Cytochrome P450 (CYP) enzymes, such as CYP3A4, and CYP3A5, P450 oxidoreductase (POR), peroxisome proliferator activated receptor alpha (PPAR-alpha), and drug transporter (ABCB1) were observed to influence concentrations of immunosuppressants (cyclosporine, everolimus, sirolimus, and tacrolimus) and outcomes in renal transplants. We carried out the present study to evaluate the prevalence and impact of these single nucleotide polymorphisms (SNPs) in adult renal transplants. SNPs were evaluated using commercial TaqMan® assays. Serum drug concentrations were estimated using immunoassays. One hundred and forty-six patients were recruited. SNPs in CYP3A5*3 were significantly associated with greater dose-adjusted cyclosporine and tacrolimus concentrations. SNPs in POR*28 were observed with significantly lower dose-adjusted concentrations, particularly with cyclosporine and tacrolimus. ABCB1 homozygous polymorphisms were observed with significantly lower time spent in the therapeutic range with cyclosporine and everolimus/sirolimus. Cyclosporine was observed in a significantly greater proportion of patients with elevated GGT, and SNPs in PPAR-alpha were significantly associated with an increased risk of this adverse event. Hypertriglyceridemia with everolimus was significantly associated with POR*28 polymorphisms. There is a need to validate the influence of these SNPs in a prospective study and develop an algorithm predicting the achievement of target concentrations.

Background: Contradictory evidence exists regarding the association between serum vitamin D levels and the severity and outcomes in coronavirus 2019 (COVID-19) infected patients. We undertook the present study to evaluate the serum vitamin D levels with the other laboratory biomarkers, and the outcomes in our critically ill patients. Methods: A retrospective observational study was carried out in 58 critically ill adults. Details on their demographics, laboratory parameters such as 25-hydroxy vitamin D [25(OH)D] levels, interleukin-6, serum ferritin, lactate dehydrogenase, creatine kinase (CK), D-dimer, C-reactive protein, fibrinogen, procalcitonin, and erythrocyte sedimentation rate were retrieved. Serum 25(OH)D levels were categorized as follows: ≥50 nmol/L – normal; 30–49 – insufficient; and <30 nmol/L – deficient. Post-hoc, we also compared the outcomes between those with 25(OH)D levels of 80 nmol/L and above, with those of <80 nmol/L. Results: Fifty-eight patients were recruited of which 31 (53.4%) died. Mean ± SD serum 25(OH)D levels amongst the study participants were 48.5 ± 27.7 nmol/L. Twenty-two (37.9%) individuals had insufficient 25(OH)D levels, and 15 (25.9%) were deficient. Eight (13.8%) participants had their serum 25(OH)D levels ≥80 nmol/L. Median (range) 25(OH)D levels were not significantly different between those who died compared to those alive [41 (20–162) vs. 41 (17–86) nmol/L; p = 0.8]. Significantly higher D-dimer levels were observed amongst those with <80 nmol/L serum 25(OH)D levels. No significant differences were observed between 25(OH)D and other laboratory biomarkers except for elevated CK in patients with insufficient 25(OH)D levels. Conclusion: We did not observe any significant differences in the serum 25(OH)D levels amongst our critically ill adults who died and who were alive at the time of their admission.

Renal transplant patients receive several immunosuppressive drug regimens that are potentially nephrotoxic for treatment. Serum creatinine is the standard for monitoring kidney function; however, cystatin C (Cys C) and kidney injury molecule-1 (KIM-1) have been found to indicate kidney injury earlier than serum creatinine and provide a better reflection of kidney function. Here, we assessed Cys C and KIM-1 serum levels in renal transplant patients receiving mycophenolate mofetil, tacrolimus, sirolimus, everolimus, or cyclosporine to evaluate kidney function. We used both the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation, which is based on creatinine and combined creatinine with Cys C, and the CKD-EPI 2012 equation, which is based on Cys C alone, to estimate glomerular filtration rate (GFR). Then, we assessed the association between serum KIM-1 and GFR < 90 mL per minute per 1.73 m 2 . We observed significantly higher serum Cys C levels in patients with the elevated serum creatinine, compared with those with normal serum creatinine. The estimated GFRs based on creatinine were significantly higher than those based on the other equations, while a significant positive correlation was observed among all equations. Serum KIM-1 levels were negatively correlated with the estimated GFRs by the CKD-EPI Cys C and the combined creatinine with Cys C equations. A serum KIM-1 level above 0.71 ng/mL is likely to indicate GFR < 90 mL per minute per 1.73 m 2 . We observed a significant correlation between serum creatinine and Cys C in our renal transplant patients. Therefore, serum KIM-1 may be used to monitor renal function when using potentially nephrotoxic drugs in renal transplants.

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