Immunosuppression Therapy in Kidney Transplantation.

Kidney transplantation is the preferred choice of treatment of end-stage kidney disease (ESKD). Improvement in surgical techniques and immunotherapy has transformed the field of kidney transplantation. Patients undergoing a kidney transplant have a 95% and 90% graft survival rate at one and 5 years. Although advances in immunosuppressive agents have reduced the incidence of acute rejection, the outcome of kidney grafts is still limited by chronic rejection and complications of these medications. The goal of kidney transplantation is to use the combination of immunosuppressive agents that best optimizes allograft and patient survival while limiting drug toxicity and complications. In this review, the immunology of transplantation is described with a focus on current immunosuppressive agents used in kidney transplantation.

Interaction between socioeconomic deprivation and likelihood of pre-emptive transplantation: influence of competing risks and referral characteristics - a retrospective study.

Socioeconomic deprivation (SED) influences likelihood of pre-emptive kidney transplantation (PET), but the mechanisms behind this are unclear. We explored the relationships between SED and patient characteristics at referral, which might explain this discrepancy. A retrospective cohort study was performed. SED was measured by Scottish Index of Multiple Deprivation (SIMD). Logistic regression evaluated predictors of PET. A competing risks survival analysis evaluated the interaction between SED and progression to end-stage kidney disease (ESKD) and death. Of 7765 patients with follow-up of 5.69 ± 6.52 years, 1298 developed ESKD requiring RRT; 113 received PET, 64 of which were from live donors. Patients receiving PET were "less deprived" with higher SIMD (5 ± 7 vs. 4 ± 5; P = 0.003). This appeared independent of overall comorbidity burden. SED was associated with a higher risk of death but not ESKD. Higher SIMD decile was associated with a higher likelihood of PET (OR 1.14, 95% CI 1.06, 1.23); the presence of diabetes and malignancy also reduced PET. SED was associated with reduced likelihood of PET after adjustment for baseline comorbidity, and this was not explained by risk of death or faster progression to ESKD. Education and outreach into transplantation should be augmented in areas with higher deprivation.

Five-year outcomes after a change from a cyclosporin-based to a 'low-dose' tacrolimus-based primary immunosuppression regimen for incident kidney transplants--the Glasgow experience.

In January 2007, our centre changed from a cyclosporin (CyA)/azathioprine (Aza)/ prednisolone (Pred) primary immunosuppression regimen (with basiliximab induction and mycophenolate mofetil [MMF] for those at immunologically high risk) to a tacrolimus (Tac) (low dose)/MMF/Pred regimen with basiliximab induction, following presentation of Symphony trial results. This analysis assesses the impact of this change on 5-year outcomes. Three hundred consecutive renal-only transplants were identified: 140 from the 2005-06 era and 160 from the 2007-08 era. The proportions of living donor (37.5 vs. 22.9%; p = 0.04) and donors after circulatory death (11.9 vs. 5.0%; p = 0.03) were higher in the 2007-08 cohort. Five-year actuarial patient survival was higher in the 2007-08 cohort (96.8 vs. 87.1%; p = 0.003), with a trend toward higher 5-year transplant survival (84.7 vs. 76.3%; p = 0.08). Estimated glomerular filtration rate (eGFR) was higher than in the 2005-06 era at 1 (53.5 vs. 44.5 ml/min/1.73m2; p = 0.0006) and 3 years (50.9 vs. 43.4 ml/min/1.73m2; p = 0.02), with a trend toward higher eGFR at 5 years (41.8 vs. 49.6 ml/min/1.73m2; p = 0.09). Differences were consistent when living donor and deceased donor transplants were analysed separately. In a "real world" population, a change from a CyA-based to a Tac (low-dose)/MMF/Pred primary immunosuppression regimen has been associated with better 5-year outcomes.

Long-term outcome of transplant renal artery stenosis managed conservatively or by radiological intervention.

The natural history and optimal treatment of transplant renal artery stenosis (TRAS) is poorly defined. Few studies reported long-term clinical outcomes. A single centre analysis of 43 patients diagnosed with TRAS 1990-2003 was performed. Twenty-seven had percutaneous intervention (including 10 patients who had >1 intervention) and 16 were managed conservatively at the discretion of the attending clinicians. Transplant function was assessed by slope of estimated glomerular filtration rate (eGFR) over five yr of follow-up. Patients in the intervention group had lower mean eGFR (36.3 mL/min/1.73 m(2) vs. 46.3 mL/min/1.73 m(2); p = 0.07) at baseline. Five transplants in the intervention group failed (including two as a direct result of intervention) and one in the conservative group failed. There was no significant difference in the rate of deterioration in renal function (mean slope of eGFR minus 0.8 mL/min/yr and minus 1.0 mL/min/yr in the intervention and conservative groups, respectively; p = 0.79). There was no significant difference in blood pressure or number of anti-hypertensive agents between the groups at any time point. Baseline Doppler ultrasound indices showed no significant correlation with slope of eGFR in either group. Our data demonstrate that selected patients with TRAS can be managed without intervention and that this approach is associated with good long-term outcome. Selection of appropriate patients for intervention remains difficult and larger randomized studies are required.

Derived equations are not precise enough to predict the adequacy of creatinine clearance in peritoneal dialysis patients.

BACKGROUND: Most renal units assess dialysis adequacy in peritoneal dialysis (PD) patients by formal 24-hour collections of urine and effluent dialysate. We sought a reliable method of predicting dialysis adequacy that allows a decrease in the frequency of these formal and cumbersome measurements. METHODS: We created a formula for estimating total creatinine clearances, then assessed the clinical utility of this formula and other published formulae in predicting adequate and inadequate dialysis in PD patients. We collected data over a 6-month period in 2001 from 288 PD patients from 9 centers in Scotland. Four out of every 5 patients were selected at random to create a formula for estimating total creatinine clearance per week, and the fifth patient was used to form a validation group. We plotted creatinine excretion against age, and the resultant linear regression equation was transformed to produce a formula for predicting total creatinine clearance per week, based on patient sex, weight, and serum creatinine. We used the data from the validation subgroup to calculate predictive values for our derived formula and data from all of the patients to calculate predictive values for the Cockcroft and Gault, Jones, and Modification of Diet in Renal Disease Study formulae. RESULTS: Neither our derived formula nor the three published formulae were sufficiently powerful to predict accurately either adequate or inadequate PD clearance. Receiver operator characteristic curves showed that no significant improvement in these predictive values could be achieved by altering either the sensitivity or the specificity. CONCLUSION: Prediction formulae are not accurate enough to detect underdialysis in PD patients.