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K Budde

Publications and source records attributed to K Budde.

At least 73 records · Page 4Linked to original sources
PubMed1999

Treatment of acute c-ANCA-positive vasculitis with mycophenolate mofetil.

Acute cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA)-positive vasculitis is usually treated with cyclophosphamide and corticosteroids. The incidence of cyclophosphamide-induced lung injury, a potentially life-threatening event, is about 1%. We report on a patient with a history of cyclophosphamide-induced lung injury 2 months after initial treatment of systemic c-ANCA-positive vasculitis. Six months later, the patient presented with acute renal failure caused by an acute relapse of vasculitis. Mycophenolate mofetil (MMF) is a potent immunosuppressive drug that recently has been shown to be effective in the maintenance therapy of c-ANCA-positive systemic vasculitis. With the patient's informed consent, we started treatment with MMF in combination with corticosteroids. Subsequently, anti-proteinase-3-titer (anti-Pr3-titer) returned to normal and renal function improved. In conclusion, MMF in combination with corticosteroids may be useful in the treatment of acute c-ANCA-positive vasculitis.

Acute Kidney Injury↗
PubMed1999

Entry-into-human study with the novel immunosuppressant SDZ RAD in stable renal transplant recipients.

AIMS: To evaluate the tolerability of single oral SDZ RAD doses in stable renal transplant recipients and the pharmacokinetics of ascending SDZ RAD doses when coadministered with steady-state cyclosporin A microemulsion (Neoral). METHODS: This randomized, double-blind, placebo-controlled, sequential study involved 54 patients in six treatment groups; a different SDZ RAD dose (0.25, 0. 75, 2.5, 7.5, 15, 25 mg) was assessed in each group. Patients received a single oral dose of SDZ RAD (n=6) or placebo (n=3) with their usual Neoral dose. SDZ RAD and cyclosporin A pharmacokinetic parameters were determined. RESULTS: All SDZ RAD doses were well tolerated, with no discontinuations due to adverse events, serious adverse events, or deaths. Similar proportions of patients receiving SDZ RAD and placebo had at least one adverse event (44% and 50%, respectively). Mean changes in laboratory variables (baseline to endpoint) showed no clinically meaningful differences between SDZ RAD and placebo groups. SDZ RAD was absorbed rapidly and showed dose-proportional pharmacokinetics (dose: 2.5-25 mg), based on systemic exposure. Multiple postabsorptive phases in the pharmacokinetic profile indicate tissue distribution. The elimination half-life ranged from 24 to 35 h across the five highest dose groups. Pharmacokinetics were similar in men and women. Co-administration of escalating single oral SDZ RAD doses did not affect steady-state cyclosporin A pharmacokinetics. CONCLUSIONS: SDZ RAD was well tolerated; safety profiles of SDZ RAD and placebo were similar. SDZ RAD pharmacokinetics were dose-proportional across the range 2.5-25 mg in conjunction with cyclosporin A-based therapy, according to systemic exposure. Cyclosporin A pharmacokinetics were not affected by coadministration of single oral doses of 0.25-25 mg SDZ RAD.

Adolescent↗
PubMed1999

Volume stress-induced peritoneal endothelin-1 release in continuous ambulatory peritoneal dialysis.

