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At least 649 records · Page 36Linked to original sources
PubMed2005

Factors associated with lipoprotein(a) in chronic kidney disease.

BACKGROUND: It is unclear whether lipoprotein(a) (Lp[a]) levels in patients with chronic kidney disease (CKD) are elevated as a result of reduced glomerular filtration rate (GFR) or other factors associated with CKD. The goal of this study is to describe the association of Lp(a) level with GFR in the context of apoprotein(a) (apo[a]) isoform size, race, and other kidney disease-related factors, such as proteinuria, serum albumin level, C-reactive protein (CRP) level, and serum lipid levels. METHODS: Lp(a) and apo(a) isoforms were measured in serum samples obtained at baseline from 804 participants in the Modification of Diet in Renal Disease study (GFR range, 13 to 55 mL/min/1.73 m2). The cross-sectional association between Lp(a) level and GFR, apo(a) isoform size, race, and other variables was analyzed in univariate and multivariate linear regression. RESULTS: Median Lp(a) level was greater in blacks than whites (97.5 versus 28.1 nmol/L; P < 0.001). Those with a low-molecular-weight apo(a) isoform size had greater Lp(a) levels than those with a high-molecular-weight apo(a) isoform size (57.5 versus 21.3 nmol/L; P < 0.001). Lp(a) level was not associated with GFR. Low-molecular-weight apo(a), black race, and greater levels of proteinuria, CRP, and triglycerides were independently associated with greater Lp(a) levels. CONCLUSION: In this population with CKD stages 3 to 4, GFR was not associated with Lp(a) level, whereas other factors related to CKD, such as proteinuria, CRP level, and triglyceride level, as well as genetic factors such as apo(a) isoform size and race, were associated with Lp(a) level.

Adolescent↗
PubMed2003

Inflammation and nutrition in renal insufficiency.

Protein-energy malnutrition (PEM) and inflammation are common in patients with chronic kidney disease (CKD) and worsen as the CKD progresses toward the end-stage renal disease (ESRD). These conditions are major predictors of poor clinical outcome in kidney failure, as reflected by a strong association between hypoalbuminemia and cardiovascular disease (CVD). It has been suggested that inflammation is the cause of both PEM and CVD and, hence, the main link among these conditions, but these hypotheses are not well established. Increased release or activation of inflammatory cytokines, such as interleukin-6 or tumor necrosis factor alpha, may suppress appetite, cause muscle proteolysis and hypoalbuminemia, and may be involved in atherogenesis. Increasing serum levels of proinflammatory cytokines caused by reduced renal function, volume overload, oxidative or carbonyl stress, decreased levels of antioxidants, increased susceptibility to infection in uremia, and the presence of comorbid conditions may lead to inflammation in CKD patients. In hemodialysis patients, the exposure to dialysis tubing and dialysis membranes, poor quality of dialysis water, back-filtration or back-diffusion of contaminants, and foreign bodies in dialysis access maybe additional causes of inflammation. Similarly, episodes of overt or latent peritonitis, peritoneal dialysis (PD) catheter and its related infections, and constant exposure to PD solution may contribute to inflammation in these patients. The degree to which PEM in dialysis patients is caused by inflammation is not clear. Because both PEM and inflammation are strongly associated with each other and can change many nutritional measures and outcome concurrently in the same direction, the terms malnutrition-inflammation complex syndrome (MICS) and/or malnutrition-inflammation-atherosclerosis (MIA) have been suggested to denote the important contribution of both of these conditions to poor clinical outcome. Maintenance dialysis patients who are underweight or who have low serum levels of cholesterol, creatinine, or homocysteine may be suffering from the MICS/MIA and its subsequent poor outcome. Consequently, obesity and hypercholesterolemia may appear protective, which is known as reverse epidemiology. Although MICS/MIA may have a significant contribution in reversing the traditional CVD risk factors in dialysis patients, it is not clear whether PEM or inflammation and their complications can be effectively managed in CKD and ESRD or whether their management improves clinical outcome.

Humans↗
PubMed2004

Coronary revascularization in patients with coronary artery disease and chronic kidney disease.

