Recently, many patients with polycystic kidney have come to see me one after another, and it is a great pity that many of them have already suffered from renal insufficiency before they pay attention to their condition. Polycystic kidney is a hereditary disease, although there are no obvious clinical symptoms, but the disease is progressive, the most important feature is the early occurrence of hypertension, close to about half of the patients combined with cerebral hemangioma, so many polycystic kidney patients are not accidents due to uremia, but brain hemorrhage! At present, there is a lack of effective treatment for polycystic kidney, and gene therapy and drug intervention are only in the figuring out stage. The most crucial measure to control the development of polycystic kidney is early detection and early intervention, avoid indiscriminate treatment to lead to unnecessary outbreak of disease! We recommend an article to tell you how polycystic kidney patients should pay attention to the usual life and treatment. Autosomal dominant polycystic kidney (ADPKD) is the most common hereditary kidney disease, with a prevalence of about 1‰-2‰, characterized clinically by progressive enlargement of renal cysts. About half of the patients with ADPKD enter end-stage renal disease (ESRD) before the age of 60, and 70% of them require renal replacement therapy (RRT) at the age of 70. This article summarizes the pathogenesis, diagnosis and management of ADPKD for your reference and learning. Clinical presentation of ADPKD The clinical presentation of patients with ADPKD is racially variable. In China, 3/4 of ADPKD patients have a family history. Common clinical manifestations include pain (76.3%), hypertension (66.7%), hematuria (47.5%), urinary tract infection (25.7%), and stones or calcifications (19.7%). female patients with ADPKD are obese, have a significantly lower risk of hematuria and hypertension than male patients, and have a higher incidence of pain than men. The pathogenesis of ADPKD ADPKD is mainly caused by defective function of polycystin 1 (PC1, encoded by PKD1) or polycystin 2 (PC2, encoded by PKD2), as shown in the following diagram: Loss of polycystin 1 (PC1) and/or polycystin 2 (PC2) activity leads to abnormalities in a variety of cellular signaling pathway biochemical molecules, including elevated levels of cAMP, mTOR complex 1, increased extracellular signal-regulated kinase (ERK) activity, enhanced Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway, decreased intracellular calcium levels and decreased 5′-AMP-activated protein kinase (AMPK) activity. This subsequently leads to cyst formation, cell proliferation and metabolic dysregulation, including altered arginine pressor (AVP) levels. Diagnosis of ADPKD Ultrasound is the most commonly used imaging method to diagnose ADPKD with a diagnostic accuracy of 96%. diagnosis of ADPKD needs to be made based on family history, number of renal cysts and age of onset. Ultrasound diagnostic criteria are: the number of unilateral or bilateral renal cysts ≥3 in patients aged 15-39 years; the number of renal cysts ≥2 per side in patients aged 40-59 years; and the number of renal cysts ≥4 per side in patients aged 60 years or older with a positive family history can be diagnosed as ADPKD. Genetic diagnosis can detect mutations in about 90% of patients with ADPKD, and the remaining 10% of patients eligible for ADPKD diagnosis do not have PKD1 and PKD2 mutations. However, genetic testing has not been routinely used for the diagnosis of ADPKD due to the high cost and complexity of the technique. Clinical indications for genetic diagnosis include: 1. exclusion of kidney donors as atypical ADPKD patients; 2. patients with negative family history need a definitive diagnosis to exclude other cystic diseases; 3. the need for pre-implantation genetic diagnosis; 4. the need for a definitive genotype to make an assessment of the patient’s prognosis or the rate of disease progression. Treatment of ADPKD 1. Blocking heredity For a long time, ADPKD has mainly relied on drug therapy to control disease progression, but the continuous development of three-generation IVF technology in recent years has allowed us to fundamentally block the heredity of ADPKD through pre-implantation genetic diagnosis. 2. Supportive treatment The KDIGO guidelines recommend the use of supportive treatment to alleviate the clinical symptoms of ADPKD and reduce the incidence of complications and morbidity and mortality. Interventions include: low salt diet, use of statins and antihypertensive drugs, adequate daily fluid intake (2-3L/d), smoking ban, avoidance of nephrotoxic drugs and caffeinated beverages. In 60-80% of patients with ADPKD who develop hypertension early in the course of the disease, the preferred treatment is a RAAS antagonist. Angiotensin-converting enzyme inhibitors are better at lowering blood pressure, reducing proteinuria and protecting renal function than calcium antagonists; for patients with chronic kidney disease (CKD) stage 4 and above or those who cannot tolerate RAAS antagonists, beta-blockers may be used instead. Because ADPKD patients have a higher lifetime cardiovascular risk and studies have shown that strict blood pressure control is beneficial in delaying the progression of kidney disease, ADPKD patients aged <50 years with residual renal function may have a blood pressure target of <110/75 mmHg; the remaining patients follow the KDIGO guideline recommendations (blood pressure should be ≤140/90 mmHg in patients with CKD without proteinuria and ≤130/90 mmHg in patients with proteinuria ≥30 mg /d patients should have blood pressure ≤130/80 mmHg). 3. Inhibition of cyst growth In recent years, clinical studies have focused on drugs that specifically inhibit cyst growth, including vasopressin 2 receptor antagonists, mTOR inhibitors, and growth inhibitor analogs. The only one currently approved for clinical use in ADPKD patients is the vasopressin 2 receptor antagonist tolvaptan, which can effectively block the endogenous cAMP pathway to inhibit cyst growth and cyst fluid secretion. It has been approved for use in the EU, UK, Japan, Canada and Korea, primarily to control the progression of nephropathy in patients with high-risk ADPKD. mTOR inhibitors (e.g. everolimus, sirolimus, etc.) exert anti-cyst proliferation effects mainly by inhibiting mTOR pathway activation in renal tubular epithelial cells. mTOR inhibitors may also lead to increased proteinuria in patients with ADPKD. Growth inhibitor analogs mainly act by inhibiting the intracellular cAMP pathway through binding to Gα receptors. Studies have shown that the growth inhibitor analogue octreotide is effective in stopping total kidney volume growth, but has poor long-term effects. Bosutinib is an Src/Bcr-Abl tyrosine kinase inhibitor. Inhibition of Src reduces cell proliferation and adhesion and is used clinically in the treatment of chronic granulocytic leukemia. phase 2 studies have found that bosutinib slows renal cyst formation, but has no benefit on renal function.