1. CRRT IN ACUTE KIDNEY INJURY
Dr Umut Selda Bayrakçı
Yıldırım Beyazıt University, Ankara, Turkey

3. Acute renal failure is not a “cute” renal failure Druml W, 2004
The epidemiologic importance of AKI as a public health problem is underscored
because renal function can easily and practically indefinitely be replaced by modern renal replacement modalities, AKI presents a rather harmless complication
Despite the advances in the ability to provide dialysis to children, the out come of AKI remains surprisingly poor
MORTALITY in critically ill patients
53 % in the ATN trial
44.7 % in the RENAL trial
It is widely believed AKI is a harmless situation. Its may be because renal function can easily and practically indefinitely be replaced by modern renal replacement modalities.
However, it is not the case actually. This opinion is in sharp contrast to evidence from several recent experimental and clinical investigations indicating that ARF has a fundamental impact on the course of disease, the evolution of associated complications and on prognosis, independently from the type and severity of the underlying disease.

4. AKI exerts a fundamental impact
Even a small reduction in the renal function (0.3 mg/dl SCr increase) is a risk factor for morbidity and mortality in hospitalized patients.
It is not a problem restricted to the kidneys
It’s a systemic disease process
AKI exerts a fundamental impact
On the course of disease
The evolution of associated complications
Prognosis
Independently from the underlying disease
It is not a problem restricted to the kidneys
It’s a systemic disease process which exerts profound effects on practically all biologic functions and organ systems
The kidneys in ARF initially are mostly “victims” of a systemic disease process, such as a shock state or sepsis. But during the further course of disease—as the acutely uremic state in- duces negative repercussions on the organism—the kidneys become “offenders”

5. Patients with ARF, die not (only) with but (also) from AKI;
acute renal failure is not a “cute” renal failure but a dangerous condition.
Druml W, Intensive Care Med 2004, Bellomo R, et al. Lancet,2012, Hobson CE et al. Circulation 2009, Coca SG et al. Am J Kidney Dis 2009, Murugan R, Kellum JA. Nat Rev Nephrol 2011
Renal replacement therapy has to be initiated early to avoid the development of an acutely uremic intoxication.

6. Management of AKI Largely supportive
Aimed preventing of life-threatening fluid or electrolyte complications
Avoiding or minimizing further renal injury
Providing appropriate nutrition to allow recovery from acute illness and renal dysfunction
Severe AKI or milder AKI in association with severe fluid overload or solute imbalance may require renal replacement therapy (RRT)
Just as the true incidence of pediatric AKI is unclear so is the optimal therapy for this condition.
Current management of AKI in the PICU is largely supportive

7. What is the OPTIMAL RRT modality
When RRT is indicated
What is the OPTIMAL RRT modality
One of the most important role of pediatric nephrologist in the ICU is to help decide in collaboration with the pediatric intensivist

8. When to start? Should clinicians wait for Frank anuria?
Unequivocal signs of uremia?
Fluid overload?
Should treatment be indicated proactively?
Are there reliable indices helping to choose RRT timing?
This is the most critical question. It really could be nice to have practical guidelines enlightining our way. Unfortunately it is not the case. Usually clinicians should find their way according to their instincts. Should clinicians wait for frank anuria or unequivocal signs of uremia or fluid overload before starting an extracorporeal therapy or should the treatment be indicated proactively? Are there reliable indices helping the operators to choose RRT timing? Back in 2001, the Acute Dialysis Quality Initiative (ADQI) workgroup defined some ‘absolute’ indications for RRT that, however, came after a con- sensus statement, not from specific clinical data (given below) (

9. Absolute indications to start RRT
Uremic complications, for example encephalopathy, pericarditis, bleeding.
Serum urea at least 36 mmol/l (100 mg/dl).
K+ at least 6 mmol/l and/or ECG abnormalities.
Mg at least 4mmol/l and/or anuria/absent deep tendon reflexes.
Serum pH 7.15 or less.
Urine output less than 200 ml/12 h or anuria.
Diuretic-resistant organ edema (i.e. pulmonary edema) in the presence of AKI.
Acute Dialysis Quality Initiative (ADQI) workgroup,2001

