User blog: Arif Khwaja

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There is a great recent post by Ajay Singh, Professor of Nephrology at Harvard on his blog The Kidney Doctor talking about the importance of communication with patients. He cites data showing that only 23% of patients are allowed to finish their opening statements when talking to doctors and astonishingly the average time to interruption is only 18 seconds!!

Yet the cost of poor communication remains high. I was reflecting on this as I did my on-call ward rounds this weekend. As in most nephrology units there were a core of dialysis patients for whom dialysis neither improves the quality of life nor life expectancy. These were mostly elderly patients with significant comorbidity many of whom were diabetic. The history was invariably one of recurrent admissions with infections, access problems and fluid overload. All foreseeable and predictable yet patients still ended up in a cycle of recurrent admissions and functional deterioration. Of course the economic cost is significant - a recent analysis of healthcare costs and mortality over the last 200 years at the Massachusetts General Hospital showed some interesting findings. Mortality has fallen precipitously since around 1970 though healthcare costs have risen exponentially. Interestingly whilst costs have continued to rise in the last 10 years mortality no longer seems to be falling - one could speculate that this is perhaps because doctors are losing the art of recognising dying patients and subjecting them to endless interventions with little benefit.

Few of us (myself included) talk about withdrawing treatment until relatively late in the course of treatment and while we like to all talk about patient choice we perhaps need to discuss conservative therapy more openly and honestly.This has been known for many years as Farrington and colleagues showed in Stevenage, UK that dialysis offered no survival advantage in the elderly with significant co-morbidity. Similarly data from the Royal Free Hospital in London showed that those elderly patients with comorbidity who opted to have dialysis did have a survival advantage... Yet virtually all this "extra-time" was spent in hospital. And we know from a large analysis of nursing home residents in the USA that 58% of patients died and only 13% maintained functional status at 1 year.

The clear message is that for many elderly patients with comorbidity, dialysis neither makes people feel better nor makes them live longer. Of course we have known this for years and as it turns out that nephrologists are actually very good at predicting who does badly on dialysis - but many (including myself) need to start listening more to patients and being much more honest with them about dialysis and recognise that whilst dialysis may be palliative for all patients, for some patients dialysis simply doesn't palliate....

 

 

 

References

 

1. Two Hundred Years of Hospital Costs and Mortality — MGH and Four Eras of Value in Medicine Gregg S. Meyer, M.D., Akinluwa A. Demehin, M.P.H., Xiu Liu, M.S., and Duncan Neuhauser, Ph.D. N Engl J Med 2012

2. Is Maximum Conservative Management an Equivalent Treatment Option to Dialysis for Elderly Patients with Significant Comorbid Disease? Rachel C. Carson*, Maciej Juszczak, Andrew Davenport, Aine BurnsCJASN October 2009 vol. 4no. 10 1611-1619

3. Smith C, Da Silva-Gane M, Chandna S, Warwicker P, Greenwood R, Farrington K: Choosing not to dialyse: Evaluation of planned non-dialytic management in a cohort of patients with end-stage renal failure. Nephron Clin Pract 95: c40– c46, 2003

4. Functional Status of Elderly Adults before and after Initiation of DialysisManjula Kurella Tamura, M.D., M.P.H., Kenneth E. Covinsky, M.D., M.P.H., Glenn M. Chertow, M.D., M.P.H., Kristine Yaffe, M.D., C. Seth Landefeld, M.D., and Charles E. McCulloch, Ph.D. N Engl J Med 2009; 361:1539-1547

5. Utility of the “Surprise” Question to Identify Dialysis Patients with High Mortality Alvin H. Moss* , Jesse Ganjoo*, Sanjay Sharma*, Julie Gansor*, Sharon Senft*, Barbara Weaner*, Cheryl Dalton*, Karen MacKay*, Beth Pellegrino*, Priya Anantharaman*, Rebecca Schmidt*  CJASN September 2008 vol 3 , no 5. 1379-1384

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
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by Arif Khwaja - Saturday, 9 June 2012, 8:21 AM
Anyone in the world

So Amgen have posted a press release outlining the results of the EVOLVE study looking at the impact of cinacalcet on death and cardiovascular events in a huge study of over 3000 patients. There was NO effect on mortality or cardiovascular events. Obviously we need to wait for more data but this is yet another negative trial in a dialysis population.  A couple of thoughts come to mind:

1) Amgen actually should be congratulated for investing in the trial but this may well be the last trial of this size we see in a dialysis population - the chances of a 'magic bullet' reducing mortality in a population as complex and diverse as a dialysis population are slim and pharma are unlikely to take the risk....

