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Picture of Meguid El Nahas
by Meguid El Nahas - Monday, 13 June 2016, 11:09 AM
Anyone in the world

Are modern days nephrologists becoming Don Quixotes fighting delusionary fights...?!

Don Quixote in the novel of Cervantes looses his mind after so much reading....and goes on a self assigned mission to fight illusionary enemies...including windmills....

Have modern days nephrologists, also lost their sense falling prey to the brainwashing unslaught of publications on CKD definition, classification, detection and prevalence...leading them to beleive that CKD, the ultimate foe is everywhere...beleiving that up to 1 in 2 of living humans will fall to that disease...and its growing "epidemic"... are they also off to fight a delusionary battle "against CKD"...

When will nephrologists stop referring to CKD (Chronic Kidney Disease) as a "disease" ?

when in reality we use functional criteria that imply a reduction in function rather than a "disease" entity...in fact, there isnt an epidemic of "CKD"... there is just a deliberate misrepresentation of what is generically termed CKD...

And, how can we label all those with a reduced kidney function as suffering from the same "Disease" when in reality they suffer from a number of underlying causes or diseases...ranging from glomerulonephritis, diabetes, hypertension, vasculitis, interstitial nephritis or hereditart kidney diseases including cystic malformations... not to mention a majority labelled as "diseased' when in reality all they suffer from is the "disease" of old age...and the associated reduction in the function of most organs including the kidneys...

Worse still, how can we have a classification that pretends a staging and continuity from CKD1 to 5...when those suffering from CKD 1 to 3a...mostly older people, seldom progress to CKD 4 or 5...whilst those who end up in CKD4 and5 often present acutely with severe renal dysfunction as in glomerulobnephritis, vasculitis, and acute kidney injury... and never go through stages 1 and 2...

Consequently, research shows that early detection to prevent CKD progression is a myth and an illusion...you would need to detect and unecessarily treat thousands for years to prevent 1 ESRD...as we are not detection and treating those who progress to ESRD...

http://www.ncbi.nlm.nih.gov/pubmed/24424348

Proteinuria changes the detection-prevention risk v benefit ratio, but then proteinuria identifies those with true disease compared to those who are labelled as "diseased"... those with glomerulonephritis, diabetic nephropathy or advanced hypertensive nephrosclerosis... compared to the community elders labelled with a "disease" they dont have...

Is it therefore time to drop this generic and misleading term "CKD"...or leave it to epidemiologists to collect and compile meaningless information on population they never saw or truly investigated...for the sake of publishing repetitive papers on the prevalence of "CKD" in communities... leave it to the Don Quixotes of Nephrology...

and revert to identify patients by their true renal abnormalities: hematuria, proteinuria, glomerulonephritis, vasculitis, lupus nephritis, diabetic nephropathy, etc...and tailor approach and treatment accordingly.

This would allow for an individualisation of management approach instead of the one size fits all current generic "CKD" prevention, diagnosis and management approach...

http://www.ncbi.nlm.nih.gov/pubmed/22189037

It is often difficult to rail against the wind...even when the wind blows in the wrong direction...but then if we dont, we get also blown off in the wrong direction...and continue for the next decades to chase and treat a "disease" that doesnt exist...Don Quixote's style...fighting delusionary windmills...those of modern day "CKD"...

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Meguid El Nahas
by Meguid El Nahas - Tuesday, 24 May 2016, 6:32 AM
Anyone in the world

An growing controversy is buidling around the use of steroids in IgA Nephropathy.

Pozzi and Locatelli showed that high dose steroids slow the progression of the nephropathy. http://www.ncbi.nlm.nih.gov/pubmed/10093981

The large STOPIGAN study showed no benefit of immunosuppresion; steroids and/or cyclophosphamide. http://www.ncbi.nlm.nih.gov/pubmed/?term=STOPIGAN%2C+NEJM

Now a Chinese study (TESTING) reported at the congress of the ERA-EDTA suggests a benefit of treatment with methylprednisolone given orally at doses of 0.6-0.8mg/kg/day for 2 months then tapering over 6-8 months; proteinuria reduction and GFR slowed down...

