Pantelis A. Sarafidis

Prevalence and Factors Associated with Hyperkalemia in Predialysis Patients Followed in a Low-Clearance Clinic

BACKGROUND AND OBJECTIVESnRecent studies evaluated the prevalence of hyperkalemia and related risk factors in patients with CKD of various stages, but there is limited relevant information in predialysis patients. This study aimed to examine the prevalence and factors associated with hyperkalemia in the structured environment of a low-clearance clinic.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnIn a cross-sectional fashion over a prespecified period of 4 months, information on serum potassium and relevant laboratory variables, comorbidities, medications, and dietician input in patients with advanced CKD under follow-up in the low-clearance clinic of our department was recorded. Univariate and multiple logistic regression analyses were used to identify factors associated with serum potassium ≥ 5.5 meq/L.nnnRESULTSnThe study population consisted of 238 patients aged 66.2 ± 4.2 years with estimated GFR of 14.5 ± 4.8 ml/min per 1.73 m(2). The prevalence of hyperkalemia. defined as potassium > 5.0, ≥ 5.5, and ≥ 6.0 meq/L., was at 54.2%, 31.5%, and 8.4%, respectively. In univariate comparisons, patients with potassium ≥ 5.5 meq/L had significantly higher urea and lower estimated GFR and serum bicarbonate; also, they were more often using sodium bicarbonate and had received potassium education and attempts for dietary potassium lowering. Use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was not associated with hyperkalemia. In multivariate analyses, estimated GFR<15 ml/min per 1.73 m(2) and sodium bicarbonate use were independently associated with hyperkalemia.nnnCONCLUSIONSnThe prevalence of hyperkalemia in predialysis patients with CKD is high. Even at this range of renal function, low estimated GFR seems to be the most important factor associated with hyperkalemia among the wide range of demographic, clinical, and laboratory characteristics studied.

Suprarenal graft fixation in endovascular abdominal aortic aneurysm repair is associated with a decrease in renal function

INTRODUCTIONnSuprarenal endograft fixation is routinely used in the endovascular repair of abdominal aortic aneurysms (EVAR) to enhance proximal endograft attachment but can be associated with an adverse outcome in renal function. This prospective study assessed the effect of suprarenal fixation on serum creatinine concentration and estimated glomerular filtration rate (eGFR), calculated by the Modified Diet in Renal Disease equation, 12 months after elective EVAR.nnnMETHODSnPatients undergoing elective EVAR were divided into suprarenal vs infrarenal fixation groups matched for age, sex, smoking, and aneurysm diameter. Serum creatinine and eGFR were measured at baseline, 6, and 12 months.nnnRESULTSnIncluded were 92 patients (two women) with a mean age of 71 ± 7 years, with 46 in each group. No device-related complications were noted. Serum creatinine did not differ significantly between groups at 6 (P = .24) or 12 (P = .08) months but significantly increased in the suprarenal group at 12 months (1.08 ± 0.36 to 1.16 ± 0.36 mg/dL; P < .001) vs baseline. The eGFR (mL/min/1.73 m(2)) did not differ significantly at baseline between the suprarenal (85 ± 27) and infrarenal (80 ± 28; P = .33) groups or at 6 months (88 ± 29 vs 77 ± 24, respectively; P = .07). At 12 months, the suprarenal group had a lower eGFR (73 ± 23) than the infrarenal group (84 ± 26; P = .027). The eGFR at 12 months showed a significant decrease in the suprarenal (80 ± 28 to 73 ± 23; P < .001) but not in the infrarenal group (85 ± 27 to 84 ± 26; P = .48). The drop in eGFR differed significantly at 12 months in the infrarenal vs the suprarenal (0.82 vs -6.94; P < .001) group. No patient progressed to end-stage renal disease or disclosed a drop in eGFR > 30%.nnnCONCLUSIONSnIn contrast to previous studies, this study suggests that suprarenal endograft fixation in elective EVAR is associated with a drop in eGFR at 12 months.

