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Picture of Arif Khwaja
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

35% of transplanted adolescent transferred to adult nephrology unit reject their kidneys within 36 months....non compliance, non-adherence, non-concordance....Transition from pediatric to adult units is a major issue with regard to transplanted adolescent...transition multi-disciplinary approach and transition clinics are key components of a smooth transition.

 

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Meguid El Nahas
by Meguid El Nahas - Wednesday, 9 May 2012, 8:58 AM
Anyone in the world

DAY2 MASTER CLASS IN KHARTOUM:

CRITICAL APPRAISAL SESSION 

MAJOR HIGHLIGHT:

DO NOT EQUATE eGFR with mGFR!!!!!!

eGFR is subject to all the confounders of changes in serum creatinine:
Diet, metabolism, GFR and Tubular secretion

MEASURED GFR IS THE ONLY MARKER OF CHANGES IN GFR AND SHOULD BE USED IN CLINICAL TRIALS TO ASSESS CKD PROGRESSION!!!!

The question is:

WHY ARE NEPHROLOGISTS RELUCTANT TO MEASURE TRUE GFR IN CLINICAL TRIALS OF CKD PROGRESSION????

Is it convenience?

Is it pressure from Sponsors to fudge the real result?

Is it just ignorance that eGFR is an inadequate marker of true GFR?

I am bewildered....!!!!!

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Meguid El Nahas
by Meguid El Nahas - Wednesday, 9 May 2012, 4:12 AM
Anyone in the world

 

Proposed KDIGO staging of AKI

 

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

4.0 mg/dl (353.6mmol/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 12 hours

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Meguid El Nahas
by Meguid El Nahas - Wednesday, 9 May 2012, 3:47 AM
Anyone in the world

 

The American College of Rheumatology (ACR) has issued the first-ever guidelines for the screening, treatment, and management of lupus nephritis (LN). 
The guidelines are published in the June issue of Arthritis Care & Research
They were initially presented at ACR 2011.

Clinical conclusions
1- the 2012 guidelines are a significant advance because they address total therapy of LN, not just short-term treatment.

2- At this time, more than half of patients with systemic lupus erythematosus develop LN within 10 years and up to 30% of those cases progress to end-stage renal disease within 15 years of diagnosis.

3- The ACR panel, which developed the guidelines, recommends renal biopsy for all patients with clinical evidence of active, previously untreated LN. 

4- They do not recommend immunosuppressive treatment for patients with class 1 (minimal mesangial immune deposits on immunofluorescence with normal light microscopy) or class 2 (mesangial hypercellularity or matrix expansion on light microscopy with immune deposits confined to mesangium) renal damage. However, they do recommend aggressive treatment for patients with class 3 or higher renal pathology.

5- Mycophenolate and cyclophosphamide plus glucocorticoids are the mainstay of treatments for induction of improvement in [LN] of serious histologic classes (except if patient is pregnant), and azathioprine [AZA] and mycophenolate are both acceptable for maintenance of improvement (except in pregnancy). Recommending pulse steroids in treatment of class 3 and 4 active proliferative disease. Rituximab or calcineurin inhibitors should be considered if standard treatments fail."

6- An algorithm for management of pregnant woman with active [LN] is included in the guidelines.The guidelines note that women should be off MMF or CYC for at least 6 weeks prior to conception.

7- Renal failure may not come quite as quickly in pure membraneous nephritis, but the long-term prognosis is not great."

8- Studies have shown that MMF is more effective than CYC in African-American woman, and this is highlighted in these guidelines."

9- Consensus on the use of calcineurin inhibitors: The agents have potential renal toxicity, but have been shown to be effective in membranous lupus during the short term.

10- The role of rituximab in LN also remains somewhat uncertain. Rituximab is listed as a relatively late intervention.

11- Recommendation to perform renal biopsies whenever the therapeutic decisions would be altered by knowing 1) histologic classification and 2) level of activity and of chronicity on the biopsy.

12- There needs to be more use of remission-inducing agents at proper doses for proper duration, transition from induction to maintenance therapies without a gap if possible, prevention of adverse effects when possible.

13- The guidelines do not address the questions of how long to treat during maintenance therapy and when begin to taper MMF because there are few data on the topic.

14- With regard to the increasing incidence of end-stage renal disease associated with LN, there are fibrotic processes plus other reasons such as hypertension that contribute to atherosclerosis. Many patients progress to renal failure not due to active nephritis, but due to the combined effects of irreversible damage accrued over many years.

