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Anyone in the world
N Engl J Med. 2017 Jun 12. doi: 10.1056/NEJMoa1611925. [Epub ahead of print]

Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes.

 The Myth:

The administration of SGLT2 (Sodium-Glucose coTransporter2) inhibitors improve cardiovascular outcomes in T2DM at high CVD risk. in CANVAS 2 such studeis were combined and concluded that the composite primary outcome of  death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke was improved by the administration of these agents. Renal outcomes also positive. Not the first time such a claim has been made. A beneficial effect that is claimed to be a class effect of all SGLT2 inhibitors.

Comments:

Once more the Pharmaceutical industry takes gulible doctors who cannot critically read a publication for a marketing ride...

As what is evident from this study is:

1. that acting as potent diuretics these drugs have an effect only on heart failure/reduction of oedema and related hospitalisation.

2. These agents have no effect on MACEs such as Myocardial infraction or strokes...

3. This is where "Composite endpoints" make them sound beneficial; whilst they are ONLY to fluid retention/heart failuire as they are potent diuretics...

4. These beneficial effects are most likely to be directly due to a significant reduction in both systolic and diastolic blood pressure; a reduction o BP of 3-4mmHg has been known for half a century to be protective against the progression of CKD in people with diabetes mellitus (Mogensen, 1976...). https://www.ncbi.nlm.nih.gov/pubmed/85044

5. THESE STUDIES DID NOT, INTENTIONALLY, COMPARE THESE SGLT2i WITH DIURETICS SUCH AS CHLORTHALIDONE OR INDAPAMIDE ALSO KNOWN TO REDUCE CVD IN DM: WHY? Because they would not have shown any therapeutic advantage...

So once more the PHARMACEUTICAL INDUSTRY wants doctors to beleive that new agents, that are potentially dangerous (more limbs amputations and fractures [likely to be due to hypotensive falls], AKI), are better than the best available therapy of diuretics...that is cheaper and as effective!

In fact, when it comes to reduction of MACEs (Major Adverse Cardiovascular Events) in people with T1 and T2DM, diuretics are as good as any other anti-hyeprtensive agent....Beta blockers, ACE inhibitors, CCB, etc...what matters in BP reduction as in this study...

https://www.ncbi.nlm.nih.gov/pubmed/27870655

IT IS HIGH TIME DOCTORS WAKE UP TO THE FACT THAT THEY ARE SOLD DANGEROUS AND COSTLY NEW AGENTS UNDER FALSE PRETENSE!

 

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Anyone in the world
Prof David Goldsmith
Nephrol Dial Transplant (2017): 1–11

doi: 10.1093/ndt/gfx072

Effect of renin–angiotensin–aldosterone system blockade in
adults with diabetes mellitus and advanced chronic kidney
disease not on dialysis: a systematic review and meta-analysis

Ionut Nistor, Johan De Sutter, Christiane Drechsler, David Goldsmith,Maria Jose Soler, Charlie Tomson, Andrzej Wiecek, Mihaela-Dora Donciu, Davide Bolignano, Wim van Biesen and Adrian Covic

Correspondence and offprint requests to: Wim Van Biesen; E-mail: Wim.VanBiesen@UGent.be

ABSTRACT
The presumed superiority of renin–angiotensin–aldosterone
system (RAAS)-blocking agents over other antihypertensive
agents in patients with diabetes to delay development of end-stage kidney disease (ESKD) has recently been challenged. In addition, there is ongoing uncertainty whether RAAS-blocking agents reduce mortality and/or delay ESKD in patients with diabetes and chronic kidney disease (CKD) stages 3–5. In this subgroup, there might be an expedited need for renal replacement therapy (RRT) when RAAS-blocking agents are used.

