Liver cyst infection outcomes in patients with autosomal dominant polycystic kidney disease.

Childhood ADPKD: Answers and more questions

Autosomal dominant (ADPKD) and autosomal recessive (ARPKD) polycystic kidney disease are caused by mutations in Pkd1/Pkd2 and Pkhd1, which encode polycystins (PCs) and fibrocystin/polyductin (FPC). Our recent study reported that a deficiency in FPC increases the severity of cystic disease in Pkd2 mutants and down-regulates PC2 in vivo, but the precise molecular mechanism of these effects is unknown (Kim, I., Fu, Y., Hui, K., Moeckel, G., Mai, W., Li, C., Liang, D., Zhao, P., Ma, J., Chen, X.-Z., George, A. L., Jr., Coffey, R. J., Feng, Z. P., and Wu, G. (2008) J. Am. Soc. Nephrol. 19, 455-468). In this study, through the use of deletion and mutagenesis strategies, we identified a PC2-binding domain in the intracellular C terminus of FPC and an FPC-binding domain in the intracellular N terminus of PC2. These binding domains provide a molecular basis for the physical interaction between PC2 and FPC. In addition, we also found that physical interaction between the binding domains of PC2 and FPC is able to prevent down-regulation of PC2 induced by loss of FPC. In vivo, we generated a mouse model of ADPKD with hypomorphic Pkd2 alleles (Pkd2nf3/nf3) and show that PC2 down-regulation is accompanied by a phenotype similar to that of Pkhd1(-/-) mice. These findings demonstrate a common mechanism underlying cystogenesis in ADPKD and ARPKD and provide insight into the molecular relationship between PC2 and FPC.

Defining a Link with Autosomal-Dominant Polycystic Kidney Disease in Mice with Congenitally Low Expression of Pkd1

Perspectives on Drug Development in Early ADPKD.

An increased understanding of the genetic, molecular and cellular mechanisms responsible for the development of polycystic kidney disease has laid out the foundation for the development of rational therapies. Many animal models where these therapies can be tested are currently available. This review summarizes the rationale for these treatments, the results of preclinical trials and the prospects for clinical trials, some already in early phases of implementation.

Anoctamin 1 induces calcium-activated chloride secretion and proliferation of renal cyst–forming epithelial cells

Intermediate Volume on Computed Tomography Imaging Defines a Fibrotic Compartment that Predicts Glomerular Filtration Rate Decline in Autosomal Dominant Polycystic Kidney Disease Patients

Detection of autosomal dominant polycystic kidney disease by NMR spectroscopic fingerprinting of urine

Evaluation of urine biomarkers of kidney injury in polycystic kidney disease

Patients with autosomal dominant polycystic kidney disease (ADPKD) have a higher risk of nephrolithiasis ([1][1]). When using unenhanced computed tomography, calculi can be identified in up to 25% of patients with ADPKD ([2][2]). Kidney stones in patients with ADPKD are usually composed of uric acid

Young Women With Polycystic Liver Disease Respond Best to Somatostatin Analogues: A Pooled Analysis of Individual Patient Data

