Slide 1

Good afternoon everybody I’m a paediatric nephrologist and being a paediatric nephrologist and while preparing this presentation I realised that I had only 18 minutes to talk about one of the most complex issues in paediatric care so I decided to limit this presentation to a few points of difference between what happens in children concerning AKI and what happens in adults and I think this maybe of interest to the audience.

Slide 2

So, we’ll briefly go through these points you see here and before starting I have to stress two main points that are necessary in my opinion to understand what follows.

Slide 3

The first point is that we have assisted during the last years to a progressive broadening of paediatric AKI epidemiology. This was due to the application of new complex treatments like heart surgery, heart transplantation, bone marrow transplantation, liver transplantation and so on. The direct consequence of this phenomenon was that now we do treat more critical children with AKI in intensive care.

The second point to be said before getting into the heart of the matter is that much more than in adult patients in critical children with AKI we suffer from lack of prospective studies, lack of treatment stratification both from medical and dialysis treatment and we see often an inconsistent control of this illness severity. Critical children were few and critical children with AKI are even fewer and one may always say luckily but when you have to deal with your results and you want to interpret them the least that can happen to you is that you have a hard time in interpreting your results.

Slide 4

This is what I was saying a few moments ago. This table has been prepared by Doctor Flynn from a series of references that you see here but what characterises these references is they are relatively old. So the picture coming out from this table is a typical picture of the distribution of the acute kidney injury aetiology you find in text books that is with the haemolytic-uremic syndrome, acute tubular necrosis, having the majority of patients and please note that sepsis and post-operative acute renal failure account only for 6% or 7% of the whole patients.

Slide 5

What if we come to our days?
This is another study by the Stu Goldstein Houston group and it’s more recent and you see that the cardiac patients, the haematology/oncology and systemic diseases account for almost the totality of patients and in particular in this series only 7% of patients had primary renal disease and patients with haemolytic-uremic syndrome were 3. So the ratio and the message is since some years the ratio of this aetiology has been inverted and is a good point of difference with adult kidney injury.

Slide 6

Another point always utilising the Houston series is the fact that the survival rate in children is evidently age-dependent and in particular, neonates and infants are the most exposed to the risk of death. The other message we learn from this table is about the cause, the genesis of the acute renal failure. You see that ischemic causes are recognised for the younger children while nephrotoxins concern adolescents and young adults.

So one may think that this different distribution of pathogenesis may have a consequence on the follow up. Here also we have a point of difference with adult kidney injury.
The adult kidney injury, as you know, has a heavy burden of problems related to comorbidity of adults during the acute episode. But when the acute episode has passed the follow up is generally good.

Slide 7

What happens in children? In series from the Houston group out of 29 children with acute renal failure 17 of them presented some signs of renal injury and in particular 13 of them had some renal involvement in terms of stage 1 or stage 2 of CKD. 9 patients had hyperfiltration and what’s most important all of them presented some degree of proteinuria. So the message is the follow up in children after an acute kidney episode deserves much more attention possibly than in adults.

Slide 8

What about Multiple organ failure? Here also we have another difference. We have learnt from this old paper from Doctor Proulx in Montreal Canada that children develop multiple organ failure earlier in ICU course with the maximum number of organ failures occurring within 72 hours of ICU admission that is almost in 90% of patients.

Slide 9

Standardisation is a problem in adults. Standing the fact that I cited before of the very low numbers that are available in paediatrics the problem is even bigger and it is very severe.

Slide 10

This is a dramatic picture of a post-cardiac surgery infected septic infant and you may see here in this picture at least 10 or 15 perhaps variables working at the same time, standardising them is really a problem. You also know the ADQI RIFLE classification which is a very interesting way, a new way to classify these problems.

Slide 11

In this slide I put the adult RIFLE classification and the paediatric one that has been adapted from the adult calcification by the Houston group always and I wanted to show you the points of difference. This may be of interest for you. The first one is of course we cannot use the concentration of creatinine since that also is age-dependent. So an estimated creatinine clearance from the Swartz formula has been proposed and on the basis of the 3 measurements in the 3 previous months and if there were no data available but doctors were aware of the normal renal function, 100 ml is considered.