Impaired renal function is associated with mortality and morbidity after endovascular abdominal aortic aneurysm repair

BACKGROUNDnRenal function may be associated with poor outcome following endovascular abdominal aortic aneurysm repair (EVAR), but this relationship has not been adequately investigated. The aim of this study is to evaluate the association of estimated glomerular filtration rate (eGFR) with cardiovascular events and all-cause mortality after EVAR.nnnMETHODSnProspective cohort study of patients undergoing elective EVAR; eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration formula, and patients were divided in four groups (eGFR ≥ 90 mL/min/1.73 m(2), group 1; 60-89, group 2; 30-59, group 3; <30, group 4). Composite end point consisted of death, nonfatal myocardial infarction, stroke, and vascular complications. Kaplan-Meier curves were constructed, and between-group comparisons were performed adjusted for variables that differed at baseline.nnnRESULTSnA total of 383 patients (mean age, 69 ± 8 years; mean abdominal aortic aneurysm diameter, 6.2 ± 1.4 cm) were included. Over a mean follow-up of 34 ± 12 months, the following events occurred: 20 deaths (5.2%), 15 nonfatal myocardial infarctions (3.9%), 9 nonfatal strokes (2.3%), and 7 peripheral vascular complications (1.8%). Patients with an eGFR <30 had the highest mortality (35%) and incidence of complications (80%) as per the end point (P = .009 and P < .001, respectively). Adjusted Cox-regression analysis showed that a higher eGFR at baseline by 1 mL/min/1.73 m(2) was associated with a 5% lower likelihood of complications as per the end point (P < .001; hazard ratio, 0.95; 95% confidence interval, 0.94-0.97) and a 6% lower likelihood of death (P < .001; hazard ratio, 0.94; 95% confidence interval, 0.92-0.97).nnnCONCLUSIONSnImpaired renal function is associated with an increase in cardiovascular events and mortality following elective EVAR.

Prevalence, Patterns of Treatment, and Control of Hypertension in Predialysis Patients with Chronic Kidney Disease

Background/Aims: Data on the prevalence, treatment and control of hypertension in patients with advanced chronic kidney disease (CKD) are limited. This study aimed to examine the above factors in a cohort of predialysis patients. Methods: During a period of 4 months, we recorded information on blood pressure (BP), comorbidities, medications and related parameters of patients followed up in the Low-Clearance Clinic of our Department. Control rates of hypertension were calculated at two thresholds: <130/80 and <140/90 mm Hg. Univariate and multiple linear regression analyses were employed to assess factors associated with BP control. Results: In the population studied [n = 238, males 58.4%, age 66.21 ± 4.2 years (mean ± SD), estimated glomerular filtration rate 14.5 ± 4.8 ml/min/1.73 m2], the prevalence of hypertension was 95.0%. Treatment rate among hypertensives was at 99.1%. On average, 3.04 ± 1.32 antihypertensive drugs were used, ranging from 1 to 7 agents. BP control rates at the <130/80 and <140/90 mm Hg thresholds were 26.5% and 48.2%, respectively. The systolic goal was achieved in 31.0% and 50.4%, whereas the diastolic goal was achieved in 67.7% and 91.2% of patients, respectively. In multivariate analysis, only black race was independently and inversely related with hypertension control (β = –0.187, p = 0.030). No specific antihypertensive class showed independent associations with control. Conclusions: Hypertension is highly prevalent in predialysis CKD patients. An almost universal treatment, employing a multi-agent regime, can help towards improved rates of control. Systolic BP is the main barrier to successful control and black race is associated with poorer control rates.

Intra-individual variability of serum hepcidin-25 in haemodialysis patients using mass spectrometry and ELISA

