energy expenditure during sitting, exercise, or the postprandial state. Within each group, energy expenditure during resting and sitting was directly correlated. During bicycling, energy expenditure was directly correlated with work performed, and the regression equation for this relationship was similar in each of the three groups. These findings suggest that for a given physical activity, energy expenditure in nondialyzed, chronically uremic patients and maintenance hemodialysis patients is not different from normal. The low energy intakes of many of these patients may be inadequate for their needs.     

Mechanisms and consequences of sympathetic hyperactivity in renal disease

Kidney impairment of different origins can lead within a short time to structural and functional maladaptations of the kidney, which may culminate in end-stage renal failure. The most common causes of chronic renal failure are due to hypertensive and diabetic renal impairment [Moore et al. 1999, Ritz et al. 1999]. Moreover, an inadequate blood pressure control in primary renal diseases further accelerates the decline of renal function. In spite of improved therapeutic measures the number of patients with chronic renal failure continues to increase dramatically [Mailloux and Haley 1998]. Cardiovascular morbidity and mortality in patients with chronic renal failure are extraordinarily high and are more frequent than that observed in the general population [Vita et al. 1999]. Measures, which can reduce the high incidence of cardiovascular complications, have priority in the treatment of chronic renal failure patients. ACE-inhibitors have been shown to be the best choice in this case. Until now a possible role for sympathetic hyperactivity has not been seriously considered although there is very good clinical and experimental evidence for such a role. This overview will give a summary of the currently known experimental and clinical findings about the role of the sympathetic nervous system in hypertension and renal disease and to expound possible therapeutic strategies.     

Relationship between renal size and hypertension in patients with chronic renal failure

BACKGROUND/AIMS: The aim of this study was to compare renal size, shape and volume in hypertensive and nonhypertensive patients with end-stage renal failure. METHODS: Patients with volume overload and diabetes mellitus, myeloma, amyloidosis, or polycystic renal disease were all excluded. Fifty patients undergoing hemodialysis for the first time were grouped as normotensive (23/50) and hypertensive (27/50). Hypertensive patients were then divided into subgroups having slight (4/27), medium (13/27), or high (10/27) hypertension. Using ultrasonographic methods, absolute renal size, relative renal size (renal length/body length), renal volume (length x width x depth x 0.52), and renal shape (width/length) were calculated. RESULTS: In hypertensive patients, right and left relative and absolute renal lengths and left renal volume were found to be significantly less than in normotensive patients. Within the hypertensive group, no significant differences were found in the parameters. There was no relationship between age, sex, height, weight, body mass index, creatinine, creatinine clearance, sodium, calcium levels, renal shape and hypertension. CONCLUSION: In this study, etiopathogenesis of the renal disease, individual and multifactorial effects, residual renal function and nephron numbers may be involved in the results. Further investigations are needed to evaluate multifactorial effects on blood pressure and kidney size in chronic renal failure patients.     

Cardiac function and structure in patients with chronic renal failure

The long-term consequences of cardiac alterations in children with chronic renal failure (CRF) and after renal transplantation (TX) are largely unknown. Studies in adults with end-stage renal disease (ESRD) assume that the fate of many pediatric patients is determined by a high cardiovascular morbidity and mortality. This review describes clinical manifestations, pathophysiology, cardiac function and structure, and management of heart disease in children with CRF and post transplant. Echocardiography and Doppler ultrasonography allow differentiation of three functional disturbances: hypercirculation, systolic left ventricular (LV) dysfunction, and diastolic LV dysfunction, in addition to analysis of LV size and myocardial mass. From adult studies LV hypertrophy is recognized as an early prognostic marker of cardiovascular disease. It is present in about half of children with ESRD and after TX. It may regress, at least in part, by control of hypertension, hypervolemia, and anemia. Experimental studies have shown that, independent of these hemodynamic complications, uremia is associated with structural abnormalities of the heart, which were also described in adult patients with ESRD. These lesions consist mainly of hypertrophy of cardiomyocytes, interstitial fibrosis, and vascular changes (rarefied capillaries, thickened arteriolar walls). Cardiac complications in children with CRF and after TX deserve regular clinical and echocardiographic monitoring in order to minimize later cardiovascular morbidity by appropriate treatment. Received: 3 December 1998 / Revised: 16 April 1999 / Accepted: 19 April 1999