M Lao

Long‐term results of treatment of chronic hepatitis B, C and D with interferon‐α in renal allograft recipients

Abstract The aim of this study was to evaluate the efficacy and safety of interferon‐a (IFN‐α) therapy of chronic hepatitis B, C and D (HBV, HCV and HDV, respectively) in renal transplant recipients. A group of 42 patients (30 males, 12 females, mean age 38 years) with documented viraemia and chronic active hepatitis (CAH) were studied, of whom 1 had HBV infection alone, 11 had HCV infection alone, 3 had HBV and HDV infection concomitantly, 12 had HBV and HCV infection concomitantly, and 2 had HBV, HCV and HDV infection concomitantly. Patients received 3 MU IFN‐α three times weekly for 6 months. After IFN‐α therapy, 18 patients (43 %) achieved normal alanine aminotransferase (ALT) activity and a partial response was observed in 12 (29%) patients. Two patients relapsed (one with HCV and one with HBV + HCV infection) immediately after the cessation of IFN‐α therapy. Repeated liver biopsy was performed in 16 patients after 6–24 months of therapy and revealed progression to cirrhosis in five patients, remission in two and stable disease in nine. None of the patients cleared HCV RNA, four patients cleared HBeAg (two also HDV), and one both HBV and HCV. Five patients died during IFN‐α therapy (one as a consequence of liver failure), and four died during the 6 months after therapy (two as a consequence of liver failure). During IFN‐α therapy renal allograft function remained stable in 31 patients and acute rejection episodes occurred in 7, of whom 5 lost their graft and all had experienced rejection episodes before. In 16 patients normalization of ALT continued during long‐term follow‐up (median 22 months, range 0–84 months). IFN‐α seemed to be moderately effective in the treatment of chronic HBV or HCV infections, but cannot be recommended for recipients infected with both HBV and HCV.

Effect of enalapril on proteinuria after kidney transplantation

We studied the effect of enalapril, an inhibitor of angiotensin-converting enzyme (iACE), on proteinuria and renal function in recipients of renal allografts. Twenty-two patients with post-transplant nephrotic syndrome were treated with incremental doses of enalapril for 1 year. Urinary protein excretion decreased after 2 months of treatment from a mean of 8.9 g/day (range 4.0–18.9 g/day) to 4.5 g/day (range 0.4–10.0 g/day; P<0.01) and remained significantly low for the rest of the study. However, in the same period, creatinine clearance did not change significantly; it went from 47.8 ml/min (range 17.1–110.3 ml/min) before treatment to 44.2 ml/min (range 16.5–88.5 ml/min) after 2 months of iACE therapy. Analysis of individual data showed that there was a significant reduction in proteinuria in 14 of the 22 patients and that the rate of deterioration of renal function did not increase in 17 of the 22 patients. We did not observe any serious side effects of enalapril administration. The results of our study prove that iACE can be used safely and effectively to reduce post-transplant proteinuria.

Human herpesvirus-6 in renal transplant recipients: Potential risk factors for the development of human herpesvirus-6 seroconversion

Herpesviruses, including human herpesvirus-6 (HHV-6), reactivate and have the potential to be pathogenic in immunocompromised patients. Little information is available regarding the correlation between immunosuppressive therapy and HHV-6 seroconversion after organ transplantation. Serum samples obtained from 120 kidney and kidney/pancreas transplant recipients were tested to explore the potential risk factors for developing HHV-6 infection including types of immunosuppression and induction/rejection therapy. Stored serum samples obtained prior to and at the 2nd, 4th, 12th and 48th weeks after transplantation were tested for anti-HHV-6 immunoglobulin (Ig)M antibodies using indirect immunofluorescence assay. Prior to transplantation and 48 weeks after transplantation the sera were additionally tested for anti-HHV-6 IgG using enzyme-linked immunoassay. Ninety-one percent of 120 recipients were HHV-6 IgG-positive before transplantation. One hundred seven of 120 patients were anti-HHV-6 IgM-negative before transplantation. Primary/secondary HHV-6 seroconversion occurred in sera of 46.6% of these 107 patients. HHV-6 seroconversion most frequently occurred 2 to 4 weeks after transplantation. There was no significant relationship between HHV-6 seroconversion and the treatment with methylprednisolone (MP). The incidence of HHV-6 seroconversion was significantly higher in subjects who were treated with the regimens including Daclizumab or Sirolimus as compared with those who were on other protocols. HHV-6 seropositivity in the Polish population of organ transplant recipients is very high. We demonstrated a trend toward association of HHV-6 seroconversion with type of immunosuppressive therapy.