There is a remarkable lack of randomized trial data on optimal management of coronary artery disease (CAD) in patients with chronic kidney disease (CKD). In fact, patients with CKD are often excluded from randomized trials that compare different treatment strategies for CAD. Because the most common cause of death in CKD patients is cardiovascular disease, it is crucial that studies are designed to determine the best therapy for CAD in this high-risk group. This article discusses the available data on coronary revascularization outcomes in CKD patients.

Chronic Disease↗
PubMed2005

Strategies for suppressing muscle atrophy in chronic kidney disease: mechanisms activating distinct proteolytic systems.

Loss of protein and lean body mass occurs commonly in patients with chronic kidney disease (CKD). CKD or conditions associated with CKD will stimulate muscle loss, but the cellular mechanisms by which these conditions cause muscle atrophy are largely undefined. In animal models of uremia and other catabolic conditions or in peritoneal dialysis patients, there is evidence that the ubiquitin-proteasome proteolytic system is activated to degrade actomyosin and myofibrillar proteins in muscle. Before the ubiquitin system can degrade muscle proteins, however, an initial cleavage of actomyosin and myofibrils must occur. Caspase-3 performs this initial cleavage of actomyosin and leaves a footprint of its activity, accumulation of a 14-kDa actin fragment in muscle. A critical step in stimulating the ubiquitin-proteasome system in muscle was recently discovered, the activation of a specific E3 ubiquitin-conjugating enzyme, atrogin-1. Both caspase-3 and the ubiquitin system, including atrogin-1, are activated when insulin signaling is impaired, and specifically when phosphatidylinositol 3 kinase activity is suppressed. Strategies that prevent a decrease in phosphatidylinositol 3 kinase activity or inhibit caspase-3 activity could lead to treatments that prevent muscle wasting in CKD patients.

Actomyosin↗
PubMed2006

Implications of chronic kidney disease for dietary treatment in cardiovascular disease.

Chronic kidney disease (CKD) often accompanies cardiovascular disease (CVD). Trends foretelling a greater burden of CKD and CVD are largely a result of increasing frequencies of obesity, hypertension, and diabetes. Nutritional therapy occupies a critical role in reducing risk factors and preventing progressive damage to the kidneys and heart. Nutritional assessment and treatment should take into account both health concerns. This review examines several diet components and eating styles for efficacy in the treatment of these conditions. A variety of dietary regimens claim to provide health benefits, but rigorous scientific validation of long-term efficacy is frequently lacking. An urgent need exists for eating styles that reduce risk of chronic diseases and that are acceptable and achievable in free-living populations. We describe our ongoing study, a randomized controlled trial comparing the American Heart Association Step II diet and a Mediterranean diet, in survivors of a first myocardial infarction. The primary end point is a composite of mortality and major CVD events. Because many in this population have CKD, indicators of kidney damage and function are prespecified secondary end points. Results of this trial should provide insight into optimal dietary interventions for persons with both CVD and CKD.

Cardiovascular Diseases↗
PubMed2007

Impact of kidney bone disease and its management on survival of patients on dialysis.

Despite the enormous cardiovascular disease epidemic and poor survival among individuals with chronic kidney disease (CKD), traditional risk factors such as hypercholesterolemia, hypertension, and obesity appear not as relevant as was previously thought, nor would their management improve survival in patients with CKD who are undergoing dialysis. On the contrary, kidney disease wasting (KDW) (also known as the malnutrition-inflammation complex), renal anemia, and kidney bone disease (KBD) appear to be the 3 most important nontraditional risk factors associated with cardiovascular disease in CKD. KBD-associated hyperparathyroidism may contribute to worsening refractory anemia and KDW/inflammation. The main cause of secondary hyperparathyroidism is active vitamin D deficiency. Hence, treatment of patients with KBD with vitamin D analogs, especially those with lesser effects on calcium and phosphorus such as paricalcitol, may be the most promising option for improving CKD outcomes. By conducting survival analyses in a 2-year (7/2001 to 6/2003) cohort of 58,058 patients on hemodialysis, we recently found that associations between high serum parathyroid hormone and increased death risk were masked by the demographic and clinical characteristics of patients, and that alkaline phosphatase had an incremental association with mortality. Administration of paricalcitol was associated with improved survival in time-varying models. We now present additional subgroup analyses that show that administration of any dose of paricalcitol, when compared with no paricalcitol, is associated with better likelihood of survival in virtually all subgroups of patients on hemodialysis. Because these associations may be secondary to bias by indication, randomized clinical trials are necessary to verify the findings of this and similar observational studies.

