Therapeutic doses of glucocorticoids: implications for oral medicine.

Glucocorticoids can cause adverse systemic side-effects ranging from iatrogenic Cushing's syndrome during treatment, to hypothalamic-pituitary-adrenal axis suppression and clinically significant adrenal insufficiency when the agents are discontinued. While the oral route of administration is most often implicated, it is now becoming more apparent that inhaled and topical administration also can cause these effects. Given the high therapeutic value of glucocorticoids, the ability to prescribe these agents while maintaining a low risk-to-benefit ratio for patients is critical. The aim of this review is to provide oral healthcare practitioners with a practical guide to commonly used glucocorticoids, their adverse effects, and perioperative use.

Posttransplant diabetes mellitus in liver transplant recipients: risk factors, temporal relationship with hepatitis C virus allograft hepatitis, and impact on mortality.

BACKGROUND: Recent studies suggest an association between diabetes mellitus and hepatitis C virus (HCV) infection. Our aim was to determine (1) the prevalence and determinants of new onset posttransplant diabetes mellitus (PTDM) in HCV (+) liver transplant (OLT) recipients, (2) the temporal relationship between recurrent allograft hepatitis and the onset of PTDM, and (3) the effects of antiviral therapy on glycemic control. METHODS: Between January of 1991 and December of 1998, of 185 OLTs performed in 176 adult patients, 47 HCV (+) cases and 111 HCV (-) controls were analyzed. We reviewed and analyzed the demographics, etiology of liver failure, pretransplant alcohol abuse, prevalence of diabetes mellitus, and clinical characteristics of both groups. In HCV (+) patients, the development of recurrent allograft hepatitis and its therapy were also studied in detail. RESULTS: The prevalence of pretransplant diabetes was similar in the two groups, whereas the prevalence of PTDM was significantly higher in HCV (+) than in HCV (-) patients (64% vs. 28%, P=0.0001). By multivariate analysis, HCV infection (hazard ratio 2.5, P=0.001) and methylprednisolone boluses (hazard ratio 1.09 per bolus, P=0.02) were found to be independent risk factors for the development of PTDM. Development of PTDM was found to be an independent risk factor for mortality (hazard ratio 3.67, P<0.0001). The cumulative mortality in HCV (+) PTDM (+) versus HCV (+) PTDM (-) patients was 56% vs. 14% (P=0.001). In HCV (+) patients with PTDM, we could identify two groups based on the temporal relationship between the allograft hepatitis and the onset of PTDM: 13 patients developed PTDM either before or in the absence of hepatitis (group A), and 12 concurrently with the diagnosis of hepatitis (group B). In gr. B, 11 of 12 patients received antiviral therapy. Normalization of liver function tests with improvement in viremia was achieved in 4 of 11 patients, who also demonstrated a marked improvement in their glycemic control. CONCLUSION: We found a high prevalence of PTDM in HCV (+) recipients. PTDM after OLT was associated with significantly increased mortality. HCV infection and methylprednisolone boluses were found to be independent risk factors for the development of PTDM. In approximately half of the HCV (+) patients with PTDM, the onset of PTDM was related to the recurrence of allograft hepatitis. Improvement in glycemic control was achieved in the patients who responded to antiviral therapy.

Managing the highly sensitized transplant recipient and B cell tolerance.

The detection of anti-donor-HLA antibodies in a renal allograft recipient's serum, either at the time of or after transplantation, is usually associated with specific antibody-mediated clinical syndromes. These can be divided temporally into three categories: hyperacute rejection, acute humoral rejection and chronic humoral rejection. With the identification of new immunosuppressive drug combinations, more-effective control of alloantibody production has been recently achieved in humans. Thus, prevention and/or treatment of antibody-mediated allograft injury are now possible. Ultimately, the induction of mixed hematopoietic chimerism may allow us to overcome the problem of allosensitization and accept an allograft without chronic immunosuppression.

Renal thrombotic microangiopathy associated with anticardiolipin antibodies in hepatitis C-positive renal allograft recipients.

Hepatitis C virus (HCV) infection has been associated with de novo or recurrent membranoproliferative glomerulonephritis and acute transplant glomerulopathy in transplanted kidneys. Recently, anticardiolipin antibodies (ACA) have been linked with chronic HCV infection. A few reports have suggested an association between ACA and renal allograft thrombosis. This study examines the clinical and pathologic features of HCV-positive renal allograft recipients at our institution. From 1990 to 1996, 379 kidney transplants were performed. We identified 18 recipients (4.8%) with HCV-positive serology pretransplant. Determination of IgG and IgM ACA was performed by enzyme-linked immunosorbent assay, using pretransplant sera. Among the 18 patients, five patients presented with biopsy-proven de novo renal thrombotic microangiopathy (RTMA), occurring 5 to 120 d (median, 14 d) after transplant. No differences in pretransplant characteristics were observed between patients with (n = 5) or without (n = 13) RTMA. All five patients had a positive ACA test (either IgG or IgM titer > 2 SD above normal), compared with only one of 13 patients without RTMA. The mean value for IgG ACA was significantly higher in the RTMA patients than in patients without RTMA (22.9 +/- 14.1 versus 6.9 +/- 4.9 IgG phospholipid units, P = 0.02); however, there were no significant differences in IgM ACA titers. Rheumatoid factor and complement C4 levels were normal in pretransplant sera of patients with RTMA. Patients with RTMA had their cyclosporine withdrawn (four of five) or the dose was decreased (one of five), and one of five underwent plasmapheresis. Four of five patients died within 5 yr after transplant, compared with no deaths in the other 13 patients. Finally, as a control group, seven HCV-negative renal allograft recipients who presented with RTMA/hemolytic uremic syndrome during the same time period were found to have normal ACA values (IgG or IgM). RTMA associated with ACA in HCV-positive renal allograft recipients may represent a new clinical entity. The occurrence of this syndrome may have deleterious consequences for patient and graft survival.

Dialysis membrane adsorption during CRRT.

Experimental and clinical studies have suggested that dialysis membrane biocompatibility may influence the morbidity and mortality of patients with acute renal failure. Complement activation by dialysis membranes may also prolong the recovery from acute renal failure. In this article, we review the concept of dialysis membrane adsorption, with particular attention to adsorption/inhibition of factor D, a highly specific serine protease of the alternative pathway of complement. The adsorptive properties of some dialysis membranes may be useful during continuous renal replacement therapies (CRRT) in critically ill patients.