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Effect of ergocalciferol supplementation on serum parathyroid hormone and serum 25-hydroxyvitamin D in chronic kidney disease.

AIM: To assess the impact of the administration of ergocalciferol on serum parathyroid hormone levels at different stages of chronic kidney disease (CKD). METHODS: A continuous series of 85 patients with stages 3-5 CKD but excluding patients on dialysis referred to the Kaiser Kidney Program were followed. Baseline serum intact parathyroid hormone (iPTH) and serum 25(OH)D levels were measured. All patients were administered ergocalciferol in doses ranging from 800 iu/day to 100,000 iu/week. We obtained serum levels of iPTH and 25(OH)D for a post-treatment endpoint after a median treatment period of 90 days. RESULTS: Pre- and post-treatment serum iPTH levels displayed a mean difference of 2.8 pmol/L (95% CI 1.3-4.4, P < 0.001). Patients with stage 4 CKD had a mean difference of 3.6 pmol/L (95% CI 1.7-5.5, P < 0.001) between pre- and post-iPTH levels. Serum iPTH levels decreased among CKD stages 3 and 5, but were not statistically significant. All CKD groups analysed in the present study had significant increases in serum 25(OH)D levels. None of the study population required cessation of vitamin D therapy and no adverse outcomes were reported. CONCLUSION: Ergocalciferol supplementation appears a safe and effective treatment for CKD populations which may raise levels of serum 25(OH)D levels and decrease iPTH levels.

Aged↗

Erythrocyte PAF-acetylhydrolase activity in various stages of chronic kidney disease: effect of long-term therapy with erythropoietin.

BACKGROUND: Erythrocytes represent an important component of the antioxidant capacity of blood, comprising, in particular, intracellular enzymes, including platelet-activating factor acetylhydrolase (PAF-AH) and glutathione peroxidase (Gpx). We evaluated the erythrocyte PAF-AH and Gpx activities in various stages of chronic kidney disease (CKD), and further investigated whether erythropoietin (EPO) administration in these patients has any influence on the enzyme activities. METHODS: Thirty-six patients (19 men and 17 women) with CKD (stages 1 to 5) participated in the study. Thirteen of them presented with CKD stage 1 to 2 (group I), whereas 23 patients presented with CKD stage 3 to 5 and randomized into two groups (i.e., groups II and III). Patients of group II (N= 11) were administered EPO subcutaneously, 50 units per kg once per week. In group III (N= 12), EPO was initiated only when the hemoglobin (Hb) levels decreased during follow-up to less than 9 g/dL. All patients were seen on an outpatient basis at 2 and 4 months. Fifteen normolipidemic age- and sex-matched healthy volunteers also participated in the study and were used as controls. The PAF-AH and Gpx activities were determined in isolated washed erythrocytes. RESULTS: The erythrocyte-associated PAF-AH and Gpx activities were higher in all CKD patient groups at baseline compared to controls, the groups II and III exhibiting significantly higher enzyme activities compared with group I. In all studied populations, both enzyme activities were negatively correlated with the creatinine clearance values. Importantly, the PAF-AH and Gpx activities were progressively decreased during the follow-up in patients not treated with EPO (group III), a phenomenon not observed in patients receiving EPO (group II), or in patients of group I. This reduction in enzyme activities was positively correlated with the decrease in the creatinine clearance values in patients of group III. CONCLUSION: Significant alterations in the erythrocyte-associated PAF-AH and Gpx activities related to the disease stage are observed in CKD patients. Administration of EPO prevented the reduction in enzyme activities observed during the progression of the renal insufficiency, thus preserving the erythrocyte defense mechanisms against oxidative stress.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism in stage 5 chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) alters the regulation of calcium and phosphate homeostasis, leading to secondary hyperparathyroidism, metabolic bone disease, soft tissue calcifications, and other metabolic derangements that have a significant impact on morbidity and mortality. The parathyroid gland is the central organ responsible for regulating these adaptive responses. Suppression of parathyroid hormone (PTH) secretion, hypertrophy, and hyperplasia are a major goal of treatment of CKD. METHODS: Current literature was reviewed and combined with the author's experience to address a number of issues regarding the optimal treatment of secondary hyperparathyroidism in hemodialysis patients. RESULTS: The calcium sensing receptor (CASR) is the most important factor regulating parathyroid gland function, and allosteric modulators of CASR, called calcimimetics, provide a novel drug therapy to suppress PTH secretion. The current use of active vitamin D analogues to suppress PTH is often limited by hypercalcemia and hyperphosphatemia. Clinical trials of cinacalcet HCl, the first calcimimetic to be approved for treatment of secondary hyperparathyroidism in CKD, have demonstrated suppression of circulating PTH levels without increments in the calcium-phosphorus (Ca x P) product, making it easier to achieve the stringent management guidelines proposed for subjects with CKD by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI). CONCLUSION: The management of disordered calcium and phosphate homeostasis in CKD patients is evolving based on our knowledge of the major importance of the calcium sensing receptor (CASR) in controlling parathyroid gland function and the potent actions of calcimimetics to target CASR. The purpose of this presentation is to provide an overview of the role of the CASR in regulation of parathyroid gland function, to examine the mechanisms whereby calcimimetics target the CASR, and to review the clinical trials that support the use of cinacalcet HCl for the treatment of secondary hyperparathyroidism in stage 5 chronic kidney disease (CKD).

