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Myths and facts in Nephrology, 2016
1. Sheffield Kidney Institute
Myths and Legends in Nephrology
Jordanian Society of Nephrology 2016
Prof Meguid El Nahas, MD, PhD, FRCP
Professor of Nephrology & Chairman
Global Kidney Academy
Sheffield, UK
6. Sheffield Kidney Institute
CKD Prevalence is rising
KDIGO CKD Classification is useful
eGFR is useful
Maximum BP reduction slows Progression
Proteinuria reduction slows Progression
ACE inhibition Slows Progression
7. Sheffield Kidney Institute
CKD Prevalence is rising
KDIGO CKD Classification is useful
eGFR is useful
Maximum BP reduction slows Progression
Proteinuria reduction slows Progression
ACE inhibition Slows Progression
39. Sheffield Kidney Institute
fils, M., Nivez, M. P., Isaac, R., Mayaud, C., Sraer,
olec. Med. 1975, 49, 301.
. P., Piamba, G., Fillastre, J. P., Ardaillou, R. Nephro-
.
, J. A., Earnshaw, M., Russell, R. G. G., Woods, C. G.
Transpl. Ass. (in the press).
nshaw, M., Heynen, G., Ledmgham, J. G. G., Oliver,
Russell, R. G. G., Woods, C. G. ibid. (in the press).
rson, R. G., Heynen, G., Ledingham, J. G. G., Russell,
R., Walton, R. J. Archs dis. Childh, (in the press).
on, J. L. E. Israel. J. med. Sci. 1971, 7, 488.
ith, R., Ledingham, J. G. G., Oliver, D. O. Proc. eur.
ss. 1971, 8, 122.
nenko, P., Meyner, A., Vallee, G., Beaugas, C. J. clin. In-
345.
53226, U.S.A.
In 31 of 34 patients with chronic renal
insufficiency caused by various diseases,
um-creatinine concentration declined
inine concentration rose from a mean of
ot;8 mg/dl over an average of 71 months.
indicate that in most cases reciprocal
e declines linearly with time as chronic
gresses. Analysis of this relation in indi-
gives an estimate of the progression of
help to determine the effects of therapy,
ed to predict when dialysis will become
Introduction
enal failure develops, serum-creatinine
easingly more rapidly. (This prediction
e well known inverse relation between
nd serum concentration of substances
-rate is constant.l If this were the case,
m-creatinine might fall linearly with
ned this hypothesis in patients who had
ilure with various causes.
Methods
ecords of all patients with chronic renal fail-
n followed in a renal clinic for at least a year
here were 34 patients in whom 7 or more cre-
tions had been performed and in whom there
a threefold increase in creatinine concentra-
r of determinations over a period of at least
sen as sufficient to determine whether there
trend in serum-creatinine with time in indi-
he reciprocal of serum-creatinine concentra-
at the Annual Meeting of the American Federation
h, Atlantic City, N.J., May 2-5, 1976, and pub-
rm (Clin. Res. 1976, 24, 407).
accompanying table. The average of the correlation
coefficients was 0.954 (excluding the patients who had
a non-linear decline in reciprocal serum-creatinine). The
95% confidence limits of the slopes averaged 17.1% of
the individual slopes, with a range of 5.6 to 32.0%.
These limits indicate the smallest change in the rate of
progression that would be detectable by this method.
Discussion
These results indicate that in most patients reciprocal
serum-creatinine concentration declines linearly as
chronic renal failure progresses. There appear to be few
Composite plot of reciprocal serum-creatinine concentration (in
mg/dl) versus months of observation in 6 patients with
chronic renal failure.
Final value for reciprocal of serum-creatinine concentration is
shown for each patient. Ordinate has uniform divisions of 0.1 dl/mg.
Diagnoses in these patients are indicated.
CKD Progression
Mitch et al 1976
1:sCr
47. Sheffield Kidney Institute
CKD Prevalence is rising
KDIGO CKD Classification is useful
eGFR is useful
Maximum BP reduction slows Progression
Proteinuria reduction slows Progression
ACE inhibition Slows Progression
67. Sheffield Kidney Institute
CKD Prevalence is rising
KDIGO CKD Classification is useful
eGFR is useful
Maximum BP reduction slows Progression
Proteinuria reduction slows Progression
ACE inhibition Slows Progression
80. Sheffield Kidney Institute
Renal outcomeswithtelmisartan, ramipril, or both, in
peopleat high vascular risk (the ONTARGETstudy):
amulticentre, randomised, double-blind, controlled trial
JohannesFEMann,RolandESchmieder ,MatthewMcQueen,LeanneDyal,Helmut Schumacher ,JanicePogue,Xingyu Wang,AldoMaggioni,
Andrzej Budaj,Suphachai Chaithiraphan,Kenneth Dickstein, MatyasKeltai, Kaj Metsärinne,Ali Oto,Alexander Parkhomenko, LeopoldoSPiegas,
TageLSvendsen, KoonKTeo,SalimYusuf, onbehalf of theONTARGETinvestigators
Summary
Background Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to
reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for
comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE
inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established
atherosclerotic vascular disease or with diabetes with end-organ damage.
MethodsThe trial ran from 2001 to 2007. After a 3-week run-in period, 25620 participants were randomly assigned to
ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a combination of both drugs (n=8502; median
follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a
composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is
registered with ClinicalTrials.gov, number NCT00153101.
