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PubMed2004

Sympathetic hyperactivity in chronic kidney disease: pathogenesis, clinical relevance, and treatment.

Cardiovascular morbidity and mortality importantly influence live expectancy of patients with chronic renal disease (CKD). Traditional risk factors are usually present, but several other factors have recently been identified. There is now evidence that CKD is often characterized by an activated sympathetic nervous system. This may contribute to the pathogenesis of renal hypertension, but it may also adversely affect prognosis independently of its effect on blood pressure. The purpose of this review is to summarize available knowledge on the role of the sympathetic nervous system in the pathogenesis of renal hypertension, its clinical relevance, and the consequences of this knowledge for the choice of treatment.

Animals↗
PubMed2004

Chronic kidney disease: the distribution of health care dollars.

BACKGROUND: The cost of care for end-stage renal disease (ESRD) is known to be high. The factors responsible for higher ESRD cost develop during chronic kidney disease (CKD), where the data on distribution of cost are limited. METHODS: This retrospective cohort study of 1995 through 1998 incident dialysis patients was performed to study the distribution of costs during the 24 months prior to initiation of dialysis. Patient data were obtained from the Centers for Medicare and Medicaid Services (CMS). Patients who were Medicare eligible for at least 2 years prior to initiation of dialysis were included in the study. Financial data were obtained from Medicare Part A and Part B claims and inflationary adjustments were made. The study period was divided into four segments based on overall distribution of cost. RESULTS: The mean age was 75 years, 51% were males, 73% were white, and 22% were black. Overall, patient comorbidity increased significantly during the study years. Cost showed a sharp increase in the last 6 months prior to initiation of dialysis. Hospitalization was the major component of cost throughout study period. Patients who initiated hemodialysis incurred a higher cost compared to patients who initiated other modes of kidney replacement therapy. Patients with diabetes or cardiovascular disease incurred higher cost compared to those who had no diabetes or cardiovascular disease, respectively. CONCLUSION: These data showed that hospitalization was the major component of the sharp increase in cost around the initiation of dialysis. Increased comorbidity was associated with higher cost. A focus on timely management of CKD may prevent future morbidity and costs.

Aged↗
PubMed2005

Does predialysis nephrology care influence patient survival after initiation of dialysis?

BACKGROUND: Early nephrology referral of patients with chronic kidney disease (CKD) has been suggested to reduce mortality after initiation of dialysis. This retrospective cohort study of incident dialysis patients between 1995 and 1998 was performed to address the association between frequency of nephrology care during the 24 months before initiation of dialysis and first-year mortality after initiation of dialysis. METHODS: Patient data were obtained from the Centers for Medicare & Medicaid Services. Patients who started dialysis between 1995 and 1998, and were Medicare-eligible for at least 24 months before initiation of dialysis, were included. One or more nephrology visits during a month was considered a month of nephrology care (MNC). RESULTS: Of the total 109,321 patients, only 50% had received nephrology care during the 24 months before initiation of dialysis. Overall, first-year mortality after initiation of dialysis was 36%. Cardiac disease was the major cause of mortality (46%). After adjusting for comorbidity, higher mortality was associated with increasing age (HR, 1.04 per year increase; 95% CI, 1.03 to 1.04) and more frequent visits to generalists (HR, 1.009 per visit increase; 95% CI, 1.003 to 1.014) and specialists (HR, 1.012 per visit increase; 95% CI, 1.011 to 1.013). Compared to patients with >/=3 MNC in the six months before initiation of dialysis, higher mortality was observed among those with no MNC during the 24 months before initiation of dialysis (HR, 1.51; 95% CI, 1.45 to 1.58), no MNC during the six months before initiation of dialysis (HR, 1.28; 95% CI, 1.20 to 1.36), and one or two MNC during the six months before initiation of dialysis (HR, 1.23; 95% CI, 1.18 to 1.29). CONCLUSION: Nephrology care before dialysis is important, and consistency of care in the immediate six months before dialysis is a predictor of mortality. Consistent nephrology care may be more important than previously thought, particularly because the frequency and severity of CKD complications increase as patients approach dialysis.

Aged↗
PubMed2005

Homocysteine in chronic kidney disease: Effect of low protein diet and repletion with B vitamins.