Chronic Disease↗

Health-related quality of life and estimates of utility in chronic kidney disease.

BACKGROUND: Health-related quality of life and estimates of utility have been carefully evaluated in persons with end-stage renal disease. Fewer studies have examined these parameters in persons with chronic kidney disease (CKD). METHODS: To determine the relations among kidney function, health-related quality of life, and estimates of utility, we administered the Kidney Disease Quality of Life Short Form 36 (KDQOL-36), Health Utilities Index (HUI)-3, and Time Trade-off (TTO) questionnaires to 205 persons with CKD. Persons with CKD stages 4 and 5 (estimated GFR <30 mL/min/1.73 m2, N= 115) were tested two to eight times over the subsequent two years. The relations among estimated glomerular filtration rate (eGFR), and changes in health-related quality of life and utility over time were estimated using mixed effect regression models. Models were adjusted for age, sex, race, and diabetes. RESULTS: Mean scores on the KDQOL-36 generic components, HUI-3, and TTO suggested considerable loss of function and well-being in CKD relative to population norms. On cross-sectional analysis, lower levels of kidney function were associated with significantly lower scores on the SF-12 Physical Health Composite (P= 0.002), the Burden of Kidney Disease subscale (P < 0.0001), and the Effects of Kidney Disease subscale (P < 0.0001) of the KDQOL-36trade mark. Kidney function was significantly associated with the TTO (P= 0.008) and global HUI-3 utility (P= 0.016) although these associations were attenuated after adjustment for diabetes. A decline in eGFR was associated with a significant increase in the reported Burden of Kidney Disease (5.0 point change per year per mL/min/1.73 m2 decline in eGFR) and with marginally significant changes in the Dexterity and Pain attributes of the HUI-3. Mean HUI-3 scores for persons with CKD stages 4 and 5, absent dialysis, were in the range previously reported for persons with stroke and severe peripheral vascular disease. CONCLUSION: Health-related quality of life and estimates of utility are distressingly low in persons with CKD. Self-reported outcomes should be considered when evaluating health policy decisions that affect this population.

Adult↗

Prevention of chronic kidney and vascular disease: toward global health equity--the Bellagio 2004 Declaration.

Chronic kidney disease (CKD) not only reflects target organ injury in systemic vascular disease in the general population and in association with diabetes, hypertension, and smoking, but it is recognized as one of the major risk factors in the pathogenesis and outcome of cardiovascular disease. Recent surveys have revealed that the prevalence of CKD, particularly the hidden mild form (mildly elevated levels of serum creatinine or urinary albumin excretion), is surprisingly high in the general population. In recent years, the global epidemic of type 2 diabetes has led to an alarming increase in the number of patients with CKD. Most patients with CKD (over 50 million individuals worldwide) succumb to cardiovascular events, while each year over 1 million develop end-stage renal failure, which requires costly treatment and in many countries of the world, unaffordable renal replacement therapy by chronic dialysis or renal transplantation. Alarmed by the immense challenge to human morbidity and the economic burden of CKD and ensuing systemic cardiovascular disease, the International Society of Nephrology convened a multidisciplinary group of expert physicians and public health leaders from around the world to develop strategies to delay and avert this bleak future by effective prevention of CKD based on awareness, early detection, and effective treatment.

