The effects of the inactivation of Hydroxyproline dehydrogenase on urinary oxalate and glycolate excretion in mouse models of primary hyperoxaluria

We describe the phenotype of the Prodh2 knock out mouse model and show that the lack of HYPDH in PH mouse models results in lower levels of urinary oxalate excretion, consistent with our previous metabolic tracer and siRNA-based knockdown studies. The double knockout mouse, Grhpr KO (PH2 model) and Prodh2 KO, prevented calcium-oxalate crystal deposition in the kidney, when placed on a 1% Hyp diet. These observations support the use of the Grhpr KO mice to screen HYPDH inhibitors in vivo. Altogether these data support HYPDH as an attractive therapeutic target for PH2 and PH3 patients.Graphical abstract
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research

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CONCLUSION: The etiological diagnosis of hereditary urinary lithiasis in our study was made with considerable delay. Cystinuria was the most frequent etiology and primary hyperoxaluria was the most serious affection. LEVEL OF EVIDENCE: 4. PMID: 31537493 [PubMed - as supplied by publisher]
Source: Progres en Urologie - Category: Urology & Nephrology Tags: Prog Urol Source Type: research
ard E Abstract Primary hyperoxaluria type 1 (PH1) is an inherited metabolic disorder caused by a deficiency of the peroxisomal enzyme alanine-glyoxylate aminotransferase (AGT), which leads to overproduction of oxalate by the liver and results in urolithiasis, nephrocalcinosis and renal failure. The only curative treatment for PH1 is combined liver and kidney transplantation, which is limited by the lack of suitable organs, significant complications, and the life-long requirement for immunosuppressive agents to maintain organ tolerance. Hepatocyte-like cells (HLCs) generated from CRISPR/Cas9 genome-edited human-ind...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research
Conclusions: The diagnosis of PH should be considered in patients with severe, recurrent calcium oxalate nephrolithiasis. Early treatment with pyridoxine reduces urinary oxalate excretion and can delay progression to end-stage renal disease (ESRD). After ESRD, intensive dialysis is needed to prevent systemic oxalate accumulation and deposition. Combined liver and kidney transplantation is curative. In our patient, we anticipate that liver transplantation will cure both the hyperoxaluria and the hypercoagulable state.Case Rep Nephrol Dial 2018;8:223 –229
Source: Case Reports in Nephrology and Dialysis - Category: Urology & Nephrology Source Type: research
We report a 23-year-old female with acute renal failure and nephrotic proteinuria. Urinalysis showed reddish brown, round crystals with dark outline, and central spicules consistent with 2,8-DHA crystals. Renal biopsy showed membranous nephropathy and 2,8-DHA nephropathy. Our patient improved with liberal fluid intake, restriction of high adenine content foods, and oral xanthine dehydrogenase inhibitor febuxostat. Early diagnosis and initiation of treatment prevent renal complications. PMID: 29657221 [PubMed - in process]
Source: Saudi Journal of Kidney Diseases and Transplantation - Category: Urology & Nephrology Authors: Tags: Saudi J Kidney Dis Transpl Source Type: research
Abstract A 27-year-old man with terminal renal failure requiring peritoneal dialysis for the past 2 years was referred to the dermatologist for evaluation of red violaceous macular skin lesions consistent with livedo reticularis. These lesions had appeared suddenly on his legs (Figure 1). He had first experienced recurrent nephrolithiasis at the age of 14. Results from urine analysis and abdominal ultrasound revealed chronic kidney failure. Because the patient had a sister with similar findings, primary hyperoxaluria (PH) was suspected and genetic testing was performed in all members of his family. The results con...
Source: Skinmed - Category: Dermatology Authors: Tags: Skinmed Source Type: research
CONCLUSION: This online "DS Toxic Table" provides clinicians, consumers, and manufacturers with a list of herbs that could potentially contribute to kidney injuries. PMID: 28755953 [PubMed - in process]
Source: Food and Chemical Toxicology - Category: Food Science Authors: Tags: Food Chem Toxicol Source Type: research
Source: Nephrology Dialysis Transplantation - Category: Urology & Nephrology Authors: Tags: NEPHROLITHIASIS AND DIVALENT IONS Source Type: research
Abstract Purpose of review To provide transplant physicians with a summary of the pathogenesis and diagnosis of adenine phosphoribosyl transferase (APRT) deficiency and primary hyperoxaluria and, focussed on kidney transplantation, and to discuss interventions aimed at preventing and treating the recurrence of crystalline nephropathy in renal transplant recipients. Source of information Pubmed literature search. Setting Primary hyperoxaluria and APRT deficiency are rare inborn errors of human metabolism....
Source: Canadian Journal of Kidney Health and Disease - Category: Urology & Nephrology Source Type: research
Uromodulin, the major protein secreted in normal urine, is exclusively produced in the thick ascending limb (TAL) cells of the kidney. The exact role uromodulin (UMOD) plays in renal physiology remains enigmatic. UMOD has been linked to water/electrolyte balance and to kidney innate immunity and it is believed to protect against urinary tract infections and renal stones. A renewed interest in UMOD has been triggered by the identification of UMOD mutations as cause of hereditary dominant renal diseases, now referred to as uromodulin-associated kidney diseases (UAKDs), presenting with tubulointerstitial fibrosis, defective u...
Source: Nephrology Dialysis Transplantation - Category: Urology & Nephrology Authors: Tags: REVIEWS - BASIC SCIENCE AND TRANSLATIONAL NEPHROLOGY Source Type: research
This study reports the epidemiological data, percentages and types of renal disorders in children seen at the pediatric nephrology center of the AlKadhymia Teaching Hospital, Baghdad, Iraq. A retrospective review of the charts of all patients, aged between one month and 14 years, who were admitted and followed-up for a period of three years from January 2009 till January 2012 were studied. The presence of renal disease based on their clinical records, laboratory tests and final diagnosis were noted. A total of 4785 children were admitted during the study period, of whom 326 renal disorders were observed in 281 children (5....
Source: Saudi Journal of Kidney Diseases and Transplantation - Category: Urology & Nephrology Authors: Tags: Saudi J Kidney Dis Transpl Source Type: research
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