CKD-602. Chong Kun Dang.
Chong Kun Dang is developing the camptothecin analog CKD-602 for the potential treatment of cancer. By August 2000, phase II trials of CKD-602 were underway.
Animals↗
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K/DOQI gets to the heart of managing dyslipidemias in patients with CKD.
There is a wealth of data in the general population regarding interventions to reduce cardiovascular risk. Unfortunately, most of these studies exclude patients with chronic kidney disease. As a result, the lack of CKD specific data has resulted in a lack of attention and intervention. With the epidemic levels of cardiovascular disease in patients on dialysis, the NKF has established these K/DOQI guidelines in an effort to get to the "heart" of dyslipidemias and ultimately to assist the health care team in their effort to improve CKD patient outcomes. In addition, the National Kidney Foundation currently has draft K/DOQI Clinical Practice Guidelines for Cardiovascular Disease in the public review process. These new guidelines will elaborate on areas not covered in the dyslipidemia guidelines.
Cardiovascular Diseases↗
Chronic kidney disease (CKD) special interest group (SIG) networking session.
The issue of reimbursement for NP is not an issue in the VA system, although it can be a barrier for the private sector. How to make this cost-effective was discussed during the networking session and will continue to be explored. The nephrology nurse is in a key position to participate in CKD clinics/programs. By virtue of his/her nursing expertise in assessment, incorporation of psychosocial factors, and patient education, the nurse can play a pivotal role in successful management of persons with CKD.
Colorado↗
Italian audit on therapy of hypertension in chronic kidney disease: the TABLE-CKD study.
A large body of evidence supports the validity of decreasing blood pressure to target levels in patients with essential hypertension to prevent cardiovascular disease. This issue becomes even more critical in chronic kidney disease because of the remarkably greater risk for cardiovascular fatal and nonfatal events. Indeed, renal patients should maintain blood pressure levels less than those suggested for the general population. Paradoxically, management of hypertension in this high-risk patient population is far from optimal and certainly worse with respect to essential hypertension. The Target Blood Pressure Levels in Chronic Kidney Disease (TABLE-CKD) study, performed in Italian patients with mild to advanced chronic kidney disease regularly followed-up by nephrologists, has shown that the prevalence of patients at target blood pressure is less than 20%. The assessment of antihypertensive strategy in these patients, however, suggests that there is room for improvement; in particular, a more aggressive treatment of volume expansion may ameliorate hypertension control in this population characterized by a high salt sensitivity of blood pressure.
Age Distribution↗
Subacute toxicity evaluation of a new camptothecin anticancer agent CKD-602 administered by intravenous injection to rats.
The subacute toxicity of a new camptothecin anticancer agent, CKD-602, was investigated after 4-week repeated intravenous administration of the chemical in Sprague-Dawley rats. The test chemical was administered intravenously to rats at dose levels of 0, 0.003, 0.013, or 0.067 mg/kg/day for males and 0, 0.004, 0.018, or 0.089 mg/kg/day for females. At the end of the treatment period, 10 rats/sex/group were sacrificed. The remaining 5 rats/sex in the vehicle control and high dose groups continued the study without treatment for 2 weeks (recovery period). During the test period, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were examined. In both sexes of the high dose group, an increase in the incidence of abnormal clinical signs and paleness of the eyes, a reduction in the body weight gain, food consumption and urine protein, and an increase in the water consumption were observed. Hematological investigations revealed a decrease in the red blood cells, hemoglobin and hematocrit and an increase in the mean corpuscular volume, mean corpuscular hemoglobin, platelets, and reticulocytes in a dose-dependent manner. Serum total cholesterol and total protein values were lower in females than those of controls, but not in males. An increase in the heart and liver weights and a decrease in the thymus weight were also found. Histopathological alterations included an increase in the incidence of atrophy of the sternal marrow, atrophy, fibrosis and mast cell hyperplasia of the femoral marrow, atrophy of the white pulp and extramedullary hematopoiesis of the spleen, atrophy of the thymus, auricular hypertrophy of the heart, extramedullary hematopoiesis and centriacinar telangiectasis of the liver, follicular degeneration of the ovary, and inflammation of the tail. The major treatment-related effects were not recovered at the end of 2-week recovery period. There were no adverse effects in the low and middle dose groups of both genders. In the present experimental conditions, the target organs were determined to be bone marrow, blood cells, spleen, liver, thymus, and heart. The no-observed-adverse-effect level was considered to be 0.013 mg/kg/day for males and 0.018 mg/kg/day for females.
