Safety and tolerance of sodium mycophenolate in patients after renal transplantation--an observational study.

BACKGROUND: Enteric-coated mycophenolate sodium (EC-MPS) was developed as an alternative agent to mycophenolate mofetil (MMF), aimed at reduction of gastrointestinal (GI) complications. METHODS: Seventy-four patients (mean age 42.3 years) switched from MMF to MPS were included in the study and followed-up for 3 months (Visit 0, Visit 2 after 1 month and Visit 3 after 3 months). The mean time from transplantation to switch was 3.7 years. During Visit 2 and 3 the following were recorded: impact of treatment change on the severity of GI symptoms (4 point scale: 1-worsening, 2-no change, 3-improvement, 4-resolution), EC-MPS tolerance, adverse events (AEs), patient compliance and physician satisfaction with treatment (4 point scale: 1-bad, 2-fair, 3-good, 4-very good). RESULTS: Sixty-three patients completed the study (85.1%). EC-MPS dose ranged from 720 to 1440 mg. GI symptom severity score averaged at 3.41. Symptoms most commonly compelling a conversion were: abdominal pain, diarrhea, abdominal colic, nausea, anorexia and vomiting. Out of 175 complaints, 144 (82%) either improved or resolved, 5 (2.86%) aggravated, and 25 (14.86%) persisted. Patient compliance and mean physician satisfaction score averaged at 3.70 and 3.02 at Visit 3, respectively. 9 AEs (2 severe) were reported. Causal relationship with the medication was suspected in 5 cases (1 case of SAE). The most common AEs were: anemia, infection (including sepsis), GI symptoms (abdominal pain, diarrhea). CONCLUSIONS: The following was concluded in our study: (1) sodium mycophenolate is well tolerated; (2) after switching from MMF to EC-MPS, gastrointestinal symptoms alleviated; (3) EC-MPS is a safe medication, with a low adverse events rate.

C4d complement split product in diagnosis of immunological activity of chronic allograft nephropathy.

INTRODUCTION: Activation of the humoral branch of the immunological response is currently believed to play an important role in pathogenesis of chronic allograft nephropathy. The impact of humoral alloreactivity, indicated by the presence of C4d deposits in peritubular capillaries of a renal allograft, on the development of chronic allograft nephropathy is a significant problem in transplantation. The aim of the study was to assess and correlate C4d expression in patients with chronic allograft nephropathy, with clinical and morphological variables, as well as to assess the impact of a change in immunosuppression regimen on posttransplant course and renal allograft morphology. PATIENTS AND METHODS: Twenty-six patients with chronic allograft nephropathy underwent biopsies to correlate C4d expression with clinical parameters and morphological findings. In all patients azathioprine was replaced with mycophenolate mofetil with additional CsA dose reduction in 12 patients. After 1 year, 14 protocol biopsies were performed. RESULTS: The frequency of C4d peritubular capillary deposition among patients with chronic allograft nephropathy was 30%. C4d expression appeared later after transplantation, was correlated with chronic allograft glomerulopathy and proteinuria but not other clinical or histological variables. C4d deposits displayed no independent impact on serum creatinine level. Proteinuria was significantly more reduced in the C4d(+) group. Progression of chronic morphological changes was significantly accelerated in the C4d(+) group. CONCLUSION: C4d peritubular capillary expression did not differentiate patients after immunosuppression enhancement, but it predisposed to progression of chronic morphological findings during 1-year observation.

Polyoma BK virus reactivation in kidney and pancreas-kidney recipients.

BK virus infection has become important factor affecting graft function in renal transplant recipients. One of the most important complication of BK infection is nephropathy in patients after renal transplantation. The aim of this study was to evaluate incidence of BK reactivation and nephropathy in our population of renal allograft recipients. One hundred twelve renal or pancreas-kidney allograft recipients were included for the 24 months follow-up. The incidence of BK nephropathy was 7.85% and viremia 27.96%. In the second study group there were 28 patients with graft function deterioration evaluated at the time of biopsy. In this group incidence of BK nephropathy was 7.1% and viral reactivation was diagnosed in 10.7% of patients. In our center, the incidence of BK nephropathy is the same as worldwide. The risk of BK virus replication is highest during first 15 months after the surgical procedure.

Tubular and glomerular proteinuria in diagnosing chronic allograft nephropathy with relevance to the degree of urinary albumin excretion.

The diagnosis of chronic allograft nephropathy (CAN) is based on pathological examination according to Banff 97 schema. The aim of the study was to evaluate the usefulness of tubular and glomerular proteinuria for noninvasive recognition of CAN. One hundred and thirty renal allograft recipients (at least 90 days after transplantation) who had undergone diagnostic allograft biopsy were included in the study. Beta2-microglobulin, alpha1-microglobulin, albumin, immunoglobulin G, total protein, and creatinine concentrations were obtained from the second morning urine specimen. Raw data and values calculated per 1 g of creatinine excreted in urine along with time after transplantation, serum creatinine, and its change over a period of 2 months prior to biopsy were taken for analysis. Urine proteins were measured using a nephelometric method. Statistical calculations were performed using MANOVA and stepwise discriminant analysis (SDA). Statistical diagnosis and staging of CAN matched the pathological method in 68% of a preliminary SDA. Therefore patients were divided into normoalbuminuric, microalbuminuric, and macroalbuminuric groups. There was no significant differences between protein excretion, except alpha1-microglobulinuria (CAN 0 vs 2, P = .018; CAN 1 vs 2, P = .041), beta2-microglobulinuria (CAN 0 vs 2, P = .026; CAN 1 vs 2, P = .0033), and total proteinuria (CAN 0 vs 2, P = .042) in the normoalbuminuric group. Nevertheless, diagnoses obtained using SDA were 89%, 91%, and 92% identical to the results of pathological examinations, for normoalbuminuric, microalbuminuric, and macroalbuminuric groups, respectively. In conclusion, tubular and glomerular proteinuria measurements may be useful for a noninvasive CAN diagnosis and staging only with regard to degree of urinary albumin excretion.

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 drug's complete withdrawal seem to be efficient and safe in low-risk kidney allograft recipients.

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.