Rehospitalization Rates in Hypertensive Emergency.

Blood Pressure Goals: How Low Is Safe in CKD?

Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients With Asymptomatic Hypertension in the Emergency Department

The Impact of APOL1 on Chronic Kidney Disease and Hypertension.

Background: Malignant hypertension is a disease characterized by severe hypertension and multi-organ damage. Sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor (ARNi), has already demonstrated the superiority of reducing blood pressure versus olmesartan in patients with hypertension. ARNi has also been shown to improve cardiac biomarkers, cardiac remodeling, and prognosis in patients with heart failure, and a new AHA/ACC/HFSA guideline (2022) redefined to recommend ARNi as first-line renin-angiotensin-system inhibitors (class 1a) in patients with HFrEF (heart failure with reduced ejection fraction). However, the evidence about the efficacy and safety of ARNi in end-stage renal disease (ESRD) patients undergoing hemodialysis has been limited. Presentation: A 23-year-old man with no prior medical history was admitted to the previous hospital with severe hypertension (blood pressure 224/159 mmHg) associated with acute kidney injury (BUN 228.5 mg/dl, serum creatinine 25.50 mg/dl) and was referred to our hospital with the initiation of hemodialysis. He was also complicated with hypertensive heart failure with a preserved ejection fraction (NT-proBNP 172113 pg/ml). Blood test results also revealed thrombocytopenia (platelet 11.9 x 103/μL), hemolytic anemia (hemoglobin 7.4 g/dl, LDH 1076 U/L, haptoglobin < 10 mg/dl), and schistocyte on the blood smear, which was suggestive of thrombotic microangiopathy. His blood cell counts and serum LDH levels improved after antihypertensive treatment. Secondary hypertension, such as primary aldosteronism, Cushing's syndrome, pheochromocytoma, and renal artery stenosis, was deniable by further examination. The elevated levels of renin (65.5 ng/ml/hr) and aldosterone (685 pg/ml) were consistent with malignant hypertension. Serum antibody tests for screening of autoimmune disease were all negative. Renal biopsy revealed findings of malignant nephrosclerosis: glomerular collapse, glomerulosclerosis, endothelial swelling, and media thickening of the arteries. Oliguria recovered during the clinical course; however, his renal function did not fully recover. An arterio-venous fistula was created, and maintenance hemodialysis two times per week was continued during hospitalization. Even though his dry weight was adjusted to normal by repeated dialysis, his blood pressure was poorly controlled to systolic blood pressure of 160–170 mmHg by calcium channel blockers, angiotensin II receptor blocker (ARB), and alpha/beta-blockers. After switching from ARB to ARNi by increasing the dose to a maximum of 400 mg, his systolic blood pressure improved to 130–140 mmHg and was stable throughout the day, assessed by ambulatory blood pressure monitoring. Conclusion: Through our experience, it is conceivable that ARNi may be helpful in the settings of resistant hypertension in ESRD patients undergoing hemodialysis.

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There is an incomplete understanding of the underlying pathophysiology in hypertensive emergencies, where severely elevated blood pressure causes acute end-organ injuries, as opposed to the long-term manifestations of chronic hypertension. Furthermore, current biomarkers are unable to detect early end-organ injuries like hypertensive encephalopathy and renal thrombotic microangiopathy. We hypothesized that circulating microRNAs (c-miRs) could identify acute and chronic complications of severe hypertension, and that combinations of c-miRs could elucidate important pathways involved. We studied the diagnostic accuracy of 145 c-miRs in Dahl salt-sensitive rats fed either a low-salt (N = 20: 0.3% NaCl) or a high-salt (N = 60: 8% NaCl) diet. Subclinical hypertensive encephalopathy and thrombotic microangiopathy were diagnosed by histopathology. In addition, heart failure with preserved ejection fraction was evaluated with echocardiography and N-terminal pro-brain natriuretic peptide; and endothelial dysfunction was studied using acetylcholine-induced aorta ring relaxation. Systolic blood pressure increased severely in animals on a high-salt diet (high-salt 205 ± 20 mm Hg vs. low-salt 152 ± 18 mm Hg, p < 0.001). Partial least squares discriminant analysis revealed 68 c-miRs discriminating between animals with and without hypertensive emergency complications. Twenty-nine c-miRs were strongly associated with hypertensive encephalopathy, 24 c-miRs with thrombotic microangiopathy, 30 c-miRs with heart failure with preserved ejection fraction, and 28 c-miRs with endothelial dysfunction. Hypertensive encephalopathy, thrombotic microangiopathy and heart failure with preserved ejection fraction were associated with deviations in many of the same c-miRs, whereas endothelial dysfunction was associated with a different set of c-miRs. Several of these c-miRs demonstrated fair to good diagnostic accuracy for a composite outcome of hypertensive encephalopathy, thrombotic microangiopathy and heart failure with preserved ejection fraction in receiver-operating-curve analyses (area-under-curve 0.75–0.88). Target prediction revealed an enrichment of genes related to several pathways relevant for cardiovascular disease (e.g., mucin type O-glycan biosynthesis, MAPK, Wnt, Hippo, and TGF-beta signaling). C-miRs could potentially serve as biomarkers of severe hypertensive end-organ injuries and elucidate important pathways involved.