2) In retrospect a perhaps more modest trial focussing on fractures and cost-effectiveness may have been more useful to practicing nephrologists. In a population where the death rate is high, from multiple aetiologies perhaps we need to start looking at the impact of multiple interventions rather than single interventions.

3) Cinacalcet is an extremely expensive drug.  Whilst there is data on the cost effectiveness of the drug it's rather weak. For those of us who work in an environment where cost is an issue need to think again about who gets the drug..... Or we could hope that in light of this data Amgen could re-evaluate the price of the drug!!!

 

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Arif Khwaja
by Arif Khwaja - Friday, 8 June 2012, 8:26 AM
Anyone in the world

There is a nice debate in this months JASN between Rifkin and Hsu about whether AKI leads to CKD. This is timely as the recent KDIGO guidelines have suggested that AKI be considered a risk factor for CKD - the logical implication of this being that all patients with AKI (including those who have completely 'recovered') be monitored for life for CKD. Rifkin and colleagues pint out that whilst its certainly biologically plausible for AKI to lead to CKD, there may be common risk factors of kidney injury that independently predispose to both AKI or CKD and furthermore its entirely plausible that CKD itself may predispose to AKI. In many ways I find the argument a bit sterile... have we not known for many years that if the AKI 'hit' is severe enough then people may be left with residual CKD whilst those wilth mild AKI appear to recover fully. As Rifkin and colleagues point out more than 500,000 AKI events occur in in the USA every year and the the vast majority recover without any significant longterm complication. The idea that all these patients need lifelong monitoring in case they get CKD is neither economically viable nor based on sound clinical judgement. An obviously pragmatic approach would be to monitor those who had severe or dialysis dependent AKI for a few years to see if CKD develops. In contrast its hard to believe that those whos have mild AKI that resolves quickly (with no comorbidity) will benefit from lifelong screening for CKD. Clearly longterm observational studies if AKI may help resolve this debate but in the meantime I suspect most nephrologist will be able to get buy just using clinical common sense....  

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Arif Khwaja
by Arif Khwaja - Monday, 28 May 2012, 7:45 PM
Anyone in the world

Once I have had a chance to digest the KDIGO guidelines I will post some thoughts. I note there has been much interest on the KDIGO guidelines on this site. A few things caught my eye - like the suggestion for fish oils in IgA nephropathy. This is based on data by Donadio and colleagues showing a beneficial effect. This has never been reproduced anywhere else and the control group in that study did extraordinarily badly - around 40% ended up on  RRT. KDIGO not unreasonably suggest that fish oils are relatively safe and therefore make a 2D recommendation about their use.

In fact 36% of all the statements in the glomerulonephritis guidelines are 2D. And to remind ourselves what does 2D mean? Well '2' is a suggestion and '1' is a recommendation. D means that the quality of evidence that the suggestion is made is ' very low - the estimate of the effect is very uncertain and often will be far from the truth'  - to me 2D sounds a lot like opinion and theres nothing wrong with opinion but we need to recognise it as opinion and not fact. If we are going to get the most out of guidelines we need to learn how to read them or perhaps just have guidelines about things for which there is good evidence.

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Anyone in the world

So last week I saw 2 patients within a few hours each of whom tells their own story. The first was in transplant clinic. She was transplanted 10 years ago and has perfect kidney function. Her BMI was 40 at the time of transplant and is now 50. She sailed through the transplant without any technical or imunnological problems. Transplantation was undoubtedly a life-saver – she had factor V Leiden mutation and was running out of access due to recurrent clotting of access.

