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.

Incidence of hospital-acquired acute kidney injury and trajectories of glomerular filtration rate in older adults.

BACKGROUND: In older adults, epidemiological data on incidence rates (IR) of hospital-acquired acute kidney injury (AKI) are scarce. Also, little is known about trajectories of kidney function before hospitalization with AKI. METHODS: We used data from biennial face-to-face study visits from the prospective Berlin Initiative Study (BIS) including community-dwelling participants aged 70+ with repeat estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin C. Primary outcome was first incident of hospital-acquired AKI assessed through linked insurance claims data. In a nested case-control study, kidney function decline prior to hospitalization with and without AKI was investigated using eGFR trajectories estimated with mixed-effects models adjusted for traditional cardiovascular comorbidities. RESULTS: Out of 2020 study participants (52.9% women; mean age 80.4 years) without prior AKI, 383 developed a first incident AKI, 1518 were hospitalized without AKI, and 119 were never hospitalized during a median follow-up of 8.8 years. IR per 1000 person years for hospital-acquired AKI was 26.8 (95% confidence interval (CI): 24.1-29.6); higher for men than women (33.9 (29.5-38.7) vs. 21.2 (18.1-24.6)). IR (CI) were lowest for persons aged 70-75 (13.1; 10.0-16.8) and highest for ≥ 90 years (54.6; 40.0-72.9). eGFR trajectories declined more steeply in men and women with AKI compared to men and women without AKI years before hospitalization. These differences in eGFR trajectories remained after adjustment for traditional comorbidities. CONCLUSION: AKI is a frequent in-hospital complication in individuals aged 70 + showing a striking increase of IR with age. eGFR decline was steeper in elderly patients with AKI compared to elderly patients without AKI years prior to hospitalization emphasising the need for long-term kidney function monitoring pre-admission to improve risk stratification.

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.

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.

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.

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 (

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.

Adaptive Monostatic System for Measuring Microwave Reflections from the Breast.

A second-generation monostatic radar system to measure microwave reflections from the human breast is presented and analyzed. The present system can measure the outline of the breast with an accuracy of ±1 mm and precisely place the microwave sensor in an adaptive matter such that microwaves are normally incident on the skin. Microwave reflections are measured between 10 MHz to 12 GHz with sensitivity of 65 to 75 dB below the input power and a total scan time of 30 min for 140 locations. The time domain reflections measured from a volunteer show fidelity above 0.98 for signals in a single scan. Finally, multiple scans of a breast phantoms demonstrate the consistency of the system in terms of recorded reflection, outline measurement, and image reconstruction.

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.

Iohexol plasma clearance measurement in older adults with chronic kidney disease-sampling time matters.

BACKGROUND: Accurate and precise measurement of GFR is important for patients with chronic kidney disease (CKD). Sampling time of exogenous filtration markers may have great impact on measured GFR (mGFR) results, but there is still uncertainty about optimal timing of plasma clearance measurement in patients with advanced CKD, for whom 24-h measurement is recommended. This satellite project of the Berlin Initiative Study evaluates whether 24-h iohexol plasma clearance reveals a clinically relevant difference compared with 5-h measurement in older adults. METHODS: In 104 participants with a mean age of 79 years and diagnosed CKD, we performed standard GFR measurement over 5 h (mGFR300) using iohexol plasma concentrations at 120, 180, 240 and 300 min after injection. With an additional sample at 1440 min, we assessed 24-h GFR measurement (mGFR1440). Study design was cross-sectional. Calculation of mGFR was conducted with a one compartment model using the Brochner-Mortensen equation to calculate the fast component. mGFR values were compared with estimated GFR values (MDRD, CKD-EPI, BIS1, Revised Lund-Malmö and Cockcroft-Gault). RESULTS: In all 104 subjects, mGFR1440 was lower than mGFR300 (23 ± 8 versus 29 ± 9 mL/min/1.73 m(2), mean ± SD; P < 0.001). mGFR1440 was highly correlated with mGFR300 (r = 0.9). The mean absolute difference mGFR300 - mGFR1440 was 5.9 mL/min/1.73 m(2) corresponding to a mean percentage difference of 29%. In individuals with eGFRCKD-EPI ≤ 30 mL/min/1.73 m(2), percentage difference of mGFR300 and mGFR1440 was even higher (35%). To predict mGFR1440 from mGFR300, we developed the correction formula: mGFR1440 = -2.175 + 0.871 × mGFR300 (1-fold standard error of estimate: ±2.3 mL/min/1.73 m(2)). The GFR estimating equation with the best accuracy and precision compared with mGFR300 and mGFR1440 was the Revised Lund Malmö. CONCLUSIONS: In elderly CKD patients, measurement of iohexol clearance up to 5 h leads to a clinically relevant overestimation of GFR compared with 24-h measurement. In clinical care, this effect should be bore in mind especially for patients with considerably reduced GFR levels. A new correction formula has been developed to predict mGFR1440 from mGFR300. For accurate GFR estimates in elderly CKD patients, we recommend the Revised Lund Malmö equation.

