The relationship between creatinine levels and weight loss is complex and multifaceted. Creatinine, a waste product from muscle metabolism, is commonly used to estimate kidney function. Weight loss, especially significant weight loss, can impact muscle mass, leading to changes in creatinine levels and potentially affecting the accuracy of kidney function estimations. This article explores the intricate relationship between creatinine, weight loss, and kidney function, considering various factors that influence this connection.
The Basics of Creatinine and GFR
Creatinine is a waste product derived from the normal breakdown of muscle tissue and the digestion of protein. The kidneys filter creatinine from the blood, and it is excreted in urine. Plasma creatinine (pCr) is frequently used to estimate Glomerular Filtration Rate (GFR), a key indicator of kidney function. Accurate assessment of GFR is important to evaluate the progression of renal disease and to monitor the effect of intervention on kidney function as well as to inform drug dosing and patient counselling.
GFR is the best index of renal function by measuring the filtering capacity of the kidneys. Since using radiolabeled exogenous markers to accurately measure GFR can be costly and time consuming, several formulas have been used to provide estimated GFR (eGFR) based on serum creatinine levels. Currently, renal function is assessed best by eGFR, as serum creatinine is an unreliable marker of kidney function.
How GFR is Estimated
Plasma creatinine is frequently used to estimate GFR, since it has proven to be an inexpensive and reliable index of kidney function. The primary determinant of creatinine generation/production is skeletal muscle mass where the final catabolite of muscular energetic metabolism is creatinine [1]. Hence, if body weight - and muscle mass in particular - changes over time and leads to changes in plasma creatinine, this may affect estimates of kidney function, without actual changes in accurately measured GFR. Whether these factors impact eGFR could depend on the equations applied, as the 4-variable Modification of Diet in Renal Disease (MDRD) [2] and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) [3] equations include plasma creatinine and would not be affected body weight changes alone. Cystatin C is a filtration marker that is less influenced by changes in muscle mass and may be a more suitable marker of renal function in subjects experiencing fast and large weight reductions [4].
Several formulas are used to estimate GFR, including the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. These equations incorporate plasma creatinine levels, age, sex, and race to estimate GFR.
Read also: Creatinine Levels and Diet
Weight Loss and Muscle Mass
Significant weight loss can lead to a reduction in muscle mass, which in turn affects creatinine production. Since creatinine is a byproduct of muscle metabolism, a decrease in muscle mass can result in lower creatinine levels. This can impact the accuracy of GFR estimations based on creatinine.
Lean limb mass is considered the best surrogate measure of skeletal muscle mass and was calculated as the total non-bone and non-fat lean mass of the extremities: Lean mass of left arm + lean mass of right arm + lean mass left leg + lean mass of right leg [9].
Creatinine-Based Equations and Weight Loss
Creatinine-based eGFR equations have not been validated in morbidly obese adults or in patients with change in body composition after RYGB [13]. Cystatin C is less affected by muscle mass and diet than is creatinine, while reports have found an association between cystatin C concentrations and body weight and fat mass [14-17]. Nonetheless, it has been anticipated that cystatin C would provide a more accurate estimate of GFR than creatinine [18].
When weight loss occurs, creatinine levels may decrease due to reduced muscle mass. This decrease in creatinine can lead to an overestimation of kidney function when using creatinine-based eGFR equations. In other words, the eGFR may appear higher than the actual GFR.
The Role of Cystatin C
Cystatin C is another marker used to estimate GFR. Unlike creatinine, cystatin C is less influenced by muscle mass and is considered a more reliable marker of renal function in individuals experiencing significant weight loss.
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Cystatin C-Based Estimates
When monitoring changes in renal function over time in patients experiencing a large weight loss, cystatin C-based estimates of GFR may be more useful.
In a prospective intervention study investigating the effects of a fast and large (mean 27 kg) weight loss, obtained by Roux-en-Y gastric bypass surgery, it was found that plasma creatinine was reduced causing increases in creatinine-based eGFR (MDRD and CKD-EPI), while cystatin C-based eGFR was unchanged (all adjusted for BSA). Lean limb mass, a surrogate measure of skeletal muscle mass, was reduced by mean 3.5 kg and might explain the reduction in plasma creatinine, since a significant correlation between these changes was found.
Measured GFR vs. Estimated GFR
Measuring GFR by inulin-clearance [19], chromium-EDTA clearance [6] or iohexol clearance [20] is considered the “gold standard” of GFR. However, it is expensive and time consuming (usually a four hour examination), and therefore not realistic as a routine measurement in clinical practice or in large-scale studies.
mGFR adjusted for extracellular volume was reduced. However GFR indexed with extracellular volume is currently not recommended [24].
