Urinary myeloid IgA Fc alpha receptor (CD89) and transglutaminase-2 as new biomarkers for active IgA nephropathy and henoch-Schönlein purpura nephritis.

BACKGROUND: IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) are glomerular diseases that share a common and central pathogenic mechanism. The formation of immune complexes containing IgA1, myeloid IgA Fc alpha receptor (FcαRI/CD89) and transglutaminase-2 (TG2) is observed in both conditions. Therefore, urinary CD89 and TG2 could be potential biomarkers to identify active IgAN/HSPN. METHODS: In this multicenter study, 160 patients with IgAN or HSPN were enrolled. Urinary concentrations of CD89 and TG2, as well as some other biochemical parameters, were measured. RESULTS: Urinary CD89 and TG2 were lower in patients with active IgAN/HSPN compared to IgAN/HSPN patients in complete remission (P < 0.001). The CD89xTG2 formula had a high ability to discriminate active from inactive IgAN/HSPN in both situations: CD89xTG2/proteinuria ratio (AUC: 0.84, P < 0.001, sensitivity: 76%, specificity: 74%) and CD89xTG2/urinary creatinine ratio (AUC: 0.82, P < 0.001, sensitivity: 75%, specificity: 74%). Significant correlations between urinary CD89 and TG2 (r = 0.711, P < 0.001), proteinuria and urinary CD89 (r = - 0.585, P < 0.001), and proteinuria and urinary TG2 (r = - 0.620, P < 0.001) were observed. CONCLUSIONS: Determination of CD89 and TG2 in urine samples can be useful to identify patients with active IgAN/HSPN.

Severe cytomegalovirus infection in a second kidney transplant recipient treated with ganciclovir, leflunomide, and immunoglobulins, with complications including seizures, acute HCV infection, drug-induced pancytopenia, diabetes, cholangitis, and multi-organ failure with fatal outcome: a case report.

BACKGROUND: Cytomegaly remains one of the most common infectious complications in organ transplant recipients, and the course of the infection may have a negative effect on survival of the transplant and recipient. CASE REPORT: We describe the case of a 32-year-old female patient who received a second kidney transplant from a cadaveric donor in July 2012, treated successfully with ganciclovir for primary CMV infection in August 2012 and then re-treated from November due to re-infection. The viral load at the start of re-treatment was 6 million copies. In view of ganciclovir treatment failure, Sando immunoglobulins were administered. Subsequently, when CMV viral load increased to 18 million copies, a decision was made to use combination treatment with leflunomide and ganciclovir. Immunosuppressive treatment was also modified by administering everolimus in view of its potential antiviral activity. Seizures, pancytopenia, diabetes, diarrhoea, and (probably) drug-induced liver damage and cholangitis were observed in the course of treatment. At 3 months of hospitalization, the patient was discharged home with viral load of 8000 copies. As treatment continuation, she received valganciclovir at the full therapeutic dose in view of very good kidney function (creatinine 0.7 mg/dl). The patient was re-hospitalized after 10 days due to fever and cough. Due to abnormal liver function test results and negative serum markers of viral hepatitis, HCV RNA was tested, with a positive result (above 10^8 copies). Subsequently, decline in clinical status, overhydration, increasing creatinine levels, hepatic failure signs, and renewed CMV DNA increase to 520 000 copies were observed. Despite intensive treatment, the patient died of multi-organ failure. CONCLUSIONS: The case described illustrates the difficulties in the treatment of CMV infection and its possible dramatic complications.

Atypical calcineurin inhibitor-induced haemolytic uremic syndrome after liver transplantation.

BACKGROUND: A case of calcineurin inhibitor (CNI)--induced haemolytic uremic syndrome (HUS) after liver transplantation leading to irreversible renal failure is described. CASE REPORT: We present case history of 25-years old male after liver transplantation due to cryptogenic cirrhosis with prolonged worsening graft function, who developed HUS. Unsatisfactory graft function was the reason of performing numerous graft biopsies. Features of acute and chronic rejection (CR) of liver were histopathologically confirmed. Vanishing bile duct syndrome as manifestation of CR was stated and immunosuppressive regimen was intensified (tacrolimus placed cyclosporin). High blood levels of tacrolimus were maintained (approximately 20-22 ng/ml) on dose 3 mg twice a day. No clinical effect was observed. Renal failure was improving (serum creatinine was 3.3 mg/dl and eGFR was 24 ml/min/1.73 m(2)). After four months of maintaining high dose of tacrolimus patient was referred to our center in order to estimate indications for liver retransplantation. On admission severe haemolytic anaemia, thrombocytopenia and acute renal failure were detected. Atypical HUS probably related to CNI was diagnosed. Tacrolimus administration was discontinued. Blood and plasma transfusion as well as plasmapheresis were implemented. Haemolysis was limited, but renal function was not improved. Renal biopsy revealed features of irreversible nephropathy in course of thrombotic microangiopathy. Despite previously maintaining high dose of CNI, there were no signs of CNI nephrotoxicity. Patient required haemodialysis. Due to necessity of haemodialysis and worsening function of liver, patient was accepted to liver and kidney transplantation. CONCLUSIONS: High CNI blood concentration in patient after liver transplantation can be atypical cause of HUS and leads to irreversible renal failure.

Catastrophic antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disease with clinical manifestations of arterial and venous thrombosis, concomitant fetal loss and the presence of antiphospholipid antibodies (APLA). This report focuses on the challenges of optimal treatment involving plasma exchange and intravenous human immunoglobulin infusions that is administered in patients with catastrophic APS (CAPS). CAPS is a rare variant of APS defined as acute failure of at least three tissues, organs or systems caused predominantly by small vessel thrombosis confirmed by histopathologic evidence. CAPS develops rapidly and leads to death in 50% of cases. We present the case of a 39-year-old male patient with APS with worsening renal function. Positive lupus anticoagulant, markedly high concentrations of anticardiolipin and anti-beta 2-glikoprotein I antibodies have been observed. According to the criteria introduced by Asherson, a catastrophic form of APS was diagnosed and the patient had been treated with low-molecular-weight heparin, glucocorticosteroids, and plasmapheresis. In order to maintain clinical improvement, the patient was given human immunoglobulins i.v. (1 g/kg body weight). After the procedure, gradual clinical improvement was observed and renal function remained stable (serum creatinine level of 1.5 mg/dl).