Chronic Kidney Disease-Mineral and Bone Disorder↗
PubMed2007

Indoxyl sulfate-lowering capacity of oral sorbents affects the prognosis of kidney function and oxidative stress in chronic kidney disease.

OBJECTIVES: Indoxyl sulfate shows nephrotoxicity and is a stimulating factor for progression of chronic kidney disease (CKD). This study was conducted to determine (1) whether the indoxyl sulfate-lowering capacity of oral sorbents (Kremezin [AST-120], Kureha Corporation, Tokyo, Japan; Merckmezin, Merck Hoei Ltd., Osaka, Japan) affects the prognosis of kidney function in CKD, and (2) whether oral sorbents reduce the markers of oxidative stress. METHODS: Rats with CKD were produced by 4/5 nephrectomy and were randomized into 3 groups: control rats, Merckmezin-treated rats, and Kremezin-treated rats. Kremezin and Merckmezin were administered to rats at a dose of 4 g/kg with powder chow for 16 weeks, whereas powder chow alone was administered to control rats. RESULTS: Administration of Kremezin significantly decreased serum and urine levels of indoxyl sulfate and serum creatinine and significantly increased creatinine clearance as compared with control values. The change in serum indoxyl sulfate noted from the initial to the final week showed a positive correlation with the change in serum creatinine and a negative correlation with the change in creatinine clearance. Kremezin significantly reduced urine levels of acrolein, a marker of oxidative stress, as compared with control levels. CONCLUSIONS: The indoxyl sulfate-lowering capacity of oral adsorbents affects the prognosis of kidney function in CKD. The more serum indoxyl sulfate is reduced, the better kidney function is preserved. Kremezin alleviates oxidative stress in the kidneys by reducing serum levels of indoxyl sulfate.

Acrolein↗
PubMed2002

Issues related to iron replacement in chronic kidney disease.

Recent epidemiologic studies show that iron deficiency occurs in the vast majority of patients with chronic kidney disease (CKD). In patients with CKD, increased iron losses and, to a lesser extent, poor oral absorption, can lead to iron-deficiency anemia. Correction of iron-deficiency anemia is preferable by the oral route, however, data on oral iron use are limited in this population. In CKD patients, parenteral iron administered with recombinant human erythropoietin (rHuEpo), is the best potential option for the correction of anemia. Nondextran iron preparations are preferable because of a reduced incidence of serious adverse events. Parenteral iron in CKD patients may not be entirely innocuous and, although commonly used, have not received Food and Drug Administration approval for use in this patient population. Exposure to intravenous (IV) iron may lead to oxidative stress, renal injury, infection, cardiovascular disease, and osteomalacia. Studies are needed to confirm the existence and magnitude of these complications. The current data suggest that the overall risk-benefit ratio favors use of IV iron when compared with untreated or partially treated iron-deficiency anemia.

Anemia, Iron-Deficiency↗
PubMed2005

Inflammation contributes to low plasma amino acid concentrations in patients with chronic kidney disease.

BACKGROUND: Inflammation and malnutrition are common in chronic kidney disease (CKD) patients, and plasma concentrations of free amino acids (AAs) in these patients are often abnormal. Malnutrition contributes to alterations in AA concentrations. OBJECTIVE: The objective was to study the effects of inflammation on plasma AA concentrations. DESIGN: Concentrations of plasma AAs, serum albumin, and several inflammatory markers were analyzed in 200 fasting, nondiabetic CKD patients who were close to the start of renal replacement therapy. The nutritional status of these patients was assessed by a subjective global assessment. RESULTS: The patients with inflammation [C-reactive protein (CRP) concentrations >10 mg/L] or malnutrition had lower AA concentrations than did the patients with no inflammation or malnutrition. The presence of both inflammation and malnutrition was associated with more marked reductions in AA concentrations than was malnutrition alone. Significant inverse correlations were observed between the plasma concentrations of most of the essential and nonessential AAs and inflammatory markers, whereas serum albumin concentrations were positively correlated with several AA concentrations. A stepwise multivariate regression analysis showed that serum CRP concentrations were independently associated with low concentrations of the sums of both nonessential AAs and all AAs. An analysis of all-cause mortality with a Kaplan-Meier test showed that the patients with higher AA concentrations had significantly better survival than did the patients with lower AA concentrations. CONCLUSIONS: Plasma AA concentrations are low in CKD patients with inflammation and are inversely correlated with concentrations of inflammatory markers. Although inflammation and malnutrition are closely related, CRP concentrations were independently associated with low concentrations of the sums of both nonessential AAs and all AAs, which suggests an independent role of inflammation as a cause of low plasma AA concentrations in CKD patients.

