3536 articles - 08.09.10
1: Nephrol Dial Transplant. 2010 Sep 3; [Epub ahead of print]
Stoycheff N, Pandya K, Okparavero A, Schiff A, Levey AS, Greene T, Stevens LA.
1Tufts Medical Center, Boston, USA.
BACKGROUND: Proteinuria is a candidate surrogate end point for randomized controlled trials (RCTs) in chronic kidney disease (CKD). There is a reasonably sound biological basis for this hypothesis, but only preliminary empirical evidence currently exists. METHODS: A systematic review and creation of a patient-level dataset of randomized controlled trials (RCTs) in CKD that reported changes in proteinuria and assessed progression of kidney disease as defined by dialysis, transplantation, death, or changes in GFR or creatinine were performed. RESULTS: Systematic review. Seventy RCTs met the eligibility criteria; 17 eligible RCTs contained analyses of proteinuria as a predictor of outcomes; 15 RCTs concluded that greater proteinuria was associated with adverse outcomes. A majority were studies of diabetic or hypertensive kidney disease and tested renin-angiotensin system blockade. Definitions of predictor and outcome variables were too variable to conduct a meta-analysis of group data. Database creation. Over 4 years was required to create the patient-level dataset. The final dataset included 34 studies and > 9000 patients with a variety of CKD types and interventions. CONCLUSIONS: There are a relatively small number of RCTs designed to rigorously test therapies for kidney disease progression. Current analyses of change in proteinuria as a predictor of CKD progression are heterogeneous and incomplete, indicating further evaluation in a pooled individual patient-level database is necessary to advance knowledge in this field.
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PMID: 20817671 [PubMed - as supplied by publisher]2: Kidney Int. 2010 Sep 1; [Epub ahead of print]
Borzych D, Rees L, Ha IS, Chua A, Valles PG, Lipka M, Zambrano P, Ahlenstiel T, Bakkaloglu SA, Spizzirri AP, Lopez L, Ozaltin F, Printza N, Hari P, Klaus G, Bak M, Vogel A, Ariceta G, Yap HK, Warady BA, Schaefer F.
[1] Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany [2] Department of Pediatric Nephrology, Medical University of Gdansk, Gdansk, Poland.
The mineral and bone disorder of chronic kidney disease remains a challenging complication in pediatric end-stage renal disease. Here, we assessed symptoms, risk factors and management of this disorder in 890 children and adolescents from 24 countries reported to the International Pediatric Peritoneal Dialysis Network Registry. Signs of this disease were most common in North American patients. The prevalence of hyperphosphatemia increased with age from 6% in young infants to 81% in adolescents. Serum parathyroid hormone (PTH) was outside the guideline targets in the majority of patients and associated with low calcium, high phosphorus, acidosis, dialysis vintage and female gender. Serum calcium was associated with dialytic calcium exposure, serum phosphorus with low residual renal function and pubertal status. PTH levels were highest in Latin America and lowest in Europe. Vitamin D and its active analogs were most frequently administered in Europe; calcium-free phosphate binders and cinacalcet in North America. Clinical and radiological symptoms markedly increased when PTH exceeded 300 pg/ml, the risk of hypercalcemia increased with levels below 100 pg/ml, and time-averaged PTH concentrations above 500 pg/ml were associated with impaired longitudinal growth. Hence, the symptoms and management of the mineral and bone disorder of chronic kidney disease in children on peritoneal dialysis showed substantial regional variation. Our findings support a PTH target range of 100-300 pg/ml in the pediatric age group.Kidney International advance online publication, 1 September 2010; doi:10.1038/ki.2010.316.
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PMID: 20811335 [PubMed - as supplied by publisher]3: Am J Kidney Dis. 2010 Aug 27; [Epub ahead of print]
Navaneethan SD, Vecchio M, Johnson DW, Saglimbene V, Graziano G, Pellegrini F, Lucisano G, Craig JC, Ruospo M, Gentile G, Manfreda VM, Querques M, Stroumza P, Torok M, Celia E, Gelfman R, Ferrari JN, Bednarek-Skublewska A, Dulawa J, Bonifati C, Hegbrant J, Wollheim C, Jannini EA, Strippoli GF.
Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH; Cochrane Renal Group, Sydney, Australia.
