Showing papers in "Nephrology Dialysis Transplantation in 2007"

EBPG on Vascular Access

Abstract: Department of Surgery, University Hospital Maastricht, The Netherlands, Nephrology, Dialysis and Intensive Care Unit; Lapeyronie University Hospital, Montpellier, France, Department of Diagnostic and Interventional Radiology, Helios Klinikum Wuppertal, University Hospital Witten/Herdecke, Germany, Medical Faculty University of Cologne, Medicine Clinic I, Hospital Merheim, Germany (retired), Department of Medicine, Division of Nephrology, Ege University Medical Faculty, Izmir, Turkey, Departement de Nephrologie JE 2411–Denutrition des Maladies Chroniques, Hopital E Herriot, France, Department of Internal Medicine, Division of Nephrology, University Hospital Maastricht, The Netherlands, Nephrology Department, Reina Sofia University Hospital, Cordoba, Spain, Division of Nephrology and Dialysis, Bolognini Hospital, Seriate, Italy, Nephrology Unit, SM Annunziata Hospital, Florence, Italy, Department of Renal Medicine, St James’s University Hospital, Leeds, UK, Department of Nephrology, Nutrition and Dietetics, Guy’s and St Thomas’ NHS Foundation Trust, London, UK (retired), Department of Medicine, Division of Nephrology, University Hospital, Wurzburg, Germany, Department of Nephrology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands and Nephrology Section, Department of Internal Medicine, University Hospital, Ghent, Belgium

EBPG Guideline on Nutrition

Abstract: Guideline 1. Prevalence of malnutrition and outcomeGuideline 2. Diagnosis and monitoring of malnutrition2.1. Diagnosis of malnutrition2.2. Monitoring and follow-up of nutritionalstatusGuideline 3. Recommendations for protein and energyintake3.1. Recommended protein intake3.2. Recommended energy intakeRecommendation 4. Recommendations for vitamins,minerals and trace elementsadministration in maintenancehaemodialysis patients.4.1. Vitamins4.2. Minerals4.3. Trace elementsGuideline 5. Treatment of malnutrition5.1. Dietary intervention5.2. Oral supplements and enteral feeding5.3. Intradialytic parenteral nutrition5.4. Anabolic agents5.5. Other interventions: daily dialysisGuideline 6. Metabolic acidosisAppendices

Adolphe Quetelet (1796–1874)—the average man and indices of obesity

Abstract: The quest for a practical index of relative body weight that began shortly after actuaries reported the increased mortality of their overweight policyholders culminated after World War II, when the relationship between weight and cardiovascular disease became the subject of epidemiological studies. It became evident then that the best index was the ratio of the weight in kilograms divided by the square of the height in meters, or the Quetelet Index described in 1832. Adolphe Quetelet (1796-1874) was a Belgian mathematician, astronomer and statistician, who developed a passionate interest in probability calculus that he applied to study human physical characteristics and social aptitudes. His pioneering cross-sectional studies of human growth led him to conclude that other than the spurts of growth after birth and during puberty, 'the weight increases as the square of the height', known as the Quetelet Index until it was termed the Body Mass Index in 1972 by Ancel Keys (1904-2004). For his application of comparative statistics to social conditions and moral issues, Quetelet is considered a founder of the social sciences. His principal work, 'A Treatise of Man and the development of his faculties' published in 1835 is considered 'one of the greatest books of the 19th century'. A tireless promoter of statistical data collection based on standard methods and definitions, Quetelet organized in 1853 the first International Statistical Congress, which launched the development of 'a uniform nomenclature of the causes of death applicable to all countries', progenitor of the current International Classification of Diseases.

Dialysis or not? A comparative survival study of patients over 75 years with chronic kidney disease stage 5

Abstract: Background. The number of elderly patients with chronic kidney disease (CKD) stage 5 is steadily increasing. Evidence is needed to inform decisionmaking for or against dialysis, especially in those patients with multiple comorbid conditions for whom dialysis may not increase survival. We therefore compared survival of elderly patients with CKD stage 5, managed either with dialysis or conservatively (without dialysis), after the management decision had been made, and explored which of several key variables were independently associated with survival. Methods. A retrospective analysis of the survival of all over 75 years with CKD stage 5 attending dedicated multidisciplinary pre-dialysis care clinics (n ¼ 129) was performed. Demographic and comorbidity data were collected on all patients. Survival was defined as the time from estimated GFR <15 ml/min to either death or study endpoint. Results. One- and two-year survival rates were 84% and 76% in the dialysis group (n ¼ 52) and 68% and 47% in the conservative group (n ¼ 77), respectively, with significantly different cumulative survival (log rank 13.6, P < 0.001). However, this survival advantage was lost in those patients with high comorbidity scores, especially when the comorbidity included ischaemic heart disease. Conclusions. In CKD stage 5 patients over 75 years, who receive specialist nephrological care early, and who follow a planned management pathway, the survival advantage of dialysis is substantially reduced by comorbidity and ischaemic heart disease in particular. Comorbidity should be a major consideration when advising elderly patients for or against dialysis.

A multi-centre evaluation of the RIFLE criteria for early acute kidney injury in critically ill patients

Abstract: BACKGROUND The Acute Dialysis Quality Initiative Working Group recently developed the RIFLE criteria, a consensus definition for acute kidney injury (AKI). We sought to evaluate the RIFLE criteria on the day of ICU admission in a large heterogenous population of critically ill patients. METHODS Retrospective interrogation of prospectively collected data from the Australian New Zealand Intensive Care Society Adult Patient Database. We evaluated 120 123 patients admitted for >/=24 h from 1 January 2000 to 31 December 2005 from 57 ICUs across Australia. RESULTS The median (IQR) age was 64.3 (50.8-75.4) years, 59.5% were male, 28.6% had co-morbid disease, 50.3% were medical admissions and the initial mean (+/-SD) APACHEII score was 16.9 (+/-7.7). According to the RIFLE criteria, on the day of admission, AKI occurred in 36.1%, with a maximum RIFLE category of Risk in 16.3%, Injury in 13.6%, and Failure 6.3%. AKI, defined by any RIFLE category, was associated with an increase in hospital mortality (OR 3.29, 95% CI 3.19-3.41, P 36% with AKI on the day of admission. For successive increases in severity of RIFLE category, there were increases in hospital mortality. The RIFLE criteria represent a simple tool for the detection and classification of AKI and for correlation with clinical outcomes.

