Fragestellung: Bei Patienten mit Typ 2 Diabetes mellitus (T2D) und vorliegender Nephropathie ist wegen des hohen Risikos der Progression zur terminalen Niereninsuffizienz und des erhöhten kardiovaskulären Risikos eine frühzeitige Therapie zur Progressionshemmung der Nierenerkrankung erforderlich. Wir analysierten verschiedene klinische Parameter von Typ 2 Diabetikern mit einer Nierenerkrankung hinsichtlich einer möglichen Einflussnahme auf die Nierenfunktion.

Fragestellung: Die arterielle Hypertonie ist eine häufige Begleiterkrankung von T2D. Liegt ein Diabetes mellitus in Kombination mit einer Nierenerkrankung vor, begünstigt die Hypertonie eine Progression der Nephropathie und erhöht als eigenständiger kardiovaskulärer Risikofaktor die Morbidität und Mortalität des Diabetikers. Der Zielblutdruck bei hypertensiven Diabetikern mit einer Nierenbeteiligung ist 120–139/70–89mmHg. Wie hoch sind die Blutdruckwerte in einem Hochrisikokollektiv von T2D mit einer Nierenerkrankung zum Zeitpunkt der Erstvorstellung in unserer Klinik? Gibt es Unterschiede hinsichtlich klinischer Parameter in Abhängigkeit vom Vorliegen einer Hypertonie?

Fragestellung: Bei Typ-2-Diabetikern (T2D) ist das kardiovaskuläre Risiko gegenüber Nichtdiabetikern deutlich erhöht. Dieses Risiko wird durch eine zusätzlich vorliegende Nierenfunktionseinschränkung weiterhin verstärkt. Die häufig anzutreffende Hämoglobinerniedri-gung niereninsuffizienter Diabetiker stellt einen weiteren eigenständigen kardiovaskulären Risikofaktor dar und fördert die Progressionsrate zur terminalen Niereninsuffizienz. Wir untersuchten, wie häufig eine Anämie in einem Kollektiv von T2D mit Nephropathie vorliegt und analysierten einflussnehmende klinische Parameter.

If non-treated or misdiagnosed, acute crescentic glomerulonephritis, clinically defined as rapidly progressive glomerulonephritis (RPGN), may lead to end-stage renal failure (ESRD) within a short time. Histologically, it is characterized by accumulation of inflammatory cells in combination with proliferation of epithelial cells in the glomerulus. According to the proposed immunopathogenic classification by Couser [7], predominantly the immunopathogenic type III without immune deposits often represents the renal manifestation of a systemic vasculitis disease, e.g. polyarteriitis or Wegener's granulomatosis. Having investigated 75 patients with acute crescentic glomerulonephritis for long-term results, we concluded that early histopathologic diagnosis by using an activity and chronicity score system may be not only a predictor for renal prognosis but also a valid supposition for differentiated immunosuppressive therapy in supplement to the clinical data on renal function. The therapeutic advantage of plasmapheresis therapy in addition to immunosuppressive therapy could not be proven.

Background/Aim: FK–506 (FK) and mycophenolic acid (MPA) are immunosuppressive agents used in kidney transplant recipients. Their effect on posttransplant thromboembolic complications is either controversial (FK) or has not been described (MPA). Thromboembolic events are among the consequences of platelet hyperaggregability which can be identified by measuring platelet aggregation. The aim of this study was to evaluate the in vitro effects of MPA and FK upon platelet activation in healthy subjects. Methods: Platelet–rich plasma from healthy volunteers (n = 18) was incubated with FK (70 ng/ml), FK vehicle, and MPA (30 μg/ml) before platelet aggregation was induced by the platelet agonists adenosine diphosphate (2 and 5 μM) and collagen 0.5 and 1.0 μg/ml). Aggregation was measured by recording the optical density. Results: MPA resulted in a significant decrease in the platelet response to collagen (1.0 μg/ml) in platelet–rich plasma, whereas FK significantly increased platelet aggregation in response to collagen (0.5 μg/ml). The vehicle of FK had no influence on platelet aggregation with either agonist. Conclusions: The decreased platelet–activating response following preincubation with MPA may favor its use in kidney transplant recipients to reduce thromboembolic events. The FK–induced enhancement of platelet aggregation shown in vitro may lead to thromboembolic complications in transplant recipients.

