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At least 757 records · Page 42Linked to original sources
PubMed2005

The receptor activator of nuclear factor-kappaB ligand inhibitor osteoprotegerin is a bone-protective agent in a rat model of chronic renal insufficiency and hyperparathyroidism.

Osteoprotegerin (OPG) acts by neutralizing the receptor activator of nuclear factor-kappaB ligand (RANKL), the primary mediator of osteoclast differentiation, function, and survival. We examined whether OPG could affect the bone loss associated with chronic kidney disease (CKD) in a rodent model of CKD and secondary hyperparathyroidism (SHPT). SHPT was induced in rats by 5/6 nephrectomy (5/6 Nx) and a 1.2% P/0.6% Ca(2+) diet. Starting 1 week after 5/6 Nx, rats were treated with vehicle (veh) or OPG-Fc (3 mg/kg, intravenously) every 2 weeks for 9 weeks. At baseline, 3, 6, and 9 weeks, blood was taken and bone mineral density (BMD) and bone mineral content (BMC) were assessed by dual-energy X-ray absorptiometry. Serum parathyroid hormone (sPTH) levels reached 912 pg/ml in 5/6 Nx rats vs. 97 pg/ml in shams at 9 weeks. OPG-Fc had no effect on sPTH or Ca(2+) levels throughout the 9-week study, indicating that SHPT was a renal effect independent of bone changes. At 3 weeks, 5/6 Nx-veh rats had osteopenia compared with sham-veh rats and 5/6 Nx-OPG-Fc rats had significantly higher percent changes in whole-body BMC, leg BMD, and lumbar BMD versus 5/6 Nx-veh rats. By 6-9 weeks, elevated sPTH was associated with reversal of bone loss and osteitis fibrosa in the proximal tibial metaphysis. OPG-Fc decreased this sPTH-driven high bone turnover, resulting in augmented thickness of proximal tibial trabeculae in 5/6 Nx rats. Thus, RANKL inhibition with OPG-Fc can block the deleterious effects of continuously elevated sPTH on bone, suggesting that RANKL may be an important therapeutic target for protecting bone in patients with CKD and SHPT.

Absorptiometry, Photon↗
PubMed2002

Pharmacokinetics of darbepoetin alfa in pediatric patients with chronic kidney disease.

Darbepoetin alfa is a novel erythropoiesis-stimulating protein with a two- to threefold longer half-life than recombinant human erythropoietin (epoetin) in adult patients with chronic kidney disease (CKD). This randomized, open-label, crossover study was conducted to determine the pharmacokinetic profile of darbepoetin alfa in pediatric patients with CKD. Twelve patients 3-16 years of age with CKD were randomized and received a single 0.5 micro g/kg dose of darbepoetin alfa administered intravenously (IV) or subcutaneously (SC). After a 14- to 16-day washout period, patients received an identical dose of darbepoetin alfa by the alternate route. After IV administration, the mean clearance of darbepoetin alfa was 2.3 ml/h per kg, with a mean terminal half-life of 22.1 h. After SC administration, absorption was rate limiting, with a mean terminal half-life of 42.8 h and a mean bioavailability of 54%. Comparison of these results with those from a previous study of darbepoetin alfa in adult patients indicated that the disposition of darbepoetin alfa administered IV or SC is similar in adult and pediatric patients, although absorption may be slightly more rapid in pediatric patients after SC dosing. The mean terminal half-life of darbepoetin alfa in this study was approximately two- to fourfold longer than that previously reported for epoetin in pediatric patients.

Adolescent↗
PubMed2004

The risk of cardiovascular disease in adults who have had childhood nephrotic syndrome.

