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Stefan Herget-Rosenthal

Publications and source records attributed to Stefan Herget-Rosenthal.

16 recordsLinked to original sources
PubMed2006

Cystatin C, kidney function and cardiovascular disease.

Cystatin C, an endogenous low-molecular-weight marker of glomerular filtration rate, has recently been shown to be associated with future cardiovascular disease in healthy elderly populations and patients with documented atherosclerosis in a dose-dependent manner that possibly reflects a very early stage of chronic renal dysfunction. At the same time, local cystatin C deficiency has been demonstrated in atherosclerotic and aneurismal lesions, suggesting a protective role of cystatin C in the vessel wall, possibly in concert with TGF-beta1. Although cystatin C is not an acute phase reactant, large epidemiological studies have documented a highly significant association between serum cystatin C and mildly increased C-reactive protein (CRP) levels, the hallmark of the chronic inflammatory state associated with atherosclerosis and chronic renal failure. Since cystatin C is produced by all nucleated cells, it is unlikely that local variations in cystatin C synthesis in diseased arteries--rather than global cystatin C production and renal elimination--should determine its serum concentration. Consequently, the present review proposes microinflammation as the unifying concept for both lines of evidence.

Animals↗
PubMed2006

Acute myocardial infarction in thrombotic microangiopathies--clinical characteristics, risk factors and outcome.

BACKGROUND: Acute myocardial infarction (AMI) has been reported and is associated with poor outcome in the course of thrombotic microangiopathies (TMA). However, data are very limited in regard to the clinical characteristics, risk factors and outcome of AMI during TMA. Furthermore, current AMI definitions based on troponins are more sensitive and specific to detect myocardial injury. METHODS: We retrospectively analysed 74 consecutive patients with 78 TMA episodes. TMA was defined as platelets below 150 x 10(9)/l, haemolytic anaemia, elevated lactate dehydrogenase (LDH) and increased red cell fragmentation, and AMI as serum troponin I above 1 ng/ml with symptoms of myocardial ischaemia and/or appropriate electrocardiography (ECG) alterations. RESULTS: AMI occurred in 14 TMA episodes (18%) (9 non- and 5 ST-segment elevation AMI). AMI occurred 5+/-3 days after TMA diagnosis, predominately in clinically suspected thrombotic thrombocytopenic purpura (TTP) as TMA subtype. Independent risk factors for subsequent AMI were TTP (RR 2.2; 95% CI 1.1-5.6), and serum LDH above 1,000 U/l (RR 2.7; 95% CI 1.3-7.2) as well as serum troponin I above 0.20 ng/ml at TMA presentation (RR 13.5; 95% CI 2.6-86.8). LDH above 1,000 U/l together with troponin I above 0.20 ng/ml had a sensitivity of 86% (95% CI 60-96%) and a specificity of 95% (95% CI 86-98%) to predict AMI in the later course of TMA. AMI contributed substantially to morbidity causing left ventricular dysfunction in three of eight survivors and potentially accounted for the death in five of six non-survivors. CONCLUSIONS: AMI is an early, frequent and severe complication during TMA. AMI occurs especially in TTP, and serum LDH above 1,000 U/l in combination with serum troponin I above 0.20 ng/ml at TMA presentation are excellent predictors of subsequent AMI.

Adult↗
PubMed2006

Magnetic resonance imaging of renal disease: recent developments and future applications.

Magnetic resonance imaging (MRI) offers the ability to non-invasively assess parenchymal and vascular renal disease. Indications for renal MRI include the evaluation of renal masses, urinary obstruction and infection, renal vasculature, and the health of transplant kidneys. The potential of MR angiography to replace invasive conventional x-ray angiography has been recognized for many years. Recent developments in MRI resulting from fast MR systems with faster gradients, new surface coil designs and the latest sequence developments coupled with innovative contrast agent administration strategies have prompted substantial progress of MRI in the diagnosis of renal disease. The goal of this article is to present the current state of MRI in diagnosing renal disease, with an emphasis on the latest developments in the evaluation of renal vascular disease.

Forecasting↗
PubMed2005

Digital fluorescence imaging of organic cation transport in freshly isolated rat proximal tubules.

The secretion of cationic drugs and endogenous metabolites is a major function of the kidney. This is accomplished by organic cation transport systems, mainly located in the proximal tubules. Here, we describe a model for continuous measurement of organic cation (OC) transport. In this model, organic cation transport in individual freshly isolated rat proximal tubules is investigated by use of digital fluorescence imaging. To directly measure organic cation transport across the basolateral membrane, the fluorescent organic cation 4-(4-dimethylaminostyryl)-N-methylpyridinium (ASP+) is used with a customized perfusion chamber. ASP+ uptake in this model displayed the characteristics of organic cation transport. Over the tested range of 1 to 50 microM, it showed a concentration-dependent uptake across the basolateral membrane. In the presence of competitive inhibitors of OC transport such as N1-methylnicotinamide+, tetraethylammonium+, and choline+, a concentration-dependent and reversible inhibition of ASP+ uptake could be documented. In conclusion, continuous measurement of organic cation transport in freshly isolated rat proximal tubules by digital fluorescence imaging using ASP+ is a useful tool for investigation of drug transport and interactions and, furthermore, may be helpful for investigation of organic cation transport under pathophysiological conditions.

