ADPKD

BACKGROUND: The management of autosomal dominant polycystic kidney disease (ADPKD) remains challenging with variable and uncertain genotype-phenotype correlations. The Mayo clinic imaging classification allows a more accurate risk stratification but is limited by the atypical imaging patterns. We aim to assess the clinical characteristics and the morphology of the cystic kidneys in a cohort of Chinese patients with ADPKD. METHOD: Ninety-eight patients with ADPKD were recruited prospectively from August 2019 to December 2020 in Prince of Wales Hospital, Hong Kong...

BACKGROUND: In animal models of ADPKD, high water intake (HWI) decreases vasopressin secretion and slows disease progression, but the efficacy of HWI in human ADPKD is uncertain. METHODS: This exploratory, prospective, crossover study of ADPKD subjects (n=7) evaluated the hypothesis that HWI slows the rate of increase in height-adjusted total kidney volume (ht-TKV; a biomarker for ADPKD progression) and reduces pain. Subjects at high risk of ADPKD progression (i...

Autosomal dominant polycystic kidney disease (ADPKD) is a rare genetic disease. Diagnosis of ADPKD is usually made by the number of renal cysts on the ultrasound for each age category. There are two types of ADPKD, and the patients with the second type have later onset of symptoms, with slower disease progression than in the first type. These patients are typically at risk of recurrent urinary tract infections, hemorrhage and rupture of cysts, end-stage renal disease, calculi, liver/pancreatic cysts, and brain aneurysm development...

Autosomal dominant polycystic kidney disease (ADPKD) is commonly caused by PKD1, and mosaic PKD1 variants result in milder phenotypes. We present the case of a 32 year-old male with chronic active Epstein-Barr virus who underwent bone marrow transplantation with chemoradiotherapy at age 9. Despite a low-frequency mosaic splicing PKD1 variant, he developed severe renal cysts and end-stage renal disease in his 30 s. This case highlights how environmental factors may contribute to the genetic predisposition to ADPKD...

BACKGROUND: There are limitations in treating advanced prostate cancer (PC), especially castration-resistant (CR) cases, in renal transplant recipients (RTRs). We describe the case of RTR with metastatic CRPC (mCRPC) treated with docetaxel. CASE REPORT: A 60-year-old man with end-stage renal disease due to autosomal-dominant polycystic kidney disease (ADPKD) underwent living-related kidney transplantation. A year later, he was diagnosed with PC (prostate-specific antigen level: 998 ng/mL)...

Background: Our study aims to comment on all ADPKD variants identified in our health area and explain how they are distributed geographically, to identify new variants, and relate the more frequent variants with their renal phenotype in terms of kidney survival. Materials and Methods: We identified patients suffering from ADPKD in a specialized consultation unit; genealogical trees were constructed from the proband. According to the ultrasound-defined modified Ravine-Pei criteria, relatives classified as at risk were offered participation in the genetic study...

Recently, arginine has been proven to play an important role in ADPKD physiopathology. Arginine auxotrophy in ADPKD induces cell hyperproliferation, blocking the normal differentiation of renal tube cells and causing cyst formation. We explored the L-arginine (Arg)-nitric oxide (NO) molecular pathway in ADPKD, a multisystemic arginine auxotrophe disease. We developed a prospective case-control study that included a group of 62 ADPKD subjects with an estimated filtration rate over 60 mL/min/1.73 mp, 26 subjects with chronic kidney disease with an eGFR > 60 mL/min/1...

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder worldwide and progresses to end-stage renal disease (ESRD). However, its precise mechanism is not fully understood. In recent years, epigenetic reprogramming has drawn increasing attention regarding its effect on cyst growth. However, considering the complexity of epigenetic mechanisms and the broad range of alterations of epigenetic components in ADPKD, identifying more specific epigenetic factors and understanding how they are mechanistically linked to promote cyst growth is relevant for the development of treatment for ADPKD...

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of multiple renal cysts causing kidney enlargement and end-stage renal disease (ESRD) in half the patients by 60 years of age. The aim of the study was to determine the genetic aetiology in Maltese patients clinically diagnosed with ADPKD and correlate the clinical features. METHODS: A total of 60 patients over 18 years of age clinically diagnosed with ADPKD were studied using a customized panel of genes that had sufficient evidence of disease diagnosis using next generation sequencing (NGS)...

The progression of autosomal dominant polycystic kidney disease (ADPKD), an inherited kidney disease, is associated with renal interstitial inflammation and fibrosis. CD74 has been known not only as a receptor of macrophage migration inhibitory factor (MIF) it can also have MIF independent functions. In this study, we report unknown roles and function of CD74 in ADPKD. We show that knockout of CD74 delays cyst growth in Pkd1 mutant kidneys. Knockout and knockdown of CD74 (1) normalize PKD associated signaling pathways, including ERK, mTOR and Rb to decrease Pkd1 mutant renal epithelial cell proliferation, (2) decrease the activation of NF-κB and the expression of MCP-1 and TNF-alpha (TNF-α) which decreases the recruitment of macrophages in Pkd1 mutant kidneys, and (3) decrease renal fibrosis in Pkd1 mutant kidneys...

