Association of hypochloremia with mortality among patients requiring continuous renal replacement therapy.

BACKGROUND: Serum chloride derangement is common in critically ill patients requiring continuous renal replacement therapy (CRRT). We aimed to assess the association between serum chloride levels before and during CRRT with mortality. METHODS: This is a retrospective cohort study of critically ill patients receiving CRRT for acute kidney injury from December 2006 through November 2015 in a tertiary referral hospital in the United States. We used logistic regression to assess serum chloride before and mean serum chloride during CRRT as predictors for 90 days mortality after CRRT initiation. The normal reference range for serum chloride was 99-108 mmol/L. RESULTS: Of 1282 eligible patients, 25%, 50%, and 25% had hypochloremia, normochloremia, and hyperchloremia, respectively. The adjusted odds ratio for 90 days mortality in patients with hypochloremia before CRRT was 1.82 (95% CI 1.29-2.55). During CRRT, 4%, 70%, 26% of patients had mean serum chloride in the hypochloremia, normochloremia, and hyperchloremia range, respectively. The adjusted odds ratio for 90 days mortality in patients with mean serum chloride during CRRT in the hypochloremia range was 2.96 (95% CI 1.43-6.12). Hyperchloremia before and during CRRT was not associated with mortality. The greater serum chloride range during CRRT was associated with increased mortality (OR 1.29; 95% CI 1.13-1.47 per 5 mmol/L increase). CONCLUSION: Hypochloremia before and during CRRT is associated with higher mortality.

Dietary Risk Factors for Incident and Recurrent Symptomatic Kidney Stones.

OBJECTIVE: To compare dietary factors between incident symptomatic stone formers and controls, and among the incident stone formers, to determine whether dietary factors were predictive of symptomatic recurrence. PATIENTS AND METHODS: We prospectively recruited 411 local incident symptomatic kidney stone formers (medical record validated) and 384 controls who were seen at Mayo Clinic in Minnesota or Florida between January 1, 2009, and August 31, 2018. Dietary factors were based on a Viocare, Inc, food frequency questionnaire administered during a baseline in-person study visit. Logistic regression compared dietary risk factors between incident symptomatic stone formers and controls. Incident stone formers were followed up for validated symptomatic recurrence in the medical record. Cox proportional hazards models estimated risk of symptomatic recurrence with dietary factors. Analyses adjusted for fluid intake, energy intake, and nondietary risk factors. RESULTS: In fully adjusted analyses, lower dietary calcium, potassium, caffeine, phytate, and fluid intake were all associated with a higher odds of an incident symptomatic kidney stone. Among incident stone formers, 73 experienced symptomatic recurrence during a median 4.1 years of follow-up. Adjusting for body mass index, fluid intake, and energy intake, lower dietary calcium and lower potassium intake were predictive of symptomatic kidney stone recurrence. With further adjustment for nondietary risk factors, lower dietary calcium intake remained a predictor of recurrence, but lower potassium intake only remained a predictor of recurrence among those not taking thiazide diuretics or calcium supplements. CONCLUSION: Enriching diets in stone formers with foods high in calcium and potassium may help prevent recurrent symptomatic kidney stones.

The effect of levocarnitine supplementation on dialysis-related hypotension: A systematic review, meta-analysis, and trial sequential analysis.

BACKGROUND: Dialysis patients have been shown to have low serum carnitine due to poor nutrition, deprivation of endogenous synthesis from kidneys, and removal by hemodialysis. Carnitine deficiency leads to impaired cardiac function and dialysis-related hypotension which are associated with increased mortality. Supplementing with levocarnitine among hemodialysis patients may diminish incidence of intradialytic hypotension. Data on this topic, however, lacks consensus. METHODS: We conducted electronic searches in PubMed, Embase and Cochrane Central Register of Controlled Trials from January 1960 to 19th November 2021 to identify randomized controlled studies (RCTs), which examined the effects of oral or intravenous levocarnitine (L-carnitine) on dialysis-related hypotension among hemodialysis patients. The secondary outcome was muscle cramps. Study results were pooled and analyzed utilizing the random-effects model. Trial sequential analysis (TSA) was performed to assess the strength of current evidence. RESULTS: Eight trials with 224 participants were included in our meta-analysis. Compared to control group, L-carnitine reduced the incidence of dialysis-related hypotension among hemodialysis patients (pooled OR = 0.26, 95% CI [0.10-0.72], p = 0.01, I2 = 76.0%). TSA demonstrated that the evidence was sufficient to conclude the finding. Five studies with 147 participants showed a reduction in the incidence of muscle cramps with L-carnitine group (pooled OR = 0.22, 95% CI [0.06-0.81], p = 0.02, I2 = 74.7%). However, TSA suggested that further high-quality studies were required. Subgroup analysis on the route of supplementation revealed that only oral but not intravenous L-carnitine significantly reduced dialysis-related hypotension. Regarding dose and duration of L-carnitine supplementation, the dose > 4,200 mg/week and duration of at least 12 weeks appeared to prevent dialysis-related hypotension. CONCLUSION: Supplementing oral L-carnitine for at least three months above 4,200 mg/week helps prevent dialysis-related hypotension. L-carnitine supplementation may ameliorate muscle cramps. Further well-powered studies are required to conclude this benefit.

