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Key Points 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

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.

In Australia, hospitalisations attributed to acute kidney injury are increasing at an average 6% per annum, and the vast majority of these cases are managed by critical care physicians instead of nephrologists. Prevalence of chronic kidney disease varies from 4.5% to 43.3% according to age and gender. As in other countries, most are unaware of their kidney disease. The number of people receiving maintenance dialysis has steadily increased in the last two decades with over 13,000 people on dialysis in 2017. The incidence of haemodialysis is approximately fivefold higher for Indigenous Australians compared to non-Indigenous Australians, and the magnitude of this difference has not changed in the last decade. Australia has the second highest prevalence of home haemodialysis and the fifth highest utilisation of peritoneal dialysis in the world. In recent years, average waiting time for a kidney transplant has shortened to 2.4 years for the most common blood group. Emerging paradigms in Australian nephrology include “green nephrology” and exploring different approaches to the burden of chronic kidney disease. Australia has a vibrant kidney research community, and the immediate future promises to be an incubator for nephrology clinicians who have ideas to test in our clinical spaces.

Background Renal biopsy is often required to obtain information for diagnosis, management and prognosis of kidney disease that can be broadly classified into acute kidney injury (AKI) and chronic kidney disease (CKD). The most common conditions identified on renal biopsy are glomerulonephritis and tubulo-interstitial disorders. There is a paucity of information on management strategies and therapeutic outcomes in AKI and CKD patients. A renal biopsy registry will provide information on biopsy-proven kidney disorders to improve disease understanding and tracking, healthcare planning, patient care and outcomes. Methods A registry of patients, that includes biopsy-proven kidney disease, was established through the collaboration of nephrologists from Queensland Hospital and Health Services and pathologists from Pathology Queensland services. The registry is in keeping with directions of the Advancing Kidney Care 2026 Collaborative, established in September 2018 as a Queensland Health initiative. Phase 1 of the registry entailed retrospective acquisition of data from all adult native kidney biopsies performed in Queensland, Australia, from 2002 to 2018. Data were also linked with the existing CKD.QLD patient registry. From 2019 onwards, phase 2 of the registry involves prospective collection of all incident consenting patients referred to Queensland public hospitals and having a renal biopsy. Annual reports on patient outcomes will be generated and disseminated. Discussion Establishment of the Queensland Renal Biopsy Registry (QRBR) aims to provide a profile of patients with biopsy-proven kidney disease that will lead to better understanding of clinico-pathological association and facilitate future research. It is expected to improve patient care and outcomes.

Background Kidney biopsy is the gold standard for diagnosing kidney disease but may result in bleeding, especially in uraemia. DDAVP (1-deamino-8-d-arginine vasopressin) may reduce uraemic bleeding but guidelines on its use are lacking. Aim To evaluate whether DDAVP reduced bleeding complications after percutaneous kidney biopsies. Methods We searched CENTRAL, PubMed, Embase, LILACS, WHO Trials Registry and ClinicalTrials.gov until May 2019 for randomised controlled trials (RCT), quasi-RCT and prospective cohort studies that compared DDAVP with placebo or no intervention, prior to native or allograft kidney biopsy. The primary outcome was post-biopsy bleeding. Secondary outcome was adverse events related to DDAVP. Results Abstracts of 270 identified papers were examined and 24 selected for evaluation. Two studies, one RCT and one prospective cohort that collectively evaluated 738 native kidney biopsies, met the inclusion criteria. One enrolled individuals with serum creatinine ≤1.5 mg/dL (132 μmol/L) and/or estimated glomerular filtration rate ≥60 mL/min/1.73 m2 while the other evaluated biopsies with serum creatinine >150 μmol/L. DDAVP was administered as a single subcutaneous dose of 0.3 μg/kg in both studies. Data were not pooled for meta-analysis due to clinical heterogeneity. GRADE quality of evidence from these two studies was low for DDAVP preventing any bleeding complication after native kidney biopsy. Low quality evidence suggested that adverse effects were not increased in DDAVP therapy. No prospective studies evaluated DDAVP in transplant kidney biopsies. Conclusion Currently available prospective data are insufficient to support the routine use of DDAVP prior to percutaneous kidney biopsies hence high quality trials are required.

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.