We conducted a meta-analysis of randomized controlled trials (RCTs) of at least 6-months duration in adult patients with diabetes who also have non-dialysis CKD stages 3–5. RCTs comparing single RAAS-blocking agents to placebo or alternative antihypertensive agents were included. Outcomes of interest were all-cause mortality, cardiovascular morbidity, progression of renal function, ESKD and adverse events. A total of nine trials (n=9797 participants with CKD stages 3–5) fit our inclusion criteria. There was no difference between the RAAS group and control group regarding all-cause mortality {relative risk [RR] 0.97 [95% confidence interval (CI) 0.85–1.10]}, cardiovascular mortality [RR 1.03 (95% CI 0.75–1.41)] and adverse events [RR1.05 (95% CI 0.89–1.25)].

There was a trend for a favourable effect for non-fatal cardiovascular events [RR0.90 (95% CI 0.81–1.00)] and a lower risk of the composite endpoint need for RRT/doubling of serum creatinine [RR0.81 (95% CI 0.70–0.92)] in the RAAS-blocking agents group versus the control group.

We found evidence that, in patients with diabetes mellitus and CKD stages 3–5, treatment with RAAS-blocking agents did not result in a clear survival advantage. The effect on renal outcomes did depend on the selected outcome measure.

COMMENTS

Another meta-analysis showing NO added advantage of RAAS Blockade over "other agents", in terms of cardioprotection.

As to renoprotection,

when will nephrologists learn that RAAS blockade impacts on tubular handling of creatinine and that creatinine/creatinine clearance related measured outcomes are confounded when these agents are used to assess CKD progression: 

https://www.ncbi.nlm.nih.gov/pubmed/12753302

The nephrology world has been obssessed with these agents since the early 80s...time to put this myth to rest...

RAAS blockers do not offer advantages over and above good BP control, and RCTs that say otherwise are seriously flawed as shown in a thorough critical appraisal of these trials undertook a few years ago:

http://www.springer.com/gp/book/9783319102917

 

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Meguid El Nahas
by Meguid El Nahas - Monday, 26 June 2017, 8:23 PM
Anyone in the world

https://www.thetimes.co.uk/article/professor-marcel-levi-dying-should-shun-treatment-and-take-final-holiday-pvsbkv0wj?shareToken=79a3e1f73a909362cfe132ca0b22a9ae

Professor Marcel Levi: Dying should shun treatment and take final holiday...

Patients who are dying should be allowed to go on a final holiday rather than be subjected to gruelling treatment, according to the boss of one of Britain’s largest NHS trusts.

Professor Marcel Levi, a practising doctor and chief executive of University College London Hospitals, said the NHS is wasting time and money treating dying patients at the end of their lives.

He said: “I often think, ‘You would be better going on holiday with your family and you may have a little shorter but a lot better end of your life.’”

Levi, who is Dutch and was previously chairman of a leading hospital in Holland, said: “I do not find the discussion, ‘Which patients should we not treat any more at the end of their lives?’ very well developed in the UK.

“The patients do get anti-cancer treatment when the oncologist, probably the patient and his or her family know it is not going to contribute a lot and it may cause a lot of safety problems and harm.

In Holland, Levi said it is common for patients to state they have had enough treatment and do not want to go back into intensive care.

In the UK, however, he said patients are automatically continuing with treatment in the absence of an honest discussion about what is going to be achieved.

“Patients who are 85 years old do not have to expect a lot of gain from haemodialysis [kidney dialysis], but they still go there three times a week. They feel terrible on the day of dialysis, they feel terrible the day after dialysis. That is six out of seven days of the week,” he said.

“Somebody should at least discuss with them, ‘Is this useful for you? Are you really having any gain of quality of life by doing this?’

“They have a very short life expectancy and we are actually spoiling the last weeks of their lives instead of making them comfortable and them spending quality time with family and friends.”

About 43% of NHS spending goes on the over-65s, according to the Nuffield Trust healthcare charity. This age group also occupies about two-thirds of hospital beds, National Audit Office figures show. Between 10% and 20% of the NHS budget is spent on people in the last year of life, a government-commissioned palliative care funding review found.

Dr Gordon Caldwell, a consultant physician at Worthing Hospital, West Sussex, agrees that British doctors — himself included — often avoid frank discussions about letting patients die.

