Association of kidney function and albuminuria with frailty worsening and death in very old adults.

BACKGROUND AND OBJECTIVES: Studies analysing the association of albuminuria and prevalent frailty in community-dwelling very old adults are scarce and lack information on incident frailty. We investigated the association of kidney function decline and increase of albuminuria with frailty worsening or death in very old adults. DESIGN: Longitudinal analyses with biennial visits of the Berlin Initiative (cohort) Study and a frailty follow-up of 2.1 years. SETTING/SUBJECTS: 1,076 participants with a mean age of 84.3 (5.6) years of whom 54% were female. METHODS: Partial proportional odds models were used to assess the association of estimated glomerular filtration rate (eGFR) decline and/or albuminuria (albumin creatinine ratio, ACR) with frailty worsening or death. RESULTS: At frailty baseline, 1,076 participants with an eGFR of 50 (13) ml/min/1.73 m2, 48% being prefrail and 31% frail were included. After median 2.1 years, 960 (90%) participants had valid information on frailty transition: 187 (17.5%) worsened and 111 (10.3%) died. In the multivariable model, the odds of frailty worsening for participants with albuminuria in combination with eGFR <60 ml/min/1.73 m2 were elevated [OR (95% CI): 2.47 (1.41-4.31)] compared to participants without albuminuria and eGFR ≥60 ml/min/1.73 m2 as there was a rapid eGFR decline of ≥3 ml/min/1.73 m2 per year [1.55 (1.04-2.33)] and albuminuria trajectories six years prior [1.53 (1.11-2.10)] to frailty baseline. The odds of death for each exposure were even higher. CONCLUSIONS: In older adults, advanced stages of CKD and albuminuria alone were associated with 2-fold odds of frailty worsening independent of death.

Concomitant presentation of thrombotic thrombocytopenic purpura, immune thrombocytopenia, and autoimmune hemolytic anemia in a patient with newly diagnosed systemic lupus erythematosus.

Thrombocytopenia is always of concern when encountered in emergency settings. We report a case of a 29-year-old women in whom a unique constellation of hematological disorders occurred. The patient had been diagnosed with idiopathic immune thrombocytopenia (ITP) in 2007, with a history of several thrombocytopenic flares. She now presented with homonymous hemianopia accompanied by thrombocytopenia and microangiopathic hemolytic anemia (MAHA) and was soon after diagnosed with a posterior stroke. Symptoms were more reminiscent of acquired thrombotic thrombocytopenic purpura (aTTP) rather than ITP. Immediate treatment with plasma exchange and caplacizumab curtailed MAHA, and progressive ischemic disease was averted. ADAMTS-13 testing confirmed the diagnosis of immune-mediated aTTP. Repeated testing for ITP, however, also showed IgG-loaded thrombocytes with the former known anti-GPIIb/IIIa specificity. Furthermore, autoimmune hemolytic anemia (AIHA) could be detected by direct antiglobulin test showing IgG and complement loading of the patient's erythrocytes. The autoimmune background of all three entities suggested an underlying systemic disease. Indeed, systemic lupus erythematosus (SLE) serology was strongly positive allowing for the diagnosis of SLE. ITP and AIHA as well as aTTP can be secondary to SLE, but emergence of all three disorders has not been reported at the same time.

Age and the Course of GFR in Persons Aged 70 and Above.