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., Author summary Amphotericin B (AmB) is the treatment of choice for systemic fungal infections. Despite its efficacy, clinical use of AmB has been associated with renal toxicity. In an attempt to improve the therapeutic effect and to reduce adverse reactions, lipid formulations of AmB were developed. Among these formulations, an in-house lipid emulsion preparation of AmB (AmB/LE) is a lower cost alternative with similar benefits. Furthermore, vitamin D is an essential nutrient for the regulation of several physiological activities. Hence, vitamin D deficiency or insufficiency can contribute to the progression of diseases and increase the risk of chronic illnesses as well. Nowadays, VDD is a health problem worldwide and its prevalence in general population is high, including the sunny and industrialized countries, where vitamin D supplementation has been successfully implemented. Thus, it is essential to monitor vitamin D levels in both patients treated with conventional or lipid formulations of AmB in order to ensure a better prognosis in the development of renal diseases.

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.

Vitamin D (VD) is a steroid hormone classically known for its key role in maintaining calcium homeostasis in the body. VD also has important immunomodulatory functions. This review explores evidence for a role of VD in attenuating the activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome. Dysregulated and inappropriate NLRP3 inflammasome activation occurs in a range of human diseases, including autoinflammatory disorders, metabolic disorders, and infections. VD appears to mediate its effects by binding of the VD receptor (VDR) to the sensor protein NLRP3, inhibiting deubiquitination and downstream inflammasome assembly. Some early clinical evidence suggests improved outcomes in inflammasome-mediated disorders when VD-deficient patients are treated with supplementation therapy.

Tenofovir (TFV) is a nucleotide analogue of adenosine monophosphate used as a first-line medication in the treatment of acquired immune deficiency syndrome and chronic hepatitis B infection. Mitochondrial toxicity seems to be the main factor involved in the TFV toxicity. TFV inhibits DNA polymerase γ, leading to decreased mitochondrial DNA and increased oxidative stress. This has been related to mitochondrial structural changes and depletion. The most predominant kidney manifestations of TFV exposure include elevation in serum creatinine and proximal tubular dysfunction. In animal studies, oxidative stress inhibition reversed TFV nephrotoxicity and might represent a new therapeutic approach. Vitamin D deficiency (VDD) is prevalent among HIV-infected individuals. Superimposed VDD and TFV use aggravates nephrotoxicity due to changes in the redox state and involvement of renin–angiotensin–aldosterone system. Thus, it is important to monitor vitamin D levels, as well as to treat VDD, in HIV-infected patients under TFV therapy.

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.

Background Ecstasy (Ec) use produces hyperthermia, excessive sweating, intense thirst, an inappropriate antidiuretic hormone secretion (SIADH) and a multisystemic toxicity due to oxidative stress (OS). Intense thirst induces high intake of pure water, which associated with SIADH, usually develops into acute hyponatremia (Hn). As Hn is induced rapidly, experiments to check if Ec acted directly on the Inner Medullary Collecting Ducts (IMCD) of rats were conducted. Rhabdomyolysis and OS were also studied because Ec is known to induce Reactive Oxygen Species (ROS) and tissue damage. To decrease OS, the antioxidant inhibitors N-acetylcysteine (NAC) and Allopurinol (Allo) were used. Methods Rats were maintained on a lithium (Li) diet to block the Vasopressin action before Ec innoculation. AQP2 (Aquaporin 2), ENaC (Epitheliun Sodium Channel) and NKCC2 (Sodium, Potassium, 2 Chloride) expression were determined by Western Blot in isolated IMCDs. The TBARS (thiobarbituric acid reactive substances) and GSH (reduced form of Glutathione) were determined in the Ec group (6 rats injected with Ec-10mg/kg), in Ec+NAC groups (NAC 100mg/Kg/bw i.p.) and in Allo+Ec groups (Allo 50mg/Kg/i.p.). Results Enhanced AQP2 expression revealed that Ec increased water transporter expression, decreased by Li diet, but the expression of the tubular transporters did not change. The Ec, Ec+NAC and Allo+Ec results showed that Ec increased TBARS and decreased GSH, showing evidence of ROS occurrence, which was protected by NAC and Allo. Rhabdomyolysis was only protected by Allo. Conclusion Results showed that Ec induced an increase in AQP2 expression, evidencing another mechanism that might contribute to cause rapid hyponatremia. In addition, they showed that NAC and Allo protected against OS, but only Allo decreased rhabdomyolysis and hyperthermia.

