Risk for Chronic Kidney Disease Progression After Acute Kidney Injury: Findings From the Chronic Renal Insufficiency Cohort Study.

BACKGROUND: Prior studies associating acute kidney injury (AKI) with more rapid subsequent loss of kidney function had methodological limitations, including inadequate control for differences between patients who had AKI and those who did not. OBJECTIVE: To determine whether AKI is independently associated with subsequent kidney function trajectory among patients with chronic kidney disease (CKD). DESIGN: Multicenter prospective cohort study. SETTING: United States. PARTICIPANTS: Patients with CKD (n = 3150). MEASUREMENTS: Hospitalized AKI was defined by a 50% or greater increase in inpatient serum creatinine (SCr) level from nadir to peak. Kidney function trajectory was assessed using estimated glomerular filtration rate (eGFR) based on SCr level (eGFRcr) or cystatin C level (eGFRcys) measured at annual study visits. RESULTS: During a median follow-up of 3.9 years, 433 participants had at least 1 AKI episode. Most episodes (92%) had stage 1 or 2 severity. There were decreases in eGFRcr (-2.30 [95% CI, -3.70 to -0.86] mL/min/1.73 m2) and eGFRcys (-3.61 [CI, -6.39 to -0.82] mL/min/1.73 m2) after AKI. However, in fully adjusted models, the decreases were attenuated to -0.38 (CI, -1.35 to 0.59) mL/min/1.73 m2 for eGFRcr and -0.15 (CI, -2.16 to 1.86) mL/min/1.73 m2 for eGFRcys, and the CI bounds included the possibility of no effect. Estimates of changes in eGFR slope after AKI determined by either SCr level (0.04 [CI, -0.30 to 0.38] mL/min/1.73 m2 per year) or cystatin C level (-0.56 [CI, -1.28 to 0.17] mL/min/1.73 m2 per year) also had CI bounds that included the possibility of no effect. LIMITATIONS: Few cases of severe AKI, no adjudication of AKI cause, and lack of information about nephrotoxic exposures after hospital discharge. CONCLUSION: After pre-AKI eGFR, proteinuria, and other covariables were accounted for, the association between mild to moderate AKI and worsening subsequent kidney function in patients with CKD was small. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.

Initial Management and Potential Opportunities to Deprescribe Dialysis among Patients with AKI-D Patients after Hospital Discharge.

SIGNIFICANCE STATEMENT: Dialysis-requiring AKI (AKI-D) now accounts for more than 15% of outpatient hemodialysis initiations; over 30% of these patients with AKI-D may have potential to recover. However, little is known about strategies currently used to treat outpatient AKI-D and screen for recovery. In this study of 1754 patients with AKI-D, we found that ( 1 ) the initial dialysis orders were similar to those of patients with contemporary incident ESKD, despite different treatment goals; ( 2 ) timed urine collections were completed in only a minority of patients; and ( 3 ) most patients with AKI-D who recovered discontinued dialysis without ever having been weaned from their initial dialysis prescription, suggesting there may be substantial opportunity to wean dialysis sooner.

Acute Kidney Injury Associates with Long-Term Increases in Plasma TNFR1, TNFR2, and KIM-1: Findings from the CRIC Study.

