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PubMed2002

Cardiovascular disease and the kidney. Tracking a killer in chronic kidney disease.

The interlinking of CVD with CKD is undeniable. CVD accounts for more than 50% of all morbidity and mortality in patients with kidney disease who have undergone renal replacement therapy, and CVD is also prevalent in patients with mild and moderately severe kidney disease. To help address the elevated risks of these patients, primary care physicians need to maintain vigilance in (1) identifying patients who have CKD and (2) implementing strategies for reducing the prevalence of CVD in this population. It is essential that patients be screened for relatively mild kidney disease by measurement of serum creatinine and urine microalbumin and by calculation of the glomerular filtration rate in mL/min/1.73 m2 using equations based on serum creatinine. Rigorous assessment of conventional risk factors, including dyslipidemia, hypertension, and diabetes, is also necessary to prevent the poor outcomes currently observed in persons with CKD. Routine use of ACE inhibitors and aspirin is encouraged in all patients with CKD, and strict glycemic and blood pressure control is recommended for optimal outcomes. In addition, patients should be screened and treated for risk factors particularly associated with kidney disease and CVD morbidity and mortality, including anemia, hyperphosphatemia, and hyperparathyroidism. Finally, physicians should be careful to avoid therapeutic nihilism in patients with kidney disease; those at highest risk of CVD are likely to receive the greatest benefit from cardiovascular therapies.

Cardiovascular Diseases↗
PubMed2004

Once-weekly epoetin alfa for treating the anemia of chronic kidney disease.

BACKGROUND AND AIM: Anemia occurs in approximately 47% of patients with chronic kidney disease (CKD) not on dialysis. Recombinant human erythropoietin (r-HuEPO, epoetin alfa) has been proven safe and effective for anemia treatment in patients with CKD using a three times-weekly regimen. The current study was conducted to evaluate the clinical safety and efficacy of a less frequent dosing regimen (once weekly) in this population. METHODS: This prospective, multicenter, open-label, non-randomized study enrolled 1,557 adult anemic (hemoglobin (Hb) < or = 10 g/dl) CKD patients not on dialysis. Epoetin alfa 10,000 U was administered subcutaneously once weekly for 16 weeks. Titration to 20,000 U once weekly at week 5 was permitted if patients had an increase in Hb < 1 g/dl. Safety and efficacy were assessed by changes in health-related quality of life (Linear Analog Scale Assessment (LASA) and Kidney Disease Questionnaire (KDQ)), changes in hematologic parameters and transfusion utilization, and incidence and severity of adverse events. RESULTS: 1,338 patients were evaluable for efficacy. Mean Hb level increased from 9.1 g/dl at baseline to 11.6 g/dl at study completion (last observed value after baseline) (p < 0.0001). Overall, 89.8% of patients responded to once-weekly dosing, exhibiting an increase in Hb level of > or = 1 g/dl from baseline. The percentage of patients that required transfusion decreased from 11.1% (baseline) to 3.7% (during the study) (p < 0.0001). All quality-of-life parameters improved significantly from baseline (p < 0.0001). Mean LASA scores for energy, activity and overall quality of life increased from baseline to study completion by 27.9 mm (70.5%), 24.5 mm (57.0%) and 22.6 mm (47.4%), respectively. All 5 KDQ domains showed statistically significant improvements (p < 0.0001). Hb change was a strong predictor for all 5 KDQ domains and the overall score (p < 0.0001). Treatment with once-weekly epoetin alfa was well tolerated, similar to that reported with three times-weekly dosing. CONCLUSION: Once-weekly epoetin alfa therapy is safe and effective for treating anemia in patients with CKD not on dialysis, and is associated with significant improvements in functional status and quality of life.

Aged↗
PubMed2005

Extended epoetin alfa dosing as maintenance treatment for the anemia of chronic kidney disease: the PROMPT study.