The association between olfactory and gustatory dysfunction and chronic kidney disease.

BACKGROUND: Olfactory and gustatory changes may contribute to poor appetite and food aversion in chronic kidney disease (CKD), though the prevalence of olfactory and gustatory dysfunction is not known in the CKD population. METHODS: We conducted a cross-sectional study among 3527 US adults aged ≥40 years old in the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2014. We measured the prevalence of olfactory and gustatory dysfunction among patients with CKD defined as eGFR < 60 ml/min/1.73m2 using the "scratch and sniff" NHANES Pocket Smell Test and quinine whole-mouth test. We also examined the association between CKD and olfactory/gustatory dysfunction, and nutritional markers. RESULTS: The prevalence of olfactory dysfunction was 30% among CKD and 15% among non-CKD (p < 0.001). The prevalence of gustatory dysfunction was 13% among CKD and 17% among non-CKD (p = 0.10). After adjusting for confounders, CKD was significantly associated with olfactory dysfunction (OR = 1.47, 95% CI [1.07, 2.01]; p = 0.02) but not gustatory dysfunction (OR = 1.76, 95%CI [0.99, 3.11]; p = 0.05). Among the CKD population, the odds of olfactory dysfunction was 72% higher for every 10 kg decrease in grip strength (OR = 1.72, 95% CI [1.39, 2.13]; adjusted p = 0.005). CONCLUSION: CKD was associated with higher odds of olfactory but not gustatory dysfunction. Olfactory dysfunction was associated with lower grip strength among those with CKD. Screening and early intervening on olfactory dysfunction among CKD may preserve muscle strength and improve nutritional status in this vulnerable population.

Hospital-acquired serum phosphate derangements and their associated in-hospital mortality.

BACKGROUND: We aimed to report the incidence of hospital-acquired hypophosphataemia and hyperphosphataemia along with their associated in-hospital mortality. METHODS: We included 15 869 adult patients hospitalised at a tertiary medical referral centre from January 2009 to December 2013, who had normal serum phosphate levels at admission and at least two serum phosphate measurements during their hospitalisation. The normal range of serum phosphate was defined as 2.5-4.2 mg/dL. In-hospital serum phosphate levels were categorised based on the occurrence of hospital-acquired hypophosphataemia and hyperphosphataemia. We analysed the association of hospital-acquired hypophosphataemia and hyperphosphataemia with in-hospital mortality using multivariable logistic regression. RESULTS: Fifty-three per cent (n=8464) of the patients developed new serum phosphate derangements during their hospitalisation. The incidence of hospital-acquired hypophosphataemia and hyperphosphataemia was 35% and 27%, respectively. Hospital-acquired hypophosphataemia and hyperphosphataemia were associated with odds ratio (OR) of 1.56 and 2.60 for in-hospital mortality, respectively (p value<0.001 for both). Compared with patients with persistently normal in-hospital phosphate levels, patients with hospital-acquired hypophosphataemia only (OR 1.64), hospital-acquired hyperphosphataemia only (OR 2.74) and both hospital-acquired hypophosphataemia and hyperphosphataemia (ie, phosphate fluctuations; OR 4.00) were significantly associated with increased in-hospital mortality (all p values <0.001). CONCLUSION: Hospital-acquired serum phosphate derangements affect approximately half of the hospitalised patients and are associated with increased in-hospital mortality rate.

Comparison of hospitalization outcomes for delivery and resource utilization between pregnant women with kidney transplants and chronic kidney disease in the United States.

