Total Kidney Volume Is the Most Valuable Predictor of ADPKD Progression
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited kidney disease, accounting for approximately 5%~10% of global adult end-stage renal disease (ESRD). There are two types of mutated genes in ADPKD, namely PKD1 (located at 16p13.3, accounting for 80% of cases) and PKD2 (located at 4q21, accounting for 20% of cases), which are characterized by the formation and development of cysts filled with cystic fluid caused by gene mutation, gradually occupying normal renal tissue and causing a sharp decline in renal function.
In recent years, research has found that some risk factors that affect the progression of ADPKD, such as total kidney volume (TKV), genotype, male, high blood pressure, proteinuria, cyst bleeding and infections, etc. Among them, TKV was determined by UFDA as a prognostic indicator of ADPKD and appeared as an endpoint indicator in many clinical trials. Previous cohort studies suggested that genotype was an equally important predictor.
Recently, the results of the third part of CRISP study were published. After a follow-up study of 14.5 years, researchers found that TKV with height correction was an independent predictor of the progression of ADPKD, and after KTV correction, genotype was no longer an indicator affecting the progression of ADPDK, which changed the understanding of previous studies. Professor Mei Changlin from Shanghai's Changezheng hospital has published a commentary about the research, published in Kidney International.
The results showed that for every 100 ml increase in TKV, the risk of progression to CKD Stage 3 increased by 1.38 times, the risk of progression to CKD Stage 4 increased by 1.42 times, the risk of progression to ESRD increased by 1.35 times, the risk of GFR decline by more than 30% was 1.61 times, and the risk of GFR decline by more than 57% was 1.43 times. However, after KTV correction, genotype is no longer a predictor of ADPKD progress. The researchers further compared the goodness of fit between the two and the prediction ability of the model, and obtained the same conclusion.
CRISP, the third part of the research is currently the longest follow-up ADPKD research with an average of 13 years, while other related clinical studies are mostly between 1 and 8 years. The significance of the research is to put forward for the first time that TKV is related with renal endpoint indicators (such as entering ESRD or kidney function declines for more than 57%) in youth ADPKD patients with normal kidney function. Another significance lies in the establishment of KTV-based ADPKD progress prediction classification, which is mainly divided into five grades (Level 1, 168 ~ 312 ml/m; Level 2, 314 ~ 429 ml/m; Level 3, 433 ~ 603; Level 4, 605 ~ 908 ml/m; Level 5, 909 ~ 2113 ml/m).
Up to now, two models have emerged in the field of ADPKD research to predict the disease progression of patients with ADPKD: Yu model and Irazabal model. These two studies have important clinical significance for ADPKD, and their predictive ability is basically similar. In order to further evaluate the significance of several prediction models in the disease progression of patients with ADPKD in China, professor Mei further analyzed 106 patients with ADPKD in China, and compared the ability of TKV, Yu, Irazabal, PROPKD and genotype to predict disease progression, and found no significant difference among the five patients. Due to limited follow-up time and sample size, this conclusion needs to be confirmed by large-scale clinical trials in the future.
ADPKD disease research still faces new challenges in the future. First, a single biomarker is not suitable as a composite indicator of ADPKD progression, and multiple biomarker composite indicators may be more appropriate. Second, in ADPKD patients, the time relationship between TKV and CKD progression needs to be further studied. Third, future studies should further compare different predictors.
In conclusion, CRISP's third part suggests that TKV is an ADPDK disease progression prediction and monitoring indicator. In addition, it suggests that TKV may be a more reliable predictor than genotype, which may have more important significance for the complex pathophysiological mechanism and treatment of ADPKD.
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