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PubMed2004

Absorption, distribution, metabolism, and excretion of CKD-732, a novel antiangiogenic fumagillin derivative, in rats, mice, and dogs.

The pharmacokinetics of CKD-732 (6-O-4-[dimethyl-aminoethoxy)cinnamoyl]-fumagillol x hemioxalate) was investigated in male SD rats and beagle dogs after bolus intravenous administration. The parent compound and metabolites obtained from in vitro and in vivo samples were determined by LC/MS. The main metabolite was isolated and identified as an N-oxide form of CKD-732 by NMR and LC/MS/MS. CKD-732 was metabolized into either M11 or others by rapid hydroxylation, demethylation, and hydrolysis. The blood level following the intravenous route declined in first-order kinetics with T(1/2)beta values of 0.72 to approximately 0.78 h for CKD-732 and 0.92 to approximately 1.09 h for M11 in rats at a dose of 7.5 to approximately 30 mg/kg. In dogs, T(1/2)beta values of CKD-732 and M11 were 1.54 and 1.79 h, respectively. Moreover, AUC values increased dose dependently for CKD-732 and M11 in rats and dogs. The CLtot and Vdss did not change significantly with increasing dose, indicating linear pharmacokinetic patterns. The excretion patterns through the urine, bile, and feces were also examined in the animals. The total amount excreted in urine, bile, and feces was 2.13% for CKD-732 and 1.29% for M11 in rats, and 1.58% for CKD-732 and 2.28% for M11 in dogs.

Absorption↗
PubMed2005

Association between body mass index and CKD in apparently healthy men.

BACKGROUND: Overweight and obesity are well-established risk factors for cardiovascular disease and decline in kidney function in individuals with existing chronic kidney disease (CKD). Conversely, their association with the development of CKD is less clear. METHODS: We evaluated the association between body mass index (BMI) and risk for CKD in a cohort of 11,104 initially healthy men who participated in the Physicians' Health Study and provided a blood sample after 14 years. BMI was calculated from self-reported weight and height. We estimated glomerular filtration rate (GFR) by using the abbreviated equation from the Modification of Diet in Renal Disease Study and defined CKD as GFR less than 60 mL/min/1.73 m2 (<1 mL/s/1.73 m2). RESULTS: After an average 14-year follow-up, 1,377 participants (12.4%) had a GFR less than 60 mL/min/1.73 m2 (<1 mL/s/1.73 m2). Higher baseline BMI was associated consistently with increased risk for CKD. Compared with participants in the lowest BMI quintile (<22.7 kg/m2), those in the highest quintile (>26.6 kg/m2) had an odds ratio (OR) of 1.45 (95% confidence interval [CI], 1.19 to 1.76; P trend <0.001) after adjusting for potential confounders. We found similar associations by using different categories of BMI. Compared with men who remained within a +/-5% range of their baseline BMI, those who reported a BMI increase greater than 10% had a significant increase in risk for CKD (OR, 1.27; 95% CI, 1.06 to 1.53). CONCLUSION: In this large cohort of initially healthy men, BMI was associated significantly with increased risk for CKD after 14 years. Strategies to decrease CKD risk might include prevention of overweight and obesity.

Adult↗
PubMed2006

Metabolic syndrome and CKD in a general Japanese population: the Hisayama Study.

BACKGROUND: Metabolic syndrome has been linked with various atherosclerotic diseases, but has not been evaluated sufficiently as a risk factor for the development of chronic kidney disease (CKD) in the general population. METHODS: We followed up 1,440 community-dwelling individuals without CKD aged 40 years or older for 5 years and examined the effects of metabolic syndrome, defined by the modified National Cholesterol Education Program Adult Treatment Panel III criteria, on the development of CKD. RESULTS: During follow-up, 88 subjects experienced CKD. The age- and sex-adjusted 5-year cumulative incidence of CKD was significantly greater in subjects with than without metabolic syndrome (10.6% versus 4.8%; P < 0.01). In multivariate analysis, even after adjustment for other confounding factors, including insulinemia, metabolic syndrome remained an independent risk factor for the occurrence of CKD (odds ratio, 2.08; 95% confidence interval [CI], 1.23 to 3.52). Compared with subjects with 1 or fewer metabolic syndrome component, multivariate-adjusted odd ratios for CKD in subjects with 2, 3, and 4 or more metabolic syndrome components were 1.13 (95% CI, 0.60 to 2.12), 1.90 (95% CI, 0.98 to 3.69), and 2.79 (95% CI, 1.32 to 5.90), respectively. The rate of change in kidney function during 5 years decreased significantly in subjects with 4 or more metabolic syndrome components compared with those with 1 or fewer component in the age group of 40 to 59 years, whereas it also was significantly low in subjects with 3 metabolic syndrome components in the group aged 60 years or older. CONCLUSION: Our findings suggest that metabolic syndrome is a significant risk factor for the development of CKD in the general population.

