RCTs in CKDs: A Waste of Time?

Written by Meguid El Nahas on Sunday, 21 May 2017. Posted in OLA Blog

RCTs in CKDs: A Waste of Time?

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!

 

 

 

Meguid El Nahas

Professor Meguid El Nahas PhD, FRCP

Chief Editor, OLA Director

Professor El Nahas was born in Cairo, Egypt and undertook his undergraduate medical education in...
Posted: 2 months 3 days ago by sawsan mohammed babiker #21460
sawsan mohammed babiker's Avatar
Totally agree with you Professor El Nahas .This what I used to tell to my patient when arrived to the clinic with wrong expectations given by other colleagues mostly from LHC, that you are going to be given treatment for your CKD by nephrologists.
Posted: 2 months 3 days ago by arif.khwaja #21461
arif.khwaja's Avatar
Completely agree

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