Showing papers in "Nephrology Dialysis Transplantation in 2008"

Association between delayed graft function and allograft and patient survival: a systematic review and meta-analysis

Abstract: Background Delayed graft function (DGF) is a common complication of renal transplantation. The short-term consequences of DGF are well known, but the long-term relationship between DGF and patient and graft survival is controversial in the published literature. We conducted a systematic review and meta-analysis to precisely estimate these relationships. Methods We performed a literature search for original studies published through March 2007 pertaining to long-term (>6 months) outcomes of DGF. The primary outcome was graft survival. Secondary outcomes were patient survival, acute rejection and kidney function. Results When compared to patients without DGF, patients with DGF had a 41% increased risk of graft loss (RR 1.41, 95% CI 1.27-1.56) at 3.2 years of follow-up. There was no significant relationship between DGF and patient survival at 5 years (RR 1.14, 95% CI 0.94-1.39). The mean creatinine in the non-DGF group was 1.6 mg/dl. Patients with DGF had a higher mean serum creatinine (0.66 mg/dl, 95% CI 0.57-0.74) compared to patients without DGF at 3.5 years of follow-up. DGF was associated with a 38% relative increase in the risk of acute rejection (RR 1.38, 95% CI 1.29-1.47). Conclusion The results of this meta-analysis emphasize and quantify the long-term detrimental association between DGF and important graft outcomes like graft survival, acute rejection and renal function. Efforts to prevent and treat DGF should be aggressively investigated in order to improve graft survival given the deficit in the number of kidney donors.

Vascular access use and outcomes: an international perspective from the dialysis outcomes and practice patterns study

Abstract: Background. A well-functioning vascular access (VA) is essential to efficient dialysis therapy. Guidelines have been implemented improving care, yet access use varies widely across countries and VA complications remain a problem. This study took advantage of the unique opportunity to utilize data from the Dialysis Outcomes and Practice Patterns Study (DOPPS) to examine international trends in VA use and trends in patient characteristics and practices associated with VA use from 1996 to 2007. DOPPS is a prospective, observational study of haemodialysis (HD) practices and patient outcomes at >300 HD units from 12 countries and has collected data thus far from >35 000 randomly selected patients. Methods. VA data were collected for each patient at study entry (1996–2007). Practice pattern data from the facility medical director, nurse manager and VA surgeon were also analysed. Results. Since 2005, a native arteriovenous fistula (AVF) was used by 67–91% of prevalent patients in Japan, Italy, Germany, France, Spain, the UK, Australia and New Zealand, and 50–59% in Belgium, Sweden and Canada. From 1996 to 2007, AVF use rose from 24% to 47% in the USA but declined in Italy, Germany and Spain. Moreover, graft use fell by 50% in the USA from 58% use in 1996 to 28% by 2007. Across three phases of data collection, patients consistently were less likely to use an AVF versus other VA types if female, of older age, having greater body mass index, diabetes, peripheral vascular disease or recurrent cellulitis/gangrene. In addition, countries with a greater prevalence of diabetes in HD patients had a significantly lower percentage of patients using an AVF. Despite poorer outcomes for central vein catheters, catheter use rose 1.5- to 3-fold among prevalent patients in many countries from 1996 to 2007, even among non-diabetic patients 18–70 years old. Furthermore, 58–73% of patients new to end-stage renal disease (ESRD) used a catheter for the initiation of HD in five countries despite 60–79% of patients having been seen by a nephrologist >4 months prior to ESRD. Patients were significantly (P < 0.05) less likely to start dialysis with a permanent VA if treated in a faciity that (1) had a longer time from referral to access surgery evaluation or from evaluation to access creation and (2) had longer time from access creation until first AVF cannulation. The median time from referral until access creation varied from 5–6 days in Italy, Japan and Germany to 40–43 days in the UK and Canada. Compared to patients using an AVF, patients with a catheter displayed significantly lower mean Kt/V levels. Conclusions. Most countries meet the contemporary National Kidney Foundation's Kidney Disease Outcomes Quality Initiative goal for AVF use; however, there is still a wide variation in VA preference. Delays between the creation and cannulation must be improved to enhance the chances of a future permanent VA. Native arteriovenous fistula is the VA of choice ensuring dialysis adequacy and better patient outcomes. Graft is, however, a better alternative than catheter for patients where the creation of an attempted AVF failed or could not be created for different reasons.

A comparison of the RIFLE and AKIN criteria for acute kidney injury in critically ill patients

Abstract: Background. The Acute Dialysis Quality Initiative Group has published a consensus definition/classification system for acute kidney injury (AKI) termed the RIFLE criteria. The Acute Kidney Injury Network (AKIN) group has recently proposed modifications to this system. It is currently unknown whether there are advantages between these criteria. Methods. We interrogated the Australian New Zealand Intensive Care Society (ANZICS) Adult Patient Database (APD) for all adult admissions to 57 ICUs from 1 January 2000 to 31 December 2005. We compared the performance of the RIFLE and AKIN criteria for diagnosis and classification of AKI and for robustness of hospital mortality. Results. We included 120 123 critically ill patients, of which 27.8% had a primary diagnosis of sepsis. We found only small differences (<1%) in the number of patients classified as having some degree of kidney injury using either the AKIN or RIFLE definition or classification systems. AKIN slightly increased the number of patients classified as Stage I injury (category R in RIFLE) (from 16.2 to 18.1%) but decreased the number of patients classified as having Stage II injury (category I in RIFLE) (13.6% versus 10.1%). The area under the ROC curve for hospital mortality was 0.66 for RIFLE and 0.67 for AKIN in all patients and it was 0.65 for both in septic patients. Conclusion. Compared to the RIFLE criteria, the AKIN criteriadonotmateriallyimprovethesensitivity,robustness and predictive ability of the definition and classification of AKI in the first 24 h after admission to ICU.

