Materiały źródłowe

• #1 Hyperoxaluria: Causes, Symptoms, Diagnosis & Treatment

  https://my.clevelandclinic.org/health/diseases/21117-hyperoxaluria

  The goal of treatment is to lower oxalate levels in your body and prevent calcium oxalate crystals from forming. […] Getting treatment for hyperoxaluria can help reduce the chances of long-term kidney damage. […] The goal of treatment is to lower the level of oxalate in your body and prevent calcium oxalate crystals from forming in your kidneys and other body tissues. Treatments could involve medication, lifestyle and dietary changes, and managing kidney stones. Your healthcare provider will recommend the best treatment based on the type of hyperoxaluria you have, your symptoms and how severe your condition is. […] For people with primary hyperoxaluria, medication options include a prescription dose of vitamin B6 (pyridoxine) to reduce oxalate levels. Thiazide diuretics are an option for people with a specific subtype of PH.

• #1 Hyperoxaluria and oxalosis – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hyperoxaluria/diagnosis-treatment/drc-20352258

  Treatment depends on the type of hyperoxaluria you have, the symptoms and how serious the disease is. How well you respond to treatment also helps your health care team decide how else to manage your condition. […] To lower the amount of calcium oxalate crystals that form in your kidneys, your doctor may suggest one or more of these treatments: […] Lumasiran (Oxlumo) is a medicine that lowers the level of oxalate in children and adults with primary hyperoxaluria. Prescription doses of vitamin B-6, also called pyridoxine, can help reduce oxalate in the urine in some people with primary hyperoxaluria. Phosphates and citrate prepared by a pharmacy and taken by mouth help keep calcium oxalate crystals from forming. […] If you have enteric hyperoxaluria, your doctor also may recommend a calcium supplement to take with meals. This could make it easier for oxalate to combine with calcium in the gut and leave the body through stool.

• #1 Treatment of primary hyperoxaluria type 1

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9113429/

  Supportive treatment for primary hyperoxaluria type 1 (PH1) focuses on high fluid intake and crystallization inhibitors. A subset of patients with specific PH1 genotypes (c.508GA and c.454TA) will respond to pyridoxine, defined as a 30% reduction in urinary oxalate excretion. The first focused treatment for PH1 using an RNA interference agent to reduce urinary oxalate was approved in 2020, and such therapies may significantly alter treatment approaches and long-term outcomes in PH1. Currently PH1 often presents with kidney function impairment and frequently results in end-stage kidney disease (ESKD). Once plasma oxalate levels exceed 30 mol/L, aggressive haemodialysis is indicated to prevent oxalosis, even if the glomerular filtration rate (GFR) remains better than for typical dialysis initiation. Liver transplantation restores hepatic alanine-glyoxylate transaminase enzyme activity, allowing glyoxylate detoxification and preventing further oxalosis. The timing and type of liver transplantation are dependent on pyridoxine sensitivity, age, weight, residual GFR and evidence of systemic oxalate deposition in extrarenal organs. In 2020, the first focused treatment for PH1 using an RNA interference (RNAi) agent to reduce UOx was approved. Pyridoxine should be prescribed for all patients for whom the diagnosis is under consideration. Responsiveness to pyridoxine is defined as a 30% relative decrease in UOx from baseline within 6 months of pyridoxine initiation. A new RNAi therapy for PH1, lumasiran, was recently approved by the US Food and Drug Administration, the European Medicines Agency (EMA) and the Medicine and Healthcare Products Regulatory Agency (MHRA). Lumasiran is administered via a subcutaneous injection given monthly for the first 4 months and then every 3 months thereafter. Another RNAi therapy, nedosiran, inhibits the hepatic lactate dehydrogenase A (LDHA) pathway and also decreases oxalate production. CLKT is curative in terms of eliminating overproduction of endogenous oxalate, and timing depends on the child’s size, overall health, systemic oxalate burden and potential confounding medical conditions unrelated to ESKD or PH1.

• #1

  https://link.springer.com/article/10.1007/s40265-022-01735-x

  Another RNAi medication, nedosiran (DCR-PHXC; Dicerna/Novo Nordisk, Bagsvrd, Denmark) interferes with the translation of liver-specific LDHA, preventing the conversion of glyoxylate to oxalate supposedly in all PH types. […] The potential long-term benefits for patients of the substrate reduction therapy based on RNAi, namely, better preservation of renal function and, at best, prevention of progression to ESKD and systemic oxalosis, remain to be confirmed. […] Vitamin B6 is cheap and known to be helpful for patients with specific genotypes. RNA interference medications are expensive but appear to be highly effective in all patients with PH1. […] Thus, the genotype, which should be known, could be the decision marker. […] If both RNAi medications fail singularly, combined administration of GO and LDHA blockers may be considered.