BACKGROUND:: Sexual dysfunction is an under-recognized problem in men and women with chronic kidney disease (CKD). The prevalence, correlates, and predictors of this condition in patients with CKD have not been evaluated comprehensively. STUDY DESIGN:: Systematic review and meta-analysis. SETTING & POPULATION:: Patients treated using dialysis (dialysis patients), patients treated using transplant (transplant recipients), and patients with CKD not treated using dialysis or transplant (nondialysis nontransplant patients with CKD). SELECTION CRITERIA FOR STUDIES:: Observational studies conducted in patients with CKD only or including a control group without CKD. PREDICTOR:: Type of study population. OUTCOMES:: Sexual dysfunction in men and women with CKD using validated tools, such as the International Index of Erectile Function, the Female Sexual Function Index (FSFI), or other measures as reported by study investigators. RESULTS:: 50 studies (8,343 patients) of variable size (range, 16-1,023 patients) were included in this review. Almost all studies explored sexual dysfunction in men and specifically erectile dysfunction. The summary estimate of erectile dysfunction in men with CKD was 70% (95% CI, 62%-77%; 21 studies, 4,389 patients). Differences in reported prevalence rates of erectile dysfunction between different studies were attributable primarily to age, study populations, and type of study tool used to assess the presence of erectile dysfunction. In women, the reported prevalence of sexual dysfunction was assessed in only 306 patients from 2 studies and ranged from 30%-80%. Compared with the general population, women with CKD had a significantly lower overall FSFI score (8 studies or subgroups, 407 patients; mean difference, -9.28; 95% CI, -12.92 to -5.64). Increasing age, diabetes mellitus, and depression consistently were found to correlate with sexual dysfunction in 20 individual studies of patients with CKD using different methods. LIMITATIONS:: Suboptimal and lack of uniform assessment of outcome measures. CONCLUSIONS:: Sexual dysfunction is highly prevalent in both men and women with CKD, especially among those on dialysis. Larger studies enrolling different ethnic groups, using validated study tools, and analyzing the influence of various factors on the development of sexual dysfunction are needed. Copyright (c) 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
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PMID: 20801572 [PubMed - as supplied by publisher]4: Nephron Clin Pract. 2010 Aug 6;117(2):c83-c88 [Epub ahead of print]
Boaz M, Katzir Z, Schwartz D, Gafter U, Biro A, Shtendik L, Kon V, Chernin G, Weinstein T.
Epidemiology and Research Unit, E. Wolfson Medical Center, Holon, Israel.
Background: Elevated phosphorus (P) and calcium (Ca)-P product (Ca x P) are associated with vascular calcification and cardiovascular disease (CVD) morbidity and CVD and all-cause mortality. Objectives: This study examined the effect of sevelamer hydrochloride exposure (regardless of calcium carbonate exposure) on carotid and femoral intima media thickness (IMT), reliable surrogate measures of prospective intimal thickening, in end-stage renal disease patients on maintenance hemodialysis. Methods: The present cross-sectional study is nested in the Sevelamer hydrochloride and ultrasound-measured femoral and carotid intima media thickness progression in end-stage renal disease (SUMMER) clinical trial. Carotid and femoral arteries were visualized in B-mode ultrasonography. Log-transformed IMT was compared by sevelamer hydrochloride exposure and modeled using multiple linear regression. Results: Forty-five subjects were exposed to sevelamer hydrochloride and 130 were not. Exposed subjects had significantly lower carotid IMT, an association which persisted in the multiple linear regression model even after controlling for potentially confounding variables including serum Ca, history of CVD and body weight. Exposed subjects had lower low-density lipoprotein cholesterol levels and significantly higher parathyroid hormone, but no differences in P, Ca and Ca x P. Conclusions: Sevelamer hydrochloride was associated with lower carotid IMT. This association may be mediated through reduction in Ca load, low-density lipoprotein cholesterol lowering or some other pleiotropic effect. Copyright (c) 2010 S. Karger AG, Basel.
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PMID: 20714166 [PubMed - as supplied by publisher]5: Nephrol Dial Transplant. 2010 Aug 13; [Epub ahead of print]
Leal VO, Mafra D, Fouque D, Anjos LA.
1Medical Science Post Graduate Program, Fluminense Federal University (UFF), Niteroi, Brazil.
BACKGROUND: Even though handgrip strength (HGS) is considered a simple and reliable method to evaluate muscle function and, indirectly, the nutritional status in clinical settings, there is still no consensus concerning its use in patients with chronic kidney disease (CKD) undergoing dialysis. This study presents a systematic review of the literature on the use of HGS as a parameter for nutritional assessment and a prognostic marker in patients on dialysis. METHODS: The MEDLINE database (1966 to October 2009) was consulted for this systematic review by using the search terms hand strength or muscle strength dynamometer and dialysis. Eighteen articles were identified and included in the analysis. RESULTS: Similar to the general population, HGS values were associated with age and gender. The analysed studies showed correlation between muscle function estimated by HGS and variables used in the assessment of muscle mass and nutritional status, as well as the prediction of clinical complications. CONCLUSIONS: The analysis indicates that HGS is a useful tool for continuous and systematic assessment of muscle mass related to nutritional status in patients on dialysis. However, it is still necessary to standardize the techniques used for HGS, especially with respect to the position of measurement, the evaluation period, the choice of arm side and the diagnostic criterion.