Costs and outcomes of acute kidney injury (AKI) following cardiac surgery

Abstract: Background. Acute kidney injury (AKI) is a recognized complication of cardiac surgery; however, the variability in costs and outcomes reported are due, in part, to different criteria for diagnosing and classifying AKI. We determined costs, resource use and mortality rate of patients. We used the serum creatinine component of the RIFLE system to classify AKI. Methods.Aretrospectivecohortstudywasconductedfrom theelectronicdatarepositoryattheUniversityofPittsburgh Medical Center of patients who underwent cardiac surgery and had an elevation (≥0.5mg/dl) of serum creatinine postoperatively. Data were compared to age- and APACHE IIImatched controls. Cost, mortality and resource use of AKI patients were determined postoperatively for each of the three RIFLE classes on the basis of changes in serum creatinine. Results. Of the 3741 admissions, 258 (6.9%) had AKI and wereclassifiedasRIFLE-R138(3.7%),RIFLE-I70(1.9%) andRIFLE-F50(1.3%).Totalanddepartmentallevelcosts, length of stay (LOS) and requirement for renal replacement therapy (RRT) were higher in AKI patients compared to controls. Statistically significant differences in all costs, mortality rate and requirement for RRT were seen in the patients stratified into RIFLE-R, RIFLE-I and RIFLE-F. Even patients with the smallest change in serum creatinine, namely RIFLE-R, had a 2.2-fold greater mortality, a 1.6fold increase in ICU LOS and 1.6-fold increase in total postoperative costs compared to controls. Discussion. Costs, LOS and mortality are higher in postoperative cardiac surgery patients who develop AKI using RIFLE criteria, and these values increase as AKI severity worsens.

Marked variation in the definition and diagnosis of delayed graft function: a systematic review

Abstract: Background. The term delayed graft function (DGF) is commonly used to describe the need for dialysis after receiving a kidney transplant. DGF increases morbidity after transplantation, prolongs hospitalization and may lead to prematuregraftfailure.VariousdefinitionsofDGFareused in the literature without a uniformly accepted technique to identify DGF. Methods. We performed a systematic review of the literaturetoidentifyallofthedifferentdefinitionsanddiagnostic techniques to identify DGF. Results. We identified 18 unique definitions for DGF and 10 diagnostic techniques to identify DGF. Conclusions. The utilization of heterogeneous clinical criteria to define DGF has certain limitations. It will lead to delayedandsometimesinaccuratediagnosisofDGF.Hence a diagnostic test that identifies DGF reliably and early is necessary. Heterogeneity, in the definitions used for DGF, hinders the evolution of a diagnostic technique to identify DGF, which requires a gold standard definition. We are in need of a new definition that is uniformly accepted across the kidney transplant community. The new definition will behelpfulinpromotingbettercommunicationamongtransplant professionals and aids in comparing clinical studies of diagnostic techniques to identify DGF and thus may facilitate clinical trials of interventions for the treatment of DGF.

Towards improved cardiovascular management: the necessity of combining blood pressure and fluid overload

Abstract: BACKGROUND Hypertension and fluid overload (FO) are well-recognized problems in the chronic kidney disease (CKD) population. While the prevalence of hypertension is well documented, little is known about the severity of FO in this population. METHODS A new bioimpedance spectroscopy device (BCM-Body Composition Monitor) was selected that allows quantitative determination of the deviation in hydration status from normal ranges (DeltaHS). Pre-dialysis systolic blood pressure (BPsys) and DeltaHS was analysed in 500 haemodialysis patients from eight dialysis centres. A graphical tool (HRP-hydration reference plot) was devised allowing DeltaHS to be combined with measurements of BPsys enabling comparison with a matched healthy population (n = 1244). RESULTS Nineteen percent of patients (n = 95) were found to have normal BPsys and DeltaHS in the normal range. Approximately one-third of patients (n = 133) exhibited reasonable control of BPsys and fluids (BPsys 150 mmHg) with a concomitant DeltaHS >2.5 L (possible volume-dependent hypertension). In contrast, 13% of patients (n = 69) were hypertensive with DeltaHS <1.1 L (possible essential hypertension). In 10% of patients (n = 52), BPsys <140 mmHg was recorded despite DeltaHS exceeding 2.5 L. CONCLUSION Our study illustrated the wide variability in BPsys regardless of the degree of DeltaHS. The HRP provides an invaluable tool for classifying patients in terms of BPsys and DeltaHS and the proximity of these parameters to reference ranges. This represents an important step towards more objective choice of strategies for the optimal treatment of hypertension and FO. Further studies are required to assess the prognostic and therapeutic role of the HRP.

Association of serum bicarbonate levels with mortality in patients with non-dialysis-dependent CKD.

Abstract: Background. Metabolic acidosis, usually manifested by low serum bicarbonate level, is common in chronic kidney disease (CKD) and appears to be associated with higher mortality in dialysis patients. It is not known whether a similar association is present in patients with non-dialysis-dependent CKD (NDD-CKD). Methods. We used multivariable-adjusted Cox models to examine the association between baseline and time-variable serum bicarbonate (measured as total CO2) with the outcomes of all-cause mortality and the composite of pre-dialysis mortality or end-stage renal disease in 1240 male patients with moderate and advanced NDD-CKD. Results. Serum bicarbonate showed a significant U-shaped association with all-cause mortality, with the highest mortality rate observed in patients with baseline serum bicarbonate levels <22 mmol/L [multivariable-adjusted hazard ratio (95% confidence interval) for patients with serum bicarbonate <22 mmol/L versus ≥22 mmol/L: 1.33 (1.05–1.69), P = 0.02] and the lowest mortality observed in patients with baseline serum bicarbonate of 26–29 mmol/L. The associations between lower serum bicarbonate level and mortality were more accentuated in subgroups of patients with better nutritional status and lower inflammation. Conclusions. Both lower and higher serum bicarbonates are associated with increased all-cause mortality in patients with moderate and advanced NDD-CKD. Clinical trials are needed to determine if therapeutic interventions aimed at optimizing serum bicarbonate can result in improved outcomes in this population.