Cardiovascular Diseases↗

Prevention of chronic kidney disease: a global challenge.

In view of the increasing number of patients requiring renal replacement therapy (RRT) every year worldwide, attention has focused over the last two decades on meeting the health care need of patients with end-stage renal failure (ESRF). More recently, increasing awareness of the growing burden of chronic kidney disease (CKD), with a large percentage of the population affected by early stages of CKD, has shifted attention and health care priority to the prevention and early detection of CKD. This article addresses issues related to general population as well as targeted screening, favoring the latter. It also examines some of the screening initiatives undertaken in both the developing and developed worlds. It also highlights the links between albuminuria, CKD, and cardiovascular disease (CVD) as an increasing number of studies identify albuminuria/proteinuria, as well as CKD as major markers of CVD. Finally, a brief review is included of primary and secondary intervention strategies for CKD and issues related to their implementation: manpower and funding.

Albuminuria↗

Chronic kidney disease and its prevention in India.

Chronic kidney disease (CKD) is an important, chronic, noncommunicable disease epidemic that affects the world, including India. Because of the absence of a renal registry in India, the true magnitude of CKD/end-stage renal disease (ESRD) is unknown. Two community-based studies, although methodologically different, have shown a prevalence of chronic renal failure of 0.16% and 0.79%. The cost of maintenance hemodialysis for a single session varies between 10 US dollars to 40 between government-run and private hospitals. The average cost of erythropoetin is approximately 150 US dollars to 200 per month. The cost of chronic ambulatory peritoneal dialysis with "Y" set at 3 exchanges per week, which most patients in India do, is US 400 US dollars per month. The cost of a renal transplant (RT) procedure is approximately US 700 US dollars to 800 in the government sector and 6000 US dollars in the private sector. The cost of immunosuppression with basic triple immunosuppression drugs (cyclosporine, steroid, and azathioprin) is US 250 US dollars per month. There are hardly any state-funded medical treatment and medical insurance facilities for CKD and ESRD patients in India. India has nearly 700 nephrologists and approximately 400 dialysis units with 1000 dialysis stations, with the majority being in the private sector. A maximum of 2% of patients can be subjected to maintenance hemodialysis. Until now, approximately 3000 patients have been initiated on chronic ambulatory peritoneal dialysis. India has approximately 100 RT centers, mostly in private setup, and not more than 3000 to 4000 RTs are performed annually. Thus, only 3% to 5% of all patients with ESRD in India get some form of renal replacement therapy. Thus, planning for prevention of CKD on a long-term basis is the only practical solution for India. It appears that even in India, diabetes and hypertension are responsible for 40% to 50% of all cases of chronic renal failure. Screening for these 2 diseases and CKD is simple and easy to perform. The best approach will be to start screening for CKD in a high-risk group, like first-degree relatives of patients with diabetes, hypertension, and CKD, and simultaneously making a platform to run the program through the existing health care system of the country. The key issue of funding the program needs to be explored. Initial funding may come from international agencies like the World Health Organization, World Bank, and International Society of Nephrology, along with support from the country itself. Ultimately, funding has to be sustained from our own existing health care system.

Community Health Services↗

Epidemiology of chronic renal disease in the Galician population: results of the pilot Spanish EPIRCE study.

BACKGROUND: Chronic kidney disease (CKD) is a major social health problem because of the aging of the population, the high incidence of diabetes mellitus, and the epidemic of silent CKD resulting from inadequate diagnosis of early chronic renal insufficiency METHODS: The sociodemographic, baseline characteristics and CKD prevalence measured by the Modification of Diet in Renal Disease formula were studied in a randomly selected sample of people aged 20 years or older in the general population. We report the results of the analysis of the EPIRCE (Estudio Epidemiológico de la Insuficiencia Renal en España) pilot study performed in Galicia, Spain, in the last quarter of 2004. RESULTS: Baseline characteristics, sociodemographic characteristics, and results of a clinical examination and blood variables were collected from 237 patients who fulfilled the study's inclusion and exclusion criteria. The mean age of the sample was 49.58 years (95% confidence interval, 47.39-51.76). The prevalence of Kidney Disease Outcomes Quality Initiative grade 3 CKD was 5.1%, but the coexistence of an albumin/creatinine ratio>30 mg/g with grade 1 to 2 CKD raised the final rate to 12.7% in this population. We found a high prevalence of hypertension (31.5%), isolated systolic hypertension (20.1%), diabetes mellitus (8%), obesity (13.1%), smoking habit (22.7%), high atherogenic index (30.8%), and high alcohol intake (24%). Risk factors significantly associated with renal disease were age [P=0.018; odds ratio (OR) 2.7], hypertension (P=0.023; OR 2.13), pulse pressure (P=0.04; OR 0.10), diabetes mellitus (P=0.08; OR 4.48), obesity (P=0.000; OR 7.7), and insulin resistance index (P=0.04; OR 4.95). CONCLUSION: The prevalence of CKD and conventional cardiovascular risk factors is high in this randomly selected sample of the general population. Secondary preventive measures are needed to detect chronic kidney impairment as early as possible and to reduce the incidence and mortality arising from the associated comorbidities.

