The Death of a Baby from the Congenital Anomalies of the Urinary Tract

Background: Advanced cell therapies with autologous, homologous cells show promise to affect reparative and restorative changes in the chronic kidney disease (CKD) nephron. 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; NCT 04115345) in adults with congenital anomalies of the kidney and urinary tract (CAKUT). Methods: Adults with surgically corrected CAKUT and CKD stages 3 and 4 signed an informed consent and served as their “own” baseline control. REACT is an active biological ingredient acquired from a percutaneous tissue acquisition from the patient’s kidney cortex. The specimen undergoes a GMP-compliant manufacturing process that harvests the selected renal cells composed of progenitors for renal repair, followed by image-guided locoregional reinjection into the patient’s renal cortex. Participants receive 2 doses at 6-month intervals. Primary outcomes are stable renal function and stable/improved quality of life. Additional exploratory endpoints include the impact of REACT on blood pressure, vitamin D levels, hemoglobin, hematocrit and kidney volume by MRI analysis. Results: Four men and 1 woman were enrolled and underwent 5 cell injections. Their characteristics were as follows: mean 52.8 years (SD 17.7 years), 1 Hispanic, 4 non-Hispanic, and 5 white. There were no renal tissue acquisition, cell injection, or cell product-related complications at baseline. Conclusion: REACT is demonstrating feasibility and patient safety in preliminary analysis. Autologous cell therapy treatment has the potential to stabilize or improve renal function in CAKUT-associated CKD to delay or avert dialysis. Patient enrollment and follow-up are underway.

Download Full-text

Functional Models for Congenital Anomalies of the Kidney and Urinary Tract

Nephron ◽

10.1159/000369313 ◽

2014 ◽

Vol 129 (1) ◽

pp. 62-67 ◽

Cited By ~ 5

Author(s):

Glenn van de Hoek ◽

Nayia Nicolaou ◽

Rachel H. Giles ◽

Nine V.A.M. Knoers ◽

Kirsten Y. Renkema ◽

...

Keyword(s):

Urinary Tract ◽

Congenital Anomalies ◽

Functional Models

Download Full-text

Ultrasound-Based Renal Parenchymal Area and Kidney Function Decline in Infants With Congenital Anomalies of the Kidney and Urinary Tract

Seminars in Nephrology ◽

10.1016/j.semnephrol.2021.09.004 ◽

2021 ◽

Vol 41 (5) ◽

pp. 427-433

Author(s):

Bernarda Viteri ◽

Mohamed Elsingergy ◽

Jennifer Roem ◽

Derek Ng ◽

Bradley Warady ◽

...

Keyword(s):

Urinary Tract ◽

Kidney Function ◽

Congenital Anomalies ◽

Kidney Function Decline

Download Full-text

CONGENITAL ANOMALIES

PEDIATRICS ◽

10.1542/peds.7.5.607 ◽

1951 ◽

Vol 7 (5) ◽

pp. 607-610

Author(s):

JOSEF WARKANY

Keyword(s):

Urinary Tract ◽

Surgical Treatment ◽

American Academy ◽

Experimental Work ◽

Congenital Anomalies ◽

Intestinal Tract ◽

Diagnostic Methods ◽

American Academy Of Pediatrics ◽

General Aspects ◽

Dietary Deficiency

I AM greatly honored by the Award which the American Academy of Pediatrics has bestowed upon me and I am certain that this recognition of our studies will stimulate my co-workers and myself to further efforts in the line of work which we began about 12 years ago. I have repeatedly had the privilege of presenting our experimental work to meetings of the American Academy of Pediatrics and it is not necessary, therefore, to describe to you again in detail the congenital anomalies induced in animals by maternal dietary deficiency. It seems preferable to give you today a brief summary of the general aspects and results of our studies and to present to you some of the conclusions which may be drawn from them. The incentive to our experimental work was a marked interest in congenital anomalies of children. Adverse factors acting in prenatal life contribute appreciably to the mortality of infants and many children go through life deformed or crippled because of unfavorable intrauterine conditions. Congenital anomalies are at the root of many chronic and of some intractable diseases of childhood, a fact which is brought out with increasing certainty by improved diagnostic methods. Without going into details I wish to point out how many congenital anomalies of the urinary tract are now recognized intra vitam, which only one or two decades ago puzzled us by their nonspecific symptoms. Congenital anomalies of the intestinal tract which were previously diagnosed as "vomiting," "malnutrition," etc., are now better understood and often accessible to surgical treatment.

Download Full-text

Whole exome sequencing identifies FOXL2, FOXA2 and FOXA3 as candidate genes for monogenic congenital anomalies of the kidneys and urinary tract

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab253 ◽

2021 ◽

Author(s):

Bixia Zheng ◽

Steve Seltzsam ◽

Chunyan Wang ◽

Luca Schierbaum ◽

Sophia Schneider ◽

...

Keyword(s):

Urinary Tract ◽

Exome Sequencing ◽

Candidate Genes ◽

Whole Exome Sequencing ◽

Congenital Anomalies ◽

De Novo ◽

Horseshoe Kidney ◽

Missense Variant ◽

Whole Exome ◽

Fox Genes

Abstract Background Congenital anomalies of the kidneys and urinary tract (CAKUT) constitute the most common cause of chronic kidney disease in the first three decades of life. Variants in four Forkhead box (FOX) transcription factors have been associated with CAKUT. We hypothesized that other FOX genes, if highly expressed in developing kidney, may also represent monogenic causes of CAKUT. Methods We here performed whole exome sequencing (WES) in 541 families with CAKUT and generated 4 lists of CAKUT candidate genes: A) 36 FOX genes showing high expression during renal development, B) 4 FOX genes known to cause CAKUT to validate list A; C) 80 genes that we identified as unique potential novel CAKUT candidate genes when performing WES in 541 CAKUT families, and D) 175 genes identified from WES as multiple potential novel CAKUT candidate genes. Results To prioritize potential novel CAKUT candidates in FOX gene family, we overlapped 36 FOX genes (list A) with list C and D of WES-derived CAKUT candidates. Intersection with list C, identified a de novo FOXL2 in-frame deletion in a patient with eyelid abnormalities and ureteropelvic junction obstruction, and a homozygous FOXA2 missense variant in a patient with horseshoe kidney. Intersection with list D, identified a heterozygous FOXA3 missense variant in a CAKUT family with multiple affected individuals. Conclusion We hereby identified FOXL2, FOXA2 and FOXA3 as novel monogenic candidate genes of CAKUT, supporting the utility of a paralog-based approach to discover mutated genes associated with human disease.

Download Full-text