Adult↗
PubMed2007

Epidemiological features of CKD in Taiwan.

BACKGROUND: The incidence of end-stage renal disease (ESRD) in Taiwan is the highest in the world. However, epidemiological features of earlier chronic kidney disease (CKD) have not been investigated. METHODS: Since implementation of the National Health Insurance Program in 1995, more than 96% of the population in Taiwan has been enrolled. A nationally representative cohort of 200,000 individuals randomly sampled from the National Health Insurance enrollees was followed up from 1996 to 2003. Clinical conditions were defined by using diagnostic codes. The prevalence and incidence of clinically recognized CKD were assessed. We also identified risk factors associated with the development of CKD. RESULTS: The prevalence of clinically recognized CKD increased from 1.99% in 1996 to 9.83% in 2003. The overall incidence rate during 1997 to 2003 was 1.35/100 person-years. The multivariate model indicates that age is a key predictor of CKD, with an odds ratio of 13.95 for the group aged 75-plus years compared with the group younger than 20 years. Other factors associated with increased risk for the development of CKD include diabetes, hypertension, hyperlipidemia, and female sex. CONCLUSION: The prevalence and incidence of CKD in Taiwan are relatively high compared with other countries. Our finding provides a reasonable explanation for the subsequent epidemic of ESRD in Taiwan. Further study is needed to identify the entire burden of CKD and the effectiveness of risk-factor modification.

Adolescent↗
PubMed2006

Applying the Growth Failure in CKD Consensus Conference: evaluation and treatment algorithm in children with chronic kidney disease.

Growth failure is a common and significant clinical problem for children with chronic kidney disease (CKD), particularly those with chronic renal insufficiency (CRI). Children with CRI (typically defined by a glomerular filtration rate [GFR] <75 mL/min/1.73 m2) who have growth impairment exhibit a variety of medical and psychological problems in addition to increased mortality. Growth failure in children with CKD is usually multifactorial in etiology, including abnormalities in the growth hormone (GH)-insulin-like growth factor (IGF)-I axis and a variety of nutritional and metabolic concerns characteristic of CKD. Proper management of these factors contributes to better growth in affected children. Although the safety and efficacy of recombinant human GH (rhGH) therapy in promoting growth in children with CKD are well established, recent data indicate that the use of rhGH administration in children with CKD and growth failure remains low. Recently, guidelines were developed by the Consensus Conference for Evaluation and Treatment of Growth Failure in Children with CKD. This paper focuses on the application of these guidelines to children with CKD.

Algorithms↗
PubMed2006

Practical approach to the diagnosis and treatment of anemia associated with CKD in elderly.

Anemia is a frequent complication of chronic kidney disease (CKD). Inadequate production of erythropoietin by the failing kidneys leads to decreased stimulation of the bone marrow to produce red blood cells (RBCs). Anemia of CKD develops early and worsens with progressive renal insufficiency. Although over 40% of patients with CKD are anemic, anemia in this population is under-recognized and undertreated. Of considerable importance, anemia is a risk factor for cardiovascular disease and is associated with higher rates of hospitalization and mortality. Despite the availability of erythropoiesis-stimulating proteins (ESPs) to stimulate RBC production in CKD patients, approximately three fourths of patients initiating dialysis have a hemoglobin <11 g/dL. The recognition of anemia of CKD begins with an estimation of glomerular filtration rate (GFR), which can be far lower than a normal serum creatinine might suggest, especially in the elderly and in those with poor nutrition and muscle mass. If GFR is <60 mL/min/1.73 m(2), hemoglobin should be checked. The anemia is diagnosed when the hemoglobin is <12 g/dL in a man or a postmenopausal woman, or <11 g/dL in a premenopausal woman. The cause of anemia should be investigated in these individuals; this can range from erythropoietin deficiency due to CKD, to deficiency of vitamin B(12) and/or folate, iron deficiency, blood loss, inflammation, malignancy, and aluminum intoxication. After other causes of anemia have been excluded, CKD is the most likely etiology, and it should be treated with an ESP. Currently, epoetin alfa and darbepoetin alfa are the only 2 ESPs approved for use in the United States. Extended dosing of ESP has potential advantages for the patient and may also improve resource utilization. Consequently, both agents have been tested for dosing at extended intervals. Adequate iron stores--defined as transferrin saturation >20% and ferritin >100 mg--as well as ESP administration are needed to produce an appropriate increase in hemoglobin. Poor response to treatment with ESP can be due to many factors, including presence of iron deficiency, inflammation, continued blood loss, and hemoglobinopathy.

