Dear Sr. Rodrigo, Thank You. I think also. But if the vasoconstriction is prolonged?

Sincerely, Zmicer.

Dear Zmicer: Prolonged vasoconstriction is the pathophysiological condition of Type 1 and type 2 hepatorenal syndrome, nevertheless acute tubular necrosis without a precipitating factor has not been observed in pathological examination of patients who have died with this condition. HRS is a condition produced by impairment in function of the kidney induced by hemodynamic and hormonal disturbances of cirrhosis.

Dear Sr. García-Compeán. Thank You.

ATN in cirrhotic patients with HRS after resolution of the infection (for example, SBP, sepsis), is connected with HRS or had been induced by that infectious episode?

Sincerely, Zmicer.

We used to say that a HRS that recovered was not really a HRS but rather a well camouflaged ATN.  Nevertheless, infection in the cirrhotic patient may be present at a subclinical level and probably lead to either HRS through continuous hemodynamic impairment or to overt ATN through sepsis and sudden circulatory failure.  Either way, i think all AKI should be addressed promptly, with vassoactive amines if circulatory failure is suspected.

Dear Zmicer. You have made a good question. HRS post resolution of SBP is possible in 30% of patients with certain risk factors such as age, previous shock, high creatinine levels, hepatic encephalopathy etc. known as SORT criteria. In this case HRS is produced by splanchnic vasodilatation secondary to bacterial toxins. Hemodynamic impairment remains even after SBP resolution. In these cases the administration of albumin reduces the occurrence of HRS. Thus HRS post resolution of SBP is not connected to ATN.

No

new consensus on AKI in cirrhotic patients in journal of hepatology. free

Dear Adrian. I saw classifications of AKI in the new and earlier documents. My question for sсreening of You opinions. As I haven't found the accurate evidences of the return.

Thank you. Sincerely, Zmicer

Dear Zmicer. 

In that case, in my oppinion the answer is that infection is ubiquitous in late stage end stage liver disease and by the bias of the  same mechanism as HRS. So i think it would be impossible to say that HRS comes "alone". In my oppinion late stage end stage liver disease is a much more complex situation  than just kidney (or HRS), liver or circulatory failure or infection and more of a mix of these conditions them. Also the condition is rather dynamic in that each prigression of the gravity of one factor will aggravate the others. Hope my reasoning is clearly expressed...

Thank You, Adrian. Clearly, in your first answer already. The term "AKI" is very correct for critically ill cirrhotic. But considering the long-term prognosis (DOI 10.1002/lt.23384) it makes sense to specify a type of kidney injury (urinary biomarkers, for example). How you think?

Best regards.

In fact acute renal failure (ARF) or AKI in cirrhotic patients has many causes. It means that there are several types of ARF. It occurs in around 20% of hospitalized cirrhotic patients. Most of them have similar patho physiology: splanchnic  vasodilatation, relative circulatory hypovolemia and renal vasoconstriction through the effect of activity of renin and aldosterone which leads to circulatory disfunction and renal failure. The precipitating factor may be most frequently infection such as SBP or in other locations, acute hypovolemia due to esophageal variceal bleeding or  drugs . HRS can occur spontaneously but is more frequently precipitated by events that worsen vasodilatation, such as spontaneous bacterial peritonitis. SBP may worsen hemodynamic state of decompensated cirrhotic by means of translocation which is associated with inflammatory cytokines and nitric oxide.

In conclusion, ARF or AKI of cirrhotic patients is indeed complex as it was previously exposed by other colleague. Nevertheless it is necessary to search a precipitating factor for better therapy of these very ill patients who suffer high short-term mortality.

Dear Diego, dear Zmicer

It is very clear indeed, as Diego points out, precipitatin factors should be adressed promptly.

Of coures not all AKI is hemodynamic (prerenal) in nature but we expect HRS to be. The cirrhotic patient might have long standing proteinuria (of numerous causes)  or leucocituria if infection is associated.

HRS should probably be viewed as a syndrome not a disease and it's origin is expected to be prerenal hemodynamic failure. In fact as a diagnostic criteria you have "in the absence of renal parenchymal disease". It is in fact the AKI of a cirrhotic patient, and a severe one that has the particuliarity that it will not respond to fluid challenge beacuse of splachnic entrapement.