In the afternoon I saw a 50 year old patient on haemodialysis. She had a BMI of 35 and had previously been active on the transplant list. She was otherwise well with no other significant comorbidity.  She was reviewed by a surgeon who felt that as she had significant central obesity, transplantation would be technically challenging and so she was suspended from the list until her BMI was 30. She asked to see me as she was in a terrible state. She was literally starving herself and had lost 8Kg but needed to lose a further 8 kg before her BMI hit the magic 30. She pleaded for me to be reactivated on the transplant list though I explained this was ultimately a surgical decision. What was clear was that i) I had never seen her look so ill as she did now she was trying to lose weight and ii) for her to maintain herself at a BMI of 30 she  would need to continue to starve herself.

So these two cases prompted me to look a bit at the literature around obesity and transplantation and the following themes emerged:

  1. While it has long been recognised that higher BMI associates with survival on dialysis there is also some data to suggest that weight loss is harmful. Molnar and colleagues looked at over 14000 wait listed dialysis patients and found that those who had loss greater than 5Kg had a death hazard ratio of 1.51. Of course this doesn’t mean necessarily that intentional weight loss is harmful but it is food for thought when telling dialysis patients to lose weight.
  2. Whilst surgical complications post transplantation ( e.g. wound infections) do increase with BMI, the data on the effect of obesity on graft survival is conflicting. Streja and colleagues analysed10,090 kidney transplant recipients were followed for up to 6 years posttransplantation. Low pretransplant BMI (<22 kg/m2) showed a trend toward higher posttransplant mortality, whereas obesity (BMI ≥ 30 kg/m2) was not associated with mortality, albeit it showed a trend toward higher graft loss. A smaller analysis of over 1000 patients showed recipient BMI to correlate with delayed graft function which of course in itself is a risk factor for poorer graft survival. In a 20 year follow up of around 1800 patients from Holland, BMI increment post transplantation and BMI at one year were both  much more powerful predictors of adverse graft and patient survival than pre-transplant BMI. Indeed pretransplant BMI didn’t have a statistically significant association with adverse outcomes
  3. The key question perhaps isn’t whether the obese are more likely to run into complications but whether they still have a survival advantage from transplantation. In an analysis of around 7000 patients who had a BMI of >30 who were wait listed for transplantation, the incidence of mortality in those who underwent transplantation was still less than half  of those who stayed on dialysis waiting for a kidney. The beneficial effect of transplantation was lost when BMI>41

 So what to do? Well given the fact that the safety of weight loss isn’t established in dialysis patients (and may be harmful in some patients) we need to be honest with patients and tell them that we don’t know whether this is safe - it may well be safe to lose weight but it may not be and so we need to tell patients that. There is no evidence to show that weight loss pre-transplant improves outcomes post-transplant and the observational data seems to suggest that patients with a pre-transplant BMI of upto 40 still gain  a survival benefit from transplantation. Therefore as ever we need to make individual decisions on a holistic evaluation of the patient taking into account all other comorbidities rather than plucking arbitrary numbers and targets out of the air. This is of course only opinion but I'm not convinced that the patient with a BMI of 35 who is currently starving herself to get to a BMI of 30, will get any health benefit from such starvation.

 References

Associations of body mass index and weight loss with mortality in transplant-waitlisted maintenance hemodialysis patients. Molnar MZ, Streja E, Kovesdy CP, Bunnapradist S, Sampaio MS, Jing J, Krishnan M, Nissenson AR, Danovitch GM, Kalantar-Zadeh K. Am J Transplant. 2011 Apr;11(4):725-36

Associations of pretransplant weight and muscle mass with mortality in renal transplant recipients. Streja E, Molnar MZ, Kovesdy CP, Bunnapradist S, Jing J, Nissenson AR, Mucsi I, Danovitch GM, Kalantar-Zadeh K. Clin J Am Soc Nephrol. 2011 Jun;6(6):1463-73.

Recipient and donor body mass index as important risk factors for delayed kidney graft function. Transplantation. 2012 Mar 15;93(5):524-9.Weissenbacher A, Jara M, Ulmer H, Biebl M, Bösmüller C, Schneeberger S, Mayer G, Pratschke J, Öllinger R.