Animals↗
The need for optimal and coordinated management of CKD.
The prevalence of impaired kidney function has been estimated to be between 10% and 20% of adult populations in most countries worldwide. Reduced kidney function has been recognized as a risk factor for poor outcomes, and thus requires attention. Key aspects of management of CKD have been defined for referred populations, but not necessarily for those unreferred. In order to improve patient outcomes, there is a need to take a more holistic approach to the problem, by coordinating the efforts of policy makers, those involved in health care system redesign, clinicians, and researchers. In so doing, there should be an improvement in both identification and management of patients with impaired kidney function, whether cared for by primary care physicians, specialists, or nephrologists, and irrespective of the health care system.
Chronic Disease↗
Modifiable risk factors for cardiovascular disease in CKD patients.
Risk factors for cardiovascular disease (CVD) have been studied extensively in CKD patients. It can be differentiated between modifiable, potentially-modifiable and non-modifiable risk factors. Nonetheless, even for easily modifiable risk factors there is still a lack of data demonstrating the benefit of common interventions, such as statin treatment for dyslipidemia, improvement of HbA1c levels in diabetic patients, implementation of physical exercise, normalization of Hgb and achievement of adequate dry weight in dialysis patients. This article gives an overview of modifiable and potentially modifiable risk factors and available modification strategies.
Cardiovascular Diseases↗
CKD patients and erythropoietin: do we need evidence-based informed consent?
BACKGROUND: Consent to therapy is increasingly requested in the form of ''informed consent''. OBJECTIVE: To validate an evidence-based informed consent form for erythropoietin (EPO) therapy and to evaluate patient opinions about the informed consent approach. METHODS: An evidence-based informed consent form was developed as part of the Evidence-Based-Medicine course at the Medical School of Turin, Italy. It was validated by anonymous questionnaires (0-10 analogical scales and open answers) administered to patients at different stages of CKD (19 pre-ESRD, 26 hemodialysis, 12 transplant patients) attending an outpatient unit of the University of Turin, to 8 nurses, and to 26 medical students. RESULTS: All individuals filled in the questionnaire. Interest in a detailed explanation of the therapy was high (median 9), as was comprehension (median 9), with no differences between patients with regard to disease stage (pre-ESRD vs. RRT) or educational level. Prior knowledge of the therapy was affected by the educational level (p=0.013 for the advantages and p=0.004 for the side effects) and the professional role (patients vs caregivers: p=0.009 for the advantages and p<0.001 for side affects); patient knowledge of the advantages (median 6) tended to increase as the disease progressed (p=0.015). The most common response by patients was that informed consent was necessary for all drugs (35.1%); 73.1% of the caregivers considered it necessary only for severe side effects. The preferred modality of consent was discussion with the caregiver during the clinical controls (42% of all cases). CONCLUSIONS: Patient interest in and comprehension of an informed consent form with a detailed explanation of the therapy was high; the caregiver's opinion was still the most valued teaching tool.
Adult↗
[Chronic kidney disease-mineral and bone disorder (CKD-MBD)].
Changes in mineral and bone metabolism are prevalent in chronic kidney disease. There are several types of renal bone disease, called 'renal osteodystrophy (ROD)'. ROD includes osteitis fibrosa, osteomalacia, adynamic bone disorder, and mixed osteodystrophy. Osteitis fibrosa is high turnover bone due to secondary hyperparathyroidism. Osteomalacia is low turnover bone concomitant of increased osteoid. Adynamic bone disorder is low turnover bone due to excessive suppression of the parathyroid glands and recently represents the major bone lesion in dialysis patients. More recently, the term 'Chronic Kidney Disease-Mineral and Bone Disorder(CKD-MBD)' was proposed to describe the clinical syndrome that develops as a systemic disorder of mineral and bone metabolism due to chronic kidney disease such as vascular calcification.