High plasma phosphate as a risk factor for decline in renal function and mortality in pre-dialysis patients

Abstract: Background. Hyperphosphataemia is associated with increased mortality in patients with chronic kidney disease (CKD) stage IV or on dialysis. Furthermore, in animal studies, elevated plasma phosphate has been shown to be associated with an accelerated decline in renal function. The aim of this study was to determine the association of plasma phosphate with renal function loss and mortality in CKD stage IV–V predialysis patients with GFR <20 ml/min/1.73 m 2 . Methods. Incident pre-dialysis patients were included between 1999 and 2001 in the multi-centre PREPARE study, and followed until 2003 or death. Rate of decline in renal function for each patient was calculated by linear regression using the Modification of Diet in Renal Disease (MDRD) formula to estimate GFR (eGFR). Results. A total of 448 patients were included [mean (SD) age 60 (15) years, eGFR 13 (5.4) ml/min/1.73 m 2 , decline in renal function 0.38 (0.95) ml/min/month]. Phosphate concentration at baseline was 4.71 (1.16) mg/dl, calcium 9.25 (0.77) mg/dl and calcium–phosphate product 43.5 (10.9) mg 2 /dl 2 . For each mg/dl higher phosphate concentration, the mean (95% CI) decline in renal function increased with 0.154 (0.071–0.237) ml/min/month. After adjustment, this association remained [b 0.178 (0.082–0.275)]. Seven percent of the patients died. Crude mortality risk was 1.25 (0.85–1.84) per mg/dl increase in phosphate, which increased to 1.62 (1.02–2.59) after adjustment. Conclusions. High plasma phosphate is an independent risk factor for a more rapid decline in renal function and a higher mortality during the pre-dialysis phase. Plasma phosphate within the normal range is likely of vital importance in pre-dialysis patients.

The relationship between the flow of arteriovenous fistula and cardiac output in haemodialysis patients

Abstract: Background. Satisfactory haemodialysis (HD) vascular access flow (Qa) is necessary for dialysis adequacy. High Qa is postulated to increase cardiac output (CO) and cause high-output cardiac failure. Aim of the present prospective study was to evaluate the relationship between Qa of arteriovenous fistulas (AVFs) and CO in order to have a closer insight into this scarcely explored aspect of HD pathophysiology. Methods. Ninety-six patients bearing an AVF entered the study. All were evaluated a priori for the existence of cardiac failure according to the functional classification of the American College of Cardiology/American Heart Association task force. Qa and CO were measured by means of the ultrasound dilution Transonic Hemodialysis Monitor HD02. Results. The mean Qa of the 65 lower arm AVFs was 0.948 � 0.428 SD l/min, whereas that of the 31 upper arm AVFs was 1.58 � 0.553 l/min. The difference was statistically significant (P < 0.001). Ten patients were classified as having high-output cardiac failure; seven of them bore an upper arm AVF. Thus, upper arm AVFs were associated with an increased risk of highoutput cardiac failure (P < 0.04, � 2 test). A third-order polynomial regression model best fitted the relationship between Qa and CO. The analysis of the regression equation identified 0.95 and 2.2 l/min as Qa cut-off points. The receiver operating characteristic curve analysis showed that Qa values � 2.0 l/min predicted the occurrence of high-output cardiac failure more accurately than two other Qa values (sensitivity 89%, specificity 100%, curve area 0.99) and three Qa/CO ratio values (cardio-pulmonary recirculation— CPR). The better performance among the latter was that of CPR values � 20% (sensitivity 100%, specificity 74.7%, curve area 0.92). Conclusions. Our prospective study shows that the relationship between Qa of AVFs and CO is complex and a third-order polynomial regression model best fits this relationship. Furthermore, it is the first study to clearly show the high predictive power for highoutput cardiac failure occurrence of Qa cut-off values � 2.0 l/min.

Sleep quality predicts quality of life and mortality risk in haemodialysis patients: Results from the Dialysis Outcomes and Practice Patterns Study (DOPPS)

Abstract: Background. Poor sleep quality (SQ) affects many haemodialysis (HD) patients and could potentially predict their morbidity, mortality, quality of life (QOL) and patterns of medication use. Methods. Data on SQ were collected from 11 351 patients in 308 dialysis units in seven countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS) between 1996 and 2001 through a patient self-reported SQ scale, ranging from 0 (worst) to 10 (best). A score of <6 reflected poor SQ. Sleep disturbance was also assessed by self-reported daytime sleepiness, feeling drained and nocturnal awakening. Logistic and multiple linear regression were used to assess predictors of SQ and associations with QOL. Cox regression examined associations with mortality. Analyses accounted for case-mix, facility clustering and country. Results. Nearly half (49%) of patients experienced poor SQ. Mean SQ scores varied by country, ranging from 4.9 in Germany to 6.5 in Japan. Patients with poor SQ were more likely to be prescribed antihistamines, antidepressants, anti-inflammatories, narcotics, gastrointestinal (GI) medications, anti-asthmatics or hypnotics. Physical exercise at least once a week (vs < once a week) was associated with lower odds of poor SQ (AOR = 0.55-0.85, P < 0.05). Poorer SQ was associated with significantly lower mental and physical component summary (MCS/PCS) scores (MCS scores 1.9-13.2 points lower and PCS scores 1.5-7.7 points lower when SQ scores were < 10 vs 10). The RR of mortality was 16% higher for HD patients with poor SQ. Conclusions. Poor SQ is common among HD patients in DOPPS countries and is independently associated with several QOL indices, medication use patterns and mortality. Assessment and management of SQ should be an important component of care.

