Age- and Sex-Specific Reference Values for Renal Volume and Association with Risk Factors for Chronic Kidney Disease in a General Population-An MRI-Based Study.

BACKGROUND: Renal volume (RV) is associated with renal function and with a variety of cardiovascular risk factors (CVRFs). We analysed RV using magnetic resonance imaging (MRI) in a large population-based study (Study of Health in Pomerania; SHIP-TREND) to find sex- and age-specific reference values for RV and to test the influence of several markers on RV. The main objective is to describe reference values for RV in people from the general population without kidney disease. METHODS: 1815 participants without kidney disease (930 women) aged 21-81 years were included in our study. Right and left RV with and without body surface area (BSA) indexation were compared among three age groups (22-39 years, 40-59 years, 60-81 years) by median and interquartile range and tested separately in women and men. RESULTS: The estimated glomerular filtration rate (eGFR), serum uric acid, and right and left RV were higher in men compared to women (all p < 0.001). Left kidneys were larger than right kidneys (both sexes). With age, RV showed a continuously decreasing trend in women and an upside-down U-shaped relation in men. In multivariable linear regression models, current smoking (ß = 14.96, 95% CI 12.12; 17.79), BSA (ß = 97.66, 95% CI 90.4; 104.93), diastolic blood pressure (ß = 0.17, 95% CI 0.01; 0.32), and eGFR (ß = 0.57, 95% CI 0.50; 0.65) were positively associated with both left and right RV, whereas uric acid (ß = -0.03, 95% CI -0.05; -0.01) showed an inverse association with RV. Interestingly, the same eGFR correlated with higher RV in men compared to women. CONCLUSION: Reference values for RV are different for age groups and sex. For any given age, female kidneys are smaller than male kidneys. RV associates positively with eGFR, but for any chosen eGFR, renal volume in females is lower compared to males. RV decreases with age, but in men showed a U-shaped correlation. This may reflect hyperfiltration and glomerular hypertrophy associated with the presence of CVRF in middle-aged males.

Carotid intima-media thickness and atherosclerotic plaques are associated with renal function decline: a 14-year longitudinal population-based study.

BACKGROUND: Chronic kidney disease (CKD) leads to increased morbidity and mortality. The underlying causes of CKD are often similar to those of atherosclerosis. We investigated whether carotid atherosclerotic parameters are associated with renal function decline. METHODS: Within the population-based Study of Health in Pomerania (SHIP), Germany, 2904 subjects were observed over 14 years. The carotid intima-media thickness (cIMT) as well as carotid plaques were measured by standardized B-mode ultrasound protocol. CKD is defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and albuminuria as urinary albumin-creatinine ratio (ACR) ≥30 mg/g. eGFR was calculated by the full age spectrum (FAS) equation and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Mixed models were applied to associate carotid parameters with change in renal function longitudinally and adjusted for confounding. RESULTS: The age range of the study sample was 25-86 years with a median of 54 years at baseline. In longitudinal analyses, subjects with high cIMT and the presence of plaques at baseline showed a greater decrease in eGFR (cIMT: FAS-eGFR: P < .001, CKD-EPI-eGFR: P < .001; plaques: FAS-eGFR: P < .001, CKD-EPI-eGFR: n.s.) as well as an increased risk of developing CKD during the follow-up (cIMT: FAS-eGFR: P = .001, CKD-EPI-eGFR: P = .04; plaques: FAS-eGFR: P = .008, CKD-EPI-eGFR: P = .001). There was no association between atherosclerotic parameters and the risk of developing albuminuria. CONCLUSIONS: cIMT and carotid plaques are associated with renal function decline as well as CKD in a population-based sample. Furthermore, the FAS equation adapts best to this study population.

[Development of quality indicators for the care of patients with chronic kidney disease : Results of a structured consensus process using the Delphi technique]. / Entwicklung von Qualitätsindikatoren für die Versorgung von Patient:innen mit chronischer Nierenerkrankung : Ergebnisse einer strukturierten Konsensfindung mittels Delphi-Verfahrens.

