Cholesterol embolisms as possible adverse drug reaction of direct oral anticoagulants.

The Netherlands Pharmacovigilance Centre Lareb has received two reports of cholesterol crystal embolisms associated with the use of a direct oral anticoagulant (DOAC). The European pharmacovigilance database contains several other cases concerning this association, and one report was published in the scientific literature. Cholesterol crystal embolisms were described in association with the use of several other antithrombotic drugs, although the role as an independent risk factor is not conclusive. The case series described in this article, indicates the possibility of an adverse drug reaction when a patient develops cholesterol crystal embolisms while using a DOAC.

[Loss of kidney function caused by implanted gentamicin sponges]. / Nierfunctieverlies door gentamicine-implantatiesponzen.

BACKGROUND: Infected joint replacements can be treated with gentamicin-containing materials for implantation. This may lead to side effects, especially in patients with impaired renal function. CASE DESCRIPTION: A 74-year-old woman underwent two surgeries for an acutely infected hip replacement. Gentamicin sponges (Garacol) were implanted during both interventions. The day after the second operation, her serum gentamicin levels had risen to toxic values. This confirmed the suspicion that she had a kidney impairment which was probably caused by the implanted gentamicin-containing sponges. In order to limit kidney damage, the patient received continuous venovenous haemodiafiltration (CVVHD). Outpatient check-up 3 months later found that the creatinine levels in the serum of the patient had normalised. CONCLUSION: Locally administered gentamicin sponges for implantation can cause therapeutic serum levels leading to systemic side effects. It is advisable to check kidney function before using the sponges. If this is reduced, it is recommended to be cautious when using these sponges for implantation. In case of toxic elevated values, CVVHD can limit kidney damage - which is reversible, given time - by accelerating gentamicin excretion.

Headache during hemodialysis - an uncommon cause for a common problem.

A hemodialysis patient is described who was suffering from headache during his dialysis sessions. This was due to a neovascular glaucoma causing an increase in intraocular pressure (IOP) during dialysis sessions. After several months his headache decreased but his IOP measurements remained high with almost similar pre- and post dialysis values. Headache during hemodialysis may be due to glaucoma, but this can disappear with time, along with a disappearance in the increase in IOP during dialysis sessions.

Eosinophilic tubulo-interstitial nephritis associated with iridocyclitis and thyreoiditis.

A patient is described with the tubulointerstitial nephritis with uveitis syndrome. The diagnosis can be difficult since it has to be differentiated from sarcoidosis, or infections like tuberculosis and toxoplasmosis. Our patient showed prompt recovery of fever, ocular symptoms and renal function after starting corticosteroids.

Severe atherosclerotic changes, including aortic occlusion, associated with hyperhomocysteinaemia and antiphospholipid antibodies.

Three patients are described with severe systemic atherosclerosis, including aortic occlusion, in the presence of a spectrum of risk factors, including hypercholesterolaemia, hypertension, a positive family history of cardiovascular problems, and hyperhomocysteinaemia. In all three patients high levels of anticardiolipin antibodies were found. The possible pathogenic role of antiphospholipid antibodies in atherosclerosis in the context of hyperhomocysteinaemia in these patients is discussed.

Morbidity and mortality during renal replacement therapy: dialysis versus transplantation.

AIM: Many patients with end-stage renal disease are eligible for renal transplantation. To enable a patient to choose between transplantation or to remain on dialysis comparable data on morbidity and mortality should be available. METHODS: Data were collected retrospectively from the medical records of all patients on the waiting list for renal transplantation and of transplanted patients during the period January 1, 1990, to January 1, 1997. All patients were dialyzed in the Kennemer Gasthuis and renal transplantation was performed in the Leiden University Medical Center (LUMC). Morbidity and mortality in both groups were compared. Morbidity was assessed by studying number, length and cause of hospital admissions. RESULTS: During the study period 102 patients had been on the waiting list and 54 patients had been transplanted in the LUMC. Mean length of stay on the waiting list before transplantation was 37 months. During the follow-up period 11 patients (10.8%) died on the waiting list and 6 patients (11.1%) died after renal transplantation. The mean length of stay on the waiting list of these two groups was much longer, being 55 months and 62 months, respectively. Length of hospitalization was significantly different between both patient groups during the first 6 months of treatment (13.24 days for those on the waiting list versus 40.75 days transplanted patients) and after 6 months (32.4 days for those on the waiting list versus 13.1 days transplanted patients). The number of hospital admissions did not differ significantly. Dialysis-related admissions constituted 47% of the total of admissions in the waiting list group and transplantation-related admissions were 43% in the transplanted group. CONCLUSION: In the present study we revealed no difference in overall mortality. However, mortality was influenced by length of stay on the waiting list. Morbidity was increased during the first 6 months after transplantation. Therapy modality greatly influenced the specific cause of morbidity.

Acute pancreatitis in peritoneal dialysis and haemodialysis: risk, clinical course, outcome, and possible aetiology.