10. When to start?
Not only the presence of AKI but also its severity should be assessed: pediatric RIFLE (Risk, Injury, Failure, Loss, End stage)
Severe AKI and/or rapidly deteriorating kidney function (towards “F” level) RRT initiation should be considered.
Particularly if there was failure to respond to initial therapy.
Critically ill patients with mild to moderate AKI (i.e. RIFLE category R/I): the most challenging
Decision should be tailored dynamically
Further research in the field of AKI led to the possibility to assess not only the presence but also the severity of AKI: the RIFLE (Risk, Injury, Failure, Loss of Function, End Stage Renal Disease) classification was proposed by the ADQI group either as a definition, intended to establish the presence or absence of the clinical syndrome of AKI in a given patient or situation, and to describe the severity of this syndrome. RIFLE was not originally designed to predict mortality or adverse outcomes, nor to trigger standardized therapeutic interventions. However, it seemed logical to assume that more severe disease should result in worse outcome. Further research in the field of AKI led to the possibility to assess not only the presence but also the severity of AKI: the RIFLE (Risk, Injury, Failure, Loss of Function, End Stage Renal Disease) classification was proposed by the ADQI group either as a definition, intended to establish the presence or absence of the clinical syndrome of AKI in a given patient or situation, and to describe the severity of this syndrome. In the presence of severe AKI and/or rapidly deteriorating kidney function (towards ‘F’ level), RRT initiation should be considered, particularly if there was failure to respond to initial therapy. However, the decision of if, and when, to initiate RRT in critically ill patients with mild-to- moderate AKI (i.e. RIFLE category R/I) is often the most challenging. It is important to recognize that the decision to initiate RRT in these patients should be ‘dynamically’ tailored on each case and not strictly rely on a single indication.

11. Sometimes we should consider RRT in earlier stages of AKI:
Severe sepsis
Reduced renal reserve
Primary diagnoses associated with high catabolic rates
(septic shock, major trauma, burn, injury)
Gastrointestinal bleeding, rhabdomyolysis placing
considerable demand on kidney function
A positive fluid balance and overt clinical fluid overload
the presence of one or more mitigating factors, such as rapidly worsening AKI and/ or overall severity of illness, severe sepsis, and reduced renal reserve, would push us to consider RRT in earlier stages of AKI. Primary diagnoses associated with high catabolic rates (e.g. septic shock, major trauma, burn injury) or those likely to place considerable demand on kidney function (i.e. gastrointestinal bleeding, rhabdo- myolysis) should be identified in the context of potential need for early initiation of RRT. Critically ill patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) receiving lung-protective ventilation may intentionally develop respiratory acidosis due to permissive hypercapnia [25]. Co-existent and/or evolving AKI in these patients will significantly impair capacity for kidney bicarbonate regeneration to buffer systemic acid- emia. Earlier RRT may prove beneficial in these patients prior to the development of severe acidemia, worsening ARDS and/or volume overload. A positive fluid balance and overt clinical fluid overload, when refractory to medical therapy (i.e. diuretics), is also an important circumstance in which RRT initiation may prove beneficial. In critically ill patients, fluid overload may be under-recognized as an important contributor to mor- bidity and mortality [26].

12. When RRT is indicated? 30 children
Children with volume excess of 10% or less improved survival
21 children on CRRT
Mean volume excess 16% survived
Mean volume excess 33% did not survived
116 children with AKI, CRRT, 13 different center
Mean volume excess 14% survived
Mean volume excess 25% did not survived
At what point should conservative management be abandoned in favor of RRT. Studies indicates that it should be started as soon as fluid overload occurs.
The first such study, which included 30 children who underwent intermittent hemodialysis for AKI after bone marrow transplantation, showed that those with volume excess of 10% or less at the time of RRT initiation had improved survival at discharge from hospital.
In a subsequent study of 21 children on continuous RRT, mean volume excess was 16% in those who survived and 33% in those who did not survive. In a study by Goldstein et al., 116 children with AKI of various causes underwent continuous RRT at 1 of 13 different centers.30 Despite variations between centers in the timing of RRT initiation and the definition of AKI, the major predictor of survival was initiation of RRT before substantial fluid excess. The patients who survived had an average volume excess of 14% above dry weight at the time of initiation of continuous RRT, as opposed to an average excess of 25% in those who did not survive.
Lane PH et al. Bone Marrow Transplant 1994, Goldstein et al Pediatrics 2001
Goldstein et al. Kidney Int 2005