• #1 Hyperoxaluria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558987/

  Treatment of a patient with hyperoxaluria includes conservative medical and surgical measures, along with the treatment of nephrolithiasis. Isolated renal stone treatment can be conservative, using fluids and alpha-blockers, or surgical if the stone or stones are larger than 4 mm, fail to pass, or become complicated by infection. […] A greater fluid intake will increase urine volume and reduce the supersaturation of calcium oxalate. Measuring and focusing on urinary volume rather than any particular oral intake goal is preferable. It is recommended that the oral intake should be sufficient to generate at least 3000 ml of urine per day. […] Potassium citrate provides adequate urinary citrate levels and keeps the urine pH at a favorable 6.2 to 6.8. Sodium citrate can be used in cases of renal failure. Adequate urinary citrate levels (optimally at 250 to 300 mg/L or 500 to 600 mg daily total in divided doses) help prevent the aggregation of calcium oxalate crystals into stones.

• #1 Hyperoxaluria: Practice Essentials, Oxalate Production and Function, Pathophysiology and Etiology

  https://emedicine.medscape.com/article/444683-overview

  Orthophosphate, in combination with pyridoxine, has been used effectively in the treatment of primary hyperoxaluria. […] Magnesium can complex with oxalate in the intestinal tract, reducing the level of available free oxalate and urinary calcium oxalate supersaturation. […] Increasing urinary volume is essential. Optimal 24-hour urinary volumes of 3-4 L/d may be needed to ameliorate the effects of severe hyperoxaluria. […] Calcium supplementation is usually beneficial and is the preferred initial treatment option for most patients with enteric hyperoxaluria. […] The most commonly recommended form is calcium citrate, because the citrate component offers an additional benefit as a natural inhibitor of calcium oxalate urinary crystallization. […] Dietary oxalate restriction, pyridoxine treatment, and other measures are important aspects of management in this group. […] Glycosaminoglycan supplementation may be of some benefit in preventing calcium oxalate stone formation when other methods are insufficiently effective and stone production continues.

• #1 Hyperoxaluria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558987/

  Orthophosphates and pyridoxine have been successfully used to treat primary and secondary hyperoxaluria. […] Magnesium supplements (usually magnesium oxide or magnesium hydroxide) reduce oxalate absorption by binding with oxalate in the intestinal tract but may promote diarrhea when used alone. […] Cholestyramine is primarily used to manage bile acid malabsorption, increasing intestinal oxalate binding and reducing absorption. […] Dietary measures do not play a major role in PH as the excess oxalate in this condition is endogenous. Early, aggressive treatment is necessary to prevent loss of renal function, so utilization of all of the above measures is reasonable, including high dose pyridoxine, orthophosphate and magnesium supplementation, increased urinary volume, pentosan polysulfate (Elmiron), Lumasiran, and intensive dialysis.

• #1 Hyperoxaluria and oxalosis – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hyperoxaluria/diagnosis-treatment/drc-20352258

  If your kidneys still work well, your doctor will likely tell you to drink more water or other fluids. This flushes the kidneys, prevents oxalate crystal buildup and helps keep kidney stones from forming. […] In general, it’s more important to pay attention to your food choices if you have enteric or diet-related hyperoxaluria. Diet changes may help lower the levels of oxalate in your urine. Your health care team may suggest that you restrict foods high in oxalates, limit salt and eat less animal protein and sugar. But diet changes may not help all people with primary hyperoxaluria. Follow your care team’s suggestions. […] If large kidney stones cause pain or block urine flow, you may need to have them removed or broken up so they can pass in the urine. […] A treatment called dialysis that takes over some of the work of your kidneys may help. But it doesn’t keep up with the amount of oxalate your body makes. A kidney transplant or kidney and liver transplant can treat primary hyperoxaluria. A liver transplant is the only treatment that might cure some types of primary hyperoxaluria.

• #1 Managing Primary Hyperoxaluria (PH) | Uncovering PH

  https://www.uncoveringph.com/managing-ph.html

  Currently, there is no FDA-approved therapy that addresses all subtypes of primary hyperoxaluria. […] Current treatment options fall under 5 categories: […] Ribonucleic acid interference (RNAi) therapy. Two RNAi therapies are approved in PH1 patients. Works by inhibiting gene expression and selectively reducing hepatic enzymes involved in the overproduction of oxalate associated with PH1. […] Pyridoxine (vitamin B6). One study showed two-thirds of patients with PH1 are completely unresponsive to pyridoxine. Trial recommended if no response, discontinue. […] Avoidance of oxalate-rich foods is recommended. […] Aggressive hydration. Adults/older adolescents: 4 liters water/day. School-age children: 2-3 liters water/day. Infants/small children: 1-1.5 liters water/day. Gastrostomy tube for infants or adults struggling with water intake.

• #1 Hyperoxaluria: Causes, Symptoms, Diagnosis & Treatment

  https://my.clevelandclinic.org/health/diseases/21117-hyperoxaluria

  For people with any type of hyperoxaluria, medication options include oral doses of potassium citrate or the combination of orthophosphate and magnesium to prevent calcium oxalate crystals from forming. […] For people with enteric hyperoxaluria, taking a calcium supplement with meals can also help. Calcium binds with oxalate, which may help oxalate leave your body through your pee and poop. […] Drinking more fluids and making changes to your diet can help with high oxalate. […] Increase your water intake to around 3 liters per day. Extra fluids help to flush oxalate from your kidneys, which prevent it from building up and creating stones or crystals. This should help all types of hyperoxaluria. […] Change your diet by limiting salt and sugar, eating less animal protein (meat, milk, eggs and fish) and avoiding foods high in oxalates. High-oxalate foods include spinach, rhubarb, beets, plums, chocolate, tea, nuts and nut butters.