He said: “Often, as doctors, we hold on to hopes of marginal benefits — ‘You could live 30 days longer, perhaps to three months’ — but omit, ‘This will involve 60 days attending hospital, so you could not go to see Snowdon and Anglesey with your grandchildren.’

“We have relatives demanding, ‘Do everything, doctor.’ Those same relatives, when the patient dies, ask, ‘He didn’t suffer, did he?’ Well, if we were honest [we would say], ‘Yes, he did because you asked us to do everything.’

“I strongly suspect many patients would want less medical interference, such as tests, treatments, last-ditch attempts at chemotherapy.

“Doctors must learn to be honest about the true likely effects of their tests and treatment — a marginal benefit in a few patients at a lot of opportunity loss. A day spent having chemotherapy is a day not with the family.”

Levi said it is up to physicians to broach the subject and it is often welcomed by patients and their families.

“It is the doctors who start the discussion. It was a bit tricky when we did this [in Holland] but it actually turned out that many, many patients and their families were extremely supportive,” he said.

“There were many families of patients who died of cancer who said, ‘If I knew before this was going to happen, we would not have done this operation or this chemotherapy.’”

Professor Karol Sikora, former chief of the World Health Organisation’s cancer programme and chief medical officer of Proton Partners International, a private cancer and healthcare specialist, said there are now more than 25 cancer drugs available that cost more than £50,000 for one year’s treatment and in most cases these would prolong life for only an extra three months.

He added: “There is so much pressure to be active, driven by the pharmaceutical industry and the breakthrough mentality. Giving patients permission to let go has got a lot harder over the last decade.”

However, Baroness Finlay, a crossbench peer and palliative care consultant, believes patients must be given the options of treatments that could help them live longer.

“Sweeping judgments about a person’s quality of life are dangerous,” she said. “Anyone can refuse or cease treatment and that wish must be respected but it becomes dangerous when people are not given the options that might help them live longer and live well.”

Judith Kerr, 94, the children’s author and illustrator who wrote The Tiger Who Came to Tea, has already made her preparations. Last year she told The Sunday Times she keeps “a little piece of pink paper signed by the doctor, saying ‘Do not resuscitate’.”

She added: “Having had a good life, to go through this misery, and at great expense to everybody else — expense not only in money but in emotion.”

COMMENTS:

The dialysis example is a generalisation as many renal units, including the Sheffield Kidney Institue, offer choice that includes conservative, non-dialytic, treatment for patients with ESRD!

Further, there are NO generalised "shoulds"...but choices and personalised options...

Too much emphasis is put on cost in this article...

Also, healthcare decisions makers are NOT the dying patients nor can they share his/her perspective...3 extra months in healthcare Management is a trivial, and often not cost effective, gain...BUT to the dying patient 3 extra months may seem a lifetime; the notion of time changes when little is left...and this is something lacking in these discussions...on end of life care!!!!

Doctors need to show compassion...but the scope and meaning of compassion varies from patient to patient; for some patients compassion may mean a "holiday", for others it may mean prolonged and painful treatment that allows marginal gains (in the doctors' eyes, but not the patient's...), and for others it may mean other choices the patient and his next of kins choose to consider...

Doctors have been for far too long the main decision makers, it is high time they share more decisions with their patients and put themselves in their place...humility in front of a dying patient and a better understanding of the nature of dying is key to an appropriate and personalised management response.

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Meguid El Nahas
by Meguid El Nahas - Monday, 26 June 2017, 8:23 PM
Anyone in the world

https://www.thetimes.co.uk/article/professor-marcel-levi-dying-should-shun-treatment-and-take-final-holiday-pvsbkv0wj?shareToken=79a3e1f73a909362cfe132ca0b22a9ae

Professor Marcel Levi: Dying should shun treatment and take final holiday...

Patients who are dying should be allowed to go on a final holiday rather than be subjected to gruelling treatment, according to the boss of one of Britain’s largest NHS trusts.

Professor Marcel Levi, a practising doctor and chief executive of University College London Hospitals, said the NHS is wasting time and money treating dying patients at the end of their lives.