BACKGROUNDnMeasurement of serum hepcidin levels may provide a useful alternative to the current methods of determining iron status in chronic haemodialysis (HD) patients. However, the biological variability of this pivotal regulator of iron homeostasis is unclear, and the impact of inflammation, dialysis clearance and iron therapy on hepcidin variability has not been established.nnnMETHODSnTwo independent studies in chronic HD patients were conducted; serum hepcidin levels were measured at the start of dialysis sessions in 20 UK patients and in 43 Dutch patients by mass spectrometry (MS). Samples from UK patients were also analysed by a competitive enzyme-linked immunosorbent assay (cELISA). Coefficient of variance (CV(1)) was calculated and potential factors affecting CV(1) were also examined.nnnRESULTSnThe median CV(1) (inter-quartile range) was 23% (17-28) for the UK MS, 26% (17-48) for the Dutch MS and 23% (17-39) for the UK cELISA. The CV(1) was similar in those patients receiving and those not receiving regular intravenous iron. The CV(1) was not associated with the degree of inflammation. Hepcidin levels were higher following an inter-dialytic period of 3 versus 2 days (P = 0.02).nnnCONCLUSIONSnThese findings suggest considerable variability of serum hepcidin levels in HD patients. Inflammation and the use of iron did not impact on the degree of variability, and hepcidin levels were higher after an inter-dialytic period of 3 versus 2 days. These findings need to be taken into account in future studies assessing the utility of serum hepcidin as a guide to the use of iron or erythropoiesis-stimulating agents therapy.

Compliance With a Structured Weight Loss Program Is Associated With Reduced Systolic Blood Pressure in Obese Patients With Chronic Kidney Disease

BACKGROUNDnThe effectiveness of lifestyle-based weight loss programs in obese patients with chronic disease has not been widely studied. This study examined the effectiveness of a weight management program (WMP), and sought to determine factors associated with successful weight loss in obese patients with chronic kidney disease (CKD).nnnMETHODSnIn this prospective cohort study, all patients with a body mass index (BMI) of >30 kg/m(2) referred to our clinic from January 2005 to December 2008 and who commenced a structured WMP of an energy-reduced renal diet, exercise, and pharmacotherapy were included in the analyses. Changes in body weight and associated variables up to 24 months were assessed with intention-to-treat mixed linear models and predictors of weight loss were identified with multiple linear regression.nnnRESULTSnOne hundred and thirty-five patients (56% male), of mean age 52.2 years and BMI 36.4 kg/m(2) commenced the WMP. Significant weight loss was achieved for all patients at 6, 12, 18, and 24 months. Weight loss at 12 months was predicted by compliance and age, but not by baseline BMI, blood pressure (BP), stage of CKD or pharmacotherapy use. Greater compliance was associated with decreased systolic BP, with no change in mean antihypertensive medication dose.nnnCONCLUSIONSnSignificant weight loss was achieved, demonstrating the effectiveness of the WMP, and compliance with a structured program improved weight loss and systolic BP.

Obesity and iron deficiency in chronic kidney disease: the putative role of hepcidin

Hepcidin is a 25-amino acid peptide with a defensinlike structure that is primarily synthesized in hepatocytes [1, 2]. It was independently isolated ~10 years ago by two groups seeking peptides with antimicrobial activity in urine [3] and plasma [4]. Hepcidin was originally shown to have a weak selective antimicrobial activity against certain bacteria; thus, its name reflected the site of major tissue expression (‘hep’ for hepatocyte) and its antimicrobial properties (‘cidin’) [1, 2]. However, soon after its isolation, independent studies suggested an important role of hepcidin in iron regulation [5, 6]; currently, a large body of evidence strongly supports the role of hepcidin as the ‘master regulator’ of iron homeostasis [2, 7]. Hepcidin reduces the efflux of recycled iron from both splenic and hepatic macrophages and also inhibits iron absorption from the gut [1, 2] (Figure 1). The cellular mechanisms of hepcidin action seem to be tissue specific. In reticuloendothelial macrophages, hepcidin was previously shown to bind to the cellular iron export channel ferroportin, inducing its internalization and subsequent degradation [8, 9]. Recent data suggest that in intestinal 50 Nephrol Dial Transplant (2012): Editorial Reviews

Ambulatory blood pressure monitoring: an invaluable tool comes of age for patients with chronic kidney disease?

