Liam F. Casserly

Independent and conjoint associations of gout and hyperuricaemia with total and cardiovascular mortality

BACKGROUND Gout and serum uric acid are associated with mortality but their simultaneous contributions have not been fully evaluated in the general population. PURPOSE To explore the independent and conjoint relationships of gout and uric acid with mortality in the US population. METHODS Mortality risks of gout and serum uric acid were determined for 15 773 participants, aged 20 years or older, in the Third National Health and Nutrition Examination Survey by linking baseline information collected during 1988-1994 with mortality data up to 2006. Multivariable Cox proportional hazards regression determined adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for each exposure and all analyses were conducted in 2011 and 2012. RESULTS Compared with subjects without a history of gout, the multivariable HR for subjects with gout were 1.42 (CI 1.12-1.82) for total and 1.58 (CI 1.13-2.19) for cardiovascular mortality. Adjusted HRs per 59.5 µmol/l (1 mg/dl) increase in uric acid were 1.16 (CI 1.10-1.22) for total and cardiovascular mortality and this pattern was consistent across disease categories. In the conjoint analysis, the adjusted HRs for mortality in the highest two uric acid quartiles were 1.64 (CI 1.08-2.51) and 1.77 (CI 1.23-2.55), respectively, for subjects with gout, and were 1.09 (CI 0.87-1.37) and 1.37 (CI (1.11-1.70), respectively, for subjects without gout, compared with those without gout in the lowest quartile. A similar pattern emerged for cardiovascular mortality. CONCLUSION Gout and serum uric acid independently associate with total and cardiovascular mortality. These risks increase with rising uric acid concentrations.

Predictive Parameters of Arteriovenous Fistula Functional Maturation in a Population of Patients with End-Stage Renal Disease

Introduction With increasing numbers of patients diagnosed with ESRD, arteriovenous fistula (AVF) maturation has become a major factor in improving both dialysis related outcomes and quality of life of those patients. Compared to other types of access it has been established that a functional AVF access is the least likely to be associated with thrombosis, infection, hospital admissions, secondary interventions to maintain patency and death. Aim Study of demographic factors implicated in the functional maturation of arteriovenous fistulas. Also, to explore any possible association between preoperative haematological investigations and functional maturation. Methods We performed a retrospective chart review of all patients with ESRD who were referred to the vascular service in the University Hospital of Limerick for creation of vascular access for HD. We included patients with primary AVFs; and excluded those who underwent secondary procedures. Results Overall AVF functional maturation rate in our study was 53.7% (52/97). Female gender showed significant association with nonmaturation (P = 0.004) and was the only predictor for non-maturation in a logistic regression model (P = 0.011). Patients who had history of renal transplant (P = 0.036), had relatively lower haemoglobin levels (P = 0.01) and were on calcium channel blockers (P = 0.001) showed better functional maturation rates. Conclusion Female gender was found to be associated with functional non-maturation, while a history kidney transplant, calcium channel-blocker agents and low haemoglobin levels were all associated with successful functional maturation. In view of the conflicting evidence in the literature, large prospective multi-centre registry-based studies with well-defined outcomes are needed.

Transferrin saturation ratio and risk of total and cardiovascular mortality in the general population

Background: The transferrin saturation (TSAT) ratio is a commonly used indicator of iron deficiency and iron overload in clinical practice but precise relationships with total and cardiovascular mortality are unclear. Purpose: To better understand this relationship, we explored the association of TSAT ratio (serum iron/total iron binding capacity) with mortality in the general population. Methods: The relationships of TSAT ratio with total and cardiovascular mortality were explored in 15 823 subjects age 20 and older from the Third National Health and Nutrition Examination Survey (1988–94). All subjects had vital status assessed through to 2006. Results: During follow-up, 9.7% died of which 4.4% were from cardiovascular disease. In unadjusted analysis, increasing TSAT ratio was inversely associated with mortality. With adjustment for baseline demographic and clinical characteristics, the TSAT–mortality relationship followed a j-shaped pattern. Compared with the referent group [ratio 23.7–31.3%: hazard ratio (HR) =1.00], subjects in the lowest two quartiles, <17.5 % and 17.5–23.7 %, experienced significantly higher mortality risks of 1.45 (1.19–1.77) and 1.27 (1.06–1.53), respectively, whereas subjects in the highest quartile, >31.3 %, experienced significantly higher mortality risks of 1.23 (1.01–1.49). The pattern of association was more pronounced for cardiovascular mortality with significantly higher mortality risks for the lowest two quartiles [HR = 2.09 (1.43–3.05) and 1.90 (1.33–2.72), respectively] and highest quartile HR = 1.59 (1.05–2.40). Conclusions: Both low and high TSAT ratios are significantly and independently associated with increased total and cardiovascular mortality. The optimal TSAT ratio associated with the greatest survival is between 24% and 40%.

