Advanced Stages Of CKD Research Articles

Medication Treatment Complexity and Adherence in Children with CKD

The complexity of CKD management in children is increased by the number of comorbid conditions. This study assessed the prevalence of comorbidities in pediatric CKD and the frequency with which multiple comorbidities present together by assessing prevalent medication use by CKD stage and diagnosis and their association with clinical or sociodemographic factors. The association between number and frequency of dosing of medications prescribed and self-report of nonadherence was also assessed. In this cross-sectional analysis of the Chronic Kidney Disease in Children study, medication use at study entry grouped by indication was examined by CKD stage, diagnosis, age, race, ethnicity, income, and CKD duration. Multivariate adjusted predictors of medication use and clustering were examined. Nonadherence was assessed by self-report of missed medications in the past 7 days. The 558 eligible participants had a median age of 11 years and median GFR of 44 ml/min per 1.73 m(2); 62% of participants were male and 78% had nonglomerular kidney disease. The number of medications for treatment of CKD comorbidities increased with advanced CKD stage (2.5-fold for stages IV versus II; P<0.001) and glomerular disease (1.4-fold versus nonglomerular; P<0.001). Three distinct medication clusters were identified that corresponded to treatment of glomerular disease, advanced renal tubular dysfunction, and proteinuric complications, respectively. Nonadherence was associated with increased medication dosing frequency (administration >2 times/d; P<0.001) but not the number of medications. Medical therapy for children with CKD is complex and is affected by glomerular diagnosis, CKD stage, and medication frequency. The need for CKD-related medication treatment cannot be easily predicted by CKD staging alone. Poorer adherence was associated with increased medication frequency, but not with the number of medical problems needing treatment. Consolidating medical treatment and reducing medication frequency may improve adherence rates in children with CKD.

Estimated Glomerular Filtration Rate Calculated By The CKD-EPI Formula Has Improved Prognostic Ability Over MDRD Formula In Patients With Newly Diagnosed, Symptomatic, Multiple Myeloma: Analysis In 1937 Patients