Age Distribution↗
PubMed2005

Identification of individuals with CKD from Medicare claims data: a validation study.

BACKGROUND: Medicare claims data might provide an efficient source for outcomes research in patients with chronic kidney disease (CKD). However, in the absence of laboratory data, one would need to identify patients with CKD from diagnosis codes associated with health care claims. The validity of this approach to identify patients with CKD has not been sufficiently studied. METHODS: From chart abstraction, we obtained the first serum creatinine measurement of 1,852 elderly Medicare beneficiaries upon hospitalization for myocardial infarction and estimated each patient's glomerular filtration rate. We then searched all Medicare claims of the preceding year for the presence of a diagnosis code for diabetic nephropathy, hypertensive nephropathy, chronic renal insufficiency, acute renal failure, and miscellaneous other renal diseases. Using the gold standard of an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 (<1.00 mL/s/1.73 m2) for definition of CKD, we calculated the sensitivity, specificity, and positive and negative predictive values for each of these diagnoses and combinations of these diagnoses. RESULTS: The sensitivity of individual diagnosis algorithms ranged from 2.7% for diabetic nephropathy to 17.5% for miscellaneous. However, miscellaneous had a lower specificity (95.5%) than all other individual diagnosis algorithms (all > or =99%). Using combinations of these algorithms improved sensitivity up to 26.6%, but at the cost of lower specificity. Positive predictive values generally were high (85.7% to 97.5%), but negative predictive values were low (32.4% to 37.4%). CONCLUSION: High positive predictive values indicate that Medicare claims data can be used to accurately identify patients with CKD for study. However, the utility of such databases for comparison of patients with CKD versus lesser degrees of CKD is limited.

Aged↗
PubMed2006

CKD risk factors reported by primary care physicians: do guidelines make a difference?

BACKGROUND: End-stage renal disease is epidemic within the United States among certain high-risk groups. The National Kidney Disease Education Program examined the awareness of chronic kidney disease (CKD) risk factors among primary care physicians who treat high-risk populations, such as African Americans, persons with diabetes, persons with hypertension, and family members of dialysis patients. METHODS: We conducted a survey of 465 primary care physicians in 4 communities with high-risk populations. Respondents were asked to score 9 potential CKD risk factors on a 4-point scale graded from "Does not increase risk at all" to "Increases risk greatly." Potential risk factors included African-American race, diabetes, hypertension, and family history of CKD. RESULTS: Respondents saw a mean of 414 +/- 222 (SD) patients/mo. Primary care physicians were more likely to report that diabetes and hypertension were significant risk factors for CKD. Conversely, 34.4% did not consider family history of kidney disease to increase the risk for CKD, and 22% of respondents did not consider African-American race a CKD risk factor. CONCLUSION: Primary care physicians need targeted education to increase awareness of populations at high risk for CKD.

Baltimore↗
PubMed2006

Plasma reduced homocysteine and other aminothiol concentrations in patients with CKD.

