Thursday, June 16, 2022

Does Gout Cause Kidney Failure

Most Common Kidney Problems

Webinar: Gout and kidney disease

Acute gout attacks can be extremely painful, but the symptoms are often brought under control with medication, and theres a chance you wont experience another painful episode. However, when uric acid is allowed to build up in the blood over a long period of time, gout can lead to widespread problems in multiple systems. In some cases, the damage can be permanent.

Your kidneys are responsible for removing excess uric acid from the bloodstream, so when theres too much of it to dispose of, the kidneys can be overworked. In turn, you could develop:

Kidney Stones

When uric acid crystals lodge in the joints, you get a gout attack when they settle in the kidneys or urinary tract, you get kidney stones. These small stones are hard and insoluble, and the larger they are, the more pain they will cause.

The sharp edges of kidney stones can physically scar your kidneys, or obstruct pathways and interfere with waste removal. If they go untreated for long enough, infections can develop.

Kidney Disease

Damaged kidneys are at a much higher risk for kidney disease, which is diagnosed when kidney function is severely reduced for three months or more. In many cases, symptoms of kidney disease are vague or mild, especially in the early stages.

Instead of relying on physical symptoms, your doctor can conduct an estimated glomerular filtration rate test or a urine albumin test to get a better idea of your kidney function.

Kidney Failure

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Effects Of Uric Acid From Innate To Adaptive Immune Cells

Uric acid modulates the adaptive immune system via innate immune cells, mostly involving dendritic cells . This feature is well exemplified by the synergistic effect of uric acid on CD8+ T cell priming, during which uric acid induces the expression of costimulatory molecules in dendritic cells. Shi et al. purified low-molecular-weight fractions from ultraviolet-treated 3T3 cells and liver cells by high-performance liquid chromatography and found that these fractions markedly enhanced the cytotoxic T lymphocyte response. The component of the low-molecular-weight fractions not only was degraded by uricase but also exhibited a mass spectrum that matched that of uric acid. Furthermore, the investigators found that uric acid stimulated dendritic cells and macrophages to express the costimulatory molecules CD80 and CD86, thereby enhancing the CD8+ T cell immune response.

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Identification Of Research Areas

Data from the literature were thematically analysed by the leaders and fellows of each literature review team to identify general issues with the currently available data with regard to gout and gout studies in people with concomitant CKD as well as specific issues with individual medications.

The research areas and general requirements for studies identified were agreed on by the leaders and fellows of each literature review team and then circulated to all authors of this Consensus Statement. Agreement was reached by consensus of all authors via e-mail, and final approval was granted by the G-CAN Board. No effort was made to prioritize the research areas.

How Can Gout Contribute To Kidney Disease

Kidney Disease &  Related Issues

There is evidence that gout can lead to kidney disease, although the connection is less established. Gout happens when there is a great amount of uric acid crystallizing, resulting in joint inflammation. These crystals technically consisted of sodium urate, but they are generally referred to as uric acid crystals. Crystals often appear in the joints, but they also accumulate in the outer ear, the skin near the joints, and the kidneys.

The crystals can cause damage and scars as they pass through the kidneys. This damage to the kidneys is thought to contribute to kidney disease and failure over time, especially if the gout is left untreated. However, some people with high concentrations of uric acid levels in the blood do not develop gout and even when they do, they can go for years without manifesting any symptoms.

Uric acid can still build up in the body even with normal kidney function. If the kidneys couldnt filter uric acid effectively, uric acid can accumulate in the blood, which can lead to gout.

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Living With Gout And Kidney Disease

When you have both gout and kidney disease, treating gout can be difficult because some medicines, such as NSAIDs, are not safe for the kidneys. Some of the most common medicines for acute and chronic gout should be adjusted or avoided when you have kidney disease. Learn more about the medicines for gout here.Additionally, some people with kidney disease take medicines that may increase their risk of gout. For example, diuretics and beta-blockers, two common medicines for high blood pressure can contribute to gout attacks. Tell your doctor about all the medicines you take so they can suggest a treatment that works best for you.If you have both gout and kidney disease, there are certain things you can do to keep both conditions under control and improve your general health.

The Relation Of Uric Acid And Ult To Kidney Outcomes

CKD leads to hyperuricemia due to decreased urinary excretion of UA. Hyperuricemia also may induce kidney dysfunction and contribute to CKD progression through a number of potential mechanisms. It is possible that controlling hyperuricemia, especially if achieved early, may reduce kidney disease risk.

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What Did This Study Do

This systematic review and meta-analysis included 16 randomised controlled trials of 1,211 adults with chronic kidney disease. Most had moderate disease with a glomerular filtration rate 30 to 60ml/min/1.73m2. People were allocated to uric acid-lowering therapy or a control group who had usual treatment or a placebo.

Trials followed people for about six or 12 months one trial carried on for 84 months.

There are several limitations which reduce our confidence in the precision of the results. The cause, severity and definition of chronic kidney disease differed between studies. The trials were small, ranging from 36 to 140 participants. Only one trial was from the UK many were from China. Most were of low quality and had a short follow-up. It is nevertheless likely that the direction of effect, at least, is reasonably certain.

