Summary
C4d immunostaining in the peritubular capillaries (PTC) is a marker of antibody‐mediated rejection (AMR). We evaluated the histopathologic diagnoses of 388 renal transplant biopsies since the implementation of routine C4d immunostaining at our center. Of these, 155 (40%) biopsies had evidence of acute cellular rejection (ACR), out of which 119 (77%) had pure ACR, 31 (20%) had ACR with concomitant features of AMR, and five (3%) had ACR with focal C4d staining. Sixty‐four (16%) biopsies exhibited features of AMR [33 (52%) pure AMR, and 31(48%) concomitant AMR and ACR]. One hundred and fifty‐five (40%) biopsies had features of interstitial fibrosis and tubular atrophy (IFTA). Of these, 20 (13%) had concomitant AMR [13 (8.5%) had pure AMR and seven (4.5%) had concomitant ACR and AMR]. Creatinine at the time of biopsy was higher in patients with mixed ACR and AMR and the clinical behavior of mixed lesions is more aggressive over time. Despite having a lower serum creatinine at the time of biopsy, patients with IFTA experienced gradual decline in graft function over time. The pathologic findings in renal allograft biopsies are often mixed and mixed lesions appear to have more aggressive clinical behavior. These findings suggest the need for change in the Banff classification system to better capture the complexity of renal allograft pathologies.
Background: Renin-angiotensin system (RAS) inhibition has proven to be helpful in reducing cardiovascular and kidney disease progression in the general population; whether kidney transplant patients would derive similar benefits is unknown. RAS inhibition also reduces posttransplantation erythrocytosis in kidney transplant recipients, but its effect on hemoglobin (Hb) levels in patients without posttransplantation erythrocytosis is unclear. Methods: The Specific Management of Anemia and Hypertension in Renal Transplant (SMAhRT) recipients study was designed to examine the cardiovascular benefits of RAS blockade with telmisartan 80 mg versus placebo, and Hb management with darbepoetin α in a randomized, double-blind, single-center controlled trial in 2,000 patients over 3 years. The primary efficacy variable was a composite of all-cause mortality, myocardial infarction or stroke. Results: The SMAhRT study was stopped prematurely due to a lower than expected event rate. At that point, 136 patients were enrolled and were followed for a mean duration of 15 months. The use of RAS blockade was not associated with an increased risk of adverse events such as worsening anemia or hyperkalemia. Likewise, the correction of Hb with darbepoetin was not associated with any increase in thrombotic events. Conclusions: This study provides insight into the safety of RAS inhibition and Hb correction with an erythrocyte-stimulating agent in kidney transplant recipients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.