Renal impairment (RI) is a common complication of myeloma and is associated with increased risk of early death. Accurate assessment of glomerular filtration rate (GFR) in patients with myeloma is important for evaluation of renal function, for drug dosing and for prognostic purposes. The method of assessment of RI and calculation of GFR is important since serum creatinine alone underestimates renal dysfunction, especially in patients of advanced age. The MDRD formula has been widely used for the calculation of GFR but the CKD-EPI formula has been increasingly used among nephrologists since 2009 (Levey et al, Ann Intern Med 2009;150:604-12). However, the performance of these two equations for the estimation of GFR and their relative prognostic ability has not been assessed in large numbers of patients with myeloma. Thus, in order to evaluate the prognostic significance of GFR as calculated by two different formulas, the MDRD and the CKD-EPI, we analyzed the data of 1937 newly diagnosed patients with symptomatic myeloma who were treated within the centers of the Greek Myeloma Study Group.The median age of the patients was 66 years (range 20-96 years); 54% were >65 years of age and 23% >75 years of age; 55% were males and 53% had an ECOG performance status ≤1. Anemia (Hb <10 g/dl) was present in 44% of the patients, low platelet counts (<130x109/l) in 13% and hypercalcemia (Ca ≥11.5 mg/dl) in 14.5%. ISS: 27% were ISS-1, 37% were ISS-2 and 36% were ISS-3, while serum LDH was elevated (≥300 IU/L) in 11.5%. Significant Bence Jones proteinuria (≥2 g/day) was present in 19%, while serum creatinine was ≥2 mg/dl in 20.5% of the patients. Frontline therapy was based on conventional chemotherapy in 64% of the patients and 36% received primary therapy with novel agents (22% IMiD-based and 14% bortezomib-based regimens). Median eGFR by the MDRD formula was 63 ml/min/1.73m2 (range 2.94-201.4 ml/min/1.73m2) vs. 61.4 ml/min/1.73m2 (range 2.51-140.4 ml/min/1.73m2) by the CKD-EPI formula (p<0.001). According to CKD stage disposition, per eGFR calculated by the MDRD 18.6%, 34.5%, 28% , 11% and 8% of patients had stage 1, 2, 3, 4 and 5 RI, respectively, while when GFR was calculated by the CKD-EPI 16.6% , 34%, 28%, 12% and 8.5% of patients had stage 1, 2, 3, 4 and 5, respectively. The difference in the disposition between the two calculation methods was significant (p<0.001): the concordance in stage disposition was 90.3%; thus, 9.7% of patients were allocated in different stages by the two methods of calculation, mainly because with CKD-EPI formula resulted in lower estimated GFR: in 19.5% of the patients the eGFR by MDRD was ≥10% higher and in 0.4% was ≥10% lower than with CKD-EPI equation, but resulted in re-classification in advanced stage of CKD in 8% of patients and in lower stage in 2% of patients. The difference in classification resulted in the downgrade of 42 patients from stage 2 to stage 3 RI, when CKD-EPI equation was used to calculate eGFR.We examined the prognostic significance in univariate analysis per CKD stage for each calculation formula: median survival for patients with CKD stage 1, 2, 3, 4 and 5, according to MDRD formula was 61, 54, 36, 30 and 23 months, respectively (p<0.001), while the respective median survival per CKD-EPI formula was 64 months, 54, 37, 25 and 23 months (p<0.001). In univariate analysis, eGFR by CKD-EPI formula resulted in higher chi-square values (χ2: 127 vs. 97 for eGFR by MDRD formula) indicating improved prognostic ability for overall survival. We also examined the predictive ability for each of the formulas of eGFR for early death at 2 months, 6 months and 12 months. Harrell's C statistic, a measure of the discriminating ability of a model was higher for eGFR by the CKD-EPI than for eGFR by the MDRD formula, either for overall survival (p=0.028) or for early death at 2 months (p<0.001), at 6 months (p<0.001) or 12 months (p<0.001) after initiation of therapy.In conclusion, for the first time we evaluated two different formulas of estimation of GFR, both based on serum creatinine, age and gender, in a large number of patients with symptomatic myeloma and we found that GFR calculated by the CKD-EPI formula reclassifies the stage of renal impairment of about 9% of patients and has better prognostic ability for survival and predictive ability for early death than the MDRD formula. We propose the broad use of CKD-EPI formula for the estimation of GFR in patients with myeloma. Disclosures:Tsatalas:Genesis Hellas: Honoraria.

Plasma and Urinary Amino Acid Metabolomic Profiling in Patients with Different Levels of Kidney Function

Patients with CKD display altered plasma amino acid profiles. This study estimated the association between the estimated GFR and urinary and plasma amino acid profiles in CKD patients. Urine and plasma samples were taken from 52 patients with different stages of CKD, and plasma samples only were taken from 25 patients on maintenance hemodialysis. Metabolic profiling was performed by liquid chromatography coupled with tandem mass spectrometry after phenylisothiocyanate derivatization. Most plasma amino acid concentrations were decreased in hemodialysis patients, whereas proline, citrulline, asparagine, asymmetric dimethylarginine, and hydroxykynurenine levels were increased (P<0.05). Both plasma levels and urinary excretion of citrulline were higher in the group of patients with advanced CKD (CKD stages 2 and 3 versus CKD stages 4 and 5; in plasma: 35.9±16.3 versus 61.8±23.6 µmol/L, P<0.01; in urine: 1.0±1.2 versus 7.1±14.3 µmol/mol creatinine, P<0.001). Plasma asymmetric dimethylarginine levels were higher in advanced CKD (CKD stages 2 and 3, 0.57±0.29; CKD stages 4 and 5, 1.02±0.48, P<0.001), whereas urinary excretion was lower (2.37±0.93 versus 1.51±1.43, P<0.001). Multivariate analyses adjusting on estimated GFR, serum albumin, proteinuria, and other covariates revealed associations between diabetes and plasma citrulline (P=0.02) and between serum sodium and plasma asymmetric dimethylarginine (P=0.03). Plasma tyrosine to phenylalanine and valine to glycine ratios were lower in advanced CKD stages (P<0.01). CKD patients have altered plasma and urinary amino acid profiles that are not corrected by dialysis. Depending on solutes, elevated plasma levels were associated with increased or decreased urinary excretion, depicting situations of uremic retention (asymmetric dimethylarginine) or systemic overproduction (citrulline). These results give some insight in the CKD-associated modifications of amino acid metabolism, which may help improve their handling.