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PMID: 20709742 [PubMed - as supplied by publisher]6: Nephron Clin Pract. 2010 Aug 6;117(2):c127-c134 [Epub ahead of print]
Molnar MZ, Mucsi I, Macdougall IC, Marsh JE, Yaqoob M, Main J, Courtney AE, Fogarty D, Mikhail A, Choukroun G, Short CD, Covic A, Goldsmith DJ.
Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary.
Background: Although it is a known predictor of mortality, there is a relative lack of recent information about anaemia in kidney transplant recipients. Thus, we now report data about the prevalence and management of post-transplant anaemia (PTA) in Europe 5 years after the TRansplant European Survey on Anemia Management (TRESAM) study. Methods: In a cross-sectional study enrolling the largest number of patients to date, data were obtained from 5,834 patients followed at 10 outpatient transplant clinics in four European countries using the American Society of Transplantation anaemia guideline. Results: More than one third (42%) of the patients were anaemic. The haemoglobin (Hb) concentration was significantly correlated with the estimated glomerular filtration rate (eGFR) (r = 0.4, p < 0.001). In multivariate analysis, eGFR, serum ferritin, age, gender, time since transplantation and centres were independently and significantly associated with Hb. Only 24% of the patients who had a Hb concentration <110 g/l were treated with an erythropoiesis-stimulating agent. The prevalence of anaemia and also the use of erythropoiesis-stimulating agents were significantly different across the different centres, suggesting substantial practice variations. Conclusions: PTA is still common and under-treated. The prevalence and management of PTA have not changed substantially since the TRESAM survey. Copyright (c) 2010 S. Karger AG, Basel.
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PMID: 20693814 [PubMed - as supplied by publisher]7: Nephrol Dial Transplant. 2010 Aug 5; [Epub ahead of print]
Specter R, Sanchorawala V, Seldin DC, Shelton A, Fennessey S, Finn KT, Zeldis JB, Dember LM.
1Renal Section, Boston University School of Medicine, Boston, USA.
BACKGROUND: Lenalidomide is an immunomodulatory agent used to treat plasma cell dyscrasias. We previously observed worsening of kidney function in a high proportion of patients with AL amyloidosis during lenalidomide treatment. The objective of this study is to characterize alterations in kidney function among patients with AL amyloidosis undergoing treatment with lenalidomide. METHODS: This is a secondary analysis of an ongoing clinical trial at a single referral centre. Forty-one patients with AL amyloidosis received lenalidomide with or without dexamethasone in monthly cycles. Kidney dysfunction was defined as >/= 50% increase in serum creatinine. Severe kidney dysfunction was defined as >/= 100% increase in serum creatinine. Recovery of renal function was defined as a return of serum creatinine to within 25% of the pre-treatment value or discontinuation of dialysis. RESULTS: Twenty-seven of 41 patients (66%) developed kidney dysfunction during lenalidomide treatment. The kidney dysfunction was severe in 13 of these patients (32%); four of whom required initiation of dialysis (10%). The median time to kidney dysfunction after starting lenalidomide was 44 days (interquartile range 15-108 days). Four of eight patients without underlying renal amyloidosis developed kidney dysfunction. Patients with severe kidney dysfunction were older and had a higher frequency of underlying renal amyloidosis, greater urinary protein excretion, and lower serum albumin. Recovery of renal function occurred in 12 patients (44%). CONCLUSIONS: Among patients with AL amyloidosis, worsening of kidney function occurs frequently during lenalidomide treatment. While a causal role of the drug has not been established, our findings suggest that kidney function should be monitored closely during treatment with this drug.
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PMID: 20693160 [PubMed - as supplied by publisher]8: Am J Kidney Dis. 2010 Aug 5; [Epub ahead of print]
Grams ME, Plantinga LC, Hedgeman E, Saran R, Myers GL, Williams DE, Powe NR; CDC CKD Surveillance Team.
Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD.