BACKGROUND AND OBJECTIVES: In older adults, data on the age-related course of GFR are scarce, which might lead to misjudgment of the clinical relevance of reduced GFR in old age. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: To describe the course of eGFR in older adults and derive reference values in population-based individuals, we used the longitudinal design of the Berlin Initiative Study (BIS) with a repeated estimation of GFR over a median of 6.1 years of follow-up. In 2069 community-dwelling older individuals (mean inclusion age 80 years, range 70-99), GFR was estimated biennially with the BIS-2 equation, including standardized creatinine and cystatin C levels, sex, and age. We described the crude and adjusted course using a mixed-effects model and analyzed the influence of death on the GFR course applying joint models. GFR slopes were compared using GFR equations on the basis of creatinine and/or cystatin C. RESULTS: We observed a decreasing, thus nonlinear, eGFR decline with increasing age in a population of old adults. The estimated 1-year slope for ages 75 and 90 diminished for men from -1.67 to -0.99 and for women from -1.52 to -0.97. The modeled mean eGFR for men aged ≥79 and women ≥78 was below 60 ml/min per 1.73 m2. Multivariable adjustment attenuated slopes only minimally. Taking death into account by applying joint models did not alter the nonlinear eGFR decline. Using eGFR equations on the basis of creatinine only showed linear slope patterns in contrast to nonlinear patterns for equations including cystatin C. CONCLUSIONS: The eGFR decline depended on sex and age and changed only marginally after multivariable adjustment but decelerated with increasing age. Equations including cystatin C demonstrated a nonlinear slope challenging the previously assumed linearity of the decline of eGFR in old age.

Clinical performance, intermediate and long-term outcomes of high-volume hemodiafiltration in patients with kidney failure.

Hemodiafiltration (HDF), in which both convective and diffusion methods are combined, yields an increased overall solute clearance compared with hemodialysis (HD), specifically for medium and larger molecular weight uremic toxins. Due to uncertainty in the treatment effects, the nephrology community still perceives the implementation of HDF and the achievement of high convective volume as complex. In this article, we review practical aspects of the implementation of HDF that can effectively deliver a high-volume HDF therapy and assure clinical performance to most patients. We also present an overview of the impact of high-volume HDF (compared to HD) on a series of relevant biochemical, patient-reported, and clinical outcomes, including uremic toxin removal, phosphate, Inflammation and oxidative stress, hemodynamic stability, cardiac outcomes, nutritional effects, health-related quality of life, morbidity, and mortality.

Control of blood pressure in older patients with heart failure and the risk of mortality: a population-based prospective cohort study.

BACKGROUND: treatment goals for blood pressure (BP) lowering in older patients with heart failure (HF) are unclear. OBJECTIVE: to assess whether BP control < 140/90 mmHg is associated with a decreased risk of mortality in older HF patients. DESIGN: population-based prospective cohort study. SETTING/SUBJECTS: participants of the Berlin Initiative Study, a prospective cohort of community-dwelling older adults launched in 2009. Clinical information was obtained in face-to-face interviews and linked to administrative healthcare data. METHODS: Cox proportional hazards models estimated adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of cardiovascular death and all-cause mortality associated with normalised BP (systolic BP < 140 mmHg and diastolic BP < 90 mmHg) compared with non-normalised BP (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) in HF patients. The primary analysis considered only baseline BP ('time-fixed'); an additional analysis updated BP during follow-up ('time-dependent'). RESULTS: at baseline, 544 patients were diagnosed with HF and treated with antihypertensive drugs (mean age 82.8 years; 45.4% female). During a median follow-up of 7.5 years and compared with non-normalised BP, normalised BP was associated with similar risks of cardiovascular death (HR, 1.24; 95% CI, 0.84-1.85) and all-cause mortality (HR, 1.16; 95% CI, 0.89-1.51) in the time-fixed analysis but with increased risks of cardiovascular death (HR, 1.79; 95% CI, 1.23-2.61) and all-cause mortality (HR, 1.48; 95% CI, 1.15-1.90) in the time-dependent analysis. CONCLUSIONS: BP control < 140/90 mmHg was not associated with a decreased risk of mortality in older HF patients. The increased risk in the time-dependent analysis requires further corroboration.

Kidney Function as Risk Factor and Predictor of Cardiovascular Outcomes and Mortality Among Older Adults.

