[The risks of tanning with the Barbie drug]. / De risico's van bruin worden met de barbiedrug.

BACKGROUND: Melanotan II, also known as 'Barbie drugs', can be purchased over the internet and in gyms to facilitate sunless tanning. The purchased product is a alpha-melanocyte-stimulating hormone (α-MSH) analogue, which stimulates the production of eumelanin to get skin pigmentation. However, previous research showed that Melanotan supports the development of new pigmented and dysplastic naevi. CASE REPORT: We report a case of a 27 year old male, with no relevant medical history, who presented at the emergency department two hours after subcutaneous self-administration of Melanotan II. He suffered from sympathomimetic symptoms and was treated with lorazepam, supplemental potassium and intravenous fluid resuscitation. CONCLUSION: This case reports underlines self-administration of Melanotan II is not without potential side effects, although Melanotan II is easily available on the internet and in gyms.

Kidney function and symptom development over time in elderly patients with advanced chronic kidney disease: results of the EQUAL cohort study.

BACKGROUND: Initiation of renal replacement therapy often results from a combination of kidney function deterioration and symptoms related to chronic kidney disease (CKD) progression. We investigated the association between kidney function decline and symptom development in patients with advanced CKD. METHODS: In the European Quality study on treatment in advanced CKD (EQUAL study), a European prospective cohort study, patients with advanced CKD aged ≥65 years and a kidney function that dropped <20 mL/min/1.73 m2 were followed for 1 year. Linear mixed-effects models were used to assess the association between kidney function decline and symptom development. The sum score for symptom number ranged from 0 to 33 and for overall symptom severity from 0 to 165, using the Dialysis Symptom Index. RESULTS: At least one kidney function estimate with symptom number or overall symptom severity was available for 1109 and 1019 patients, respectively. The mean (95% confidence interval) annual kidney function decline was 1.70 (1.32; 2.08) mL/min/1.73 m2. The mean overall increase in symptom number and severity was 0.73 (0.28; 1.19) and 2.93 (1.34; 4.52) per year, respectively. A cross-sectional association between the level of kidney function and symptoms was lacking. Furthermore, kidney function at cohort entry was not associated with symptom development. However, each mL/min/1.73 m2 of annual kidney function decline was associated with an extra annual increase of 0.23 (0.07; 0.39) in the number of symptoms and 0.87 (0.35; 1.40) in overall symptom severity. CONCLUSIONS: A faster kidney function decline was associated with a steeper increase in both symptom number and severity. Considering the modest association, our results seem to suggest that repeated thorough assessment of symptom development during outpatient clinic visits, in addition to the monitoring of kidney function decline, is important for clinical decision-making.

Patency Outcomes of Arteriovenous Fistulas and Grafts for Hemodialysis Access: A Trade-Off between Nonmaturation and Long-Term Complications.

Background: Arteriovenous fistulas (AVFs) for hemodialysis (HD) are often associated with better outcomes than arteriovenous grafts (AVGs). We aimed to investigate vascular access (VA) outcomes and assessed if AVF nonmaturation outweighs long-term complications of AVGs. Methods: In this multicenter, retrospective cohort study in The Netherlands, 1- and 3-year primary, primary assisted, secondary, and functional patency rates were calculated, and the incidence of adverse events and procedures was assessed. Functional patency of RCAVFs, upper arm AVFs, and AVGs was compared using Cox analyses. Results: In total, 1041 patients who received their first VA were included, of whom 863 had VAs that successfully matured. These patients were analyzed with a median follow-up of 25 months. The 1-year functional patency rates were 67%±2.0% for RCAVFs, 83%±2.0% for upper arm AVFs, and 85%±3.5% for AVGs. Three-year functional patency rates were 62%±2.0% for RCAVFs, 74%±2.0% for upper arm AVFs, and 69%±5% for AVGs. AVGs required more procedures per year (3.3 per year) of functional patency when compared with upper arm AVFs (1.8 per year). Conclusions: The functional patency of AVFs and AVGs is comparable, although AVGs required more interventions to maintain usability for HD. The choice of VA is a trade-off between short-term advantages, favoring AVGs, and long-term advantages, favoring AVFs. Which VA is most appropriate depends on the patient's prognosis and preferences.