• #1 Hyperoxaluria: Causes, Symptoms, Diagnosis & Treatment

  https://my.clevelandclinic.org/health/diseases/21117-hyperoxaluria

  Adding calcium-rich foods to meals can help reduce oxalate levels. Calcium naturally binds to oxalate, so eating calcium-rich foods at meals helps with this. […] If you have kidney stones, the stones may pass on their own by drinking lots of water. If your kidney stones don’t pass, your healthcare provider may need to remove them. […] If hyperoxaluria becomes severe, your kidneys may not work as well. If this happens, kidney dialysis can help. If you have primary hyperoxaluria, organ transplantation (kidney, liver or both) may be necessary. The type of transplant depends on the specific type of primary hyperoxaluria. […] If you receive a diagnosis of enteric or dietary hyperoxaluria, you should follow your healthcare provider’s treatment plan to reduce complications from the condition.

• #1 Managing Primary Hyperoxaluria (PH) | Uncovering PH

  https://www.uncoveringph.com/managing-ph.html

  Oral potassium citrate or orthophosphate when glomerular filtration rate (GFR) is well preserved. Oral sodium citrate for lower GFR rates at risk for hyperkalemia. […] Percutaneous nephrolithotomy (PCNL), or ureteroscopy when PCNL is not indicated. While PCNL confers the highest stone-free rate, it also carries a higher rate of complications and recovery time. […] Not recommended: extracorporeal shock wave lithotripsy (ESWL), which can contribute to kidney injury and kidney failure in patients with PH. […] Intermittent hemodialysis (HD), as often as 6 days/week, with additional peritoneal dialysis (PD) in some patients. Recommended for patients with plasma oxalate levels 30-45 mol/L. […] Dialysis is not able to sufficiently remove all endogenously overproduced oxalate. Even in patients receiving a combination of daily HD and PD, a weekly elimination of less than half of endogenously produced oxalate can be achieved.

• #1 Managing Primary Hyperoxaluria (PH) | Uncovering PH

  https://www.uncoveringph.com/managing-ph.html

  Simultaneous liver-kidney transplant recommended at chronic kidney disease (CKD) stage 3b. […] 34% to 46% of patients with PH1 and 11% of patients with PH2 may require an organ transplant. […] 23% to 36% of transplanted organs may fail within 5 years of transplant. […] Kidney and liver transplant recipients require lifelong immunosuppression. […] Primary hyperoxaluria creates significant burden for patients and caregivers as they try to manage their disease; despite their efforts, most remain fearful of developing stones and continued kidney damage. A survey showed that 94% of patients hope for new therapies that would prevent dialysis, organ transplant, and oxalosis, and/or improve chances of a normal life span.

• #1 Primary hyperoxaluria | Nefrología

  https://www.revistanefrologia.com/en-comentarios-primary-hyperoxaluria-articulo-X2013251414054186

  The isolated use of renal transplantation has yielded unfortunate results. […] Therefore, given the high risk of rapid development of nephrocalcinosis, isolated renal transplantation should be reserved for less severe forms of PH, with a reasonable good response to conservative measures and vitamin B6. […] Once there is a firm diagnosis of PH, the priority and potentially curative treatment is liver transplantation. […] Early liver transplantation, that is, before there is irreversible kidney damage, should be the option of choice in severe cases if we have an accurate and early diagnosis.

• #1 Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope | Nature Reviews Nephrology

  https://www.nature.com/articles/s41581-022-00661-1

  In response to these developments, members of OxalEurope a network of European scientists and physicians who specialize in PH and the metabolic workgroup of the European Rare Kidney Disease Reference Network (ERKNet), formed a workgroup. […] We aim to make clinical practice recommendations for worldwide application and have therefore added statements for countries with restricted financial and medical means. […] We also propose key future research questions in the field, which may further help practitioners in clinical decision making. […] The diagnostic work-up for patients with estimated glomerular filtration rate (eGFR) 30ml/min/1.73m2 and suspected primary hyperoxaluria (PH) should include at least two urine oxalate assessments (preferably from a 24h urine collection). […] If genetic assessment reveals a mutation consistent with vitamin B6 (VB6; also known as pyridoxine) non-responsive PH1, RNA interference (RNAi) therapy is indicated.