RATIONALE & OBJECTIVE: Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR) are associated with cardiovascular events in the general population but their utility among older adults is unclear. We investigated the associations of eGFR and UACR with stroke, myocardial infarction (MI), and death among older adults. STUDY DESIGN: Population-based cohort study. SETTING & PARTICIPANTS: 1,581 participants (aged≥70 years) in the Berlin Initiative Study (BIS) without prior stroke or MI. EXPOSURES & PREDICTORS: Serum creatinine- and cystatin C-based eGFR, UACR categories, and measured GFR (n=436). OUTCOMES: Stroke, MI, and all-cause mortality. ANALYTICAL APPROACH: HRs and 95% CIs derived from multivariable-adjusted Cox proportional hazards models for association analyses. Net reclassification improvement (NRI) and C statistic differences comparing the predictive benefit of kidney measures with a traditional cardiovascular risk model. RESULTS: During a median follow-up of 8.2 years, 193 strokes, 125 MIs, and 531 deaths occurred. Independent of UACR, when GFR was estimated using the creatinine- and cystatin C-based BIS equation, eGFR of 45 to 59mL/min/1.73m2 (vs eGFR>60mL/min/1.73m2) was associated with stroke (HR, 2.23; 95% CI, 1.55-3.21) but not MI or all-cause mortality. For those with eGFR<45mL/min/1.73m2, the HRs were 1.99 (95% CI, 1.23-3.20) for stroke, 1.38 (95% CI, 0.81-2.36) for MI, and 1.57 (95% CI, 1.20-2.06) for mortality. Compared with UACR<30mg/g, UACR of 30 to 300mg/g was not associated with stroke (HR, 0.91; 95% CI, 0.63-1.33) but was associated with MI (HR, 1.65; 95% CI, 1.09-2.51) and all-cause mortality (HR, 1.63; 95% CI, 1.34-1.98). Prediction analysis for stroke showed significant positive NRI for eGFR calculated using the cystatin C-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the creatinine- and cystatin C-based BIS and Full Age Spectrum equations. UACR demonstrated significant positive NRIs for MI and mortality. LIMITATIONS: eGFR and UACR categorization based on single assessments; lack of cause-specific death data. CONCLUSIONS: eGFR of 45 to 59mL/min/1.73m2 without albuminuria was associated with stroke but not MI or all-cause mortality in older adults. In contrast, UACR of 30 to 300mg/g was associated with MI and all-cause mortality but not with stroke. Furthermore, cystatin C-based eGFR improved risk prediction for stroke in this cohort of older adults.

The International Society of Renal Nutrition and Metabolism Commentary on the National Kidney Foundation and Academy of Nutrition and Dietetics KDOQI Clinical Practice Guideline for Nutrition in Chronic Kidney Disease.

The Academy of Nutrition and Dietetics and the National Kidney Foundation collaborated to provide an update to the Clinical Practice Guidelines (CPG) for nutrition in chronic kidney disease (CKD). These guidelines provide a valuable update to many aspects of the nutrition care process. They include changes in the recommendations for nutrition screening and assessment, macronutrients, and targets for electrolytes and minerals. The International Society of Renal Nutrition and Metabolism assembled a special review panel of experts and evaluated these recommendations prior to public review. As one of the highlights of the CPG, the recommended dietary protein intake range for patients with diabetic kidney disease is 0.6-0.8 g/kg/day, whereas for CKD patients without diabetes it is 0.55-0.6 g/kg/day. The International Society of Renal Nutrition and Metabolism endorses the CPG with the suggestion that clinicians may consider a more streamlined target of 0.6-0.8 g/kg/day, regardless of CKD etiology, while striving to achieve intakes closer to 0.6 g/kg/day. For implementation of these guidelines, it will be important that all stakeholders work to detect kidney disease early to ensure effective primary and secondary prevention. Once identified, patients should be referred to registered dietitians or the region-specific equivalent, for individualized medical nutrition therapy to slow the progression of CKD. As we turn our attention to the new CPG, we as the renal nutrition community should come together to strengthen the evidence base by standardizing outcomes, increasing collaboration, and funding well-designed observational studies and randomized controlled trials with nutritional and dietary interventions in patients with CKD.