Arthritis Care Res. 2012;64:797-808.
 
[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Meguid El Nahas
by Meguid El Nahas - Thursday, 3 May 2012, 9:09 AM
Anyone in the world

 

Annals of Internal Medicine

Screening for, Monitoring, and Treatment of Chronic Kidney Disease Stages 1 to 3: A Systematic Review for the U.S. Preventive Services Task Force and for an American College of Physicians Clinical Practice Guideline

Howard A. Fink, MD, MPH; Areef Ishani, MD, MS; Brent C. Taylor, PhD, MPH; Nancy L. Greer, PhD; Roderick MacDonald, MS; Dominic Rossini, MD; Sameea Sadiq, MD; Srilakshmi Lankireddy, MD; Robert L. Kane, MD; and Timothy J. Wilt, MD, MPH 

This is a balanced systematic review of the literature relating to the impact of treatment including ACE inhibitors and ARBs on outcomes in CKD; ESRD and Mortality. The authors conclude that the evidence is in general fair but seldom strong and therefore current recommendations for screening and early treatment to prevent hard endpoints such as death or ESRD are weak.

They also reported that the evidence for strict BP control is weak.

They conclude that the role of screening or monitoring in improving outcomes is uncertain as hardly any study reviewed addressed that point. And that the evidence for benefit is strongest for ACE inhibitors and ARBs, and more specifically in patients with albuminuria combined with diabetes and cardiovascular disease. 

This manuscript should be read by all those interested in the management of CKD as it shows the limitations of available data and highlights the value of careful and systematic analysis.

Read the full article on OLA:

https://www.gkaonlineacademy.com/resources/library/cat_view/6-ckd

 

 

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

Inherited Kidney Diseases Workshop (IKDW), Cairo 2012

 

Inherited Kidney Diseases Workshop was held in Cairo on April 19-20, 2012 as an ERA-EDTA CME course and organized by the Egyptian Group for Orphan Renal Diseases (EGORD) in partnership with the Global Kidney Academy and in collaboration of the Egyptian Society of Pediatric Nephrology & Transplantation (ESPNT).

Why an Inherited Kidney Diseases Workshop in the region?

Basically because Patients afflicted with these diseases are not treated equally to those with more common illnesses presumably due to:

  1. Disease related factors since many of these diseases are complex and have genetic or metabolic causes, only few physicians are aware of it whereas the majority is unlikely to have the necessary experience to diagnose or to offer a treatment, hence the delay in diagnosis and therapy. Also, the small patient populations with phenotypic variability imply limited knowledge of natural course which is all too often difficult to define.
  2. Country/Region related factors as most of the regional countries are emerging countries with limited health expenditure, let alone their struggle with the common and endemic illnesses consuming most of an essentially constrained    health budget. Moreover, the striking rates of consanguineous marriages in the region with the increased likelihood of autosomal  recessive diseases.

Professor Meguid El Nahas gave an outstanding lecture "Genetics of Kidney Diseases" and highlighted the relevance of genetics of albuminuria, hematuria as well as decreased GFR and its decline in CKD.

Dr John Sayer (UK) gave a comprehensive overview on "Cystic kidney diseases: approach and genetic updates" highlighting the phenotypic variability and genetic heterogeneity of most of these diseases.

Professor Elena Levtchnko (Belgium) gave a comprehensive review on cystinosis.  She particularly discussed the practical tools for diagnosis and treatment which should preferably start in the first year of life.

Professor Moin Saleem (UK) discussed the systematic approach of SRNS and the algorithm for genetic mutational analysis. He also came across the hereditary podocytopathies highlighting the variable clinical phenotypes and the principle genes involved in the genetic variants of SRNS.

Professor Constantinos Deltas (Cyprus) discussed the genetics of familial hematuria with the cypriotic experience showing that TBMN is not as always benign as previously thought. C3 glomerulonephritis CFHR 5 Nephropathy, with broad phenotypic variability is common in Cyprus. Interestingly all patients had mutations in COL4A3/COL4A4 genes as founder mutations.

IKDW managed to blow the whistle paving the way for more concrete actions to be taken to further promote awareness of inherited kidney diseases among the medical community in the region. The diagnostic and therapeutic hurdles should not be viewed as insurmountable since there is compelling medical and ethical reasons to address the needs of these patients.

The IKDW lectures will be available on OLA soon!

 

 

 
 
 

 

 

 

 

 

 

 

[ 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 ]