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Parameters of haemostasis, endothelial cell markers and lipid peroxide levels were studied in 64 Type 1 (insulin-dependent) and 94 Type 2 (non-insulin-dependent) diabetic patients according to their urinary albumin excretion rate in comparison with age-matched control subjects. We determined plasma levels of fibrinogen (Clauss' method), coagulation factor VII:activity (clotting assay), factor VII antigen, protein C and S antigen, von Willebrand factor antigen, D-dimer concentration (ELISA), and lipid peroxide levels (thiobarbituric acid) in relation to urinary albumin excretion rate (RIA). Significant positive correlations were found between urinary albumin excretion rate and plasma fibrinogen (p < 0.005, p < 0.02), factor VII activity (p < 0.0002, p < 0.002), factor VII antigen (p < 0.0001, p < 0.001), protein C (p < 0.003, p < 0.05), and lipid peroxides (p < 0.02, p < 0.004) in Type 1 as well as in Type 2 diabetes. Von Willebrand factor (p < 0.001) and protein S (p < 0.0005) correlated with albuminuria only in patients with Type 1 diabetes. Although most of the haemostatic abnormalities are already found in normoalbuminuric patients, the significant positive correlations to urinary albumin excretion indicate that endothelial cell damage and coagulation disorders deteriorate with the progression of diabetic nephropathy.

Abstract. Mycophenolate mofetil (MMF), being effectively used as immunosuppressant in transplant medicine, has recently attracted interest as therapeutic agent for autoimmune diseases (AID). For these patients, no pharmacokinetic (PK) data are available. This study is an investigation of single-dose concentration-time profiles of 1 g off MMF in 16 patients with AID, including 10 patients with ANCA-associated vasculitis and 6 patients with systemic lupus erythematosus, and compares them with profiles of 16 renal transplant recipients (RTX). Mycophenolic acid (MPA) blood levels were measured by both HPLC and EMIT, and MPA-glucuronide was determined by HPLC. In AID, mean MPA concentrations at 12 h were significantly higher compared with RTX (4.1 Ϯ 3.27 versus 1.8 Ϯ 1.15 mg/L; P ϭ 0.018), whereas peak concentrations were lower (P ϭ 0.017). However, mean MPA-AUC at 12 h as well as at 24 h were comparable between both groups. In contrast to RTX, there was an association in AID between MPA trough levels at 12 h and at 24 h with AUC 0-12 (P Ͻ 0.05 and P Ͻ 0.01). MPA trough concentrations at 24 h provided an estimation of AUC 0-24 h in both patient groups (P Ͻ 0.001 and P Ͻ 0.01; AID and RTX, respectively). Compared with RTX, MPA-PK seems to be less affected in AID by renal function. Inter-individual variability of PK parameters was high in both groups. These data indicate that there are differences of MPA-PK between RTX and AID. The use of therapeutic drug monitoring in patients with AID appears to be clinically practicable and may be valuable to optimize individual immunosuppressive therapy.The positive experience with mycophenolate mofetil (MMF) in the field of solid organ transplantation made this drug attractive for the treatment of several autoimmune diseases (1-4). Promising data derived from pilot studies suggests a therapeutic potential of MMF in the treatment of ANCA-associated small vessel vasculitis (ASVV) and systemic lupus erythematosus (SLE) (5,6). In a randomized trial from Hong Kong comparing MMF with cyclophosphamide in patients with diffuse proliferative lupus nephritis, remission and relapse rate were comparable in both groups, whereas MMF was better tolerated (7). Nevertheless, for these patients neither recommendations for optimal dosage of MMF nor data concerning drug exposure of MMF are available.In kidney transplant recipients, several studies have shown a relationship between pharmacokinetic (PK) parameters with efficacy and toxicity. While patients with a low area under the concentration-time curve (AUC) of the active metabolite mycophenolic acid (MPA) appear to be at high risk for experiencing graft rejection (8), a relationship between MPA-PK and adverse effects has been found (9). Higher dosages like 3 g/d were associated with an increased occurrence of adverse effects; therefore, MMF is usually administered at a fixed daily dose of 2 g/d divided into two applications (10). However, the considerable individual variability and changes over time of PK parameters of MPA (10,11) as well as drug ...

ObjectivesThe qualitative results of SARS-CoV-2 specific real-time reverse transcription (RT) PCR are used for initial diagnosis and follow-up of Covid-19 patients and asymptomatic virus carriers. However, clinical decision-making and health management policies often are based additionally on cycle threshold (Ct) values (i.e., quantitative results) to guide patient care, segregation and discharge management of individuals testing positive. Therefore, an analysis of inter-protocol variability is needed to assess the comparability of the quantitative results.MethodsCt values reported in a SARS-CoV-2 virus genome detection external quality assessment challenge were analyzed. Three positive and two negative samples were distributed to participating test laboratories. Qualitative results (positive/negative) and quantitative results (Ct values) were assessed.ResultsA total of 66 laboratories participated, contributing results from 101 distinct test systems and reporting Ct values for a total of 92 different protocols. In all three positive samples, the means of the Ct values for the E-, N-, S-, RdRp-, and ORF1ab-genes varied by less than two cycles. However, 7.7% of reported results deviated by more than ±4.0 (maximum 18.0) cycles from the respective individual means. These larger deviations appear to be systematic errors.ConclusionsIn an attempt to use PCR diagnostics beyond the identification of infected individuals, laboratories are frequently requested to report Ct values along with a qualitative result. This study highlights the limitations of interpreting Ct values from the various SARS-CoV genome detection protocols and suggests that standardization is necessary in the reporting of Ct values with respect to the target gene.