Background Acute kidney injury (AKI) is the most severe complication of rhabdomyolysis. Allopurinol (Allo), a xanthine oxidase inhibitor, has been in the spotlight in the last decade due to new therapeutic applications related to its potent antioxidant effect. The aim of this study was to evaluate the efficacy of Allo in the prevention and treatment of rhabdomyolysis-associated AKI. Methods Male Wistar rats were divided into five groups: saline control group; prophylactic Allo (300 mg/L of drinking water, 7 days); glycerol (50%, 5 ml/kg, IM); prophylactic Allo + glycerol; and therapeutic Allo (50 mg/Kg, IV, 30 min after glycerol injection) + glycerol. Results Glycerol-injected rats showed markedly reduced glomerular filtration rate associated with renal vasoconstriction, renal tubular damage, increased oxidative stress, apoptosis and inflammation. Allo ameliorated all these alterations. We found 8-isoprostane-PGF2a (F2-IsoP) as a main factor involved in the oxidative stress-mediated renal vasoconstriction following rhabdomyolysis. Allo reduced F2-IsoP renal expression and restored renal blood flow. Allo also reduced oxidative stress in the damaged muscle, attenuated muscle lesion/inflammation and accelerated muscular recovery. Moreover, we showed new insights into the pathogenesis of rhabdomyolysis-associated AKI, whereas Allo treatment reduced renal inflammation by decreasing renal tissue uric acid levels and consequently inhibiting the inflammasome cascade. Conclusions Allo treatment attenuates renal dysfunction in a model of rhabdomyolysis-associated AKI by reducing oxidative stress (systemic, renal and muscular), apoptosis and inflammation. This may represent a new therapeutic approach for rhabdomyolysis-associated AKI – a new use for an old and widely available medication.

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 no grupo TDF, em associação com um aumento da expressão renal do SRAA. Ratos do grupo TDF apresentaram menor excreção renal de sódio e maior expressão renal de transportadores de sódio. Conclusões: Esta é a primeira descrição, a partir de um modelo experimental, que a utilização do TDF durante a gestação resulta em hiperativação do SRAA, aumento da expressão dos transportadores renais de sódio e hipertensão arterial da prole 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 sodium transporters and hypertension of the offspring

Conversion to sirolimus (SRL)-based immunosuppression in renal transplant recipients is an alternative for chronic allograft dysfunction (CAD), cancer and viral infections. We sought to analyze the indications for and safety and efficacy of conversion to SRL among renal transplant patients.We examined a retrospective cohort, using medical records of renal transplant recipients18 years old who had their immunosuppressive regimen converted to a SRL-based treatment. Data analysis included the indication for conversion, time posttransplant, as well as urine protein and serum creatinine at conversion and 6 months thereafter. The end points included death, graft loss and/or discontinuation of SRL.We included 112 patients in this series who had indications for conversion: fungal, polyomavirus, or cytomegalovirus infection (n = 32), CAD (n = 30), cancer (n = 21), immunologic (n = 3), and other reasons (n = 26). Changes in immunosuppression were performed at 41 ± 57 months posttransplant or later in cancer patients. SRL was discontinued in 9 patients owing to adverse events such as edema, proteinuria, mucositis, or pneumonitis. Graft loss was observed in 19 patients, and death in 6. In 87 patients with functioning grafts, protein/creatinine ratios increased from 0.28 ± 0.03 (conversion) to 0.63 ± 0.09 (after 6 months; P.001). Serum creatinine decreased from 2.24 ± 0.13 (conversion) to 1.89 ± 0.75 mg/dL (after 6 months; P.001). Graft survival was 88% at 1 and 80% at 3 years after conversion.In, SRL was well tolerated; conversion to SRL improved graft function with a slight increase in proteinuria.