Acute renal failure in patients with severe sepsis and septic shock—a significant independent risk factor for mortality: results from the German Prevalence Study

Abstract: Background. Sound data about the prevalence of acute renal failure (ARF) among patients with severe sepsis and septic shock are lacking. Further, it is not known whether ARF is an independent risk factor for mortalityinsepticpatientsormerelyanindicatorofdisease severity. Methods. A prospective cross-sectional one-day prevalence study was carried out in a representative sample of German ICUs, divided into five strata ( 600 beds; university hospitals). 3877 patients were screened of whom 415 had severe sepsis and septic shock. Results. Fourteen patients (3.4%) had chronic dialysisdependent RF and were excluded from analysis. Of the remaining 401 patients, 166 (41.4%) had ARF, as defined by a rise in creatinine above twice the upper limit of normal and/or a drop in urine output to <0.5 ml/kg bodyweight. Median APACHE II score was 22 in patients with ARF and 16 in patients without ARF (p<0.0001). Patients with severe sepsis/septic shock had an overall hospital mortality of 55.2%. Hospital mortality in patients with ARF was 67.3% and without ARF 42.8% (p<0.0001). After adjustment for APACHE II score and age, ARF remained a significant independent risk factor for death [odds ratio (OR) 2.11, 95% confidence interval (CI) 1.27-3.52]. Mortality in septic patients was not associated with pre-existing, non-dialysis-dependent chronic kidney disease, whereas in dialysis-dependent patients with sepsis mortality increased to 86%.

Mineral metabolism parameters throughout chronic kidney disease stages 1–5—achievement of K/DOQI target ranges

Abstract: Background. Dialysis Outcomes and Practice Patterns Study has shown that the proportion of haemodialysis patients with adequate mineral metabolism parameters according to the Kidney Disease Outcome Quality Initiative (K/DOQI) guidelines is very low. The adequacy of such parameters in relation to the recommended ranges in patients with different chronic kidney disease (CKD) stages has not been reported. The objective of this study is to provide an in-depth description of mineral metabolism in the early stages of CKD in a European population, and to compare it with current recommendations for stages 3–5 (K/DOQI guidelines). Methods. A total of 1836 patients were classified into stages 1–5 according to K/DOQI guidelines. The following clinical and biochemical data were recorded: age, gender, CKD aetiology, presence of diabetes, serum creatinine, creatinine clearance, serum phos

EBPG guideline on haemodynamic instability

Abstract: 1. Evaluation of the patient1.1 Assessment of dry weight1.2 Measurement of blood pressure and heart rateduring dialysis1.3 Cardiac evaluation2. Lifestyle interventions2.1 Sodium restriction2.2 Food and caffeine intake during dialysis3. Factors relation to the dialysis treatment3.1 Manipulation of ultrafiltration3.1.1 Ultrafiltration profiling3.1.2 Blood volume controlled ultrafiltration3.2 Dialysate composition.3.2.1 High sodium dialysis and sodium profiling3.2.2 Dialysate buffer3.2.3 Dialysate calcium3.2.4 Other components of dialysate3.3 Dialysis membranes/contamination ofdialysate.3.4 Dialysate temperature.3.5 Convective techniques and isolatedultrafiltration.3.5.1 Convective techniques3.5.2 Isolated ultrafiltration3.6 Dialysis duration and frequency.3.7 Switch to peritoneal dialysis.4. Antihypertensive drugs and preventive medication4.1 Antihypertensive drugs4.2 Preventive vasoactive agents4.3 Carnitine5. Stratified approach to prevent IDH6. Treatment of IDH6.1 Trendelenburg position6.2 Stopping ultrafiltration6.3 Infusion fluids6.4 Protocol

Associations between vascular calcification, arterial stiffness and bone mineral density in chronic kidney disease

Abstract: Background. Vascular calcification (VC) and arterial stiffness are major contributors to cardiovascular (CV) disease inchronickidneydisease(CKD).Bothareindependentpredictors of CV mortality and are inversely correlated with bone mineral density (BMD). Few studies have addressed the extent of VC in the pre-dialysis CKD population, with associated measurements of BMD and arterial compliance. Methods. We report cross-sectional data on 48 patients with CKD (GFR 17–55 ml/min) assessing the prevalence of VC and its associations. All patients had computed tomography (CT) scans through abdominal aorta and superficial femoral arteries (SFAs) to determine VC, pulse wave velocity (PWV) using SphygmoCor device (AtCor PWV Inc., Westmead, Australia) measuring arterial stiffness, and dual-energy X-ray absorptiometry (DEXA) scans to determine BMD, as well as serum markers of renal function and mineral metabolism. Results. Patients, 71% male, 54% diabetic, had a median age64.5years.MeanestimatedGFRwas35.1 ±10ml/min. Mean PWV was 10.0 ± 4.5 m/s and mean aortic VC score was 421.5 ± 244 Hounsfield units, with 90% of subjects having some aortic VC present. In univariate linear regression analysis, aortic VC correlated positively with age (r 0.50, P < 0.001), triglycerides (r 0.47, P = 0.002) and PWV (r 0.33, P = 0.03). There was also greater VC with declining renal function (r −0.28, P = 0.05). There was no significant association between VC and serum markers of mineral metabolism, however phosphate and Ca × P correlated positively with PWV (r 0.35, P = 0.02, r 0.36, P = 0.02, respectively). There was also a positive association between PWV and triglycerides (P = 0.008), and a trend towards greater PWV with increasing age (P = 0.09). In multivariate regression analysis only increasing age and triglyceride levels were significantly associated with aortic VC and PWV. Mean spine and femoral T-scores on DEXA