Calcium Metabolism Disorders↗
Clinic versus home blood pressure measurements in patients with CKD.
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Comment↗
Candidate risk factors for cardiovascular disease in CKD.
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Cardiovascular Diseases↗
Design of precision therapeutics for a CKD risk allele by targeting Shroom3-Rock interaction.
Enhancer variants in Shroom3 associate with renal fibrosis (TIF), but with reduced albuminuria. Detailed mechanisms for these pleiotropic effects are unclear. Here, we focus on identifying the specific profibrotic Shroom3 motif and separating this from its anti-proteinuric function. Given the role for Rho-kinases (Rock) in TIF, and the interaction of Rock with Shroom3 ASD2-domain, we hypothesized that Shroom3-mediated Rock-activation is crucial for profibrotic function. To test this, we develop transgenic tools that overexpress wild-type- (WT-Sh3) or ASD2-domain deletion- Shroom3 (ASD2Δ-Sh3). During TIF, Shroom3 and Rock co-expression occur in injured tubular cells and fibroblasts. In tubular- & fibroblast- lines, ASD2Δ-Sh3 overexpression reduce Rock activation, and pro-fibrotic/pro-inflammatory transcripts downstream of TGFβ1/Wnt/Ctnnb1-signaling vs WT-Sh3. In vivo, inducible global-, or tubular-specific-, but not fibroblast-specific-, ASD2Δ-Sh3 overexpression mitigate TIF, vs WT-Sh3 overexpression. Importantly, ASD2Δ-Sh3 mice do not develop albuminuria, while overexpression of a distinct Fyn-binding deficient mutant Shroom3 (FBDM-Sh3) induces albuminuria. We then develop small molecule inhibitors of Shroom3-Rock interaction (P2Is) and confirm Rock inhibition with these agents in WT-Sh3 cell lines. Our lead P2I from these studies, BT1137, mitigates Rock-activation, profibrotic signaling and TIF in WT-Sh3 mice. Hence, we delineate the profibrotic Shroom3 motif and develop therapeutics for kidney disease from Shroom3 excess.
Animals↗
Is i.v. iron really superior in CKD patients not on dialysis?
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Administration, Oral↗
Clinical pharmacists as multidisciplinary health care providers in the management of CKD: a joint opinion by the Nephrology and Ambulatory Care Practice and Research Networks of the American College of Clinical Pharmacy.
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Bone Diseases, Metabolic↗
Vitamin D deficiency in CKD: why should we care?
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Calcitriol↗
Administration of intravenous iron sucrose as a 2-minute push to CKD patients: a prospective evaluation of 2,297 injections.
BACKGROUND: Intravenous iron supplementation is an integral part of the management of anemia in patients with chronic kidney disease. Traditionally, this has been administered as an infusion over 1 or more hours, which requires the use of intravenous fluids and administration tubing, along with extra demands on patient and nursing time. METHODS: We prospectively investigated the safety and practicality of administering iron sucrose, 200 mg, as a bolus injection over 2 minutes in patients with chronic kidney disease. A total of 2,297 injections were administered to 657 patients. Any adverse events were recorded, including acute anaphylactoid reactions to the iron injection, along with the presence or absence of metallic taste and phlebitis, and these were classified as "serious" and "nonserious." RESULTS: The most common adverse event was a mild and transient metallic taste that occurred during 412 injections (17.9%); in no case was this of significant distress to the patient. Excluding this, 2,240 injections (97.5%) proceeded uneventfully, and no case of phlebitis was recorded. Adverse events other than metallic taste were recorded in association with 57 injections (2.5%). Seven of these were caused by an acute anaphylactoid reaction to the intravenous iron. All 7 acute reactions resolved completely within 30 minutes with no sequelae, and none required hospitalization. The remaining 50 adverse events consisted of pain during the injection (n = 31), pain after the injection with or without some bruising (n = 9), nausea/gastrointestinal symptoms (n = 3), lethargy (n = 4), and lightheadedness (n = 3). CONCLUSION: Administration of 200 mg of iron sucrose as an intravenous bolus injection over 2 minutes is a practical dosing regimen in patients with chronic kidney disease, resulting in considerable savings in time and cost.
