RESUMO
PURPOSE: This study assessed the clinical and immunological outcomes of SARS-CoV-2-infected patients with risk factors for severe disease depending on their immunological status. METHODS: In this retrospective study with single follow-up visit, clinical outcome and humoral immunity was monitored in SARS-CoV-2 infected patients at risk. The results were compared based on the patients' initial immunological status: unvaccinated (UV), patients who did not develop neutralizing antibodies after vaccination (vaccine non-responders, VNR), and patients who expressed neutralizing antibodies after vaccination (vaccine responders, VR). Patients who lacked neutralizing antibodies (VNR and UV) were treated with nMABs. RESULTS: In total, 113 patients at risk of severe COVID-19 consented to participate in the study. VR and UV were not admitted to the hospital. During the observation period, UVs had the highest rate of SARS-CoV-2 re-infections. Three of 41 VNRs (7.3%) were hospitalized due to severe COVID-19, with two of them having undergone iatrogenic B-cell depletion. The humoral immune response after infection was significantly lower in the VNR group than in the VR group in terms of anti-N, anti-receptor-binding domain (RBD), anti-S antibody titers, and anti-S antibody avidity. In a sub-analysis of VNR, B cell-deficient non-responders had significantly lower levels of anti-N antibodies and anti-S avidity after infection than other VNRs. CONCLUSION: VNR, particularly B-cell-depleted VNR, remained at risk of hospitalization due to COVID-19. In the VR group, however, no clinical complications or severe disease were observed, despite not receiving nMAbs. Tailoring the administration of nMABs according to patient vaccination and immunological status may be advisable.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Centros de Atenção Terciária , Humanos , COVID-19/imunologia , COVID-19/prevenção & controle , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , SARS-CoV-2/imunologia , Alemanha , Idoso , Anticorpos Antivirais/sangue , Adulto , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/imunologia , Seguimentos , Estudos Prospectivos , Imunidade Humoral , Vacinação , Resultado do TratamentoRESUMO
It is currently not clear whether the concentration-time curves of the immunosuppressants differ with respect to the CYP3A5, MDR1, or MRP2 genotype in dose-adapted stable kidney transplant patients. Dose/trough concentration ratios were obtained in 134 tacrolimus and 20 sirolimus-treated patients, and plasma concentration-time profiles were obtained from 16 (tacrolimus) and 10 (sirolimus) patients. Genotyping was carried out for CYP3A5 6986A>G; ABCB1 2677G>T/A, 3435C>T and ABCC2 -24C>T; 1249G>A; 3972C>T. Dose/trough concentration ratios were 0.67+/-0.3 and 1.36+/-0.73 x 10(3) l (P<0.00001) for tacrolimus and 0.42+/-0.17 and 0.84+/-0.46 x 10(3) l (P=0.18) for sirolimus in CYP3A5 non-expressors and expressors. The unadjusted tacrolimus area under curve (AUC)(0-12) was 106.8+/-17.5 ng/ml x h compared with 133.3+/-42.2 ng/ml x h (P=0.37) without affecting serum creatinine. Mean unadjusted AUC(0-24) of sirolimus did not differ significantly either. Therefore, CYP3A5 expressor status and not transporter variants is a main determinant of oral clearance, particularly for tacrolimus. Dose adaptation according to trough levels, however, appears to be sufficient to maintain similar concentration-time profiles.