EBPG guideline on dialysis strategies

Abstract: Department of Renal Medicine, St James’s University Hospital, Leeds, UK, Nephrology Department, Reina Sofia University Hospital, Cordoba, Spain, Division of Nephrology and Dialysis, Bolognini Hospital, Seriate, Italy, Department of Medicine, Division of Nephrology, Ege University Medical Faculty, Izmir, Turkey, Nephrology, Dialysis and Intensive Care Unit, Lapeyronie University Hospital, Montpellier, France, Departement de Nephrologie JE 2411 Denutrition des Maladies Chroniques, Hopital E Herriot, France, Department of Diagnostic and Interventional Radiology, Helios Klinikum Wuppertal, University Hospital Witten/Herdecke, Germany, Medical Faculty University of Cologne, Medicine Clinic I, Hospital Merheim, Germany (retired), Department of Internal Medicine, Division of Nephrology, University Hospital Maastricht, The Netherlands, Nephrology Unit, SM Annunziata Hospital, Florence, Italy, Department of Surgery, University Hospital Maastricht, The Netherlands, Department of Nephrology, Nutrition and Dietetics, Guy’s and St Thomas’ NHS Foundation Trust, London, UK (retired), Department of Medicine, Division of Nephrology, University Hospital, Wurzburg, Germany, Department of Nephrology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands and Nephrology Section, Department of Internal Medicine, University Hospital, Ghent, Belgium

Association between high ultrafiltration rates and mortality in uraemic patients on regular haemodialysis. A 5-year prospective observational multicentre study

Abstract: Background. High ultrafiltration rate on haemodialysis (HD) stresses the cardiovascular system and could have a negative effect on survival. Methods. The effect of ultrafiltration rate (UFR; ml/h/ kg BW) on mortality was prospectively evaluated in a cohort of 287 prevalent uraemic patients in regular HD from 1 January 2000 to 31 December 2005. Patients: 165 men and 122 women, age 66 � 13 years, on regular HD for at least 6 months, median: 48 months (range 6–372 months). Mean UFR was 12.7 � 3.5 ml/h/kg BW, Kt/V: 1.27 � 0.13, body weight (BW): 62 � 13 kg, PCRn: 1.11 � 0.20 g/kg/day, duration of dialysis: median 240 min (range 180–300 min), mean arterial blood pressure (MAP) 99 � 9 mm/Hg. One hundred and forty nine patients (52%) died, mainly for cardiovascular reasons (69%). Multivariate Cox regression analysis was utilized to evaluate the effect on mortality of UFR, age, sex, dialytic vintage, cardiovascular disease (CVD), diabetes, dialysis modality, duration of HD, BW, interdialytic weight gain (IWG), body mass index (BMI), MAP, pulse pressure (PP), Kt/V, PCRn. Results. Age (HR 1.06; CI 1.04–1.08; P < 0.0001), PCRn (HR 0.17, CI 0.07–0.43; P < 0.0001), diabetes (HR 1.81, CI 1.24–2.47; P ¼ 0.007), CVD (HR 1.86; CI 1.32–2.62; P ¼ 0.007) and UFR (HR 1.22; CI 1.16–1.28; P < 0.0001) were identified as factors independently correlated to survival. We estimated the discrimination potential of UFR, evaluated at baseline, in predicting death at 5 years, calculating the relative receiver operating characteristic (ROC) curves and the cut-off that minimizes the absolute difference between sensitivity and specificity. Conclusions. High UFRs are independently associated with increased mortality risk in HD patients. Better survival was observed with UFR < 12.37 ml/h/kg BW. For patients with higher UFRs, longer or more frequent dialysis sessions should be considered in order to prevent the deleterious consequences of excessive UFR.

Case-control study of gadodiamide-related nephrogenic systemic fibrosis

Abstract: Background. Nephrogenic systemic fibrosis may be caused by gadolinium (Gd)-containing magnetic resonance imaging contrast agents. Most reported cases were associated with one particular agent, gadodiamide. Yet, unidentified cofactors might explain why only a minority of renal failure patients exposed to gadodiamide develop nephrogenic systemic fibrosis. Methods. We conducted a case-control study of 19 histologically verified cases and 19 sex- and agematched controls. All subjects had chronic renal failure when exposed to gadodiamide. Clinical, biochemical and pharmacological data were retrieved from medical records.

Macrophages contribute to the development of renal fibrosis following ischaemia/reperfusion-induced acute kidney injury

Abstract: Background. Ischaemia/reperfusion is a major cause of acute kidney injury and can result in poor long-term graft function. Although most of the patients with acute kidney injury recover their renal function, significant portion of patients suffer from progressive deterioration of renal function. A persistent inflammatory response might be associated with long-term changes following acute ischaemia/reperfusion. Macrophages are known to infiltrate into tubulointersitium in animal models of chronic kidney disease. However, the role of macrophages in long-term changes after ischaemia/reperfusion remains unknown. We aimed to investigate the role of macrophages on the development of tubulointerstitial fibrosis and functional impairment following acute ischaemia/reperfusion injury by depleting macrophages with liposome clodronate. Methods. Male Sprague-Dawley rats underwent right nephrectomy and clamping of left renal vascular pedicle or sham operation. Liposome clodronate or phosphate buffered saline was administered for 8 weeks. Biochemical and histological renal damage and gene expression of various cytokines were assessed at 4 and 8 weeks after ischaemia/reperfusion. Results. Ischaemic/reperfusion injury resulted in persistent inflammation and tubulointerstital fibrosis with decreased creatinine clearance and increased urinary albumin excretion at 4 and 8 weeks. Macrophage depletion attenuated those changes. This beneficial effect was accompanied with a decrease in gene expression of inflammatory and profibrotic cytokines. Conclusions. These results suggest that macrophages play an important role in mediating persistent inflammation and fibrosis after ischaemia/reperfusion leading to a development of chronic kidney disease. Strategies targeting macrophage infiltration or activation can be useful in the prevention of development of chronic kidney disease following ischaemic injury.

