Associations Between Dietary Potassium Intake From Different Food Sources and Hyperkalemia in Patients With Chronic Kidney Disease.

OBJECTIVE: Previous studies reported mixed results on associations between dietary potassium intake and hyperkalemia in patients with chronic kidney disease (CKD). This study investigated the association between potassium intake from different food sources and hyperkalemia in patients with non-dialysis-dependent CKD. METHODS: A total of 285 patients were recruited at a university hospital and 2 city hospitals in Tokyo. Dietary potassium intake was estimated by a validated diet history questionnaire. Associations of potassium intake from all foods and individual food groups with serum potassium were examined by multivariable linear regression among potassium binder nonusers. An association between tertile groups of potassium intake and hyperkalemia, defined as serum potassium ≥5.0 mEq/L, was evaluated by multivariable logistic regression. RESULTS: Among 245 potassium binder nonusers, total potassium intake was weakly associated with serum potassium (regression coefficient = 0.147, 95% confidence interval (CI): 0.018-0.277), while an association with hyperkalemia was not observed (first vs third tertile: adjusted odds ratio = 0.98, 95% CI: 0.29-3.26). As for food groups, potassium intakes from potatoes, pulses, and green/yellow vegetables were positively associated with serum potassium. Patients in the highest tertile of potassium intake from potatoes had higher odds of hyperkalemia as compared to those in the lowest tertile (adjusted odds ratio = 4.12, 95% CI: 1.19-14.34). CONCLUSION: Total potassium intake was weakly associated with serum potassium, but not with hyperkalemia. Potassium intake from potatoes was associated with hyperkalemia. These findings highlight the importance of considering food sources of potassium in the management of hyperkalemia in CKD.

Post-infectious Proliferative Glomerulonephritis with Monoclonal Immunoglobulin G Deposits Associated with Complement Factor H Mutation.

A 55-year-old man developed rapidly progressive glomerulonephritis and nephrotic syndrome. A kidney biopsy specimen showed diffuse proliferative and crescentic glomerulonephritis with monoclonal IgG1κ, humps, and nephritis-associated plasmin receptor, indicating infection-associated proliferative glomerulonephritis with monoclonal immunoglobulin G deposits (PGNMID). Despite dialysis-dependent renal failure, symptomatic therapy resulted in spontaneous recovery of the renal function, mimicking post-infectious glomerulonephritis (PIGN). A heterozygous complement factor H mutation was detected by comprehensive genetic testing of alternative pathway regulatory genes, which might lead to persistent infection-triggered alternative pathway activation and account for severe glomerulonephritis. Post-infectious PGNMID and PIGN might share common clinical presentations and pathogenesis related to the complement pathway.

Early response to erythropoiesis-stimulating agents in non-dialysis chronic kidney disease patients.

BACKGROUND: Renal anemia complicated with chronic kidney disease is usually treated with erythropoiesis-stimulating agents (ESAs). However, few studies have compared the early response of hemoglobin (Hb) to different kinds of ESAs. METHODS: The effects of three types of ESAs-epoetin alfa or beta (EPO), darbepoetin alfa (DPO), and epoetin beta pegol (EPObp)-on renal anemia were followed in 416 pre-dialysis chronic kidney disease (CKD) patients. After the initial 12-week administration of ESAs, ΔHb/ESA dose/kg was calculated as an index of efficacy of each ESA. Furthermore, independent variables associated with ΔHb/ESA dose/kg (dependent variable) were determined using multiple linear regression analysis. The ten independent variables selected for analysis were: presence of diabetic nephropathy, estimated glomerular filtration rate (eGFR), Hb, albumin, iron (Fe), transferrin saturation (TSAT), ferritin, phosphate (P), intact parathyroid hormone (iPTH), and C-reactive protein. RESULTS: The efficacy of DPO and EPObp were similar and higher than EPO. TSAT was most strongly correlated with ΔHb/EPO dose/kg in all three types of ESAs. Other significant independent factors were Hb, albumin, P, iPTH, and diabetic nephropathy in the EPO group, eGFR in the DPO group, and Fe in the EPObp group. The adjusted coefficient of determination (R (2)) ranged from 0.415 to 0.520 in the three ESA groups. CONCLUSIONS: The study results suggest that TSAT is the best predictor of the initial 12-week responsiveness to ESA, irrespective of the type. Variables not investigated in this study also affect responsiveness to ESA in Japanese pre-dialysis CKD patients.

