Identifikation von Biomarkern bei renalen und vaskulären Erkrankungen

Der akute Nierenschaden (AKI, acute kidney injury) ist eine plötzlich auftretende Verschlechterung der glomerulären Filtrationsrate (GFR). Viele unterschiedliche Ursachen sind bekannt. Klassischerweise werden sie in prärenal, renal und postrenal eingeteilt. Seit vielen Jahren ist die Biomarker Forschung beim AKI von großem Interesse. Themen mit besonders hoher Beachtung sind die frühzeitige Diagnosestellung des AKI, die Identifkation von Ursachen des Nierenschadens und die Prognoseabschätzung. In meinen Arbeiten haben wir uns mit der Identifikation solcher Biomarker beschäftigt und dazu unter anderem difference gel electrophoresis (DIGE) als analytische Methode eingesetzt. Wir haben mit DIGE differentiell regulierte Proteine nach herzchirurgischen Operationen im Urin identifiziert, welche auf die Ursache eines Nierenschadens hinweisen. Ausserdem haben wir Marker für die Prognose des AKIs gesucht und insulin-like growth factor binding protein 7 (IGFBP-7) als neuen Biomarker für die renale Prognose identifiziert. In einer weiteren Studie zeigte sich die Kynurenin-Säure als potentieller Marker für die renale Prognose beim AKI. In einer klinischen Studie haben wir die GFR vor und nach perkutanem Aortenklappenersatz beobachtet. Dabei konnten wir feststellen, dass sich bei mehr als 50 % der Patienten die GFR nach Behebung der Aortenstenose verbesserte. Wir konnten mehrere Risikofaktoren für das Auftreten eines AKIs bei diesen Patienten identifizieren, wie den transapikale Zugang, das Auftreten einer Inflammation mit erhöhtem CRP oder erniedrigter Thrombozytenzahl sowie die Transfusion von Erythrozyten. Bei Patienten mit Aortenaneurysma aufgrund eines Marfan Syndroms haben wir mit DIGE eine erhöhte Fragmentierung von Filamin-A festgestellt. Ursache dieser Fragmentierung war eine erhöhte Aktivität der Protease Calpain-2. Zusammengefasst haben wir durch unterschiedliche Methoden Biomarker bei renalen und vaskulären Erkrankungen identifiziert

Risk of acute kidney injury in patients with severe aortic valve stenosis undergoing transcatheter valve replacement

Background.Transcatheter aortic valve implantation (TAVI) for high-risk and inoperable patients with severe aortic stenosis is an emerging procedure in cardiovascular medicine. Little is known of the impact of TAVI on renal function. Methods. We analysed retrospectively renal baseline characteristics and outcome in 58 patients including 2 patients on chronic haemodialysis undergoing TAVI at our institution. Acute kidney injury (AKI) was defined according to the RIFLE classification. Results. Fifty-eight patients with severe symptomatic aortic stenosis not considered suitable for conventional surgical valve replacement with a mean age of 83 ± 5 years underwent TAVI. Two patients died during transfemoral valve implantation and two patients in the first month after TAVI resulting in a 30-day mortality of 6.9%. Vascular access was transfemoral in 46 patients and transapical in 12. Estimated glomerular filtration rate (eGFR) increased in 30 patients (56%). Fifteen patients (28%) developed AKI, of which four patients had to be dialyzed temporarily and one remained on chronic renal replacement therapy. Risk factors for AKI comprised, among others, transapical access, number of blood transfusions, postinterventional thrombocytopaenia and severe inflammatory response syndrome (SIRS). Conclusions. TAVI is feasible in patients with a high burden of comorbidities and in patients with pre-existing end-stage renal disease who would be otherwise not considered as candidates for conventional aortic valve replacement. Although GFR improved in more than half of the patients, this benefit was associated with a risk of postinterventional AKI. Future investigations should define preventive measures of peri-procedural kidney injur

Molecular Diagnosis of Analbuminemia: A New Case Caused by a Nonsense Mutation in the Albumin Gene

