Hyperuricemia In Chronic Kidney Disease Research Articles

Hyperurikemia in chronic kidney disease stage 4 — the issue of suitability of urate-lowering therapy

For almost 20 years, the issue of hyperuricemia has been studied in nephrology, rheumatology, cardiology, endocrinology, and neurology areas of medicine. In all countries of the world, new aspects of this clinical symptom are being revealed almost simultaneously, some facts are being disproved, and updated practical recommendations are being implemented. The main medical axiom now is that hyperuricemia is a symptom of chronic kidney disease (CKD) of any stage, but the pathogenetic mechanisms of the effect of a high uric acid level on kidney function are not known for sure. It is necessary to correct its level under certain clinical and laboratory criteria in order to reduce the risk of cardiovascular disease and the risk of increased mortality, to influence the course of diabetes and possibly prevent obesity. There are still a lot of questions and unexplained facts. For example, what is the role of hyperuricemia in CKD, what level of uric acid reduction is safe and appropriate? What is the causal relationship between uric acid levels and CKD progression? Is the treatment of asymptomatic hyperuricemia effective for absolutely all patients? Is a differentiated approach to lowering the level of uric acid necessary depending on the stage of CKD? When should one take into account the physiological positive effect of hyperuricemia on kidney and vascular cells and not prescribe urate-lowering therapy? Our observation of two patients, which took place within the randomized patient-oriented study “Development of technology to preserve kidney function in patients with CKD and hyperuricemia”, does not provide direct answers to all these questions, but allows us to assume that hyperuricemia can be compensatory for kidney function, and it will not always be appropriate to actively reduce its level. The article aims to draw attention to the fact that when hyperuricemia causes hyperfiltration to preserve kidney function, lowering its level may be inappropriate for absolutely all patients. And maybe in certain conditions and individual clinical situation, the doctor has the option not to prescribe this type of therapy without negative consequences for kidney function.

Management of asymptomatic hyperuricemia in chronic kidney disease: A proposed stepwise approach

Serum uric acid levels are frequently elevated in patients with chronic kidney disease (CKD). The relatively modest hyperuricaemia in CKD may reflect the reduced efficiency of renal excretion of urate. In the past two decades, basic research has shown that hyperuricaemia plays a causal role in the progression of CKD through direct renal injury. However, clinical studies have reported conflicting results, hence there is much controversy about the scope of treating asymptomatic hyperuricaemia to prevent or reduce the rate of CKD progression. In this review, we highlight the most recent guidelines and clinical trials that tested the use of urate-lowering therapy in the management of asymptomatic hyperuricaemia in CKD patients. Keywords: uric acid, hyperuricaemia, chronic kidney disease

Managing hyperuricemia and gout in chronic kidney disease: a clinical conundrum.

There is controversy regarding the impact of hyperuricemia on the progression of chronic kidney disease (CKD), and gout remains sub optimally managed in this population. We discuss the prescribing of drugs for the treatment of gout in patients with CKD. There is a lack of consensus from expert guidelines, and prescribers have concerns regarding the risk of adverse reactions from medicines used to treat gout. These situations appear to contribute to suboptimal management of gout in this cohort. Recent data have challenged the role of urate lowering therapy (ULT) in the management of asymptomatic hyperuricemia in CKD. ULT should be commenced in all patients with severe, recurrent disease, tophaceous gout and evidence of joint damage. Most international guidelines recommend a treat-to-target approach for the management of gout. In CKD, ULT should be started at low dose with up titration adjusted to serum urate levels, rather than being based on the creatinine clearance. If patients fail first-line therapy, alternative agents are utilized, the specific agent depending on ease of access, burden of disease and other comorbidities. This approach should be incorporated into routine practice to ensure optimal treatment of gout in CKD. More research is required to investigate whether treatment of asymptomatic hyperuricemia has clinical benefits.

