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Individuals carrying a germline CDKN2Apathogenic variant (PV) are at a high risk of developing pancreatic ductal adenocarcinoma. Risk stratification could allow tailored surveillance. To develop a Fine‐Gray prediction model for the risk of PDAC in carriers of a CDKN2APV. Data from two large Dutch pancreatic cancer surveillance programs were used. A limited set of predictor variables were selected bsased on previous literature and the clinical expertise of the study group. A total of 506 CDKN2APV carriers were included, among whom we showed a substantial lifetime risk of PDAC (23%). The model identifies having a first‐degree relative with PDAC (B= 0.7256) and a history of smoking (B= 0.4776) as significant risk factors. However, the model shows limited discrimination (c‐statistic 0.64) and calibration. Our study highlights the high lifetime risk of PDAC in carriers of a CDKN2APV. While identifying significant risk factors such as family history of PDAC and smoking, our prediction model shows limited precision, highlighting the need for additional factors such as biomarkers to improve its clinical utility for tailored surveillance of high‐risk individuals.

Introduction: It is assumed that identification and correction of asymptomatic stenoses in the vascular access circuit will prevent thrombosis that would require urgent intervention to continue hemodialysis treatment. However, the evidence base for this assumption is limited. Recent international clinical practice guidelines reach different conclusions on the use of surveillance for vascular access flow dysfunction and recommend further research to inform clinical practice.Methods: The FLOW trial is a double-blind, multicenter, randomized controlled trial with a 1:1 individual participant treatment allocation ratio over two study arms. In the intervention group, only symptomatic vascular access stenoses detected by clinical monitoring are treated, whereas in the comparison group asymptomatic stenoses detected by surveillance using monthly dilution flow measurements are treated as well. Hemodialysis patients with a functional arteriovenous vascular access are enrolled. The primary outcome is the access-related intervention rate that will be analyzed using a general linear model with Poisson distribution. Secondary outcomes include patient satisfaction, access-related serious adverse events, and quality of the surveillance process. A cost effectiveness analysis and budget impact analysis will also be conducted. The study requires 828 patient-years of follow-up in 417 participants to detect a difference of 0.25 access-related interventions per year between study groups.Discussion: As one of the largest randomized controlled trials assessing the clinical impact of vascular access surveillance using a strong double-blinded study design, we believe the FLOW trial will provide much-needed evidence to improve vascular access care for hemodialysis patients.

Prognostic models can strongly support individualized care provision and well-informed shared decision making. There has been an upsurge of prognostic research in the field of nephrology, but the uptake of prognostic models in clinical practice remains limited. Therefore, we map out the research field of prognostic models for kidney patients and provide directions on how to proceed from here. We performed a scoping review of studies developing, validating, or updating a prognostic model for patients with CKD. We searched all published models in PubMed and Embase and report predicted outcomes, methodological quality, and validation and/or updating efforts. We found 602 studies, of which 30.1% concerned CKD populations, 31.6% dialysis populations, and 38.4% kidney transplantation populations. The most frequently predicted outcomes were mortality (n=129), kidney disease progression (n=75), and kidney graft survival (n=54). Most studies provided discrimination measures (80.4%), but much less showed calibration results (43.4%). Of the 415 development studies, 28.0% did not perform any validation and 57.6% performed only internal validation. Moreover, only 111 models (26.7%) were externally validated either in the development study itself or in an independent external validation study. Finally, in 45.8% of development studies no useable version of the model was reported. To conclude, many prognostic models have been developed for patients with CKD, mainly for outcomes related to kidney disease progression and patient/graft survival. To bridge the gap between prediction research and kidney patient care, patient-reported outcomes, methodological rigor, complete reporting of prognostic models, external validation, updating, and impact assessment urgently need more attention.

Purpose: Obesity may promote kidney damage through hemodynamic and hormonal effects. We investigated the association between body mass index (BMI), total body fat (TBF) and chronic kidney disease (CKD) and whether hypertension, diabetes, leptin and adiponectin mediated these associations. Methods: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, 6671 participants (45–65 y) were included. We defined CKD as eGFR <60 ml/min/1.73 m2and/or moderately increased albuminuria. The percentage of mediation was calculated using general structural equation modeling, adjusted for potential confounding factors age, sex, smoking, ethnicity, physical activity and Dutch healthy diet index. Results: At baseline mean (SD) age was 56 (6), BMI 26.3 (4.4), 44% men, and 4% had CKD. Higher BMI and TBF were associated with 1.08 (95%CI 1.05; 1.11) and 1.05-fold (95%CI 1.02; 1.08) increased odds of CKD, respectively. As adiponectin was not associated with any of the outcomes, it was not studied further as a mediating factor. The association between BMI and CKD was 8.5% (95%CI 0.5; 16.5) mediated by diabetes and 22.3% (95%CI 7.5; 37.2) by hypertension. In addition, the association between TBF and CKD was 9.6% (95%CI −0.4; 19.6) mediated by diabetes and 22.4% (95%CI 4.2; 40.6) by hypertension. We could not confirm mediation by leptin in the association between BMI and CKD (35.6% [95%CI −18.8; 90.3]), nor between TBF and CKD (59.7% [95%CI −7.1; 126.6]). Conclusion: Our results suggest that the relations between BMI, TBF and CKD are in part mediated by diabetes and hypertension.