Impact of renal transplantation on survival in end-stage renal disease patients with elevated body mass index. Glanton CW, Kao TC, Cruess D, Agodoa LY, Abbott KC. Kidney Int. 2003 Feb;63(2):647-53.

 Effect of obesity on the outcome of kidney transplantation: a 20-year follow-up.Hoogeveen EK, Aalten J, Rothman KJ, Roodnat JI, Mallat MJ, Borm G, Weimar W, Hoitsma AJ, de Fijter JW. Transplantation. 2011 Apr 27;91(8):869-74.

 

 

 

 

 

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
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by Arif Khwaja - Friday, 18 May 2012, 7:18 AM
Anyone in the world

An interesting pilot, proof of concept study is published in JASN online today looking at the role of renal dennervation in patients with resistatnt hypertension and CKD. In the last couple of years a number of studies have suggested that renal dennervation maybe useful in the management of resistant hypertension and larger scale clinical trials are currently underway to test this hypothesis. As yet however there have been no studies in the CKD population. The rationale is that there is increased renal sympathetic activation in CKD and further that activation of the renal afferent sympathetic system in response to CKD also increases central sympathetic activation. Renal denervation involves placing a radiofrequency catheter in the renal artery ( accessed by femoral artery) to allow ablation of renal sympathetic chain.

In this study by Hering and colleagues from Melbourne, 15 patients with CKD 3/4, a mean office BP of around 174/9, taking an average of 5.6 drugs underwent the procedure. At follow up that is between 3-12 months there was no difference in creatine-based eGFR or cystatin C suggesting that the procedure has no adverse effects on kidney function. Mean changes in office systolic and diastolic BP at 1, 3, 6, and 12 months were −34/−14, −25/−11, −32/−15, and −33/−19 mmHg, respectively. Interestingly and perhaps disappointingly the mean 24 hour BP and daytime BP didnt change. However there was a significant reduction in nightime systolic BP on 24 hour monitoring falling from a mean of 154 to 144mmHg at 6 months. i.e. there was a restoration of nightime dipping of BP - lack of nightime dipping is a stronger predictor of CV events than daytime BP. Interestingly there was no significant change in the number of medications being taken at the end of the study. The lack of effect on daytime BP is not easily explainable but the numbers are of course small and there is  substantial intrpatient variability. Peripheral arterial stiffness as assessed by augmentation index was significantly reduced at 3 months suggesting that the effect on blood pressure was real. There were reductions in proteinuria, BNP and increases in hamegloblin at 3 months but these did not reach statistical significance.

Theres clearly a long way to go before we know whether this technique will impact on meaningful outcomes but in CKD but as the authors say this preliminary study provides guidance for the design of further cinical trials to evaluate the short and long term effects of the technique in CKD.

References

 

  1. Medline
  2.  
    Medline
  3.  
    Abstract/FREE Full Text
  4. Renal Denervation in moderate to severe CKD. Hering D et al. http://jasn.asnjournals.org/content/early/2012/05/16/ASN.2011111062.abstract

 

 

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
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by Arif Khwaja - Wednesday, 16 May 2012, 3:34 PM
Anyone in the world

The recently published KDIGO guidelines provide a welcome and timely synthesis of the evidence base to support the management of AKI.The guidelines focused on 4 key domains: i) AKI Definition, ii) Prevention and Treatment of AKI, iii) Contrast-induced AKI and iv) Dialysis Interventions for the treatment of AKI.