He said: “I often think, ‘You would be better going on holiday with your family and you may have a little shorter but a lot better end of your life.’”

Levi, who is Dutch and was previously chairman of a leading hospital in Holland, said: “I do not find the discussion, ‘Which patients should we not treat any more at the end of their lives?’ very well developed in the UK.

“The patients do get anti-cancer treatment when the oncologist, probably the patient and his or her family know it is not going to contribute a lot and it may cause a lot of safety problems and harm.

In Holland, Levi said it is common for patients to state they have had enough treatment and do not want to go back into intensive care.

In the UK, however, he said patients are automatically continuing with treatment in the absence of an honest discussion about what is going to be achieved.

“Patients who are 85 years old do not have to expect a lot of gain from haemodialysis [kidney dialysis], but they still go there three times a week. They feel terrible on the day of dialysis, they feel terrible the day after dialysis. That is six out of seven days of the week,” he said.

“Somebody should at least discuss with them, ‘Is this useful for you? Are you really having any gain of quality of life by doing this?’

“They have a very short life expectancy and we are actually spoiling the last weeks of their lives instead of making them comfortable and them spending quality time with family and friends.”

About 43% of NHS spending goes on the over-65s, according to the Nuffield Trust healthcare charity. This age group also occupies about two-thirds of hospital beds, National Audit Office figures show. Between 10% and 20% of the NHS budget is spent on people in the last year of life, a government-commissioned palliative care funding review found.

Dr Gordon Caldwell, a consultant physician at Worthing Hospital, West Sussex, agrees that British doctors — himself included — often avoid frank discussions about letting patients die.

He said: “Often, as doctors, we hold on to hopes of marginal benefits — ‘You could live 30 days longer, perhaps to three months’ — but omit, ‘This will involve 60 days attending hospital, so you could not go to see Snowdon and Anglesey with your grandchildren.’

“We have relatives demanding, ‘Do everything, doctor.’ Those same relatives, when the patient dies, ask, ‘He didn’t suffer, did he?’ Well, if we were honest [we would say], ‘Yes, he did because you asked us to do everything.’

“I strongly suspect many patients would want less medical interference, such as tests, treatments, last-ditch attempts at chemotherapy.

“Doctors must learn to be honest about the true likely effects of their tests and treatment — a marginal benefit in a few patients at a lot of opportunity loss. A day spent having chemotherapy is a day not with the family.”

Levi said it is up to physicians to broach the subject and it is often welcomed by patients and their families.

“It is the doctors who start the discussion. It was a bit tricky when we did this [in Holland] but it actually turned out that many, many patients and their families were extremely supportive,” he said.

“There were many families of patients who died of cancer who said, ‘If I knew before this was going to happen, we would not have done this operation or this chemotherapy.’”

Professor Karol Sikora, former chief of the World Health Organisation’s cancer programme and chief medical officer of Proton Partners International, a private cancer and healthcare specialist, said there are now more than 25 cancer drugs available that cost more than £50,000 for one year’s treatment and in most cases these would prolong life for only an extra three months.

He added: “There is so much pressure to be active, driven by the pharmaceutical industry and the breakthrough mentality. Giving patients permission to let go has got a lot harder over the last decade.”

However, Baroness Finlay, a crossbench peer and palliative care consultant, believes patients must be given the options of treatments that could help them live longer.

“Sweeping judgments about a person’s quality of life are dangerous,” she said. “Anyone can refuse or cease treatment and that wish must be respected but it becomes dangerous when people are not given the options that might help them live longer and live well.”

Judith Kerr, 94, the children’s author and illustrator who wrote The Tiger Who Came to Tea, has already made her preparations. Last year she told The Sunday Times she keeps “a little piece of pink paper signed by the doctor, saying ‘Do not resuscitate’.”

She added: “Having had a good life, to go through this misery, and at great expense to everybody else — expense not only in money but in emotion.”

COMMENTS:

The dialysis example is a generalisation as many renal units, including the Sheffield Kidney Institue, offer choice that includes conservative, non-dialytic, treatment for patients with ESRD!

