Gunter Kleinberger

Elimination of amino acids in acute renal failure

Plasma amino acid concentrations and the elimination of parenterally administered amino acids were investigated in 12 patients with nonhypercatabolic acute renal failure. A distinctive plasma amino acid pattern could be observed: plasma concentrations of phenylalanine and methionine were increased, those of valine and leucine decreased. Of the nonessential amino acids, cystine, taurine und tyrosine had elevated but none of them reduced plasma concentrations. The elimination of amino acids was evaluated in a monocompartment model after bolus injection of an amino acid solution containing essential and nonessential amino acids. Pharmacokinetic parameters of 17 amino acids were calculated. The mean elimination half-time was raised by 25%. The elimination half-time of phenylalanine, methionine, glutamic acid, proline and ornithine was increased. Histidine was the only amino acid with--however insignificantly--accelerated elimination from the intravascular compartment. The total clearance rate and total transfer rate was not altered (107 and 97% of normal, respectively). The clearance of threonine, lysine, serine, glycine and histidine was increased, of valine, phenylalanine, glutamic acid and to a minor degree of methionine was decreased. The transfer rate of methionine, lysine, glycine was elevated, of valine, aspartic acid, glutamic acid and ornithine reduced. The demonstration of these pronounced alterations of amino acid elimination in acute renal failure may have major consequences in parenteral amino acid therapy.

Hemodynamic, pulmonary, and renal reactions to inadvertent transfusion of outdated blood.

A patient who received an erroneous transfusion of outdated and partly homogenized blood is reported. Although marked hemoglobinemia was present, only transient hemodynamic, pulmonary, and renal alterations were observed. Massive embolism of microaggregates and norepinephrine release might explain our findings. Dopamine (3 micrograms/kg . min) might have beneficial effects on renal function in this pseudohemolytic transfusion reaction.

Reproducibility of thermal-dye lung water measurements by a lung water computer in critically ill patients

Reproducibility of thermal-dye extravascular lung water (EVLW) estimation by a lung water computer was studied by performing ten consecutive measurements in 45 critically ill patients. EVLW ranged over a wide spectrum from 187 to 1163 ml (2.4 to 18.6 ml/kg). The mean coefficient of variation of ten consecutive measurements was 13.6%. Spontaneously breathing patients showed significantly (p less than .05) higher coefficients of variation (16.1 +/- 6.8%) than patients on mechanical ventilation (10.8 +/- 4.2%). Other factors affecting reproducibility could not be clearly identified. Because in lung water estimation mean values of consecutive measurements are compared, we defined an EVLW determination as the mean value of three consecutive EVLW measurements. When comparing consecutive EVLW determinations in hemodynamically stable patients, we found in many that consecutive EVLW determinations varied no more than +/- 15%. These differences probably have to be attributed to the reproducibility of EVLW measurements and have to be considered, when changes in thermal-dye lung water measured by a lung water computer are discussed.

Anemia Associated with Lactic Acidosis

A case of severe anemia complicated with lactic acidosis (blood lactic acid concentration 17.5 mmol/l) is presented. Circulatory failure and other causes of lactic acid accumulation could be excluded.

Systemic Candidiasis Complicating Bone Marrow Transplantation in Aplastic Anemia

A 17-year-old male patient with aplastic anemia underwent bone marrow transplantation and succumbed 4 days after marrow infusion from sudden myocardial failure. Fever of unknown origin (FUO) had accompanied the patients course from admission until death. The cause of death was fungus myocarditis, which had escaped detection in vivo, in spite of a daily culture program for bacteria and fungi, and a close monitoring of the patients circulation and ventricular performance. Commonly applied diagnostic criteria for systemic mycosis, such as topical colonization, malfunction of invaded organs and positive fungus cultures failed to provide a timely diagnosis. With regard to the problems in diagnosing systemic mycosis, the potential stem cell toxicity of antifungal drugs and the need for immunosuppressive therapy prior to marrow infusion, we strongly recommend not to start the transplantation procedure unless FUO has been treated successfully.

Fettstoffwechsel und Fettverwertung bei Niereninsuffizienz

Beim akuten und chronischen Nierenversagen wird haufig eine Fett-stoffwechselstorung beobachtet, wobei die Hyperlipoproteinamie vom Typ IV vorherrscht. Die Lipoproteine sind pathologisch zusammengesetzt, der Triglyceridgehalt der LDL und VLDL ist erhoht, der Cholesterin-Anteil der HDL vermindert. Das Muster der freien Fettsauren im Plasma ist geandert, vor allem bei Dialysepatienten ist ein Mangel an der essentiellen Fettsaure Linolsaure nachweisbar. Wesentlichste Ursache der uramischen Fettstoffwechselstorung ist eine Behinderung des Lipoprotein-Abbaues durch Hemmung des Lipoproteinlipasensystems. Dadurch wird eine Akkumulation von Triglycerid-reichen VLDL, IDL und Remnants verursacht, wobei letzteren eine wichtige Rolle in der Atherogenese zugeschrieben wird. Nur bei Sonderformen des chronischen Nierenversagens (nephrotisches Syndrom, Zustand nach Nierentransplantation) ist auch eine erhohte Lipid-Synthese bzw. Turnover nachweisbar. Die klinische Bedeutung der uramischen Fettstoffwechselstorung liegt darin, daβ kunstliche Fettemulsionen ahnlich wie physiologische VLDL Partikel abgebaut werden. Daher ist die Eliminationsrate von intravenos zugefuhrtem Fett vermindert (bei akutem Nierenversagen Verdopplung der Eliminationshalbwertszeit auf 28 Minuten). Weder das chronische noch das akute Nierenversagen stellen jedoch fur sich eine Kontraindikation zur parenteralen Fettgabe dar. Die Dosis muβ jedoch der Fahigkeit des Organismus, das zugefuhrte Substrat zu verwerten, angepaβt werden. Als gunstigste Dosierung hat sich 1 g Fett/kg KG/d erwiesen, wodurch etwa 20% des Energiebedarfes des Organismus durch Fett gedeckt werden und unter der nur selten ein Ansteigen des Plasmatriglyceridspiegels auf uber 350 mg% beobachtet wird. Der Plasma-Karnitin-Spiegel ist bei akutem und nicht-dialysepflichti-gem chronischen Nierenversagen erhoht. Bei Dialysepatienten, aber auch bei nierentransplantierten Patienten findet sich eine verminderte Karnitin-Konzentration. Hauptursachen dafur sind eine verminderte renale Karnitin-Synthese, eine eingeschrankte alimentare Zufuhr und der Verlust durch die Dialysatormembran. Eine Substitution von L-Karnitin ist moglicherweise bei Dialysepatienten sinnvoll, da unter einer Karnitin-Therapie ein Abfall der Triglyceridkonzentration und vereinzelt ein Ansteigen des HDL Cholesteringehaltes und eine Normalisierung der Fetteliminationsrate beobachtet wurden.