The availability of electronic health records and access to a large number of routine measurements of serum creatinine and urinary albumin enhance the possibilities for epidemiologic research in kidney disease. However, the frequency of health care use and laboratory testing is determined by health status and indication, imposing certain challenges when identifying patients with kidney injury or disease, when using markers of kidney function as covariates, or when evaluating kidney outcomes. Depending on the specific research question, this may influence the interpretation, generalizability, and/or validity of study results. This review illustrates the heterogeneity of working definitions of kidney disease in the scientific literature and discusses advantages and limitations of the most commonly used approaches using 3 examples. We summarize ways to identify and overcome possible biases and conclude by proposing a framework for reporting definitions of exposures and outcomes in studies of kidney disease using routinely collected health care data.

Background: Technique survival is a core outcome for peritoneal dialysis (PD), according to Standardized Outcomes in Nephrology-Peritoneal Dialysis. This study aimed to identify modifiable causes and risk factors of technique failure in a large Dutch cohort using standardised definitions.Methods: Patients who participated in the retrospective Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes cohort study and started PD between 2012 and 2016 were included and followed until 1 January 2017. The primary outcome was technique failure, defined as transfer to in-centre haemodialysis for ≥ 30 days or death. Death-censored technique failure was analysed as secondary outcome. Cox regression models and competing risk models were used to assess the association between potential risk factors and technique failure.Results: A total of 695 patients were included, of whom 318 experienced technique failure during follow-up. Technique failure rate in the first year was 29%, while the death-censored technique failure rate was 23%. Infections were the most common modifiable cause for technique failure, accounting for 20% of all causes during the entire follow-up. Leakage and catheter problems were important causes within the first 6 months of PD treatment (both accounting for 15%). APD use was associated with a lower risk of technique failure (hazard ratio 0.66, 95% confidence interval 0.53–0.83).Conclusion: Infections, leakage and catheter problems were important modifiable causes for technique failure. As the first-year death-censored technique failure rate remains high, future studies should focus on infection prevention and catheter access to improve technique survival.

OBJECTIVE--The 5-5 homozygous CNDP1 (camosinase) genotype is associated with a reduced risk of diabetic nephropathy. We investigated whether this association is sex specific and independent of susceptibility for type 2 diabetes. RESEARCH DESIGN AND METHODS--Three separate groups of 114, 90, and 66 patients with type 2 diabetes and diabetic nephropathy were included in this study and compared with 93 patients with type 2 diabetes for >15 years without diabetic nephropathy and 472 population control subjects. The diabetes control group was used to determine an association in the three patient groups separately, and the population control group was used to estimate the genotype risk [odds ratio (CI)] for the population in a pooled analysis. The population control subjects were also compared with 562 patients with type 2 diabetes without diabetic nephropathy to determine whether the association was independent of type 2 diabetes. The CNDP1 genotype was determined by fragment analysis after PCR amplification. RESULTS--The frequency of the 5-5 homozygous genotype was 28, 36, and 41% in the three diabetic nephropathy patient groups and 43 and 42% in the diabetic and population control subjects, respectively. The 5-5 homozygous genotype occurred significantly less frequently in women in all three patient groups compared with diabetic control subjects. The genotype risk for the population was estimated to be 0.5 (0.30-0.68) in women and 1.2 (0.77-1.69) in men. The 562 patients with type 2 diabetes without diabetic nephropathy did not differ from the general population (P = 0.23). CONCLUSIONS--This study suggests that the association between the CNDP1 gene and diabetic nephropathy is sex specific and independent of susceptibility for type 2 diabetes. Diabetes 59:1555-1559, 2010, Only 20-40% of patients with type 1 or type 2 diabetes will develop diabetic nephropathy, and if no signs of nephropathy are present in the first 15 years after diagnosis [...]

