Individualizing pharmacotherapy in patients with renal impairment: the validity of the Modification of Diet in Renal Disease formula in specific patient populations with a glomerular filtration rate below 60 ml/min. A systematic review.

Willemijn L Eppenga,Cornelis Kramers,Michel Wensing,Peter A G M De Smet,Jack F M Wetzels,Hieronymus J Derijks

doi:10.1371/journal.pone.0116403

Abstract

BackgroundThe Modification of Diet in Renal Disease (MDRD) formula is widely used in clinical practice to assess the correct drug dose. This formula is based on serum creatinine levels which might be influenced by chronic diseases itself or the effects of the chronic diseases. We conducted a systematic review to determine the validity of the MDRD formula in specific patient populations with renal impairment: elderly, hospitalized and obese patients, patients with cardiovascular disease, cancer, chronic respiratory diseases, diabetes mellitus, liver cirrhosis and human immunodeficiency virus.Methods and FindingsWe searched for articles in Pubmed published from January 1999 through January 2014. Selection criteria were (1) patients with a glomerular filtration rate (GFR) < 60 ml/min (/1.73m2), (2) MDRD formula compared with a gold standard and (3) statistical analysis focused on bias, precision and/or accuracy. Data extraction was done by the first author and checked by a second author. A bias of 20% or less, a precision of 30% or less and an accuracy expressed as P30% of 80% or higher were indicators of the validity of the MDRD formula. In total we included 27 studies. The number of patients included ranged from 8 to 1831. The gold standard and measurement method used varied across the studies. For none of the specific patient populations the studies provided sufficient evidence of validity of the MDRD formula regarding the three parameters. For patients with diabetes mellitus and liver cirrhosis, hospitalized patients and elderly with moderate to severe renal impairment we concluded that the MDRD formula is not valid. Limitations of the review are the lack of considering the method of measuring serum creatinine levels and the type of gold standard used.ConclusionIn several specific patient populations with renal impairment the use of the MDRD formula is not valid or has uncertain validity.

Highlights

We focused on studies in patients with a measured glomerular filtration rate (GFR) or estimated GFR < 60 ml/min(/1.73m2)
We found two studies, which conducted a subanalysis about the validity of the Modification of Diet in Renal Disease (MDRD)-4 formula in obese patients (BMI > 30 kg/m2)
The numbers of patients in the selected separate studies were low and only the measurement of the GFR in the study of Bolke et al seemed robust. These studies suggest that the estimated GFR (eGFR) calculated with the MDRD formula in cancer patients with moderate to severe renal impairment may be substantially different from the measured GFR (mGFR) for a substantial number of patients

Summary

Introduction

Chronic kidney disease (CKD) is a common condition and affects up to 13% of the population. [1] CKD is defined as a glomerular filtration rate (GFR) < 60 ml/min/1.73m2 or evidence of kidney damage (proteinuria, haematuria and/or abnormalities of the kidney) for at least 3 months regardless of underlying cause.[2,3] CKD is associated with adverse outcomes, such as kidney failure, cardiovascular diseases and death.[2,4,5] Since laboratories routinely report the estimated GFR (eGFR) if serum creatinine testing is ordered, the awareness of impaired renal function among physicians has increased in recent years.[6,7,8]The eGFR is used to diagnose CKD or to monitor its course in patients with kidney disease, and to guide decisions in pharmacotherapy. [56,90,91,92,93,94] In patients with end-stage heart failure, irreversibly impaired renal function precludes eligibility for heart transplantation.[95] In addition, patients with cardiovascular diseases are at risk for polypharmacy and the use of drugs that require dosage adjustment in renal impairment.[96,97] an accurate method to estimate GFR is essential.[98] Both cancer and its drug therapies can lead to renal impairment.[99] Renal impairment in patients with cancer is highly prevalent and has major clinical implications. Comorbidities and the use of nephrotoxic antiretroviral drugs might lead to a higher risk for developing impaired renal function.[122,123,124] In addition, the use of renally excreted drugs is prevalent, accurate estimation of renal function is an important component of personalized HIV care.[117,125]

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