Urinary Interleukin-18 is an Acute Kidney Injury Biomarker in Critically Ill Children

Abstract: Background. Urinary interleukin-18 (uIL-18) is an earlier acute kidney injury (AKI) biomarker than serum creatinine (SCr) in specific populations. In the present study, the relationship between uIL-18 and AKI was determined in a heterogeneous group of critically ill children. Methods. We studied critically ill children to determine whether uIL-18 was an early predictor of AKI. SCr was determined daily for up to 14 days from mechanical ventilation initiation and up to four serial urine specimens were collected for the uIL-18 measurement. AKI was graded by paediatric modified risk, injury, failure, loss, end-stage kidneydisease(pRIFLE)criteria.Day0wasdefinedastheday of attaining pRIFLE AKI. Results. One hundred thirty-seven children aged 6.5 ± 6.4 years (53% male) were studied. The peak levels of IL-18 correlated with the severity of AKI by pRIFLE classification (P < 0.05). In non-septic AKI patients, uIL-18 rose to a level higher than control levels 2 days prior to a significant rise in SCr. Urinary IL-18 concentration from the first urine specimen was associated with AKI development within 48 h (odds ratio = 3.5, P < 0.05) independent of the paediatric risk of mortality (PRISM II) score. Urinary IL18concentration ≥100pg/mlhadaspecificityandnegative predictive value of 81 and 83% to predict AKI development within 24 h. Urinary IL-18 ≥200 pg/ml collected within 24 h of Day 0 had a specificity and positive predictive value of 93 and 88% respectively to predict the AKI duration ≥48 h. Urinary IL-18 was associated with mortality (odds ratio =1.29,P <0.05), independent of the PRISM IIscore. Conclusions.Urinary IL-18 risesprior to SCr innon-septic critically ill children, predicts severity of AKI and is an independent predictor of mortality.

An epidemic of chronic kidney disease: fact or fiction?

Abstract: The publication of the Kidney Disease Outcomes and Quality Initiative (KDOQI) clinical practice guidelines for the evaluation, classification and stratification of chronic kidney disease (CKD) in February of 2002 was a landmark event [1]. This effort has profoundly impacted clinical practice, helped bring some order to a chaotic system of nomenclature and stimulated a resurgence of interest in this longneglected domain of clinical nephrology [2]. The nephrology community is now using a definition of the five stages of CKD, based on the presence of ‘kidney damage’ and/or reduced estimated glomerular filtration rate (eGFR) for 3 months or more [1,3]. However, it is noteworthy that three of the five stages of CKD (stages 3, 4 and 5) were arbitrarily defined and based solely on the absolute threshold of eGFR (standardized to 1.73 m2 body surface area) without any requirement for concomitant evidence of ‘kidney damage’, such as proteinuria or adjustment for age and gender [2]. These levels of eGFR, combined with the similarly arbitrary selection of a time dimension (≥3 months) for their persistence to establish ‘chronicity’, became the ‘gold-standard’ for definition of a ‘disease’. The abbreviated modification of diet in renal disease (MDRD) equation for deriving an estimate of true glomerular filtration rate (GFR) from values of serum creatinine (calibrated to the standard used to derive the formula) quickly became the most widely used method for determination of eGFR, despite its lack of validation in subjects without CKD or across a wide spectrum of ages, body habitus, diet, ethnicity and geographic location [4]. Because of inaccuracies, relative to true GFR, when eGFR is >60 ml/min/1.73 m2 reporting of specific values of eGFR was recommended only when calculated values of <60 ml/min/1.73 m2 were obtained [5]. Despite

A Comparison of GFR estimating formulae based upon s-cystatin C and s-creatinine and a combination of the two

Abstract: Background. Current recommendations (KDIGO and NKF-K/DOQI) are that patients with chronic kidney diseases (CKD) should be classified in stages 1–5 based on GFR. A serum creatinine-based prediction equation (abbreviated MDRD formula) can be used to estimate GFR (eGFR). Cystatin C has been proposed as an alternative filtration marker to creatinine. We present validation of currently used formulae for eGFR based upon s-creatinine and s-cystatin C and we compare two different methods for the determination of cystatin C. Methods. S-cystatin C and s-creatinine were measured in 644 patients referred for determination of GFR by plasma clearanceofiohexolduringtheperiod1June2004to31December 2005. S-cystatin C was determined by turbidimetry using two different reagents (DAKO A/S and Gentian A/S). The644patientsweredividedintotwogroups.Group1was used to calculate own eGFR-formulae based on s-cystatin C (Orebro-cyst). Group 2 was used to validate the formulae.Threecreatinine-basedequations(Cockcroft–Gault, MDRD and Jelliffe) and seven cystatin C-based (Larsson, Hoek,Filler,leBricon,GrubbandOrebro-cystDAKO,Gentian) were evaluated. Evaluation was done according to the recommendations by K/DOQI. Results. In the test sample (group 2) mean GFR (iohexol clearance) was 50.4 ml/min/1.73 m 2 (range 12–150)-mean s-cystatinC(DAKOAS)was1.63mg/landmeans-cystatin C (Gentian AS) 1.92 mg/l. The s-cystatin C concentrations obtained by the Gentian method were approximately 10% lower than the DAKO method within the normal GFR range but were approximately 40% higher within the low GFR range. Bias for the creatinine-based equations was in the range –0.9 to 5.9 ml/min/1.73 m 2 and for the cystatin C-based equations in range –2.4 to 7.9 ml/min/ 1.73 m 2 . Accuracy within 30% ranged from 68.6 to 80.4% and 54.0 to 82.9%, respectively. By combining both, an accuracy within 30% for 87.0% could be reached (MDRD/cystatin C by Gentian). Overall the patients were correctly classified for the different stages of CKD in 62.1–

Kidney dysfunction as a risk factor for first symptomatic stroke events in a general Japanese population--the Ohasama study.