Aggressive blood pressure reduction and renin–angiotensin system blockade in chronic kidney disease: time for re-evaluation?

Malignant hypertension (MHT), also known as accelerated-malignant hypertension or malignant-phase hypertension, is the most severe form of arterial hypertension. It is defined clinically as high blood pressure (BP) levels associated with lesions of the retinal fundus (flame-shaped hemorrhages, exudates, or cotton wool spots, with or without papilledema). Despite the availability of a vast range of antihypertensive agents, MHT continues to be a significant clinical challenge. Although its prevalence is very low, the absolute number of new cases has not changed over the past decades. While the role of the activation of the renin-angiotensin-aldosterone system and endothelial dysfunction in the pathogenesis of MHT has been well described, recent studies have indicated that the immune system may also play an important role in the development of this condition. Patients with MHT are characterized by pronounced target organ damage, including structural and functional cardiac abnormalities. MHT is frequently complicated by renal insufficiency and end-stage renal disease. The survival rates for patients with MHT have improved considerably with increased availability of antihypertensive treatment. However, renal insufficiency and end-stage renal disease still remain a significant cause of morbidity and mortality in this patient group. In conclusion, MHT is not a "vanishing disease" because there is a relatively stable number of new cases per year. Nonetheless, prognosis and survival rates in these patients have improved significantly owing to earlier detection, stricter BP control, lower BP targets, better choice of antihypertensive drugs, and availability of hemodialysis and renal transplantation.