Background: The subjective global assessment of nutritional status (SGA) is used to assess the nutritional status of chronic dialysis patients, but longitudinal data in relation to mortality risk are lacking. Objective: Our objective was to study the long-term and time-dependent associations of the SGA with mortality risk in chronic dialysis patients. Design: In a prospective, longitudinal, observational, multicenter study of incident dialysis patients, the 7-point SGA [7 = normal nutritional status; 1 = severe protein-energy wasting (PEW)] was assessed 3 and 6 mo after the start of dialysis and subsequently every 6 mo during 7 y of follow-up. With Cox regression analysis, we calculated hazard ratios (HRs) of the baseline and time-dependent SGA measurements, adjusted for age, sex, treatment modality, primary kidney diseases, and comorbidity. Results: In total, 1601 patients were included [mean ([+ or -]SD) age: 59 [+ or -] 15 y; 61% men; 23% with moderate PEW ([SGA.sub.4-5]), and 5% with severe PEW ([SGA.sub.1-3])]. There was a dose-dependent trend of the 7-point SGA with mortality. Compared with a normal nutritional status at baseline, [SGA.sub.4-5] (HR: 1.6; 95% CI: 1.3, 1.9) and [SGA.sub.1-3] (HR: 2.1; 95% CI: 1.5, 2.8) were associated with an increase in 7-y mortality. Time-dependently, these associations were stronger: [SGA.sub.4-5] (HR: 2.1; 95% CI: 1.7, 2.5) and [SGA.sub.1-3] (HR: 5.0; 95% CI: 3.8, 6.5). Conclusions: In dialysis patients, PEW at baseline assessed with SGA was associated with a 2-fold increased mortality risk in 7 y of follow-up. Time-dependently, this association was even stronger, which indicated that PEW was associated with a remarkably high risk of short-term mortality. These data imply that the 7-point SGA may validly distinguish different degrees of PEW associated with increasing risks of mortality.

OBJECTIVE--South Asians have a high prevalence of central obesity. When the diagnosis of diabetes is made, they have a very high risk of developing renal failure. In the current study, [...]

Background: Increasing evidence indicates that adult body composition is associated with prenatal and infancy weight gain, but the relative importance of different time periods has not been elucidated. Objective: The objective was to study the association between prenatal, early postnatal, and late infancy weight gain and body mass index (BMI), fat mass, and fat distribution in young adulthood. Design: We included 403 men and women aged 19 y from a Dutch national prospective follow-up study who were born at Results: Birth weight SD scores were positively associated with weight, height, BMI SD scores, and fat-free mass at age 19 y but not with fat mass, percentage body fat, or fat distribution. Early postnatal and late infancy weight gain were positively associated with adult height, weight, BMI. waist circumference SD scores, fat mass, fat-free mass, and percentage body fat but not with waist-to-hip ratio SD scores or subscapular-to-triceps ratio. Conclusions: In infants born very preterm, weight gain before 32 wk of gestation is positively associated with adult body size but not with body composition and fat distribution. More early postnatal and. to a lesser extent, late infancy weight gain are associated with higher BMI SD scores and percentage body fat and more abdominal fat at age 19 y. KEY WORDS Birth weight, early postnatal growth, prematurity, body mass index, body composition, fat-free mass, fat distribution, young adulthood, Netherlands

Background: Differences in symptom burden, treatment satisfaction and autonomy between patients receiving peritoneal dialysis and haemodialysis could be reflected by a difference in symptom dimensions of anxiety and depression. The aim of this study is to assess differences in prevalence and symptom dimensions of anxiety and depression between patients receiving peritoneal dialysis and haemodialysis.Methods: Baseline data from the Depression Related Factors and Outcomes in Dialysis Patients With Various Ethnicities and Races Study were used. Symptoms of anxiety and depression were measured with the Beck Anxiety Inventory and Beck Depression Inventory– second edition. Linear and logistic regression models were used to compare anxiety and depression total scores and somatic and subjective/cognitive symptom dimension scores between patients receiving peritoneal dialysis and haemodialysis, adjusted for potential confounders.Results: In total, 84 patients receiving peritoneal dialysis and 601 patients receiving haemodialysis were included. Clinically significant symptoms of anxiety and depression were present in respectively 22% and 43% of the patients, with no differences between dialysis modality. Both modalities scored high on the somatic symptom dimensions and on individual somatic items. Almost all patients reported symptoms related to loss of energy and sleep.Conclusion: No differences in symptom dimensions of anxiety and depression were found between patients receiving peritoneal dialysis and haemodialysis. The high prevalence of somatic symptom dimensions in both groups underscores the possible interaction between somatic and psychiatric symptoms in dialysis patients and the need for early recognition and treatment of symptoms of anxiety and depression regardless of treatment modalities.

