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PubMed2006

The incidence of end-stage renal disease in India: a population-based study.

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are emerging public health problems in developing countries, and need changes in health-care policy. ESRD incidence data are not available from large parts of the developing world including South Asia. We report the ESRD incidence in a large urban population in India. ESRD incidence was estimated for four consecutive calendar years (2002-2005) among 572 029 subjects residing in 36 of the 56 wards of the city of Bhopal. These subjects are beneficiaries of free health care in a hospital established after the 1984 Union Carbide Industrial Accident. Crude and age-adjusted incidence rates were calculated. A total of 346 new ESRD patients were diagnosed during the study period; 86 in 2002, 82 in 2003, 85 in 2004, and 93 in 2005. Average crude and age-adjusted incidence rates were 151 and 232 per million population, respectively. The mean age was 47 years, and 58% were males. Diabetic nephropathy was the commonest (44%) cause of ESRD. This study provides the first population-based ESRD incidence data from India and reveals it to be higher than previously estimated. Diabetic nephropathy is the leading cause of ESRD. Changes are required in health-care policy for optimal care of CKD patients and efficient resource utilization for management of those with ESRD.

Adult↗
PubMed2006

Nuclear receptors link gender dimorphism of renal disease progression.

Profound gender differences in the progression of chronic kidney disease (CKD) remain poorly understood. Differential expression of the genes for male- and female-specific proteins in the kidney has been proposed to account for this clinical phenomenon. Lu and colleagues provide evidence that the signaling pathways of the nuclear receptors ERalpha, AR and PPARalpha are associated with gender differences in CKD progression.

Animals↗
PubMed2006

Pleiotropic effects of the non-calcium phosphate binder sevelamer.

The number of chronic kidney disease (CKD) patients and related adverse outcomes has dramatically increased worldwide in the past decade. Therefore, numerous experimental and clinical studies have recently addressed the underlying mechanisms, in particular the marked increase in cardiovascular mortality. Hyperphosphatemia is a major problem in these patients with advanced stage of CKD. Its control by calcium-containing phosphate binders is effective, but at the price of potentially noxious calcium overload. Sevelamer hydrochloride is a phosphate binder that offers an effective control of hyperphosphatemia as calcium-rich binders but without increase of calcium load. Beyond the control of phosphate, sevelamer seems to exert pleiotropic effects which include the correction of lipid abnormalities and the clearance of some uremic toxins.

Chelating Agents↗
PubMed2006

A new era in phosphate binder therapy: what are the options?

Dietary restriction of phosphorus and current dialysis prescription are unable to maintain phosphorus levels within the recommended range (2.7-5.5 mg/dl) in patients with advanced chronic kidney disease (CKD). Therefore, phosphate binders that limit the absorption of dietary phosphorus are commonly prescribed for this patient group. The first phosphate binders were introduced more than 30 years ago and included aluminum salts; however, although effective binders, the use of these agents was subsequently restricted because of concerns over aluminum accumulation in the central nervous system, bone, and hematopoietic cells. In subsequent years, calcium salts, namely calcium carbonate and calcium acetate, became the most widely used phosphate binders; however, increasing evidence now suggests that prolonged use of these agents increases the total body calcium load, induces adynamic bone, and potentially increases the risk of cardiovascular and soft tissue calcification. Sevelamer is the first phosphate-binding agent that is non-absorbed, calcium-free, and metal-free. To date, this agent has been shown to effectively control serum phosphorus levels in patients with CKD. It may also attenuate coronary and aortic calcification and has a number of other beneficial effects on lipid metabolism and inflammation among others. Lanthanum carbonate is another new agent that is reported to provide similar phosphate control to calcium-based phosphate binders but concerns that the long-term administration of such compound may lead to tissue accumulation may limit its use.

Chelating Agents↗
PubMed2006

Comprehensive suppression of the renin-angiotensin-aldosterone system in chronic kidney disease: covering all of the bases.

Reducing proteinuria and blood pressure in chronic kidney disease (CKD) decreases rate of progression. Inhibition of the renin-angiotensin system by angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers is beneficial in reducing proteinuria but incomplete in suppressing aldosterone production and its renal effects. Adding aldosterone receptor blockers to these other agents may further halt the progression of CKD.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Homocysteine induces mesangial cell apoptosis via activation of p38-mitogen-activated protein kinase.