Hypertension among people with chronic kidney disease (CKD) is an established risk factor for acceleration of atherosclerotic cardiovascular disease and progression of kidney injury to end-stage renal disease (ESRD).1, 2 Randomized trials have demonstrated that blood pressure (BP)-lowering is translated into a profound benefit on cardiovascular and kidney outcomes.1 However, the optimal levels at which BP should be targeted remains an area surrounded by substantial controversy that is reflected by the discrepancy in BP target recommendations for patients with CKD across guidelines released during 2012-2018 (Table 1). The 2012 Kidney Disease Improving Global Outcomes (KDIGO) guideline recommended a lower BP target of <130/80 mmHg only for CKD patients with persistent albuminuria [defined as albuminuria ≥30 mg/24-h or urinary-albumin-to-creatinine-ratio (UACR) ≥30 mg/g in a random urine specimen].2 In contrast, the 2014 guideline released by the eighth Joint National Committee (JNC8) did not differentiate the BP targets by the level of albuminuria. There was a uniform recommendation to lower BP to levels <140/90 mmHg regardless of the level of kidney function or UACR.5 The controversy was further magnified in more recent guidelines released after the publication of the Systolic Blood Pressure Intervention Trial (SPRINT).6 This landmark trial was prematurely terminated because of an impressive cardiovascular benefit with a lower (<120 mmHg) vs a standard (<140 mmHg) systolic BP (SBP) target in non-diabetic patients with clinic BP ≥ 130/80 mmHg and a high cardiovascular risk profile. Based on the results of SPRINT, the 2017 American Heart Association/American College of Cardiology (AHA/ACC) guideline reappraised the definition of hypertension and recommended a lower BP target of <130/80 mmHg for all patients at high cardiovascular risk, including those with CKD.4 The European Society of Hypertension/European Society of Cardiology (ESH/ESC) did not follow the same approach. In their 2018 guideline, the recommendation for patients with CKD was to lower SBP within the range of 130-139 mmHg and to individualize the intensity of treatment based on its tolerability.3 In this article, we explore the above-described heterogeneity across recent guidelines, providing a critical evaluation of randomized trials that compared a lower vs a standard BP target among patients with CKD. We raise the issue of research-grade BP monitoring method that was implemented in SPRINT and we ask the question whether the impressive results of this trial can be translated into benefit for our patients when intensification of antihypertensive therapy is guided by routine clinic BP recordings. The effect of intensive BP-lowering on kidney outcomes was explored in three separate randomized trials that enrolled non-diabetic patients with CKD (Table 2). The Modification of Diet in Renal Disease (MDRD) followed a 2 × 2 factorial design and randomized 840 patients with GFR 13-55 mL/min/1.73 m2 to two different levels of dietary protein intake and to achieve a lower mean BP (MBP) of <92 mmHg (approximately <125/75 mmHg) vs a standard MBP of 102-107 mmHg (approximately 135/85-140/90 mmHg).7 Over a 2.2-year-long follow-up, the rate of GFR decline did not differ between the lower- and standard-MBP arms. Intensive BP-lowering did not improve the combined outcome of ESRD or death [relative risk (RR): 0.85; 95% confidence interval (CI): 0.60-1.22].7 In the African American Study of Kidney Disease and Hypertension (AASK), 1094 African Americans with hypertensive nephrosclerosis were randomized to a lower vs a standard MBP target (<92 mmHg vs 102-107 mmHg) and to initiate antihypertensive therapy with metoprolol (50-200 mg/d), ramipril (2.5-10 mg/d), or amlodipine (5-10 mg/d) in a 2 × 3 factorial design.8 Over a follow-up of 3-6.4 years, compared with the standard MBP target, intensive BP-lowering had no benefit on the combined outcome of ≥50% decline in GFR, ESRD, or death (risk reduction: 2%; 95% CI: −22% to 21%).8 In the Ramipril Efficacy in Nephropathy trial 2 (REIN-2), 338 patients with non-diabetic, proteinuric CKD already treated with ramipril (2.5-5 mg/d) were randomized to intensified BP-lowering (goal BP <130/80 mmHg) or to standard BP control (diastolic BP <90 mmHg).9 Add-on therapy with felodipine (5-10 mg/d) was administered to achieve the assigned BP targets. REIN-2 was prematurely terminated at a median follow-up of 19 months due to futility. The risk of ESRD was similar in the intensive- and standard-BP groups (HR: 1.00; 95% CI: 0.61-1.64).9 Thus, during their randomized phase, none of these three trials showed that intensive BP-lowering is an effective strategy to halt the progression of kidney injury to ESRD. Post hoc analyses of the MDRD and AASK trials, however, support the notion that the level of proteinuria may act as treatment effect modifier. When MDRD participants were stratified into subgroups by the level of proteinuria at baseline, intensive BP-lowering was associated with a slower rate of GFR decline during follow-up in those with baseline proteinuria of 1-3 g/d or >3g/d. In the proteinuria stratum of <1 g/d, the rate of GFR decline did not differ between the lower- and standard-MBP arms.7 After the completion of the trial phase of AASK, participants were inserted into a cohort phase during which their BP was targeted to levels <130/80 mmHg. Over the entire follow-up of 9.1 years (trial plus cohort phase), the composite outcome of doubling of serum creatinine, ESRD, or death did not differ between those initially randomized to the lower vs those initially randomized to the standard MBP target (HR: 0.91; 95% CI: 0.77-1.08).11 However, there was a significant interaction between the randomized arm and level of baseline proteinuria for the composite kidney outcome (P = .02 for the interaction). In those with proteinuria >0.22 g/d, initial randomization to the lower BP target was associated with 27% reduction in the composite kidney outcome (HR: 0.73; 95% CI: 0.58-0.93). This benefit was not evident in those with baseline proteinuria ≤0.22 g/d (HR: 1.18; 95% CI: 0.93-1.50).11 Another post hoc analysis incorporating data from 840 MDRD participants with an extended follow-up of 9.2 years (trial plus cohort phase) showed that compared with the standard BP target, those initially randomized to intensive BP-lowering had 32% reduced risk of developing ESRD (HR: 0.68; 95% CI: 0.57-0.82).12 Based on this evidence, the 2012 KDIGO guideline recommended a lower BP target of <130/80 mmHg for CKD patients with persistent albuminuria.2 It has to be noted, however, that the strength of this recommendation was labeled as level 2 and the quality of evidence supporting this guidance was graded as level C. This guidance was based mainly on low-quality evidence from the aforementioned post hoc analyses of the MDRD and AASK trials. The observational nature of this data cannot demonstrate direct cause-and-effect associations. This scientific basis was considered insufficient/weak to mandate a reappraisal of BP targets for CKD patients in JNC8.5 Thus, the discrepancy between these two guidelines is not so large. In our interpretation, a level 2C recommendation by the 2012 KDIGO guideline is a clear recognition of the gap in the existing evidence and a call for future research. The effect of intensive BP-lowering on cardiovascular morbidity and all-cause mortality was evaluated in a prespecified post hoc analysis of 2,646 SPRINT participants with eGFR of 20-59 mL/min/1.73 m2.10 The separation between the intensive- and standard-arm was an average difference of −12.3 mmHg in SBP levels. Intensively treated participants required on average ~1 additional antihypertensive medication to achieve the assigned SBP target. This post hoc