Discrepancies and Implications
The study hypothesis was that change in creatinine-based eGFR would be different than change in mGFR, since a large weight reduction would lead to a reduction in muscle mass affecting plasma creatinine levels without impacting BSA-corrected mGFR. The primary findings were that absolute mGFR was reduced, BSA-corrected mGFR and cystatin C-based eGFR were unchanged, while creatinine-based eGFR was increased after a weight reduction of mean 27 kg. By applying robust methods for determination of body composition, we were able to demonstrate that changes in muscle mass correlated with changes in plasma creatinine.
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Other studies have demonstrated similar results. In a study of 37 patients, a weight loss of 37 kg six months after surgery was associated with a significant reduction in mean creatinine, and accordingly an increase in MDRD, while Cockcroft Gault eGFR (including both creatinine and body weight) was decreased [25]. A small prospective study demonstrated that BSA-corrected mGFR, determined using clearance of iothalamate, was reduced in a cohort of 11 women during the first year after bariatric surgery. Notably, serum creatinine and creatinine-based eGFR did not identify this change in renal function, which was explained by a large reduction in creatinine production. Preoperatively, the CKD-EPI equation underestimated mGFR; postoperatively, mGFR was overestimated due to the reduction in body weight and muscle mass [12]. Of note, these studies did not measure actual changes in body composition.
Weight Loss Methods and Renal Function
The impact of weight loss on renal function can vary depending on the method used to achieve weight loss. For example, bariatric surgery, such as Roux-en-Y gastric bypass (RYGB), can result in rapid and significant weight loss, which may have a different effect on renal function compared to gradual weight loss through diet and exercise.
Bariatric Surgery and GFR
In a prospective intervention study, the effects of a fast and large (mean 27 kg) weight loss, obtained by Roux-en-Y gastric bypass surgery, found a reduction in absolute mGFR, while BSA-corrected mGFR was unchanged. Plasma creatinine was reduced causing increases in creatinine-based eGFR (MDRD and CKD-EPI), while cystatin C-based eGFR was unchanged (all adjusted for BSA).
Obesity and Renal Function
Obesity is an independent risk factor for renal injury. Sympathetic nerve activation may have an important role of the pathogenesis of obesity, and hypertension may underpin the development of cardiovascular events.
Weight Loss Benefits
Intentional weight loss (WL) reduced the risk of the onset and development of hypertension,12, 13 diabetes14 and renal injury15 in overweight or obese individuals.
In obese subjects, obesity-related glomerular hyperfiltration,27 elevated sympathetic nervous activity,12, 13, 28, 29, 30 insulin resistance and stimulation of the renin-angiotensin-aldosterone system (RAS)30, 31 are ameliorated after WL.
In conclusion, WL improved renal function (as evident from measures of creatinine and CCr) in overweight individuals. Basal plasma NE levels and total body fat mass could be predictors for improvement in renal function associated with WL.
The Role of Creatine Supplementation
Creatine is a naturally occurring compound in the body that helps supply energy to muscles. It is also a popular supplement among athletes and bodybuilders.
Creatine and Body Composition
Creatine supplementation in combination with resistance training has been shown to increase lean tissue mass in adults ≥50 years of age. The combination of creatine supplementation and resistance training may decrease fat mass more than resistance training alone.
Results from the meta-analyses showed that adults ≥50 years of age who supplemented with creatine during resistance training experienced a greater reduction in body fat percentage (0.55%, p = 0.04) compared to those on placebo during resistance training. Despite no statistical difference (p = 0.13), adults supplementing with creatine lost ~0.5 kg more fat mass compared to those on placebo.
Implications for Clinical Practice
The findings discussed in this article have important implications for clinical practice. Healthcare professionals should be aware of the potential impact of weight loss on creatinine levels and GFR estimations.
Recommendations
- When assessing kidney function in patients undergoing weight loss, consider using cystatin C-based eGFR equations in addition to creatinine-based equations.
- Interpret eGFR results with caution in individuals experiencing significant weight loss, taking into account changes in muscle mass.
- Consider measuring GFR directly using inulin clearance, chromium-EDTA clearance, or iohexol clearance in situations where accurate assessment of kidney function is critical.
- Encourage weight loss through lifestyle interventions, including diet and exercise, to improve overall health and reduce the risk of kidney disease.
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