Hepatorenal Syndrome—Novel Insights into Diagnostics and Treatment
Abstract
:1. Introduction
2. Pathogenesis of the Onset of Hepatorenal Syndrome
3. Diagnosis
3.1. Renal Dysfunction Biomarkers in Patients with Impaired Liver Function
3.1.1. Functional Biomarkers—Glomerular Filtration Rate Estimation
Serum Creatine
Cystatin C
3.1.2. Tubular Injury Biomarkers and Diagnostic Methods
Interleukin 18
NGAL
L-FABP
KIM-1
Other ATN Biomarkers
3.1.3. Biomarkers of Cell Cycle Arrest
3.2. HRS Diagnostic Criteria
3.3. Differential Diagnosis
3.3.1. Prerenal AKI and HRS-AKI
3.3.2. ATN-AKI and HRS-AKI
3.3.3. Postrenal AKI and HRS-AKI
4. Treatment of HRS-AKI
4.1. Supportive Management
4.2. Pharmacological Therapy
4.2.1. Vasoconstrictive Drugs
Terlipressin
Noradrenaline
Midodrine and Octreotide
4.2.2. Albumin
4.3. Transjugular Intrahepatic Portosystemic Shunts (TIPS)
4.4. Renal Replacement Therapy (RRT)
4.5. Liver Transplant (LT)
4.6. Simultaneous Liver-Kidney Transplantation (SLKT)
4.7. Novel Therapies
4.7.1. Molecular Absorbent Recirculating System (MARS)
4.7.2. Fractionated Plasma Separation and Adsorption System (Prometheus)
4.7.3. Therapeutic Plasma Exchange (TPE)
4.7.4. Plasma Diafiltration (PDF)
4.7.5. Selepressin
4.7.6. Serelaxin
4.7.7. Nebivolol
4.7.8. Pentoxifylline
4.7.9. Rifaximin
4.7.10. Fucoidan
4.7.11. Stem Cell Therapy
4.8. Prevention of HRS-AKI
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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HRS-AKI | HRS-CKD |
---|---|
Rapid deterioration in renal function with acute kidney injury, marked increase in serum creatinine, typically defined by a significant decrease in kidney function over a short period (usually less than two weeks) | Slower, more gradual decline in kidney function, representing a chronic kidney disease state, often characterized by a chronic, insidious onset in patients with advanced liver disease and associated hepatic and circulatory abnormalities |
Creatinine | Cystatin C | |
---|---|---|
Formation | Mostly Skeletal Muscles | All Nucleated Cells |
Elimination | Renal
Bacterial creatininase Factors increasing extrarenal elimination:
| Renal Filtrated in glomeruli Factors influencing tubular handling:
|
Clinical conditions modifying serum levels of biomarker | Increase:
| Increase:
|
AKI | HRS-AKI |
---|---|
Meeting one of the following criteria is sufficient for diagnosis:
|
|
CKD | HRS-CKD |
---|---|
Either of the following for at least 3 months
| Both criteria must be fulfilled for at least 3 months.
|
Form of Treatment | Grade of Recommendation |
---|---|
Terlipressin plus albumin | Strongly recommended, supported by evidence from randomized, controlled trials, should be considered a first-line treatment |
Vasoconstrictors plus albumin | Strongly recommended for all patients |
Noradrenaline plus albumin | A weaker recommendation can be considered as an alternative to terlipressin based on evidence from randomized, controlled trials |
Midodrine with octreotide plus albumin | Recommended as a treatment option only when terlipressin or noradrenaline are unavailable since its efficacy is much lower than that of terlipressin |
RRT | Not recommended as a standard option of treatment, the decision to initiate RRT should be based on the individual severity of HRS-AKI |
LT | Strongly recommended, supported by evidence from randomized, controlled trials, as the best treatment option for all patients, regardless of their response to drug therapy |
SLKT | Not recommended as a standard option of treatment and should be considered based on individual indications |
Other therapies with poor evidence | |
TIPS | Not recommended as a standard option of treatment |
MARS | Not recommended as a standard option of treatment |
FPSA | Not recommended as a standard option of treatment |
TPE | Not recommended as a standard option of treatment |
Not recommended as a standard option of treatment | |
Selepressin | Not recommended as a standard option of treatment |
Serelaxin | Not recommended as a standard option of treatment |
Nebivolol | Not recommended as a standard option of treatment |
Pentoxifylline | Not recommended as a standard option of treatment |
Rifaximin | Not recommended as a standard option of treatment |
Fucoidan | Not recommended as a standard option of treatment |
Stem cell therapy | Not recommended as a standard option of treatment |
Liver Transplant General Indications |
---|
Acute liver failure |
Hepatic artery thrombosis within 14 days of liver transplant |
Cirrhosis with:
|
Primary hepatic neoplasms:
|
Inborn metabolic conditions:
|
MELD score |
Simultaneous Liver-Kidney Transplantation Indications |
---|
AKI ≥ 6 consecutive weeks with one or a combination of both (weekly documentation)
|
CKD with GFR ≤ 60 mL/min for >90 days with one of the following:
|
Metabolic diseases |
Safety net: Any patient who is registered on the kidney waitlist between 60 and 365 days after LT and is either on chronic hemodialysis or has an eGFR < 20 mL/min will qualify for increased priority |
Factor | 1 Point | 2 Points | 3 Points |
---|---|---|---|
Encephalopathy | None | Grade I or II | Grade III or IV |
Ascites | None | Slight | Moderate |
Total bilirubin (mg/mL) | <2 | 2–3 | >3 |
Serum Albumin (mg/mL) | >3.5 | 2.8–3.5 | <2.8 |
INR (s) | <1.7 | 1.7–2.2 | >2.2 |
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Badura, K.; Frąk, W.; Hajdys, J.; Majchrowicz, G.; Młynarska, E.; Rysz, J.; Franczyk, B. Hepatorenal Syndrome—Novel Insights into Diagnostics and Treatment. Int. J. Mol. Sci. 2023, 24, 17469. https://doi.org/10.3390/ijms242417469
Badura K, Frąk W, Hajdys J, Majchrowicz G, Młynarska E, Rysz J, Franczyk B. Hepatorenal Syndrome—Novel Insights into Diagnostics and Treatment. International Journal of Molecular Sciences. 2023; 24(24):17469. https://doi.org/10.3390/ijms242417469
Chicago/Turabian StyleBadura, Krzysztof, Weronika Frąk, Joanna Hajdys, Gabriela Majchrowicz, Ewelina Młynarska, Jacek Rysz, and Beata Franczyk. 2023. "Hepatorenal Syndrome—Novel Insights into Diagnostics and Treatment" International Journal of Molecular Sciences 24, no. 24: 17469. https://doi.org/10.3390/ijms242417469