The aim of this study was to explore the changes in nutritional status before dialysis initiation and to identify modifiable risk factors of nutritional status decline in older adults with advanced renal disease.

Background: In Europe, the number of elderly end-stage kidney disease patients is increasing. Few of those patients receive peritoneal dialysis (PD), as many cannot perform PD autonomously. Assisted PD programmes are available in most European countries, but the percentage of patients receiving assisted PD varies considerably. Hence, we assessed which factors are associated with the availability of an assisted PD programme at a centre level and whether the availability of this programme is associated with proportion of home dialysis patients.Methods: An online survey was sent to healthcare professionals of European nephrology units. After selecting one respondent per centre, the associations were explored by χ2tests and (ordinal) logistic regression.Results: In total, 609 respondents completed the survey. Subsequently, 288 respondents from individual centres were identified; 58% worked in a centre with an assisted PD programme. Factors associated with availability of an assisted PD programme were Western European and Scandinavian countries (OR: 5.73; 95% CI: 3.07–10.68), non-academic centres (OR: 2.01; 95% CI: 1.09–3.72) and centres with a dedicated team for education (OR: 2.87; 95% CI: 1.35–6.11). Most Eastern & Central European respondents reported that the proportion of incidentand prevalenthome dialysis patients was <10% (72% and 63%), while 27% of Scandinavian respondents reported a proportion of >30% for both incidentand prevalenthome dialysis patients. Availability of an assisted PD programme was associated with a higher incidence (cumulative OR: 1.91; 95% CI: 1.21–3.01) and prevalence (cumulative OR: 2.81; 95% CI: 1.76–4.47) of patients on home dialysis.Conclusions: Assisted PD was more commonly offered among non-academic centres with a dedicated team for education across Europe, especially among Western European and Scandinavian countries where higher incidence and prevalence of home dialysis patients was reported.

To evaluate the effectiveness and sustainability of self-managed sodium restriction in patients with chronic kidney disease.

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Anxiety symptoms are common in dialysis patients and have a large impact on quality of life. The association of anxiety symptoms with adverse clinical outcomes in dialysis patients is largely unknown. This study examined the association of anxiety symptoms with hospitalization and mortality in patients receiving maintenance dialysis.

Background: The main limitations of central venous catheters for haemodialysis access are infections and catheter malfunction. Our objective was to assess whether precurved non-tunnelled central venous catheters are comparable to tunnelled central venous catheters in terms of infection and catheter malfunction and to assess whether precurved non-tunnelled catheters are superior to straight catheters.Materials and methods: In this retrospective, observational cohort study, adult patients in whom a central venous catheter for haemodialysis was inserted between 2012 and 2016 were included. The primary endpoint was a combined endpoint consisting of the first occurrence of either an infection or catheter malfunction. The secondary endpoint was a combined endpoint of the removal of the central venous catheter due to either an infection or a catheter malfunction. Using multivariable analysis, cause-specific hazard ratios for endpoints were calculated for tunnelled catheter versus precurved non-tunnelled catheter, tunnelled catheter versus non-tunnelled catheter, and precurved versus straight non-tunnelled catheter.Results: A total of 1603 patients were included. No difference in reaching the primary endpoint was seen between tunnelled catheters, compared to precurved non-tunnelled catheters (hazard ratio, 0.91; 95% confidence interval, 0.70–1.19, p = 0.48). Tunnelled catheters were removed less often, compared to precurved non-tunnelled catheters (hazard ratio, 0.65; 95% confidence interval, 0.46–0.93; p = 0.02). A trend for less infections and catheter malfunctions was seen in precurved jugular non-tunnelled catheters compared to straight non-tunnelled catheters (hazard ratio, 0.60; 95% confidence interval, 0.24–1.50; p = 0.28) and were removed less often (hazard ratio, 0.41; 95% confidence interval, 0.18–0.93; p = 0.03).Conclusion: Tunnelled central venous catheters and precurved non-tunnelled central venous catheters showed no difference in reaching the combined endpoint of catheter-related infections and catheter malfunction. Tunnelled catheters get removed less often because of infection/malfunction than precurved non-tunnelled catheters.

