Controversies and practical management of patients with gout and chronic kidney disease.

Uric acid is a toxin retained with advancing kidney disease. Clinical manifestations of hyperuricemia include gout and systemic inflammation that are associated with increased risk of cardiovascular mortality. As many as one-third of all patients with chronic kidney disease have a history of gout, yet <25% of these patients are effectively treated to target serum urate levels of ≤6 mg/dl. A major reason for ineffective management of gout and hyperuricemia is the complexity in managing these patients, with some medications contraindicated and others requiring special dosing, potential drug interactions, and other factors. Consequently, many nephrologists do not primarily manage gout despite it being a common complication of chronic kidney disease, leaving management to the primary physician or rheumatologist. We believe that kidney specialists should consider gout as a major complication of chronic kidney disease and actively manage it in their patients. Here, we present insights from nephrologists and rheumatologists for a team approach to gout management that includes the nephrologist.

Caffeine Inhibits Both Basal and Insulin-Activated Urate Transport.

OBJECTIVE: Caffeine, an adenosine receptor antagonist, is a potent central nervous system stimulant that also impairs insulin signaling. Recent studies have suggested that coffee consumption lowers serum urate (SU) and protects against gout by unknown mechanisms. We hypothesized that caffeine lowers SU by affecting activity of urate transporters. METHODS: We examined the effect of caffeine and adenosine on basal and insulin stimulation of net 14C-urate uptake in the human renal proximal tubule cell line PTC-05 and on individual urate transporters expressed in Xenopus laevis oocytes. RESULTS: We found that caffeine and adenosine efficiently inhibited both basal and insulin stimulation of net 14C-urate uptake mediated by endogenous urate transporters in PTC-05 cells. In oocytes expressing individual urate transporters, caffeine (>0.2 mM) more efficiently inhibited the basal urate transport activity of GLUT9 isoforms, OAT4, OAT1, OAT3, NPT1, ABCG2, and ABCC4 than did adenosine without significantly affecting URAT1 and OAT10. However, unlike adenosine, caffeine at lower concentrations (<0.2 mM) very effectively inhibited insulin activation of urate transport activity of GLUT9, OAT10, OAT1, OAT3, NPT1, ABCG2, and ABCC4 by blocking activation of Akt and extracellular signal-regulated kinase. CONCLUSION: We postulate that inhibition of urate transport activity of the re-absorptive transporters GLUT9, OAT10, and OAT4 by caffeine is a key mechanism in its urate-lowering effects. Additionally, the ability of caffeine to block insulin-activated urate transport by GLUT9a and OAT10 suggests greater relative inhibition of these transporters in hyperinsulinemia.

Sublethal Toxicity of 17 Per- and Polyfluoroalkyl Substances with Diverse Structures to Ceriodaphnia dubia, Hyalella azteca, and Chironomus dilutus.

Seven-day sublethal toxicity tests were performed with the freshwater invertebrates Ceriodaphnia dubia, Hyalella azteca, and Chironomus dilutus to determine the effects of per- or polyfluorinated alkyl substances (PFAS) of varying chain length within four classes: perfluoroalkyl carboxylic acids (PFCAs), perfluoroalkyl sulfonic acids (PFSAs), perfluoroalkane sulfonamides, and fluorotelomer sulfonic acids. In general, toxicity increased with increasing chain length, but the slopes of these relationships varied markedly by species and chemical class. The toxicity of individual PFCAs was similar among species. The toxicity of PFSAs was similar to PFCAs for C. dubia and H. azteca, whereas PFSAs were much more toxic to C. dilutus, with median effect concentrations (EC50s) as low as 0.022 mg perfluorooctane sulfonate (PFOS)/L and 0.012 mg perfluorononane sulfonate (PFNS)/L. Despite the high sensitivity to PFOS and PFNS, C. dilutus was not very sensitive to structurally similar fluorotelomer sulfonates (6:2 and 8:2). Perfluoroalkane sulfonamides were the most toxic class tested among all species (e.g., EC50s of 0.011 and 0.017 mg perfluorooctane sulfonamide/L for C. dilutus and H. azteca, respectively). The differences in toxicity among species and chemical classes suggest that mechanisms of PFAS toxicity may differ as a function of both. Environ Toxicol Chem 2024;43:359-373. Published 2023. This article is a U.S. Government work and is in the public domain in the USA.

