Potential Benefits of Renal Diets on Cardiovascular Risk Factors in Chronic Kidney Disease Patients

Dietary manipulation, including protein, phosphorus, and sodium restriction, when coupled with the vegetarian nature of the renal diet and ketoacid supplementation can potentially exert a cardiovascular protective effect in chronic renal failure patients by acting on both traditional and nontraditional cardiovascular risk factors. Blood pressure control may be favored by the reduction of sodium intake and by the vegetarian nature of the diet, which is very important also for lowering serum cholesterol and improving plasma lipid profile. The low protein and phosphorus intake has a crucial role for reducing proteinuria and preventing and reversing hyperphosphatemia and secondary hyperparathyroidism, which are major causes of the vascular calcifications, cardiac damage, and mortality risk of uremic patients. The reduction of nitrogenous waste products and lowering of serum PTH levels may also help ameliorate insulin sensitivity and metabolic control in diabetic patients, as well as increase the responsiveness to erythropoietin therapy, thus allowing greater control of anemia. Protein-restricted diets may have also anti-inflammatory and anti-oxidant properties.

Thus, putting aside the still debatable effects on the progression of renal disease and the more admitted effects on uremic signs and symptoms, it is possible that a proper nutritional treatment early in the course of renal disease may be useful also to reduce the cardiovascular risk in the renal patient. However, conclusive data cannot yet be drawn because quality studies are lacking in this field; future studies should be planned to assess the effect of renal diets on hard outcomes, as cardiovascular events or mortality.     

Role of carnitine in modulating acute-phase protein synthesis in hemodialysis patients.

Increased serum levels of C-reactive protein (CRP) in uremic and dialysis patients are associated with low serum prealbumin and albumin concentrations and increased mortality and greater risk of cardiovascular disease. Proinflammatory cytokines may cause malnutrition by increasing protein catabolism. Many studies have shown that L-carnitine supplementation leads to improvements in several conditions seen in uremic patients, including cardiac complications, impaired exercise and functional capacities, muscle symptoms, increased symptomatic intradialytic hypotension, and erythropoietin-resistant anemia. L-carnitine therapy may either suppress the inflammatory response or act independently on both inflammation and appetite and/or anabolic processes. Moreover, L-carnitine may suppress proinflammatory cytokines in sick individuals without renal disease and may improve protein synthesis or nitrogen balance in patients without renal disease and in hemodialysis and peritoneal dialysis patients. In a pilot study, we provided preliminary evidence that treatment with L-carnitine, 20 mg/kg 3 times weekly at the end of each hemodialysis treatment, was associated with a reduction in serum CRP levels and improvement in anabolic status. The improvement or normalization of serum concentrations of serum CRP also was correlated with increased serum concentrations of albumin, transferrin, and blood hemoglobin. The possibility that some or all of these changes may have been caused by improved nutritional intake cannot be ruled out. Further randomized clinical trials will be necessary to confirm the role of L-carnitine as a modulator of inflammatory protein synthesis in hemodialysis patients.     

The clinical significance of vascular calcification in young patients with end-stage renal disease

Mortality statistics of young adults with childhood-onset end-stage renal disease (ESRD) show that cardiovascular disease (CVD) is responsible for most deaths on dialysis and after transplantation. This is most likely explained by the presence of a multitude of traditional and non-traditional risk factors in uremia, promoting the combination of classical atherosclerosis, uremic vasculopathy, and uremic cardiomyopathy. Vascular (arterial) calcifications occur with a high prevalence in young adults and their presence correlates with non-traditional risk factors, markers of inflammation, intake of calcium-containing phosphate binders, and the calcium-phosphorus product in serum. This might be explained by a high positive calcium and phosphorus balance in ESRD patients, which may be comparatively higher in the young. In addition, treatment with active vitamin D preparations may enhance the positive calcium and phosphorus balance and have a direct calcifying effect on the arterial wall. The biological process of vascular calcification resembles osteogenesis. These data indicate that vascular calcifications are related to non-traditional risk factors, inflammatory mechanisms, and disturbances in calcium and phosphorus metabolism in uremia. They provide strong evidence for a change in the current management of renal osteodystrophy in children and adolescents with ESRD.     