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Objective: Arteriovenous fistulas for hemodialysis vascular access are a burden for the cardiovascular system. After successful kidney transplantation, prophylactic arteriovenous fistula ligation may improve cardiac outcomes; however, evidence is scarce. This survey investigates physicians’ preference for management of arteriovenous fistulas and identifies the factors associated with preference for either arteriovenous fistula ligation or maintenance.Materials and methods: A survey was sent to members of eight national and international Nephrology and Vascular Surgery societies. The survey comprised eight case vignettes of asymptomatic patients with a functioning arteriovenous fistula after kidney transplantation. Characteristics possibly associated with treatment preferences were arteriovenous fistula flow, left ventricular ejection fraction, and patient age. Respondents were asked to state preference to maintain or ligate the arteriovenous fistula. Linear mixed-effects models were used to investigate the association of treatment preference with case characteristics.Results: A total of 585 surveys were returned. A reduced left ventricular ejection fraction of 30% (beta 0.60, 95% confidence interval 0.55; 0.65) and a high flow of 2500 mL/min (beta 0.46, 95% confidence interval 0.41; 0.51) were associated with a higher preference for arteriovenous fistula ligation. Disagreement among respondents was considerable, as in four out of eight cases less than 70% of respondents agreed on the arteriovenous fistula management strategy.Conclusion: Although respondents recognize a reduced left ventricular ejection fraction and a high flow as the risk factors, the high disagreement on management preferences suggests that evidence is inconclusive to recommend arteriovenous fistula ligation or maintenance after kidney transplantation. More research is needed to determine optimal arteriovenous fistula management after successful kidney transplantation.

Prevalence and risk factors for protein-energy wasting (PEW) are poorly studied in the nondialysis, older population with advanced chronic kidney disease (CKD). Our aim was to evaluate the prevalence of PEW in advanced stage CKD patients aged greater than 65 years. Furthermore, we aimed to describe risk factors for PEW in the overall study population and among obese individuals.

Background Obesity increases risk of hypertension and diabetes, the leading causes of end-stage renal disease. The effect of obesity on kidney function decline in stable post-myocardial infarction patients is poorly documented. This relation was investigated in a large cohort of older post-myocardial infarction patients.Design Data were analysed from 2410 post-myocardial infarction patients in the Alpha Omega Trial, aged 60–80 years receiving optimal pharmacotherapy treatment (79% men, 18% diabetes).Methods Cystatin C based estimated glomerular filtration rate (eGFRcysC) was calculated at baseline and after 41 months, using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Obesity was defined as body mass index ≥ 30 kg/m2and high waist circumference as ≥102 and ≥88 cm for men and women. The relation between body mass index, waist circumference and annual eGFRcysCdecline was evaluated by linear regression.Results At baseline, mean (standard deviation) eGFRcysCwas 81.5 (19.6) ml/min/1.73 m2, 23% of all patients were obese. After multivariable adjustment, the annual mean (95% confidence interval) eGFRcysCdecline in men and women was –1.45 (–1.59 to –1.31) and –0.92 (–1.20 to –0.63) ml/min/1.73 m2, respectively (p= 0.001). Obese versus non-obese patients and patients with high versus normal waist circumference experienced greater annual eGFRcysCdecline. Men and women showed an additional annual eGFRcysCdecline of –0.35 (–0.56 to –0.14) and –0.21 (–0.55 to 0.14) ml/min/1.73 m2per 5 kg/m2body mass index increment (pfor interaction 0.3).Conclusions High compared to normal body mass index or waist circumference were associated with more rapid kidney function decline in older stable post-myocardial infarction patients receiving optimal drug therapy.

CKD is an inherently systemic diseaseEnergy balance, innate immunity and neuroendocrine control of organ function are highly integrated biological processes; such integration is disrupted by loss of kidney function, which generates a high risk clinical phenotypeThe clinical profile of chronic kidney disease (CKD) includes inflammation, malnutrition, altered activity of the autonomic and central nervous systems, and cardiopulmonary, vascular and bone diseaseThe gut and the lung are emerging as critical mediators of the interaction between the kidney and the environment, and are involved in cardiovascular disease and other systemic complications of CKDAlterations in macrovascular and microvascular function induced by sleep apnoea, inflammation and oxidative stress increase the risk of brain disease in CKDThe application of omics sciences will enable in-depth studies of the pathophysiology and treatment of CKD

Hypokalemia may accelerate kidney function decline. Both hypo- and hyperkalemia can cause sudden cardiac death. However, little is known about the relationship between serum potassium and death or the occurrence of kidney failure requiring replacement therapy (KRT). We investigated this relationship in older people with chronic kidney disease (CKD) stage 4-5.