Uraemic symptom burden and clinical condition in women and men of ≥65 years of age with advanced chronic kidney disease: results from the EQUAL study.

BACKGROUND: The epidemiology and prognosis of chronic kidney disease (CKD) differ by sex. We aimed to compare symptom prevalence and the clinical state in women and men of ≥65 years of age with advanced CKD receiving routine nephrology care. METHODS: The European QUALity study on treatment in advanced chronic kidney disease (EQUAL) study follows patients from six European countries of ≥65 years of age years whose estimated glomerular filtration rate (eGFR) dropped to ≤20 mL/min/1.73 m2 for the first time during the last 6 months. The Dialysis Symptom Index was used to assess the prevalence and severity of 33 uraemic symptoms. Data on the clinical state at baseline were collected from medical records. Prevalence was standardized using the age distribution of women as the reference. RESULTS: The results in women (n = 512) and men (n = 967) did not differ with age (77.0 versus 75.7 years) or eGFR (19.0 versus 18.5). The median number of symptoms was 14 [interquartile range (IQR) 9-19] in women, and 11 (IQR 7-16) in men. Women most frequently reported fatigue {39% [95% confidence interval (CI) 34-45]} and bone/joint pain [37% (95% CI 32-42)] as severe symptoms, whereas more men reported difficulty in becoming sexually aroused [32% (95% CI 28-35)] and a decreased interest in sex [31% (95% CI 28-35)]. Anaemia [73% (95% CI 69-77) versus 85% (95% CI 82-87)] was less common in women than in men, as were smoking history and cardiovascular comorbidity. However, a diagnosis of liver disease other than cirrhosis, psychiatric disease and mild malnutrition were more common among women. CONCLUSIONS: Women in secondary care with an incident eGFR ≤20 mL/min/1.73 m2 reported a higher symptom burden, while their clinical state was considered similar or even more favourable as compared with men.

No consensus on physicians' preferences on vascular access management after kidney transplantation: Results of a multi-national survey.

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.

Pitfalls of linear regression for estimating slopes over time and how to avoid them by using linear mixed-effects models.

Clinical epidemiological studies often focus on investigating the underlying causes of disease. For instance, a nephrologist may be interested in the association between blood pressure and the development of chronic kidney disease (CKD). However, instead of focusing on the mere occurrence of CKD, the decline of kidney function over time might be the outcome of interest. For examining this kidney function trajectory, patients are typically followed over time with their kidney function estimated at several time points. During follow-up, some patients may drop out earlier than others and for different reasons. Furthermore, some patients may have greater kidney function at study entry or faster kidney function decline than others. Also, a substantial heterogeneity may exist in the number of kidney function estimates available for each patient. This heterogeneity with respect to kidney function, dropout and number of kidney function estimates is important to take into account when estimating kidney function trajectories. In general, two methods are used in the literature to estimate kidney function trajectories over time: linear regression to estimate individual slopes and the linear mixed-effects model (LMM), i.e. repeated measures analysis. Importantly, the linear regression method does not properly take into account the above-mentioned heterogeneity, whereas the LMM is able to retain all information and variability in the data. However, the underlying concepts, use and interpretation of LMMs are not always straightforward. Therefore we illustrate this using a clinical example and offer a framework of how to model and interpret the LMM.

Decline of kidney function during the pre-dialysis period in chronic kidney disease patients: a systematic review and meta-analysis.

