Use Of Allopurinol Research Articles

Allopurinol and Cardiovascular Events: Time-Related Biases in Observational Studies.

Several observational studies reported that allopurinol, an effective treatment for gout, was associated with important reductions in cardiovascular (CV) events, with calls for large, randomized trials, although some results were conflicting. The present study was undertaken to assess the extent of time-related biases in these observational studies. We searched the literature for all observational studies reporting on allopurinol and CV events, focusing on 2 time-related biases. Time-related confounding bias results from studies using cohorts of patients all exposed to allopurinol, with comparisons based on episodes of allopurinol discontinuation, where confounding factors are not updated over follow-up time. Immortal time bias arises from the exposure misclassification of periods of cohort follow-up during which the outcome under study cannot occur. We identified 12 studies, of which 8 were affected by time-related confounding bias or immortal time bias, while the remaining 4 studies avoided these biases. The studies affected by time-related confounding bias resulted in significant reductions in the incidence of CV events with allopurinol use (pooled hazard ratio [HR] 0.88 [95% confidence interval (95% CI) 0.85-0.92]), as did the studies affected by immortal time bias (pooled HR 0.79 [95% CI 0.72-0.87]). The 4 studies that avoided these biases resulted in a pooled HR of 1.07 (95% CI 0.91-1.25). Observational studies reporting significantly reduced incidence of CV events with allopurinol use were affected by time-related biases. Overall, studies that avoided these biases did not find a protective effect. The ALL-HEART randomized trial will provide important and accurate evidence on the potential effectiveness of allopurinol on CV outcomes.

Hyperuricemia is associated with secondary hyperparathyroidism in patients with chronic kidney disease.

Hyperuricemia is common among patients with chronic kidney disease (CKD). In the general population, hyperuricemia is associated with secondary hyperparathyroidism (SHPT), in a mechanism that involves vitamin D metabolism. Data for patients with CKD, however, are scarce. We aimed to evaluate the relationship between hyperuricemia and mineral and bone metabolism, particularly hyperparathyroidism. This is a retrospective study that included 922 adult patients with stages 3, 4, or 5 CKD, not on dialysis. Clinical, demographic, and biochemical data were collected from charts and included uric acid, parathyroid hormone (PTH), 25(OH)-vitamin D, calcium, phosphate, renal function (estimated glomerular filtration rate-eGFR), and medications such as allopurinol, furosemide, and cholecalciferol. SHPT was defined as PTH > 65pg/ml. Our patients were mostly Caucasian women, with a mean age of 64 ± 16years. SHPT and hyperuricemia were observed in 70% and 62.4% of patients, respectively. Patients with SHPT presented higher levels of uric acid (7.2 ± 1.8 vs. 6.6 ± 1.7 mg/dL, p = 0.0001) and a higher frequency of hyperuricemia (66% vs. 33%, p = 0.0001). Patients with hyperuricemia were mostly female, with lower eGFR, higher phosphate, and higher PTH. The risk of hypovitaminosis D was higher among patients with SHPT (69.7% vs. 53.1%, p = 0.0001). Hyperuricemia remained independently associated with hyperparathyroidism, (p = 0.033) even after adjustments for eGFR, calcium, phosphate, hypovitaminosis D, and use of allopurinol, calcitriol, furosemide, and cholecalciferol. Hyperuricemia seems to be a contributing factor for SHPT in patients with CKD. The mechanisms behind this finding have yet to be elucidated.

POSSIBILITIES OF RENOPROTECTION IN PATIENTS WITH CHRONIC KIDNEY DISEASE AND HYPERURICEMIA.

The aim: To determine efficacy and safety of allopurinol and febuxostat in treatment of patients with CKD to reduce the sUA level and analyze its influence on glomerular filtration rate (GFR). Materials and methods: The study included 45 CKD patients (stages 3b-5) without other severe/decompensated diseases and contraindications to the allopurinol/febuxostat. All patients underwent a comprehensive clinical and laboratory examination, and were divided into the study groups: Group I (28 patients, 61,3±3,2 y.o., CKD3b-12, CKD4-10, on hemodialysis-6 patients) received febuxostat, Group II (24 patients, 60,7±4,1y.o., CKD3b-9, CKD4-10, on hemodialysis -5 patients) took allopurinol. Results: Achievement of the target level of sUA was significantly often registered in Group I: after 1 month - in 45.5% (in group II - in 15.9%, p<0.001); after 3 months - in 67.5% (in group II - 21.2% p<0.01); after 6 months, these figures were 90% and 37.1%, respectively (p<0.01). sUA level <300 μmol/l was accompanied by significant positive GFR changes in group I patients; in group II there was a gradual progression of GFR deterioration in 31.8% of patients. Conclusions: In patients with pre-dialysis stages of CKD febuxostat demonstrates renoprotective abilities. Use of febuxostat in patients with CKD stage 3b-4 and in patients on hemodialysis is safe and more effective for target sUA level achievement than the use of allopurinol.