A Longitudinal Study of Left Ventricular Function and Structure from CKD to ESRD

Abnormal left ventricular structure and function are associated with increased risk of adverse outcomes among patients with CKD and ESRD. A better understanding of changes in left ventricular mass and ejection fraction during the transition from CKD to ESRD may provide important insights to opportunities to improve cardiac outcomes. This was a longitudinal study of a subset of participants of the Chronic Renal Insufficiency Cohort who were enrolled from 2003 to 2007 and followed through January of 2011. Participants were included if they had serial echocardiograms performed at advanced CKD (defined as estimated GFR<20 ml/min per 1.73 m(2)) and again after ESRD (defined as need for hemodialysis or peritoneal dialysis). A total of 190 participants (44% female, 66% black) had echocardiograms during advanced CKD and after ESRD. Mean (SD) estimated GFR at advanced CKD was 16.9 (3.5) ml/min per 1.73 m(2). Mean (SD) time between the advanced CKD echocardiogram and ESRD echocardiogram was 2.0 (1.0) years. There was no significant change in left ventricular mass index (62.3-59.5 g/m(2.7), P=0.10) between advanced CKD and ESRD; however, ejection fraction significantly decreased (53%-50%, P=0.002). Interactions for age, race, dialysis modality, and diabetes status were not significant (P>0.05). Mean left ventricular mass index did not change significantly from advanced CKD to ESRD; however, ejection fraction declined during this transition period. Although left ventricular mass index is fixed by advanced stages of CKD, ejection fraction decline during more advanced stages of CKD may be an important contributor to cardiovascular disease and mortality after dialysis.

GFR estimation in the morbidly obese pre- and postbariatric surgery: one size does not fit all

Glomerular hyperfiltration commonly associated with obesity is expected to improve postbariatric surgery. However, formula-based glomerular filtration rate (GFR) estimation in these patients is limited by body size confounders necessitating use of modified equations, the reliability of which remains uncertain. In this study, various GFR-estimating formulae were compared in morbidly obese patients at baseline and postbariatric surgery. Through a retrospective chart review, we identified 220 patients who had undergone this procedure, with over 6-month follow-up, during which major weight reduction was achieved. A significant decrease in BP and glomerular hyperfiltration was observed, though there was large variability in GFR estimation using the different formulae. Gross over and underestimation was observed which improved with correction for body size confounders especially lean body weight (LBW). Postoperatively, significant attenuation in estimated GFR was demonstrated when LBW or body surface area-adjusted versions were used. In a subgroup of patients with chronic kidney disease, a significant improvement in GFR was seen postoperatively with the LBW-modified formula but there were again inconsistencies when using other equations. Though clinicians must be critical in the application of GFR estimates to patient care, LBW adjustment appears to be the most practical solution to its estimation in the obese patients. This is particularly true for patients with normal renal function but appears to be also applicable to those with compromised kidney function. Future studies are needed to compare these equations with a gold standard GFR measure as well as to explore whether the renal benefits from bariatric surgery are sustained or seen in more advanced CKD stages.

Acute renal failure in the elderly: epidemiology and clinical features

Structural and functional alterations affecting the aging kidney predispose to an increased risk of acute renal failure (ARF) in the elderly. This is a common problem becoming more relevant because of an increase in life expectancy. The epidemiology of ARF in the elderly is far from being well assessed, because of the lack of uniform definition criteria, variable etiology, coexistence of several comorbidities, and the various clinical settings and geographic areas where the condition is managed, with a higher incidence in developed regions where elderly patients predominate. In 2004, the Acute Dialysis Quality Initiative group proposed the RIFLE criteria for diagnosis and stratification of ARF. More recently, the Acute Kidney Injury Network proposed several refinements to the RIFLE criteria, and the use of the term acute kidney injury (AKI) has been suggested to mean any abrupt reduction in kidney function, while restricting use of the term ARF to severe dysfunction requiring renal replacement treatment. Although in elderly patients the more frequent forms of AKI are functional or obstructive, parenchymal AKI, such as acute tubular necrosis and contrast-induced nephropathy, still frequently occur. Elderly patients with chronic renal disease (CKD) who develop AKI are at high risk for mortality, and are prone to non-recovery from AKI and progression to more advanced stages of CKD and even to end-stage renal disease. Panels of AKI biomarkers are likely to improve early diagnosis and treatment, thus reducing morbidity and mortality of older patients from this condition in the future.

