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Biomedical subjects

B Grabensee

Publications and source records attributed to B Grabensee.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Acute renal failure in hantavirus infections].

BACKGROUND: The acute renal failure remains a diagnostic challenge for the clinician. CASE REPORTS: Between 1991 and 1996, acute renal failure caused by hantavirus infection was diagnosed in 4 previously healthy male patients. Main symptoms consisted of fever, headache, arthralgia, lumbar and abdominal pain as well as a decline in diuresis. The ultrasonography showed a slight splenomegaly in 2 patients. The clinical chemistry showed elevated serum creatinine from 2.2 mg/dl to 6.7 mg/dl and thrombocytopenia from 4000 to 150,000/microliter. The examination of the urine showed slight proteinuria and microhematuria. The kidney biopsy of 1 patient showed a reversible damage of the tubuli. The pathologic findings normalized within 3 weeks in 3 patients without need for dialysis. One patient developed a severe clinical course with acute renal failure and pulmonary edema requiring dialysis. In all patients, the renal function improved.

Acute Kidney Injury↗
PubMed2000

[Atrial natriuretic peptide as an indicator of mild postoperative cardiac dysfunction after uncomplicated bypass surgery].

Plasma levels of ANP (pg/ml; radioimmunoassay) as a parameter for postischemic dysfunction and levels of Troponin T (TnT) (ng/ml; ELISA test) as a parameter for postischemic cellular damage were determined in 15 patients with coronary artery disease (CAD) (mean age: 58 +/- 6.1 years; 13 m, 2 w; with no history of myocardial infarction and no signs for congestive heart failure) prior to, during and after extracorporal circulation (ECC). Under standardized conditions during the ECC basic parameters concerning the cardial hemodynamic (heart rate (HR); systolic (RRsys, mmHg), diastolic pressure (RR dia, mmHg) central venous pressure (CVP, mmHg); left atrial pressure (LAP, mmHg); left ventricular enddiastolic pressure (LVEDP, mmHg)) and ECG monitoring blood samples were performed: 1) prior to operation (op); 2) prior to CPB; 3) 1 h CPB; 4) 5 min after CPB; 5) 1 h after CPB; 6) 6 h postoperative (postop); 7) 24 h postop; 8) 48 h postop; 9) 10 days postop. Also the left atrial diameter (LAD, mm) and the left ventricular enddiastolic diameter at Q (LVEDD, mm) pre- and postop were documented with m-mode echocardiography (Echo) and ejection fraction (EF, %) was calculated. The bypass operations were performed with intermittent aortic cross-clamping with open venae cavae (CVP: 0-5 mmHg) and moderate hypothermia. For the determination of ANP levels and TnT levels in arterial and venous blood, a double-antibody (AB) radioimmunoassay and an ELISA test were used. Concerning the patients with CAD there was a maximal increase of ANP from preoperative 90 +/- 10 (M +/- SEM) pg/ml (p < 0.05) up to intraoperative 380 +/- 38 pg/ml. Ten days postop, the ANP level was with 262 +/- 33 pg/ml still increased threefold in comparison to the preoperative level. TnT showed an increase from preoperative 0.02 +/- 0.01 ng/ml up to intraoperative 3.44 +/- 0.47 ng/ml. Ten days postop the TnT concentration was at the preoperative level with 0.13 +/- 0.11 ng/ml. Five minutes after bypass up to 48 h postop, ANP and TnT levels were correlated (p < 0.05, r = 3.4). There was an increase of the LAD from preoperative 42.2 +/- 1.1 mm up to 46.8 +/- 1.2 mm (p < 0.05) 10 days postop as determined by m-mode echo. LVEDD and EF changed from preoperative 51.1 +/- 0.9 mm and 73 +/- 2% to 54.5 +/- 1.2 mm and 65 +/- 4% 10 days postop. The significant increase of TnT (172-fold) indicates the cellular, myocardial injury, caused by the operation without signs in ECG recordings and no signs of congestive heart failure. The significantly increased ANP level up to the 10th day postop indicate sa very sensitive prolonged, postischemic dysfunction, which is not compensated 10 days postop.