13. When RRT is indicated? As soon as fluid overload occurs
unless there is excessive solute load
Reasonable TRESHOLD for initiation of RRT:
fluid overload of 15%
*BUN levels at initiation of RRT was not associated with survival
(increased in nonsurvivors)
Bunchman TE.Nature Clinical Practice 2008
Studies indicate that it is best to begin RRT in children as soon as fluid overload occurs, unless there is excessive solute load.
Blood urea nitrogen level (solute clearance) at initiation of RRT was not associated with survival, although it was increased in non-survivors. Based on the published studies, a reasonable threshold for initiation of RRT would be a fluid overload of 15%.

14. When to start? 1847 ICU patients with AKI requiring RRT
Relationship between biochemical, physiological and comorbid factors at time of RRT start and ICU mortality
Independent risk factors for ICU mortality
Mechanical ventilation
Oligoanuria
Serum urea
Cardiovascular failure
Failure to correct acidosis and development of more organ failure within 48 hours of RR
Survivors tended to have higher creatinine and lower urea levels at the start of RTT
YH Chou et al. Crit Care
n a recent interesting retrospective analysis in 1847 critically ill patients with AKI patients requiring RRT, Ostermann and Chang [34] evaluated the relationship between biochemical, physiological and comorbid factors at time of RRT start and ICU mortality. Multivariate analysis showed that at time of initiation of RRT, independent risk factors for ICU mortality were, among others, mechanical ventilation (OR 6.03), oligoanuria (OR 1.6), age (OR 1.03), serum urea (OR 1.004) and cardiovascular failure (OR 1.3). A higher pH at initiation of RRT was independently associated with a better outcome. Failure to correct acidosis and development of more organ failure within 48 h after initiation of RRT were also associated with an increased risk of dying in ICU.

15. Take home message-1
RRT should be recommended for AKI in critically ill patients before organ failure and and metabolic derangements have reached the slippery threshold of irreversibility!!
The message of this research seems to remark that RRT should be commenced for AKI critically ill patients before organ failure and metabolic derangements have reached the slippery threshold of irreversibility.
Creatinine is not an ideal biomarker for decision on RRT timing
New biomarkers will hopefully improve the performance
of creatinine, urea and RIFLE

16. The message-2
The decision when to start RRT should be established case by case and guided by
Associated dysfunction of other organ systems
patients’ AKI severity
Urine output
Serum pH
locally available technics and devices

17. Stuivenberg Hospital Acute Renal Failure Project (SHARF)
RRT patients have higher mortality (43 vs 58%)
Longer ICU and hospital stay compared to patients treated with conservative approach
Elseviers MM et al. Crit Care 2010
In this delicate and difficult debate, a recent provocative observation from Stuivenberg Hospital Acute Renal Failure (SHARF) project, showed that RRT patients had a higher mortality (43 versus 58%) as well as a longer ICU and hospital stay compared to patients treated with conservative approach (volume, electrolyte, acid-base homeostasis and specific drug management without dialysis) [37􏰀􏰀]. A higher mortality in the RRT group was confirmed after multiple adjustments and the authors concluded that the higher mortality expected in AKI patients receiving RRT versus conservative treatment can not only be explained by a higher disease severity in the RRT group: early RRT, in this context, would result as definitely detrimental.