Further, there are NO generalised "shoulds"...but choices and personalised options...

 

Too much emphasis is put on cost in this article...

Also, healthcare decisions makers are NOT the dying patients not can they share his/her perspective...3 extra months in healthcare Management is a trivial, and often not cost effective, gain...BUT to the dying patient 3 extra months may seem a lifetime; th enotion of time changes with little left...and this is something lacking in these discussions...on end of life care!!!!

Doctors need to show compassion...but the scope and meaning of compassion varies from patient to patient; for some patients compassion may mean a "holiday", for others it may mean prolonged and painful treatment that allows marginal gains (in the doctors' eys, but not the patient...), and for others it may mean other choices the patient and his next of kins choose to consider...

Doctors have been for far too long the main decision makers, it is high time they share more decisions with their patients and put themselves in their place...

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Meguid El Nahas
by Meguid El Nahas - Thursday, 22 June 2017, 9:28 PM
Anyone in the world

I read more than once this paper and failed to understand it...

N Engl J Med. 2017 Jun 15;376(24):2349-2357. doi: 10.1056/NEJMoa1614329.

Single-Nephron Glomerular Filtration Rate in Healthy Adults.

 
Total measured GFR doesnt seem to change much with age...
 
Age related reduction in Nephron numbers doesnt seem associated with compensatory growth of remnant nephrons...not surprising, well known in animal models of renal mass reduction that compensatory renal growth is blunted with age!
 
Nephrosclerosis associated reduction in nephron numbers is associated with compensatroy glomerular growth, that maintain total GFR; well thats good news and shows that compensatory growth and hyperfiltration are a good and not a bad thing...physiological rather than pathological as we were led to beleive...
 
Obesity and excessive height are associated with single nephron hyperfiltration...so what...?!
 
Overall, I failed to quite grasp the publication message,

 CAN SOMEBODY EXPLAINS ITS FINDINGS TO ME....?! 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Meguid El Nahas
by Meguid El Nahas - Tuesday, 30 May 2017, 4:17 PM
Anyone in the world

PRECISION MEDICINE, a term that has crept into the medical lexicom that baffles me...

I am told that PRECISION MEDICINE is: "...based on accurate diagnosis and tailored interventions through the use of improved diagnostic tests and clinical data...."

It seems to me that, that is what medicine and physicians have been aiming to do for centuries...they called it "Medicine"...not precise, sophisticated or spun...just medical practice aimed at improved healthcare delivery through improved diagnostic and prognostic methods...

Sadly, the medical profession is drifting towards replacing real medical breakthroughs by "PROMISING LABELS AND NAMES" that mask the fact that little advances are being made...but by using sophisticated names such as PRECISION MEDICINE, the impression is that real advances and breakthrough are being acheived..in other words replacing factual progress by virtual progress...by spun progress!

So lets forget about PRECISION MEDICINE...and stick to good clinical practice...clinical governance...or just MEDICINE!

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Meguid El Nahas
by Meguid El Nahas - Sunday, 21 May 2017, 2:17 PM
Anyone in the world

Many Nephrologists seem preoccupied by planning randomised control trials (RCTs) to slow the progression of CKD (Chronic Kidney Disease)...

What a folly...!!!!

As if CKD is a disease...it is a simplified definition of reduced kidney function based on changes in eGFR; but anything but a "DISEASE"!!!

...no more than reduced visual or hearing acuity is a disease...they are symptoms of a number of various diseases...

no more than cancer is a homogeneous disease than can be cured with a single magic bullit...

CKD has a number of aetiologies that are operational when "CKD" RCT trials are planned to slow the progression of CKD 3 to 5...

Patients with chronic hypertensive renal disease (nephrosclerosis) tend to progress in phases dependent to a large extent on phases of uncontrolled and accelerated hypertension...

Patients with Diabetic Kidney Disease (DKD) tend to progress in phases often accelerated by poor diabetes control, intercurrent bouts of hypertension of atherosclerotic ischemic nephropathy (T2DM in the elderly) as well as intercurrent infections and superimposed bouts of proliferative glomerulonephritis...not to mention bouts of AKI !

