Troponin I levels and postoperative myocardial infarction following renal transplantation.

BACKGROUND: The relationship of routine postoperative troponin I (TnI) monitoring in kidney transplant recipients and in-hospital myocardial infarction (MI) is not known. METHODS: This observational study evaluated the prevalence of abnormal postoperative TnI (Ortho Clinical Diagnostics assay) in 376 consecutive kidney or kidney/pancreas transplant recipients. In-hospital MI was adjudicated using the universal definition. Rates of death and coronary revascularizations at 1 year were studied. Logistic regression analysis was performed to identify independent predictors of abnormal TnI. RESULTS: Ninety-five (25%) recipients had abnormal TnI (>0.04 ng/ml) following transplantation. Abnormal TnI levels were more common in older (mean age: 52.2 ± 13.4 vs. 48.3 ± 13.2 years, p = 0.01), diabetic (57.9 vs. 45.6%, p = 0.04), and prior coronary artery disease (31.6 vs. 20.3%, p = 0.02) patients. In-hospital MI occurred in 6 patients (1.6%). All subsequent in-hospital cardiovascular events occurred in the abnormal postoperative TnI group; most in those with TnI levels >1 ng/ml. Previous coronary artery disease was the only independent predictor of a postoperative TnI level >1 ng/ml in multivariate analysis (odds ratio 4.61, 95% confidence interval 1.49-14.32). At 1 year there was no significant difference in death (3.2 vs. 1.8%, p = 0.42) and borderline significant difference in coronary revascularization (5.3 vs. 1.4%, p = 0.049) in abnormal versus normal TnI groups. CONCLUSIONS: In-hospital MI was infrequent, but abnormal TnI highly prevalent following renal transplantation. Normal TnI levels following renal transplantation had a high negative predictive value in excluding patients likely to develop subsequent postoperative MI. The role of a higher TnI cut-off for screening for postoperative MI in high-risk subgroups deserves future prospective evaluation.

Similar outcomes with different rates of delayed graft function may reflect center practice, not center performance.

To better understand the implications for considering delayed graft function (DGF) as a performance measure, we compared outcomes associated with a 2- to 3-fold difference in the incidence of DGF at two transplant centers. We analyzed 5072 kidney transplantations between 1984 and 2006 at the University of Minnesota Medical Center (UMMC) and Hennepin County Medical Center (HCMC). In logistic regression the adjusted odds ratio for DGF at HCMC versus UMMC was 3.11 (95% Confidence Interval [CI]= 2.49-3.89) for deceased donors and 2.24 (CI = 1.45-3.47) for living donors. In Cox analysis of 4957 transplantations, slow graft function (SGF; creatinine >or=3.0 mg/dL [230 micromol/L] on day 5 without dialysis) was associated with graft failure at UMMC (Relative Risk [RR]= 1.43, CI = 1.25-1.64), but not HCMC (RR = 0.99, CI = 0.77-1.28). RR's of DGF were similar at both centers. Thus, the lower incidence of DGF at UMMC likely resulted in a higher incidence and higher risk of SGF compared to HCMC. Indeed, graft survival for recipients with DGF at HCMC was similar (p = 0.3741) to that of recipients with SGF at UMMC. We conclude that dialysis per se is likely not a cause of worse graft outcomes. A better definition is needed to measure early graft dysfunction and its effects across transplant programs.

Pregnancy outcomes after kidney donation.

