Decrease in urinary creatinine excretion in early stage chronic kidney disease.
BACKGROUND
Little is known about muscle mass loss in early stage chronic kidney disease (CKD). We used 24-hour urinary creatinine excretion rate to assess determinants of muscle mass and its evolution with kidney function decline. We also described the range of urinary creatinine concentration in this population.


METHODS
We included 1072 men and 537 women with non-dialysis CKD stages 1 to 5, all of them with repeated measurements of glomerular filtration rate (mGFR) by (51)Cr-EDTA renal clearance and several nutritional markers. In those with stage 1 to 4 at baseline, we used a mixed model to study factors associated with urinary creatinine excretion rate and its change over time.


RESULTS
Baseline mean urinary creatinine excretion decreased from 15.3 ± 3.1 to 12.1 ± 3.3 mmol/24 h (0.20 ± 0.03 to 0.15 ± 0.04 mmol/kg/24 h) in men, with mGFR falling from ≥ 60 to <15 mL/min/1.73 m(2), and from 9.6 ± 1.9 to 7.6 ± 2.5 (0.16 ± 0.03 to 0.12 ± 0.03) in women. In addition to mGFR, an older age, diabetes, and lower levels of body mass index, proteinuria, and protein intake assessed by urinary urea were associated with lower mean urinary creatinine excretion at baseline. Mean annual decline in mGFR was 1.53 ± 0.12 mL/min/1.73 m(2) per year and that of urinary creatinine excretion rate, 0.28 ± 0.02 mmol/24 h per year. Patients with fast annual decline in mGFR of 5 mL/min/1.73 m(2) had a decrease in urinary creatinine excretion more than twice as big as in those with stable mGFR, independent of changes in urinary urea as well as of other determinants of low muscle mass.


CONCLUSIONS
Decrease in 24-hour urinary creatinine excretion rate may appear early in CKD patients, and is greater the more mGFR declines independent of lowering protein intake assessed by 24-hour urinary urea. Normalizing urine analytes for creatininuria may overestimate their concentration in patients with reduced kidney function and low muscle mass.
CESP, Centre for Epidemiology and Population Health, INSERM Unit 1018, Villejuif, France; University Paris-Sud 11, UMRS 1018, Villejuif, France.
Elena
E
Tynkevich
AP-HP, Hôpital Bichat, Department of Physiology, Paris, France.
Martin
M
Flamant
AP-HP, Hôpital Tenon, Department of Physiology, Paris, France; INSERM UNIT 702, Paris, France; University Pierre et Marie Curie-Paris 6, UMRS 702, Paris, France.
Jean-Philippe
JP
Haymann
CESP, Centre for Epidemiology and Population Health, INSERM Unit 1018, Villejuif, France; University Paris-Sud 11, UMRS 1018, Villejuif, France.
Marie
M
Metzger
AP-HP, Hôpital Européen Georges Pompidou, Department of Nephrology, Paris, France; AP-HP, Hôpital Européen Georges Pompidou, DHU Common and Rare Arterial Diseases, Paris, France.
Eric
E
Thervet
INSERM UNIT 702, Paris, France; University Pierre et Marie Curie-Paris 6, UMRS 702, Paris, France; AP-HP, Hôpital Tenon, Department of Nephrology, Paris, France.
Jean-Jacques
JJ
Boffa
AP-HP, Hôpital Bichat, Department of Nephrology, Paris, France.
François
F
Vrtovsnik
University Paris Descartes-Paris 5, UMRS 775, Paris, France; AP-HP, Hôpital Européen Georges Pompidou, Department of Physiology, Paris, France.
Pascal
P
Houillier
CESP, Centre for Epidemiology and Population Health, INSERM Unit 1018, Villejuif, France.
Marc
M
Froissart
CESP, Centre for Epidemiology and Population Health, INSERM Unit 1018, Villejuif, France; University Paris-Sud 11, UMRS 1018, Villejuif, France.
Bénédicte
B
Stengel
D000367:Age Factors; D015992:Body Mass Index; D003404:Creatinine / Q000652:urine*; D005006:Ethnicity; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D009929:Organ Size; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000473:pathology / Q000503:physiopathology*; D012307:Risk Factors; D012737:Sex Factors
D003404:Creatinine