Rate of Change in Renal Function and Mortality in Elderly Treated Hypertensive Patients.
BACKGROUND AND OBJECTIVES:
Evidence relating the rate of change in renal function, measured as eGFR, after antihypertensive treatment in elderly patients to clinical outcome is sparse. This study characterized the rate of change in eGFR after commencement of antihypertensive treatment in an elderly population, the factors associated with eGFR rate change, and the rate's association with all-cause and cardiovascular mortality.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
Data from the Second Australian National Blood Pressure study were used, where 6083 hypertensive participants aged ≥65 years were enrolled during 1995-1997 and followed for a median of 4.1 years (in-trial). Following the Second Australian National Blood Pressure study, participants were followed-up for a further median 6.9 years (post-trial). The annual rate of change in the eGFR was calculated in 4940 participants using creatinine measurements during the in-trial period and classified into quintiles (Q) on the basis of the following eGFR changes: rapid decline (Q1), decline (Q2), stable (Q3), increase (Q4), and rapid increase (Q5).
A rapid decline in eGFR in comparison with those with stable eGFRs during the in-trial period was associated with older age, living in a rural area, wider pulse pressure at baseline, receiving diuretic-based therapy, taking multiple antihypertensive drugs, and having blood pressure <140/90 mmHg during the study. However, a rapid increase in eGFR was observed in younger women and those with a higher cholesterol level. After adjustment for baseline and in-trial covariates, Cox-proportional hazard models showed a significantly greater risk for both all-cause (hazard ratio, 1.28; 95% confidence interval, 1.09 to 1.52; P=0.003) and cardiovascular (hazard ratio, 1.40; 95% confidence interval, 1.11 to 1.76; P=0.004) mortality in the rapid decline group compared with the stable group over a median of 7.2 years after the last eGFR measure. No significant association with mortality was observed for a rapid increase in eGFR.
In elderly persons with treated hypertension, a rapid decline in eGFR is associated with a higher risk of mortality.
There is something wrong with the world of publications and journals... So elderly patients with rapidly declining eGFR are more likely to die?!
And cjASN has a reasonable impact factor... !!!!!
We are drowning in information ... Most of it associative, a lot of it a rehash of previous work... And it means we can't see the wood from the trees ... The value of a publication now is primarily for the author rather than the wider readership...its like satellite TV ... Hundreds of channels but hardly anything worth watching!!!
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.
Hypertension contributes to cardiovascular morbidity and mortality. We assessed the safety and efficacy of a central iliac arteriovenous anastomosis to alter the mechanical arterial properties and reduce blood pressure in patients with uncontrolled hypertension.
We enrolled patients in this open-label, multicentre, prospective, randomised, controlled trial between October, 2012, and April, 2014. Eligible patients had baseline office systolic blood pressure of 140 mm Hg or higher and average daytime ambulatory blood pressure of 135 mm Hg or higher systolic and 85 mm Hg or higher diastolic despite antihypertensive treatment. Patients were randomly allocated in a 1:1 ratio to undergo implantation of an arteriovenous coupler device plus current pharmaceutical treatment or to maintain current treatment alone (control). The primary endpoint was mean change from baseline in office and 24 h ambulatory systolic blood pressure at 6 months. Analysis was by modified intention to treat (all patients remaining in follow-up at 6 months). This trial is registered with ClinicalTrials.gov, number NCT01642498.
83 (43%) of 195 patients screened were assigned arteriovenous coupler therapy (n=44) or normal care (n=39). Mean office systolic blood pressure reduced by 26·9 (SD 23·9) mm Hg in the arteriovenous coupler group (p<0·0001) and by 3·7 (21·2) mm Hg in the control group (p=0·31). Mean systolic 24 h ambulatory blood pressure reduced by 13·5 (18·8) mm Hg (p<0·0001) in arteriovenous coupler recipients and by 0·5 (15·8) mm Hg (p=0·86) in controls. Implantation of the arteriovenous coupler was associated with late ipsilateral venous stenosis in 12 (29%) of 42 patients and was treatable with venoplasty or stenting.
Arteriovenous anastomosis was associated with significantly reduced blood pressure and hypertensive complications. This approach might be a useful adjunctive therapy for patients with uncontrolled hypertension.
This pilot study pertains to treat resistant hypertension by the creation of an iliac AV shunt...
Whilst seemingly promising, it is another example of the BIG INDUSTRIAL MEDICAL COMPLEX intrusion into clinical practice; the use of a potentially harmful, not to say dangerous, interventions to treat patients who may not need it (those whose SBP is above 140mmHg, whilst their age if over 70....) or who may be controlled otherwise...by a 4th antihypertensive agent...or better compliance...25-30% of so called resistant hypertensives are non compliant:
The AV shunt intervention exposes patients to a number of serious complications such as DVT as well as potential ischemic lower limb changes...
It is also an example of the BIG INDUSTRIAL MEDICAL COMPLEX influence on publishers...the publication in the Lancet, a seemingly serious journal, of a pilot study with short and inadequate follow-up as well as devoid of control/sham intervention group not to mention compliance to medical checks... In other words, a pilot, proof of concept, study with a number of serious limitations...published in a top medical journal...?!
This intrusion of the INDUSTRIAL MEDICAL COMPLEX was already demonstrated in patients with "resistant" hypertension by the Renal Sympathetic Denervation (RDN) clinical trials, SIMPLICITY...mostly badly designed an uncontrolled until SIMPLICITY HTN 3 showed no benefit...