BACKGROUND: Hyperhomocysteinemia, a risk factor for cardiovascular disease, is present in the majority of patients with chronic kidney disease (CKD). Several studies indicated that the moiety of homocysteine (Hcy) with an unbound -SH group (reduced Hcy [rHcy]) is the atherogenic molecule. This study is designed to examine the relation between different forms of Hcy and other aminothiols in hemodialysis (HD) patients, peritoneal dialysis (PD) patients, and nondialyzed patients with CKD. METHODS: rHcy, free Hcy (fHcy), and total Hcy (tHcy), as well as different forms of cysteine, cysteinyl-glycine, and glutathione, were studied by using a high-performance liquid chromatography technique in 19 HD patients, 12 PD patients, 47 patients with CKD, and 15 control subjects. RESULTS: In PD patients, tHcy levels were 2.8 times greater compared with controls, and in HD patients and those with CKD, 2.1 and 1.9 times greater, respectively. Mean rHcy/tHcy ratios were significantly greater in both HD (P < 0.05) and PD patients (P < 0.01), but did not differ in patients with CKD compared with controls. The decrease in rHcy levels during 1 HD treatment was smaller than that in tHcy and fHcy levels, and rHcy/tHcy ratio increased (before HD, 1.25% +/- 0.44%; after HD, 1.44% +/- 0.66%; P < 0.05). CONCLUSION: Levels of rHcy and other aminothiols are markedly increased in patients with impaired renal function. In dialysis patients, rHcy/tHcy ratio is markedly elevated and shows greater variability than in patients with CKD and controls. We conclude that because rHcy is believed to induce endothelial dysfunction and may be part of the accelerated atherogenic process in patients with CKD, plasma rHcy level could be a more relevant marker of cardiovascular disease risk than tHcy level.

Adult↗
PubMed2006

Silent cerebral white matter lesions and their relationship with vascular risk factors in middle-aged predialysis patients with CKD.

BACKGROUND: Silent cerebral white matter lesions are observed on magnetic resonance imaging (MRI) scans in elderly people, and they are related to vascular risk factors, particularly hypertension. No data on the prevalence and risk factors of white matter lesions in patients with chronic kidney disease (CKD) are available. The aim is to analyze the prevalence of white matter lesions and their determinants in this population. METHODS: We studied 52 patients without diabetes with CKD (stage 3 or 4) aged 30 to 60 years (average, 49 years) and a group of 32 normotensive control subjects. MRI studies were performed and subcortical and periventricular white matter lesions were evaluated by using semiquantitative measures. Patients were classified into 2 groups depending on the presence or absence of white matter lesions. Echocardiographic studies and measures of markers of systemic inflammation (C-reactive protein and interleukin 6) also were performed. RESULTS: White matter lesions were more prevalent in patients with CKD than controls (33% versus 6%; P = 0.008). Patients with CKD who had white matter lesions were older; had a greater history of cardiovascular disease and vascular nephropathy as a primary cause of renal disease and greater levels of systolic blood pressure, pulse pressure, left ventricular mass index, and C-reactive protein; and were administered more antihypertensive drugs than patients with CKD without white matter lesions. Stage and duration of CKD were not related to the presence of white matter lesions. After adjusting for several factors, only vascular nephropathy (odds ratio, 15.6; 95% confidence interval, 1.27 to 191.54; P = 0.03) independently predicted an increased risk for white matter lesions. CONCLUSION: One third of middle-aged patients with CKD have silent cerebral white matter lesions. Vascular nephropathy seems to be the most important factor related to the presence of these lesions, suggesting that white matter lesions reflect ischemic brain damage caused by generalized vascular damage.

Adult↗
PubMed2006

Insulin resistance, inflammation, and blood pressure determine vascular dysfunction in CKD.

