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Cardiovascular disease is a major cause of morbidity and mortality in chronic kidney disease. Radionuclide-based methods can be used for analyses on the perfusion of coronary arteries and ventricular function. The present study reports the use of a new procedure for continuous measurements of left ventricle function during a dialytic session with the use of a recently developed portable gamma radiation detector (ventricular function study system). On average, left ventricle ejection fraction and stroke volume progressively and continuously decreased throughout the session (end session versus baseline: -13.8% for ejection fraction, -25.9% for stroke volume, P<.02). A biphasic response was found for heart rate: a transient modest decrease (at session midpoint, -4.2%) followed by an increase up to values higher than baseline (end session, +4.7%). Cardiac output decreased by 10.4% at session midpoint (P=.023 versus baseline) without further reduction in the following hours. Mean changes in systolic pressure paralleled data for cardiac output. Individual changes in indices of left ventricle function were scattered and strongly were correlated with thickness of interventricular septum and telediastolic left ventricular volume measured by standard echocardiogram in the interdialytic period (R>.75, P<.05). Data indicate that the ventricular function study system could be a powerful tool for characterization of the profile of left ventricular function in hemodialyzed patients.

Hyperhomocysteinemia, highly prevalent in well-nourished patients with chronic renal failure and in uremia, causes toxic effects that can be envisioned in terms of cardiovascular risk increase. However, its effects on cellular metabolism and on gene expression, not to mention receptor regulation, only recently are being evaluated. For example, it has been shown that hypomethylation induced by hyperhomocysteinemia can alter erythrocyte membrane protein repair and gene expression. In addition, increased plasma protein L-isoaspartyl content, related to hyperhomocysteinemia and uremic toxicity, determines specific effects on protein function, with a reduced binding of homocysteine to albumin. We propose that uremia is a state in which proteins present a widespread derangement of structure-function relationships.

Since the very early manned missions in space, a state of anemia associated with reduced erythropoietin levels and reduced plasma volume was disclosed. The reduction in red blood cell mass is driven by a process of selective hemolysis, which has been named neocytolysis. This phenomenon also occurs in people living at a high altitude who descend rapidly to sea level. The origin of the signal leading to destruction of newly produced red blood cells probably is located in central circulation, but the operating mechanism is unknown. The importance of plasma cell volume reduction in the genesis of a lower red cell mass also is supported by the inverse correlation seen at moderate altitude. People arriving at moderate altitude have increased erythropoietin concentration that decreases after a few days and is in inverse correlation with central venous pressure. Studies under simulated microgravity conditions in human beings (bed rest, head-down tilt at -6 degrees , water immersion) and in rats provide further insight in unraveling the mechanism of astronauts' anemia, a problem difficult to study in space because of the limited availability of spaceflights.

Renal dysfunction is a constant feature of congestive heart failure and is a stronger predictor of mortality than left ventricular ejection fraction or New York Heart Association classification. In heart failure, a reduction of glomerular filtration rate and renal plasma flow occurs, although the filtration fraction increases. There are many reason for this pattern. A reduction in effective circulating volume stimulates sympathetic activity and the renin-angiotensin-aldosterone system, and it is associated with increased concentrations of atrial natriuretic peptide, brain natriuretic peptide, and tumor necrosis factor alpha. Because in chronic kidney disease heart dysfunction commonly is present, an efficient cardiologist-nephrologist interaction should be promoted.

The moderate increase in urinary albumin excretion defined as microalbuminuria is not rare and is associated with cardiovascular risk factors. Microalbuminuria prevalence is low in the absence of cardiovascular risk factors and progressively increases with the number cardiovascular risk factors. The main correlate of microalbuminuria is blood pressure, either systolic or diastolic pressure. The relation between blood pressure and microalbuminuria is continuous and graded because the microalbuminuria prevalence increases with the severity of hypertension. Among hypertensive patients on drug treatment, blood pressure control is associated with a low prevalence of microalbuminuria. Thus, blood pressure appears as a determinant of microalbuminuria rather than a mere correlate. For hypercholesterolemia, smoking, and diabetes, data are less strong but point to an independent positive association with microalbuminuria. Altogether, data indicate that microalbuminuria in the population reflects the presence of cardiovascular risk factors. Data on microalbuminuria and coronary heart disease support this idea. There is a continuous and graded relation between urinary albumin excretion and coronary heart disease prevalence. High urinary albumin excretion is likely a sign of vascular damage existing both at the renal and cardiac levels and induced by 1 or more uncontrolled cardiovascular risk factors.