AIM: To determine whether extended epoetin alfa dosing schedules of up to once every four weeks are as effective as weekly dosing in maintaining hemoglobin (Hb) levels in patients with anemia of chronic kidney disease (CKD). METHODS: This randomized, open-label trial enrolled patients with anemia of CKD not on dialysis. Patients were required to have a stable Hb level (> or = 11.0 g/dl) and to have been previously receiving epoetin alfa for two or more months. Patients were randomized to one of four subcutaneously administered epoetin alfa dosing regimens: 10,000 units (U) once weekly (QW), 20,000 U every two weeks (Q2W), 30,000 U every three weeks (Q3W) or 40,000 U every four weeks (Q4W). Dose reductions, but not escalations, were permitted. Patients received treatment for a total of 16 weeks. The primary endpoint for the trial was the mean final Hb measurements of the QW, Q2W, Q3W, and Q4W groups. The primary efficacy analyses were non-inferiority assessments of the mean final Hb measurements of the Q2W, Q3W, and Q4W groups, compared with the QW group. The primary efficacy analyses were performed using a modified intent-to-treat (MITT) population, defined as all patients meeting all inclusion/exclusion criteria (or, if not satisfying all criteria, were granted an exemption at study entry), and who were randomized and received at least one dose of study medication. A per-protocol population, based on all patients who met the MITT criteria and completed the entire study, was used to evaluate the robustness of the MITT results. Quality of life was assessed for all dosing groups throughout the study. Safety was based on all patients randomized who received at least one dose of study medication. RESULTS: A total of 519 patients were enrolled; 445 were included in the MITT population. The four treatment groups were comparable with respect to baseline characteristics. The primary etiologies of CKD were diabetes (45.7%) and hypertension (29.9%). The mean baseline Hb, serum creatinine and glomerular filtration rate for all patients were 11.9 +/- 0.8 g/dl, 3.1 mg/dl, and 21.1 ml/min/1.73 m2, respectively. The mean baseline transferrin saturation was 25.2% and the mean ferritin was 201.9 ng/ml for all patients. All groups had a mean final Hb of > 11.0 g/dl. The mean final Hb levels of the Q2W and Q4W groups were statistically non-inferior to the QW group. The results of the per-protocol analysis were consistent with the MITT results. In addition, 93.5%, 89.5%, 77.2%, and 76.0% of patients maintained a mean Hb > or = 11.0 g/dl throughout the course of the study in the QW, Q2W, Q3W, and Q4W groups, respectively. Quality of life was maintained or improved from baseline to final within each dosing group. There were no significant differences in the mean final quality of life scores between the QW group and the Q2W, Q3W, and Q4W groups. Among the 513 patients evaluated for safety, epoetin alfa was well tolerated with no differences in adverse events between groups. The incidence of thrombotic adverse events was low (2.5% of patients), as was mortality (1.4% of patients). CONCLUSIONS: Approximately 90% of patients dosed once every two weeks and over 75% of patients dosed once every three or four weeks maintained mean Hb levels > or = 11.0 g/dl, consistent with the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. This study suggests that extended epoetin alfa dosing schedules are effective and safe for maintaining Hb, and may offer the possibility of increased flexibility and convenience for the majority of patients with the anemia of CKD.

Aged↗
PubMed2006

The impact of over-the-counter vitamin D supplements on vitamin D and parathyroid hormone levels in chronic kidney disease.

BACKGROUND: In addition to the known disturbances in mineral metabolism and vitamin D activation, the majority of patients with chronic kidney disease (CKD) do not have sufficient vitamin D stores. The impact of supplementation with low-dose, nonactive forms of vitamin D (calciferol) on parathyroid hormone (PTH) levels in this population is unknown, however. METHODS: A cross-sectional evaluation of vitamin D levels, intact parathyroid hormone (iPTH) and other laboratory results in 108 stage 3 and stage 4 CKD patients according to their intake of over-the-counter vitamin D. RESULTS: 37 patients took 400 IU of vitamin D daily with supplemental calcium and 71 did not. Compared to subjects who did not take it, patients who were on the supplement had higher 25(OH)D (31 +/- 15 vs. 17 +/- 9) ng/ml, higher 1,25(OH)D (21 +/- 12 vs. 16 +/- 9) pg/ml, lower iPTH (75 +/- 48 vs. 144 +/- 100) pg/ml and were more likely to meet K-DOQI PTH guidelines. However, these subjects were more likely to have oversuppressed iPTH values. The groups did not differ with regard to demographics, glomerular filtration rate and calcium and phosphorus levels. CONCLUSIONS: Vitamin D supplements may be a valuable tool in the prevention and treatment of hyperparathyroidism in patients with stages 3 and 4 CKD. CKD patients who have oversuppressed PTH need to be asked about their vitamin supplement intake.