BACKGROUND: This study aimed to assess outcomes of delivery hospitalizations, including acute kidney injury (AKI), obstetric and foetal events and resource utilization among pregnant women with kidney transplants compared with pregnant women with no known kidney disease and those with chronic kidney disease (CKD) Stages 3-5. METHOD: Hospitalizations for delivery in the US were identified using the enhanced delivery identification method in the National Inpatient Sample dataset from the years 2009 to 2014. Diagnoses of CKD Stages 3-5, kidney transplantation, along with obstetric events, delivery methods and foetal events were identified using ICD-9-CM diagnosis and procedure codes. Patients with no known kidney disease group were identified by excluding any diagnoses of CKD, end stage kidney disease, and kidney transplant. Multivariable logistic regression accounting for the survey weights and matched regression was conducted to investigate the risk of maternal and foetal complications in women with kidney transplants, compared with women with no kidney transplants and no known kidney disease, and to women with CKD Stages 3-5. RESULT: A total of 5, 408, 215 hospitalizations resulting in deliveries were identified from 2009 to 2014, including 405 women with CKD Stages 3-5, 295 women with functioning kidney transplants, and 5, 405, 499 women with no known kidney disease. Compared with pregnant women with no known kidney disease, pregnant kidney transplant recipients were at higher odds of hypertensive disorders of pregnancy (OR = 3.11, 95% CI [2.26, 4.28]), preeclampsia/eclampsia/HELLP syndrome (OR = 3.42, 95% CI [2.54, 4.60]), preterm delivery (OR = 2.46, 95% CI [1.75, 3.45]), foetal growth restriction (OR = 1.74, 95% CI [1.01, 3.00]) and AKI (OR = 10.46, 95% CI [5.33, 20.56]). There were no significant differences in rates of gestational diabetes or caesarean section. Pregnant women with kidney transplants had 1.30-times longer lengths of stay and 1.28-times higher costs of hospitalization. However, pregnant women with CKD Stages 3-5 were at higher odds of AKI (OR = 5.29, 95% CI [2.41, 11.59]), preeclampsia/eclampsia/HELLP syndrome (OR = 1.72, 95% CI [1.07, 2.76]) and foetal deaths (OR = 3.20, 95% CI [1.06, 10.24]), and had 1.28-times longer hospital stays and 1.37-times higher costs of hospitalization compared with pregnant women with kidney transplant. CONCLUSION: Pregnant women with kidney transplant were more likely to experience adverse events during delivery and had longer lengths of stay and higher total charges when compared with women with no known kidney disease. However, pregnant women with moderate to severe CKD were more likely to experience serious complications than kidney transplant recipients.

Outcomes of Kidney Transplant Recipients with Sickle Cell Disease: An Analysis of the 2000-2019 UNOS/OPTN Database.

BACKGROUND: Lower patient survival has been observed in sickle cell disease (SCD) patients who go on to receive a kidney transplant. This study aimed to assess the post-transplant outcomes of SCD kidney transplant recipients in the contemporary era. METHODS: We used the OPTN/UNOS database to identify first-time kidney transplant recipients from 2010 through 2019. We compared patient and allograft survival between recipients with SCD (n = 105) vs. all other diagnoses (non-SCD, n = 146,325) as the reported cause of end-stage kidney disease. We examined whether post-transplant outcomes improved among SCD in the recent era (2010-2019), compared to the early era (2000-2009). RESULTS: After adjusting for differences in baseline characteristics, SCD was significantly associated with lower patient survival (HR 2.87; 95% CI 1.75-4.68) and death-censored graft survival (HR 1.98; 95% CI 1.30-3.01), compared to non-SCD recipients. The lower patient survival and death-censored graft survival in SCD recipients were consistently observed in comparison to outcomes of recipients with diabetes, glomerular disease, and hypertension as the cause of end-stage kidney disease. There was no significant difference in death censored graft survival (HR 0.99; 95% CI 0.51-1.73, p = 0.98) and patient survival (HR 0.93; 95% CI 0.50-1.74, p = 0.82) of SCD recipients in the recent versus early era. CONCLUSIONS: Patient and allograft survival in SCD kidney recipients were worse than recipients with other diagnoses. Overall SCD patient and allograft outcomes in the recent era did not improve from the early era. The findings of our study should not discourage kidney transplantation for ESKD patients with SCD due to a known survival benefit of transplantation compared with remaining on dialysis. Urgent future studies are needed to identify strategies to improve patient and allograft survival in SCD kidney recipients. In addition, it may be reasonable to assign risk adjustment for SCD patients.

Risk of Symptomatic Kidney Stones During and After Pregnancy.

