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 Table of Contents  
REVIEW ARTICLE
Year : 2021  |  Volume : 1  |  Issue : 1  |  Page : 2-10

Renal dysfunction in chronic liver disease: Current concepts, classification, and management


Institute of Gastroenterology, Hepatobiliary Sciences and Transplantation, SRM Institute for Medical Science, Chennai, Tamil Nadu, India

Date of Submission06-Aug-2020
Date of Acceptance06-Aug-2020
Date of Web Publication04-Dec-2020

Correspondence Address:
Rohan Yewale
Institute of Gastroenterology, Hepatobiliary Sciences and Transplantation, SRM Institute for Medical Science, 1, Jawaharlal Nehru Road, Vadapalani, Chennai - 600 026, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ghep.ghep_9_20

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  Abstract 


Renal dysfunction is not uncommon in patients with cirrhosis, particularly as disease advances and the liver function decompensates. This review discusses the various types of renal dysfunction that may occur, the current classification of these kinds of kidney injury, and the rational management of these disorders based on the pathophysiology of these conditions.

Keywords: Acute kidney dysfunction, acute kidney injury, chronic kidney disease, cirrhosis, hepatorenal syndrome


How to cite this article:
Yewale R, Ramakrishna BS. Renal dysfunction in chronic liver disease: Current concepts, classification, and management. Gastroenterol Hepatol Endosc Pract 2021;1:2-10

How to cite this URL:
Yewale R, Ramakrishna BS. Renal dysfunction in chronic liver disease: Current concepts, classification, and management. Gastroenterol Hepatol Endosc Pract [serial online] 2021 [cited 2021 Apr 22];1:2-10. Available from: http://www.ghepjournal.com/text.asp?2021/1/1/2/302223




  Introduction Top


Renal function is often impaired in patients with chronic liver disease. Such dysfunction is a dynamic phenomenon with a spectrum ranging from acute kidney injury (AKI) or acute kidney dysfunction (AKD) to chronic kidney disease (CKD). AKI is one of the most frequently encountered complications in patients with decompensated chronic liver disease with an estimated prevalence of 20%–50% among hospitalized patients.[1],[2],[3],[4] Patients with cirrhosis are more prone to develop renal failure compared to individuals without liver disease.[5] Our understanding of the pathophysiology, definition, and grading of various subtypes of renal dysfunction in chronic liver disease and their management has evolved over the years. Recent guidelines and literature provide a holistic, pathophysiology-based approach to patient management. This review article summarizes our current concepts of renal dysfunction in chronic liver disease.


  Historical Perspective Top


The association of fulminant renal failure with diseases of liver and biliary tract has been known for over 150 years and was first reported, in 1863 by Austin Flint, in a case series of patients with cirrhosis and ascites. James Gordon Heyd described a fulminant clinical deterioration following bilio-hepatic surgery or appendectomy, characterized by anuria and a rise in blood urea nitrogen despite 24–36 h of apparently normal renal function prior to surgery. This was called Flint’s syndrome or Heyd’s syndrome and later referred to as “hepatorenal failure.”[6],[7],[8],[9] In 1927, Furtwangler reported a case series on fulminant cortical necrosis in both kidneys following hepatic trauma.[10] The first consensus conference to decide on a uniform definition of hepatorenal syndrome (HRS) held in 1978 in Sassary, Italy, defined the condition as an acute renal dysfunction associated with extensive renal sodium retention in patients with acute or chronic liver disease.[11],[12] Over the following decade, renal impairment in patients with cirrhosis was defined as a serum creatinine (sCr) value ≥1.5 g/dL because this was considered an index of glomerular filtration rate (GFR) <40 mL/min.[13] In the past two decades, two different types of HRS were distinguished – Type 1 being a fulminant decline in renal function in patients with advanced liver disease associated with a detrimental prognosis, and Type 2 being a slowly progressive “functional renal failure” that typically occurred in patients with refractory ascites. Currently, these traditional, fixed sCr threshold value and urine output-based, diagnostic criteria have been replaced by the Acute Kidney Injury Network and Kidney Disease Improving Global Outcome (KDIGO) diagnostic criteria for AKI, respectively, specifically adapted for patients with cirrhosis in order to improve applicability to clinical practice.[14],[15],[16] These are called the International Club of Ascites (ICA)–AKI/adapted KDIGO criteria.