BACKGROUND: Chronic kidney disease (CKD) is a common condition, especially in the elderly. In order to prevent progression and complications of the disease, guideline-adherent outpatient care of patients with CKD should be prioritized. Quality indicators (QIs) can be used to measure and evaluate the quality of ambulatory care for patients with CKD. QIs specifically made for evaluating CKD care in Germany are not yet available. The goal of this work was to develop QIs for the quality assessment of outpatient care for patients over the age of 70 with CKD not requiring dialysis. MATERIALS AND METHODS: QIs were operationalized from the recommendations of the German national guideline for CKD and others were proposed based on a published review of international QIs. The resulting QIs were divided into sets based on routine data (e.g., health insurance billing data) and data collection in practices (chart review). A panel of experts from various disciplines as well as a patient representative evaluated the proposed QIs in a two-stage Delphi process via online survey in October 2021 and January 2022 and a final consensus conference in March 2022. In addition, ranking lists of the most important QIs from each set were created. RESULTS: An incidence indicator and a prevalence indicator were established; these were not subject to vote. Further, 21 QIs were voted upon by the expert panel. The seven most important QIs in each set (billing data or chart review) were selected. Only one QI was rated by the expert panel as not suitable for additional use in adults under the age of 70 years. DISCUSSION: The QIs will enable the evaluation of the quality of outpatient care for patients with CKD with the long-term aim of optimizing guideline-adherent outpatient care.

Renal angiotensin I-converting enzyme-deficient mice are protected against aristolochic acid nephropathy.

The renal renin-angiotensin system (RAS) is involved in the development of chronic kidney disease. Here, we investigated whether mice with reduced renal angiotensin I-converting enzyme (ACE-/-) are protected against aristolochic acid nephropathy (AAN). To further elucidate potential molecular mechanisms, we assessed the renal abundances of several major RAS components. AAN was induced using aristolochic acid I (AAI). Glomerular filtration rate (GFR) was determined using inulin clearance and renal protein abundances of renin, angiotensinogen, angiotensin I-converting enzyme (ACE) 2, and Mas receptor (Mas) were determined in ACE-/- and C57BL/6J control mice by Western blot analyses. Renal ACE activity was determined using a colorimetric assay and renal angiotensin (Ang) (1-7) concentration was determined by ELISA. GFR was similar in vehicle-treated mice of both strains. AAI decreased GFR in controls but not in ACE-/- mice. Furthermore, AAI decreased renal ACE activity in controls but not in ACE-/- mice. Vehicle-treated ACE-/- mice had significantly higher renal ACE2 and Mas protein abundances than controls. AAI decreased renal ACE2 protein abundance in both strains. Furthermore, AAI increased renal Mas protein abundance, although the latter effect did not reach statistical significance in the ACE-/- mice. Renal Ang(1-7) concentration was similar in vehicle-treated mice of both strains. AAI increased renal Ang(1-7) concentration in the ACE-/- mice but not in the controls. Mice with reduced renal ACE are protected against AAN. Our data suggest that in the face of renal ACE deficiency, AAI may activate the ACE2/Ang(1-7)/Mas axis, which in turn may deploy its reno-protective effects.

Monitoring and management of chronic kidney disease in ambulatory care - analysis of clinical and claims data from a population-based study.

BACKGROUND: Although chronic kidney disease (CKD) is highly prevalent in the general population, little research has been conducted on CKD management in ambulatory care. Objective was to assess management and quality of care by evaluating CKD coding in ambulatory care, patient diagnosis awareness, frequency of monitoring and whether appropriate patients are referred to nephrology. METHODS: Clinical data from the population-based cohort Study of Health in Pomerania (SHIP-START) were matched with claims data of the Association of Statutory Health Insurance Physicians. Quality of care was evaluated according international and German recommendations. RESULTS: Data from 1778 participants (56% female, mean age 59 years) were analysed. 10% had eGFR < 60 ml/min/1.73m2 (mean age 74 years), 15% had albuminuria. 21% had CKD as defined by KDIGO. 20% of these were coded and 7% self-reported having CKD. Coding increased with GFR stage (G3a 20%, G3b 61%, G4 75%, G5 100%). Serum creatinine and urinary dip stick testing were billed in the majority of all participants regardless of renal function. Testing frequency partially surpassed recommendations. Nephrology consultation was billed in few cases with stage G3b-G4. CONCLUSION: CKD coding increased with stage and was performed reliably in stages ≥ G4, while CKD awareness was low. Adherence to monitoring and referral criteria varied, depending on the applicability of monitoring criteria. For assessing quality of care, consent on monitoring, patient education, referral criteria and coordination of care needs to be established, accounting for patient related factors, including age and comorbidity. TRIAL REGISTRATION: This study was prospectively registered as DRKS00009812 in the German Clinical Trials Register (DRKS).