Hyperuricemia in Chronic Kidney Disease: a role yet to be explained

Hyperuricemia in Chronic Kidney Disease: a role yet to be explained

Correlation of Uric Acid with Glomerular Filtration Rate in Chronic Kidney Disease

Chronic Kidney Disease is a worldwide public health problem that affects millions of people from all racial and ethnic groups. Identification of a Chronic Kidney Disease is a major risk factor for cardiovascular morbidity and mortality and is attributed to hyperuricemia. Evidences show that high serum uric acid contribute directly to glomerulosclerosis, interstitial fibrosis and atherosclerosis that correction of hyperuricemia associated with Chronic Kidney Disease will slow the progression of chronic renal failure. This study is done to correlate between serum uric acid level and estimated glomerular filtration rate in chronic kidney disease patients. A hospital based cross-sectional study on chronic kidney disease patients including 57 patients on conservative treatment attending Bir Hospital with diagnosis of chronic kidney disease was performed. Detailed clinical history, examination and investigations including uric acid were done. Chronic Kidney Disease staging was done according to estimated glomerular filtration rate estimated by Cockcroft-Gault equation. Prevalence rate of hyperuricemia in Chronic Kidney Disease and its stages were calculated and compared with each other. A total of 57 Chronic Kidney Disease cases were enrolled, with male to female ratio of 2:1 and mean age 51.63±17.75 years. Hyperuricemia was present in 55 (96.49%) of study population. Though prevalence of hyperuricemia increased with Chronic Kidney Disease stage, there was no significant difference in mean value of uric acid in different stages. Hyperuricemia and stages of Chronic Kidney Disease had negative correlation which was statistically significant. Hyperuricemia is highly prevalent among Chronic Kidney Disease patients with conservative management. The severity of hyperuricemia increases as Chronic Kidney Disease stage progresses.

Study of therapeutic efficacy of febuxostat in chronic kidney disease stage IIIA to stage VD.

Hyperuricemia [serum uric acid (SUA) >7.0 mg/dL] which is common in chronic renal diseases is associated with augmented vascular events. In addition to nonpharmacological therapy, hypouricosuric drugs reduce UA levels. The current study was a prospective observational study of six months duration November 2016 to April 2017 done to determine the efficacy of febuxostat in patients with hyperuricemia in chronic kidney disease (CKD) stage G3a to G5 and to correlate any association with reduction of hypertension, improvement in glomerular filtration rate (GFR), and reduction in comorbidities. The study was carried out at the Department of Nephrology, Owaisi Hospital and Research Center, Hyderabad. One hundred and ten patients were screened, of which 53 patients wherein stage G3a to G5 were recruited and SUA levels were obtained after inclusion criteria. SUA >6.0 in females and 7.0 in males were recruited. The drug febuxostat 40 mg was given once day to all patients with stage G3a to G5D with elevate uric acid levels >7.0 in males and more than 6.0 in females and three samples of UA were obtained monthly. The mean of GFR, blood pressure (BP), and SUA levels were obtained before and after the therapy. Of the 53 patients, males were 32 (60.3%), and females were 21 (39.6%). Mean age of the patients were 36.5 years. Mean UA levels before the start of febuxostat therapy were 8.6, and after adding febuxostat, it was 5.10 at the end of the third visit. The mean BP drop was 7.2 ± 2.1 mm in systolic BP (from 154-147 mm Hg) and diastolic BP drop was 93 ± 2.5 mm Hg (5.1 mm Hg). The mean GFR improved from 50.3 to 53.3 mL/min after the start of febuxostat. Febuxostat in asymptomatic CKD patients improves UA levels, BP and estimated GFR at low dose without any adverse events and no cardiac-related events.

Hyperuricemia and Progression of Chronic Kidney Disease: Role of Phenotype Transition of Renal Tubular and Endothelial Cells.