Effects of Raloxifene on Bone Metabolism in Hemodialysis Patients

Effects of Raloxifene on Bone Metabolism in Hemodialysis Patients

The D&amp;T Report

The D&amp;T Report

Effects of the Use of Non-Calcium Phosphate Binders in the Control and Outcome of Vascular Calcifications: A Review of Clinical Trials on CKD Patients

Vascular calcifications produce a high impact on morbidity and mortality rates in patients affected by chronic kidney disease and mineral bone disorder (CKD-MBD). Effects are manifested from the more advanced stages of CKD (stages 3-4), particularly in patients undergoing dialysis (CKD5D). In recent years, a large number of therapeutic options have been successfully used in the treatment of secondary hyperparathyroidism (SHPT), despite eliciting less marked effects on nonbone calcifications associated with CKD-MBD. In addition to the use of Vitamin D and analogues, more recently treatment with calcimimetic drugs has also been undertaken. The present paper aims to analyze comparative and efficacy studies undertaken to assess particularly the impact on morbidity and mortality rates of non-calcium phosphate binders. Moreover, the mechanism of action underlying the depositing of calcium and phosphate along blood vessel walls, irrespective of the specific contribution provided in reducing the typical phosphate levels observed in CKD largely at more advanced stages of the disease, will be investigated. The aim of this paper therefore is to evaluate which phosphate binders are characterised by the above action and the mechanisms through which these are manifested.

Cardiovascular Autonomic Neuropathyin Chronic Kidney Diseases

INTRODUCTION:&#x0D; This study was conducted to explore cardiovascular autonomic neuropathy and its pattern in chronic kidney disease patients.&#x0D; METHODS:&#x0D; Autonomic function using five standard tests was examined in 20 diabetic patients with CKD, 20 age and sex matched diabetic patients without CKD and 20 age and sex matched controls. Analysis of difference between the autonomic function was done in the three groups using Chi-square test or Fischer's test.&#x0D; RESULTS:&#x0D; Total 20 (100%) diabetic CKD patients were found to have autonomic neuropathy. Of these, 2 (10%) patients had early parasympathetic damage, 8 (40%) patients had definite parasympathetic damage, and 10 (50%) patients had combined damage. Heart rate response to standing was statistically significant (p = 0.014) among diabetic CKD patients when compared with diabetic patients without CKD. Combined form of autonomicdysfunction was more frequent in advanced stages of diabetic CKD. Three (42.85%) patients in stage 3 CKD, 4 (66.66%) patients in stage 4 CKD and 5 (71.42%) patients in stage 5 CKD, had combined autonomic failure.&#x0D; CONCLUSIONS:&#x0D; Autonomic neuropathy is common in native Nepalese diabetic CKD patients. Heart rate response to standing is significantly abnormal in diabetic CKD patients in comparison with diabetes mellitus patient without CKD. Severity of autonomic dysfunction increases with severity of CKD..&#x0D; KEYWORDS: cardiovascualr autonomic neuropathy, chronic kidney disease, diabetes mellitus.

Serum C-reactive protein and thioredoxin levels in subjects with mildly reduced glomerular filtration rate