In T2DM, DKD is most hereogeneous ranfing from diabetic nephropathy, to hypertensive nephropathy to atherosclerotic ischemic nephropathy; the severity of the proteinuria in these patients mirrors the underlying rane og pathologies.

Patients with primary glomerulonephritis tend to progress based on genetic variability (FSGS), the severity of proteinuria (reflecting the underlying podocytopathy) or the poor quality of associated hypertension control...

Patients with vasculitis and secondary glomerulonephritis tend to progress depending on the activity of the underlying vasculitis procvess and the associated immune deregulation and /or autoantibody titres...

Patients with chronic interstitial nephropathies tend to progress upon continuing exposure to nephrotoxins such as NSAIDs, analgesics, agricultural toxins (CINAC/CKDu)...

ADPKD progression tends to a larg eextent to depend on the progression of cystic malformations...

So, how can a single therapeutic approach to slow the progression of "CKD" make any sense?! 

This notion is based on the notion of a "final common pathway" that implies that progression of all the above nephropathies follows the same pathophysiology mechanisms; a notion that flies in the face of the above;

a common fibrotic pathway may be operational at CKD4-5, but most RCTs do not aim to retard or reverse established, endstage, fibrosis...instead they aim to retard CKD at an earlier stage (CKD3) when the "final common pathway' may not predominate as outlined above.

So it is high time, we stop considering CKD a DISEASE, but instead a DEFINITION and a STAGING process of a number of nephropathies!

It is also high time, we stop wasting time and money looking for a SINGLE magic treatment that slows the progression of all forms of CKD, but instead tailor the therapies to the nephropathy under consideration!

A better understanding of the "DISEASE" under treatment may lead to more enlightened approaches to the management of CKDs; progress is being made in some nephropathies when the targeting the underlying pathophysiology as in ADPKD is showing some promise...

Also, a better understanding of "CKD"; in the community (cCKD) reflects to a large extent the ageing process of vessels and the kidneys, prevention and treatment is that of prevention and treatment of ageing-associated comorbidities...primarily minimising vascular pathologies.

Referred CKD (rCKD), seen in renal units and tertiary Nephrology centres is due to a large extent to the herogeneous range of nephropathies outlined above...those, to a large extent, cannot be prevented (GN, Vasculitis, ADPKD, etc...), and reflect a range of pathways that lead to progressive renal insufficiency; treatment should depend on addressing those pathways.

In conclusion,

CKD IS A DEFINITION OF SYMPTOMATIC REDUCTION OF KIDNEY FUNCTION AND NOT A SINGLE DISEASE!

Treating symptoms does not prevent or slow CKD progression!

 

 

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Meguid El Nahas
by Meguid El Nahas - Monday, 15 May 2017, 12:33 PM
Anyone in the world

 

 

 

 

I read this month (May 2017) Kidney International whilst in an emerging country teaching to emerging doctors on clinical aspects of Kidney Disease.

Once more, I found very few articles of relevance to those practicing clinical nephrology, never mind those practicing it in emerging countries...

Only 6 of 23 publications were useful or relevant, the rest was more suitable information for researchers in western academic institutions where research on Treg lymphocytes, Zipper proteins, myeloid derived suppressor cells, mitochondrial targeted peptide, alpha-klotho or autophagy is of relevance or interest...

KI, the publishing organ of the International Society of Nephrology (ISN), should pay more attention to jobbing nephrologists at the sharp end of patients' care than basic science researchers in their ivory towers.

the ISN has insisted for decades that it pays particular attention to nephrology in Emerging countries with a number of initiatives supporting such mission and assertion.

However, its major journal, KI, doesnt seem consistent with that mission. I urge the editor of KI and its Editorial Board to give clinicians a better read and to give those practicing in emerging countries more than 2-3 articles/issue of relevance to their clinical practice and CNE!

In answer to the question: Is KI Fit For Purpose? I would say: 

YES, for Western Privileged, high economies, Academia, with limited clinical impact...