Residual kidney function contributes substantially to solute clearance in dialysis patients but cannot be assessed without urine collection. We used serum filtration markers to develop dialysis-specific equations to estimate urinary urea clearance without the need for urine collection. In our development cohort, we measured 24-hour urine clearances under close supervision in 44 patients and validated these equations in 826 patients from the Netherlands Cooperative Study on the Adequacy of Dialysis. For the development and validation cohorts, median urinary urea clearance was 2.6 and 2.4 ml/min, respectively. During the 24-hour visit in the development cohort, serum β-trace protein concentrations remained in steady state but concentrations of all other markers increased. In the validation cohort, bias (median measured minus estimated clearance) was low for all equations. Precision was significantly better for β-trace protein and β2-microglobulin equations and the accuracy was significantly greater for β-trace protein, β2-microglobulin, and cystatin C equations, compared with the urea plus creatinine equation. Area under the receiver operator characteristic curve for detecting measured urinary urea clearance by equation-estimated urinary urea clearance (both 2 ml/min or more) were 0.821, 0.850, and 0.796 for β-trace protein, β2-microglobulin, and cystatin C equations, respectively; significantly greater than the 0.663 for the urea plus creatinine equation. Thus, residual renal function can be estimated in dialysis patients without urine collections.

Background and objectives Cancer antigen 125 (CA125) reflects the mesothelial cell mass lining the peritoneal membrane in individual patients. A decline or absence of mesothelial cells can be observed with duration of peritoneal dialysis (PD) therapy. Technique failure due to peritoneal membrane malfunction becomes of greater importance after 2 years of PD therapy in comparison to the initial period. In this study, we aimed to investigate the association between effluent CA125 and technique survival in incident PD patients with a PD therapy period of at least 2 years.Methods Within the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD), a Dutch multicenter cohort including 2,000 incident dialysis patients, we identified all PD patients who developed technique failure after 2 years of PD therapy and randomly selected a number of them as cases in a nested case-control study. Controls were PD patients matched on follow-up time without technique failure. Cases and controls were included if they had a dialysate specimen available within 24 ± 6 months of PD therapy for retrospective CA125 determinations. Odds ratios for technique failure related to CA125 were estimated. We used a prospective cohort with incident PD patients from the Academic Medical Center–University of Amsterdam (AMC) for replication of effect estimates. In these patients, absolute risk of technique failure was estimated and related to effluent CA125 levels.Results A total of 38 PD patients were selected from the NECOSAD cohort. From the AMC cohort as replication cohort, 91 PD patients were included. Incidence rates of PD technique failure per 100 patient-years were 16.3 in the NECOSAD cohort and 12.9 in the AMC cohort. In both study populations CA125 levels below 12 – 14 kU/L were associated with an increased risk for technique failure. Technique survival rates in the AMC were 87% in patients with levels of CA125 above 12.1 kU/L and 65% for those with CA125 levels below this threshold after a maximum 5-year follow-up.Conclusions Patients with high CA125 levels after at least 2 years of PD therapy tend to have better technique survival than patients with low CA125 levels. These results support the importance of effluent CA125 as a risk factor for dropout in long-term PD therapy.

To examine the prevalence of and risk factors for malnutrition at the start of specialized predialysis care.

Patients with chronic kidney disease (CKD) have increased risk of all-cause mortality; the elevated cardiovascular mortality in patients with end-stage renal disease is particularly well documented. Lately, the increased noncardiovascular mortality in these patients has gained particular attention. In this article, both cardiovascular and noncardiovascular mortality in CKD are discussed, with specific attention paid to studies that provide details of noncardiovascular causes of death. Examples are provided of several cardiovascular risk factors that also seem to be associated with noncardiovascular mortality, including levels of fetuin-A, troponin T, and C-reactive protein, as well as vitamin D deficiency and proteinuria. Potential pathophysiological mechanisms (such as inflammatory reactions and the uraemic milieu) that might explain the increased cardiovascular and noncardiovascular mortality in CKD are also discussed. Future research should not only focus on preventing cardiovascular mortality, but also on studying noncardiovascular mortality and the potential link between causal pathways of cardiovascular mortality and noncardiovascular mortality in CKD.

The cardiorenal syndrome represents a final common pathway for renal and congestive heart failure and heralds a poor prognosis. Factors that link the failing heart and the failing kidneys—the so-called cardiorenal connectors—are, therefore, of clinical and therapeutic interest. Alterations in the levels and function of thyroid hormones that fit the spectrum of nonthyroidal illnesses could be considered to be cardiorenal connectors as both renal failure and heart failure progress with the development of nonthyroidal illness. In addition, circumstantial evidence suggests that nonthyroidal illness can induce deterioration in the function of the heart and the kidneys via multiple pathways. As a consequence, these reciprocal associations could result in a vicious cycle of deterioration that likely contributes to increased mortality. In this Review, we describe the evidence for a pathophysiological role of nonthyroidal illness in the cardiorenal syndrome. We also discuss the available data from studies that have investigated the efficacy of thyroid hormone replacement therapy in patients with renal failure and the rationale for interventional trials to examine the effects of normalization of the thyroid hormone profile in patients with renal failure and congestive heart failure.