Assuntos
Sistema Enzimático do Citocromo P-450/genética , Transplante de Rim , Sirolimo/farmacocinética , Tacrolimo/farmacocinética , Adulto , Idoso , Área Sob a Curva , Disponibilidade Biológica , Bloqueadores dos Canais de Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/farmacocinética , Bloqueadores dos Canais de Cálcio/uso terapêutico , Citocromo P-450 CYP3A , Sistema Enzimático do Citocromo P-450/metabolismo , Quimioterapia Combinada , Feminino , Variação Genética , Genótipo , Meia-Vida , Humanos , Imunossupressores/metabolismo , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Proteína 2 Associada à Farmacorresistência Múltipla , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/metabolismo , Ácido Micofenólico/farmacocinética , Ácido Micofenólico/uso terapêutico , Prednisolona/metabolismo , Prednisolona/farmacocinética , Prednisolona/uso terapêutico , Sirolimo/metabolismo , Sirolimo/uso terapêutico , Tacrolimo/metabolismo , Tacrolimo/uso terapêuticoRESUMO
INTRODUCTION: Nephrolithiasis in a transplanted kidney is an uncommon complication and may lead to an acute deterioration in renal function. Different techniques for stone treatment are known. In this case, we were successful by using percutaneous nephrolithotomy for the removal of the stone. CASE REPORT: A 65-year-old male patient was found with urinary retention II degrees two months after renal transplantation. A stone in the upper pole calix was found as the probable cause. Percutaneous nephrolithotomy with a 15-Charr Storz mininephroscope was used successfully to disintegrate and remove the stone. CONCLUSION: In comparison to other techniques for the removal of stones, percutaneous nephrolithotomy is a secure method in the treatment of nephrolithiasis in a transplanted kidney. This technique treats the renal stone in one session. We used a 15-Charr Storz mininephroscope which is less invasive than the usually used nephroscopes with a bigger lumen.
Assuntos
Cálculos Renais/cirurgia , Cálices Renais , Transplante de Rim , Nefrostomia Percutânea , Idoso , Humanos , Rim , Cálculos Renais/diagnóstico por imagem , Masculino , Nefrostomia Percutânea/instrumentação , Radiografia , Resultado do TratamentoRESUMO
OBJECTIVE: Therapy of elevated cholesterol serum concentrations is often necessary in patients with kidney transplants. However, the pharmacokinetics of HMG-CoA reductase inhibitors when administered in combination with sirolimus and cyclosporin A (CsA) have not been determined. The aim of this study was to investigate the pharmacokinetics of cerivastatin when administered in combination with sirolimus in patients with kidney transplants, and to review the literature with regard to the differences in pharmacological behavior between sirolimus, CsA and tacrolimus. METHODS: Patients (n = 7) with a stable and functioning kidney transplant and elevated LDL cholesterol serum concentrations were included in the study. After an observation period of 3 months, and whilst receiving sirolimus and CsA, cerivastatin (0.2 mg daily) was administered for a period of 3 months. Pharmacokinetic parameters were calculated on Day 1 and 3 months after initiation of cerivastatin therapy. Routine laboratory parameters and clinical adverse events were monitored throughout the study period. RESULTS: Single-dose cerivastatin AUC was 2 to 3-fold higher in comparison to published values obtained in healthy subjects. The accumulation ratio of cerivastatin (after 3 months/ Day 1) was 1.6. Sirolimus and CsA trough levels, and the sirolimus AUC did not differ after single dose and multiple doses of cerivastatin. CONCLUSIONS: The combination therapy of cerivastatin with sirolimus and CsA leads to a significant increase in cerivastatin exposure. Additional drug monitoring of sirolimus and CsA is not necessary.
Assuntos
Ciclosporina/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Imunossupressores/administração & dosagem , Transplante de Rim , Piridinas/farmacocinética , Sirolimo/administração & dosagem , Adulto , Área Sob a Curva , Ciclosporina/sangue , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Imunossupressores/sangue , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Piridinas/uso terapêutico , Sirolimo/sangue , Sirolimo/uso terapêuticoRESUMO
We report the case of a patient who experienced anuric renal transplant failure for 44 days after living related kidney transplantation. Immunosuppressive and other therapies were carefully adapted to the findings of frequent renal transplant biopsies, which ultimately led to excellent graft function.
