Mineral and electrolyte metabolism最新文献

Heart failure of class IV NYHA has a very severe prognosis. Its most frequent electrolytic alterations are hyponatremia, hypokalemia, and hypomagnesemia which can cause serious arrhythmias and sudden death. The regulation of the electrolytic equilibrium by means of pharmacological therapy becomes impossible in patients with severe heart failure resistant to strong doses of diuretics in the oligo-anuric phase. This study focused on the use of daily hemofiltration in a group of patients suffering from cardiac insufficiency of class IV NYHA. The results have been evaluated over 1 year.

This article summarizes briefly some factors responsible for edema in chronic congestive heart failure. It is now generally thought that so-called 'backward failure' is a manifestation of diastolic dysfunction, while systolic 'pump failure' is a disease that depends on two key factors: an inadequate cardiac output, and renal salt and water retention. The key elements involved in what might be termed the 'integrated volume response' are hemodynamic and renal factors. The hemodynamic factors include vasoconstriction, tachycardia and a reduced venous capacitance. These responses occur within minutes, while salt and water retention occurs over days to weeks. The key renal elements modulating sodium retention in congestive heart failure include, at a minimum, four variables. First, there is a reduction in renal blood flow produced by the almost simultaneous operation of alpha- and beta-catecholamines, antidiuretic hormone, the endothelins, and angiotensin II. Second, activation of the tubuloglomerular feedback system enhances intrarenal angiotensin II release, which augments proximal sodium absorption. In addition, beta-catechols also enhance proximal sodium absorption. A third key element involved in renal sodium retention is activation of apical sodium channels, ENaC, of principal cells in the cortical collecting tubule by aldosterone and by vasopressin. Finally, the inner medullary collecting duct becomes resistant to the action of atrial natriuretic peptide, thus adding a final dimension to the syndrome of sodium retention in underfilling.

Most large observational studies available today establish that moderate hyperhomocysteinemia, either genetically or nutritionally determined, is an independent risk factor for myocardial infarction, stroke, and thromboembolic disease. This is also true for chronic renal failure patients, who exhibit a high prevalence of hyperhomocysteinemia (85-100%), which reaches high plasma concentrations (20-40 microM, while control values range between 8 and 12 microM). After a renal transplant, homocysteine levels decrease, but tend to be higher than normal. The cause of hyperhomocysteinemia in renal failure is still obscure, since recent data have questioned the previous notion that a net homocysteine renal extraction and/or excretion take place in man. No matter the cause of its increase, the sulfur amino acid homocysteine is thought to induce an increment in cardiovascular risk through three basic biochemical mechanisms: (1) homocysteine oxidation, with H2O2 generation; (2) hypomethylation through S-adenosylhomocysteine accumulation, and (3) protein acylation by homocysteine thiolactone. The final result is membrane protein damage, endothelial damage, and endothelial cell growth inhibition, among other effects. Hyperhomocysteinemia, in general, is susceptible of therapeutic intervention with the vitamins involved in its metabolism. Depending on the cause, vitamin B6, vitamin B12, betaine, and/or folic acid can be effectively utilized. Chronic renal failure patients benefit from folic acid in high dosage: 1-2 mg are usually not effective ('relative folate resistance'), while 5-15 mg reduce homocysteine levels to a 'normative' range (<15 microM) in a substantial group of patients. Good results are also obtained in transplant patients, best with a combination of folic and vitamin B6. The results of the interventional trials focusing on the possible reduction in cardiovascular risk after homocysteine-lowering therapy, both in the general population and in end-stage renal disease, are expected soon, as well as the genetic and biochemical studies in suitable models, with the aim to clarify the cause-effect link suggested by the numerous observational and basic science studies.

In patients with severe heart failure life expectancy is short, the quality of life is affected, and the service costs are very high. Drug therapies remain restricted despite continuous clinical research. Therefore new therapeutic approaches have been attempted to improve the signs and symptoms of the disorder. In our study we followed patients suffering from class-IV cardiac failure concomitant with chronic renal failure. The patients were initially treated by means of hemofiltration, and subsequently they underwent a personalized dialysis program. The survival rate after 2 years was 62.5%. In 7 of the 8 patients the results revealed a drop to a class-III condition. The hospitalization period was limited to a few days. Early dialytic therapy represents a reality for such patients.

Fluid retention following reduction in the glomerular filtration rate causes extracellular fluid volume expansion that reduces tubular reabsorption by residual nephrons, thereby maintaining the external sodium balance. The price paid for this is salt-dependent hypertension. Thus, loop diuretics are the best treatment for uremic hypertension. Diuretics are also used in chronic renal failure to treat edema due to nephrotic syndrome and congestive heart failure (CHF). In nephrotics, edema is often refractory to diuretics because of low plasma protein, depletion of the intravascular compartment, decrease in the protein-bound fraction of the diuretic in peritubular blood, and increase in tubular fluid. Thus, higher doses are needed. In uremics with CHF the efficacy of diuretics may be hampered because of the reduced renal blood flow. The association of dopamine (1-1.5 microg/kg body weight/min) may overcome this resistance; improvement in cardiac function by dialysis ultrafiltration may also help. Diuretic resistance is sometimes observed; it may be overcome by the following procedures: in CHF by the use of digitalis and/or angiotensin-converting enzyme inhibitors; by substitution of an ineffective loop diuretic for another one; by using larger doses of diuretic; by intravenous infusion rather than bolus therapy, and by a combination of diuretics acting in different segments of the tubule: loop diuretic+thiazide+amiloride. Intravenous infusion of 20% albumin has also been suggested.

