The economic burden of end-stage renal disease in Canada

End-stage renal disease (ESRD) is a serious illness with significant health consequences and high-cost treatment options. This study estimates direct and indirect cost associated with ESRD from a societal perspective. A prevalence-based approach was used to estimate direct health-care costs and productivity losses from short- and long-term disability. An incident-based human capital approach was used to estimate mortality costs as the sum of the discounted present value of current and future productivity losses from premature deaths. Less than 0.1% of Canadians have ESRD; however, the disease generated direct health-care costs of $1.3 billion in the year 2000. The amount of direct spending per person with ESRD is much more than the average spending per person for all health-care conditions. Adding indirect morbidity and mortality cost brings the total burden associated with ESRD to $1.9 billion. This economic impact is higher than that for skin or infectious diseases, about the same as for genitourinary or endocrine diseases, but lower than that for conditions such as cancer or stroke. This economic weight is borne by a relatively small number of individuals. With the rapid increase in the incidence of ESRD, these findings may be useful in setting priorities for research, prevention programs, and in the planning of treatments. A better understanding of the scope and magnitude of the total economic burden of ESRD would help to inform those making policy decisions.     

The broader burden of end-stage renal disease on children and their families

When a child has end-stage renal disease and requires dialysis, a heavy personal and financial toll can be extracted from the caregivers and the family. Tsai et al. have demonstrated an adverse effect on the psychosocial and socioeconomic well-being of caregivers of children on chronic peritoneal dialysis. These findings raise other questions and force us to think about support for the caregiver as well as the patient.     

Oxysterols are increased in plasma of end-stage renal disease patients

BACKGROUND/AIMS: Oxidative stress occurs in chronic renal failure patients undergoing hemodialysis (HD). The objective of our study was to measure oxidation products of cholesterols, so-called oxysterols, in the serum of HD patients in comparison to healthy control persons. METHODS: In 42 HD patients, plasma oxysterols were measured before and after HD. The values were compared with those in 40 healthy controls. The following cholesterol derivatives were analyzed: dienes, 7beta-OH, beta-epoxy, alpha-epoxy, 20alpha-OH, alpha-triol, and 7-keto cholesterol. RESULTS: In HD patients, serum levels of oxysterols are increased in comparison to controls. The highest values were measured for beta-epoxy cholesterol and for 20alpha-OH cholesterol. During HD oxysterol concentrations increased, obviously by water removal and concentration of nondialyzable compounds. CONCLUSION: Due to oxidative stress which is known as a typical sign of chronic renal failure the plasma concentrations of oxysterols are also significantly increased in comparison to healthy controls. This underlines the data on accelerated lipid peroxidation in end-stage renal disease (ESRD) patients. Accumulated oxysterols which are accused of exerting atherosclerosis-stimulating effects, which can contribute to the increased cardiovascular risk of ESRD patients, could either induce atherosclerosis via signaling or chronic effects. Direct chemical reactions stimulating plaque formation can be excluded because of the low levels of oxysterols. The share of oxysterols within the total cholesterol ranges from 4 to 15 per thousand.     

Plasma reduced homocysteine concentrations are increased in end-stage renal disease

BACKGROUND: Plasma total homocysteine (tHcy) concentrations> 15 micromol/L are associated with an increased risk of cardiovascular disease. This is especially the case in end-stage renal disease (ESRD), in which tHcy concentrations commonly range between 20 and 30 micromol/L. Adverse vascular or prothrombotic effects associated with hyperhomocysteinemia are assumed to be mediated by the free sulfhydryl (reduced) form of the molecule (rHcy), but data based on fluorescence high-pressure liquid chromatography (HPLC) indicate that rHcy concentrations are not increased in ESRD despite two- to threefold elevations in tHcy. METHODS: We developed a sensitive method for measuring plasma rHcy concentrations in which freshly drawn blood is incubated with sodium iodoacetate, and the resulting S-carboxymethylhomocysteine is analyzed by gas chromatography mass spectrometry. RESULTS: Unlike with the earlier methodology, we found plasma rHcy concentrations two to four times higher than normal in ESRD. These concentrations were lowered by hemodialysis and were proportional to plasma tHcy over the range of tHcy concentrations that has been associated with increased cardiovascular risk (r2 = 0.39, P < 0.0001). CONCLUSIONS: These results support the hypothesis that homocysteine could directly mediate vascular disease through mechanisms related to the reactivity of its free sulfhydryl group. It remains to be determined how much of the variability between plasma tHcy and rHcy is due to analytical variation and how much is due to biologic factors that separately influence concentrations of the disease marker, tHcy, and its presumed mediator, rHcy.     

