This comment addresses the work of Wang and Li (DOI: 10.1007/s12293-009-0012-0, hereafter referred to as WL) published online on September 01, 2009 in a (special) issue of Memetic Computing. We respectfully beg to differ in opinion with WL and argue that the concept of multi-strategy evolutionary search used by WL is not particularly novel. Similar ideas have been presented elsewhere, and these publications date back to at least early 2007. For instance, in a series of papers published in PNAS (2007), SSSAJ (2008), WRR (2008), IEEE-TEVC (2009), JH (2010), Vrugt and coworkers have introduced AMALGAM, a multi-method (or ensemble) search approach to solve emerging single and multiple objective search and optimization problems. In the past few years, MATLAB, C++, Python, and R implementations of AMALGAM have been distributed extensively among researchers and practitioners in various fields of study.

RATIONALE & OBJECTIVE: The Kidney Failure Risk Equation (KFRE) predicts the 2-year risk of kidney failure for patients with chronic kidney disease (CKD). Translating KFRE-predicted risk or estimated glomerular filtration rate (eGFR) into time to kidney failure could inform decision making for patients approaching kidney failure. STUDY DESIGN: Retrospective cohort. SETTING & PARTICIPANTS: CKD Outcomes and Practice Patterns Study (CKDOPPS) cohort of patients with an eGFR<60mL/min/1.73m2 from 34 US nephrology practices (2013-2021). EXPOSURE: 2-year KFRE risk or eGFR. OUTCOME: Kidney failure defined as initiation of dialysis or kidney transplantation. ANALYTICAL APPROACH: Accelerated failure time (Weibull) models used to estimate the median, 25th, and 75th percentile times to kidney failure starting from KFRE values of 20%, 40%, and 50%, and from eGFR values of 20, 15, and 10mL/min/1.73m2. We examined variability in time to kidney failure by age, sex, race, diabetes status, albuminuria, and blood pressure. RESULTS: Overall, 1,641 participants were included (mean age 69±13 years; median eGFR of 28mL/min/1.73m2 [IQR 20-37mL/min/1.73 m2]). Over a median follow-up period of 19 months (IQR, 12-30 months), 268 participants developed kidney failure, and 180 died before reaching kidney failure. The median estimated time to kidney failure was widely variable across patient characteristics from an eGFR of 20mL/min/1.73m2 and was shorter for younger age, male sex, Black (versus non-Black), diabetes (vs no diabetes), higher albuminuria, and higher blood pressure. Estimated times to kidney failure were comparably less variable across these characteristics for KFRE thresholds and eGFR of 15 or 10mL/min/1.73m2. LIMITATIONS: Inability to account for competing risks when estimating time to kidney failure. CONCLUSIONS: Among those with eGFR<15mL/min/1.73m2 or KFRE risk>40%), both KFRE risk and eGFR showed similar relationships with time to kidney failure. Our results demonstrate that estimating time to kidney failure in advanced CKD can inform clinical decisions and patient counseling on prognosis, regardless of whether estimates are based on eGFR or the KFRE. PLAIN-LANGUAGE SUMMARY: Clinicians often talk to patients with advanced chronic kidney disease about the level of kidney function expressed as the estimated glomerular filtration rate (eGFR) and about the risk of developing kidney failure, which can be estimated using the Kidney Failure Risk Equation (KFRE). In a cohort of patients with advanced chronic kidney disease, we examined how eGFR and KFRE risk predictions corresponded to the time patients had until reaching kidney failure. Among those with eGFR<15mL/min/1.73m2 or KFRE risk > 40%), both KFRE risk and eGFR showed similar relationships with time to kidney failure. Estimating time to kidney failure in advanced CKD using either eGFR or KFRE can inform clinical decisions and patient counseling on prognosis.

Background and objectives

Anemia management changed substantially among dialysis patients in the United States around the time of implementation of the new Centers for Medicare & Medicaid Services bundled payment system and erythropoiesis-stimulating agent (ESA) label change in 2011. Among these, average ferritin levels increased dramatically and have remained high since; this study sought to gain understanding of this sustained rise in ferritin levels.