Until a few years ago, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) were considered essential only to the control of linear growth, glucose homeostasis, and for the maintenance of skeletal muscle mass. A large body of evidence recently coming from animal and human studies has unequivocally proven that the heart is a target organ for the GH/IGF-1 axis. Specifically GH exerts both direct and indirect cardiovascular actions. Among the direct effects, the ability of GH to trigger cardiac tissue growth plays a pivotal role. Another direct effect is to augment cardiac contractility, independent of myocardial growth. Direct effects of GH also include the improvement of myocardial energetics and mechanical efficiency. Indirect effects of GH on the heart include decreased peripheral vascular resistance (PVR), expansion of blood volume, increased glomerular filtration rate, enhanced respiratory activity, increased skeletal muscle performance, and psychological well-being. Among them, the most consistently found is the decrease of PVR. GH may also raise preload through its sodium-retaining action and its interference with the hormonal system that regulates water and electrolyte metabolism. Particularly important is the effect of GH on skeletal muscle mass and performance. Taking into account that heart failure is characterized by left ventricular dilation, reduced cardiac contractility, and increase of wall stress and peripheral vascular resistance, GH may be beneficial for treatment of heart failure. Animal studies and preliminary human trials have confirmed the validity of the GH approach to the treatment of heart failure. Larger placebo-controlled human studies represent the main focus of future investigations.

We recently demonstrated that indoxyl sulfate is a stimulating factor for the progression of chronic renal failure (CRF). In this study we determined whether the urine or serum levels of indoxyl sulfate are related to the progression rate of CRF in undialyzed uremic patients. Fifty-five CRF patients with a serum creatinine of >2 mg/dl who had not been treated with an oral sorbent (AST-120) were randomly enrolled in the study. We measured the serum and urine levels of indoxyl sulfate, and estimated the recent progression rate of CRF as the slope of the reciprocal serum creatinine versus time (1/S-Cr-time) plot. The mean urinary amount of indoxyl sulfate in the patients was 60 mg/day. Those with indoxyl sulfate urine levels of >60 mg/day had a significantly faster progression rate of CRF than those with <60 mg/day. Especially, those patients with indoxyl sulfate urine levels of >90 mg/day had the highest CRF progression rate and those with indoxyl sulfate urine levels of <30 mg/day had the slowest CRF progression rate. Urinary indoxyl sulfate had a significantly negative correlation with the slope of the 1/S-Cr-time plot. However, the serum level of indoxyl sulfate or the ratio of serum indoxyl sulfate to creatinine was not significantly correlated with the slope of the 1/S-Cr-time plot. In conclusion, high urine levels of indoxyl sulfate are related with a rapid progression of CRF in undialyzed uremic patients. Thus, urinary indoxyl sulfate is one of the clinical factors that affect CRF progression.

Arterial hypertension-related renal damage is an increasingly common problem recently, because approximately 25% of patients currently treated with dialysis were hypertensive before renal replacement therapy was started. Hypertension is also known as a metabolic disease, while carbohydrate, purine and lipid disturbances are the features of this syndrome. On the other hand, the progression of renal disease depends on the extent of tubulointerstitial injury. For this reason, we undertook a study to evaluate the relationship between excretion of the markers of tubular damage (NAG) and some parameters of carbohydrate, purine and lipid metabolism in untreated essential hypertension. Both healthy volunteers (n = 15) aged 32. 6+/-7.8 and essential hypertensives (n = 25) aged 37.24+/-11.39 underwent the same tests. These tests were performed at 2-day intervals: intravenous glucose tolerance test with 0.5 g/kg b.w. as 40% glucose solution and oral fructose load test with 1.0 g/kg b.w. Area under glucose curve (GA) and serum uric acid post-fructose (PUAA) were calculated. Fasting: insulin, total cholesterol and LDL, triglycerides, free fatty acids (FFA) and urine excretion of NAG, albumin were determined. Glomerular filtration rate was estimated as creatinine clearance. Hypertensives showed statistically higher BMI (p<0.007), NAG (p<0.02), total cholesterol (p<0.01), LDL (p<0.007), FFA (p<0.007), insulin (p<0.01), PGA (p<0.01) and PUAA (p<0.03). NAG excretion correlated positively with WHR (r = 0.40), MAP (r = 0.47) and PUAA (r = 0.47) in hypertensives only. We presume that tubular injury at an early stage of renal damage in patients with essential hypertension could be a part of metabolic syndrome X.

Cardiac hypertrophy, a well-known independent risk factor for cardiovascular death, is a very frequent complication in ESRD patients. Its frequency tends to be even higher in dialyzed patients due to the fact that the current dialytic treatments are unable to keep under a satisfactory control the various responsible factors and particularly the blood pressure, which is largely the most important. Daily hemodialysis, a more frequent schedule consisting of 6-7 sessions/week lasting 2 or more hours, has definitely proved its superiority in controlling blood pressure and in improving anemia, and thus has the requisites for positively influencing cardiac hypertrophy. In fact, a series of studies, both retrospective and prospective, performed during the last years by our group, have confirmed that this new, more frequent and thus more physiological schedule, is able not only to stop the progression of the cardiac hypertrophy in uremic patients but also to revert toward the normality, in a relatively short time. This appears to be essentially a consequence of the excellent blood pressure control, which in turn derives from the easier control of the true dry weight, achievable with this type of dialytic treatment.