Animals↗
PubMed2004

Prognostic value of tubular proteinuria and enzymuria in nonoliguric acute tubular necrosis.

BACKGROUND: Acute tubular necrosis (ATN) has high mortality, especially in patients who require renal replacement therapy (RRT). We prospectively studied the diagnostic accuracy of the urinary excretion of low-molecular-weight proteins and enzymes as predictors of a need for RRT in ATN. METHODS: In 73 consecutive patients with initially nonoliguric ATN, we measured urinary excretion of alpha(1)- and beta(2)-microglobulin, cystatin C, retinol-binding protein, alpha-glutathione S-transferase, gamma-glutamyltransferase, lactate dehydrogenase, and N-acetyl-beta-D-glucosaminidase early in the course of ATN. RESULTS: Twenty-six patients (36%) required RRT a median of 4 (interquartile range, 2-6) days after detection of proteinuria and enzymuria. Patients who required RRT had higher urinary cystatin C and alpha(1)-microglobulin [median (interquartile range), 1.7 (1.2-4.1) and 34.5 (26.6-45.1) g/mol of creatinine] than patients who did not require RRT [0.1 (0.02-0.5) and 8.0 (5.0-17.5) g/mol of creatinine]. Urinary excretion of cystatin C and alpha(1)-microglobulin had the highest diagnostic accuracies in identifying patients requiring RRT as indicated by the largest areas under the ROC curves: 0.92 (95% confidence interval, 0.86-0.96) and 0.86 (0.78-0.92), respectively. Sensitivity and specificity were 92% (95% confidence interval, 83-96%) and 83% (73-90%), respectively, for urinary cystatin C >1 g/mol of creatinine, and 88% (78-93%) and 81% (70-88%) for urinary alpha(1)-microglobulin >20 g/mol of creatinine. CONCLUSION: In nonoliguric ATN, increased urinary excretion of cystatin C and alpha(1)-microglobulin may predict an unfavorable outcome, as reflected by the requirement for RRT.

Aged↗
PubMed2004

Early detection of acute renal failure by serum cystatin C.

BACKGROUND: Acute renal failure (ARF) is associated with high mortality. Presently, no specific therapy for ARF exists. Therefore, early detection of ARF is critical to prevent its progression. However, serum creatinine, the standard marker to detect ARF, demonstrates major limitations. We prospectively evaluated whether serum cystatin C detected ARF earlier than serum creatinine. METHODS: In 85 patients at high risk to develop ARF, serum creatinine and cystatin C were determined daily. ARF was defined according to the Risk of renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function, and ESRD (RIFLE) classification when creatinine increased by >/=50% (R-criteria), by >/=100% (I-criteria), or by >/=200% (F-criteria). In analogy, ARF was detected when cystatin C increased by >/=50%, by >/=100%, or by >/=200%. RESULTS: Forty-four patients developed ARF and 41 served as controls. In ARF by R-, I-, and F-criteria, the increase of cystatin C significantly preceded that of creatinine. Specifically, serum cystatin C increased already by >/=50% 1.5 +/- 0.6 days earlier compared to creatinine. Serum cystatin C demonstrated a high diagnostic value to detect ARF as indicated by area under the curve of the ROC analysis of 0.82 and 0.97 on the two days before the R-criteria was fulfilled by creatinine. Cystatin C detected ARF according to the R-criteria with a sensitivity of 55% and 82% on these days, respectively. Cystatin C also performed excellently, detecting ARF defined by the I- and F-criteria two days prior to creatinine, and moderately well predicting renal replacement therapy in the further course of ARF. Additionally, low T(3)- or T(3)/T(4) syndrome, glucocorticoid deficiency and excess did not affect cystatin C levels, adding to its usefulness in critically ill patients with ARF. CONCLUSION: Serum cystatin C is a useful detection marker of ARF, and may detect ARF one to two days earlier than creatinine.

Acute Kidney Injury↗
PubMed2004

Measurement of urinary cystatin C by particle-enhanced nephelometric immunoassay: precision, interferences, stability and reference range.