Analbuminemia is a rare autosomal recessive disorder manifested by the absence, or severe reduction, of circulating serum albumin (ALB). We report here a new case diagnosed in a 45 years old man of Southwestern Asian origin, living in Switzerland, on the basis of his low ALB concentration (0.9 g/L) in the absence of renal or gastrointestinal protein loss, or liver dysfunction. The clinical diagnosis was confirmed by a mutational analysis of the albumin (ALB) gene, carried out by single-strand conformational polymorphism (SSCP), heteroduplex analysis (HA), and DNA sequencing. This screening of the ALB gene revealed that the proband is homozygous for two mutations: the insertion of a T in a stretch of eight Ts spanning positions c.1289 + 23–c.1289 + 30 of intron 10 and a c.802 G > T transversion in exon 7. Whereas the presence of an additional T in the poly-T tract has no direct deleterious effect, the latter nonsense mutation changes the codon GAA for Glu244 to the stop codon TAA, resulting in a premature termination of the polypeptide chain. The putative protein product would have a length of only 243 amino acid residues instead of the normal 585 found in the mature serum albumin, but no evidence for the presence in serum of such a truncated polypeptide chain could be obtained by two dimensional electrophoresis and western blotting analysis

Qualität in der Shuntchirurgie

Um die Qualität von Dialysezugängen zu verbessern, müssen Daten von Operationen und deren Langzeitergebnisse systematisch und vollständig dokumentiert werden. In der Schweiz verfügt das Swissvasc-Register 2.0 [1] seit 2019 über einen speziellen Datensatz zur Shuntchirurgie. Nun wurden erstmals diese Daten für ein Tertiärspital ausgewertet

Effect of transcutaneous electrical muscle stimulation and passive cycling movements on blood pressure and removal of urea and phosphate during hemodialysis

BACKGROUND: Intradialytic exercise has been described to improve blood pressure stability and dialysis efficacy. However, comorbid conditions in the dialysis population often preclude the widespread use of active intradialytic exercise. Therefore, we investigated the effect of intradialytic transcutaneous muscle stimulation (TEMS) and passive cycling movements (PCMs) on blood pressure and dialysis efficacy in patients. STUDY DESIGN: Prospective, controlled, randomized, crossover investigation. SETTING ; PARTICIPANTS: Ten patients were randomly allocated to TEMS, PCMs, or no intervention (NI) for 9 consecutive dialysis sessions. INTERVENTION: Participants were studied with NI, PCMs using a motor-driven ergometer, and bilateral TEMS of the leg musculature. Individual dialysis prescriptions were unchanged during the investigation. OUTCOMES ; MEASUREMENTS: The effect of TEMS and PCMs on blood pressure and dialysis efficacy in patients was assessed. RESULTS: Mean blood pressure increased from 121/64 +/- 21/15 mm Hg with NI to 132/69 +/- 21/15 mm Hg (P < 0.001) during sessions with PCMs and 125/66 +/- 22/16 mm Hg (P < 0.05) during sessions with TEMS. Urea and phosphate removal during dialysis were significantly (P < 0.001) greater with TEMS (19.4 +/- 3.7 g/dialysis and 1,197 +/- 265 mg/dialysis) or PCMs (20.1 +/- 3.4 g/dialysis and 1,172 +/- 315 mg/dialysis) than with NI (15.1 +/- 3.9 g/dialysis and 895 +/- 202 mg/dialysis). Body weight, ultrafiltration, Kt/V, and increases in hemoglobin and albumin levels during dialysis did not differ among the NI, PCMs, and TEMS groups. LIMITATIONS: The study design does not allow extension of the findings to prolonged treatment. CONCLUSION: Future studies during longer observation periods will have to prove the persistence of these acute findings. Both TEMS and PCMs deserve future investigations in dialysis patients because they increase intradialytic blood pressure and facilitate urea and phosphate removal when applied short term

Use of the pentasaccharide fondaparinux as an anticoagulant during haemodialysis

No data about the use of the pentasaccharide fondaparinux, a highly selective indirect inhibitor of factor Xa, in patients treated with haemodialysis are available. Therefore, we investigated the pharmacokinetics and -dynamics of fondaparinux in 12 patients during haemodialysis. The anti-Xa activity (expressed as fondaparinux equivalent) was monitored, a semiquantitative clotting scale (SQCS) ranging from 0 (no visible traces of coagula) to 3 (complete clotting of the dialysis circuit) was applied, and the digital compression time necessary to achieve haemostasis at the puncture site was determined. After an initial period, when the regular heparin dose was replaced once weekly by fondaparinux, 0.05 mg/kg, the pentasaccharide was administered for nine consecutive haemodialysis sessions. Peak anti-Xa activity increased from 0.61 +/- 0.14 microg/l after the first dose to 0.89 +/- 0.24 microg/l after dose 9 (P < 0.001), whereas predialysis anti-Xa activity steadily rose to 0.32 +/- 0.09 microg/l (P < 0.001). A sufficient but slightly less effective anticoagulation with a mean SQCS of 1.19 +/- 0.71 (n = 121) was obtained by fondaparinux as compared with 0.65 +/- 0.58 (n = 60, P < 0.005) by 4,825 +/- 1,703 U of unfractionated heparin. Mean digital compression time rose slightly during fondaparinux from 23.7 +/- 7.4 minutes to 24.8 +/- 7.5 minutes (P < 0.05) and, more important, six of the 12 patients reported minor bleeding problems during the interdialytic interval. Thus, fondaparinux can be used to prevent circuit clotting during haemodialysis; however, accumulation results in an interdialytic increase of anti-Xa activity. Therefore, fondaparinux should be reserved for patients requiring systemic anticoagulation on the days off dialysis