RATIONALE & OBJECTIVE: There are several well-known anatomical and physiological changes during pregnancy that could contribute to kidney stone formation, but evidence that they increase the risk of kidney stones during pregnancy is lacking. We determined whether there was an increased risk of a first-time symptomatic kidney stone during and after pregnancy. STUDY DESIGN: A population-based matched case-control study. SETTING & PARTICIPANTS: 945 female first-time symptomatic kidney stone formers aged 15-45 years and 1,890 age-matched female controls in Olmsted County, MN, from 1984-2012. The index date was the date of onset of a symptomatic kidney stone for both the case and her matched controls. EXPOSURE: The primary exposure was pregnancy with assessment for variation in risk across different time intervals before, during, and after pregnancy. Medical records were manually reviewed to determine the conception and delivery dates for pregnancies. OUTCOME: Medical record-validated first-time symptomatic kidney stone. ANALYTICAL APPROACH: Conditional and unconditional multivariable logistic regression analysis. RESULTS: Compared with nonpregnant women, the odds of a symptomatic kidney stone forming in women was similar in the first trimester (OR, 0.92; P=0.8), began to increase during the second trimester (OR, 2.00; P=0.007), further increased during the third trimester (OR, 2.69; P=0.001), peaked at 0 to 3 months after delivery (OR, 3.53; P<0.001), and returned to baseline by 1year after delivery. These associations persisted after adjustment for age and race or for diabetes mellitus, hypertension, and obesity. These results did not significantly differ by age, race, time period, or number of prior pregnancies. Having a prior pregnancy (delivery date>1year ago) was also associated with a first-time symptomatic kidney stone (OR, 1.27; P=0.01). LIMITATIONS: Observational study design in a predominantly White population. The exact timing of stone formation cannot be determined. CONCLUSIONS: Pregnancy increases the risk of a first-time symptomatic kidney stone. This risk peaks close to delivery and then improves by 1 year after delivery, though a modest risk of a kidney stone still exists beyond 1 year after delivery.

Comparison of invasive treatment strategies in patients with non-ST elevation acute coronary syndrome: A systematic review and meta-analysis.

Objective: To compare the mortality associated with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with non-ST elevation acute coronary syndrome (NSTE-ACS). Methods: We searched publications from PubMed, Embase, Web of Science, and the Cochrane Library from inception until December 23, 2020. All randomized clinical trials (RCTs) and observational studies comparing all-cause mortality after treatment with CABG versus PCI for patients with NSTE-ACS with minimum follow-up of 6 months were included. Restricted mean survival time (RMST) differences from RCTs and adjusted RMST differences from observational studies were computed by reconstructing time-to-event data from published Kaplan-Meier curves. Extracted hazard ratios (HRs) were also assessed as a secondary analysis. Results: Our systematic review included an individual participant data analysis of 3 RCTs and 8 observational studies. A meta-regression showed a significant association between log-transformed HRs and duration of follow-up (-0.009 [95% confidence interval (CI), -0.002 to -0.016] log-HR per 1-year longer follow-up; P = .037), suggesting a violation of the proportional hazard assumption. Analysis of 6 studies with available RMST data showed a significant inverse association between adjusted RMST differences and cutoff years (slope, -0.028 [95% CI, -0.042 to -0.013] year difference per 1-year longer cutoff; P < .005), suggesting a longer survival benefit in the CABG arm compared with the PCI arm with longer follow-up. Conclusions: There was a trend toward a benefit of CABG compared with PCI in the longer follow-up in patients with NSTE-ACS. A large, well-designed RCT with longer follow-up is needed to obtain definitive evidence on this topic.

Inpatient Burden and Mortality of Methanol Intoxication in the United States.

