Late onset tacrolimus-induced life-threatening polyneuropathy in a kidney transplant recipient patient

A 59-year-old kidney recipient was diagnosed with a late onset of severe chronic inflammatory demyelinating polyradiculoneuropathy and almost fully recovered after stopping tacrolimus and one course of intravenous immunoglobulin treatment. Unique features of this patient are the unusually long time lapse between initiation of tacrolimus and the adverse effect (10 years), a strong causality link and several arguments pointing toward an inflammatory etiology. When facing new neurological signs and symptoms in graft recipients, it is important to bear in mind the possibility of a drug-induced adverse event. Discontinuation of the suspect drug and immunomodulation are useful treatment options

Disposition of valganciclovir during continuous renal replacement therapy in two lung transplant recipients

Objectives To determine whether valganciclovir 450 mg every 48 h for cytomegalovirus (CMV) prophylaxis provides appropriate ganciclovir exposure in solid organ transplant recipients during continuous renal replacement therapy (CRRT). Patients and methods Ganciclovir pharmacokinetics was intensively studied in two lung transplant recipients under valganciclovir 450 mg every 48 h over one dosing interval. In vitro experiments using blank whole blood spiked with ganciclovir further investigated exchanges between plasma and erythrocytes. Results Ganciclovir disposition was characterized by apparent total body clearance of 3.3 and 5.8 L/h, terminal half-life of 16.9 and 14.1 h, and apparent volume of distribution of 60.3 and 104.9 L in Patients 1 and 2, respectively. The observed sieving coefficient was 1.05 and 0.96, and the haemofiltration clearance was 3.3 and 3.1 L/h. In vitro experiments confirmed rapid efflux of ganciclovir from red blood cells into plasma, increasing the apparent efficacy of haemofiltration. Conclusions A valganciclovir dosage of 450 mg every 48 h appears adequate for patients under CRRT requiring prophylaxis for CMV infection, providing concentration levels in the range reported for 900 mg once daily dosing outside renal failur

Is the left-right scale a valid measure of ideology? Individual-level variation in associations with "left" and "right" and left-right self-placement

In order to measure ideology, political scientists heavily rely on the so-called left-right scale. Left and right are, however, abstract political concepts and may trigger different associations among respondents. If these associations vary systematically with other variables this may induce bias in the empirical study of ideology. We illustrate this problem using a unique survey that asked respondents open-ended questions regarding the meanings they attribute to the concepts "left" and "right". We assess and categorize this textual data using topic modeling techniques. Our analysis shows that variation in respondents’ associations is systematically related to their self-placement on the left-right scale and also to variables such as education and respondents’ cultural background (East vs. West Germany). Our findings indicate that the interpersonal comparability of the left-right scale across individuals is impaired. More generally, our study suggests that we need more research on how respondents interpret various abstract concepts that we regularly use in survey questions

Absence of mTOR Inhibitor Effect on Hepatic Cyst Growth: A Case Report of a Kidney Transplant Recipient with Autosomal Dominant Polycystic Kidney Disease.

Some experimental studies have suggested a beneficial effect of the mammalian target of rapamycin (mTOR) inhibitor use on hepatic and renal cyst growth in patients with autosomal dominant polycystic kidney disease (ADPKD). However, the results of clinical studies are conflicting and the role of mTOR inhibitors is still uncertain. We report the case of a patient with ADPKD who underwent deceased kidney transplantation because of an end-stage renal disease. The evolution was uneventful with an excellent graft function under cyclosporine (CsA) monotherapy. Some years later, the patient developed a symptomatic hepatomegaly due to growth of cysts. CsA was replaced by sirolimus, an mTOR inhibitor, in order to reduce or control the increase in the cyst and liver volume. Despite the switch, the hepatic volume increased by 25% in two years. Finally sirolimus was stopped because of the lack of effect on hepatic cyst growth and the presence of sirolimus side effects. The interest of our case resides in the followup by MRI imaging during the mTOR inhibitor treatment and 15 months after the restart of the initial immunosuppressive therapy. This observation indicates that mTOR inhibitors did not have significant effect on cyst-associated hepatic growth in our patient, which is consistent with some results of recent large clinical studies

Role du pathologiste dans la pathologie renale. [The crucial role of the pathologist in renal disease]