BACKGROUND: Accurate classification of individuals with kidney disease is vital to research and public health efforts aimed at improving health outcomes. Our objective is to identify and synthesize published literature evaluating the accuracy of existing data sources related to kidney disease. STUDY DESIGN: A systematic review of studies seeking to validate the accuracy of the underlying data relevant to kidney disease. SETTING & POPULATION: US-based and international studies covering a wide range of both outpatient and inpatient study populations. SELECTION CRITERIA FOR STUDIES: Any English-language study investigating the prevalence or cause of kidney disease, existence of comorbid conditions, or cause of death in patients with chronic kidney disease (CKD). All definitions and stages of CKD, including end-stage renal disease (ESRD), were accepted. INDEX TESTS: Presence of a kidney disease-related variable in existing data sets, including administrative data sets and disease registries. REFERENCE TESTS: Presence of a kidney disease-related variable defined using laboratory criteria or medical record review. RESULTS: 30 studies were identified. Most studies investigated the accuracy of kidney disease reporting, comparing coded renal disease with that defined using estimated glomerular filtration rate. The sensitivity of coded renal disease varied widely (0.08-0.83). Specificity was higher, with all studies reporting values >/=0.90. Studies evaluating the cause of CKD, comorbid conditions, and cause of death in patients with CKD used ESRD or transplant populations exclusively, and accuracy was highly variable compared with ESRD registry data. LIMITATIONS: Only English-language studies were evaluated. CONCLUSIONS: Given the heterogeneous results of validation studies, a variety of attributes of existing data sources, including the accuracy of individual data items within these sources, should be considered carefully before use in research, quality improvement, and public health efforts. Copyright (c) 2010 National Kidney Foundation, Inc. All rights reserved.
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PMID: 20692079 [PubMed - as supplied by publisher]9: Nephron Clin Pract. 2010 Aug 4;117(1):c74-c82 [Epub ahead of print]
Cancela AL, Oliveira RB, Graciolli FG, Dos Reis LM, Barreto F, Barreto DV, Cuppari L, Jorgetti V, Carvalho AB, Canziani ME, Moyses RM.
Universidade de Sao Paulo, Sao Paulo, Brazil.
Background: Fibroblast growth factor 23 (FGF23) concentrations increase early in chronic kidney disease (CKD), and the influence of current CKD-mineral and bone disorder (MBD) therapies on serum FGF23 levels is still under investigation. Methods: In this post-hoc analysis of a randomized clinical trial, phosphate binders and calcitriol were washed out of 72 hemodialysis patients who were then submitted to bone biopsy, coronary tomography and biochemical measures, including FGF23. They were randomized to receive sevelamer or calcium acetate for 1 year and the prescription of calcitriol and the calcium concentration in the dialysate were adjusted according to serum calcium, phosphate and PTH and bone biopsy diagnosis. Results: At baseline, bone biopsy showed that 58.3% had low-turnover bone disease, whereas 38.9% had high-turnover bone disease, with no significant differences between them with regard to FGF23. Median baseline FGF23 serum levels were elevated and correlated positively with serum phosphate. After 1 year, serum FGF23 decreased significantly. Repeated measures ANOVA analysis showed that the use of a 3.5-mEq/l calcium concentration in the dialysate, as well as the administration of calcitriol and a calcium-based phosphate binder were associated with higher final serum FGF23 levels.Conclusions: Taken together, our results confirm that the current CKD-MBD therapies have an effect on serum levels of FGF23. Since FGF23 is emerging as a potential treatment target, our findings should be taken into account in the decision on how to manage CKD-MBD therapy. Copyright (c) 2010 S. Karger AG, Basel.
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PMID: 20689328 [PubMed - as supplied by publisher]10: Nephron Clin Pract. 2010 Aug 3;117(1):c1-c7 [Epub ahead of print]
Minghetti P, Rocco P, Del Vecchio L, Locatelli F.
Department of Pharmaceutical Sciences 'P. Pratesi', Universita degli Studi di Milano, Milan, Italy.
The patent expirations for many biotechnological medicines have prompted the development of copies of biological medicinal products. Unlike generics, biosimilars are similar but not identical to their reference product, because their chemical characteristics are directly related to the manufacturing process which cannot be precisely duplicated. The regulatory policy for biosimilars is complex and in Europe it is regulated mainly by guidelines issued by the European Medicines Agency (EMEA); additional product-class specific guidelines have been developed as in the case of recombinant human erythropoietin (rHuEPO). In 2008, the experience gained with this drug has prompted the development of a new guideline, currently in draft. In this review we critically discuss aspects related to EMEA guidelines, particularly focusing on rHuEPO. Copyright (c) 2010 S. Karger AG, Basel.
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PMID: 20689318 [PubMed - as supplied by publisher]11: Kidney Int. 2010 Sep;78(6):539-45. Epub 2010 Jul 28.
Lattanzio MR, Weir MR.
Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
A misinterpretation of the results from ONTARGET (Ongoing Telmisartan alone and in combination with ramipril Global Endpoint Trial) has sparked both efficacy and safety concerns within the nephrology community regarding the utilization of dual RAAS blockade to achieve more desirable renal outcomes. Two important considerations are requisite prior to interpreting these results, specifically: the context of the cohort studied (non-proteinuric CKD patients at low risk of progression) and the inadequate power of the study to assess renal outcomes. The cardiac and renal protection afforded from dual RAAS blockade in select populations, particularly proteinuric CKD and CHF, is supported by literature. Moreover, the response to dual RAAS blockade involving different combinations of ACE inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and direct renin inhibitors, may not be uniform amongst all patient populations. Will we continue to withhold the appropriate medical therapy from certain individuals based on misconstrued data? The proceedings provide a critical analysis of the ONTARGET study and an evidence-based substantiation for the utilization of various forms of dual RAAS blockade in proteinuric kidney disease and beyond.
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PMID: 20668429 [PubMed - in process]12: Kidney Int. 2010 Jul 21; [Epub ahead of print]
Pierchala BA, Munoz MR, Tsui CC.
Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA.
Podocytes are morphologically complex cells, the junctions of which form critical elements of the final filtration barrier. Disruption of their foot processes and slit diaphragms occur early in the development of many glomerular diseases. Here, we biochemically purified fractions enriched with slit diaphragm proteins and performed a proteomic analysis to identify new components of this important structure. Several known slit diaphragm proteins were found, such as podocin and nephrin, confirming the validity of the purification scheme. However, proteins on the apical membrane such as podocalyxin were neither enriched nor identified in our analysis. The chloride intracellular channel protein 5 (CLIC5), predominantly expressed in podocytes, was enriched in these fractions and localized in the foot process apical and basal membranes. CLIC5 colocalized and associated with the ezrin/radixin/moesin complex and with podocalyxin in podocytes in vivo. It is important to note that CLIC5(-/-) mice were found to have significantly decreased foot process length, widespread foot process abnormalities, and developed proteinuria. The ezrin/radixin/moesin complex and podocalyxin were significantly decreased in podocytes from CLIC5(-/-) mice. Thus, our study identifies CLIC5 as a new component that is enriched in and necessary for foot process integrity and podocyte function in vivo.Kidney International advance online publication, 21 July 2010; doi:10.1038/ki.2010.212.
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PMID: 20664558 [PubMed - as supplied by publisher]13: Am J Kidney Dis. 2010 Jul 12; [Epub ahead of print]
Tung J, Carlisle E, Smieja M, Kim PT, Lee CH.
St. Joseph's Healthcare, Ontario, Canada.
BACKGROUND: The Centers for Disease Control and Prevention recommend immunizing susceptible high-risk groups, such as hemodialysis patients, against hepatitis B virus. However, hemodialysis patients may not develop seroprotective antibodies despite receiving high doses of the vaccine. Recent reports indicate that combined vaccination against hepatitis B and hepatitis A viruses may improve the immunogenicity of hepatitis B vaccine in healthy individuals, but the effectiveness of this strategy in hemodialysis patients is unknown. STUDY DESIGN: Prospective randomized controlled trial. SETTING & PARTICIPANTS: Hepatitis B virus-seronegative hemodialysis patients with undetectable antibody levels at baseline. INTERVENTION: Intramuscular administration of Twinrix (inactivated hepatitis A virus [720 ELISA units] and purified hepatitis B virus surface antigen [20 mug]; GlaxoSmithKline) and Engerix-B (purified hepatitis B virus surface antigen [20 mug]) at 0, 1, and 6 months plus Engerix-B, 40 mug, at month 2 (intervention arm) or Engerix-B, 40 mug, at 0, 1, 2, and 6 months (control arm). Both groups received a total dose of 160 mug of hepatitis B antigen. OUTCOMES: The primary outcome was the difference in seroprotection rates at 7 months, defined by antibody titers >10 mIU/mL. The secondary outcome was frequency of adverse events. MEASUREMENTS: Antibody response at months 3 and 7. RESULTS: 96 patients were enrolled, and 73 completed the investigation. At 3 months, there was no difference in the groups' seroprotection rates (25% vs 27%; P = 0.4). At the completion of the vaccination series, using per-protocol analysis, 27 of 40 (68%) and 16 of 33 (49%) had antibody titers >10 mIU/mL in the treatment and control groups, respectively (P = 0.05; RR, 1.4; absolute abatement, 19%). Intention-to-treat analysis showed 58% and 38% seroprotection rates in the treatment and control groups, respectively (P = 0.02; RR, 1.5; absolute abatement, 20%). There was no difference in adverse events. LIMITATIONS: Lack of evidence of long-term protection. CONCLUSION: Vaccination of hemodialysis patients with a combined hepatitis A and hepatitis B regimen resulted in a statistically significant and clinically important improvement in seroprotection against hepatitis B virus compared with hepatitis B monovalent vaccine. Copyright (c) 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
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PMID: 20630640 [PubMed - as supplied by publisher]14: Am J Kidney Dis. 2010 Aug;56(2):189-218. Epub 2010 Jul 2.