Hyperhomocysteinemia is prevalent among patients with chronic kidney disease (CKD) and has been linked to progressive kidney and vascular diseases. Increased glomerular mesangial cell (MC) turnover, including proliferation and apoptosis, is a hallmark of CKD. Activation of p38-mitogen-activated protein kinase (p38-MAPK) has been linked to apoptosis in many cell lines. Accordingly, we studied the effect of homocysteine (Hcy) on MC p38-MAPK signalling and apoptosis. Hcy (50 microM/24 h) increased MC apoptosis as determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL) and single-stranded DNA (ssDNA) analysis. In addition to increases in pro-caspase-3 protein and caspase-3 activity, cells exposed to Hcy manifested enhanced reactive oxygen species content. Hcy increased p38-MAPK activity (fivefold), with maximal effect at 50 microM and 20 min; p38-MAPK activation was attenuated by N-acetylcysteine (Nac) and catalase (Cat), further indicating that the effect was via oxidative stress. Confocal microscopy revealed activation and nuclear translocation of p38-MAPK that was attenuated by Cat. In addition, Hcy-induced apoptosis as determined by TUNEL and ssDNA assay was abrogated by Nac, Cat, and SB203580 (p38-MAPK inhibitor). We conclude that in MC, Hcy (i) activates p38-MAPK and increases p38MAPK nuclear translocation via an oxidative stress dependent mechanism and (ii) induces DNA damage and apoptosis that is dependent on oxidative stress and p38-MAPK activation.

Animals↗
PubMed2006

Cost of applying the K/DOQI guidelines for bone metabolism and disease to a cohort of chronic hemodialysis patients.

Hyperphosphatemia is a common feature of advanced chronic kidney disease (CKD) and is treated routinely with oral calcium-based phosphate binders. In 2003, the National Kidney Foundation Kidney Disease Outcomes and Quality Initiative (K/DOQI) published Clinical Practice Guidelines (CPGs) for the treatment of Bone Metabolism and Disease in CKD. These advocate broad usage of expensive non-calcium-based phosphate binders such as sevelamer. This study was designed to determine the cost of implementation of the K/DOQI CPGs as they pertain to phosphate binding in a large Canadian hemodialysis (HD) unit. Laboratory and medication data for all chronic HD patients at the Ottawa Hospital were reviewed (n=416). Patients meeting each of the relevant K/DOQI guidelines were identified. Where guidelines would recommend a switch to non-calcium binders, equivalent sevelamer doses were estimated. The cost of implementing each guideline was then calculated individually and an estimate total cost of implementing all the guidelines was derived. Overall, 53% (222) patients fulfilled at least one criterion for sevelamer use. The yearly cost of implementation of the K/DOQI guidelines at this center was estimated at 500,605 dollars (American dollars). Given the significant cost, widespread adoption of the K/DOQI CPGs for Bone Metabolism and Disease should await the publication of compelling data demonstrating significant improved outcomes in patients treated with sevelamer.

Aged↗
PubMed2005

Prognostic potential of brain natriuretic peptide (BNP) in predialysis chronic kidney disease patients.

In the present study, we investigated the potential of N-BNP (N-terminal B-type natriuretic peptide) as a prognostic marker for risk of CV (cardiovascular) events, overall mortality and progression to ESRD (end-stage renal disease) in a cohort of 83 pre-dialysis CKD (chronic kidney disease) patients without clinical evidence of heart failure. During the study, ten patients reached the combined end point of overall mortality and/or CV event. Univariate factors associated with the combined end point were plasma N-BNP (P < 0.0005), creatinine (P < 0.002), systolic blood pressure (P < 0.009) and age (P < 0.015). N-BNP levels were higher in patients with CV events (P < 0.0005). Cox model regression analysis yielded log10 N-BNP (hazard ratio, 9.608; P < 0.007) and pre-existing CV disease (hazard ratio, 4.571; P < 0.029) as independent predictors of overall mortality or CV events. Kaplan-Meier analysis curves for the subgroup with supramedian creatinine levels (225 micromol/l) showed significant separation of the curves stratified for plasma N-BNP levels above and below the group median (291 pmol/l) for all end points. Receiver-operator-characteristic curves for N-BNP (355 pmol/l cut-off) demonstrated a specificity of 65.8% at a sensitivity of 100% for predicting CV events/overall mortality. The measurement of plasma N-BNP may aid in the risk stratification of pre-dialysis CKD patients. The high sensitivity and negative predictive value (100%) may enable the selection of patients who could safely be excluded from further investigations, resulting in better focusing of resources.

