The Effect of Renal pH on Ischemia‐Reperfusion‐Induced Acute Kidney Injury

Abstract

Acute kidney injury (AKI) is a major public health issue associated with significant cost, extensive morbidity and increased mortality. However, no specific therapy to prevent or treat AKI is available, and the pathophysiological mechanisms of AKI remain unclear. Renal pH is related to dietary acid‐base load and affects the function of epithelial cells. Renal alkali intervention has been demonstrated to improve renal function and slow the decline in glomerular filtration rate (GFR) in the normal population and patients with chronic kidney disease. However, the role of renal pH in AKI is still not known.In the present study, we hypothesized that elevations in renal pH protect against the development of ischemia reperfusion injury (IRI)‐induced AKI. AKI was induced in C57BL/6J mice by 18 minutes of ischemia bilateral clamping of renal pedicles. The mice that were performed same surgery without clamping pedicels were taken as sham group. The mice were then divided into three groups (n=6 per group) treated for 14 days with 0.5% NaCl, 0.72% NaHCO3 (same mEq of Na+ as in NaCl), or 0.46% NH4Cl (same mEq of Cl− as in NaCl).Urine pH was significantly increased to 7.8±0.5 in the NaHCO3 treated group and decreased to 6.8±0.3 in the NH4Cl treated group, compared with the NaCl group (7.3±0.3). Plasma creatinine was measured 7 and 14 days after IRI to evaluate renal injury. The plasma creatinine was substantially increased in all three groups compared with the sham‐operated group (0.08±0.02 mg/dl) 7 days after IRI, with the NH4Cl group being the highest (0.98±0.15 mg/dl), followed by the NaCl group (0.71±0.11 mg/dl) and the NaHCO3 group (0.47±0.09 mg/dl). There was no significant difference in plasma creatinine between the three groups at 14 days after IR. To evaluate kidney function, GFR was measured by the clearance of plasma FITC‐insulin with a single bolus injection in conscious mice at baseline as well as 7 and 14 days after IRI. GFR decreased by 44.5% (244.7±9.1 to 135.8±13 μl/min) in the NH4Cl group, 31.8% (228.3±11 to 155.52±8.4 μl/min) in the NaCl group and 21.2% (237.6±7.5 to 187.3±14 μl/min) in the NaHCO3 group 7 days after IRI. The GFR returned to near baseline in all three groups at 14 days after IRI.In summary, these results indicate that renal acidification aggravates whereas alkalization protects against the development of IR‐induced AKI.