Low erythropoietin levels predict faster renal function decline in diabetic patients with anemia: a prospective cohort study

Elevated erythropoietin (EPO) levels have been reported to predict poor survival in various populations including diabetic patients. However, data regarding its impact on renal outcomes are scarce. We conducted a single-center, prospective cohort study of 339 type 2 diabetic patients with anemia. The primary outcome was the estimated glomerular filtration rate (eGFR) slope for two years. We performed multiple linear regression and restricted cubic spline analyses to assess the association of serum EPO levels with the renal outcome. Chronic kidney disease (CKD) was defined as eGFR 30 mg/g creatinine. Median baseline EPO and eGFR level were 14.4 IU/L and 53 mL/min/1.73 m2, respectively. Inappropriately low EPO levels were observed in 73% of anemic patients and 59% of anemic patients even without CKD, suggesting that EPO deficiency precedes the onset of CKD in diabetes mellitus. Multivariable analysis revealed that iron status and hemoglobin levels were major determinants of EPO levels. Median eGFR slope was −1.3 mL/min/1.73 m2/year. We found that low EPO levels, but not low hemoglobin levels, were associated with a faster decline in eGFR, independent of clinically relevant factors. The eGFR decline was steeper, particularly when the EPO level was below the upper limit of normal. Lower EPO concentrations were associated with rapid eGFR decline, especially in patients with iron deficiency (P for interaction = 0.01). Relative EPO deficiency should be considered as a culprit in anemia of unknown etiology in diabetic patients, even those without CKD. Low EPO levels, especially when accompanied by poor iron status, are predictive of rapid loss of renal function.Fujita Y., Doi Y., Hamano T., et al. Low erythropoietin levels predict faster renal function decline in diabetic patients with anemia: a prospective cohort study. Scientific Reports 9, 14871 (2019); https://doi.org/10.1038/s41598-019-51207-8

Serum phosphate levels modify the impact of parathyroid hormone levels on renal outcomes in kidney transplant recipients

Separate assessment of mineral bone disorder (MBD) parameters including calcium, phosphate, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D (1,25D) predict renal outcomes in kidney transplant recipients (KTRs), with conflicting results. To date, data simultaneously evaluating these parameters and interwoven relations on renal outcomes are scarce. We conducted a prospective long-term follow-up cohort study included 263 KTRs with grafts functioning at least 1 year after transplantation. The outcome was a composite of estimated GFR halving and graft loss. Cox regression analyses were employed to evaluate associations between a panel of six MBD parameters and renal outcomes. The outcome occurred in 98 KTRs during a median follow-up of 10.7 years. In a multivariate Cox analysis, intact PTH (iPTH), phosphate, and 1,25D levels were associated with the outcome (hazard ratio, 1.60 per log scale; 95% confidence interval, 1.19–2.14, 1.60 per mg/dL; 1.14–2.23 and 0.82 per 10 pg/mL; 0.68–0.99, respectively). Competing risk analysis with death as a competing event yielded a similar result. After stratification into four groups by iPTH and phosphate medians, high risks associated with high iPTH was not observed in KTRs with low phosphate levels (P-interaction < 0.1). Only KTRs not receiving active vitamin D, poor 1,25D status predicted the worse outcome (P-interaction < 0.1). High iPTH, phosphate, and low 1,25D, but not FGF23, levels predicted poor renal outcomes. Simultaneous evaluation of PTH and phosphate levels may provide additional information regarding renal allograft prognosis.Doi Y., Hamano T., Ichimaru N., et al. Serum phosphate levels modify the impact of parathyroid hormone levels on renal outcomes in kidney transplant recipients. Scientific Reports 10, 13766 (2020); https://doi.org/10.1038/s41598-020-70709-4

Understanding measurements of vitality in patients with chronic kidney disease: connecting a quality-of-life scale to daily activities.

[Background]Many patients with chronic kidney disease (CKD) suffer from fatigue caused by anemia, but that anemia can be reversed. Successful treatment can be measured as a decrease in fatigue and an increase in energy or vitality, particularly on the vitality (VT) subscale of the SF-36. Changes in VT scores are most commonly interpreted in terms of minimally important differences or standardized effect sizes, but neither a minimally important difference nor a standardized effect size provides information about how patients’ activities are affected. Therefore, we analyzed the association between differences in VT scores and a variable that is meaningful to patients and to society the frequency of going out. [Study Design]Questionnaire survey. Analyses of differences among participants at bseline, and analyses of differences within participants over time. [Setting and Participants]CKD patients who were not on dialysis and were involved in a study of anti-anemia therapy. [Predictor]VT scores. [Outcome]Frequency of going out. [Measurements]VT scores and the frequency of going out. [Results]At baseline, higher VT scores and younger age were associated with going out more often, while sex and the presence of diabetic nephropathy were not associated with the frequency of going out. Greater changes in VT scores over time were associated with greater changes in the frequency of going out, in univariate and multivariate analyses. [Conclusions]At baseline, VT was associated with the frequency of going out. Increases in VT were also associated with increases in the frequency of going out. These results show how VT scores can be linked to daily activities that are important to individual patients and to society

GUANIDINOACETIC ACID(GAA) IN PATIENTS WITH CHRONIC KIDNEY DISEASE(CKD) AND DIABETES MELLITUS(DM)