analysis showed the absence of interaction between the randomized arm and the level of eGFR at baseline for the primary cardiovascular outcome of SPRINT (P ≥ .30 for the interaction). The occurrence of the primary cardiovascular outcome did not differ between the intensive- and standard-arm (HR: 0.81; 95% CI: 0.63-1.05),10 possibly because this post hoc analysis was underpowered to detect a significant between-arm difference in the subgroup of SPRINT participants with eGFR <60 mL/min/1.73 m2. However, intensive BP-lowering provoked a significant 28% reduction in the risk of all-cause death (HR: 0.72; 95% CI: 0.53-0.99).10 Intensive BP-lowering in this post hoc analysis of SPRINT had no benefit on the composite kidney outcome of ≥50% decline in eGFR or ESRD (HR: 0.90; 95% CI: 0.44-1.83).10 Notably, this composite kidney outcome occurred in only 15 participants in the intensive-arm and in 16 participants in the standard-arm. This low incidence rate is not surprising, since patients with proteinuria >1 g/d who would presumably carry a higher risk of kidney injury progression were excluded from SPRINT. Although this trial was not originally designed to assess the efficacy of intensive BP-lowering on kidney outcomes like MDRD and AASK, the results of SPRINT were interpreted as a proof of the cardioprotective benefit of this strategy and provided the scientific basis to recommend a lower BP target of <130/80 mmHg for patients with CKD in the 2017 AHA/ACC guideline.4 The same clinical-trial evidence was interpreted differentially by the 2018 ESH/ESC guideline3 and the question that arises is whether the more conservative approach of European hypertension specialists is reasonable and evidence-based. Of note, the 2018 ESH/ESC guideline3 provided a more conservative recommendation on BP targets particularly for patients with CKD and not for other patient populations. Whether this differentiation is attributable to issues related to the tolerability of intensive BP-lowering in the CKD setting (ie, higher prosperity of these patients to adverse events, higher risk of acute kidney injury episodes, etch) or to other reasons remains another area of uncertainty. The diagnostic accuracy, reproducibility, and predictive value of BP recordings taken at the environment of clinic should be interpreted within the context of the actual methodology implemented (such as, type of BP monitor, the seated rest period before BP measurement, the presence of observer, the number of BP recordings).13 In SPRINT, clinic BP was measured with a fully automated oscillometric device that obtained triplicate recordings after a 5-minute seated rest and often without the presence of observer.6 This research-grade BP monitoring technique differs substantially from routine clinic BP recordings. A meta-analysis of 31 diagnostic-test studies (incorporating data from 9279 participants) showed that fully automated clinic SBP was similar with the reference-standard ambulatory daytime SBP [mean difference (MD): 0.3 mmHg; 95% CI: −1.1 to 1.7 mmHg].14 In contrast, routine clinic SBP overestimated ambulatory daytime SBP by 14.5 mmHg (MD: 14.5 mmHg; 95% CI: 11.8-17.2 mmHg).14 The importance of standardization in BP measurement methodology was highlighted by another meta-analysis of 10 diagnostic-test studies showing that unattended recordings were similar with attended clinic BP recordings, when the same device and measurement methodology was implemented.15 These meta-analyses, however, quantified only the average differences between BP monitoring techniques and did not explore their actual levels of agreement. In a diagnostic-test study that included 275 patients with stage 3-4 CKD and clinic BP <140/90 mmHg, participants underwent clinic BP monitoring with the research-grade technique that was implemented in SPRINT. On the same day, participants had their clinic BP recorded without specification of a 5-minute seated rest.16 Research-grade clinic SBP was by 12.7 mmHg lower than routine clinic SBP (MD: −12.7 mmHg; 95% CI: −14.7 to −10.7 mmHg) and the 95% levels of agreement between these two techniques were ranging from −46.1 to 20.7 mmHg. Research-grade clinic SBP underestimated the reference-standard ambulatory daytime SBP by 7.9 mmHg (MD: −7.9 mmHg; 95% CI: −9.4 to −6.4 mmHg), whereas the 95% levels of agreement were once again wide and were ranging from −33.2 to 17.4 mmHg. Whereas fully automated clinic SBP and ambulatory daytime SBP were significantly associated with echocardiographically documented left ventricular hypertrophy, routine clinic SBP could not detect evidence of target-organ damage.16 Taken together, the above evidence from diagnostic-test studies suggests that the differentiation in recommended BP targets between the American and European guidelines may be simply the tip of the iceberg. Guideline groups have taken into consideration the above-described variability between research-grade and routine clinic BP recordings. Recognizing that the adoption of a research-grade BP monitoring technique like that of SPRINT in daily clinical practice would probably be problematic, the recommended BP targets were adjusted to a higher level from that of the achieved clinic SBP of 121.2 mmHg in the intensive-arm of SPRINT. In our interpretation, a lower or a higher algebraic adjustment for the average bias inserted by routine clinic BP recordings remains an oversimplification.17 An algebraic adjustment for the average differences provides little to no reflection of the actual variability between research-grade and routine clinic BP at the level of individual patients, given the wide 95% levels of agreement between these two techniques in diagnostic-test studies.16 Thus, implementation of intensive BP targets in daily clinical practice necessitates the optimization of our BP measurement methodology. In other words, if antihypertensive therapy continues to be guided by what is already done in routine clinical practice, then intensive BP-lowering may not be beneficial. Evidence to support that intensive BP-lowering to levels <130/80 mmHg is an effective strategy to delay the progression of kidney injury to ESKD is weak. All randomized trials that compared a lower vs a standard BP target in patients with CKD failed to show a benefit of intensive BP-lowering on kidney outcomes.7-9 The notion that intensive BP-lowering is beneficial for those with proteinuric CKD is based on low-quality evidence from post hoc analysis of the MDRD and AASK with an extended observational follow-up after the completion of the randomized phase of these two trials.11, 12 In accordance with the results of MDRD, AASK, and REIN-2, in a post hoc analysis of 2646 SPRINT participants with eGFR <60 mL/min/1.73 m2, intensive BP-lowering did not improve the composite kidney outcome.10 This post hoc analysis, however, provided some evidence to support a potential benefit of intensive BP-lowering on survival and cardiovascular outcomes.10 Even if we interpret this evidence as a proof of cardioprotection, we believe that this benefit may not be generalizable to the majority of our patients if antihypertensive therapy continues to be guided by BP recordings taken under routine clinical practice conditions. In our view, individualization of the intensity of therapy based on its tolerability and optimization of our BP measurement methodology represent important steps to improve BP control and clinical outcomes in this high-risk population. The wider adoption of home or ambulatory BP monitoring is another important step to improve the management of hypertension among patients with CKD. The authors have no conflicts of interest to disclose. Literature search: PIG, VV; Drafting the manuscript: PIG; Revisions on the initial draft: PEZ, VL; Approval of the final paper: VV, VL, PEZ.