BACKGROUND: Some markers of inflammation-TNF receptors 1 and 2 (TNFR1 and TNFR2)-are independently associated with progressive CKD, as is a marker of proximal tubule injury, kidney injury molecule 1 (KIM-1). However, whether an episode of hospitalized AKI may cause long-term changes in these biomarkers is unknown. METHODS: Among adult participants in the Chronic Renal Insufficiency Cohort (CRIC) study, we identified 198 episodes of hospitalized AKI (defined as peak/nadir inpatient serum creatinine values ≥1.5). For each AKI hospitalization, we found the best matched non-AKI hospitalization (unique patients), using prehospitalization characteristics, including eGFR and urine protein/creatinine ratio. We measured TNFR1, TNFR2, and KIM-1 in banked plasma samples collected at annual CRIC study visits before and after the hospitalization (a median of 7 months before and 5 months after hospitalization). RESULTS: In the AKI and non-AKI groups, we found similar prehospitalization median levels of TNFR1 (1373 pg/ml versus 1371 pg/ml, for AKI and non-AKI, respectively), TNFR2 (47,141 pg/ml versus 46,135 pg/ml, respectively), and KIM-1 (857 pg/ml versus 719 pg/ml, respectively). Compared with matched study participants who did not experience AKI, study participants who did experience AKI had greater increases in TNFR1 (23% versus 10%, P<0.01), TNFR2 (10% versus 3%, P<0.01), and KIM-1 (13% versus -2%, P<0.01). CONCLUSIONS: Among patients with CKD, AKI during hospitalization was associated with increases in plasma TNFR1, TNFR2, and KIM-1 several months after their hospitalization. These results highlight a potential mechanism by which AKI may contribute to more rapid loss of kidney function months to years after the acute insult.

Absence of long-term changes in urine biomarkers after AKI: findings from the CRIC study.

BACKGROUND: Mechanisms by which AKI leads to CKD progression remain unclear. Several urine biomarkers have been identified as independent predictors of progressive CKD. It is unknown whether AKI may result in long-term changes in these urine biomarkers, which may mediate the effect of AKI on CKD progression. METHODS: We selected 198 episodes of hospitalized AKI (defined as peak/nadir inpatient serum creatinine values ≥ 1.5) among adult participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. We matched the best non-AKI hospitalization (unique patients) for each AKI hospitalization using pre-hospitalization characteristics including eGFR and urine protein/creatinine ratio. Biomarkers were measured in banked urine samples collected at annual CRIC study visits. RESULTS: Urine biomarker measurements occurred a median of 7 months before and 5 months after hospitalization. There were no significant differences in the change in urine biomarker-to-creatinine ratio between the AKI and non-AKI groups: KIM-1/Cr + 9% vs + 7%, MCP-1/Cr + 4% vs + 1%, YKL-40/Cr + 7% vs -20%, EGF/Cr -11% vs -8%, UMOD/Cr -2% vs -7% and albumin/Cr + 17% vs + 13% (all p > 0.05). CONCLUSION: In this cohort of adults with CKD, AKI did not associate with long-term changes in urine biomarkers.

Central venous pressure and the risk of diuretic-associated acute kidney injury in patients after cardiac surgery.

BACKGROUND: When prescribing diuretics in the postcardiac surgical intensive care unit (ICU), clinicians may use central venous pressure (CVP) to assess volume status and the risk of acute kidney injury (AKI). In this study, we examined how the risk of diuretic-associated AKI varied with CVP in patients undergoing cardiac surgery. METHODS: We used the Medical Information Mart for Intensive Care database to study adults admitted to the postcardiac surgical ICU at an urban, academic medical center between 2001 and 2012. We examined the odds of AKI per 1-mm Hg increase in CVP among patients receiving intravenous loop diuretics using multivariable adjusted logistic regression. We examined the risk of AKI among patients with diuretic use (vs nonuse) across tertiles of CVP using inverse probability treatment weighting. RESULTS: Among 4,164 patients receiving intravenous loop diuretics, the adjusted odds of subsequent AKI were 1.11 (95% CI 1.08-1.13) times higher per mm Hg increase in mean CVP. This association was log-linear across the entire range of CVPs observed. In the analysis of diuretic use (n = 5,396), the adjusted risk ratio for AKI with diuretic use (vs nonuse) was 1.33 (95% CI 1.21-1.47) and did not materially differ across tertile of CVP. CONCLUSIONS: Higher rather than lower CVP is an independent marker of AKI risk. The risk of AKI associated with diuretic use may not be influenced by CVP. Novel methods of assessing volume status and AKI risk are needed to guide patient selection for diuretic therapy.

AKI-A Relevant Safety End Point?