In long-term peritoneal dialysis, functional deterioration of the peritoneal membrane is often associated with proliferative processes of the involved tissues leading to peritoneal fibrosis. In continuous ambulatory peritoneal dialysis (CAPD), failure to achieve target values for adequacy of dialysis is commonly corrected by increasing dwell volume; in case of ultrafiltration failure, osmolarity of the dialysate gets increased. In a prospective study, the impact of increasing dwell volume from 1500 ml to 2500 ml per dwell (volume trial) or changing the osmolarity of the dialysate from 1.36 to 3.86% glucose (hyperosmolarity trial) on the peritoneal endothelin-1 (ET-1) release was analyzed. ET-1 is known to exert significant proliferative activities on a variety of cell types leading to an accumulation of extracellular matrix. A highly significant difference in the cumulative peritoneal ET-1 synthesis was found between the low- and high-volume exchange, whereas differences in the hyperosmolarity setting were only moderate. Sixty minutes after initiating dialysis, the cumulative ET-1 synthesis was 2367 +/- 1023 fmol for the 1500 ml versus 6062 +/- 1419 fmol for the 2500 dwell (P < 0.0001) and 4572 +/- 969 fmol versus 6124 +/- 1473 fmol for the 1.36 and 3.86% glucose dwell (P < 0.05), respectively. In conclusion, increasing dwell volume leads to a strong activation of the peritoneal paracrine endothelin system. Because ET-1, apart from being a potent vasoactive peptide, contributes to fibrotic remodeling, this study indicates that volume stress-induced ET-1 release might contribute to structural alteration of the peritoneal membrane in long-term peritoneal dialysis.

Dialysis Solutions↗
PubMed1998

Mycophenolate mofetil pharmacokinetics in renal transplant recipients on peritoneal dialysis.

We prospectively studied the impact of peritoneal dialysis (PD) on the pharmacokinetics of mycophenolic acid (MPA) in five patients following renal transplantation. Three patients had a glomerular filtration rate (GFR) of less than 10 ml/min and two had a GFR of more than 40 ml/min. Pharmacokinetics of MPA and of its main metabolite, mycophenolic acid glucuronide (MPAG), were studied during two consecutive 12-h periods (with and without PD). After initiation of PD in patients with severe renal impairment (GFR < 10 ml/ min), MPA-area-under-the-concentration-curve (AUC) decreased up to 59% and MPAG-AUC decreased up to 26%. We did not observe any substantial changes in the MPA-AUC or MPAG-AUC of either patient with a GFR above 40 ml/min. Patients with a reduced GFR had much higher MPAG values than patients with a GFR above 40 ml/l; yet, we did not observe any differences in the MPA values. We found a significant inverse correlation between GFR and MPA-AUC (r = 0.81, P < 0.05) and between GFR and MPAG-AUC (r = 0.94, P < 0.01). While MPA was found only in traces in the peritoneal ultrafiltrate, the cumulative amount of MPAG removed by PD reached up to 2 g/ 12 h, representing 1.2 g of MPA. This is the first report describing a reduction in MPA-AUC and MPAG-AUC during PD. Further studies are needed to completely understand the pharmacokinetics of mycophenolate mofetil during PD.

Adult↗
PubMed1998

The quality of life in end stage renal disease care.

The improved prognosis and survival statistics of both renal transplantation and dialysis have focused attention on the quality of life offered by these treatments. Using a standardized questionnaire, we assessed the quality of life of 612 patients undergoing renal replacement therapy at our center. Of these patients, 359 had been transplanted and 253 patients were on dialysis. Concerning the sociodemographic data, only the time on specific treatment was longer in dialysis patients than in transplanted patients (49.2 versus 55.6 months, P < 0.05). Most complaints were more common in dialysis patients than in transplanted patients. Only the side effects of medication were seen more in transplanted patients (P < 0.005). Life satisfaction was higher in transplanted patients than in dialysis patients. Dialysis patients were more anxious (P < 0.05) and more depressed (P < 0.001) than transplanted patients. Transplanted patients also felt that they had more social support than did dialysis patients. Overall life quality was almost equal between patients on hemodialysis and patients on peritoneal dialysis, and between patients on the waiting list for transplantation and those not on the waiting list. Despite a significantly better quality of life after renal transplantation, the percentage of patients working remained unchanged. (57.5% versus 57.8%, P = n.s.). We conclude that despite an improved quality of life after renal transplantation, these patients are economically not more productive than patients on dialysis.

Female↗
PubMed1998

Pharmacokinetics of mycophenolate mofetil in renal transplant recipients on peritoneal dialysis.