Aged↗
PubMed2002

Overcoming barriers to the early detection and treatment of chronic kidney disease and improving outcomes for end-stage renal disease.

Chronic kidney disease (CKD) is a growing public health problem. Morbidity and mortality rates from CKD and end-stage renal disease remain high despite the advent of new knowledge, therapies, and clinical practice guidelines. Consequently, the reasons for the underdiagnosis and undertreatment of CKD must be addressed and appropriate preventive and therapeutic interventions implemented. Managed care organizations (MCOs) can facilitate this process by implementing intervention programs that target clinicians and patients with kidney disease. These programs should promote 1) early detection of CKD and comorbid conditions; 2) use of appropriate outcome measures to stratify patient care; 3) implementation of strategies to delay disease progression and prevent or treat complications; and 4) adequate preparation for and timely initiation of renal replacement therapy. Early detection and proactive care of predialysis patients not only improve outcomes and quality of life, but also reduce costs for society and MCOs.

Anemia↗
PubMed2003

Management of patients with chronic kidney disease at Kaiser Permanente.

In the Southern California Kaiser Permanente health plan, all patients having serum creatinine measured will automatically have their GFR reported. Those with reduced GFR are identified and classified into one of the five CKD stages. The PCPs are encouraged to be involved in the care of patients in CKD stages 1-3. Education, guidelines, and algorithms are provided to the PCPs, and nephrology consultation is encouraged. Patients in CKD stage 3 with significant risk factors for developing ESRD and those in CKD stages 4 and 5 are referred to nephrologists. Patients are encouraged to participate [table: see text] in their own care by attending the educational classes provided.

Health Maintenance Organizations↗
PubMed2004

[Hypertension, dyslipidemia and cardiovascular risk in chronic renal disease].

Cardiovascular disease is the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). The presence of CKD whether manifested by albuminuria or reduction in glomerular filtration rate is an independent risk factor for cardiovascular outcome. This is mainly due to both an overexpression of traditional cardiovascular risk factors, and the onset of new factors which are peculiar of CKD. In this revision the role of arterial hypertension and of dyslipidemia is analyzed in detail. Most interventional trials have demonstrated that a reduction of blood pressure and the normalization of lipid profile are associated with a significant reduction in the incidence of major cardiovascular events and mortality. According to the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) recommendations, patients with CKD, regardless of the stage of disease, should be considered the highest risk group for cardiovascular events. For these patients the NKF-K/DOQI guidelines recommend strict blood pressure control, renin-angiotensin system blockade, and the use of statins with target LDL cholesterol levels < 100 mg/dl.

Aged↗
PubMed2004

Troponin I and T levels in renal failure patients without acute coronary syndrome: a systematic review of the literature.

BACKGROUND: Debate surrounds the interpretation of troponin assays for the diagnosis and prognosis of cardiac disease in patients with renal failure. OBJECTIVES: To systematically review the diagnostic and prognostic test characteristics of quantitative serum cardiac troponin I (cTnI) and T (cTnT) in renal failure patients without acute coronary syndrome (ACS) symptoms. METHODS: English-language literature was identified through searching MEDLINE from 1966 to August 2003 and reviewing reference lists. Studies were excluded if they did not meet research objectives, had fewer than 10 patients or focused primarily on nonrenal patients. Of 119 potential studies, 39 articles with over 349 patients with chronic kidney disease (CKD) and 3899 hemodialysis patients were selected for abstraction. RESULTS: Among CKD and hemodialysis patients without ACS symptoms, cTnI had a mean specificity of 97% (95% CI 93% to 99%) and 96% (95% CI 94% to 98%), respectively, using the myocardial infarction cut-off threshold. The mean specificity of cTnT compared less favourably at 85% (95% CI 75% to 93%) and 71% (95% CI 64% to 77%) for CKD and hemodialysis patients, respectively. In hemodialysis patients without ACS symptoms, positive and negative likelihood ratios for all-cause mortality over 12 to 24 months for cTnT were 4.5 (95% CI 2.9 to 7.1) and 0.6 (95% CI 0.4 to 0.8), and for cTnI were 1.6 (95% CI 0.9 to 2.9) and 1.0 (95% CI 0.9 to 1.1), respectively. CONCLUSIONS: In CKD and hemodialysis patients without ACS symptoms, troponin I, at the myocardial infarction cut-off threshold, is unlikely to be falsely elevated. Among hemodialysis patients without ACS symptoms, a positive troponin T helps predict all-cause mortality.

