Dialysis patients have absolute and functional iron deficiencies. Traditionally, oral iron preparations have been insufficient to maintain iron stores to support erythropoiesis, especially in the ...setting of the ubiquitous use of erythropoiesis‐stimulating agents. This has led to the widespread adoption of intravenous iron protocols designed to maintain iron stores at levels that are much higher than for patients not on dialysis. These protocols are often developed by dialysis providers and may be largely independent of the treating nephrologist. Concerns about multiple risks associated with the use of intravenous iron persist. Despite this, mean ferritin levels in the United States have risen, partly due to more intravenous iron use and partly due to reduced erythropoiesis‐stimulating agent use. Questions about the relationship of intravenous iron to infection, cardiac, and hepatobiliary risks remain. The failure of oral iron preparations to maintain iron stores continues to prompt the use of intravenous iron. Recently, studies with oral ferric citrate as a phosphate binder have shown improved iron stores and maintenance of hemoglobin, and studies with soluble ferric pyrophosphate added to dialysate have shown both maintenance of iron stores and hemoglobin. With new iron options that affect iron stores in dialysis patients, the use of intravenous iron and its potential risks may wane.
Arterial stiffness, typically assessed as the aortic pulse wave velocity (PWV), and central blood pressure levels may be indicators of cardiovascular disease (CVD) risk. This ancillary study to the ...Systolic Blood Pressure Intervention Trial (SPRINT) obtained baseline assessments (at randomization) of PWV and central systolic blood pressure (C-SBP) to: 1) characterize these vascular measurements in the SPRINT cohort, and 2) test the hypotheses that PWV and C-SBP are associated with glucose homeostasis and markers of chronic kidney disease (CKD). The SphygmoCor® CPV device was used to assess carotid-femoral PWV and its pulse wave analysis study protocol was used to obtain C-SBP. Valid results were obtained from 652 participants. Mean (±SD) PWV and C-SBP for the SPRINT cohort were 10.7 ± 2.7 m/s and 132.0 ± 17.9 mm Hg respectively. Linear regression analyses for PWV and C-SBP results adjusted for age, sex, and race/ethnicity in relation to several markers of glucose homeostasis and CKD did not identify any significant associations with the exception of a marginally statistically significant and modest association between PWV and urine albumin-to-creatinine ratio (linear regression estimate ± SE, 0.001 ± 0.0006; P-value 0.046). In a subset of SPRINT participants, PWV was significantly higher than in prior studies of normotensive persons, as expected. For older age groups in the SPRINT cohort (age > 60 years), PWV was compared with a reference population of hypertensive individuals. There were no compelling associations noted between PWV or C-SBP and markers of glucose homeostasis or CKD.
NCT01206062.
Introduction
The REVOLUTIONIZE I study aimed to characterize the relationships between medical nutrition therapy (MNT) and hyperkalemia recurrence in patients with stage 3–4 chronic kidney disease ...(CKD) and hyperkalemia who received MNT in real-world clinical practice.
Methods
This observational cohort study used de-identified electronic health record data from patients aged ≥ 18 years with stage 3–4 CKD who received MNT between January 2019 and October 2022 and had hyperkalemia (serum potassium > 5.0 mmol/L) within 30 days before MNT. Patients were followed for 6 months or until the first censoring event (death, prescription of outpatient potassium binder, or study end). The primary outcome was the percentage of patients with ≥ 1 hyperkalemia recurrence during follow-up. Secondary outcomes included the number of hyperkalemia recurrences per patient, time to each recurrence, and hyperkalemia-related healthcare resource utilization. Exploratory outcomes included all-cause healthcare resource utilization and mortality.
Results
The final cohort comprised 2048 patients; 1503 (73.4%) patients remained uncensored after 6 months. During the 6-month follow-up period, 56.0% of patients had ≥ 1 hyperkalemia recurrence and 37.4% had ≥ 1 recurrence within the first month. Patients with ≥ 1 hyperkalemia recurrence during follow-up had a mean ± standard deviation (SD) of 2.6 ± 2.2 recurrences. The mean ± SD time to first hyperkalemia recurrence was 45 ± 46 days; the time between recurrences decreased with subsequent episodes. Hyperkalemia-related hospitalizations and emergency department visits were recorded for 13.7% and 1.5% of patients, respectively. Sensitivity analyses showed that results were consistent across patient subgroups, including those with comorbid heart failure and patients receiving renin–angiotensin–aldosterone system inhibitor therapy at baseline.
Conclusion
Most patients with stage 3–4 CKD had hyperkalemia recurrence, and MNT alone was inadequate to prevent recurrence. These patients may require additional long-term treatment, such as novel potassium binders, to maintain normokalemia and prevent hyperkalemia recurrence following MNT.