Biomarkers↗
PubMedDate not supplied

Hemodynamic cardiovascular risk factors in chronic kidney disease: what are the effects of intervention?

Left ventricular (LV) volume and pressure overload occur frequently in chronic kidney disease (CKD). Anemia is a risk factor for left ventricular hypertrophy (LVH) and dilatation, heart failure, and death. Normalization of hemoglobin with erythropoietin may prevent LVH and dilatation in CKD, but in patients in later phases of their cardiac disease, this intervention is not of benefit. Increased vascular volume causes hypertension, which in turn causes LVH, cardiac failure, and ischemic heart disease (IHD). Manifestations of arteriosclerosis are associated with adverse cardiac outcomes, and angiotensin converting enzyme (ACE) inhibitors may improve LVH and markers of arteriosclerosis. Aortic stenosis in dialysis patients occurs infrequently, but may deteriorate rapidly. The hemodialysis milieu is the quintessential model of LV overload cardiomyopathy.

Aortic Valve Stenosis↗
PubMedDate not supplied

Applying multiple interventions in chronic kidney disease.

The medical, social, and financial burdens posed by end-stage renal disease (ESRD) are many and growing rapidly. People generally reach ESRD as a result of chronic progressive kidney disease. Advancing kidney disease is associated with several treatable complications, which if poorly managed reduce the length and quality of life. In addition, there are strong links between chronic kidney disease (CKD) and cardiovascular disease (CVD). Many people with less advanced CKD will die or suffer complications of CVD before reaching ESRD. Efficacious interventions, such as lowering blood pressure and treating dyslipidemia, can substantially reduce the progression of both kidney and cardiovascular disease. Careful management of these complex and interrelated diseases and risk factors requires detailed longitudinal and focused care which does not seem to be optimally delivered by health service practitioners organized in traditional ways. A disease management approach offers promise in this setting, but requires further study of clinical and economic impact.

Cardiovascular Diseases↗
PubMedDate not supplied

Peritoneal dialysis underutilization: the impact of an interventional nephrology peritoneal dialysis access program.

Peritoneal dialysis (PD) is an underutilized form of renal replacement therapy. Recent data have emphasized that only 12% of end-stage renal disease (ESRD) patients are initiated on this form of therapy in the United States. Patients requiring PD have most often been referred to general surgeons for catheter placement. This has incurred additional delays in starting treatment and loss of decision-making control by the referring nephrologist. To address this issue, we developed and incorporated our own PD access placement program into the preexisting chronic kidney disease (CKD) education program. To date, 46 patients have undergone 71 procedures. These included 51 (72%) PD catheter insertions, 14 (20%) removals, and 6 (8%) repositioning procedures for poor drainage. PD catheter insertion was performed peritoneoscopically under local anesthesia and a Fogarty catheter was used to reposition a migrated catheter. All of the procedures were performed by nephrologists in a dedicated interventional nephrology (IN) laboratory. All six repositioning procedures failed to restore optimal drainage. Five of these patients had the catheter removed and a new catheter placed during the same procedure. Of these five patients, one had recurrence of poor drainage and opted for hemodialysis (HD). The sixth patient declined reinsertion and chose HD. Of the remaining seven removal procedures, three were due to fungal peritonitis, one due to bowel perforation, one due to severe depression, one due to transplant, and one catheter was removed at the request of the primary physician in a terminally ill patient. Eight of the 51 catheter insertions were during the initial admission of a catastrophic dialysis start. Two of these patients started acute PD and avoided catheter placement for HD. Thirty-seven of 46 patients have a functional PD catheter with a follow-up of 8.6 +/- 0.8 (mean +/- SE) months. During an 18-month period our PD population has increased from 43 to 80 patients. We conclude that a dedicated PD access placement program coupled with a CKD education program can have a dramatic impact on patient choice and PD growth.

Adult↗
PubMed2002

Preventive health care measures before and after start of renal replacement therapy.