Abstract: Background. Chronic Kidney Disease (CKD) has been shown to be a risk factor for mortality as well as for morbidity such as cardiovascular disease (CVD) in the general population. However, in the context of CVD events, there is a difference in the incidence of cardiac and stroke events between Western and Asian populations. Although a high prevalence of stroke is a characteristic feature in Japanese populations, it is unclear whether CKD constitutes a risk for stroke events. Methods. To clarify this issue, we estimated creatinine clearance and obtained dipstick tests from spot-urine samples in 1977 subjects (mean 62.9-years-old, men/ women: 731/1246) from a general Japanese population. First symptomatic stroke events and all-cause mortality were analysed according to stratification of kidney function and by positive tests for macroalbuminuria using a Cox proportional hazards regression model adjusted for possible confounding factors. Results. During the observation period (mean 7.76 years), we recorded 112 events of first symptomatic stroke and 187 deaths (58 cases due to CVD). After adjustment for all variables, we found that increases in relative hazard (RH) for the first symptomatic stroke events were associated with decreasing kidney function (RH, 3.1; 95% CI, 1.24–7.84 in Ccr 70 ml/min) and with the presence of macroalbuminuria (RH, 1.4; 95% CI, 0.80–2.41). Conclusion. Decreased kidney function increased the risk of first symptomatic stroke events in a general

Predictors of new-onset decline in kidney function in a general middle-european population.

Abstract: Background. Limited epidemiological data are available on predictors of new-onset kidney disease. Methods. In this longitudinal cohort study, 17 375 apparently healthy volunteers of the general Viennese population (46.4% women, age range 20–84 years, men 20–89 years) performed a baseline examination at some time within the study period (1990–2005) and completed a median of two follow-up examinations [interquartile range (IQR) 1 to 4]; the median follow-up period was 7 years (IQR 4 to 11). The outcome of interest was the development of kidney disease, defined as a decrease of the glomerular filtration rate (GFR) <60 ml/min/1.73 m 2 at the follow-up examinations [calculated by the abbreviated modification of diet in renal disease (MDRD) equation]. Logistic generalized estimating equations were used to analyse the relationship between the covariates and the outcome variable. Results. The following parameters [odds ratios (OR) with 95% confidence intervals] predicted new-onset kidney disease: Age (increase by 5 years), OR = 1.36 (1.34–1.40); NationalKidneyFoundation-chronickidneydisease(NKFCKD)stage1withproteinuria(+),OR =1.39(1.10–1.75); NKF-CKD stage 1 with proteinuria (≥++), OR = 2.07 (1.11–3.87);NKF-CKDstage2withproteinuria(+),OR = 2.71 (2.10–3.51); NKF-CKD stage 2 with proteinuria (≥++), OR = 3.80 (2.29–6.31); body mass index, OR = 1.04 (1.02–1.06); current-smoker, OR = 1.20 (1.01– 1.43); performing no sports, OR = 1.57 (1.27–1.95); uric acid (increase by 2 mg/dl), OR = 1.69 (1.59–1.80); HDLcholesterol(decreaseby10mg/dl),OR =1.12(1.07–1.17); hypertension stage 1, OR = 1.35 (1.08–1.67); hypertension

Mycophenolate mofetil versus cyclophosphamide for inducing remission of ANCA vasculitis with moderate renal involvement

Abstract: OBJECTIVE We performed a single-centre non-blinded clinical trial to compare the clinical efficacies of mycophenolate mofetil (MMF) and intermittent cyclophosphamide (CTX) pulse therapy as induction treatments in patients with antineutrophil cytoplasmic antibody (ANCA) vasculitis (AAV) and moderate renal involvement. METHODS Patients with active AAV and serum creatinine <500 micromol/L received either MMF treatment (MMF group) or monthly CTX pulse therapy (CTX group) for 6 months. Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). The disease activity, remission rate, renal function and adverse reactions were compared between the two groups. RESULTS A total of 35 patients (15 male, 20 female: aged 49.1 +/- 12.2 years) were enrolled, with 18 in the MMF group and 17 in the CTX group. Of the 35 patients, 28 were MPO-ANCA positive and 2 were PR3-ANCA positive. Four patients were lost to follow-up in the CTX group. At Month 6, BVAS scores were much lower in the MMF group than in the CTX group (0.2 +/- 0.89 versus 2.6 +/- 1.7, P < 0.05). In the intent-to-treatment analysis, 14 of 18 patients (77.8%) treated with MMF and 8 of 17 patients receiving CTX (47.1%) had complete remission with an absolute difference of 30.7%. Eight of 18 patients (44.4%) in the MMF group and 2 of 17 patients (15.4%) in the CTX group recovered renal function. Serum ANCA decreased to normal in 41.7% of patients in the MMF group and in 16.7% in the CTX group. Side effects in the MMF group were pneumonia (1), herpes zoster (1) and gastrointestinal symptoms (2), and in the CTX group were leukocytopenia (1), gastrointestinal distress (4) and pneumonia (1). CONCLUSION Our study suggests that MMF effectively ameliorates disease activity and considerably improves renal function in patients with AAV. Further large-scale multicentre prospective randomized controlled trials will be needed to confirm these findings.

Cannulating in haemodialysis: rope-ladder or buttonhole technique?