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Infographic
Plain Language Summary
Patients with chronic kidney disease (CKD) typically receive dietary counseling from a registered dietician, referred to as medical nutrition therapy, to help reduce their risk of complications of CKD while addressing their specific nutritional needs. Patients with CKD have an increased risk of elevated blood potassium levels (hyperkalemia), which has potentially life-threatening consequences. Although medical nutrition therapy may help patients with hyperkalemia to manage their dietary potassium intake, its effects in preventing recurrence are unclear. Our aim was to determine whether medical nutrition therapy can help prevent hyperkalemia recurrence after an initial event in patients with non-dialysis-dependent (stage 3–4) CKD in real-world clinical practice. We used data from de-identified electronic health records to study hyperkalemia recurrence over 6 months in patients with stage 3–4 CKD who received medical nutrition therapy within 30 days after experiencing hyperkalemia. Over half of the patients (56.0%) had at least one hyperkalemia recurrence within an average of 45 days during the 6 months after medical nutrition therapy; these patients had an average of 2.6 distinct recurrences in 6 months. In patients with two or more hyperkalemia recurrences, the time between these became shorter than 30 days. Our real-world study results show that hyperkalemia is a chronic, recurring condition in patients with stage 3–4 CKD, and that medical nutrition therapy is not enough to prevent its recurrence. This suggests that these patients may need additional long-term treatment for hyperkalemia, such as novel potassium binder therapy, to prevent hyperkalemia recurrence.
Background Most dialysis patients require phosphate binders to control hyperphosphatemia. Ferric citrate has been tested in phase 2 trials as a phosphate binder. This trial was designed as a ...dose-response and efficacy trial. Study Design Prospective, phase 3, multicenter, open-label, randomized clinical trial. Setting & Participants 151 participants with hyperphosphatemia on maintenance hemodialysis therapy. Intervention Fixed dose of ferric citrate taken orally as a phosphate binder for up to 28 days (1, 6, or 8 g/d in 51, 52, and 48 participants, respectively). Outcomes Primary outcome is dose-response of ferric citrate on serum phosphorus level; secondary outcomes are safety and tolerability. Measurements Serum chemistry tests including phosphorus, safety data. Results 151 participants received at least one dose of ferric citrate. Mean baseline phosphorus levels were 7.3 ± 1.7 (SD) mg/dL in the 1-g/d group, 7.6 ± 1.7 mg/dL in the 6-g/d group, and 7.5 ± 1.6 mg/dL in the 8-g/d group. Phosphorus levels decreased in a dose-dependent manner (mean change at end of treatment, −0.1 ± 1.3 mg/dL in the 1-g/d group, −1.9 ± 1.7 mg/dL in the 6-g/d group, and −2.1 ± 2.0 mg/dL in the 8-g/d group). The mean difference in reduction in phosphorus levels between the 6- and 1-g/d groups was 1.3 mg/dL (95% CI, 0.69 to 1.9; P < 0.001), between the 8- and 1-g/d groups was 1.5 mg/dL (95% CI, 0.86 to 2.1; P < 0.001), and between the 8- and 6-g/d groups was 0.21 mg/dL (95% CI, −0.39 to 0.81; P = 0.5). The most common adverse event was stool discoloration. Limitations Sample size and duration confirm efficacy, but limit our ability to confirm safety. Conclusions Ferric citrate is efficacious as a phosphate binder in a dose-dependent manner. A phase 3 trial is ongoing to confirm safety and efficacy.
The Systolic BP Intervention Trial (SPRINT) found that intensive versus standard systolic BP control (targeting <120 or <140 mm Hg, respectively) reduced the risks of death and major cardiovascular ...events in persons with elevated cardiovascular disease risk. However, the intensive intervention was associated with an early decline in eGFR, and the clinical implications of this early decline are unclear.
In a
analysis of SPRINT, we defined change in eGFR as the percentage change in eGFR at 6 months compared with baseline. We performed causal mediation analyses to separate the overall effects of the randomized systolic BP intervention on the SPRINT primary cardiovascular composite and all-cause mortality into indirect effects (mediated by percentage change in eGFR) and direct effects (mediated through pathways other than percentage change in eGFR).
About 10.3% of the 4270 participants in the intensive group had a ≥20% eGFR decline versus 4.4% of the 4256 participants in the standard arm (
<0.001). After the 6-month visit, there were 591 cardiovascular composite events during 27,849 person-years of follow-up. The hazard ratios for total effect, direct effect, and indirect effect of the intervention on the cardiovascular composite were 0.67 (95% confidence interval 95% CI, 0.56 to 0.78), 0.68 (95% CI, 0.57 to 0.79), and 0.99 (95% CI, 0.95 to 1.03), respectively. All-cause mortality results were similar.
Although intensive systolic BP lowering resulted in greater early decline in eGFR, there was no evidence that the reduction in eGFR owing to intensive systolic BP lowering attenuated the beneficial effects of this intervention on cardiovascular events or all-cause mortality.