  Acute Kidney Injury, Acute Kidney Dysfunction, and Chronic Kidney Disease Top


Renal dysfunction in patients with cirrhosis may present in multiple ways. Patients may present for the first time to hospital with an illness with decompensation of liver function, jaundice, and possible sepsis and found on investigation to have abnormal renal function. Patients who have been stable with well-compensated liver disease may present with an acute illness that progresses over the course of hospitalization and have worsening of renal function on a previously normal baseline. On the other hand, there may be patients under regular treatment for ascites and fluid retention whose ascites becomes difficult to control and evaluation reveals deterioration of previously stable renal function. There are several factors, listed in [Table 1], that contribute to deterioration of renal function in patients with cirrhosis.
Table 1: Factors precipitating kidney dysfunction in patients with cirrhosis

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AKI in cirrhosis is currently defined as per the ICA-AKI/adapted KDIGO criteria as an acute increase in sCr of ≥0.3 mg/dL within 48 h or by 50% from a stable baseline sCr within 3 months (presumed to have developed within the past 7 days when no prior readings are available).[16] The main change from the former criteria were (1) abandoning the arbitrary threshold of sCr ≥1.5 mg/dL defined previously and (2) removal of urine output as a criterion. These changes were instituted in order to avoid underdiagnosing milder cases and nonoliguric AKI.[17],[18] This modification arose as the result of the observation that there is a spectrum of cirrhotic patients with ascites. At one end, some patients maintain preserved GFR, despite being oliguric due to avid sodium and water retention. At the other end of the spectrum, some have increased urine output due to the use of diuretics.[16],[19] The only situation in which urine output criteria for AKI appear to be useful is in critically ill patients in the intensive care unit.[20] In these patients, it has been proposed to add urine output ≤0.5 mL/h for >6 h in addition to the ICA-KDIGO-adapted diagnostic criteria of AKI.[21] AKI in patients with chronic liver disease is classified into three subtypes as follows: (1) prerenal AKI which includes prerenal azotemia and hepato-renal syndrome (HRS-AKI); (2) intrinsic or intrarenal AKI (mainly represented by acute tubular necrosis [ATN]); and (3) postrenal AKI. AKI in cirrhosis can be stratified into three stages of progressively increasing severity. Stage 1 AKI is defined by rather small changes in sCr, whereas Stages 2 and 3 AKI are defined by a two-fold and three-fold increase in sCr, respectively [Table 2].[16],[22] Stage 1 is further substratified into Stage 1a (sCr <1.5 mg/dL) and Stage 1b (sCr >1.5 mg/dL). The baseline sCr value has also been used to segregate patients into “community acquired” and “nosocomial” AKI, with the latter carrying a more dismal prognosis.
Table 2: Current definitions of various types of renal dysfunction in cirrhosis

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AKD is a newly defined and distinct entity of renal impairment in cirrhosis, and this may or may not be associated with AKI.[23],[24] AKD is defined as per KDIGO guidelines by a GFR <60 mL/min/1.73 m2 for <3 months, or a decrease in GFR ≥35% for <3 months, or an increase in sCr <50% within the last 3 months. It is, in a sense, a forerunner of CKD as it will be redesignated as “CKD by duration” once the impaired renal function continues for >3 months.

The third entity of renal dysfunction in cirrhosis is CKD which is defined as a GFR <60 mL/min/1.73 m2 estimated by sCr-based formulas, with or without the signs of renal parenchymal damage (proteinuria/hematuria/ultrasonography abnormalities) for at least 3 months. The presence of comorbidities such as systemic hypertension, diabetes mellitus, and specific causes such as virus-induced glomerulopathy or IgA nephropathy can be contributory to the development of CKD in this population.[25] Recent studies highlighting a “structural” component of renal impairment along with the already-known functional impairment of HRS, add further weightage to the development of CKD in cirrhosis. Thus, CKD by itself may be related or unrelated to liver disease.

It is crucial to understand that the above are not totally distinct or mutually exclusive entities, and one can often encounter an overlap in these conditions; for example, a cirrhotic patient can present with AKI superimposed on CKD.


