Cakut

A range of renal and urinary tract malformations that vary from complete renal agenesis , to renal hypodysplasia, MULTICYSTIC DYSPLASTIC KIDNEY, duplex renal collecting system, ureteropelvic junction obstruction (UPJO), megaureter, posterior urethral valves (PUV), and vesicoureteral reflux (VUR). Up to 10% of cases are familial (autosomal dominant), although these are frequently asymptomatic or less severe; thus, PENETRANCE is incomplete. CAKUT occurs in 1 in 500 live births, and is lethal 1 in 2,000 births, it can also occur with other congenital anomalies, such as papillorenal syndrome (OMIM: 120330). OMIM: 610805

Also Known As:

Networked: 172 relevant articles (4 outcomes, 33 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Cakut
2.	Congenital Abnormalities (Deformity)
3.	Renal Insufficiency (Renal Failure)
4.	Kidney Diseases (Kidney Disease)
5.	Infertility (Sterility)

Experts

1.	Hildebrandt, Friedhelm: 12 articles (01/2022 - 01/2009)
2.	Tasic, Velibor: 11 articles (01/2022 - 01/2009)
3.	Shril, Shirlee: 9 articles (01/2022 - 01/2016)
4.	Xu, Hong: 8 articles (01/2022 - 01/2019)
5.	Chen, Jing: 8 articles (11/2021 - 01/2016)
6.	Bauer, Stuart B: 7 articles (01/2022 - 01/2016)
7.	Connaughton, Dervla M: 7 articles (01/2022 - 01/2018)
8.	Mann, Nina: 7 articles (01/2022 - 08/2017)
9.	Nakayama, Makiko: 7 articles (01/2022 - 06/2010)
10.	Shen, Qian: 7 articles (01/2022 - 01/2019)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Cakut:

1.	Glial Cell Line-Derived Neurotrophic Factor (GDNF)IBA 07/01/2012 - "Although reduction in GDNF dosage improved CAKUT it did not affect delayed mesenchyme regression. " 01/01/2019 - "Studies in mice suggest that perturbations of the GDNF-Ret signaling pathway are a major genetic cause of congenital anomalies of the kidney and urinary tract (CAKUT). " 11/01/2012 - "We sequenced GDNF, SPRY1 and RET in 122 unrelated living CAKUT patients to discover deleterious mutations that cause CAKUT. " 03/01/2009 - "RET mutations were found in 5 patients (4 HSCR, 1 HSCR + CAKUT, 0 CAKUT) and GDNF mutations in 3 (2 HSCR, 1 CAKUT, 0 HSCR + CAKUT). " 03/01/2009 - "Therefore, we designed a prospective study aimed at determining the prevalence of CAKUT in HSCR patients and at identifying RET, glial cell line-derived neurotrophic factor (GDNF), and GDNF family receptor alpha1 (GFRalpha1) mutations or haplotypes associated with this subset of HSCR patients. "
2.	Biomarkers (Surrogate Marker)IBA 02/10/2023 - "Future advances in the management of CAKUT will depend on improved biomarkers and imaging techniques." 01/01/2021 - "This prospective study was designed to determine whether urinary biomarkers can predict progressive deterioration of kidney function in children with CAKUT. " 01/01/2021 - "Urinary biomarkers as point-of-care tests for predicting progressive deterioration of kidney function in congenital anomalies of kidney and urinary tract: trefoil family factors (TFFs) as the emerging biomarkers." 04/01/2019 - "Prospective Study on Several Urinary Biomarkers as Indicators of Renal Damage in Children with CAKUT." 01/01/2019 - "We see great potential for combined -omics approaches that include next generation sequencing in the identification of CAKUT-specific biomarkers, which is necessary to optimize the care for CAKUT patients."
3.	U 0126 (UO 126)IBA 01/01/2023 - "Additionally, a single dose of 30 mg/kg U0126 on day 10.5 embryos (E10.5) was most effective for reducing CAKUT incidence and ectopic UB outgrowth in Robo2PB/+Gen1PB/+ mice. " 01/01/2023 - "Thus, we explored the effect of the MAPK/ERK inhibitor U0126 in the CAKUT phenotype in Robo2PB/+Gen1PB/+ mice. " 01/01/2023 - "Intraperitoneal injection of U0126 during pregnancy prevented the development of the CAKUT phenotype in Robo2PB/+Gen1PB/+ mice. "
4.	Proteins (Proteins, Gene)FDA Link 04/28/2023 - "Target protein expression patterns in kidney development and the early postnatal period observed in this study could indicate that switching between canonical and non-canonical Wnt signaling is crucial for normal nephrogenesis, while the defective Dab1 gene product in yotari mice may promote CAKUT due to interfering with this process." 05/01/2016 - "The present study showed that INM exists in the ureteric epithelium and suggests that INM may be related with the CAKUT etiology via primary ciliary protein function. " 12/01/2011 - "Animal experiments demonstrate that alterations in genes crucial for kidney development can cause experimental CAKUT, while expression studies implicate mislocalization and/or aberrant levels of the encoded proteins in human CAKUT. " 07/01/2008 - "Our studies show novel proteins may cooperate with HNF1beta in human metanephric development and propose that E4F1 and ZFP36L1 are CAKUT genes. " 11/10/2023 - "Our work thus identifies a key role for DLG1 in mediating ciliary targeting of PC2 and other proteins and implicates ciliary dysfunction as a possible contributing factor to CAKUT."
5.	MicroRNAs (MicroRNA)IBA 10/22/2022 - "The study aimed to identify and functionally interpret miRNAs most frequently affected by rare CNVs in CAKUT and to estimate the overall burden of rare CNVs on miRNA genes in CAKUT. " 01/01/2023 - "We aimed to construct interaction network of previously bioinformatically associated miRNAs with CAKUT differentially expressed genes in order to prioritize those associated with fibrotic process and to experimentally validate the expression of selected miRNAs in CAKUT patients compared to control group. " 10/22/2022 - "Understanding the potential of CNV-affected miRNAs to participate in CAKUT as genetic drivers represent a crucial implication for the development of novel therapeutic approaches." 10/22/2022 - "miRNA genes are frequently affected by rare CNVs in CAKUT patients. " 10/22/2022 - "An over/underrepresentation of miRNA genes in rare CNVs associated with CAKUT was observed in multiple chromosomes, such as chr16, chr20, and chr21. "
6.	Messenger RNA (mRNA)IBA 01/01/2023 - "Sc-mRNA expression data of human fetal kidney can be utilized to prioritize WES-derived CAKUT candidate genes. " 01/01/2023 - "We analyzed single-cell mRNA (sc-mRNA) transcriptomics data of human fetal kidney for temporal sc-mRNA co-expression of 40 known CAKUT genes. " 12/08/2022 - "The RT-qPCR analysis revealed a significantly higher FGFR2 mRNA expression score in the CAKUT kidneys compared to the CTRL. " 01/01/2010 - "The expression of AT2R mRNA in human CAKUT was established for the first time and was not affected by -1332A/G polymorphism in children with CAKUT." 01/01/2010 - "The expression of Ex 1/2/3 and Ex 1/3 transcript splice variants of the AT2R mRNA were detected in human CAKUT tissue. "
7.	Vitamin DFDA LinkGeneric 01/01/2021 - "We observed limited overlap between vitamin D targets and CAKUT-related gene sets. " 01/01/2021 - "In this study, we aimed to investigate whether vitamin A or vitamin D could have a role in CAKUT aetiology. " 01/01/2021 - "In this study, we collected vitamin A and vitamin D target genes and computed their overlap with CAKUT-related gene sets. " 01/01/2021 - "For this purpose we collected vitamin A and vitamin D target genes and computed their overlap with CAKUT-related gene sets. " 01/01/2021 - "Overlap of vitamin A and vitamin D target genes with CAKUT-related processes."
8.	Vitamin A (Retinol)FDA LinkGeneric 01/01/2021 - "We however observed that vitamin A target genes significantly overlap with multiple CAKUT-related gene sets, including CAKUT causal and differentially expressed genes, and genes involved in renal system development. " 01/01/2021 - "We observed significant overlaps between vitamin A target genes and CAKUT causal genes, or with genes involved in renal system development, which indicates that an excess or deficiency of vitamin A might be relevant to a broad range of urogenital abnormalities." 01/01/2021 - "In this study, we aimed to investigate whether vitamin A or vitamin D could have a role in CAKUT aetiology. " 01/01/2021 - "In this study, we collected vitamin A and vitamin D target genes and computed their overlap with CAKUT-related gene sets. " 01/01/2021 - "For this purpose we collected vitamin A and vitamin D target genes and computed their overlap with CAKUT-related gene sets. "
9.	Peptidyl-Dipeptidase A (Angiotensin Converting Enzyme)IBA 08/01/2017 - "The aim of this study was to investigate the association of an insertion/deletion (I/D) polymorphism in angiotensin-converting enzyme (ACE) gene with serum ACE level in relation to the type and severity of malformations from congenital anomalies of the kidney and urinary tract (CAKUT) spectrum. " 12/01/2004 - "Angiotensin I-converting enzyme (ACE) and angiotensin type 2 receptor (AT2R) gene polymorphisms have been associated with an increased incidence of congenital anomalies of the kidney and urinary tract (CAKUT). " 11/01/2022 - "This study was done to identify the effect of polymorphisms in paired-box gene 2 (PAX2), bone morphogenetic protein (BMP)-4, angiotensin-converting enzyme (ACE), and angiotensin II receptor Type 2 (AGTR2) nephrogenic genes on the development of CAKUT. "
10.	CytokinesIBA 01/01/2013 - "Therefore, the aim of this paper is to revise general aspects of cytokines and the link between cytokines, CAKUT, and CKD by including experimental and clinical evidence. " 01/01/2013 - "Interactions between cytokines, congenital anomalies of kidney and urinary tract and chronic kidney disease." 02/01/2019 - "Additionally, our study supposes that immunoregulatory cytokine IL-10 might have a significant role in CAKUT." 01/01/2013 - "In this regard, recent studies suggest a role for cytokines and chemokines in the pathophysiology of CAKUT and for the progression to CKD. "