Peripheral vascular calcification in long-haemodialysis patients: associated factors and survival consequences

Abstract: Background. Vascular calcifications (VCs) are frequently observedinchronickidneydisease(CKD)andhaemodialysis(HD)patients.Theyhavebeenassociatedwithnumerous factors, particularly hyperphosphataemia, excess calcium load, hypertension and increased mortality rate. The purpose of this study is to measure VCs in long-HD patients with good blood pressure and phosphate control, with the occasionaluseofsevelamer,usingaplainradiologicalscore to identify the associated factors and effects on the 1-year survival rate. Methods. We studied HD patients from one centre using a semi-quantitativescorerangingfrom0to3accordingtothe severity and extent of VCs. The following patients’ characteristics were compared according to their VC scores: medical history, treatments, blood pressure, standard biological data, fibroblast growth factor (FGF) 23, osteoprotegerin (OPG), whole PTH, β-crosslaps, bone alkaline phosphatases and bone mineral density scores. One-year survival analyses were also performed. Results. Among the 250 HD patients of the centre, 161 were studied; the mean age was 67.2 ± 13 years, 45% of the subjects were females, 35% were diabetics, and they had been on dialysis for between 1–486 months (median: 45 months) with a 3 × 5–3 × 8 h dialysis schedule using 1.5 mmol/l dialysate calcium and providing a mean 2.25 ± 0.5 Kt/V. Only 17% of the patients were free from VCs and 11% had severe VCs. The factors associated with VCs were classified into ‘classic’ (age, diabetes, male gender, tobacco use, inflammation, more frequent warfarin treatment and peripheral vascular and cardiac diseases) and ‘non-traditional’ (higher FGF-23 and OPG serum levels, low albumin serum levels and low alfacalcidol and CaCO3 use). In logistic regression, only age, diabetes and FGF-23 serum levels were associated with VC scores of 2 and 3. The patients with a score of 3 had a higher 1-year mortality rate (RR 2.1; P = 0.01) as compared to patients with a 0 score.

Chronic inflammation and mortality in haemodialysis: effect of different renal replacement therapies. Results from the RISCAVID study

Abstract: Background. The ‘RISchio CArdiovascolare nei pazienti afferenti all’ Area Vasta In Dialisi’ (RISCAVID) study is an observational and prospective trial including the whole chronic haemodialysis (HD) population in the northwest part of Tuscany (1.235 million people). The aim of the study was to elucidate the relevance of traditional and nontraditional risk factors of mortality and morbidity in HD patients as well as the impact of different HD modalities. Methods. A total of 757 HD patients (mean age 66 ± 14 years, mean dialytic age 70 ± 76 months, diabetes 19%) were prospectively followed up for 30 months and all-cause mortality, cardiovascular (CV) mortality and non-fatal CV events (acute myocardial infarction and stroke) were registered. At the time of the enrolment, demographic, clinical and laboratory data of the whole population were entered into a centralized database. Serum albumin, high-sensitive C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-8 (IL-8) were centrally determined at the start of the study. Patients were stratified into three groups according to the HD modality: standard bicarbonate HD (BHD) (n = 424), haemodiafiltration (HDF) with sterile bags (n = 204) and online HDF (n = 129). The Cox proportional hazards regression assessed adjusted differences in CV morbidity and mortality risk; a multivariate analysis was also performed.

Incidence, prevalence and mortality trends of dialysis end-stage renal disease in Taiwan from 1990 to 2001: the impact of national health insurance

Abstract: Background Incident and prevalent (I&P) rates in dialysis end-stage renal disease (ESRD) patients in Taiwan increased rapidly following the launch of National Health Insurance (NHI) in 1995. Our aim was to explore the impact of NHI on the status and trends of ESRD epidemiology in Taiwan. Methods This study was conducted using retrospective cohort analysis of data collected from the Taiwan national dialysis registry. Results From 1990 to 2001, I&P rates of ESRD patients increased 2.6 times from 126 to 331 per million populations (pmp) and 3.46 times from 382 to 1322 pmp, respectively. Increasing ESRD was seen in patients who were middle-aged, elderly and who had diabetic nephropathy as their primary renal disease. The mean age of I&P patients increased by 7.2 years and 7.1 years, respectively. All of these parameters increased markedly in 1995, the year of NHI implementation. First-year mortality decreased to 7.8 per 1000 patient-months in 1994, and then increased to 18.0 in 2001. The cumulative survival rate of the elderly subgroup (age >65) in the incident 1990-1994 cohort was greater than in the 1995-1999 cohort. These data indicated that NHI implementation significantly influenced the inflow and the mortality of ESRD patients. Conclusion In addition to presenting ESRD epidemiology in Taiwan, this study demonstrated that NHI implementation stimulated the growth of treated ESRD populations. Preventive plans mounted against chronic kidney diseases will be essential to reduce the growth of ESRD patient numbers and consequent economic burdens.

The cost of renal dialysis in a UK setting—a multicentre study

Abstract: Background. The UK National Health Service (NHS) will fund renal services using Payment by Results (PbR), from 2009. Central to the success of PbR will be the creation of tariffs that reflect the true cost of medical services. We have therefore estimated the cost of different dialysis modalities in the Cardiff and Vale NHS Trust and six other hospitals in the UK. Methods. We used semi-structured interviews with nephrologists, head nurses and business managers to identify the steps involved in delivering the different dialysis modalities. We assigned costs to these using published figures or suppliers’ published price lists. The study used mixed costing methods. Dialysis costs were estimated by a combination of microcosting and a top-down approach. Where we did not have access to detailed accounts, we applied values for Cardiff. Results. The most efficient modalities were automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD), the mean annual costs of which were £21 655 and £15 570, respectively. Hospital-based haemodialysis (HD) cost £35 023 per annum and satelliteunit-based HD cost £32 669. The cost of home-based HD was £20 764 per year (based on data from only one unit). ThemaincostdriversforPDwerethecostsofsolutionsand management of anaemia. For HD they were costs of disposables, nursing, the overheads associated with running the unit and management of anaemia. Conclusions. Renal tariffs for PbR need to reflect the true costofdialysisprovisionifchoicesaboutmodalitiesarenot tobe influenced by erroneous estimatesof cost. Knowledge of the true costs of modalities will also maximize the number of established renal failure patients treated by dialysis within the limited funds available from the NHS.