  Hepatorenal Syndrome Top


For a long time, HRS was defined as “a functional renal failure caused by intra-renal vasoconstriction which occurs in patients with end-stage liver disease as well as in patients with acute liver failure or alcoholic hepatitis.”[12],[13] Type 1 and Type 2 HRS were historically classified based on time frame of the increase in sCr.[12],[13] Recent studies have challenged this traditional definition of HRS (which emphasizes on a purely “functional” nature of renal impairment) as well as its classification into subtypes 1 and 2. The basis of argument against this traditional concept was formed by the following points raised over the last few years:(1) pathogenesis of HRS includes both hemodynamic and inflammatory changes; (2) absence of renal parenchymal damage, defining the functional nature, has never been proven by renal biopsies;[26],[27] (3) absence of significant proteinuria and/or hematuria may not rule out renal lesions, particularly tubular and interstitial lesions;[13] (4) studies assessing novel kidney biomarkers such as urine neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C have particularly shown that tubular damage can occur in patients with HRS-AKI;[28],[29],[30],[31] and (5) HRS-AKI can also occur in patients with underlying CKD. A recent article proposed that HRS be defined as one possible phenotype of renal dysfunction that occurs in patients with liver disease, particularly in those with cirrhosis and ascites. In these patients, HRS may be precipitated by hepatic (alcohol abuse, flare of hepatitis, and drugs) and/or extrahepatic (bacterial infections and/or bacterial translocation) factors.[21] The European Association for the Study of the Liver (EASL) CPG on decompensated chronic liver disease classifies HRS into two types – (1) HRS-AKI, formerly known as type 1 HRS and (2) HRS-non AKI (HRS-NAKI), formerly known as type 2 HRS (24). HRS-AKI is defined as ≥ Stage 1A ICA-AKI that is diagnosed after other causes of renal failure have been ruled out [Figure 1]. From a clinical perspective, HRS-AKI is characterized by a rapid rise in sCr and progressive oliguria in the absence of other identifiable causes of AKI such as hypovolemia, shock, parenchymal renal diseases, urinary tract obstruction, and use of nephrotoxins.[13],[16] In contrast to prerenal azotemia, renal function in HRS-AKI does not improve by withdrawal of diuretics and plasma expansion using intravenous albumin.[32] It can develop spontaneously or be triggered by a precipitating event that causes deterioration of the systemic circulation, most prominently bacterial infections such as spontaneous bacterial peritonitis or variceal bleeding.[12],[33],[34] Paradoxically, there have been reports that nonselective beta-blockers indicated for variceal bleed prophylaxis might also trigger HRS-AKI due to their impact on the systemic circulation.[35]
Figure 1: Nomenclature of hepatorenal syndrome type of renal dysfunction in cirrhosis,[21] as per new diagnostic criteria proposed for hepatorenal syndrome-acute kidney injury: (1) Cirrhosis; acute liver failure; acute-on-chronic liver failure, (2) increase in serum creatinine ≥0.3 mg/dL within 48 h or ≥50% from baseline value according to International Club of Ascites consensus document and/or urinary output≤0.5 mL/kg body weight ≥6 h, (3) no full or partial response, according to the International Club of Ascites consensus document, after at least 2 days of diuretic withdrawal and volume expansion with albumin. The recommended dose of albumin is 1 g/kg of body weight per day to a maximum of 100 g/day, (4) absence of shock, (5) no current or recent treatment with nephrotoxic drugs, (6) absence of parenchymal disease as indicated by proteinuria >500 mg/day, microhematuria (>50 red blood cells/high-power field), urinary injury biomarkers (if available) and/or abnormal renal ultrasonography. Suggestion of renal vasoconstriction with FENa of <0.2% (with levels <0.1% being highly predictive)

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The other type of HRS, HRS-NAKI (previously, HRS type 2), is characterized by a stable or slowly progressive impairment in renal function in patients with decompensated liver disease who suffer from refractory ascites.[36] The term HRS-NAKI signifies that, this type of HRS should fulfill the criteria for HRS but not for AKI. A recent article proposed that HRS-NAKI be further subclassified as HRS-AKD and HRS-CKD based on persistent reduction in GFR for less than and more than 3 months, respectively.[21] Patients with this entity usually develop oliguria over a course of several weeks or months, marked by excessive salt and water retention and a slow but steady incline in renal retention parameters.[13],[37] However, this entity is challenging to diagnose in clinical practice because it is a diagnosis of exclusion. To complicate matters further, according to the Acute Dialysis Quality Initiative group, CKD due to other causes may often develop on the top of HRS-Type 2 in cirrhotic patients.[36] In general, prognosis in HRS-CKD is poor, but more favorable when compared to HRS-AKI.[37],[38],[39],[40] This evolving, complex classification of renal dysfunction in cirrhosis and the varied overlapping presentations is simplified and summarized in [Figure 1], [Figure 2] and [Table 2].
Figure 2: The spectrum of renal dysfunction in cirrhosis