BACKGROUND: This study aimed to assess inpatient prevalence, characteristics, outcomes, and resource utilization of hospitalization for methanol intoxication in the United States. MATERIALS AND METHODS: A total of 603 hospitalized patients with a primary diagnosis of methanol intoxication from 2003 to 2014 were identified in the National Inpatient Sample database. The inpatient prevalence, clinical characteristics, treatments, outcomes, resource utilization, were investigated. Multivariable logistic regression was performed to identify factors independently associated with in-hospital mortality. RESULTS: The overall inpatient prevalence of methanol intoxication among hospitalized patients was 6.4 cases per 1,000,000 admissions in the United States. The mean age was 38±18 (range 0-86) years. 44% used methanol for suicidal attempts. 20% of admissions required mechanical ventilation, and 40% required renal replacement therapy. The three most common complications were metabolic acidosis (44%), hypokalemia (18%), and visual impairment or optic neuritis (8%). The three most common end-organ failures were renal failure (22%), respiratory failure (21%), and neurological failure (17%). 6.5% died in the hospital. Factors associated with increased in-hospital mortality included alcohol drinking, hypernatremia, renal failure, respiratory failure, circulatory failure, and neurological failure. The mean length of hospital stay was 4.0 days. The mean hospitalization cost per patient was $43,222 CONCLUSION: The inpatient prevalence of methanol intoxication in the United States was 6.4 cases per 1,000,000 admissions. The risk of in-hospital mortality mainly depended on the number of end-organ failures.

The impact of race on hospitalization outcomes for goodpasture's syndrome in the United States: nationwide inpatient sample 2003-2014.

BACKGROUND: Goodpasture's syndrome is a rare and life-threatening autoimmune disease. While Goodpasture's syndrome is well described in Caucasian and Asian populations, its prevalence and outcomes among African American and Hispanic populations are unclear. We conducted this study to assess the impacts of race on hospital outcomes among patients with Goodpasture's syndrome. METHODS: The National Inpatient Sample database was used to identify hospitalized patients with a principal diagnosis of Goodpasture's syndrome from 2003 to 2014. Goodpasture's syndrome patients were grouped based on their race. The differences in-hospital supportive care for organ failure and outcomes between Caucasian, African American, and Hispanic Goodpasture's syndrome patients were assessed using logistic regression analysis. RESULTS: Nine hundred and sixty-four patients were hospitalized with a primary diagnosis of Goodpasture's syndrome. Of these, 786 were included in the analysis: 622 (79%) were Caucasian, 73 (9%) were African American, and 91 (12%) were Hispanic. Hispanics had significantly lower use of plasmapheresis. The use for mechanical ventilation, noninvasive ventilation support, and renal replacement therapy in African Americans and Hispanics were comparable to Caucasians. There was no significant difference in organ failure, sepsis, and in-hospital mortality between African Americans and Caucasians. In contrast, Hispanics had higher in-hospital mortality than Caucasians but similar risk of organ failure and sepsis. CONCLUSION: African American and Hispanic populations account for 9% and 12% of hospitalizations for Goodpasture's syndrome, respectively. While there is no significant difference in in-hospital mortality between African Americans and Caucasians, Hispanics with Goodpasture's syndrome carry a higher in-hospital mortality compared to Caucasians.

Trends in the prevalence of kidney stones in the United States from 2007 to 2016.

The overall prevalence of kidney stones (KS) in the US rose from 3.2% in 1980 to 10.1% in 2016, but the trends in important subgroups have not been reported. We examined the prevalence trends of KS in subgroups of age, sex and race in the US and identified relevant laboratory factors associated with a history of KS using National Health and Nutrition Examination Survey (NHANES) data. We conducted a cross-sectional study among 28,209 US adults aged ≥ 20 years old in the NHANES from 2007 to 2016. We calculated the prevalence of a self-reported history of KS by using weights and standardized to the 2010 US Census population. We also compared relevant laboratory values according to the history of KS. The prevalence of KS decreased from 8.7% in 2007-2008 to 7.2% in 2011-2012 but then increased to 9.0% in 2013-2014 and 10.1% in 2015-2016. However, the overall prevalence of KS increased over 2007-2016 (p-trend = 0.02). Prevalence of KS among men was higher than women. Among men aged 20-79, there were significant quadratic trends in the prevalence of KS. Whereas, the prevalence of KS increased as a linear trend among women aged 20-59 years over 2007-2016. There were no consistent trends in the prevalence of KS by race. The prevalence trend of KS among non-Hispanic whites was 9.8% from 2007 to 2010 then dropped to 7.9% in 2011-2012 and increased to 10.6% in 2013-2014 and 12.1% in 2015-2016. A similar trend was also observed among non-Hispanic blacks. Among Hispanic, the prevalence of KS was 7.6% in 2007-2008 and 7.4% in 2009-2010 and then fluctuated over the next several time periods. For non-Hispanic Asians, the range was 4.4-4.6%. Regarding relevant laboratory factors, after adjusting for sex, race, age, BMI, smoking status, alcohol drinking, history of diabetes and gout, urine albumin-creatinine ratio and serum osmolality were independently associated with the history of KS in women and men. In conclusion, there was substantial variability in KS prevalence across individual 2-year time periods. This variation of period-specific prevalence values emphasizes the importance of looking at long-term trends and using more than a single 2-year cycle in analyses to increase the precision of the estimate. However, there was an overall increase in the prevalence of KS over 2007-2016.