• #1 Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope | Nature Reviews Nephrology

  https://www.nature.com/articles/s41581-022-00661-1

  Patients who are partially responsive to VB6 therapy may also be eligible for RNAi therapy if hyperoxaluria persists. […] We recommend adapting fluid management to optimize urinary oxalate excretion as determined by a morning spot urine analysis. […] Pyridoxine (vitamin B6) is effective in lowering urinary oxalate excretion in a subgroup of patients with PH1. […] We therefore recommend starting pyridoxine supplementation in all patients suspected to have PH and in all patients with genetically proven PH1. […] Dialysis treatment may be indicated in patients with PH who have progressed to stage 45 CKD before the development of uraemia, depending on the potential risk of systemic oxalosis. […] Clinical indications for early onset of dialysis are high plasma oxalate levels despite oxalate-lowering therapy (RNAi therapy or pyridoxine) and signs of systemic oxalosis.

• #1 Hyperoxaluria: Practice Essentials, Oxalate Production and Function, Pathophysiology and Etiology

  https://emedicine.medscape.com/article/444683-overview

  Treatment depends to some extent on the underlying etiology and severity of the hyperoxaluria. However, many treatments (eg, dietary measures) can be used in any case of hyperoxaluria, and treatments can be combined for increased efficacy. […] Initial first-line therapies include a low-oxalate diet while maintaining adequate calcium intake, pyridoxine (vitamin B6), increased fluids, and optimization of other calcium oxalate nephrolithiasis risk factors. […] Calcium supplements are the initial treatment of choice for enteric hyperoxaluria, along with a low-fat diet, antidiarrheal therapy, and sufficient potassium citrate supplementation to maintain optimal urinary citrate levels. […] When initial treatment is insufficient to adequately control excessive urinary oxalate excretion, add orthophosphate supplementation, magnesium supplementation, or both.

• #1 Hyperoxaluria: Practice Essentials, Oxalate Production and Function, Pathophysiology and Etiology

  https://emedicine.medscape.com/article/444683-overview

  Oxalate-binding agents such as calcium (preferred) or iron (if hypercalciuria is present) can be used. […] If further treatment is necessary, cholestyramine can be added. […] In cases of kidney failure, intensive dialysis can be considered. Liver or combined liver-kidney transplantation should be considered in patients with primary hyperoxaluria. […] Patients with primary hyperoxaluria usually present with a urinary oxalate level in excess of 100 mg/d. Early medical treatment is required to decrease the oxalate level and to prevent deterioration of renal function. Early liver-kidney transplantation is often required for definitive cure. […] Dietary oxalate restrictions are of no substantial benefit in this type of hyperoxaluric disease. Several medications have been useful. […] High-dose pyridoxine may reduce the production of oxalate by enhancing the conversion of glyoxylate to glycine, thereby reducing the substrate available for metabolism to oxalate.

• #1 Primary and secondary hyperoxaluria: Understanding the enigma

  https://www.wjgnet.com/2220-6124/full/v4/i2/235.htm

  Dietary interventions do not play a major role in the management of primary hyperoxaluria as absorption of oxalate from the intestine is very small. […] On the other hand, diet modification is a very important element in the treatment of secondary hyperoxaluria where efforts should be made to reduce oxalate intake in the diet. […] Pyridoxine supplementation has been shown to be beneficial in patients with PH1. […] Alkalinization of the urine is well known to prevent stone formation as citrate complexes with calcium and thus decreases the amount of calcium oxalate available for precipitation. […] For management of renal stones, endoscopy is currently the procedure of choice as it allows direct visualization of the stones. […] Patients reaching ESRD need optimization of renal replacement therapy to ensure adequate oxalate removal. […] Transplantation must be planned when GFR falls between 15-30 mL/min per 1.73 m2. […] In secondary hyperoxaluria, there is a paucity of data regarding renal transplantation in those who develop ESRD.

• #1 An Unusual Presentation of a Child with Hyperoxaluria

  https://brieflands.com/articles/apid-67357

  Hyperoxaluria is a common abnormal finding in patients with nephrolithiasis, especially in children in contrary to adults. Overall, it is a rare disorder with the four main types of primary, enteric, dietary and idiopathic. The disorder is characterized by overproduction of oxalate that leads to nephrocalcinosis and eventual development of end-stage renal failure. […] The case illustrates the need for the early diagnosis of this disorder to prevent systemic oxalosis that affects many organs resulting in severe morbidity and mortality and raising the suspicion of primary hyperoxaluria in childhood progressive renal failure with massive nephrocalcinosis, especially if accompanied by a positive family history. In these cases, complications should be explained to increase drug compliance. […] Early diagnosis and treatment can prevent renal failure and lifelong dependence to dialysis. Combined liver-kidney transplantation is recommended as the treatment of choice in patients with primary hypercalciuria and ESRD.

• #1 Perspectives in primary hyperoxaluria — historical, current and future clinical interventions | Nature Reviews Urology

  https://www.nature.com/articles/s41585-021-00543-4

  New therapeutics being developed for PHs take advantage of biochemical knowledge about oxalate synthesis and metabolism to specifically target these pathways, with the goal of decreasing the accumulation and deposition of plasma oxalate in the body. […] New therapeutics can be divided into classes, and include substrate reduction therapy, intestinal oxalate degradation, chaperone therapy, enzyme restoration therapy and targeting of the inflammasome. […] Lumasiran, a mRNA therapeutic targeting glycolate oxidase, was the first primary hyperoxaluria-specific therapeutic approved by the European Medicines Agency and the FDA in 2020. […] Future work includes further clinical trials for promising therapeutics in the pipeline, identification of biomarkers of response to PH-directed therapy, optimization of drug development and delivery of new therapeutics.