The analysis of biopsy specimens by a pathologist allows a precise diagnosis in the majority of cases. This diagnosis needs to be correlated with the relevant clinical information during a multidisciplinary board in order to yield an optimal clinicopathological diagnosis. The staging and the activity of the histological lesions described by the pathologist will significantly contribute to the modality of treatment and will help to estimate the course of the disease and eventually prepare the patient for dialysis and/or transplantation

Dysfonction d'une bioprothese mitrale, hemolyse et insuffisance renale aigue. [Malfunction of a mitral bioprosthesis, hemolysis and acute renal insufficiency]

Intravascular hemolysis is a rare complication following valvular replacement, particularly with bioprostheses. It is generally secondary to prosthetic malfunction and is the cause of anemia. We report a rare case of acute renal insufficiency and severe hemolysis caused by malfunction of a bioprosthesis in the mitral position

[IgA nephropathy: what you have need to know in 2005]

Although considered as a benign glomerulopathy, IgA nephropathy (IgAN) is now a well-known cause of end-stage renal disease (ESRD). Fifty percent of people suffering from IgAN developp renal insufficiency and 20 to 30% may reach ESRD after 20 to 25 years of evolution. ACEI is indicated to obtain a thigh control of blood pressure and to reduce proteinuria. Corticosteroids alone or in association with immunosuppressants are indicated for agressive, proliferative form of the disease or when there is an unfavorable outcome despite symptomatic treatment

Incidence of Infectious Complications in Kidney Transplant Recipients Receiving Induction with Basiliximab, Thymoglobulin or Both

Background: The possible additional risk of infection in patients receiving induction with both basiliximab (Ba) and thymoglobulin (Th) is unclear. We assessed the 1-year incidence of infectious complications in 3 groups of kidney transplant recipients according to the type of induction therapy received.Methods: We compared the incidence of infection at 1 year in 3 groups of patients at our institution: fi rst transplant recipients received Ba 20mg at days 0 and 4 (Group Ba); in case of retransplantation or if PRA was >20% patients received Th 1 mg/kg for 3-5 days (Group Th); in case of delayed graft function (DGF), Ba was discontinued and Th was initiated (Group Ba+Th) or prolonged in Group Th. Kaplan-Meier curves were used to calculate the incidence of infection. A Cox analysis was used to identify risk factors for the development of infection.Results: Over 5 years, 170 consecutive kidney transplant recipients were performed:n=113 in Group Ba, n=39 in Group Th and n=18 in Group Ba+Th. As expected, more patients in Group Th received a second transplant (p<0.001). No differences in CMV serostatus were observed between groups (p=0.9). Incidences of CMV infection, CMV disease, BK viremia, BK nephropathy and urinary tract infection (UTI) is shown in Table 1. Table 1 Group Ba (n=113) Group Th (n=38) Group Ba+Th (n=18) CMV infection 31 (27%) 20 (51%) 8 (44%) CMV disease 7 (6%) 4 (10%) 0 BK viremia 11 (8%) 5 (13%) 4 (22%) BK nephropathy 5 (4%) 1 (2%) 2 (11%) UTI 43 (38%) 23 (59%) 6 (33%) Incidences of infection according to type of induction In a multivariate model taking into account CMV serostatus, age, pretransplant dialysis, type of organ transplanted, number of transplants and type of induction, Group Ba carried a lower risk of CMV infection (OR 0.45, p=0.006), and UTI (OR=0.6, p=0.05), but there were no differences in CMV disease (p=0.38). There was a trend towards higher incidence of BK viremia, but not nephropathy in Group Ba+Th (OR 2.2, p=0.23). There were no signifi cant differences in kidney function or graft loss at 1 year between groups.Conclusion: By multivariate analysis, we observed a lower risk of CMV infection andUTI in patients receiving Ba. The group Ba+Th had a similar risk for infection than the group receiving Th alone. Larger studies are needed to clarify whether combining Ba+Th in the setting of DGF may increase the risk of infectious complications, in particular BK infection

Aspects cliniques et génétiques du syndrome d’Alport

Microscopic haematuria of glomerular origin, without known aetiology, should raise the suspicion of Alport Syndrome IASI in children as well as in adults. The genetic mutations causing AS lie in the genes encoding for the alpha3, alpha4 and alpha5 chains of the collagen type IV, the main constituent of glomerular basement membranes (GBM). The various mutations and modes of transmission of the disease account for the heterogeneous clinical presentations. No specific treatment of AS is currently available. However, a better understanding of the GBM's ultrastructure, in particular of type IV collagen, will hopefully enable the identification of novel therapeutic targets