Biomarkers↗
PubMed2004

[Vitamin D supplementation for chronic kidney disease according to the guideline issued by DOQI].

Supplementation of vitamin D in food is available in Japan, therefore, vitamin D deficiency is not likely to occur in our country. But, in the case of nephrotic syndrome and strict dietary protein restriction, low serum 25(OH)D level might develop in chronic kidney disease (CKD)patients. Guideline issued by National Kidney Foundation as DOQI recommend the use of vitamin D2 (ergocalciferol) when serum 25(OH)D level in CKD patients become less than 30 ng/mL. In addition, for the CKD patients with stage 5, the use of active vitamin D3 is recommended because a conversion to 1,25(OH)2D3, which is the most potent vitamin D, might be impossible in these patients. However, vitamin D2 product as a supplementary medicine is not available in Japan unfortunately. In this context, I try to explain the background of the recommendation of vitamin D2 for CKD patients.

Biomarkers↗
PubMed2004

Short-term effect of folic acid supplementation in renal transplant recipients and chronic kidney disease patients with comparable renal function impairment.

Recent evidence suggested that the efficacy of folic acid supplementation in reducing plasma total homocysteine (Hcy) concentration might be similar in renal transplant recipients (RTR) and chronic kidney disease (CKD) patients with a comparable degree of reduction of renal function. However, a direct comparison of the response to high dose folic acid supplementation between renal transplant recipients and CKD patients has never been made. Therefore, the goal of this study was to evaluate the response to folic acid (5 mg/day) supplementation in 15 stable renal transplant recipients with evidence of chronic allograft nephropathy, and in 15 CKD (stage 3) patients matched for age, sex and renal function living in the area of Skopje, Macedonia. After 12 weeks of folic acid supplementation, plasma total Hcy concentrations were significantly reduced in the two groups. Percent reduction of plasma total Hcy levels was nearly identical in the two groups (25.7% vs 24.5%, p = NS). These results confirm previous findings regarding the efficacy of folic acid therapy given separately to either renal transplant recipients or CKD patients, and extend them to a direct confirmation of identical efficacy.

Adult↗
PubMedDate not supplied

Blood pressure control and comorbidity in a nephrology clinic.

BACKGROUND: Many patients with established hypertension have poorly controlled blood pressure (BP). We studied demographic and clinical characteristics related to hypertension and analyzed the relationships between BP control and comorbidity. METHODS: This study was based on 414 consecutive hypertensive out-patients referred to our nephrology clinic. We recorded systolic and diastolic BP, age, gender, body mass index, total cholesterol, family history of hypertension, glomerular filtration rate (GFR), 24-hr proteinuria, diabetes, coronary artery disease, smoking habits and antihypertensive drug treatment. BP control was considered optimal if BP was < 130/80 mmHg in patients with diabetes or chronic kidney disease (CKD), if BP was < 125/75 mmHg in CKD with proteinuria > 1 g/24 hr and if BP was < 140/90 mmHg in patients with no comorbidity. Multivariate logistic regression analysis was used to investigate the association between BP control and predictors. RESULTS: Only 26.6% of patients had adequately controlled BP. Eighty-five percent of patients aged > 65 yrs had uncontrolled systolic hypertension. Univariate analysis showed a significant association between poor BP control and age >65 yrs, family history of hypertension, diabetes, CKD with or without proteinuria > 1 g/24 hr and total cholesterol > 220 mg/dL. Multivariate logistic regression showed that age > 65 yrs, diabetes and CKD with or without proteinuria > 1 g/24 hr were significantly and independently associated with poor BP control. CONCLUSIONS: Inadequate hypertension control is a common cause for referral to our out-patient nephrology clinic. Our data confirm that elderly patients, diabetic patients and nephropathic patients are difficult to treat; and therefore, deserve the highest quality clinical attention.