While increased risk of cardiovascular disease (CVD) in patients with hyperlipidemia, chronic kidney disease (CKD), or end-stage renal disease (ESRD) is well documented, transient hyperlipidemia or intermittent renal disease as a consequence of relapsing nephrotic syndrome (NS) has not been studied. To investigate this enigma, 62 patients, between 25 and 53 years of age, who had steroid-responsive/dependent NS during childhood, were identified from the records of the Division of Pediatric Nephrology at Yale School of Medicine. Forty patients were located and contacted to ascertain symptoms or occurrences of CVD via a telephone interview. At the time of follow-up, 23-46 years after cessation of NS, none of these patients had ESRD or CKD. Three patients had experienced a myocardial infarction (MI): a 32-year-old male with a family history of CVD; a 41-year-old male with a history of heavy smoking, hypertension, diabetes mellitus, and elevated cholesterol; a 31-year-old male after a cocaine overdose. The occurrence of events (8%) and mortality from CVD (none) in this cohort of patients is comparable to patients of a similar age in the general population and is lower than that of patients of the same age who are on dialysis. The data suggest that relapsing NS during childhood does not place patients at increased risk for CVD mortality or morbidity compared with the general population. Consequently, it would appear that factors related to persistent proteinuria or renal insufficiency, rather than transient proteinuria and renal disease, contribute to the CVD documented in patients with CKD or ESRD.

Adolescent↗
PubMed2005

The use of levo-carnitine in children with renal disease: a review and a call for future studies.

Carnitine is an amino acid derivative that has a key role in the regulation of fatty acid metabolism and ATP formation. Carnitine deficiency has been described in various conditions, including chronic kidney disease (CKD) and end stage renal disease (ESRD). The deficiency of this micronutrient is postulated to lead to adverse effects across multiple organ systems. There is a paucity of information on carnitine deficiency and its effects in the pediatric CKD and ESRD populations. Currently, there is no evidence supporting the routine use of carnitine supplementation in children with ESRD. In this article, we review the pathophysiology, pharmacokinetics and the potential effects of levo-carnitine supplementation with a focus on the pediatric CKD and ESRD populations. Finally, potential future directions of research are discussed.

Anemia↗
PubMed2006

Darbepoetin alfa for the treatment of anemia in pediatric patients with chronic kidney disease.

Darbepoetin alfa, an erythropoiesis-stimulating glycoprotein, has proved efficacious in the treatment of anemia of chronic kidney disease (CKD) in adult subjects. However, little information is available from pediatric populations. We conducted an open-label, non-inferiority, 28-week study comparing the efficacy of darbepoetin alfa with that of recombinant human erythropoietin (rHuEpo) in pediatric subjects with CKD. Subjects, aged 1-18, who were receiving stable rHuEpo treatment (n=124) were randomized (1:2) to either continue receiving rHuEpo or convert to darbepoetin alfa, with doses titrated to achieve and maintain hemoglobin (Hb) levels between 10.0 and 12.5 g/dl. Darbepoetin alfa was considered to be non-inferior to rHuEpo if the lower limit of the two-sided 95% confidence interval (CI) for the difference in the mean change in Hb between the two treatment groups was above -1.0 g/dl. The adjusted mean change in Hb between the baseline and the evaluation period for the rHuEpo and darbepoetin alfa groups was -0.16 g/dl and 0.15 g/dl, respectively, with a difference of 0.31 g/dl (95% CI: -0.45, 1.07) between the means. These results, and the comparable safety profiles, demonstrate that darbepoetin alfa is non-inferior to rHuEpo in the treatment of anemia in pediatric patients with CKD.

Anemia↗
PubMed2006

FGF23: its role in renal bone disease.

Fibroblast growth factor 23 (FGF23) is a recently characterized peptide hormone produced mainly in the bone. It is secreted in response to dietary phosphorus load, and its main function is the promotion of urinary phosphate excretion and the suppression of active vitamin D (1,25D) production in the kidney. As such, FGF23 plays an important role in the maintenance of systemic phosphate homeostasis. In the advanced stages of chronic kidney disease (CKD), the kidney cannot excrete a phosphate load even in the presence of high levels of FGF23. This results in both hyperphosphatemia and a low level of 1,25D that stimulates the secretion of parathyroid hormone (PTH), leading to the development of secondary hyperparathyroidism. In chronic dialysis patients without residual renal function, FGF23 levels become extremely high due to stimulation by vitamin D therapy as well as by high levels of serum phosphate and PTH. Recent investigations have demonstrated that serum FGF23 level can be a useful marker for the prediction of the future development of refractory hyperparathyroidism and the response to vitamin D therapy in dialysis patients. In addition, putative protective roles of FGF23 against calcification have also been speculated on. Further elucidation of the mechanisms of FGF23 action will be needed to understand the various roles of FGF23 in CKD-Mineral and Bone Disorder (CKD-MBD).

Animals↗
PubMed2006

The central nervous system in childhood chronic kidney disease.