There are no available epidemiologic studies about the impact of ethnicity on outcomes of patients treated with peritoneal dialysis (PD) in South America. This study aims to assess the effect of ethnicity on the mortality of incident PD patients in Brazil.

Little is known about the criteria nephrologists use in the decision of when to start renal replacement therapy (RRT) in early referred adult patients. We evaluated opinions of European nephrologists on the decision for when to start RRT.

AbstractBackground/Aims:Proteinuria is a risk marker for progression of chronic kidney disease (CKD) and treatment with an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEi/ARB) is beneficial in these patients. However, little is known about proteinuria and ACEi/ARB treatment in patients on specialized predialysis care. Therefore, we investigated the association of urinary protein excretion (UPE) and ACEi/ARB treatment with renal function decline (RFD) and/or the start of renal replacement therapy (RRT) in patients on predialysis care. Methods:In the PREPARE-1 cohort, 547 incident predialysis patients (CKD stages IV–V), referred as part of the usual care to outpatient clinics of eight Dutch hospitals, were included (1999–2001) and followed until the start of RRT, mortality, or January 1, 2008. The main outcomes were rate of RFD, estimated as the slope of available eGFR measurements, and the start of RRT. Results:Patients with mild proteinuria (>0.3 to ≤1.0 g/24 h) had an adjusted additional RFD of 0.35 ml/min/1.73 m2/month (95 CI: 0.01; 0.68) and a higher rate of starting RRT [adjusted HR: 1.70 (1.05; 2.77)] compared with patients without proteinuria (≤0.3 g/24 h). With every consecutive UPE category (>1.0 to ≤3.0, >3.0 to ≤6.0, and >6.0 g/24 h), RFD accelerated and the start of RRT was earlier. Furthermore, patients starting (n = 16) or continuing (n = 133) treatment with ACEi/ARBs during predialysis care had a lower rate of starting RRT compared with patients not using treatment [n = 152, adjusted HR: 0.56 (0.29; 1.08) and 0.90 (0.68; 1.20), respectively]. Conclusion:In patients on predialysis care, we confirmed that proteinuria is a risk marker for the progression of CKD. Furthermore, no evidence was present that the use of ACEi/ARBs is deleterious.Copyright © 2012 S. Karger AG, Basel

♦ Background and Objectives In automated peritoneal dialysis (APD), a patient's peritoneal membrane is more intensively exposed to fresh dialysate than it is in continuous ambulatory peritoneal dialysis (CAPD). Our aim was to study, in incident peritoneal dialysis (PD) patients, the influence of APD—compared with that of CAPD—on peritoneal transport over 4 years.♦ Design, Setting, Participants, and Measurements Patients were included if at least 2 annual standard permeability analyses (SPAs) performed with 3.86% glucose were available while the patient was using the same modality with which they had started PD (APD or CAPD). Patients were followed until their first modality switch. Differences in the pattern of SPA outcomes over time were tested using repeated-measures models adjusted for age, sex, comorbidity, primary kidney disease, and year of PD start.♦ Results The 59 CAPD patients enrolled were older than the 47 APD patients enrolled (mean age: 58 ± 14 years vs 49 ± 14 years; p< 0.01), and they had started PD earlier (mean start year: 2000 vs 2002). Over time, no differences in solute (p> 0.19) or fluid transport (p> 0.13) were observed. Similarly, free water transport (p= 0.43) and small-pore transport (p= 0.31) were not different between the modalities. Over time, patients on APD showed a faster decline in effective lymphatic absorption rate (ELAR: p= 0.02) and in transcapillary ultrafiltration (TCUF: p= 0.07, adjusted p= 0.05). Further adjustment did not change the results.♦ Conclusions Compared with patients starting on CAPD, those starting on APD experienced a faster decline in ELAR and TCUF. Other transport parameters were not different over time between the groups.

Depressive symptoms seem to pose a risk factor for mortality among patients on dialysis. It is currently unknown whether the association is only short-lived and whether associations over time depend on specific causes of mortality.

