Treatment persistence to tolvaptan in patients with autosomal dominant polycystic kidney disease: a secondary use of data analysis of patients in the IMADJIN® dataset.

BACKGROUND: Tolvaptan is the only available disease-modifying treatment for autosomal dominant polycystic kidney disease (ADPKD). Prior to October 2020 access to tolvaptan in Australia was restricted by a controlled monitoring and distribution program called IMADJIN®. Focusing on hepatic safety, the IMADJIN® program collected real-world data on patients with ADPKD. A retrospective, secondary data analysis of the IMADJIN® dataset was undertaken to determine the time to all-cause discontinuation of tolvaptan in Australia. METHODS: Demographic and treatment data from 17 September 2018 to 30 September 2020 were extracted from the IMADJIN® dataset. Treatment persistence was analyzed using Kaplan-Meier methods, and Cox's proportional hazard models were used to analyze differences in treatment persistence by age, sex and location. RESULTS: Four hundred seventy-nine patients with ADPKD were included in the analysis. After a median follow-up of 12.0 months (95% confidence interval [CI] 2.6, 23.4), the Kaplan-Meier estimation of 12-month persistence was 76.7% (95% CI 72.2, 80.5%). 114 (23.8%) patients discontinued treatment; sex, state, and remoteness did not significantly affect treatment persistence. Patients in the youngest tertile were more likely to discontinue compared to older ages (p = 0.049). Reasons for discontinuation included: aquaretic tolerability (4.2%), hepatic adverse events (abnormal liver function tests) (2.1%), disease progression (1.5%), and acute kidney injury (0.2%). Patients with a lack of aquaretic tolerance had shorter time to discontinuation. Hepatic toxicity events were initially observed 3 months after tolvaptan initiation and were less prevalent over time. CONCLUSIONS: Persistence to tolvaptan in the real-world IMADJIN® dataset was 76%. Discontinuation due to hepatic events was low. Prescribers should take extra care when initiating treatment in younger patients as they are more likely to discontinue tolvaptan compared to older individuals. Nevertheless, the precise reason for this observation remains to be elucidated.

Bleeding Complications of Percutaneous Kidney Biopsy: Does Gender Matter?

The incidence of bleeding complications after percutaneous kidney biopsies is low.Female sex may be associated with a greater risk for bleeding complications after percutaneous kidney biopsies.This association and the plausible mechanisms require further evaluation in prospective study.

Pharmacotherapy for hyperuricaemia in hypertensive patients.