Dietary Uptake of Highly Hydrophobic Chemicals by Rainbow Trout (Oncorhynchus Mykiss).

Rainbow trout (Oncorhynchus mykiss) was exposed through the diet to a mixture of non-ionic organic chemicals for 28 d, followed by a depuration phase, in accordance with OECD method 305. The mixture included hexachlorobenzene (HCB), 2,2',5,5'-tetrachlorobiphenyl (PCB-52), 2,2',5,5'-hexachlorobiphenyl (PCB-153), decachlorobiphenyl (PCB-209), decabromodiphenyl ether (BDE209), decabromodiphenyl ethane (DBDPE), bis-(2-ethylhexyl)-3,4,5,6-tetrabromophthalate (TBPH), perchloro-p-terphenyl (p-TCP), perchloro-m-terphenyl (m-TCP), and perchloro-p-quaterphenyl (p-QTCP), the latter six of which are considered highly hydrophobic based on n-octanol/water partition coefficients (KOW) greater than 108. All chemicals had first-order uptake and elimination kinetics except p-QTCP, whose kinetics could not be verified due to limitations of analytical detection in the elimination phase. For HCB and PCBs, the growth-corrected elimination rates (k2g), assimilation efficiencies (α), and biomagnification factors (BMFL) corrected for lipid content compared well with literature values. For the highly hydrophobic chemicals, elimination rates were faster than the rates for HCB and PCBs, and α's and BMFLs were much lower than those of HCB and PCBs, i.e., ranging from 0.019 to 2.8%, and from 0.000051 to 0.023 (g-lipid/g-lipid), respectively. As a result, the highly hydrophobic organic chemicals were found be much less bioavailable and bioaccumulative than HCB and PCBs. Based on the current laboratory dietary exposures, none of the highly hydrophobic substances would be expected to biomagnify, but Trophic Magnification Factors (TMFs) > 1 have been reported from field studies for TBPH and DBDPE. Additional research is needed to understand and reconcile the apparent inconsistencies in these two lines of evidence for bioaccumulation assessment.

Review of DDT, DDE, DDD, DDMU and DDMS Toxicity Data for Organisms Used in Estuarine and Marine Sediment Toxicity Tests.

The open literature was searched for laboratory toxicity data for marine/estuarine organisms exposed to dichlorodiphenyltrichloroethane (DDT) and its degradation products of dichlorodiphenyldichloroethylene (DDE), dichlorodiphenyldichloroethane (DDD), dichlorodiphenylchloroethylene (DDMU), and dichlorodiphenylchloroethane (DDMS). The goal of the review was to determine water-column toxicity values that could be used for porewater-based assessment of sediment toxicity. Data for individual compounds (and isomers thereof) in this group were very limited; most available data were for mixtures of multiple compounds, some defined and others undefined. Further, the majority of relevant studies involved exposure to spiked or field-contaminated sediment (rather than waterborne exposure), which requires inferring concentration in porewater from bulk sediment. Comparing data on the basis of effect concentrations for water or inferred concentration in sediment pore water, the lower reported effect concentrations were in the range of 0.05 to 0.1 µg/L, generally in studies of longer duration and/or evaluating sub-lethal effects. Because field exposures are generally to mixtures of these compounds in varied proportions, additional data on chemical-specific toxicity would aid in pore-water based toxicity assessment for marine/estuarine sediments contaminated with DDT-related chemicals.

Genetic and Physiological Effects of Insulin-Like Growth Factor-1 (IGF-1) on Human Urate Homeostasis.