Design, setting, participants, & measurements

Trends in mean ferritin, hemoglobin, IV iron dose, and ESA dose from 2009 to 2013 were examined in 9735 patients from 91 United States Dialysis Outcomes and Practice Patterns Study facilities. Linear mixed models were used to assess the extent to which intravenous (IV) iron and ESA dose accounted for patients' changes in ferritin over time.

Results

Mean ESA dose and hemoglobin levels declined throughout the study. Mean IV iron dose increased from 210 mg/mo in 2009-2010 to a peak of 280 mg/mo in 2011, then declined back to 200 mg/mo and remained stable from 2012 to 2013. Mean ferritin increased from 601 ng/ml in the third quarter of 2009 to 887 ng/ml in the first quarter of 2012; models suggest that higher IV iron dosing was a primary determinant during 2011, but lower ESA doses contributed to the sustained high ferritin levels thereafter. In a subset of 17 facilities that decreased IV iron dose in 2011, mean ferritin rose by 120 ng/ml to 764 ng/ml, which appeared to be primarily due to ESA reduction. Together, changes in IV iron and ESA doses accounted for 46% of the increase in ferritin over the study period.

Conclusions

In contrast to expectations, the rise in average IV iron dose did not persist beyond 2011. The sustained rise in ferritin levels in United States dialysis patients after policy changes in 2011, to average levels well in excess of 800 ng/ml, appeared to be partly due to reductions in ESA dosing and not solely IV iron dosing practices. The effect of these changes in ferritin on health outcomes requires further investigation.

Background

Seasonal variations may exist in transitioning to dialysis, kidney transplantation and related outcomes among end-stage renal disease (ESRD) patients. Elucidating these variations may have major clinical and healthcare policy implications for better resource allocation across seasons.

Methods

Using the United States Renal Data System database from 1 January 2000 to 31 December 2013, we calculated monthly counts of transitioning to dialysis or first transplantation and deaths. Crude monthly transition fraction was defined as the number of new ESRD patients divided by all ESRD patients on the first day of each month. Similar fractions were calculated for all-cause and cause-specific mortality and transplantation.

Results

The increasing trend of the annual transition to ESRD plateaued during 2009-2012 (n = 126 264), and dropped drastically in 2013 (n = 117 372). Independent of secular trends, monthly transition to ESRD was lowest in July (1.65%) and highest in January (1.97%) of each year. All-cause, cardiovascular and infectious mortalities were lowest in July or August (1.32, 0.58 and 0.15%, respectively) and highest in January (1.56, 0.71 and 0.19%, respectively). Kidney transplantation was highest in June (0.33%), and this peak was mainly attributed to living kidney transplantation in summer months. Transplant failure showed a similar seasonal variation to naïve transition, peaking in January (0.65%) and nadiring in September (0.56%).

Conclusions

Transitioning to ESRD and adverse events among ESRD people were more frequent in winter and less frequent in summer, whereas kidney transplantation showed the reverse trend. The potential causes and implications of these consistent seasonal variations warrant more investigation.

Background

The feasibility of using health system data to estimate prevalence of chronic kidney disease (CKD) stages 3-5 was explored.

Study design

Cohort study.

Setting & participants

A 5% national random sample of patients from the Veterans Affairs (VA) health care system, enrollees in a managed care plan in Michigan (M-CARE), and participants from the 2005-2006 National Health and Nutrition Examination Survey (NHANES).

Predictor

Observed CKD prevalence estimates in the health system population were calculated as patients with an available outpatient serum creatinine measurement with estimated glomerular filtration rate <60 mL/min/1.73 m(2), among those with at least one outpatient visit during the year.

Outcomes & measurements

A logistic regression model was fitted using data from the 2005-2006 NHANES to predict CKD prevalence in those untested for serum creatinine in the health system population, adjusted for demographics and comorbid conditions. Model results then were combined with the observed prevalence in tested patients to derive an overall predicted prevalence of CKD within the health systems.

Results

Patients in the VA system were older, had more comorbid conditions, and were more likely to be tested for serum creatinine than those in the M-CARE system. Observed prevalences of CKD stages 3-5 were 15.6% and 0.9% in the VA and M-CARE systems, respectively. Using data from NHANES, the overall predicted prevalences of CKD were 20.4% and 1.6% in the VA and M-CARE systems, respectively.

