Catherine Girardin

Lack of Benefit of Early Protocol Biopsies in Renal Transplant Patients Receiving TAC and MMF: A Randomized Study

We conducted a randomized, multicenter study to determine whether treatment of subclinical rejection with increased corticosteroids resulted in beneficial outcomes in renal transplant patients receiving tacrolimus (TAC), mycophenolate mofetil (MMF) and prednisone. One hundred and twenty‐one patients were randomized to biopsies at 0,1,2,3 and 6 months (Biopsy arm), and 119 to biopsies at 0 and 6 months only (Control arm). The primary endpoint of the study was the prevalence of the sum of the interstitial and tubular scores (ci + ct)> 2 (Banff) at 6 months. Secondary endpoints included clinical and subclinical rejection and renal function. At 6 months, 34.8% of the Biopsy and 20.5% of the Control arm patients had a ci + ct score ≥ 2 (p = 0.07). Between months 0 and 6, clinical rejection episodes were 12 in 10 Biopsy arm patients and 8 in 8 Control arm patients (p = 0.44). Overall prevalence of subclinical rejection in the Biopsy arm was 4.6%. Creatinine clearance at 6 months was 72.9 ± 21.7 in the Biopsy and 68.90 mL/min ± 18.35 mL/min in the Control arm patients (p = 0.18). In conclusion, we found no benefit to the procurement of early protocol biopsies in renal transplant patients receiving TAC, MMF and prednisone, at least in the short term. This is likely due to their low prevalence of subclinical rejection.

Factors associated with progression of interstitial fibrosis in renal transplant patients receiving tacrolimus and mycophenolate mofetil.

Background. We recently reported a randomized study in renal transplant patients (RTP) receiving tacrolimus, mycophenolate mofetil, and prednisone in which patients who had early protocol biopsies (PBx) derived no benefit compared with controls (no PBx) at 6 months, likely due to the low prevalence of subclinical rejection. We report on the follow-up of these patients to 24 months at which time a repeat PBx and tests of renal function were performed. Methods. Of the 240 RTP randomized, 22 were excluded for a protocol violation. Approximately 75% of the remaining 218 (111 PBx and 107 controls) completed the study. Results. At 24 months, graft function was excellent with a mean creatinine clearance of approximately 74 mL/min and negligible proteinuria; however, the prevalence of interstitial fibrosis and tubular atrophy (IF/TA)—ci + ct more than or equal to 2—increased from approximately 3% at baseline to up to 40% to 50%. By logistic regression analysis, the only independent positive correlate of IF/TA was transplantation with a deceased donor. However, by post hoc analysis, use of angiotensin-II-converting enzyme inhibitors or angiotensin II receptor blockers was negatively correlated with both the prevalence of IF/TA at 24 months and its progression between 6 and 24 months in RTP that had paired biopsies. Conclusions. A regimen of tacrolimus, mycophenolate mofetil, and prednisone results in excellent renal function at 24 months posttransplant but with a progressive increase in IF/TA. A potential inhibitory effect of angiotensin-II-converting enzyme inhibitor/angiotensin II receptor blockers on IF/TA is suggested that requires confirmation in a randomized study.

Impact of Transplant-Related Stressors and Feelings of Indebtedness on Psychosocial Adjustment Following Kidney Transplantation

Forty-seven patients answered a questionnaire about stress, feelings of indebtedness toward the donor, and psychosocial adjustment following kidney transplantation. The combination of age, general life stress, and transplant-related stress explained 47% of the variance in psychosocial adjustment. Areas of adjustment most influenced by this combination of predictors included attitudes toward health care, domestic, vocational, social adjustment, and psychological distress. Younger patients endorsed higher levels of transplant-related stress and higher levels of psychological distress. Moderate to intense feelings of indebtedness toward the donor were common but were unrelated to psychosocial adjustment posttransplant.

Evaluation of a Preemptive Strategy for BK Polyomavirus-Associated Nephropathy Based on Prospective Monitoring of BK Viremia: A Kidney Transplantation Center Experience

INTRODUCTION BK polyomavirus-associated nephropathy (BKPVAN) is a major cause of renal failure early after kidney transplantation. The present study reports the preliminary results of prospective monitoring including a preemptive strategy for BKPVAN during the first year after kidney transplantation. METHODS We monitored BK virus DNA in blood at months 1, 2, 3, 6, 9, and 12 among 92 subjects who received induction therapy (basiliximab or antithymocyte globulin), and maintenance immunosuppression with prednisone, mycophenolate mofetil, and tacrolimus. Patients with two or more consecutive measurements of viral load >10(4) copies/mL were treated with a stepwise approach including dose reduction or discontinuation of mycophenolate mofetil eventually followed by reduction of tacrolimus and introduction of leflunomide. RESULTS Within 1 year, seven (7%) patients displayed sustained BK viremia at a median of 92 days after transplantation. Among 68 patients who underwent a renal allograft biopsy, seven were diagnosed as BKPVAN at a median of 15 weeks after transplantation. The diagnosis was achieved by a surveillance biopsy in four patients with stable renal function. BKPVAN was preceded by asymptomatic viremia except for two cases in whom BK viremia occurred at 6 or 11 months, after the histological diagnosis. At 12 months, six patients had cleared their viremia. Serum creatinine levels had stabilized in six recipients with BKPVAN estimated renal function was 43.7 ± 16.3 mL/min in patients with viremia and/or BKPVAN versus 61.3 ± 20.1 mL/min among patients who never became viremic (P = .03). None of the patients with viremia and/or BKPVAN lost the allograft. CONCLUSION BKPVAN may occur early after kidney transplantation, at a low or undetectable viremia or at some weeks after the first positive viremia. Intensive monitoring during the first 4 months after transplantation together with early protocol biopsies or interventions prompted by BK viremia may optimize BKPVAN diagnosis at a subclinical stage, thus avoiding renal dysfunction.