Outcomes of kidney retransplantation in recipients with prior posttransplant lymphoproliferative disorders: An analysis of the 2000-2019 UNOS/OPTN database.

This study utilized the UNOS database to assess clinical outcomes after kidney retransplantation in patients with a history of posttransplant lymphoproliferative disease (PTLD). Among second kidney transplant patients from 2000 to 2019, 254 had history of PTLD in their first kidney transplant, whereas 28,113 did not. After a second kidney transplant, PTLD occurred in 2.8% and 0.8% of patients with and without history of PTLD, respectively (p = .001). Over a median follow-up time of 4.5 years after a second kidney transplant, 5-year death-censored graft failure was 9.5% vs. 12.6% (p = .21), all-cause mortality was 8.3% vs. 11.8% (p = .51), and 1-year acute rejection was 11.0% vs. 9.3% (p = .36) in the PTLD vs. non-PTLD groups, respectively. There was no significant difference in death-censored graft failure, mortality, and acute rejection between PTLD and non-PTLD groups in adjusted analysis and after propensity score matching. We conclude that graft survival, patient survival, and acute rejection after kidney retransplantation are comparable between patients with and without history of PTLD, but PTLD occurrence after kidney retransplantation remains higher in patients with history of PTLD.

Febuxostat as a renoprotective agent for treatment of hyperuricaemia: a meta-analysis of randomised controlled trials.

BACKGROUND: The objective of this meta-analysis of randomised controlled clinical trials (RCT) was to evaluate the effects of febuxostat on kidney function in patients with hyperuricaemia. AIMS: Febuxostat is a xanthine oxidase inhibitor that decreases uric acid production. Recent studies suggested the renoprotective effect of febuxostat among hyperuricaemia patients. The aim of this study was to evaluate the effects of febuxostat on kidney function in patients with hyperuricaemia. METHODS: We conducted electronic searches in PubMed, Embase and Cochrane Central Register of Controlled Trials from January 1960 to July 2019 to identify RCT that examined the effects of febuxostat in adult patients with hyperuricaemia on serum creatinine, estimated glomerular filtration rate (eGFR), albuminuria, blood pressure parameters, major cardiovascular events, diarrhoea, joint pain, stroke and arrhythmia. RESULTS: Nine RCT with 2141 participants were included in this meta-analysis. Compared to placebo, the febuxostat group showed a higher eGFR at 6 months with a weighted mean difference (WMD) of 2.86 mL/min/1.73 m2 (P < 0.001), as well as the end of studies (eGFR WMD 2.69 mL/min/1.73 m2 , P < 0.001). There was also lower serum creatinine (SrCr WMD = -0.04 mg/dL, P < 0.001), reduction in systolic blood pressure (SBP WMD = -1.18 mmHg, P < 0.001) and diastolic blood pressure (DBP WMD = -1.14 mmHg, P = 0.04). There was no statistical difference between febuxostat and placebo in major cardiovascular events, diarrhoea, joint symptoms, stroke events and arrhythmia. Subgroup analysis among chronic kidney disease showed the febuxostat group had higher eGFR than the placebo group (eGFR WMD = 2.69 mL/min/1.73 m2 , P < 0.001). CONCLUSION: Treating hyperuricaemia with febuxostat may slow the progression of chronic kidney disease irrespective of baseline renal function without significantly associated increased risks of major cardiovascular events, diarrhoea, joint symptoms, arrhythmia and stroke, compared to placebo.

Epidemiology of cannabis use and associated outcomes among kidney transplant recipients: A meta-analysis.

