Browsing by Author "Cullaro, Giuseppe"

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    Acute Kidney Injury in Patients with Cirrhosis and Chronic Kidney Disease: Results from the HRS-HARMONY Consortium
    (Elsevier, 2024) St. Hillien, Shelsea A.; Robinson, Jevon E.; Ouyang, Tianqi; Patidar, Kavish R.; Belcher, Justin M.; Cullaro, Giuseppe; Regner, Kevin R.; Chung, Raymond T.; Ufere, Nneka; Velez, Juan Carlos Q.; Neyra, Javier A.; Asrani, Sumeet K.; Wadei, Hani; Teixeira, J. Pedro; Saly, Danielle L.; Levitsky, Josh; Orman, Eric; Sawinski, Deirdre; Dageforde, Leigh Anne; Allegrietti, Andrew S.; Medicine, School of Medicine
    Background & Aims Chronic kidney disease (CKD) frequency is increasing in patients with cirrhosis and these individuals often experience acute kidney injury (AKI). Direct comparisons of outcomes between AKI-only versus AKI on CKD (AoCKD) among patients with cirrhosis are not well described. Methods A total of 2057 patients with cirrhosis and AKI across 11 hospital networks from the HRS-HARMONY consortium were analyzed (70% AKI-only and 30% AoCKD). The primary outcome was unadjusted and adjusted 90-day mortality, with transplant as a competing risk, using Fine and Gray analysis. Results Compared with patients with AKI-only, patients with AoCKD had higher median admission creatinine (2.25 [interquartile range, 1.7–3.2] vs 1.83 [1.38–2.58] mg/dL) and peak creatinine (2.79 [2.12–4] vs 2.42 [1.85–3.50] mg/dL) but better liver function parameters (total bilirubin 1.5 [interquartile range, 0.7–3.1] vs 3.4 [1.5–9.3] mg/dL; and international normalized ratio 1.4 [interquartile range, 1.2–1.8] vs 1.7 [1.39–2.2]; P < .001 for all). Patients with AoCKD were more likely to have metabolic dysfunction associated steatotic liver disease cirrhosis (31% vs 17%) and less likely to have alcohol-associated liver disease (26% vs 45%; P < .001 for both). Patients with AKI-only had higher unadjusted mortality (39% vs 30%), rate of intensive care unit admission (52% vs 35%; P < .001 for both), and use of renal-replacement therapy (20% vs 15%; P = .005). After adjusting for age, race, sex, transplant listing status, and Model for End-Stage Liver Disease–Sodium score, AoCKD was associated with a lower 90-day mortality compared with AKI-only (subhazard ratio, 0.72; 95% confidence interval, 0.61–0.87). Conclusions In hospitalized patients with AKI and cirrhosis, AoCKD was associated with lower 90-day mortality compared with AKI-only. This may be caused by the impact of worse liver function parameters in the AKI-only group on short-term outcomes. Further study of the complicated interplay between acute and chronic kidney disease in cirrhosis is needed.
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    Association of Hepatorenal Syndrome-Acute Kidney Injury with Mortality in Patients with Cirrhosis Requiring Renal Replacement Therapy: Results from the HRS-HARMONY Consortium
    (Wolters Kluwer, 2025) Cama-Olivares, Augusto; Ouyang, Tianqi; Takeuchi, Tomonori; St. Hillien, Shelsea A.; Robinson, Jevon E.; Chung, Raymond T.; Cullaro, Giuseppe; Karvellas, Constantine J.; Levitsky, Josh; Orman, Eric S.; Patidar, Kavish R.; Regner, Kevin R.; Saly, Danielle L.; Sawinski, Deirdre; Sharma, Pratima; Teixeira, J. Pedro; Ufere, Nneka N.; Velez, Juan Carlos Q.; Wadei, Hani M.; Wahid, Nabeel; Allegretti, Andrew S.; Neyra, Javier A.; Belcher, Justin M.; HRS-HARMONY Consortium; Medicine, School of Medicine
    Key Points: In patients with cirrhosis and AKI requiring renal replacement therapy (RRT), hepatorenal syndrome-AKI was not associated with an increased 90-day mortality when compared with other AKI etiologies. Etiology of AKI may not be a critical factor regarding decisions to trial RRT in acutely ill patients with cirrhosis and AKI. Although elevated, mortality rates in this study are comparable with those reported in general hospitalized patients with AKI requiring RRT. Background: While AKI requiring renal replacement therapy (AKI-RRT) is associated with increased mortality in heterogeneous inpatient populations, the epidemiology of AKI-RRT in hospitalized patients with cirrhosis is not fully known. Herein, we evaluated the association of etiology of AKI with mortality