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Advances in Kidney Disease and Health Sep 2023Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder occurring in approximately 1:1000 individuals. ADPKD is characterized... (Review)
Review
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder occurring in approximately 1:1000 individuals. ADPKD is characterized by gradual cyst expansion and kidney enlargement and is a slowly progressive disorder where patients typically initiate renal replacement therapy in the sixth decade of life. The vast majority of women with ADPKD become pregnant in the third or fourth decade, often before knowing that they have ADPKD, in the setting of normal kidney function or chronic kidney disease Stage 1. In ADPKD, pregnancy outcomes for mother and baby differ from the general population, and long-term consequences of maternal complications from pregnancy are common in ADPKD. In the current era of genetic testing, options to consider pre-implantation genetic screening are becoming more available. This chapter will review renal physiologic and anatomic changes that occur in pregnancy, the potential impact of ADPKD on maternal and fetal outcomes, medical management during pregnancy, the impact of pregnancy on long-term outcomes in women with ADPKD, and options for families with ADPKD planning to undergo pregnancy with regard to genetic testing.
Topics: Pregnancy; Humans; Female; Polycystic Kidney, Autosomal Dominant; Pregnancy Outcome; Cysts; Renal Insufficiency, Chronic
PubMed: 38032583
DOI: 10.1053/j.akdh.2023.10.006 -
Clinical Journal of the American... Nov 2023Prostaglandin E2 (PGE2) plays a physiological role in osmoregulation, a process that is affected early in autosomal dominant polycystic kidney disease (ADPKD). PGE2 has...
BACKGROUND
Prostaglandin E2 (PGE2) plays a physiological role in osmoregulation, a process that is affected early in autosomal dominant polycystic kidney disease (ADPKD). PGE2 has also been implicated in the pathogenesis of ADPKD in preclinical models, but human data are limited. Here, we hypothesized that urinary PGE2 excretion is associated with impaired osmoregulation, disease severity, and disease progression in human ADPKD.
METHODS
Urinary excretions of PGE2 and its metabolite (PGEM) were measured in a prospective cohort of patients with ADPKD. The associations between urinary PGE2 and PGEM excretions, markers of osmoregulation, eGFR and height-adjusted total kidney volume were assessed using linear regression models. Cox regression and linear mixed models were used for the longitudinal analysis of the associations between urinary PGE2 and PGEM excretions and disease progression defined as 40% eGFR loss or kidney failure, and change in eGFR over time. In two intervention studies, we quantified the effect of starting tolvaptan and adding hydrochlorothiazide to tolvaptan on urinary PGE2 and PGEM excretions.
RESULTS
In 562 patients with ADPKD (61% female, eGFR 63±28 ml/min per 1.73 m 2 ), higher urinary PGE2 or PGEM excretions were independently associated with higher plasma copeptin, lower urine osmolality, lower eGFR, and greater total kidney volume. Participants with higher baseline urinary PGE2 and PGEM excretions had a higher risk of 40% eGFR loss or kidney failure (hazard ratio, 1.28; 95% confidence interval [CI], 1.13 to 1.46 and hazard ratio, 1.50; 95% CI, 1.26 to 1.80 per two-fold higher urinary PGE2 or PGEM excretions) and a faster change in eGFR over time (-0.39 [95% CI, -0.59 to -0.20] and -0.53 [95% CI, -0.75 to -0.31] ml/min per 1.73 m 2 per year). In the intervention studies, urinary PGEM excretion was higher after starting tolvaptan, while urinary PGE2 excretion was higher after adding hydrochlorothiazide to tolvaptan.
CONCLUSIONS
Higher urinary PGE2 and PGEM excretions in patients with ADPKD are associated with impaired osmoregulation, disease severity, and progression.
Topics: Humans; Female; Male; Polycystic Kidney, Autosomal Dominant; Tolvaptan; Dinoprostone; Prospective Studies; Osmoregulation; Disease Progression; Kidney; Renal Insufficiency; Hydrochlorothiazide; Glomerular Filtration Rate; Antidiuretic Hormone Receptor Antagonists
PubMed: 37574650
DOI: 10.2215/CJN.0000000000000269 -
Kidney360 Dec 2023Patients with autosomal dominant polycystic kidney disease benefit from specialized care over their lifetimes, starting with diagnosis of the condition with ongoing... (Review)
Review
Patients with autosomal dominant polycystic kidney disease benefit from specialized care over their lifetimes, starting with diagnosis of the condition with ongoing discussion of both the renal course and extra-renal issues. Both renal and extra-renal issues may continue to cause major morbidity even after successful kidney transplant or initiation of RRT, and extra-renal disease aspects should always be considered as part of routine management. In this review, we will focus on updates in pain/depression screening, cardiac manifestations, liver and pancreatic cysts, kidney stone management, and genetic counseling. In some instances, we have shared our current clinical practice rather than an evidence-based guideline. We anticipate more standardization of care after the release of the Kidney Disease Improving Global Outcomes guidelines for management in autosomal dominant polycystic kidney disease later this year.