The outcome of pregnancy in kidney donors has generally been viewed to be favorable. We determined fetal and maternal outcomes in a large cohort of kidney donors. A total of 2102 women have donated a kidney at our institution; 1589 donors responded to our pregnancy surveys; 1085 reported 3213 pregnancies and 504 reported none. Fetal and maternal outcomes in postdonation pregnancies were comparable to published rates in the general population. Postdonation (vs. predonation) pregnancies were associated with a lower likelihood of full-term deliveries (73.7% vs. 84.6%, p = 0.0004) and a higher likelihood of fetal loss (19.2% vs. 11.3%, p < 0.0001). Postdonation pregnancies were also associated with a higher risk of gestational diabetes (2.7% vs. 0.7%, p = 0.0001), gestational hypertension (5.7% vs. 0.6%, p < 0.0001), proteinuria (4.3% vs. 1.1%, p < 0.0001) and preeclampsia (5.5% vs. 0.8%, p < 0.0001). Women who had both pre- and post-donation pregnancies were also more likely to have these adverse maternal outcomes in their postdonation pregnancies. In this large survey of previous living donors in a single center, fetal and maternal outcomes and pregnancy outcomes after kidney donation were similar to those reported in the general population, but inferior to predonation pregnancy outcomes.

Earlier is not necessarily better in preemptive kidney transplantation.

While preemptive (before chronic dialysis) transplantation is associated with improved graft survival, it is unclear whether higher versus lower pretransplant kidney function is associated with even better graft survival after preemptive transplantation. We examined 671 first, preemptive, kidney-only transplantations at Hennepin County Medical Center and the University of Minnesota Medical Center 1984-2006. We estimated pretransplant glomerular filtration rate (eGFR, mL/min/1.73 m(2)) using the Modification of Diet in Renal Disease (MDRD) equation with Group 1: <10.0 (7.3 +/- 1.7, N = 324), Group 2: 10.0-14.9 (12.0 +/- 1.4, N = 217) and Group 3: >or=15.0 (21.1 +/- 10.0, N = 130). The mean difference in eGFR for Group 1 versus 3 was 13.8 pretransplant, 16.3 on day 1 and 13.9 on day 2 posttransplant. By week 1 and year 1 posttransplant, the differences between Groups 1 and 3 reduced to 6.3 and 4.5 mL/min/1.73 m(2), respectively. The adjusted relative risk (RR; Cox analysis) for graft failure was not significantly lower with higher pretransplant eGFR (reference eGFR <10.0); RR = 0.99 (95% confidence interval = 0.68-1.44, p = 0.9432) for eGFR 10.0-14.9; RR = 1.35 (0.89-2.05, p = 0.1588) for eGFR >or=15. Thus, early preemptive transplantation with higher eGFR does not necessarily improve graft survival after kidney transplantation, compared to preemptive transplantation with lower pretransplant eGFR.

GDNF rescues nonpeptidergic unmyelinated primary afferents in streptozotocin-treated diabetic mice.

Sensory deficits induced by diabetes commonly affect small unmyelinated peptidergic and nonpeptidergic sensory neurons. The peptidergic population responds to nerve growth factor (NGF), while the nonpeptidergic DRG neurons postnatally switch their dependency from NGF to glial cell line-derived neurotrophic factor (GDNF). Recent studies have demonstrated that deficient NGF support of peptidergic nociceptors is involved in problems with small-fiber diabetic neuropathy. To determine if nonpeptidergic GDNF-responsive neurons are similarly affected by hyperglycemia, diabetes was induced in mice using streptozotocin (STZ). Four weeks following diabetes induction, staining of axon terminals of nonpeptidergic unmyelinated neurons labeled with the isolectin IB4 or enzyme activity for thiamine monophosphatase (TMP) was reduced in lamina IIi of the lumbar dorsal horn, particularly in the medial region which receives distal sciatic afferents. In contrast, NGF-responsive CGRP-immunoreactive (ir) axons showed no or only a slight decrease in spinal terminations. Insulin treatment in diabetic mice failed to improve deficits in IB4/TMP central afferents. To test whether GDNF or NGF could restore spinal deficits in nonpeptidergic afferents, STZ-treated mice were treated intrathecally for 2 weeks with NGF or GDNF. NGF administration enhanced CGRP-ir staining but failed to improve IB4/TMP projections. GDNF treatment had no effect on CGRP-ir projections but restored TMP labeling in lamina IIi. Our results demonstrate that nonpeptidergic unmyelinated sensory neurons are vulnerable to diabetes and that GDNF administration can selectively reverse deficits caused by diabetes in the IB4/TMP subpopulation.