Abstract: Background. The standard technique for fistula cannulation, the rope-ladder technique, is problematic for patients with short fistula lengths and for patients in whom the fistula is difficult to cannulate. The buttonhole technique, cannulation of exactly the same site, offers the advantage of an easy cannulation procedure. However, it can be used only in native fistulas and cannulation is preferably executed by a 'single-sticker'. This study was conducted to compare these cannulation techniques using objective parameters. Methods. We introduced the buttonhole technique for self-cannulating home haemodialysis patients and compared it with baseline data obtained with the rope-ladder technique. Thirty-three patients with a native arteriovenous fistula were observed prospectively during 18 months on the following parameters: cannulating ease, number of bad sticks, pain, time of compression after cannula removal, bleeding, infectious complications and aneurysm formation. Results. With the buttonhole method, cannulating ease improved distinctly, which was especially favourable in patients with a short fistula vein. Reported cannulation pain did not change significantly. The incidence of bad sticks decreased significantly, as well as time of compression after cannula removal, without increased incidence of bleeding. Three patients developed a local skin infection of their buttonhole during the study, after which the disinfection routine prior to cannulation was changed. Conclusions. Compared with the rope-ladder technique, the buttonhole method offers the advantage of an easier cannulation procedure with less bad sticks, which has a special benefit for patients with limited access cannulation sites or with a fistula which is difficult to cannulate. Prolonged compression times or re-bleeding episodes did not occur, but precautions have to be taken in order to prevent infectious complications. The buttonhole method can contribute considerably to the cannulating ease of self-cannulating patients, thus providing a better quality of life.

Treatment targets in renal fibrosis

Abstract: Renal fibrosis is the principal process underlying the progression of chronic kidney disease (CKD) to endstage renal disease (ESRD). It is a relatively uniform response involving glomerulosclerosis, tubulointerstitial fibrosis and changes in renal vasculature (loss of glomerular and peritubular capillaries) (Figure 1). Of these, tubulointerstitial fibrosis has evolved as the most consistent predictor of an irreversible loss of renal function and progression to ESRD [1]. Mechanisms contributing to tubulointerstitial injury and tubular atrophy include glomerular proteinuria, chronic hypoxia, misdirected glomerular ultrafiltration, tubular protein leakage and direct toxic insults of e.g. drugs (reviewed in detail elsewhere [1–6]) . Direct or indirect tubulointerstitial injury via oxidative stress and various effector molecules trigger cellular responses like (i) tubular epithelial cell (TEC) apoptosis, (ii) activation of fibroblasts and their phenotypic switch to myofibroblasts, (iii) influx and/or proliferation of lymphocytes/macrophages, fibrocytes (the circulating fibroblast precursors), fibroblasts as well as (iv) epithelial-to-mesenchymal transition (EMT) of TECs. Renal fibrosis provides an excellent treatment target, since a large variety of pathophysiologically distinct diseases converge finally into this single process. However, we still do not have effective therapies, nor does such a therapy exist in most other types of organ fibrosis. Why? As part of the vital repair process, the regulation and redundancy in this system must be highly effective. The consequence is an amazingly complicated process that involves many cell types and mediators [1,2,4,5,7]. Not unexpectedly, monotherapeutic approaches, or even a combination of therapies, fail to completely stop the progression of renal fibrosis [8–10]. In addition, not all combination therapies can be additive [11]. When identifying new targets or validating potential therapeutic options, we are confronted with several problems:

Association between the metabolic syndrome and chronic kidney disease in Chinese adults

Abstract: Background. The metabolic syndrome is a common risk factor for cardiovascular and chronic kidney disease (CKD) in Western populations. We examined the relationship between the metabolic syndrome and risk of CKD in Chinese adults.Methods. A cross-sectional survey was conducted in a nationally representative sample of 15 160 Chinese adults aged 35-74 years. The metabolic syndrome was defined as the presence of three or more of the following risk factors: elevated blood pressure, low high density lipoprotein (HDL)-cholesterol, high triglycerides, elevated plasma glucose and abdominal obesity. CKD was defined as an estimated glomerular filtration rate <60 ml/min/1.73 m 2 and elevated serum creatinine was defined as ≥1.14 mg/dl in men and ≥0.97 mg/dl in women (≥95th percentile of serum creatinine in Chinese men and women aged 35-44 years without hypertension or diabetes, respectively).Results. The multivariate-adjusted odds ratios [95% confidence interval (CI)] of CKD and elevated serum creatinine in participants with compared to those without the metabolic syndrome were 1.64 (1.16, 2.32) and 1.36 (1.07, 1.73), respectively. Compared to participants without any components of the metabolic syndrome, the multivariate-adjusted odds ratios (95% CI) of CKD were 1.51 (1.02, 2.23), 1.50 (0.97, 2.32), 2.13 (1.30, 3.50) and 2.72 (1.50, 4.93) for those with 1, 2, 3, and 4 or 5 components, respectively. The corresponding multivariate-adjusted odds ratios (95% CI) of elevated serum creatinine were 1.11 (0.88, 1.40), 1.39 (1.07, 2.04), 1.47 (1.06, 2.04) and 2.00 (1.32, 3.03), respectively.Conclusions. These findings suggest that the metabolic syndrome might be an important risk factor for CKD in Chinese adults.