Anaemia management in patients with chronic kidney disease: a position statement by the Anaemia Working Group of European Renal Best Practice (ERBP)

Abstract: 1Department of Nephrology, Dialysis and Renal Transplantation, ‘A. Manzoni’ Hospital, Lecco, Italy, 2Department of Nephrology, Dialysis and Transplantation, C. I. Parhon University Hospital, University of Medicine Gr. T. Popa, Iasi, Romania, 3Department of Nephrology and Hypertension, University of Erlangen-Nuremberg, Nuremberg, Germany, 4Department of Nephrology, Endocrinology and Metabolic Diseases, Medical University of Silesia, Katowice, Francuska, Poland and 5Nephrology Section, University Hospital, Ghent, Belgium

Indoxyl sulphate promotes aortic calcification with expression of osteoblast-specific proteins in hypertensive rats.

Abstract: Background Stage 5 chronic kidney disease (CKD) is associated with enhanced aortic calcification. The aim of this study was to determine if the administration of indoxyl sulphate (IS), a uraemic toxin, stimulates the progression of aortic calcification. Methods The rat groups consisted of (i) Dahl salt-resistant normotensive rats (DR) with intake of 0.3% salt, (ii) Dahl salt-sensitive hypertensive rats (DS) with intake of 2.0% salt and (iii) Dahl salt-sensitive hypertensive IS-administered rats (DS-IS) with intake of 2.0% salt and 200 mg/kg of IS in water. After 30 weeks, their aortic and kidney tissues were excised for histological and immunohistochemical analyses. Results Severe vascular calcification was observed by von Kossa staining in the arcuate aorta of all the DS-IS rats, but hardly in DS or DR rats. Immunohistochemistry demonstrated that osteopontin, core binding factor 1 (Cbfal), alkaline phosphatase (ALP), osteocalcin, IS and organic anion transporter (OAT) 3 were colocalized in the cells embedded in the aortic calcification area of DS-IS rats. Wall thickness was significantly increased in arcuate, thoracic and abdominal aortas of DS-IS rats compared with DS and DR rats. DS-IS rats showed significantly increased extent of glomerular hypertrophy, mesangial expansion, Masson's trichrome-positive tubulointerstitial area and glomerular and tubulointerstitial expression of transforming growth factor-ssl as compared with DS and DR rats. Conclusions IS induced aortic calcification with expression of osteoblast-specific proteins and aortic wall thickening. IS is not only a nephrotoxin but also a vascular toxin, and may contribute to the progression of aortic calcification in stage 5 CKD patients.

Pregnancy in women with pre-existing lupus nephritis: predictors of fetal and maternal outcome.

Abstract: Background. Only few data are available on pregnancy in patients with lupus nephritis (LN) diagnosed before conception. The aim of this study was to identify the risk factors for complicated pregnancy in women with pre-existing LN. Methods. In a multicentre study, we collected data on 113 pregnancies occurring in 81 women with pre-existing biopsy-proven LN. Primary outcomes were fetal loss including perinatal death and renal flares during and 12 months after pregnancy. Univariate and logistic regression analyses were used to identify predictors of outcomes. Results. Renal biopsy performed 7.2 ± 4.9 years before pregnancy showed the following WHO classes: 6 patients in II, 8 in III, 48 in IV and 19 in V At conception, most patients were in complete (49%) or partial (27%) remission. There were nine spontaneous abortions, one stillbirth and five neonatal deaths. Thirty-one deliveries were preterm. Birth weight was <2500 g in 34 newborns. During pregnancy or after delivery, there were 34 renal flares, most of which (20) were reversible. Three patients had a progressive decline of glomerular filtration rate (one on dialysis). At logistic regression analysis, the pregnancy outcome was predicted by hypocomplementaemia at conception (RR 19.02; 90% CI 4.58-78.96) and aspirin during pregnancy (RR 0.11; 90% CI 0.03-0.38). Renal flare was predicted by renal status (partial remission RR 3.0; 90% CI 1.23-7.34, nonremission RR 9.0; 90% CI 3.59-22.57). Conclusions. Pregnancy can be successful in most women with pre-existing LN, even for those with a severe renal involvement at onset. Renal flares during and after pregnancy are not uncommon and can be predicted by renal status assessed before pregnancy. Normocomplementaemia and low-dose aspirin therapy during pregnancy are independent predictors of a favourable fetal outcome.

Nephropathy in males and females with Fabry disease: cross-sectional description of patients before treatment with enzyme replacement therapy

Abstract: Background. Fabry disease, an X-linked genetic disorder with deficient α-galactosidase A activity, is characterized by kidney disease and kidney failure. The spectrum of kidney disease has not been well defined, especially in female patients. Methods. We did a cross-sectional retrospective analysis of natural history of glomerular filtration rate (estimated— eGFR), albuminuria and proteinuria in 1262 adult patients (585 males, 677 females) from the Fabry Registry. Results. Twenty-eight percent of males (age 20–79 years) and 13% of females (age 20–82 years) had chronic kidney disease (CKD) with eGFR 300 mg/24 h) was demonstrated in 43 and 26% of males and females with CKD stage 1, respectively, and the proportions were higher with more severe kidney involvement. However, 11% of males and 28% of females with eGFR 30 mg/24 h. Systemic blood pressure was ≥130/80 mmHg in 48% and 67% of patients with eGFR ≥ and <60 ml/min/1.73 m 2 , respectively, with no significant differences between males and females. Proteinuria values were significantly correlated with systolic blood pressure in both sexes. Conclusions. Kidney involvement in Fabry disease is more prevalent and heterogeneous than previously reported. Proteinuria is an early complication, but may not be overt in patients with advanced kidney disease. This analysis, which includes more females than males, confirms that a significant proportion of females suffer moderate to severe kidney involvement in Fabry disease.

