Sanja Balen

Association of Kidney Graft Loss With De Novo Produced Donor-Specific and Non-Donor-Specific HLA Antibodies Detected by Single Antigen Testing

Background The association of donor-specific HLA antibodies (DSA) with kidney graft failure has been addressed previously; however, the majority of studies were based on small numbers of patients with graft failure. Methods We investigated 83 patients with failed kidney transplants for a possible association of de novo development and persistence or loss of pre-existing DSA with graft failure. Single Antigen Bead assay-detected DSA and non-DSA antibodies were compared between patients with graft loss and matched controls with functioning grafts. Results The incidence of weak de novo DSA or non-DSA at a mean fluorescence intensity of 500 or higher was higher in the graft loss than in the nonrejector group (76% vs 40%, P < 0.001). Because of the low number of patients developing de novo DSA, the DSA results did not reach statistical significance (only 22% of patients with graft loss developed de novo DSA). However, at all cutoffs, there was a significantly higher rate of graft loss in patients with de novo non-DSA. The incidence of strong pretransplant DSA that persist after transplantation was higher in the graft loss group (10% vs 1%, P = 0.034). When C1q-binding ability in sera of rejectors and nonrejectors with posttransplant de novo or persistent DSA was compared, none of the nonrejectors demonstrated C1q positivity, whereas 43% of patients with graft loss showed C1q-positive antibodies, although not necessarily donor-specific (P < 0.001). Conclusions Our data show that the posttransplant presence of persisting or de novo HLA antibodies, especially if C1q binding, is associated with graft loss, even if the antibodies are not specific for mismatched donor HLA.

Donor-specific antibodies require preactivated immune system to harm renal transplant

Highlights • Pretransplant DSA have a deleterious impact on graft survival only in the presence of high pretransplant serum levels of sCD30.• The majority of patients with pretransplant DSA might be transplanted safely without special pretreatment measures. Kidney transplantation in the presence of donor-specific HLA antibodies (DSA) is associated with a high failure rate due to antibody-mediated rejection. Many centers avoid transplantations if DSA are present. Others perform such transplantations after removal of DSA by apheresis under potent immunosuppression. We provide strong evidence that DSA positive recipients reject their grafts at a high rate only if the immune activation marker sCD30 is also high, suggesting that T-cell help from an activated immune system is necessary for pretransplant DSA to exert a deleterious effect on the graft. High-risk patients with DSA and sCD30 may benefit from special treatment measures. The presence of DSA alone may not be deleterious.

Left ventricle diastolic dysfunction in obese patients with newly diagnosed arterial hypertension.

ZusammenfassungHINTERGRUND: Arterielle Hypertonie und Adipositas sind als unabhängige Risikofaktoren der linksventrikulären diastolischen Dysfunktion schon lange bekannt; ebenso bekannt ist die häufige Koexistenz von arterieller Hypertonie und Adipositas. Daten über die linksventrikuläre diastolische Dysfunktion bei adipösen Patienten mit neu diagnostizierter arterieller Hypertonie gibt es allerdings bisher nur wenige. Diese Studie wurde durchgeführt, um die Prävalenz der linksventrikulären diastolischen Dysfunktion bei adipösen Patienten mit neu diagnostizierter arterieller Hypertonie zu erheben. METHODEN: 125 adipöse Patienten wurden in unsere Studie einbezogen, davon 65 mit neu diagnostizierter arterieller Hypertonie. Alter, Geschlecht und Body Mass Index der Hypertoniker waren mit der Gruppe der 60 adipösen Nicht-Hypertoniker vergleichbar. Die linksventrikuläre diastolische Funktion wurde mittels Doppler-Echokardiographie durch Messung folgender Parameter erhoben: Geschwindigkeit des Mitral-Influx (E- und A-Welle), E-Wellen-Dezelerationszeit, isovolumetrische Relaxationszeit, linksatriale und linksventrikuläre Diameter, intraventrikuläre Septumdicke und linksventrikuläre Herzmasse. Ein E/A-Verhältnis <1 wurde als diastolische Dysfunktion aufgefasst. ERGEBNISSE: Bei neu diagnostizierten adipösen Hypertonikern wurden signifikant höhere A-Wellen, signifikant niedrigere E/A Verhältnisse, signifikant längere E-Wellen-Dezelerationszeiten und signifikant größere linke Vorhöfe gefunden. Die Spitzengeschwindigkeit der E-wellen unterschied sich nicht signifikant. Auch in der Prävalenz der linksventrikulären Hypertrophie und der linksventrikulären Herzmasse wurde kein signifikanter Unterschied gefunden. Die Prävalenz der diastolischen Dysfunktion war bei den adipösen Patienten mit neu diagnostizierter arterieller Hypertonie signifikant häufiger. KONKLUSION: Die Studie weist auf einen signifikanten Beitrag der neu diagnostizierten arteriellen Hypertonie zur Verschlechterung der diastolischen Funktion des linken Ventrikels bei adipösen Patienten – noch vor dem Nachweis struktureller Änderungen – hin.SummaryBACKGROUND: The frequent coexistence of obesity and arterial hypertension is well known. Although both conditions have been identified as independent risk factors for impaired left ventricular diastolic function, there is a paucity of data on the dysfunction among obese patients with newly diagnosed arterial hypertension. The study was performed to determine the prevalence of diastolic dysfunction in obese individuals with newly diagnosed arterial hypertension and to compare it with the prevalence in normotensive obese persons. METHODS: We enrolled 125 obese patients: 65 with newly diagnosed hypertension and 60 normotensive patients matched for age, sex and body mass index. Left ventricular diastolic function was assessed from the following Doppler-echocardiographic measurements: mitral inflow velocities (E and A wave), E wave deceleration time, isovolumetric relaxation time, left atrial and left ventricular diameters, left ventricular wall thickness and left ventricular heart mass index. Diastolic dysfunction was considered when the E/A ratio was <1. RESULTS: We found significantly higher A wave, lower E/A ratio, longer E deceleration time and a bigger left atrium in obese patients with newly diagnosed arterial hypertension. We did not find significant differences in E wave peak velocities between the two groups. Although there was no difference in left ventricle heart mass or the prevalence of left ventricle hypertrophy, the prevalence of diastolic dysfunction was higher in the group with newly diagnosed arterial hypertension. CONCLUSION: This study suggests that newly diagnosed arterial hypertension significantly contributes to impairment of left ventricular diastolic function in obese patients before development of structural aberrations detectable on echocardiography.