BACKGROUND: Conventional cardiovascular risk equations underestimate the risk for cardiovascular disease (CVD) in patients with chronic kidney disease (CKD), implying a role for novel risk factors. Our aim was to compare vascular function and arterial compliance, known markers of CVD, between patients with CKD and healthy controls and examine their association with traditional and novel CVD risk factors. METHODS: Vascular function was determined by using high-resolution ultrasonography to measure brachial artery endothelial-dependent flow-mediated dilatation (FMD) and endothelial-independent glyceryl trinitrate (GTN)-mediated dilatation. Arterial compliance was measured by using pulse contour analysis to generate large-artery (C1) and small-artery (C2) compliance. We also examined the relationship between vascular function, arterial compliance and blood pressure, lipid and lipoprotein levels, insulin resistance, inflammation, oxidative stress, and calcium and phosphate levels in 105 patients with CKD and 40 healthy controls. RESULTS: Vascular function and arterial compliance were significantly impaired in patients with CKD compared with healthy controls: mean FMD, 3.8% +/- 0.3% (SE) versus 5.7% +/- 0.6%; GTN-mediated dilatation, 15.7% +/- 0.9% versus 19.6% +/- 1.0%; C1, geometric mean, 12.1 mL/mm Hg; 95% confidence interval (CI), 11.2 to 13.1 versus 15.1 mL/mm Hg; 95% CI, 13.7 to 16.5; and C2, 3.8 mL/mm Hg; 95% CI, 3.4 to 4.3 versus 5.0 mL/mm Hg; 95% CI, 4.2 to 6.0; all P < 0.05. Patients with CKD had greater waist-hip ratios, systolic blood pressures (SBPs), pulse pressures, triglyceride levels, oxidized low-density lipoprotein levels, high-sensitivity interleukin 6 levels, and Homeostasis Model Assessment (HOMA) scores (all P < 0.05) and lower high-density lipoprotein levels (P < 0.001). In patients with CKD, HOMA score and SBP were associated negatively with FMD (model R(2) = 0.28; P < 0.001), and SBP and waist-hip ratio were associated negatively with GTN-mediated dilatation (model R(2) = 0.25; P < 0.001). Pulse pressure was associated negatively with C1 (R(2) = 0.37; P < 0.001), and pulse pressure and high-sensitivity interleukin 6 level were associated negatively with C2 (model R(2) = 0.36; P < 0.001). CONCLUSION: Insulin resistance, inflammation, systolic hypertension, and increased pulse pressure, but not dyslipidemia, were associated with vascular dysfunction and may be targets for future interventional strategies to reduce CVD risk in patients with CKD.

Adolescent↗
PubMed2005

B-type natriuretic peptide (BNP) and amino-terminal proBNP in patients with CKD: relationship to renal function and left ventricular hypertrophy.

BACKGROUND: Most patients with chronic kidney disease (CKD) develop cardiovascular complications. Natriuretic peptides are novel markers that can be used to identify and monitor heart failure, but the effect of renal disease on these markers is not fully understood. The aim of the present study is to explore the relationship among circulating B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) concentrations and clinical variables in a cohort of patients with CKD. METHODS: Plasma BNP and NT-proBNP concentrations and left ventricular (LV) mass index were measured in 213 predialysis patients with CKD. RESULTS: Plasma BNP and NT-proBNP concentrations increased with declining estimated glomerular filtration rate (GFR; P < 0.0001). Estimated GFR had an independent effect on plasma BNP (P = 0.0028) and, to a greater extent, plasma NT-proBNP (P < 0.0001) concentrations: mean BNP concentration increased by 20.6% per 10-mL/min/1.73 m2 (0.17-mL/s) reduction in estimated GFR compared with 37.7% for NT-proBNP. NT-proBNP/BNP ratio increased with CKD stage (P < 0.0001). Median plasma BNP and NT-proBNP concentrations were greater in patients with LV hypertrophy (P < 0.0001), and LV mass index had an independent effect on both BNP (P = 0.0223) and NT-proBNP (P < 0.0017). CONCLUSION: Estimated GFR and LV mass index have independent effects on both plasma BNP and NT-proBNP concentrations in patients with CKD. NT-proBNP appears to be affected more by declining kidney function, in keeping with the hypothesis that its clearance is predominantly renal. Our data have significant implications for application of these peptides as cardiac biomarkers in patients with CKD.

Aged↗
PubMed2006

Identification and referral of patients with progressive CKD: a national study.