The full summary of clinical practice statements is available at www.kdigo.org but a key recommendation is that clinicians effectively adopt the previously published AKI Network definition and staging. The rationale for the staging system comes from a plethora of studies showing that the risk of death and renal replacement therapy (RRT) increases with each stage. Furthermore evidence suggesting patients in whom AKI resolves are at increased risk of death, CKD and cardiovascular disease has prompted KDIGO to make an ungraded suggestion that all those with resolved AKI should be considered to be at increased risk of CKD and be managed as per the KDOQI guidelines for individuals at risk of CKD.  However whilst there is no doubt that standardising the definition and staging of AKI provides a clear framework for studying outcomes in both epidemiological and clinical research the bedside utility of the proposed classification and staging maybe be questioned by many 'real-world' practicing clinicians. In particular it is not clear how staging will alter immediate management and outcomes. As with the CKD classification sustem the danger is that an epidemiological tool gets imposed onto clinical practice without any evidence that the classification system per se can improve outcomes or can lead to specific interventions. Furthermore the evidence that monitoring people  with resolved AKI as being at risk of CKD can i) prevent the onset of CKD or ii) is cost-effective is not presented.

Many other recommendations are made most of which are eminently sensible/obvious (e.g. use vasopressors for those with shock) but a few caught my eye:

  1. recommended use of oral NAC in contrast nephropathy – despite v weak evidence, plus the fact that NAC has poor oral bioavailability and increases tubular secretion of creatinine
     
  2. that regional citrate be the anticoagulant of choice in CRRT unless the patient is shocked/has liver disease – of course these are the very patients that are most likely to be on CRRT and given the complexities of citrate use it’s a shame no practical protocol was provided…
     
  3. that dialysis dose be measured in AKI either by using Kt/V ( almost certainly meaningless in a catabolic patient with AKI) or the effluent flow rate in CRRT – again no evidence from the Veterans and Australasian studies that dose of RRT in AKI has any impact on survival.
     
  4. support the use of CRRT in haemodynamically unstable patients whilst this is routine practice in many places the meta-analyses indicate this again has no impact on patient outcomes… and as well all know CRRT is rarely continuous.
     
  5. The use of insulin to maintain glycaemic control despite the risks of hypoglycaemia.

 

As with previous KDIGO reviews, the clear message is that there is a lack of evidence (particularly, well-designed interventional outcome studies) to underpin much of our everyday clinical practice. Indeed only 14.8% of the recommendations were graded '1A' whilst 63.9% of the recommendations were level 2. Thus these are not prescriptive guidelines but provided nuanced guidance for the clinician. The KDIGO co-chairs bullishly argue that recommendations should be made even when the evidence is weak as clinicians often ask "what do the experts do?" – this may be true but as history tells us the track record of expert opinion in the absence of evidence can often be deeply flawed.

The recommendation that an empirical definition and staging system be used in the management of AKI will arouse controversy and debate. As yet no data has been presented to show that these tools in themselves can improve outcomes in AKI and many clinicians will be wary about implementing what is essentially a research-based diagnostic and staging system into the clinical arena in the absence of such data – as was the case in CKD........

References

  1. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW: Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 2005;16:3365-3370.
  2. Clinical practice Guidelines for Acute Kidney Injury 2012. http://www.kdigo.org/clinical_practice_guidelines/AKI.php
  3. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A: Acute kidney injury network: Report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007;11:R31.
  4. Rabindranath K, Adams J, Macleod AM, Muirhead N: Intermittent versus continuous renal replacement therapy for acute renal failure in adults. Cochrane Database Syst Rev 2007:CD003773.
  5. Palevsky PM, Zhang JH, O'Connor TZ, Chertow GM, Crowley ST, Choudhury D, Finkel K, Kellum JA, Paganini E, Schein RM, Smith MW, Swanson KM, Thompson BT, Vijayan A, Watnick S, Star RA, Peduzzi P: Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 2008;359:7-20.
  6. lomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, McArthur C, McGuinness S, Myburgh J, Norton R, Scheinkestel C, Su S: Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med 2009;361:1627-1638.
[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Anyone in the world
Published this month in JAMA by Matsushita and al on behalf of the CKD prognosis consortium a reevaluation of CKD prevalence in communities as well as the implications in term of all cause and cardiovascular mortality.
 