Does established vascular kidney disease exist?

In patients with heart failure, chronic kidney disease is common and associated with a higher risk of renal events than in patients without chronic kidney disease. We assessed the renal effects of angiotensin/neprilysin inhibition in patients who have heart failure with preserved ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction). In this randomized, double-blind, event-driven trial, we assigned 4822 patients who had heart failure with preserved ejection fraction to receive sacubitril/valsartan (n=2419) or valsartan (n=2403). Herein, we present the results of the prespecified renal composite outcome (time to first occurrence of either: ≥50% reduction in estimated glomerular filtration rate (eGFR), end-stage renal disease, or death from renal causes), the individual components of this composite, and the influence of therapy on eGFR slope. At randomization, eGFR was 63±19 mL·min-1·1.73 m-2. At study closure, the composite renal outcome occurred in 33 patients (1.4%) assigned to sacubitril/valsartan and 64 patients (2.7%) assigned to valsartan (hazard ratio, 0.50 [95% CI, 0.33-0.77]; P=0.001). The treatment effect on the composite renal end point did not differ according to the baseline eGFR (<60 versus ≥60 mL·min-1·1.73 m-2 (P-interaction=0.92). The decline in eGFR was less for sacubitril/valsartan than for valsartan (-2.0 [95% CI, -2.2 to -1.9] versus -2.7 [95% CI, -2.8 to -2.5] mL·min-1·1.73 m-2 per year). In patients with heart failure with preserved ejection fraction, sacubitril/valsartan reduced the risk of renal events, and slowed decline in eGFR, in comparison with valsartan. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.