Slide 12

The other difference is a slightly longer time for the urine output that is for the oliguria observation and this is a first step in order to minimise the possible influence of pre-renal azotemia which in the children is much more frequent than in adults. These are the results. To my knowledge there are 3 papers published that utilised the paediatric RIFLE and this is the most known one by Doctor Arikan from the Stu Goldstein group and 52 out of 150 patients entered the study and 31 were admitted with an R category almost 70% with an I or an F.

This is the second step of minimisation and it is utilised as a surrogate of the differential diagnosis between pre-renal azotemia and AKI. It consists in observing and making a second point of observation at 48 hours. I’m sorry for that this is 48 after admission and you see that even in this way almost 70% of these patients had persistent acute kidney injury and what is most important is that in the end this category here that is the I or the F had a higher percentage of death although the need for dialysis was not significantly different.

Slide 13

This very hazed scenario of children we have a very important observation that was made in 2002 utilising the paediatric CRRT registry data in the United States. FO stands for fluid overload and you know possibly I think the story it’s not an invention of paediatricians, it was utilised in adults years before but it was re-evaluated in this context and the fluid overload is calculated as the fluid accumulation between the admission and the ICU and the initiation of any dialysis treatment.

Slide 14

This is the first of a series of multiple regression analyses that were made but the results are always the same, the percentage of fluid overload is always stronger than very heavy variables such as age, weight, central venous pressure or the use of pressure and it’s even more interesting to see that if we consider the percentage of fluid overload categories starting from less than 5 to over 15, the Kaplan-Meier survival estimates are ordered exactly by the extent of the fluid overload.
So 10% of fluid overload is almost invariably associated with a bad prognosis once dialysis child started. It’s a very useful tool, it’s a very useful information tool to have both in order to treat a trial both in order to speak with families.

Slide 15

What about dialysis? I will just give you a few points and one point that I think is of interest to you, the first one is just an epidemiologic observation that CRRT has become very fashionable also in the paediatric world you see from ‘95 to the year 2003 the green columns and this is CRRT has increased and obviously PD and HD have decreased parallely. So we’ll talk about CRRT what happens in CVVH what about dialysis dose? The Claudio Ronco paper has been cited before ad you know the 35 ml/kg as the cut-off beyond which you have a significantly better survival.

Slide 16

35/kg is 2.5 l on a 70 kg adult. Now if we consider the expected total body water for this subject here the adult and we do a Kt/V, this is the result, this is the clearance in CVVH that this is the UF volume and if we divide that by the total body volume, we have this.
What happens in paediatric patients? Let’s consider an average child of 25 kg, this is a reachable task with our machinery and our circuits and our filters today and we can easily drive 1.2 l/hour from this child here and get these results in terms of Kt/V but see what happens in a neonate.

Slide 17

This is another way to look at it. Doctor Maxwell from Michigan proposed 2L/ 1.73 m2 and you see that the other columns are the Ronco’s categories put together from 70 kg to 5 kg and you see that at 30 kg or less no difference in 45 ml that was the highest Ronco’s category versus 2l/1.73 m2. There’s no difference.

Slide 18

So rather I want to conclude this small dialysis parenthesis I made showing you something different always from the paediatric CRRT registry. Possibly the great extent of variation of survival among all underlying diseases, they vary from almost 100% of haemolytic uremic syndrome to liver transplantation 17 and possibly this is much more important than the dialysis dose.

Slide 19

This is our series and you see here this is acute renal failure with multiple organ failure. Almost 70% of survival rate while cardio surgery is only 20% and children with – error of metabolism is right 50% so there’s a wide range of survival and this is clearly depending on underlying disease.

Slide 20

So in conclusion paediatric acute kidney injury results more commonly from a systemic illness or its treatment with younger or more critically ill patients at greater risk. Paediatric acute kidney injury survivors are at risk for developing chronic sequelae. Multiple organ failure in development and death occur earlier than in adults.