BACKGROUND: Data are limited on the determinants of homocysteine (tHcy) and its relationship with nutritional indices, and dietary protein intake, in the earlier stages of chronic kidney disease (CKD). METHODS: Levels of tHcy were assayed at baseline (N= 804) and 1 year postrandomization (N= 678) in the Modification of Diet in Renal Disease (MDRD) Study [study A, glomerular filtration rate (GFR) 25 to 55 mL/min/1.73 m(2) and study B GFR 13 to 24 mL/min/1.73 m(2)]. Participants were randomly assigned to different blood pressure targets and protein diets and all subjects received a multivitamin supplement containing 1 mg of folic acid, 10 mg pyridoxal 5'-phosphate (PLP) and 6 mug of vitamin B(12). Multivariable analyses were used to evaluate determinants of tHcy at baseline and 1 year. RESULTS: The prevalence of hyperhomocysteinemia (tHcy >15 mumol/L) at baseline was 56% in study A and 85% in study B. Baseline tHcy was negatively correlated with measures of body fat and dietary protein intake. Folate, vitamin B(12), and GFR were the major determinants of tHcy levels. Of the patients with hyperhomocysteinemia at baseline, 49% and 24% reduced their tHcy levels at 1 year to < or =15 micromol/L in study A and study B, respectively. There was no association between dietary protein intake and odds of developing hyperhomocysteinemia at 1 year in study A (P= 0.94) or study B (P= 0.10). CONCLUSION: Hyperhomocysteinemia is partly amenable to correction by vitamin supplementation in CKD stages 3 and 4. There is insufficient evidence to suggest that low tHcy is associated with poor nutritional status in the MDRD Study cohort. B vitamins and GFR, but not dietary protein, are the major determinants of tHcy in this patient population.

Analysis of Variance↗
PubMed2005

Progression of coronary artery calcification in diabetics with and without chronic kidney disease.

BACKGROUND: Rapid progression of coronary artery calcification (CAC) has been reported among individuals with end-stage renal disease (ESRD). There is limited information on the progression of CAC during earlier stages of diabetic chronic kidney disease (CKD). METHODS: In a prospective, cohort study of type 2 diabetic individuals (N = 90; normoalbuminuric diabetic controls, 30; diabetic nephropathy, DN, 60), electron-beam computed tomography (EBCT) was repeated at an average interval of 19 months. All scan images were acquired at end-systole to minimize interscan variability. In order to eliminate the dependence of the residual error from interscan variability on baseline CAC scores, square root transformed CAC scores were used for analyses of progression of coronary calcification. RESULTS: Repeat EBCT scans were completed in 68 subjects (diabetic controls: 23; DN: 45). There was a highly significant relationship between the proportion of subjects with progressive CAC and renal disease-DN who progressed to ESRD, 80%; DN who did not progress to ESRD, 30%; and diabetic controls, 13% (P < 0.001). Similarly, the magnitude of change was significantly related to renal disease (DN who progressed to ESRD > DN who did not progress to ESRD > diabetic controls, P < 0.001). Using logistic regression and controlling for non-dialyzed DN, ESRD and inter-scan interval, advanced age was the only significant variable associated with progression of CAC. Finally, serum creatinine and baseline CAC score emerged as independent predictors for the magnitude of increase in CAC. CONCLUSION: Progression of CAC is apparent among individuals with DN both before and after ESRD. However, the risk factors associated with progression of CAC may differ at different stages of CKD.

Calcinosis↗
PubMed2005

The impact of education on chronic kidney disease patients' plans to initiate dialysis with self-care dialysis: a randomized trial.