Increased urinary excretion of kynurenic acid is associated with non-recovery from acute kidney injury in critically ill patients.

BACKGROUND Acute kidney injury (AKI) is often observed in critically ill patients and is associated with high morbidity and mortality. Non-recovery from AKI has a negative impact on the prognosis of affected patients and early risk stratification seems key to improve clinical outcomes. We analyzed metabolites of a conserved key inflammatory pathway (i.e. tryptophan degradation pathway) in serial urine samples of patients with AKI. METHODS One hundred twelve ICU patients with AKI were included in a prospective observational analysis. After exclusion criteria, 92 patients were eligible for analysis. Serial urine samples were collected and tryptophan levels including key tryptophan metabolites were measured using tandem mass spectrometry. RESULTS Sixty-seven patients recovered in the first 7 days of AKI (early recovery, ER) whereas n = 25 had late-/non-recovery (LNR). Urinary concentrations of tryptophan, kynurenine, 3-OH anthranillic acid, serotonine, and kynurenine/tryptophan were significantly lower in LNR patients. In contrast, creatinine normalized excretion of kynurenic acid (KynA) was substantially increased in LNR patients (7.59 ± 6.81 vs. 3.19 ± 3.44 (ER) μmol/mmol, p <  0.005). High urinary KynA excretion was associated with higher RIFLE class, longer AKI duration, increased need for RRT, and 30-day mortality. Logistic regression revealed KynA as the single most important predictor of renal recovery on days 1 and 2 of AKI. CONCLUSIONS Increased urinary levels of kynurenic acid, a key inflammatory metabolite of the tryprophan degradation pathway, are associated with adverse renal and clinical outcomes in critically ill patients with AKI. Urinary KynA may serve as an early risk stratificator in respective patients with AKI

Nocturnal dipping behaviour in normotensive white children and young adults in response to changes in salt intake

Nocturnal nondipping is a feature of salt-sensitive, hypertensive individuals. In normotensive children and adults, the impact of salt intake on circadian blood pressure (BP) rhythm is not well defined

Risk of acute kidney injury in patients with severe aortic valve stenosis undergoing transcatheter valve replacement

BACKGROUND: Transcatheter aortic valve implantation (TAVI) for high-risk and inoperable patients with severe aortic stenosis is an emerging procedure in cardiovascular medicine. Little is known of the impact of TAVI on renal function. METHODS: We analysed retrospectively renal baseline characteristics and outcome in 58 patients including 2 patients on chronic haemodialysis undergoing TAVI at our institution. Acute kidney injury (AKI) was defined according to the RIFLE classification. RESULTS: Fifty-eight patients with severe symptomatic aortic stenosis not considered suitable for conventional surgical valve replacement with a mean age of 83 +/- 5 years underwent TAVI. Two patients died during transfemoral valve implantation and two patients in the first month after TAVI resulting in a 30-day mortality of 6.9%. Vascular access was transfemoral in 46 patients and transapical in 12. Estimated glomerular filtration rate (eGFR) increased in 30 patients (56%). Fifteen patients (28%) developed AKI, of which four patients had to be dialyzed temporarily and one remained on chronic renal replacement therapy. Risk factors for AKI comprised, among others, transapical access, number of blood transfusions, postinterventional thrombocytopaenia and severe inflammatory response syndrome (SIRS). CONCLUSIONS: TAVI is feasible in patients with a high burden of comorbidities and in patients with pre-existing end-stage renal disease who would be otherwise not considered as candidates for conventional aortic valve replacement. Although GFR improved in more than half of the patients, this benefit was associated with a risk of postinterventional AKI. Future investigations should define preventive measures of peri-procedural kidney injury

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