Reducing severe cutaneous adverse and type B adverse drug reactions using pre-stored human leukocyte antigen genotypes.

BackgroundSeveral type B adverse drug reactions (ADRs), especially severe cutaneous adverse reactions (SCARs), are associated with particular human leukocyte antigen (HLA) genotypes. However, pre‐stored HLA information obtained from other clinical workups has not been used to prevent ADRs. We aimed to simulate the preemptive use of pre‐stored HLA information in electronic medical records to evaluate whether this information can prevent ADRs.MethodsWe analyzed the incidence and the risk of ADRs for selected HLA alleles (HLA‐B*57:01, HLA‐B*58:01, HLA‐A*31:01, HLA‐B*15:02, HLA‐B*15:11, HLA‐B*13:01, HLA‐B*59:01, and HLA‐A*32:01) and seven drugs (abacavir, allopurinol, carbamazepine, oxcarbazepine, dapsone, methazolamide, and vancomycin) using pre‐stored HLA information of transplant patients based on the Pharmacogenomics Knowledge Base guidelines and experts' consensus.ResultsAmong 11,988 HLA‐tested transplant patients, 4092 (34.1%) had high‐risk HLA alleles, 4583 (38.2%) were prescribed risk drugs, and 580 (4.8%) experienced type B ADRs. Patients with HLA‐B*58:01 had a significantly higher incidence of type B ADR and SCARs associated with allopurinol use than that of patients without HLA‐B*58:01 (17.2% vs. 11.9%, odds ratio [OR] 1.53 [95% confidence interval {CI} 1.09–2.13], p = 0.001, 2.3% versus 0.3%, OR 7.13 [95% CI 2.19–22.69], p < 0.001). Higher risks of type B ADR and SCARs were observed in patients taking carbamazepine or oxcarbazepine if they had one of HLA‐A*31:01, HLA‐B*15:02, or HLA‐B*15:11 alleles. Vancomycin and dapsone use in HLA‐A*32:01 and HLA‐B*13:01 carriers, respectively, showed trends toward increased risk of type B ADRs.ConclusionUtilization of pre‐stored HLA data can prevent type B ADRs including SCARs by screening high‐risk patients.

Steven Johnson Syndrome Due to Allopurinol Use

Introduction Steven Johnson syndrome is a severe cutaneous adverse reaction that develops especially against drugs and has an increasing incidence. The mortality rate in the elderly population is quite high compared to other age groups. Rapid diagnosis, early recognition, and discontinuation of the responsible drug reduce the mortality rate in patients admitted to the emergency department. The most important step in treatment is supportive treatment. Case We present a 70-year-old woman with a history of hypertension, coronary artery disease, known renal failure, and adrenal insufficiency. Steven Johnson syndrome developed. We emphasized that the use of allopurinol due to known renal failure and hyperuricemia increased the mortality rate by causing acute kidney damage, and after its rapid diagnosis and treatment, it positively affected mortality. The patient was admitted to the internal medicine service with a pre-diagnosis of Steven Johnson syndrome in the emergency department and was discharged with recommendations after 26 days of hospitalization. Conclusion Because of the rapid spread and rapid deterioration of the general condition in severe cutaneous reactions such as Steven Johnson, mortality is important to make a rapid diagnosis, to determine the etiology, and to start treatment early.

Update on gout management: what is old and what is new.