Prevalence of albuminuria and renal insufficiency and associated clinical factors in type 2 diabetes: the Japan Diabetes Clinical Data Management study (JDDM15)

Abstract: Background. Microalbuminuria is widely accepted as the first clinical sign of diabetic nephropathy. However, normoalbuminuric type 2 diabetic patients who have renal insufficiency (RI), i.e. low estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 , exist. We explored the prevalence of such patients and associated clinical factors. Methods. We investigated the distribution of patients when stratified by albuminuria stages and chronic kidney disease (CKD) stages in a large-scale population of Japanese type 2 diabetic patients (N = 3297), and the common and independent factors for albuminuria and low eGFR. Results. The proportion of subjects with low eGFR was 15.3% (506/3297), which was 11.4% among those with normoalbuminuria (NA) (262/2298), 14.9% among those with microalbuminuria (105/705) and 47.3% among those with macroalbuminuria (139/294). There were 262 patientswithNAandloweGFR,and63.4%ofthemhadneither diabetic retinopathy nor neuropathy. They were older and included a higher proportion of women and patients with hypertension, hyperlipidaemia and cardiovascular disease (CVD), and fewer smokers compared with those with NA and preserved eGFR. Multiple logistic regression analysis revealed that factors commonly associated with RI and albuminuria were hypertension, CVD and proliferative retinopathy. Factors independently associated with RI were age, duration of diabetes, A1C (negative), hyperlipidaemia, smoking (negative) and macroalbuminuria, whereas those associated with albuminuria were male sex, BMI, A1C, simple retinopathy and RI. Conclusions. A significant proportion of type 2 diabetic patients have normoalbuminuric RI. Renal disease in type Correspondence and offprint requests to: Hiroki Yokoyama, Jiyugaoka Medical Clinic, Internal Medicine, West 6, South 6-4-3, Obihiro 0800016, Japan. Tel: +81-155-20-5011; Fax: +81-155-20-5015; E-mail: hiroki@m2.octv.ne.jp 2 diabetes could be heterogeneous, implying the possibility of involvement of renal atherosclerosis and lipid toxicity.

The benefit of salt restriction in the treatment of end-stage renal disease by haemodialysis

Abstract: Background. Most haemodialysis (HD) centres use antihypertensive drugs for the management of hypertension, whereas some centres apply dietary salt restriction strategy. In this retrospective cross-sectional study, we assessed the effectiveness and cardiac consequences of these two strategies. Methods. We enrolled all patients from two dialysis centres, who had been on a standard HD programme at the same centre for at least 1 year. All patients underwent echocardiographic evaluation. Clinical data were obtained from patients’ charts. Centre A (n = 190) practiced ‘salt restriction’ strategy and Centre B (n = 204) practiced antihypertensive-based strategy. Salt restriction was defined as managing high blood pressure (BP) via lowering dry weight by strict salt restriction and insistent ultrafiltration without using anti-hypertensive drugs. Results. There was no difference regarding age, gender, diabetes, history of cardiovascular disease and efficiency of dialysis between centres. Antihypertensive drugs were used in 7% of the patients in Centre A and 42% in Centre B( P < 0.01); interdialytic weight gain was significantly lower in Centre A (2.29 ± 0.83 kgversus 3.31 ± 1.12 kg, P < 0.001). Mean systolic and diastolic blood pressures were similar in the two centres. However, Centre A had lower left ventricular (LV) mass (indexed for height 2.7 :5 9 ± 16 versus 74 ± 27 g/m 2.7 , P < 0.0001). The frequency of LV hypertrophy was lower in Centre A (74% versus 88%, P < 0.001). Diastolic and systolic functions were better preserved in Centre A. Intradialytic hypotension (hypotensive episodes/100 patient sessions) was more frequent in Centre B (11 versus 27, P <0.01). Conclusions. This cross-sectional study suggests that salt restriction and reduced prescription of antihypertensive drugs may limit LV hypertrophy, better preserve LV functions and reduce intradialytic hypotension in HD patients.

Cardiovascular and renal outcome in subjects with K/DOQI stage 1-3 chronic kidney disease: the importance of urinary albumin excretion.

Abstract: Background. The Kidney Disease Outcomes Quality Initiative guidelines aim to define chronic kidney disease (CKD) and classify its stages. Stage 3 CKD generally receives more attention than stage 1 or 2, because the more impaired glomerular filtration rate (GFR) in stage 3 suggests a higher cardiovascular and renal risk. In this study we evaluated cardiovascular and renal outcome in subjects with stage 1 and 2 CKD. For comparison, we also studied these outcomes in stage 3 CKD. Methods. We used data of 8495 subjects of the PREVEND study, a prospective community-based cohort study, with data on urinary albumin excretion (UAE) and serum creatinine available. As measure of cardiovascular outcome, combined cardiovascular morbidity and mortality was used. As renal outcome, mean annual change of estimated GFR (eGFR) was used. Results. 6905 subjects had no CKD; 243, 856 and 491 subjects had stage 1, 2 and 3 CKD, respectively. During a median follow-up of 7.5 years 565 cardiovascular events occurred. Incidence rates of cardiovascular events were higher (P 30 mg/24 h, age- and sex-adjusted HRs for CVD were 1.0 (0.7-1.4) and 1.6 (1.1-2.3) and the change in eGFR was 0.2 versus -0.3 ml/min/1.73 m(2)/year, respectively. Conclusion. Subjects with stage 1 or 2 CKD have an increased risk for adverse cardiovascular and renal outcome and should receive equal attention as subjects with stage 3 CKD. Subdividing stage 3 CKD according to the presence or absence of a UAE > 30 mg/24 h improves risk stratification within this stage.