Little is known about the pharmacokinetics of mycophenolatic acid (MPA) in the early posttransplant period after renal transplantation. We studied the impact of peritoneal dialysis on the pharmacokinetics of MPA in 5 patients following renal transplantation (3-6 weeks after transplantation). Three patients had a glomerular filtration rate (GFR) of less than 10 ml/min, 1 patient had a GFR of 32, and 1 of 58 ml/min. Pharmacokinetics of MPA and its main metabolite mycophenolic acid glucuronide (MPAG) were studied on 2 consecutive days (12-hour intervals: with and without peritoneal dialysis). Dosing of MPA was 2 x 1 g/day. MPA and MPAG concentrations were determined by HPLC methods. After initiation of peritoneal dialysis in patients with severe renal impairment (GFR < 10 ml/min) MPA area under the concentration curve (AUC) decreased substantially (15-59%). The calculated clearance of MPA was higher (14.6 vs 8.1 ml/min/kg) on the day of peritoneal dialysis than during the dwell-free day. MPAG-AUC decreased up to 26% in these patients. In both patients with a GFR > 30 ml/min we observed an increase of MPA-AUC on the day of peritoneal dialysis and a decreased MPA clearance. MPAG-AUCs remained stable. Patients with a reduced GFR had much higher MPAG values than patients with a GFR 30 ml/l, however, we did not observe any differences for the MPA levels. We found a significant inverse correlation between GFR and MPAG-AUC (r = 0.91, p < 0.05). While MPA was found only in traces in the peritoneal ultrafiltrate, the cumulative amount of MPAG removed by peritoneal dialysis reached up to 2 g per 12 hours, representing up to 1.2 g of MPA. This is the first report describing a reduction of MPA- and MPAG-AUC during peritoneal dialysis. Further studies are needed to better understand the pharmacokinetics of mycophenolat mofetil during peritoneal dialysis.

Adult↗
PubMed1997

Interleukin-8 expression in patients after renal transplantation.

Cellular invasion and cytokine release are important steps in the initiation of rejection. We studied the release of interleukin-8 (IL-8), a potent proinflammatory and chemotactic cytokine, and its prognostic significance in predicting rejection after renal transplantation. Serum and urine samples were analyzed with an IL-8-specific sandwich enzyme-linked immunosorbent assay. Biopsy tissue specimens (n = 20) were snap-frozen and examined with immunohistochemistry using two monoclonal antibodies against human IL-8 (4G9 and 2A8). Serum IL-8 measurements were of no value in predicting rejection due to low sensitivity (24%). In 45 biopsy-proven acute rejections (< 2 months after transplantation), urinary IL-8 concentrations were elevated in 62% (298 +/- 54 pg/mL; P < 0.01), preceding clinical diagnosis of rejection. After treatment, the IL-8 concentration in urine decreased back to normal (33 +/- 4 pg/mL; P < 0.01). The highest urinary IL-8 concentrations were seen in patients with biopsy-proven rejection in combination with acute tubular necrosis (610 +/- 150 pg/mL). This finding was independent of renal function and urinary volume. Only three of 15 rejection episodes in patients more than 2 months after transplantation showed an elevated IL-8 concentration in urine (94 +/- 60 pg/mL). In 10 of 23 patients with infection, a significant increase of IL-8 in urine was observed as well (157 +/- 67 pg/mL; P < 0.05). IL-8-positive staining was found within interstitial mononuclear cells of all biopsy specimens showing rejection. Additionally, the antibody 4G9 stained arteriolar smooth muscle and tubular cells. Interestingly, a few IL-8-positive cells were present in two donor kidneys before transplantation was performed; control tissue was negative. Further investigations are necessary to determine the clinical value of urinary IL-8 determinations in the diagnosis of rejection and to evaluate the role of IL-8 in the pathogenesis of acute allograft rejection.

Enzyme-Linked Immunosorbent Assay↗