All these studies rely on creatinine derived measurements of GFR and NEVER a MEASURED GFR....???!!!!

They seem to overlook the effect of prolonged corticotherapy on muscle mass potentially contributing to a fall in serum creatinine and consequently an apparent improvement in estimated GFR...an unbeleivable AMNESIA of the effects of steroid therapy on the muscle and serum creatinine?!

Finally, why should immunosuppression or steroids benefit a nephropathy with little or no inflammtory reaction; mesangial proliferation is seldom associated with a glomerular inflammtory reaction...

As to the notion of IgAN being an auto-immune disease with anti-IgA autoantibodies...well, this has weak support and such auto-antobody is seldom mentioned or measured in RCTs pertaining to impact on it...?!

IgAN is a metabolic abnormality that leads to abnormal traffic and or overproduction of an aberrantly glycosylated IgA1 characterized by galactose deficiency of some hinge-region O-linked glycans. This IgA1 subequently sticks ro is uptaked by the mesangium and leads to glomerular damage with hematuria, proteinuria and progressive CKD in a minority: http://www.ncbi.nlm.nih.gov/pubmed/27189177

Therapies based on the manipulation of the abnormal glycosylation of IgA1 would make better sense that this nephrological obssession with immunosuppression...

Selective depletion of Gd-IgA1-producing cells via glycan engineering may be a more logical approach...vindicating 30 years of research in the field, rather than ignoring that research and hanging one's hat on a doubtful concept of clinical relevance namely auto-immunity...

http://www.ncbi.nlm.nih.gov/pubmed/25604055

STOP TESTING FLAWED HYPOTHESIS AND BUILD ON RESEARCH FINDINGS TO COME UP WITH PLAUSIBLE ALTERNATIVE THERAPIES FOR IgA NEPHROPATHY!

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Meguid El Nahas
by Meguid El Nahas - Tuesday, 24 May 2016, 6:32 AM
Anyone in the world

An growing controversy is buidling around the use of steroids in IgA Nephropathy.

Pozzi and Locatelli showed that high dose steroids slow the progression of the nephropathy. http://www.ncbi.nlm.nih.gov/pubmed/10093981

The large STOPIGAN study showed no benefit of immunosuppresion; steroids and/or cyclophosphamide. http://www.ncbi.nlm.nih.gov/pubmed/?term=STOPIGAN%2C+NEJM

Now a Chinese study (TESTING) reported at the congress of the ERA-EDTA suggests a benefit of treatment with methylprednisolone given orally at doses of 0.6-0.8mg/kg/day for 2 months then tapering over 6-8 months; proteinuria reduction and GFR slowed down...

All these studies rely on creatinine derived measurements of GFR and NEVER a MEASURED GFR....???!!!!

They seem to overlook the effect of prolonged corticotherapy on muscle mass potentially contributing to a fall in serum creatinine and consequently an apparent improvement in estimated GFR...an unbeleivable AMNESIA of the effects of steroid therapy on the muscle and serum creatinine?!

Finally, why should immunosuppression or steroids benefit a nephropathy with little or no inflammtory reaction; mesangial proliferation is seldom associated with a glomerular inflammtory reaction...

As to the notion of IgAN being an auto-immune disease with anti-IgA autoantibodies...well, this has weak support and such auto-antobody is seldom mentioned or measured in RCTs pertaining to impact on it...?!

IgAN is a metabolic abnormality that leads to abnormal traffic and or overproduction of an aberrantly glycosylated IgA1 characterized by galactose deficiency of some hinge-region O-linked glycans. This IgA1 subequently sticks ro is uptaked by the mesangium and leads to glomerular damage with hematuria, proteinuria and progressive CKD in a minority: http://www.ncbi.nlm.nih.gov/pubmed/27189177

Therapies based on the manipulation of the abnormal glycosylation of IgA1 would make better sense that this nephrological obssession with immunosuppression...

Selective depletion of Gd-IgA1-producing cells via glycan engineering may be a more logical approach...vindicating 30 years of research in the field, rather than ignoring that research and hanging one's hat on a doubtful concept of clinical relevance namley auto-immunity...

http://www.ncbi.nlm.nih.gov/pubmed/25604055

 

 

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Meguid El Nahas
by Meguid El Nahas - Tuesday, 24 May 2016, 6:32 AM
Anyone in the world

An growing controversy is buidling around the use of steroids in IgA Nephropathy.

