Adam Rumjon

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

BACKGROUND AND OBJECTIVES Recent 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. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In 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. RESULTS The 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. CONCLUSIONS The 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.

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

BACKGROUND Measurement 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. METHODS Two 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. RESULTS The 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). CONCLUSIONS These 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.

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.

Statement of Concern about a Commercial Assay Used to Measure Soluble Hemojuvelin in Humans Reply

pany to detect and measure recombinant human HJV protein and sHJV in cell-conditioned media from HJV-transfected cells. We examined the ability of the USCN ELISA to detect known quantities of fulllength, purified recombinant human HJV protein (hHJV.his; RD USCN Life Science Inc., Wuhan, China). In order to assess the performance of this ELISA, we acquired this kit from the same comPublished online: September 22, 2012

A novel technique for repositioning, under local anesthetic, malfunctioning and migrated peritoneal dialysis catheters.

3. Kang EW, Nam JY, Yoo TH, Shin SK, Kang SW, Han DS, et al. Clinical implications of subclinical hypothyroidism in continuous ambulatory peritoneal dialysis patients. Am J Nephrol 2008; 28:908–13. 4. Tatar E, Sezis Demirci M, Kircelli F, Gungor O, Yaprak M, Asci G, et al. The association between thyroid hormones and arterial stiffness in peritoneal dialysis patients. Int Urol Nephrol 2012; 44:601–5. 5. Ng YY, Wu SC, Lin HD, Hu FH, Hou CC, Chou YY, et al. Prevalence of clinical and subclinical thyroid disease in a peritoneal dialysis population. Perit Dial Int 2012; 32:86–93. 6. Carrero JJ, Qureshi AR, Axelsson J, Yilmaz MI, Rehnmark S, Witt MR, et al. Clinical and biochemical implications of low thyroid hormone levels (total and free forms) in euthyroid patients with chronic kidney disease. J Intern Med 2007; 262:690–701. doi:10.3747/pdi.2012.00098

Contents Vol. 124, 2013

Chronic Kidney Disease and Hypertension A. Levin, Vancouver, B.C. R. Gansevoort, Groningen Acute Kidney Injury R. Mehta, San Diego, Calif. N. Kolhe, Derby Dialysis J. Daugirdas, Chicago, Ill. C. Hutchison, Hawkes Bay C. Fraansen, Groningen Patient Subjective Experience, Healthcare Delivery and Innovation in Practice R. Fluck, Derby E. Brown, London Crossover States with Non-Renal Organ Systems C. Chan, Toronto, Ont. T. Breidthardt, Basel N. Selby, Derby Transplantation A. Chandraker, Boston, Mass. A. Salama, London Editor-in-Chief

Obesity does not influence hepcidin and hemojuvelin levels in hemodialysis patients.

Background/Aims: Clinical studies have shown increased levels of hepcidin causing functional iron deficiency in obese individuals. This study examined whether obesity contributes to increased hepcidin and hemojuvelin levels in adult hemodialysis patients. Methods: In a case-control design, 37 obese [body mass index (BMI) >30 kg/m2] stable hemodialysis patients and 37 patients with normal BMI (20-25 kg/m2), matched for age, gender and race, who fulfilled a strict set of inclusion and exclusion criteria were included in the study. Serum hepcidin and hemojuvelin, markers of iron status and inflammation, and routine hematological and biochemical variables were measured on samples obtained prior to the midweek hemodialysis session. Results: Obese and nonobese patients (BMI 35.1 ± 3.4 vs. 22.8 ± 1.4 kg/m2; p < 0.001) were similar with regard to basic comorbidities and use of erythropoietin and iron. Levels of hemoglobin, hypochromic red cells and reticulocytes were similar in the two groups. Serum iron and transferrin saturation levels were on the low side and not different between obese and lean individuals; total iron-binding capacity showed a trend towards higher levels in obese patients (48.4 ± 8.3 vs. 44.9 ± 7.4 μmol/l; p = 0.065). Levels of serum ferritin (651 ± 302 vs. 705 ± 327 μg/l; p = 0.46), hepcidin (118.3 ± 67.7 vs. 119.3 ± 78.0 ng/ml; p = 0.95) and hemojuvelin (1.90 ± 1.11 vs. 1.94 ± 1.24 mg/l; p = 0.90) were high but similar between the two groups. Serum hepcidin showed a significant correlation only with ferritin (r = 0.287, p = 0.013). Conclusions: Hepcidin and hemojuvelin levels are already considerably elevated in dialysis patients, but obesity does not have an additional impact. Further studies should examine whether increased weight contributes towards hepcidin elevation in predialysis individuals, in whom there is a lesser burden of systemic inflammation.