Effects of Cardiovascular Events on End-Stage Renal Disease and Mortality in Patients With Chronic Kidney Disease Before Dialysis.

Cardiovascular events (CVEs) are major complications in patients with chronic kidney disease (CKD). However, few studies have investigated the effects of CVEs on end-stage renal disease (ESRD) and mortality of pre-dialysis patients. We followed 377 CKD patients who were at stage ≥G3 at first clinic visit in the Shuuwa General Hospital between April 2005 and July 2014. After taking baseline patient data, we evaluated renal survival rates and all-cause and CVE-related mortality in patients with CVEs [(+)CVEs] and without CVEs [(-)CVEs]. A total of 99 CVEs occurred in 93 study patients (57.0% cardiac events, 43.0% cerebrovascular events, and 6.5% peripheral artery disease events). During the study period, 127 patients reached ESRD over a median of 4.51 years' follow-up. Kaplan-Meier analysis found longer renal survival rates in the (-)CVEs group compared with the (+)CVEs group. Forty patients died during the study period over a median of 5.43 years' follow-up. Survival rates for all-cause and CVE-related mortality of (-)CVEs patients were higher than in (+)CVEs patients. After adjustment for sex, age, current smoking, blood pressure, diabetes, estimated glomerular filtration rate, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, left ventricular hypertrophy, body mass index, albumin, hemoglobin, calcium, phosphate, C-reactive protein, and spot urine protein, the occurrence of CVEs was still a significant risk factor for ESRD (HR 1.516, P = 0.017) and all-cause mortality (HR 7.871, P < 0.001). Our findings suggest that the occurrence of CVEs is a potent risk factor for ESRD and mortality in CKD patients before dialysis.

Responsiveness to erythropoiesis-stimulating agents and renal survival in patients with chronic kidney disease.

BACKGROUND: Renal anemia of chronic kidney disease (CKD) is generally treated by erythropoiesis-stimulating agents (ESAs). However, there are individual differences in patients' responsiveness to ESA, which may affect the prognosis of CKD. METHODS: The effect of ESAs on hemoglobin was followed in 297 CKD patients with renal anemia. Three types of ESA, epoetin alfa or beta, darbepoetin alfa, and epoetin beta pegol, were used in this study and dose of ESA was converted to that of epoetin using a dose conversion ratio (epoetin:darbepoetin alfa:epoetin beta pegol = 200:1:0.93). After initial 12-week administration of ESAs, the patients were divided into three groups: poor, intermediate, and good responders based on ΔHb/week/epoetin dose as an index. Hemoglobin values were followed for 144 weeks. RESULTS: Initial patient characteristics--including age, body mass index, hemoglobin, estimated glomerular filtration rate, transferrin saturation, ferritin, albumin, calcium, parathyroid hormone, C-reactive protein, and urine protein--were similar in the three responder groups, except phosphate in the poor responder group was significantly higher than in the other two groups. The period from ESA use to renal death (RD) was significantly shortest in the poor responder group, and the number of RD patients was fewer in the good responder group. Multivariate Cox regression revealed that low final ΔHb(ΔHb from ESA use to just before dialysis)/week/epoetin dose, and low Hb after 12-week ESA use were significant factors related to responsiveness to ESA, suggesting that hyporesponsiveness to ESA was a risk factor for RD. Cox regression also found that hyperphosphatemia and diabetic nephropathy were risks for RD as well. CONCLUSIONS: The study results suggest that hyporesponsiveness to ESA after the first 12-week administration as well as after 12 weeks is a risk for RD in pre-dialysis CKD patients. Furthermore, hyperphosphatemia and diabetic nephropathy are risk factors for RD.