Adult↗
PubMed2004

Measuring nutritional status in children with chronic kidney disease.

Children with chronic kidney disease (CKD) are at risk of protein-energy malnutrition. Existing clinical practice guidelines recognize this and recommend specific methods to assess nutritional status in patients with CKD. This review summarizes the methods for nutritional assessment currently recommended in the United States for children with CKD and details the strengths and limitations of these techniques in the clinical setting. Dietary assessment, serum albumin, height, estimated dry weight, weight/height index, upper arm anthropometry, head circumference, and the protein equivalent of nitrogen appearance are reviewed. We also describe methods for body-composition assessment, such as dual-energy X-ray absorptiometry, bioelectrical impedance analysis (BIA), total body potassium, densitometry, and in vivo neutron activation analysis, pointing out some advantages and disadvantages of each. In CKD, fluid overload is the most important factor leading to misinterpretation of nutritional assessment measures. Abnormalities in the distribution of fat and lean tissue may also compromise the interpretation of some anthropometric measures. In addition, metabolic abnormalities may influence the results obtained by some techniques. Issues specific to evaluating nutritional status in the pediatric population are also discussed, including normalization of nutritional measures to body size and sexual maturity. We stress the importance of expressing body-composition measures relative to height in a population in whom short stature is highly prevalent.

Adolescent↗
PubMed2005

Inflammation is associated with increased energy expenditure in patients with chronic kidney disease.

BACKGROUND: Inflammation, a clinical condition observed in patients with chronic kidney disease (CKD), may be related to increased resting energy expenditure (REE). OBJECTIVES: The main objective was to investigate the relation between inflammation and REE in patients with CKD who are not undergoing dialysis. We also aimed to analyze whether a decrease in C-reactive protein (CRP) would result in a reduction in REE. DESIGN: This study enrolled 132 patients with CKD who were not undergoing dialysis, who had creatinine clearance from 5 to 65 mL.min(-1).1.73 m(-2), and who were 53.6 +/- 16 y old; 82 (62.1%) were men. Twenty-nine patients had clinical signs of infection. REE was measured by using indirect calorimetry, and inflammation was evaluated by using high-sensitivity CRP measurement. Patients were divided according to tertiles of CRP with the following intertertile ranges: first tertile, CRP < or = 0.14 mg/dL (n = 43); second tertile, CRP 0.15-0.59 mg/dL (n = 46); and third tertile, CRP > or = 0.60 mg/dL (n = 43). REE was measured before and after treatment in 10 patients who had inflammation or infection. RESULTS: After adjustment for age, sex, and lean body mass, the REE of the third (1395 kcal/d; P = 0.02) and second (1355 kcal/d; P = 0.04) tertiles was significantly higher than that of the first tertile (1286 kcal/d). In the multiple linear regression analysis (n = 132), the independent determinants of REE were lean body mass, CRP, and age (R2 = 0.55). After treatment of infection in a subgroup of 10 patients, it was observed that a significant reduction in CRP concentration was accompanied by a significant reduction of 174 +/- 165 kcal that accounted for 13% of the initial REE. CONCLUSION: This study showed that inflammation is associated with increased REE in patients with CKD.

Anthropometry↗
PubMed2002

The importance of early detection of chronic kidney disease.

