Biomedical subjects

Anke Schwarz

Publications and source records attributed to Anke Schwarz.

7 recordsLinked to original sources

PubMed2003

Elevated numbers of circulating endothelial cells in renal transplant recipients.

BACKGROUND: Damage of microvascular endothelial cells is a salient feature of acute vascular rejection and chronic allograft nephropathy, yet specific blood markers of ongoing endothelial injury are currently unavailable. Circulating endothelial cells have recently been established as a novel marker of endothelial damage in a variety of vascular disorders. METHODS: We studied 129 renal transplant recipients who underwent percutaneous graft biopsy. Circulating endothelial cells were isolated with immunomagnetic anti-CD146-coated Dynabeads. Cells were stained with acridine and counted. To verify their endothelial origin, staining for Ulex europaeus lectin 1 (UEA-1) was performed in parallel. Twenty-one healthy controls were also studied. RESULTS: On biopsy, seven patients had acute vascular rejection, 15 patients had acute tubulointerstitial rejection, 14 patients had borderline rejection, and 93 patients had no rejection. Patients with acute vascular rejection had the highest cell numbers (72+/-39 cells/mL) when compared with all other patients (P<0.02). Regardless of their biopsy findings, however, all other renal transplant recipients had significantly higher numbers of circulating endothelial cells (25+/-20 cells/mL) than healthy controls (7+/-5 cells/mL, P<0.001). Finally, there was a significant correlation of cell numbers and serum cyclosporine A trough levels. By contrast, there was no correlation with serum creatinine, age, or the number of immunosuppressive drugs. CONCLUSIONS: The number of circulating endothelial cells is a novel marker of endothelial damage in renal transplant recipients. Further studies must now evaluate the origin of these cells, corroborate the clinical significance of our findings, and delineate the influence of calcineurin inhibitors.

Acute Disease↗

PubMed2003

The renal arterial resistance index and renal allograft survival.

BACKGROUND: Most renal transplants fail because of chronic allograft nephropathy or because the recipient dies, but no reliable factor predicting long-term outcome has been identified. We tested whether a renal arterial resistance index of less than 80 was predictive of long-term allograft survival. METHODS: The renal segmental arterial resistance index (the percentage reduction of the end-diastolic flow as compared with the systolic flow) was measured by Doppler ultrasonography in 601 patients at least three months after transplantation between August 1997 and November 1998. All patients were followed for three or more years. The combined end point was a decrease of 50 percent or more in the creatinine clearance rate, allograft failure (indicated by the need for dialysis), or death. RESULTS: A total of 122 patients (20 percent) had a resistance index of 80 or higher. Eighty-four of these patients (69 percent) had a decrease of 50 percent or more in creatinine clearance, as compared with 56 of the 479 patients with a resistance index of less than 80 (12 percent); 57 patients with a higher resistance index (47 percent) required dialysis, as compared with 43 patients with a lower resistance index (9 percent); and 36 patients with a higher resistance index (30 percent) died, as compared with 33 patients with a lower resistance index (7 percent) (P<0.001 for all comparisons). A total of 107 patients with a higher resistance index (88 percent) reached the combined end point, as compared with 83 of those with a lower resistance index (17 percent, P<0.001). The multivariate relative risk of graft loss among patients with a higher resistance index was 9.1 (95 percent confidence interval, 6.6 to 12.7). Proteinuria (protein excretion, 1 g per day or more), symptomatic cytomegalovirus infection, and a creatinine clearance rate of less than 30 ml per minute per 1.73 m2 of body-surface area after transplantation also increased the risk. CONCLUSIONS: A renal arterial resistance index of 80 or higher measured at least three months after transplantation is associated with poor subsequent allograft performance and death.

Biopsy↗

PubMed2003

Circulating endothelial cells are a novel marker of cyclosporine-induced endothelial damage.

