Chronic kidney disease (CKD) is a major global health issue characterized by progressive loss of renal function and structural damage. One of the key contributors to CKD progression is metabolic acidosis, which arises due to impaired acid excretion and reduced bicarbonate levels. This condition not only exacerbates renal injury but also accelerates glomerulosclerosis and tubulointerstitial fibrosis. Alkali therapy, particularly through sodium bicarbonate supplementation, has emerged as a promising intervention to slow CKD progression. In this study, we investigated the effects of dietary sodium bicarbonate on kidney function and pathology in a 5/6 nephrectomized rat model—a well-established experimental system for chronic renal failure.
Male Sprague-Dawley rats underwent partial nephrectomy to induce remnant kidney disease. Following surgery, animals were divided into two groups: one received a diet supplemented with sodium bicarbonate (NaHCO₃), while the other received an equivalent amount of sodium chloride (NaCl). Both diets contained 20% casein to standardize protein intake. Over a 10-week period, serum bicarbonate levels significantly increased in the NaHCO₃ group compared to controls, indicating effective correction of metabolic acidosis. Glomerular filtration rate (GFR), calculated from urea and creatinine clearance, was markedly higher in the alkali-treated group at both week 4 and week 10. Notably, GFR remained stable in the NaHCO₃ group, whereas it declined progressively in the NaCl group, suggesting that alkali therapy preserved renal function.
Histopathological analysis revealed significant protection against structural damage in the NaHCO₃ group. The glomerulosclerosis index was significantly lower at weeks 4 (0.17 ± 0.04 vs. 0.47 ± 0.06, P < 0.001) and 10 (0.66 ± 0.06 vs. 0.99 ± 0.07, P = 0.001). Similarly, tubulointerstitial (TI) lesion indices were reduced—by approximately half at week 4 (0.45 ± 0.01 vs. 0.92 ± 0.12, P = 0.004) and by three-quarters at week 10 (1.33 ± 0.12 vs. 1.80 ± 0.12, P = 0.010). These findings demonstrate that alkali therapy attenuates both glomerular and interstitial injury. At the molecular level, immunoblotting and immunohistochemistry showed that expression of the apical Na⁺/H⁺ exchanger type 3 (NHE3) was significantly downregulated in the NaHCO₃ group at week 4 (10.1 ± 4.25 vs. 100 ± 21.1, P = 0.007), with a trend toward reduction at week 10.Simvastatin Ferroptosis Apical NHE3 reactivity was also diminished, indicating functional suppression.4-(1H-Pyrazol-4-yl)pyridine Technical Information Moreover, endothelin-1 (ET-1) levels in kidney tissue were significantly lower in the NaHCO₃ group at week 10 (0.PMID:35161821 32 ± 0.15 vs. 1.14 ± 0.20 pg/mL/mg protein, P = 0.021), suggesting reduced vasoconstrictive and pro-fibrotic signaling. Expression of other transporters such as NKCC2, NBC, pendrin, and H⁺-ATPase remained unchanged, highlighting the specificity of NHE3 modulation.
These results indicate that alkali therapy ameliorates CKD progression primarily through inhibition of NHE3 activity and suppression of ET-1. By reducing intracellular sodium and hydrogen ion accumulation, alkali therapy may alleviate cellular stress, inflammation, and fibrogenic pathways in the remaining kidney. Thus, targeting NHE3 represents a potential therapeutic strategy for slowing renal decline in chronic kidney disease.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com