Despite the absence of precise epidemiological data, we know there are a great many patients in the conservative phase of chronic kidney disease (CKD). The incidence and prevalence of renal replacement therapy (RRT) is increasing worldwide. As well as being a large and growing clinical problem, CKD is of an economic and organizational concern, since RRT consumes a considerable proportion of health care resources. In this context, any medical intervention that may prevent the progression of CKD towards end-stage renal disease (ESRD) is extremely important. Improving the patients' cardiovascular status is also a major objective in the management of this population, as cardiovascular disease (CVD) is the leading cause of morbidity and mortality for dialysis patients. Several interventions to delay the progressive loss of renal function and/or to prevent the development of CVD are now available. These include low-protein diets; correction of calcium-phosphate disorders and anaemia; blood pressure and proteinuria control; and smoking cessation. Other interventions, such as the administration of lipid-lowering agents, anti-inflammatory drugs, and anti-oxidant agents are emerging as particularly promising therapeutic approaches, although prospective, controlled, randomized clinical trials are needed to demonstrate their clinical usefulness. Intervention in the conservative phase of CKD is likely to be more effective if performed as early as possible in the course of the disease, since it has been widely demonstrated that early and regular nephrology specialist care is associated with decreased morbidity and mortality.

Anemia↗
PubMed2002

Non-erythropoietin-based anaemia management in chronic kidney disease.

Renal anaemia starts earlier in the progression of chronic kidney disease (CKD) than was previously thought and is often inadequately monitored and treated. Current treatment guidelines recommend giving recombinant erythropoietin (rHuEPO) as soon as haemoglobin (Hb) concentration falls below 11 g/dl and alternative causes of anaemia have been ruled out. Recent studies show that, in practice, few patients receive rHuEPO in the pre-dialysis period and Hb concentrations are often <9 g/dl at the start of haemodialysis. This is at odds with best practice since renal anaemia is a major risk factor for left ventricular hypertrophy. Many factors other than provision of rHuEPO therapy can affect the occurrence and severity of renal anaemia. Iron deficiency is the most common cause of resistance to rHuEPO and appropriate use of iron supplementation in patients with CKD is still being debated. The acute-phase immune response has a more significant role in renal anaemia and rHuEPO resistance than previously believed, as demonstrated by the need for higher rHuEPO doses in patients with raised levels of C-reactive protein. Women often need higher doses of rHuEPO than men, which may be related to differences in androgen levels between the sexes. Low erythropoietin concentrations are a major factor in diabetic nephropathy. Correction of anaemia with rHuEPO may slow progression of CKD by reducing oxidative stress. These and other factors need to be considered for the optimal treatment of patients with anaemia of CKD.

Anemia↗
PubMed2002

The relationship of haemoglobin level and survival: direct or indirect effects?

The relationship between haemoglobin (Hb) level and survival in patients with chronic kidney disease (CKD) is complex. This paper explores the physiological basis for the hypothesis that Hb level and survival are causally related in this patient group, and assesses the current state of knowledge from clinical studies. Issues related to the methodology and analysis of clinical studies limit the certainty with which conclusions regarding the direct relationship between Hb level and survival can be drawn. The data support the concepts that Hb level is associated with survival in patients both with and without CKD, that changes in Hb level are associated with cardiovascular disease (CVD), and that CVD is prevalent in patients with CKD. Hb level is affected by nutritional status, inflammation, and the availability and effectiveness of human recombinant erythropoietin (rHuEPO) therapy, as well as by the degree of kidney function. Thus, the complexity of the relationships between Hb level, CVD and survival in patients with CKD requires further study from both the mechanistic and the clinical perspective. Properly designed clinical trials with survival as an endpoint, as well as data from prospectively measured modifiers of Hb levels and other markers of CVD, are needed to determine the physiological and statistical interaction of these factors in clinical practice.

Apoptosis↗
PubMed2004

Could anti-inflammatory cytokine therapy improve poor treatment outcomes in dialysis patients?