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Pathophysiology of hepatorenal syndrome

The pathophysiological concept of renal dysfunction in cirrhosis has attained more clarity in recent years. HRS, although the prototype of AKI, does not reflect the entire spectrum of renal dysfunction in cirrhosis. An important differential diagnosis for HRS-AKI is ATN.[4] It is mainly caused by ischemic damage to renal tubules following a hypotensive event, such as variceal bleeding or sepsis. Clinical presentation of ATN is often very similar to HRS, and routine biomarkers are often unable to properly discriminate between these entities.[4],[41] As discussed previously, terms such as AKD and CKD are being increasingly used in cirrhotic patients as they add chronicity to the renal dysfunction of cirrhosis. One of the reasons could be due to the rising prevalence of CKD in cirrhotic patients (especially non-alcoholic steatohepatitis-related cirrhosis), due to simultaneous presence of comorbidities such as diabetes, hypertension, and atherosclerosis.[42] Thus, at any point of time, a cirrhotic patient may present with AKI, AKD, CKD, or an overlap of these conditions. The various types of renal dysfunction in cirrhosis need to be viewed as a continuum rather than as isolated entities. Our understanding of the mechanism of HRS too has undergone metamorphosis over the past decade with recent emphasis on the role of sepsis and addition of “structural” component to the pathogenesis of HRS.

According to the classical vasodilatation theory, hypoperfusion is the central mechanism of renal injury in patients with advanced cirrhosis, and ascites is considered a prerequisite for the development of HRS.[12],[43],[44] Schrier’s hypothesis states that, in the early stages of compensated cirrhosis, there is intense splanchnic vasodilation attributable to translocation of bacteria and their products from the gut. These molecules themselves, and by upregulation of cytokines and hormones such as nitric oxide, cause splanchnic vasodilatation. This leads to a marked reduction in systemic vascular resistance which is initially counterbalanced by an increase in cardiac output which helps in maintaining adequate renal perfusion. With advancement in cirrhosis, splanchnic vasodilation intensifies further, leading to the activation of systemic vasoconstrictor systems such as the renin–angiotensin–aldosterone system and arginine vasopressin. This results in renal sodium and water retention, leading to the development of ascites and edema; the “effective” circulatory volume remains compromised. In the most advanced stages, renal vasoconstriction overwhelms the capacity of the heart to increase cardiac output. The associated cirrhotic cardiomyopathy and situations of hemodynamic stress such as volume loss (e.g., due to diuretics, dehydration, or gastrointestinal bleeding) or bacterial infections, aggravates the hemodynamic changes, leading to AKI. Renal protective mechanisms set in, leading to release of vasodilator prostaglandins that dampen the vasoconstriction.[45],[46] The injudicious use of drugs such as nonsteroidal anti-inflammatory agents (NSAIDs), which inhibit prostaglandin release, can trigger the cascade of AKI in patients with advanced cirrhosis.

The role of sepsis and the systemic inflammatory response has attracted attention in recent years. Until 2007, sepsis was considered an exclusion criterion for HRS.[12] Over the years, it has been noticed that infections resulting in sepsis account for majority of hospitalization episodes in patients with advanced cirrhosis. This specific cohort frequently develops AKI during hospitalization. AKI may be unrelated to altered renal blood flow in such cases. It has been hypothesized that sepsis causes redistribution of blood flow out of the cortex inducing cortico-medullary junction ischemia and intrarenal microvascular changes, which indirectly impact tubular and glomerular function.[47] There is reduction in GFR owing to an imbalance between pre- and postglomerular resistance. Even in the absence of bacterial infection, cirrhosis is associated with systemic inflammation that correlates to the severity of liver disease and portal hypertension.[48] The synergistic interplay of inflammation and microvascular dysfunction further amplifies the effect of pathogen-associated molecular patterns (PAMPs) released during bacterial translocation from the gut and damage-associated molecular patterns (DAMPs) released due to direct liver injury. These PAMPs and DAMPs are recognized by specific pattern recognition receptors mainly the toll-like receptors located on endothelial cell surfaces of the microvasculature of various organs, leading to the production and release of pro-inflammatory cytokines.[47],[48],[49],[50] Inflammation spills over from the splanchnic to systemic circulation, leading to SIRS and extrahepatic organ failure, most commonly involving the kidneys. There is mitochondria-mediated metabolic downregulation and re-prioritization of cell functions favoring survival processes above all others. The end result is a sacrifice of vital tubular absorptive and secretory functions, thereby contributing to the “structural” component of renal dysfunction in cirrhosis even though it does not manifest as significant hematuria, proteinuria, or gross renal parenchymal changes.[21] [Figure 3] summarizes the pathophysiology of renal dysfunction in cirrhosis.
Figure 3: Pathophysiology of renal dysfunction in cirrhosis. CO: Cardiac output, RAAS: Renin–angiotensin–aldosterone system, AVP: Arginine vasopressin, ECV: Effective circulatory volume, CCM: Cirrhotic cardiomyopathy, CMJ: Cortico-medullary junction, PAMPs: Pathogen-associated molecular patterns, DAMPs: Damage-associated molecular patterns, TLR4: Toll-like receptor type 4