Bia M, Adey DB, Bloom RD, Chan L, Kulkarni S, Tomlanovich S.
Yale School of Medicine, New Haven, CT 06520-8029, USA.
In response to recently published KDIGO (Kidney Disease: Improving Global Outcomes) guidelines for the care of kidney transplant recipients (KTRs), the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) organized a working group of transplant nephrologists and surgeons to review these guidelines and comment on their relevance and applicability for US KTRs. The following commentaries on the KDIGO guidelines represent the consensus of our work group. The KDIGO transplant guidelines concentrated on aspects of transplant care most important to this population in the posttransplant period, such as immunosuppression, infection, malignancy, and cardiovascular care. Our KDOQI work group concurred with many of the KDIGO recommendations except in some important areas related to immunosuppression, in which decisions in the United States are largely made by transplant centers and are dependent in part on the specific patient population served. Most, but not all, KDIGO guidelines are relevant to US patients. However, implementation of many may remain a major challenge because of issues of limitation in resources needed to assist in the tasks of educating, counseling, and implementing and maintaining lifestyle changes. Although very few of the guidelines are based on evidence that is strong enough to justify their being used as the basis of policy or performance measures, they offer an excellent road map to navigate the complex care of KTRs. Copyright (c) 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Publication Types: Research Support, Non-U.S. Gov't
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PMID: 20598411 [PubMed - indexed for MEDLINE]15: Nephrol Dial Transplant. 2010 Sep;25(9):2846-50. Epub 2010 Jun 29.
Locatelli F, Aljama P, Canaud B, Covic A, De Francisco A, Macdougall IC, Wiecek A, Vanholder R; Anaemia Working Group of European Renal Best Practice (ERBP).
Department of Nephrology, Dialysis and Renal Transplant, Alessandro Manzoni Hospital, Lecco, Italy. nefrologia@ospedale.lecco.it
The European Renal Best Practice (ERBP), which are issued by ERA-EDTA, are suggestions for clinical practice in areas in which evidence is lacking or weak, together with position statements on recently published randomized controlled trials, or on existing guidelines and recommendations. In 2009, the Anaemia Working Group of ERBP published its first position statement about the haemoglobin target to aim for with erythropoietin-stimulating agents (ESA) and on issues that were not covered by K-DOQI in 2006-07. This second position paper of the group follows the publication of the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) Study. This multi-centre, placebo-controlled trial compared cardiovascular and renal outcomes in 4038 patients with type 2 diabetes, chronic kidney disease not on dialysis, and anaemia who were randomized to complete anaemia correction (haemoglobin target of 13 g/dL using darbepoetin alpha) or placebo (with a haemoglobin rescue value of 9 g/dL). Following the findings of the TREAT study, the Anaemia Working Group of ERBP maintains its view that 'Hb values of 11-12 g/dL should be generally sought in the CKD population without intentionally exceeding 13 g/dL' and that the doses of ESA therapy to achieve the target haemoglobin should also be considered. More caution is suggested when treating anaemia with ESA therapy in patients with type 2 diabetes not undergoing dialysis (and probably in diabetics at all CKD stages). In those with ischaemic heart disease or with a previous history of stroke, possible benefits should be weighed up against an increased risk of stroke recurrence, when deciding which Hb level to aim for. These recommendations are not intended to represent a new guideline as they are not the result of a systematic review of the evidence.
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PMID: 20591813 [PubMed - in process]16: Nephrol Dial Transplant. 2010 Jun 27; [Epub ahead of print]
Tong A, Howell M, Wong G, Webster AC, Howard K, Craig JC.
1Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW 2145, Australia.
