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Title: Studies in chronic allograft nephropathy
Author: Stoves, John
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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Clinical management of renal transplant recipients (RTRs) should include anticipation, prevention, early detection and optimal of CAN. Pilot studies of mycophenolate mofetil (MMF) treatment for CAN are small, use non-reference measures of renal function and lack comparative control group data. We have performed a multicentre prospective controlled study involving adult CsA-treated RTRs with biopsy-proven CAN and a negatively sloping reciprocal of serum creatine versus time (ROCT) plot. The treatments were: A. MMF and reduced dose CsA; B. Tacrolimus for CsA; C. Continuation of CsA. Results. The study involved 42 patients over 36/12 (7/99 – 6/02). GFR (99mTc-DTPA clearance) was measured at baseline and 6/12. One patient in group A another in group B started dialysis prior to study completion. 7 patients in group A reported new gastro-intestinal symptoms and 3 developed progressive anaemia necessitating MMF dose reduction. CsA dose was reduced by 24% (interquartile range (IQR) 14% - 27%) in group A, giving an end-of-study trough CsA blood level (C0) of 99 (IQR 90-113) ng/ml. The maintenance dose of MMF in group A was 1.5 (IQR 1.5 -2) g/day. The end-of-study tacrolimus C0 in group B was 7 (IQR 5 – 9) ng/ml. The end-of-study CsA C0 in group C was 163 (IQR 145 – 215) ng/ml. Comparison of ROCT slopes before (-12/12 – 0) and after (0 – 6/12) intervention revealed a treatment advantage for group A (p < 0.05). Comparison of the pre-study and 3/12 – 12/12 ROCT slopes (to isolate the early effect of CsA dose reduction on renal transplant haemodynamics) showed a non-significant difference between treatment groups (group A vs group C, p = 0.08). The GFR analysis also suggested a treatment advantage for group A (p = 0.05). Exclusion of patients with initial GFR (GFR0) < 20 ml/min/1.73m2 gave a result that was statistically and clinically more striking (n = 27, p < 0.05). An ANCOVA model showed that GFR0 predicted therapeutic response (p < 0.05). Conclusions. There is more effective preservation of renal function in CAN with a regimen of MMF/reduced dose CsA as compared to tacrolimus-for-CsA and standard dose CsA regimens, at least in the short term. The CsA dose reduction component of the regimen is likely to be of particular importance. Other findings suggest that early intervention is beneficial.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available