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As heart transplantation becomes much more common primary care physicians will play a key role in preventing, detecting, and treating the short-term and long-term complications of this procedure. These complications include chiefly graft rejection and accelerated coronary artery disease, but also dyslipidemia, hypertension, diabetes mellitus, kidney failure, gout, osteoporosis, and malignancy.
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PMID:Long-term medical complications of heart transplantation: information for the primary care physician. 1099 25

The less rigorous attention to the management of the complications of chronic renal insufficiency (CRI) and its comorbid conditions has potentially tragic consequences. In fact, with early recognition and intervention, many of the complications of CRI and its comorbid conditions can be ameliorated or prevented. We review here the most prevalent, troublesome, and potentially preventable complications and comorbidities of CRI with a view toward developing high-quality, cost-effective strategies for delivering early interventional care. Complications of CRI include malnutrition, anemia, disorders of divalent ion metabolism and osteodystrophy, metabolic acidosis, and dyslipidemia. Important comorbid conditions of CRI are hypertension, diabetes mellitus, and cardiovascular disease. Clinical intuition suggests that early intervention will avert morbidity related to the hypoalbuminemia and other nutritional disorders of CRI, the metabolic acidosis, and the dyslipidemias, but prospective data are lacking at present. Correction of anemia, usually with recombinant human erythropoietin, may be key to the prevention of cardiac disease and other comorbidities of CRI. Incipient disorders of bone and mineral metabolism are managed prospectively using such measures as protein restriction to reduce phosphorus intake, phosphate binders, calcium supplementation, and vitamin D analogues. Hypertension, whatever its original etiology, is clearly an important risk factor for the progression of kidney failure and for the development of diffuse vascular disease; appropriate and aggressive treatment is essential. In patients with diabetic nephropathy, the principles of both primary and secondary prevention have been validated in several large trials of glycemic and blood pressure control. The seeds of these insidious, challenging, and costly comorbid conditions are sown very early in CRI, at a time when they are-in theory-most amenable to intervention. We therefore must be as proactive as possible in the timely implementation of relatively simple therapies that have the potential to prevent some of these adverse outcomes of CRI.
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PMID:Complications of chronic renal insufficiency: beyond cardiovascular disease. 1111 56

Patients with end-stage renal failure are a high-risk group for atherosclerotic cardiovascular disease and commonly have dyslipidemia as a major factor. Dietary manipulation is the recommended first line of therapy for reducing lipid levels in people with normal renal function; however, complex dietary requirements of dialysis-treated patients with end-stage renal failure impose significant constraints. In this study, we evaluated the effect of trying to comply with established lipid-lowering recommendations superimposed on our normally prescribed dialysis diet over 14 weeks in stable subjects treated with either hemodialysis (HD) or chronic peritoneal dialysis (PD). Of 306 dialysis patients screened, 75 subjects were enrolled; 8 subjects did not complete the study. In the remainder, HD subjects (n = 41) decreased saturated fat intakes by 18% overall and cholesterol intakes by 16%. This was associated with a decrease in total cholesterol levels from 232 +/- 8 to 209 +/- 4 mg/dL (mean +/- SEM; P = 0.007) and low-density lipoprotein cholesterol levels from 147 +/- 4 to 131 +/- 4 mg/dL (P = 0.009). However, energy intakes decreased by almost 10%. There were no statistically significant changes in PD patients (n = 26). Only 24.4% of HD (10 of 41 patients) and 15.4% of PD patients (4 of 26 patients) normalized their lipid levels. Considerable problems were encountered in maintaining compliance with the modified dialysis diets. This study shows that if adhered to, properly constructed dialysis diets are close to optimal lipid-lowering recommendations. Further dietary manipulation is difficult, leads to little benefit in the majority, and is accompanied by added problems of adherence. We conclude that the vast majority of dyslipidemic patients with end-stage renal failure require pharmacological therapy.
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PMID:Effect of lipid-lowering dietary recommendations on the nutritional intake and lipid profiles of chronic peritoneal dialysis and hemodialysis patients. 1138 90

Products of non-enzymatic glycation accumulate both in diabetic and non-diabetic patients with renal failure. The increase in concentration is presumably due to increased generation, secondary to oxidative stress and due to decreased (renal) elimination; whether accumulation of AGEs of dietary origin plays a role is currently under investigation. AGE's have been related to progression of diabetic (and possibly also non-diabetic) renal disease and to a number of complications of the uremic syndrome. These comprise beta-2-microglobulin-derived dialysis-related amyloidosis, dyslipidemia, vascular dysfunction and accelerated atherogenesis. A specific case is AGE related damage to the peritoneal membrane in CAPD patients. Removal of AGE by dialysis is negligible and even high flux dialysis eliminates only a quantitatively limited amount of AGE. In contrast, a rapid decrease of AGE concentrations in plasma is noted after renal transplantation. Dietary AGEs may contribute significantly to the total AGE load of the body, particularly in uremia.
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PMID:Advanced glycation endproducts (AGEs) as uremic toxins. 1145 83