Adult↗

Anemia management and chronic renal failure progression.

Analysis of the biologic effects of erythropoietin and pathophysiology of chronic kidney diseases (CKD) suggests that treatment with erythropoiesis-stimulating agents (ESA) could slow the progression of CKD. By decreasing hypoxia and oxidative stress, it could prevent the development of interstitial fibrosis and the destruction of tubular cells. It could have direct protective effects on tubular cells through its antiapoptotic properties. It could help maintain the integrity of the interstitial capillary network through its effects on endothelial cells. Thus, suggesting that correcting anemia with ESA could slow the progression of CKD is biologically plausible. In patients with CKD, three small prospective studies and a retrospective study have suggested that treatment with ESA may have protective effects. Post-hoc analysis of the Reduction in Endpoints in Noninsulin-dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan study has also shown that anemia was an independent risk factor for progression of nephropathy in patients with type 2 diabetes. In addition, a large clinical trial, which had to be stopped prematurely because of labeling change for subcutaneous administration of epoetin alfa, suggests that complete normalization of hemoglobin levels is safe in CKD patients not on dialysis and without severe cardiovascular disease. Thus, it seems reasonable to advocate starting a large randomized, prospective study to determine if normalization of hemoglobin concentration can effectively slow the progression of CKD.

Anemia↗

Connections between vascular calcification and progression of chronic kidney disease: therapeutic alternatives.

We have shown that renal injury and chronic kidney disease (CKD) directly inhibit skeletal anabolism, and that stimulation of bone formation decreases the serum phosphate. Most recently, these observations were rediscovered in low-density lipoprotein receptor null mice fed high-fat/cholesterol diets, a model of the metabolic syndrome (hypertension, obesity, dyslipidemia, and insulin resistance). We had demonstrated that these mice have vascular calcification (VC) of both the intimal atherosclerotic type and medial type. We have shown that VC is worsened by CKD and ameliorated by bone morphogenetic protein -7 (BMP-7). The finding that high-fat-fed low-density lipoprotein receptor null animals without CKD have hyperphosphatemia led us to examine the skeletons of these mice. We found significant reductions in bone formation rates, associated with increased VC and superimposing CKD results in the adynamic bone disorder (ABD), while VC was worsened and hyperphosphatemia persisted. A pathological link between abnormal bone mineralization and VC through the serum phosphorus was demonstrated by the partial effectiveness of directly reducing the serum phosphate by a phosphate binder that had no skeletal action. BMP-7 treatment corrected the ABD and corrected hyperphosphatemia, compatible with BMP-7-driven stimulation of skeletal phosphate deposition reducing plasma phosphate and thereby removing a major stimulus to VC. Thus, in the metabolic syndrome with CKD, a reduction in bone-forming potential of osteogenic cells leads to ABD producing hyperphosphatemia and VC, processes ameliorated by the skeletal anabolic agent BMP-7, in part through increased bone formation and skeletal deposition of phosphate, and in part through direct actions on vascular smooth muscle cells. We have demonstrated that the processes leading to vascular calcification begin with even mild levels of renal injury before demonstrable hyperphosphatemia, and they are preventable and treatable. Therefore, early intervention in CKD is warranted and may affect mortality of the disease.

Animals↗

Management of advanced chronic kidney disease in primary care - current data from Germany.