Assuntos
Transplante de Rim/fisiologia , Adulto , Idoso , Creatinina/sangue , Pai , Feminino , Humanos , Transplante de Rim/patologia , Doadores Vivos , Masculino , Diálise Peritoneal Ambulatorial Contínua , Fatores de Tempo , Resultado do TratamentoRESUMO
Cytochrome P450 3A4 (CYP3A4) is a major drug-metabolizing enzyme that is widely investigated. So far, no homozygous inactive variant has been described. We report on a 19-year-old kidney transplant patient suffering from Alport syndrome, who experienced unexpected high tacrolimus plasma trough levels during immunosuppressant therapy. Because nonadherence, liver failure, or drug-drug interactions could be excluded, we hypothesized a diminished metabolism of the drug caused by mutations in the main detoxification enzyme, CYP3A4. Exome sequencing revealed a novel single-nucleotide polymorphism (c.802C>T) resulting in a premature stop codon in CYP3A4 exon 5. Accordingly, no CYP3A4 protein could be detected in kidney biopsy tissue, and there was lack of expression in HepG2 cells transiently transfected with the mutated CYP3A4. In addition, the patient harbored inactive CYP3A5*3, resulting in loss of function of the entire CYP3A locus, explaining the deteriorated tacrolimus clearance. This is, to our knowledge, the first case of a complete failure of CYP3A4 in humans.
Assuntos
Citocromo P-450 CYP3A/genética , Imunossupressores/farmacocinética , Transplante de Rim , Tacrolimo/farmacocinética , Citocromo P-450 CYP3A/metabolismo , Genótipo , Células Hep G2 , Humanos , Masculino , Mutação , Polimorfismo de Nucleotídeo Único , Transfecção , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Beyond the medical history, the clinical exam and lab findings, non-invasive ultrasound parameters such as kidney size and Doppler values (e.g. the resistive index) are important tools assisting clinical decision making in the monitoring of renal allografts. The gold standard for the diagnosis of renal allograft dysfunction remains the renal biopsy; while an invasive procedure, the justifiable necessity for this derives from its definitive nature a requirement beyond the synopses of all non-invasive tools. "Acoustic Radiation Force Impulse Imaging"(ARFI)-quantification is a novel ultrasound-based technology measuring tissue elasticity properties. So far experience related to this new method has not been reported in renal transplant follow-up. The purpose of this study was to evaluate changes in ARFI-measurements between clinically stable renal allografts and biopsy-proven transplant dysfunction. METHODS: We employed "Virtual Touch™ tissue quantification" (Siemens Acuson, S2000) for the quantitative measurement of tissue stiffness in the cortex of transplant kidneys. We performed initial baseline and later disease-evaluative ultrasound examinations in 8 renal transplant patients in a prospective study design. Patients were first examined during stable allograft function with a routine post-transplant renal ultrasound protocol. A second follow-up examination was carried out on subsequent presentation with transplant dysfunction prior to allograft biopsy and histological evaluation. All patiens were examined using ARFI-quantification (15 measurements/kidney). Resistive indices (RI) were calculated using pulsed-wave Doppler ultrasound, and transplant kidney size was measured on B-mode ultrasound images. All biopsies were evaluated histologically by a reference nephropathologist unaware of the results of the ultrasound studies. Histopathological diagnoses were based on biopsy results, taking clinical and laboratory findings into account. Finally we calculated the relative changes in ARFI-quantification, resistive indices and the absolute change of kidney size on a percentage basis at these defined assessment times and compared the results with the final pathologic diagnosis. RESULTS: Histological results enumerated five cases of acute T-cell-mediated rejection, one case of calcineurin inhibitor toxicity and two cases of acute tubular necrosis. Calcineurin inhibitor toxicity and acute tubular necrosis were subsumed as "other pathologies". Mean ARFI-values showed an average increase of more than 15% percent in transplants with histologically proven acute rejection whereas no increase was seen in transplants with other pathologies. Mean RI-values showed no increase either in the diagnostic group of acute rejection, nor in the group with other pathologies. Kidney size showed a mean absolute increase of 0.5 centimetres in allografts with acute rejection, whereas a mean decrease of 0.17 centimetres was seen in the group with other pathologies. CONCLUSION: As shown before in other studies, RI values and kidney size are of doubtful utility in the evaluation of kidney allograft dysfunction. ARFI-based elasticity measurement shows promise as a complementary non-invasive parameter in follow-on diagnosis of renal allograft rejection.
