There is an interesting publication in JASN online by Remuzzi’s group looking at the effect of angiotensin II inhibition on glomerular vasculature. They use micro-CT and scanning EM to study the effect of RAS inhibition in Munich Wistar Fromter (MWF) rats that spontaneously develop kidney disease with age. Untreated MWF rats develop glomerusclerosis and interstitial fibrosis and micro-CT data showed a reduction of spatial density in arteries and veins in the kidney - in essence a reduction in vascular volume relative to total kidney volume. This effect was reversed by treatment with losaratan and lisinopril which the authors describe as regeneration of the vasculature on the basis that vascular volume increased once treatment started. Scanning electron microscopy data appeared to show that RAS blocked increased glomerular capillary (GC) volume and length. The authors state that this results in increased functional GC and thereby increasing filtering surface area. Losartan and Lisinopril both appeared to reduce mRNA expression of profibrotic mediators such as TGFbeta and endothelin as well as reducing the expression of alpha-smooth muscle actin in both glomerular and interstitial capillaries - which the authors take as a sign of inhibition of endo-mesenchymal transition.

Central arteriovenous anastomosis for the treatment of patients with uncontrolled hypertension (the ROX CONTROL HTN study): a randomised controlled trial.

Is There a Real Global Epidemic of Chronic Kidney Disease?

Numerous publications have asserted that the global prevalence of chronic kidney disease (CKD) in adults is generally between 10-13% (as determined from the KDOQI or KDIGO Classification schema, but using one-off, non-age calibrated determinations for identification of CKD ) and that the burden of this disease has reached “epidemic” proportions.  In some developed countries (e.g. USA) the population-based prevalence rate of CKD has levelled off, at least in most adult age groups, and some countries have a much lower prevalence of CKD (e.g. Italy) than the global averages.  A new and monumental study has put a fresh perspective to the issue of the global burden of CKD (Global Burden of Disease Study 2013 Collaborators, The Lancet, June 8, 2015 – on-line).  This seminal study of the incidence, prevalence and years lived with disability (YLD) for 301 acute and chronic diseases (including CKD) and injuries in 188 countries during 1990 and 2013 sheds new light on the purported “epidemic” CKD.  The data (35,620 distinct sources) were derived and analyzed in a fashion different from those publications using KDOQI or KDIGO criteria so they may not be strictly comparable.  The inclusion of both adults and children may have also altered the prevalence data compared to KDOQI and KDIGO, which are confined to adults only.

Nevertheless the observations are quite informative.   There were 324,666,000 cases of CKD in 1990 and 471,916,000 cases of CKD in 2013; after adjusted for aging and population growth the prevalence rate of CKD (per 100,000 population) actually declined overall by about  5% between 1990 and 2013.  But the change in adjusted global prevalence rate between 1990- and 2013 was not uniform among the causes of CKD; to wit, the adjusted global prevalence rates of CKD due to glomerulonephritis and hypertension declined by 13.54% and 10.74% respectively whilst the adjusted global prevalence rates of CKD due to diabetes or other causes increased by 11.85% and 3.12% respectively.  If the global population was 7.1 Billion in 2013 about 6.7% had some form of CKD; about 20% of which could be attributed to diabetes.  The inclusion of children in both the denominator and numerator in this analysis may have diluted the overall prevalence rates of CKD, to some degee. But taken at face value, these figures indicate that generic CKD as a whole is not occurring in “epidemic” proportions globally, but that there are very worrisome trends over the last 2 decades in that CKD due to diabetes is a major and growing global problem.     Correspondingly, the  reported age and population standardized YLD rose by 10.6% and 6.9% for CKD due to Diabetes and other causes respectively between 1990 and 2013 whilst the  age and population YLD fell 22.4% and 6.9% for CKD due to hypertension and glomerulonephritis respectively for a net decline in the YLD burden of CKD on a global basis.

Translating these intriguing findings into an action plan for control of the global disease burden linked to CKD is a difficult task and undoubtedly the answers will be different for developing compared to developed nations and depend greatly on the importance of CKD relative to other public health priorities (e.g. electrification, potable water, infectious disease, etc).  What does seem abundantly clear, at least to me, is that the focus should not be on generic CKD, but rather on the problem of diabetes and its parent obesity.  In my opinion, what the globe urgently needs is a coherent, culture-adapted approach to detection, prevention and management of obesity and diabetes (“diabesity”)—and not a population- based early detection program for generic CKD.  Furthermore, more research leading to better understanding and treatments for the complex triad of obesity, diabetes and CKD are greatly needed. We should recognize that a global epidemic of generic CKD simply does not exist and relentlessly devote our energy to mitigating the world-wide problem of too many calories of the wrong kind and lack of energy consuming activities so as to avoid the CKD complications of “diabesity”.  