NO, for Nephrologists in deprived low and Middle economy countries, who struggle to keep renal diseases and their ravages at bay...

KI may be fit for a purpose...but not the most relevant!

 

 

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

Obesity and new onset of CKD:

https://www.ncbi.nlm.nih.gov/pubmed/28187985

Obesity but not overweight increases risk of CKD (eGFR <60 and albuminuria) in the general population. A systematic review and Meta-analysis of 39 cohorts, 630,677 individuals showed an association between BMI >30kg/m2 and risk of low eGFR and albuminuria. Whilst many of the studies included adjusted the risk of CKD/Albuminuria to other risk factors associated with CD such as hypertension and smoking, the impact of obesity-related confounders remains unclear, in spite of adjustement for co-morbidities.

Limitations:

Concern has to be expressed over the use of MDRD eGFR estimation in the obese where it is poorly validated. Also, single measurement of eGFR does NOT define CKD...nephrologists seem to forget that a single eGFR value is not sufficient to label an individual as suffering from CKD as KDOQI recommends 2 of 3 positive values over a 3 months period as evidence of chronicity.

Finally, is BMI the best marker of obesity...as individuals with a high body weight due to a high muscle mass would have a higher serum creatinine than others and potentially a lower eGFR...whilst central obesity with a high abdominal fat content and a raised waist circumference/waist-Hip ratio seems a more accurate predictor of obesity-related outcomes...

This was recently highlighted in a study where there were no significant statistical interactions between WHR and obesity status (BMI) and central obesity was found to be associated with adverse cardiac dysfunction.

https://www.ncbi.nlm.nih.gov/pubmed/27307550

https://www.ncbi.nlm.nih.gov/pubmed/26337249

In other words, eGFR and BMI may be inaccurate parameters to evaluate the impact of OBESITY on RENAL FUNCTIONAL OUTCOMES; better studies need to be divised with more accurate measurements of both renal function and central obesity and better validation of CKD!

Compiling poor data, through meta-analysis, may improve quantity...but does not improve overall quality nor does it justify hasty conclusions. 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
Picture of Meguid El Nahas
by Meguid El Nahas - Monday, 15 May 2017, 12:11 PM
Anyone in the world

Obesity and new onset of CKD:

https://www.ncbi.nlm.nih.gov/pubmed/28187985

Obesity but not overweight increases risk of CKD (eGFR <60 and albuminuria) in the general population. A systematic review and Meta-analysis of 39 cohorts, 630,677 individuals showed an association between BMI >30kg/m2 and risk of low eGFR and albuminuria. Whilst many of the studies included adjusted the risk of CKD/Albuminuria to other risk factors associated with CD such as hypertension and smoking, the impact of obesity-related confounders remains unclear, in spite of adjustement for co-morbidities.

Limitations:

Concern has to be expressed over the use of MDRD eGFR estimation in the obese where it is poorly validated. Also, single measurement of eGFR does NOT define CKD...nephrologists seem to forget that a single eGFR value is not sufficient to label an individual as suffering from CKD as KDOQI recommends 2 of 3 positive values over a 3 months period as evidence of chronicity.

Finally, is BMI the best marker of obesity...as individuals with a high body weight due to a high muscle mass would have a higher serum creatinine than others and potentially a lower eGFR...whilst central obesity with a high abdominal fat content and a raised waist circumference/waist-Hip ratio seems a more accurate predictor of obesity-related outcomes...

This was recently highlighted in a study where there were no significant statistical interactions between WHR and obesity status (BMI) and central obesity was found to be associated with adverse cardiac dysfunction.

https://www.ncbi.nlm.nih.gov/pubmed/27307550

https://www.ncbi.nlm.nih.gov/pubmed/26337249

In other words, eGFR and BMI may be inaccurate parameters to evaluate the impact of OBESITY on RENAL FUNCTIONAL OUTCOMES; better studeis need to be divised with more accurate measurements of both renal function and central obesity and better validation of CKD!

 

 

 

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]
 
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