Gout, urate, and crystal deposition disease最新文献

The evidence regarding allopurinol's effects on renal function among people with hyperuricemia and gout has been conflicting, though clinicians are often cautious about using allopurinol in chronic kidney disease (CKD). We sought to examine the relation between allopurinol use in those with gout and CKD and the risk of worsening renal function. We conducted a time-stratified propensity score (PS)-matched cohort study on the IQVIA Medical Research Data representative of the UK general population. Among participants 18-89 years old with gout and CKD 3-4 not on urate-lowering therapy within one year prior, we identified new users of allopurinol and matched them 1:1 with a non-user. We analyzed the relation between incident allopurinol use and the changes in the eGFR at one year of follow-up using linear regression adjusted for the potential confounders included in the PS model. We PS-matched 10,716 allopurinol initiators to 10,716 non-users, among whom 42% were female, the mean age was 74 years and 7% had CKD4. The progression to dialysis or kidney transplant was similar in both groups. The mean eGFR prior to the study entry was 48.4 mL/min among allopurinol initiators and 49.5 mL/min among non-users, while the last eGFR within one year was 49.4 and 49.7 mL/min, respectively. The allopurinol initiators had an adjusted mean increase in the eGFR of 0.81 mL/min (95% CI 0.57-1.05) greater than that of non-users. Among those with gout and CKD 3-4, allopurinol did not worsen renal function and may have slightly improved it, suggesting that allopurinol is not detrimental to patients with gout who have CKD.

Background: The gold standard for crystal arthritis diagnosis relies on the identification of either monosodium urate (MSU) or calcium pyrophosphate (CPP) crystals in synovial fluid. With the goal of enhanced crystal detection, we adapted a standard compensated polarized light microscope (CPLM) with a polarized digital camera and multi-focal depth imaging capabilities to create digital images from synovial fluid mounted on microscope slides. Using this single-shot computational polarized light microscopy (SCPLM) method, we compared rates of crystal detection and raters' preference for image.

Methods: Microscope slides from patients with either CPP, MSU, or no crystals in synovial fluid were acquired using CPLM and SCPLM methodologies. Detection rate, sensitivity, and specificity were evaluated by presenting expert crystal raters with (randomly sorted) CPLM and SCPLM digital images, from FOV above clinical samples. For each FOV and each method, each rater was asked to identify crystal suspects and their level of certainty for each crystal suspect and crystal type (MSU vs. CPP).

Results: For the 283 crystal suspects evaluated, SCPLM resulted in higher crystal detection rates than did CPLM, for both CPP (51%. vs. 28%) and MSU (78% vs. 46%) crystals. Similarly, sensitivity was greater for SCPLM for CPP (0.63 vs. 0.35) and MSU (0.88 vs. 0.52) without giving up much specificity resulting in higher AUC.

Conclusions: Subjective and objective measures of greater detection and higher certainty were observed for SCPLM over CPLM, particularly for CPP crystals. The digital data associated with these images can ultimately be incorporated into an automated crystal detection system that provides a quantitative report on crystal count, size, and morphology.

Many preclinical reports have coalesced to identify a strong association between obesity and increased levels of uric acid (UA) in tissues and, importantly in the circulation (hyperuricemia). Unfortunately, nearly all these studies were conducted with male mice or, in one case, female mice without a side-by-side male cohort. Therefore, the relationship between obesity and hyperuricemia in female mice remains undefined. This lack of clarity in the field has considerable impact as the downstream effects of obesity and allied hyperuricemia are extensive, resulting in many comorbidities including cardiovascular dysfunction, chronic kidney disease and nonalcoholic fatty liver disease (NAFLD). Herein we begin to address this issue by revealing phenotypic and metabolic responses to diet-induced obesity (DIO) in a side-by-side male vs. female C57BL/6J study. Beginning at 6 weeks of age, mice were exposed to either an obesogenic diet (60% calories from fat) or control diet (10% calories from fat) for 19 weeks. Similar to numerous reported observations with the 60% diet, male mice experienced significant weight gain over time, elevated fasting blood glucose, impaired glucose tolerance and significantly elevated circulating uric acid levels (2.54 ± 0.33 mg/dL) compared to age-matched lean male controls (1.53 ± 0.19 mg/dL). As expected, the female mice experienced a slower rate of weight gain compared to the males; however, they also developed elevated fasting blood glucose and impaired glucose tolerance compared to age-matched lean controls. Countervailing our previous report whereby the control diet for the female-only study was vivarium standard chow (18% calories from fat), the obese female mice did demonstrate significantly elevated circulating UA levels (2.55 ± 0.15 mg/dL) compared to the proper control (1.68 ± 0.12 mg/dL). This affirms that the choice of control diet is crucial for reaching durable conclusions. In toto, these results, for the first time, reveal elevated circulating UA to be a similar long-term response to obesogenic feeding for both males and females and mirrors clinical observations demonstrating hyperuricemia in obesity for both sexes.