Neurodevelopmental deficits in pediatric and adult survivors of childhood onset chronic kidney disease (CKD) have been documented for many years. This paper reviews the available literature on central nervous system involvement incurred in childhood CKD. The studies reviewed include recent work in neuroimaging, electrophysiology, and neuropsychology, along with commentary on school functioning and long-term outcomes. The paper concludes with suggestions for monitoring the neurodevelopmental status and pursuing appropriate early interventions for children with CKD.

Achievement↗
PubMed2006

Ca2+-Mg2+-dependent ATP-ase activity and calcium homeostasis in children with chronic kidney disease.

Extracellular calcium concentrations in humans are thousands times higher than within cells. Maintenance of such gradient requires specific regulation including intracellular stores, Ca binding proteins and transmembrane protein systems. The aim of the study was to estimate PMCA (plasma membrane Ca-transporting adenosine triphosphatase; ATPase 3.6.1.38) activity and calcium homeostasis in erythrocytes of children with chronic kidney disease (CKD). Twenty-one children wth CKD stages 1-3 (group I) and 18 healthy children (group II) were examined. Group I was divided into two subgroups: Ia (8 patients with normal intact parathyroid hormone, iPTH, serum levels) and Ib (13 patients with increased iPTH). iPTH, urea, creatinine, inorganic phosphorus, cytosolic Ca2+ in red blood cells (R-Ca), and PMCA were determined. Significantly elevated R-Ca levels were observed in children from subgroup Ib in comparison with group II and subgroup Ia. The lowest activity of PMCA was found in subgroup Ia and Ib in comparison with group II. There was a negative correlation between PMCA and R-Ca in group Ia and Ib (r=-0.8, r=-0.9, respectively). In children with CKD treated conservatively, activity of PMCA in erythrocytes is disturbed. An increase in R-Ca and decrease in PMCA activity are also observed.

Adolescent↗
PubMed2006

Cardiovascular complications of pediatric chronic kidney disease.

Cardiovascular disease (CVD) mortality is a leading cause of death in adult chronic kidney disease (CKD), with exceptionally high rates in young adults, according to the Task Force on Cardiovascular Disease. Recent data indicate that cardiovascular complications are already present in children with CKD. This review summarizes the current literature on cardiac risk factors, mortality and morbidity in children with CKD.

Calcinosis↗
PubMed2005

Factors influencing the development of end-stage renal disease.

Epidemiological evidence is needed to design effective strategies for preventing chronic kidney disease (CKD) and end-stage renal disease (ESRD). Several types of health check are routinely performed in Japan, including the screening of asymptomatic individuals, but the potential benefits of these procedures remain unknown. We evaluated the predictors of ESRD, using community-based mass screening and a dialysis registry. This approach revealed the significance of proteinuria, hypertension, obesity, anemia, and high fasting plasma glucose levels (which indicate diabetes mellitus; DM), for the risk of developing ESRD. Lifestyle-related factors, such as smoking, alcohol consumption, and low levels of exercise, are also associated with these conditions and, in particular, with a high risk of ESRD. Over-nutrition and low levels of exercise can ultimately lead to DM, hypertension, hyperlipidemia, and obesity, and are important risk factors worldwide for cardiovascular diseases, CKD, and ESRD. The early detection and treatment of predictors of ESRD, along with appropriate treatment for CKD, may decrease the incidence of ESRD. In addition, the economic burden caused by the costs of dialysis presents a compelling argument for implementing a cost-effective preventive strategy against ESRD.

Humans↗
PubMed2006

An investigation into the microbial clogging potential of selected filter media as a result of biodegradation of a high-strength sulphate-rich alkaline leachate.