• #1

  https://link.springer.com/article/10.1007/s40265-022-01735-x

  Future treatment possibilities are on the horizon, for example, substrate reduction therapy with small molecules or gene editing, induced pluripotent stem cell-derived autologous hepatocyte-like cell transplantation, or gene therapy with newly developed vector technologies. […] The standard treatment of care has included, classically, hyperhydration, crystallization inhibitors, and vitamin B6 (VB6), the latter in PH1. […] If kidney function declines, dialysis and transplantation are performed. […] Hyperhydration remains the hallmark of conservative treatment for all stone diseases, here including all types of PH. […] Of paramount importance for both the idiopathic kidney stone formers, and patients with PH is treatment with anti-lithogenic substances, for example, citrate and magnesium.

• #1 Navigating the Evolving Landscape of Primary Hyperoxaluria: Traditional Management Defied by the Rise of Novel Molecular Drugs

  https://www.mdpi.com/2218-273X/14/5/511

  Oxalate decarboxylase (ODC) and oxalate oxidase (OxO), the oxalate-degrading enzymes under investigation for drug development, degrade oxalate into human-safe products, despite both originating from non-mammalian proteins. […] Certain metallic cations also possess the capacity to modulate oxalate metabolism. […] Vitamin B6 (pyridoxine), metabolized in the body to pyridoxal 5′-phosphate (PLP; biologically active form), functions as a critical cofactor and chaperone for AGT enzymes, restoring lost enzyme function in PH1 through mechanisms related to increased expression, catalytic activity and peroxisomal input to AGT enzymes. […] PH patients at CKD stage 4–5, even without progressing to ESRD, require assessment for systemic oxalosis risk to evaluate the need for dialysis therapy. […] Surgical interventions for PH-related kidney stones are conventional, but, given the rarity of the disease, special consideration is warranted for treatment indications and potential side effects.

• #1 Hyperoxaluria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558987/

  In November 2020, the FDA and the European Medicines Agency approved using lumasiran for type I PH. It is the first available, effective therapy for PH short of combined liver/kidney transplantation. […] Nedosiran, like lumasiran, is also an RNA interference therapy designed to target hepatic lactate dehydrogenase (LDH), which converts glyoxalate to oxalate. […] The role of dialysis is controversial. Serum oxalate levels of 30 to 45 mol/L lead to tissue deposition, and dialysis aims to keep the oxalate level below that to prevent supersaturation. […] The procedures to choose from are 1) an isolated liver transplant, 2) an isolated renal transplant, or 3) a combined liver-renal transplant. […] Future therapies for controlling hyperoxaluria being investigated include the following: Vitamin E and other antioxidant supplementation, recombinant gene therapy to replace defective hepatic enzymes, intestinal oxalate transport (SLC) blockers, especially SLC26A3 and S1C26A6, hepatocyte cell transplantation, organic marine hydrocolloid, RNA interference therapy, and use of gene-editing technology (CRISPR) to correct specific enzyme pathways for PH.

• #1 Hyperoxaluria: Causes, Symptoms, Diagnosis & Treatment

  https://my.clevelandclinic.org/health/diseases/21117-hyperoxaluria

  The goal is to protect your kidneys by preventing kidney stones and calcium oxalate deposits in other body tissues. People with enteric and dietary hyperoxaluria can find relief with medication and lifestyle and dietary changes. […] Your healthcare provider will talk with you about your type of hyperoxaluria and provide a treatment plan to best manage it. It’s critical for people living with hyperoxaluria to follow their provider’s treatment plan and have regular exams with their urologist or primary care provider.

• #1 Primary hyperoxaluria | Nefrología

  https://www.revistanefrologia.com/en-comentarios-primary-hyperoxaluria-articulo-X2013251414054186

  The use of vitamin D analogues may have an adverse effect on these patients, due to an increase in calcium absorption and, as a result, they may cause an oversaturation of calcium oxalate. […] Although mammals cannot metabolise oxalate, other living beings have enzymes such as oxalate oxidase and oxalate decarboxylase, which are capable of degrading it and they may provide a new solution for preventing the accumulation of oxalate in PHO. […] Pyridoxine (vitamin B6) is perhaps the only method capable of effectively reducing oxalate production, but it is only applicable to cases of PH-I. […] Management of lithiasis in PH involves the normal concomitant presence of nephrocalcinosis. […] Once renal failure has been established, all the general measures mentioned are usually ineffective and renal replacement therapy must be planned.

• #1

  https://journals.lww.com/cjasn/fulltext/2020/07000/primary_hyperoxaluria__the_patient_and_caregiver.2.aspx

  Living with primary hyperoxaluria, a rare genetic disease with excess oxalate production leading to frequent kidney stones, kidney impairment, and oxalosis, presents many challenges to patients, caregivers, and their families. […] The patient and caregiver perspectives listed in this paper as well as the survey findings were derived from the respondents from the survey and meetings and highlight the daily challenges and the great need for new therapies. […] For patients with preserved kidney function, treatments are directed at reducing stone formation and preventing further kidney injury with significant fluid intake and multiple daily doses of medications. […] The consequences of kidney failure can be particularly grave in primary hyperoxaluria because plasma oxalate levels rise rapidly, leading to oxalosis.