in hospitalized patients with cirrhosis and AKI-RRT in a multicentric contemporary cohort. Methods: This is a multicenter retrospective cohort study using data from the HRS-HARMONY consortium, which included 11 US hospital network systems. Consecutive adult patients admitted in 2019 with cirrhosis and AKI-RRT were included. The primary outcome was 90-day mortality, and the main independent variable was AKI etiology, classified as hepatorenal syndrome (HRS-AKI) versus other (non–HRS-AKI). AKI etiology was determined by at least two independent adjudicators. We performed Fine and Gray subdistribution hazard analyses adjusting for relevant clinical variables. Results: Of 2063 hospitalized patients with cirrhosis and AKI, 374 (18.1%) had AKI-RRT. Among them, 65 (17.4%) had HRS-AKI and 309 (82.6%) had non–HRS-AKI, which included acute tubular necrosis in most cases (62.6%). Continuous renal replacement therapy was used as the initial modality in 264 (71%) of patients, while intermittent hemodialysis was used in 108 (29%). The HRS-AKI (versus non–HRS-AKI) group received more vasoconstrictors for HRS management (81.5% versus 67.9%), whereas the non–HRS-AKI group received more mechanical ventilation (64.3% versus 50.8%) and more continuous renal replacement therapy (versus intermittent hemodialysis) as the initial RRT modality (73.9% versus 56.9%). In the adjusted model, HRS-AKI (versus non–HRS-AKI) was not independently associated with increased 90-day mortality (subdistribution hazard ratio, 1.36; 95% confidence interval, 0.95 to 1.94). Conclusions: In this multicenter contemporary cohort of hospitalized adult patients with cirrhosis and AKI-RRT, HRS-AKI was not independently associated with an increased risk of 90-day mortality when compared with other AKI etiologies. The etiology of AKI appears less relevant than previously considered when evaluating the prognosis of hospitalized adult patients with cirrhosis and AKI requiring RRT.
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    Longer time to recovery from acute kidney injury is associated with major adverse kidney events in patients with cirrhosis
    (Wiley, 2023) Patidar, Kavish R.; Naved, Mobasshir A.; Kabir, Shaowli; Grama, Ananth; Allegretti, Andrew S.; Cullaro, Giuseppe; Asrani, Sumeet K.; Worden, Astin; Desai, Archita P.; Ghabril, Marwan S.; Nephew, Lauren D.; Orman, Eric S.; Medicine, School of Medicine
    Background: In patients with cirrhosis and acute kidney injury (AKI), longer time to AKI-recovery may increase the risk of subsequent major-adverse-kidney-events (MAKE). Aims: To examine the association between timing of AKI-recovery and risk of MAKE in patients with cirrhosis. Methods: Hospitalised patients with cirrhosis and AKI (n = 5937) in a nationwide database were assessed for time to AKI-recovery and followed for 180-days. Timing of AKI-recovery (return of serum creatinine <0.3 mg/dL of baseline) from AKI-onset was grouped by Acute-Disease-Quality-Initiative Renal Recovery consensus: 0-2, 3-7, and >7-days. Primary outcome was MAKE at 90-180-days. MAKE is an accepted clinical endpoint in AKI and defined as the composite outcome of ≥25% decline in estimated-glomerular-filtration-rate (eGFR) compared with baseline with the development of de-novo chronic-kidney-disease (CKD) stage ≥3 or CKD progression (≥50% reduction in eGFR compared with baseline) or new haemodialysis or death. Landmark competing-risk multivariable analysis was performed to determine the independent association between timing of AKI-recovery and risk of MAKE. Results: 4655 (75%) achieved AKI-recovery: 0-2 (60%), 3-7 (31%), and >7-days (9%). Cumulative-incidence of MAKE was 15%, 20%, and 29% for 0-2, 3-7, >7-days recovery groups, respectively. On adjusted multivariable competing-risk analysis, compared to 0-2-days, recovery at 3-7 and >7-days was independently associated with an increased risk for MAKE: sHR 1.45 (95% CI 1.01-2.09, p = 0.042), sHR 2.33 (95% CI 1.40-3.90, p = 0.001), respectively. Conclusion: Longer time to recovery is associated with an increased risk of MAKE in patients with cirrhosis and AKI. Further research should examine interventions to shorten AKI-recovery time and its impact on subsequent outcomes.