The adolescent with end-stage renal disease

The adolescent with ESRD is frequently immature in relationship to chronological age. Growth and pubertal development are major concerns for the adolescent with ESRD. If renal failure had its onset prior to adolescence, it is likely that puberty will be delayed and ultimate adult height retarded for the patient requiring ESRD care during the adolescent period. Non-compliance with the therapeutic regimen is a major clinical problem encountered in the management of the adolescent. Significant morbidity can result from non-compliance with the dialysis regimen and non-compliance is a major cause of allograft loss in the adolescent transplant recipient. The special needs of the adolescent must be considered if ESRD care is to be successful.     

The safety of heparins in end-stage renal disease

In patients on chronic dialysis, unfractionated heparin (UFH) is the most commonly used agent for anticoagulation of the hemodialysis extracorporeal circuit, for hemodialysis catheter "locking" between dialysis treatments, and for nondialysis indications such as venous thromboembolic disease, peripheral vascular disease, and acute coronary artery disease. Potentially serious complications of UFH, such as hemorrhage, osteoporosis, and thrombocytopenia, have led to consideration of other options for anticoagulation, including low molecular weight heparin (LMWH) and direct thrombin inhibitors (DTIs). LMWH can be used for anticoagulation of the hemodialysis circuit, but whether this has significant benefit compared to UFH remains to be proven. Because of the somewhat unpredictable risk of severe bleeding complications when LMWH is used for other indications in dialysis patients, UFH rather than LMWH is preferred for treatment of thromboembolic disease in these patients. DTIs have been used for anticoagulation in dialysis patients with heparin-induced thrombocytopenia (HIT), with argatroban being the preferred agent if heparin-free hemodialysis cannot be performed. UFH still remains the preferred anticoagulant in the vast majority of dialysis patients requiring systemic anticoagulation and for anticoagulation of the extracorporeal hemodialysis circuit.     

Hyperphosphatemia in end-stage renal disease

Hyperphosphatemia occurs universally in end-stage renal disease (ESRD) unless efforts are made to prevent positive phosphate balance. Positive phosphate balance results from the loss of renal elimination of phosphate and continued obligatory intestinal absorption of dietary phosphate. Increased efflux of phosphate from bone because of excess parathyroid hormone-mediated bone resorption can also contribute to increased serum phosphate concentrations in the setting of severe hyperparathyroidism. It is important to treat hyperphosphatemia because it contributes to the pathogenesis of hyperparathyroidism, vascular calcifications, and increased cardiovascular mortality in ESRD patients. Attaining a neutral phosphate balance, which is the key to the management of hyperphosphatemia in ESRD, is a challenge. Control of phosphorus depends on its removal during dialysis and the limitation of gastrointestinal absorption by dietary phosphate restriction and chelation of phosphate. Knowledge of the quantitative aspects of phosphate balance is useful in optimizing our use of phosphate binders, dialysis frequency, and vitamin D sterols. The development of new phosphate binders and efforts to find new ways to inhibit gastrointestinal absorption of phosphate will lead to improvements in the control of serum phosphate levels in ESRD.     

Thrombosis in end-stage renal disease

Although renal failure has classically been associated with a bleeding tendency, thrombotic events are common among patients with end-stage renal disease (ESRD). A variety of thrombosis-favoring hematologic alterations have been demonstrated in these patients. In addition, "nontraditional" risk factors for thrombosis, such as hyperhomocysteinemia, endothelial dysfunction, inflammation, and malnutrition, are present in a significant proportion of chronic dialysis patients. Hemodialysis (HD) vascular access thrombosis, ischemic heart disease, and renal allograft thrombosis are well-recognized complications in these patients. Deep venous thrombosis and pulmonary embolism are viewed as rare in chronic dialysis patients, but recent studies suggest that this perception should be reconsidered. Several ESRD treatment factors such as recombinant erythropoietin (EPO) administration, dialyzer bioincompatibility, and calcineurin inhibitor administration may have prothrombotic effects. In this article we review the pathogenesis and clinical manifestations of thrombosis in ESRD and evaluate the evidence that chronic renal failure or its management predisposes to thrombotic events.     