• #1

  https://journals.lww.com/cjasn/fulltext/2020/07000/primary_hyperoxaluria__the_patient_and_caregiver.2.aspx

  Because dialysis is only partially effective in handling the oxalate load, hemodialysis 6 days per week in addition to daily peritoneal dialysis may be required. […] The survey demonstrated that 94% of patients desired new therapies that would prevent dialysis, kidney or liver transplant, avoid oxalosis, and/or improve chances of a normal life span. […] We need better medications which would reduce oxalate levels and methods to preserve current kidney function. […] Families desperately seek new treatment options to reduce the frequency of kidney stones, the need for organ transplantation, kidney failure, and oxalosis.

• #1 Hyperoxaluria and oxalosis – Care at Mayo Clinic – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hyperoxaluria/care-at-mayo-clinic/mac-20352260

  The Mayo Clinic Hyperoxaluria Center in Minnesota brings together experts from many specialties to design a personalized treatment plan. Your treatment plan is based on what type of hyperoxaluria you have, how severe it is and any related conditions. Mayo Clinic coordinates your testing and medical appointments to speed the process of diagnosis and treatment. A doctor who specializes in kidney diseases (nephrologist) often manages your care. […] Mayo Clinic offers a range of services, from treatment to reduce oxalate in your urine to minimally invasive procedures for kidney stone treatment and removal. Or, if needed for severe hyperoxaluria, Mayo Clinic surgeons can perform kidney or kidney-liver transplants. […] Mayo Clinic provides outstanding transplant teams, led by highly skilled surgeons and medical transplant teams experienced in the care of people with primary hyperoxaluria.

• #1 Primary Hyperoxaluria – Rare Kidney Stone Consortium

  https://www.rarekidneystones.org/hyperoxaluria/

  The goals in treating PH patients are to keep the level of oxalate in the urine and the body as low as possible, to minimize the formation of kidney stones, and to maintain the patient’s kidney health. […] Treatment needs to be individualized for PH patients and needs to take into account each patient’s needs, the type and severity of disease and how well the patient responds to treatment.

• #2 Hyperoxaluria and oxalosis – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/hyperoxaluria/diagnosis-treatment/drc-20352258

  Treatment depends on the type of hyperoxaluria you have, the symptoms and how serious the disease is. How well you respond to treatment also helps your health care team decide how else to manage your condition. […] To lower the amount of calcium oxalate crystals that form in your kidneys, your doctor may suggest one or more of these treatments: […] Lumasiran (Oxlumo) is a medicine that lowers the level of oxalate in children and adults with primary hyperoxaluria. Prescription doses of vitamin B-6, also called pyridoxine, can help reduce oxalate in the urine in some people with primary hyperoxaluria. Phosphates and citrate prepared by a pharmacy and taken by mouth help keep calcium oxalate crystals from forming. […] If you have enteric hyperoxaluria, your doctor also may recommend a calcium supplement to take with meals. This could make it easier for oxalate to combine with calcium in the gut and leave the body through stool.

• #2 Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope | Nature Reviews Nephrology

  https://www.nature.com/articles/s41581-022-00661-1

  Liver transplantation remains the only cure for PH1. […] A substantial body of evidence demonstrates that liver transplantation can reverse hyperoxaluria and prevent the further development of oxalate-related disease in patients with PH1. […] For patients with PH and kidney failure who undergo kidney transplantation, combined liver and kidney transplantation (CLKT) results in better kidney graft survival than isolated kidney transplantation. […] Two RNAi therapies are now available or under trial for patients with PH1. […] Lumasiran (Oxlumo; Alnylam) has received marketing authorization by the EMA and FDA as an orphan drug for the treatment of PH1. […] Nedosiran (Dicerna/Novo Nordisk) is another RNAi drug, which is designed to inhibit the production of l-lactate dehydrogenase A (LDHA), which is essential for the cytosolic conversion of glyoxylate into oxalate. […] Both RNAi therapies have been shown to be highly effective in lowering endogenous oxalate production in patients with PH1, and early clinical outcome data are encouraging.

• #2 Treatments for Primary Hyperoxaluria Type 1

  https://www.webmd.com/kidney-stones/primary-hyperoxaluria-type-1-treat

  When you have primary hyperoxaluria type 1 (PH1), too much of a natural substance called oxalate collects in your kidneys. To prevent the serious kidney damage that can result, your doctor will try to reduce the buildup of oxalate in your body. […] Your doctor may also recommend one or more of these treatments. […] Lumasiran (Oxlumo). This is the first medication approved specifically for use in adults and children for reducing the amount of oxalate your body produces. It can usually bring levels to normal within 24 hours. […] Nedosiran (Rivfloza). This works to inhibit oxalate production in your urine. […] Pyridoxine (Vitamin B6). When taken in prescription-level doses, this vitamin can greatly reduce the amount of oxalate in your urine. It doesn’t work for everyone, though. […] Potassium citrate or pyrophosphate. These salts work by forming complexes with calcium making oxalate stones less likely to form. Your doctor will probably tell you to take one or more of them several times throughout the day.

