Elke Schaeffner - Academia.edu (original) (raw)

Papers by Elke Schaeffner

Transplant International, Mar 1, 2007

Disturbances in calcium and phosphate metabolism have been linked to increased mortality in hemod... more Disturbances in calcium and phosphate metabolism have been linked to increased mortality in hemodialysis patients, but not in kidney transplant recipients (KTR). We enrolled 733 KTR from the Vienna General Hospital into this study. Detailed demographic, clinical, laboratory, and transplant-related information was collected at baseline. We used the Austrian Dialysis and Transplantation Registry for follow-up. Using multivariate proportional hazard regression, we examined the independent associations between serum calcium, serum phosphate, and calcium phosphate (CaPO 4) product with the outcomes of death from any cause and kidney allograft loss. Over a median follow-up of >6 years, 154 patients died and 259 kidney allografts were lost. Associations with serum calcium, phosphate concentrations, and CaPO 4 product concentrations were found for allograft loss, but not for patient mortality. Patients in the highest quintile of phosphate concentration and CaPO 4 product had an increased risk for allograft loss compared with patients in the lowest quintile of these parameters (hazards ratio, HR ¼ 2.15; 95% confidence interval, CI: 1.36-3.40 and HR ¼ 1.72; 95% CI: 1.10-2.71, respectively). High calcium levels were associated with a reduced risk for allograft loss. Results were even more pronounced for death-censored allograft loss. High concentrations of serum phosphate and CaPO 4 product were associated with an increased risk for allograft loss in these KTR, whereas high serum calcium concentrations seemed to lower the risk.

American Journal of Kidney Diseases, Mar 1, 2006

Transplant International, Jun 1, 2007

In kidney transplant recipients (KTR), C-reactive protein (CRP) has been shown to be associated w... more In kidney transplant recipients (KTR), C-reactive protein (CRP) has been shown to be associated with increased mortality, but data on this association within the high-sensitivity (hs) range of CRP (<5 mg/l) are lacking. We prospectively studied 710 prevalent and stable KTR over >6 years. We thawed frozen plasma and measured baseline hs-CRP using an ultrasensitive assay. Detailed clinical and demographic baseline characteristics were available for study. We stratified patients by quartile of hs-CRP within the hs range (<5 mg/l), and also included KTRs whose hs-CRP was above the hs range (>5-10 and >10 mg/l). We used multivariate proportional hazards models to test for independent associations. After careful multivariate adjustment, we found a J-shaped association between hs-CRP and mortality. Compared with KTR whose hs-CRP was in the second lowest quartile of hs-CRP (0.06-1.26 mg/l), patients in the lowest quartile (<0.06 mg/l) had more than twice their mortality risk (HR ¼ 2.07; 95% CI: 1.05-4.07), as did patients whose hs-CRP was ‡2.44 mg/l (all HRs >2.27). No association was found between hs-CRP and death-censored allograft loss. In contrast to the general population, the association between hs-CRP and mortality in KTRs is not linear, but J-shaped, suggesting that KTRs with very low hs-CRP may also be at increased risk of death.

American Journal of Kidney Diseases, 2006

Clinical Kidney Journal, 2021

In the vast majority of cases, glomerular filtration rate (GFR) is estimated using serum creatini... more In the vast majority of cases, glomerular filtration rate (GFR) is estimated using serum creatinine, which is highly influenced by age, sex, muscle mass, body composition, severe chronic illness and many other factors. This often leads to misclassification of patients or potentially puts patients at risk for inappropriate clinical decisions. Possible solutions are the use of cystatin C as an alternative endogenous marker or performing direct measurement of GFR using an exogenous marker such as iohexol. The purpose of this review is to highlight clinical scenarios and conditions such as extreme body composition, Black race, disagreement between creatinine- and cystatin C–based estimated GFR (eGFR), drug dosing, liver cirrhosis, advanced chronic kidney disease and the transition to kidney replacement therapy, non-kidney solid organ transplant recipients and living kidney donors where creatinine-based GFR estimation may be invalid. In contrast to the majority of literature on measured ...

BMC Nephrology

Background Measuring glomerular filtration rate (GFR) using iohexol plasma clearance has been pro... more Background Measuring glomerular filtration rate (GFR) using iohexol plasma clearance has been proposed as the preferred way for GFR determination. The extended multiple-sample protocol is based on fitting the full concentration-time decay-curve, and from the obtained fit-parameters, the area under the curve (AUC) and GFR (the injected dose divided by the AUC) were calculated. The goal of the current study is to evaluate the impact of different fitting procedures on the precision of GFR-results obtained from the full concentration-time curve, and compare these results with those obtained with simplified multiple-samples and single-sample protocols. Methods The concentration-time curves of 8 samples at times 30, 60, 90, 120, 150, 180, 240 and 300 min after bolus injection of iohexol of 570 adults, aged 70+, from the Berlin Initiative Study (BIS), were analysed. The fit-parameters for the two-compartment model (double-exponential decay curve), and from these, the AUC and GFR were obtai...