Patients with end-stage renal disease are prone to hemorrhagic complications and simultaneously are at risk for a variety of thrombotic complications such as thrombosis of dialysis blood access, the subclavian vein, coronary arteries, cerebral vessel, and retinal veins, as well as priapism. The study was devised for the following purposes: (1) to identify the markers of thrombophilia in hemodialyzed patients, (2) to establish a role for antiphospholipid antibodies in thrombosis of the vascular access, (3) to characterize phospholipid antibodies in hemodialysis patients, and (4) to study the effects of dialysis on coagulation cascade. A group of 20 hemodialysis patients with no thrombotic complications (NTC) and 20 hemodialysis patients with thrombotic complications (TC) were studied along with 400 volunteer blood donors. Patients with systemic lupus erythematosus and those with nephrotic syndrome were excluded. All patients underwent a screening prothrombin time, activated partial thromboplastin time, fibrinogen (Fg), coagulation factors of the intrinsic and extrinsic pathways, antithrombin III (AT-III), protein C (PC), protein S (PS), resistance to activated protein C, prothrombin activation fragment 1+2 (F1+2), plasminogen, tissue type plasminogen activator (t-PA), plasminogen tissue activator inhibitor type-1 (PAI-1), anticardiolipin antibodies type M and G (ACA-IgM and ACA-IgG), lupus anticoagulant antibodies, and antiprothrombin antibodies type M and G (aPT-IgM and aPT-IgG). The study showed that PAI-1, F 1+2, factor VIII, ACA-IgM, and aPT-IgM levels were increased significantly over controls both in TC and NTC, however, they could distinguish patients with thrombotic complications from those without, being increased maximally in the former group. The novelty of the study is represented by the significant aPT increase that was observed in non-systemic lupus erythematosus hemodialysis patients, and particularly in those with thrombotic events. In addition, there was a reduction of factor XII during the treatment. It is possible to assume in the TC group and, to a lesser extent, also in the NTC group that endothelial cells liberate PAI-1 in the vascular lumen, which causes hypofibrinolysis. In addition, an excess of factor VIII is activated by endothelial dysfunction with subsequent activation of the coagulation cascade as shown by increased F1+2 and fibrinogen. ACA-IgM, in turn, is capable of interfering with the system of protein C, a potent anticoagulant factor that inactivates cofactors Va and VIIIa. They also induce the expression of procoagulant factors on the surface of the endothelial cells. In conclusion, the hypercoagulable state caused by alterations of coagulation and fibrinolytic factors is a cause of vascular access dysfunction and thrombosis of other vessels.

In the general population, hyperhomocysteinemia is an independent risk factor for cardiovascular disease (ischemic disease, such as stroke and myocardial infarction, and arterial and venous thrombosis). We can presume that the association is causal, based on the example of homocystinuria, and on the evidence put forward by several basic science and epidemiologic studies. However, the results of large intervention trials, which may grant further support to this hypothesis, are not yet available. In chronic renal failure and in uremia, the evidence that is offered by carefully performed prospective studies also indicate the presence of an association, although some studies suggest reverse epidemiology. The mechanisms underlying the association, and able to explain the several toxic effects of homocysteine, related or not to cardiovascular disease, are unclear. Oxidation, nitrosylation, and hypomethylation are among the postulated mechanisms. In uremia, protein hypomethylation interferes with protein repair; DNA hypomethylation impairs regulation of gene expression, whereas folate treatment reverts such alterations. Acylation, another structural modification able to impair protein function, is a possible mediator of homocysteine toxicity.

