Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020500 (hyperoxaluria)
 912 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperoxaluria can lead to multiple pathologic conditions such as recurrent urolithiasis, oxalosis, nephrocalcinosis and even renal failure, but there is no known oxalate-degrading pathway in the human body, and current therapeutic options for patients with hyperoxaluria are limited. Oxalyl-CoA decarboxylase and formyl-CoA transferase are the key enzymes in the oxalate catabolism of Oxalobacter formigenes which dwell in the intestine of vertebrates and have an important symbiotic relationship with their hosts. The aim of this study was to insert the oxalate-degrading enzyme genes into human embryo kidney (HEK) 293 cells and to evaluate if the oxalate-degrading enzymes could be expressed in these cells and keep their enzyme activity. We present here the cloning of the two genes from O. formigenes and their subsequent expression in HEK293 cells. The results showed that the expression of oxalyl-CoA decarboxylase and formyl-CoA transferase was confirmed by RT-PCR and Western blotting, and the proteins were located in the cytoplasm of transfected cells. Furthermore, the transfected cells were capable to a certain degree of degrading oxalate. These findings suggest that the transfer of oxalate-degrading enzyme genes into human cells is possibly a potential candidate for the gene therapy of hyperoxaluria.
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PMID:Stable expression of the oxc and frc genes from Oxalobacter formigenes in human embryo kidney 293 cells: implications for gene therapy of hyperoxaluria. 1778 82

A 5-month-old female infant who had chronic diarrhea and acute renal failure was referred to Chulalongkorn Hospital for further investigation and management. Laboratory investigation revealed elevated blood urea nitrogen and creatinine level, hypocalcemia, hyperphosphatemia, and hyponatremia. Ultrasonography of the kidneys showed normal size with bilateral hyperechoic kidneys. Eyes examination was compatible with oxalosis maculopathy. Urine organic acid analysis revealed peak of oxalate and glycolate. Clinical impression concluded acute renal failure from hyperoxaluria. The patient underwent continuous venovenous hemodiafiltration (CVVH-DF) with regional citrate anticoagulation and expired on day 13 after admission. Pathological examination of kidney necropsy revealed diffuse intraluminal deposition of oxalate crystals within the renal parenchyma. Primary hyperoxaluria is a very rare disease and has rarely been reported in Thailand. In the presented case, the diagnosis was delayed due to uncommon presentation and unavailability of diagnostic laboratory.
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PMID:Primary hyperoxaluria. 1792 1

We report 3 cases of primary oxalosis with nephrocalcinosis and severe renal failure. Extrarenal involvement was noted in bones in 3 cases, the heart in 2 cases, the central nervous system in 2 cases, the skin in 1 case and the eye in 1 case. The 3 patients presented with acute digestive disorders. Ultrasonography and CT scans showed digestive wall calcifications in addition to the classic appearance of primary oxalosis such as nephrocalcinosis or bone involvement. Primary hyperoxaluria is characterized by a calcium deposit in different tissues, mainly in kidneys. Digestive wall involvement has never been reported in the literature. Primary oxaluria should be considered in the presence of such a deposit in the gut wall.
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PMID:[Exceptional digestive location of crystal deposits in primary hyperoxaluria]. 1974 2