Hyperthyroidism in end-stage renal disease

We report the 2nd patient to have hyperthyroidism while on maintenance hemodialysis. This case is instructive because the diagnosis of hyperthyroidism in uremic patients is difficult due to similar signs and symptoms. This case report describes, for the first time, the unique interaction between hemodialysis and thyrotoxic heart disease. Paroxysmal atrial fibrillation and severe hypotension interfered with all hemodialyses. Only the correction of the hyperthyroid state and withdrawal of all beta-blocking agents allowed resumption of normal hemodialysis. The delayed gastric emptying and hypercalcemia ultimately resolved with return to the euthyroid state and did not recur during 10 months of follow-up.     

Exercise in end-stage renal disease

Available studies indicate that exercise tolerance in renal patients is low. Although significant improvements in maximal oxygen consumption have been reported following exercise training in these patients, there may be physiologic limitations to the attainable levels of aerobic capacity due to the multisystemic nature of the disease. Long-term exercise training may result in other medical benefits. Compliance to regular exercise in hemodialysis patients remains a problem, however, exercise training during the dialysis treatment may prove beneficial in terms of compliance and supervision.     

Measuring the burden of illness for end-stage renal disease: some heavy lifting required

Estimates for the burden of illness (BOI) attributable to end-stage renal disease (ESRD) in Canada are presented in the article by Zelmer. This Commentary describes the methodology of BOI analysis, its role in formulating public policy, and the potential application to improving care for ESRD.     

The clinicopathological characteristics in renal cell carcinoma with end-stage renal disease

OBJECTIVES: The influence and the interdependence of pathological and clinical factors on prognostic differences between renal cell carcinoma (RCC) with end-stage renal disease (ESRD) and RCC without ESRD after nephrectomy has remained unclear. We compare the clinicopathological features between RCC with and without ESRD. MATERIALS AND METHODS: From June 1993 to May 2000, 150 RCC patients who underwent nephrectomy were pathologically defined to have pT1 to pT3NXM0. The patients were followed for 1 to 84 months (median 30 months) after the surgery. Total of 16 patients with ESRD and 134 patients without ESRD were studied, and the differences of clinicopathological features between two groups were statistically compared. RESULTS: We compare the clinicopathological features between RCC with and without ESRD. Patients' age, tumor size, rate of incidental cancer, pathological T stage, and grade were not significantly different between two groups. The 5-year recurrence-free probability rate was significantly higher in patients without ESRD than in patients with ESRD (log-rank test: p = 0.04). The status of ESRD, patients age and pathological T stage were significant predictors of recurrence when analyzed by Cox proportional hazards analysis (p = 0.01, p = 0.03 and p = 0.02, respectively). CONCLUSIONS: This study demonstrated that the ESRD is an independent prognostic factor in RCC patients after surgery. These results reflect that the patients with ESRD have higher risk of tumor progression. Therefore, early detection of tumors is particularly important in these patients by regular abdominal ultrasound or CT screening.     

Calciphylaxis in pediatric end-stage renal disease

Calciphylaxis is a rare, but life-threatening complication of end-stage renal disease (ESRD) that has been reported mostly in adult patients. The exact etiology is unknown, but the disease is commonly associated with a high calcium-phosphorus product and elevated levels of parathyroid hormone (PTH). We herein review the published reports on calciphylaxis in ESRD patients less than 18 years old and report the case of a patient with severe calciphylaxis who presented with lower extremity pain, muscle tenderness and difficulty in walking. The serum PTH was low, and the calcium-phosphorus product was normal. The diagnosis of calciphylaxis was confirmed by a muscle biopsy. Treatment with low calcium peritoneal dialysate and substitution of calcium-based phosphorus binders with sevelamer (Renagel) was unsuccessful. The patients clinical condition progressed to extensive soft tissue calcification and ulcerating skin lesions. Nine months after the onset of symptoms, the patient died of cardiopulmonary arrest.     

Chronic pain in end-stage renal disease

A growing body of literature has shown that chronic pain is common for patients with end-stage renal disease (ESRD), is typically moderate or severe, and impacts virtually every aspect of health-related quality of life. Unfortunately, there is a lack of clinical and research focus in this area in nephrology, and pain in ESRD is undertreated. This article will review the epidemiology of chronic pain in ESRD, discuss basic principles of pain assessment and management, and highlight some of the challenges in pain management in ESRD with the hope of guiding health professionals in the effective management of pain in patients with ESRD.     

Digital gangrene in end-stage renal disease

Ischemic complications presenting as digital gangrene occurring in a patient of end-stage renal disease undergoing haemodialysis is rarely reported in literature. We report one such case of dry gangrene of a single finger in a 53 years old male undergoing haemodialysis. The condition was likely a steal phenomenon secondary to the surgical angioaccess for dialysis.