A special, supplemented 'vegan' diet for nephrotic patients.

High dietary protein intake, in the past recommended for nephrotic syndrome, does not improve hypoproteinemia and may accelerate progressive renal damage. In contrast, low-protein diets reduce proteinuria and preserve renal function in experimental renal models of nephrotic syndrome. In this study, 20 steroid-resistant, nephrotic patients were treated with a pure vegetarian, low-protein diet, supplemented with essential amino acids and ketoanalogues (supplemented vegan diet, SVD) for 4.6 +/- 3.1 months. Before the study, these patients followed an unrestricted protein, low-sodium diet (LSD). Proteinuria, daily urea nitrogen excretion and creatinine clearance decreased significantly on SVD. A similar lowering effect of SVD was observed on serum total cholesterol. Seven of the 20 patients changed from LSD to SVD and vice-versa on 3 occasions, and in all cases, we found an increase of proteinuria during the LSD period. Serum albumin, HDL cholesterol, triglycerides and anthropometric measurements did not change on SVD. Our data suggest that SVD exerts a favorable effect on proteinuria and hypercholesterolemia in nephrotic patients, without inducing clinical or laboratory signs of malnutrition.     

Nutritional considerations and the indications for dialysis

Evidence of a reduction in dietary protein intake and some indices of nutritional status in chronic renal failure (CRF) patients consuming unrestricted diets has led some individuals to recommend that low-protein diets be avoided and that dialysis should be initiated if the protein intake declines below 0.8 g protein/kg/day. However, evidence indicates that when properly implemented, low-protein diets are safe and can maintain lean body mass even during long-term therapy. This is because CRF patients are able to activate normal compensatory responses when protein intake is restricted, and their protein and energy requirements are similar to healthy subjects. Because low-protein diets ameliorate uremic symptoms and some of its metabolic complications, dietary therapy should be attempted in all patients with progressive CRF. The recommendation to initiate dialysis when the protein intake declines below 0.8 g/kg/day should be viewed with skepticism because mortality risk is increased in end-stage renal disease (ESRD) patients and dialysis therapy does not improve protein and energy intake or ameliorate malnutrition.     

Eleven reasons to control the protein intake of patients with chronic kidney disease

For many years patients with chronic kidney disease have been advised to control the protein content of their diet. This advice has been given on the basis of a number of reported metabolic effects of lowering protein intake, such as lowering serum urea nitrogen levels, improving phosphocalcic metabolism and insulin resistance and, more recently, ameliorating proteinuria (independent of antiproteinuric medications). The effects on the progression of kidney disease, although spectacular in experimental studies, have been less convincing in humans. It is possible that flawed design of clinical trials is responsible for this discrepancy. In this Review, we comment on experimental findings that indicate that limiting protein intake protects the kidney and ameliorates uremic symptoms, outline how the body adapts to a reduction in protein intake, and describe the metabolic benefits to the patient. We then review the evidence from randomized controlled trials and meta-analyses that pertains to the effects of low-protein diets in adults with chronic kidney disease.     

The effect of the American Heart Association step one diet on hyperlipidemia following renal transplantation

Cardiovascular disease is a frequent cause of morbidity and mortality following renal transplantation. The percentage of deaths due to ischemic cardiovascular disease and cerebrovascular accidents nearly equals that caused by infection among patients receiving their first transplant, according to data from the European Dialysis and Transplant Association Registry. Hypercholesterolemia is a risk factor for cardiovascular disease frequently identified following renal transplantation, and diets low in fat and cholesterol have been suggested as treatment. Previous studies have not reported the response of LDL cholesterol to dietary treatment, and it is this form of cholesterol that is most closely related to cardiovascular disease. The American Heart Association has provided nutritionists with guidelines for the treatment of hyperlipidemic patients which include the Step One Diet. Previous dietary studies of renal transplant recipients have allowed a slightly higher intake of fat than that currently recommended by the AHA. We wondered if an easily reproducible diet well known to nutritionists such as the AHA Step One Diet would be effective in lowering cholesterol levels in hyperlipidemic renal transplant recipients. The purpose of our study was not to define the mechanisms of posttransplant hyperlipidemia, but rather to assess the effectiveness of dietary intervention on hyperlipidemia following renal transplantation.     