Although the clinical implication of hyperuricemia in chronic kidney disease has been an issue of active debate, recent data suggested a causative role of uric acid (UA) in the development of renal disease. Afferent arteriopathy, an induction of oxidative stress and an activation of local inflammation, have been regarded as the mechanisms of UA-induced renal disease, which contribute to glomerular hypertrophy and interstitial fibrosis via endothelial dysfunction. However, there have been rare studies on the direct effect of UA on phenotype transition of renal cells such as epithelial-to-mesenchymal transition (EMT) or endothelial-to-mesenchymal transition (EndoMT). We have reported that UA-induced EMT of cultured renal tubular cells, which was blocked by the organic anion transport inhibitor, probenecid. UA increased the expression of snail and slug, the transcriptional repressors of E-cadherin, which resulted in a downregulation of E-cadherin production. UA also increased the degradation of E-cadherin via ubiquitination. UA also induced EndoMT with an increase in ROS generation and glycocalyx shedding of cultured vascular endothelial cells. Treatment with antioxidants ameliorated UA-induced EndoMT. In the kidney of hyperuricemic rats, there was an evidence of EMT before the development of significant tubulointerstitial fibrosis, as shown by decreased E-cadherin expression and an increased α-smooth muscle actin (α-SMA) in renal tubular cells. Allopurinol significantly inhibited UA-induced EMT with an amelioration of renal fibrosis. In addition, endothelial staining in peritubular capillaries (PTC) was substantially decreased with de-novo expression of α-SMA in endothelial cells of PTC. Key Messages: UA per se induced a phenotypic transition of epithelial and endothelial cells via an induction of oxidative stress and glycocalyx shedding, which could be one of the mechanisms of UA-induced kidney disease.

Treatment of Hyperuricemia in Chronic Kidney Disease.

Hyperuricemia may be a major contributor to the development or progression of chronic kidney disease (CKD). Although there is no clear cutoff uric acid (UA) value associated to the risk for kidney damage, it appears to be an increased risk as UA rises. Lifestyle interventions such as exercise, weight reduction, low consumption of purine-rich meat, or avoiding high fructose intake are recommended for all hyperuricemic patients. Lowering urate drugs such as allopurinol or febuxostat may be an option as a renoprotective agent; yet, randomized clinical trials evaluating the safety and efficacy of these drugs are limited to a small number of single-center studies. Several ongoing clinical trials aim to evaluate the safety and efficacy of these drugs. As of today, there is insufficient evidence to recommend the widespread use of UA-lowering therapy to prevent or slow down the progression of CKD. The purpose of this review is to summarize the evidence and future perspectives about the treatment of hyperuricemia in the prevention and progression of CKD.

Management of Gout and Hyperuricemia in CKD

Hyperuricemia and gout, the clinical manifestation of monosodium urate crystal deposition, are common in patients with chronic kidney disease (CKD). Although the presence of CKD poses additional challenges in gout management, effective urate lowering is possible for most patients with CKD. Initial doses of urate-lowering therapy are lower than in the non-CKD population, whereas incremental dose escalation is guided by regular monitoring of serum urate levels to reach the target level of<6mg/dL (or<5mg/dL for patients with tophi). Management of gout flares with presently available agents can be more challenging due to potential nephrotoxicity and/or contraindications in the setting of other common comorbid conditions. At present, asymptomatic hyperuricemia is not an indication for urate-lowering therapy, though emerging data may support a potential renoprotective effect.

Hyperuricemia in Patients with Chronic Renal Failure in the General Hospital of National Reference of N’Djamena (Chad)