Referral criteria for chronic kidney disease: implications for disease management and healthcare expenditure-analysis of a population-based sample.

BACKGROUND: Clinical practice guidelines recommend specialist referral according to different criteria. The aim was to assess recommended and observed referral rate and health care expenditure according to recommendations from: • Kidney Disease Improving Global Outcomes (KDIGO,2012) • National Institute for Health and Care Excellence (NICE,2014) • German Society of Nephrology/German Society of Internal Medicine (DGfN/DGIM,2015) • German College of General Practitioners and Family Physicians (DEGAM,2019) • Kidney failure risk equation (NICE,2021) METHODS: Data of the population-based cohort Study of Health in Pomerania were matched with claims data. Proportion of subjects meeting referral criteria and corresponding health care expenditures were calculated and projected to the population of Mecklenburg-Vorpommern. RESULTS: Data from 1927 subjects were analysed. Overall proportion of subjects meeting referral criteria ranged from 4.9% (DEGAM) to 8.3% (DGfN/DGIM). The majority of patients eligible for referral were ≥ 60 years. In subjects older than 60 years, differences were even more pronounced, and rates ranged from 9.7% (DEGAM) to 16.5% (DGfN/DGIM). Estimated population level costs varied between €1,432,440 (DEGAM) and €2,386,186 (DGfN/DGIM). From 190 patients with eGFR < 60 ml/min, 15 had a risk of end stage renal disease > 5% within the next 5 years. CONCLUSIONS: Applying different referral criteria results in different referral rates and costs. Referral rates exceed actually observed consultation rates. Criteria need to be evaluated in terms of available workforce, resources and regarding over- and underutilization of nephrology services.

Potentially inappropriate medication in patients with chronic kidney disease and elderly patients.

BACKGROUND: Most patients with chronic kidney disease (CKD) are old, comorbid, and subjected to polypharmacy. This study describes prevalence and predictors of potentially inappropriate medication (PIM) in CKD patients. MATERIALS AND METHODS: Medication plans of CKD patients of the "Greifswald Approach to Individualized Medicine" cross-sectional study (GANI_MED) were checked for PIM based on kidney function (PIM-K) and PIM for elderly patients (PIM-E). PIM-K were defined by prescription instructions of product labeling. PIM-E were defined by BEERS, -PRISCUS, and FORTA criteria. Predictors for PIM were identified through multiple stepwise regression. RESULTS: 375 patients were included (age: 67.9 ± 13.5 years; estimated glomerular filtration rate (eGFR): 23.3 ± 18.6 mL/min/1.73m2; prescriptions: 11.1 ± 4.7). 44.5% of all CKD patients had PIM-K, and 43.2 to 79.0% of all elderly patients had PIM-E. Polypharmacy and reduced eGFR were predictors for PIM. The risk for PIM-K was increased by 3.8 (95% confidence interval (CI): 1.5 - 9.6) with 10 or more prescriptions and by 8.7 (95% CI: 1.3 - 58.5) with an eGFR below 30 mL/min/1.73m2. On average, elderly patients with 10 or more prescriptions had 3.0 ± 1.7 PIM-E. CONCLUSION: Polypharmacy, PIM-K, and PIM-E affect many CKD patients and can lead to adverse events. Deprescribing and targeted prescribing may improve the outcome of CKD patients and elderly patients.

Long-term prognosis after kidney donation: a propensity score matched comparison of living donors and non-donors from two population cohorts.