So What Is The Cause Of This Condition

Goutful: Gout and Kidney Disease

Well I am glad you asked essentially gout is the deposit of monosodium urate crystals in and around the joints, which are caused by increased levels of uric acid. Uric acid is formed when purines are broken down. Purines are found in certain foods such as meat, peas, and alcohol, and also occur naturally in our cells. High levels of uric acid cause inflammation and damage to joints and soft tissues. So gout can be either caused by the overproduction or under excretion of uric acid, such as in kidney disease. Gout can be a very common occurrence in those suffering from under functioning kidneys.

Here is a list of the major contributing factors, and risk factors, of gout:

  • Kidney failure
  • Bone fracture or surgical procedure
  • Polynesian background
  • High blood pressure
  • Lead crystal glasses: Lead toxicity is a cause of gout . Leaded crystal decreases renal urate excretion.

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Conflict Of Interest Statement

R.J.J. and T.N. have patent applications related to lowering uric acid as a means to prevent or treat diabetic nephropathy, insulin resistance and features of metabolic syndrome and also have stock in Revascor, a new company interested in lowering uric acid as a treatment for hypertension and metabolic syndrome. R.J.J. is also on the Scientific Board of Amway, has grants with the NIH, State of Colorado, Amway, Cardero, Danone and Questcor, and stock with Cardero and NCD Therapeutics. RJJ is also author of The Sugar Fix and The Fat Switch that discusses the role of fructose and uric acid in the epidemic of obesity and diabetes. All other authors have no disclosures. The results presented in this paper have not been published previously in whole or in part, and have not been influenced by the COI.

Why Was This Study Needed

Moderate to severe kidney disease affects 2.6 million people in England. It has a variety of causes including diabetes and inflammation. Management aims to slow progression through a variety of measures including lowering blood pressure, blood thinners, stopping smoking and dietary advice.

Uric acid is a breakdown product of blood cells and foods rich in purines. Blood levels are often high in people with impaired kidneys. It is not known whether this is a cause or consequence of chronic kidney disease.

There has been renewed interest in the relationship between uric acid levels and kidney disease with recent research showing a possible link between uric acid and the worsening of kidney disease in patients with and without diabetes. There has been conflicting evidence about whether reducing the levels of uric acid can limit the decline in kidney function or cardiovascular disease. The researchers aimed to address this through pooling the available research.

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Other Foods High In Purines

  • Asparagus, mushrooms, spinach, cauliflower
  • Animal organs
  • Dried beans and peas
  • Organ meat: tongue, liver, brains, kidney, and sweetbreads
  • Some Fish/Seafood: codfish, trout, haddock, mackerel, herring, sardines, anchovies, scallops, mussels
  • Red meat: beef, veal, lamb, and pork
  • Wild game: rabbit, venison, quail, pheasant, goose, duck
  • Dates, prunes, lychees, plums

Gout And Kidney Disease

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Most commonly, kidney disease can cause gout. However, gout may also lead to kidney disease. Since uric acid is filtered through the kidneys, the two diseases are related. 1 out of 10 people with chronic kidney disease have gout, and an even higher percentage of people with gout have kidney disease. Many people with kidney disease have uncontrolled gout which can make kidney disease worse, and lead to other complications.

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Keep Your Kidneys Healthy If You Have Chronic Gout

Treating is a matter of keeping your uric acid levels down with medication and diet. If the most common uric acid reducer, allopurinol , doesnt work for you or you cant tolerate it, there are other medications your doctor can give you. Some of them, however, including febuxostat , probenecid , and lesinurad , may adversely affect your kidneys, especially if you already have kidney disease. You still have options, though. Pegloticase is a medicine given by injection that can work quickly and effectively to lower uric acid levels. It does not affect the kidneys or worsen kidney disease. Sometimes, pegloticase can become less effective over time, so its important you follow a diet that can help lower your uric acid levels as well.

A good diet for chronic gout is one that is low in purines, which are the substances that form uric acid in your body. Avoid alcoholparticularly beeras well as meat and shellfish, which are all high in purines. There is evidence that cherries lower uric acid, so consider adding cherry extract or cherry juice to your daily routine. If you have kidney problems, be sure to talk to your doctor about how much liquid you should have each day, so that you dont overtax those hard-working organs.

Level Of Renal Function Precluding Ult

Because most large RCTs have excluded people with substantial renal impairment, there are few data from RCTs to inform decisions about when specific ULTs should not be used on the basis of kidney function. No studies have specifically examined the risks and benefits of not treating gout in people with CKD with ULT, and all current guidelines recommend ULT treatment in this population. In many patients, but not all, untreated gout causes considerable morbidity in its own right, and in those with CKD the only option for treating flares might be long-term corticosteroids, which is associated with further morbidity.