Consequences of hyperphosphatemia and elevated levels of the calcium-phosphorus product in dialysis patients

Control of serum phosphorus levels is a central goal in the management of patients with chronic renal failure. Inadequate control of serum phosphorus leads to elevated levels of the calcium-phosphorus product. This plays a pivotal role in vascular calcification, cardiovascular disease, calciphylaxis, and death. Elevated phosphorus and elevated levels of the calcium-phosphorus product are both significant predictors of cardiovascular mortality, at phosphorus and calcium-phosphorus product levels that were considered safe until recently. A lowering of levels such that phosphorus is maintained between 2.2 and 5.5 mg/dl, calcium-phosphorus product is below 55 mg(2)/dl(2), and serum calcium is at 9.2-9.6 mg/dl, respectively, might well be the goal of therapeutic management strategies.     

Serum oxalic acid in uremia: effect of a low-protein diet supplemented with essential amino acids and ketoanalogues

Serum oxalic acid (sOx) was determined with a new, specific enzymatic method in 73 uremic patients and the values were plotted against serum creatinine. 41 patients received a free mixed diet, and 32 similar patients were given a low-nitrogen diet supplemented with essential amino acids, ketoanalogues, and calcium carbonate (AD). A significant correlation was found between serum creatinine and sOx levels in patients following a free mixed diet, while no correlation appeared in patients on AD: The sOx concentrations were significantly lower and even normal in this group, and a significant reduction of sOx occurred in 10 patients with chronic renal failure, who changed from a free mixed diet to the AD. The lowering of sOx concentration in patients following AD is attributed both to low intake of its metabolic precursors and to the oral calcium carbonate supplementation.     

Effect of various protein diets on growth, renal function, and survival of uremic rats.

The effects on growth, renal function, and survival of three isocaloric diets of various protein content (14, 27, and 37 g/100 g in diets I, II, and III, respectively) were compared in uremic rats and in controls. Diet I provided the minimal requirements in all amino acids for gorwing rats. In controls fed ad lib, weight and length gain were better with high protein diets, whereas they were inversely related to the diet protein content in uremic rats. The higher the protein intake, the higher the progressive elevation of BUN and serum creatinine and the mortality rate. Because proteins were supplied by fish flour, their increase was associated with increased mineral content, and the conclusions are restricted to the use of natural proteins: a moderately restricted protein diet securing only the minimal requirements had a beneficial effect on growth and survival of rats with reduced kidney mass. Avoiding any excess in proteins from the early stage of renal disease is suggested.     

Hidden Sources of Phosphorus in the Typical American Diet: Does it Matter in Nephrology?

Elevated serum phosphorus is a major, preventable etiologic factor associated with the increased cardiovascular morbidity and mortality of dialysis patients. An important determinant of serum phosphorus is the dietary intake of this mineral; this makes dietary restriction of phosphorus a cornerstone for the prevention and treatment of hyperphosphatemia. The average daily dietary intake of phosphorus is about 1550 mg for males and 1000 mg for females. In general, foods high in protein are also high in phosphorus. These figures, however, are changing as phosphates are currently being added to a large number of processed foods including meats, cheeses, dressings, beverages, and bakery products. As a result, and depending on the food choices, such additives may increase the phosphorus intake by as a much as 1 g/day. Moreover, nutrient composition tables usually do not include the phosphorus from these additives, resulting in an underestimate of the dietary intake of phosphorus in our patients. Our goal is to convey an understanding of the phosphorus content of the current American diet to better equip nephrologists in their attempt to control hyperphosphatemia.     