Hypernatraemia in critically ill patients: too little water and too much salt

Abstract: textBackground. Our objective was to study the risk factors and mechanisms of hypernatraemia in critically ill patients, a common and potentially serious problem. Methods. In 2005, all patients admitted to the medical, surgical or neurological intensive care unit (ICU) of a university hospital were reviewed. A 1:2 matched case-control study was performed, defining cases as patients who developed a serum sodium ≥150 mmol/l in the ICU. Results. One hundred and thirty cases with ICU-acquired hypernatraemia (141 ± 3 to 156 ± 6 mmol/l) were compared to 260 controls. Sepsis (9% versus 2%), hypokalaemia (53% versus 34%), renal dysfunction (53% versus 13%), hypoalbuminaemia (91% versus 55%), the use of mannitol (10% versus 1%) and use of sodium bicarbonate (23% versus 0.4%) were more common in cases (P < 0.05 for all) and were independently associated with hypernatraemia. During the development of hypernatraemia, fluid balance was negative in 80 cases (-31 ± 2 ml/kg/day), but positive in 50 cases (72 ± 3 ml/kg/day). Cases with a positive fluid balance received more sodium plus potassium (148 ± 2 versus 133 ± 3 mmol/l, P < 0.001). On average, cases were polyuric (40 ± 5 ml/kg). Mortality was higher in cases (48% versus 10%, P < 0.001), for which hypernatraemia was an independent predictor (odds ratio 4.3, 95% confidence interval 2.5 to 7.2). Conclusions. Hypernatraemia seems to develop in the ICU because various factors promote renal water loss, which is then corrected with too little water or overcorrected with relatively hypertonic fluids. Therapy should therefore rely on adding electrolyte-free water and/or creating a negative sodium balance. Adjustments in intravenous fluid regimens may prevent hypernatraemia.

Renal dysfunction in acute stroke: an independent predictor of long-term all combined vascular events and overall mortality

Abstract: Background. Acute stroke is the third leading cause of death in western societies after ischemic heart disease and cancer. Although it is an emergency disease sharing the same atherosclerotic risk factors with ischemic heart disease, the association of renal function and stroke is poorly investigated.Thepresentstudyaimsatassessingrenalfunction status in patients with acute stroke and investigate any prognostic significance on the outcome. Methods. This is a prospective study of hospitalized firstever stroke patients over 10 years. The study population comprised 1350 patients admitted within 24 h from stroke onset and followed up for 1 to 120 months or until death. Patients were divided in 3 groups on the basis of the estimated Glomerular Filtration Rate (eGFR) that was calculated from the abbreviated equation of the Modification Diet for Renal Disease in ml/min/1.73m 2 of body surface area: Group-A comprised patients who had eGFR >60, group-B those with 30 ≤ eGFR ≤ 60 and group-C patients with eGFR < 30. Patients with Acute Kidney Injury (AKI) were excluded from the study. The main outcome measures were overall mortality and the composite new cardiovascular events (myocardial infarction, recurrent stroke, vascular death) among the 3 groups during the follow-up period. Results. Almost 1/3 (28.08%) of our acute stroke patients presented with moderate (group B) or severe (group C) renal dysfunction as estimated by eGFR. After adjusting for basic demographic, stroke risk factors and stroke severity onadmission,eGFRwasanindependentpredictorofstroke mortality at 10 years. Patients in groups B and C had an increased probability of death during follow-up: Hazard ratio = 1.21 with 95% CI 1.01–1.46, p < 0.05 and Hazard ratio = 1.76 with 95% CI 1.14–2.73, p < 0.05 respectively, compared topatients belonging togroup A. Theprobability of death from any cause was significantly different among groups (log rank test 55.4, p = 0.001) during the follow-up

Short daily haemodialysis: survival in 415 patients treated for 1006 patient-years

Abstract: BACKGROUND Survival statistics for daily haemodialysis are lacking as most centres providing this have treated only a small number of patients for short observation times. We pooled our 23-year, 1006-patient-year, five-centre experience of 415 patients treated by short daily haemodialysis. METHODS One hundred and fifty patients were treated in-centre, most because of medical complications and 265 by home or self-care haemodialysis. Patients were on daily haemodialysis for 29 +/- 31 (0-272) months. Forty-two percent had primary and 31% had secondary renal failure. Treatment time was 136 +/- 35 min, frequency 5.8 +/- 0.5 times/week and weekly stdKt/V 2.7 +/- 0.55. RESULTS Eighty-five patients (20%) died; 5-year cumulative survival was 68 +/- 4.1% and 10-year survival was 42 +/- 9%. Age, secondary renal failure and in-centre dialysis were associated with mortality, while gender, frequency of dialysis (5, 6 or 7 per week), continent, country and blood access were not. Survival was compared with matched patients from the USRDS 2005 Data Report using the standardized mortality ratio and cumulative survival curves. Both comparisons showed that the survival of the daily haemodialysis patients was 2-3 times higher and the predicted 50% survival time 2.3-10.9 years longer than that of the matched US haemodialysis patients. Survival of patients dialyzing daily at home was similar to that of age-matched recipients of deceased donor renal transplants. CONCLUSIONS Survival of patients on short daily haemodialysis was 2-3 times better than that of matched three times weekly haemodialysis patients reported by the USRDS.

Obesity-induced glomerular hyperfiltration: its involvement in the pathogenesis of tubular sodium reabsorption.

Abstract: Background. Obesity is associated with hypertension and glomerular hyperfiltration. A major mechanism responsible for the obesity-associated hypertension is renal salt retention. An increased glomerular filtration fraction (FF) is expected to raise postglomerular oncotic pressure and to increase proximal tubular sodium reabsorption. The aim of the present study was to verify whether obesity-associated hyperfiltration leads to increased postglomerularoncoticpressureandincreasedproximalsodium reabsorption. Methods. Twelve obese subjects (BMI >36) and 19 lean subjectsparticipatedinthestudy.Theyunderwentmeasurement of glomerular filtration rate (GFR), renal plasma flow (RPF) and fractional excretion of lithium (FE Li). Results. GFR, RPF and FF were 61%, 28% and 29% higher, respectively, in the obese than in the control group (P <0.00001 for GFR,P <0.005 for RPF andP <0.00005 for FF). Half of the obese group had increased FF with increasedGFR,whiletheotherhalfhadnormalFFwithhighnormal or increased GFR. Postglomerular oncotic pressure was 13% higher (P <0.03) and FE Li was 33% lower (P <0.005) in the obese group with high FF than in the leangroup.PostglomerularoncoticpressureandFELiwere normal in the obese group with normal FF. Conclusions. These results suggest that glomerular hyperfiltration may lead to increased proximal tubular sodium reabsorption in the obese.