Helicobacter cinaedi kidney cyst infection and bacteremia in a patient with autosomal dominant polycystic kidney disease.

A 48-year-old man with autosomal dominant polycystic kidney disease (ADPKD) was admitted to our hospital with a 5-day history of lower right back pain, high-grade fever, and arthralgia. He was diagnosed with right kidney cyst infection and bacteremia due to Helicobacter cinaedi (H. cinaedi) based on these symptoms, highly elevated CRP (32.25 mg/dL), abdominal magnetic resonance imaging findings, and the identification of H. cinaedi from blood cultures using PCR and sequence analysis of the 16S ribosomal DNA gene. Intravenous cefotaxime 0.5 g twice daily followed by meropenem 0.5 g twice daily and ciprofloxacin 200 mg twice daily were partially effective; oral doxycycline added at 200 mg/day finally eradicated the infection. Total duration of antimicrobial therapy was 9 weeks. H. cinaedi infections typically present as bacteremia with or without cellulitis in immunocompromised patients such as those with AIDS or malignant disease. To our knowledge, this is the first report describing an ADPKD patient with H. cinaedi cyst infection. Although H. cinaedi infections are increasingly recognized, even in immunocompetent subjects, numerous cases may still be overlooked given that this bacterium is slow-growing, and is difficult to culture, be Gram-stained, and identify on phenotypic tests. Consideration of this bacterium as a possible pathogen and sufficient duration of incubation with molecular testing are necessary in treating ADPKD patients with cyst infection.

Rate of ankle-brachial index decline predicts cardiovascular mortality in hemodialysis patients.

Chronic kidney disease is a risk factor for cardiovascular mortality and morbidity of cardiovascular events (CVEs). We obtained baseline data regarding blood biochemistry, ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV) and echocardiographic parameters from 300 patients on hemodialysis in 2005. We also measured ABI and baPWV annually from June 2005 until June 2012 and calculated rates of changes in ABI and baPWV to identify factors associated with CVEs. Seventy-three patients died of cardiovascular disease and 199 CVEs occurred in 164 patients during the study period. Cardiac, cerebrovascular and peripheral artery disease (PAD) events occurred in 124, 43 and 32 patients, respectively, and 30 patients had more than two types of CVEs. Analysis using the Cox proportional hazards model showed that a higher rate of decline in ABI (hazard ratio [HR], 4.034; P < 0.001) was the most significant risk factor for decreased patient survival. Multivariate Cox analysis revealed that a higher rate of ABI decline (HR, 2.342; P < 0.001) was a significant risk factor for cardiac events, and that a lower baseline ABI was a risk factor for cerebrovascular (HR, 0.793; P = 0.03) and PAD (HR, 0.595; P < 0.0001) events. Our findings suggested that the rate of a decline in ABI and the baseline ABI value are potent correlation factors for survival and CVE morbidity among patients on hemodialysis in Japan.

Effects of three kinds of erythropoiesis-stimulating agents on renal anemia in Japanese non-dialysis chronic kidney disease patients.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are standard therapy for chronic kidney disease (CKD) patients with renal anemia. However, few studies have compared the effects of different ESAs on anemia in identical pre-dialysis CKD patients. METHODS: Seventy-nine patients who switched from epoetin beta to darbepoetin alfa (Group 1), and 82 patients who switched from darbepoetin alfa to epoetin beta pegol (Group 2) were enrolled in this study. Clinical and laboratory parameters were assessed for 6 months before and after switching ESAs. The prevalence of adverse events, the dose conversion ratio of ESAs, and the frequency of ESA administration were also analyzed. RESULTS: Analysis of variance showed that switching ESAs did not significantly change hemoglobin levels for the study duration in both groups (mean hemoglobin 10.3-10.5 g/dL in Group 1 and 10.4-10.7 g/dL in Group 2). Estimated glomerular filtration rate, blood pressure, transferrin saturation, ferritin, and albumin remained constant in both groups. The prevalence of adverse effects was quite low (0-3.8 %) during both 6-month study periods. The mean dose conversion ratio for epoetin beta:darbepoetin alfa was 163.7 units:1 µg and for darbepoetin alfa:epoetin beta pegol was 1.08 µg:1 µg. The intervals of ESA administration significantly differed (epoetin beta pegol > darbepoetin alfa > epoetin beta). CONCLUSIONS: Epoetin beta, darbepoetin alfa, and epoetin beta pegol are effective and well-tolerated agents for managing anemia in Japanese pre-dialysis CKD patients. The intervals of ESA administration to maintain a patient's target hemoglobin were longer in the order of epoetin beta pegol > darbepoetin alfa > epoetin beta.