"Main Outcome Measures All-cause mortality (84 482 deaths from 40 cohorts), cardiovascular mortality (22 176 events from 28 cohorts), and end-stage renal disease (ESRD) (7644 events from 21 cohorts) during 9.4 million person-years of follow-up; the median of mean follow-up time across cohorts was 7.4 years (interquartile range, 4.2-10.5 years).
Results Estimated GFR was classified into 6categories(>90,60-89,45-59,30-44,15- 29, and <15 mL/min/1.73 m2) by both equations. Compared with the MDRD Study equation, 24.4% and 0.6% of participants from general population cohorts were reclassified to a higher and lower estimated GFR category, respectively, by the CKD-EPI equation, and the prevalence of CKD stages 3 to 5 (estimated GFR
[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Anyone in the world

For a number of years some nephrologists have advocated online hemodiafiltration (HDF) as the therapy of choice in chronic dialysis patients. The theory being that enhanced convective removal of middle molecules allows the removal of uraemic toxins that contribute to the inflammatory state in haemodialysis and promote cardiovascular disease.  A number of observational studies have shown a survival benefit of HDF.

This months JASN publishes the results of the Dutch CONTRAST RCT that compared HDF to low flux dialysis in 714 RRT patients. Ultra pure water was used in both arms of the study. There was good separation of beta two micro globulin between the two groups indicating good convective removal with HDF. It appears to be a very  well conducted study.
The results are disappointing. There was no difference in the primary endpoint of death after three years of therapy. Nor was there any difference in fatal and non-fatal cardiovascular outcomes between the two groups. In a post-hoc analysis of patients who achieved a delivered convective volume of > 21.95litres there was an associated reduction in mortality. However as the authors clearly state this kind of post-hoc analysis does not support the use of HDF. Indeed it maybe those that achieved the higher convective volumes simply had better vascular access and few patients achieved these volumes.
What may explain the lack of effect of HDF... A number of explanations are possible including i) the beneficial effects of HDF in observational studies is due to the use of ultra pure water.. In this study the control groups also dialysed with ultra pure water.ii) "beneficial" mediators as well as uraemia toxins are removed by HDF iii) the follow up of 3 years is too short to realise any benefit iv) the HDF dose delivered was simply too low... In fact few patients achieved the intended convective volume of 24 litres v) the wrong end-point was chosen - perhaps intradialtic hypotension would be a more appropriate endpoint or a quality of life measure. vi) the treatment is no more effective than modern-day conventional HD!!
The latter may well be true and once the Turkish HDF study and others are published in the next year or so we will have the answer for sure. ... Of course HDF was non-inferior to standard dialysis so if cost is not an issue the it would be perfectly reasonable to use HDF - though the environmental cost may be significantly higher with HDF.
For now as is so often the case expert opinion supported by observational data once again has been found wanting...
 
Reference

http://jasn.asnjournals.org/content/early/2012/04/26/ASN.2011121140.abstract?papetoc

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Arif Khwaja
by Arif Khwaja - Monday, 23 April 2012, 6:34 PM
Anyone in the world

The recently published KDIGO guidelines provide a welcome and timely synthesis of the evidence base to support the management of AKI.The guidelines focused on 4 key domains: i) AKI Definition, ii) Prevention and Treatment of AKI, iii) Contrast-induced AKI and iv) Dialysis Interventions for the treatment of AKI.

The full summary of clinical practice statements is available at www.kdigo.org but a key recommendation is that clinicians effectively adopt the previously published AKI Network definition and staging  of AKI as follows:

  • An increase in serum creatinine by ³0.3mg/dl (³26.5mmol/l) within 48 hours or an
  • Increase in serum creatinine to ³1.5 times baseline within the previous seven days or
  • Urine volume £0.5ml/kg/hours for 6 hours.