AbstractA systematic review aims to synthesize all available individual studies on a certain topic and uses explicit and reproducible methods for searching the literature, while a meta-analysis is a mathematical synthesis of the results of these individual studies. Because of the explosion of information in the scientific literature, these study designs can be useful tools to summarize the knowledge on a particular subject. In addition, combining individual studies in a meta-analysis increases statistical power, resulting in more precise effect estimates. Even though all parts of the specific methodology of systematic reviews include steps to minimize bias, both investigators and readers should be aware of potential biases like poor study quality and heterogeneity between studies. This paper explains how systematic reviews and meta-analyses should be performed and how to critically appraise them, based on an example from the nephrology literature.Copyright © 2011 S. Karger AG, Basel

AbstractIn contrast to the Kaplan-Meier method, Cox proportional hazards regression can provide an effect estimate by quantifying the difference in survival between patient groups and can adjust for confounding effects of other variables. The purpose of this article is to explain the basic concepts of the Cox regression method, and to provide some guidance regarding the presentation of the results.Copyright © 2011 S. Karger AG, Basel

AbstractGenetic association studies are a means to investigate the causal role of genes in diseases in order to unravel pathways involved in the etiology of disease. There are two types of genetic association studies: hypothesis-driven studies, i.e. candidate gene studies, targeting genes with a known or presumed role in pathways or diseases of interest, and non-hypothesis-driven studies, i.e. genome-wide association studies, aiming for the discovery of new genetic associations. This educational article is an introduction to genetic association studies for nephrologists and researchers in the domain of kidney disease.Copyright © 2011 S. Karger AG, Basel

AbstractMany clinical epidemiological studies investigate whether a certain exposure, or risk factor, is associated with the incidence of disease or mortality. It may be of interest to study whether this association is different in different types of patients, or to study joint effects. To investigate whether the effect of one risk factor differs across the strata of another risk factor, the presence of interaction among two risk factors can be examined. In statistics, interaction refers to the inclusion of a product term of two risk factors in a statistical model. Statistical interaction thereby evaluates whether the association deviates from either additivity or multiplicativity, depending on the scale of the model. From a public health perspective, the assessment of interaction on an additive scale may be most relevant. For a transparent presentation of interaction effects, it is recommended to report the separate effect of each exposure as well as the joint effect compared to the unexposed group as a joint reference category to permit evaluation of interaction on both an additive and multiplicative scale.Copyright © 2011 S. Karger AG, Basel

AbstractInteraction is the situation whereby the association of one risk factor with a certain outcome variable differs across strata of another risk factor. From a public health perspective, the assessment of interaction on an additive scale may be most relevant. Although additive models exist, logistic and Cox regression models are the most commonly used models in epidemiology. The resulting relative risks can be translated to an additive scale. The present paper presents surrogate measures to evaluate the presence of additive interaction when dealing with data on a multiplicative scale (relative risks). For a transparent presentation of interaction effects it is recommended to report the separate effect of each exposure as well as their joint effect compared to the unexposed group as joint reference category to permit evaluation of interaction on both an additive and multiplicative scale.Copyright © 2011 S. Karger AG, Basel

AbstractThe Kaplan-Meier (KM) method is used to analyze ‘time-to-event’ data. The outcome in KM analysis often includes all-cause mortality, but could also include other outcomes such as the occurrence of a cardiovascular event. The purpose of this article is to explain the basic concepts of the KM method, to provide some guidance regarding the presentation of the KM results and to discuss some important limitations of this method. To do this, we use a clinical example derived from the nephrology literature.Copyright © 2011 S. Karger AG, Basel

Randomized clinical trials are expensive and time consuming. Therefore, strategies are needed to prioritise tracks for drug development. Genetic association studies may provide such a strategy by considering the differences between genotypes as a proxy for a natural, lifelong, randomized at conception, clinical trial. Previously an association with better survival was found in dialysis patients with systemic inflammation carrying a deletion variant of the CC-chemokine receptor 5 (CCR5). We hypothesized that in an analogous manner, pharmacological CCR5 blockade could protect against inflammation-driven mortality and estimated if such a treatment would be cost-effective.

AbstractThe sample size is the number of patients or other experimental units that need to be included in a study to answer the research question. Pre-study calculation of the sample size is important; if a sample size is too small, one will not be able to detect an effect, while a sample that is too large may be a waste of time and money. Methods to calculate the sample size are explained in statistical textbooks, but because there are many different formulas available, it can be difficult for investigators to decide which method to use. Moreover, these calculations are prone to errors, because small changes in the selected parameters can lead to large differences in the sample size. This paper explains the basic principles of sample size calculations and demonstrates how to perform such a calculation for a simple study design.Copyright © 2011 S. Karger AG, Basel