BACKGROUND:Nonsteroidal anti-inflammatory drugs (NSAIDs) induce an inhibition of cyclooxygenase (COX), an enzyme that makes prostaglandins. Two isoforms of COX exist: COX-1 represents the constitutively expressed enzyme, whereas COX-2 is the inducible isoform. This study investigated the role of COX-2 in the inflammatory processes of the kidneys of rats with passive Heymann nephritis (PHN), and focused of the effect of a selective COX-2 inhibitor, flosulide. COX-2-selective inhibitors are thought to represent potent anti-inflammatory agents without major renal side effects.METHODS:PHN was induced by injecting heterologous Fx1A antiserum into female Wistar rats. Two treatment groups, each consisting of 12 rats with PHN, received either 3 or 9 mg of flosulide/kg body wt/day and were compared with untreated controls. After four weeks, the generation of thromboxane B2 (TxB2) and 6-keto-PGF1alpha were determined in renal tissue and in urine. COX-2 protein expression was investigated by Western blotting using a selective antibody.RESULTS:Rats with PHN exhibited a marked proteinuria of 71 +/- 8 mg/24 hr as compared with 2.0 +/- 0.3 mg/24 hr in healthy controls (P < 0.01). Treatment with flosulide reduced the proteinuria to 26.1 +/- 9 mg/24 hr at 3 mg flosulide/kg body wt/day and 35.5 +/- 6 mg/24 hr at 9 mg/kg body wt/day, which was equivalent to a reduction of proteinuria by a maximum of 65% (P < 0.05). This was accompanied by an increase in glomerular TxB2 from 3073 +/- 355 to 5255 +/- 1041 pg/mg glomerular protein and 6-keto-PGF1alpha from 1702 +/- 161 to 2724 +/- 770 pg/mg glomerular protein in rats with PHN. COX-2 protein expression was also highly elevated in comparison to healthy controls. Low-dose flosulide treatment had no effect on COX protein expression and renal prostaglandin formation. High-dose flosulide treatment reduced renal prostaglandin production and caused a marked decline in COX-1 and COX-2 protein expression. Urine prostanoid excretion remained unchanged in all therapeutic groups. There was a small though significant reduction in renal creatinine clearance from 0.86 ml +/- 0.2/min in untreated controls to 0.6 ml +/- 0.1/min in flosulide-treated rats with PHN (P < 0.01) after four weeks.CONCLUSIONS:Under the influence of flosulide, a highly COX-2-selective inhibitor, we observed an antiproteinuric drug effect. The inflammation in PHN induced COX-2 protein expression that was not affected by low-dose flosulide. COX-1 and COX-2 protein expression was affected by high-dose flosulide, which therefore might lose its selectivity. High-dose flosulide induced a decrease in glomerular prostanoid production possibly because of COX-1 inhibition. Our results suggest that the therapeutic use of flosulide in proteinuria seems advantageous and deserves further studies because the basal prostaglandin levels remain unchanged in the low-dose-treated group, indicating that the compensatory capacity of prostaglandin production, which is essential for the regulation of renal hemodynamics, is maintained.

BACKGROUND:In the tropic sea there are carnivore fishes, e.g. the "peak bass", that incorporate toxin producing seaweed and can cause the ciguatera intoxication. Due to the frequent tourism to tropic regions even more cases of ciguatera intoxication can be seen in Europe. The late phase of ciguatera intoxication has hardly been recognized due to its different unspecific symptoms. In some cases ciguatera intoxication can even grow a vital threatening.CASE DESCRIPTION:Four patients from a travel group addressed us 4 and 14 days after breaking off their holidays in the Dominican republic. They presented complex neurological symptoms including paraesthesia, nervousness, inverse temperature perception, muscle cramps, headache and dizziness. The physical and apparative investigation of the patients, whose age ranked between 22 and 31 years, was totally unobtrusive. Essential for the diagnosis of ciguatera intoxication was the clue to the symptom causing dinner at their holiday location existing of "peak bass and lemon sauce". First symptoms in all members of the travel group were diarrhea, sickness and sweating. In this late phase only a symptomatic therapy could be offered.CONCLUSION:The here described cases show the importance of a comprehensive information for tropic travellers as for physicians accounted to in the acute phase of ciguatera intoxication, because recognized early enough (within the first 24 hours) the total symptomatology of ciguatera intoxication can be prevented effectively by intravenous infusions of mannitol.