Topics: Humans; Polycystic Kidney, Autosomal Dominant; Kidney; Kidney Transplantation; Kidney Calculi; Patient Care
PubMed: 38010035
DOI: 10.34067/KID.0000000000000296 -
Microcirculation (New York, N.Y. : 1994) May 2024PKD1 (polycystin 1) and PKD2 (polycystin 2) are expressed in a variety of different cell types, including arterial smooth muscle and endothelial cells. PKD1 is a... (Review)
Review
PKD1 (polycystin 1) and PKD2 (polycystin 2) are expressed in a variety of different cell types, including arterial smooth muscle and endothelial cells. PKD1 is a transmembrane domain protein with a large extracellular N-terminus that is proposed to act as a mechanosensor and receptor. PKD2 is a member of the transient receptor potential (TRP) channel superfamily which is also termed TRPP1. Mutations in the genes which encode PKD1 and PKD2 lead to autosomal dominant polycystic kidney disease (ADPKD). ADPKD is one of the most prevalent monogenic disorders in humans and is associated with extrarenal and vascular complications, including hypertension. Recent studies have uncovered mechanisms of activation and physiological functions of PKD1 and PKD2 in arterial smooth muscle and endothelial cells. It has also been found that PKD function is altered in the vasculature during ADPKD and hypertension. We will summarize this work and discuss future possibilities for this area of research.
Topics: TRPP Cation Channels; Humans; Polycystic Kidney, Autosomal Dominant; Animals; Muscle, Smooth, Vascular; Hypertension; Mutation; Endothelial Cells
PubMed: 37823335
DOI: 10.1111/micc.12834 -
Pediatric Nephrology (Berlin, Germany) Aug 2023Glomerular hyperfiltration (GHF) is a phenomenon that can occur in various clinical conditions affecting the kidneys such as sickle cell disease, diabetes mellitus,... (Review)
Review
Glomerular hyperfiltration (GHF) is a phenomenon that can occur in various clinical conditions affecting the kidneys such as sickle cell disease, diabetes mellitus, autosomal dominant polycystic kidney disease, and solitary functioning kidney. Yet, the pathophysiological mechanisms vary from one disease to another and are not well understood. More so, it has been demonstrated that GHF may occur at the single-nephron in some clinical conditions while in others at the whole-kidney level. In this review, we explore the pathophysiological mechanisms of GHF in relation to various clinical conditions in the pediatric population. In addition, we discuss the role and mechanism of action of important factors such as gender, low birth weight, and race in the pathogenesis of GHF. Finally, in this current review, we further highlight the consequences of GHF in the progression of kidney disease.
Topics: Child; Humans; Clinical Relevance; Glomerular Filtration Rate; Kidney Glomerulus; Kidney; Polycystic Kidney, Autosomal Dominant
PubMed: 36472656
DOI: 10.1007/s00467-022-05826-5 -
PloS One 2023PKD1 is the most commonly mutated gene causing autosomal dominant polycystic kidney disease (ADPKD). It encodes Polycystin-1 (PC1), a putative membrane protein that...
PKD1 is the most commonly mutated gene causing autosomal dominant polycystic kidney disease (ADPKD). It encodes Polycystin-1 (PC1), a putative membrane protein that undergoes a set of incompletely characterized post-transcriptional cleavage steps and has been reported to localize in multiple subcellular locations, including the primary cilium and mitochondria. However, direct visualization of PC1 and detailed characterization of its binding partners remain challenging. We now report a new mouse model with HA epitopes and eGFP knocked-in frame into the endogenous mouse Pkd1 gene by CRISPR/Cas9. Using this model, we sought to visualize endogenous PC1-eGFP and performed affinity-purification mass spectrometry (AP-MS) and network analyses. We show that the modified Pkd1 allele is fully functional but the eGFP-tagged protein cannot be detected without signal amplification by secondary antibodies. Using nanobody-coupled beads and large quantities of tissue, AP-MS identified an in vivo PC1 interactome, which is enriched for mitochondrial proteins and components of metabolic pathways. These studies suggest this mouse model and interactome data will be useful to understand PC1 function, but that new methods and brighter tags will be required to track endogenous PC1.
Topics: Mice; Animals; TRPP Cation Channels; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Disease Models, Animal
PubMed: 37540694
DOI: 10.1371/journal.pone.0289778 -
Yi Chuan = Hereditas Jul 2023Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small vessel disease in... (Review)
Review
Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small vessel disease in adults. Many CADASIL cases were reported after was identified as the causative gene of CADASIL. However, there is still no specific and effective therapies for CADASIL. In this review, we summarize recent research progress on disease models, symptomatic treatments and potential therapies for CADASIL, thereby providing a reference for follow-up CADASIL treatment research.
Topics: Adult; Humans; CADASIL; Leukoencephalopathies; Magnetic Resonance Imaging; Mutation
PubMed: 37503581
DOI: 10.16288/j.yczz.23-023