Microvascular endothelial cells play a key role in transplant immunology. They are also important targets for calcineurin inhibitors. We recently demonstrated elevated numbers of circulating endothelial cells in renal transplant recipients with and without rejection in comparison with healthy controls. Because these patients received either cyclosporine or tacrolimus, we speculated that endothelial damage from calcineurin inhibitors might be responsible for these findings. In the present study, we tested the hypothesis that treatment with calcineurin inhibitors leads to an increase in circulating endothelial cells. We studied 57 renal transplant recipients: 19 on a calcineurin inhibitor-free immunosuppressive regimen and 38 patients on a standard immunosuppressive regimen, including cyclosporine, and matched them for age and serum creatinine. Endothelial cells were isolated from peripheral blood with anti-CD-146-coated immunomagnetic Dynabeads and were counted by fluorescence microscopy. Patients with cyclosporine therapy had elevated numbers of circulating endothelial cells (median 26, range 12 to 82 cells/mL) compared with healthy controls (median 6, range 0 to 82 cells/mL; P<0.001). Patients without calcineurin inhibitor treatment had significantly lower cell numbers (median 12, range 0 to 32 cells/mL; P<0.003) and were not significantly different from normal, untreated controls. In conclusion, renal transplant recipients who do not receive calcineurin inhibitors have significantly lower numbers of circulating endothelial cells than their age- and creatinine-matched counterparts who receive these drugs. We suggest that elevated numbers of circulating endothelial cells indicate damage from calcineurin inhibitors in renal transplant recipients and that circulating endothelial cells are a novel marker of endothelial damage.

Adult↗

PubMed2003

Incidence of polyomavirus-nephropathy in renal allografts: influence of modern immunosuppressive drugs.

BACKGROUND: In recent years an increasing number of cases with polyomavirus (PV)-nephropathy after renal transplantation were reported from several transplant centres. New, highly potent immunosuppressive drugs like tacrolimus or mycophenolate mofetil were accused as risk factors for this increase. However, data about the incidence of PV-nephropathy in correlation to different immunosuppressive therapy concepts are lacking. METHODS: All renal transplant biopsies performed at Hannover Medical School between 1999 and 2001 (n=1276) were immunohistochemically screened for the presence of PV-specific proteins. The results were correlated to the different immunosuppressive therapy protocols and patients with PV-nephropathy were compared with a matched control group. RESULTS: PV-nephropathy was found in <1% of all investigated allograft biopsies (11/1276) and in approximately 1% of all patients (7/638), respectively. All patients being immunohistochemically positive for PV-specific proteins also showed the typical morphological changes of PV-nephropathy. Four out of seven patients with PV-nephropathy were under triple immunosuppression comprising tacrolimus and mycophenolate mofetil. Under this immunosuppressive therapy protocol an eight times higher incidence and a 13 times higher risk (multivariate odds ratio 12.7) of PV-nephropathy was observed in our patients compared with the control group. CONCLUSIONS: PV-nephropathy is a rare but serious complication after renal transplantation. A small group of patients under intensive immunosuppression comprising tacrolimus in combination with mycophenolate mofetil has a significantly increased risk of acquiring this deleterious complication.

Adolescent↗

PubMed2003

The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification.

Ectopic calcification is a frequent complication of many degenerative diseases. Here we identify the serum protein alpha2-Heremans-Schmid glycoprotein (Ahsg, also known as fetuin-A) as an important inhibitor of ectopic calcification acting on the systemic level. Ahsg-deficient mice are phenotypically normal, but develop severe calcification of various organs on a mineral and vitamin D-rich diet and on a normal diet when the deficiency is combined with a DBA/2 genetic background. This phenotype is not associated with apparent changes in calcium and phosphate homeostasis, but with a decreased inhibitory activity of the Ahsg-deficient extracellular fluid on mineral formation. The same underlying principle may contribute to many calcifying disorders including calciphylaxis, a syndrome of severe systemic calcification in patients with chronic renal failure. Taken together, our data demonstrate a critical role of Ahsg as an inhibitor of unwanted mineralization and provide a novel therapeutic concept to prevent ectopic calcification accompanying various diseases.

Animals↗

PubMed2002

A swollen neck.

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Adolescent↗

PubMed1983

Analgesic dilemma in chronic hemodialysis patients.

Analgesic drug abuse led to end-stage renal disease in 31% of 122 patients in a cross-sectional investigation at our center. Addiction to analgesics and tranquilizers remained a serious problem in these patients even after they were placed on chronic hemodialysis. There is strong evidence that drug addiction leading to end-stage renal disease and chronic hemodialysis correlates with a special type of personality typified by the 60-year-old depressive woman suffering from chronic headache.

Adult↗