Development and validation of a mathematical equation to estimate glomerular filtration rate in cirrhosis: The royal free hospital cirrhosis glomerular filtration rate

Kalafateli, Maria; Wickham, Fred; Burniston, Maria; Cholongitas, Εvangelos; Theocharidou, Eleni; Garcovich, Matteo; O’Beirne, James; Westbrook, Rachel; Leandro, Gioacchino; Burroughs, Andrew K.; Tsochatzis, Emmanuel

doi:10.1002/hep.28891

Cited by 62 publications

(81 citation statements)

References 26 publications

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“…At baseline, none of the enrolled patients with SAH documented high serum creatinine level, suggesting normal functioning of the kidneys. Further, serum creatinine‐based estimation of glomerular filtration rate18 was found to be >90 mL/minute/1.73 m 2 in all patients, confirming the absence of kidney injury in these patients. The laboratory staff performing the experiments was unaware of the clinical details.…”

Section: Methodssupporting

confidence: 59%

Baseline urine metabolic phenotype in patients with severe alcoholic hepatitis and its association with outcome

Maras

Das

Sharma

et al. 2018

Hepatology Communications

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Severe alcoholic hepatitis (SAH) has a high mortality rate, and corticosteroid therapy is effective in 60% patients. This study aimed to investigate a baseline metabolic phenotype that could help stratify patients not likely to respond to steroid therapy and to have an unfavorable outcome. Baseline urine metabolome was studied in patients with SAH using ultra‐high performance liquid chromatography and high‐resolution mass spectrometry. Patients were categorized as responders (Rs, n = 52) and nonresponders (NRs, n = 8) at day 7 according to the Lille score. Multivariate projection analysis identified metabolites in the discovery cohort (n = 60) and assessed these in a validation cohort of 80 patients (60 Rs, 20 NRs). A total of 212 features were annotated by using metabolomic/biochemical/spectral databases for metabolite identification. After a stringent selection procedure, a total of nine urinary metabolites linked to mitochondrial functions significantly discriminated nonresponders, most importantly by increased acetyl‐L‐carnitine (12‐fold), octanoylcarnitine (4‐fold), decanoylcarnitine (4‐fold), and alpha‐ketoglutaric acid (2‐fold) levels. Additionally, urinary acetyl‐L‐carnitine and 3‐hydroxysebasic acid discriminated nonsurvivors (P < 0.01). These urinary metabolites significantly correlated to severity indices and mortality (r > 0.3; P < 0.01) and were associated with nonresponse (odds ratio >3.0; P < 0.001). In the validation cohort, baseline urinary acetyl‐L‐carnitine documented an area under the receiver operating curve of 0.96 (0.85‐0.99) for nonresponse prediction and a hazard ratio of 3.5 (1.5‐8.3) for the prediction of mortality in patients with SAH. Acetyl‐L‐carnitine at a level of >2,500 ng/mL reliably segregated survivors from nonsurvivors (P < 0.01, log‐rank test) in our study cohort. Conclusion: Urinary metabolome signatures related to mitochondrial functions can predict pretherapy steroid response and disease outcome in patients with SAH. (Hepatology Communications 2018;2:628‐643)

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Section: Methodssupporting

confidence: 59%

Baseline urine metabolic phenotype in patients with severe alcoholic hepatitis and its association with outcome

Maras

Das

Sharma

et al. 2018

Hepatology Communications

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“…Although debated, modified diet for renal disease‐6 (MDRD‐6) of the various available equations has been found to be most accurate and reliable reflection of renal function in cirrhosis patients, as it incorporates two important variables namely blood urea nitrogen and serum albumin, which can be affected in liver disease . Recently, a model from Royal Free Hospital has been reported to be more accurate than other existing equations including MDRD‐6, in predicting the true GFR as measured using the iothalamate clearance .…”

Section: Reasons For Heterogeneity In Allocation Of Slk Transplantationmentioning

confidence: 99%

Simultaneous liver kidney transplantation

et al. 2019

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Summary Kidney injury is frequently seen in patients with end‐stage liver disease from cirrhosis and liver failure. Among selected patients, simultaneous liver kidney (SLK) transplantation provides improved post‐transplant graft and patient outcomes compared to liver transplantation (LT) alone. We conducted the review of the existing literature on SLK transplant criteria and outcomes. Since the introduction of the model for end‐stage disease (MELD) score in 2002, there has been an increased use of SLK transplantation. The criteria for SLK allocation are relatively homogeneous among patients with end‐stage renal disease with cirrhosis and among patients with cirrhosis and chronic kidney disease. However, these are quite heterogeneous among patients with cirrhosis and acute kidney injury (AKI), mainly because of inability to accurately differentiate cause of AKI, especially hepatorenal syndrome versus intrarenal aetiology. Clearly, there is an unmet need of urine biomarkers of tubular injury and/or clinical models to accurately stratify AKI aetiology and to predict renal recovery after LT as basis to best utilize the scarce donor kidney pool. In this regard, it remains to be seen whether recently implemented policies by the organ procurement transplant network can fulfil the goal of saving donor kidneys and optimal allocation of SLK.

