A4982 Effects of obesity on urinary acid excretion and kidney injury in chronic kidney disease

Objectives: Obesity predisposes hypertensives to chronic kidney disease (CKD). Obese patients tend to have high protein and NaCl intakes resulting in acid loading, which may induce or worsen metabolic acidosis upon CKD. The effects of obesity on urinary acid excretion in CKD patients and animal models were examined. Methods: The ability for urinary acid excretion in 28 outpatients with CKD (CKD stages G2 and G3) under the treatment with diet therapy and medication was examined by 24-h urine collection. Urinary acid was calculated by total amount of ammonium and titratable acid excretions. The parameters were compared between non-obese and obese patients. To further investigate using animal models, BALB/c (BALB) mice and KKAy/TaJcl (KKAy) mice, which exhibit obesity, hypertension, and hyperglycemia, were subjected to NH4Cl drinking for 20 weeks. Results: Diastolic blood pressure and percentage of diabetes were higher in obese patients than in non-obese patients. Urinary acid excretion was lower and protein and NaCl intakes were higher in obese patients, suggesting that subclinical metabolic acidosis occurs in obese patients. Urinary acid excretion was increased in KKAy mice in response to NH4Cl drinking until 10 weeks and was decreased thereafter, while the increase was maintained during 20 weeks of NH4Cl loading in BALB mice. Histology showed dilation of proximal tubules in NH4Cl-loaded KKAy mice, but not in BALB mice. Expression of neutrophil gelatinase-associated lipocalin (NGAL) mRNA was higher in KKAy mice at basal condition and was enhanced by NH4Cl loading. Blood pressure was not affected by NH4Cl loading both in BALB and KKAy mice. Conclusion: Obesity in CKD may induce subclinical metabolic acidosis and could potentially facilitate kidney injury upon chronic acid loading.