BackgroundChronic kidney disease (CKD) is a newly recognized high-risk condition for cardiovascular disease (CVD), and previous studies reported the changes in inflammation and oxidative stress in advanced stages of CKD. We compared the levels of serum biomarkers for inflammation and oxidative stress between subjects with normal and mildly reduced glomerular filtration rate (GFR).MethodsThe subjects were 182 participants of a health check-up program including those with normal (≥ 90 mL/min/1.73 m2, N = 79) and mildly reduced eGFR (60-89 mL/min/1.73 m2, N = 103) which was calculated based on serum creatinine, age and sex. We excluded those with reduced eGFR < 60 mL/min/1.73 m2. No one had proteinuria. We measured serum levels of C-reactive protein (CRP) and thioredoxin (TRX) as the markers of inflammation and oxidative stress, respectively.ResultsAs compared with subjects with normal eGFR, those with mildly reduced eGFR had increased levels of both CRP and TRX. Also, eGFR was inversely correlated with these biomarkers. The associations of eGFR with these biomarkers remained significant after adjustment for age and sex. When adjustment was done for eight possible confounders, CRP showed significant association with systolic blood pressure, high density lipoprotein cholesterol (HDL-C) and non-HDL-C, whereas TRX was associated with sex significantly, and with eGFR and systolic blood pressure at borderline significance.ConclusionsWe showed the increased levels of CRP and TRX in subjects with mildly reduced eGFR. The eGFR-CRP link and the eGFR-TRX link appeared to be mediated, at least partly, by the alterations in blood pressure and plasma lipids in these subjects.

Management of hyperphosphatemia ; phosphate-binder

Numerous experimental and clinical studies have recently addressed the underlying mechanisms in particular the marked increase in cardiovascular mortality in patients with CKD. Hyperphosphatemia is a major problem in these patients with advanced stage of CKD. Calcium carbonate became the most widely used phosphate binders ; however, increasing evidence now suggests that prolonged use of these agents increases the total body calcium load, induces adynamic bone, and potentially increases the risk of cardiovascular and soft tissue calcification. Sevelamer is the first phosphate-binding agent that is non-absorbed, calcium-free, and metal-free. To date, this agent has been shown to effectively control serum phosphorus levels in patients with CKD. It may also attenuate coronary and aortic calcification and has a number of other beneficial effects on lipid metabolism and inflammation among others.

Recent Clinical Trials of Pharmacologic Cardiovascular Interventions in Patients with Chronic Kidney Disease

End stage kidney disease (ESKD) is associated with a 10- to 20-fold increased risk of cardiovascular mortality compared with age- and sex-matched controls without CKD. In spite of this marked increase in risk, the vast majority of cardiovascular intervention clinical trials to date have specifically excluded subjects with CKD. The aim of this paper is to critically review the recently published clinical trial evidence that cardiac outcomes in CKD patients are modified by cardiovascular risk factor interventions, including erythropoiesis stimulating agent therapy (US Normal Hematocrit, CHOIR and CREATE trials), statins (PPP, 4D and ALERT), fibrates (VA-HIT), folic acid (ASFAST, US folic acid trial, HOST), anti-oxidative stress therapy (SPACE, HOPE and ATIC), N-acetylcysteine, sevelamer (D-COR), cinacalcet (Cunningham meta-analysis), carvedilol, angiotensin converting enzyme inhibitor (FOSIDIAL), telmisartan, aspirin (HOT study re-analysis) and multidisciplinary multiple cardiovascular risk factor intervention clinics (LANDMARK). Although none of these studies could be considered conclusive, the negative trials to date should raise significant concerns about the heavy reliance of current clinical practice guidelines on extrapolation of findings from cardiovascular intervention trials in the general population. It may be that cardiovascular disease in dialysis populations is less amenable to intervention, either because of the advanced stage of CKD or because the pathogenesis of cardiovascular disease in CKD patients is different to that in the general population. Further large, well-conducted, multi-centre randomised controlled trials in this area are urgently required.

NSF: WHAT WE KNOW AND WHAT WE NEED TO KNOW: Nephrogenic Systemic Fibrosis: Recommendations for Gadolinium‐Based Contrast Use in Patients with Kidney Disease

AbstractNephrogenic systemic fibrosis is a systemic disorder characterized by widespread tissue fibrosis. Gadolinium‐based contrast (GBC) was recently noted as a possible trigger for this disease. The vast majority of cases occur in patients with ESRD receiving hemodialysis or peritoneal dialysis. However, approximately 10% of cases develop in patients with AKI (many requiring dialysis), advanced CKD stage 4, and CKD stage 5 not receiving renal replacement therapy. Recommendations to guide the use of GBC in patients with underlying kidney disease are presented. These clinical practice guidelines should be individualized and considered in consultation with the ordering physician, radiologist, and nephrologist.