Scientific Reports, 2018

Plasma clearance of iohexol is a key tool to precisely determine glomerular filtration rate (GFR)... more Plasma clearance of iohexol is a key tool to precisely determine glomerular filtration rate (GFR) in clinical research and clinical practice. Despite evidence that iohexol pharmacokinetics are described best by three-compartment models, two-compartment approaches (Schwartz approach) are customary, which might result in avoidable bias and imprecision. We aimed to provide a population pharmacokinetic (popPK) model of iohexol by re-evaluating data from the Berlin Initiative Study (BIS) to compare respective clearance estimates to the Schwartz approach and to assess the impact of revised clearance estimates on the BIS equations. A popPK model was developed based on iohexol plasma samples (8–10 per subject, iohexol dose 3235 mg) from 570 elderly patients. A three-compartment model appropriately described the pharmacokinetics of iohexol (clearance 57.4 mL/min, CV 33%). Compared to the three-compartment model, clearance values were overestimated by the Schwartz approach (bias 6.5 mL/min), ...

Scientific reports, Jan 4, 2018

We evaluated genetics of hyperuricemia and gout, their interaction with kidney function and medic... more We evaluated genetics of hyperuricemia and gout, their interaction with kidney function and medication intake in chronic kidney disease (CKD) patients. Genome-wide association studies (GWAS) of urate and gout were performed in 4941 CKD patients in the German Chronic Kidney Disease (GCKD) study. Effect estimates of 26 known urate-associated population-based single nucleotide polymorphisms (SNPs) were examined. Interactions of urate-associated variants with urate-altering medications and clinical characteristics of gout were evaluated. Genome-wide significant associations with serum urate and gout were identified for known loci at SLC2A9 and ABCG2, but not for novel loci. Effects of the 26 known SNPs were of similar magnitude in CKD patients compared to population-based individuals, except for SNPs at ABCG2 that showed greater effects in CKD. Gene-medication interactions were not significant when accounting for multiple testing. Associations with gout in specific joints were significa...

Data in Brief, 2017

The data presented in this article are related to the research article entitled "The Diagnostic V... more The data presented in this article are related to the research article entitled "The Diagnostic Value of Rescaled Renal Biomarkers Serum Creatinine and Serum Cystatin C and their Relation with Measured Glomerular Filtration Rate" (Pottel et al. (2017) [1]). Data are presented demonstrating the rationale for the normalization or rescaling Contents lists available at ScienceDirect

Journal of Renal Nutrition, 2017

Correct determination of glomerular filtration rate (GFR) as an indicator of kidney function bear... more Correct determination of glomerular filtration rate (GFR) as an indicator of kidney function bears great importance because clinical decision-making depends on it at many occasions. During the last years, a huge body of literature has been published on estimation and measurement of GFR. The increasing pace with which novel estimation formulae, current and newer biomarkers, assay standardization procedures as well as invasive measurement methods of GFR were published, has been overwhelming for many clinicians. This concise review summarizes central issues in determining kidney function by listing some of the most important publications. It explains fundamental principles in GFR estimation and measurement, the influence of clinical characteristics on endogenous biomarkers, and obstacles in biomarker assessment. Thus, it is thought to be a guide for clinicians through the confusing jungle of GFR determination.

Transplant international : official journal of the European Society for Organ Transplantation, 2007

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2011

BACKGROUND: Chronic kidney disease (CKD) is increasingly recognized as a global health problem. T... more BACKGROUND: Chronic kidney disease (CKD) is increasingly recognized as a global health problem. The conditions leading to CKD, the health impact of CKD and the prognosis differ markedly between affected individuals. In particular, renal failure and cardiovascular mortality are competing risks for CKD patients. Opportunities for targeted intervention are very limited so far and require an improved understanding of the natural course of CKD, of the risk factors associated with various clinical end points and co-morbidities as well as of the underlying pathogenic mechanisms. METHODS: The German Chronic Kidney Disease (GCKD) study is a prospective observational national cohort study. It aims to enrol a total of 5000 patients with CKD of various aetiologies, who are under nephrological care, and to follow them for up to 10 years. At the time of enrolment, male and female patients have an estimated glomerular filtration rate (eGFR) of 30-60 mL/min × 1.73m(2) or overt proteinuria in the pr...

Journal of the American Society of Nephrology, 2019

Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, su... more Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m2. This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR <75 ml/min per 1.73 m2, whereas in ...