Social support predicts survival in dialysis patients

Abstract: Background. Social support is a consistent predictor of survival, as evidenced in empirical studies in patients with cancer or cardiovascular disease. In the area of renal diseases, this topic has not yet been studied extensively. This study, therefore, aimed to investigate the association between social support and survival for patients on dialysis. Methods. Between December 1998 and January 2002, 528 incident haemodialysis (HD) and peritoneal dialysis (PD) patients from multiple centres in The Netherlands were consecutively recruited as part of the NECOSAD-2 study. Patients completed the Social Support List (SSL) at 3 months after the start of dialysis. The SSL measured two aspects of social support: interaction and discrepancy. Cox regression analysis was used to estimate all-cause mortality risk from baseline till censor date on 1 January 2005. Results. Perceiving a discrepancy between expected and received social support was associated with increased mortality: social companionship (RRadj: 1.06, 95% CI: 1.00–1.13), daily emotional support (RRadj: 1.10, 95% CI: 1.02–1.18), and total support (RRadj: 1.02, 95% CI: 1.00–1.04). This association was similar for PD and HD patients. Social support (interaction) was not associated with survival, neither in the whole sample nor when stratified by therapy modality. Conclusions. These results point to the importance of psychosocial risk factors for mortality in patients on dialysis. More efforts are needed to improve support for these patients.

Heart rate variability (HRV) in kidney failure: measurement and consequences of reduced HRV

Abstract: A common cause of death in end-stage renal disease (ESRD) patients on dialysis is sudden cardiac death (SCD). Compared to the general population, the percentage of cardiovascular deaths that are attributed to SCD is higher in patients treated by dialysis. While coronary artery disease (CAD) is the predominant cause of SCD in dialysis patients, reduced heart rate variability (HRV) may play a role in the higher risk of SCD among other risk factors. HRV refers to beat-to-beat alterations in heart rate as measured by periodic variation in the R-R interval. HRV provides a non-invasive method for investigating autonomic input into the heart. It quantifies the amount by which the R-R interval or heart rate changes from one cardiac cycle to the next. The autonomic nervous system transmits impulses from the central nervous system to peripheral organs and is responsible for controlling the heart rate, blood pressure and respiratory activity. In normal individuals, without cardiac disease, the heart rate has a high degree of beat-to-beat variability. HRV fluctuates with respiration: it increases with inspiration and decreases with expiration and is primarily mediated by parasympathetic activity. HRV has been used to evaluate and quantify the cardiac risk associated with a variety of conditions including cardiac disorders, stroke, multiple sclerosis and diabetes. In this narrative review, we will examine the association between HRV and SCD. This report explains the measurement of HRV and the consequences of reduced HRV in the general population and dialysis patients. Lastly, this review will outline the possible use of HRV as a clinical predictor for SCD in the dialysis population. The current understanding of SCD based on HRV findings among the ESRD population support the use of more aggressive treatment of CAD; greater use of angiotensin converting enzyme inhibitor (ACE-i)/angiotensin receptor blockers (ARBs) and beta-blockers and more frequent and/or nocturnal haemodialysis to improve the survival of a patient with kidney failure.

The long-term outcome of 93 patients with proliferative lupus nephritis

Abstract: Background. Few data are available about the verylong-term outcome of patients with proliferative lupusnephritis.Methods. Ninety-three Italian patients with biopsy-proven proliferative lupus nephritis (15 with class III, 9with class IIIþV, 64 with class IV and 5 with classIVþV) followed for a median follow-up of 15 years ina single renal unit were considered for this observa-tional study. Patients were treated with an inductiontreatment consisting of high doses of corticosteroidsplus immunosuppressive agents in the more severecases. This treatment was repeated in the event of arenal flare. Then corticosteroids and immunosuppres-sive agents were reduced to the minimal effective dosefor maintenance.Results. Renal survival including death was 97% at10 years and 82% at 20 years. At the last follow-upvisit, 59 patients were in complete renal remission,18 were in partial renal remission, four patients hadchronic renal insufficiency, six had entered end-stagerenal disease and six patients had died.At multivariate analysis the lack of achievement ofcomplete renal remission and the occurrence ofnephritic flares were significantly correlated bothwith the risk of doubling plasma creatinine and deathor dialysis. Those patients who entered complete renalremission had significantly less probability of develop-ing nephritic flares.Conclusion. The long-term prognosis of Caucasianpatients with proliferative lupus nephritis may bebetter than usually thought. Favorable factors forgood long-term outcome are the achievement ofcomplete renal remission, the absence of nephriticflares and their complete reversibility after therapy.Keywords: immunosuppressive therapy; long-termrenal survival; lupus nephritis

Human mesenchymal stem cells inhibit antibody production induced in vitro by allostimulation.

Abstract: Background Antibodies directed against alloantigens are implicated in the pathogenesis of several immune reactions complicating transplantation, including humoral rejection after solid organ transplantation. Mesenchymal stem cells (MSCs) have immunomodulatory capacity, since in vivo they may prolong skin graft survival in the animal model and can rescue patients with life-threatening graft-versus-host disease. Methods To investigate whether MSCs exert an inhibitory effect on antibody production during allostimulation, we stimulated peripheral blood mononuclear cells, obtained from healthy controls or sensitized patients undergoing dialysis for end-stage renal failure, in mixed lymphocyte culture (MLC), and evaluated immunoglobulin production either in the absence or in the presence of third-party allogeneic MSCs. We also evaluated the effect of MSCs on B-cell allostimulation performed adding to MLC a polyclonal stimulus delivered by an agonist anti-CD40 monoclonal antibody. Results We found that the addition of MSCs at the beginning of MLC considerably inhibited immunoglobulin production in standard MLC, irrespective of the MSC dose employed. Conversely, immunoglobulin secretion induced by direct CD40-CD40L binding was not significantly inhibited. Furthermore, we demonstrated, in one sensitized patient, that secretion of donor-specific anti-HLA class I antibodies detected both in baseline serum and in the supernatant of control MLC was inhibited by the addition of MSCs. Mechanistically, the addition of MSCs induced a striking decrease of IL-5 production in the cultures. Conclusions Our findings suggest that third-party MSC are able to suppress allo-specific antibody production in vitro, and may therefore help overcome a positive cross-match in sensitized transplant recipients.