BACKGROUND AND PURPOSE: The objective is to demonstrate feasibility of quantitative susceptibility mapping (QSM) in autosomal dominant polycystic kidney disease (ADPKD) patients and to compare imaging findings with traditional T1/T2w magnetic resonance imaging (MRI). METHODS: Thirty-three consecutive patients (11 male, 22 female) diagnosed with ADPKD were initially selected. QSM images were reconstructed from the multiecho gradient echo data and compared to co-registered T2w, T1w, and CT images...

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by heterogeneous variants in the PKD1 and PKD2 genes. Genetic analysis of PKD1 has been challenging due to homology with 6 PKD1 pseudogenes and high GC content. METHODS: A single-tube multiplex long-range-PCR and long-read sequencing-based assay termed "comprehensive analysis of ADPKD" (CAPKD) was developed and evaluated in 170 unrelated patients by comparing to control methods including next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification...

INTRODUCTION: ADPKD patients may have more imaging studies than patients with other forms of chronic kidney disease (CKD). We characterized the imaging burden of ADPKD patients relative to a CKD population to determine which factors lead to increased imaging in ADPKD patients. METHODS: We retrospectively reviewed patients seen at Yale Nephrology between January 2012 and January 2021. We collected demographic, clinical, and imaging data through automated query and manual chart review...

A rare congenital hepatobiliary disorder called Caroli's disease is characterized by multifocal segmental dilatation of intrahepatic bile ducts that can affect the entire liver or only specific areas of it. Coexisting conditions with Caroli's disease include autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD). ADPKD results in the development of cysts, which are tiny fluid-filled sacs, in the kidneys. Caroli's disease is considered a rare disorder, affecting a small number of individuals worldwide...

Autosomal dominant polycystic kidney disease (ADPKD) has long been considered a genetic renal disorder, but emerging evidence suggests that the immune microenvironment within the kidney plays a pivotal role in disease progression and severity. In recent years, the previously obscure cytokine interleukin-37 has proved a strong inhibitor of innate immunity in multiple disease models. However, its role in ADPKD has not received scrutiny. In a provocative study published in the current issue, Zylberberg et al...

The importance of P-stereogenic heterocycles has been widely recognized with their extensive use as privileged chiral ligands and bioactive compounds. The catalytic asymmetric synthesis of P-stereogenic phosphindane derivatives, however, remains a challenging task. Herein, we report a catalytic kinetic resolution of phosphindole oxides via rhodium-catalyzed diastereo- and enantioselective conjugate addition to access enantiopure P-stereogenic phosphindane and phosphindole derivatives. This kinetic resolution method features high efficiency (s factor up to >1057), excellent stereoselectivities (all >20:1 dr, up to >99% ee), and a broad substrate scope...

RATIONALE & OBJECTIVE: Alport Syndrome (AS) is the most common genetic glomerular disease caused by mutations that affect Type IV collagen. However, the clinical characteristics and significance of AS with kidney cysts are not well defined. This study investigated the prevalence and clinical significance of cystic kidney phenotype in AS. STUDY DESIGN: Retrospective cohort study. SETTING: & Participants: One hundred-eight patients with AS and a comparison cohort of 79 patients with IgA Nephropathy (IgAN)...

Autosomal dominant polycystic kidney disease (ADPKD), the most common hereditary kidney disease, accounts for approximately 10% of the patients on kidney transplantation waitlists. High rates of complications including hemorrhage, infections, nephrolithiasis and kidney size-related compressive complaints have been reported among ADPKD patients. Therefore, the need for routine native nephrectomy and timing of such procedure in ADPKD patients being prepared for transplantation are debated. Even though pre-transplant nephrectomy has the potential to provide fewer infectious complications due to lack of immunosuppressive medication use, such procedure has been associated with longer hospital stay, loss of residual kidney function and need for dialysis...

BACKGROUND: Although the mechanisms underlying cyst enlargement in autosomal dominant polycystic kidney disease (ADPKD) are becoming clearer, those of renal dysfunction are not fully understood. In particular, total kidney volume (TKV) and renal function do not always correspond. To elucidate this discrepancy, we studied in detail glomerular hemodynamic changes during ADPKD progression. METHODS: Sixty-one ADPKD patients with baseline height-adjusted TKV (Ht-TKV) of 933±537 ml/m and serum creatinine of 1...

The dysregulated intracellular cAMP in the kidneys drives cystogenesis and progression in autosomal dominant polycystic kidney disease (ADPKD). Mounting evidence supports that vasopressin V2 receptor (V2 R) antagonism effectively reduces cAMP levels, validating this receptor as a therapeutic target. Tolvaptan, an FDA-approved V2 R antagonist, shows limitations in its clinical efficacy for ADPKD treatment. Therefore, the pursuit of better-in-class V2 R antagonists with an improved efficacy remains pressing. Herein, we synthesized a set of peptide V2 R antagonists...