Acute kidney injury (AKI) is a common outcome evaluated in clinical studies, often as a safety end point in a variety of cardiovascular, kidney disease, and other clinical trials. AKI end points that include modest increases in serum creatinine levels from baseline may not associate with patient-centered outcomes such as initiation of dialysis, sustained decline in kidney function, or death. Surprisingly, data from several randomized controlled trials have suggested that in certain settings, the development of AKI may be associated with favorable outcomes. AKI safety end points that are nonspecific and may not associate with patient-centered outcomes could result in beneficial therapies being inappropriately withheld or never developed for commercial use. We review several issues related to commonly used AKI definitions and suggest that future work in AKI use more patient-centered AKI end points such as major adverse kidney events at 30 days or other later time points.

Patient and Provider Characteristics Associated With Sodium-Glucose Cotransporter 2 Inhibitor Prescription in Patients With Diabetes and Proteinuric Chronic Kidney Disease.

Despite accumulating evidence of cardiorenal benefits from sodium-glucose cotransporter 2 (SGLT2) inhibitors, prescription of agents in this drug class may be limited by concerns regarding adverse effects and interdisciplinary care coordination. To investigate these potential barriers, we performed a cross-sectional study of SGLT2 inhibitor prescriptions in 2017 in 3,779 adults with type 2 diabetes and proteinuric chronic kidney disease from a nationwide database. Only 173 (5%) of these patients received an SGLT2 inhibitor in 2017. Younger age, renin-angiotensin-aldosterone system inhibitor prescription, and higher estimated glomerular filtration rate were associated with SGLT2 inhibitor prescription. Primary care providers were responsible for the majority of the prescriptions. Continued efforts should be made to track and improve SGLT2 inhibitor use in indicated populations.

Optimum Care of AKI Survivors Not Requiring Dialysis after Discharge: An AKINow Recovery Workgroup Report.

AKI survivors experience gaps in care that contribute to worse outcomes, experience, and cost.Challenges to optimal care include issues with information transfer, education, collaborative care, and use of digital health tools.Research is needed to study these challenges and inform optimal use of diagnostic and therapeutic interventions to promote recovery AKI affects one in five hospitalized patients and is associated with poor short-term and long-term clinical and patient-centered outcomes. Among those who survive to discharge, significant gaps in documentation, education, communication, and follow-up have been observed. The American Society of Nephrology established the AKINow taskforce to address these gaps and improve AKI care. The AKINow Recovery workgroup convened two focus groups, one each focused on dialysis-independent and dialysis-requiring AKI, to summarize the key considerations, challenges, and opportunities in the care of AKI survivors. This article highlights the discussion surrounding care of AKI survivors discharged without the need for dialysis. On May 3, 2022, 48 patients and multidisciplinary clinicians from diverse settings were gathered virtually. The agenda included a patient testimonial, plenary sessions, facilitated small group discussions, and debriefing. Core challenges and opportunities for AKI care identified were in the domains of transitions of care, education, collaborative care delivery, diagnostic and therapeutic interventions, and digital health applications. Integrated multispecialty care delivery was identified as one of the greatest challenges to AKI survivor care. Adequate templates for communication and documentation; education of patients, care partners, and clinicians about AKI; and a well-coordinated multidisciplinary posthospital follow-up plan form the basis for a successful care transition at hospital discharge. The AKINow Recovery workgroup concluded that advancements in evidence-based, patient-centered care of AKI survivors are needed to improve health outcomes, care quality, and patient and provider experience. Tools are being developed by the AKINow Recovery workgroup for use at the hospital discharge to facilitate care continuity.

Probing the Association between Acute Kidney Injury and Cardiovascular Outcomes.