18. Which is the best dialysis modality

19. The two most important factors that influence choice of dialysis:
The indication for dialysis
Overall clinical status of the patients
*The decision will be based upon
Specific patient characteristics
Patients requirements/limitations
The status of major organ systems
From a clinical standpoint, the two most-important fac- tors that influence choice of a dialysis modality are the indication for dialysis and the overall clinical status of the patient. Indications for dialysis are well known and are summarized in Table
Each of these problems can be managed to some extent by conservative measures, but dialysis will become necessary when conservative measures fail to keep these problems under adequate control
mple, the patient who is mildly fluid overloaded, but not experiencing respiratory compromise or significant pulmonary edema, may not require rapid fluid removal, and therefore, might be able to be managed with a gradu- al modality such as peritoneal dialysis (PD). On the oth- er hand, a patient with significant metabolic acidosis and hypotension requiring inotropic support would likely be a poor candidate for intermittent hemodialysis (HD), but could potentially be managed by either hemofiltration or PD. The goal of such a comprehensive patient assess- ment, therefore, would be to determine the major need to be filled by dialysis for that patient (i.e., ultrafiltration vs. solute clearance), as well as what is feasible or possi- ble given the overall clinical status of the patient.
These clinical factors interact in important ways. And this point the decision depends on fine tuning and finally the decision is the state of the art of your knowledge.
The status of major organ systems should be assessed.
In addition, occasional patients may benefit from the institution of dialytic support in order to provide the necessary nutrition to aid in their recovery from ARF or its underlying cause

20. LOCAL EXPERTISE with specific dialysis techniques Facility experience
Local resources
The last bu not the least most important point is the expertise and economic status of the institution. This is the case especially in CVVH

21. Should intermittent RRT or continuous RRT be used
No suitable powered randomized controlled trials
Results of present studies do not suggest a difference in patient survival
On the basis of patient survival all seem to be acceptable
State of the art
Clinical status of the patient
Intermittent HD requires careful use in patients with impaired hemodynamic status
Should intermittent renal replacement therapy or continuous renal replacement therapy be used? No suitably powered randomised controlled trials have been done to address this question. However, results of small-to-medium-sized studies do not suggest a difference in patient survival. Thus, on the basis of patient survival, intermittent haemodialysis, slow low- efficiency dialysis, and continuous renal replacement therapy all seem to be acceptable options.122

22. CVVH
Venovenous forms of CRRT is considered superior to other forms of CRRT because of
Lover risk of hemorrhage
Less frequent circuit clotting
More predictable driving pressure through the hemofilter
CRRT has became popular for the support of critically ill pediatric patients.
The development of pump-driven volumetric control CRRT machines with small extracorporeal volumes has lead to the vide spread use of venovenous forms of CRRT

23. Advantages of CVVH Continuous solute clearance and ultrafiltration
Gradual removal provided by hemofiltration
**Ideal modality for patients with cardiovascular instability and hypotension
Continuous removal
Fluid restriction is usually unnecessary
Freedom to provide large volumes of nutritional support, drugs, blood products etc..
Continuous hemofiltration1 has a number of distinct ad- vantages in the management of patients with ARF. Chief among these is that it provides continuous solute clear- ance and ultrafiltration, thereby mimicking to some ex- tent the functions of the normal kidney [1, 3]. The gradu- al nature of fluid removal provided by hemofiltration makes it an ideal modality for many patients with cardio- vascular instability and hypotension. Furthermore, since fluid is removed on a continuous basis, fluid restriction is usually unnecessary in patients being treated with he- mofiltration, which provides much greater freedom than HD to provide large volumes of nutritional support, ei- ther enteral or parenteral. On the other hand, at least one study has demonstrated increased losses of amino acids in patients undergoing hemofiltration [62]; increasing the amino acid content of the total parenteral nutrition (TPN) solution can usually minimize this problem.

24. Advantages of CVVH Specific metabolic advantage
Wide variety of metabolic problems can be corrected easily
Severe metabolic acidosis
Lactic acidosis
Electrolyte abnormalities (s.a. hyperkalemia)
Superior control of uremia than intermittent HD
It can also be adopted to gradually correct hyperosmolar states
Less likely to lead to cerebral edema
Removal of mediators of inflammation
Hemofiltration may also have specific metabolic ad- vantages compared with other dialysis modalities. Be- cause the composition of the dialysate is adjustable in many hemofiltration systems, a wide variety of metabol- ic derangements can be easily corrected with hemofiltra- tion, including severe metabolic acidosis, lactic acidosis, and electrolyte abnormalities such as hyperkalemia. It has been reported that hemofiltration provides superior control of uremia than intermittent HD [63]. Hemofiltra- tion can also be adapted to gradually correct hyperosmo- lar states [64], and may be less likely to lead to cerebral edema than intermittent HD [58]. In addition, several au- thors have recently begun to explore the possible bene- fits from hemofiltration with respect to removal of medi- ators of inflammation [65, 66]. Such substances, which contribute to the pathogenesis of the sepsis syndrome, appear to be cleared to some extent by hemofiltration, due to the relatively small size of these molecules and the properties of the membranes used for hemofiltratio