BACKGROUND: Urinary excretion of the low molecular weight protein cystatin C is a marker of renal disorders and a good predictor of the severity of acute tubular necrosis. We evaluated the measurement of urinary cystatin C and determined its reference range. METHODS: Measurement of urinary cystatin C by particle-enhanced nephelometric immunoassay (PENIA) in 102 patients with various renal disorders and 133 healthy controls. We assessed the influence of pH and temperature, interferences on urinary cystatin C measurement, as well as cystatin C adsorption to plastic. RESULTS: The upper reference value for urinary cystatin C was 0.28 mg/L, independent of age and gender. Accuracy and linearity (r(2)=0.996) were excellent. Intra- and inter-assay precision were < or =4.8% and < or =5.2%, respectively. Albumin (< or =160 g/L), bilirubin (< or =500 micromol/L) and haemoglobin (< or =210 micromol/L) did not show interferences. Urinary cystatin C was stable, at urine pH> or =5, at -20 degrees C and 4 degrees C for 7 days, and at 20 degrees C for 48 h. Freezing and thawing did not influence urinary cystatin C concentration. There was no adsorption of cystatin C to plastic. CONCLUSION: Urinary cystatin C measurement by PENIA is precise. High stability and no interference add to the practicability of urinary cystatin C as a routine biochemical test.

Adult↗
PubMed2003

Serum ferritin and survival of renal transplant recipients: a prospective 10-year cohort study.

Increased serum ferritin is frequent in renal transplant recipients. This reflects iron overload due to blood transfusions given to treat renal anaemia. Previous studies suggested excess mortality in non-renal transplant recipients with iron overload. We hypothesized that serum ferritin levels above 1100 ng/ml may be associated with increased long-term mortality in renal transplant recipients. Twenty consecutive renal transplant recipients with high levels of serum ferritin and 20 renal transplant recipients with normal serum ferritin levels, matched for age and gender, were prospectively studied for 10 years. Nine patients (45%) with increased serum ferritin died during follow-up, compared to four controls (20%). Univariate and multivariate analysis identified multiple blood transfusions (>40 units) prior to transplantation as being associated with higher mortality in renal transplant recipients (risk ratio (RR): 3.1, confidence interval (CI): 1.1-9.2; P=0.03). These data suggest that serum ferritin levels above 1100 ng/ml due to multiple blood transfusions causing iron overload is a relevant factor that increases mortality.

Adult↗
PubMed2003

Effect of quercetin on hypoxic injury in freshly isolated rat proximal tubules.

The bioflavonoid quercetin, which has antioxidant properties, protects renal tubular epithelial cells from oxidant-induced injury by inhibiting lipid peroxidation. We examined the effect of quercetin on hypoxia-induced injury in freshly isolated rat renal proximal tubules. Hypoxia induced rapid loss of cellular ATP, followed by functional and structural alterations measured as a decrease in tubular potassium content and sequentially by an increase in lactate dehydrogenase release. Furthermore, hypoxia increased lipid peroxidation, measured as thiobarbituric acid-reactive substances. Quercetin significantly inhibited hypoxia-induced functional and structural tubular injury in addition to lipid peroxidation but did not alter hypoxia-induced ATP depletion. These results demonstrate the potency of the bioflavonoid quercetin in protecting proximal tubules from hypoxic injury, which is independent of tubular energy metabolism and may be related to the inhibition of lipid peroxidation.

Acute Kidney Injury↗
PubMed2003

ATP protects, by way of receptor-mediated mechanisms, against hypoxia-induced injury in renal proximal tubules.

We examined the effect of ATP on hypoxia-induced injury in freshly isolated rat renal proximal tubules and compared it with the effects of stable ATP analogues and ATP degradation products. Extracellular ATP significantly reduced hypoxia-induced structural cell damage (lactate dehydrogenase release). P(2)-receptor agonistic ATP analogues, including 2'-methylthio-ATP (2-Me-S-ATP), were also protective. In contrast, the P(1)-agonistic degradation products AMP and adenosine were not protective. Hypoxia-induced functional cell damage (loss of cellular potassium) was not changed by ATP or 2-Me-S-ATP. We therefore conclude that the protective property of ATP is not based on an effect of the degradation products or on a direct effect on cellular energy metabolism. The data indicate that the protective effect of ATP is mediated by P(2) receptors.

Adenosine↗
PubMed2003

Newly developed techniques to study and diagnose acute renal failure.

Progress in treating human acute renal failure (ARF) is dependent on developing techniques that allow for the rapid diagnosis, quantification of injury, further understanding of the pathophysiology, and the effects of therapy. Therefore, four techniques that will facilitate this progress are described and illustrated by four different investigative teams. Techniques to measure rapid changes in GFR are available for rapid diagnosis and quantification of ARF in humans. State-of-the-art magnetic resonance imaging (MRI) presently allows for enhanced resolution of regional renal blood flow and functional evaluations in patients. Furthermore, new probes and techniques for MRI that allow for identification and quantitation of inflammation, applicable to human ARF, are being developed and tested in animal models. Finally, two-photon microscopy will allow for four-dimensional cellular and subcellular studies in animal models of ARF providing rapid insights into pathophysiology and the therapeutic effects of a variety of promising agents. Further development and utilization of these techniques, especially in concert with genetic, proteomic, and molecular approaches, will allow for needed insights into the pathophysiology and therapy in human ARF.

Acute Kidney Injury↗