BACKGROUND: This is the second update of this systematic review. High blood pressure represents a major public health problem. Worldwide, approximately one-fourth of the adult population has hypertension. Epidemiological and experimental studies suggest a link between hyperuricaemia and hypertension. Hyperuricaemia affects 25% to 40% of those with untreated hypertension; a much lower prevalence has been reported in those with normotension or in the general population. However, whether lowering serum uric acid (UA) might lower blood pressure (BP), is an unanswered question. OBJECTIVES: To determine whether UA-lowering agents reduce BP in people with primary hypertension or prehypertension, compared with placebo. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to May 2020: the Cochrane Hypertension Specialised Register, CENTRAL 2018, Issue 12, MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched LILACS (1982 to May 2020), and contacted authors of relevant papers regarding further published and unpublished work. The searches had no language or date restrictions. SELECTION CRITERIA: To be included in this updated review, the studies had to meet the following criteria: 1) randomised or quasi-randomised, with a group assigned to receive a UA-lowering agent and another group assigned to receive placebo; 2) double-blind, single-blind, or open-label; 3) parallel or cross-over trial design; 4) cross-over trials had to have a washout period of at least two weeks; 5) minimum treatment duration of four weeks; 6) participants had to have a diagnosis of essential hypertension or prehypertension plus hyperuricaemia (serum UA greater than 6 mg/dL in women, 7 mg/dL in men, and 5.5 mg/dL in children or adolescents); 7) outcome measures included change in 24-hour ambulatory systolic or diastolic BP, or both; or clinic-measured systolic or diastolic BP, or both. DATA COLLECTION AND ANALYSIS: The two review authors independently collected the data using a data extraction form, and resolved any disagreements via discussion. We assessed risk of bias using the Cochrane 'Risk of bias' tool. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: In this review update, we screened 722 records, selected 26 full-text reports for evaluation. We identified no ongoing studies and did not add any new studies. We included three randomised controlled trials (RCTs), enrolling 211 people with hypertension or prehypertension, plus hyperuricaemia. Low-certainty evidence from three RCTs found inconclusive results between those who received UA-lowering drugs and placebo, in 24-hour ambulatory systolic (MD -6.2 mmHg, 95% CI -12.8 to 0.5) or diastolic BP (-3.9 mmHg, 95% CI -9.2 to 1.4). Low-certainty evidence from two RCTs found that UA-lowering drugs reduced clinic-measured systolic BP (-8.43 mmHg, 95% CI -15.24 to -1.62) but results for clinic-measured diastolic BP were inconclusive (-6.45 mmHg, 95% CI -13.60 to 0.70). High-certainty evidence from three RCTs found that serum UA levels were reduced by 3.1 mg/dL (95% CI 2.4 to 3.8) in the participants that received UA-lowering drugs. Low-certainty evidence from three RCTs found inconclusive results regarding the occurrence of adverse events between those who received UA-lowering drugs and placebo (RR 1.86, 95% CI 0.43 to 8.10). AUTHORS' CONCLUSIONS: In this updated Cochrane Review, the current RCT data are insufficient to know whether UA-lowering therapy lowers BP. More studies are needed.

Vitamin D deficiency is a potential risk factor for lipid Amphotericin B nephrotoxicity.

Invasive fungal infections (IFI) is a worldwide serious health problem and Amphotericin B (AmB) has been considered the drug of choice for IFI treatment. Despite its efficacy, clinical use of AmB has been associated with renal toxicity. Some lines of evidence have shown that an extemporaneous lipid emulsion preparation of AmB (AmB/LE) was able to attenuate nephrotoxicity, presenting similar benefits at a lower cost. Studies have been demonstrating that hypovitaminosis D may hasten the progression of kidney disease and reflect on a worse prognosis in cases of drug-induced nephrotoxicity. In view of the high worldwide incidence of hypovitaminosis D, the aim of this study was to investigate whether vitamin D deficiency may induce AmB/LE-related nephrotoxicity. Wistar rats were divided into four groups: control, received a standard diet for 34 days; AmB/LE, received a standard diet for 34 days and AmB/LE (5 mg/kg/day) intraperitoneally in the last 4 days; VDD, received a vitamin D-free diet for 34 days; and VDD+AmB/LE, received a vitamin D-free diet for 34 days and AmB/LE as described. At the end of the protocol, animals were euthanized and blood, urine and renal tissue samples were collected in order to evaluate AmB/LE effects on renal function and morphology. Association of AmB/LE and vitamin D deficiency led to diminished glomerular filtration rate and increased tubular injury, evidenced by reduced renal protein expression of NaPi-IIa and TRPM6 leading to hyperphosphaturia / hypermagnesuria. VDD+AmB/LE rats also presented alterations in the PTH-Klotho-FGF-23 signaling axis, urinary concentrating defect and hypertension, probably due to an inappropriate activation of the renin-angiotensin-aldosterone system. Hence, it is important to monitor vitamin D levels in AmB/LE treated patients, since vitamin D deficiency induces AmB/LE nephrotoxicity.

Radiological Tenckhoff catheter insertion for peritoneal dialysis: A cost-effective approach.