25. Cost of dialysis equipment (in U.S. dollars)
Modality
Manual PD
Automated PD
İntermittent HD
Continious HF
Device
Ultra Set (Y-set)
Freedom cycler C3
Prisma
Manufacturer
Baxter
Fresenius
Gambro
Cost per unit
$6.95
$12,295.00
$18,000.00
$25,000.00
Cost of additional supplies
1.5% Dianeal $24.43/2 L
Pediatric tubing set $32.00 each
100HG dialyzer $50.00 each;
M60 hemofilter set (filter and bloodlines) $ each
Peritoneal dialysate as at left
pediatric bloodlines $11.40 each
Normocarb dialysate concentrate $20.00/3.0L
The equipment is amongst the most expensive on the market as far as dialysis equipment is concerned (Table 3), and some centers may not be able to afford to establish hemofiltration programs for this reason. In addition to the expensive equipment, a specialized nursing staff is usually required, with dialysis nurses initiating the hemofiltration treatments in most pediatric centers, and ICU nurses taking over once the patient has been stabilized on the hemofiltration circuit. This increases the labor cost for hemofiltration compared with other modalities [70], as not only is a skilled ICU nurse required, but also a skilled dialysis nurse. However, the diThe equipment is amongst the most expensive on the market as far as dialysis equipment is concerned (Table 3), and some centers may not be able to afford to establish hemofiltration programs for this reason. In ad- dition to the expensive equipment, a specialized nursing staff is usually required, with dialysis nurses initiating the hemofiltration treatments in most pediatric centers, and ICU nurses taking over once the patient has been stabilized on the hemofiltration circuit. This increases the labor cost for hemofiltration compared with other modalities [70], as not only is a skilled ICU nurse re- quired, but also a skilled dialysis nurse. However, the di- alysis nursing time may be less with he
alysis nursing time may be less with he
Flynn JT, Pediatr Nephrol 2002

26. WHICH IS THE BEST DIALYSIS MODALITY?
GUIDANCE FROM THE LITERATURE

27. 1995: 42 children (following repair of congenital heart dis): 21 PD
21 HF; 9 CAVH, 12 CVVH
Survival: identical
Fluid removal, urea and creatinine clearance, and caloric
intake superior in HF
Fleming et al, J Thoracic Cardiovasc Surg, 1995
Fleming et al. [76] performed an important compari- son of PD and hemofiltration in They retrospec- tively compared 42 children who required renal replace- ment therapy (RRT) following repair of congenital heart disease. Indications for RRT in the study included olig- uria, fluid overload, hyperkalemia, and provision of TPN. Twenty-one patients received PD and 21 patients received hemofiltration, with 9 of those receiving arte- riovenous hemofiltration and 12 venovenous; 34 patients received RRT for more than 24 h. Time of initiation of RRT was not standardized, and consequently varied sig- nificantly among the patients. Of the 42 patients in the study, 90% required inotropic support, 36% required re- peat operation for their congenital heart disease, and 18% had sepsis. Survival was identical for patients treat- ed with PD compared with those treated with hemofiltra- tion (38%). However, fluid removal, urea and creatinine clearance, and caloric intake were superior in the hemo- filtration groups compared with the group who received PD. From these data, the authors concluded that hemofil- tration was superior to PD in this clinical setting. While this conclusion may be true for children who develop oliguria following open-heart surgery, these results may not apply to patients with other underlying diagnoses. In addition, although caloric intake and solute clearance were superior in the group that received hemofiltration, the data did not indicate that these benefits conferred any survival advantage. Thus, as indicated in other recently published series [39, 77, 78], PD remains a via
almost every paper on dialysis in pediatric ARF utilized PD, probably because of a perception in the past that HD was technically difficult in infants and young children. Although successful HD in infants has subsequently been reported [75], and may now be con- sidered routine in many centers,
Adults: Because of limitations in clearance and difficulties in fluid removal PD is rarely used in ARF
Pediatrics: PD used to be the first choice; technical difficulties of HD in infants and young adults