Adult↗
PubMed2000

AL-amyloidosis of the kidney initially presenting as minimal change glomerulonephritis.

Small amounts of amyloid in kidney biopsy specimens may be missed on routine examination unless specifically targeted. Occasionally, this oversight results in a diagnosis of minimal change glomerulonephritis (MCGN). This misdiagnosis may be facilitated by the fact that typical "minimal changes" with flattening and effacement of the epithelial foot processes can be found in capillary loops directly affected by amyloid deposition as well as in capillary loops of glomeruli with only mild amyloid deposition in the mesangium. Repeatedly, the diagnosis of MCGN had to be corrected to renal amyloidosis when re-examination by special techniques succeeded in detecting even small amounts of amyloid fibrils. We present the case of a previously healthy 49-year-old man who suddenly developed nephrotic syndrome. A first renal biopsy showed MCGN. Proteinuria remained refractory to immunosuppressive treatments, and creatinine clearance deteriorated rapidly. Two years later, a repeat renal biopsy showed AL-amyloidosis. In this case, re-examination of the first biopsy in the light of the final diagnosis again did not show any deposition of amyloid fibrils. We suspect that proteinuria and epithelial podocyte changes in amyloidosis are caused by factors other than deposition of amyloid fibrils itself. Possibly a cytokine release during the early fibril formation leads to abnormalities even before the typical structural changes of renal amyloidosis can be detected. This is analogous to the hypothesis of a circulating factor that leads to proteinuria in focal segmental glomerulosclerosis or the speculation of altered lymphokine expression associated with the development of MCGN in Hodgkin's disease.

Amyloidosis↗
PubMed2000

Effect of acute intravenous ace-inhibition on the intrarenal doppler flow characteristics in hypertensive patients with and without unilateral renal artery stenosis.

Assessment of intrarenal doppler signals is of particular importance in screening for renal artery stenosis. We studied the effect of acute ACE-inhibition (1,25 mg enalaprilate i.v.) on intrarenal resistive indices in 10 hypertensive patients with unilateral renal artery stenosis versus 10 patients with essential hypertension. Any changes limited to poststenotic vessels could possibly improve the diagnostic value of duplex sonography. After ACE-inhibition a significant fall of the intrarenal Resistive Index occurred in both patient groups. In cases of unilateral renal artery stenosis we saw a tendency to an increased side difference of the Resistive Index due to a greater fall on the poststenotic side. Therefore a clear advantage of duplex scanning after acute ACE-inhibition due to a limited effect of enalaprilate on poststenotic vessels was not found. The results suggest that the vascular resistance and not only the degree of renal artery stenosis is of significance for the characteristics of the doppler signal.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Prostaglandin E1: a new agent for the prevention of renal dysfunction in high risk patients caused by radiocontrast media? PGE1 Study Group.

BACKGROUND: Acute renal failure following the administration of radiocontrast media (RCM) is a complication found especially in patients with impaired renal function. Within the limits of a pilot study, the objective was to (a) show the effectiveness and compatibility of prostaglandin E(1) (PGE(1)=Alprostadil) in preventing acute renal failure in patients with elevated levels of serum creatinine and (b) to identify the most appropriate PGE(1)-dose. METHODS: 130 patients with renal impairment (serum creatinine >/=1.5 mg/dl) were included in the study prior to intravascular RCM injection. The patients received one of three different doses of PGE(1) (10, 20, or 40 ng/kg bodyweight/min) or placebo (physiologic sodium chloride solution) intravenously over a time period of 6 h (beginning 1 h prior to RCM application). Serum creatinine was measured 12, 24, and 48 h post RCM-application and creatinine clearance was determined with two 12 h collection periods, as well as one 24 h collection within 48 h post RCM administration. Adverse events during PGE(1) administration were recorded. RESULTS: In the placebo group, the mean elevation of serum creatinine was markedly higher (0.72 mg/dl) 48 h after RCM administration compared with the three PGE(1) groups (0.3 mg/dl in the 10 ng/kg/min group, 0. 12 mg in the 20 ng/kg/min group, and 0.29 mg/dl in the 40 ng/kg/min group). No clinically relevant changes were seen regarding the creatinine clearance in the four groups examined. CONCLUSIONS: Results from this pilot-study suggest that intravenous PGE(1) may be used efficaciously and safely to prevent RCM-induced renal dysfunction in patients with pre-existing impaired renal function.

