QT prolongation and near fatal cardiac arrhythmia after intravenous tacrolimus administration: a case report.

BACKGROUND: The use of immunosuppressant agents is mandatory in the long-term management of transplant recipients. Herein, we report a case of near fatal cardiac arrhythmia related to the use of intravenous tacrolimus in a 35-year-old woman undergoing renal transplantation. METHODS: The patient had no previous history of cardiac disease, but an initial electrocardiogram demonstrated slightly prolonged QT and QTc intervals and normal sinus rhythm. Postsurgical immunosuppression included intravenous tacrolimus and methylprednisolone. During intravenous tacrolimus infusion, marked QT prolongation occurred. The patient suffered recurrent runs of torsade de pointes, refractory to aggressive medical management and requiring numerous defibrillations. Rapid atrial pacing eventually controlled the arrhythmia. RESULTS: We note not only a temporal association, but also a direct linear relationship, between this arrhythmia and blood tacrolimus levels. CONCLUSION: We believe this case presents a little recognized hazard associated with the use of intravenous tacrolimus and points to the need for careful predrug screening for QT prolongation. Tacrolimus has been shown to effect intracellular calcium and to prolong the action potential duration experimentally. This suggests that an increase in the intracellular calcium may underlie torsades de pointes associated with intravenous tacrolimus.

Polycystic kidneys do maintain good endocrine function.

We develop here the hypothesis that polycystic kidneys (PCK) may maintain, to a certain extent, the ability to perform endocrine functions. We know that patients with adult polycystic kidney disease (APCKD) produce more erythropoietin and maintain a higher hematocrit than patients with other primary diseases of the kidneys. It is possible that they synthesize more 1,25 and 24,25 Vit D3 and metabolize better the parathyroid hormone and other hormones. If it is correct, they may have fewer signs of secondary hyperparathyroidism and less bone marrow fibrosis which along with increased erythropoietin production would explain the higher hematocrit.

Captopril-associated cholestatic jaundice.

Captopril, the competitive inhibitor of angiotensin-converting enzyme, is of considerable benefit in difficult-to-manage forms of hypertension. Its use has been associated with various untoward effects, but hepatic injury has not been widely reported. We treated a patient with captopril-associated cholestatic jaundice; a review of cases reported to the drug manufacturer and a review of the literature showed 13 additional cases of hepatic injury associated with captopril. In 9 of these the jaundice was categorized as cholestatic, and in 4 of the remaining 5 as mixed cholestatic-hepatocellular. These findings show that jaundice may be an idiosyncratic side effect of captopril, and that captopril-associated jaundice characteristically has strongly cholestatic features.

Ontogeny and localization of the IgG Fc receptor of rabbit ciliary processes.

We have previously demonstrated the presence of IgG Fc binding sites in adult rabbit ciliary processes. The present study of 22 perinatal rabbit eyes defines the age-related expression of the IgG receptor activity and the selective localization of this activity on the posterior portions of the ciliary processes where it appears to be associated with the superficial non-pigmented epithelium. Our findings indicate that the rabbit ciliary processes IgG binding activity is only slightly expressed at birth but develops rapidly after birth, reaching adult levels within 2 weeks. Moreover, our results support the concept of important regional specialization within the ciliary body and suggest that the posterior ciliary processes, like other tissues similarly endowed with IgG binding sites, may have specialized immune functions.

Extracorporeal immunomodulation (EIM) by plasmaleukapheresis (PLP) in the treatment of steroid resistant renal rejection.

We report the use of plasmaleukapheresis (PLP) to treat renal allograft rejection which had failed to respond to conventional pulse corticosteroid therapy. Twenty-three patients who failed to respond to at least 3 boluses of IV methylprednisolone received PLP. Sixteen of these patients had either complete (12) or partial (4) response to PLP. In the responding group, the mean serum creatinine was 1.5 +/- 0.3 mg/dl. In the partially responding group, the mean serum creatinine was 3.9 +/- 0.3 mg/dl. Plasmaleukapheresis resulted in the reduction in levels of circulating immune complexes (CIC), and T and B cells. Circulating null cell levels increased. All 5 patients with low (less than 10%) pretransplant cytotoxic antibody levels had complete response to plasmaleukapheresis. We conclude that PLP, perhaps by removal of CIC, antibody and/or population of circulating T or B cells, may be capable of reversing steroid resistant rejection, especially in patients with low levels of pretransplant cytotoxic antibodies.

Binding sites for immunoglobulin G in rabbit ciliary processes.

This article demonstrates the presence of selective binding activity for the Fc fragment of IgG on the ciliary processes of rabbit eye. Other parts of the eye, including the cornea, iris, choroid, and retina, were negative for such activity. Binding activity was demonstrated in vitro by the specific adherence of IgG-coated sheep red blood cells (IgGEA) to the ciliary processes in frozen sections of whole rabbit eye. IgGEA binding was specifically blocked by IgG but not by albumin or the F(ab')2 fragment of IgG. The data suggest that the ciliary processes, like the choroid plexus and the renal interstitium, have intrinsic binding activity for Fc IgG, which might be involved in the local entrapment of immune components present either in the circulation or in the aqueous humor.

Binding sites for immune components in human choroid plexus.

In immunologically mediated disorders such as systemic lupus erythematosus and experimental serum sickness, immunoglobulin and complement amy be localized in the choroid plexus. This report demonstrates the presence of binding activity for the Fc fragment of IgG in 34 of 36 samples of human choroid plexus. We suggest that the number, distribution, and avidity of these Ig receptors may modulate the occurrence and/or severity of central nervous system symptoms in patients with immunologically mediated systemic diseases.

Extracorporeal treatment of salicylate or acetaminophen poisoning--is there a role?

Hemodialysis or sorbent hemoperfusion has been used in the management of clinical overdose of salicylates or acetaminophen. Hemodialysis offers considerable benefit in severe salicylate poisoning and is preferred to hemoperfusion or peritoneal dialysis, since it more rapidly corrects acid-base and electrolyte abnormalities than does hemoperfusion, and since it is clearly more efficient than is peritoneal dialysis for the removal of salicylates. Charcoal hemoperfusion in animal studies and hemodialysis in man have been shown to accelerate acetaminophen elimination from the body. Hemodialysis and hemoperfusion are of questionable benefit in clinical acetaminophen overdose. However, our clinical experience to date with charcoal hemoperfusion in "late" acetaminophen overdose has been associated with a less notable increase in liver enzyme concentrations in comparison with results of retrospective studies of series of patients treated or not treated with sulfhydryl donors.