BACKGROUND: Non-adherence to medication regimens after kidney transplantation is a major risk factor for acute rejection and graft loss, yet little is known about the perspectives of kidney transplant recipients on medicine taking. This study aimed to describe the beliefs, experiences and perspectives of kidney transplant recipients on medicine taking. METHODS: We conducted a systematic review of qualitative studies of medicine taking after kidney transplantation. Five electronic databases (to Week 3 of January 2010) were searched. Thematic synthesis of the results and conclusions reported in each included study was performed to develop descriptive and analytical themes. RESULTS: We included seven studies involving 207 participants. The six themes identified were (i) attitudes towards medicine taking, its impact on lifestyle, self-image, relationships and outlook on life; (ii) inadvertent forgetfulness, preoccupation with life commitments; (iii) medication properties; (iv) structure of healthcare services, poor access to pharmacy or affordable medications and conflicting medical appointments; (v) personal efforts in managing medications, organizing and devising strategies for taking medicines on time; and (vi) availability of external social support. These underpinned five reported medicine-taking behaviours including not taking medicines, seeking to change medications or dose, missing a dose, varying the timing of doses and vigilant adherence. CONCLUSIONS: Considering patients' attitudes, priorities, current life events, commitments, support systems and healthcare structures can inform interventions to promote concordance between prescribed medication and medicine-taking behaviours. This may improve treatment outcomes and mitigate the risks of non-adherence-related rejection.
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PMID: 20584734 [PubMed - as supplied by publisher]17: J Am Soc Nephrol. 2010 Jul;21(7):1223-32. Epub 2010 Jun 17.
Kestenbaum B, Glazer NL, Kottgen A, Felix JF, Hwang SJ, Liu Y, Lohman K, Kritchevsky SB, Hausman DB, Petersen AK, Gieger C, Ried JS, Meitinger T, Strom TM, Wichmann HE, Campbell H, Hayward C, Rudan I, de Boer IH, Psaty BM, Rice KM, Chen YD, Li M, Arking DE, Boerwinkle E, Coresh J, Yang Q, Levy D, van Rooij FJ, Dehghan A, Rivadeneira F, Uitterlinden AG, Hofman A, van Duijn CM, Shlipak MG, Kao WH, Witteman JC, Siscovick DS, Fox CS.
Division of Nephrology, Department of Medicine, University of Washington, Kidney Research Institute, Seattle, Washington 98104-2499, USA. brk@u.washington.edu
Phosphorus is an essential mineral that maintains cellular energy and mineralizes the skeleton. Because complex actions of ion transporters and regulatory hormones regulate serum phosphorus concentrations, genetic variation may determine interindividual variation in phosphorus metabolism. Here, we report a comprehensive genome-wide association study of serum phosphorus concentration. We evaluated 16,264 participants of European ancestry from the Cardiovascular Heath Study, Atherosclerosis Risk in Communities Study, Framingham Offspring Study, and the Rotterdam Study. We excluded participants with an estimated GFR <45 ml/min per 1.73 m(2) to focus on phosphorus metabolism under normal conditions. We imputed genotypes to approximately 2.5 million single-nucleotide polymorphisms in the HapMap and combined study-specific findings using meta-analysis. We tested top polymorphisms from discovery cohorts in a 5444-person replication sample. Polymorphisms in seven loci with minor allele frequencies 0.08 to 0.49 associate with serum phosphorus concentration (P = 3.5 x 10(-16) to 3.6 x 10(-7)). Three loci were near genes encoding the kidney-specific type IIa sodium phosphate co-transporter (SLC34A1), the calcium-sensing receptor (CASR), and fibroblast growth factor 23 (FGF23), proteins that contribute to phosphorus metabolism. We also identified genes encoding phosphatases, kinases, and phosphodiesterases that have yet-undetermined roles in phosphorus homeostasis. In the replication sample, five of seven top polymorphisms associate with serum phosphorous concentrations (P < 0.05 for each). In conclusion, common genetic variants associate with serum phosphorus in the general population. Further study of the loci identified in this study may help elucidate mechanisms of phosphorus regulation.
Publication Types: Meta-Analysis Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20558539&dopt=ExternalLink
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PMID: 20558539 [PubMed - indexed for MEDLINE]18: Kidney Int. 2010 Sep;78(6):598-604. Epub 2010 Jun 16.
Sharma AP, Filler G, Dwight P, Clark WF.
Division of Nephrology, Department of Pediatrics, Children's Hospital, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada. ajay.sharma@lhsc.on.ca
Many uncontrolled studies and a subsequent meta-analysis suggest that hemolytic uremic syndrome (HUS) with a positive history for diarrhea is associated with a significant increase in chronic renal disease. Two recent controlled studies that followed children with this type of HUS after Escherichia coli O157:H7 outbreaks, and where the controls were selected from a group exposed in the outbreak, gave conflicting results. To clarify this apparent difference, we retrospectively compared a cohort of 30 children with sporadic diarrhea-positive HUS with 30 healthy controls who had no history of bloody diarrhea or HUS and who had similar age and gender. Significantly more children with previous HUS than the controls had albuminuria over a median follow-up of 6.2 years. Of these albuminuric patients, one-third had macroalbuminuria compared with none of the controls. Following HUS, children were three times more prone to hypertension and prehypertension, although the difference was not statistically significant. Glomerular filtration rates, estimated by cystatin C, were significantly lower by 30 ml/min/1.73 m(2). Thus, children with sporadic HUS with positive history of diarrhea compared with unexposed controls had a higher prevalence of chronic renal disease; results consistent with the meta-analysis. Prospective studies with appropriate controls are needed to completely resolve this issue.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20555321&dopt=ExternalLink
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PMID: 20555321 [PubMed - in process]19: J Am Soc Nephrol. 2010 Aug;21(8):1381-9. Epub 2010 Jun 10.