BACKGROUND: Compared with in-center hemodialysis, self-care dialysis (including home and self-care hemodialysis and peritoneal dialysis) is less resource intensive and associated with similar clinical outcomes. However, utilization of self-care dialysis has been very low. We performed a randomized controlled trial in predialysis patients with chronic kidney disease (CKD) (GFR <30 mL/min) to determine the impact of a patient-centered educational intervention on patients' intention to initiate dialysis with self-care dialysis. METHODS: Seventy patients with CKD who were receiving care in a multidisciplinary predialysis clinic were randomized to receive either (1) a two-phase patient-centered educational intervention (phase 1 included educational booklets and a 15-minute video on self-care dialysis; phase 2 included a 90-minute small group interactive educational session on self-care dialysis) in addition to their regular multidisciplinary care, or (2) ongoing standard care and education in the multidisciplinary predialysis clinic. The primary outcome was patients' intention to initiate dialysis with self-care dialysis, assessed by questionnaire. RESULTS: Thirty-five patients were randomized to standard care; 34 completed the study. Thirty-five patients were randomized to the educational intervention; 30 completed phase 1 and 28 completed phase 2. By study end, significantly more patients in the intervention group (82.1%) intended to start dialysis with self-care dialysis compared with the standard care group (50%, P= 0.015). This difference persisted after controlling for the small baseline differences among patients in the two study groups (P= 0.004). CONCLUSION: A two-phase educational intervention can increase the proportion of patients who intend to initiate dialysis with self-care dialysis.

Aged↗
PubMed2005

Progressive accumulation of lanthanum in the liver of normal and uremic rats.

BACKGROUND: The loss of renal function in chronic kidney disease (CKD) patients leads to a variety of metabolic disturbances that promote the development of secondary hyperparathyroidism (SH) and bone disease. One of these alterations, hyperphosphatemia, is a persistent problem in patients with CKD and is an important factor in the development and severity of SH as well as coronary artery and cardiac valve calcification. To help control serum phosphorus (P), phosphate binders are used to minimize intestinal absorption of P in these patients. Since the use of aluminum- and calcium-based phosphate binders can result in severe side effects, other phosphate binders have been proposed. One of these is lanthanum (La) carbonate. METHODS: Since there is some controversy as to the degree La is absorbed by the intestine, whether it is deposited in tissues, and what effect its prolonged use would have in patients with chronic renal failure, we studied normal and uremic rats fed a control diet or a diet with La carbonate (1.5% elemental La) for 45, 90, or 110 days. RESULTS: As expected, plasma creatinine increased after the induction of uremia and continued to increase with time. At 45 and 90 days, dietary La produced a reduction in plasma P in normal rats (N + La) [45 days: 3.15 +/- 0.35 vs. normal control (NC) 4.41 +/- 0.15 mg/dL, P < 0.01; 90 days: 3.20 +/- 0.30 vs. 4.09 +/- 0.15 mg/dL, P < 0.05], but not at 110 days. Plasma P was initially lower (45 days) in both groups of La-treated rats (U + La: 3.47 +/- 0.28 vs. UC: 4.91 +/- 0.27 mg/dL, P < 0.01), but was not at 90 and 110 days. Whole blood La content was not increased in rats fed the La diet and is, therefore, not a good indicator of the La content of tissue. La was increased in kidney, femur, and especially liver in normal and uremic rats fed the La diet. Uremia markedly enhanced tissue accumulation of La (liver, 110 days: N + La: 849 +/- 152 vs. U + La: 2676 +/- 479 ng/g wet wt, P < 0.01), which increased in a time-dependent manner. The increase in La in the liver of normal rats was 44-fold compared to control and 98-fold in the liver of uremic rats compared to uremic control. CONCLUSION: La accumulates in tissues, most strikingly in the liver, and renal failure accelerates the accumulation. While this was a relatively short-term study, La accumulation increased in a time-dependent manner. The effect of long-term La treatment on patients with chronic renal insufficiency needs to be evaluated.

Animal Feed↗
PubMed2005

Is it the agent or the blood pressure level that matters for renal and vascular protection in chronic nephropathies?

Over the recent years, it has been clearly documented that hypertension and proteinuria are the major factors responsible for progression of chronic kidney disease (CKD). Therefore, a target BP of at least 130/80 mm Hg has been suggested in order to reduce the rate of progression and cardiovascular mortality. Some antihypertensive agents, such as ACE inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), and perhaps calcium channel blockers (CCBs), may also be capable of reducing CKD progression because they halt some of the pathogenetic mechanisms involved in renal damage, some of which is unrelated to reduction of proteinuria, per se. Although this specific effect seemed to be partially independent of blood pressure reduction, it remains controversial whether these drugs are really superior to other antihypertensive agents when blood pressure values recommended by guidelines are achieved. This issue is still a matter of debate because in published trials, target and achieved blood pressure values were constantly higher than those recommended today. Nevertheless, available findings seem to indicate that the renoprotective effect of these agents is at least partially independent of a better BP control. The only way to definitely solve this issue would be a new randomized trial. However, the clinical relevance of this trial is debatable, considering that we need all the drugs available to reach these recommended BP values.