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“…We derived a set of equations based on longitudinal data in over 12,000 protocol measurements of GFR and validated in a large national data set. We were able to build on objective and easily ascertained variables that are already used and scrutinized in current iterations . We examined time points both before and after transplantation, and across distinct levels of renal dysfunction.…”

Section: Discussionmentioning

confidence: 99%

“…A separate model was derived for low‐mGFR and high‐mGFR subsets in each of the 6 time intervals. Addition of liver disease–specific factors (e.g., serum sodium, ascites, international normalized ratio [INR], bilirubin), either separately or in combination, did not improve the performance characteristics of the equations in the pretransplant setting …”

Section: Methodsmentioning

confidence: 99%

A Model for Glomerular Filtration Rate Assessment in Liver Disease (GRAIL) in the Presence of Renal Dysfunction[Link]

et al. 2019

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Estimation of glomerular filtration rate (eGFR) in patients with liver disease is suboptimal in the presence of renal dysfunction. We developed a model for GFR assessment in liver disease (GRAIL) before and after liver transplantation (LT). GRAIL was derived using objective variables (creatinine, blood urea nitrogen, age, gender, race, and albumin) to estimate GFR based on timing of measurement relative to LT and degree of renal dysfunction (www.bswh.md/grail). The measured GFR (mGFR) by iothalamate clearance (n = 12,122, 1985‐2015) at protocol time points before/after LT was used as reference. GRAIL was compared with the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) and Modification of Diet in Renal Disease (MDRD‐4, MDRD‐6) equations for mGFR < 30 mL/min/1.73 m2. Prediction of development of chronic kidney disease (mGFR < 20 mL/min/1.73 m2, initiation of chronic dialysis) and listing or receipt of kidney transplantation within 5 years was examined in internal cohort (n = 785) and external validation (n = 68,217, 2001‐2015). GRAIL had less bias and was more accurate and precise as compared with CKD‐EPI, MDRD‐4, and MDRD‐6 at time points before/after LT for low GFR. For mGFR < 30 mL/min/1.73 m2, the median difference (eGFR–mGFR) was GRAIL: 5.24 (9.65) mL/min/1.73 m2 as compared with CKD‐EPI: 8.70 (18.24) mL/min/1.73 m2, MDRD‐4: 8.82 (17.38) mL/min/1.73 m2, and MDRD‐6: 6.53 (14.42) mL/min/1.73 m2. Before LT, GRAIL correctly classified 75% as having mGFR < 30 mL/min/1.73 m2 versus 36.1% (CKD‐EPI), 36.1% (MDRD‐4), and 52.8% (MDRD‐6) (P < 0.01). An eGFR < 30 mL/min/1.73 m2 by GRAIL predicted development of CKD (26.9% versus 4.6% CKD‐EPI, 5.9% MDRD‐4, and 10.5% MDRD‐6) in center data and needing kidney after LT (48.3% versus 22.0% CKD‐EPI versus 23.1% MDRD‐4 versus 48.3% MDRD‐6, P < 0.01) in national data within 5 years after LT. Conclusion: GRAIL may serve as an alternative model to estimate GFR among patients with liver disease before and after LT at low GFR.

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Development and validation of a mathematical equation to estimate glomerular filtration rate in cirrhosis: The royal free hospital cirrhosis glomerular filtration rate

Abstract: We developed and validated a new accurate model for GFR assessment in cirrhosis, the Royal Free Hospital cirrhosis GFR, using readily available variables; this remains to be tested and incorporated in prognostic scores in patients with cirrhosis. (Hepatology 2017;65:582-591).

Cited by 62 publications

References 26 publications

Baseline urine metabolic phenotype in patients with severe alcoholic hepatitis and its association with outcome

Baseline urine metabolic phenotype in patients with severe alcoholic hepatitis and its association with outcome

Simultaneous liver kidney transplantation

A Model for Glomerular Filtration Rate Assessment in Liver Disease (GRAIL) in the Presence of Renal Dysfunction[Link]

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