INTRODUCTION: Radiological insertion of Tenckhoff catheters can be an alternative option for peritoneal dialysis access creation, as compared to surgical catheter insertion. This study will review the outcomes and complications of radiological Tenckhoff catheter insertion in a metropolitan renal service and compare costs between surgical and radiological insertion. METHODS: Data were collected prospectively for all patients who had a Tenckhoff catheter insertion for peritoneal dialysis (PD) under radiological guidance at our hospital from May 2014 to November 2016. The type of catheter used and complications, including peri-catheter leak, exit site infection and peritonitis were reviewed. Follow-up data were also collected at points 3, 6 and 12 months from catheter insertion. Costing data were obtained from Queensland Health Electronic Reporting System (QHERS) data, average staff salaries and consumable contract price lists. RESULTS: In the 30-month evaluation period, 70 catheters were inserted. Two patients had an unsuccessful procedure due to the presence of abdominal adhesions. Seven patients had an episode of peri-catheter leak, and four patients had an exit site infection following catheter insertion. Peritonitis was observed in nine patients during the study period. The majority of patients (90%) remained on peritoneal dialysis at 3-month follow-up. The average costs of surgical and radiological insertion were noted to be AUD$7788.34 and AUD$1597.35, respectively. CONCLUSION: Radiological Tenckhoff catheter insertion for peritoneal dialysis appears to be an attractive and cost-effective option given less waiting periods for the procedure, the relatively low cost of insertion and comparable rates of complications.

Allopurinol attenuates acute kidney injury following Bothrops jararaca envenomation.

Snakebites have been recognized as a neglected public health problem in several tropical and subtropical countries. Bothrops snakebites frequently complicate with acute kidney injury (AKI) with relevant morbidity and mortality. To date, the only treatment available for Bothrops envenomation is the intravenous administration of antivenom despite its several limitations. Therefore, the study of novel therapies in Bothrops envenomation is compelling. The aim of this study was to evaluate the protective effect of Allopurinol (Allo) in an experimental model of Bothrops jararaca venom (BJ)-associated AKI. Five groups of Wistar rats were studied: Sham, Allo, BJ, BJ+Allo, BJ+ipAllo. BJ (0.25 mg/kg) was intravenously injected during 40'. Saline at same dose and infusion rate was administered to Sham and Allo groups. Allo and BJ+Allo groups received Allo (300 mg/L) in the drinking water 7 days prior to Saline or BJ infusion respectively. BJ+ipAllo rats received intraperitoneal Allo (25 mg/Kg) 40' after BJ infusion. BJ rats showed markedly reduced glomerular filtration rate (GFR, inulin clearance) associated with intense renal vasoconstriction, hemolysis, hemoglobinuria, reduced glutathione and increased systemic and renal markers of nitro-oxidative stress (Nitrotyrosine). Allo ameliorated GFR, renal blood flow (RBF), renal vascular resistance and arterial lactate levels. In addition, Allo was associated with increased serum glutathione as well as reduced levels of plasma and renal Nitrotyrosine. Our data show that Allo attenuated BJ-associated AKI, reduced oxidative stress, improved renal hemodynamics and organ perfusion. It might represent a novel adjuvant approach for Bothrops envenomation, a new use for an old and widely available drug.

Vitamin D and Infectious Diseases: Simple Bystander or Contributing Factor?

Vitamin D (VD) is a fat-soluble steroid essential for life in higher animals. It is technically a pro-hormone present in few food types and produced endogenously in the skin by a photochemical reaction. In recent decades, several studies have suggested that VD contributes to diverse processes extending far beyond mineral homeostasis. The machinery for VD production and its receptor have been reported in multiple tissues, where they have a pivotal role in modulating the immune system. Similarly, vitamin D deficiency (VDD) has been in the spotlight as a major global public healthcare burden. VDD is highly prevalent throughout different regions of the world, including tropical and subtropical countries. Moreover, VDD may affect host immunity leading to an increased incidence and severity of several infectious diseases. In this review, we discuss new insights on VD physiology as well as the relationship between VD status and various infectious diseases such as tuberculosis, respiratory tract infections, human immunodeficiency virus, fungal infections and sepsis. Finally, we critically review the latest evidence on VD monitoring and supplementation in the setting of infectious diseases.

Pharmacotherapy for hyperuricemia in hypertensive patients.