Uremia alters HDL composition and function

Functional impairment of HDL may contribute to the excess cardiovascular mortality experienced by patients with renal disease, but the effect of advanced renal disease on the composition and function of HDL is not well understood. Here, we used mass spectrometry and biochemical analyses to study alterations in the proteome and lipid composition of HDL isolated from patients on maintenance hemodialysis. We identified a significant increase in the amount of acute phase protein serum amyloid A1, albumin, lipoprotein-associated phospholipase A2, and apoC-III composing uremic HDL. Furthermore, uremic HDL contained reduced phospholipid and increased triglyceride and lysophospholipid. With regard to function, these changes impaired the ability of uremic HDL to promote cholesterol efflux from macrophages. In summary, the altered composition of HDL in renal disease seems to inhibit its cardioprotective properties. Assessing HDL composition and function in renal disease may help identify patients at increased risk for cardiovascular disease.     

Autoantibodies against oxidized LDL in chronic renal failure: role of renal function, diet, and lipids

Lipid peroxidation (LP) has recently been suggested to trigger the atherosclerotic process as well as to worsen the progression of renal disease. Autoantibodies against oxidized low-density lipoproteins (Ox-LDLAb) were considered to provide a sensitive marker to detect LDL oxidation in vivo. To date few studies have been reported on Ox-LDLAb levels in patients with different degrees of renal failure. The aim of this study was to evaluate the influences of renal function, dietary manipulation, and lipids on Ox-LDLAb concentrations in uremic patients either on conservative or replacement therapy. Seventy-one patients (42 males, 29 females) aged 60 +/- 19 years with chronic renal failure (CRF) of different etiology and degree were divided into four groups according to serum creatinine levels [sCr(mg/dl)] and diet: CRF I > or = 1.5-3.0, CRF II > 3.0-5.5, and CRF III > 5.5 were all patients on a conventional low-protein diet, while a fourth group included patients on a vegetarian diet supplemented with keto analogues and amino acids (CRF SD >3.0). A further group was represented by patients on dialysis therapy. All patients were examined for Ox-LDLAb, triglycerides (TG), total cholesterol, HDL and LDL cholesterol, and apolipoproteins Apo A1, Apo B, and Lp(a). The results were compared with those of 20 controls (9 males and 11 females) aged 52 +/- 11 years with sCr <1.5 mg/dl. Ox-LDLAb increased, although not significantly, with TG and Lp(a) from the early stages of CRF along with the deterioration of renal function. However, TG and Lp(a) levels were significantly higher in all groups of patients except those on vegetarian diet (CRF SD). This group also showed the lowest Ox-LDLAb levels. No relationship was observed between lipids or apolipoproteins and Ox-LDLAb. Hyperlipidemic patients did not show higher Ox-LDLAb levels than normolipidemics. Our results show a progressive increase of LP as the renal function declines, which may account for the increased risk of cardiovascular disease reported in uremia. Dialysis does not correct significantly the oxidative state observed in patients with end-stage renal disease. Vegan diet, by reducing LP, TG, and Lp(a), is supposed to decrease the risk of cardiovascular disease and worth being reconsidered as an alternative effective therapeutic tool in patients with advanced CRF.     

The statins--therapeutic diversity in renal disease?

PURPOSE OF REVIEW: Statins significantly reduce cholesterol synthesis and reduce cardiovascular morbidity and mortality. In addition, they appear to have beneficial effects independent of their ability to lower cholesterol. Recent publications suggesting a potential role for statin therapy in chronic renal insufficiency, hypertension and following organ transplantation are reviewed. RECENT FINDINGS: Pharmacokinetic studies have shown statins to be well-tolerated and effective in patients on long-term haemodialysis, providing equivalent control of lipid levels to that seen in matched controls. Preliminary clinical trials suggest that statins may have beneficial disease-modifying effects in chronic inflammatory disease. Furthermore, immunosuppressive and immunomodulatory actions may confer benefit following cardiac transplantation, but this remains to be demonstrated definitively in renal transplant patients. Data to date suggest that, in addition to reduction of cardiovascular risk, statins may help slow the progress of chronic renal insufficiency, particularly in patients with proteinuria. Addition of statin therapy may also contribute to the control of systemic and pulmonary hypertension. SUMMARY: Encouraging data in support of a wider spectrum of use for statins are emerging. In addition to reduction of cardiovascular risk through lipid lowering, they may represent an important adjunctive therapy in patients with chronic kidney diseases and post-transplantation. However, further large, well-designed clinical trials are required before their widespread use can be recommended in this setting.     