Pozzi and Locatelli showed that high dose steroids slow the progression of the nephropathy. http://www.ncbi.nlm.nih.gov/pubmed/10093981

The large STOPIGAN study showed no benefit of immunosuppresion; steroids and/or cyclophosphamide. http://www.ncbi.nlm.nih.gov/pubmed/?term=STOPIGAN%2C+NEJM

Now a Chinese study (TESTING) reported at the congress of the ERA-EDTA suggests a benefit of treatment with methylprednisolone given orally at doses of 0.6-0.8mg/kg/day for 2 months then tapering over 6-8 months; proteinuria reduction and GFR slowed down...

All these studies rely on creatinine derived measurements of GFR and NEVER a MEASURED GFR....???!!!!

They seem to overlook the effect of prolonged corticotherapy on muscle mass potentially contributing to a fall in serum creatinine and consequently an apparent improvement in estimated GFR...an unbeleivable AMNESIA of the effects of steroid therapy on the muscle and serum creatinine?!

Finally, why should immunosuppression or steroids benefit a nephropathy with little or no inflammtory reaction; mesangial proliferation is seldom associated with a glomerular inflammtory reaction...

As to the notion of IgAN being an auto-immune disease with anti-IgA autoantibodies...well, this has weak support and such auto-antobody is seldom mentioned or measured in RCTs pertaining to impact on it...?!

IgAN is a metabolic abnormality that leads to abnormal traffic and or overproduction of an aberrantly glycosylated IgA1 characterized by galactose deficiency of some hinge-region O-linked glycans. This IgA1 subequently sticks ro is uptaked by the mesangium and leads to glomerular damage with hematuria, proteinuria and progressive CKD in a minority: http://www.ncbi.nlm.nih.gov/pubmed/27189177

Therapies based on the manipulation of the abnormal glycosylation of IgA1 would make better sense that this nephrological obssession with immunosuppression...

Selective depletion of Gd-IgA1-producing cells via glycan engineering may be a more logical approach...vindicating 30 years of research in the field, rather than ignoring that research and hanging one's hat on a doubtful concept of clinical relevance namley auto-immunity...

http://www.ncbi.nlm.nih.gov/pubmed/25604055

 

 

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Meguid El Nahas
by Meguid El Nahas - Monday, 9 May 2016, 6:44 AM
Anyone in the world
J Am Soc Nephrol. 2016 Apr 14. pii: ASN.2015121377. [Epub ahead of print]

Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD.

Abstract

The association between proton pump inhibitors (PPI) use and risk of acute interstitial nephritis has been described. However, whether exposure toPPI associates with incident CKDCKD progression, or ESRD is not known. We used Department of Veterans Affairs national databases to build a primary cohort of new users of PPI (n=173,321) and new users of histamine H2-receptor antagonists (H2blockers;n=20,270) and followed these patients over 5 years to ascertain renal outcomes. In adjusted Cox survival models, the PPI group, compared with the H2blockers group, had an increased risk of incident eGFR<60 ml/min per 1.73 m2and of incident CKD (hazard ratio [HR], 1.22; 95% confidence interval [95% CI], 1.18 to 1.26; and HR, 1.28; 95% CI, 1.23 to 1.34, respectively). Patients treated with PPI also had a significantly elevated risk of doubling of serum creatinine level (HR, 1.53; 95% CI, 1.42 to 1.65), of eGFR decline >30% (HR, 1.32; 95% CI, 1.28 to 1.37), and of ESRD (HR, 1.96; 95% CI, 1.21 to 3.18). Furthermore, we detected a graded association between duration of PPI exposure and risk of renal outcomes among those exposed to PPI for 31-90, 91-180, 181-360, and 361-720 days compared with those exposed for ≤30 days. Examination of risk of renal outcomes in 1:1 propensity score-matched cohorts of patients taking H2blockers versus patients taking PPI and patients taking PPI versus controls yielded consistent results. Our results suggest that PPI exposure associates with increased risk of incident CKDCKD progression, and ESRD.