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  Management of Renal Dysfunction in Cirrhosis Top


The first step when a cirrhotic patient presents with deranged renal function parameters, is to confirm the presence of an AKI as per the definition and criteria discussed above[23],[24] [Table 1]. This initial triage is essential as the AKI subset demands prompt attention and specific treatment based on its grade and subtype. Patients without AKI, but with an identifiable cause of CKD, need to be further evaluated and managed just as any other CKD patient depending on the GFR-based stage of CKD. With progression of CKD, these patients may need some form of renal replacement therapy. The HRS-NAKI group of patients is unlikely to show significant improvement in renal parameters with conventional vasoconstrictor and volume expansion-directed therapies. Liver transplant (LT) still remains the only definite line of management for this group. The decision to perform a simultaneous liver kidney transplant versus LT alone is determined by the ability to predict renal recovery after LT. Studies have shown that factors such as age, comorbidities, and intrinsic renal disease adversely affect renal recovery and patient survival 1 and 5 years after LT.[51] There is still a dearth of data which can guide the clinician in accurately predicting renal recovery in the HRS group of patients, and this remains an upcoming area of research. The following section summarizes the step-wise management of cirrhotic patients who present with AKI.

The initial step of management of AKI Stage 1A involves early recognition and correction of potential trigger events to prevent further deterioration of renal function.[16],[22] This includes a detailed review of current medication (NSAIDs, beta-blockers nephrotoxic antibiotics such as aminoglycosides, and over-the-counter drugs) and contrast agents. In volume-depleted patients, diuretics should be withdrawn and plasma volume expansion should be attempted with human albumin or packed red blood cell transfusion in cases of hypotension due to gastrointestinal blood loss. Infections can often trigger a cascade of AKI, and thus appropriate cultures and other screening tests should be done to rule out any form of sepsis. Early empiric antibiotic therapy is recommended on clinical suspicion of infection, based on local epidemiology and resistance patterns.[52],[53],[54] In case of therapeutic response, which is defined as a decrease of sCr to a value within 0.3 mg/dL of baseline, patients should be followed closely for early detection of recurrent episodes of AKI by repeating sCr every 2–4 days during hospitalization and every 2–4 weeks during the first 6 months after discharge.[16],[55]

In case of AKI Stage >1A or progression to a higher AKI stage, the next step would be to identify the subtype of AKI. This step dictates further line of patient management. Improvement or resolution of AKI with initial volume expansion indicates presence of prerenal azotemia, whereas persistence or progression of AKI indicates HRS-AKI or intrinsic AKI (ATN).[24] Distinguishing between HRS-AKI and intrinsic AKI or ATN purely on clinical grounds, can be difficult even for the most experienced physicians. Patients often end up becoming subject to a “kitchen sink” approach to management, wherein many inappropriately receive aggressive volume expansion as well as upfront vasoconstrictor therapy. This may lead to wrongful wastage of resources and even lead to worsening of the patient’s general condition. Studies have shown that vasoconstrictor use should be restricted to the HRS-AKI group of patients, as they are less effective in improving renal parameters in patients with intrinsic AKI or ATN.[56] The gold standard for diagnosis of ATN is kidney biopsy which is almost never attempted in cirrhotic patients due to the presence of ascites and deranged coagulation parameters. The potential role of novel urinary biomarkers such as urine NGAL, interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and liver-type fatty acid binding protein (L-FABP) in diagnosing the type of AKI has been the subject of research over the last decade. Urinary level of NGAL, KIM-1, IL-18, L-FABP, and albumin was found to be significantly higher in patients with ATN than those without ATN.[29] Across the majority of studies, only urine NGAL levels have found to be remarkably consistent in patients with HRS-AKI, suggesting its potential value to distinguish primarily functional AKI from structural AKI in patients with cirrhosis.[57],[58],[59],[60] Until these novel biomarkers of AKI become widely available, simple tests such as urine microscopic examination for varied types of casts, urine fractionated excretion of sodium (FENa), and urine spot protein creatinine ratio can potentially assist clinicians in differentiating prerenal AKI from intrinsic AKI or ATN. FENa is specifically useful in distinguishing functional from structural renal disease. In functional AKI such as PRA, structurally intact renal tubules are sodium avid due to renal hypoperfusion leading to a value <1%. With structural injury such as ATN, tubular sodium reabsorption is limited, leading to high FENa values >2%–3%. However, with advanced cirrhosis, sodium avidity is pronounced and thus, even patients with ATN typically have FENa <1%, precluding its clinical utility. Recent studies suggest that FENa with a new lower cutoff of 0.2% may be useful for distinguishing HRS from ATN.[61] Ultrasound pelvis can potentially rule out any obvious obstructive uropathy as a cause of postrenal AKI.

