Renal involvement in mushroom poisoning: The case of Orellanus syndrome

none8Although mushroom poisoning is a rare cause of acute renal injury, in some cases it may lead to the development of a severe and irreversible renal failure. Orellanus syndrome is the most important example of organic renal damage related to mushroom consumption. It is caused by the ingestion of orellanine, the main toxin of different types of Cortinarius mushrooms (Cortinarius speciosissimus, C. orellanus, C. orellanoides, etc.), and it is characterized by progressive clinical phases with a predominant kidney involvement, finally requiring renal replacement therapy in about 10% of cases. Renal damage is often late and associated with a histological picture of interstitial nephritis. Diagnosis is essentially clinical and no specific therapy has been shown to be effective in preventing and treating renal damage. Here, we describe the case of a patient with mixed wild mushroom poisoning, presenting the typical clinical signs and course of the Orellanus syndrome. This case offers us the opportunity to review the main clinical features of this severe and little-known intoxication.openEsposito, P; La Porta, E; Calatroni, M; Bianzina, S; Libetta, C; Gregorini, M; Rampino, T; Dal Canton, AEsposito, P; La Porta, E; Calatroni, M; Bianzina, S; Libetta, Carmelo; Gregorini, Marilena; Rampino, Teresa; DAL CANTON, Antoni

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

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Mechanisms underlying sCD40 production in hemodialysis patients.

CD40 and its ligand (CD40L) regulate several cellular functions, including T and B-cell activation. The soluble form of CD40 (sCD40) antagonizes CD40/CD40L interaction. Patients undergoing hemodialysis (HD) present elevated sCD40 serum levels, which underlying molecular mechanisms are unknown. We studied sCD40 serum and urinary levels, CD40 membrane and gene expression and membrane shedding in HD, uremic not-HD patients (UR) and healthy subjects (N). We found that in HD sCD40 serum levels were higher than UR and N, being significantly elevated in anuric patients, and that sCD40 correlated to renal function in UR subjects, who presented also a reduced sCD40 urinary excretion rate. HD and UR presented reduced CD40 membrane and gene expression. The concentration of TNF-α converting enzyme (TACE), responsible for CD40 cleavage was not different between HD and N. Therefore the reduced renal clearance is the main cause of elevated sCD40 levels in HD. This finding could have relevant clinical implications

CD40/SCD40 imbalance in hemodialysis patients.

We read with great interest the paper by Pawlak et al. [1] recently published in Clinical Biochemistry. The authors demonstrated that the serum levels of soluble CD40 (sCD40), a natural antagonist of CD40/CD40L system, are high in patients on hemodialysis (HD) and are strictly related to renal residual function (RRF). Elevated sCD40 serum levels have been reported in the clinical setting of chronic kidney disease, peritoneal dialysis, and HD and have been related to the deficient response to hepatitis B vaccination found in those patients [2] and [3]. In addition, it has been recently described that, in HD patients, the reduction of sCD40 levels by a treatment with a high permeability dialytic membrane is associated to a significant increase of anti-HBs antibody titer [4]. Therefore, a role for sCD40 in uremic immunodeficiency has been hypothesized and it is currently under investigation. In order to evaluate the CD40/sCD40 balance in HD patients, we performed an observational study comparing CD40 B-cell membrane expression and sCD40 serum levels among HD patients, uremic patients not on HD (UR) and, also, healthy subjects (HS). Fourteen stable patients (mean ± SD; age, 65.1 ± 13.6 years) on regular thrice-weekly bicarbonate HD for at least 6 months were enrolled. Patients affected by conditions influencing the immune response, such as acute infections, active immunological diseases, immunosuppressive therapy, previous transplantation, or history of malignancies, were excluded from the study. Control samples were taken from 7 UR (age, 68.8 ± 8.5 years) and 8 HS (age, 47.9 ± 11.5 years). Blood samples were collected before HD treatment. sCD40 serum levels were measured by an enzyme-linked immunosorbent assay (Bender MedSystems). CD40+ B lymphocytes were defined by CD20 and CD40 cell membrane co-expression, analyzed by flow cytometry using anti-CD20 and anti-CD40 mAbs (BD Biosciences). Demographic factors, RRF, and dialytic adequacy, evaluated by a single-pool urea kinetic model (spKt/V) and Charlson comorbidity index (CI), were recorded. Glomerular filtration rate was estimated by the Modification of Diet in Renal Disease (MDRD) formula (eGFR) [5]. sCD40 serum levels resulted significantly higher in HD than in HS and UR (Table 1). In the group of patients undergoing HD, serum sCD40 concentrations were significantly higher in anuric patients (N = 5) compared to those with RRF (N = 9) (1392.3 ± 633.3 vs. 507.9 ± 290.5, P < 0.05, respectively), whereas they did not correlate with spKt/V and CI. Similarly, in UR patients, serum sCD40 levels were indirectly correlated with eGFR (UR eGFR = 16.5 ± 6.6 mL/min; r2 = 0.93; P = 0.03). Moreover, CD40 B-cell membrane expression was also impaired in UR and HD patients, who presented a significantly lower number of CD20+CD40+ cells, expressed as both absolute number and percentage of total lymphocytes, compared to HS (Table 1). Our data confirm and further reinforce Pawlak's findings, highlighting the fact that uremic patients show an imbalance in the CD40 co-stimulatory pathway. In particular, HD patients present a modified CD40/sCD40 pattern with a lower number of CD40+ B-cells associated to higher sCD40 serum levels, when compared to HS. The clinical impact of this imbalance is still unknown, but it could well explain those humoral and cellular immune dysfunctions described in uremic patients [6] and [7]. The loss of renal function plays a key role in this CD40/sCD40 imbalance, as proven by the relationship between sCD40 serum levels and renal function in both UR and HD patients. However, the influence of other factors, such as biocompatibility of dialytic devices and inflammatory state, cannot be ruled out and should be investigated in larger, specifically designed studies

CD40/SCD40 imbalance in hemodialysis patients.