OBJECTIVE: To describe utilization of preventive health care measures in patients with chronic kidney disease (CKD), both in the year prior to onset of renal replacement therapy (RRT), and in the first year of RRT. METHODS: We identified a large cohort of patients with CKD in the New Jersey Medicaid and Medicare programs with fixed enrollment into the cohort at 1 year prior to RRT. We applied commonly used quality assurance instruments (Health Plan Employer Data and Information Set measures) and defined levels and correlates of use of preventive care measures before and after RRT. These included mammography, Pap smear testing, prostate cancer screening, diabetic eye exams, and glycosylated hemoglobin testing (HbA1c). We employed logistic regression models with adjustment for age, race, gender, comorbidity, timing of first nephrologist contact, socioeconomic status, and calendar year of first RRT. RESULTS: Overall, screening rates were low with the exception of diabetic eye exams. Prostate cancer screening, diabetic eye exams, and HbA1c testing were performed less often after onset of RRT compared to the year before (P < .05). Although screening rates before RRT improved considerably over the period of observation for these measures (P < .05), this was not the case once patients were on RRT. CONCLUSIONS: Preventive health care interventions remain underutilized among RRT patients. Greater attention to such preventive measures could lead to significant improvements in the health status of such vulnerable patients. Thus, quality improvement of the general health care for patients on RRT should become a priority in renal health policy.

Cohort Studies↗
PubMed2004

[Vascular risk factors and renal failure].

Patients with chronic kidney disease (CKD) have a substantially increased risk of cardiovascular disease (CVD) compared with the general population. The high prevalence of established traditional risk factors for atherosclerosis (diabetes, hypertension, dyslipidemia) in these patients undoubtedly contributes to the accelerated rate of vascular disease. In addition, several hypotheses have emerged to explain the high prevalence of CVD in patients with chronic renal failure. Growing evidence has been gathered over the last 15 years regarding the role of uremia-related risk factors such as inflammation and oxidant stress in the pathogenesis of atherosclerosis in subjects with renal failure. This paper will review current knowledge regarding the potential role of these non-traditional or uremia-related risk factors for atherosclerosis with special emphasis on prevalence, cardiac risk, and management in patients with CKD.

Cardiovascular Diseases↗
PubMed2001

Cardiovascular disease in patients with chronic kidney disease: getting to the heart of the matter.

The high prevalence of cardiovascular disease (CVD) in patients with kidney disease is well described. This Canadian, multicenter, observational cohort study reports the prevalence and risk factors of CVD associated with kidney disease, in a cohort of patients with established chronic kidney disease (CKD), who are followed-up by nephrologists. This analysis sought to answer 2 questions: (1) in patients with established CKD, are the prevalence and progression of CVD accounted for by conventional or uremia-related risk factors, and (2) to what extent can progression to renal replacement therapy (RRT) be explained by CVD versus traditional risk factors for kidney disease? This study population consists of 313 patients (predominantly men) who had a mean age of 56 years and a mean creatinine clearance of 36 mL/min. Thirty percent were diabetic. The overall prevalence of CVD was 46%, and was independent of severity of kidney dysfunction (P = 0.700). The median follow-up time was 23 months, for a total of 462 patient years. We note the overall incidence of CVD events (new CVD or worsening of CVD) was 47/244 (20%). The best predictors of new CVD events among those without preexisting CVD were diabetes (odds ratio [OR] = 5.35, P = 0.018) and age (OR = 1.26, P = 0.08). In those with preexisting CVD, low diastolic pressure (DP) (OR =.72, P = 0.004) and high triglycerides (OR = 1.48, P = 0.019) at baseline were independent predictors of progression of CVD. We could not determine an independent impact of kidney function on CVD in the overall cohort. Furthermore, we determined that the presence of CVD itself confers an increased risk for progression to RRT (relative risk [RR] = 1.58, P = 0.047), adjusted for kidney function. This is the first in-depth analysis of CVD in a cohort of patients with established chronic kidney disease who are not on dialysis. The question regarding the impact of the altered biology of uremia in contributing to CVD progression remains unanswered, and clearly needs further study. However, the findings do raise the issue of whether aggressive treatment of CVD and risk factors might, in fact, reduce progression to RRT. Further large-scale, observational studies as well as interventional studies are needed to more clearly understand the complex biology of cardiovascular and kidney disease progression.

Age Distribution↗
PubMed2002

Randomized, controlled trial of darbepoetin alfa for the treatment of anemia in hemodialysis patients.