BACKGROUND: Live donor nephrectomy is a safe procedure. However, long-term donor prognosis is debated, necessitating high-quality studies. METHODS: A follow-up study of 761 living kidney donors was conducted, who visited the outpatient clinic and were propensity score matched and compared to 1522 non-donors from population-based cohort studies. Primary outcome was kidney function. Secondary outcomes were BMI (kg/m2), incidences of hypertension, diabetes, cardiovascular events, cardiovascular and overall mortality, and quality of life. RESULTS: Median follow-up after donation was 8.0 years. Donors had an increase in serum creatinine of 26 µmol/l (95% CI 24-28), a decrease in eGFR of 27 ml/min/1.73 m2 (95% CI - 29 to - 26), and an eGFR decline of 32% (95% CI 30-33) as compared to non-donors. There was no difference in outcomes between the groups for ESRD, microalbuminuria, BMI, incidence of diabetes or cardiovascular events, and mortality. A lower risk of new-onset hypertension (OR 0.45, 95% CI 0.33-0.62) was found among donors. The EQ-5D health-related scores were higher among donors, whereas the SF-12 physical and mental component scores were lower. CONCLUSION: Loss of kidney mass after live donation does not translate into negative long-term outcomes in terms of morbidity and mortality compared to non-donors. TRIAL REGISTRATION: Dutch Trial Register NTR3795.

Long-term Association of Periodontitis With Decreased Kidney Function.

RATIONALE & OBJECTIVE: Previous studies have yielded inconclusive findings regarding the relationship between periodontitis and kidney function. We sought to investigate whether periodontitis is associated with subsequent decreases in kidney function (reductions in estimated glomerular filtration rate [eGFR] and increased urinary albumin-creatinine ratio [UACR]) in the general population. STUDY DESIGN: Population-based cohort study. SETTING & PARTICIPANTS: We used baseline and 11-year follow-up data from 2,297 and 1,512 adult participants, respectively, in the Study of Health in Pomerania (SHIP). Age range was limited to 20 to 59 years to avoid the potential influence of tooth loss. EXPOSURES: Periodontal status defined by periodontal pocket probing depth (PPD) and clinical attachment level. Mean levels and the percentage of sites ≥ 3mm was determined for either all sites (PPD) or interproximal sites (clinical attachment level). All PPDs≥4mm were summed to calculate the total PPD. OUTCOMES: GFR estimated from serum creatinine and serum cystatin C (eGFRcr-cys). Moderately increased albuminuria defined as UACR>30mg/g. ANALYTICAL APPROACH: Adjusted linear and logistic mixed regression models. RESULTS: At baseline and follow-up, average eGFRcr-cys was 118.3 and 105.0mL/min/1.73m2, respectively. Using mixed models, no consistently significant associations between periodontitis variables and eGFRcr-cys were detected. Long-term changes in UACR were inconsistently associated with periodontitis measures. After imputation of missing data, associations were either attenuated or no longer detectable. LIMITATIONS: Because periodontal assessments were performed using a partial recording protocol, periodontal disease severity estimates might have been underestimated, resulting in attenuated effect estimates. CONCLUSIONS: We found no consistent evidence for an association between periodontitis and decreased kidney function. In contrast to previous studies, these results do not support the hypothesis that periodontitis is an important risk factor for chronic kidney disease.

[Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study]. / Arzneimittelverordnung bei Patienten mit chronischer Niereninsuffizienz in der hausärztlichen Versorgung.