The global burden of gout is rising, as are the prevalence of associated comorbidities, all-cause mortality and societal costs. In this review, we discuss recent advances in epidemiology and treatment strategies for gout. Genetic factors and obesity are prominent contributors to hyperuricemia and gout, while dietary factors contribute to less variance in serum urate, though can still have some contribution to population attributable risk. A consensus statement by the Gout, Hyperuricemia and Crystal-Associated Disease Network outlined appropriate terminology regarding gout, which will aid in communication about various aspects of the disease. The 2020 American College of Rheumatology gout guideline offers comprehensive evidence-based recommendations for the management of hyperuricemia using urate-lowering therapy, prophylaxis when initiating urate-lowering therapy, treatment of gout flare and adjunctive management strategies. There is improved understanding of risk factors for allopurinol hypersensitivity syndrome and well tolerated use of allopurinol in chronic kidney disease. Trial data have provided new insights regarding cardiovascular risk with febuxostat. Several new drug therapies are being tested for both urate-lowering efficacy and gout flare management. Although there have been significant advances in understanding of risk factors and treatment approaches, gout remains suboptimally managed. There is substantial need for improving gout management efforts and gout education among patients and clinicians.

Drug interactions with angiotensin-converting enzyme inhibitors

We reviewed potentially clinically significant drug–drug interactions (DDIs) with angiotensin-converting enzyme inhibitors (ACEIs) using Stockley’s Drug Interactions books and two online DDI databases. We identified &gt;10 such DDIs and described their mechanisms, clinical evidence and importance, as well as their management. Most DDIs with ACEIs were pharmacodynamic; only a few were pharmacokinetic. Most DDIs with ACEIs involved drugs that can lead to excessive reduction of blood pressure, hyperkalemia and impaired renal function. There is some evidence linking ACEIs with the induction of lithium toxicity. Severe hypersensitivity reactions may occur in patients treated with ACEIs with concomitant use of allopurinol or parenteral applications of iron. ACEIs should be combined carefully with hepatotoxic drugs due to their own potential hepatotoxic effects. The prevalence of adverse drug reactions due to DDIs might be high because they are prescribed frequently. Fortunately, most of such DDIs can be managed by clinical and laboratory monitoring of patients or by dosage adjustments of concomitantly used drugs.

Risk of Hematologic Events With Coadministration of Methotrexate and the Breast Cancer Resistance Protein Inhibitor Febuxostat.

The breast cancer resistance protein (BCRP) is a key drug transporter found in the liver, kidney, central nervous system, and gastrointestinal tract. Due to the wide expression of BCRP, interactions of other drugs with methotrexate (MTX) may differ in oral and intravenous MTX users, and understanding of these interactions may be useful in preventing severe adverse events. Febuxostat, a urate-lowering drug, inhibits BCRP. The objective of this study was to clarify the differences in the drug-drug interaction profiles of oral and intravenous methotrexate, associated with BCRP. We analyzed the Japanese Adverse Drug Event Report database and compared the frequency of hematologic events in patients taking oral and intravenous MTX, with or without the concomitant use of febuxostat or allopurinol. Hematologic events were defined as pancytopenia and neutropenia. Multiple logistic regression analysis was then used to identify the risk factors for hematologic events in oral and intravenous MTX users. We identified 8 453 oral and 810 intravenous MTX users with 546 and 126 cases of hematologic events, respectively. Compared with those not using febuxostat, a disproportionate number of hematologic events was observed in intravenous MTX users concomitantly using febuxostat (P < 0.01). The multivariate logistic analysis of intravenous MTX users showed that hematologic events were significantly associated with febuxostat use (P < 0.01) and age ≥ 60 years (P < 0.01). Our findings suggest that patients being treated with intravenous MTX who concomitantly use febuxostat may be at an increased risk of hematologic events, presumably due to BCRP-mediated drug-drug interaction.

A Possible Guide as a Tool to Complementary Effects of New Coronavirus

At the end of 2019, Sars-CoV-2 was identified and has since spread in the world. Coronavirus is commonly caused by upper respiratory tract and severe acute respiratory syndrome in humans. Due to the novel nature of the virus and high mortality among high-risk people, today health care providers used several medications with different mechanisms to overcome this virus. The course of COVID-19 represents three stages that have different symptoms and used different drugs depends on each stage. Ultimately the minority of patients progress to stage III with high mortality. The aim of this study is a comprehensive review of COVID-19 adjuvant therapies. We explained the current study on the use of Glucocorticoids, Interferon, Vitamin C, Tocilizumab, Anakinra, Pentoxifylline, IVIG, Allopurinol, Ivermectin, and Selenium in sepsis, pneumonia, and ARDS and we suggested a new protocol for prescribing each medication currently used in COVID-19 Outbreak.