Nephrology Dialysis Transplantation, 2012

NDT Plus, 2009

Antineutrophil cytoplasmic antibodies-associated vasculitis (AAV) is a well-described cause of mu... more Antineutrophil cytoplasmic antibodies-associated vasculitis (AAV) is a well-described cause of multiple organ involvement including rapidly progressive pauci-immune crescentic glomerulonephritis. Kidney transplantation (KTx) is considered the treatment of choice in patients with end-stage renal disease (ESRD) due to AAV. Patient and graft survival in AAV after KTx is favourable and comparable with other non-diabetic causes of ESRD. While relapse of AAV is high in dialysis patients (up to 50%), it decreases after KTx (8.6-22.2%). Yet, relapse may occur at any time after KTx and transplant involvement has been documented in at least 25 cases. Therapeutic guidelines for the management of AAV after KTx do not exist and clinical management is a controversial discussion. We present two unusual cases of young males with smouldering AAV who recently underwent KTx at our hospital. Case 1 experienced repeated relapses after KTx and was finally successfully treated with rituximab. Case 2 received rituximab pre-emptively before living kidney donation and remained free of flairs. Prompted by theses two cases, we reviewed the literature focusing on the right point of time for transplantation, risk assessment, role of antineutrophil cytoplasmic antibodies, clinical presentation of flairs and immunosuppression in smouldering Wegener's granulomatosis (WG) and in relapse, including individualized treatment with rituximab.

Journal of the American Society of Nephrology

Despite extensive knowledge about abnormal lipid patterns in patients with end-stage renal diseas... more Despite extensive knowledge about abnormal lipid patterns in patients with end-stage renal disease, the association between cholesterol and the development of renal dysfunction is unclear. We evaluated this association in a prospective cohort study among 4,483 initially healthy men participating in the Physicians' Health Study who provided blood samples in 1982 and 1996. Main outcome measures were elevated creatinine, defined as Ն1.5 mg/dl (133 mol/L), and reduced estimated creatinine clearance, defined as Յ55 ml/ min. Cholesterol parameters included total cholesterol (Ͻ200, 200 to 239, and Ն240 mg/dl), HDL (Ͻ40 or Ն40 mg/dl), total non-HDL cholesterol, and the ratio of total cholesterol to HDL. We used logistic regression to calculate age-and multivariable adjusted odds ratios as a measure for the relative risk. After 14 yr, 134 men (3.0%) had elevated creatinine and 244 (5.4%) had reduced creatinine clearance. The multivariable relative risk for elevated creatinine was 1.77 (95% confidence interval [CI], 1.10 to 2.86) for total cholesterol Ն240 mg/dl, 2.16 (95% CI, 1.42 to 3.27) for HDL Ͻ40 mg/dl, 2.34 (95% CI, 1.34 to 4.07) for the highest quartile of total cholesterol/HDL ratio (Ն6.8), and 2.16 (95% CI, 1.22 to 3.80) for the highest quartile of non-HDL cholesterol (Ն196.1). Similar although smaller associations were observed between cholesterol parameters and reduced creatinine clearance. Elevated total cholesterol, high non-HDL cholesterol, a high ratio of total cholesterol/HDL, and low HDL in particular were significantly associated with an increased risk of developing renal dysfunction in men with an initial creatinine Ͻ1.5 mg/dl. Over the last decade, the prevalence of ESRD doubled in the United States (1). Because specific treatments are lacking for most chronic nephropathies that progress to ESRD, prevention must play an important role in combating this disease. The identification of modifiable risk factors for the initiation of renal dysfunction is a necessary first step toward establishing prevention strategies and possibly devising new treatments. Established risk factors for ESRD currently include diabetes and hypertension (2).

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, Jan 4, 2015

Accurate and precise measurement of GFR is important for patients with chronic kidney disease (CK... more 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. 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 co...

Fundamental & clinical pharmacology, Jan 27, 2015

The prevalence of diabetes mellitus (DM) and renal impairment rises with age making regular estim... more The prevalence of diabetes mellitus (DM) and renal impairment rises with age making regular estimation of glomerular filtration rate (eGFR) in older diabetics necessary. The present study investigated the differences among available estimating equations in assessing eGFR in older diabetics and examined the use of oral antidiabetic drugs (OADs) in relation to renal function. DM patients were participants of the Berlin Initiative Study (BIS), a population-based cohort study initiated in 2009 in Berlin, Germany, in order to evaluate kidney function in people ≥ 70 years. GFR was estimated with the creatinine-based CKD-EPICREA (Chronic Kidney Disease Epidemiology Collaboration), the MDRD (Modification of Diet in Renal Diseases), and the BIS1 equation, and was directly measured (mGFR) with iohexol clearance as a gold standard in a subgroup (n=137). Creatinine clearance was estimated with the Cockcroft-Gault equation (CrCl). DM prevalence was 26% (539 of 2070 overall participants). The ant...