Molecular evidence of nosocomial Pneumocystis jirovecii transmission among 16 patients after kidney transplantation.

In recent years, clusters of Pneumocystis jirovecii (formerly Pneumocystis carinii) pneumonia (PCP) among immunocompromised individuals have been reported. Mostly, the source of infections was suspected to be within the clinical settings when transplant recipients and PCP patients shared hospital facilities. We report on a cluster of 16 renal transplant recipients positive for P. jirovecii. None of them received anti-Pneumocystis prophylaxis prior to P. jirovecii detection. Epidemiological studies revealed that 15 of them had received kidney transplants at a German university hospital and attended the same inpatient and outpatient clinic from January through September 2006. Multilocus sequence typing (MLST) was performed on the following genes: ITS1, beta-tub, 26S, and mt26S. P. jirovecii DNA was available from 14 patients and showed identical MLST types among these renal transplant recipients. Surprisingly, one patient who was treated at a different nephrological center and reported no personal contact with patients from the renal transplantation cluster harbored an identical P. jirovecii MLST type. Three HIV-positive patients and one bone-marrow-transplanted hematologic malignancy patient--treated at different medical centers--were used as controls, and different MLST types were revealed. Interestingly, in three of the four previously described regions, new alleles were detected, and one new polymorphism was observed in the mt26S region. The epidemiological data and the genotyping results strongly suggest a nosocomial patient-to-patient transmission of P. jirovecii as the predominant transmission route. Therefore, strict segregation and isolation of P. jirovecii-positive/suspected patients in clinical settings seems warranted.

Malacoplakia in a renal transplant recipient.

Malacoplakia is a rare, inflammatory condition characterized histologically by distinct histiocytes with pathognomonic inclusion calcospherules called Michaelis-Gutmann bodies. It most often affects the urinary tract of immunocompromised patients. We describe a case of renal allograft parenchymal malacoplakia in a transplant recipient. Moreover, we report the imaging and histological findings and review the literature of this rare disorder.

State of the art of low-density lipoprotein apheresis in the year 2003.

Low-density lipoprotein (LDL) apheresis is a last-resort treatment for hypercholesterolemic patients resistant to conservative lipid-lowering therapy. In the extracorporeal circuit, LDL, Lp(a) and coagulation factors are selectively eliminated, while the beneficial proteins like high-density lipoprotein, albumin and immunoglobulins are returned to the patient. Clinical effects of LDL apheresis comprise improvement of symptoms like angina and exercise tolerance, reduction of clinical coronary events like unstable angina, need for angioplasty or bypass operation, myocardial infarction and ultimately coronary mortality. The reduction of atherogenic lipoproteins and of coagulation factors by LDL apheresis (LA) positively influences hemorheology, endothelial function and coronary reserve. In the controlled LAARS, LA significantly improved the electrocardiographic signs of myocardial ischemia in the treadmill test. In angiographically controlled trials such as LARS and L-CAPS, a reduction of progression of coronary lesions was observed; in favorable cases, regression of the stenoses could be documented. In addition, in the LDL apheresis coronary morphology trial, LA decreased the coronary plaque area. The Hokuriku trial documented a 72% decrease of coronary events (MACE) in the LA group vs. controls treated only by statins. In longitudinal studies, the incidence of MACE after regular LA decreased compared with the preapheresis period in the same patients. Apart from coronary heart disease, recent studies indicate a positive effect of LA also on carotid artery stenoses and peripheral vascular disease. Prospective randomized studies showed the beneficial effects of cascade filtration on age-related macular degeneration and of heparin-induced LDL precipitation apheresis on acute inner ear deafness.

Efficacy and safety of DALI-LDL-apheresis in two patients treated with the angiotensin II-receptor 1 antagonist losartan.

Direct adsorption of lipids (DALI) is the first low-density lipoprotein (LDL)-apheresis technique capable of adsorbing LDL and lipoprotein (a) directly from whole blood. The adsorber consists of negatively charged polyacrylate ligands linked to a Eupergit matrix. Negatively charged ligands give rise to activation of bradykinin, which is rapidly degraded by the angiotensin converting enzyme (ACE). Thus, angiotensin converting enzyme inhibitors are contraindicated in DALI-LDL-apheresis. This is the first paper to describe the efficacy and safety of DALI-LDL-apheresis in patients treated with 50 mg of the angiotensin II-receptor 1 antagonist (ARA) losartan. Two hypercholesterolemic patients were treated for 79 patient months with weekly or biweekly DALI sessions (N = 221 sessions). Approximately 1.4 patient blood volumes were treated per session. Acute reductions of LDL-cholesterol (63%) and lipoprotein (a) (62%) exceeded 60% and laboratory safety parameters remained in the apheresis typical range. Mean bradykinin plasma levels peaked in the efferent line post-adsorber at 1000 mL of treated blood volume; 467 fmol/mL (N = 6 sessions) in the ARA-treated patients and 671 fmol/mL (N = 9 sessions) in a control group of three DALI patients without ARA medication (P = 0.69, n.s.). Clinically, the DALI sessions for the ARA-treated patients were completely uneventful and blood pressure was not significantly different in the two groups. In summary, according to this retrospective pilot study, DALI-LDL-apheresis was shown for the first time to be safe and effective in patients on ARA medication.

Effect of Apheresis for ABO and HLA Desensitization on Anti-Measles Antibody Titers in Renal Transplantation.

Desensitization strategies for ABO-incompatible renal transplants with plasma exchange (PE) or specific immunoadsorption (IA) decrease immunoglobulin levels. After recent measles outbreak and decreasing vaccination rates, we studied the impact of apheresis on anti-measles antibodies. Anti-measles antibodies were measured before desensitization, before transplantation and during followup in 12 patients with ABO incompatibility (2x PE only, 8x IA only, and 2x IA and PE) and 3 patients with donor-specific HLA antibodies (all PE). Patients received rituximab, IVIG, and standard immunosuppressive therapy. All patients had detectable anti-measles antibodies before desensitization (mean 3238 mU/l, range 560-8100). After 3-6 PE sessions, titers decreased significantly to 1710 mU/l (P < 0.05), in one patient to nondetectable values, while IA only maintained protective titers. After a median followup of 64 days, anti-measles antibodies returned to baseline in all patients. Immunity against measles was temporarily reduced by apheresis but remained detectable in most patients at time of transplantation. Desensitization maintains long-term protective immunity against measles.