Assuntos
Técnicas de Imagem por Elasticidade , Transplante de Rim , Rim/diagnóstico por imagem , Disfunção Primária do Enxerto/diagnóstico por imagem , Adolescente , Adulto , Idoso , Biópsia , Elasticidade , Feminino , Seguimentos , Rejeição de Enxerto/diagnóstico por imagem , Rejeição de Enxerto/patologia , Rejeição de Enxerto/fisiopatologia , Humanos , Imunidade Celular , Imunossupressores/efeitos adversos , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/diagnóstico por imagem , Nefropatias/patologia , Necrose Tubular Aguda/diagnóstico por imagem , Necrose Tubular Aguda/patologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/patologia , Disfunção Primária do Enxerto/patologia , Disfunção Primária do Enxerto/fisiopatologia , Estudos Prospectivos , Subpopulações de Linfócitos T/imunologia , Ultrassonografia Doppler em CoresRESUMO
The pharmacokinetics of mycophenolic acid (MPA) was studied in 23 kidney transplant recipients with stable, long-term graft function who were receiving mycophenolate mofetil (MMF) in combination with either tacrolimus or sirolimus therapy. After 500 mg MMF, the mean MPA area under the curve (AUC) was significantly lower in sirolimus-treated patients than in those treated with tacrolimus (35.4 +/- 32.3 vs. 77.1 +/- 67.5 mg/l). MPA peak plasma concentration (C(max)) and MPA trough plasma concentration (C(min)) were significantly higher in patients who received tacrolimus than in those who received sirolimus. There were no significant differences between the two groups with respect to MPA time to maximum concentration (T(max)), MPA-glucuronide (MPAG) AUC, MPAG C(max), MPAG C(min), MPAG T(max), MPA-acyl-glucuronide (AcMPAG) AUC, AcMPAG C(max), AcMPAG C(min), and AcMPAG T(max). In conclusion, MPA exposure is greater in tacrolimus-treated patients than in those treated with sirolimus during maintenance immunosuppression after kidney transplant. It is suggested that the influence of tacrolimus on the pharmacokinetics of MPA reflects an interaction of the two agents at the level of their intestinal absorption.
Assuntos
Imunossupressores/farmacocinética , Transplante de Rim , Ácido Micofenólico/análogos & derivados , Sirolimo/farmacologia , Tacrolimo/farmacologia , Adulto , Idoso , Área Sob a Curva , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/farmacocinética , Ácido Micofenólico/uso terapêutico , Sirolimo/uso terapêutico , Tacrolimo/uso terapêuticoRESUMO
Kidney transplantation is the best option for all patients with terminal renal failure. Kidney transplantation is not only associated with an improved quality of life in comparison to all other renal replacement therapies, this method also offers a significantly extended lifespan. Therefore, the option for transplantation has to be verified for every patient with renal failure. Graft and patient survival is best when transplantation is carried out just before starting dialysis treatment. Realistically, only living donor transplantation offers the option of sparing the recipient a long waiting period on dialysis. Although transplantation from living donors is superior to cadaveric kidney transplantation, a small risk remains for the donor. Kidney transplantation and the immunosuppressive therapy are associated with an increased risk for certain types of infection, an increased tumour risk and an increased risk for cardiovascular complications. To address these problems, specific recommendations for patient surveillance have been provided by different transplantation societies.