Richard J. Glassock, MD

Geffen School of Medicine at UCLA

 June 8, 2015

Prof Richard Glassock wrote in reference to the latest publication in the Lancet on the Global Burden of Disease Study 2013: (The Lancet On line 8th of June 2015)

It represents massive data collection and a complicated analysis but the main message is that except for diabetes related  CKD, most forms of CKD are decreasing (since 1990) in total prevalence and years lost to disability. 

The only "epidemic" of CKD is that related to diabetes, and indirectly to obesity. 

The public health authorities around the world should not be focusing on detection of CKD, per se, as a problem, but instead should be energetically trying to curtail diabetes, by focusing on its origins; diet (composition and energy content) and activity level. 

Claims that the world is trapped in an out-of-control epidemic of CKD represent mis-information at its worst, as these claims obfuscate the real issue; diabetes and its micro- and macro-vascular complications. 

Screening programs for CKD are socially irresponsible, if they detract from addressing the real problem- diabesity (diabetes due to obesity), a potentially preventable disorder-- easily detected but difficult to treat.

Food for thought!!!

My Comments:

The global "epidemic" of CKD has been an ill founded concept based on very poor epidemiology and/or rather poor biostatistics.

http://www.ncbi.nlm.nih.gov/pubmed/23497858

This had a number of consequences, that I condemn:

1. Raised awareness of CKD, but overinflated its scale...claiming to affect 1 in 2 individual over a lifetime…

2. Medicalised the ageing process, by falsely claiming that CKD affected millions over the age of 65...thus confusing true CKD with age-related decline in kidney function…

3. Generated an industry of lightweight biostatistical analyses based on poorly collected and seldom validated data…published as irrefutable facts…

http://www.ncbi.nlm.nih.gov/pubmed/23588748

http://www.ncbi.nlm.nih.gov/pubmed/23497858

4. Raised the profile of Nephrology as a subspeciality, but at the price of misinformation...or to be kind, an unfounded truth...

http://www.ncbi.nlm.nih.gov/pubmed/23727165

5. Increased “Nephrologists” income in countries where their income stems from recognising, diagnosing, and cashing on, false diseases in an alarmed and misinformed population…

6. Failed to distinguish true CKD from community based older individuals with reduced kidney function…

7. Overburdened Nephrologists worldwide by unnecessary referrals of older patients with mild to moderate, but stable, age-related impaired kidney function; thus distracting them from their true task of dealing with primary and progressive nephropathies!

8.  Increased prescription of potentially nephrotoxic agents such as ACE inhibitors in the elderly without a shred of evidence that it protected from early CKD progression or delayed ESRD, and in spite of evidence to the contrary:

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

9. Generated more diseases, namely AKI, in elderly individuals prescribed ACE inhibitors for dubious and ill founded indications…:

http://www.ncbi.nlm.nih.gov/pubmed/?term=tomson+C%2C+AKI%2C+ACE+inhibitors

10. Overlooked the true burden of disease; namely Hypertension and Diabetes, thus leaving them significantly under-diagnosed and under-treated!

Shame on us as a professional body to have jumped uncritically on this bandwagon…

”Castles built on sand, soon collapse…”

Blog based on a lecture by Professor Samir Mallat at the Global Kidney Academy Master Class held in Prague on 7 June 2015.

SIMPLICITY HTN3 showed no effect of renal sympathetic denervation (RSD) on the control of hypertension.

Subgroup analyses of SIMPLICITY3 suggest that the effect may not be as negative as initially thought:

1. Those <65y may respond to RSD

2. Non African Americans may respond to RSD

3. Those NOT on alpha blockers may respond to RSD

4. The number of ablation bursts >10 may be beneficial

5. The circumferential denervation may be most effective

http://www.ncbi.nlm.nih.gov/pubmed/25744017

Consequently, more studies are planned.

http://www.ncbi.nlm.nih.gov/pubmed/?term=Simplicity+3+study%2C+resistant+hypertension

Is that good clinical research, following leads from posthoc and subgroup analyses, to establish new evidence?

or

is it the perseverance of the medical industrial complex that has invested heavily in that technology and doesnt want to ditch it...?

along with

medical practitioners who saw a potential source of income and private practice and dont want to give it up...?

The verdict is out...