Surgical complications observed in simultaneous pancreas-kidney transplantation : Thirteen years of experience of one center

SIMULTANEOUS pancreas and kidney transplantation (SPKTx) is the procedure of choice for a majority of transplant candidates with end-stage renal disease and diabetes mellitus. Recent evidence supports its benefits on the maintenance of normoglycemia and the arrest or even possibily of reversal of diabetic complications, such as vasculopathy, nephropathy, and neuropathy. However, pancreas transplant has been associated with the highest surgical complication rate of all the routinely performed organ transplant procedures. A significant number of pancreas grafts are lost early post-transplant secondary to surgical complications. Over the last decade, the operative procedure has been refined and immunosuppressive regiments have improved such that 1-year graft survival routinely exceeds 75%. The purpose of this study was to assess our improved results and to determine other risk factors that may help us decrease the complication rate further.

C4d complement split product expression in chronic rejection of renal allograft

Chronic allograft rejection remains the major cause of late renal graft loss. Its pathogenesis is complex, depending on both immunological and nonimmunological factors. An important role in development of chronic rejection is ascribed to an ongoing immunological reaction mainly of the humoral type. C4d complement split product, as a stable fragment of complement degradation activated by antigen-antibody complexes, is considered to be an indicator of humoral activity in allografts. The aim of the present study was to establish a correlation between C4d expression and morphological findings specific for chronic rejection among biopsy specimens from patients with deteriorating graft function versus protocol biopsy specimens versus biopsy specimens of native kidneys with glomerular diseases. C4d deposits in peritubular capillaries and glomeruli were observed in 83% of patients with morphological changes of chronic rejection. No C4d expression was found in the protocol biopsy group. C4d deposits in glomeruli localizations were found in kidneys from patients with glomerulopathies; the pattern of distribution was similar to that for antibodies characteristic for glomerulonephritis. There was a positive correlation between C4d expression and morphological features of chronic rejection. In our opinion, only peritubular capillary localization is specific for a rejection process; glomerular localization is nonspecific and probably secondary to antigen-antibody complex deposition in course of some types of glomerulopathies.

Polyomavirus BK infection

Because it is an important factor affecting renal transplant function, BK infections are significant problem in posttransplant. BK nephropathy develops in 5% of renal allograft recipients, in most cases within the first year after the procedure. The gold standard for BK nephropathy diagnosis is still immunohistochemical staining for large T antigen in graft biopsy specimens. The aim of the present study was to evaluate the incidence of and factors influencing BK nephropathy in our renal allograft population. Among 89 renal or pancreas/kidney allograft recipients, BKV DNA was detected in 1 or more serum samples in 17 patients but BK nephropathy was diagnosed in only 1 case. Plasmacytic tubulitis was an exclusive feature in PCR-positive patients with 2 (20%) cases but no such findings in the PCR-negative group. In 40% of patients in the PCR-positive group at least 1 rejection episode was diagnosed versus 22% in the PCR-negative group. There were no significant differences in both groups according to total ischemia time, immunosuppressive treatments, or mean serum creatinine at 1 year after transplantation.

Cyclosporine A blood concentration during pregnancy in renal allograft recipients

Abstract Pregnancy‐induced changes increase hazards associated with cyclosporine (CsA) treatment. Blood CsA trough levels (C0) were estimated in 15 pregnant renal allograft recipients treated with prednisolone + CsA + azathioprine using the TDx Abbott fluorescent polarization immunoassay. Despite therapeutical dose levels of CsA administered during pregnancy (3.52‐3.67 and 3.59 mg/kg body weight in the first, second, and third trimesters, respectively), C0 significantly decreased (first trimester 130.8 ± 36.9, second 92.0 ± 32.7, and third 99.0 ± 36.9 ng/ml). The mean increase of patients body weight in miD‐pregnancy was 3.0 ± 2.19 kg and was associated with a significant (P < 0.05) fall in a hematocrit value (from 42 ± 4.9 % prior to pregnancy to 34 ± 6% at the 20th week). We postulate that C0 concentration does not reflect the true exposure to CsA as no episodes of acute graft rejection were observed during pregnancy.