Assuntos
Falência Renal Crônica/cirurgia , Transplante de Rim , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Testes de Função Renal , Doadores Vivos , Infecções Oportunistas/etiologia , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Terapia de Substituição Renal , Obtenção de Tecidos e ÓrgãosRESUMO
Despite the lack of nephrotoxicity, adverse effects of the new antiproliferative immunosuppressant everolimus have been reported. By varying time point and dose of everolimus treatment as well as the degree of glomerular injury, the specific conditions and potential mechanisms leading to adverse actions in the anti-Thy1 model have been determined. Only the combination of early and high-dose everolimus treatment (1-3 mg/kg bw) with a severe glomerular lesion ('full-dose' anti-Thy1 model) caused adverse effects with a high mortality rate, progressive apoptosis, crescent formation and glomerulosclerosis. In contrast, either later start or low-dose (0.3 mg/kg bw) therapy or treatment of a less severe lesion ('reduced dose' anti-Thy1 model) appeared to be relatively safe for the glomerular architecture. The adverse effects of everolimus were linked to its marked inhibition of endothelial cell, but not necessarily mesangial cell proliferation. In addition, everolimus markedly inhibited the angiogenic cytokine vascular endothelial growth factor in nephritic glomeruli in vivo. These experimental results suggest special caution regarding the use of everolimus in all situations of severe glomerular cell injury requiring extensive capillary repair, where at least adaption to a low dose needs to be considered.
Assuntos
Glomerulonefrite/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/induzido quimicamente , Imunossupressores/toxicidade , Glomérulos Renais/efeitos dos fármacos , Sirolimo/análogos & derivados , Aneurisma/induzido quimicamente , Aneurisma/patologia , Animais , Apoptose/efeitos dos fármacos , Capilares/patologia , Divisão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Everolimo , Glomerulonefrite/patologia , Glomerulosclerose Segmentar e Focal/patologia , Imunossupressores/farmacologia , Isoanticorpos , Glomérulos Renais/irrigação sanguínea , Glomérulos Renais/patologia , Transplante de Rim , Masculino , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/patologia , Ratos , Ratos Sprague-Dawley , Sirolimo/farmacologia , Sirolimo/toxicidade , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The risk to acquire opportunistic infections is clearly increased in patients receiving immunosuppressive therapeutic regimens following organ transplantation or during treatment of autoimmune disorders. The modulation of the immune system can alter the clinical symptoms and the course of infectious diseases, including diagnostic signs such as fever or pathological changes in radiographs or blood cell counts. However, a rapid diagnosis and start of treatment is essential in these patients. Thus, a correct interpretation of even mild symptoms in the initial phase of an infectious disease is essential for establishing a diagnosis and initiation of a therapy at an early stage. Therefore, it is necessary that the clinical hallmarks of these diseases are widely known and that physicians treating these patients cooperate closely with transplant centers.
Assuntos
Tolerância Imunológica/imunologia , Terapia de Imunossupressão/efeitos adversos , Infecções Oportunistas/imunologia , Imunologia de Transplantes/imunologia , Biópsia , Diagnóstico Diferencial , Febre de Causa Desconhecida/etiologia , Febre de Causa Desconhecida/imunologia , Humanos , Micoses/imunologia , Micoses/patologia , Infecções Oportunistas/patologia , Prognóstico , Viroses/imunologia , Viroses/patologiaRESUMO
Mutations in the COL4A5 gene encoding the alpha 5 chain of type IV collagen have been found in linkage with X-chromosomal Alport syndrome (AS). To identify COL4A5 mutations in patients from Germany with clinically defined AS, DNA from 20 unrelated patients was analyzed by conventional Southern blotting. By using full length alpha 5(IV) cDNA probes, large COL4A5 deletions could be detected in two patients. In one case, a 34 kb deletion affecting the 14 most 3' exons of the gene was observed. The second patient harbored a complete COL4A5 deletion. In both cases, functional alpha 5(IV) mRNA was unlikely to be present. Clinically, both patients developed end-stage renal failure before age 30. Furthermore, they had characteristic retinal flecks, and sensorineural hearing loss with typical changes on the audiogram. The patient with the complete deletion of COL4A5 lost the renal allograft due to an anti-GBM mediated glomerulonephritis.