BACKGROUND: High blood pressure represents a major public health problem. Worldwide, approximately one-fourth of the adult population has hypertension. Epidemiological and experimental studies suggest a link between hyperuricemia and hypertension. Hyperuricemia affects 25% to 40 % of individuals with untreated hypertension; a much lower prevalence has been reported in normotensives or in the general population. However, whether lowering serum uric acid (UA) might lower blood pressure (BP) is an unanswered question. OBJECTIVES: To determine whether UA-lowering agents reduce BP in patients with primary hypertension or prehypertension compared with placebo. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to February 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 2), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched LILACS up to March 2016 and contacted authors of relevant papers regarding further published and unpublished work. SELECTION CRITERIA: To be included in this review, the studies had to meet the following criteria: 1) randomized or quasi-randomized, with a group assigned to receive a UA-lowering agent and another group assigned to receive placebo; 2) double-blind, single-blind or open-label; 3) parallel or cross-over trial; 4) cross-over trials had to have a washout period of at least two weeks; 5) minimum treatment duration of four weeks; 6) participants had to have a diagnosis of essential hypertension or prehypertension, and hyperuricemia (serum UA greater than 6 mg/dL in women, 7 mg/dL in men and 5.5 mg/dL in children/adolescents); 7) outcome measures assessed included change in clinic systolic, diastolic or 24-hour ambulatory BP. DATA COLLECTION AND ANALYSIS: The two review authors independently collected the data using a data extraction form, and resolved any disagreements via discussion. We assessed risk of bias using the Cochrane Collaboration' Risk of bias' tool. MAIN RESULTS: In this review update, we examined the abstracts of 349 identified papers and selected 21 for evaluation. We also identified three ongoing studies, the results of which are not yet available. Three other randomized controlled trials (RCTs) (two new), enrolling individuals with hypertension or prehypertension, and hyperuricemia, met the inclusion criteria for the review and were included in the meta-analysis. Low quality of evidence from three RCTs indicate no reduction in systolic (MD -6.2 mmHg, 95% CI -12.8 to 0.5) or diastolic (-3.9 mmHg, 95% CI -9.2 to 1.4) 24-hour ambulatory BP with UA-lowering drugs compared with placebo. Low quality of evidence from two RCTs reveal a reduction of systolic clinic BP (-8.43 mmHg, 95% CI -15.24 to -1.62) but not diastolic clinic BP (-6.45 mmHg, 95% CI -13.60 to 0.70). High quality of evidence from three RCTs indicates that serum UA levels were reduced by 3.1 mg/dL (95% CI 2.4 to 3.8) in the participants that received UA-lowering drugs. Very low quality of evidence from three RCTs suggests that withdrawals due to adverse effects were not increased with UA-lowering therapy (RR 1.86, 95% CI 0.43 to 8.10). AUTHORS' CONCLUSIONS: In this updated systematic review, the RCT data available at present are insufficient to know whether UA-lowering therapy also lowers BP. More studies are needed.

N-acetylcysteine protects against star fruit-induced acute kidney injury.

BACKGROUND: Star fruit (SF) is a popular fruit, commonly cultivated in many tropical countries, that contains large amount of oxalate. Acute oxalate nephropathy and direct renal tubular damage through release of free radicals are the main mechanisms involved in SF-induced acute kidney injury (AKI). The aim of this study was to evaluate the protective effect of N-acetylcysteine (NAC) on SF-induced nephrotoxicity due to its potent antioxidant effect. MATERIALS AND METHODS: Male Wistar rats received SF juice (4 mL/100 g body weight) by gavage after a 12 h fasting and water deprivation. Fasting and water deprivation continued for 6 h thereafter to warrant juice absorption. Thereafter, animals were allocated to three experimental groups: SF (n = 6): received tap water; SF + NAC (n = 6): received NAC (4.8 g/L) in drinking water for 48 h after gavage; and Sham (n = 6): no interventions. After 48 h, inulin clearance studies were performed to determine glomerular filtration rate. In a second series of experiment, rats were housed in metabolic cages for additional assessments. RESULTS: SF rats showed markedly reduced inulin clearance associated with hyperoxaluria, renal tubular damage, increased oxidative stress and inflammation. NAC treatment ameliorated all these alterations. Under polarized light microscopy, SF rats exhibited intense calcium oxalate birefringence crystals deposition, dilation of renal tubules and tubular epithelial degeneration, which were attenuate by NAC therapy. CONCLUSIONS: Our data show that therapeutic NAC attenuates renal dysfunction in a model of acute oxalate nephropathy following SF ingestion by reducing oxidative stress, oxaluria, and inflammation. This might represent a novel indication of NAC for the treatment of SF-induced AKI.