28. 1997: Comparison of HD and hemofiltration in pediatric ARF
122 children with ARF (retrospective)
58 HD
64 HF
Survival: 83% in HD, 48% in HF group
Higher percentage of children with primary renal dis in HD group
Higher percentage of patients with sepsis in HF group,
greater severity of illness in HF
Maxvold et al; Am J Kid Dis 1997
A comparison of HD and hemofiltration in pediatric ARF was published by Maxvold et al. in 1997 [74]. They retrospectively studied 122 children with ARF, 58 who underwent intermittent HD, and 64 who underwent he- mofiltration. Clinical characteristics of the two groups were similar in terms of patient age and patient weight. There was a higher percentage of children with primaryrenal disease in the HD group, compared with a higher percentage of patients with sepsis in the hemofiltration group. Similarly, hypotension and the need for vasopres- sor support were more common in the hemofiltration group, suggesting a greater severity of underlying illness in those children. This was reflected in the patient sur- vival, which was much greater in the HD group (83%) than in the hemofiltration group (48%). Most dramatical- ly, survival was 96% for patients with primary renal dis- ease treated with HD compared with 31% for sepsis-re- lated ARF treated with hemofiltration, again reflecting the greater severity of illness in the hemofiltration group. Other aspects of the modality comparison in

29. Comparison of 3 dialysis modality
279 children with ARF and/or inborn errors of metabolism (retrospective)
59 PD
140 HF
80 HD
Overall survival was 53%
Variation in survival among modalities for certain diagnoses
Finally, there has been one study that has directly compared all three dialysis modalities in children with ARF. This was a retrospective review, again by investi- gators at the University of Michigan, of 279 children who received RRT over a 7-year period for treatment of ARF and/or inborn areas of metabolism; 59 of the chil- dren received PD, 140 hemofiltration, and 80 intermit- tent HD. Overall patient survival was 53%, with some variation in survival among modalities for certain diag- noses

30. Comparison of 3 dialysis modality
ARF following bone marrow transplant
%78 intermittent HD
33% PD
21% HF
ARF following repair of congenital heart disease
100% intermittent HD
33% PD
50% HF
Hemodynamic instability
affect patient outcome
predictive of modality choice
patients who were the most hemodynamically unstable were usually
treated with either HF or PD whereas stable patients were usually
treated with intermittent HD.
. For example, while overall survival in patients with ARF following bone marrow transplant was 42%, such patients treated with intermittent HD had a survival of 78% compared with survivals of 33% for those treated with PD and 21% for those treated with hemofiltration. Conversely, patients with ARF following repair of con- genital heart disease had an overall survival of 39%, with 100% survival for those treated with intermittent HD, 33% survival for those treated with PD, and 50% survival for those treated with hemofiltration.
Hemody- namic instability was felt to not only affect patient out- come, but also was predictive of modality choice: pa- tients who were the most hemodynamically unstable were usually treated with either hemofiltration or PD, whereas stable patients were usually treated with inter- mittent HD.
Bunchman TE, J Am Soc Nephrl, 1999, abstr

31. Single center study designs Small patient numbers
Limitations:
Retrospective
Single center study designs
Small patient numbers
Homogenous patient populations: results couldn’t be generalized
Since the advent of hemofiltration, however, several studies have appeared in the pediatric ARF literature that have compared hemofiltration with other dialysis modal- ities. Before reviewing selected papers from this litera- ture, it is important to point out that all of these studies suffer from significant limitations, including retrospec- tive, single-center study designs, small patient numbers (some studies), and homogeneous patient populations that do not allow for generalization of study results. Despite these flaws, however, these studies do provide useful insights.