Wu S, Kim C, Baer L, Zhu X.
Division of Hematology and Oncology, Stony Brook University Medical Center, Stony Brook, New York, USA. shenhong.wu@stonybrook.edu
Treatment with the chemotherapeutic agent bevacizumab, a humanized mAb that neutralizes vascular endothelial growth factor, can lead to proteinuria and renal damage. The risk factors and clinical outcomes of renal adverse events are not well understood. We performed a systematic review and meta-analysis of published randomized, controlled trials to assess the overall risk for severe proteinuria with bevacizumab. We analyzed data from 16 studies comprising 12,268 patients with a variety of tumors. The incidence of high-grade (grade 3 or 4) proteinuria with bevacizumab was 2.2% (95% confidence interval [CI] 1.2 to 4.3%). Compared with chemotherapy alone, bevacizumab combined with chemotherapy significantly increased the risk for high-grade proteinuria (relative risk 4.79; 95% CI 2.71 to 8.46) and nephrotic syndrome (relative risk 7.78; 95% CI 1.80 to 33.62); higher dosages of bevacizumab associated with increased risk for proteinuria. Regarding tumor type, renal cell carcinoma associated with the highest risk (cumulative incidence 10.2%). We did not detect a significant difference between platinum- and non-platinum-based concurrent chemotherapy with regard to risk for high-grade proteinuria (P = 0.39). In conclusion, the addition of bevacizumab to chemotherapy significantly increases the risk for high-grade proteinuria and nephrotic syndrome.
Publication Types: Meta-Analysis Research Support, Non-U.S. Gov't Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20538785&dopt=ExternalLink
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PMID: 20538785 [PubMed - indexed for MEDLINE]20: Am J Kidney Dis. 2010 Aug;56(2):325-37. Epub 2010 Jun 9.
Rozen-Zvi B, Yahav D, Gheorghiade M, Korzets A, Leibovici L, Gafter U.
Department of Nephrology and Hypertension, Rabin Medical Center, Petah-Tikva, and the Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel. benayarz@gmail.com
BACKGROUND: In patients with euvolemic and hypervolemic hyponatremia, the effect of vasopressin antagonists is yet undefined. STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). SETTING & POPULATION: In- and outpatients with euvolemic or hypervolemic hyponatremia. SELECTION CRITERIA FOR STUDIES: We included all RCTs regardless of publication status or language. INTERVENTION: Vasopressin antagonists with or without fluid restriction versus placebo or no treatment with or without fluid restriction. OUTCOMES: Response rate defined as normalization of serum sodium level or significant increase in serum sodium level at 3-7 days (primary) and later, change from baseline serum sodium level at 3-7 days and later, adverse events, rate of rapid sodium level correction, and rate of hypernatremia. RESULTS: 15 RCTs were identified. Vasopressin antagonist treatment significantly increased response rate both early (RR, 3.15; 95% CI, 2.27-4.37; 11 trials) and late (RR, 2.27; 95% CI, 1.79-2.89; 4 trials). Response rates were high in trials assessing mostly euvolemic patients and those assessing mostly hypervolemic patients, with greater effect estimate in the former. Change from baseline serum sodium level was significantly increased both early (weighted mean difference, 5.27 mEq/L; 95% CI, 4.27-6.26, 13 trials) and late (weighted mean difference, 3.49 mEq/L; 95% CI, 2.56-4.41, 8 trials). Although there was an increased rate of rapid sodium correction (RR, 2.52; 95% CI, 1.26-5.08, 8 trials) with vasopressin antagonists, hypernatremia rates were not significantly higher (RR, 2.21; 95% CI, 0.61-7.96; 5 trials), adverse events were not increased, and there were no reports of osmotic demyelination syndrome. LIMITATIONS: Significant heterogeneity in the primary outcome. CONCLUSIONS: Vasopressin antagonists are effective for the treatment of hypervolemic and euvolemic hyponatremia. Copyright (c) 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Publication Types: Meta-Analysis Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20538391&dopt=ExternalLink
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PMID: 20538391 [PubMed - indexed for MEDLINE]