Animals↗
PubMed2005

Prevalence of silent kidney disease in Hong Kong: the screening for Hong Kong Asymptomatic Renal Population and Evaluation (SHARE) program.

BACKGROUND: End-stage renal disease (ESRD) is epidemic worldwide. In Hong Kong, the annual incidence of ESRD has risen from 100 pmp (per million population) in 1996 to 140 pmp in 2003. SHARE (Screening for Hong Kong Asymptomatic Renal Population and Evaluation program) is a population-based screening program aimed at identifying the prevalence of unrecognized renal disease in asymptomatic individuals, allowing further evaluation and disease-modifying interventions. METHODS: From November to December 2003, SHARE was conducted in several large residential communities in Hong Kong. The screening tool included a questionnaire documenting demographics and history or family history of diabetes mellitus (DM), hypertension (HT), and chronic kidney disease (CKD), together with on-site measurements of blood pressure (BP) and urine dipstick for protein, blood, and glucose. RESULTS: There were a total of 1811 participants. One thousand two hundred and one subjects were entered into the final analysis. Among the 1201 who were apparently "healthy" (asymptomatic and without history of DM, HT, or CKD), the prevalence of positive (> or =1+) urine dipstick for protein, glucose, blood, protein or blood, any urine abnormality, and HT (BP> or =140/90) was 3.2%, 1.7%, 13.8%, 16%, 17.4%, and 8.7%, respectively. Thirty three percent of the age over 60 years old group had either hypertension or urine abnormalities, compared with 24.0% in the 41- to 60-year-old group and 9.7% in the 20- to 40-year-old group. Having a family history of diabetes or hypertension increases the risk of having urine abnormalities, while a family history of hypertension also increases the risk of high blood pressure. CONCLUSION: It is concluded that subclinical abnormalities in urinalysis or BP readings are prevalent across all age groups in the adult population. An effective screening program at the primary care level that identifies these subjects for further evaluation is warranted, and the public in Hong Kong should be educated toward the significance of such findings in order to have regular health check for asymptomatic renal diseases.

Adult↗
PubMed2005

Calcimimetics: a new tool for management of hyperparathyroidism and renal osteodystrophy in patients with chronic kidney disease.

Calcimimetics: a new tool for management of hyperparathyroidism and renal osteodystrophy in patients with chronic kidney disease. Epidemiologic, clinical, and basic scientific studies led to an explosion in our understanding of disorders of mineral metabolism in the chronic kidney disease (CKD) patient. These advances are not always translated into improved care of renal osteodystrophy in CKD-5 patients. The introduction of a new class of drugs, calcimimetics, allows improved control of abnormal calcium/phosphorus metabolism. The calcimimetics compliment, rather than replace, current treatment options for secondary hyperparathyroidism in the chronic disease patient.

Aniline Compounds↗
PubMed2005

Chronic renal diseases as a public health problem: epidemiology, social, and economic implications.

The impact of chronic kidney disease (CKD) on the global burden of diseases is probably underestimated by current methods of evaluation. However, CKD are emerging as a major health problem. First, the costs of renal replacement therapy are excedingly high and are consuming a significant proportion of health care budgets of developed countries, while in developing countries are out of reach. Second, complex interaction are clearly emerging between chronic kidney, cardiovascular disease, and diabetes.

Adult↗
PubMedDate not supplied

Gene polymorphism association studies in dialysis: cardiovascular disease.

Cardiovascular disease (CVD) is the most important cause of morbidity and mortality in dialysis patients. The high prevalence of CVD is due to the cumulative effects of multiple risk factors from the early stages of chronic kidney disease (CKD). Familial predispositions to CVD, CKD, and their respective risk factors are well known, and it is likely that genetic factors determine the interindividual variability in risks for disease. Advances in genomic technology have facilitated the study of genetic variation--most commonly single nucleotide polymorphisms (SNPs) in candidate genes--and their associations with disease. This review examines CVD in dialysis patients as a model of a complex disease, discusses the approach to gene polymorphism association studies, including the roles of gene-environment and gene-gene interactions and provides an overview of available studies.