Association between the use of allopurinol and risk of increased thyroid-stimulating hormone level

Allopurinol is the first-line agent for patients with gout, including those with moderate‐to‐severe chronic kidney disease. However, increased thyroid-stimulating hormone (TSH) levels are observed in patients with long-term allopurinol treatment. This large-scale, nested case–control, retrospective observational study analysed the association between allopurinol use and increased TSH levels. A common data model based on an electronic medical record database of 19,200,973 patients from seven hospitals between January 1997 and September 2020 was used. Individuals aged > 19 years in South Korea with at least one record of a blood TSH test were included. Data of 59,307 cases with TSH levels > 4.5 mIU/L and 236,508 controls matched for sex, age (± 5), and cohort registration date (± 30 days) were analysed. An association between the risk of increased TSH and allopurinol use in participants from five hospitals was observed. A meta-analysis (I2 = 0) showed that the OR was 1.51 (95% confidence interval: 1.32–1.72) in both the fixed and random effects models. The allopurinol intake group demonstrated that increased TSH did not significantly affect free thyroxine and thyroxine levels. After the index date, some diseases were likely to occur in patients with subclinical hypothyroidism and hypothyroidism. Allopurinol administration may induce subclinical hypothyroidism.

S3616 The Concomitant Use of Allopurinol and Azathioprine Leading to Dangerous Myelosuppression in a Patient With Ulcerative Colitis

S3616 The Concomitant Use of Allopurinol and Azathioprine Leading to Dangerous Myelosuppression in a Patient With Ulcerative Colitis

Hyperuricemia and Its Association With Ischemic Stroke.

Elevated serum uric acid (SUA) levels have been associated with an increased risk of cardiovascular (CV) disease and acute ischemic stroke (AIS) as well as many other medical conditions. AIS is a CV complication that is the second most common cause of mortality worldwide. It results from reduced blood flow to the brain by means of thrombosis, embolism, or systemic hypoperfusion. Studies have demonstrated an association between SUA levels and CV events, with a significant dose-response relationship between elevated SUA levels and stroke risk. Since the relationship between SUA levels and AIS risk has been established, studies are also being conducted in order to evaluate whether antihyperuricemic drugs can lower this risk. Allopurinol use in hyperuricemic patients has been shown to decrease the risk of major CV events, which include AIS. This narrative review aims to investigate the role of SUA as an independent risk factor for AIS along with the proposed biological mechanisms by thoroughly appraising research findings from relevant full-text articles and abstracts indexed in PubMed and the Cochrane Library. In this literature, we will be discussing hyperuricemia, AIS, the association between the two, and the use of antihyperuricemic medications on stroke prognosis. This review will also shed new light on studies that have begun to provide insight into the predictive role of hyperuricemia in AIS.

Allopurinol adherence, persistence and patterns of use in individuals with diabetes and gout: A retrospective, population-based cohort analysis

ObjectiveThere has been growing interest in the potential role for allopurinol to reduce cardiovascular events in people with diabetes. While adherence to allopurinol is poor in those with gout, our aim was to characterize persistence, patterns of use, and predictors of allopurinol use in a population-based cohort of individuals with diabetes and gout. MethodsIndividuals with diabetes older than 66 (thus eligible for prescription medication coverage) and newly prescribed allopurinol were followed for up to three years in a retrospective cohort study. Allopurinol use patterns were categorized as adherer (used continuously throughout follow-up), interrupter (non-persistent but subsequently resumed), or discontinuer (non-persistent with no subsequent resumption). Main outcomes were allopurinol non-persistence (no subsequent prescription accounting for a grace period), and indicators of gout severity throughout follow-up (prescriptions for prednisone or colchicine, outpatient gout visits, hospitalization/emergency department visits for gout). Outcome frequencies were determined, a multivariable Cox proportional hazards model evaluated associations between predictors and non-persistence, and zero-inflated negative binomial (ZINB) models evaluated associations between allopurinol use pattern and indicators of gout severity. Results22,056 individuals were followed for a maximum of 3.0 years (17,410 with 3 years of follow-up). 9092 (41.2%) were non-persistent with allopurinol. Higher risks of non-persistence were associated with female sex (HR, 95% CI: 1.28, 1.23–1.33), dementia (1.23, 1.11–1.35), and an outpatient visit for gout in the prior year (1.19, 1.09–1.29). There were 12,964 (58.8%) allopurinol adherers, 4618 interrupters (20.9%), and 4474 (20.3%) discontinuers. Allopurinol interrupters and discontinuers had indicators of more severe gout over time compared to adherers, including greater odds of being prescribed prednisone. ConclusionAllopurinol non-persistence and interruptions were frequent in individuals with diabetes and gout and were associated with prescriptions for prednisone. Suboptimal allopurinol adherence may not only increase the risk of gout complications in this population but also potentially diabetes complications through greater prednisone use and its negative effects on glycemic control.