Do patient-reported measures of symptoms and health status predict mortality in hemodialysis? An assessment of POS-S Renal and EQ-5D

Introduction Experience with the use of patient‐reported outcome measures such as EQ‐5D and the symptom module of the Palliative care Outcome Scale—Renal Version (POS‐S Renal) as mortality prediction tools in hemodialysis is limited.

Plasma fibrinogen associates independently with total and cardiovascular mortality among subjects with normal and reduced kidney function in the general population

BACKGROUND The contribution of novel risk factors to mortality in chronic kidney disease remains controversial. AIM To explore the association of plasma fibrinogen with mortality among individuals with normal and reduced kidney function. METHODS We identified 9184 subjects, age 40 and over from the Third National Health and Nutrition Examination Survey (1988-94) with vital status assessed through 2006. Plasma fibrinogen was modeled as continuous variable and in quartile groups (0 to <7.7, 7.7 to <9.0, 9.0 to <10.5 and ≥ 10.5 µmol/l) with total and cardiovascular mortality across categories of glomerular filtration rate (eGFR); <60, 60-90, >90 ml/min/1.73 m(2) using Cox regression. RESULTS In multivariate analysis, the adjusted hazard ratio (HR) per 1 µmol/l (34 mg/dl) increase in fibrinogen was 1.07 [95% confidence interval (CI) 1.04-1.09] for total mortality and 1.06 (95% CI 1.03-1.09) for cardiovascular mortality. The adjusted HR for total mortality was 1.05 (1.01-1.09) for subjects with eGFR 60-90 ml/min/1.73 m(2) and 1.06 (1.02-1.10) for subjects with eGFR <60 ml/min/1.73 m(2). Subjects in the highest quartiles within each eGFR category; >90, 60-90 and <60 ml/min/1.73 m(2) experienced HRs of 1.45 (95% CI 1.03-2.03), 1.35 (95% CI 1.00-1.83) and 1.72 (95% CI 1.14-2.58), respectively, compared with subjects in the lowest quartile group. The patterns were similar for cardiovascular mortality. CONCLUSIONS Plasma fibrinogen associates with mortality among subjects with mild to moderate kidney impairment as it does in subjects with normal kidney function and should be considered a therapeutic target for cardiovascular risk reduction.

Uncommon side effect with a commonly used targeted agent: sunitinib-induced nephrotic syndrome in a patient with metastatic renal cell carcinoma

The authors report the case of a 67-year-old woman with metastatic renal cell carcinoma (RCC) without prior nephrectomy, who had received long-term exposure (38 months) to the oral multi-targeted tyrosine kinase inhibitor (TKI), sunitinib. She had a sustained clinical and radiological response to her therapy, but had this therapy discontinued due to the rare development of nephrotic syndrome.

Ciprofloxacin-associated choreoathetosis in a haemodialysis patient.

This report describes a case of drug-associated choreoathetosis in a patient receiving ciprofloxacin. A 72-year-old haemodialysis patient presented with a 4-day history of progressive weakness, restlessness and involuntary movements of all limbs. He had been prescribed ciprofloxacin 500 mg twice daily for a lower respiratory tract infection 7 days previously. He had generalised choreoathetosis affecting both upper and lower limbs. The temporal relationship with drug exposure and a dose which was on the upper limit for his renal impairment implicated ciprofloxacin as the culprit. His symptoms completely resolved within 1 week of drug withdrawal and never recurred subsequently.