BACKGROUND: Patients hospitalized with AKI have higher subsequent risks of heart failure, atherosclerotic cardiovascular events, and mortality than their counterparts without AKI, but these higher risks may be due to differences in prehospitalization patient characteristics, including the baseline level of estimated glomerular filtration rate (eGFR), the rate of prior eGFR decline, and the proteinuria level, rather than AKI itself. METHODS: Among 2177 adult participants in the Chronic Renal Insufficiency Cohort study who were hospitalized in 2013-2019, we compared subsequent risks of heart failure, atherosclerotic cardiovascular events, and mortality between those with serum creatinine-based AKI (495 patients) and those without AKI (1682 patients). We report both crude associations and associations sequentially adjusted for prehospitalization characteristics including eGFR, eGFR slope, and urine protein-creatinine ratio (UPCR). RESULTS: Compared with patients hospitalized without AKI, those with hospitalized AKI had lower eGFR prehospitalization (42 versus 49 ml/min per 1.73 m 2 ), faster chronic loss of eGFR prehospitalization (-0.84 versus -0.51 ml/min per 1.73 m 2 per year), and more proteinuria prehospitalization (UPCR 0.28 versus 0.16 g/g); they also had higher prehospitalization systolic BP (130 versus 127 mm Hg; P < 0.01 for all comparisons). Adjustment for prehospitalization patient characteristics attenuated associations between AKI and all three outcomes, but AKI remained an independent risk factor. Attenuation of risk was similar after adjustment for absolute eGFR, eGFR slope, or proteinuria, individually or in combination. CONCLUSIONS: Prehospitalization variables including eGFR, eGFR slope, and proteinuria confounded associations between AKI and adverse cardiovascular outcomes, but these associations remained significant after adjusting for prehospitalization variables.

Submaximal Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Dosing Among Persons With Proteinuria.

For persons with proteinuria, angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) are treatment mainstays for reducing kidney disease progression. Guidelines for managing hypertension and chronic kidney disease recommend titrating to the maximum ACEi/ARB dose tolerated. Using deidentified national electronic health record data from the Optum Labs Data Warehouse, we examined ACEi/ARB dosing among adults with proteinuria-defined as either a urine albumin to creatinine ratio of 30 mg/g or greater or a protein to creatinine ratio of 150 mg/g or greater-who were prescribed an ACEi/ARB medication between January 1, 2017, and December 31, 2018. Among 100,238 included patients (mean age, 65.1 years; 49,523 [49.4%] female), 29,883 (29.8%) were taking maximal ACEi/ARB doses. Among 74,287 patients without potential contraindications to dose escalation (systolic blood pressure <120 mm Hg, estimated glomerular filtration rate <15 mL/min per 1.73 m2, serum potassium level greater than 5.0 mEq/L, or acute kidney injury within the prior year), the frequency of maximal ACEi/ARB dosing was 32.3% (24,025 patients). In adjusted analyses, age less than 40 years, female sex, Hispanic ethnicity, lower urine albumin to creatinine ratio, lack of diabetes, heart failure, lower blood pressure, higher serum potassium level, and prior acute kidney injury were associated with lower odds of maximal ACEi/ARB dosing. Having a prior nephrologist visit was not associated with maximal dosing. Our results suggest that greater attention toward optimizing the dose of ACEi/ARB therapy may represent an opportunity to improve chronic kidney disease care and reduce excess morbidity and mortality associated with disease progression.

Barriers to ACEI/ARB Use in Proteinuric Chronic Kidney Disease: An Observational Study.

OBJECTIVE: To assess present angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) use among patients with proteinuric chronic kidney disease (CKD) and examine barriers limiting this guideline-concordant care. PATIENTS AND METHODS: Using a nationwide database containing patient-level claims and integrated clinical information, we examined current ACEI/ARB prescriptions on the index date (April 15, 2017) and prior ACEI/ARB use in 41,743 insured adults with proteinuric CKD. Using multivariable logistic regression, we estimated adjusted associations between current ACEI/ARB use and putative barriers including past acute kidney injury (AKI), hyperkalemia, advanced CKD, and lack of nephrology care. RESULTS: Only 49% (n=20,641) of patients had an active ACEI/ARB prescription on the index date, but 87% (n=36,199) had been previously prescribed an ACEI/ARB. Use was lower in patients with past AKI, hyperkalemia, CKD stages 4 or 5, and a lack of nephrology care (adjusted odds ratios were 0.61 [95% CI, 0.58 to 0.64], 0.76 [95% CI, 0.72 to 0.80], 0.48 [95% CI, 0.45 to 0.51], and 0.85 [95% CI, 0.81 to 0.89], respectively). CONCLUSION: Discontinuing, rather than never initiating, ACEI/ARB treatment limits guideline-concordant care in proteinuric CKD. Past AKI, hyperkalemia, advanced CKD, and lack of nephrology care were associated with lower use of ACEIs/ARBs, but these putative barriers may in many instances be inappropriate (AKI and advanced CKD) or modifiable (hyperkalemia and lack of nephrology care).