32. Intermittent HD vs CRRT
Multicentre, prospective, randomized, controlled trial
316 adults, AKI patients
Mortality:
intermittent HD:62.5%
CRRT: 58.1%
Modality of RRT has no impact on the outcome in ICU
Rins RL et al. Nephrol Dial Transplant 2009
Single center, randomized, controlled trial (CONVINT)
252 adult AKI patients
Survival rate: 39.5% IHD
43.9% CVVH
No significant difference regarding mortality, renal outcome measures or survival
Schefold JC et al. Critical Care 2014
In the study presented here, we compared, prospectively and randomized, IRRT and CRRT in 314 AKI patients ad- mitted to the ICU and found no difference in hospital mor- tality, hospital length of stay and renal recovery at discharge between both patient groups. The use of the SHARF score for correction of disease severity enabled the confirmation that CRRT showed no survival benefit, even in critically ill patients. Since evidence is growing about the comparable outcome for both modalities, consensus is also growing to merely consider the different treatment options as comple- mentary.

33. Intermittent HD vs CVVH
Multicenter, randomized and prospective study (21 center, Hemodiafe Study Group)
Adults with multiorgan dysfunction syndrome and AKI
Rate of survival did not differ between the intermittent HD and CVVH
Vinsonneau C et al, The Lancet, 2006

34. Intermittent HD vs CVVH
ATN and RENAL studies suggest that CVVH might help with renal recovery
Meta-analysis studies reveals no difference in long term dialysis dependency
Ghahramani N et al. Nephrology 2008

35. Suggested modality choice in pediatric ARF
Goal of dialysis
Hemodynamic status
modality
Ultrafiltration
Normotensive
hypotensive
Intermittent HD (w isolated UF)
Continuous HF or PD
Urea clearance
Intermittent HD or PD
Treatment of hperkalemia
Either normotensive
or hypotensive
Intermittent HD
Correction of metabolic acidosis
Any
Treatment of Hyperphosphatemia
Any; continuous hemofiltration possibly superior
Flynn JT. Pediatr Nephrol 2002

36. RRT modality: conclusion
Few data available regarding pediatric patients
Decision: empirical
Consider:
Underlying disease
Severity of illness
Advantages and disadvantages of the various modalities available locally
Cost
Although survival was somewhat the same/better in intermittent HD group, provision of HF most likely contributed to the survival of many patients who might not survived had HF not available
Maxvold NJ et al. Am J Kid Dis 1997 (abstr)

37. Conclusion Combination
CRRT: early correction of hemodynamic instability as long as multiorgan failure exist
Classic intermittent HD for long lasting-isolated AKI
Rins RL et al. Nephrol Dial Transplant 2009
Probably in the future, a combination of CRRT for early correction of haemodynamic instability, intensive, daily IRRT (SLEDD) as long as multiple organ failure ex- ists and classic intermittent haemodialysis for long-lasting and isolated AKI, have to be used as complementary Extra Corporeal Treatment Modalities.

38. Dose of CVVH in AKI
Expression of how much dialysis should be prescribed in order to achieve a certain level of blood cleansing
Dose relies on
Patient clinical picture (catabolic rate, muscle mass, presence of pulmonary edema, fever, dysionemia etc.)
Solute to clear (water, urea, electrolytes, cytokines..)
The final desired blood level of the target solute
In CVVH (small solute) clearance is essentially considered equal to UF rate

39. VA/NIH ARF trial network (ATN) study
Optimal RRT dose in ICU: 2 multicenter clinical trials Compare normal or less intensive renal support to intensive therapy
RENAL
VA/NIH ARF trial network (ATN) study
1124 patients
25 ml/kg/h CVVHDF vs 40 ml/kg/h
N England J Med, 2009
1500 patients
20 ml/kg/h CVVHDF/ thrice weekly IHD vs 35 ml/kg/h/daily IHD
N England J Med, 2009
As far as RRT dose is con- cerned, after about 10 years from the milestone trial that first suggested the possible impact of RRT intensity on patients’ outcome [11], two multicenter clinical trials examined the issue of the optimal RRT dose in critically ill patients: the randomized evaluation of normal versus augmented level (RENAL) replacement therapy study [12] and the VA/NIH Acute Renal Failure Trial Network (ATN) study [13]. The RENAL and ATN studies were designed to compare ‘normal’ or ‘less intensive’ renal support to an ‘augmented’ or ‘intensive’ therapy: in particular, the RENAL study compared 25 ml/kg per h continuous veno-venous hemodiafiltration (CVVHDF) to 40 ml/kg per h and the ATN study 20 ml/kg per h CVVHDF or thrice weekly intermittent dialysis to 35 ml/kg/h CVVHDF or daily intermittent dialysis. Sur- prisingly, both studies showed no benefit in outcomes by increases in intensity of RRT dose, essentially confuting
No benefit in outcomes by increases in intensity of RRT dose