PURPOSE: Substantial heterogeneity exists in reported kidney function decline in pre-dialysis chronic kidney disease (CKD). By design, kidney function decline can be studied in CKD 3-5 cohorts or dialysis-based studies. In the latter, patients are selected based on the fact that they initiated dialysis, possibly leading to an overestimation of the true underlying kidney function decline in the pre-dialysis period. We performed a systematic review and meta-analysis to compare the kidney function decline during pre-dialysis in CKD stage 3-5 patients, in these two different study types. PATIENTS AND METHODS: We searched PubMed, EMBASE, Web of Science and Cochrane to identify eligible studies reporting an estimated glomerular filtration rate (eGFR) decline (mL/min/1.73 m2) in adult pre-dialysis CKD patients. Random-effects meta-analysis was performed to obtain weighted mean annual eGFR decline. RESULTS: We included 60 studies (43 CKD 3-5 cohorts and 17 dialysis-based studies). The meta-analysis yielded a weighted annual mean (95% CI) eGFR decline during pre-dialysis of 2.4 (95% CI: 2.2, 2.6) mL/min/1.73 m2 in CKD 3-5 cohorts compared to 8.5 (95% CI: 6.8, 10.1) in dialysis-based studies (difference 6.0 [95% CI: 4.8, 7.2]). CONCLUSION: To conclude, dialysis-based studies report faster mean annual eGFR decline during pre-dialysis than CKD 3-5 cohorts. Thus, eGFR decline data from CKD 3-5 cohorts should be used to guide clinical decision making in CKD patients and for power calculations in randomized controlled trials with CKD progression during pre-dialysis as the outcome.

Lower serum calcium is independently associated with CKD progression.

Disturbances in calcium metabolism are common in individuals with chronic kidney disease (CKD), but whether they are associated with subsequent kidney function decline is less clear. In a CKD 3-5 cohort of 15,755 adult citizens of Stockholm with creatinine tests taken during 2006-2011 and concurrent calcium testing at cohort entry, we investigated the association between baseline serum calcium and the subsequent change in estimated glomerular filtration rate (eGFR, by CKD-EPI) decline using linear mixed models. Mean (SD) baseline corrected serum calcium was 9.6 (0.5) mg/dL. Mean (95%-confidence interval [CI]) eGFR decline was -0.82 (-0.90; -0.74) mL/min/1.73 m2/year. In advanced CKD stages, higher baseline serum calcium was associated with less rapid kidney function decline. The adjusted change (95%-CI) in eGFR decline associated with each mg/dL increase in baseline serum calcium was -0.10 (-0.28; 0.26), 0.39 (0.07; 0.71), 0.34 (-0.02; 0.70) and 0.68 (0.36; 1.00) mL/min/1.73 m2/year for individuals in CKD stage 3a, 3b, 4, and 5, respectively. In a subgroup of patients using vitamin D supplements, the association between baseline serum calcium and CKD progression was eliminated, especially in CKD stage 3b and 4. To conclude, in individuals with CKD stage 3b to 5, lower baseline corrected serum calcium, rather than higher baseline serum calcium, associated with a more rapid CKD progression. Lower serum corrected calcium seems to be indicative for vitamin D deficiency.

Arteriovenous Fistula Maturation Failure in a Large Cohort of Hemodialysis Patients in the Netherlands.

OBJECTIVES: Radiocephalic arteriovenous fistulas (RCAVF) are the preferred vascular access (VA) for hemodialysis (HD). Cohort studies from North America revealed that nonmaturation is a significant disadvantage of RCAVFs compared to other VAs. DESIGN: This present retrospective study describes the incidence of nonmaturation of AVFs and functional failure of arteriovenous grafts (AVG) in a multicentre cohort in the Netherlands and attempts to create a prediction model for nonmaturation of RCAVFs. Furthermore, the efficacy of interventions to promote maturation as well as the variability between hemodialysis centers was evaluated. MATERIALS: Medical records from 8 hospitals from 1997 to 2016 were retrospectively evaluated for VA type, maturation/primary success and demographics and comorbidities. METHODS: A prediction model was created for RCAVF nonmaturation using multivariate logistic regression analysis, selecting significant predictors using backward selection. Discrimination and calibration of the model were assessed. RESULTS: 1383 AVFs and 273 AVGs were included in 1221 patients. Overall nonmaturation was 24% for RCAVFs, and 11% for upper arm AVFs. The functional failure rate for AVGs was 6%. The nonmaturation rate of contralateral RCAVFs after failure of an RCAVF was 22%. Procedures to improve RCAVF maturation were successful in 98/142 cases (69%). Predictors for nonmaturation were female gender, peripheral vascular disease, cerebrovascular disease and a cephalic vein diameter <2.5 mm, but the prediction model lacked sensitivity and specificity predicting individual RCAVF nonmaturation (C-statistic 0.629). CONCLUSION: Nonmaturation rates are highest for RCAVFs, but nonmaturation could not be predicted with demographic parameters.