SIGNIFICANCE STATEMENT: Hyperinsulinemia induces hyperuricemia by activating net renal urate reabsorption in the renal proximal tubule. The basolateral reabsorptive urate transporter GLUT9a appears to be the dominant target for insulin. By contrast, IGF-1 infusion reduces serum urate (SU), through mechanisms unknown. Genetic variants of IGF1R associated with reduced SU have increased IGF-1R expression and interact with genes encoding the GLUT9 and ABCG2 urate transporters, in a sex-specific fashion, which controls the SU level. Activation of IGF-1/IGF-1R signaling in Xenopus oocytes modestly activates GLUT9a and inhibits insulin's stimulatory effect on the transporter, which also activates multiple secretory urate transporters-ABCG2, ABCC4, OAT1, and OAT3. The results collectively suggest that IGF-1 reduces SU by activating secretory urate transporters and inhibiting insulin's action on GLUT9a. BACKGROUND: Metabolic syndrome and hyperinsulinemia are associated with hyperuricemia. Insulin infusion in healthy volunteers elevates serum urate (SU) by activating net urate reabsorption in the renal proximal tubule, whereas IGF-1 infusion reduces SU by mechanisms unknown. Variation within the IGF1R gene also affects SU levels. METHODS: Colocalization analyses of a SU genome-wide association studies signal at IGF1R and expression quantitative trait loci signals in cis using COLOC2, RT-PCR, Western blotting, and urate transport assays in transfected HEK 293T cells and in Xenopus laevis oocytes. RESULTS: Genetic association at IGF1R with SU is stronger in women and is mediated by control of IGF1R expression. Inheritance of the urate-lowering homozygous genotype at the SLC2A9 locus is associated with a differential effect of IGF1R genotype between men and women. IGF-1, through IGF-1R, stimulated urate uptake in human renal proximal tubule epithelial cells and transfected HEK 293T cells, through activation of IRS1, PI3/Akt, MEK/ERK, and p38 MAPK; urate uptake was inhibited in the presence of uricosuric drugs, specific inhibitors of protein tyrosine kinase, PI3 kinase (PI3K), ERK, and p38 MAPK. In X. laevis oocytes expressing ten individual urate transporters, IGF-1 through endogenous IGF-1R stimulated urate transport mediated by GLUT9, OAT1, OAT3, ABCG2, and ABCC4 and inhibited insulin's stimulatory action on GLUT9a and OAT3. IGF-1 significantly activated Akt and ERK. Specific inhibitors of PI3K, ERK, and PKC significantly affected IGF-1 stimulation of urate transport in oocytes. CONCLUSIONS: The combined results of infusion, genetics, and transport experiments suggest that IGF-1 reduces SU by activating urate secretory transporters and inhibiting insulin's action.

Effects of elevated serum urate on cardiometabolic and kidney function markers in a randomised clinical trial of inosine supplementation.

In observational studies, serum urate positively associates with cardiometabolic and kidney diseases. We analyzed data from a randomised placebo-controlled trial to determine whether moderate hyperuricemia induced by inosine affects cardiometabolic and kidney function markers. One hundred and twenty post-menopausal women were recruited into a 6-month randomised, double-blind, placebo-controlled trial of inosine for bone health. Change from baseline in the following pre-specified endpoints was analyzed: body mass index; blood pressure; lipid profile; C-reactive protein; fasting glucose; insulin; HbA1c; serum creatinine; and estimated glomerular filtration rate (eGFR). Despite increases in serum urate levels (+ 0.17 mmol/L at week 6, P < 0.0001), no significant between-group differences were observed in cardiometabolic markers, with the exception of lower fasting glucose concentrations with inosine at week 19. In the inosine group, change in serum urate correlated with change in serum creatinine (r = 0.41, P = 0.0012). However, there was no between-group difference in serum creatinine values. Over the entire study period, there was no significant difference in eGFR (ANCOVA P = 0.13). Reduction in eGFR was greater in the inosine group at Week 13 (mean difference - 4.6 mL/min/1.73 m2, false detection rate P = 0.025), with no between-group difference in eGFR at other time points. These data indicate that increased serum urate does not negatively influence body mass index, blood pressure, lipid profile, or glycaemic control. Serum urate changes associated with inosine intake correlate with changes in serum creatinine, but this does not lead to clinically important reduction in kidney function over 6 months.Clinical trial registration number: Australia and New Zealand Clinical Trials Registry (ACTRN12617000940370), registered 30/06/2017.

Acute Toxicity of Major Geochemical Ions to Fathead Minnows (Pimephales promelas): Part B-Modeling Ion Toxicity.