The quality of chronic kidney disease (CKD) care and the control of CKD progression factors and of comorbid conditions according to current recommendations in primary care were investigated in this retrospective cohort study of 127 consecutive CKD patients. CKD was advanced (glomerular filtration rate 21 +/- 10 ml/min). Fifty-seven per cent of patients had been evaluated to clarify CKD aetiology. Blood pressure was substantially elevated (148 +/- 20/83 +/- 11 mmHg) and only 39% of patients achieved target blood pressure levels. At a mean HbA(1c) of 6.5 +/- 1.1%, glycaemic control was good in 63% of diabetics. Mean haemoglobin was 10.8 +/- 1.8 g/dl, and anaemia was adequately controlled in 49%. In 42% the management of bone disease and in 80% the nutritional status was sufficient. Angiotensin converting enzyme inhibitors or angiotensin-2-receptor blockers was used in 59% of patients with diabetic nephropathy or proteinuria above 1 g/day. High-total quality of care was only achieved in 35% which suggests that the management of advanced CKD in primary care is suboptimal.

Blood Pressure↗

Vitamin D insufficiency and deficiency in chronic kidney disease. A single center observational study.

BACKGROUND: Kidney disease has been identified as a risk factor for vitamin D deficiency in hospitalized patients, and low levels of 25-hydroxyvitamin D have been suggested to be a risk factor for hyperparathyroidism in patients with chronic kidney disease (CKD). However, little is known about the magnitude of vitamin D deficiency in patients with CKD living in the United States. METHODS: In this regard, we examined the levels of 25(OH)D in 43 patients with CKD and serum creatinine between 1 and 5 mg/dl (calculated glomerular filtration rate 111-11 ml/min per 1.73 m2) as well as in 103 patients undergoing hemodialysis. RESULTS: In the predialysis patients, we found that 37 of the 43 patients (86%) had suboptimal levels of vitamin D (<30 ng/ml). Regression analysis indicated that there was a negative correlation between 25(OH)D and intact parathyroid hormone (PTH). Alkaline phosphatase showed a similar but less sensitive relationship. Serum albumin levels correlated with 25(OH)D levels. In contrast to findings reported in normal individuals, the levels of calcitriol correlated with those of 25(OH)D in the patients with CKD. In the group undergoing maintenance hemodialyis, we found that 97% of the patients had vitamin D levels in the suboptimal range, and there was no correlation of 25(OH)D levels with either PTH or serum albumin values. These data indicate that vitamin D insufficiency and deficiency are highly prevalent in patients with CKD and may play a role in the development of hyperparathyroidism. The functional significance of low levels of 25(OH)D in patients with stage 5 CKD remains to be determined.

Female↗

Cardiovascular calcification in end stage renal disease.

Extensive atherosclerosis and heavy vascular and valvular calcifications are common complications of end stage chronic kidney disease (CKD-V) and are related to a high incidence of cardiovascular events. In CKD-V vascular calcifications occur both in the subintimal space and in the runica media. Intimal calcification is associated with atherosclerosis and is therefore a universal finding. On the contrary, medial calcification is characteristically associated with advanced CKD and diabetes mellitus. Numerous metabolic and endocrine abnormalities, primarily involving calcium and phosphorus metabolism, are found in CKD. Furthermore, CKD-V is believed to be a state of heightened inflammation and oxidative stress. All of these dysfunctions occur early in the course of the renal failure and likely contribute to the development and progression of vascular calcification and atherosclerosis. This review is centred on the pathobiology of vascular calcification in CKD-V, its detection with modern imaging modalities and the therapeutic approaches currently available to slow its progression.

Calcinosis↗

Arterial compliance in elderly men with chronic kidney disease.

BACKGROUND/AIM: Chronic kidney disease (CKD) is associated with decreased arterial compliance (AC). The stage of development of impaired arterial function in CKD in relation to loss of glomerular filtration rate (GFR) is not known. This study's aim was to evaluate the relationship between GFR and AC in patients with CKD. METHODS: We recruited 91 men aged > or =60 years with GFR 15-89 ml/min (mean 47 +/- 21) to evaluate the relationship between GFR and AC in a cross-sectional study. We measured AC at the brachial artery with an oscillometric device (brachial artery distensibility; BAD). RESULTS: There was no correlation between GFR and BAD (r = 0.08, p = 0.44). When stratified according to CKD stages, all groups showed decreased BAD compared with reference values, and there were no differences among them (one-way ANOVA). Bivariate analyses showed statistically significant correlations between BAD and age (r = -0.23, p = 0.03), antihypertensive drug number (r = 0.27, p = 0.009) and serum hemoglobin (r = 0.24, p = 0.02), but only age and antihypertensive drug number remained significant markers of BAD in a multiple regression model. CONCLUSION: Older men with CKD have impaired arterial function, but GFR and CKD stage have no relationship to the degree of decrease in brachial artery distensibility.