The research examines the potential for bio-clogging in filter packs containing fine sand of the type typically used in extraction wells for pumping leachates containing fine particulate matter, such as cement kiln dust (CKD). Three filter media with different particle sizes were used: 1.7-4.75, 0.35-1.0, and 0.235-0.45 mm. Each sand filter was tested using a leachate recirculating column reactor with a free drainage layer, on top of which was placed the filtration medium which was kept saturated and at a positive hydrostatic head by a 2-l reservoir of leachate. The leachate was collected from a landfill site that had been used for the co-disposal of municipal solid waste (MSW) and CKD. The leachate used was filtered by passing through a Whatman GFA filter paper before being added to the reactors in order to eliminate as far as possible the non-biological clogging which might have resulted from the introduction of particulate matter in the form of CKD. The filters and a control experiment were run under anaerobic conditions at 35 degrees C. The bio-clogging potential was observed by taking differential manometer readings from manometers located in the drainage and reservoir sections of the reactor. No clogging was detected using the coarser of the filter media, but there was some clogging when a finer filter medium was used. Head space gas analysis indicated that methanogenic activity was inhibited and analysis of the liquid phase indicated that the microbial process responsible for removal of chemical oxygen demand (COD) was principally one of sulphate reduction.

Alkalies↗
PubMed2006

The epidemics of cardiovascular disease in elderly patients with chronic kidney disease--two facets of the same problem.

There is increasing evidence that even mild renal dysfunction is a novel potent cardiovascular risk factor in the general elderly population. With more severe renal impairment, cardiovascular risk increases proportionately. This issue deserves attention, as chronic kidney disease (CKD) is predominantly a disease of the elderly, and the mean age of end-stage renal disease patients entering dialysis is growing constantly. In the dialysis population, when clinically significant cardiovascular disease (CVD) (particularly congestive heart failure) is present, survival is worse. Thus, every effort should be made to identify and treat cardiovascular risk factor in the early stages of CKD. However, elderly renal patients receive less proper cardiovascular therapy compared to non-renal subjects of the same age. This review deals briefly with the most significant data published in the last decade on CVD in elderly with CKD.

Age Factors↗
PubMed2005

Chronic kidney disease in adolescents.

Chronic kidney disease (CKD) involves a fixed deficit or progressive deterioration in kidney function, producing variable losses of normal physiologic functions. In adolescents, CKD results from a wide range of causes. Because of the broad spectrum of disease, the physician providing primary care to the adolescent must be knowledgeable about findings leading to the diagnosis of CKD and must understand the physiologic basis for therapeutic management. Complications of normal renal function loss include issues of fluid, electrolyte, and acid-base balance, as well as development of anemia, cardiovascular disease, metabolic bone disease, and growth failure. Goals of therapy include anticipation and replacement of lost physiologic functions so that the adolescent can grow and develop normally.

Adolescent↗
PubMed2006

The use of invasive cardiac procedures after acute myocardial infarction in long-term dialysis patients.

BACKGROUND: Dialysis patients have an excessive risk of cardiovascular death after myocardial infarction (MI). Underutilization of cardiac therapies may partially explain this risk, but whether patients on maintenance dialysis have differential rates of coronary angiography or revascularization during admission for MI compared with patients not on dialysis and whether these differences are explained by the presence of comorbid illness were uncertain. METHODS: We analyzed 154,692 patients with a primary diagnosis of MI in the 2001 National Inpatient Sample, and we compared procedure use in patients on long-term dialysis, patients with non-dialysis-dependent chronic kidney disease (CKD), or normal renal function. RESULTS: Dialysis patients and patients with dialysis-independent CKD were significantly less likely to undergo coronary angiography than patients with normal renal function (39% and 34% vs 56%). They were also less likely to undergo coronary revascularization (19% and 23% vs 41%) or to have a coronary intervention after diagnostic angiography (46% and 62% vs 70%). After adjustment, these differences remained, with a lower likelihood of angiography (42% and 45% vs 56%), revascularization (22% and 31% vs 41%), or coronary intervention after diagnostic angiography (52% and 66% vs 70%). CONCLUSIONS: Despite a high mortality rate after MI, patients on dialysis are markedly less likely than patients with dialysis-independent CKD or normal renal function to undergo diagnostic angiography or coronary revascularization after admission for MI. Additional studies to determine how these disparities are related to mortality are warranted.

Aged↗
PubMed2003

Hepatic drug metabolism and transport in patients with kidney disease.