Allopurinol attenuates acute kidney injury following Bothrops jararaca envenomation

Snakebites have been recognized as a neglected public health problem in several tropical and subtropical countries. Bothrops snakebites frequently complicate with acute kidney injury (AKI) with relevant morbidity and mortality. To date, the only treatment available for Bothrops envenomation is the intravenous administration of antivenom despite its several limitations. Therefore, the study of novel therapies in Bothrops envenomation is compelling. The aim of this study was to evaluate the protective effect of Allopurinol (Allo) in an experimental model of Bothrops jararaca venom (BJ)-associated AKI. Five groups of Wistar rats were studied: Sham, Allo, BJ, BJ+Allo, BJ+ipAllo. BJ (0.25 mg/kg) was intravenously injected during 40'. Saline at same dose and infusion rate was administered to Sham and Allo groups. Allo and BJ+Allo groups received Allo (300 mg/L) in the drinking water 7 days prior to Saline or BJ infusion respectively. BJ+ipAllo rats received intraperitoneal Allo (25 mg/Kg) 40' after BJ infusion. BJ rats showed markedly reduced glomerular filtration rate (GFR, inulin clearance) associated with intense renal vasoconstriction, hemolysis, hemoglobinuria, reduced glutathione and increased systemic and renal markers of nitro-oxidative stress (Nitrotyrosine). Allo ameliorated GFR, renal blood flow (RBF), renal vascular resistance and arterial lactate levels. In addition, Allo was associated with increased serum glutathione as well as reduced levels of plasma and renal Nitrotyrosine. Our data show that Allo attenuated BJ-associated AKI, reduced oxidative stress, improved renal hemodynamics and organ perfusion. It might represent a novel adjuvant approach for Bothrops envenomation, a new use for an old and widely available drug.

Tenofovir during pregnancy in rats: a novel pathway for programmed hypertension in the offspring.

OBJECTIVES: To evaluate the occurrence of systemic and renal abnormalities in the offspring of Wistar rats exposed to tenofovir disoproxil fumarate (DF) during pregnancy. METHODS: Female Wistar rats received a standard diet, with or without addition of tenofovir DF (100 mg/kg diet), 1 week before mating and during pregnancy. Offspring from the tenofovir DF group were placed with an untreated foster mother during breastfeeding and compared with offspring from rats maintained on a standard diet during mating and pregnancy (control). Control and tenofovir DF were followed up at 3 and 6 months of age. Monthly body weight and systolic blood pressure (SBP), glomerular counts, renal function, biochemical parameters, angiotensin II, renal renin angiotensin aldosterone system (RAAS) and renal sodium transporters were analysed. RESULTS: Tenofovir DF offspring showed lower birth weight compared with the control group. After the third month, growth among the tenofovir DF group experienced a rapid catch-up. SBP increased progressively after the second month of age in the tenofovir DF group. Nephron number did not differ between the groups; however, the tenofovir DF group showed glomerular structural changes. Plasma aldosterone was higher in the tenofovir DF group, associated with a significant increase in renal expression of RAAS. The tenofovir DF rats showed up-regulation of renal sodium transporters and consequently lower urinary sodium excretion. CONCLUSIONS: This is the first demonstration using an experimental model that maternal exposure to tenofovir DF during gestation results in overactivation of RAAS, up-regulation of renal sodium transporters and hypertension in the offspring.