We read with great interest the paper by Pawlak et al. [1] recently published in Clinical Biochemistry. The authors demonstrated that the serum levels of soluble CD40 (sCD40), a natural antagonist of CD40/CD40L system, are high in patients on hemodialysis (HD) and are strictly related to renal residual function (RRF). Elevated sCD40 serum levels have been reported in the clinical setting of chronic kidney disease, peritoneal dialysis, and HD and have been related to the deficient response to hepatitis B vaccination found in those patients [2] and [3]. In addition, it has been recently described that, in HD patients, the reduction of sCD40 levels by a treatment with a high permeability dialytic membrane is associated to a significant increase of anti-HBs antibody titer [4]. Therefore, a role for sCD40 in uremic immunodeficiency has been hypothesized and it is currently under investigation. In order to evaluate the CD40/sCD40 balance in HD patients, we performed an observational study comparing CD40 B-cell membrane expression and sCD40 serum levels among HD patients, uremic patients not on HD (UR) and, also, healthy subjects (HS). Fourteen stable patients (mean ± SD; age, 65.1 ± 13.6 years) on regular thrice-weekly bicarbonate HD for at least 6 months were enrolled. Patients affected by conditions influencing the immune response, such as acute infections, active immunological diseases, immunosuppressive therapy, previous transplantation, or history of malignancies, were excluded from the study. Control samples were taken from 7 UR (age, 68.8 ± 8.5 years) and 8 HS (age, 47.9 ± 11.5 years). Blood samples were collected before HD treatment. sCD40 serum levels were measured by an enzyme-linked immunosorbent assay (Bender MedSystems). CD40+ B lymphocytes were defined by CD20 and CD40 cell membrane co-expression, analyzed by flow cytometry using anti-CD20 and anti-CD40 mAbs (BD Biosciences). Demographic factors, RRF, and dialytic adequacy, evaluated by a single-pool urea kinetic model (spKt/V) and Charlson comorbidity index (CI), were recorded. Glomerular filtration rate was estimated by the Modification of Diet in Renal Disease (MDRD) formula (eGFR) [5]. sCD40 serum levels resulted significantly higher in HD than in HS and UR (Table 1). In the group of patients undergoing HD, serum sCD40 concentrations were significantly higher in anuric patients (N = 5) compared to those with RRF (N = 9) (1392.3 ± 633.3 vs. 507.9 ± 290.5, P < 0.05, respectively), whereas they did not correlate with spKt/V and CI. Similarly, in UR patients, serum sCD40 levels were indirectly correlated with eGFR (UR eGFR = 16.5 ± 6.6 mL/min; r2 = 0.93; P = 0.03). Moreover, CD40 B-cell membrane expression was also impaired in UR and HD patients, who presented a significantly lower number of CD20+CD40+ cells, expressed as both absolute number and percentage of total lymphocytes, compared to HS (Table 1). Our data confirm and further reinforce Pawlak's findings, highlighting the fact that uremic patients show an imbalance in the CD40 co-stimulatory pathway. In particular, HD patients present a modified CD40/sCD40 pattern with a lower number of CD40+ B-cells associated to higher sCD40 serum levels, when compared to HS. The clinical impact of this imbalance is still unknown, but it could well explain those humoral and cellular immune dysfunctions described in uremic patients [6] and [7]. The loss of renal function plays a key role in this CD40/sCD40 imbalance, as proven by the relationship between sCD40 serum levels and renal function in both UR and HD patients. However, the influence of other factors, such as biocompatibility of dialytic devices and inflammatory state, cannot be ruled out and should be investigated in larger, specifically designed studies

Mechanisms underlying sCD40 production in hemodialysis patients

CD40 and its ligand (CD40L) regulate several cellular functions, including T and B-cell activation. The soluble form of CD40 (sCD40) antagonizes CD40/CD40L interaction. Patients undergoing hemodialysis (HD) present elevated sCD40 serum levels, which underlying molecular mechanisms are unknown. We studied sCD40 serum and urinary levels, CD40 membrane and gene expression and membrane shedding in HD, uremic not-HD patients (UR) and healthy subjects (N). We found that in HD sCD40 serum levels were higher than UR and N, being significantly elevated in anuric patients, and that sCD40 correlated to renal function in UR subjects, who presented also a reduced sCD40 urinary excretion rate. HD and UR presented reduced CD40 membrane and gene expression. The concentration of TNF-α converting enzyme (TACE), responsible for CD40 cleavage was not different between HD and N. Therefore the reduced renal clearance is the main cause of elevated sCD40 levels in HD. This finding could have relevant clinical implications