Acute Kidney Injury↗
PubMed2000

Post-transplant distal-limb bone-marrow oedema: MR imaging and therapeutic considerations.

BACKGROUND: In recent years a previously unrecognized pain syndrome of the distal lower limbs after organ transplantation has been noted. A relationship to cyclosporin A was suspected, but no clear aetiology and pathogenesis have been established. METHODS: During the last 30 months we diagnosed the pain syndrome in 10 patients after renal transplantation. We prospectively followed and evaluated the patients during their clinical courses and through pathological laboratory findings and magnetic resonance imaging (MRI). RESULTS: In all patients symptoms developed within 6 months of transplantation after otherwise uncomplicated clinical courses without graft rejection episodes. Impressive bone-marrow oedema on MRI as well as elevated serum alkaline phosphatase was seen in all patients, and often exceeded the duration of clinical symptoms. All patients were instructed to avoid stress to the extremities through immobility, and steroid doses were tapered down. Within 14 weeks, eight patients were free of symptoms. Two patients have not experienced remission after 3 and 4 months respectively. None of the patients developed signs of osteonecrosis. CONCLUSION: Post-transplant distal limb bone-marrow oedema presents with distinct clinical findings and signs of bone-marrow oedema on MRI. Proven standard treatment does not exist. In our experience the elevation of the extremities, the strict avoidance of physical strain, and a stepwise withdrawal of steroids facilitates progressive disappearance of symptoms. Long-term damage to the affected ostial structures has not been seen, in contrast to avascular femoral-head necrosis.

Adult↗
PubMed2000

Influence of mycophenolic acid and FK-506 on human platelet activation in vitro.

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 microg/ml) before platelet aggregation was induced by the platelet agonists adenosine diphosphate (2 and 5 microM) and collagen 0.5 and 1.0 microg/ml). Aggregation was measured by recording the optical density. RESULTS: MPA resulted in a significant decrease in the platelet response to collagen (1.0 microg/ml) in platelet-rich plasma, whereas FK significantly increased platelet aggregation in response to collagen (0.5 microg/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.

Adenosine Diphosphate↗
PubMed1999

[Systemic Al-amyloidosis. Clinical course and limits of melphalan therapy].

BACKGROUND: Despite significant effects of melphalan and prednisone in the therapy of systemic AL-amyloidosis, overall prognosis is poor and remission of clinical symptoms cannot generally be expected. The course of the disease and results of therapy are possibly influenced by the degree and distribution of organ manifestation at the time of diagnosis. We report a group of patients with renal involvement as the main manifestation of disease. PATIENTS: Fifteen patients with systemic Al-amyloidosis without symptomatic myeloma (4 women, 11 men, median age 61 [34 to 71] years) have been attended to at our department and were treated throughout the course of the disease. RESULTS: Since primary symptoms were frequently unspecific, the maximum time to diagnosis came to 28 months. Renal involvement was primarily evident at the time of diagnosis when all patients manifested proteinuria or renal insufficiency. Ten patients were treated with a melphalan and prednisone containing chemotherapeutic protocol. A significant clinical improvement was observed in no case. One patient in an advanced stage of disease died after the administration of a high-dose regimen of melphalan with blood stem-cell support subsequent to sepsis. CONCLUSION: We do not see an absolute indication for chemotherapy. The unfavorable prognosis--14 patients died an average of 13 months after diagnosis--requires a particularly careful consideration of potential benefits and possible risks accompanying cytostatic therapy.

Adult↗
PubMed1999

[Incidence of cardiovascular risk factors and complications after kidney transplantation].