Self-reported medication in community-dwelling older adults in Germany: results from the Berlin Initiative Study.

BACKGROUND: Older adults have the highest drug utilization due to multimorbidity. Although the number of people over age 70 is expected to double within the next decades, population-based data on their medication patterns are scarce especially in combination with polypharmacy and potentially inappropriate medication (PIM). Our objective was to analyse the frequency of polypharmacy, pattern of prescription (PD) and over-the-counter (OTC) drug usage, and PIMs according to age and gender in a population-based cohort of very old adults in Germany. METHODS: Cross-sectional baseline data of the Berlin Initiative Study, a prospective cohort study of community-dwelling adults aged ≥70 years with a standardized interview including demographics, lifestyle variables, co-morbidities, and medication assessment were analysed. Medication data were coded using the Anatomical Therapeutic Chemical (ATC) classification. Age- and sex-standardized descriptive analysis of polypharmacy (≥5 drugs, PD and OTC vs. PD only and regular and on demand drugs vs regular only), medication frequency and distribution, including PIMs, was performed by age (

Acute Renal Failure of Nosocomial Origin.

BACKGROUND: 10-20% of hospitalized patients develop acute kidney injury (AKI)/acute renal failure during their hospital stay. The mortality of nosocomial AKI is approximately 30%. METHODS: This review is based on relevant publications retrieved by a search in multiple databases (PubMed and Uptodate), archives, and pertinent medical journals. RESULTS: The most common causes of nosocomial AKI are volume depletion, sepsis, heart diseases, polytrauma, liver diseases, and drug toxicity. AKI can also be of postrenal (obstructive) origin, or a result of renal diseases including glomeruloneph- ritis, vasculitis, tubulointerstitial nephritis, and cholesterol embolism. In about 13% of cases, nosocomial AKI develops on the basis of pre-existing chronic renal disease. Patients with AKI are at elevated risk of developing chronic renal disease and must be followed up appropriately after they are discharged from the hospital. Indispens- able elements of the evaluation of nosocomial AKI include renal ultrasonography, the exclusion of postrenal obstruction, urine chemistry, and microbiological urinaly- sis. Potentially nephrotoxic drugs and those that impair renal hemodynamics must be avoided to the greatest possible extent in patients with acute renal damage. Hypotension must be avoided as well. CONCLUSION: Early, specific nephrological diagnosis and treatment are important components of the management of nosocomial AKI, particularly because causally directed treatment is available for some of the conditions that underlie it.

Control of blood pressure and risk of mortality in a cohort of older adults: the Berlin Initiative Study.

AIMS: To assess whether blood pressure (BP) values below 140/90 mmHg during antihypertensive treatment are associated with a decreased risk of all-cause mortality in community-dwelling older adults. METHODS AND RESULTS: Within the Berlin Initiative Study, we assembled a cohort of patients ≥70 years treated with antihypertensive drugs at baseline (November 2009-June 2011). End of prospective follow-up was December 2016. Cox proportional hazards models yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause mortality associated with normalized BP [systolic BP (SBP) <140 mmHg and diastolic BP (DBP) <90 mmHg] compared with non-normalized BP (SBP ≥140 mmHg or DBP ≥90 mmHg) overall and after stratification by age or previous cardiovascular events. Among 1628 patients (mean age 81 years) on antihypertensive drugs, 636 exhibited normalized BP. During 8853 person-years of follow-up, 469 patients died. Compared with non-normalized BP, normalized BP was associated with an increased risk of all-cause mortality (incidence rates: 60.3 vs. 48.5 per 1000/year; HR 1.26; 95% CI 1.04-1.54). Increased risks were observed in patients ≥80 years (102.2 vs. 77.5 per 1000/year; HR 1.40; 95% CI 1.12-1.74) and with previous cardiovascular events (98.3 vs. 63.6 per 1000/year; HR 1.61; 95% CI 1.14-2.27) but not in patients aged 70-79 years (22.6 vs. 22.7 per 1000/year; HR 0.83; 95% CI 0.54-1.27) or without previous cardiovascular events (45.2 vs. 44.4 per 1000/year; HR 1.16, 95% CI 0.90-1.48). CONCLUSION: Blood pressure values below 140/90 mmHg during antihypertensive treatment may be associated with an increased risk of mortality in octogenarians or elderly patients with previous cardiovascular events.