Lower serum sodium level predicts higher risk of infection-related hospitalization in maintenance hemodialysis patients: an observational cohort study.

BACKGROUND: Hyponatremia is associated with increased mortality in chronic kidney disease with and without end-stage renal disease (ESRD). Increasing evidence suggests that hyponatremia is not only a marker of severe underlying disease, but also a direct contributor to mortality. However, specific pathogenesis or diseases contributing to mortality in the hyponatremic population are unknown. This study aimed to clarify the relationship between serum sodium level (sNa) and infection risk in ESRD patients. METHODS: This observational cohort study included 332 patients on maintenance hemodialysis in our dialysis unit in May 2009. The mean of 3 monthly measurements of glucose-corrected sNa before each dialysis session in May, June, and July 2009 was applied as baseline sNa. The primary endpoint was first infection-related hospitalization (IRH), and the secondary endpoint was death of any cause. Data were analyzed using Cox hazards modeling, adjusted for baseline demographics and characteristics, or laboratory data. Patients were followed until transfer, kidney transplantation, death, or study end on January 31, 2013. RESULTS: Mean sNa was 138.9 mEq/L (1st tertile: <138.0, n = 104; 2nd tertile: 138.0-140.0, n = 116; 3rd tertile: >140.0, n = 112). During 39.5 months' mean follow-up, 57 patients experienced IRH (56.4/1,000 patient-years overall; 89.7/1,000 in 1st tertile; 57.9/1,000 in 2nd tertile; 28.0/1,000 in 3rd tertile), and 68 patients died. The hazard ratio (HR) for IRH was higher for the 1st and 2nd tertiles than the 3rd tertile (unadjusted HR, 3.20; 95% confidence interval (CI), 1.54-6.64; p = 0.002; adjusted HR, 2.36; 95% CI, 1.10-5.04; p = 0.027; and unadjusted HR, 2.07; 95% CI, 0.98-4.40; p = 0.058; adjusted HR, 2.11; 95% CI, 0.99-4.51; p = 0.054 respectively). In a continuous model, higher sNa was associated with lower risk of IRH (adjusted HR, 0.90; 95% CI, 0.81-0.99; p = 0.040), and lower all-cause mortality (adjusted HR, 0.91; 95% CI, 0.83-1.00; p = 0.049). CONCLUSIONS: Lower sNa is an independent predictor of higher risk for infection-related hospitalization in maintenance hemodialysis patients. Infectious disease may partially account for the increased mortality observed in the hyponatremic population with ESRD.

The impact of hyporesponsiveness to erythropoietin-stimulating agents on time-dependent mortality risk among CKD stage 5D patients: a single-center cohort study.