Aging↗

Imbalance between detached circulating endothelial cells and endothelial progenitor cells in chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) display endothelial dysfunction and are at a high risk for atherosclerotic cardiovascular disease (CVD). Recent studies suggest that circulating detached endothelial cells (CECs) and stimulated endothelial progenitor cells (EPCs) from the bone marrow may reflect endothelial damage. METHODS: We correlated the levels of CECs expressing the endothelial cell inflammation marker (MICA+ cells) and EPCs (Tie-2+ or VEGFR-2+ cells) in a population of 19 (55 +/- 3 years; 42% males) patients with advanced CKD (median glomerular filtration rate 8 ml/min). In addition, the levels of CD-31+ cells were investigated. Twenty healthy age- (49 +/- 2 years) and gender- (50% men) matched subjects served as controls. RESULTS: CECs expressing MICA were increased (7.6 +/- 2.7 vs. 1.6 +/- 0.3%; p < 0.05) in CKD patients, however EPCs expressing Tie-2 or VEGFR-2 were significantly decreased (0.16 +/- 0.07 vs. 0.53 +/- 0.15%; p < 0.05, and 0.42 +/- 0.10 vs. 2.80 +/- 0.72%; p < 0.01, respectively) as compared to controls. Furthermore, we also found that the levels of CD-31+ cells were significantly elevated (22.8 +/- 4.2 vs. 9.4 +/- 0.8%; p < 0.01) in CKD patients. Patients on angiotensin-converting enzyme (ACE) inhibitors tended (p = 0.06) to have higher levels of VEGFR-2+ cells (0.57 +/- 0.14 vs. 0.16 +/- 0.11%). CONCLUSION: Our results suggest that there is a marked imbalance between the CEC and EPC numbers in patients with CKD. Further research is needed to evaluate the independent role of inflammatory endothelial markers as well as the effects of ACE inhibitors on mobilization of EPCs in patients with advanced CKD.

Cell Count↗

Body mass index and the risk of chronic renal failure: the Asian experience.

BACKGROUND: There is a worldwide obesity epidemic, and the number of patients requiring dialysis because of obesity-related renal disease such as diabetes mellitus and hypertension is increasing. Obesity increases the risk of cardiovascular disease and premature death due to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Although the effect of obesity might differ among races, obesity has a significant impact on CKD and ESRD. METHODS: We examined the relationship between obesity (i.e., body mass index [BMI]) and CKD or ESRD using a community based screening registry in Okinawa, Japan. For this purpose, we used a general screening registry (1983, 1993, and 2003), the ESRD patient registry (1971-2000), a hospital-based cardiovascular disease registry (1988-1990), and a hospital-based screening registry (2003). RESULTS: The prevalence of obesity, based on a BMI>or=30 kg/m2, was 3.5% (1983), 4.7% (1993), and 6.2% (2003) in the general adult population. The incidence of ESRD increased when BMI increased, particularly in men. In the hospital-based screening study, the number of components of metabolic syndrome was significantly related with the prevalence of CKD. The relationship was linear when the modified National Cholesterol Education Program criteria were used to define abdominal obesity as a waist circumference of 85 cm or more in men and 90 cm or more in women. CONCLUSION: Although prospective studies are needed, our findings indicate that obesity, including metabolic syndrome, is a potential treatable cause of CKD and ESRD. Rigorous efforts should be made to optimize weight to reduce the risk of CKD and ESRD by a judicious combination of diet, exercise, and psychologic therapies.

Adult↗

Secondary hyperparathyroidism in chronic kidney disease: focus on clinical consequences and vitamin D therapies.