Effect of uric acid-lowering therapy on renal function in patients with chronic kidney disease: a systematic review and meta-analysis

BackgroundWhether uric acid (UA)-lowering therapy (ULT) is effective in reducing the progression of renal dysfunction in patients with chronic kidney disease (CKD) remains controversial. Since several advances have been made in therapies for hyperuricemia, including novel xanthine oxidoreductase (XOR) inhibitors, we conducted a systematic review to clarify the effectiveness of ULT in preserving renal function among CKD patients.MethodsIn this systematic review, the MEDLINE database was searched up to June 2019. We included complete randomized controlled trials comparing renal events between adult non-dialyzed CKD patients, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, with and without ULTs. Changes in eGFR were expressed as the mean difference (MD). The incidence of dichotomous outcomes was expressed as a risk ratio. This review was performed using the predefined protocol published in PROSPERO (CRD 42019140346).ResultsEleven studies with 4277 CKD patients were included. Drugs used in the intervention groups of all studies were XOR inhibitors (allopurinol, febuxostat or topiroxostat). Although patients with ULT tended to show superior preservation of eGFR as compared to those without ULT, no significant differences were identified (MD, 2.52; 95% confidence interval, − 0.15 to 5.18). In subgroup analysis, the use of allopurinol was associated with superior preservation of eGFR, whereas the newer XOR inhibitors, febuxostat and topiroxostat, showed no significant effects on eGFR changes. Neither incidence of end-stage kidney disease nor treatment-emergent adverse events differed significantly between groups.ConclusionsThe present systematic review and meta-analysis suggested that CKD patients with ULT tend to show superior eGFR preservation as compared to patients without ULT, but further studies are needed to verify the renoprotective effects of ULT.

Allopurinol attenuates postoperative pain and modulates the purinergic system in patients undergoing abdominal hysterectomy: a randomized controlled trial.

Allopurinol is a potent inhibitor of the enzyme xanthine oxidase used primarily in the treatment of hyperuricemia and gout. The aim of this study was to compare the analgesic efficacy of preanesthetic allopurinol versus placebo on postoperative pain and anxiety in patients undergoing abdominal hysterectomy. This is a prospective, double-blinded, placebo-controlled, randomized clinical trial. We investigated 54 patients scheduled to undergo elective abdominal hysterectomy. Patients were randomly assigned to receive either oral allopurinol 300mg (n = 27) or placebo (n = 27) the night before and 1h before surgery. Patients were submitted to evaluation of pain and anxiety before the treatment, for 24h postoperatively, 30 and 90days after surgery. Cerebrospinal fluid was collected at the time of the spinal anesthesia to perform the measurement of the central levels of purines. Preoperative administration of allopurinol was effective in reducing postoperative pain 2h after surgery. Allopurinol caused a reduction of approximately 40% in pain scores measured by the visual analogue pain scale after surgery (p < 0.05). No differences were found between groups in anxiety scores after surgery. There was a significant change in the cerebrospinal fluid concentrations of xanthine and uric acid before surgery (p < 0.01). This study showed a short-term benefit of the use of allopurinol as a preanesthetic medication since it was related to a reduction on pain scores 2h after surgery. The purinergic system is a potential target for new analgesic drugs. New studies investigating more selective purine derivatives in the management of pain should be performed. Brazilian Registry of Clinical Trials-ReBEC #RBR-9pw58p.

Effectiveness of Allopurinol in Reducing Mortality: Time-Related Biases in Observational Studies.