The incidence, management, and evolution of rapamycin-related side effects in kidney transplant recipients

Conversion from a calcineurin‐inhibitor‐based immunosuppression to a rapamycin‐based immunosuppression may preserve kidney graft function. The side effects of rapamycin can limit its usefulness, but their management and evolution are rarely reported in clinical trials. We performed a retrospective cohort study in patients transplanted before December 31, 2008 and who received rapamycin to replace calcineurin inhibitors. In 219 patients studied, 98% presented ≥1 side effects after starting rapamycin. Side effects occurring in ≥10% of patients were dyslipidemia (52%, 95% confidence interval (CI): 45–59%), peripheral edema (37%, 95%CI: 31–43%), cytopenia (36%, 95% CI: 30–42%), acne (29%, 95% CI: 23–35%), proteinuria (23%, 95% CI: 17–29%), and oral ulcers 14% (95% CI: 10–18%). Proteinuria, ulcers, and edema were difficult to manage and were more likely to cause cessation of rapamycin. Rapamycin was discontinued in 46% of patients (95% CI: 40–52%). Age (odds ratio [OR] per 10‐yr increase: 1.29, 95% CI: 1.05–1.59) and obesity (OR: 2.57, 95% CI: 1.10–6.01) were independently associated with cessation of rapamycin. We conclude that successful control of dyslipidemia and cytopenia can be achieved without discontinuing rapamycin. Most other side effects are harder to manage. Leaner and younger patients are less likely to discontinue rapamycin due to side effects.

Mycobacterium genavense and chronic intermittent diarrhea in a kidney and pancreas transplant recipient.

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The Evolution of Kidney Function After Lung Transplantation: A Retrospective Cohort Study

BACKGROUND Little information exists regarding the rate of kidney functional loss after lung transplantation. The aim of this study was to assess the evolution of kidney function after lung transplantation, seeking to identify a pretransplant glomerular filtration rate (GFR) threshold under which dual lung-kidney transplantation should be considered. PATIENTS AND METHODS We performed a single-center, retrospective cohort study among patients who received a first lung transplant. GFR was measured with the MDRD7 equation immediately before and up to 10 years after transplantation. A hierarchical model of linear regression was used to determine the evolution of GFR over time. RESULTS We studied 241 subjects whose mean GFR was 92 +/- 33 mL/min/1.73 m(2) immediately before transplantation. The GFR declined quickly during the first posttransplant month (-24 mL/min/1.73 m(2) vs baseline; 95% confidence interval [CI]: -27, -21 mL/min/1.73 m(2)). It decreased slightly between 1 and 12 months (-34 mL/min/1.73 m(2) at 12 months vs baseline; 95% CI: -37, -31 mL/min/1.73 m(2)) and then stabilized up to 10 years after transplantation. GFR loss varied according to the baseline GFR. In patients with baseline GFR < or = 60 mL/min/1.73 m(2), the GFR declined by 9 mL/min/1.73 m(2) (95% CI = 6-15) at 1 year and was stable there after. CONCLUSION GFR declines rapidly in the first month and at 1 year after lung transplantation, stabilizing thereafter. Because they are likely to develop eligibility for kidney transplantation in the 1 to 2 years following lung transplantation, we believe that dual lung-kidney transplantation should definitely be considered for subjects with a baseline GFR < or = 35 mL/min/1.73 m(2).

Low-dose tacrolimus, trough-monitored mycophenolate mofetil, and planned steroid withdrawal for cadaveric kidney transplantation: a single center experience.

SEVERAL STUDIES have shown excellent graft survival and low rates of acute rejection when tacrolimus (TAC) was combined with a fixed dose of mycophenolate mofetil (MMF) and steroids. Further optimization of MMF using trough mycophenolate acid (MPA) blood levels monitoring may allow the use of lower TAC levels and steroid discontinuation. The current study is a retrospective analysis of our experience with low-dose TAC combined with trough MPA monitoring and steroid withdrawal.

Stabilization of renal function after the first year of follow‐up in kidney transplant recipients treated for significant BK polyomavirus infection or BK polyomavirus‐associated nephropathy

BK polyomavirus virus (BKPyV) screening and immunosuppression reduction effectively prevent graft loss due to BKPyV‐associated nephropathy (BKPVAN) during the first year after transplantation. The aim of our study was to evaluate the impact of this infection during longer follow‐up periods.

Varicella Zoster Virus Vasculopathy After Kidney Transplantation.

CASE 1 A 64-year-old woman developed left lower limb paresis with sciatica 3 weeks after kidney transplantation, complicated by confusion, fever, and generalized zoster rash 2weeks later. Her immunosuppression consisted of tacrolimus, mycophenolate mofetil (MMF), and prednisone without any antiviral prophylaxis (pretransplant serostatus positive for cytomegalovirus IgG, herpes simplex virus 1 IgG, EpsteinBarr virus nuclear antigen IgG, and VZV IgG). She had received an induction with basilixumab, and she never experienced acute rejection. On admission, cerebrospinal fluid (CSF) analysis showed mild pleocytosis with positive VZV using polymerase chain reaction. Brain magnetic resonance imaging (MRI) was normal. The MRI of the lumbar spine showed changes consistent with arachnoiditis. The MMF was discontinued and intravenous acyclovir (10 mg/kg 3 times daily) was started. Twelve days later, confusion worsened. Brain CT demonstrated subarachnoid hemorrhage