Vitamin D (VD) is a pro-hormone essential for life in higher animals. It is present in few types of foods and is produced endogenously in the skin by a photochemical reaction. The final step of VD activation occurs in the kidneys involving a second hydroxylation reaction to generate the biologically active metabolite 1,25(OH)2-VD. Extrarenal 1α-hydroxylation has also been described to have an important role in autocrine and paracrine signaling. Vitamin D deficiency (VDD) has been in the spotlight as a major public health-care issue with an estimated prevalence of more than a billion people worldwide. Among individuals with chronic kidney disease (CKD), VDD prevalence has been reported to be as high as 80%. Classically VD plays a pivotal role in calcium and phosphorus homeostasis. Nevertheless, there is a growing body of evidence supporting the importance of VD in many vital nonskeletal biological processes such as endothelial function, renin-angiotensin-aldosterone system modulation, redox balance and innate and adaptive immunity. In individuals with CKD, VDD has been associated with albuminuria, faster progression of kidney disease and increased all-cause mortality. Recent guidelines support VD supplementation in CKD based on extrapolation from cohorts conducted in the general population. In this review, we discuss new insights on the multifactorial pathophysiology of VDD in CKD as well as how it may negatively modulate different organs and systems. We also critically review the latest evidence and controversies of VD monitoring and supplementation in CKD patients.

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., Author summary Snakebites have been recognized as a neglected public health problem in several tropical and subtropical countries. Snakes from the genus Bothrops are the most common snakes found in Latin America. Bothrops snakebites frequently complicate with kidney impairment with increased risk of death. The only treatment currently available for Bothrops envenomation is the infusion of antivenom. Therefore, the study of novel therapies to prevent kidney failure caused by snakebites is compelling. Allopurinol is a drug commonly used to treat gout which also presents beneficial antioxidant properties. The aim of this study was to evaluate the protective effect of Allopurinol in a rat experimental model of Bothrops envenomation. In our study, rats that received the infusion of the snake venom presented with reduced kidney function which was improved by Allopurinol. Overall, Allopurinol might represent a novel approach to prevent kidney failure in victims of Bothrops snakebites. This could be a new use for an old and widely available drug.

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.

To the Editor: In the review “Effect of Allopurinol on Blood Pressure: A Systematic Review and Meta-Analysis,” the authors conclude that allopurinol and other xanthine oxidase inhibitors may be used as adjunctive antihypertensive agent. This meta-analysis was performed that included heterogeneous studies as well as trials with poor methodological quality, eg, Siu and colleagues (2006) (an open, nonplacebo-controlled trial including individuals with and without hypertension in which allopurinol decreased only systolic blood BP); Kanbay and colleagues (2007) (open, nonrandomized, nonplacebo-controlled study enrolling normotensive and hypertensive individuals); and Kanbay and colleagues (2011) (an open, nonplacebo-controlled trial including adults with normal blood pressure. Positive results of allopurinol were seen in decreasing systolic but not diastolic BP). Inclusion of these studies may have strengthened the BP-lowering effect of allopurinol. Furthermore, one can reasonably assume that several studies enrolling normotensive individuals are inadequate to support the conclusion that allopurinol may be used to treat hypertension. In the systematic review “Pharmacotherapy for Hyperuricemia in Hypertensive Patients” (Cochrane Database of Systematic Reviews), which has more rigorous entry criteria, the authors found that, to date, there is only one study designed to answer whether allopurinol treatment has a positive effect in reducing BP in hypertensive individuals. Feig and colleagues conducted a double-blind, placebo-controlled, crossover trial that randomized 30 adolescents (11–17 years), newly diagnosed with stage I primary hypertension and with serum uric acid >6 mg/dL, to receive allopurinol 200 mg twice daily for 4 weeks and placebo for 4 weeks with a 2-week washout period between treatments. Although it was a well-conducted study, it had a few limitations, as follows: small sample size; exclusion of more severe hypertensive individuals; short duration of treatment, not sufficient to detect adverse events associated with allopurinol or to evaluate whether the effect on BP is sustained after long-term therapy; and the reserved external validity, extending only to adolescents with mild new diagnosis of hypertension. Another concern is how clinicians might interpret the conclusion of this review. Treatment with allopurinol is not free of risks and interactions. Although rare, serious side effects can be associated with allopurinol therapy, such as fatal Stevens-Johnson syndrome and chronic interstitial nephritis. Therefore, increased incidence of side effects can be observed with the increased prescription of allopurinol. Thus, in light of current evidence, recommendation (or encouraging use) of allopurinol or other hypouricemic agent as initial or adjuvant treatment of hypertension is premature and more “RCTs” are needed.