OBJECTIVE: Cannabis is the most commonly used recreational drug in the United States, and transplant acceptability for cannabis using candidates varies among transplant centers. However, the prevalence and impact of cannabis use on outcomes of kidney transplant recipients remain unclear. This study aimed to summarize the prevalence and impact of cannabis use on outcomes after kidney transplantation. METHODS: A literature search was performed using Ovid MEDLINE, EMBASE, and The Cochrane Library Databases from inception until September 2019 to identify studies assessing the prevalence of cannabis use among kidney transplant recipients, and reported adverse outcomes after kidney transplantation. Effect estimates from the individual studies were obtained and combined utilizing random-effects, generic inverse variance method of DerSimonian-Laird. RESULTS: A total of four cohort studies with a total of 55 897 kidney transplant recipients were enrolled. Overall, the pooled estimated prevalence of cannabis use was 3.2% (95% CI 0.4%-20.5%). While the use of cannabis was not significantly associated with all-cause allograft failure (OR = 1.31, 95% CI 0.70-2.46) or mortality (OR = 1.52, 95% CI 0.59-3.92), the use of cannabis among kidney transplant recipients was significantly associated with increased death-censored graft failure with pooled OR of 1.72 (95% CI 1.13-2.60). CONCLUSIONS: The overall estimated prevalence of cannabis use among kidney transplant recipients is 3.2%. The use of cannabis is associated with increased death-censored graft failure, but not mortality after kidney transplantation.

Inpatient burden and mortality of heatstroke in the United States.

BACKGROUND: This study aimed to assess inpatient prevalence, characteristics, outcomes, and resource utilisation of hospitalisation for heatstroke in the United States. Additionally, this study aimed to explore factors associated with in-hospital mortalities of heatstroke. METHODS: The 2003-2014 National Inpatient Sample database was used to identify hospitalised patients with a principal diagnosis of heatstroke. The inpatient prevalence, clinical characteristics, in-hospital treatments, outcomes, length of hospital stay, and hospitalisation cost were studied. Multivariable logistic regression was performed to identify independent factors associated with in-hospital mortality. RESULTS: A total of 3372 patients were primarily admitted for heatstroke, accounting for an overall inpatient prevalence of heatstroke amongst hospitalised patients of 36.3 cases per 1 000 000 admissions in the United States with an increasing trend during the study period (P < .001). Age 40-59 was the most prevalent age group. During the hospital stay, 20% required mechanical ventilation, and 2% received renal replacement therapy. Rhabdomyolysis was the most common complication. Renal failure was the most common end-organ failure, followed by neurological, respiratory, metabolic, hematologic, circulatory, and liver systems. The in-hospital mortality rate of heatstroke hospitalisation was 5% with a decreasing trend during the study period (P < .001). The presence of end-organ failure was associated with increased in-hospital mortality, whereas more recent years of hospitalisation was associated with decreased in-hospital mortality. The median length of hospital stay was 2 days. The median hospitalisation cost was $17 372. CONCLUSION: The inpatient prevalence of heatstroke in the United States increased, while the in-hospital mortality of heatstroke decreased.

Zika Virus Disease Comparing Children and Adults in a Dengue-Endemic Setting.

Acute Zika virus (ZIKV) infection may mimic dengue virus (DENV) infection. We aimed to study the clinical difference of ZIKV disease among suspected non-severe DENV patients comparing children and adults. Patients with acute illness suspected of DENV disease plus no evidence of plasma leakage at the Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand, were enrolled from December 2016 to September 2018. Clinical data including DENV rapid diagnostic test (RDT) results were collected. Zika virus diagnosis was confirmed by real-time reverse transcription PCR on urine. Of 291 (180 pediatric and 111 adult) cases enrolled, 27 (10 pediatric and 17 adult) confirmed ZIKV cases were found. Rash was more frequent among pediatric ZIKV than pediatric non-ZIKV cases (100% versus 60%, P = 0.01). Rash, arthralgia, and conjunctivitis were more frequent among adult ZIKV than adult non-ZIKV cases (100% versus 29.8%, 64.7% versus 26.6%, 52.9% versus 9.7%, all P < 0.01, respectively). The median (interquartile range [IQR]) duration of rash was 4.5 (3.0, 7.25) days and 6.0 (4.5, 7.0) days in pediatric and adults ZIKV cases, respectively. Pediatric ZIKV cases had more fever (100% versus 58.5%, P = 0.03) but less arthralgia (20% versus 64.7%, P = 0.04) and less conjunctivitis (10% versus 52.9%, P = 0.04) than adult ZIKV cases. No ZIKV cases with DENV RDTs performed around day 3 of illness were positive for dengue nonstructural protein 1 (NS1) antigen. In dengue-endemic settings, rash and fever in children, and rash, arthralgia, and conjunctivitis in adults, particularly if rash persists for ≥ 3 days, plus negative dengue NS1 Ag during early febrile phase should prompt ZIKV diagnostic testing.