This is not bad to sumarise all it has been said here: http://onlinelibrary.wiley.com/doi/10.1111/jgh.12709/pdf

Best regards

Adrian

Dear Adrian and Dear Zmicer

Adrian, I agree with your last comment.  Then, one can conclude that HRS is a prerenal, non responding to vascular volume expanders and non renal parenchimal condition,  exclusive of cirrhotic patients ,occurring spontaneously or secondary to a precipitating factor. Right?

It leads to answer  Zmicer´s question :Type 1 hepatorenal syndrome (HRS) does not  lead to acute tubular necrosis (ATN) in the absence of other insult.

Best regards both

Thanks all! The attached link an addition to your answers.

This study has presented that levels of urinary biomarker of tubular damage (uNGAL) was low in patients with type 1 HRS and remained low during the 7-day observation period. According to authors, these data are suggestive of absence of significant tubular injury in type 1 HRS.

Sincerely, Zmicer

Article Urinary neutrophil gelatinase-associated lipocalin predicts ...

Hello. Continuing to study this topic, I think, that my question still remains actual.

1) “In case of non-responsiveness to vasoconstrictors and albumin, how long does type 1 HRS remain a functional disease before acute tubular necrosis develops?” - In this article: http://gut.bmj.com/content/60/5/702.full

2) Among patients who have not responded to administration of vasoconstrictors and albumin with type 1 HRS, was observed a progressive increase in the urinary excretion of γ-glutamyltranspeptidase (biomarker of tubular damage) - In this article: http://onlinelibrary.wiley.com/doi/10.1002/hep.510290629/epdf. This observation suggests the possibility that a progression from type 1 HRS to acute tubular necrosis can occur in cirrhotic patients.

 Can we use the term HRS, without determination of markers of tubular damage, as of today?

Sincerely, Zmicer

Type 1 HRS is different from Type 2 HRS , in that in addition to splanchnic vasodilatation & ascites , secondary factors such as GI bleed , SBP , Overdiuresis , nephrotoxic drugs & large volume paracentesis can cause AKI . Type 1 HRS is a rapid onset of renal failure & Type 2 HRS is prerenal azotemia . In addition , the criteria to define & classify severity of  AKI ( KDIGO ) have changed & terms such as prerenal azotemia are not used . The AKI criteria is based on serum creatinine & urine output . AKI is classified as stage 1 , 2 & 3 . Therefore , Type 1 HRS can lead to ATN & dialysis may be needed to treat AKI . It is essential to modify the HRS criteria , based on the new AKI criteria . I agree with Dzmitry Haurlenka that renal biomarkers are valuable to assess severity of AKI & the article also suggests modifying the criteria of HRS .

Advanced renal dysfunction in cirrhotic patients is known as HRS and its pathophysiology involves portal hypertension leading to splanchnic arterial vasodilatation. The resultant primary systemic arterial vasodilatation unloads the arterial stretch receptors in the carotid sinus and aortic arch. This baroreceptor response then triggers the compensatory activation of the neurohumoral axis with stimulation of the renin–angiotensin–aldosterone system, sympathetic nervous system and arginine vasopressin and then contributes to maintenance of blood pressure by increasing systemic vascular resistance along with the secondary increase in cardiac output. While this compensatory neurohumoral activation attenuates any hypotension secondary to arterial vasodilatation, renal vasoconstriction with sodium and water retention also occurs. This resultant diminished renal function is, however, of a functional nature and thus should not be considered ATN. But I agree with Ihsan Ates uncontrolled HRS (specially in a critically ill patient) may lead to ischaemic tubular necrosis  These patients must be managed, if possible, in an intensive care unit.

Maybe ATN explains 50% of non-responsiveness to vasoconstrictors and

albumin.

Dear Dzmitry

You are right. Around 10% of patients with cirrhosis and AKI have ATN. Therefore  some of those who do not respond to vasoconstrictors and albumin certainly may have ATN.  Mortality of ATN is very high (almost 60%).Granular casts in urine may help for distinction between both entities. Nevertheless this finding is not present in all ATN patients. Sometimes precise diagnosis is a challenge.

Best regards.