40. Conclusion Normal dose: 20-30 ml/kg/h for continuous therapy
Ricci Z, Ronco C. Current Opinion Critical Care, 2011
Overt underdialysis might be harmful in ICU!!
Be careful about the discrepancy between prescribed and delivered dose!!!
THE BEST EVIDENCE CURRENTLY AVAILABLE SUGGESTS THAT HEMOFILTRATION SHOULD BE PRESCRIBED AT 25 TO 30 ML · KG−1 · H−1.
In this light, the ATN and RENAL studies were rigorous clinical trials and minimized greatly the discrepancy between prescribed and delivered dose: as recently confirmed by the DOse REsponse Multicentre International (DoReMi) Collaborative Initiative, the difference between prescription and delivery of CRRT relies on therapy downtime (the amount of time the CRRT does not run in a 24-h period), clotting of the circuit (the cause of the majority of unexpected treatment stops), vascular access problems (that push clinicians to modify therapy settings) and prescription errors (some operators in the field of acute RRT do not really know how to correctly prescribe) [16􏰀]. Hence, when in clinical practice, 20 – 25 ml/kg per h is prescribed during CRRT, consistently with those in the RENAL and ATN studies, the possibility of a significant reduction in dialysis dose delivery should be considered. In practice, clinicians need to over-prescribe RRT with a 25% safety margin, targeting 30–35ml/kg per h in order to achieve the ‘adequate’ delivered dose [14􏰀].

41. DOse REsponse Multicenter International Collaborative Initiative (DoReMi)
The difference between prescribed and delivered dose
Relies on therapy downtime (the amount of time the CRRT does not run in a 24 h period),
clotting of the circuit,
Vascular access problems
Prescription errors
Crit Care 2009
When you prescribe ml/kg/h during CRRT significant reduction in
dialysis dose delivery should be considered!

42. In practice you may need to over- prescribe RRT with 25% of safety margin
Recommendation: ml/kg/h?
Kellum JA, Ronco C Nat Rev Nephrol 2010
Ricci Z, Ronco C. Curr Opin in Crit Care, 2011
The currently recommended dosage is ml/kg/g, However, in order to achieve this dose in clinical practice, prescriptions of 25–30 ml · kg−1 · h−1 are generally required, and close monitoring of dose delivery is advised.

43. Anticoagulation Low dose heparin Citrate anticoagulation
10-20 IU/kg bolus
10-20 IU/kg/h continuous drip (target activated clotting time: s or partial tromboplastin time that is double the normal value)
Citrate anticoagulation
No anticoagulation
One of the major disadvantages of CRRT is the need of continuous anticoagulation.

44. When to stop? No randomized controlled trials addressing this issue
Observational studies have suggested that urine output can be used to predict successful cessation of CRRT
Spontaneous urine output >500 ml/day? (adult)
Uchino S et al. Crit Care Med 2009

45. Complications of CVVH Common in both CVVH and IHD High cost
Technological complexity
Specialized nursing staff usually required
Hypothermia
Membrane bioincompatibility
Acid-base imbalance
Electrolyte imbalance
Removal of drugs and nutrients
Volume depletion
Common in both CVVH and IHD

46. Long-term outcomes Mortality is high
At least 10% of children who survive AKI have evidence of
Hyperfiltration
Hypertension
Microalbuminuria
Puts them at risk of long term progressive loss of kidney function
Long term follow-up is important!
Early intervention with ACE inhibitors, angiotensin receptor blockers or other renoprotective therapies if necessary
Askenazi DJ et al. Kidney Int 2006

47. Firdevs Çalkanoğlu