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.

Novel techniques and innovation in blood purification: a clinical update from Kidney Disease: Improving Global Outcomes.

Mortality in patients with end-stage renal disease (ESRD) remains unacceptably high. Emerging techniques and advances in dialysis technology have the potential to improve clinical outcomes in the ESRD population. This report summarizes the deliberations and recommendations of a conference sponsored by Kidney Disease: Improving Global Outcomes to address the following questions: (1) what is the appropriate frequency and duration of hemodialysis; (2) how should we optimize water quality and dialysate composition; and (3) what technical innovations in blood purification and bioengineering can result in better clinical outcomes? The conference report will augment our current understanding of clinical practice in blood purification and will pose several high-priority research questions.

Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism.

Protein energy wasting (PEW) is common in patients with chronic kidney disease (CKD) and is associated with adverse clinical outcomes, especially in individuals receiving maintenance dialysis therapy. A multitude of factors can affect the nutritional and metabolic status of CKD patients requiring a combination of therapeutic maneuvers to prevent or reverse protein and energy depletion. These include optimizing dietary nutrient intake, appropriate treatment of metabolic disturbances such as metabolic acidosis, systemic inflammation, and hormonal deficiencies, and prescribing optimized dialytic regimens. In patients where oral dietary intake from regular meals cannot maintain adequate nutritional status, nutritional supplementation, administered orally, enterally, or parenterally, is shown to be effective in replenishing protein and energy stores. In clinical practice, the advantages of oral nutritional supplements include proven efficacy, safety, and compliance. Anabolic strategies such as anabolic steroids, growth hormone, and exercise, in combination with nutritional supplementation or alone, have been shown to improve protein stores and represent potential additional approaches for the treatment of PEW. Appetite stimulants, anti-inflammatory interventions, and newer anabolic agents are emerging as novel therapies. While numerous epidemiological data suggest that an improvement in biomarkers of nutritional status is associated with improved survival, there are no large randomized clinical trials that have tested the effectiveness of nutritional interventions on mortality and morbidity.

Calf bioimpedance spectroscopy for determination of dry weight in hemodialysis patients: effects on hypertension and left ventricular hypertrophy.

BACKGROUND/AIMS: Dry weight estimation in hemodialysis patients is still a substantial problem. Despite meticulous clinical assessment, fluid overload is common, leading to hypertension and left ventricular hypertrophy (LVH). Segmental calf bioimpedance spectroscopy (cBIS) is a novel tool for dry weight assessment. Here we tested the hypothesis, that its clinical routine use reduces arterial hypertension and left ventricular mass. METHODS: Left ventricular mass (determined by magnetic resonance imaging), blood pressure and antihypertensive medication (defined daily doses, ddd) were assessed at baseline (BL). Thereafter post-dialytic target weight was reduced until cBIS-defined dry weight was reached (DW). During a 6-month follow up, DW was re-evaluated monthly by cBIS and end-dialytic weight was adjusted correspondingly. At the end, left ventricular mass, blood pressure and antihypertensive medication were determined a 3rd time (follow-up, FU). RESULTS: Eleven out of 15 patients were available for analysis after 6 months. Left ventricular mass showed a declining trend during the study period (Mean±SD; BL 145±54 g; DW 142±55 g; FU 137±52 g; p=0.61, linear mixed model). Comparable results were obtained for systolic blood pressure (BL 158±18 mmHg; DW 144±19 mmHg; FU 149±21 mmHg; p=0.07), and antihypertensive medication (BL 3.28±2.82ddd; DW 2.86±2.81ddd; FU 3.36±3.05ddd; p=0.37). CONCLUSIONS: We conclude that attainment of dry weight assessed by cBIS tends to reduce left ventricular mass and blood pressure while antihypertensive medication remains unchanged. While the study was underpowered, its results provide an important hypothesis generating data basis for the design of larger studies.

Hospitalization and mortality in hemodialysis patients: association with hemoglobin variability.

BACKGROUND/AIMS: Hemodialysis patients show complications associated with low or high hemoglobin (Hb), which occur frequently in clinical practice. We sought to determine the clinical importance of these changes in Hb levels. METHODS: From our clinic cohorts, we identified 1,634 who met inclusion criteria for analysis of hospitalization frequency and 1,953 analysis of mortality; many patients were in both groups. Hb excursions outside the target range (11-12.5 g/dl) were studied in relation to patient outcomes. RESULTS: Hb measures below range were associated with more frequent hospitalization (p < 0.001), increased length of stay (p < 0.001), and increased mortality (p < 0.01), whereas Hb above range was associated with a reduced frequency of hospitalization (p < 0.01) and shorter length of stay (p < 0.01), and tended to be associated with reduced mortality. CONCLUSIONS: Excursions below range were associated with negative outcomes, but excursions above range were either beneficial or neutral. Our findings indicate that clinicians should focus on low Hb as a negative indicator of patient status, whereas transient Hb above range is a marker for patient health and well-being.