Introduction: Hyperuricemia is defined as a level of serum uric acid greater than or equal to 70 mg/l (420 μmol/l) in men and 60 mg/l (360 μmol/l) in women. Several studies have shown that it is a risk factor or a factor of progression of chronic kidney disease. Recent experimental and epidemiological data correlate the association of hyperuricemia with chronic kidney disease (CKD), arterial hypertension and cardiovascular diseases, thus raising the question of the usefulness of therapeutics in the prevention of renal diseases. The objective of this study is to seek a link between chronic kidney disease and hyperuricemia. Materials and Methods: This is a descriptive and analytical study conducted at hemodialysis unit and cardiology service of General Hospital of National reference of N’Djamena (Chad) from 1th January to 1th October 2013 (10 months). We included all chronic kidney disease patients hospitalized in hemodialysis unit and cardiology service who presented associated hyperuricemia. Results: There were 712 CKD patients who were hospitalized. Among them, there were 108 patients who were included in the study and who had hyperuricemia as a prevalence of 15.20%. The average age of patients was 35.5 years and the sex ratio was 3/1. The age group between 40 to 60 years represented 54.6%. There were 41.7% of traders. Hypertensive patients accounted for 49.1%; association of diabetes and hypertension was noted in 12.90%. Renal insufficiency was moderate in 43.5% of patients. Hyperuricemia was present in more than 90% of patients. Profession, age, hematuria, proteinuria and hypertension were statistically positively related to hyperuricemia. Treatment consisted of prescribing allopurinol in 84% of patients. In more than 11% of patients the progression was unfavorable. Conclusion: The implication of hyperuricemia in chronic kidney disease has been proved in several recent studies. However, randomized studies at very long scales have to be carried out to conclude from its real impact on the prevention and treatment of chronic kidney disease.

Uric Acid and Chronic Kidney Disease: New Understanding of an Old Problem

Although an elevation of serum uric acid level is often associated with chronic kidney disease (CKD), it remains controversial whether hyperuricemia per se is a true risk factor for the development or aggravation of CKD. Recent epidemiologic studies in healthy populations or in subjects with established kidney disease have reported the independent role of uric acid in lowering glomerular filtration rate and increasing the risk for new-onset kidney disease. Furthermore, lowering uric acid in patients with established renal disease has been reported to stabilize renal function independent of other confounders, suggesting a causative role of elevated uric acid in progression of CKD, rather than as an incidental finding related to CKD severity. In this manuscript we will discuss the potential role of uric acid in the development and aggravation of CKD based on epidemiologic, clinical and experimental studies. Given the worldwide epidemic of CKD, the importance of identifying modifiable risk factors of CKD, and the clinical implication of hyperuricemia in CKD, we propose large randomized clinical trials to investigate whether uric acid-lowering therapy can slow the progression of CKD.

Efficacy and (Pharmaco)Kinetics of One Single Dose of Rasburicase in Patients with Chronic Kidney Disease

Aims: Hyperuricemia is a risk factor associated with cardiovascular and renal disease. Recently, rasburicase, a recombinant urate oxidase, has been developed for the treatment of hyperuricemia in patients with primarily hematological malignancies. We studied the pharmacokinetics and metabolism of rasburicase in the treatment of chronic asymptomatic hyperuricemia in chronic kidney disease (CKD) patients. Materials and Methods: We studied 9 CKD patients with hyperuricemia, whose mean serum acid concentration was 10.2 (range 8.3–15.8) mg/dl. No study subject was taking allopurinol (3/9 are allopurinol intolerant). Patients were treated with rasburicase (0.2 mg/kg/day) in single dose by intravenous infusion over a 30-min period. Serum samples were collected after 1, 4, 8, 24, 48 and 72 h, after 1 week, and after 1 month. To evaluate the efficacy of rasburicase, plasma and urinary concentrations of uric acid were determined by the standard method; the plasma activity of rasburicase was determined using a new assay developed by our laboratory (chromatography-mass method, a colorimetric 96-well microtiter plate assay). Results: All the treated patients experienced a rapid reduction in their plasma uric acid concentration. Data showed an undetectable value within 1 h of treatment. The rasburicase effect ended after 50 h, with a slow increase in the plasma level of uric acid. Conclusion: A single dose of rasburicase is highly effective and well tolerated in the treatment of hyperuricemia in selected CKD patients.

194: Outcomes Associated With Hyperuricemia in Chronic Kidney Disease

194: Outcomes Associated With Hyperuricemia in Chronic Kidney Disease