PH1 is an inborn error of the metabolism in which a functional deficiency of the liver-specific peroxisomal enzyme, AGT, causes hyperoxaluria and hyperglycolic aciduria. Infantile PH1 is the most aggressive form of this disease, leading to early nephrocalcinosis, systemic oxalosis, and end-stage renal failure. Infantile PH1 is rapidly fatal in children unless timely liver-kidney transplantation is performed to correct both the hepatic enzyme defect and the renal end-organ damage. The surgical procedure can be further complicated in infants and young children, who are at higher risk for vascular anomalies, such as IVC thrombosis. Although recently a limited number of children with IVC thrombosis have underwent successful kidney transplantation, successful multi-organ transplantation in a child with complete IVC thrombosis is quite rare. We report here the interesting and technically difficult case of a three-yr-old girl with a complete thrombosis of the IVC, who was the recipient of combined split liver and kidney transplantation for infantile PH1. Although initial delayed renal graft function with mild-to-moderate acute rejection was observed, the patient rapidly regained renal function after steroid boluses, and was soon hemodialysis-independent, with good diuresis. Serum and plasma oxalate levels progressively decreased; although, to date they are still above normal. Hepatic and renal function indices were at, or approaching, normal values when the patient was discharged 15-wk post-transplant, and the patient continues to do well, with close and frequent follow-up. This is the first report of a successful double-organ transplant in a pediatric patient presenting with infantile PH1 complicated by complete IVC thrombosis.
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PMID:Combined split liver and kidney transplantation in a three-year-old child with primary hyperoxaluria type 1 and complete thrombosis of the inferior vena cava. 1979 27

With advancements in the operative techniques, patient survival following liver transplantation (LTx) has increased substantially. This has led to the acceleration of pre-existing kidney disease because of immunosuppressive nephrotoxicity making additional kidney transplantation (KTx) inevitable. On the other hand, in a growing number of patients on the waiting list to receive liver, long waiting time has resulted in adverse effect of decompensated liver on the kidney function. During the last two decades, the transplant community has considered combined liver kidney transplantation (CLKTx) to overcome this problem. The aim of our study is to present an overview of our experience as well as a review of the literature in CLKTx and to discuss the controversy in this regard. All performed CLKTx (n = 22) at our institution as well as all available reported case series focusing on CLKTx are extracted. The references of the manuscripts were cross-checked to implement further articles into the review. The analyzed parameters include demographic data, indication for LTx and KTx, duration on the waiting list, Model for End-Stage Liver Disease (MELD) score, Child-Turcotte-Pugh (CTP) score, immunosuppressive regimen, post-transplant complications, graft and patient survival, and cause of death. From 1988 to 2009, a total of 22 CLKTx were performed at our institution. The median age of the patients at the time of CLKTx was 44.8 (range: 4.5-58.3 yr). The indications for LTx were liver cirrhosis, hyperoxaluria type 1, polycystic liver disease, primary or secondary sclerosing cholangitis, malignant hepatic epithelioid hemangioendothelioma, cystinosis, and congenital biliary fibrosis. The KTx indications were end-stage renal disease of various causes, hyperoxaluria type 1, polycystic kidney disease, and cystinosis. The mean follow-up duration for CLKTx patients were 4.6 +/- 3.5 yr (range: 0.5-12 yr). Overall, the most important encountered complications were sepsis (n = 8), liver failure leading to retransplantation (n = 4), liver rejection (n = 3), and kidney rejection (n = 1). The overall patient survival rate was 80%. Review of the literature showed that from 1984 to 2008, 3536 CLKTx cases were reported. The main indications for CLKTx were oxalosis of both organs, liver cirrhosis and chronic renal failure, polycystic liver and kidney disease, and liver cirrhosis along with hepatorenal syndrome (HRS). The most common encountered complications following CLKTx were infection, bleeding, biliary complications, retransplantation of the liver, acute hepatic artery thrombosis, and retransplantation of the kidney. From the available data regarding the need for post-operative dialysis (n = 673), a total of 175 recipients (26%) required hemodialysis. During the follow-up period, 154 episodes of liver rejection (4.3%) and 113 episodes of kidney rejection (3.2%) occurred. The cumulative 1, 2, 3, and 5 yr survival of both organs were 78.2%, 74.4%, 62.4%, and 60.9%, respectively. Additionally, the cumulative 1, 2, 3, and 5 yr patient survival were 84.9%, 52.8%, 45.4%, and 42.6%, respectively. The total number of reported deaths was 181 of 2808 cases (6.4%), from them the cause of death in 99 (55%) cases was sepsis. It can be concluded that there is still no definitive evidence of better graft and patient survival in CLKTx recipients when compared with LTx alone because of the complexity of the exact definition of irreversible kidney function in LTx candidates. Additionally, CLKTx is better to be performed earlier than isolated LTx and KTx leading to the avoidance of deterioration of clinical status, high rate of graft loss, and mortality. Shorter graft ischemia time and more effective immunosuppressive regimens can reduce the incidence of graft malfunctioning in CLKTx patients. Providing a model to reliably determine the need for CLKTx seems necessary. Such a model can be shaped based upon new and precise markers of renal function, and modification of MELD system.
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PMID:A single center experience of combined liver kidney transplantation. 1993 Mar 23