Intensive systolic blood pressure (SBP) control improved outcomes in SPRINT (Systolic Blood Pressure Intervention Trial). Our objective was to expand on reported findings by analysis of baseline ...characteristics, primary outcomes, adverse events, follow-up blood pressure, and medication use differences by baseline SBP (tertile 1 T1, <132; tertile 2 T2, 132-145; and tertile 3 T3, >145 mm Hg). Participants with higher baseline SBP tertile were more often women and older, had higher cardiovascular risk, and lower utilization of antihypertensive medications, statins, and aspirin. Achieved SBP in both treatment arms was slightly higher in T2 and T3 compared with T1 and fewer in the T3 groups achieved SBP targets compared with T1 and T2 groups. The primary composite outcome with intensive versus standard SBP treatment was reduced by 30% in T1, 23% in T2, and 17% in T3 with no evidence of an interaction (
=0.77). Event rates were lower in the intensive arm, and there was no evidence that this benefit differed by SBP tertile. There was no difference in the hazard for serious adverse events in any of the 3 tertiles. Medication utilization differed across the SBP tertiles at baseline with a lesser percentage of diuretics and angiotensin-converting enzyme inhibitors/angiotensin receptor blocker drugs in the higher tertiles-a finding that reversed during the trial. The beneficial effects of intensive SBP lowering were not modified by the level of baseline SBP. Within the parameters of this population, these findings add support for clinicians to treat blood pressure to goal irrespective of baseline SBP.
Ferric citrate (FC) is a phosphate binder with shown efficacy and additional effects on iron stores and use of intravenous (iv) iron and erythropoiesis-stimulating agents (ESAs). We provide detailed ...analyses of changes in iron/hematologic parameters and iv iron/ESA use at time points throughout the active control period of a phase 3 international randomized clinical trial. In all, 441 subjects were randomized (292 to FC and 149 to sevelamer carbonate and/or calcium acetate active control (AC)) and followed for 52 weeks. Subjects on FC had increased ferritin and transferrin saturation (TSAT) levels compared with subjects on AC by week 12 (change in ferritin, 114.1±29.35 ng/ml; P<0.001; change in TSAT, 8.62%±1.57%; P<0.001). Change in TSAT plateaued at this point, whereas change in ferritin increased through week 24, remaining relatively stable thereafter. Subjects on FC needed less iv iron compared with subjects on AC over 52 weeks (median interquartile range dose=12.9 1.0-28.9 versus 26.8 13.4-47.6 mg/wk; P<0.001), and the percentage of subjects not requiring iv iron was higher with FC (P<0.001). Cumulative ESA over 52 weeks was lower with FC than AC (median interquartile range dose=5303 2023-9695 versus 6954 2664-12,375 units/wk; P=0.04). Overall, 90.3% of subjects on FC and 89.3% of subjects on AC experienced adverse events. In conclusion, treatment with FC as a phosphate binder results in increased iron parameters apparent after 12 weeks and reduces iv iron and ESA use while maintaining hemoglobin over 52 weeks, with a safety profile similar to that of available binders.
Background A doubling of serum creatinine value, corresponding to a 57% decline in estimated glomerular filtration rate (eGFR), is used frequently as a component of a composite kidney end point in ...clinical trials in type 2 diabetes. The aim of this study was to determine whether alternative end points defined by smaller declines in eGFR would improve the statistical power of these clinical trials. Study Design Post hoc analyses of 2 multinational randomized controlled trials (Reduction of End Points in Non–Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan RENAAL and Irbesartan Diabetic Nephropathy Trial IDNT) that assessed the treatment effect of the angiotensin receptor blockers (ARBs) losartan and irbesartan. Setting & Participants 1,513 (RENAAL) and 1,715 (IDNT) adult patients with type 2 diabetes and nephropathy. Predictor Established versus alternative end points defined as a confirmed doubling of serum creatinine level versus confirmed eGFR decline of 57%, 40%, 30%, or 20% as a component of a composite end point of end-stage renal disease or eGFR < 15 mL/min/1.73 m2. Outcomes Numbers of patients reaching end points, precision (standard error), and significance ( z score) of ARB treatment effect (HR) during follow-up. Results Lesser eGFR declines resulted in a greater number of patients reaching end points in both treatment groups and lower standard error of the HR, but the effect on z score was counterbalanced by attenuation of the HR. When calculating the eGFR decline from month 3, attenuation of the HR was less pronounced. Limitations Post hoc analysis. Conclusions Despite increases in precision of the treatment effect, eGFR declines less than a doubling of serum creatinine value did not consistently improve statistical power of the clinical trials due to attenuation of the treatment effect. Attenuation of the treatment effect appears to be due in part to acute effects of ARBs on eGFR. These findings should be taken into account when using lesser eGFR declines as alternative end points for clinical trials.
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