The disposition of many drugs is altered in patients with acute (AKD) and chronic kidney disease (CKD). A decline in renal clearance of several drugs has been correlated significantly with residual renal function (ie, creatinine clearance) of subjects. Reductions in nonrenal clearance of some compounds also have been reported and associated with clearance of markers of oxidative and/or conjugative metabolism or P-glycoprotein-mediated transport. Although initial accounts of reduced hepatic microsomal cytochrome P-450 (CYP) content and activity in animal models of AKD and CKD were published almost 25 years ago, it is only in the last decade that technical advances in molecular biology and clinical pharmacology have enabled researchers to begin to characterize the phenotypic expression of individual enzymes and, importantly, distinguish the molecular and/or genetic basis for these changes. The selective modulation of hepatic CYP enzyme activity observed in kidney disease is caused, at least in part, by differentially altered expression of several CYP isoforms. This review summarizes data available through June 2003 regarding the effect of AKD and CKD on drug metabolism. Knowledge of the impact and nature of these alterations associated with kidney disease may facilitate the individualization of medication management in this patient population.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Ability of troponin T to predict angiographic coronary artery disease in patients with chronic kidney disease.

Association between angiographic coronary artery disease and cardiac troponin T levels has been observed in patients with normal kidney function; however, this association remains unsettled in patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD). Over a 12-month period we retrospectively reviewed coronary angiograms (CAs) performed in 194 hospitalized patients with presumed acute myocardial injury. About 50% of the ESRD and 30% of the CKD patients had normal CAs. Troponin T levels significantly correlated with CAs in patients with normal kidney function (r = 0.4, p = 0.005) but not in ESRD and CKD patients (r = 0.2, p = NS, respectively).

Coronary Angiography↗
PubMed2006

Prevalence of uncontrolled hypertension in patients with Fabry disease.

BACKGROUND: Fabry disease is a rare X-linked disease arising from deficiency of alpha-galactosidase A. It results in early death related to renal, cardiac, and cerebrovascular disease, which are also important outcomes in patients with elevated blood pressure (BP). The prevalence of uncontrolled hypertension, as well as the effect of enzyme replacement therapy on BP, in patients with Fabry disease is unknown. METHODS: We examined uncontrolled hypertension (systolic BP [SBP] >or=130 mm Hg or diastolic BP [DBP] >or=80 mm Hg) among 391 patients with Fabry disease who were participating in the Fabry Outcome Survey (FOS). RESULTS: Uncontrolled hypertension was present in 57% of men and 47% of women. In patients with chronic kidney disease (CKD) stage 1 (n100), median SBP was 120 mm Hg and median DBP was 74 mm Hg. In patients with CKD stage 2 (n172), median SBP was 125 mm Hg and median DBP was 75 mm Hg. In patients with CKD stage 3 (n63), median SBP was 130 mm Hg and median DBP was 75 mm Hg. There was a significant decrease in both SBP and DBP during a 2-year course of enzyme replacement therapy. CONCLUSIONS: This study revealed a high prevalence of uncontrolled hypertension among patients with Fabry disease. Thus there is a need to improve BP control and renoprotection in patients with Fabry disease.

Antihypertensive Agents↗
PubMed2006

Low-level environmental exposure to lead and progressive chronic kidney diseases.

PURPOSE: To determine whether low-normal body lead burden (BLB) accelerates progressive renal insufficiency in nondiabetic patients with chronic kidney diseases (CKD). METHODS: One hundred eight CKD patients (serum creatinine between 1.5 and 2.9 mg/dL) with low-normal BLB (<80 microg) and no lead exposure history were observed for 24 months. Following the observation, 32 patients with low-normal BLB (> or =20 microg and <80 microg) were randomly assigned to chelation and control groups. The chelation group patients were given edetate calcium disodium (EDTA) chelation therapy for 3 months and repeated chelation therapy during the following 24 months to maintain their BLB below 20 mug, while the control group patients underwent placebo therapy. The primary endpoint was an increased serum creatinine level to 1.25 times the baseline value. The secondary endpoint was temporal changes in renal function. RESULTS: The primary endpoint occurred in 14 patients in the observation period. Baseline BLB was the important risk factor in determining progressive renal insufficiency. The mean glomerular filtration rate (GFR) change in the chelation group patients was 6.6+/-10.7 mL/min/1.73m(2), compared with -4.6+/-4.3 mL/min/1.73 m2 in control group patients (P <.001) at the end of the intervention period. The mean decrease in GFR per year of chelation group patients was lower than that of control group patients during the repeated chelation period. CONCLUSION: Environmental exposure to lead, even at low level, may accelerate progressive renal insufficiency of nondiabetic patients with CKD.

Adult↗