• #2 Hyperoxaluria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558987/

  Dietary modifications in secondary hyperoxaluria are useful and easily applied. Although randomized controlled trials have proven that restricting dietary calcium is detrimental, the beneficial effect of calcium supplementation in protecting against oxalate stones is less clear. […] Pyridoxine (vitamin B6) should be supplemented to help patients reduce their hyperoxaluria, sometimes significantly. This has been studied extensively in type I PH. Activated vitamin B6 pyridoxal 5-phosphate is a cofactor for alanine-glyoxylate aminotransferase (AGT) and is thought to increase the stability and effectiveness of the AGT enzyme. […] Oxalobacter formigenes, although involved in the pathogenesis of hyperoxaluria when deficient, confer only limited benefit when given as an oral supplement. […] NLRP3 is 1 of 3 cytosolic proteins activated by oxalate crystals, resulting in IL-1 release and causing inflammatory tubular epithelial injury. Novel inhibitors of NLRP3 and IL-1 are promising therapeutics that may be useful in the future for hyperoxaluria (both primary and secondary), as well as for CKD in general.

• #2 Hyperoxaluria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558987/

  Orthophosphates and pyridoxine have been successfully used to treat primary and secondary hyperoxaluria. […] Magnesium supplements (usually magnesium oxide or magnesium hydroxide) reduce oxalate absorption by binding with oxalate in the intestinal tract but may promote diarrhea when used alone. […] Cholestyramine is primarily used to manage bile acid malabsorption, increasing intestinal oxalate binding and reducing absorption. […] Dietary measures do not play a major role in PH as the excess oxalate in this condition is endogenous. Early, aggressive treatment is necessary to prevent loss of renal function, so utilization of all of the above measures is reasonable, including high dose pyridoxine, orthophosphate and magnesium supplementation, increased urinary volume, pentosan polysulfate (Elmiron), Lumasiran, and intensive dialysis.

• #2 Hyperoxaluria: Causes, Symptoms, Diagnosis & Treatment

  https://my.clevelandclinic.org/health/diseases/21117-hyperoxaluria

  For people with any type of hyperoxaluria, medication options include oral doses of potassium citrate or the combination of orthophosphate and magnesium to prevent calcium oxalate crystals from forming. […] For people with enteric hyperoxaluria, taking a calcium supplement with meals can also help. Calcium binds with oxalate, which may help oxalate leave your body through your pee and poop. […] Drinking more fluids and making changes to your diet can help with high oxalate. […] Increase your water intake to around 3 liters per day. Extra fluids help to flush oxalate from your kidneys, which prevent it from building up and creating stones or crystals. This should help all types of hyperoxaluria. […] Change your diet by limiting salt and sugar, eating less animal protein (meat, milk, eggs and fish) and avoiding foods high in oxalates. High-oxalate foods include spinach, rhubarb, beets, plums, chocolate, tea, nuts and nut butters.

• #2 Hyperoxaluria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558987/

  Treatment of a patient with hyperoxaluria includes conservative medical and surgical measures, along with the treatment of nephrolithiasis. Isolated renal stone treatment can be conservative, using fluids and alpha-blockers, or surgical if the stone or stones are larger than 4 mm, fail to pass, or become complicated by infection. […] A greater fluid intake will increase urine volume and reduce the supersaturation of calcium oxalate. Measuring and focusing on urinary volume rather than any particular oral intake goal is preferable. It is recommended that the oral intake should be sufficient to generate at least 3000 ml of urine per day. […] Potassium citrate provides adequate urinary citrate levels and keeps the urine pH at a favorable 6.2 to 6.8. Sodium citrate can be used in cases of renal failure. Adequate urinary citrate levels (optimally at 250 to 300 mg/L or 500 to 600 mg daily total in divided doses) help prevent the aggregation of calcium oxalate crystals into stones.

• #2 Primary and secondary hyperoxaluria: Understanding the enigma

  https://www.wjgnet.com/2220-6124/full/v4/i2/235.htm

  Dietary interventions do not play a major role in the management of primary hyperoxaluria as absorption of oxalate from the intestine is very small. […] On the other hand, diet modification is a very important element in the treatment of secondary hyperoxaluria where efforts should be made to reduce oxalate intake in the diet. […] Pyridoxine supplementation has been shown to be beneficial in patients with PH1. […] Alkalinization of the urine is well known to prevent stone formation as citrate complexes with calcium and thus decreases the amount of calcium oxalate available for precipitation. […] For management of renal stones, endoscopy is currently the procedure of choice as it allows direct visualization of the stones. […] Patients reaching ESRD need optimization of renal replacement therapy to ensure adequate oxalate removal. […] Transplantation must be planned when GFR falls between 15-30 mL/min per 1.73 m2. […] In secondary hyperoxaluria, there is a paucity of data regarding renal transplantation in those who develop ESRD.