French national health insurance has carried out two nationwide surveys as part of its programme intended to improve the care given to patients with hypertension, focusing on affiliates diagnosed with severe hypertension entitled to exemption from co-payments (patients are reimbursed 100 per cent for all care related to the corresponding disorder). The objective was to measure the difference between observed care and the quality of care delineated in the guidelines (1997) elaborated by the National Agency for Healthcare Accreditation and Evaluation (ANAES). The before and after comparison was designed to determine whether actual care is in accordance with the guideline's standards. The initial survey took place from 31 May to 12 November 1999 over the entire French territory (metropolitan and overseas departments) and concerned a representative sample of patients whose ages ranged from 20 to 80 years at the time they qualified for exemption from co-payments for severe hypertension. The method used for comparison involved the calculation of a number of different evaluation parameters, the principal one being blood pressure control, using the systolic (PAS) and diastolic (PAD) pressures reported by attending physicians. Other evaluation parameters included the quality of the therapeutic strategy utilized. A total of 10,665 patients were enrolled in the survey by using information gathered from 8377 practicing physicians. Extrapolated to the entire population in 1999, the results can be applied to 50,383 patients. The average age was 63 years and the patients had been treated for hypertension for an average of 9 years. In addition to severe hypertension, 64 per cent of the patients had other significant high-risk factors for cardiovascular disease: 44 per cent had dyslipidemia, 28 per cent had diabetes mellitus, 15 per cent were smokers. In 41 per cent of cases, the patients' blood pressures were well controlled (systolic and diastolic pressures below 140/90 mmHg or, for patients older than 60 years with only isolated systolic hypertension, systolic pressure equal to or lower than 160 mmHg); in 12 per cent of cases the patients' blood pressures were equal to the limit values; in 47 per cent of cases blood pressure was poorly controlled. Diabetics had poorly controlled blood pressure in 85 per cent of cases (systolic or diastolic pressures greater than 130/85 mmHg) and, similarly, 94 per cent of the patients who were in renal failure were poorly controlled (systolic or diastolic pressures greater than 125/75 mmHg). Preferential prescription with a particular therapeutic class, because of an existing comorbidity, was found in 68 per cent of patients whereas potentially contraindicated therapeutic classes were prescribed in 27 per cent. The daily cost of anti-hypertensive drug therapy was estimated at 8.05 francs per day per patient. Extrapolated to the study population in 1999, this represents 148.1 million francs. Less than 1 per cent of this observed cost (1.1 million francs) was economized by prescribing less expensive, alternative drug specialties in spite of the fact that an estimated 9.6 million francs could have been saved if these equivalent, alternative drugs had been prescribed. The potential saving corresponds to 6.5 per cent of the total observed cost. The care given to severely hypertensive patients is sub-optimum when compared with the ANAES guidelines (1997). In public health terms, the most preoccupying feature is poor blood pressure control because it occurs in a patient population with a high cardiovascular risk. These findings fully justify the continuation and amplification of the actions undertaken in this nationwide public health programme concerning the medical care given to hypertensive patients.
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PMID:[Treatment of severe arterial hypertension: cost of drug prescriptions in accordance with ANAES guidelines]. 1147 61

In the last few decades, clinical and experimental data have established microalbuminuria/proteinuria as an independent risk factor for renal disease and for progression of renal disease in patients with diabetes and in those with essential hypertension. Reduction of proteinuria with the use of angiotensin-converting enzyme inhibitors has been shown in clinical trials to delay or stabilize the rate of progression of renal disease. This effect appears to be independent of any effect on blood pressure control. In conjunction with other therapeutic interventions such as dietary modification and control of serum lipids, it appears that for at least a subgroup of patients, it is possible to delay or prevent progression of kidney failure. More recently, evidence has accumulated that establishes microalbuminuria/proteinuria as an independent risk factor for cardiovascular morbidity and mortality even in those without other clinical evidence of kidney disease. There is frequently a clustering of risk factors in these individuals that includes insulin resistance, salt-sensitivity, hypertension, and dyslipidemia. The mechanism of this relationship of proteinuria and cardiovascular disease is unclear, but the presence of proteinuria as a marker for cardiovascular disease has important implications for the identification and treatment of individuals at risk.
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PMID:Proteinuria and cardiovascular disease. 1157 14