OBJECTIVE: To assess vitamin D-based treatment approaches for secondary hyperparathyroidism and its complications. DATA SOURCES: A literature search was performed using MEDLINE (1990-February 28, 2006). Key words used were chronic kidney disease and vitamin D to identify relevant papers published in English. STUDY SELECTION AND DATA EXTRACTION: From the database of articles generated, 48 papers were identified. Titles and abstracts were examined to identify those directly related to the objective. Discussion was expanded through the bibliographies of cited articles. DATA SYNTHESIS: The increasing prevalence of chronic kidney disease (CKD) in the US indicates an urgent need for treatment strategies to delay or prevent disease progression. Abnormalities in phosphorus and calcium homeostasis, vitamin D levels, and the subsequent development of secondary hyperparathyroidism (SHPT) are secondary complications of CKD associated with increased morbidity and mortality. Management options include dietary phosphorus restriction, phosphate binders and/or calcium supplementation, vitamin D supplementation, and calcimimetics. Vitamin D supplementation has received increased attention given the prevalence of vitamin D deficiency in patients with CKD and the beneficial effect of correcting this deficiency. CONCLUSIONS: Early identification and intervention appropriate to the stage of CKD are likely to improve patient outcomes. Improved knowledge of interactions between vitamin D and vitamin D receptors has led to the development of vitamin D analogs and calcimimetics, which offer benefits in the management of SHPT. Integrating available treatment options into practice to achieve optimal therapeutic goals of SHPT based on the stage of CKD is a significant challenge for pharmacists managing patients with CKD.

Humans↗

Measures of renal function, BMD, bone loss, and osteoporotic fracture in older adults: the Rancho Bernardo study.

UNLABELLED: The association between bone and renal function in healthy seniors is not well studied. In this cross-sectional and longitudinal study in 1713 older men and women, creatinine clearance was significantly associated with hip BMD. If confirmed, this may warrant adding mild to moderate renal dysfunction as an indication for osteoporosis screening. INTRODUCTION: This study determined the cross-sectional and longitudinal association between measures of renal function and BMD, bone loss, and osteoporotic fracture in older adults. It determined which measure of renal function--creatinine clearance by the Cockcroft-Gault (CG) equation, estimated glomerular filtration rate by the Modification of Diet in Renal Disease (MDRD) equation, or serum creatinine--is most strongly associated with BMD and osteoporotic fracture. MATERIALS AND METHODS: This was a cross-sectional and prospective study in older community-dwelling men and women. Between 1992 and 1995, 1713 participants (average age, 71.3 +/- 11.1 years) completed standardized questionnaires, physical examinations, laboratory testing, and bone densitometry; 1023 participants returned for a follow-up visit in 1997-1999, an average of 4.1 +/- 0.9 years later. RESULTS: Calculated renal function declined with age (p < 0.001). Renal function was categorized by Kidney Disease Outcomes Quality Initiative (K/DOQI) chronic kidney disease (CKD) stage. By the CG equation, at baseline, 5.5% of participants had stage 1 CKD (glomerular filtration rate > or = 90 ml/min/1.73 m(2)), 43.0% had stage 2 CKD (60-89 ml/min/1.73 m(2)), 48.8% had stage 3 CKD (30-59 ml/min/1.73 m(2)), and 2.7% had stages 4 and 5 CKD (<30 ml/min/1.73 m(2)). Using the MDRD equation, these percents were 7.0%, 61.7%, 30.9%, and 0.5%, respectively. In cross-sectional analyses, there was a significant linear association between creatinine clearance by CG or glomerular filtration rate by MDRD and hip BMD. In prospective analyses, there was an average annual bone loss of 0.6% and a significant association between baseline CG and 4-year hip bone loss. There was no association between baseline MDRD or serum creatinine and bone loss. At baseline, 180 of 1713 participants (11%) reported at least one clinical fracture of the hip, femur, forearm, or wrist; 79 (8%) reported new clinical fractures during follow-up. Baseline renal function by any measure was not significantly associated with prevalent or incident clinical fractures. CONCLUSIONS: Although renal function measured by both CG and MDRD was associated with BMD in cross-sectional analyses, only creatinine clearance by CG predicted 4-year bone loss. If confirmed, this should be the preferred method for assessing the association between renal function and BMD. Cross-sectional associations between renal function and BMD were strongest at higher CKD stage. None of the baseline renal function estimates was associated with prevalent or incident fractures, perhaps reflecting the multifactorial etiology of fractures beyond BMD. If further studies in the elderly confirm renal function as an important predictor of bone loss and fracture, this may warrant adding mild to moderate renal dysfunction as an indication for osteoporosis screening.

Absorptiometry, Photon↗