Cardiovascular Diseases↗
PubMedDate not supplied

Venous mapping using venography and the risk of radiocontrast-induced nephropathy.

Venous mapping using venography has been considered to be the gold standard for identifying veins suitable for arteriovenous fistula (AVF) creation. By utilizing a radiocontrast medium, however, venography introduces the risk of radiocontrast-induced nephropathy. The risk of this complication in the chronic kidney disease (CKD) population has not been previously studied. Twenty-five consecutive patients (CKD stage 4 and 5) undergoing venography were enrolled in this study. Patients were advised not to fast for the procedure and were encouraged to take oral fluids. Radiocontrast-induced nephropathy was defined as a 20% decrease in the estimated glomerular filtration rate (GFR) from the baseline value at 48 hours after contrast administration. Weekly telephone calls were made for a total of 4 weeks to assess the need for dialysis. Venography was performed by interventional nephrology using 10-20 cc of low osmolarity contrast medium. Data were collected prospectively. Median age was 48.9 +/- 7.8 years and 52% of the patients had diabetes. Complete sets of pre- and postprocedure GFRs were available in 21 patients. At 48 hours, there were no differences between the pre- and postprocedure GFRs. At the third week, one patient developed flu-like symptoms with severe gastroenteritis and was hospitalized for volume depletion. This patient initiated dialysis during the hospital stay. We conclude that at 48 hours, our cohort did not develop radiocontrast-induced nephropathy. During the 4-week phone call follow-up, only one patient needed dialysis. Large-scale studies with a longer follow-up using GFR estimation are needed to confirm these preliminary findings.

Acute Kidney Injury↗
PubMedDate not supplied

Overutilization of central venous catheters in incident hemodialysis patients: reasons and potential resolution strategies.

Even after adjusting for comorbidities, the outcomes in hemodialysis (HD) patients using a central venous catheter (CVC) as dialysis access are worse than in those with a permanent vascular access. In spite of this, nationwide data suggest that only about 25% of incident HD patients initiate dialysis with an arteriovenous fistula. We conducted a retrospective study to identify reasons and resolution strategies for CVC use in patients who initiated HD at an academic medical center with a well-established chronic kidney disease (CKD) clinic and a dedicated vascular surgeon. Estimated glomerular filtration rate (eGFR) loss over time to record progression of patients to HD was also examined. The charts of 170 consecutive patients were reviewed. Ninety-two percent were found to initiate HD using a CVC. Three factors explained 93% of all CVC in our cohort: absence of adequate predialysis care (45%), acute illness with failure to recover from an episode of acute renal failure (31%), and patient's failure to adhere to scheduled clinic or surgical appointments (17%). In addition, analyses of eGFR suggest that the velocity of GFR loss rather than a defined degree of renal function might be a better trigger for vascular access referral. We conclude that early referral, a close follow up of CKD patients who initiate dialysis due to acute illness, and patient education may have a positive impact to counteract overutilization of CVCs for dialysis. The rate in eGFR decline might also be used to calculate the referral time adequate for fistula creation.

Acute Kidney Injury↗
PubMed2005

Reversibility of 'secondary hypercalcitoninemia' after kidney transplantation.

Whether the increase of calcitonin (CT) concentration in patients with chronic kidney disease (CKD) is reversible or not after kidney transplantation is not known. We examined the effect of kidney transplantation on basal and pentagastrin-stimulated CT in CKD patients with elevated screening CT levels. Before transplantation, the median basal CT concentration of 17 patients was 31 pg/mL (13-76), and decreased to 8 pg/mL (4-28) at 23 months (2-34) after kidney transplantation (p < 0.00005). The maximum concentration of pentagastrin-stimulated CT was 63 pg/mL (25-110) before transplantation and decreased to 20 pg/mL (8-91) (p < 0.00005) thereafter. There was a linear association between CT and calcium as well as between phosphorus and parathyroid hormone at the time of screening. After transplantation, CT correlated with serum creatinine. Therefore, the increase of CT concentration in patients with impaired kidney function presumably reflects 'secondary hypercalcitoninemia' due to C-cell hyperactivity.