Mathematical models are presented for the acute median lethal concentrations of major geochemical ions (Na+ , K+ , Ca2+ , Mg2+ , Cl- , SO4 2- , HCO3 - /CO3 2- ) to fathead minnows (Pimephales promelas), based on an extensive series of experiments presented in a companion article. Toxicity relationships across different dilution waters, individual salts, and salt mixtures suggest six independent mechanisms of toxicity to consider in modeling efforts, including Mg/Ca-specific toxicity, osmolarity-related toxicity, SO4 -specific toxicity, K-specific toxicity, effects of high pH/alkalinity, and a multiple ion-related toxicity at low Ca distinct from the other mechanisms. Models are evaluated using chemical activity-based exposure metrics pertinent to each mechanism, but concentration-based alternative models that are simpler to apply are also addressed. These models are compared to those previously provided for Ceriodaphnia dubia, and various issues regarding their application to risk assessments are discussed. Environ Toxicol Chem 2022;41:2095-2106. © 2022 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Prescribing Patterns of Sodium-Glucose Cotransporter-2 Inhibitors in Patients with CKD: A Cross-Sectional Registry Analysis.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) reduce kidney disease progression and mortality in patients with chronic kidney disease (CKD), regardless of diabetes status. However, the prescribing patterns of these novel therapeutics in the CKD population in real-world settings remain largely unknown. Methods: This cross-sectional study included adults with stages 3-5 CKD included in the Mass General Brigham (MGB) CKD registry in March 2021. We described the adoption of SGLT-2i therapy and evaluated factors associated with SGLT-2i prescription using multivariable logistic regression models in the CKD population, with and without diabetes. Results: A total of 72,240 patients with CKD met the inclusion criteria, 31,688 (44%) of whom were men and 61,265 (85%) White. A total of 22,653 (31%) patients were in the diabetic cohort, and 49,587 (69%) were in the nondiabetic cohort. SGLT-2i prescription was 6% in the diabetic cohort and 0.3% in the nondiabetic cohort. In multivariable analyses, younger Black men with a history of heart failure, use of cardiovascular medications, and at least one cardiologist visit in the previous year were associated with higher odds of SGLT-2i prescription in both diabetic and nondiabetic cohorts. Among patients with diabetes, advanced CKD stages were associated with lower odds of SGLT-2i prescription, whereas urine dipstick test and at least one subspecialist visit in the previous year were associated with higher odds of SGLT-2i prescription. In the nondiabetic cohort, CKD stage, urine dipstick test, and at least one nephrologist visit in the previous year were not significantly associated with SGLT-2i prescription. Conclusions: In this registry study, prescription of SGLT-2i was low in the CKD population, particularly among patients without diabetes.

Acute Toxicity of Major Geochemical Ions to Fathead Minnows (Pimephales Promelas): Part A-Observed Relationships for Individual Salts and Salt Mixtures.

The results of a series of experiments on the acute toxicity of major geochemical ions (Na+ , K+ , Ca2+ , Mg2+ , Cl- , SO4 2- , HCO3 - /CO3 2- ) to fathead minnows (Pimephales promelas) are reported. Tests of individual major ion salts in various dilution waters demonstrated that the toxicities of Na, Mg, and K salts decrease as the overall ion content of the dilution water increases. For Na and Mg salts, this is attributable to Ca content as previously reported for Ceriodaphnia dubia. For K salts, the cause is unclear, but it is not due to Na as reported for C. dubia. In an unregulated test at high pH (9.3), NaHCO3 was also found to be twice as toxic compared to when the pH was reduced to 8.4. Experiments with binary salt mixtures indicated the existence of multiple independent mechanisms of action. These include K-specific toxicity and Ca/Mg-specific toxicity previously reported for C. dubia, but also apparent toxicities related to SO4 and to high pH/alkalinity in CO3 /HCO3 -dominated exposures. Previous work with C. dubia also suggested a general ion toxicity involving all ions that was correlated with osmolarity. For fathead minnow, similar correlations were observed, but multiple mechanisms were indicated. At higher Ca, this general toxicity could be attributable to osmotic effects, but at lower Ca, osmolarity may be more a covariate than a cause, with this toxicity being related to a combined effect of ions other than via osmolarity. Environ Toxicol Chem 2022;41:2078-2094. © 2022 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Zoledronic Acid-Associated Fanconi Syndrome in Patients With Cancer.

Zoledronic acid (ZA) is an antiresorptive agent typically used for fracture prevention in postmenopausal osteoporosis, malignancy-associated metastatic bone lesions, and as a treatment for hypercalcemia. ZA is excreted almost entirely by the kidney; as a result, a reduction in renal clearance can lead to its accumulation and potential renal toxicity. Although uncommon, acute kidney injury (AKI) from intravenous bisphosphonates has been described, with different patterns including tubulointerstitial nephritis, acute tubular necrosis, as well as focal segmental glomerulosclerosis. Here we present 4 patients with an underlying malignancy who each developed evidence of generalized proximal tubular dysfunction, also known as Fanconi syndrome, approximately 1 week after receiving treatment with ZA. On presentation, all patients had AKI, low serum bicarbonate levels, abnormal urinary acidification, hypophosphatemia, hypokalemia, and increased urine amino acid excretion or renal glycosuria. Based on the temporal association between ZA infusion and the development of these electrolyte abnormalities, each case is highly suggestive of ZA-associated Fanconi syndrome. Due to the severity of presentation, all required discontinuation of ZA and ongoing electrolyte repletion. Nephrologists and oncologists should be aware of this complication and consider ZA as a possible trigger of new-onset Fanconi syndrome.