Administração de tenofovir em ratas Wistar durante a gestação: efeitos na prole / Administration of tenofovir during pregnancy in Wistar rats: effects on the offspring

Introdução: Tenofovir disoproxil fumarate (TDF) é um inibidor da transcriptase reversa análogo nucleotídeo que tem sido usado por gestantes para o tratamento da infecção pelo vírus da imunodeficiência humana (HIV), bem como para a prevenção da transmissão vertical do vírus. Até o momento, não há estudos experimentais ou em humanos sobre a incidência de alterações renais nos fetos expostos a esquemas contendo TDF. Objetivo: Verificar a ocorrência de alterações renais e sistêmicas fetais causadas pelo uso do TDF durante a gestação. Metodologia: Ratos Wistar fêmeas receberam dieta padrão com ou sem adição de TDF (100mg/Kg de dieta) desde uma semana antes do cruzamento até o parto. A prole proveniente do grupo TDF foi colocada com uma mãe adotiva não tratada durante o período de amamentação e foi comparada com a prole de ratas que receberam dieta padrão durante a gestação (grupo controle). Controle e TDF foram acompanhados até três (n=9 para cada grupo) e seis (n=12 e n=10, respectivamente) meses de idade. Foram avaliados: peso corporal (PC) e pressão arterial sistólica (PAS) mensais, contagem de glomérulos, função renal (através do clearance de inulina), parâmetros bioquímicos (proteinúria, colesterol total, sódio e potássio séricos e urinários), e expressão proteica do tecido renal para componentes do sistema renina angiotensina aldosterona (SRAA) e para transportadores de sódio. Resultados: A prole TDF apresentou menor PC ao nascimento em comparação com o controle. Após o 3º mês, o grupo TDF demonstrou um crescimento compensatório, atingindo o sexto mês com maior PC. O peso renal foi menor no grupo TDF, porém, não houve diferença do número de néfrons entre os grupos. O grupo TDF apresentou alterações estruturais glomerulares. Observou-se também um aumento progressivo da PAS após o segundo mês de idade no grupo TDF. Não houve diferença estatística na função renal entre os grupos. Os níveis plasmáticos de aldosterona foram mais elevados...

Introduction: Tenofovir disoproxil fumarato (TDF) is a nucleotide reverse transcriptase inhibitor that has been used in pregnants for treatment of maternal HIV infection and for prevention of vertical transmission. Currently, there are no published studies providing data regarding the occurrence of renal abnormalities in fetuses exposed to TDF-containing regimens. Objective: To evaluate the occurrence of systemic and renal abnormalities in offspring of Wistar rats exposed to TDF during pregnancy. Methods: Female Wistar rats received a standard diet, with or without addition of TDF (100 mg/Kg diet), one week before mating and during pregnancy. Offspring from the TDF group were placed with an untreated foster mother during breastfeeding and compared with offspring from rats maintained on a standard diet during mating and pregnancy (control). Control and TDF were followed up at three and six months of age. Analyzed data: monthly body weight and systolic blood pressure (SBP), glomerular counting, renal function, biochemical parameters, and renal tissue immunoblotting for renin angiotensin aldosterone system (RAAS) and renal sodium transporters. Results: TDF offspring showed lower birth weight compared with the control group. After the third month, growth among the TDF group experienced a rapid catch-up. SBP increased progressively after the second month of age in the TDF group. The nephron number did not differ between groups. The TDF group showed glomerular structural changes. There was no significant difference in renal function between the groups studied. Plasma aldosterone was higher in the TDF group, associated with a significant increase in renal expression of RAAS. The TDF rats showed upregulation of renal sodium transporters and consequently lower urinary sodium excretion. Conclusions: This is the first demonstration using an experimental model that maternal exposure to TDF during gestation results in over activation of RAAS, upregulation of renal...