Slide 21

The RIFLE may represent an important tool to overcome paediatric AKI lack of standardisation and in critical children a high dialysis dose is an easy reachable task how this can affect outcome remains to be established. Fluid overload is a new important marker in the paediatric acute kidney injury outcome evaluation. Low fluid resuscitation policy to prevent it and early intervention to correct it have to be recommended.

Slide 22

This is a very old aphorism in paediatrics, kids are not just small adults it’s a different argument and possibly in this particular case it’s particularly true.

Slide 23

Let me thank all the doctors and nurses in my unit and in the ICU of my hospital and personally Zaccaria Ricci at the ICU of cardiology and 3 very special friends Claudio and Tim and Stu Goldstein for very precious advice all through the years of this experience. I thank you for your attention.

Slide 24

Chairman: Thank you very much Doctor Picca for this very elegant overview any questions, remarks form the floor so far? I have a question or just to remark on something that puzzled me while listening to your talk. If dose is not or less an issue in paediatrics because of the smaller volume, I can imagine that in contrast something like vascular access might be more problematic than in adults and if you consider that the rate of those children becoming chronic kidney patients so that preservation of vascular access is probably even more important than in adult patients with AKI, I don’t understand why PD goes down and CRRT where you spoil central access probably and for something that is probably futile why that is becoming more popular?

Dr Picca: This is a very good point. I don’t want to get into the commercial aspect of the problem that is possibly imaginable but I do perform CRRT very often. Parenteral nutrition for instance, is a big point of difference between PD and CRRT and also with SLEDD or with intermittent hemodialysis. Children do have a very accelerated catabolism much more than adult patients. Leaving them more than 24-48 hours without nutrition is a big problem, it means to expose them to risk of any possible problems, added problems. So CRRT is very comfortable from this point of view, you can dose and modulate input you give in terms of volume and then retire. It’s not a question of clearance, it’s a question of fluid balance.

Chairman: Then again if you do PD, you can use glucose and you can give aminoacids.

Dr Picca: No this is quite well known, quite a certain point the ultrafiltration you get with PD although if the infant for instance if the infant’s peritoneum has a -- between the peritoneum surface and body surface area in a neonate is double compared with the adult, so you are from a theoretical point of view this is an advantage but even knowing this and having this large peritoneal surface, almost invariable the UF rate is not enough to guarantee for instance a good parenteral nutrition. Parental nutrition in my opinion is one of the main points to use CRRT in paediatrics.

Chairman: Ok other remarks, questions?

Question: My question is about the estimation of the fluid overload in children. If I have understood well, you rely on the change in the body weight. Do you think it is a sufficient parameter and what do you think is correct for a correct estimate of the central volume overload apart from central venous pressure measurements?

Dr Picca: Well, I frankly cannot answer since all the data we have about fluid overload were calculated this way. So in critical children, for instance, it’s almost impossible to have body weight because from a practical point of view what you have in your bed and it’s very difficult to calculate even with modern balance. So you do your fluid balance on paper just taking into account what is the historical accumulation and that’s the pCRT and Stu Goldstein papers have been published using this method here. I cannot answer because I do not know.

Chairman: I think there is one more question from the same microphone.

Question: Let me join the Chairman’s comment about your elegant presentation I would like to ask you actually we seek a better indicator than mortality which looks very rough and not related with the procedure which has been used. Do you think that other indicators like for instance recovery of renal function and the time – between the induction of renal failure and the stabilisation of values of renal function can be accounted for because nobody has reported this way of measurement of beneficial effects of the treatment?

Dr Picca: You’re absolutely right, the point is that we have a lack from this point of view. There is no data, not enough data. You’ve seen before that now, for instance, we have an idea that of the possible consequence of AKI on the residual renal function and on the long term outcome of renal function but this is really just a neonate let me say point and we really have to but your point is really good. Of course when one is starting an experience in terms of decades so we are younger by definition compared to the adult but younger also in experience I think that this data will come out in a few years.

Chairman: Thank you very much. So I would like to close this session with a kind of appeal that it’s very clear that in this very important field there is still a lot of research to be done and a lot of investigations to be made and I think there is a place for nephrology over there. I thank you for your attention and enjoy the evening.