Effective removal of protein-bound uraemic solutes by different convective strategies: a prospective trial

Abstract: Background. Although different on-line convective removal strategies are available, there are no studies comparing the efficiency of solute removal for the three main options [post-dilution haemodiafiltration (post-HDF), pre-dilution haemodiafiltration (pre-HDF) and pre-dilution haemofiltration (pre-HF)] in parallel. Methods. In this study, we compared post-HDF (Polyflux 170), pre-HDF (Polyflux 170) and pre-HF (Polyflux 210) in 14 patients. Parallelism of the evaluation protocols consisted in applying the same blood flow, dialysis time and effective convection (22.9 +/- 1.7 versus 22.2 +/- 2.0 L, P = NS) in pre-HDF versus post-HDF, and the same blood flow and dialysis time while comparing pre-HDF and pre-HF (1:1 dilution). With pre-HF, ultrafiltration was maximized and resulted in an effective convective volume of 28.5 L. We studied water-soluble compounds (urea, creatinine, uric acid), protein-bound compounds (hippuric acid, indole acetic acid, indoxylsulfate and p-cresylsulfate) and beta(2)-microglobulin (beta M-2). Results. Post-HDF was superior to pre-HDF for water-soluble compounds and beta M-2, whereas there was no difference for protein-bound compounds. Pre-HDF was superior to pre-HF for water-soluble compounds and protein-bound compounds. In contrast, removal of beta M-2 for pre-HF was higher than for pre-HDF, but it did not differ from that obtained with post-HDF. Conclusions. It is concluded that post-dilution is superior to pre-dilution HDF under conditions of similar convective volume, and that HDF is superior to HF in pre-dilution, with the exception of removal of beta M-2. Overall, post-HDF is the most efficient convective strategy among those tested.

Thrombotic microangiopathy secondary to VEGF pathway inhibition by sunitinib

Abstract: Background Drugs targeting the VEGF pathway are associated with renal adverse events, including proteinuria, hypertension and thrombotic microangiopathy (TMA). Most cases of TMA are reported secondary to bevacizumab. It was shown recently that sunitinib, a small molecule inhibiting several tyrosine kinase receptors, including VEGF receptors, can also induce proteinuria, hypertension and biological features of TMA. Case. A 44-year-old woman with a history of malignant skin hidradenoma was started on sunitinib for refractory disease. She developed hypertension after 2 weeks and low-grade proteinuria after 4 weeks. Renal function remained normal, and biological signs of TMA were absent. A renal biopsy was performed 6 months later as proteinuria persisted, demonstrating typical features of TMA. The patient was given irbesartan, and sunitinib was continued for 3 months after diagnosis. Over this period, blood pressure and renal function remained stable and proteinuria became undetectable. Conclusion We report on the first case of histologically documented TMA secondary to sunitinib and provide detailed description of renal histological involvement. This suggests that all anti-VEGF drugs may share a common risk for developing renal adverse events, including TMA. Our case highlights the possible discrepancy between mild clinical manifestation on one hand and severe TMA features on renal biopsy on the other hand and pleads for large indication of renal biopsy in this setting. The renin-angiotensin system blockers may be considered in patients with mild clinical manifestations and in the absence of therapeutic alternative to anti-VEGF drugs.

The circulating calcification inhibitors, fetuin-A and osteoprotegerin, but not Matrix Gla protein, are associated with vascular stiffness and calcification in children on dialysis

Abstract: Background. Vascular calcification occurs in the majority of patients with chronic kidney disease, but a subset of patients does not develop calcification despite exposure to a similar uraemic environment. Physiological inhibitors of calcification, fetuin-A, osteoprotegerin (OPG) and undercarboxylated-matrix Gla protein (uc-MGP) may play a role in preventing the development and progression of ectopic calcification, but there are scarce and conflicting data from clinical studies.Methods. We measured fetuin-A, OPG and uc-MGP in 61 children on dialysis and studied their associations with clinical, biochemical and vascular measures.Results. Fetuin-A and OPG were higher and uc-MGP lower in dialysis patients than controls. In controls, fetuin-A and OPG increased with age. Fetuin-A showed an inverse correlation with dialysis vintage (P = 0.0013), time-averaged serum phosphate (P = 0.03) and hs-CRP (P = 0.001). Aortic pulse wave velocity (PWV) and augmentation index showed a negative correlation with fetuin-A while a positive correlation was seen with PWV and OPG. Patients with calcification had lower fetuin-A and higher OPG than those without calcification. On multiple linear regression analysis Fetuin-A independently predicted aortic PWV (P = 0.004, ss = -0.45, model R-2 = 48%) and fetuin-A and OPG predicted cardiac calcification (P = 0.02, ss = -0.29 and P = 0.014, ss = 0.33, respectively, model R-2 = 32%).Conclusions. This is the first study to define normal levels of the calcification inhibitors in children and show that fetuin-A and OPG are associated with increased vascular stiffness and calcification in children on dialysis. Higher levels of fetuin-A in children suggest a possible protective upregulation of fetuin-A in the early stages of exposure to the pro-calcific and pro-inflammatory uraemic environment.

The changing spectrum of primary glomerular diseases within 15 years: a survey of 3331 patients in a single Chinese centre.