Efficacy and Safety of SGLT-2 Inhibitors for Treatment of Diabetes Mellitus among Kidney Transplant Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: The objective of this systematic review was to evaluate the efficacy and safety profiles of sodium-glucose co-transporter 2 (SGLT-2) inhibitors for treatment of diabetes mellitus (DM) among kidney transplant patients. METHODS: We conducted electronic searches in Medline, Embase, Scopus, and Cochrane databases from inception through April 2020 to identify studies that investigated the efficacy and safety of SGLT-2 inhibitors in kidney transplant patients with DM. Study results were pooled and analyzed utilizing random-effects model. RESULTS: Eight studies with 132 patients (baseline estimated glomerular filtration rate (eGFR) of 64.5 ± 19.9 mL/min/1.73m2) treated with SGLT-2 inhibitors were included in our meta-analysis. SGLT-2 inhibitors demonstrated significantly lower hemoglobin A1c (HbA1c) (WMD = -0.56% [95%CI: -0.97, -0.16]; p = 0.007) and body weight (WMD = -2.16 kg [95%CI: -3.08, -1.24]; p < 0.001) at end of study compared to baseline level. There were no significant changes in eGFR, serum creatinine, urine protein creatinine ratio, and blood pressure. By subgroup analysis, empagliflozin demonstrated a significant reduction in body mass index (BMI) and body weight. Canagliflozin revealed a significant decrease in HbA1C and systolic blood pressure. In terms of safety profiles, fourteen patients had urinary tract infection. Only one had genital mycosis, one had acute kidney injury, and one had cellulitis. There were no reported cases of euglycemic ketoacidosis or acute rejection during the treatment. CONCLUSION: Among kidney transplant patients with excellent kidney function, SGLT-2 inhibitors for treatment of DM are effective in lowering HbA1C, reducing body weight, and preserving kidney function without reporting of serious adverse events, including euglycemic ketoacidosis and acute rejection.

Treatment of C3 Glomerulopathy in Adult Kidney Transplant Recipients: A Systematic Review.

BACKGROUND: C3 glomerulopathy (C3G), a rare glomerular disease mediated by alternative complement pathway dysregulation, is associated with a high rate of recurrence and graft loss after kidney transplantation (KTx). We aimed to assess the efficacy of different treatments for C3G recurrence after KTx. METHODS: Databases (MEDLINE, EMBASE, and Cochrane Database) were searched from inception through 3 May, 2019. Studies were included that reported outcomes of adult KTx recipients with C3G. Effect estimates from individual studies were combined using the random-effects, generic inverse variance method of DerSimonian and Laird., The protocol for this meta-analysis is registered with PROSPERO (no. CRD42019125718). RESULTS: Twelve studies (7 cohort studies and 5 case series) consisting of 122 KTx patients with C3G (73 C3 glomerulonephritis (C3GN) and 49 dense deposit disease (DDD)) were included. The pooled estimated rates of allograft loss among KTx patients with C3G were 33% (95% CI: 12-57%) after eculizumab, 42% (95% CI: 2-89%) after therapeutic plasma exchange (TPE), and 81% (95% CI: 50-100%) after rituximab. Subgroup analysis based on type of C3G was performed. Pooled estimated rates of allograft loss in C3GN KTx patients were 22% (95% CI: 5-46%) after eculizumab, 56% (95% CI: 6-100%) after TPE, and 70% (95% CI: 24-100%) after rituximab. Pooled estimated rates of allograft loss in DDD KTx patients were 53% (95% CI: 0-100%) after eculizumab. Data on allograft loss in DDD after TPE (1 case series, 0/2 (0%) allograft loss at 6 months) and rituximab (1 cohort, 3/3 (100%) allograft loss) were limited. Among 66 patients (38 C3GN, 28 DDD) who received no treatment (due to stable allograft function at presentation and/or clinical judgment of physicians), pooled estimated rates of allograft loss were 32% (95% CI: 7-64%) and 53% (95% CI: 28-77%) for C3GN and DDD, respectively. Among treated C3G patients, data on soluble membrane attack complex of complement (sMAC) were limited to patients treated with eculizumab (N = 7). 80% of patients with elevated sMAC before eculizumab responded to treatment. In addition, all patients who responded to eculizumab had normal sMAC levels after post-eculizumab. CONCLUSIONS: Our study suggests that the lowest incidence of allograft loss (33%) among KTX patients with C3G are those treated with eculizumab. Among those who received no treatment for C3G due to stable allograft function, there is a high incidence of allograft loss of 32% in C3GN and 53% in DDD. sMAC level may help to select good responders to eculizumab.