Comments:

PPI have been over prescribed and over used in the last 2 decades...

Whilst we all came across many cases of AIN due to PPIs, new concern about incident and progressive CKD linked to PPIs is being raised (see above).

This is difficult to ascertain in terms of causality as these associations are often biased and confounded by indication...like analgesics and CKD...those with underlying medical problems, comorbidities, consume them...then of course those same individuals are at increased risk of CKD...and ESRD! Also, those with ischemic heart disease and atherosclerotic renal ischemia are often given anti-platelet agents and...PPIs prophylactically...

Of interest, a similar association has been put forward between PPIs and CVD, adverse cardiac events,

http://www.ncbi.nlm.nih.gov/pubmed/24386430

...the same logic of "confounded by indication" may underly such association; those with CVD are often are on anti-platelt agents and...PPIs prophylactically?!

However, the use of PPIs in renal transplant recipients, in association with steroids, has been linked to osteoporosis and fractures... in fact, there are 34 studies in almost 2 million participants that have reported an association between PPIs and risk of fracture...http://www.ncbi.nlm.nih.gov/pubmed/25209137

...here again, this association doesnt prove causality as older patients are prescribed PPIs more than younger individuals...and the former also tend to be more prone to falls and fractures...

PPIs are more expensive than H2-blockers and tend to be for life...with rebound acidity making rapid withdrawal quite difficult...

So, should we still prescribe them...with doubts over their association with CVD, MBD, CKD progression and ESRD... or is it time to ditch them?!

Share your views on OLA.

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

MAREMAR STUDY: CKD CLASSIFICATION, TIME TO RE-THINK?

 

https://www.researchgate.net/publication/297892002_Maremar_prevalence_of_chronic_kidney_disease_how_to_avoid_over-diagnosis_and_under-diagnosis

 

The MAREMAR study of CKD diagnosis and detection in Morocco is now published. This long awaited publication is an example of good quality epidemiology aimed at defining the prevalence of true CKD in Morocco.

A stratified, randomized, representative
 sample of 10,524 participants was studied. Weight, height, blood pressure, proteinuria (dipstick), plasma creatinine, estimated glomerular filtration rate, and fasting glycemia were measured.

Also, testing was repeated within 2 weeks and eGFR reassessed at 3, 6 and 12 months.

More interestingly, the authors compared “CKD” as defined by the cut off definition of KDOQI/KDIGO of 60ml/min to a more age-sensitive and more sensible classification based on the deviation from the percentile range for age; less than 3rd percentile.

This study highlights major points:

  1. Upon re-testing (Dipstix testing and/or eGFR) at 3 months, as recommended by KDOQI CKD definition and classification, 25-30% were found to be false positive and no longer classified as suffering from CKD; a sobering lesson for all those “epidemiological” reports of CKD prevalence that test the population ONCE and claim to define prevalence rates of CKD…RE TESTING IS A MUST TO DEFINE CKD.
  2. More interestingly, when CKD was defined as eGFR levels below the 3rd percentile for the individual's age-sex matched population, the study highlighted the serious shortcomings of the current cut off of 60ml/min/1.73m2 that is currently applied to all ages and genders: The MAREMAR showed that for younger individuals the current classification based on the 60ml/min arbitrary cut-off point, significantly UNDERDIAGNOSED CKD, whilst in older individuals over the age of 60 years, the current cut off significantly OVERDIAGNOSED CKD, mainly in those previously classified as CKD3A.
  3. When a study such as MAREMAR, that is well conducted with expertly validated methodologies, is undertaken, the prevalence of CKD (eGFR <60) falls to as low as 1.6% of the general population, a value well below the misleading prevalences reported in other poorly conducted studies claiming ~5-10%. Also, proteinuria is detected consistently in as few as 1.3%, again a prevalence well below the values previously branded upon single testing for ~7-10%.

MAREMAR is a landmark publication and a must read for all those aspiring to do epidemiological surveys on CKD in their populations. It shows that well conducted epidemiological studies can be undertaken. It also shows how they should be conducted with careful validation of methodologies and interpretation of results.