BACKGROUND: Hyporesponsiveness to a large dose of erythropoietin-stimulating agents (ESA) could increase mortality risk among chronic kidney disease patients. This study aimed to assess a safe dose of ESA and the impact of hyporesponsiveness to ESA on mortality risk among hemodialyzed patients. METHODS: Patients on hemodialysis were enrolled in this cohort study. The first year was used to assess the longitudinal dialysis status of patients; the subsequent 2 years were used to assess the time-dependent risk of mortality. RESULTS: Of the 349 subjects enrolled, 40 died within 2 years. When subjects were stratified by epoetin dose and hemoglobin level into four groups, those who had low hemoglobin despite a high dose of epoetin were associated with the highest risk of mortality among the four groups (adjusted hazard ratio 2.73; 95 % confidence interval 1.20-6.24). These highest-risk subjects had lower serum albumin and higher serum ferritin than any of the other subjects. The impact of serum albumin and serum ferritin on mortality risk in an unadjusted Cox proportional hazards model was attenuated in an adjusted model which included factors of low hemoglobin and higher ESA. A dose of epoetin up to 9000 U/week had no impact on mortality risk as long as hemoglobin levels stayed above 10 g/dL. CONCLUSIONS: Hyporesponsiveness to ESA was associated with an increased risk of mortality. There was no sign of increased mortality risk associated with epoetin itself up to a total dose of 9000 U/week.

Type II diabetes mellitus is a risk factor for heart failure in pre-dialysis patients.

Chronic kidney disease (CKD) increases the risk of developing cardiovascular diseases such as heart failure (HF) and ischemic heart disease (IHD). The characteristics of patients with CKD complicated with HF at the time of starting hemodialysis have not yet been evaluated. We enrolled 347 patients in this study and compared gender, age, body mass index, laboratory data, causative disease, complications, and echocardiographic findings between groups with (n = 105) and without (n = 242) HF. Type II diabetic nephropathy and estimated glomerular filtration rate (eGFR; mL/min/1.73 m(2) ) were the independent factors for HF (OR: 3.004, 95% CI: 1.754 to 5.146 and OR: 1.215, 95% CI: 1.101 to 1.330, [per 1 mL/min/1.73 m(2) increase], respectively). The higher GFR appeared to be not a risk factor for HF, probably because the HF group included patients who required periodic dialysis to prevent fatal HF, even if their renal function was not extremely deteriorated. The prevalence of hypertension, IHD and values of body mass index, triglycerides, and LDL-cholesterol did not differ between these two groups. Echocardiographic data showed that left ventricular mass index was an independent risk factor for HF (OR: 1.006, 95% CI: 1.001 to 1.012, per 1 g/m(2) increase) and more than half of the patients appeared to have left ventricular diastolic dysfunction. Our findings suggest that not only CKD, but also type II DM, is a potent risk for left ventricular dysfunction, which causes HF and IHD in pre-dialysis patients with CKD.

Effects of sevelamer hydrochloride on mortality, lipid abnormality and arterial stiffness in hemodialyzed patients: a propensity-matched observational study.

BACKGROUND: Cause-and-effect associations between sevelamer hydrochloride (HCl) and mortality have yet to be clarified. The effects of sevelamer HCl on mortality, lipid abnormality and arterial stiffness were examined in patients with chronic kidney disease stage 5D. METHODS: The effects of sevelamer HCl were studied by a single-center cohort study that was conducted from January 1, 2005 to December 31, 2008 (n = 483). By the end of the study, 172 patients (Sevelamer group) had succeeded in continuing sevelamer HCl for >6 months (median 37 months), and 300 patients (Control group) had received calcium carbonate (n = 264) or no phosphate binder (n = 36). The mortality and other outcomes were compared between these two groups after matching by a propensity score calculated using age, gender, diabetes prevalence, and dialysis vintage. RESULTS: All-cause [hazard ratio (HR) 0.4, P = 0.02] and cardiovascular (CV)-cause [HR 0.29, P = 0.03] cumulative mortality were significantly lower in the matched Sevelamer group than in the matched Control group. The matched Sevelamer group showed increased high-density lipoprotein cholesterol (P = 0.003) and no change in pulse wave velocity (PWV) and ankle-brachial index (ABI), whereas the matched Control group showed increased serum low-density lipoprotein (LDL) cholesterol (P = 0.003), increased PWV (P = 0.03), and decreased ABI (P = 0.0009). Change in serum LDL cholesterol level correlated inversely with sevelamer HCl dosage (P = 0.02). CONCLUSIONS: Reduced mortality in patients with sevelamer HCl may, at least in part, be explained by an improvement in dyslipidemia and arterial stiffness by sevelamer HCl.

