Protein energy-wasting associated with nephrotic syndrome – the comparison of metabolic pattern in severe nephrosis to different stages of chronic kidney disease

Abstract

Background: Nephrotic syndrome (NS) is associated with a hypercatabolic state expressed as an exacerbated degradation of muscle mass. However, the clinical significance of this phenomenon has not yet been investigated. The aim of the study was to evaluate the nutritional status of patients with severe NS (defined as nephrotic range proteinuria with hypoalbuminemia ≤2.5 g/dL) and estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m 2 in comparison to patients in different stages of chronic kidney disease (CKD). Methods: Twenty men with severe NS (NS group) and 40 men without proteinuria similar in term of serum creatinine (control group) were included into the study. A retrospective cohort of 40 men with CKD stage G4 (PreD group) and 20 haemodialysis men (HD group) were added to the analysis after matching for age, height and weight using propensity score matching. The bioimpedance spectroscopy and biochemical nutritional markers were evaluated. Results: Nephrotic patients had a significantly lower lean tissue mass (LTM; p = 0.035) and index (a quotient of LTM over height squared, LTI; p = 0.068), with an expected deficiency of LTM by 3.2 kg, and LTI by 0.9 kg/m 2 when compared to the control group. A significant lean tissue deficit (defined as LTI below the lower limit of the reference range by 1.0 kg/m 2) was observed in 12.5% of patients in the control group in comparison to 31.7% with advanced CKD (PreD+HD; p = 0.032) and 50% with NS (p = 0.003). NS group presented with higher phosphorus (p = 0.029), uric acid (p = 0.002) and blood urea (p = 0.049) than the control group. Blood urea was strongly negatively correlated with LTM in NS (r = − 0.64, p = 0.002). Nine nephrotic patients (45%) were identified as hypercatabolic based on severe hyperphosphatemia (> 5.0 mg/dL) and/or hyperuricemia (> 8.0 mg/dL), and were characterized by higher blood urea and lower prealbumin, as well as LTM lower by 5.6 kg than in less catabolic individuals. Conclusions: In term of lean tissue amount, NS group was more similar to advanced CKD than to the control group. We concluded that specific metabolic pattern with elevated phosphorus, uric acid and blood urea, and lean tissue deficiency may be defined as protein-energy wasting associated with nephrotic syndrome (neph-PEW).

Metabolomics Profiling of Nephrotic Syndrome towards Biomarker Discovery

“…In the present work, metabolomics analysis of NS has detected an alteration in the amino acids’ metabolic pathways including arginine, proline, and tryptophan metabolism; arginine, phenylalanine, tyrosine, and tryptophan biosynthesis. These results are consistent with the well-known dysregulation of protein anabolism and catabolism in NS patients [ 28 , 29 ]. Moreover, inadequate protein intake and amino acid depletion are associated with NS [ 28 ].…”

“…These results are consistent with the well-known dysregulation of protein anabolism and catabolism in NS patients [ 28 , 29 ]. Moreover, inadequate protein intake and amino acid depletion are associated with NS [ 28 ]. The metabolites of amino acids are linked with the pathogenesis of NS [ 30 , 31 ].…”

Utility of muscle ultrasound in nutritional assessment of children with nephrotic syndrome

“…PEW in NS, like PEW in CKD, is related to an acceleration in atherosclerosis development, even in children [ 31 ]. Patients with severe NS hyperphosphatemia, hyperuricemia, and fluid overload have recognized independent risk factors of cardiovascular events as well [ 6 ]. Moreover, PEW causes the patient’s immune system to deteriorate and respond abnormally; as a result, the patient is more vulnerable to infections and their sequelae [ 32 ].…”

“…Proteinuria, in addition to the inflammation associated with chronic disease, can contribute to PEW, resulting in an accelerated loss of lean body mass (LBM), which can also have a negative impact on morbidity and mortality [ 5 ]. Protein-energy wasting associated with NS (neph-PEW) defines a specific metabolic pattern in patients with NS with elevated phosphorus, uric acid, blood urea, and lean tissue deficiency [ 6 ].…”

“…Pathophysiological studies have linked NS to a hypercatabolic state characterized by accelerated muscle mass loss as the increased hepatic synthesis is not enough to compensate for the total loss, resulting in a decreased rate of protein turnover of other protein pools and amino acid mobilization from muscle [ 6 , 7 ].…”