Oral anti-hepatitis B virus nucleoside (acid) analogs mainly include nucleoside analogs (lamivudine, entecavir, tipifudine, etc.) and nucleotide analogs (adefovir, tenofovir, etc.). Among them, nucleoside analogs are excreted by the glomerulus in their original form after filtration and are easily accumulated in the epithelial cells of the proximal tubule, thus producing nephrotoxicity. Adefovir (ADV) was approved for the treatment of chronic hepatitis B (CHB) in 2002 and launched in China in 2005. By 2008, the number of people taking ADV worldwide was about 410,000/year. Tenofovir (TFV) for the treatment of CHB in adults is currently in phase III clinical trials in China and will soon be approved for use in China. The dose of ADV 10 mg/d is usually considered safe, but in recent years, it has been reported in the literature that 10 mg/d in the treatment of CHB can also cause nephrotoxicity, mainly proximal tubular damage, which can manifest as Fanconi syndrome. Therefore, nephrotoxicity of nucleotides has become a problem that cannot be ignored, and clinicians need to raise awareness of the nephrotoxicity of these drugs for early detection and early treatment. According to the literature, ADV nephrotoxicity is mainly related to the following factors: (1) dose and duration of administration; (2) previous history of kidney injury; (3) combination of nephrotoxic drugs; (4) children, elderly or low weight individuals; (5) genetic factors. Nucleoside analogs are mainly secreted out of the body through the renal tubules, and are prone to renal tubular damage. proximal tubular lesions caused by ADV are thought to be the result of direct nephrotoxicity and mitochondrial toxicity. The nephrotoxicity is mainly related to the enrichment of drug by organic anion transport protein 1 (HOAT-1) and the blocked excretion of drug by multidrug resistance-associated protein 2 (Mrp2) in the human proximal tubule. Mrp2 is an ATP-dependent drug efflux pump localized at the parietal side of the proximal tubule, which mainly mediates the active secretion of ADV and its excretion from the body. The mechanism of TFV renal damage is similar to that of ADV. The clinical manifestations of Fanconi syndrome caused by nucleotide analogues: 1. Fanconi syndrome is a renal tubular dysfunctional disease, mainly caused by damage to the epithelial cells of the proximal tubule, which results in a complex transport dysfunction, with prominent loss of urinary glucose, amino acids, phosphate and uric acid, as well as loss of small molecule protein and electrolytes. Adult-acquired Fanconi syndrome is often characterized by osteoporosis. The diagnosis and differential diagnosis of Fanconi syndrome caused by nucleotides: 1. History of nucleotide administration. 2. 2. Clinical manifestations: insidious onset, no obvious symptoms in the early stage, bone pain is more prominent in the later stage, and muscle strength may be reduced. 3. Ancillary tests: impaired proximal tubular function such as amino aciduria, phosphaturia, renal diabetes, tubular proteinuria, hypophosphatemia, hypouricemia, hypokalemia, etc. Generally, amino aciduria, renal diabetes and phosphaturia are the basic diagnostic indicators. 4, need to be distinguished from the following diseases: congenital genetic factors such as cystine storage disease, glycogen storage disease, Lowe syndrome caused by Fanconi syndrome and other drugs, toxins caused by the proximal tubular damage. Recovery of renal damage after drug discontinuation also supports this diagnosis. Treatment of Fanconi syndrome caused by nucleotides There is no unified treatment principle reported in the literature, and the key is to discontinue nucleotides and replace them with other types of antiviral drugs. Some studies recommend that patients with severe hypophosphatemia should be treated with phosphorus supplementation, usually with potassium or sodium phosphate orally or intravenously, 1000 mg/d orally for mild hypophosphatemia (0.8-0. 96 mmol/L) and 1000 mg/d orally or intravenously for 2-6 h for moderate hypophosphatemia 0.3-0.8 mmol/L (2.5-5.0 mg/kg). Severe low blood phosphorus (<0.3 mmol/L) intravenous phosphorus supplementation for 2-6 h (2.5-5.0 mg/kg). The prognosis of Fanconi syndrome caused by nucleotides is good. Fanconi syndrome caused by drugs can be reversed after removing the cause and the prognosis is good. Some studies have reported hypophosphatemia with proteinuria and renal impairment even after discontinuation of ADV and supplemental calcium and phosphorus therapy. Prevention of Fanconi syndrome due to nucleotides: 1. In view of the renal damage of nucleotides mentioned above, patients who intend to use these drugs clinically should undergo baseline assessment of renal function and calculate glomerular filtration rate (GFR) before use, and the drug should be reduced for patients with chronic renal insufficiency; the British HIV Association recommends that patients who start using TFV should have their GFR monitored every 4 weeks during the first year. The British HIV Association recommends that patients starting TFV should have their GFR, serum phosphorus, urine test paper (urine glucose), and urine polymerase chain reaction (PCR) monitored every 4 weeks for the first year. In addition, the use of drug transporter inhibitors is another way to prevent renal damage from nucleotides.