Hypertension after kidney transplantation.

BACKGROUND: Few studies have examined the possible role of blood pressure (BP), independent of acute rejection and graft function, on outcomes after kidney transplantation. METHODS: We investigated the prevalence, treatment, control, and clinical correlates of hypertension and its association with outcomes, using multivariate analyses with time-dependent covariates, in a retrospective cohort of 1,666 kidney transplant recipients. RESULTS: Hypertension was common, and its control was poor. For example, at 1 year, only 55.5% had a BP less than 140 mm Hg. Control improved only slightly in 1993-2002 compared to 1976-2002, even as patients administered 2 or more antihypertensive medications at 1 year increased from 43.5% to 54.6%. Independent correlates of higher BP included male sex, age, donor age, diabetes, body mass index, the presence of native kidneys, and delayed graft function. Previous acute rejection was associated with higher BP at virtually all times after transplantation, and these associations were independent of estimated creatinine clearance (C(Cr)). Conversely, an association between BP and subsequent acute rejection was not statistically significant when differences in C(Cr) were taken into account. After adjusting for the effects of acute rejection, C(Cr), and other variables, each 10 mm Hg of systolic BP was associated with an increased relative risk for graft failure (1.12; 95% confidence interval, 1.08 to 1.15; P < 0.0001), death-censored graft failure (1.17; 1.12 to 1.22; P < 0.0001), and death (1.18; 1.12 to 1.23; P < 0.0001). CONCLUSION: High BP is closely tied to graft function, but nevertheless is an independent risk factor for graft failure and mortality. Better strategies are needed to control BP after kidney transplantation.

Defining the risk of elective cyclosporine withdrawal in stable kidney transplant recipients.

Although it is known that elective cyclosporine (CsA) withdrawal increases the risk for acute rejection, few studies have been large enough to identify risk factors for acute rejection after CsA withdrawal. We examined risk factors for acute rejection in 464 kidney transplant recipients who underwent elective CsA withdrawal. The incidence of acute rejection within 6 months of CsA withdrawal was 20/141 (14.2%) in the period January 1986 to May 1989, but only 14/323 (4.5%) since May 1989 (p = 0.0002). Among those transplanted since May 1989, the incidence was 5/20 (25%) for those with both 2 HLA-B and 2 HLA-DR mismatches, compared with only 9/298 (3.0%) for those with fewer mismatches (p < 0.0001). In Cox proportional hazards analysis, risk factors for acute rejection within 6 months, or at any time after elective CsA withdrawal, were date of transplant January 1986 to May 1989 (compared with more recently May 1989 to March 1999), younger age, obesity, as well as B and DR mismatches. Recipient race (83% were white), acute rejection during the first year before withdrawal (31%), mycophenolate mofetil (17%), and other variables failed to predict postwithdrawal acute rejection. We concluded that avoiding CsA withdrawal in the relatively small number of recipients with both 2 HLA-B and 2 HLA-DR mismatches could further reduce our already low incidence of acute rejection following elective CsA withdrawal.

A thirty percent chronic decline in inverse serum creatinine is an excellent predictor of late renal allograft failure.

We previously reported that the percentage of change in inverse serum creatinine (Delta1/Cr) was the best of several time-dependent serum creatinine-derived predictors of renal allograft failure in patients not administered cyclosporine (CsA). To further validate the utility of Delta1/Cr, we collected creatinine levels (mean, 90.7 +/- 45.2 creatinine measurements) in 100 patients treated for 6.7 +/- 5.9 years with CsA. We also validated Delta1/Cr using a limited creatinine-sampling strategy, then performed multivariate Cox proportional hazards analysis of 1,663 transplantations. A time-dependent covariate determined by the date of first chronic decline (excluding creatinine levels from periods of acute rejection) in Delta1/Cr to less than -30% of baseline similarly was predictive of graft failure in 101 patients treated without CsA (relative risk, 5.04; 95% confidence interval, 2.18 to 11.6; P = 0.0002) and 100 patients treated with CsA (relative risk, 5.02; 95% confidence interval, 2.50 to 10.1; P < 0.0001). A limited creatinine-sampling strategy (measured at 1 week, 1, 3, 6, 12, 18, 24, and 36 months, and each year thereafter) reduced the ability of Delta1/Cr less than -30% to predict graft failure. In 1,663 patients, Delta1/Cr less than -30% first occurred a median of 1.0 years posttransplantation (n = 792 of 1,663 patients) and 3.0 years before graft failure (n = 478 of 897 patients with graft failure). In a multivariate model (n = 1,663) that included baseline function, acute rejection, and other covariates, Delta1/Cr less than -30% was a strong independent predictor of graft failure (relative risk, 2.56; 95% confidence interval, 2.12 to 3.09; P < 0.0001). Thus, Delta1/Cr less than -30% is an excellent predictor of graft failure that is similarly predictive in patients treated with and without CsA. A limited sampling strategy for creatinine diminishes, but does not negate, the usefulness of Delta1/Cr less than -30%.