Mortality in dialysis patients is greater than that in the general population across all age groups. The disparity in mortality is greatest among patients aged under 35 years. Chronic kidney disease (CKD) is associated with the malnutrition, inflammation and atherosclerosis (MIA) syndrome, which helps to explain the high mortality rates among patients with CKD. Paradoxically, CKD patients exhibit signs of immune suppression as well as immune system activation. Chronic inflammation and immune system activation are not only integral to the MIA syndrome, but also may underlie resistance to erythropoietin treatment in patients with anaemia. Chronic immune system activation is reflected by abnormally raised T-lymphocyte and monocyte expression of both pro- and anti-inflammatory cytokines. Patients who respond well to erythropoietin treatment exhibit fairly normal expression of these cytokines. Patients who persistently fail to respond, however, express abnormally raised levels of the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), which are also known to inhibit erythropoiesis. Paradoxically, these patients also express abnormally high levels of the anti-inflammatory cytokines interleukin (IL)-10 and IL-13. Although anti-inflammatory in nature, these cytokines might also affect erythropoiesis. One strategy to overcome the problem of chronic inflammation in anaemic patients with CKD may be treatment with the phosphodiesterase inhibitor, pentoxifylline. Preliminary results suggest that once-daily treatment with 400 mg of pentoxifylline orally not only can reduce T-cell expression of TNF-alpha and IFN-gamma, but can also restore the response to erythropoietin and improve haemoglobin levels. Ongoing studies will investigate further the use of pentoxifylline in erythropoietin resistance.

CD4-Positive T-Lymphocytes↗
PubMed2005

Extended epoetin alfa dosing in chronic kidney disease patients: a retrospective review.

BACKGROUND: The effectiveness of extended dosing of epoetin alfa beyond once-weekly (QW) has not been well explored in patients being treated for anaemia of chronic kidney disease (CKD). The current study was undertaken to assess the effectiveness of extended dosing in maintaining haemoglobin (Hb) levels in this population. METHODS: A retrospective chart review was conducted to assess the efficacy of extended epoetin alfa dosing in patients being treated for CKD-related anaemia. Eligible patients were to have received epoetin alfa once every 2 weeks (Q2W), 3 weeks (Q3W), 4 weeks (Q4W), or >Q4W administered subcutaneously for at least 3 months to maintain Hb > or = 11.0 g/dl. Patients were > or =18 years with serum creatinine 1.5 to 6.0 mg/dl for females and 2.0 to 6.0 mg/dl for males, and were not receiving renal replacement therapy. Epoetin alfa dose and dosing frequency were adjusted during treatment at the clinician's discretion. For analysis, patients were stratified into dosing groups based on their most dominant dosing regimen. RESULTS: 243 patients (mean age, 71.5 years; 79% white, 54% female) who received extended epoetin alfa dosing for a mean of 10.3 months were eligible for analysis. Mean baseline estimated glomerular filtration rate and mean serum creatinine were 21.2 ml/min/1.73 m(2) and 3.1 mg/dl, respectively. Primary causes of CKD included hypertension (36%) and diabetes (28%). Most patients (82%) receiving an extended epoetin alfa regimen maintained Hb > or =11.0 g/dl. The most common dosing regimen was Q2W (51%). Mean Hb for each dosing group was maintained between 11.6 g/dl and 12.4 g/dl during the study, and glomerular filtration rate remained stable. Epoetin alfa was well tolerated across all groups. CONCLUSIONS: Data from private community nephrology practices showed that extended epoetin alfa dosing effectively maintained Hb > or =11.0 g/dl in 82% of these selected patients being treated for anaemia of CKD.

Aged↗
PubMed2005

Effectiveness of a multidisciplinary kidney disease clinic in achieving treatment guideline targets.