The treatment of gout with allopurinol is effective at reducing urate levels and the frequency of flares. Several observational studies have shown important reductions in mortality with allopurinol use, with wide variations in results. We undertook this review to assess the extent of bias in these studies, particularly time-related biases such as immortal time bias. We searched the literature to identify all observational studies describing the effect of allopurinol use versus nonuse on all-cause mortality. We identified 12 observational studies, of which 3 were affected by immortal time bias and 3 by immeasurable time bias, while the remaining 6 studies avoided these time-related biases. Reductions in all-cause mortality with allopurinol use were observed among the studies with immortal time bias, with a pooled hazard ratio (HR) of death associated with allopurinol of 0.71 (95% confidence interval [95% CI] 0.50-1.01), as well as in those with immeasurable time bias (pooled HR 0.62 [95% CI 0.56-0.67]). The 6 studies that avoided these biases demonstrated a null effect of allopurinol on mortality (pooled HR 0.99 [95% CI 0.87-1.11]), though the lack of an analysis based on treatment adherence may have attenuated the effect. Observational studies are important to provide real-world data on medication effects. The observational studies showing significantly decreased mortality with allopurinol treatment cannot be used as evidence, however, mainly due to time-related biases that tend to greatly exaggerate the potential benefit of treatments. The ALL-HEART randomized trial, which is currently underway and evaluates the effect of adding allopurinol to usual care (compared to no added treatment), will provide reliable evidence on mortality.

Mortality in Patients With Gout Treated With Allopurinol: A Systematic Review and Meta‐Analysis

Urate-lowering therapy (predominantly allopurinol) is highly effective as a treatment for gout, but its wider long-term effects remain unclear. This systematic review and meta-analysis aimed to ascertain the association between mortality and the use of allopurinol in patients with gout. Medline, Embase, CINAHL, and the Cochrane Library were searched from inception to August 2018. Articles eligible for inclusion used a cohort design and examined cardiovascular or all-cause mortality in patients diagnosed with gout and prescribed allopurinol. Information on study characteristics, design, sample size, and mortality risk estimates were extracted. Article quality was assessed using the Newcastle-Ottawa Scale. Included articles were described in a narrative synthesis and, where possible, risk estimate data were pooled. Four articles reported a hazard ratio (HR) risk estimate for all-cause mortality in patients with gout using allopurinol, and 2 of these also reported cardiovascular mortality. Two articles found allopurinol to be protective in patients with gout, 1 found no statistically significant association, and 1 found no statistically significant effect of escalation of allopurinol dosage on all-cause or cardiovascular-related mortality. Data pooling was possible for all-cause mortality and found no association between allopurinol use in patients with gout and all-cause mortality compared to patients with gout not using allopurinol (adjusted HR 0.80 [95% confidence interval 0.60-1.05]). There was no significant association between all-cause mortality and allopurinol use in people with gout. However, the number of included studies was small, suggesting that further studies are needed.

Use of Allopurinol in Slowing the Progress of Chronic Kidney Disease Stage III and IV

Background: Hyperuricemia is associated with the event of hypertension and renal disease progression. The aim of the study was to evaluate the role of allopurinol in slowing the progression of chronic kidney disease (CKD) stage III and IV.&#x0D; Methods: This study was prospective interventional study was carried out in department of Nephrology, Sir Salimullah Medical College and Mitford Hospital, Dhaka, during the period of January 2014 to December 2014. On the basis of inclusion and exclusion criteria a total of 80CKD patients were enrolled in this study.80 patients were distributed in two groups. 40 patients were placed in treatment group and 40 patients were placed in control group. Purposive sampling method was followed.40 patients of treatment group were administered allopurinol 100 mg daily. Clinical, hematologic, and biochemical parameters were measured at baseline, at 4th month and 8th month of treatment.&#x0D; Results: No significant differences were seen between baseline SBP, DBP, Hb and HbA1c with 4th month and 8th follow up in both treatment group and control group. eGFR was significantly less declined at 4th months and 8thmonths in patient treated with allopurinol (treatment group). A negative Pearson’s correlation (r= -0.104; p=0.524) was found between uric acid with eGFR at 8th month in treatment group and significant positive Pearson’s correlation (r= 0.559 p=0.001) was found with CRP level. eGFR was significantly more declined at 4th months and 8th months in patient of control group. In control group a negative Pearson’s correlation (r= -0.126 p=0.437) was found between uric acid with eGFR at 8th month and positive Pearson’s correlation (r= 0.275 p=0193) was found with CRP level.&#x0D; Conclusions: Uric acid and CRP were significantly declined at 8th months in treatment group. Thus eGFR progression was significantly slow in treatment group at 4thmonths and 8th months from baseline due to positive effect of allopurinol by reducing inflammatory process that causes by high uric acid.&#x0D; Bangladesh J Medicine July 2021; 32(2) : 85-89