This article starts with a concise synopsis of the history of edema. The role of underfilling, overflow, antidiuretic hormone, and acquaporins is subsequently discussed. Emphasis is given to the use of diuretics in edematous patients. The role and risks of albumin infusion are illustrated. The new hypothesis of pulse reverse osmosis is discussed. The final section deals with the measurement of colloid osmotic pressure in the clinical setting., (Copyright 2001 by W.B. Saunders Company)

Increased tubule sodium reabsorption has been largely suspected in liver cirrhosis (LC), however studies in humans have produced contrasting results. Therefore to ascertain the entity of renal sodium handling in LC this study was devised. A total of 13 patients with child A LC were studied along with 26 age-sex matched healthy controls (HC). Patients and controls were kept on daily Na-intake of 100 mmol for at last 1 week, by measuring glomerular filtration rate (GFR; inulin) and lithium clearance. We have calculated (1) C(Li); (2) the absolute reabsorption of isotonic fluid in the proximal tubule (APR) as GFR - C(LI); (3) the fractional proximal sodium reabsorption (FPRNa) as 1 - (C(Li)/GFR); (4) the absolute distal reabsorption of sodium (ADRNa) as (C(LI) - C(Na)) x P(Na;) and (5) the fractional distal sodium reabsorption (FDRNa) as (C(LI) - C(Na))/C(Li). GFR was significantly lower in LC (P<.001), C(Li) was significantly higher in LC than in HC (P<.001). APRNa and FPRNa were reduced in LC (P<.0001). ADRNa was higher in LC than in HC (P<.001). No difference was found for FDRNa. In conclusion, lithium clearance discloses an increase sodium reabsorption in distal tubule in humans with LC., (Copyright 2001 by W.B. Saunders Company)

An increase in glomerular filtration rate (GFR) induces adaptive changes in tubular function to prevent the urinary loss of water and electrolytes. This is also true for acid-base balance: the increase in filtered bicarbonate load will stimulate H+ secretion at the level of several segments including the proximal tubule, the loop of Henle, and the distal tubule. There is an activation of both the luminal Na+/H+ exchanger and H(+)-ATPase, and basal-lateral Na(+)-HCO3- cotransport which allows an increase in luminal H+ secretion and basal lateral HCO3- exit. The stimulation of electrolyte reabsorption is very important at the level of the thick ascending limb of Henle, a segment that shows consistent hypertrophy in many models of hyperfiltration. Along this segment, increased Na+ and Cl- reabsorption has been found in rats receiving a high-protein diet. The ensuing reduced Na+ and Cl- concentrations, at the level of the macula densa, could weaken the signal responsible for initiating the tubuloglomerular feedback (TGF), thus allowing GFR to increase.

This article analyzes 57 reports published in the years 1983 through 1964 that addressed the issue of the renal hemodynamic response to an oral protein load. Seventy-three groups are reported in those studies: 52 were healthy subjects (n = 627) and 21 had renal disease (n = 256); 47 were studied using inulin (n = 407 healthy people and 112 renal patients); 26 groups were studied using creatinine (n = 220 healthy people and 144 renal patients). Patients with liver cirrhosis were also analyzed. There was great heterogeneity in methodology used, emphasizing the need for standardization. The role of plasma amino acids, glucagon, insulin, growth hormone, PGE2, 6-ketoPGA1 alpha, brain-gut peptides, ANP, AVP, dopamine, and kinins in promoting the renal hemodynamic response to an oral protein load is discussed.

Renal reserve in children is related to changes in renal plasma flow (RPF) in health and renal disease. Peak glomerular flow rate (GFR) correlates with peak RPF. The renal hemodynamic response to protein is associated with a decrease in renal vascular resistance. Studies in children are less numerous than in adults. The main findings of the studies on renal reserve in children have disclosed the following: (1) the lack of an age dependency, (2) the normalcy of renal reserve in renal disease, (3) the return of renal reserve in type 1 diabetes mellitus by a reduction in protein intake, and (4) the suppressibility of renal reserve by somatostatin infusion.

The available data on the association between the cellular handling of sodium and high BP indicate that alteration of these parameters could be linked to the level of high BP. Limited data are available with regard to the association between BP and these aspects of the intracellular ion metabolism in childhood. The study of intracellular ion metabolism in children could help clarify the pathogenesis and etiology of essential hypertension by providing an opportunity to study this relationship before the effects of possible determinants of adult BP (ie, age, body weight, diet, physical activity) affect ion transport and modify its effect on BP. Specifically, familial predisposition to hypertension, growth and maturation, and the various components of body size need to be studied further to determine their role in the relationship between Na-Li CT and RBC Na and BP. Better understanding of this complex association could help elucidate the pathophysiology of essential hypertension.