Therapies and Procedures

1.	Cell- and Tissue-Based Therapy (Cell Therapy) 01/01/2021 - "We present our protocol and preliminary analysis of an IRB-approved, phase I single-group, open-label trial that tests the safety and efficacy of Renal Autologous Cell Therapy (REACT; NCT04115345) in adults with congenital anomalies of the kidney and urinary tract (CAKUT). " 01/01/2021 - "Autologous cell therapy treatment has the potential to stabilize or improve renal function in CAKUT-associated CKD to delay or avert dialysis. "
2.	Renal Replacement Therapy (Therapies, Renal Replacement) 01/01/2013 - "This study assessed the age at onset of renal replacement therapy (RRT) and patient and renal graft survival in patients with CAKUT across the entire age range. " 01/01/2022 - "We performed trio WES on five infants with severe CAKUT (undergoing fetal interventions and/or those who initiated renal replacement therapy (RRT) within 1 month of life) and their parents as well as three singletons. " 02/01/2016 - "Congenital anomalies of the kidney and urinary tract (CAKUT) are 1 of the major factors in young adults needing renal replacement therapy, but there is little extensive assessment of their incidence and risk factors. " 01/01/2011 - "Any of these anomalies may have long-term sequelae, and CAKUT is the primary cause for renal replacement therapy in childhood. " 11/01/2023 - "Congenital anomalies of the kidney and urinary tract (CAKUT) are the predominant cause of chronic kidney disease (CKD) and the need for kidney replacement therapy (KRT) in children. "
3.	Protein-Restricted Diet (Diet, Protein Restricted) 01/01/2020 - "The present study aimed to establish an intrauterine low-protein diet roundabout 2 (Robo2) mutant mouse model and found that the intrauterine low-protein diet led to significantly increased CAKUT phenotypes in Robo2PB/+ mice offspring, dominant by a duplicated collecting system. " 01/01/2019 - "In this study, we reported that intrauterine low-protein diet can cause congenital anomalies of the kidney and urinary tract (CAKUT) phenotypes, which was dominated by the duplicated collecting system phenotype. " 01/01/2020 - "An intrauterine low-protein diet can also cause CAKUT in offspring, dominated by the duplicated collecting system phenotype. " 01/01/2019 - "Thus, we showed correlation between intrauterine low-protein diet and CAKUT in offspring." 01/01/2019 - "Slit2/Robo2 and Spry1 expression levels were decreased, Ret expression was increased, and downstream p-Akt activity enhanced with apoptosis abnormal in ureteric bud tissue, which may be the mechanisms that intrauterine low-protein diet causes increased incidence of CAKUT in offspring. "
4.	Kidney Transplantation 06/01/2023 - "Those with anatomic causes of CAKUT started on dialysis have significantly reduced access to kidney transplantations compared to individuals with inherited causes of CAKUT who were initiated on dialysis. " 06/01/2023 - "There are notable disparities in kidney transplantation rates among CAKUT subgroups. " 06/01/2023 - "Among the subset of individuals with CAKUT as the attributed cause of ESKD, we found a lower likelihood of kidney transplantation in those with anatomic causes of CAKUT compared to those with inherited causes of CAKUT (adjusted HR 0.85; 0.81-0.90). " 06/01/2023 - "Overall, we found an increased likelihood of kidney transplantation access for participants with CAKUT compared to those without CAKUT (HR 1.23; 95% CI 1.20-1.27). " 04/01/2023 - "We compared long-term outcomes after kidney transplantation (KTx) in patients with and without congenital anomalies of the kidney and urinary tract (CAKUT). "
5.	Transplantation 04/01/2023 - "In multivariate Cox regression analyses, CAKUT (HR: 0.469; 95% CI: 0.320-0.687; p < 0.001) and PRA positivity before transplantation (HR: 3.756; 95% CI: 1.507-9.364; p = 0.005) predicted graft loss. " 11/02/2023 - "Conclusion Patients with CAKUT, who received induction therapy and small children were hospitalized more frequently after transplantation. " 06/01/2023 - "We compared transplantation access in the US based on whether the etiology of kidney disease was secondary to CAKUT, and additionally by CAKUT subgroups (anatomic vs. inherited causes of CAKUT). " 01/01/2020 - "Younger age, shorter time since transplantation, male sex, higher body mass index (BMI), high cyclosporine A (CSA) trough levels, and a primary renal disease other than congenital anomalies of the kidney and urinary tract (CAKUT) were significantly associated with higher systolic BP z-score. " 01/01/2022 - "In the subgroup of patients with congenital anomalies of the kidney and urinary tract (CAKUT) those were significantly younger at onset of dialysis (p < 0.001) and at time of transplantation (p < 0.001), also they were less in body weight (p < 0.01), and body size (p < 0.001), this subgroup was larger in era 2. HLA mismatch data, serum creatinine, and GFR yield comparable results in both groups. "