ditionally, hypertension diagnosis is based on clinic BP measurements during three separate visits, while other available strategies, such as home measurements and ambulatory BP monitoring (ABPM), the ‘gold standard’ of diagnosis, are reserved for uncertain cases, including suspicion of ‘white-coat’ and ‘masked’ hypertension [2] . A very important recent study [9] compared the costeffectiveness of the three aforementioned strategies for diagnosis of essential hypertension. The authors performed a Markov-model analysis on a hypothetical primary-care population older than 40 years with a screening BP reading 1 140/90 mm Hg. They concluded that ABPM was clearly the most cost-effective strategy, producing cost-savings for all genderand age-stratified groups studied and gains in quality-adjusted life years (QALYs) for older subjects. Clearly, the greater cost-effectiveness of ABPM was due to higher diagnostic accuracy in detecting hypertension [10] , leading to effective treatment and associated reductions in cardiovascular events in more hypertensive individuals, and less unnecessary treatment of people without hypertension. Several methodological strengths support the validity of this study’s conclusions [9] . The model was run separately for ten genderand age-stratified groups; the study time horizon was particularly long and a reasonable annual discount rate was applied; periodic rechecking of BP was incorporated to allow for the possibility that peoHypertension is the most common chronic disease in the Western world, with a documented prevalence of 25– 30% of adults in developed societies [1] , and a major risk factor for cardiovascular events; thus, it is no wonder why it is considered the most important attributable cause of death worldwide [2] . Chronic kidney disease (CKD), on the other hand, is another major public health issue; it is also a potent risk factor for cardiovascular morbidity and mortality, and it has a prevalence of around 10% of adults, with incident end-stage renal disease (ESRD) increasing much faster than expected from CKD growth [3] . Elevated blood pressure (BP) is an established cause, but can also be a consequence of kidney injury [4] , and hypertension prevalence rates are 1 90% in individuals with advanced CKD [5] . Thus, all previous major guidelines in the field have put increased emphasis on the quick diagnosis and aggressive control of BP in CKD patients [2, 4, 6, 7] . Despite substantial efforts from health authorities and effective treatment options being available for decades, BP control rates in the general population remain low in many countries [8] and they are even worse in CKD patients [5] . Of note, reduced hypertension awareness leading to inadequate treatment is proposed as a major factor contributing to poor control, both in the general population and individuals with CKD [5, 8] , highlighting the need for proper diagnosis of elevated BP levels. TraPublished online: February 15, 2012 Nephrology American Journal of

Serum Hemojuvelin and Hepcidin Levels in Chronic Kidney Disease

Background: Hemojuvelin (HJV) has recently emerged as one of a number of significant regulators of iron homeostasis and hepcidin expression. Recently, an immunoassay has been developed to measure circulating levels of soluble HJV (sHJV). The aim of this study was to measure serum hepcidin and sHJV levels in a chronic kidney disease (CKD) population. Methods: A total of 93 patients participated in the study (31 hemodialysis, 31 non-dialysis, 31 transplant recipients), and were matched for age and gender. Serum samples were taken for measurement of hepcidin-25 and sHJV, along with standard hematological, biochemical and inflammatory markers, and univariate/multivariate analyses were performed. Results: Serum sHJV levels were markedly elevated in the hemodialysis patients (2,619 ± 1,445 ng/ml) compared to the CKD (590 ± 344 ng/ml) and transplant recipients (870 ± 638 ng/ml) (p < 0.001), normal range 370–890 ng/ml. There was a strong correlation between serum ferritin and sHJV, which remained after adjustment for potential confounders (beta 0.92, p < 0.001). In the univariate analysis, sHJV levels correlated with serum hepcidin but this was not evident in the multivariate analysis. No associations were seen between sHJV and markers of inflammation or eGFR. Conclusions: sHJV is elevated in hemodialysis patients compared to non-dialysis CKD patients. There was no association between sHJV and eGFR (in the non-dialysis groups), suggesting that factors other than decreased renal clearance are responsible for the high sHJV levels. The strong association between sHJV and ferritin suggests an interdependent relationship, although further studies are required to elucidate the possible mechanism(s) for this.

Cardiorenal disease development under chronic renin–angiotensin–aldosterone system suppression

Drugs suppressing the renin-angiotensin-aldosterone system (RAAS) are now widely used to treat patients all along the cardiorenal continuum. It supposes that many patients, in particular those with arterial hypertension are treated with converting-enzyme inhibitors and angiotensin receptor blockers for years during which the development and prograssion of cardiorenal disease can be observed. The meaning of this progression in the presence of RAAS suppression requires to be clarified and to be treated in order to diminish the velocity of progression of cardiorenal disease.