BACKGROUND: Many drugs require dose adjustment or are contraindicated in patients with chronic kidney disease (CKD) to avoid adverse events. The aims of this study were to assess if medication was appropriately dose adjusted in patients with CKD in primary care, to identify medications that were frequently prescribed inappropriately and to identify factors predicting mal-prescription. METHODS: We conducted a cross-sectional observational study in 34 general practioners' offices, assessing the medication of patients with CKD stage ≥ 3 according to the corresponding pharmaceutical product information. Additional information was extracted from recommendations of scientific societies and regulatory authorities. Contraindicated and overdosed medications were identified. Predictive factors for inadequate prescribing were analyzed with multiple logistic regression. RESULTS: 589 patients (Ø 78 years, 63 % female) with CKD stage ≥ 3 were included. A total of 5102 medications were extracted from the medication sheets (94,6 % regular, 5,4 % "as needed"). 4,2 % were judged as being inadequate according to pharmaceutical information (2,1 % contraindicated, 2,1 % overdosed). 173 patients (29 %) had ≥ 1 inadequate prescription. The proportion of inadequate prescriptions fell to 3,5 % after adjustment for the most recent recommendations of scientific societies and regulatory authorities. Most frequent inappropriate prescriptions were ACE-inhibitors, diuretics, oral antidiabetic drugs, methotrexate and potassium supplements. Most important predictors for inadequate prescriptions were CKD stage ≥ 3b and number of medications. CONCLUSION: A quarter of all patients had a least one inadequate prescription. The overall proportion of inadequately prescribed drugs was low. Adjustment for recommendations by scientific societies and regulatory authorities further reduced the number of inadequate prescriptions. Valid data on the clinical relevance of inadequate prescriptions is scarce and further research is required. Because of the time and effort needed to assess all medications, future quality improvement projects should focus on CKD stage ≥ 3b, patients with polypharmacy and crucial medication.

[Management of Patients with CKD in Clinical Practice]. / Chronische Nierenerkrankungen ­ was der Praktiker wissen sollte.

Chronic kidney disease (CKD) affects between 3 and 17 % of the population in Europe, especially elderly persons. CKD is a clinical syndrome which may develop in patients with e. g. diabetes mellitus, arterial hypertension or autoimmune diseases. A poorer renal function - especially in old age - is to be considered irrespective of the medication. Many antibiotics and painkillers require dose adjustments. Therapy should be done in a manner which is suitable for indication. Polypharmacy should be avoided as far as possible. Diuretics and RAAS inhibitors are useful drugs in therapy of CKD. Changes of lifestyle are important, so as weight reduction, restriction of salt and fructose, sufficient drinking, strict control of blood glucose, blood pressure and hypercholesterolaemia. Additional acute lesions have to be avoided ("acute-on-chronic renal failure").

Serum protease activity in chronic kidney disease patients: The GANI_MED renal cohort.

Serum or plasma proteases have been associated with various diseases including cancer, inflammation, or reno-cardiovascular diseases. We aimed to investigate whether the enzymatic activities of serum proteases are associated with the estimated glomerular filtration rate (eGFR) in patients with different stages of chronic kidney disease (CKD). Our study population comprised 268 participants of the "Greifswald Approach to Individualized Medicine" (GANI_MED) cohort. Enzymatic activity of aminopeptidase A, aminopeptidase B, alanyl (membrane) aminopeptidase, insulin-regulated aminopeptidase, puromycin-sensitive aminopeptidase, leucine aminopeptidase 3, prolyl-endopeptidase (PEP), dipeptidyl peptidase 4 (DPP4), angiotensin I-converting enzyme, and angiotensin I-converting enzyme 2 (ACE2) proteases was measured in serum. Linear regression of the respective protease was performed on kidney function adjusted for age and sex. Kidney function was modeled either by the continuous Modification of Diet in Renal Disease (MDRD)-based eGFR or dichotomized by eGFR < 15 mL/min/1.73 m2 or <45 mL/min/1.73 m2, respectively. Results with a false discovery rate below 0.05 were deemed statistically significant. Among the 10 proteases investigated, only the activities of ACE2 and DPP4 were correlated with eGFR. Patients with lowest eGFR exhibited highest DPP4 and ACE2 activities. DPP4 and PEP were correlated with age, but all other serum protease activities showed no associations with age or sex. Our data indicate that ACE2 and DPP4 enzymatic activity are associated with the eGFR in patients with CKD. This finding distinguishes ACE2 and DPP4 from other serum peptidases analyzed and clearly indicates that further analyses are warranted to identify the precise role of these serum ectopeptidases in the pathogenesis of CKD and to fully elucidate underlying molecular mechanisms. Impact statement • Renal and cardiac diseases are very common and often occur concomitantly, resulting in increased morbidity and mortality. Understanding of molecular mechanisms linking both diseases is limited, available fragmentary data point to a role of the renin-angiotensin system (RAS) and, in particular, Ras-related peptidases. • Here, a comprehensive analysis of serum peptidase activities in patients with different stages of chronic kidney disease (CKD) is presented, with special emphasis given to RAS peptidases • The serum activities of the peptidases angiotensin I-converting enzyme 2 and dipeptidyl peptidase 4 were identified as closely associated with kidney function, specifically with the estimated glomerular filtration rate. The findings are discussed in the context of available data suggesting protective roles for both enzymes in reno-cardiac diseases. • The data add to our understanding of pathomechanisms underlying development and progression of CKD and indicate that both enzymes might represent potential pharmacological targets for the preservation of renal function.