Aged↗
PubMed2005

Hyperlipidaemia in chronic kidney disease.

Cardiovascular disease is a major cause of mortality and morbidity in patients with chronic kidney disease (CKD). The prevalence of hyperlipidaemia or dyslipidaemias is much higher compared to the general population. Total or low-density lipoprotein (LDL) cholesterol is highest in patients with chronic renal impairment. The majority of patients with CKD do not develop renal failure; indeed, most of them die of cardiovascular causes before the development of renal failure. The K/DOQI (Kidney Disease Outcomes Quality Initiative) guidelines on dyslipidaemias in CKD suggest that all patients should therefore be evaluated for dyslipidaemias. They should have a complete fasting lipid profile with total, LDL and high-density lipoprotein cholesterol, and triglycerides measured to identify those at risk and those who require treatment. Generally, the treatment approach parallels that suggested by the National Cholesterol Education Program Adult Treatment Panel III guidelines, in which the main focus of treatment is the level of LDL cholesterol. Patients with CKD should be considered a "very high risk" category and aggressive therapeutic intervention initiated to reduce the risk of cardiovascular events.

Cholesterol, LDL↗
PubMed2005

The deadly triangle of anemia, renal insufficiency, and cardiovascular disease: implications for prognosis and treatment.

Recently there has been considerable interest in the associations between blood hemoglobin (Hb) level, renal function, and cardiovascular disease. Anemia is a common feature of end-stage renal disease, but it also accompanies lesser degrees of chronic kidney disease (CKD). The degree of anemia roughly approximates the severity of CKD. Anemia seen in diabetes has been linked to diabetic nephropathy; however, diabetes itself affects the hematologic system in several ways. Anemia is associated with left ventricular hypertrophy, cardiovascular morbidity, progressive loss of kidney function, and poor quality of life. Anemia seems to act as a mortality multiplier; that is, at every decrease in Hb below 12 g/dL, mortality increases in patients with CKD, cardiovascular disease, and those with both. Unlike blood transfusion, treatment of anemia with exogenous erythropoietin in patients with cardiorenal disease has shown promise in reducing morbidity and in improving survival and quality of life. Increasing the Hb level from less than 10 g/dL to 12 g/dL has resulted in favorable changes in left ventricular remodeling, improved ejection fraction, improved functional classification, and higher levels of peak oxygen consumption with exercise testing. Clinical trials are underway to test the role of erythropoietin in patients with CKD and in patients with heart failure.

Anemia↗
PubMed2005

Nutrition in children with kidney disease: pitfalls of popular assessment methods.

Children with chronic kidney disease (CKD) are considered at high risk for protein-energy malnutrition. Clinical practice guidelines generally recommend an evaluation of numerous nutritional parameters to give a complete and accurate picture of nutritional status. This review summarizes the potential limitations of commonly used methods of nutritional assessmentin the setting of CKD. Unrecognized fluid overload and inappropriate normalization of body composition measures are the most important factors leading to misinterpretation of the nutritional assessment in CKD. The importance of expressing body composition measures relative to height or height-age in a population in whom short stature and pubertal delay are highly prevalent is emphasized. The limitations of growth as a marker for nutritional status are also addressed. In addition, the prevailing belief that children with CKD are at high risk for malnutrition is challenged.

Adolescent↗
PubMed2005

Late onset renal failure from angiotensin blockade (LORFFAB): a prospective thirty-month Mayo Health System clinic experience.

