ABSTRACT
Hypercalcemia is a common and potentially serious electrolyte abnormality that is often observed in patients with chronic kidney disease (CKD). When malignancy is considered, parathyroid hormone-related protein (PTHrP) levels are often measured. PTHrP is produced by cancer cells and mimics the effects of parathyroid hormone (PTH) to elevate serum calcium concentrations. The amino and carboxy termini of PTHrP are of functional relevance. C-terminal PTHrP levels accumulate with CKD and can be elevated in normocalcemic CKD patients who lack malignancy. The existence of amino (N)-terminal and carboxy (C)-terminal PTHrP assays and how their concentrations are impacted by CKD are reviewed herein. The case of a patient on maintenance hemodialysis who developed prolonged hypercalcemia with elevated PTHrP concentrations is presented. The workup revealed suppressed intact PTH, low 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D levels. The initial PTHrP assay returned elevated. However, it was unappreciated that it was the C-terminal assay and the patient underwent an unnecessary search for malignancy. A subsequent N-terminal PTHrP assay returned within the normal range. Many commercial labs run the C-terminal PTHrP assay as their first-line test. This can lead to inaccurate differential diagnoses in hypercalcemic patients with CKD. We emphasize the need to specifically request N-terminal PTHrP assays in patients with advanced kidney disease when humoral hypercalcemia of malignancy is suspected.
ABSTRACT
BACKGROUND: Acute kidney injury (AKI) is a common cause of morbidity and mortality. It mainly targets the renal tubular epithelium with pathological changes, referred to as acute tubular injury. The latter is followed by a regenerative response that is difficult to visualize on routine hematoxylin and eosin (H&E) stains. In this study, we examined the regenerative capacity of renal tubules by correlating vimentin (VIM) immunohistochemical (IHC) expression and pathological findings of AKI and renal tubular regeneration (RTR) on H&E. METHODS: We reviewed 23 autopsies performed in the clinical setting of AKI and RTR. VIM expression was scored in the renal cortical tubular epithelium using a statistical cutoff ≥ 3% for high expression and < 3% for low expression. RESULTS: Of the 23 kidney tissues examined, seven (30.4%) had low VIM expression, and 16 (69.6%) had high VIM expression. Kidney tissues with evidence of AKI and RTR had significantly higher VIM expression. Renal peritubular microenvironment features showing regenerative changes on H&E were associated with high VIM expression. In the univariate model, kidney tissues with RTR were 18-fold more likely to have high VIM expression. CONCLUSIONS: In conclusion, our findings suggest that VIM could serve as an IHC marker for RTR following AKI. However, correlation with H&E findings remains critical to excluding chronic tubular damage. Collectively, our preliminary results pave the way for future studies including a larger sample size to validate the use of VIM as a reliable biomarker for RTR.
ABSTRACT
In developed countries, tuberculosis remains a health care challenge due to human immunodeficiency virus (HIV) and immigration from endemic regions. The Centers for Disease Control and Prevention reported 9557 new cases in 2015, with extrapulmonary involvement in 20.2% of the cases. We present a 33-year-old woman from Cape Town, South Africa, who developed abdominal pain and fever while working on a cruise ship. She sought medical where she underwent computed tomography of her chest, abdomen, and pelvis with findings suggestive of pulmonary tuberculosis and an 8.9-cm pelvic mass. HIV testing was positive and the patient was started on antiretroviral therapy. Bronchoscopy confirmed the presence of acid-fast bacilli, and she was started on rifampin, isoniazid, pyrazinamide, and ethambutol. She remained persistently febrile, raising suspicion for immune reconstitution inflammatory syndrome. However, despite empiric antibiotics, the patient remained persistently febrile, tachycardic, and on day 10 of admission she went into ventricular fibrillation and expired. Autopsy revealed an occlusive thrombus in the left main pulmonary artery in addition to necrotizing granulomata in multiple organs and bilateral tubo-ovarian abscesses. Postmortem cultures for were positive for Mycobacterium tuberculosis, all consistent with disseminated Mycobacterium tuberculosis. Although previous reports underscore the association between tuberculosis and hypercoagulability, the exact mechanism remains unknown. In this article, we report a case of disseminated tuberculosis complicated by bilateral tubo-ovarian abscesses with fatal pulmonary thrombus formation.