BACKGROUND AND AIMS The risk of urinary tract stone formation in patients with autosomal dominant polycystic kidney disease (ADPKD) is 20%, twice as high as in the normal population. The most important reason for this increased tendency to stone disease is thought to be anatomic changes in the kidney. To investigate metabolic factors that predispose to urinary system stone formation in individuals with ADPKD. METHOD A total of 180 volunteers who applied to our outpatient clinic between December 2019 and May 2021 were included in the study. Four groups were formed: patients with ADPKD and urinary system stones (ADPKD + STONE) (n = 42), patients with ADPKD but no stones (ADPKD + STONE FREE) (n = 43), stone patients without ADPKD (STONE) (n = 47) and healthy controls (HEALTHY) (n = 48) groups. Spot urine pH, 24-h urine volume, calcium, uric acid, oxalate, citrate, sodium and magnesium parameters were measured. STONE group data were obtained retrospectively. Along with these parameters, serum electrolyte, parathormone (PTH), ferritin, albumin, creatinine, urea and uric acid values were also compared. A P value of <.05 was considered significant for statistical analysis. RESULTS There was no statistically significant difference between the four groups in terms of age and gender (P > .05). The citrate value in 24-h urine was significantly lower in the ADPKD + STONE and ADPKD + STONE-FREE groups than the STONE and HEALTHY groups (P < .05). The citrate value in the 24-h urine was significantly lower in the STONE group than in the HEALTHY group (P < .05). The citrate value in 24-h urine did not differ significantly between the ADPKD + STONE and ADPKD + STONE FREE groups (P > .05). In the ADPKD + STONE and ADPKD + STONE-FREE groups, the 24-h urinary calcium value was significantly lower than the STONE and HEALTHY groups (P < .05). In the STONE group, the 24-h urinary calcium value was significantly higher than the HEALTHY group (P < .05). There was no significant difference in the 24-h urinary calcium value between the ADPKD + STONE and ADPKD + STONE FREE groups (P > .05). The uric acid level in 24-h urine was significantly lower in the ADPKD + STONE and ADPKD + STONE-FREE groups than in the HEALTHY group (P < .05). The uric acid value in the 24-h urine did not differ significantly between the ODPBH + STONE, ADPKD + STONE-FREE and STONE groups (P > .05). The uric acid value in 24-h urine did not differ significantly between the STONE and HEALTHY groups (P > .05). Oxalate, sodium and magnesium values in 24-h urine and 24-h urine volume did not differ significantly between the groups (P > .05). Urine pH value was significantly lower in the ADPKD + STONE, ADPKD + STONE-FREE and STONE groups than in the HEALTHY group (P < .05). The pH value did not differ significantly between ADPKD + STONE, ADPKD + STONE-FREE and STONE groups (P > .05). Serum PTH values were significantly higher in the ADPKD + STONE and ADPKD + STONE-FREE groups than in the HEALTHY group (P < .05). The PTH values did not differ significantly between the STONE and HEALTHY groups (P > .05). PTH values did not differ significantly between ODPBH + STONE, ADPKD + STONE-FREE and STONE groups (P > .05). There was no significant difference between the groups in terms of serum ferritin, sodium, potassium, calcium, phosphorus, magnesium and uric acid values (P > .05). CONCLUSION In our study, 24-h urine citrate level was found to be significantly lower in both ADPKD + STONE and ADPKD + STONE-FREE patients compared to the volunteers in the STONE and HEALTHY groups (P < .05). In conclusion, patients with ADPKD should also be evaluated for hypocitraturia in the outpatient clinic.

Informatics-guided drug repurposing for Autosomal Dominant Polycystic Kidney Disease (ADPKD).

Chest Mass in a Newborn Infant.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease in Western countries. The prevalence is between 2.4/10,000 and 3.9/10,000. ADPKD represents a systemic disease resulting in deterioration in renal function. Until now, mutations in two genes (PKD1 and PKD2) have been identified. Recently, the European Medicines Agency (EMA) approved the use of the vasopressin V2 receptor antagonist tolvaptan to slow the progression of cyst development and renal insufficiency connected with ADPKD in adult patients with chronic kidney disease stages 1-3 at initiation of treatment with evidence of rapidly progressing disease. Whereas the EMA approved the release of tolvaptan, the US Food and Drug Administration (FDA) requested further data on side effects and the selection of patient cohorts who may benefit from treatment. Summary: This review focused on advances in the management and treatment of ADPKD in Western countries. Key Message: ADPKD represents the fourth most common cause of end-stage renal disease (ESRD) in Western countries. ADPKD is a multisystemic disease characterized by the progressive development of bilateral renal cysts, resulting in enlargement of the kidney volume due to cystic formations, hypertension, hematuria, and loss of renal function. ADPKD is associated with high inter- and intrafamilial variability in disease appearance and progression. Patients with PKD1 mutations typically have a more severe phenotype than those with PKD2 mutations. ADPKD is under intensive investigation. Vasopressin and the associated cyclic adenosine monophosphate-related signaling pathways have been demonstrated to be important contributors to cyst growth in ADPKD. Supportive treatments are recommended with the aim of reducing morbidity and mortality associated with disease manifestations. In the past years, several agents have been investigated in ADPKD patients, including mTOR inhibitors, somatostatin analogs, statins, and vasopressin V2 receptor antagonists. 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 ESRD. 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.