BACKGROUND: Worsening azotemia following initiation of angiotensin blockade (AB), in patients with CKD, RAS with/without precipitating factors is recognized. Small increases in serum creatinine following initiation of AB occur and must not warrant drug discontinuation. We anecdotally had observed improvement in CKD in patients with normal renal arteries and no precipitating factors, following termination of AB. The worldwide ESRD epidemic, coincident with increasing use of AB, prompted us to hypothesize a late-onset azotemia in such CKD patients. MATERIAL/METHODS: Over 30 months, 103 patients with worsening azotemia, while on AB were evaluated. Ninety-seven patients with abnormal MRA and/or with precipitating factors were excluded. In the remaining five, AB was discontinued, and GFR monitored. RESULTS: One male, four females, mean age 66.2 years. Three diabetic/hypertensives, one SLE/hypertensive, one diabetic/kidney transplant recipient. Mean stable AB, 25.2 months, (6-66 months). Mean follow up, 11.8 months. One month following discontinuation of AB, GFR increased by a mean 45%. Mean serum creatinine decreased from 2.9+/-0.9 to 1.8+/-0.4 mg/dL (p=0.04). Uremic symptoms in 3, hyperkalemia in one, secondary hyperparathyroidism in one, resolved. Two with anemia, now require less erythropoietin. CONCLUSIONS: We called this unrecognized potentially reversible late-onset worsening azotemia, occurring several months to years on stable AB, in CKD patients with normal renal arteries, without precipitating factors, late-onset renal failure from angiotensin blockade (LORFFAB). Pathophysiologically, the concept of microvascular RAS is invoked. The extent of LORFFAB, with millions of patients worldwide on AB, remains conjectural and warrants further investigation.

Aged↗
PubMedDate not supplied

Management of hypertension in chronic kidney disease: the Italian multicentric study.

BACKGROUND: Guidelines have indicated the achievement of blood pressure target (BP <130/80 mmHg) as a priority in the conservative treatment of chronic kidney disease (CKD), but the current implementation of these recommendations in clinical practice is unknown. METHODS: We assessed control rates, treatment and clinical correlates of hypertension in 1201 adult non-dialyzed CKD patients followed up by a nephrologist for at least 6 months. RESULTS: Estimated glomerular filtration rate (GFR) was 32 (SD 15) mL/min/1.73 m2. BP target was not achieved in 88% of patients (95% confidence interval (95% CI): 86-90%). In 84% of patients, BP levels were also above the target at the first visit to the nephrology unit 4.5 yrs previously. The risk of not achieving BP target during the nephro-logy follow-up was associated with older age (odds ratio (OR): 1.24, 95% CI 1.06-1.45, p=0.008), diabetes (OR: 2.25, 95% CI 1.20-4.20, p=0.011), and the duration of hypertension (OR: 1.13, 95% CI 1.02-1.24, p=0.016). Among patients with uncontrolled BP, about 70% received multidrug antihypertensive therapy including renin-angiotensin system (RAS) inhibitors; conversely, diuretic treatment was prescribed in a minority of patients (37%), and at insufficient doses in half the cases, despite the insufficient implementation of a low salt diet (18%). CONCLUSIONS: BP target was not reached in most CKD patients routinely seen in the renal clinics. The main barrier to guideline implementation is possibly the inadequate treatment of extracellular volume expansion despite the large prevalence of factors, such as older age and diabetes, which further enhance the intrinsic BP salt sensitivity of CKD.

Aged↗
PubMed2005

Automated reporting of GFR--coming soon to a laboratory near you!

BACKGROUND: Serum creatinine concentration is an unreliable and insensitive marker of chronic kidney disease (CKD). To improve CKD detection, Australasian guidelines have recently recommended that laboratories calculate and report an estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula with every request for serum creatinine concentration. OBJECTIVE: This articles aims to provide timely information to health professionals about how to appropriately interpret and act upon eGFR reports. It also discusses the treatments shown to reduce renal and cardiovascular risk in CKD patients, and the indications for nephrologist referral. DISCUSSION: The accuracy and precision of eGFRs are reasonable in most adults in whom calculated values are ENTITY lt 60 mL/min/1.73 m2. However, eGFRs should be interpreted with caution in some settings (particularly patients with eGFRs ENTITY gt 60 mL/min/1.73 m2 and children). Automatic laboratory reporting of eGFR will enhance early detection of CKD, allow the timely institution of appropriate reno- and cardio-protective therapies, and better inform decisions regarding the prescription of renally excreted medications.

Adult↗