BACKGROUND: It is unclear whether primary care physicians (PCPs) and nephrologists differ in their recognition of progressive chronic kidney disease (CKD), agree on diagnostic and referral strategies, and identify similar barriers to caring for patients. METHODS: We conducted a national study of PCPs and nephrologists in the United States through a questionnaire describing a PCP caring for a patient with progressing CKD and questions to assess recognition of kidney dysfunction and approaches to diagnostic evaluation and referral. We identified participant and patient characteristics independently associated with CKD recognition and referral. RESULTS: We randomly identified a national sample of 304 physicians (126 nephrologists [39% response rate], 89 family physicians [28% response rate], and 89 general internists [28% response rate]). PCPs recognized CKD less (adjusted percentage, 59%; 95% confidence interval [CI], 47 to 69, family physicians; adjusted percentage, 78%; 95% CI, 67 to 86, general internists; adjusted percentage, 97%; 95% CI, 93 to 99, nephrologists; P < 0.01), differed from nephrologists in their recommendations for diagnostic testing, and recommended referral less (adjusted percentage, 76%; 95% CI, 65 to 84, family physicians; adjusted percentage, 81%; 95% CI, 70 to 89, general internists; adjusted percentage, 99%; 95% CI, 95 to 100, nephrologists; P < 0.01). PCPs differed from nephrologists in their expected intensity of specialists' involvement in care (16%, family physicians; 20%, general internists; 6%, nephrologists recommending nephrologist input monthly to every 6 months; P = 0.01). Lack of awareness of clinical practice guidelines and lack of clinical and administrative resources were identified as important barriers to care. CONCLUSION: PCPs recognize and recommend specialist care for progressive CKD less than nephrologists and differ in their clinical evaluations and expectations for referral. Improved dissemination of existing guidelines and targeted education in conjunction with efforts to build consensus among PCPs and nephrologists regarding their roles in the care of patients with CKD, including the collaborative development of clinical practice guidelines, could enhance patient care.

Chronic Disease↗
PubMed2006

Oxidative stress is progressively enhanced with advancing stages of CKD.

BACKGROUND: Oxidative stress appears to have a central role in the pathophysiological process of uremia and its complications, including cardiovascular disease. However, there is little evidence to suggest how early oxidative stress starts developing during the progression of chronic kidney disease (CKD). The aim of this study is to assess oxidative stress activity in a cross-sectional study of patients with CKD stages 1 to 4. METHODS: Eighty-seven steady patients (47 men, 40 women) with a median age of 62 years (range, 28 to 84 years) and mean estimated glomerular filtration rate (eGFR) of 57 mL/min (0.95 mL/s) were studied. Levels of plasma 8-isoprostanes (8-epiPGF2a) and serum total antioxidant status (TAS) were used as markers of oxidative stress. 8-epiPGF2a levels were determined by using an enzyme-linked immunosorbent assay method, whereas a chromatometric method was used to determine TAS. RESULTS: Plasma 8-epiPGF2a levels increased significantly as CKD stages advanced (P < 0.001). There was a highly significant inverse correlation between 8-epiPGF2a level and GFR (P < 0.01). Serum TAS levels also increased in a similar fashion (P < 0.009) and showed a significant inverse correlation with GFR (P < 0.01). 8-epiPGF2a and TAS levels showed a positive correlation (P < 0.05). Multiple regression analysis showed that the most significant predictor variable for 8-epiPGF2a level was eGFR, whereas the association between eGFR and TAS was affected strongly by confounding variables, mainly uric acid level. CONCLUSION: Oxidative stress appears to increase as CKD progresses and correlates significantly with level of renal function. Increased TAS seems to be dependent on several confounding variables, including increased uric acid levels, and therefore does not seem to be a reliable method for assessing the antioxidant capacity of patients with CKD. These results suggest that larger studies using the correct markers to assess the timing and complex interplay of oxidative stress and other risk factors during the progression of CKD should be carried out.

Adult↗
PubMed2005

General pharmacology of CKD-732, a new anticancer agent: effects on central nervous, cardiovascular, and respiratory system.

CKD-732 [6-O-(4-dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate] is a new fumagillin anticancer drug that belongs to an angiogenesis inhibitor. Its effect on the central nervous system (CNS), general behavior, cardiovascular-respiratory system and the other organ systems were studied. CKD-732 was intravenously administered with the dosages of 10, 30, 40 or 50 mg/kg and the highest dosage of 50 mg/kg prolonged the hexobarbital-induced sleep time. CKD-732 at the dosage of 50 mg/kg, also, caused the decrease of body temperature from 15 to 120 min after the administration, which was recovered at 240 min. In the study of the effects on gastric secretion, CKD-732 induced the increase of pH and decrease of total acidity. However, CKD-732 showed no effect on general behavior, spontaneous locomotor activity, motor coordination, analgesia, convulsion, mean arterial pressure, and cardiac functions except for heart rate of isolated rat heart, respiration, isolated smooth muscle, intestinal charcoal transport and renal function. Based on the results, we suggested that CKD-732 is safe general pharmacologically at clinical supposed dose (1.75 mg/kg) and demonstrated to have much better safety than other fumagillin derivatives.

Animals↗
PubMed2003

Connecting the dots: caring for the patient with progressive CKD.