BACKGROUND: We have demonstrated previously that at referral most chronic kidney disease (CKD) patients have suboptimal metabolic and hypertension control. Although several studies suggest that CKD clinics improve patient outcome, in fact there are minimal published data describing the actual effect of such clinics on these parameters. METHODS: We performed a historical prospective review of a cohort of 340 CKD patients referred to our multidsciplinary clinic in 1998 or 1999, with estimated creatinine clearance (CCr) <60 ml/min. Data regarding blood pressure (BP) control, metabolic/anaemia parameters, medications, access planning and dialysis starts were collected. RESULTS: The number of patients followed was 234, 144, 100 and 70 at years 1-4 of follow-up, respectively. Twenty-five percent of the patients were diabetic, and 25% were suspected to have ischaemic nephropathy; mean age was 67+/-15 years. Although phosphate control improved from referral, below a CCr of 30 ml/min, 27% of visits showed hyperphosphataemia. Thirty-one percent of patients with CCr <15 ml/min had haemoglobin <100 g/l at follow-up despite the availability of erythropoietin. BP improved from a mean of 151/80 mmHg at referral to 137/75 mmHg in subsequent visits. At follow-up visits, 62% of BPs were still >130 mmHg systolic or 85 mmHg diastolic. For proteinuric patients (>1 g/day), 75% of follow-up visits showed BP >125/75 mmHg, despite angiotensin-converting enzyme inhibitor use increasing from 35% at referral to 79% at follow-up. Twenty-four percent of patients started renal replacement therapy, initially haemodialysis (HD) in 57%, peritoneal dialysis (PD) in 35% and pre-emptive transplant in 8%. Thirty-eight percent of dialysis starts occurred within 6 months of referral, but PD was the modality in half of these. Only half of the HD patients started using an aterio-venous fistula, and of those using a central catheter 11 of 24 had been followed >6 months, but only four of them had attempted fistula creation. CONCLUSIONS: CKD clinic attendance was associated with improvements in metabolic and BP control, and was able to facilitate the use of PD even for late referrals. However, even the multidisciplinary model with nephrologists, nurse educators and dietitians was unable to achieve guideline-recommended metabolic, anaemia, BP and access targets for a significant number of patients.

Aged↗
PubMed2005

VEGF -460 genotype plays an important role in progression to chronic kidney disease stage 5.

BACKGROUND: Changes in renal vasculature, with vascular and interstitial fibrosis, are hallmarks of progression to chronic kidney disease (CKD) stage 5. Vascular endothelial growth factor (VEGF) is a potent angiogenic and vascular permeability factor. Transforming growth factor-beta1 (TGF-beta1) plays a critical role in promoting extracellular matrix (ECM) deposition and fibrosis. This study investigates whether genetic polymorphisms of VEGF or TGF-beta1 are associated with (i) progressive decline in renal function in patients with glomerular disorders (cohort 1) and (ii) predisposition to CKD stage 5 in a separate group of renal transplant recipients with various primary diseases (cohort 2). METHODS: Two patient groups were studied. Cohort 1 comprised 91 patients with biopsy-proven glomerular disease who were followed-up for 5 years before categorization as either non-progressors (with stable serum creatinine or < or =30% increase over 5 years, n = 39) or progressors (requiring dialysis, transplantation or whose serum creatinine increased by >30% over 5 years, n = 52). Cohort 2 comprised 107 patients with various primary renal diseases, who had reached CKD stage 5 and undergone renal transplantation at the time of study. All patients were genotyped for the VEGF polymorphisms at positions -460 (C/T) and +405 (G/C). Linkage disequilibrium (LD) was established using EHplus. SNPHAP was used to estimate haplotype frequency and to infer haplotypes to all patients. Cohort 1 patients were genotyped for the TGF-beta1 polymorphisms at positions -800, -509, codons 10 and 25. Genotyping was performed by polymerase chain reaction-restriction length polymorphism (PCR-RFLP). RESULTS: In cohort 1, there was a significant increase in frequency of the -460 VEGF CC genotype 30.8 vs 5.1%, P = 0.008; odds ratio (OR), CC vs TT 10.67, 95% confidence interval (CI), 1.94-58.72 and C allele 56.7 vs 37.2%, P = 0.009; OR 2.22, 95% CI, 1.21-4.04, in the progressor patients when compared with the non-progressors. In cohort 2, there was a significant increase in the VEGF -460 CC genotype when compared with healthy volunteers 37 vs 20.8%, P = 0.011; OR CC vs TT 1.59, 95% CI, 0.72-3.51. The -460 and +405 polymorphisms were in LD P < 0.00007. There were significant differences in diplotype (haplotype pair) frequencies in cohort 1 and 2, P = 0.018, which confirmed the importance of the -460C allele. There were no associations between the VEGF +405 or TGF-beta1 polymorphisms and progressive renal disease. CONCLUSION: In this study, we have demonstrated an association between the VEGF -460 polymorphism and progression to CKD stage 5. The function of this polymorphism remains unclear although previous evidence suggests that promoter constructs containing this single nucleotide polymorphism (SNP) have been associated with increased activity. Clearly there is a role for TGF-beta1 in chronic kidney disease. However, this study found no associations with four TGF-beta1 polymorphisms in this cohort.

Biopsy↗