Gonadal Development in Smallmouth Bass (Micropterus Dolomieu) Reared in the Absence and Presence of 17-α-Ethinylestradiol.

Testicular oocytes in wild adult bass (Micropterus spp.) are considered a potential indication of exposure to estrogenic compounds in municipal, agricultural, or industrial wastewater. However, our ability to interpret links between testicular oocyte occurrence in wild fish species and environmental pollutants is limited by our understanding of normal and abnormal gonadal development. We previously reported low-to-moderate testicular oocyte prevalence (7%-38%) among adult male bass collected from Minnesota waters with no known sources of estrogenic compounds. In the present study, two experiments were conducted in which smallmouth bass (Micropterus dolomieu) fry were exposed to control water or 17-α-ethinylestradiol (EE2) during gonadal differentiation, then reared in clean water for an additional period. Histological samples were evaluated at several time points during the exposure and grow-out periods, and the sequence and timing of gonadal development in the presence of estrogen were compared with that of control fish. Testicular oocytes were not observed in any control or EE2-exposed fish. Among groups exposed to 1.2 or 5.1 ng/L EE2 in Experiment 1 or 3.0 ng/L EE2 in Experiment 2, ovaries were observed in 100% of fish up to 90 days after exposure ceased, and approximately half of those ovaries had abnormal characteristics, suggesting that they likely developed in sex-reversed males. Groups exposed to 0.1, 0.4, or 1.0 ng/L in Experiment 2 developed histologically normal ovaries and testes in proportions not significantly different from 1:1. These findings suggest that, while presumably able to cause sex reversal, juvenile exposure to EE2 may not be a unique cause of testicular oocytes in wild bass, although the long-term outcomes of exposure are unknown. Environ Toxicol Chem 2022;41:1416-1428. © 2022 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Association of acidic urine pH with impaired renal function in primary gout patients: a Chinese population-based cross-sectional study.

BACKGROUND: Patients with gout frequently have low urinary pH, which is associated with the nephrolithiasis. However, the specific distribution of urinary pH and potential relationship of acidic urine pH to broader manifestations of kidney disease in gout are still poorly understood. METHODS: A 2016-2020 population-based cross-sectional study was conducted among 3565 gout patients in the dedicated gout clinic of the Affiliated Hospital of Qingdao University to investigate the association between low urinary pH and kidney disease. We studied patients that we defined to have "primary gout", based on the absence of > stage 2 CKD. All subjects underwent 14 days of medication washout and 3-day standardized metabolic diet. We obtained general medical information, blood and urine biochemistries, and renal ultrasound examination on the day of the visit. The primary readouts were urine pH, eGFR, nephrolithiasis, renal cysts, microhematuria, and proteinuria. Patients were assigned into 5 subgroups (urine pH ≤5.0, 5.0 6.9), aligning with the clinical significance of urine pH. RESULTS: Overall, the median urine pH and eGFR of all patients was 5.63 (IQR 5.37~6.09), and 98.32 (IQR 86.03~110.6), with acidic urine in 46.5% of patients. The prevalence of nephrolithiasis, microhematuria, and proteinuria were 16.9%, 49.5%, and 6.9%, respectively. By univariate analysis, eGFR was significantly associated with age, sex, duration of gout, tophus, body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, serum utare, hypertension, diabetes, and urine pH. On multivariable analysis, eGFR was associated with age, sex, diastolic blood pressure, serum uric acid, hypertension, diabetes, and urine pH. Acidic urine pH, especially urine pH < 5.0, was significantly associated with the prevalence of kidney disease, including > stage 1 CKD, nephrolithiasis, kidney cyst, and microhematuria. Patients with 6.2 ≤ urine pH ≤ 6.9 and SU ≤ 480 µmol/L had the highest eGFR with the lowest prevalence of nephrolithiasis, microhematuria, and proteinuria. CONCLUSIONS: Approximately half of gout subjects had acidic urine pH. Urine pH < 5.0 was associated with significantly increased nephrolithiasis, renal cyst, microhematuria, and proteinuria. The results support prospective clinical investigation of urinary alkalinization in selected gout patients with acidic urine pH.