BACKGROUND: Darbepoetin alfa (Aranesp; Amgen, Thousand Oaks, CA) is a new erythropoiesis-stimulating protein with a threefold longer terminal half-life than recombinant human erythropoietin (epoetin) in patients with chronic kidney disease (CKD). The purpose of this randomized, double-blind, noninferiority study is to determine whether darbepoetin alfa is as effective as epoetin for the treatment of anemia in hemodialysis patients when administered at a reduced dosing frequency. METHODS: Patients receiving epoetin therapy were randomized to continue epoetin administered intravenously (IV) three times weekly (n = 338) or change to darbepoetin alfa administered IV once weekly (n = 169). The dose of darbepoetin alfa or epoetin was individually titrated to maintain hemoglobin concentrations within -1.0 to +1.5 g/dL (-10 to +15 g/L) of patients' baseline values and within a range of 9.0 to 13.0 g/dL (90 to 130 g/L) for up to 28 weeks (20-week dose-titration period followed by an 8-week evaluation period). The primary end point was change in hemoglobin level between baseline and the evaluation period (weeks 21 to 28). RESULTS: Mean changes in hemoglobin levels from baseline to the evaluation period were 0.24 +/- 0.10 (SE) g/dL (2.4 +/- 1.0 g/L) in the darbepoetin alfa group and 0.11 +/- 0.07 g/dL (1.1 +/- 0.7 g/L) in the epoetin group, a difference of 0.13 g/dL (95% confidence interval [CI], -0.08 +/- 0.33 [1.3 g/L; 95% CI, -0.8 to 3.3]). This difference was not statistically significant or clinically relevant despite the reduced frequency of darbepoetin alfa administration. The safety profile of darbepoetin alfa was similar to that of epoetin, and no antibody formation to either treatment was detected. CONCLUSION: These results show that darbepoetin alfa maintains hemoglobin concentrations as effectively and safely as epoetin in patients with CKD, but with a reduced dosing frequency.

Adult↗
PubMed2002

Iron sucrose: the oldest iron therapy becomes new.

Several parenteral iron preparations are now available. This article focuses on iron sucrose, a hematinic, used more widely than any other for more than five decades, chiefly in Europe and now available in North America. Iron sucrose has an average molecular weight of 34 to 60 kd, and after intravenous (IV) administration, it distributes into a volume equal to that of plasma, with a terminal half-life of 5 to 6 hours. Transferrin and ferritin levels can be measured reliably 48 hours after IV administration of this agent. Iron sucrose carries no "black-box" warning, and a test dose is not required before it is administered. Doses of 100 mg can be administered over several minutes, and larger doses up to 300 mg can be administered within 60 minutes. The efficacy of iron sucrose has been shown in patients with chronic kidney disease (CKD) both before and after the initiation of dialysis therapy. Iron sucrose, like iron gluconate, has been associated with a markedly lower incidence of life-threatening anaphylactoid reactions and may be administered safely to those with previously documented intolerance to iron dextran or iron gluconate. Nonanaphylactoid reactions, including non-life-threatening hypotension, nausea, and exanthema, also are extremely uncommon with iron sucrose. Management of patients with the anemia of CKD mandates that we carefully examine the effectiveness and safety of this oldest of iron preparations and the accumulating present-day data regarding it and contemporaneous agents.

Chronic Disease↗
PubMed2005

Kidney and kidney related chronic diseases in South Africa and chronic disease intervention program experiences.

The burden of chronic kidney disease (CKD) is rising in the world and the greatest burden is likely in developing countries such as South Africa (SA). This burden is related to the increase of 130% in noncommunicable diseases (NCD) such as diabetes and hypertension. SA has an additional burden of human immunodeficiency virus (HIV), which has infected 19.9% of adults and contributes to 30% of deaths. NCDs remain the major causes of death (37%). Hypertension is considered as a cause of end-stage renal disease (ESRD) in 34.6% of Blacks, 4.3% Whites, 20.9% of mixed race people, and 13.9% of Indians. Diabetes is believed to occur in 10% to 16% of South Africans. These risk factors, together with a high HIV/CKD burden (8%), result in a large burden of CKD. Other nontraditional risk factors, such as low birth weight, must also be considered. Despite rates of ESRD suspected to be about 400 per million population (pmp), only 99 pmp receive renal replacement therapy (RRT). Novel methods have to be established in the developing world to tackle the NCD and communicable disease burden. This article investigates the option of an integrated approach to chronic diseases as an answer to some of this burden. Both an urban-based and a rural-based NCD prevention and treatment program are reviewed.

Humans↗
PubMed2005

Hypertension in children with chronic kidney disease.

Hypertension occurs commonly in children with chronic kidney disease (CKD) and undoubtedly contributes to the progression of disease. This review summarizes the role of hypertension in the progression of CKD in children and highlights the central role played by the renin-angiotensin system in this relentless process. Strategies for reno-protection are discussed, and treatment recommendations are made for control of hypertension in this patient population.

Child↗