Limitations

Health system data quality was limited by missing data for laboratory results and race. A single estimated glomerular filtration rate value was used to define CKD, rather than persistence over 3 months.

Conclusions

Estimation of CKD prevalence within health care systems is feasible, but discrepancies between observed and predicted prevalences suggest that this approach is dependent on data availability and quality of information for comorbid conditions, as well as the frequency of testing for CKD in the health care system.

Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that arises from the mesothelial surface of the pleural and peritoneal cavities, the pericardium, and rarely, the tunica vaginalis. The incidence of MPM is expected to increase worldwide in the next two decades. However, even with the use of multimodality treatment, MPM remains challenging to treat, with a 5-year survival rate of less than 5%. The International Association for the Study of Lung Cancer has gathered experts in different areas of mesothelioma research and management to summarize the most significant scientific advances and new frontiers related to mesothelioma therapeutics.

Background

Longer nephrology care before end-stage renal disease (ESRD) has been linked with better outcomes.

Methods

We investigated whether longer pre-end-stage renal disease (ESRD) nephrology care was associated with lower mortality at both the patient and state levels among 443 761 incident ESRD patients identified in the USA between 2006 and 2010.

Results

Overall, 33% of new ESRD patients had received no prior nephrology care, while 28% had received care for >12 months. At the patient level, predictors of >12 months of nephrology care included having health insurance, white race, younger age, diabetes, hypertension and US region. Longer pre-ESRD nephrology care was associated with lower first-year mortality (adjusted hazard ratio = 0.58 for >12 months versus no care; 95% confidence interval 0.57-0.59), higher albumin and hemoglobin, choice of peritoneal dialysis and native fistula and discussion of transplantation options. Living in a state with a 10% higher proportion of patients receiving >12 months of pre-ESRD care was associated with a 9.3% lower relative mortality rate, standardized for case mix (R (2) = 0.47; P < 0.001).

Conclusions

This study represents the largest cohort of incident ESRD patients to date. Although we did not follow patients before ESRD onset, our findings, both at the individual patient and state levels, reflect the importance of early nephrology care among those with chronic kidney disease.

Predialysis volume overload is the sum of interdialytic weight gain (IDWG) and residual postdialysis volume overload. It results mostly from failure to achieve an adequate volume status at the end of the dialysis session. Recent developments in bioimpedance spectroscopy and possibly relative plasma volume monitoring permit noninvasive volume status assessment in hemodialysis patients. A large proportion of patients have previously been shown to be chronically volume overloaded predialysis (defined as >15% above 'normal' extracellular fluid volume, equivalent to >2.5 liters on average), and to exhibit a more than twofold increased mortality risk. By contrast, the magnitude of the mortality risk associated with IDWG is much smaller and only evident with very large weight gains. Here we review the available evidence on volume overload and IDWG, and question the use of IDWG as an indicator of 'nonadherence' by describing its association with postdialysis volume depletion. We also demonstrate the relationship between IDWG, volume overload and predialysis serum sodium concentration, and comment on salt intake. Discriminating between volume overload and IDWG will likely lead to a more appropriate management of fluid withdrawal during dialysis. Consensually, the present authors agree that this discrimination should be among the primary goals for dialysis caretakers today. In consequence, we recommend objective measures of volume status beyond mere evaluations of IDWG.

Pheochromocytomas are neural crest-derived tumors that arise from inherited or sporadic mutations in at least six independent genes. The proteins encoded by these multiple genes regulate distinct functions. We show here a functional link between tumors with VHL mutations and those with disruption of the genes encoding for succinate dehydrogenase (SDH) subunits B (SDHB) and D (SDHD). A transcription profile of reduced oxidoreductase is detected in all three of these tumor types, together with an angiogenesis/hypoxia profile typical of VHL dysfunction. The oxidoreductase defect, not previously detected in VHL-null tumors, is explained by suppression of the SDHB protein, a component of mitochondrial complex II. The decrease in SDHB is also noted in tumors with SDHD mutations. Gain-of-function and loss-of-function analyses show that the link between hypoxia signals (via VHL) and mitochondrial signals (via SDH) is mediated by HIF1alpha. These findings explain the shared features of pheochromocytomas with VHL and SDH mutations and suggest an additional mechanism for increased HIF1alpha activity in tumors.