Acute rejection in non-compliant renal allograft recipients: a distinct morphology.

Non-compliance for immunosuppressive medication is frequent in renal transplant recipients, and associated with late acute rejection and graft loss. Although numerous studies were published on risk factors and outcome, no data are available on the histopathology of the 'non-compliant' allograft. As non-compliant patients swing between subtherapeutic and toxic doses of immunosuppression, trough levels show large variation. We questioned whether the histology of acute rejection in non-compliers (i) differs from the 'classical' acute rejection; (ii) shows more concomitant calcineurin-inhibitor toxicity; (iii) is associated with C4d and plasma cell (PC)-rich infiltrates. Based on validated interview methods/self reporting, 145 adult renal allograft recipients, transplanted for greater than one yr, on cyclosporine A and corticosteroids, were categorized as either compliant or non-compliant. Non-compliance was defined in 32 patients (22.1%). All late (greater than one yr) allograft biopsies were reviewed (Banff) and immuno-stained for C4d. Computerized morphometry was performed on late biopsies with features of acute cellular rejection. Sixty-two patients had > or =1 late biopsy [41 (36.2%) compliant/21 (65.6%) non-compliant; p = 0.0043], comprising a pool of 90 biopsies (61 compliant/29 non-compliant; p = 0.0303). 'Non-compliant' biopsies had higher scores of C4d (p = 0.0092), acute tubular damage (p = 0.0058), and peritubular capillaritis (p = 0.0070). 'Non-compliant' biopsies with acute cellular rejection showed less interstitial edema (p = 0.0165), more interstitial infiltrate (p = 0.0100), more interstitial fibrosis (p = 0.0277), and more tubular atrophy (p = 0.0197). PC-rich infiltrates correlated with C4d (p = 0.0080). Detection of non-compliance is mandatory as it represents an important cause of graft loss. This study describes histologic features of renal allograft biopsies in non-compliant patients that could help identifying this patient profile.

Nonadherence with diet and fluid restrictions among adults having hemodialysis.

PURPOSE: To describe the prevalence of nonadherence with the prescribed diet and fluid restrictions among patients receiving hemodialysis. METHODS: A multicenter cross-sectional design with 916 patients recruited from 18 dialysis centers in Germany and Belgium. The Dialysis Diet and Fluid Nonadherence Questionnaire (DDFQ) was used to measure patients' nonadherence. FINDINGS: The results showed that many patients had difficulty following diet (81.4%) and fluid (74.6%) restrictions. Younger male patients and smokers were at highest risk for non-adherence. Higher levels of interdialysis weight gain were associated with nonadherence. CONCLUSIONS: The findings indicate the need to continue to monitor and study hemodialysis patients' adherence behavior longitudinally and to design interventions to enhance adherence.

Prospective study on late consequences of subclinical non-compliance with immunosuppressive therapy in renal transplant patients.

In this prospective study we compared the incidence of late acute rejections (LAR) and changes in serum-creatinine over time between compliers and noncompliers with immunosuppressive therapy more than 1 year post transplantation and explored the relative contribution of non-compliance and other risk factors in the occurrence of LAR. One hundred and forty-six adult renal transplant recipients were followed during a 5-year period. Patients were interviewed at the beginning of the study and categorized as non-compliers if they admitted to have skipped immunosuppressive medication on a regular basis during the previous 12 months. The occurrence of LAR during the follow-up period was recorded. We identified 22.6% non-compliers of which 21.2% experienced a late acute rejection compared with 8% in the group of compliers at 5 years postinclusion (p < 0.05). Kaplan-Meier survival analysis showed a decreased rejection free time in non-compliers compared with compliers (p = 0.03). Non-compliant patients had a 3.2 higher risk of LAR (Cox regression analysis, p = 0.005). Non-compliers experienced a higher increase in serum-creatinine over time (Linear Mixed Models, p < 0.001). Non-compliance in renal transplant patients more than 1-year post transplantation is associated with an increased risk for LAR and a higher increase in serum-creatinine during the following 5 years.