Declining Mortality Rates despite Increases in Clinical Coronary Artery Disease among US Dialysis Patients: A National Registry Study

Background/Aims: Coronary artery disease (CAD) is a major risk factor for death on dialysis. The objective of this study was to compare prevalent trends and patterns of survival in successive national cohorts. Methods: National data on 823,753 incident dialysis patients, aged 18 and over, were analyzed from the US Renal Data System from 1995 to 2004. The prevalence of CAD was compared across calendar years by sex and race categorized as; White, Black, Asian and Native American/Alaskan Native (Native Am). Two-year mortality rates were determined for annual cohorts and multivariable Cox regression compared hazard ratios (HR) and 95% confidence intervals. Results: From 1995 to 2004, the annual prevalence of CAD increased significantly in men from 25.2 to 30.1% and in women from 22.1 to 25.3%, p < 0.001. For men, the rise in prevalence was largely due to increases among Black men and older White men. For women, the pattern was similar. During this period, death rates decreased significantly from 379 to 348 and from 396 to 357 per 1,000 person-years in men and women respectively. Multivariate analysis identified significant reductions in mortality with advancing calendar year for White (HR 0.98 (0.98-0.99)), Asian (HR 0.93 (0.91-0.96)), and Native Am men (HR 0.95 (0.90-0.99)), and for White (HR 0.99 (0.98-0.99)) and Native Am women (HR 0.93 (0.89-0.98)). No significant trends were observed for Black patients. Conclusions: Despite a rising burden of CAD among incident US dialysis patients, mortality rates have fallen for most groups. Substantial racial disparities remain.

Outcomes of kidney transplantation in Alport syndrome compared with other forms of renal disease

Abstract Introduction: Alport syndrome is an inherited renal disease characterized by hematuria, renal failure, hearing loss and a lamellated glomerular basement membrane. Patients with Alport syndrome who undergo renal transplantation have been shown to have patient and graft survival rates similar to or better than those of patients with other renal diseases. Methods: In this national case series, based in Beaumont Hospital Dublin, we studied the cohort of patients who underwent renal transplantation over the past 33 years, recorded prospectively in the Irish Renal Transplant Registry, and categorized them according to the presence or absence of Alport syndrome. The main outcomes assessed were patient and renal allograft survival. Results: Fifty-one patients diagnosed with Alport syndrome in Beaumont Hospital received 62 transplants between 1982 and 2014. The comparison group of non-Alport patients comprised 3430 patients for 3865 transplants. Twenty-year Alport patient survival rate was 70.2%, compared to 44.8% for patients with other renal diseases (p = .01). Factors associated with patient survival included younger age at transplantation as well as differences in recipient sex, donor age, cold ischemia time, and episodes of acute rejection. Twenty-year graft survival was 46.8% for patients with Alport syndrome compared to 30.2% for those with non-Alport disease (p = .11). Conclusions: Adjusting for baseline differences between the groups, patients with end-stage kidney disease (ESKD) due to Alport syndrome have similar patient and graft survival to those with other causes of ESKD. This indicates that early diagnosis and management can lead to favorable outcomes for this patient cohort.

Acetaminophen-induced anion gap metabolic acidosis secondary to 5-oxoproline: a case report.

Introduction5-oxoproline (pyroglutamic acid), an organic acid intermediate of the gamma-glutamyl cycle, is a rare cause of high anion gap metabolic acidosis. Acetaminophen and several other drugs have been implicated in the development of transient 5-oxoprolinemia in adults. We believe that reporting all cases of 5-oxoprolinemia will contribute to a better understanding of this disease. Here, we report the case of a patient who developed transient 5-oxoprolinemia following therapeutic acetaminophen use.Case presentationA 75-year-old Caucasian woman was initially admitted for treatment of an infected hip prosthesis and subsequently developed transient high anion gap metabolic acidosis. Our patient received 40g of acetaminophen over a 10-day period. After the more common causes of high anion gap metabolic acidosis were excluded, a urinary organic acid screen revealed a markedly increased level of 5-oxoproline. The acidosis resolved completely after discontinuation of the acetaminophen.Conclusion5-oxoproline acidosis is an uncommon cause of high anion gap metabolic acidosis; however, it is likely that it is under-diagnosed as awareness of the condition remains low and testing can only be performed at specialized laboratories. The diagnosis should be suspected in cases of anion gap metabolic acidosis, particularly in patients with recent acetaminophen use in combination with sepsis, malnutrition, liver disease, pregnancy or renal failure. This case has particular interest in medicine, especially for the specialties of nephrology and orthopedics. We hope that it will add more information to the literature about this rare condition.