Aristolochic acid nephropathy: variation in presentation and prognosis

Background. Aristolochic acid nephropathy (AAN) is a worldwide problem and one of the common causes of chronic kidney disease (CKD) in China. Methods. Three hundred patients diagnosed as AAN from 1997 to 2006 were enrolled. Medical histories of Chinese herb ingestion, clinical-pathological features and risk factors for renal failure were recorded. Patients were followed up for 2-156 months. Factors involved in the prognosis of AAN were investigated. Results. The 300 patients with AAN manifested three clinical subtypes, including acute kidney injury (acute AAN) in 13 patients, abrupt tubular dysfunction with normal serum creatinine (Scr) levels in seven cases and chronic tubulointerstitial nephropathy with decreased estimated glomerular filtration rate (eGFR) (chronic AAN) in 280 cases. The acute AAN cases had the highest aristolochic acid (AA)-I intake per day and developed progressive kidney failure during 1-7 years follow-up. The tubular dysfunction AAN patients had the lowest cumulative AA-I intake and were able to keep normal Scr levels during 2-8 years follow-up. The chronic AAN patients took the lowest AA-I dose per day but with the longest period and the highest cumulative dosage and exhibited a very large range of eGFR changing rate (from -21.6 to 5.2, median -3.5 mL/min/year). The cumulative AA-I intake (r = 0.330, P = 0.045) and the time course from the termination of AA medication to the start of follow-up (r = -0.430, P = 0.009) were found to be independent factors correlated with the decrease rate of eGFR in the chronic AAN patients. AA and the metabolites could be detected in a high frequency in patients who had stopped herbal medication for 1 year, which indicates a rather long washout time for these chemicals. Conclusions. AAN has variant phenotypes with distinct prognosis, which is determined by the variable AA medications. With better understanding of toxic and environmental causes for kidney injury, there would be a better chance to uncover the causal factors of cases of 'CKD without known causes' which is crucial for improving the disease outcomes.