Biomarkers
Biomarkers can help diagnosis because they can point to the presence or severity of sepsis, although their exact role in the management of sepsis remains undefined. A 2013 review concluded moderate-quality evidence exists to support the use of the procalcitonin level as a method to distinguish sepsis from non-infectious causes of SIRS. The same review found the sensitivity of the test to be 77% and the specificity to be 79%. The authors suggested that procalcitonin may serve as a helpful diagnostic marker for sepsis, but cautioned that its level alone does not definitively make the diagnosis. A 2012 systematic review found that soluble urokinase-type plasminogen activator receptor (SuPAR) is a nonspecific marker of inflammation and does not accurately diagnose sepsis. This same review concluded, however, that SuPAR has prognostic value, as higher SuPAR levels are associated with an increased rate of death in those with sepsis. Serial measurement of lactate levels (approximately every 4 to 6 hours) may guide treatment and is associated with lower mortality in sepsis. Differential diagnosis
The differential diagnosis for sepsis is broad and has to examine (to exclude) the non-infectious conditions that may cause the systemic signs of SIRS: alcohol withdrawal, acute pancreatitis, burns, pulmonary embolism, thyrotoxicosis, anaphylaxis, adrenal insufficiency, and neurogenic shock. Hyperinflammatory syndromes such as hemophagocytic lymphohistiocytosis (HLH) may have similar symptoms and are on the differential diagnosis.
Adverse effects
Voclosporin has a boxed warning for malignancies and serious infections. Patients taking Voclosporin along with other immunosuppressants have an increased risk for developing malignancies and serious infections that may lead to hospitalization or death. The most common adverse reactions of voclosporin were (>3%), glomerular filtration rate decreased, hypertension, diarrhea, headache, anemia, cough, urinary tract infection, abdominal pain(upper), dyspepsia, alopecia, renal impairment, abdominal pain, mouth ulceration, fatigue. tremor, acute kidney injury, and decreased appetite. Pharmacology
Voclosporin is a cyclosporin A analog, similar to cyclosporin A with modifications on an amino acid within one region that allows the drug to bind to Calcineurin. Voclosporin inhibits calcineurin, which then blocks the production of IL-2 and T-cell mediated immune responses. As a result of the calcineurin inhibition, podocytes (cells within the kidneys) are stabilized while inflammation is reduced. Reduction of inflammation within the kidneys prevents further renal damage. Pharmacokinetics
When administered on an empty stomach, the median Tmax of voclosporin is 1.5 hours. The AUC is estimated to be 7693 ng/mL and the Cmax  is estimated at 955 ng/mL. The volume of distribution is approximately 2,154 L and distributes within the red blood cells. The distribution between the plasma and whole blood is affected by temperature and concentration. The protein binding of voclosporin is 97%. The average terminal half-life of voclosporin is 63.6 L/h. The drug is mainly metabolized by the CYP3A4 hepatic cytochrome enzyme. Pharmacologic activity is mainly attributed to the parent molecule itself, with the major metabolite being 8-fold less potent than the parent drug.