The Clinical Manifestation and Management of Autosomal Dominant Polycystic Kidney Disease in China.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic hereditary kidney disease characterized by progressive enlargement of renal cysts. The incidence is 1-2‰ worldwide. Mutations in two genes (PKD1 and PKD2) cause ADPKD. Currently, there is no pharmaceutical treatment available for ADPKD patients in China. Summary: This review focused on advances in clinical manifestation, gene diagnosis, risk factors, and management of ADPKD in China. There is an age-dependent increase in total kidney volume (TKV) and decrease in renal function in Chinese ADPKD patients. ADPKD is more severe in males than in females. Great progress has been made in molecular diagnosis in the last two decades. Nephrologists found many novel PKD mutations in Chinese ADPKD patients early through polymerase chain reaction, and then through liquid chromatography in 2000s, and recently through next-generation sequencing. Major predictive factors for ADPKD progression are age, PKD genotype, sex, estimated glomerular filtration rate (eGFR), and TKV. With respect to the management of ADPKD, inhibitors targeting mTOR and cAMP are the focus of clinical trials. Triptolide has been used to treat ADPKD patients in clinical trials in China. Triptolide significantly protected eGFR of ADPKD patients compared with placebo. KEY MESSAGES: ADPKD affects about 1.5 million people in China. An additional PKD gene besides PKD1 and PKD2 was not found in the Chinese. The prevalence of intracranial aneurysm in Chinese ADPKD patients was 12.4%. The predictive factors for eGFR decrease in Chinese ADPKD patients are TKV, proteinuria, history of hypertension, and age. The treatment strategies in clinical trials for ADPKD patients in China are similar to those in the West except for triptolide. FACTS FROM EAST AND WEST: (1) ADPKD is diagnosed globally by ultrasound detection of kidney enlargement and presence of cysts. Recent analyses of variants of the PKD1 and PKD2 genes by next-generation sequencing in Chinese and Western ADPKD patients might lead to the development of reliable genetic tests. (2) Besides lifestyle changes (low-salt diet, sufficient fluid intake, and no smoking), blood pressure control is the primary nonspecific treatment recommended by Kidney Disease - Improving Global Outcomes (KDIGO) for ADPKD patients. How low the blood pressure target should be and what the means of achieving it are remain open questions depending on the severity of chronic kidney disease and the age of the patients. In a recent Chinese study, diagnostic needle aspiration and laparoscopic unroofing surgery successfully improved infection, pain, and hypertension. Peritoneal dialysis was found to be a feasible treatment for most Chinese ADPKD patients with end-stage renal disease. In most Western centers, patients without contraindication are selected for peritoneal dialysis. Kidney transplantation with concurrent bilateral nephrectomy was successful in relieving hypertension and infection in Chinese ADPKD patients. In Western countries, sequential surgical intervention with kidney transplantation after nephrectomy, or the other way round, is preferred in order to reduce risks. (3) The vasopressin 2 receptor antagonist tolvaptan was approved in Europe, Canada, Japan, and Korea to slow down progression of kidney disease in ADPKD patients. Tolvaptan is not yet approved in the USA or in China. mTOR pathway-targeting drugs are currently under evaluation: mTOR inhibitors could slow down the increase in total kidney volume in a cohort of Western and Japanese ADPKD patients. Western studies as well as an ongoing study in China failed to show benefit from rapamycin. A study performed in Italy indicates protective effects of the somatostatin analog octreotide in ADPKD patients. Western and Chinese studies revealed a potential beneficial effect of triptolide, the active substance of the traditional Chinese medicine Tripterygium wilfordii (Lei Gong Teng) to prevent worsening in ADPKD patients.