Assuntos
Colágeno/genética , Deleção de Genes , Nefrite Hereditária/genética , Adolescente , Adulto , Sequência de Bases , DNA/genética , Análise Mutacional de DNA , Sondas de DNA , Feminino , Ligação Genética , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem , Cromossomo XRESUMO
BACKGROUND: Mycophenolate mofetil (MMF) is used for immunosuppression after renal transplantation because it reduces lymphocyte proliferation by inhibiting inosine monophosphate dehydrogenase (IMPDH) in lymphocytes and GTP biosynthesis. In the present study we asked if therapeutic concentrations of MMF might interfere with mesangial cell (MC) proliferation which is involved in inflammatory proliferative glomerular diseases. METHODS: Rat and human MCs were growth-arrested by withdrawal of fetal calf serum (FCS) and stimulated by addition of FCS, platelet-derived growth factor (PDGF) or lysophosphatidic acid (LPA). Different concentrations of MMF (0.019-10 microM) were added concomitantly in the presence or absence of guanosine. MC proliferation was determined by [3H]thymidine incorporation. Cell viability was assessed by trypan blue exclusion. Apoptotic nuclei were stained using the Hoechst dye H33258. Cytosolic free Ca2+ concentrations were determined with the fluorescent calcium chelator fura-2-AM. RESULTS: MMF inhibited mitogen-induced rat MC proliferation with an IC50 of 0.45 +/- 0.13 microM. Human MCs proved to be even more sensitive (IC50 0.19 +/- 0.06 microM). Inhibition of MC proliferation was reversible and not accompanied by cellular necrosis or apoptosis. Addition of guanosine prevented the antiproliferative effect of MMF, indicating that inhibition of IMPDH is responsible for decreased MC proliferation. Early signalling events of GTP-binding-protein-coupled receptors, such as changes in intracellular Ca2+ levels were not affected by MMF. CONCLUSIONS: The results show that MMF has a concentration-dependent antiproliferative effect on cultured MCs in the therapeutic range, which might be a rationale for the use of this drug in the treatment of mesangial proliferative glomerulonephritis.
Assuntos
Mesângio Glomerular/efeitos dos fármacos , Guanosina/metabolismo , Imunossupressores/farmacologia , Ácido Micofenólico/análogos & derivados , Animais , Apoptose , Cálcio/metabolismo , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Meios de Cultura Livres de Soro , Citosol/metabolismo , Mesângio Glomerular/citologia , Mesângio Glomerular/metabolismo , Guanosina/farmacologia , Humanos , IMP Desidrogenase/antagonistas & inibidores , Artéria Ilíaca , Lisofosfolipídeos/farmacologia , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Ácido Micofenólico/farmacologia , Necrose , Fator de Crescimento Derivado de Plaquetas/farmacologia , RatosRESUMO
BACKGROUND: Hyperlipidaemia is an important risk factor for cardiovascular disease in renal transplant recipients. The aim of this study was to test the efficacy and possible drug-drug interactions of the new HMG-CoA reductase inhibitors (statins) atorvastatin and cerivastatin in cyclosporin A (CsA)-treated renal transplant patients. Subjects and methods. Thirty patients with stable graft function and LDL cholesterol of 130 mg/dl were randomly assigned to active treatment groups (10 mg atorvastatin or 0.2 mg cerivastatin), or a control group. CsA blood trough levels were controlled on a weekly basis and adapted if they changed more than 25% from baseline values (100-150 ng/ml). Lipid levels and routine laboratory parameters before and after a treatment period of 3 months were compared. RESULTS: In the group treated with cerivastatin no significant changes in CsA blood trough levels occurred (CsA 116+/-21 ng/ml vs 110+/-20 ng/ml). In contrast, in the group treated with atorvastatin, four of 10 patients had a rise in CsA blood trough levels of more than 25% within 7-14 days of starting therapy. In the remaining patients no significant changes in CsA drug levels occurred. After therapy with atorvastatin or cerivastatin, total cholesterol, LDL cholesterol, and triglycerides were significantly lower compared with baseline conditions. No changes of CsA or lipoprotein levels were present in the control group. CONCLUSION: In our study population both statins were very effective in lowering elevated LDL cholesterol levels. Cerivastatin did not influence CsA blood trough levels, whereas atorvastatin increased CsA levels in four of 10 patients. Further research in a larger study is necessary in order to confirm these results and to investigate the possible reasons for this drug interaction.