Nutrition and outcome on renal replacement therapy of patients with chronic renal failure treated by a supplemented very low protein diet

Protein-restricted diets are prescribed in patients with chronic renal failure (CRF) to alleviate uremic symptoms and to slow the progression of CRF. The potential deleterious effects of protein restriction on nutritional status and clinical outcome of patients with CRF have raised concern. In this study, data were collected from 1985 to 1998 on 239 consecutive patients (age 50.2 +/- 15.6 yr) with advanced CRF (GFR 13.1 +/- 4.8 ml/min) to whom a supplemented very low protein diet (SVLPD) providing 0.3 g protein, 35 kcal, and 5 to 7 mg of inorganic phosphorus per kg per day was administered for a mean duration of 29.6 +/- 25.1 mo. The diet was supplemented with essential amino acids and ketoanalogs, calcium carbonate, iron, and multivitamins. During SVLPD, protein intake decreased from 0.85 +/- 0.23 to 0.43 +/- 0.11 g/kg per d, and body mass index and serum albumin concentration remained unchanged overall. Fourteen patients died during SVLPD; death was unrelated to nutritional parameters. Hemodialysis was initiated after SVLPD in 165 patients at a mean GFR of 5.8 +/-1.5 ml/min. During an average of 54 mo on hemodialysis, mortality was low (2.4% after 1 yr) and correlated to age only, not to nutritional parameters observed at the end of SVLPD. Similar results were obtained in 66 transplanted patients (12 were not dialyzed before transplantation). SVLPD can be safely used in patients with CRF without adverse effects on the clinical and nutritional status of the patients. Due to the preservation of nutritional status and the correction of uremic symptoms, the initiation of dialysis was deferred in these patients. The outcome of patients on renal replacement therapy is not affected by prior treatment with SVLPD during the predialysis phase of CRF.     

Conflicting dietary advice for adhering to low-sodium and low-phosphorus diets.

OBJECTIVE: To elucidate conflicts that patients face when advised to limit multiple nutrients in their diet. DESIGN: We analyzed the phosphorus content of low-sodium foods compared with their regular-sodium content counterparts, and the sodium content of low-phosphorus foods compared with foods containing higher levels of phosphorus. Low-sodium and low-phosphorus foods were identified with the use of recommendations from National Kidney Foundation patient information Web sites. Content of sodium and phosphorus was quantified with use of the US Department of Agriculture (USDA) Nutrient Database. SETTING: Review and analysis of publicly available patient information Web sites and nutrient databases. MAIN OUTCOME MEASURE: Phosphorus content of low- versus regular-sodium-containing foods, and sodium content of low- versus high-phosphorus-containing foods. RESULTS: Of 47 low-sodium foods, 32 had identical phosphorus content--8 higher and 7 lower--compared with regular-sodium alternatives. Of 9 foods recommended as low-phosphorus alternatives to high-phosphorus choices, 4 had higher sodium content and 5 had lower, with considerable variability. However, choosing servings of 4 low-sodium alternatives could increase ingestion of phosphorus by up to 16% of recommended intake, and choosing servings of 4 low-phosphorus alternatives could increase ingestion of sodium by more than 20% of recommended intake. CONCLUSION: Adhering to a complex renal diet is extremely difficult for patients with chronic kidney disease. Balancing sodium and phosphorus restrictions is particularly challenging, especially as food choices low in one nutrient may not be low in the other. To help patients follow these diets, alternative methods of achieving dietary restrictions of multiple, often conflicting, components may be needed.     

Effect of sodium intake on single nephron glomerular filtration rate and sodium reabsorption in experimental uremia.