Low‐dose heparin: a novel approach in immunosuppression

Abstract Very low subcutaneous doses of standard and low molecular weight heparin inhibited the traffic of sensitized lymphocytes to a graft site, reduced in situ mono‐nuclear cell infiltration and prolonged skin allograft survival in mice. Similar effects were caused by low doses of oral heparin, while higher oral doses prolonged graft survival. Our results suggest that oral heparin may have immunosuppressive properties applicable in clinical transplantation.

The role of the protocol biopsies in renal allograft recipients

Subclinical rejection and long-term cyclosporine nephrotoxicity are well-known risk factors of chronic allograft nephropathy. In a prospective study 32 low-risk patients were randomized to either a reduced CsA dose (5 mg/kg/d) and daclizumab (group A, n = 16) for 7 months posttransplant with subsequent CsA tapering/withdrawal, or to a normal CsA dose (10 mg/kg/day) without daclizumab (group B, n = 16). Both groups received MMF and prednisone. Protocol biopsies were obtained at engraftment and 3 and 12 months after Tx. The number of rejection episodes was the primary endpoint. The secondary endpoints were: renal function, histological parameters related to CsA, and serum levels of TGF-beta and PDGF-BB. A low incidence of clinically suspected rejection episodes was observed (19% in group A and 12.4% in group B; P = NS). Although protocol biopsies showed 12 subclinical rejection episodes (six in group A, six in group B), serum creatinine levels were not different between the examined groups at 3 months. However, at 12 months, there was a statistically improved mean creatinine level in group A patients (1.2 mg/dL +/- 0.5 in group A vs 1.54 mg/dL in group B; P <.05). Chronic histopathologic changes were significant for biopsies at 3 and 12 months in both groups compared to the baseline findings for protocol biopsies (with no differences between groups, or between 3 and 12 months in both groups). Serum TGF-beta and PDGF-BB did not differ between the groups. Protocol biopsies may be useful to monitor safety and efficiency of new immunosuppressive protocols. Immunosuppressive regimens with low CsA doses followed by the drugs complete withdrawal seem to be efficient and safe in low-risk kidney allograft recipients.

Pneumonia in kidney allograft recipients

Infectious complications, including pneumonia, remain one of the leading causes of morbidity and mortality in kidney allograft recipients. The aim of the study was to evaluate the relationship between pneumonia occurrence and treatment duration and recipient age, cause of native kidney insufficiency, dialysis duration, time between transplantation and onset, HLA matching, PRA immunosuppressive protocol, acute rejection incidence and treatment, kidney function at the pneumonia onset, as well as presence of comorbid conditions. One hundred and twenty pneumonia cases occurred in kidney allograft recipients transplanted between 1991 and 2000 with 12 to 120 months follow-up. Twenty five percentage of pneumonia episodes were diagnosed during the first posttransplant month, 25% between 2 and 6 months, and 25% at 0.5 to 3 years. Treatment duration measured from pneumonia onset to the study endpoint of recovery, which was defined as antibiotic withdrawal, show 50% of patient we cured after 15 days and 75% after 24 days of treatment. The risk of prolonged pneumonia treatment was associated with: second versus first kidney transplantation with RR = 2.3 (P <.02) and medians of treated time 28 versus 15 days; as well as serum creatinine level above 2 mg/dL (RR = 1.4; P <.098). Exposure to enhanced-potency immunosuppressive protocols including induction therapy with mono- or polyclonal antibodies increased the RR = 1.65 (P <.02), and lengthened the time to 18 versus 14 days. Maintenance immunosuppression with agents other than cyclosporine also enhanced the risk. (RR = 2.18; P <.068).