Importance of Glomerular Filtration Rate Determination and its Role in Drug-Dose Adjustments with Special Reference to Oncology

Abstract

Glomerular filtration Rate (GFR) measured in steady state is the best marker of kidney function. Glomerular filtration rate can be determined using exogenous markers like inulin, iothalamate, or iohexol (mGFR), or estimated using endogenous markers like creatinine and cystatin C (eGFR). Several equations are available, CKD-EPI equation is the recommended equation as per current guidelines. CKD-EPI creatinine equation refit (without the race variable) – 2021, and CKD-EPI creatinine - cystatin C equation refit (without the race variable)-2021 are the most recent recommendations from the National Kidney Foundation and the American Society of Nephrology. Dose modifications of many drugs are needed in kidney dysfunction. In chronic kidney disease, as the kidney function is stable, determination of GFR is more accurate and can be used to modify the drug doses. Since the kidney function is not stable in acute kidney injury, determination of GFR is more difficult and it is not accurate. This makes it difficult to use it for determining dose modifications of drugs. Therapeutic drug level monitoring, and adjusting the dose based on pharmacokinetics/pharmacodynamics knowledge of the drug could be helpful in such cases. In oncology, accurate GFR measurement is crucial for adjusting the doses of chemotherapeutic agents to avoid toxicity and ensure efficacy, as cancer patients often have compromised kidney function due to the disease or its treatment. In this manuscript, we review all these aspects to provide a comprehensive understanding of GFR measurement and its implications in drug-dose adjustments, with a particular focus on how accurate GFR assessment is essential for optimizing chemotherapy dosing in oncology patients to minimize toxicity and maximize therapeutic efficacy. Frequently, medical professionals need to depend on online calculators to get the value of eGFR, as these equations can be complicated. Scientific calculators can be used too, but that is not a common practice in nephrology clinics. The authors have shown in this paper how to use Microsoft Excel to create personal calculators, so that eGFR may be calculated by medical professionals and dialysis staff even when internet is not available due to institutional policies or otherwise. The ‘Appendix’ section given at the end of the paper shows how to create these personal calculators in Microsoft excel. Calculators for CKD-EPI equations can also be developed in excel, however the calculations are more complex, so I prefer using the programming language python to develop these calculators. In this paper, the authors have shown only the excel based calculators for CG equation and MDRD-4 (re-expressed) equation.