Pharmacotherapy for hyperuricemia in hypertensive patients.

BACKGROUND: High blood pressure represents a major public health problem. Worldwide, approximately one fourth of the adult population has hypertension. Epidemiological and experimental studies suggest a linkage between hyperuricemia and hypertension. Hyperuricemia affects 25-40 % of patients with untreated hypertension. A much lower prevalence has been reported in normotensives or in the general population. However, whether lowering serum uric acid (SUA) might lower blood pressure (BP) is an unanswered question. OBJECTIVES: To determine whether uric acid lowering agents reduce BP in patients with primary hypertension. SEARCH METHODS: Electronic searches of the following sources were performed without language restriction: Cochrane Hypertension Group Specialised Register (1946 to May 2012), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2012 Issue 4), MEDLINE (1946 to May 2012), EMBASE (1974 to May 2012), LILACS (1982 to July 2012), Scirus and ClinicalTrials.gov. Authors of relevant papers were also contacted regarding further published and unpublished work. SELECTION CRITERIA: To be included in this review, the studies had to meet the following criteria: 1) Randomised or quasi-randomised with a group assigned to receive a uric acid lowering agent and another group assigned to receive placebo; 2) Double-blind, single-blind or open label; 3) Parallel or crossover trial; 4) For crossover trial, a washout period of at least two weeks; 5) Minimum treatment duration of four weeks; 6) Participants with diagnosis of essential hypertension and hyperuricemia, serum uric acid greater than 6 in women, 7 in men and 5.5 in children/adolescents; 7) Outcome measures includes change in casual or ambulatory, systolic or diastolic blood pressure. DATA COLLECTION AND ANALYSIS: Two independent reviewers collected the data using a data extraction form. Disagreements were resolved by discussion. Risk of bias was accessed by the Cochrane Collaboration Risk of Bias Tool. MAIN RESULTS: Three hundred and thirty-six abstracts were examined. One study (enrolling hypertensive and hyperuricemic patients) met the inclusion criteria for the review and was independently rated by both authors. No other studies were identified by the supplementary searches. The study identified as eligible for this review was a randomised controlled trial conducted in the USA (FEIG 2008 ) . This well designed double-blind, placebo-controlled, crossover trial randomised 30 adolescents (11-17 years), newly diagnosed stage 1 primary hypertension and with SUA ≥ 6mg/dl, to receive allopurinol 200 mg twice daily for 4 weeks, and placebo for 4 weeks, with a 2 week washout period between treatments. Casual BP during the allopurinol phase decreased - 6.9 mmHg (95 % CI, - 4.5 to - 9.3), systolic, and - 5.1 mmHg (95 % CI, - 2.5 to - 7.8), diastolic, versus during the placebo phase, - 2.0 mmHg (95 % CI, 0.3 to - 4.3) systolic and - 2.4 mmHg (95 % CI, 0.2 to - 4.1) diastolic. For the secondary outcome (change in 24 ambulatory BP), change in systolic BP with allopurinol was - 6.3 mmHg (95 % CI, - 3.8 to - 8.9), systolic, and - 4.6 mmHg (95% CI, - 2.4 to - 6.8), diastolic, and with placebo, 0.8 mmHg (95 % CI, 3.4 to - 2.9) systolic and - 0.3 mmHg (95 % CI, 2.3 to - 2.1) diastolic. P-value results ranged from 0.004 to 0.05. No participant dropout occurred and no adverse effects were seen in patients treated with allopurinol. AUTHORS' CONCLUSIONS: Meta-analysis was not possible in this systematic review. In the one study that matched the inclusion criteria allopurinol decreased "in office" and ambulatory systolic and diastolic BP. Because there was only one included RCT, the number of patients providing data on pharmacotherapy for hyperuricemia in hypertension is small and restricted to adolescents with recently diagnosed mild essential hypertension. Hence, there is insufficient evidence to recommend the use of allopurinol or other hypouricemic drugs as an initial or adjuvant treatment of hypertension and more RCTs are needed.