Discrepant post filter ionized calcium concentrations by common blood gas analyzers in CRRT using regional citrate anticoagulation.

INTRODUCTION: Ionized calcium (iCa) concentration is often used in critical care and measured using blood gas analyzers at the point of care. Controlling and adjusting regional citrate anticoagulation (RCA) for continuous renal replacement therapy (CRRT) involves measuring the iCa concentration in two samples: systemic with physiological iCa concentrations and post filter samples with very low iCa concentrations. However, modern blood gas analyzers are optimized for physiological iCa concentrations which might make them less suitable for measuring low iCa in blood with a high concentration of citrate. We present results of iCa measurements from six different blood gas analyzers and the impact on clinical decisions based on the recommendations of the dialysis' device manufacturer. METHOD: The iCa concentrations of systemic and post filter samples were measured using six distinct, frequently used blood gas analyzers. We obtained iCa results of 74 systemic and 84 post filter samples from patients undergoing RCA for CRRT at the University Medicine of Greifswald. RESULTS: The systemic samples showed concordant results on all analyzers with median iCa concentrations ranging from 1.07 to 1.16 mmol/L. The medians of iCa concentrations for post filter samples ranged from 0.21 to 0.50 mmol/L. Results of >70% of the post filter samples would lead to major differences in decisions regarding citrate flow depending on the instrument used. CONCLUSION: Measurements of iCa in post filter samples may give misleading information in monitoring the RCA. Recommendations of the dialysis manufacturer need to be revised. Meanwhile, little weight should be given to post filter iCa. Reference methods for low iCa in whole blood containing citrate should be established.

Regional variation of chronic kidney disease in Germany: results from two population-based surveys.

BACKGROUND/AIMS: Due to the increasing prevalence of risk factors for chronic kidney disease (CKD), kidney dysfunction becomes a major public health problem. We investigated the CKD prevalence and determined to what extent the variation of risk factors explains the different CKD prevalence in Germany. METHODS: We analyzed data from 6,054 participants, aged 31 to 82 years, from the Study of Health in Pomerania (SHIP-1) in Northeast Germany and the Cooperative Health Research in the Region of Augsburg (KORA F4) Study in Southern Germany. Regional differences in selected percentiles corresponding to the cutpoints for estimated glomerular filtration rate (eGFR, <60 ml/min per 1.73 m(2)) and albumin-to-creatinine ratio (ACR, ≥30 mg/g) were tested using quantile regression models that adjusted for CKD risk factors. RESULTS: The prevalence of decreased eGFRcreatinine-cystatinC (5.9 vs. 3.1 %, p <0.001) and albuminuria (20.2 vs. 8.8 %, p<0.001) were higher in SHIP-1 than in KORA F4. The differential distribution of risk factors explained 18-21% of the regional differences of decreased eGFRcreatinine-cystatinC and high ACR. CONCLUSIONS: The CKD prevalence is higher in Northeast than in Southern Germany. Differences in the prevalence of risk factors partly explain the higher disease burden of CKD in Northeast than in Southern Germany.

Inverse association of estimated cystatin C- and creatinine-based glomerular filtration rate with left ventricular mass: Results from the Study of Health in Pomerania.