Oxalate arthropathy is a rare cause of arthritis characterized by deposition of calcium oxalate crystals within synovial fluid. This condition typically occurs in patients with underlying primary or secondary hyperoxaluria. Primary hyperoxaluria constitutes a group of genetic disorders resulting in endogenous overproduction of oxalate, whereas secondary hyperoxaluria results from gastrointestinal disorders associated with fat malabsorption and increased absorption of dietary oxalate. In both conditions, oxalate crystals can deposit in the kidney leading to renal failure. Since oxalate is primarily renally eliminated, it accumulates throughout the body in renal failure, a state termed oxalosis. Affected organs can include bones, joints, heart, eyes, and skin. Since patients can present with renal failure and oxalosis before the underlying diagnosis of hyperoxaluria has been made, it is important to consider hyperoxaluria in patients who present with unexplained soft tissue crystal deposition. The best treatment of oxalosis is prevention. If patients present with advanced disease, treatment of oxalate arthritis consists of symptom management and control of the underlying disease process.
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PMID:Update on oxalate crystal disease. 2366 69

Type 1 primary hyperoxaluria is a genetic disorder caused by deficiency of the liver-specific peroxisomal enzyme alanine-glyoxylate aminotransferase. This enzyme deficiency leads to excess oxalate production and deposition of calcium oxalate salts, resulting in kidney failure and systemic oxalosis. Aside from combined liver/kidney transplantation, no curative treatment exists. Various strategies for optimizing dialysis treatment have been evaluated, but neither conventional hemodialysis nor peritoneal dialysis can keep pace with oxalate production in this patient population. In this report, we describe a patient with end-stage renal disease from type 1 primary hyperoxaluria managed with nocturnal home hemodialysis. Performing hemodialysis 8-10 hours each night with blood flow of 350 mL/min and total dialysate volume of 60 L, she has maintained pre- and postdialysis serum oxalate levels at or below the level of supersaturation. We also review published literature regarding oxalate removal in various modalities of dialysis in patients with type 1 primary hyperoxaluria. In our patient, nocturnal hemodialysis has controlled serum oxalate levels better than conventional hemodialysis therapies. Home nocturnal hemodialysis should be considered an option for management of patients with end-stage renal disease from type 1 hyperoxaluria who are awaiting transplantation.
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PMID:Nocturnal home hemodialysis for a patient with type 1 hyperoxaluria. 2383 Aug

Renal oxalate deposition can be seen with primary hyperoxaluria, malabsorptive states, ethylene glycol toxicity and, rarely, with excessive vitamin C ingestion. We report a case of secondary hyperoxaluria in which the diagnosis was not considered initially because there was no past history of urinary calculi and no evidence of nephrocalcinosis on plain X-ray of the abdomen and ultrasonography. The disease was detected and diagnosed only after kidney transplantation. Secondary oxalosis can cause graft loss or delayed graft function. Biopsy of the allograft should be carefully examined for oxalate deposits even in the absence of a family history. When oxalosis is diagnosed, intensifying hemodialysis (HD) to eliminate calcium oxalate can help in the recovery of renal function in some cases. Systematic vitamin C supplementation in HD patients should be avoided as it can be a cause of secondary oxalosis.
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PMID:Secondary oxalosis due to excess vitamin C intake: a cause of graft loss in a renal transplant recipient. 2443 93