Findings784 patientspermanently discontinued randomised therapy during the trial because of hypotensive symptoms
(406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of eventsfor the composite primary
outcome was similar for telmisartan (n=1147 [13· 4%]) and ramipril (1150 [13· 5%]; hazard ratio [H R] 1· 00, 95% CI
0· 92–1· 09), but was increased with combination therapy (1233 [14.5%]; H R 1· 09, 1· 01–1· 18, p=0· 037). The secondary
renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2· 21%]) and ramipril (174
[2· 03%]; H R 1· 09, 0· 89–1· 34) and more frequent with combination therapy (212 [2· 49%]: H R 1· 24, 1· 01–1· 51,
p=0· 038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan
(–2· 82 [SD 17· 2] mL/ min/ 1· 73 m² vs −4· 12 [17· 4], p<0· 0001) or combination therapy (−6· 11 [17· 9], p<0· 0001). The
increase in urinary albumin excretion was less with telmisartan (p=0· 004) or with combination therapy (p=0· 001) than
with ramipril.
Interpretation In people at high vascular risk, telmisartan’s effects on major renal outcomes are similar to ramipril.
Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major
renal outcomes.
Funding Boehringer-Ingelheim.
Introduction
Clinical trials of angiotensin-converting enzyme (ACE)
inhibitors and angiotensin receptor blockers (ARB) have
shown that these drugs reduce albuminuria, as well as
renal risk—ie, loss of glomerular filtration rate (GFR) and
need for dialysis in those with advanced renal disease.1
progressive renal insufficiency.3
Further reduction of
proteinuria by combined ACE inhibitor and ARB therapy
could theoretically protect the kidney from chronic kidney
failure compared with either agent alone.3
Proteinuria has
also been linked with increased cardiovascular morbidity .4
Combining ACE inhibitors with an ARB might also lead
5
NOTES FOR PRESENTERS:
Key points to raise:
The graph above illustrates a rise in recorded prevalence of CKD stages 3–5 arising from the inclusion of a CKD indicator set within the primary care quality and outcomes framework from April 2006.
In preparation for the inclusion of CKD within the QOF, from April 2005 laboratories began to provide estimated glomerular filtration rates (eGFR) (an indication of CKD) alongside routine serum creatinine testing results.
The five-stage classification system for CKD was introduced into the UK in 2001.
In the year to March 2007 approximately 1.5 million people in England were diagnosed with CKD (Department of Health 2007).
It is estimated that there are approximately 2 million unrecorded cases of CKD in England (Information Centre analysis of a sample of anonymised GP patient records using IMS Disease Analyzer).
Additional information:
Between April 2001 and 2004 facilities for identifying CKD using eGFR were not freely available.
Related NICE guidance includes:
Type 2 diabetes: the management of type 2 diabetes (update). NICE clinical guideline 66 (2008).
Anaemia management in people with chronic kidney disease. NICE clinical guideline 39 (2006).
Hypertension: management of hypertension in adults in primary care. NICE clinical guideline 34 (partial update of NICE clinical guideline 18) (2006).
This guidance sits within the following policy context:
Department of Health (2007) Vascular disease – briefing pack for strategic health authorities
Department of Health (2007) The national service framework for renal services: second progress report
Department of Health (2006) Supporting people with long-term conditions to self-care: a guide to developing local strategies and good practice
Department of Health (2005) Renal services information strategy: supporting part two of the national service framework for renal services
Department of Health (2005) National service framework for renal services - Part two: chronic kidney disease, acute renal failure and end of life care
Department of Health (2005) Supporting people with long term conditions: an NHS and social care model to support local innovation and integration
Department of Health (2001) National service framework for diabetes: standards
NOTES FOR PRESENTERS:
Key points to raise:
The graph above illustrates a rise in recorded prevalence of CKD stages 3–5 arising from the inclusion of a CKD indicator set within the primary care quality and outcomes framework from April 2006.
In preparation for the inclusion of CKD within the QOF, from April 2005 laboratories began to provide estimated glomerular filtration rates (eGFR) (an indication of CKD) alongside routine serum creatinine testing results.
The five-stage classification system for CKD was introduced into the UK in 2001.
In the year to March 2007 approximately 1.5 million people in England were diagnosed with CKD (Department of Health 2007).
It is estimated that there are approximately 2 million unrecorded cases of CKD in England (Information Centre analysis of a sample of anonymised GP patient records using IMS Disease Analyzer).
Additional information:
Between April 2001 and 2004 facilities for identifying CKD using eGFR were not freely available.
Related NICE guidance includes:
Type 2 diabetes: the management of type 2 diabetes (update). NICE clinical guideline 66 (2008).
Anaemia management in people with chronic kidney disease. NICE clinical guideline 39 (2006).
Hypertension: management of hypertension in adults in primary care. NICE clinical guideline 34 (partial update of NICE clinical guideline 18) (2006).
This guidance sits within the following policy context:
Department of Health (2007) Vascular disease – briefing pack for strategic health authorities
Department of Health (2007) The national service framework for renal services: second progress report
Department of Health (2006) Supporting people with long-term conditions to self-care: a guide to developing local strategies and good practice
Department of Health (2005) Renal services information strategy: supporting part two of the national service framework for renal services
Department of Health (2005) National service framework for renal services - Part two: chronic kidney disease, acute renal failure and end of life care
Department of Health (2005) Supporting people with long term conditions: an NHS and social care model to support local innovation and integration
Department of Health (2001) National service framework for diabetes: standards