BACKGROUND: Cardiovascular disease is a leading cause of death after renal transplantation (RTx), and the incidence is considerably higher than in the general population. Aim of this study was to evaluate the incidence of atherosclerotic cardiovascular complications after RTx, the prevalence of cardiovascular risk factors, prior to and following RTx, and the association between the risk factors and complications. PATIENTS AND METHODS: Analysis of atherosclerotic cardiovascular diseases (coronary artery disease, cerebral and peripheral vascular disease) and cardiovascular risk factors before and after transplantation in 427 renal transplant recipients between 1987 and 1992 (mean age at transplantation 45 +/- 12 years, 58% male, 7% diabetics) with a mean posttransplant follow-up of 28 +/- 20 months. RESULTS: Following RTx 11.7% developed atherosclerotic cardiovascular diseases, the majority coronary artery disease (9.8%). The comparison of risk factors 12 months before and 24 months following transplantation showed: The prevalence of systemic hypertension (from 67% to 86%), diabetes mellitus (from 7% to 16%) and obesity with a body mass index > 25 kg/m2 (from 26% to 48%) had increased significantly whereas the number of smokers halved to 20%. The triglycerides decreased significantly (from 235 +/- 144 mg/dl to 217 +/- 122 mg/dl). The total and HDL cholesterol rose significantly (from 232 +/- 65 mg/dl to 273 +/- 62 mg/dl and from 47 +/- 29 mg/dl to 56 +/- 21 mg/dl, respectively). The LDL cholesterol increase was insignificant (from 180 +/- 62 mg/dl to 189 +/- 53 mg/dl). In the univariate analysis, cardiovascular diseases were significantly associated with male gender, age over 50 years, diabetes mellitus (DM), smoking, total cholesterol > 200 mg/dl, LDL cholesterol > 180 mg/dl, HDL cholesterol < 55 mg/dl, fibrinogen > 350 mg/dl, body mass index > 25 kg/m2, and more than 2 antihypertensive agents per day. The Cox proportional hazards model revealed DM with a relative risk (RR) of 4.3, age > 50 years (RR = 2.7), body mass index > 25 kg/m2 (RR = 2.6), smoking (RR = 2.5), and LDL cholesterol > 180 mg/dl (RR = 2.3) as independent risk factors. CONCLUSIONS: The high incidence of cardiovascular disease following renal transplantation is mainly due to a high prevalence and accumulation of classical risk factors before and following transplantation. The treatment of the risk factors must be effective and introduced early in the course of renal failure, further, they must be continued following transplantation. Future prospective studies should evaluate the success of treatment regarding reduction of cardiovascular morbidity and mortality in this high risk population.

Age Distribution↗
PubMed1999

Inhibitory effect of uremic solutions on protein-DNA-complex formation of the vitamin D receptor and other members of the nuclear receptor superfamily.

Chronic renal failure is often associated with a resistance to the biologically active form of vitamin D(3), the nuclear hormone 1alpha, 25-dihydroxyvitamin D(3) (VD). The actions of VD are mediated by the vitamin D receptor (VDR), a ligand-dependent transcription factor that binds as a dimeric complex with the retinoid X receptor (RXR) to specific DNA binding sites in the promoter regions of primary VD responding genes, referred to as VD response elements (VDREs). It could be shown in this study that uremic solutions derived from ultrafiltrate from hemodialysis patients and dialysate from peritoneal dialysis patients had an inhibitory effect on the complex formation and ligand inducibility of VDR-RXR heterodimers on different VDRE types. This inhibition was attributed to the formation of Schiff bases between "reactive aldehydes" and lysine residues of the DNA binding domain (DBD) of the VDR, but point mutagenesis data of different lysine residues in this study could not confirm this idea. However, the inhibitory effect of uremic solutions could also be observed for the complex formation of other homo- or heterodimer forming nuclear receptors, whereas an as a monomer binding nuclear receptor did not appear to be affected. These results indicate that VDR is a target of substances in uremic solutions in vitro, but also to some extent other nuclear receptors (i.e., other endocrine signaling systems) may be affected by renal failure.

DNA-Binding Proteins↗
PubMed1999

[Ciguatera poisoning. Growing differential diagnostic significance in the age of foreign tourism].

