Value of Intraoperative Parathyroid Hormone Assay during Parathyroidectomy in Dialysis and Renal Transplant Patients with Secondary and Tertiary Hyperparathyroidism.

BACKGROUND: In dialysis and renal transplant patients with secondary and tertiary hyperparathyroidism (HPT), the value of intraoperative parathyroid hormone (ioPTH) during parathyroidectomy (PTX) and its association with long-term PTH levels are unknown. The present study aims at evaluating the relationship of ioPTH with long-term PTH levels post-PTX in dialysis and renal transplant patients in a single-center study. METHODS: The ioPTH was measured in 57 dialysis patients (33 females and 24 males) and 18 renal transplant recipients (12 males and 6 females) who underwent PTX from 2005 to 2015 for refractory HPT. Near-total PTX was performed in 56 patients and total PTX with autotransplantation in 20 patients. The PTH monitoring included 3 samples: pre-intubation, 10- and 20-min (pre-ioPTH, 10-ioPTH, and 20-ioPTH) post parathyroid gland excision. Patients were followed up for up to 5 years. RESULTS: In the dialysis group, the median (25th-75th percentile) pre-, 10-, and 20-ioPTH levels were 1,447 pg/mL (938-2,176), 143 pg/mL (78-244) and 112 pg/mL (59-153) respectively. In the renal transplant group, pre-, 10-, and 20-ioPTH levels were 273 pg/mL (180-403), 42 pg/mL (25-72), and 34 pg/mL (23-45) respectively. All patients in the transplant group had a functional kidney transplant at the time of PTX with a median serum creatinine of 1.3 mg/dL (1.2-1.7) and estimated glomerular filtration rate of 55 mL/min (40-60). The median time between renal transplant and PTX surgeries was 22 months (7-81). The last median follow-up PTH level was 66 pg/mL (15-201) in the dialysis group and 54 pg/mL (17-72) in the transplant group (p = 0.438). The mean time for last PTH post-PTX was 2.3 ± 2.0 years. In both groups, there was no significant difference between 20-ioPTH and any-time post-PTX PTH levels (p = 0.6 and p = 0.9). Nineteen patients (25%) were readmitted within 90 days because of hypocalcemia. One patient in the dialysis group was readmitted for post-PTX hematoma evacuation. No patient required repeat PTX because of recurrent HPT that was refractory to medical therapy. Only one dialysis patient required repeat PTX because the first procedure failed. CONCLUSIONS: The 20-ioPTH is a good indicator of long-term PTH levels in dialysis and renal transplant patients. Hypocalcemia is a common complication, particularly in dialysis patients, and it is the main reason for readmission after PTX. Hypoparathyroidism is a potential concern after PTX in dialysis patients.

Acetylation of histone H3 at the nucleosome dyad alters DNA-histone binding.

Histone post-translational modifications are essential for regulating and facilitating biological processes such as RNA transcription and DNA repair. Fifteen modifications are located in the DNA-histone dyad interface and include the acetylation of H3-K115 (H3-K115Ac) and H3-K122 (H3-K122Ac), but the functional consequences of these modifications are unknown. We have prepared semisynthetic histone H3 acetylated at Lys-115 and/or Lys-122 by expressed protein ligation and incorporated them into single nucleosomes. Competitive reconstitution analysis demonstrated that the acetylation of H3-K115 and H3-K122 reduces the free energy of histone octamer binding. Restriction enzyme kinetic analysis suggests that these histone modifications do not alter DNA accessibility near the sites of modification. However, acetylation of H3-K122 increases the rate of thermal repositioning. Remarkably, Lys --> Gln substitution mutations, which are used to mimic Lys acetylation, do not fully duplicate the effects of the H3-K115Ac or H3-K122Ac modifications. Our results are consistent with the conclusion that acetylation in the dyad interface reduces DNA-histone interaction(s), which may facilitate nucleosome repositioning and/or assembly/disassembly.