BACKGROUND: Left ventricular hypertrophy (LVH) is an independent predictor of cardiovascular disease in the general population and in patients with chronic kidney disease. The objective of this study was to investigate the association of estimated glomerular filtration rate (eGFR) with left ventricular mass index (LVMI), LVH and left ventricular geometry. A question of clinical relevance is whether estimated glomerular filtration rate based on cystatin C (eGFRcystatinC) is a better marker for cardiovascular risk than estimated glomerular filtration rate based on creatinine (eGFRcreatinine). METHODS: The study sample included 2830 individuals from the population-based Study of Health in Pomerania (SHIP). LVH was defined as echocardiographic LVMI >48 g/m(2.7) in men and >44 g/m(2.7) in women. Kidney function, as assessed by eGFR, was determined from established equations: the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and a cystatin-based multivariable equation. RESULTS: We found an inverse association between eGFR and LVMI. This association was stronger in models with eGFRcystatinC than in models with eGFRcreatinine. Subjects with moderately-to-severely decreased kidney function (defined as eGFR 15-<60 mL/min per 1.73 m(2)) had higher odds for abnormal geometric patterns of the left ventricle than subjects with normal eGFR when eGFRcystatinC was used. CONCLUSIONS: The findings suggest that eGFRcystatinC is superior to eGFRcreatinine for assessing the risk of cardiovascular disease.

Age- and sex-specific reference limits for creatinine, cystatin C and the estimated glomerular filtration rate.

BACKGROUND: Early detection of patients with chronic kidney disease is of great importance. This study developed reference limits for serum creatinine and serum cystatin C concentrations and for the estimated glomerular filtration rate (eGFR) in healthy subjects from the general population aged 25-65 years. METHODS: This study defined a reference population including 985 subjects from the first follow-up of the Study of Health in Pomerania. Serum creatinine was measured with a modified kinetic Jaffé method. Serum cystatin C was measured with a nephelometric assay. The eGFR was calculated from serum creatinine according to the Cockcroft-Gault (eGFR(CG)) and the Modification of Diet in Renal Disease (eGFR(MDRD)) equation, respectively, as well as from serum cystatin C according to the formula by Larsson (eGFR(Larsson)). Non-parametric quantile regression was used to estimate the reference limits. For serum creatinine and serum cystatin C the 95th percentile and for eGFR(CG), eGFR(MDRD) and eGFR(Larsson) the 5th percentile were selected as reference limits. All data was weighted to reflect the age- and sex-structure of the German population in 2008. RESULTS: The reference limits for serum creatinine (men: 1.11-1.23 mg/dL; women: 0.93-1.00 mg/dL) and serum cystatin C levels (men: 0.92-1.04 mg/L; women: 0.84-1.02 mg/L) increased with advancing age. The reference limits for eGFR decreased with increasing age (eGFR(CG) men: 106.0-64.7 mL/min, women 84.4-57.9 mL/min; eGFR(MDRD) men: 82.5-62.2 mL/min/1.73 m², women 75.0-58.2 mL/min/1.73 m²; eGFR(Larsson) men: 85.5-72.9 mL/min, women 94.5-75.7 mL/min). CONCLUSIONS: This study presents age- and sex-specific reference limits for five measures of renal function based on quantile regression models.

Comparative evaluation of multimedia driven, interactive, and case-based teaching in heart surgery.

BACKGROUND: Multimedia-augmented instruction with various approaches is used in heart surgery. There is little evidence which instructional techniques and media are of advantage to impart knowledge more effectively and lead to better application of knowledge in the operation room. METHODS: Sixty-nine students learned with an interactive, case-based teaching (ICBT) course about aortic valve replacement. They were compared with historic controls exposed to identical information provided by a multimedia module presenting content systematically (SMM; n = 69) and a print medium (PM; n = 57). Motivation, computer knowledge, and didactic quality were evaluated with psychometric tests. All groups performed multiple choice pretests and posttests and participated in live surgery during which their performance was assessed. RESULTS: All groups had equal computer knowledge, but the ICBT group felt significantly less-motivated and more challenged. Multiple choice posttest results were comparable (ICBT 80.2% +/- 10.9%, SMM 76.7% +/- 13.3%, PM 76.9% +/- 11.1). During surgery, the ICBT (79.2% +/- 16%) and SMM groups (82.9% +/- 10%) performed significantly better than the PM group (64.7% +/- 12%; both p < 0.0001). Overall didactic assessment was significantly worse in the ICBT group when compared with the SMM and PM groups. CONCLUSIONS: For novices in heart surgery, ICBT was less motivating than traditionally structured content (SMM and PM). The ICBT did not improve performance in the operation room. However, both multimedia groups could better apply their knowledge during live surgery. The PM is as effective as multimedia when factual knowledge has to be retained.