The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients: A randomized controlled trial.

OBJECTIVE: We report on the effect of hemoadsorption therapy to reduce cytokines in septic patients with respiratory failure. METHODS: This was a randomized, controlled, open-label, multicenter trial. Mechanically ventilated patients with severe sepsis or septic shock and acute lung injury or acute respiratory distress syndrome were eligible for study inclusion. Patients were randomly assigned to either therapy with CytoSorb hemoperfusion for 6 hours per day for up to 7 consecutive days (treatment), or no hemoperfusion (control). Primary outcome was change in normalized IL-6-serum concentrations during study day 1 and 7. RESULTS: 97 of the 100 randomized patients were analyzed. We were not able to detect differences in systemic plasma IL-6 levels between the two groups (n = 75; p = 0.15). Significant IL-6 elimination, averaging between 5 and 18% per blood pass throughout the entire treatment period was recorded. In the unadjusted analysis, 60-day-mortality was significantly higher in the treatment group (44.7%) compared to the control group (26.0%; p = 0.039). The proportion of patients receiving renal replacement therapy at the time of enrollment was higher in the treatment group (31.9%) when compared to the control group (16.3%). After adjustment for patient morbidity and baseline imbalances, no association of hemoperfusion with mortality was found (p = 0.19). CONCLUSIONS: In this patient population with predominantly septic shock and multiple organ failure, hemoadsorption removed IL-6 but this did not lead to lower plasma IL-6-levels. We did not detect statistically significant differences in the secondary outcomes multiple organ dysfunction score, ventilation time and time course of oxygenation.

Calf Resistivity Values in Chronic Kidney Disease in a Caucasian Population.

BACKGROUND: Continuous intradialytic calf bioimpedance spectroscopy (cBIS) allows assessment of changes in calf extracellular fluid volume (ECV) to determine dry weight (DW) in hemodialysis patients. During dialysis, calf ECV decreases until excessive ECV has been removed and normalized resistivity ρN,5 rises to values comparable to those of a normal population (cBIS-DW). It is not clear whether chronic kidney disease (CKD) itself influences ρN,5 and whether normal values depend on race and ethnicity. METHODS: Therefore, we determined ρN,5 in 2 populations consisting of 35 healthy Caucasians and 37 with CKD in KDIGO stages G2-G4. Calf resistivity was determined using a bioimpedance spectrum analyzer (Xitron Technologies, San Diego, CA, USA) and was normalized for body mass index. RESULTS: ρN,5 was significantly higher in healthy subjects than in CKD patients (males: 18.2 ± 2.2 vs. 15.0 ± 2.8 × 10-2·Ωm3kg-1, p < 0.001; females: 19.7 ± 3.2 vs. 16.4 ± 3.3 × 10-2·Ωm3kg-1, p = 0.009). ρN,5 in Caucasians was significantly lower than in previously examined North American healthy subjects with prevailing African American race or Hispanic ethnicity (males: 18.2 ± 2.2 vs. 20.5 ± 2.0 × 10-2·Ωm3kg-1, p < 0.001; females: 19.7 ± 3.2 vs. 21.7 ± 2.6 × 10-2·Ωm3kg-1, p = 0.026). CONCLUSION: We present the first determination of ρN,5 values in a Caucasian healthy as well as a non-dialysis dependent CKD population. Both groups differ significantly. Due to higher amounts of extracellular water, subclinical fluid overload already occurs in pre-dialysis stages of CKD. ρN,5 in Caucasians differs significantly from previously established normal ranges in other races/ethnicities. Population-based reference ranges should be established and used in the future to determine DW by means of cBIS.