Sodium balance, clearance and micropuncture studies were performed on three groups of uremic rats in which renal mass was reduced experimentally by approximately 85%. All animals received a sodium-free synthetic diet to which a measured amount of NaCl was added. Sodium intake was 3 mEq/day in one group, 1 mEq/day in a second group and 0.13 mEq/day in the third. In the latter, the Na intake was reduced (from an initial level of 1 mEq/day) as renal mass was reduced in proportion to the estimated reduction in renal mass in an effort to obviate the requirement for an increased natriuresis/nephron. Clearance and micropuncture studies also were performed in a group of normal rats maintained on 1 mEq/day of Na. All three groups of uremic rats on the standard diet maintained external Na balance. Single nephron glomerular filtration rate (SNGFR) in superficial nephrons was increased in all three groups of uremic rats and seemed to be independent of the Na intake; fractional fluid reabsorption was decreased in the proximal tubules in all three groups of uremic rats. Furthermore, absolute proximal Na reabsorption was markedly increased; and calculated values for distal reabsorption were markedly increased in all groups of uremic rats. The data suggest that the increase in SNGFR and the decrease in tubular fluid to plasma (TF/P) inulin ratios in superficial proximal tubules correlate poorly with the dictates for an increase in sodium excretion rate per residual nephron. These data also have implications regarding the operation of the control system in the regulation of external Na balance in uremia.     

Sevelamer hydrochloride attenuates kidney and cardiovascular calcifications in long-term experimental uremia

BACKGROUND: In chronic renal failure (CRF), hyperphosphatemia and an elevated calcium-phosphate product are associated with vascular calcification and increased cardiovascular morbidity and mortality. Previous data have demonstrated that 3-month treatment of uremic rats with sevelamer was associated with less nephrocalcinosis compared to calcium carbonate (CaCO3), despite similar control of serum phosphorus, calcium-phosphorus product (Ca x P product), and secondary hyperparathyroidism. There was no evidence of aortic calcification after 3 months of uremia (J Am Soc Nephrol 13:2299-2308, 2002). The present studies explore the influence of sevelamer and CaCO3 on cardiovascular and kidney calcifications in long-term experimental uremia over 6 months. METHODS: Normal and 5/6 nephrectomized rats (U) were fed a high phosphorus (HP) diet for 6 months. Two phosphate binders, CaCO3 and sevelamer, were administered and their influence on hyperphosphatemia, secondary hyperparathyroidism, kidney/myocardial/aortic calcification, and renal function was compared. RESULTS: All uremic rats began the study with the same degree of renal failure. Sevelamer was as effective as CaCO3 in reducing serum phosphorus, Ca x P product, and attenuating secondary hyperparathyroidism. Despite similar serum cholesterol levels, rats in the U-HP + sevelamer group had markedly lower calcium deposition in the myocardium and aorta (myocardium, 72 +/- 4 microg/g wet tissue; aorta, 736 +/- 156 microg/g wet tissue) compared to rats in either the U-HP + CaCO3 group (myocardium, 179 +/- 48, P < 0.05; aorta, 1308 +/- 343, P < 0.05) or the U-HP group (myocardium, 98 +/- 10, NS; aorta, 2150 +/- 447, P < 0.05). Dual immunohistochemical analysis for calcium and endothelial cell markers demonstrated that myocardial calcium deposition was intravascular within capillaries. Furthermore, calcium deposition in the kidney of uremic rats treated with sevelamer (582 +/- 111 microg/g wet tissue) was lower than that found in uremic rats treated with CaCO3 (1196 +/- 180 microg/g wet tissue). Sevelamer-treated rats had less deterioration in renal function with an associated lower serum creatinine, higher creatinine clearance, and less proteinuria. There was no difference in overall mortality between the three experimental groups. CONCLUSION: In long-term experimental CRF, in addition to controlling serum phosphorus and secondary hyperparathyroidism as efficiently as CaCO3, treatment with the phosphate-binder sevelamer attenuates vascular and kidney calcification.     