Multimedia-driven teaching significantly improves students' performance when compared with a print medium.

BACKGROUND: In this study, we compared the educational value of a multimedia module about aortic valve replacement as a preparation for the operating room with a print medium of identical content. METHODS: One hundred twenty-six students were randomly assigned in a prospective study to either use the multimedia course (n = 69) or a print version (n = 57). A 20-item multiple-choice test was performed before and after learning with the respective medium. Both groups participated in an operation during which they were evaluated with 28 standardized tasks and questions. Individual motivation, computer literacy, and didactic quality of both media were assessed with psychometric tests. RESULTS: There were no significant differences in the multiple-choice pretest (multimedia, 30.6% +/- 12.4% versus print, 27.9% +/- 11.4%) and posttest responses (multimedia, 76.7% +/- 13.3% versus print, 76.9% +/- 11.1). Mean percentage of correct answers during the operation was 82.9% +/- 10% in the online group and 64.7% +/- 12% in the print group (p < 0.0001). The multimedia group needed significantly (p < 0.001) less study time (105 +/- 24 minutes) when compared with the text group (122 +/- 30 minutes). There were no statistically significant differences in motivation, computer literacy, and didactic quality of either medium. CONCLUSIONS: Regarding factual knowledge, there is no difference between multimedia-driven learning and a print medium. During heart operations, when understanding of complex temporal and spatial events is essential, students' performance is significantly improved by multimedia-enhanced teaching. The latter further proved to be more efficient in terms of study time.

Intimal hyperplasia and expression of transforming growth factor-beta1 in saphenous veins and internal mammary arteries before coronary artery surgery.

BACKGROUND: The development of fibromuscular intimal hyperplasia and subsequent graft failure remains an urgent problem in cardiac surgery. Transforming growth factor-beta1 (TGF-beta1) is involved in the pathogenesis of arteriosclerosis through induction of extracellular matrix proteins. We tested the hypothesis that intimal hyperplasia is already present in human saphenous veins and left internal mammary arteries before coronary artery bypass surgery and is associated with an increased expression of TGF-beta1. METHODS: Forty-six segments of saphenous veins and 27 of left internal mammary arteries were collected from 50 patients undergoing coronary artery bypass surgery. Morphometric analysis was performed by microscopic computer analysis. Immunohistochemistry was performed with antibodies directed against TGF-beta1, its latent binding protein (LTBP-1) and its type 2 receptor (RII). RESULTS: The incidence of intimal hyperplasia was significantly higher in saphenous veins (67.4%) than in mammary arteries (29.6%; p < 0.05). Saphenous veins and mammary arteries with intimal hyperplasia expressed more TGF-beta1 (endothelial and intimal layers) and LTBP-1 (intimal and medial layers) when compared with corresponding vessels without hyperplasia (both groups p < 0.05). Endothelial and intimal RII expression was significantly higher in saphenous veins with intimal hyperplasia as compared with saphenous veins without hyperplasia (p < 0.05). Transforming growth factor-beta1 staining in the intima correlated with the presence of an intimal hyperplasia in saphenous veins (rho = 0.317) and mammary arteries (rho = 0.428). CONCLUSIONS: Local TGF-beta1 expression is associated with the presence of intimal hyperplasia in the examined vessels. Preexisting intimal hyperplasia is more prevalent and serious in saphenous veins than in left internal mammary arteries, giving further explanation to the superior long-term results of left internal mammary grafts.