Objectives: A hospital-based retrospective study was undertaken among the adult patients presenting to document the incidence of hypertensive urgency (HTN-U) and emergency while the secondary objectives included clinical presentations, disposition from emergency room, and inhospital mortality. Materials and Methods: All patients were evaluated by vital signs, clinical examination as well as relevant laboratory tests and radiological tests. Patients with target organ damage were grouped under the hypertensive emergency (HTN-E) group ( n = 104) and patients without target organ damage were included under the HTN-U group ( n = 52). The data were analyzed using GraphPad Prism (vs. 9.4.1) and MedCalc (vs. 20.118). Results: The incidence of HTN-E and HTN-U was 68.4% and 31.6%, respectively. The most common symptom observed in patients with HTN-E was breathlessness (53.8%), followed by chest pain (34.6%) and headache (27.9%). While, in HTN-U patients, most patients reported chest pain (43.8%), headache (39.6%), and epistaxis (22.9%). Majority of the patients in both the groups presented with signs of tachycardia, tachypnea, and hypoxia. The mortality in HTN-E and HTN-U patients was 15.4% and 2.1%, respectively. Among 104 patients with HTN-E, 53.8% each of the patients had acute heart failure and acute pulmonary edema. While, in HTN-U patients, acute pulmonary edema and acute coronary syndrome were observed in 2.1% each of the study subjects. Conclusion: Patients at high risk or end-organ damage should be immediately referred to the emergency department from the outpatient settings, as a rapid reduction in blood pressure is essential over minutes to hours, to prevent further organ damage.

Background: Cardiorenal syndrome is a well-known concept. However, in contrast to extensive investigations of chronic kidney disease (CKD) as a risk factor of cardiovascular disease (CVD), whether CVD increases long-term risk of end-stage renal disease (ESRD) is much less studied. Methods: In 8,881 participants of the Atherosclerosis Risk in Communities Study who attended visit 4 (1996-1998), we assessed the association of incident hospitalization with major CVD (heart failure, atrial fibrillation, coronary heart disease, and stroke) with subsequent risk of ESRD. Hospitalization with CVD was entered into multivariable Cox models as a time-varying exposure to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Results: Baseline mean age was 62 years, 59% were female, 22% were black, and 5.5% had eGFR 15-60 ml/min/1.73m 2 . During a median follow-up of 15.9 years, there were 141 cases of ESRD. In multivariable Cox analysis, each incident CVD subtype was independently associated with increased risk of ESRD, with the highest HR for heart failure (HR, 16.9 [95%CI, 11.6-24.7]), followed by coronary heart disease, atrial fibrillation, and stroke (Model 2 in Table ). The association remained significant across CVD subtypes except for atrial fibrillation, when all CVD subtypes were simultaneously entered into a Cox model as time-varying exposures (Model 3 in Table ). The results were similar when modeling death as a competing risk, and consistent across subgroups of age, sex, race, diabetes, and CKD. When analyzing confirmed events of heart failure with preserved ejection fraction (HFpEF) (n=205) and reduced ejection fraction (HFrEF) (n=190), the association was particularly evident for HFpEF (10.8 [5.9-19.7]) compared to HFrEF (4.9 [2.0-11.7]). Conclusions: These findings support CVD as a potent risk factor of ESRD. Patients with CVD, particularly heart failure, should be recognized as a high risk population for ESRD. Distinct contribution of HFpEF vs. HFrEF to ESRD deserves future investigations.

52-Year-Old Woman With Fever, Diaphoresis, and Abdominal Pain

Worsening renal function during intensive blood pressure control: another example of not prognostically relevant creatinine rise?