Reducing Phlebotomy in Hemodialysis Patients: A Quality Improvement Study.

RATIONALE & OBJECTIVE: Hospitalized patients receiving hemodialysis frequently have routine, daily laboratory studies drawn by peripheral venipuncture-a painful process that damages peripheral veins that may be needed for future dialysis access. Some of these peripheral venipunctures are likely preventable by drawing blood samples off the hemodialysis machine circuit. We describe an initiative to allow and encourage blood to be drawn "with dialysis." STUDY DESIGN: Quality improvement study. SETTING & PARTICIPANTS: Non-critically ill adult patients treated with hemodialysis at Stanford Health Care between September 2018 and September 2019. QUALITY IMPROVEMENT ACTIVITIES: We modified the electronic health record to allow providers to order laboratory studies with the frequency "with dialysis." Use of the "with dialysis" frequency was promoted through educational efforts aimed at primary medical teams, nephrology consult staff, and nephrology advanced practice providers. OUTCOMES: We tracked the number of "with dialysis" blood draws and the number of eligible patients per week during the first year of implementation. ANALYTICAL APPROACH: The number of "with dialysis" blood draws and eligible patients per week were measured over time. Cost savings were estimated by multiplying the difference in cost between peripheral venipuncture and "with dialysis" blood draw by the number of "with dialysis" blood draws performed. RESULTS: Uptake during the first year of implementation was an average of 6.3 "with dialysis" draws per 100 eligible patients per week. Estimated savings exceeded $7,000 in the first year of the program. LIMITATIONS: Our single-center study may not be generalizable to other institutions, especially those without dialysis ordering and laboratory ordering housed within the same electronic system. We were unable to track additional outcomes, including the number of peripheral venipunctures and delays in laboratory results. CONCLUSIONS: The prevention of unnecessary peripheral venipuncture in hospitalized patients receiving hemodialysis is a promising and valuable quality improvement target, which may be aided by the electronic health record. Future work is needed to increase recognition and use of "with dialysis"blood work options.

Estimated effects of early diuretic use in critical illness.

OBJECTIVE: To estimate the effects of diuretic use during the first 24 hours of an intensive care unit stay on in-hospital mortality and other clinical outcomes including acute kidney injury and duration of mechanical ventilation. DESIGN: Retrospective cohort study. SETTING: Urban, academic medical center. PATIENTS: Adult patients admitted to medical or cardiac ICUs between 2001 and 2012, excluding those on maintenance dialysis or with ICU length of stay < 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 13,589 patients: 2,606 with and 10,983 without early diuretic use (loop diuretic exposure during the first 24 hours of an ICU stay). Propensity score matching generated 2523 pairs with well-balanced baseline characteristics. Early diuretic use was unassociated with in-hospital mortality (risk ratio 1.01, 99.5% confidence interval 0.83-1.22). We found no evidence of associations with ICU or hospital length of stay, or duration or provision of mechanical ventilation. Early diuretic use was associated with higher rates of subsequent acute kidney injury (risk ratio 1.41, 99.5% confidence interval 1.25 to 1.59) and electrolyte abnormalities. Results were not materially different in subgroups of patients with heart failure, chronic kidney disease, or acute lung injury. CONCLUSIONS: Early diuretic use in critical illness was unassociated with in-hospital mortality, ICU or hospital length of stay, or duration of mechanical ventilation, but risks of acute kidney injury and electrolyte abnormalities were higher.