• #2 Treatments for Primary Hyperoxaluria Type 1

  https://www.webmd.com/kidney-stones/primary-hyperoxaluria-type-1-treat

  If these treatments don’t stop your condition from getting worse, you might eventually need dialysis or a combined kidney and liver transplant. […] Dialysis. When medication and lifestyle changes don’t help enough, your kidneys eventually stop working. You may need to get hemodialysis. It helps to remove the extra oxalate from your blood, as well as clean the blood and remove fluid like your kidneys would normally do. […] The only cure for primary hyperoxaluria type 1 is a liver transplant. A transplanted liver from a healthy donor will make the enzymes your body needs to break down oxalate. […] Because PH1 often damages the kidneys, too, some people may need both a liver and kidney transplant. These operations can be done at the same time, or you can have a liver transplant followed by a kidney transplant.

• #2

  https://link.springer.com/article/10.1007/s40265-022-01735-x

  No renal replacement therapy, daily hemodialysis (HD), nor its combination with peritoneal dialysis is able to sufficiently remove the endogenously overproduced oxalate. […] Liver transplantation (LTx) cures the enzyme defect in PH1 and hence, sequential or combined liver/kidney transplantation (LKTx) and pre-emptive LTx are possible procedures. […] One PH1-specific treatment option is the oral application of VB6. […] It has been observed for several decades that a variable number of patients with PH1 (up to 50%) with residual AGT activity show a reduction in Uox following administration of pharmacologic doses of PLP. […] RNA interference (RNAi) therapeutics work at the level of messenger RNA (mRNA) translation. […] A first RNAi drug, lumasiran (Oxlumo; Alnylam Pharmaceuticals, Cambridge, MA, USA), was recently approved (end of 2020) by the US Food and Drug Administration and the European Medicines Agency for the treatment of PH1 and has been available via prescription since January 2021 in some countries.

• #2 Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope | Nature Reviews Nephrology

  https://www.nature.com/articles/s41581-022-00661-1

  In response to these developments, members of OxalEurope a network of European scientists and physicians who specialize in PH and the metabolic workgroup of the European Rare Kidney Disease Reference Network (ERKNet), formed a workgroup. […] We aim to make clinical practice recommendations for worldwide application and have therefore added statements for countries with restricted financial and medical means. […] We also propose key future research questions in the field, which may further help practitioners in clinical decision making. […] The diagnostic work-up for patients with estimated glomerular filtration rate (eGFR) 30ml/min/1.73m2 and suspected primary hyperoxaluria (PH) should include at least two urine oxalate assessments (preferably from a 24h urine collection). […] If genetic assessment reveals a mutation consistent with vitamin B6 (VB6; also known as pyridoxine) non-responsive PH1, RNA interference (RNAi) therapy is indicated.

• #2 Hyperoxaluria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558987/

  In November 2020, the FDA and the European Medicines Agency approved using lumasiran for type I PH. It is the first available, effective therapy for PH short of combined liver/kidney transplantation. […] Nedosiran, like lumasiran, is also an RNA interference therapy designed to target hepatic lactate dehydrogenase (LDH), which converts glyoxalate to oxalate. […] The role of dialysis is controversial. Serum oxalate levels of 30 to 45 mol/L lead to tissue deposition, and dialysis aims to keep the oxalate level below that to prevent supersaturation. […] The procedures to choose from are 1) an isolated liver transplant, 2) an isolated renal transplant, or 3) a combined liver-renal transplant. […] Future therapies for controlling hyperoxaluria being investigated include the following: Vitamin E and other antioxidant supplementation, recombinant gene therapy to replace defective hepatic enzymes, intestinal oxalate transport (SLC) blockers, especially SLC26A3 and S1C26A6, hepatocyte cell transplantation, organic marine hydrocolloid, RNA interference therapy, and use of gene-editing technology (CRISPR) to correct specific enzyme pathways for PH.

• #3 Treatments for Primary Hyperoxaluria Type 1

  https://www.webmd.com/kidney-stones/primary-hyperoxaluria-type-1-treat

  When you have primary hyperoxaluria type 1 (PH1), too much of a natural substance called oxalate collects in your kidneys. To prevent the serious kidney damage that can result, your doctor will try to reduce the buildup of oxalate in your body. […] Your doctor may also recommend one or more of these treatments. […] Lumasiran (Oxlumo). This is the first medication approved specifically for use in adults and children for reducing the amount of oxalate your body produces. It can usually bring levels to normal within 24 hours. […] Nedosiran (Rivfloza). This works to inhibit oxalate production in your urine. […] Pyridoxine (Vitamin B6). When taken in prescription-level doses, this vitamin can greatly reduce the amount of oxalate in your urine. It doesn’t work for everyone, though. […] Potassium citrate or pyrophosphate. These salts work by forming complexes with calcium making oxalate stones less likely to form. Your doctor will probably tell you to take one or more of them several times throughout the day.

Zobacz więcej