Primary hyperoxaluria (PH) occurs due to an autosomal recessive hereditary disorder of the metabolism of glyoxylate, which causes excessive oxalate production. The most frequent and serious disorder is due to enzyme deficit of alanine-glyoxylate aminotransferase (PH type I) specific to hepatic peroxisome. As oxalate is not metabolised in humans and is excreted through the kidneys, the kidney is the first organ affected, causing recurrent lithiasis, nephrocalcinosis and early renal failure. With advance of renal failure, particularly in patients on haemodialysis (HD), calcium oxalate is massively deposited in tissues, which is known as oxalosis. Diagnosis is based on family history, the presence of urolithiasis and/or nephrocalcinosis, hyperoxaluria, oxalate deposits in tissue forming granulomas, molecular analysis of DNA and enzyme analysis if applicable. High diagnostic suspicion is required; therefore, unfortunately, in many cases it is diagnosed after its recurrence following kidney transplantation. Conservative management of this disease (high liquid intake, pyridoxine and crystallisation inhibitors) needs to be adopted early in order to delay kidney damage. Treatment by dialysis is ineffective in treating excess oxalate. After the kidney transplant, we normally observe a rapid appearance of oxalate deposits in the graft and the results of this technique are discouraging, with very few exceptions. Pre-emptive liver transplantation, or simultaneous liver and kidney transplants when there is already irreversible damage to the kidney, is the treatment of choice to treat the underlying disease and suppress oxalate overproduction. Given its condition as a rare disease and its genetic and clinical heterogeneity, it is not possible to gain evidence through randomised clinical trials. As a result, the recommendations are established by groups of experts based on publications of renowned scientific rigour. In this regard, a group of European experts (OxalEurope) has drawn up recommendations for diagnosis and treatment, which were published in 2012.
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PMID:Primary hyperoxaluria. 2479 59

Hyperoxaluria is characterized by an increased urinary excretion of oxalate. Primary and secondary hyperoxaluria are two distinct clinical expressions of hyperoxaluria. Primary hyperoxaluria is an inherited error of metabolism due to defective enzyme activity. In contrast, secondary hyperoxaluria is caused by increased dietary ingestion of oxalate, precursors of oxalate or alteration in intestinal microflora. The disease spectrum extends from recurrent kidney stones, nephrocalcinosis and urinary tract infections to chronic kidney disease and end stage renal disease. When calcium oxalate burden exceeds the renal excretory ability, calcium oxalate starts to deposit in various organ systems in a process called systemic oxalosis. Increased urinary oxalate levels help to make the diagnosis while plasma oxalate levels are likely to be more accurate when patients develop chronic kidney disease. Definitive diagnosis of primary hyperoxaluria is achieved by genetic studies and if genetic studies prove inconclusive, liver biopsy is undertaken to establish diagnosis. Diagnostic clues pointing towards secondary hyperoxaluria are a supportive dietary history and tests to detect increased intestinal absorption of oxalate. Conservative treatment for both types of hyperoxaluria includes vigorous hydration and crystallization inhibitors to decrease calcium oxalate precipitation. Pyridoxine is also found to be helpful in approximately 30% patients with primary hyperoxaluria type 1. Liver-kidney and isolated kidney transplantation are the treatment of choice in primary hyperoxaluria type 1 and type 2 respectively. Data is scarce on role of transplantation in primary hyperoxaluria type 3 where there are no reports of end stage renal disease so far. There are ongoing investigations into newer modalities of diagnosis and treatment of hyperoxaluria. Clinical differentiation between primary and secondary hyperoxaluria and further between the types of primary hyperoxaluria is very important because of implications in treatment and diagnosis. Hyperoxaluria continues to be a challenging disease and a high index of clinical suspicion is often the first step on the path to accurate diagnosis and management.
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PMID:Primary and secondary hyperoxaluria: Understanding the enigma. 2594 37


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