 

Stage

Serum Creatinine

Urine Output

1

1.5-1.9 times baseline

OR

³0.3mg/dl (³26.5mmol/l) increase

<0.5ml/kg/hour for 6-12 hours

2

2.0-2.9 times baseline

<0.5ml/kg/hour for ³12 hours

3

3 times baseline

OR

³4.0 mg/dl (³353.6mmol/l) increase

OR initiation of renal replacement therapy

OR in patients less than 18 years a decrease in eGFR <35mls/minute/1.73m2

<0.3ml/kg/hour for ³24 hours OR

Anuria ³12 hours

 

The rationale for the staging system comes from a plethora of studies showing that the risk of death and renal replacement therapy (RRT) increases with each stage. Furthermore evidence suggesting patients in whom AKI resolves are at increased risk of death, CKD and cardiovascular disease has prompted KDIGO to make an ungraded suggestion that all those with resolved AKI should be considered to be at increased risk of CKD and be managed as per the KDOQI guidelines for individuals at risk of CKD.  However whilst there is no doubt that standardising the definition and staging of AKI provides a clear framework for studying outcomes in both epidemiological and clinical research the bedside utility of the proposed classification and staging maybe be questioned by many 'real-world' practicing clinicians. In particular it is not clear how staging will alter immediate management and outcomes. As with the CKD classification sustem the danger is that an epidemiological tool gets imposed onto clinical practice without any evidence that the classification system per se can improve outcomes or can lead to specific interventions. Furthermore the evidence that monitoring people  with resolved AKI as being at risk of CKD can i) prevent the onset of CKD or ii) is cost-effective is not presented.

Many other recommendations are made most of which are eminently sensible/obvious (e.g. use vasopressors for those with shock) but a few caught my eye:

  1. recommended use of oral NAC in contrast nephropathy – despite v weak evidence, plus the fact that NAC has poor oral bioavailability and increases tubular secretion of creatinine
     
  2. that regional citrate be the anticoagulant of choice in CRRT unless the patient is shocked/has liver disease – of course these are the very patients that are most likely to be on CRRT and given the complexities of citrate use it’s a shame no practical protocol was provided…
     
  3. that dialysis dose be measured in AKI either by using Kt/V ( almost certainly meaningless in a catabolic patient with AKI) or the effluent flow rate in CRRT – again no evidence from the Veterans and Australasian studies that dose of RRT in AKI has any impact on survival.
     
  4. support the use of CRRT in haemodynamically unstable patients whilst this is routine practice in many places the meta-analyses indicate this again has no impact on patient outcomes… and as well all know CRRT is rarely continuous.
     
  5. The use of insulin to maintain glycaemic control despite the risks of hypoglycaemia.

 

As with previous KDIGO reviews, the clear message is that there is a lack of evidence (particularly, well-designed interventional outcome studies) to underpin much of our everyday clinical practice. Indeed only 14.8% of the recommendations were graded '1A' whilst 63.9% of the recommendations were level 2. Thus these are not prescriptive guidelines but provided nuanced guidance for the clinician. The KDIGO co-chairs bullishly argue that recommendations should be made even when the evidence is weak as clinicians often ask "what do the experts do?" – this may be true but as history tells us the track record of expert opinion in the absence of evidence can often be deeply flawed.

The recommendation that an empirical definition and staging system be used in the management of AKI will arouse controversy and debate. As yet no data has been presented to show that these tools in themselves can improve outcomes in AKI and many clinicians will be wary about implementing what is essentially a research-based diagnostic and staging system into the clinical arena in the absence of such data – as was the case in CKD........

References

  1. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW: Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 2005;16:3365-3370.
  2. Clinical practice Guidelines for Acute Kidney Injury 2012. http://www.kdigo.org/clinical_practice_guidelines/AKI.php
  3. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A: Acute kidney injury network: Report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007;11:R31.
  4. Rabindranath K, Adams J, Macleod AM, Muirhead N: Intermittent versus continuous renal replacement therapy for acute renal failure in adults. Cochrane Database Syst Rev 2007:CD003773.
  5. Palevsky PM, Zhang JH, O'Connor TZ, Chertow GM, Crowley ST, Choudhury D, Finkel K, Kellum JA, Paganini E, Schein RM, Smith MW, Swanson KM, Thompson BT, Vijayan A, Watnick S, Star RA, Peduzzi P: Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 2008;359:7-20.
  6. lomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, McArthur C, McGuinness S, Myburgh J, Norton R, Scheinkestel C, Su S: Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med 2009;361:1627-1638.
[ Modified: Thursday, 1 January 1970, 1:00 AM ]