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Epidemiology Of The Association

Some genetic studies also suggest that hyperuricemia may confer risk for CKD, especially in Mexican American, Native American, and Italian populations2020 Macias-Kauffer LR, Villamil-Ramirez H, Leon-Mimila P, Jacobo-Albavera L, Posadas-Romero C, Posadas-Sanchez R, et al. Genetic contributors to serum uric acid levels in Mexicans and their effect on premature coronary artery disease. Int J Cardiol. 2019 Mar 279:168-73.,3636 Testa A, Mallamaci F, Spoto B, Pisano A, Sanguedolce MC, Tripepi G, et al. Association of a polymorphism in a gene encoding a urate transporter with CKD progression. Clin J Am Soc Nephrol. 2014 Jun 9:1059-65.,3737 Voruganti VS, Franceschini N, Haack K, Laston S, MacCluer JW, Umans JG, et al. Replication of the effect of SLC2A9 genetic variation on serum uric acid levels in American Indians. Eur J Hum Genet. 2014 Jul 22:938-43.. However, a recent large Mendelian randomization study did not find any association between serum uric acid, eGFR, and CKD77 Jordan DM, Choi HK, Verbanck M, Topless R, Won HH, Nadkarni G, et al. No causal effects of serum urate levels on the risk of chronic kidney disease: a Mendelian randomization study. PLoS Med. 2019 Jan 16:e1002725..

How Is Gout Treated

Uric Acid and Kidney Diseases

Schedule an appointment if you suspect symptoms similar to gout for proper treatment. Gout treatment is categorized into two, focusing on two different problems. The first type of treatment addresses the pain and inflammation related to gout episodes. The second treatment lowers the uric acid level in the blood. The type of medication you should take depends on the frequency and severity of your gout symptom,s as well as other health conditions you may have.

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Uric Acid As A Marker Of Kidney Disease: Review Of The Current Literature

Abdo Asmar

1Department of Internal Medicine, University of Central Florida, College of Medicine, Orlando, FL 32827, USA

2Orlando VA Medical Center, Orlando, FL 32827, USA

Abstract

Uric acid has been implicated in the pathophysiology of renal disease however renal clearance makes a causal relationship difficult to prove. We examine the current literature to support a potential role of uric acid in the development of kidney disease and to determine the potential to use uric acid as a marker for future renal decline. After review, we conclude that uric acid is definitively linked to the development of chronic kidney disease and can be a poor prognostic factor for the development of acute renal failure, as well. However, further human research is needed before predictive models utilizing uric acid can be developed and used in the clinical setting.

1. Introduction

2. Pathophysiology of Uric Acid in Development and Progression of Renal Disease

3. Hyperuricemia and Risk of Development of Renal Disease

Finally, Weiner et al. performed a prospective cohort study following over 13,000 people with normal kidney function and found that 7.9% of the cohort developed renal disease by follow-up at 8.5 years. Logistic regression models determined that a baseline elevated serum uric acid level predicted worsening renal function irrespective of age, gender, race, diabetes, hypertension, alcohol use, smoking, lipids, and baseline renal function .

Appropriate Dosing Of Xois

As mentioned above, allopurinol dosing in CKD is one of the most controversial areas in gout management owing to the risk of AHS in people with CKD. On the basis of primarily case series and a retrospective casecontrol study, there is general agreement that the starting dose of allopurinol should be low and increased slowly, although no prospective trial data are available to prove or disprove the rationale that such an approach will reduce the risk of AHS. Use of allopurinol is further complicated by the large inter-individual variability in the dose required to achieve the target serum urate concentration . Despite data suggesting that allopurinol dose escalation can achieve target serum urate concentrations even in those with kidney impairment,,, the belief that the allopurinol dose should be reduced in people with CKD remains pervasive. In comparison to allopurinol, febuxostat has a narrower dose range and there has been more willingness to use febuxostat in people with CKD. In the largest study of febuxostat in CKD, which enrolled 96 people with an eGFR in the range 1550ml/min/1.73m2, febuxostat 6080mg daily was associated with a reduction in serum urate concentration with no decline in renal function.

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Management Of Gout In Ckd

The management of gout follows the same four principles regardless of the presence of CKD: 1) lower SUA 2) provide prophylaxis while initiating ULT 3) treat gout flares and 4) optimize dietary and lifestyle factors as appropriate. Over a prolonged period of time with adequate management of hyperuricemia, defined as maintenance of a SUA level < 6 mg/dL or < 5 mg/dL for those with tophaceous gout, gout flares will diminish in frequency and severity, with eventual cessation of flares, and tophi can be prevented and/or resolve.

Kidney Disease Can Lead To Gout

Gout and Kidney Disease

When you have chronic kidney disease , your kidneys do not work as well as they should to filter wastes out of your body. Uric acid is a waste product that is naturally found in your blood. When you have kidney disease, your kidneys cannot filter out uric acid as well as they should. Too much uric acid building up in the body may cause gout.Most people with early stage kidney disease do not know they have it. Gout can be a warning sign of kidney disease. Ask your doctor if you should be tested for kidney disease when you have gout.

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Are Your Kidney Stones Due To Gout Or Something Else

According to the American Urological Foundation, kidney stones can cause severe and sharp pain, specifically in the back and abdomen, as well as while urinating. They could also cause nausea, vomiting, blood in urine, or frequent urination.

These symptoms could point to any of the four types of kidney stones, which are classified based on what they are made of:

  • Calcium

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