The effect of different diets on urine composition and the risk of calcium oxalate crystallisation in healthy subjects

OBJECTIVE: The aim of the study was to determine the impact of defined diet modifications on urine composition and the risk of calcium oxalate crystallisation. METHODS: Ten healthy male volunteers consumed a self-selected diet (SD) for 14 days, and three different standard diets for a period of 5 days each. Whereas the western-type diet (WD) is representative of the usual dietary habits, the normal mixed diet (ND) and the ovo-lacto-vegetarian diet (VD) were calculated according to the requirements. RESULTS: The risk of calcium oxalate crystallisation, calculated as relative supersaturation (EQUIL2) from urine composition, was highest during ingestion of diets SD and WD. The intake of diet ND resulted in a significant decrease in relative supersaturation with calcium oxalate by 58% (p<0.05) compared with diet WD, due to a significant decline in urinary calcium and uric acid excretion and a significant increase in urinary volume, pH-value and citrate excretion. In spite of an increase in urinary pH, citrate and magnesium excretion and a decline in calcium excretion, no further significant decrease in the risk of calcium oxalate crystallisation was observed on diet VD, due to a significant increase in urinary oxalate by 30% (p<0.05) on average. CONCLUSIONS: The change of usual dietary habits for a normal mixed diet significantly reduces the risk of calcium oxalate crystallisation. With a vegetarian diet a similar decline in urinary supersaturation with calcium oxalate can be achieved compared to a normal mixed diet. Since urinary oxalate excretion increased significantly, a vegetarian diet without adequate intake of calcium may not be recommended to patients with mild hyperoxaluria.     

Special characteristics of atherosclerosis in chronic renal failure

Cardiovascular complications are a major clinical problem in patients with chronic kidney disease and end stage renal failure. Death from cardiac causes accounts for 40%-50% of all deaths in these patients and is thus up to 20 times more common in uremic patients than in the general population. Cardiovascular pathology in patients with renal failure is complex, but accelerated atherosclerosis has repeatedly been discussed as one major cause. The prevalence of coronary atheroma in uremic patients is approximately 30% by autopsy and coronary angiography studies. Not only is the prevalence of atherosclerotic lesions very high, but also the case fatality rate of myocardial infarction. Recently, excess mortality in uremic patients having had a myocardial infarct was noted; the one year mortality was 55.4% and 62.3% in uremic patients with and without diabetes, respectively, compared to about 10-15% in non-uremic patients. This study goes beyond the well-known notion that urea is associated with more severe atherosclerosis and shows that, in addition, the adaptation to coronary perfusion deficits is inappropriate. Recent clinical and autoptical studies in pre-dialysis and dialysis cohorts have documented increased intima and media thickness which appear early in the course of renal disease; Vascular wall thickening in renal failure seems to be modified at least in part by parathyroidhormone (PTH) and endothelin-1 (ET-1) which are both elevated in patients with renal failure. In experimental renal failure a direct effect of high phosphorus diet in arterial wall thickening was also documented. In addition to thickening of the vascular wall marked structural alterations were noted in renal failure i.e. a decrease in elastic fibre content and an increase in extracellular matrix. Furthermore, increased calcification of coronary atherosclerotic plaques and of the media of the aorta and some peripheral arteries has been documented in patients with renal failure. Factors contributing to this increased calcification process may be deposition of abundant circulating calcium, microinflammation, oxidative stress, de novo expression of bone morphogenous proteins and lack of inhibitors of calcifcation. These changes in vascular wall composition may alter vessel elasticity and thus contribute to impaired vessel function in renal failure. It is obvious from the above mentioned facts that cardiovascular disease in the renal patient is certainly multifaetorial in origin. There are, however, important issues to adress in the future, like (I) the characterization of vascular morphology in the different vascular beds, (II) the pathomechanisms of vascular and plaque calcification as well as the potential beneficial effect of rigorous control of non-classical risk factors (i.e. high P or Ca x P, inflammation, oxidative stress, etc.), (III) an additive or supraadditive effect of various classical and non-classical risk factors and (IV) the role of diabetes mellitus in modifying these vascular alterations.