Association Between Proton Pump Inhibitor Use and Risk of Progression of Chronic Kidney Disease.

BACKGROUND & AIMS: Proton pump inhibitors (PPI) have been associated with acute kidney injury and recent studies suggest that they may be associated with the risk of chronic kidney disease (CKD). METHODS: We performed a retrospective analysis using the Stockholm creatinine measurements database, which contains information on diagnoses, dispensation claims, and laboratory test results for all citizens in the Stockholm region from 2007 through 2010. We identified new users of PPIs (n = 105,305) and new users of H2 blockers (H2B; n = 9578); data on renal outcomes were collected for a median 2.7 years. The primary outcome was progression CKD, defined as doubling of creatinine or decrease in estimated glomerular filtration rate of 30% or more. Secondary outcomes were end-stage renal disease and acute kidney injury. Complete collection of repeated PPI and H2B dispensations at pharmacies in Sweden allowed modeling the time-dependent risk associated with cumulative PPI exposure. RESULTS: Users of PPIs, compared with users of H2Bs, had an increased risk for doubled levels of creatinine (1985 events; adjusted hazard ratio [HR], 1.26; 95% CI, 1.05-1.51) and decrease in estimated glomerular filtration rate of 30% or more (11,045 events; 1.26; 95% CI, 1.16-1.36). PPI use also associated with development of end-stage renal disease (HR, 2.40; 95% CI, 0.76-7.58) and acute kidney injury (HR, 1.30; 95% CI, 1.00-1.69). There was a graded association between cumulative exposure to PPIs and risk of CKD progression. This was not the case for cumulative H2B use. CONCLUSIONS: Initiation of PPI therapy and cumulative PPI exposure is associate with increased risk of CKD progression in a large, North European healthcare system. Although consistent, the association was modest in magnitude, and cannot exclude residual confounding.

Effect of glomerular filtration rate at dialysis initiation on survival in patients with advanced chronic kidney disease: what is the effect of lead-time bias?

PURPOSE: Current clinical guidelines recommend to initiate dialysis in the presence of symptoms or signs attributable to kidney failure, often with a glomerular filtration rate (GFR) of 5-10 mL/min/1.73 m2. Little evidence exists about the optimal kidney function to start dialysis. Thus far, most observational studies have been limited by lead-time bias. Only a few studies have accounted for lead-time bias, and showed contradictory results. We examined the effect of GFR at dialysis initiation on survival in chronic kidney disease patients, and the role of lead-time bias therein. We used both kidney function based on 24-hour urine collection (measured GFR [mGFR]) and estimated GFR (eGFR). MATERIALS AND METHODS: A total of 1,143 patients with eGFR data at dialysis initiation and 852 patients with mGFR data were included from the NECOSAD cohort. Cox regression was used to adjust for potential confounders. To examine the effect of lead-time bias, survival was counted from the time of dialysis initiation or from a common starting point (GFR 20 mL/min/1.73 m2), using linear interpolation models. RESULTS: Without lead-time correction, no difference between early and late starters was present based on eGFR (hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.81-1.3). However, after lead-time correction, early initiation showed a survival disadvantage (HR between 1.1 [95% CI 0.82-1.48] and 1.33 [95% CI 1.05-1.68]). Based on mGFR, the potential survival benefit for early starters without lead-time correction (HR 0.8, 95% CI 0.62-1.03) completely disappeared after lead-time correction (HR between 0.94 [95% CI 0.65-1.34] and 1.21 [95% CI 0.95-1.56]). Dialysis start time differed about a year between early and late initiation. CONCLUSION: Lead-time bias is not only a methodological problem but also has clinical impact when assessing the optimal kidney function to start dialysis. Therefore, lead-time bias is extremely important to correct for. Taking account of lead-time bias, this controlled study showed that early dialysis initiation (eGFR >7.9, mGFR >6.6 mL/min/1.73 m2) was not associated with an improvement in survival. Based on kidney function, this study suggests that in some patients, dialysis could be started even later than an eGFR <5.7 and mGFR <4.3 mL/min/1.73 m2.