BUT...the MEDICAL INDUSTRIAL COMPLEX...doesnt rest its case but pursue and encourage the greed of interventionists amongst private physicians...who saw in such method a major source of unethical income...by all sorts of subgroup analyses and posthoc analyses claiming benefits...:
in Japan: http://www.ncbi.nlm.nih.gov/pubmed/26102846
In subgroups: http://www.ncbi.nlm.nih.gov/pubmed/24914028
Younger patients: http://www.ncbi.nlm.nih.gov/pubmed/25565369
Number of bursts...
In other words, the MEDICAL INDUSTRIAL COMPLEX feeds on:
1. Pseudo clinical indications
2. Poorly managed patients, by conventional means
3. Credulous physicians who think any new technology is an advance...
4. Greedy physicians who make money out of new interventions at the expense of their patients' safety or benefit...in countries where private medicine thrives...
5. Medical Journals attracted by medical technical innovations...even when poorly designed, or pilot, studies underpin the findings...
IT IS HIGH TIME WE, AS A PROFESSION, PUT PATIENTS BENEFIT AND SAFETY BEFORE GADGETRY AND PROFIT...
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!!!
The global "epidemic" of CKD has been an ill founded concept based on very poor epidemiology and/or rather poor biostatistics.
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…
4. Raised the profile of Nephrology as a subspeciality, but at the price of misinformation...or to be kind, an unfounded truth...
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:
9. Generated more diseases, namely AKI, in elderly individuals prescribed ACE inhibitors for dubious and ill founded indications…:
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
Consequently, more studies are planned.
Is that good clinical research, following leads from posthoc and subgroup analyses, to establish new evidence?
is it the perseverance of the medical industrial complex that has invested heavily in that technology and doesnt want to ditch it...?
medical practitioners who saw a potential source of income and private practice and dont want to give it up...?
The verdict is out...
- Summary (text)
- Abstract (text)
- PMID List
- My Bibliography
- Citation manager
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.
Serum bicarbonate varies over time in chronic kidney disease (CKD) patients, and this variability may portend poor cardiovascular outcomes. The aim of this study was to conduct a time-updated longitudinal analysis to evaluate the association of serum bicarbonate with long-term clinical outcomes: heart failure, atherosclerotic events, renal events (halving of estimated glomerular filtration rate [eGFR] or end-stage renal disease), and mortality.
METHODS AND RESULTS:
Serum bicarbonate was measured annually, in 3586 participants with CKD, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. Marginal structural models were created to allow for integration of all available bicarbonate measurements and proper adjustment for time-dependent confounding. During the 6 years follow-up, 512 participants developed congestive heart failure (26/1000 person-years) and 749 developed renal events (37/1000 person-years). The risk of heart failure and death was significantly higher for participants who maintained serum bicarbonate >26 mmol/L for the entire duration of follow-up (hazard ratio [HR] 1.66; 95% confidence interval [CI], 1.23 to 2.23, and HR 1.36, 95% CI 1.02 to 1.82, respectively) compared with participants who kept their bicarbonate 22 to 26 mmol/L, after adjusting for demographics, co-morbidities, medications including diuretics, eGFR, and proteinuria. Participants who maintained serum bicarbonate <22 mmol/L had almost a 2-fold increased risk of renal disease progression (HR 1.97; 95% CI, 1.50 to 2.57) compared with participants with bicarbonate 22 to 26 mmol/L.
In this large CKD cohort, persistent serum bicarbonate >26 mmol/L was associated with increased risk of heart failure events and mortality. Further studies are needed to determine the optimal range of serum bicarbonate in CKD to prevent adverse clinical outcomes.
The Nephrology community has been led to beleive with weak evidence that increased serum bicarbonate levels slows CKD progression (1-3). Whilst little doubt exists in Nephrologists' mind that metabolic acidosis in CKD is harmful, increased emphasis has been over the last 5 years on aiming for higher than normal serum bicarbonate levels to slow CKD progression and delay ESRD (1-3).
Now data published this month from a CRIC cohort seems to confirm that impression with patients with CKD and serum bicarbonate levels >26mmol/l have a significant decrease incidence of adverse renal events including ESRD compared to those with sBic <22mmol/l. However, the same cohort study shows an alarming increase in congestive heart failure and death rate in those whose serum bicarbonate levels exceeds 26mmol/l...!!!!
Previous NHANES III observations suggested that low serum Bicarbonate levels <22mmol/l are associated with increased mortality in CKD patients (3).
So it seems to me that optimal serum bicarbonate levels in patients with CKD may be between 24-26mmol/l, thus aiming at minimising CKD progression whilst avoiding metabolic alkalosis and its negative effects on the myocardium resulting in congestive heart failure and death. In other words, keeping serum bicarbonate levels within the middle of the normal range (24-26mmol/l) may prove that moderation is the best option for CKD patients!
1. de Brito-Ashurst I, Varagunam M, Raftery MJ, Yaqoob MM. Bicarbonate
supplementation slows progression of CKD and improves nutritional status. J
Am Soc Nephrol. 2009;20:2075–2084.
2. Raphael KL, Wei G, Baird BC, Greene T, Beddhu S. Higher serum bicarbonate levels within the normal range are associated with better survival and renal outcomes in African Americans. Kidney Int. 2011;79:356–362.
3. Raphael KL, Zhang Y, Wei G, Greene T, Cheung AK, Beddhu S. Serum bicarbonate and mortality in adults in NHANES III. Nephrol Dial Transplant. 2013;28:1207–1213.
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?
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!)