Abstract: BACKGROUND Primary glomerular disease (PGD) is the leading cause of end-stage renal disease (ESRD) in China. With the development of socioeconomic status of Chinese people in the last two decades, PGD in ESRD is intent to decrease. However, whether this affects the spectrum of PGD is not clear. The aim of the current study is to investigate the changing spectrum of PGD in China. METHODS The records of 5398 consecutive native renal biopsies performed in adults (>or=14 years of age) in our centre between 1993 and 2007 were retrospectively analysed. The criteria for renal biopsy and pathologic diagnosis were kept unchanged. The patients were grouped according to a 5-year interval, 1993-97 (period 1), 1998-2002 (period 2) and 2003-07 (period 3). Then they were divided into four groups according to age for stratified analysis: 14-24 years, 25-44 years, 45-59 years and the elderly (>or=60 years). RESULTS Three thousand, three hundred and thirty-one patients were diagnosed with PGD. PGD remained the most common renal disease, accounting for 65.9%, 57.7% and 63.2% in period 1, 2 and 3, respectively, without any significant difference. The proportion of elder patients increased significantly from 0% in 1993 to 9.1% in 2007 (P < 0.001). Within 1993-97, the leading PGD was IgA nephropathy (50.7%), followed by non-IgA MsPGN (19.9%), membranous nephropathy (MN) (13.3%) and minimal change disease (MCD) (6.3%), while within 2003-07, the most common PGD was still IgAN (58.2%), but followed by MN (14.3%), MCD (13.4%) and non-IgA MsPGN (7.0%). The age-adjusted frequency of IgAN and MCD increased significantly from period 1 to period 3 (P < 0.01 and P < 0.001, respectively), while that of non-IgA MsPGN, EnPGN and MPGN decreased significantly (P < 0.001, P < 0.01 and P < 0.05, respectively). There was no significant change in the age-adjusted frequency of FSGS, MN and CreGN during the study period. However, when patients were stratified by age, a sixfold increase in frequency of FSGS was identified in the 14- to 24-year group (P < 0.01). CONCLUSIONS The spectrum of primary glomerulonephritis has changed within the last 15 years. The relative frequency of non-IgA MsPGN, EnPGN and MPGN decreased significantly, while that of MCD and IgA nephropathy increased significantly. The relative frequency of FSGS increased significantly in younger patients.

Excess mortality due to interaction between protein-energy wasting, inflammation and cardiovascular disease in chronic dialysis patients

Abstract: BACKGROUND: Protein-energy wasting (PEW), inflammation and cardiovascular diseases (CVD) clearly contribute to the high mortality in chronic dialysis. Our aim was to examine the presence of additive interaction between these three risk factors in their association with long-term mortality in dialysis patients. METHODS: Patients from a prospective multi-centre cohort study among ESRD patients starting with their first dialysis treatment [the Netherlands Co-operative Study on the Adequacy of Dialysis-2 (NECOSAD-II)] with complete data on these risk factors were included (n = 815, age: 59 +/- 15 years, 60% men, 65% HD). Hazard ratios (HR) were calculated for all-cause mortality in 7 years of follow-up. The presence of interaction between the three risk factors was examined, based on additivity of effects. RESULTS: Of all patients, 10% only suffered from PEW (1-5 on the 7-point subjective global assessment), 11% from inflammation (CRP >/=10 mg/L), 14% from CVD and 22% had any combination of two components. Only 6% of the patients had all three risk factors. Patients with either PEW (HR: 1.6, 95% CI: 1.3-2.0), inflammation (1.6, 1.3-2.0) or CVD (1.7, 1.4-2.1) had an increased mortality risk. In patients with all three risk factors, the crude mortality rate of 45/100 person-years was 16 deaths/100 person-years higher than expected from the addition of the solo effects of PEW, inflammation and CVD. The relative excess risk due to interaction was 2.9 (95% CI: 0.3-5.4), implying additive interaction. After adjustment for age, sex, treatment modality, primary kidney diseases, diabetes and malignancy the HR for patients with all three risk factors was 4.8 (95% CI: 3.2-7.2). CONCLUSIONS: The concurrent presence of PEW, inflammation and CVD increased the mortality risk strikingly more than expected, implying that PEW interacts with inflammation and CVD in dialysis patients

Gadolinium-based contrast agents and nephrogenic systemic fibrosis: a systematic review and meta-analysis

Abstract: Background. In the past decade, more than 200 cases of nephrogenic systemic fibrosis (NSF) have been identified, primarily among patients with advanced kidney disease. Multiple studies have suggested an association between gadolinium-based contrast agents (GBCAs) and NSF. We performed a systematic review and meta-analysis to examine this potential association. Methods. A systematic review of studies examining the associationbetweenanyGBCAandNSFwasperformed.A search for controlled studies was conducted in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. If controlled data for a GBCA was not available, we searched for case reports and series. Relevant data were extracted and meta-analyses were performed. Results.Sevenof144identifiedstudiesmetinclusioncriteria;gadodiamidewasthesoleorpredominantGBCAinfour of these; one study exclusively examined gadopentetate. Other GBCAs were not specifically examined in controlled or uncontrolled studies. Meta-analysis of controlled trials demonstrated a significant association between GBCA exposure and NSF [odds ratio (OR) 26.7; 95% confidence interval (CI) 10.3–69.4] and gadodiamide and NSF (OR 20.0; 95% CI 3.7–107.8). Examination of the evidence using established criteria suggested that this association was causal. Conclusions. The current state of evidence suggests an association and potentially causal link between the use of GBCAs and the development of NSF among patients with advanced kidney disease. Additional study is warranted to clarify the potential association of GBCAs other than gadodiamide with NSF.

Five-year outcomes of severe acute kidney injury requiring renal replacement therapy

Abstract: Background. Current research priorities in critical care medicine are focusing on long-term outcomes of survivors of critical illness. Severe acute kidney injury (AKI) is a commonoccurrenceinintensivecare.However,fewstudies have followed up these patients beyond 12 months after hospital discharge. Methods. Of a cohort of 425 patients, 226 survivors with severe AKI necessitating renal replacement therapy (RRT) were followed up for 60 months after hospital discharge. Noneofthesepatientshadpre-existingkidneydisease.Vital status and renal function were documented annually for 5 years. Results. None of the discharged or transferred patients was dependent on RRT; 57% had complete recovery and 43% had partial recovery of renal function. During the first year after hospital discharge, 18% of survivors died, during the second year 4% and during the third to fifth year 2% per year. At 5 years, 25% of the cohort were still alive. Further improvement in renal function (eGFR) was noted in 26 patients within the first year only. Deterioration of renal function occurred in eight patients. At 5 years, renal function was normal in 86% of the remaining survivors, it was impaired in 9% and 5% of the patients alive needed dialysis again. The proportional Cox regression analysis model showed that pre-existing extrarenal comorbidity, surgery and partial recovery of renal function were independent determinants of long-term survival. Conclusions. This prospective observational study indicates that severe AKI is not only a determinant of excess in-hospital case fatalities of critically ill patients, but it also carries significant implications for long-term mortality.