Two novel equations to estimate kidney function in persons aged 70 years or older.

BACKGROUND: In older adults, current equations to estimate glomerular filtration rate (GFR) are not validated and may misclassify elderly persons in terms of their stage of chronic kidney disease. OBJECTIVE: To derive the Berlin Initiative Study (BIS) equation, a novel estimator of GFR in elderly participants. DESIGN: Cross-sectional. Data were split for analysis into 2 sets for equation development and internal validation. SETTING: Random community-based population of a large insurance company. PARTICIPANTS: 610 participants aged 70 years or older (mean age, 78.5 years). INTERVENTION: Iohexol plasma clearance measurement as gold standard. MEASUREMENTS: GFR, measured as the plasma clearance of the endogenous marker iohexol, to compare performance of existing equations of estimated GFR with measured GFR of the gold standard; estimation of measured GFR from standardized creatinine and cystatin C levels, sex, and age in the learning sample; and comparison of the BIS equations (BIS1: creatinine-based; BIS2: creatinine- and cystatin C-based) with other estimating equations and determination of bias, precision, and accuracy in the validation sample. RESULTS: The new BIS2 equation yielded the smallest bias followed by the creatinine-based BIS1 and Cockcroft-Gault equations. All other equations considerably overestimated GFR. The BIS equations confirmed a high prevalence of persons older than 70 years with a GFR less than 60 mL/min per 1.73 m2 (BIS1, 50.4%; BIS2, 47.4%; measured GFR, 47.9%). The total misclassification rate for this criterion was smallest for the BIS2 equation (11.6%), followed by the cystatin C equation 2 (15.1%) proposed by the Chronic Kidney Disease Epidemiology Collaboration. Among the creatinine-based equations, BIS1 had the smallest misclassification rate (17.2%), followed by the Chronic Kidney Disease Epidemiology Collaboration equation (20.4%). LIMITATION: There was no validation by an external data set. CONCLUSION: The BIS2 equation should be used to estimate GFR in persons aged 70 years or older with normal or mild to moderately reduced kidney function. If cystatin C is not available, the BIS1 equation is an acceptable alternative. PRIMARY FUNDING SOURCE: Kuratorium für Dialyse und Nierentransplatation (KfH) Foundation of Preventive Medicine.

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.

Slope analysis of blood volume and calf bioimpedance monitoring in hemodialysis patients.

BACKGROUND: Continuous intradialytic bioelectrical impedance spectroscopy of the calf (cBIS) monitors changes in calf extracellular fluid volume (cECV), thus allowing estimation of hydration in end-stage renal disease patients. Blood volume monitoring (BVM) during hemodialysis (HD) provides information about relative changes in intravascular volume, which indirectly reflects plasma refilling. We hypothesize that the rate of plasma refilling changes when cBIS-determined dry weight (BIS-DW) is reached. METHODS: Post-HD weight was reduced from baseline (BL) in 15 patients until dry weight was reached according to cBIS criteria (BIS-DW). The slopes of cBIS and BVM curves were analysed during the first 30 and last 20 min in 31 BL treatments, which were compared to the slopes during 31 treatments when BIS-DW was reached. RESULTS: During BL treatments, BVM slopes did not differ between the first 30 and last 20 min (-0.112 ± 0.157%/min versus -0.089 ± 0.036, P = n.s.), while cBIS slopes were generally steeper at the beginning than at the end of HD (-0.184 ± 0.139%/min versus 0.10 ± 0.127, P < 0.01). During BIS-DW treatments, BVM and cBIS slopes were steeper at the beginning than at the end (BVM: -0.131 ± 0.122 versus -0.064 ± 0.051, P < 0.01; cBIS: -0.192 ± 0.129 versus -0.035 ± 0.012, P < 0.001) and the cBIS slopes were steeper than BVM slopes at the beginning of HD. This relationship is inverted at the end of HD, when BIS-DW is reached (beginning: -0.192 ± 0.129 versus -0.131 ± 0.122, P < 0.05, end: -0.035 ± 0.012 versus -0.064 ± 0.051, P = 0.05). CONCLUSIONS: This study demonstrates that cECV changes faster at the beginning than at the end of HD. A reversal steepness of the cBIS slope in relation to BVM slope is observed at the time when BIS-DW is reached. Therefore, combined analysis of cBIS and BVM aiming at clinical end points may be useful to assess the relationship between plasma refilling and tissue hydration during dialysis.

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.