A

 The most practical way to separate age-related decline in eGFR from that associated with bona-fide kidney disease might be a persistent dipstick proteinuria of > 1+. While somewhat lacking in sensitivity it has reasonable specificity.  One needs to be careful about use of urine albumin to creatinine ratios (UACR) in the elderly as the expected decline in creatinine excretion with age (and frailty) leads to overestimation of albumin excretion, and thereby mis classification when one uses a KDIGO advocated schema.

A quick update from the late clinical trials session from the ERA-EDTA which was a high quality session

Persistent High Serum Bicarbonate and the Risk of Heart Failure in Patients With Chronic Kidney Disease (CKD): A Report From the Chronic Renal Insufficiency Cohort (CRIC) Study.

The Gap between Theoretical and Practical/Clinically relevant Nephrology Knowledge grows with the type of teaching and conferences given in emerging countries and elsewhere...

Endless lectures...when the speaker shows off his/her knowledge and doesnt care about how much is useful or retainable by the audience...IT IS HIGH TIME THESE USELESS CONFERENCES STOP AND/OR CHANGE....

It is high time that lectures and conferences are audience centered rather than speakers centered...

Does anybody ask the DELEGATES what they would like to listen to...what their educational needs are...??? NO, instead they are given a form of education that is not targeted to their needs...but instead to the needs...promotion...recognition...of the SPEAKERS...!!!!!

I remember at a meeting, convdentional lecture loaded meeting, asking the delegates on Day 2 questions relating to ALL the lectures they listened to on Day 1...hardly one remembered anything meaningful...????

PASSIVE and UNTARGETED teaching is a waste of time for the delegates...and more so to the patients they meant to treat and translate their knowledge to benefit from...

So WHY is it going on...because of the CHRONIC AND HABITUAL SPEAKERS MAFIA... because of ACADEMIC EGOS...because of the HIDDEN AGENDAS OF NATIONAL AND INTERNATIONAL LEARNED SOCIETIES...because of the NOT SO HIDDEN AGENDA OF BIG PHARMA...

Therefore, this may not change but what can change is the way we perceive and receive these teachings....WITH A CRITICAL MIND...WITH A REFLECTIVE MIND...that allows us to filter the MEANINGFUL from the MEANINGLESS...

And always ask the speaker the 5 WHATS:

1. What is the clinical NEED and need for your lecture?

2. What is the EVIDENCE upon which you base your statements?

3. What is the RELEVANCE of what you teach to MY PATIENTS?

Then..

4. What is the risk versus benefit of what you are teaching us?

5. What is the cost versus benefit of the approach you are recommending?

LETS START THIS PROCESS AND CHALLENGE THE SPEAKER!

(give her examples that you have come across of bad teachers!)

Growing evidence is implicating a genetic absis for CKD in African-Americans linked to mutations in the APOL1 gene. A genetic mutation that served sub-saharan Africans well some 10,000 years ago as it confered trypanolytic activity against trypanosoma brucei...but now comes to cost them a susceptibility to non diabetic CKD including primary and secondary FSGS (1).

More recently, it has also become apparent that such mutations in the APOL1 gene may confer increased susceptibility to renal allograft failure; not as much in black recipients but in relation to balck donors. Renal allografts with APOL1 G1 and G2 mutations variants have considerably shorter allograft survival (2).

Consequently, the question is now raised as to whether Blacks with such AOPL1 mutations should donate their kidneys or not? In two respects, first whether such allograft will have a poorer outcome, second, whether the donor, if young, would be susceptible later in life to a nephropathy on his/her remaining kidney. Those may develop the unfavorable CKD/FSGS phenotype later in life.

This concern applies to both living as well as deceased donors. Two (G1 and G2) APLO1 risk variant kidneys may be avoided or used where expanded criteria donor kidneys are considered, as they have a greater probability of early allograft failure.

In the era of rapid sequencing and PCR based genotyping, time may have come for a better genetic evaluation of kidney donors (3).

However, such  approach whilst affordable and applicable in high economies is unlikely to be either practical or affordable in low and middle economy countries where most black individuals and those of African ancestry live...all too often medical guidelines and recommendations made in Western countries and Western publications overlook the fact that the world is not confined to the West, but also East and South...in those, genotyping of any kind is not an option, whilst renal transplantation may be a survival option in the absence of other forms of renal replacement therapies such as dialysis. Instead, a more careful clinical and laboratory evaluation of black donors is warranted, with careful family history (of CKD) souhgt, a careful evaluation of their kidney function and microalbuminuria, as well as more cautious, or agressive, management of these potentially higher risk of failure kidneys. 

References:

1. Genovese et al. Science 2010;329:841-45.

2. Reeves-Daniel et al. Am J Transpl 2011;11:1025-30.

3. Freedman and Julian. Kidney Int 2015; 87:671-73.