Aberrant promoter hypermethylation, also known as epigenetics, is thought to be a promising biomarker approach to diagnose malignancies. Kidney repair after injury is a recapitulation of normal morphogenesis, with similarities to malignant transformation. We hypothesized that changes in urine epigenetics could be a biomarker approach during early kidney transplant injury and repair. We examined urine DNA for aberrant methylation of 2 gene promoters (DAPK CALCA) by quantitative methylation specific PCR from 13 deceased and 10 living donor kidney transplant recipients on postoperative day 2 and 65 healthy controls. Results were compared with clinical outcomes and to results of the kidney biopsy. Transplant recipients were significantly more likely to have aberrant hypermethylation of the CALCA gene promoter in urine than healthy controls (100% vs. 31%, p<0.0001). There was increased CALCA hypermethylation in the urine of deceased vs. living donor transplants (21.60 +/− 12.5 vs. 12.19 +/− 4.7 P=0.04). Furthermore, there was a trend towards increased aberrant hypermethylation of urine CALCA in patients with biopsy-proven acute tubular necrosis vs. acute rejection and slow or prompt graft function (mean: 20.40 +/− 6.9, 13.87 +/− 6.49, 17.17 +/− 13.4, P=0.67). However, there was no difference of CALCA hypermethylation in urine of patients with delayed graft function vs. those with slow or prompt graft function (16.9 +/− 6.2 vs. 18.5 +/− 13.7, respectively; P=0.5). There was no aberrant hypermethylation of DAPK in the urine of transplant patients. Urine epigenetics is a promising biomarker approach for acute ischemic injury in transplantation that merits future study.
SummaryPituitary adenomas are usually solitary lesions. Rarely, patients may present with two distinct pituitary tumors. We report a case of synchronous secretory pituitary adenomas in a woman who initially presented with elevated prolactin levels. She was initially treated with cabergoline, but, after many years, she began developing symptoms consistent with acromegaly. Imaging revealed two distinct tumors within the pituitary gland. Endocrinological investigation confirmed acromegaly. At the time of surgery, two separate tumors were identified and resected. Pathological analysis demonstrated one tumor as a prolactinoma, and the other tumor as a GH-secreting adenoma. Postoperatively, her GH and IGF1 levels normalized, while the prolactin level remained slightly above normal. This case highlights that GH and prolactin level elevation is not always from co-secretion by the same adenoma.Learning points Synchronous pituitary adenomas represent <0.5% of pituitary tumors requiring surgery.In the setting of elevated GH and prolactin levels, one cannot assume that they are co-secreted by the same adenoma.A careful study of hormonal workup and pre-operative imaging is necessary for synchronous pituitary adenomas to assure resection of both tumors.
Charcoal hemoperfusion is an effective treatment in acute drug intoxication with small volume of distribution. For certain drugs, clearance rates are higher with hemoperfusion than hemodialysis. We describe a patient with severe valproic acid overdose who developed severe hemolysis and acute renal failure related to charcoal hemoperfusion treatment. A 50‐year‐old female was admitted to the hospital following valproic acid overdose. Initial valproic acid level was 73.6 mg/L, and she was treated with oral activated charcoal. Four hours later she developed mental status changes with valproic acid level at 490.9 mg/L and prolonged QT interval. Charcoal hemoperfusion was started with blood flow rate 400 ml/min. Patient developed bleeding with evidence of severe Before(*C.H.) After (C.H.) Hemoglobin12.1 gm/DL7.6 gm/DLHematocrit35.5 gm/DL21.1 gm/DLPlatelet count268,000 tho/ul43,000 tho/ulL.D.H90 IU/L2494 IU/LValproic Acid490.9 mg/L74.1 mg/L * C.H. (Charcoal Hemoperfusion) Blood – evidence of massive hemolysis intra‐vascular hemolysis, shown in table (no evidence of HUS/TTP). She received transfusion of packed red blood cells, platelets, and fibrin. Over the next few days she developed oligouric acute renal failure requiring hemodialysis for 2 weeks. Eventually hemolysis resolved and the renal function improved (kidney biopsy was consistent with acute tubular necrosis). To our knowledge, this is the first reported case of severe intravascular hemolysis occurring during the charcoal hemoperfusion treatment. Etiology includes mechanical trauma to the red cells, probably related to high blood flow rate through the charcoal column.
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