Volume expansion in the initial stages may be achieved by the use of human albumin 1 g/kg/day for 48 h.[24] If AKI worsens or fails to resolve, guidelines suggest that albumin should be continued with the addition of vasoconstrictor medication once intrinsic AKI has been ruled out.[24] The following three types of vasoconstrictors (which act against the splanchnic vasodilation) are currently available for the treatment of HRS-AKI: terlipressin, noradrenaline, and the combination of midodrine with octreotide. Terlipressin is the most widely investigated of the available vasoconstrictors, and current guidelines suggest combining terlipressin with human albumin 20–40 g/day as the treatment of choice for HRS-AKI.[24],[62],[63],[64],[65] Terlipressin can be administered as continuous intravenous infusion from 2 to 12 mg/day or as intravenous boluses up to 2 mg every 4 h.[66] Continuous intravenous infusion is associated with fewer side effects – diarrhea, angina, abdominal ischemia, and circulatory overload – compared to bolus doses.[66] The end point of this combined treatment modality is proposed as drop in sCr value within 0.3 mg of the patient’s baseline creatinine or up to a maximum of 14 days.[24] Patients with HRS-NAKI seldom respond to this form of therapy and are currently not considered for the use of terlipressin plus albumin even if they are on the waitlist for LT. Norepinephrine (dose 0.5–3 mg/h) is an alternative to terlipressin in resource-limited settings, and three studies have shown it to be as effective as terlipressin when combined with albumin, for the treatment of HRS-AKI.[67],[68] The last of the available vasoconstrictor drugs is the combination of midodrine (an alpha-1 agonist) and octreotide (a somatostatin analog) together with human albumin. This triple-combination therapy has shown to be useful, albeit less effective as compared to the combination of terlipressin and albumin.[69],[70] Finally, it is important to note that creatinine largely impacts the model for end stage liver disease (MELD) score and can work in favor of pushing the patient upward on the MELD-based LT list. A recent review article throws light on the paradoxical effect of response to treatment of AKI, possibly delaying LT by lowering the MELD score.[21] The same group also proposed consideration of baseline MELD at the time of hospitalization or consideration of pharmacological treatment of HRS as dialysis while computing the MELD score, in order to negate this paradox.[21],[71] [Figure 4] summarizes the management for renal dysfunction in cirrhosis partly modified and adapted from the recent EASL guidelines.
Figure 4: Management of renal dysfunction in cirrhosis (partly modified and adapted from EASL CPG for decompensated cirrhosis, J Hepatol, 2018.)[24] AKI: Acute kidney injury, AKD: Acute kidney dysfunction, CKD: Chronic kidney disease, HRS-NAKI: Hepatorenal syndrome-nonacute kidney injury, PRBC: Packed red blood cells, HRS: Hepatorenal syndrome

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  Conclusion Top


Renal dysfunction in the form of AKI forms one of the most common reasons for hospitalization of cirrhotic patients with decompensation or as part of acute-on chronic liver failure. The nomenclature, pathophysiology, and management strategy for renal dysfunction in cirrhosis have evolved drastically with time. With the recent advent and expected widespread availability of novel biomarkers of acute and chronic kidney injury in the upcoming decade, the existing protocols are bound to change further. This review article summarizes the currently available literature on this subject. At the same time, it is essential to periodically keep ourselves abreast in the near future, bearing in mind the dynamic nature of this phenomenon.

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Introduction
Historical Persp...
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Hepatorenal Syndrome
Management of Re...
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