Adult↗
Associations of metabolic syndrome with inflammation in CKD: results From the Third National Health and Nutrition Examination Survey (NHANES III).
BACKGROUND: Although metabolic syndrome is associated with inflammation in the general population, it is unknown whether similar associations exist in patients with chronic kidney disease. METHODS: +7 cross-sectional associations of metabolic syndrome and its component conditions (diabetes, hypertension, hypertriglyceridemia, abdominal obesity, and low high-density lipoprotein cholesterol level) with inflammation (C-reactive protein level > 3 mg/L) were examined by using logistic regression models in groups with high (>90 mL/min/1.73 m2 [>1.50 mL/s]), moderate (45 to 89 mL/min/1.73 m2 [0.75 to 1.49 mL/s]), and low (<45 mL/min/1.73 m2 [<0.75 mL/s]) creatinine clearances in 15,314 subjects participating in the Third National Health and Nutrition Examination Survey. RESULTS: Adjusted for demographics, smoking, history of myocardial infarction or stroke, exercise level, and use of cholesterol medications, the presence of metabolic syndrome was associated with greater odds for inflammation in the groups with high (odds ratio, 2.55; 95% confidence interval [CI], 1.99 to 3.27), moderate (odds ratio, 2.17; 95% CI, 1.81 to 2.60), and low (odds ratio, 1.87; 95% CI, 1.36 to 2.56) creatinine clearances. When all 5 components of metabolic syndrome were included in the same model, only hypertension, abdominal obesity, and low high-density lipoprotein level were associated significantly with inflammation in all 3 groups. There also was a graded association between number of component conditions of metabolic syndrome and inflammation within each creatinine-clearance group. CONCLUSION: Metabolic syndrome is associated with inflammation in patients with varying levels of kidney function. Future studies are warranted to determine in patients with chronic kidney disease whether there is a synergistic effect of metabolic syndrome and inflammation on the incidence of atherosclerotic events and whether interventions targeted toward metabolic syndrome might modulate inflammation.
Adult↗
Allocation of deceased donor kidneys for transplantation: opinions of patients with CKD.
BACKGROUND: Deceased donor kidney allocation schemes are designed to balance optimal utility with equity of access. The aim of this single-center survey is to seek patient opinion about the relative importance of factors used to determine the optimal transplant recipient in kidney allocation schemes. METHODS: In each of 8 scenarios, participants were invited to select which 1 of 2 hypothetical patients should receive a kidney. RESULTS: Two hundred thirty-two of 295 invited patients (78.6%) completed the questionnaire: 104 of 153 invited hemodialysis patients (68.0%) and 128 of 142 invited patients with functioning transplants (90.1%). Only 6.0% of participants agreed with current UK Transplant (UKT) and United Network for Organ Sharing (UNOS) allocation to a patient not yet on dialysis therapy who had been on the transplant waiting list longer than a patient already on dialysis therapy. Only 24.6% of participants agreed with the UKT and UNOS schemes that the transplant survival advantage associated with HLA matching warranted allocation of a kidney to a patient who had been waiting 2 years in preference to a patient waiting 7 years. Participants also were opposed to the use of recipient age and balance of exchange agreements (that reward centers with high rates of organ retrieval). The majority agreed with UKT and UNOS that recipient sex should not be used to allocate kidneys and allocation should favor recipients who have waited longer. CONCLUSION: Patients disagreed with several aspects of current allocation systems. Analysis of patient opinion should be taken into consideration when attempting to optimize the use of this scarce health resource.
Adolescent↗