Plasma vitamin C levels in ESRD patients and occurrence of hypochromic erythrocytes.

INTRODUCTION: The achievement of erythropoiesis in hemodialysis (HD) patients is typically managed with erythropoiesis-stimulating-agents (ESA's) and intravenous iron (IV-iron). Using this treatment strategy, HD patients frequently show an elevated fraction of red blood cells (RBC) with hemoglobin (Hb) content per cell that is below the normal range, called hypochromic RBC. The low Hb content per RBC is the result of the clinical challenge of providing sufficient iron content to the bone marrow during erythropoiesis. Vitamin C supplements have been used to increase Hb levels in HD patients with refractory anemia, which supports the hypothesis that vitamin C mobilizes iron needed for Hb synthesis. METHODS: We conducted a cross-sectional survey in 149 prevalent HD patients of the percent hypochromic RBC, defined as RBC with Hb < 300 ng/uL of packed RBC, in relation to plasma vitamin C levels. We also measured high-sensitivity CRP, (hs-CRP), iron, and ferritin levels. and calculated ESA dose. FINDINGS: High plasma levels of vitamin C were negatively associated with hypochromic RBC (P < 0.003), and high ESA doses were positively associated (P < 0.001). There was no significant association of hs-CRP with percent hypochromic RBC. DISCUSSION: This finding supports the hypothesis that vitamin C mobilizes iron stores, improves iron delivery to the bone marrow, and increase the fraction of RBC with normal Hb content. Further research is warranted on development of protocols for safe and effective use of supplemental vitamin C for management of renal anemia.

Prevalence of reduced kidney function and albuminuria in older adults: the Berlin Initiative Study.

BACKGROUND: Although CKD is said to increase among older adults, epidemiologic data on kidney function in people ≥70 years of age are scarce. The Berlin Initiative Study (BIS) aims to fill this gap by evaluating the CKD burden in older adults. METHODS: The BIS is a prospective population-based cohort study whose participants are members of Germany's biggest insurance company. This cross-sectional analysis (i) gives a detailed baseline characterization of the participants, (ii) analyses the representativeness of the cohort's disease profile, (iii) assesses GFR and albuminuria levels across age categories, (iv) associates cardiovascular risk factors with GFR as well as albuminuria and (v) compares means of GFR values according to different estimating equations with measured GFR. RESULTS: A total of 2069 participants (52.6% female, mean age 80.4 years) were enrolled: 26.1% were diabetic, 78.8% were on antihypertensive medication, 8.7% had experienced a stroke, 14% a myocardial infarction, 22.6% had cancer, 17.8% were anaemic and 26.5% were obese. The distribution of comorbidities in the BIS cohort was very similar to that in the insurance 'source population'. Creatinine and cystatin C as well as the albumin:creatinine ratio (ACR) increased with increasing age. After multivariate adjustments, reduced GFR and elevated ACR were associated with most cardiovascular risk factors. The prevalence of a GFR <60 mL/min/1.73 m 2 ranged from 38 to 62% depending on the estimation equation used. CONCLUSIONS: The BIS is a very well-characterized, representative cohort of older adults. Participants with an ACR ≥30 had significantly higher odds for most cardiovascular risk factors compared with an ACR <30 mg/g. Kidney function declined and ACR rose with increasing age.

Morbidity, mortality and quality of life in the ageing haemodialysis population: results from the ELDERLY study.

