Chronic kidney disease (CKD) encompasses a group of diverse diseases that are associated with accumulating kidney damage and a decline in glomerular filtration rate (GFR). These conditions can be of an acquired or genetic nature and, in many cases, interactions between genetics and the environment also play a role in disease manifestation and severity. In this review, we focus on genetically inherited chronic kidney diseases and dissect the links between canonical and non-canonical Wnt signalling, and this umbrella of conditions that result in kidney damage. Most of the current evidence on the role of Wnt signalling in CKD is gathered from studies in polycystic kidney disease (PKD) and nephronophthisis (NPHP) and reveals the involvement of β-catenin. Nevertheless, recent findings have also linked planar cell polarity (PCP) signalling to CKD, with further studies being required to fully understand the links and molecular mechanisms.
The definition of a rare disease in the European Union describes genetic disorders that affect less than 1 in 2,000 people per individual disease; collectively these numbers amount to millions of individuals globally, who usually manifest a rare disease early on in life. At present, there are at least 8,000 known rare conditions, of which only some are clearly molecularly defined. Over the recent years, the use of genetic diagnosis is gaining ground into informing clinical practice, particularly in the field of rare diseases, where diagnosis is difficult. To demonstrate the complexity of genetic diagnosis for rare diseases, we focus on Ciliopathies as an example of a group of rare diseases where an accurate diagnosis has proven a challenge and novel practices driven by scientists are needed to help bridge the gap between clinical and molecular diagnosis. Current diagnostic difficulties lie with the vast multitude of genes associated with Ciliopathies and trouble in distinguishing between Ciliopathies presenting with similar phenotypes. Moreover, Ciliopathies such as Autosomal Recessive Polycystic Kidney Disease (ARPKD) and Meckel-Gruber syndrome (MKS) present with early phenotypes and may require the analysis of samples from foetuses with a suspected Ciliopathy. Advancements in Next Generation Sequencing (NGS) have now enabled assessing a larger number of target genes, to ensure an accurate diagnosis. The aim of this review is to provide an overview of current diagnostic techniques relevant to Ciliopathies and discuss the applications and limitations associated with these techniques.
Polycystic Kidney Disease (PKD) refers to a group of disorders, driven by the formation of cysts in renal tubular cells and is currently one of the leading causes of end-stage renal disease. The range of symptoms observed in PKD is due to mutations in cilia-localising genes, resulting in changes in cellular signalling. As such, compounds that are currently in preclinical and clinical trials target some of these signalling pathways that are dysregulated in PKD. In this review, we highlight these pathways including cAMP, EGF and AMPK signalling and drugs that target them and may show promise in lessening the disease burden of PKD patients. At present, tolvaptan is the only approved therapy for ADPKD, however, it carries several adverse side effects whilst comparatively, no pharmacological drug is approved for ARPKD treatment. Aside from this, drugs that have been the subject of multiple clinical trials such as metformin, which targets AMPK signalling and somatostatins, which target cAMP signalling have shown great promise in reducing cyst formation and cellular proliferation. This review also discusses other potential and novel targets that can be used for future interventions, such as β-catenin and TAZ, where research has shown that a reduction in the overexpression of these signalling components results in amelioration of disease phenotype. Thus, it becomes apparent that well-designed preclinical investigations and future clinical trials into these pathways and other potential signalling targets are crucial in bettering disease prognosis for PKD patients and could lead to personalised therapy approaches.
Background: SARS-CoV-2 is a coronavirus that has rapidly spread across the world with a detrimental effect on the global population. Several reports have highlighted an increased mortality rate and a higher severity of COVID-19 infection in chronic kidney disease (CKD) individuals. Upon the development of various SARS-CoV-2 vaccines, mRNA vaccines including BNT162b2 and mRNA-1273 were deemed safe, with a high efficacy in preventing COVID-19 in the general population. This review investigates whether SARS-CoV-2 mRNA vaccines are as effective in triggering an immune response in Dialysis Patients (DPs) and Kidney Transplant Recipients (KTRs) and if a third dose is required in this population. Methods: A systematic search employing the PRISMA criteria was conducted in several major databases, with the data being extracted from publications for the period January 2021 to May 2022 (PROSPERO: CRD42022338514, June 15, 2022). Results: 80 studies were included in this analysis with a total cohort number of 15,059 participants. Overall, 85.29% (OR = 17.08, 95% CI = 15.84-18.42, I2 = 98%) and 41.06% (OR = 0.52, 95% CI = 0.48-0.5, I2 = 95%) of DPs and KTRs included in this review showed positive seroconversion after two doses of either mRNA vaccine, respectively. A total 76% (OR = 6.53, 95% CI = 5.63-7.5, I2 = 96%) of the cohort given a third dose of an mRNA vaccine demonstrated positive seroconversion, with 61.86% (OR = 2.31, 95% CI = 1.95-2.75 I2 = 95%) of the cohort that was assessed for a cellular response displaying a positive response. Conclusions: This data emphasises a reduced incidence of a positive immune response in DPs and KTRs compared to healthy controls, albeit a better response in DPs than when compared to KTRs alone was observed. A third dose appears to increase the occurrence of an immune response in the overall DP/KTR cohort.
Background: SARS-CoV-2 is a coronavirus that has rapidly spread across the world with a detrimental effect on the global population. Several reports have highlighted an increased mortality rate and a higher severity of COVID-19 infection in chronic kidney disease (CKD) individuals. Upon the development of various SARS-CoV-2 vaccines, mRNA vaccines including BNT162b2 and mRNA-1273 were deemed safe, with a high efficacy in preventing COVID-19 in the general population. This review investigates whether SARS-CoV-2 mRNA vaccines are as effective in triggering an immune response in Dialysis Patients (DPs) and Kidney Transplant Recipients (KTRs) and if a third dose is required in this population. Methods: A systematic search employing the PRISMA criteria was conducted in several major databases, with the data being extracted from publications for the period January 2021 to May 2022 (PROSPERO: CRD42022338514, June 15, 2022). Results: 80 studies were included in this analysis with a total cohort number of 15,059 participants. Overall, 85.29% (OR = 17.08, 95% CI = 15.84-18.42, I2 = 98%) and 41.06% (OR = 0.52, 95% CI = 0.48-0.5, I2 = 95%) of DPs and KTRs included in this review showed positive seroconversion after two doses of either mRNA vaccine, respectively. A total 76% (OR = 6.53, 95% CI = 5.63-7.5, I2 = 96%) of the cohort given a third dose of an mRNA vaccine demonstrated positive seroconversion, with 61.86% (OR = 2.31, 95% CI = 1.95-2.75 I2 = 95%) of the cohort that was assessed for a cellular response displaying a positive response. Conclusions: This data emphasises a reduced incidence of a positive immune response in DPs and KTRs compared to healthy controls, albeit a better response in DPs than when compared to KTRs alone was observed. A third dose appears to increase the occurrence of an immune response in the overall DP/KTR cohort.
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