Diagnostic usefulness of bone mineral density and biochemical markers of bone turnover in predicting fracture in CKD stage 5D patients--a single-center cohort study.

BACKGROUND: In chronic kidney disease stage 5D, diagnostic usefulness of bone mineral density (BMD) in predicting fracture has not been established because of variable results in previous studies. The reason for this may be the heterogeneity of underlying pathogenesis of the fracture. METHODS: BMD was measured annually and serum biochemistry monthly for 485 hemodialyzed patients from April 2003 to March 2008, and all fractures were recorded. RESULTS: Forty-six new episodes of any type of fracture and 29 cases of prevalent spine fracture were recorded. Serum bone-specific alkaline phosphatase (b-AP) was a very useful surrogate marker for any type of incident fracture risk [area under curve (AUC) = 0.766, P < 0.0001]. A significantly greater risk of any type of incident fracture was associated with parathyroid hormone (PTH) levels either <150 pg/mL [hazard ratio (HR) = 3.47, P < 0.01] or >300 pg/mL (HR = 5.88, P < 0.0001) compared with 150-300 pg/mL. Receiver-operating characteristic analysis demonstrated a significant predictive power for incident of any type of fracture by BMD at the total hip (AUC = 0.760, P < 0.0001) and other hip regions in females in the lower PTH group (PTH < 204 pg/mL). BMDs at every site but whole body or lumbar spine had significant power to discriminate prevalent spine fracture regardless of gender or PTH. CONCLUSIONS: Hemodialyzed patients with low or high PTH or increased b-AP had a high fracture risk. BMD by Dual Energy X-ray Absorptiometry (DEXA), especially at the total hip region, was useful to predict any type of incident of fracture for females with low PTH or to discriminate prevalent spine fracture for every patient.

Effect of anemia on cardiac disorders in pre-dialysis patients immediately before starting hemodialysis.

INTRODUCTION: Anemia is a common complication of patients with chronic kidney disease (CKD), which not only lowers their quality of life but also potentially causes cardiovascular diseases such as congestive heart failure and coronary heart disease, and accelerates the progression of renal dysfunction. METHODS: Pre-dialysis patients were assigned to groups A, B, C or D based on hemoglobin levels of ≤ 8.9 (n = 48), 9.0-9.9 (n = 63), 10-10.9 (n = 53), and ≥ 11.0 g/dL (n = 39), respectively. Cardiac function was estimated using echocardiography to clarify the relationship between anemia and cardiac disorders in patients with CKD immediately before starting hemodialysis. RESULTS: Left ventricular ejection fraction (LVEF) was significantly higher in group D than in groups A and B. The fractions with an LVEF of less than 50% were 16.7, 4.8, 1.9, and 0% in groups A, B, C, and D, respectively. Posterior wall thickness was statistically thicker and the deceleration time of the early diastolic wave was longer in groups A and B, respectively, than in groups C and D. The left ventricular mass index in group D was significantly lower than in any other groups. CONCLUSION: Anemia in pre-dialysis patients with CKD is a probable cause of impaired left ventricular systolic function and progressive left ventricular hypertrophy. Our results suggest that Hb levels should be maintained at >11 g/dL by EPO administration from the perspective of protecting cardiac function, although the upper limit of the target Hb level was undetermined.

Calcium-alkali syndrome-like symptoms manifested by daily alphacalcidol and thiazide.

A 73-year-old man was admitted with complaints of a 2-month history of generalized weakness and numbness. Laboratory examination revealed hypercalcemia, metabolic alkalosis, and kidney injury, similar to the traditional milk-alkali syndrome. The clinical history and the response to therapy indicated that alphacalcidol and thiazide taken daily were the cause. Recently, it has been recommended the term "milk-alkali syndrome" be replaced by "calcium-alkali syndrome", which broadens the definition of the condition. This case suggests that the calcium-alkali syndrome can occur without calcium and alkali, but rather with alphacalcidol and a thiazide diuretic.