GAA is the precursor of creatine, an essential in the energy metabolism of muscle and nerve tissue. GAA is mainly produced in the kidney. GAA production was reported to be suppressed in the streptozotocin-induced DM rats. However, GAA metabolism has not been really investigated in CKD or DM patients. In this study, we determined serum level(S) and urinary excretion(U) of GAA and creatinine(Cr) in patients with chronic glomerulonephritis (CGN) and DM. The subjects were 15 healthy adults, 92 patients with CGN and 27 patients with non insulin-dependent DM nephropathy. S and U-GAA were determined with HPLC. As shown in the Table describing mean values, U-GAA of early stage CKD patients was significantly lower than healthy subject. And S-GAA decreased with loss of renal function or with U-Cr, especially in DM patients. N S-Cr U-Cr S-GAA U-GAA (mg/dL) (mg/day) (μg/dL) (mg/day) Normal 15 0.9 1633 38.2 103.0 CGN(Ccr>90mL/min) 12 1 1742 41.1 41.3⁎ CGN(Ccr<90mL/min) 24 1.5⁎ 1385⁎ 37.7 39.2⁎ CGN(Ccr<30mL/min) 56 7.1⁎ 715⁎ 24.4⁎ 5.9⁎ DM(Ccr>60mL/min) 16 0.9 775⁎ 27.8⁎ 46.2⁎ DM(Ccr<60mL/min) 11 5.0⁎ 581⁎ 22.1⁎ 2.3⁎ In conclusion, GAA production in the kidney decreased in CKD patients, suggesting GAA deficiency was a reason of muscle wasting of CKD and DM patients

Effects of guanidinoacetic acid(gaa) supplementation in rats with chronic renal failure(crf)

GAA is the precursor of creatine(CRT), an essential in the energy metabolism of muscle and nerve tissue. GAA is mainly produced in the kidney. We reported the GAA deficiency in CRF patients. This study was designed to assess the effects of GAA supplementation(10 mg,100 mg/day orally for 4 weeks respectively) for the muscle capabilities in CRF rats prepared by 5/6 nephrectomy. Muscle power was assessed by the sliding angle of the inclined screen test, and physical strength was evaluated by the time to survive in water (forced swimming method). GAA and CRT concentrations in serum, muscle and other organs were significantly decreased in CRF rats. GAA administrations significantly increased CRT content in muscle, and improved muscle capabilities dose-dependently. muscle power physical strength sliding angle; ° swimming time; min Sham 55.2±0.9 52.0±3.8 CRF(GAA 0) 42.3±1.9* 21.9±1.2* CRF(GAA 10 mg) 47.4±1.3*$25.5±1.1*$ CRF(GAA 100 mg) 48.8±2.1*$29.0±3.3*$ *; p<0.05 vs Sham $; p<0.05 vs GAA 0In conclusion, we demonstrated a deficiency of GAA and CRT, and muscle weekness in CRF rats. However, oral GAA supplementation could recover muscle content of CRT and muscle capabilities in these rats

Hemodialysis-associated hypotension as an independent risk factor for two-year mortality in hemodialysis patients

Hemodialysis-associated hypotension as an independent risk factor for two-year mortality in hemodialysis patients.BackgroundThe relationship between blood pressure (BP) and mortality in hemodialysis patients has remained controversial. Some studies suggested that a lower pre- or postdialysis BP was associated with excess mortality, while others showed poorer outcome in patients with uncontrolled hypertension. We conducted a multicenter prospective cohort study to evaluate the impact of hemodialysis-associated hypotension on mortality.MethodsWe recruited 1244 patients (685 males; mean age, 60 ± 13 years) who underwent hemodialysis in 28 units during the two-year study period beginning in December 1999. Pre-, intra-, and postdialysis BP, and BP upon standing soon after hemodialysis, were measured in all patients at entry. Logistic regression analysis was used to assess the effect on mortality of pre-, intra-, and postdialysis BP, a fall in BP during hemodialysis, and a fall in BP upon standing soon after hemodialysis.ResultsDuring the study period, 149 patients died. Logistic models identified the lowest intradialysis systolic blood pressure (SBP) and degree of fall in SBP upon standing soon after hemodialysis as significant factors affecting mortality, but not pre- or postdialysis SBP and diastolic BP. The adjusted odds ratio for death was 0.79 (95% CI 0.64–0.98) when the lowest intradialysis SBP was analyzed in increments of 20 mm Hg, and was 0.82 (95% CI 0.67–0.98) when the fall in SBP upon standing soon after hemodialysis was analyzed in increments of 10 mm Hg.ConclusionThese results suggest that intradialysis hypotension and orthostatic hypotension after hemodialysis are significant and independent factors affecting mortality in hemodialysis patients

Influence of diet, exercise, and dietician’s on the incidence and survival of japanese dialysis patients

It is known that there are distinct regional differences in the incidence and prevalence of dialysis, as well as the survival of dialysis patients in Japan. We investigated the relationship between diet, the level of exercise, and the incidence of dialysis due to diabetes mellitus (DM) and chronic glomerulonephritis (CGN). We also investigated the influence of access to full-time and part-time dieticians at dialysis centers on survival. We used data for the 47 prefectures of Japan from the National Nutrition Survey 1995-99 (n=38,003) and the Japanese Society for Dialysis Therapy 2005-07 (n=45,033). The impact of each factor was assessed by univariate regression analysis. Univariate analysis showed that body mass index (BMI) (r=0.296, p=0.022), intake of fish and shellfish (r=−0.254, p=0.043), and the intake of meat (r=0.275, p=0.031) were correlated with the incidence of new patients starting dialysis due to DM. In addition, the BMI (r=0.355, p=0.014), number of steps walked daily (r=−0.358, p=0.014), intake of green and yellow vegetables (r=−0.424, p=0.003), intake of fish and shellfish (r=−0.358, p=0.014), and intake of milk (r=−0.529, p<0.001) were correlated with the incidence of new patients starting dialysis due to CGN. Access to full-time dieticians was correlated with the 1-year survival of new dialysis patients (r=0.294, p=0.023), but not access to part-time dieticians. We conclude that nutritional advice might play an important role in survival in dialysis patients