BACKGROUND: It has been suggested that the incidence of acute pancreatitis in patients with end stage renal failure is increased. AIMS: To assess the risk of acute pancreatitis in patients on long term peritoneal dialysis and long term haemodialysis compared with the general population, to evaluate its clinical course and outcome, and to identify possible aetiological factors. PATIENTS: All patients who were maintained on long term peritoneal dialysis and/or haemodialysis (total dialysis time more than six weeks) from January 1989 to March 1998 in a large general hospital in The Netherlands. METHODS: Retrospective cohort study. Standardised ratios (as an approximate relative risk) between the incidence of acute pancreatitis in haemodialysis or peritoneal dialysis and the general population were calculated. Possible risk factors were identified. Patients with and without acute pancreatitis were compared. RESULTS: In 269 patients on haemodialysis (total of 614 person years), one patient developed an attack of acute pancreatitis. Patients on haemodialysis did not show an increased risk for acute pancreatitis compared with the general population (standardised ratio 11; 95% confidence interval (CI) 0.275 to 60.5). In 128 patients on peritoneal dialysis (total of 241 person years), seven patients had nine attacks of acute pancreatitis. Patients on peritoneal dialysis had a significantly and highly increased risk for acute pancreatitis (standardised ratio 249; 95% CI 114 to 473). Mortality in this series of nine attacks was 11%. No single aetiological risk factor could be identified. CONCLUSIONS: The risk of acute pancreatitis in patients on long term peritoneal dialysis is significantly and highly increased compared with the general population. The underlying causal mechanisms remain to be elucidated.

Colonic pseudo-obstruction due to beta2-microglobulin amyloidosis after long-term haemodialysis.

Beta2-microglobulin (A beta2M) amyloidosis is a relatively new secondary amyloidosis associated with renal failure and haemo- and peritoneal dialysis. Although beta2-microglobulin depositions are systemic, clinical manifestations are limited to articular and para-articular disease in most cases. A very limited number of patients have been reported with extra-articular manifestations including those of the gastrointestinal tract. We report on a patient who was treated with haemodialysis for 23 years and developed colonic pseudo-obstruction due to A beta2M amyloidosis.

Acute renal failure due to self-medication.

A patient with rhabdomyolysis and transient renal failure due to auto injection of the procaine containing drug "Gerovital" is described. This case illustrates the hazards of self-regulated alternative treatment.

Methimazole-induced agranulocytosis preceded by transient granulocytopenia. A case report.

A 36-year-old patient, euthyroid under methimazole treatment, was admitted because of an active Graves' ophthalmopathy and found to have a transient granulocytopenia. Forty-five days after this episode she developed classical agranulocytosis because of which the methimazole was stopped. The agranulocytosis occurred more than 20 months after the initiation of antithyroid drug therapy. Other causes for the initial phase of granulocytopenia were not found.

Erythrocyte deformability, endothelin levels, and renal function in cyclosporin-treated renal transplant recipients: effects of intervention with fish oil and corn oil.

Twenty nine stable renal transplant recipients, 10 receiving cyclosporin, 10 cyclosporin-prednisolone and nine azathioprine-prednisolone were supplemented in a double blind randomization cross-over study with fish oil and corn oil for a period of 4 months each. Erythrocyte deformability was reduced in the cyclosporin-treated patients and returned to normal values after supplementation of either oil. The oil supplementation resulted in an increased polyunsaturated fatty acid content in the plasma phospholipids. An increased erythrocyte membrane polyunsaturated fatty acid content might correct the lower erythrocyte deformability in cyclosporin treated patients. Therefore, it is probable that these changes are membrane-related. The oil supplementation had no effect on glomerular filtration rate, effective renal plasma flow, filtration fraction or blood pressure, which does not exclude effects of the cyclosporin-induced rigidified erythrocytes in the acute phase of renal transplantation. Decreased erythrocyte deformability could play a role in the cyclosporin-induced deterioration of renal haemodynamics. This may enhance the effects of endothelin, as these patients also had elevated endothelin levels.

No decreased erythrocyte deformability in type 1 (insulin-dependent) diabetes, either by filtration or by ektacytometry.

A lower erythrocyte deformability, which causes impairment of the microcirculation, is postulated to contribute to diabetic organ complications. Erythrocyte deformability was measured in four groups of type 1 (insulin-dependent) diabetic subjects and 30 controls by filtration and ektacytometry. Twenty-five patients without organ complications, 21 with microalbuminuria, 13 with overt nephropathy and 12 with leg ulceration were studied. No decreased erythrocyte deformability was found in any of the diabetic groups with either technique, and neither did the total group of 71 diabetic subjects have a lower erythrocyte deformability when compared with the controls. In order to imitate local conditions in the kidney, erythrocyte deformability was also measured in hyperosmolar solutions. Again no differences were found between the diabetic groups separately or as a whole and the controls. Furthermore no correlation was found between erythrocyte deformability and the plasma glucose or glycosylated haemoglobin level.