Genetic and Physiological Effects of Insulin on Human Urate Homeostasis.

Insulin and hyperinsulinemia reduce renal fractional excretion of urate (FeU) and play a key role in the genesis of hyperuricemia and gout, via uncharacterized mechanisms. To explore this association further we studied the effects of genetic variation in insulin-associated pathways on serum urate (SU) levels and the physiological effects of insulin on urate transporters. We found that urate-associated variants in the human insulin (INS), insulin receptor (INSR), and insulin receptor substrate-1 (IRS1) loci associate with the expression of the insulin-like growth factor 2, IRS1, INSR, and ZNF358 genes; additionally, we found genetic interaction between SLC2A9 and the three loci, most evident in women. We also found that insulin stimulates the expression of GLUT9 and increases [14C]-urate uptake in human proximal tubular cells (PTC-05) and HEK293T cells, transport activity that was effectively abrogated by uricosurics or inhibitors of protein tyrosine kinase (PTK), PI3 kinase, MEK/ERK, or p38 MAPK. Heterologous expression of individual urate transporters in Xenopus oocytes revealed that the [14C]-urate transport activities of GLUT9a, GLUT9b, OAT10, OAT3, OAT1, NPT1 and ABCG2 are directly activated by insulin signaling, through PI3 kinase (PI3K)/Akt, MEK/ERK and/or p38 MAPK. Given that the high-capacity urate transporter GLUT9a is the exclusive basolateral exit pathway for reabsorbed urate from the renal proximal tubule into the blood, that insulin stimulates both GLUT9 expression and urate transport activity more than other urate transporters, and that SLC2A9 shows genetic interaction with urate-associated insulin-signaling loci, we postulate that the anti-uricosuric effect of insulin is primarily due to the enhanced expression and activation of GLUT9.

Stochastic Framework for Addressing Chemical Partitioning and Bioavailability in Contaminated Sediment Assessment and Management.

Passive sampling to quantify net partitioning of hydrophobic organic contaminants between the porewater and solid phase has advanced risk management for contaminated sediments. Direct porewater (Cfree) measures represent the best way to predict adverse effects to biota. However, when the need arises to convert between solid-phase concentration (Ctotal) and Cfree, a wide variation in observed sediment-porewater partition coefficients (KTOC) is observed due to intractable complexities in binding phases. We propose a stochastic framework in which a given Ctotal is mapped to an estimated range of Cfree through variability in passive sampling-derived KTOC relationships. This mapping can be used to pair estimated Cfree with biological effects data or inversely to translate a measured or assumed Cfree to an estimated Ctotal. We apply the framework to both an effects threshold for polycyclic aromatic hydrocarbon (PAH) toxicity and an aggregate adverse impact on an assemblage of species. The stochastic framework is based on a "bioavailability ratio" (BR), which reflects the extent to which potency-weighted, aggregate PAH partitioning to the solid-phase is greater than that predicted by default, KOW-based KTOC values. Along a continuum of Ctotal, we use the BR to derive an estimate for the probability that Cfree will exceed a threshold. By explicitly describing the variability of KTOC and BR, estimates of risk posed by sediment-associated contaminants can be more transparent and nuanced.

Management of gout in chronic kidney disease: a G-CAN Consensus Statement on the research priorities.

Gout and chronic kidney disease (CKD) frequently coexist, but quality evidence to guide gout management in people with CKD is lacking. Use of urate-lowering therapy (ULT) in the context of advanced CKD varies greatly, and professional bodies have issued conflicting recommendations regarding the treatment of gout in people with concomitant CKD. As a result, confusion exists among medical professionals about the appropriate management of people with gout and CKD. This Consensus Statement from the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) discusses the evidence and/or lack thereof for the management of gout in people with CKD and identifies key areas for research to address the challenges faced in the management of gout and CKD. These discussions, which address areas for research both in general as well as related to specific medications used to treat gout flares or as ULT, are supported by separately published G-CAN systematic literature reviews. This Consensus Statement is not intended as a guideline for the management of gout in CKD; rather, it analyses the available literature on the safety and efficacy of drugs used in gout management to identify important gaps in knowledge and associated areas for research.