The approach we take to CKD in the KDIPPP Clinic represents a complicated regimen. It's not something we can do by ourselves, and it requires an integrated team approach. The team approach includes many different individuals all working together (see Fig. 2, p. 25). If we are to be successful, the initiative must include collaboration from the primary care physicians (PCPs), providers, and patients. Patients need to be screened yearly for serum creatinine, blood glucose, and blood pressure if they are at risk for CKD. Creatinine should be expressed as a GFR. Examine the urine to see if it is abnormal and check for microalbuminuria. The PCP, the patient, and the nephrologist must team up to establish the balance of care (see Fig. 3, p. 26). As the CKD patient progresses from the presence of risk factors to CKD Stages 1, 2, 3, and finally 4 and 5, the input from the PCP and the nephrologist gradually changes, from nearly full-time PCP care in the early stages to nearly full-time nephrology team care in the later stages. When patients migrate through progression, prevention, education, access placement, and RRT, the degree of involvement and interaction must be individualized. I recommend follow-up every year or two for patients in CKD Stages 1 and 2; follow-up every six months for Stage 3, and increased nephrology input as CKD progresses. We need to work together to treat these patients. If we do, then we're going to end up with better patient outcomes and better lives. The KDIPPP Clinic has been successful at meeting these goals.

Disease Progression↗
PubMed2006

Regulation of parathyroid function in chronic kidney disease (CKD).

In chronic kidney disease (CKD), several abnormalities in bone and mineral metabolism develop in the majority of patients. The parathyroid plays a very important role in regulating bone and mineral metabolism; thus, control of parathyroid function is one of the main targets of the management of CKD-mineral and bone disorder (CKD-MBD). In the development of secondary hyperparathyroidism, it has recently been suggested that fibroblast growth factor 23 (FGF23) plays a crucial role, both as a phosphaturic factor and as a suppressor of active vitamin D (1,25D) production in the kidney. FGF23 is originally secreted to prevent hyperphosphatemia in CKD, but this occurs at the expense of low 1,25D and hyperparathyroidism ("trade-off" hypothesis revisited). Furthermore, recent data suggest that FGF23 could be another useful marker for the prognosis of hyperparathyroidism, because a high serum level may reflect the cumulative dose of vitamin D analogues previously administered. We have also demonstrated that severe hyperparathyroidism was associated with the production and secretion of a new form of parathyroid hormone (PTH) molecule, which can be detected by third-generation assays for PTH, but not by the second-generation assays. For the regression of already established nodular hyperplasia, the more advanced type of parathyroid hyperplasia, it is certainly necessary, in the near future, to develop new agents that specifically induce apoptosis in parathyroid cells. Until such agents are developed, prevention and early recognition of nodular hyperplasia is mandatory for the effective and safe management of hyperparathyroidism in CKD.

Animals↗
PubMed2006

Prevalence and predictors of cardiovascular calcium in chronic kidney disease (from the Prospective Longitudinal RRI-CKD Study).

Although the determinants of cardiovascular calcium have been well described in dialysis patients, the prevalence and predictors in predialysis chronic kidney disease (CKD) are less known. One hundred six patients with CKD from the Renal Research Institute-CKD Study underwent multidetector computed tomography for the assessment of calcium deposition at the level of coronary arteries, thoracic aorta, aortic valve, and mitral valve. Cardiovascular risk factors and renal function-related parameters (glomerular filtration rate, glomerular filtration rate slope, serum creatinine, serum urea nitrogen, hemoglobin, albumin, calcium, phosphate, and parathyroid hormone) were included in multivariate regression models to predict cardiovascular calcium. Prevalences of calcium deposition at the level of coronary arteries, thoracic aorta, aortic valve, and mitral valve were 69%, 46%, 39%, and 16%, respectively. On multivariate analysis, coronary artery calcium score was predicted by age (p < 0.0001), gender (p = 0.0001), diabetes (p = 0.024), and history of coronary artery disease (p = 0.016), but not by renal function related parameters. Similarly, renal function related parameters were not predictive of aortic or valvular calcium. In conclusion, predialysis CKD is associated with a high prevalence of cardiovascular calcium. The extent of cardiovascular calcium in patients with predialysis CKD is related to some of the traditional risk factors for atherosclerosis but not to indexes of abnormal renal function or progression in renal dysfunction.

Adult↗