MO427SAFE USE OF ALLOPURINOL TO TREAT ACUTE URIC ACID NEPHROPATHY IN PREGNANCY: A CASE REPORT

Abstract Introduction Acute uric acid nephropathy (UAN) is characterized by acute kidney injury (AKI) due to uric acid crystal precipitation within the distal tubules and collecting ducts. We present a young woman, with a history of hyperuricaemia, who was treated with allopurinol for acute UAN during her first pregnancy. She also continued allopurinol treatment during her second pregnancy for prevention of further acute UAN. To the author’s knowledge, this is the first case report of biopsy-confirmed acute UAN during pregnancy. Case report A 20 year old woman, who was 13 weeks pregnant, was admitted with AKI. Past medical history included chronic kidney disease (CKD) and gout since the age of 17. She had an extensive family history of CKD and gout (without diagnosis, despite genetic testing). She had been on daily allopurinol 300mg, but this was stopped 8 weeks prior by her rheumatology team due to concerns about teratogenicity. At that time serum creatinine was at her baseline of 100 μmol/L (normal range 50-120 μmol/L) and serum uric acid had been 740 μmol/L (normal range 140-360 μmol/L). On admission, she felt well and was euvolemic. Serum creatinine was now 352 μmol/L and her serum uric acid level was 1720 μmol/L, with an elevated urine uric acid to creatinine ratio of 1.1. She underwent renal biopsy, which showed significant deposition of uric acid crystals in the renal tubules, confirming a diagnosis of acute UAN. She was given intravenous fluids. The uncertainties of allopurinol use in pregnancy were discussed with her, and she was restarted on allopurinol 200 mg daily. Over the next 3 weeks, serum uric acid decreased to 470 μmol/L and serum creatinine to 116 μmol/L. She was maintained on allopurinol during her pregnancy and delivered a healthy baby girl. She was advised against further pregnancies due to increased risk of maternal and fetal complications. However, three years later she presented at 15 weeks’ gestation. After a discussion regarding the potential teratogenic effects of allopurinol versus the risk of recurrent severe AKI due to acute UAN if it was again discontinued, she chose to continue allopurinol. The pregnancy proceeded without complication. Her daughters are now 8 and 5 years old. They do not have any congenital malformations, though both have mild to moderate learning difficulties. Discussion Allopurinol is approved for the treatment of hyperuricaemia outside of pregnancy, but given it interrupts purine synthesis there is a biologically plausible concern regarding teratogenicity. However, in our patient with long-standing hyperuricaemia it was the discontinuation of allopurinol that precipitated AKI due to the resultant crystal formation when serum uric acid reached very high levels. Biopsy confirmation of acute UAN was vital in this case, given the possibility of missing an alternative diagnosis and the risks of giving empirical allopurinol therapy. Once the diagnosis for her severe AKI was confirmed, it was clear our patient would benefit from uric acid lowering therapy. Our patient had two healthy girls despite using allopurinol from week 16 in her first pregnancy and throughout her second pregnancy. Unfortunately, both girls have mild to moderate learning needs, though it is unprovable whether allopurinol was causative as no study has followed up long term outcomes after foetal exposure during pregnancy.

Allopurinol for fibromyalgia pain in adults: A randomized controlled trial.

Allopurinol is a potent inhibitor of the enzyme xanthine oxidase used in the treatment of hyperuricemia and gout. Because it is well known that purines exert multiple affects on pain transmission, we hypothesized that the inhibition of xanthine oxidase by allopurinol could be a valid strategy to treat pain in humans. This study aimed to compare the analgesic efficacy of oral allopurinol versus placebo as an adjuvant therapy in patients displaying fibromyalgia. This randomized, double-blinded, placebo-controlled study included 60 women with the diagnosis of fibromyalgia. Patients were randomly assigned to receive either oral allopurinol 300mg (n=31) or placebo (n=29) twice daily during 30days. The patients were submitted to evaluation for pain sensitivity, anxiety, depression, and functional status before treatment, and 15 and 30days thereafter. Oral administration of allopurinol 300mg twice daily was ineffective in improving pain scores measured by several tools up to 30days of treatment (P>0.05). Additionally, no significant effects of allopurinol over anxiety, depressive symptoms, and functional status of fibromyalgia patients were observed in the present study. Although previous findings indicated that allopurinol could present intrinsic analgesic effects in both animals and humans, this study showed no benefit of the use of oral allopurinol as an adjuvant strategy during 30days in women displaying fibromyalgia. However, considering previous promising results, new prospective studies are still valid to further investigate allopurinol and more selective purine derivatives in the management of pain syndromes.