Background: In the tropic sea there are carnivore fishes, e.g. the "peak bass", that incorporate toxin producing seaweed and can cause the ciguatera intoxication. Due to the frequent tourism to tropic regions even more cases of ciguatera intoxication can be seen in Europe. The late phase of ciguatera intoxication has hardly been recognized due to its different unspecific symptoms. In some cases ciguatera intoxication can even grow a vital threatening.Case Description: Four patients from a travel group addressed us 4 and 14 days after breaking off their holidays in the Dominican republic. They presented complex neurological symptoms including paraesthesia, nervousness, inverse temperature perception, muscle cramps, headache and dizziness. The physical and apparative investigation of the patients, whose age ranged between 22 and 31 years, was totally unobtrusive. Essential for the diagnosis of ciguatera intoxication was the clue to the symptom causing dinner at their holiday location existing of "peak bass and lemon sauce". First symptoms in all members of the travel group were diarrhea, sickness and sweatening. In this late phase only a symptomatic therapy could be offered.Conclusion: The here described cases show the importance of a comprehensive information for tropic travellers as for physicians accounted to in the acute phase of ciguatera intoxication, because recognized early enough (within the first 24 hours) the total symptomatology of ciguatera intoxication can be prevented effectively by intravenous infusions of mannitol.

From 1.1.1993 to 12.31.1995 we performed 761 consecutive biopsies on 509 non-selected patients. The most frequent diagnoses in 351 biopsies (39.4%) on native kidneys were 262 cases of glomerulonephritis (74.6%) and 167 of so-called benign nephrosclerosis (47.6%). With 410 biopsies (60.6%) on allograft kidneys 219 cases (78%) showed signs of interstitial rejection, 14 cases (5%) vascular and 49 cases (17%) interstitial as well as vascular rejection. Only after 5 biopsies (0.66%) clinical relevant complications (3 perirenal haematomas, 1 AV fistula, 1 vesical tamponade) appeared. Again percutaneous renal biopsy is proven to be a diagnostically efficient and safe tool at the same time even when used in a large number of non-selected patients, so that an ambulant performance may be discussed. The relatively frequent diagnosis of a so-called benign nephrosclerosis seems to indicate the need for an intensified examination of this disease.

If nontreated or misdiagnosed, acute crescentic glomerulonephritis, clinically defined as rapidly progressive glomerulonephritis (RPGN), may led to end-stage renal failure (ESRD) within a short time. Histologically, it is characterized by accumulation of inflammatory cells in combination with proliferation of epithelial cells in the glomerulus. According to the proposed immunopathogenic classification by Couser (7), predominantly the immunopathogenic type III without immune deposits often represents the renal manifestation of a systemic vasculitic disease, for example, polyarteriitis or Wegener's granulomatosis. Having investigated 75 patients with acute crescentic glomerulonephritis in respect to their long-term results, we conclude that an early histopathologic diagnosis by using an activity and chronicity score system may not only be a predictor for renal prognosis but also be a valid supposition for differentiated immunosuppressive therapy in supplement to the clinical data on renal function. A therapeutic advantage of a plasmapheresis therapy additionally to the immunosuppressive therapy could not be proven.

Antibodies against factor VIII occur in about 15–35% of hemophilia A patients and induce refractoriness to factor VIII substitution. In most cases, these antibodies are of the IgG class. Strategies to avoid or to treat such inhibitors are controversial. In very rare cases, factor VIII inhibitors also develop in nonhemophilic patients. Although there are anecdotal reports that these antibodies may disappear spontaneously without occurrence of bleeding tendencies, in the majority of patients the clinical course is characterized by severe hemorrhages. From 1980 to 1995, we observed ten nonhemophilic patients with acquired factor VIII inhibitors at our hospital. In most cases, a sudden bleeding tendency was observed shortly after an injury or surgery. Coagulation tests showed a prolonged aPTT and a decreased F VIII level. Other deficiencies of blood-clotting factors and acquired or hereditary von Willebrand's disease were excluded. Therapy with F VIII concentrates did not produce the expected increase. Measurement of F VIII inhibitor levels in Bethesda units/ml (BU/ml) revealed maximal values in the range of 2–128 BU/ml. Immunosuppressive therapy with azathioprine or cyclophosphamide in combination with methylprednisolone led to complete disappearance of the inhibitor, normalization of the coagulation tests, and complete remission of the bleeding tendency in seven treated patients within 6 weeks. Although the clinical course is not predictable and inhibitors may disappear spontaneously, combined therapy with methylprednisolone and azathioprine or cyclophosphamide is recommended for patients with bleeding tendency. In pregnancy, therapy should be started only with methylprednisolone; post-partum, azathioprine should be used additionally if methylprednisolone as a single drug does not lead to complete remission. In emergency situations, therapy with high doses of human factor VIII concentrate may be used. When bleeding does not cease, the additional use of activated prothrombin-complex concentrates or porcine factor VIII is indicated. Possible side effects may include hepatitis and short-lived intravascular thrombin production.