BACKGROUND: The physical-functional and social-emotional health as well as survival of the elderly (≥75 years of age) haemodialysis patient is commonly thought to be poor. In a prospective, multicentre, non-interventional, observational study, the morbidity, mortality and quality of life (QoL) in this patient group were examined and compared with a younger cohort. METHODS: In 92 German dialysis centres, 2507 prevalent patients 19-98 years of age on haemodialysis for a median of 19.2 months were included in a drug monitoring study of darbepoetin alfa. To examine outcome and QoL parameters, 24 months of follow-up data in the age cohorts <75 and ≥75 years were analysed. Treatment parameters, adverse and intercurrent events, hospitalizations, morbidity and mortality were assessed. QoL was evaluated by means of the 47-item Functional Assessment of Chronic Illness Therapy-Anaemia score (FACT-An, version 4). RESULTS: The 2-year mortality rate was 34.7% for the older cohort and 15.8% for the younger cohort. The mortality rate for the haemodialysed elderly patients was 6.2% higher in absolute value compared with the age-matched background population. A powerful predictor of survival was the baseline FACT-An score and a close correlation with the 20-item anaemia subscale (AnS) was demonstrated. While the social QoL in the elderly patients was more stable than in the younger cohort (leading to equivalent values at the end of the study period), a pronounced deterioration of physical and functional status was observed. The median number of all-cause hospital days per patient-year was 12.3 for the elderly cohort and 8.9 for the younger patient population. The overall 24-month hospitalization rate was only marginally higher in the elderly cohort (34.0 versus 33.3%). CONCLUSIONS: In this observational study, the mortality rate of elderly haemodialysis patients was not exceedingly high compared with the age-matched background population. Furthermore, the hospitalization rate was only slightly higher compared with the younger age group and the median yearly hospitalization time trended lower compared with registry data. The social well-being of elderly haemodialysis patients showed a less pronounced decline over time and was equal to the score of the younger cohort at the end of the study period. The physical and functional status in the elderly patients was lower and showed a sharper decline over time. The baseline FACT-An score correlated closely with the 24-month survival probability.

[Practical aspects in the use of biosimilar insulins]. / Praktische Aspekte im Umgang mit Insulin-Biosimilars.

Following the market authorization of the first insulin biosimilar in 2014, further approvals are to be expected due to patent expiry of several originator insulins. Knowledge of the manufacturing and the characteristics of these pharmaceutical products is important for their rationale and safe use by the physician, the pharmacist and the patient.Biosimilars are not generics, but similar or comparable, yet not identical versions of the originator biopharmaceutical. Marketing authorization in the EU is granted only after passing a stringent procedure. So far, there is no evidence of problems specifically associated with insulin biosimilars. However, shifting a patient from an originator insulin to a biosimilar (or vice versa) should be done with care and under close monitoring. Automatic substitution of biosimilars in the pharmacy is not permitted in Germany. Administration devices also have a significant impact on safe use.

Comparison of fluid volume estimates in chronic hemodialysis patients by bioimpedance, direct isotopic, and dilution methods.

Bioimpedance analysis (BIA) is accepted for the assessment of total-body water (TBW), intracellular fluid (ICF) and extracellular fluid (ECF). We aimed to compare precision and accuracy of single and multi-frequency-BIA to direct estimation methods (DEMs) of TBW, ECF, and ICF in hemodialysis patients. Linear regression analysis of volume estimates in 49 patients by single- and multi-frequency-BIA correlated significantly with DEMs. Bland-Altman analysis (BAA) found systemic bias for ECF single-frequency-BIA vs. ECF-DEMs. No other systematic biases were found. Proportional errors were found by BAA of ICF and ECF assessments with single- and multi-frequency bioimpedance spectroscopy compared to the DEMs. Comparisons of indirect methods (IEMs) to DEMs showed no significant differences and proportional errors. Root mean-squared-error analysis suggested slightly better accuracy and precision of ICF single-frequency-BIA vs. DEMs over ICF multi-frequency-BIA and IEMs to DEMs, and slightly better performance for ECF multi-frequency-BIA over both respective other methods. Compared to DEMs, there is slightly better accuracy for ECF multi- over single-frequency-BIA and ICF single- over multi-frequency-BIA. However the margin of differences between direct and indirect methods suggests that none of the analyzed methods served as a true "gold standard", because indirect methods are almost equally precise compared to DEMs.