Adult↗
PubMed2005

Predicting glomerular filtration rate in kidney transplantation: are the K/DOQI guidelines applicable?

The kidney disease outcomes quality initiative (K/DOQI) guidelines introduced a classification of chronic kidney disease (CKD) based on the level of kidney function. In order to predict the glomerular filtration rate (GFR), they specifically recommended the use of the modification of diet in renal disease (MDRD) study and Cockcroft-Gault (C-G) equations. Since the performance of these estimates has been questioned, we sought to determine whether these recommendations might be applicable in renal transplantation. Following the K/DOQI methodology, we compared the GFR estimated by the MDRD and C-G equations with 476 inulin clearances performed in 284 renal transplant recipients. Even though the MDRD equations provided a better prediction than C-G formula, none of them reached the level of accuracy required by the K/DOQI standards. At least, 25% of the calculated GFR gave a prediction beyond 30% of the corresponding inulin clearance value. In addition, when classified according to their predicted GFR, less than two-thirds of the transplant patients turned out to be assigned to the correct stage of CKD. We conclude that, in renal transplantation, the predictive performance of both C-G and MDRD study equations appears to be particularly impaired and may potentially compromise the validity of the K/DOQI guidelines if implemented in their current form.

Biomarkers↗
PubMed2006

Plasma lipoprotein abnormalities in hemodialysis patients--clinical implications and therapeutic guidelines.

Patients with advanced stages of chronic kidney disease (CKD) have an increased risk of death from cardiovascular disease (CVD). Dyslipidemias are associated with atherosclerotic vascular changes and the risk of occurrence of acute myocardial infarction in hemodialysis patients. However, management of dyslipidemia in hemodialysis patients does not appear to be actively carried out in routine practice. Presumably, there are three reasons for this reluctance to lipid-lowering in hemodialysis patients. First, there are epidemiological data showing the inverse relationship between cholesterol and mortality rate; a high cholesterol predicts a better survival. Second, lipids are not usually measured using standard fasting serum, but a non-fasting specimen. Third, although hypertriglyceridemia is the most common abnormality, fibrates are contraindicated in patients with renal failure because of a high risk of rhabdomyolysis. These issues are discussed in the current review article. Based on published work, lipid lowering would not increase the death rate if carried out without worsening malnutrition. The National Kidney Foundation K/DOQI Clinical Practice Guidelines recommend a reduction in fasting LDL-C below 100 mg/dL for the prevention of CVD in dialysis patients. Practically, however, the use of non-HDL-C measured by casual blood samples might be sufficient for the risk assessment in many hemodialysis patients. Statins are a good choice for lipid-lowering in dialysis patients. Furthermore, lipoprotein profile might be improved by an inventive use of dialyzer membranes, dialysate solutions, and other dialysis-related medications. For severe hypercholesterolemia, LDL-apheresis is another choice for consideration. Further studies are needed to clearly prove the benefit of lipid reduction in hemodialysis patients and those with CKD at earlier stages.

Atherosclerosis↗
PubMed2006

Uremic syndrome and end-stage renal disease: physical manifestations and beyond.

PURPOSE: This review summarizes data concerning the incidence, definition, pathophysiology, and physical manifestations of patients with uremic syndrome. DATA SOURCES: Data sources utilized in writing this article included the National Kidney Foundation Guidelines, the United States Renal Data System, textbooks of medicine and pathophysiology, and medical care and nursing journals. CONCLUSIONS: Early identification of kidney disease in the early stages is essential to preserving kidney function for as long as possible. The progression of chronic kidney disease (CKD) and the manifestations of uremic syndrome leading to end-stage renal failure (ESRF) are often not addressed in the literature for nurse practitioners. IMPLICATIONS FOR PRACTICE: Patients with progressing CKD and ESRF often present in the primary care setting for treatment of acute and chronic conditions not pertaining to their renal status (e.g., viral upper respiratory infections, diabetes, hypertension). Nurse practitioners need to be knowledgeable about the subtle early presentation of uremic syndrome and ESRF, risk factors for kidney disease, assessment tools to make the diagnosis and stage the disease, treatment of this disease, as well as psychological, economic, and the social impact that ESRF imposes on individuals, families, communities, and the healthcare system as a whole when the chronic disease has progressed to end stage.

Anemia↗