Clinical data have established microalbuminuria/proteinuria as an independent risk factor for the development and progression of renal disease in patients with either diabetes or essential hypertension. Decreased kidney function is associated with increased cardiovascular risk, even at modest reductions in estimated creatinine clearance (to approximately 60 mL/min/1.73 m(2)) or modest elevations in serum creatinine (>1.4 mg/dL). Treatment with angiotensin-converting enzyme inhibitors has been shown in clinical trials to delay or stabilize the rate of progression of renal disease. Reduction in cardiovascular events, such as stroke and myocardial infarction, also has been shown in these high-risk individuals. These effects are dependent and independent of blood pressure control, suggesting a nonhemodynamic effect in blockade of the renin-angiotensin system. In conjunction with other therapeutic interventions, such as dietary modification and control of serum lipids, it appears that for at least a subgroup of patients it is possible to delay or prevent progression of kidney failure. There frequently is a clustering of risk factors in these individuals, including insulin resistance, salt sensitivity, hypertension, and dyslipidemia. The mechanism of the relationship between albuminuria and cardiovascular disease is unclear but may be related to endothelial cell dysfunction. Nonetheless, the presence of microalbuminuria/proteinuria as a marker for cardiovascular disease has important implications for the identification and treatment of individuals at risk.
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PMID:Metabolic pathogenesis of cardiorenal disease. 1172 77

During the course of developing clinical practice guidelines to improve outcomes of dialysis patients, it became evident that there existed an even greater opportunity to improve outcomes for all individuals with kidney disease, from the earliest stage of kidney injury through the entire spectrum of its progression to kidney failure, when replacement therapy becomes necessary. The development and adoption of a public health approach to the progressive course of chronic kidney disease could allow for the application of interventional strategies to prevent the loss of kidney function in some cases, to slow the progression of kidney disease in many others, and to ameliorate the complication or comorbidities in those with progressive kidney disease. In order to respond to this need, a new initiative, termed the Kidney Disease Outcomes Quality Initiative (K/DOQI), was launched in January of 2000. This article summarizes the recommendations of the first three set of clinical practice guidelines being developed under this new initiative: Chronic Kidney Disease: Evaluation, Classification and Stratification; Bone Metabolism and Disease in Chronic Kidney Disease, and Dyslipidemias in Kidney Failure.
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PMID:Impact of the new K/DOQI guidelines. 1180 66

The incidence of diabetic nephropathy has declined these last decades, but diabetes mellitus still remains the commonest cause of end-stage renal failure, due to an increased prevalence of diabetes mellitus and a longer life expectancy for diabetic patients. The aim of this review is to describe the natural history of diabetic nephropathy and discuss the influence of many factors such as genetic and non-genetic progression promoters, hypertension, hyperglycemia, dyslipidemia, proteinuria and tobacco. Because only a comprehensive treatment strategy of these promoters will reduce the risk of end-stage renal failure, the inclusion of cardiovascular risk factors management and the screening of cardiovascular disease will further contribute to reduce the very high mortality of diabetic patients suffering of diabetic nephropathy.
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PMID:[Diabetic nephropathies: therapeutic aspects]. 1182 Jan 69

This thesis is based on clinical studies including virtually all patients treated with peritoneal dialysis in Gothenburg during the 1990s. The patients had a fundamentally altered body composition compared to healthy subjects, characterised by a reduction in body cell mass and body fat already at start of dialysis. During PD treatment. a further decrease in body cell mass was observed. Energy stores tended to normalise during the first years of treatment and remained constant thereafter, or declined subsequently. Extracellular water, calculated from the four-compartment model, was increased when patients started PD treatment and increased further, in parallel to the reduction in body cell mass. These alterations were seen in combination with a normal. or slightly reduced, body weight. Standard methods of assessing nutritional status may therefore not be valid in the dialysis population. Prediction equations to estimate total body water, used in measurements of dialysis adequacy, give erroneous results in PD patients, as shown in a study on our PD population. This may have important clinical consequences, especially in wasted patients. Reduced muscle mass is a marker of protein-energy malnutrition, and therefore simple and reliable methods to measure muscle mass are warranted. When lean body mass was calculated from creatinine generation rate and compared to lean body mass estimated from measurements of total body potassium. the agreement between the two methods was low. Furthermore, when repeated measurements of creatinine generation rate were performed, the variation coefficient was unacceptably high. Thus. creatinine generation rate cannot be recommended as a method to evaluate somatic protein status in PD patients. The lipoprotein metabolic derangements are pronounced in PD patients. in which a further increase in cholesterol and cholesterol-rich apoB-containing lipoproteins are added to the already pre-existing renal dyslipidemia. characterised by increased concentration of triglycerides and triglyceride-rich complex lipoproteins. There are indications that dialytic variables may influence this development. When peritoneal function was assessed by the Peritoneal Dialysis Capacity test at start of dialysis, it was observed that peritoneal function reflected patient characteristics and co-morbidity. Patients with systemic disease had enhanced diffusion capacity compared to patients with primary renal disorders. Furthermore, in patients with more severe co-morbidity. peritoneal protein losses were increased. Finally, elderly patients had ultrafiltration conditions that were different from those of younger patients. Peritoneal function remained essentially stable during medium-long term follow up. Body composition features in dialysis patients are similar to those seen in severe disease in general. Thus, it is difficult to separate the effects of malnutrition from the effects of the underlying disease. Specific standards for nutritional status adapted for patients with renal failure are required.
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PMID:Nutritional status in peritoneal dialysis: studies in body composition, lipoprotein metabolism and peritoneal function. 1205 16


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