MAREMAR shows that CKD classification based on a SINGLE 60ML/MIN CUT OFF POINT FOR ALL AGES IS NOT FIT FOR PURPOSE; age and gender sensitive classification based on deviations from age and gender specific population norms (percentiles between 3-97th) is the way forward. This can be easily automated and reported. It will free millions worldwide from the misleading label of “CKD” based on an artificial and arbitrary cut off point.

IT IS HIGH TIME WE, AS NEPHROLOGISTS, RE-THINK THE CKD DEFINITION.

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Meguid El Nahas
by Meguid El Nahas - Sunday, 24 April 2016, 9:04 PM
Anyone in the world

http://www.ncbi.nlm.nih.gov/pubmed/27061677

The latest analysis by the Non-Communicable Disease worldwide collaboration gives an intriguing picture of the prevalence of Diabetes Mellitus (DM) worldwide.

Age-standardised prevalence, shows:

NO increase in prevalence of DM from 1980 to 2014 in Europe!

NO overall increase in Africa

NO increase in Central and Latin America

NO increase in Japan

Significant increase in the Middle East and North Africa

Significant increase in Central Asia

So how can we explain the absence of increase in the prevalence of DM in Europe, Central and Latin America or Japan where the prevalence of OBESITY has considerably increased, along with other regions of the world?!

http://www.ncbi.nlm.nih.gov/pubmed/25391910

Does this mean that the “epidemic” of DM is only due in Europe, Latin America, Japan and parts of Asia to the ageing of the populations and not Obesity….?!

On the other hand, genetic factors may explain the rise in the prevalence of DM in the Middle East, North Africa as well as in Polynesia? In these regions, DM (mainly T2DM) may be a two hit phenomenon where genetic predisposition combined with environmental factors, such as diet and obesity, may be required for the phenotypic expression of the disease.

Is the dogma linking DM and Obesity a geographical phenomenon that doesn't apply to Europe?

Is the increase prevalence of DM in Europe merely the reflection of the ageing of the population?

Is it time to rethink the “association” linking obesity to Diabetes mellitus?

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Meguid El Nahas
by Meguid El Nahas - Wednesday, 13 April 2016, 6:00 AM
Anyone in the world

http://www.ncbi.nlm.nih.gov/pubmed/27057075

This excellent paper proposes an age-sensitive CKD classification:

<40 years: CKD threshold = 75 ml/min

40-65years: CKD threshold = 60 ml/min

>65 years: CKD threshold =45 ml/min

this in the absence of other corroborating signs of kidney damage.

It is high time we move away from one classification and one CKD threshold (60 ml/min) for all...

It is also high time to appreciate that CKD is not a single disease...with a single definition...and a single classification...

A GFR of 60 ml/min in a 25 year old patient with glomerulonephritis is a very different proposition than a GFR of 60 in a 75 year old with longstanding hypertension...

GFR thresholds are therefore meaningless in isolation as they serve no medical or clinical purpose...in fact, they have not changed clinical practice of referred patients with kidney damage...they only generated interest and research by "epidemiologists" that created a "Disease" to generate interest in a small subspecialty that looked for a way to enhance its significance by claiming that 1 in 4 of the general population, 1 in 3, 1 in 2 in a lifetime, is or will...suffer from CKD...

In my opinion, it is high time to drop CKD thresholds all together and define referred kidney damage patients by their medical condition, as to the general population define those affected by their underlying condition (hypertension, diabetes) and detail the degree and nature of their kidney damage.

 

 

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

This is an interesting blog by Dr Ben Goldacre who basically is arguing that academic journals are effectively not a 'fit for purpose' arena to publish results of clinical trials.
 
He also makes the point that the usually impossible to get Clinical Study Reports are much more helpful to evaluate the benefits and harms of an intervention than the published paper.
 

 

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

This is an interesting, (though long) blog by Dr Ben Goldacre who basically is arguing that academic journals are effectively not a 'fit for purpose' arena to publish results of clinical trials.
 
He also makes the point that the usually impossible to get Clinical Study Reports are much more helpful to evaluate the benefits and harms of an intervention than the published paper.
 
[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
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