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.

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.