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.

Adult↗
PubMed1999

The use of different buffers during continuous hemofiltration in critically ill patients with acute renal failure.

OBJECTIVE: To determine the impact of different hemofiltration (HF) replacement fluids on the acid-base status and cardiovascular hemodynamics in patients with acute renal failure (ARF) and continuous veno-venous hemofiltration (CVVH). DESIGN: Prospective, cohort study. SETTING: Intensive Care Unit of the Heinrich Heine University Hospital, Düsseldorf, Germany. SUBJECT AND METHODS: One hundred and thirty-two critically ill patients with acute renal failure and continuous veno-venous HF were studied. Fifty-two patients were subjected to lactate-based (group 1), and 32 to acetate-based hemofiltration (group 2) while 48 (group 3) were treated with bicarbonate-based buffer hemofiltration fluid. Fifty-seven had a septic, and 75 a cardiovascular, origin of the ARF. Creatinine, blood urea nitrogen (BUN), serum bicarbonate, arterial pH, lactate and Apache II scores were noted daily. MAIN RESULTS: The mean CVVH duration was 9.8 +/- 8.1 days, mortality was 65%. No difference was present between the groups under investigation with regard to the main clinical parameters. Lactate- and bicarbonate-based hemofiltration led to significantly higher serum bicarbonate and arterial pH values as compared to the acetate-based hemofiltration. Serum bicarbonate values at 48 h after the initiation of CVVH treatment were 25.7 +/- 3.8 mmol/l (p < 0.001) in group 1, 20.6 +/- 3.1 mmol/l in group 2 and 23.3 +/- 3.9 mmol/l (p < 0.001) in group 3. While a lack of increase in serum bicarbonate and arterial pH was correlated to poor prognosis in lactate- and bicarbonate-based hemofiltration, no such observation was made in acetate-based hemofiltration. Cardiovascular hemodynamics were superior in patients treated with lactate- and bicarbonate-based buffer solution as compared to those treated with acetate-based buffer solution. CONCLUSIONS: The degree of correction of acidosis during hemofiltration was determined by patient outcome in patients treated with lactate- and bicarbonate-based buffer solutions, but not in patients receiving acetate-buffered solution. Bicarbonate and lactate-based buffer solutions were found to be superior to acetate-based replacement fluid.

APACHE↗
PubMed1999

Reduced incidence of acute renal graft failure in patients treated with peritoneal dialysis compared with hemodialysis.

In a case-control study performed in two centers, the incidence of delayed graft function (DGF), defined as the necessity to perform dialysis after transplantation, was analyzed according to prior treatment with continuous ambulatory peritoneal dialysis (CAPD; n = 117) or hemodialysis (HD; n = 117). The patients were matched for age, sex, HLA compatibility, and cold ischemia time. The patients were followed up for 6 months to monitor renal graft function (serum creatinine [Screa] level immediately after transplantation, at 6 weeks, at 6 months) and postoperative complications. No significant differences were found in the warm ischemia time of the graft or previous time on dialysis. DGF occurred in 27 CAPD patients (23.1%) and 59 HD patients (50.4%; P < 0.0001). The decline in Screa level after transplantation was faster in CAPD patients: the time for Screa level to decrease 50% after transplantation (T1/2Screa) was reached after 5.0 +/- 6.6 days in the CAPD group compared with 9.8 +/- 11.5 days in the HD group (P < 0.0001). A greater number of patients developed acute rejection episodes in the CAPD group (P < 0. 05), but Screa level was not different in the two groups 6 weeks and 6 months after transplantation. No differences were observed in infectious or surgical complications. This study shows that immediate renal function after transplantation is better in CAPD patients and that peritoneal dialysis should be considered as a first choice for pretransplantation therapeutic modality.

Adult↗
PubMed1999

Percutaneous renal biopsy: three years of experience with the biopty gun in 761 cases--a survey of results and complications.

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.

Adult↗
PubMed1999

Effect of flosulide, a selective cyclooxygenase 2 inhibitor, on passive heymann nephritis in the rat.

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.

Animals↗