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    Performance of race-neutral eGFR equations in patients with decompensated cirrhosis
    (Wolters Kluwer, 2025) Fallahzadeh, Mohammad Amin; Allegretti, Andrew S.; Nadim, Mitra K.; Mahmud, Nadim; Patidar, Kavish R.; Cullaro, Giuseppe; Saracino, Giovanna; Asrani, Sumeet K.; Medicine, School of Medicine
    The 2021 Chronic Kidney Disease Epidemiology Collaboration equation [CKD-EPI 2021] is a race-neutral equation recently developed and rapidly implemented as a reference standard to estimate glomerular filtration rate(GFR). However, its role in cirrhosis has not been examined especially in low GFR. We analyzed the performance of CKD-EPI 2021 compared to other equations with protocol-measured GFR (mGFR) in cirrhosis. We analyzed 2090 unique adult patients with cirrhosis undergoing protocol GFR measurements using iothalamate clearance from 1985 to 2015 when listed for liver transplantation at Baylor University in Dallas and Fort Worth, Texas. Using mGFR as a reference standard, the CKD-EPI 2021 was compared to CKD-EPI 2012, Modification of Diet in Renal Disease-4, Modification of Diet in Renal Disease-6, Royal Free Hospital, and GFR Assessment in Liver disease overall and in certain subgroups (ascites, mGFR ≤ 30 mL/min/1.73 m 2 , diagnosis, Model for End-Stage Liver Disease and gender). We examined bias (difference between eGFR and mGFR), accuracy (p30: eGFR within ± 30% of mGFR) and agreement between eGFR and mGFR categories. CKD-EPI 2021 had the second lowest bias across the entire range of GFR after GFR Assessment in Liver disease (6.6 vs. 4.6 mL/min/1.73 m 2 , respectively, p < 0.001). The accuracy of CKD-EPI 2021 was similar to CKD-EPI 2012 (p30 = 67.8% vs. 67.9%, respectively) which was higher than the other equations ( p < 0.001). It had a similar performance in patients with ascites, by diagnoses, Model for End-Stage Liver Disease subgroups, by gender, and in non-Black patients. However, it had a relatively higher overestimation in mGFR ≤ 30 mL/min/1.73 m 2 than most equations (18.5 mL/min/1.73m 2 , p < 0.001). Specifically, 64% of patients with mGFR ≤ 30 mL/min/1.73m 2 were incorrectly classified as a less severe CKD stage by CKD-EPI 2021. In Blacks, CKD-EPI 2021 underestimated eGFR by 17.9 mL/min/1.73 m 2 , which was higher than the alternate equations except for Royal Free Hospital ( p < 0.001). The novel race-neutral eGFR equation, CKD-EPI 2021, improves the GFR estimation overall but may not accurately capture true kidney function in cirrhosis, specifically at low GFR. There is an urgent need for a race-neutral equation in liver disease reflecting the complexity of kidney function physiology unique to cirrhosis, given implications for organ allocation and dual organ transplant.
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    Prognostic significance of acute kidney injury stage 1B in hospitalized patients with cirrhosis: A US nationwide study
    (Wolters Kluwer, 2024) Patidar, Kavish R.; Cullaro, Giuseppe; Naved, Mobasshir A.; Kabir, Shaowli; Grama, Ananth; Orman, Eric S.; Piano, Salvatore; Allegretti, Andrew S.; Medicine, School of Medicine
    Understanding the prognostic significance of acute kidney injury (AKI) stage 1B [serum creatinine (sCr) ≥1.5 mg/dL] compared with stage 1A (sCr < 1.5 mg/dL) in a US population is important as it can impact initial management decisions for AKI in hospitalized cirrhosis patients. Therefore, we aimed to define outcomes associated with stage 1B in a nationwide US cohort of hospitalized cirrhosis patients with AKI. Hospitalized cirrhosis patients with AKI in the Cerner-Health-Facts database from January 2009 to September 2017 (n = 6250) were assessed for AKI stage 1 (≥1.5-2-fold increase in sCr from baseline) and were followed for 90 days for outcomes. The primary outcome was 90-day mortality; secondary outcomes were in-hospital AKI progression and AKI recovery. Competing-risk multivariable analysis was performed to determine the independent association between stage 1B, 90-day mortality (liver transplant as a competing risk), and AKI recovery (death/liver transplant as a competing risk). Multivariable logistic regression analysis was performed to determine the independent association between stage 1B and AKI progression. In all, 4654 patients with stage 1 were analyzed: 1A (44.3%) and 1B (55.7%). Stage 1B patients had a significantly higher cumulative incidence of 90-day mortality compared with stage 1A patients, 27.2% versus 19.7% ( p < 0.001). In multivariable competing-risk analysis, patients with stage 1B (vs. 1A) had a higher risk for mortality at 90 days [sHR 1.52 (95% CI 1.20-1.92), p = 0.001] and decreased probability for AKI recovery [sHR 0.76 (95% CI 0.69-0.83), p < 0.001]. Furthermore, in multivariable logistic regression analysis, AKI stage 1B (vs. 1A) was independently associated with AKI progression, OR 1.42 (95% CI 1.14-1.72) ( p < 0.001). AKI stage 1B patients have a significantly higher risk for 90-day mortality, AKI progression, and reduced probability of AKI recovery compared with AKI stage 1A patients. These results could guide initial management decisions for AKI in hospitalized patients with cirrhosis.
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    Recent Advances in the Management of Hepatorenal Syndrome: A US Perspective
    (Elsevier, 2023) Patidar, Kavish R.; Piano, Salvatore; Cullaro, Giuseppe; Belcher, Justin M.; Allegretti, Andrew S.; HRS-Harmony Consortia; Medicine, School of Medicine