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.

The 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.We 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 (/1.73 m2), (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.In several specific patient populations with renal impairment the use of the MDRD formula is not valid or has uncertain validity

Risk of Lactic Acidosis or Elevated Lactate Concentrations in Metformin Users With Renal Impairment: A Population-Based Cohort Study

OBJECTIVE The objective of this study was to determine whether treatment with metformin in patients with renal impairment is associated with a higher risk of lactic acidosis or elevated lactate concentrations compared with users of a noninsulin antidiabetic drug (NIAD) who had never used metformin. RESEARCH DESIGN AND METHODS A cohort of 223,968 metformin users and 34,571 diabetic patients who had never used metformin were identified from the Clinical Practice Research Datalink (CPRD). The primary outcome was defined as either a CPRD READ code of lactic acidosis or a record of a plasma lactate concentration &gt;5 mmol/L. The associations between renal impairment, dose of metformin, and the risk of lactic acidosis or elevated lactate concentrations were determined with time-dependent Cox models and expressed as hazard ratios (HRs). RESULTS The crude incidence of lactic acidosis or elevated lactate concentrations in current metformin users was 7.4 per 100,000 person-years (vs. 2.2 per 100,000 person-years in nonusers). Compared with nonusers, risk of lactic acidosis or elevated lactate concentrations in current metformin users was significantly associated with a renal function &lt;60 mL/min/1.73 m 2 (adjusted HR 6.37 [95% CI 1.48-27.5]). The increased risk among patients with impaired renal function was further increased in users of ‡730 g of metformin in the preceding year (adjusted HR 11.8 [95% CI 2.27-61.5]) and in users of a recent high daily dose (&gt;2 g) of metformin (adjusted HR 13.0 [95% CI 2.36-72.0]). CONCLUSIONS Our study is consistent with current recommendations that the renal function of metformin users should be adequately monitored and that the dose of metformin should be adjusted, if necessary, if renal function falls below 60 mL/min/1.73 m 2 . There is good evidence that metformin reduces the long-term incidence of macrovascular complications in type 2 diabetes mellitus, especially among overweight patients (1-3). In contrast to alternative oral noninsulin antidiabetic drugs (NIADs) and insulin, metformin is not associated with a risk of hypoglycemia (3-5). The most serious adverse event that has been observed during metformin use is lactic acidosis, which i

Risk of lactic acidosis or elevated lactate concentrations in metformin users with renal impairment : a population-based cohort study

OBJECTIVE: The objective of this study was to determine whether treatment with metformin in patients with renal impairment is associated with a higher risk of lactic acidosis or elevated lactate concentrations compared with users of a noninsulin antidiabetic drug (NIAD) who had never used metformin. RESEARCH DESIGN AND METHODS: A cohort of 223,968 metformin users and 34,571 diabetic patients who had never used metformin were identified from the Clinical Practice Research Datalink (CPRD).The primary outcome was defined as either a CPRD READ code lactic acidosis or a record of a plasma lactate concentration >5 mmol/L. The associations between renal impairment, dose of metformin, and the risk of lactic acidosis or elevated lactate concentrations were determined with time-dependent Cox models and expressed as hazard ratios (HRs). RESULTS: The crude incidence of lactic acidosis or elevated lactate concentrations in current metformin users was 7.4 per 100,000 person-years (vs. 2.2 per 100,000 person-years in nonusers). Compared with nonusers, risk of lactic acidosis or elevated lactate concentrations in current metformin users was significantly associated with a renal function 2 g) of metformin (adjusted HR 13.0 [95% CI 2.36-72.0]). CONCLUSIONS: Our study is consistent with current recommendations that the renal function of metformin users should be adequately monitored and that the dose of metformin should be adjusted, if necessary, if renal function falls below 60 mL/min/1.73 m(2)

Validity of the MDRD in specific patient populations.

<p>* Not all parameters were reported in the included articles. Especially when it came to subanalysis of patients with an eGFR < 60 ml/min.1.73m².</p><p>^$ When individual data were available we calculated missing parameters ourselves.</p><p>^<i>≠</i> The MDRD-formula used was not reported. Given the time at which the study was conducted, we assume that the re-expressed MDRD-formula was used.</p><p>Validity of the MDRD in specific patient populations.</p

Validity of the MDRD formula in different patient populations.

<p>* The MDRD formula is not valid in patients on the internal medicine and nephrology ward. For other hospitalized patients it is not tested.</p><p>Validity of the MDRD formula in different patient populations.</p

Definitions outcome measurements.

<p>* Preferred definition because a relative scale provides a more relevant metric.</p><p>^‡ In some articles the mean percentage difference was called the mean percentage error (MPE).</p><p>^§ Preferred definition of accuracy. We limited our search to P₁₀, P₂₀, P₃₀ and P₅₀.</p><p>Definitions outcome measurements.</p

Determinants of serum creatinine level.

<p>Determinants of serum creatinine level.</p

Flow of study selection.

<p>Flow of study selection.</p

Precision and accuracy.

<p>Source: <a href="http://www.nrcan.gc.ca/minerals-metals/non-destructive-testing/application/2914" target="_blank">http://www.nrcan.gc.ca/minerals-metals/non-destructive-testing/application/2914</a>,</p