Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.
Background The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known. Methods We randomly assigned patients to receive 10 mg or 25 mg of empagliflozin or placebo once daily. The primary composite outcome was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, as analyzed in the pooled empagliflozin group versus the placebo group. The key secondary composite outcome was the primary outcome plus hospitalization for unstable angina. Results A total of 7020 patients were treated (median observation time, 3.1 years). The primary outcome occurred in 490 of 4687 patients (10.5%) in the pooled empagliflozin group and in 282 of 2333 patients (12.1%) in the placebo group (hazard ratio in the empagliflozin group, 0.86; 95.02% confidence interval, 0.74 to 0.99; P=0.04 for superiority). There were no significant between-group differences in the rates of myocardial infarction or stroke, but in the empagliflozin group there were significantly lower rates of death from cardiovascular causes (3.7%, vs. 5.9% in the placebo group; 38% relative risk reduction), hospitalization for heart failure (2.7% and 4.1%, respectively; 35% relative risk reduction), and death from any cause (5.7% and 8.3%, respectively; 32% relative risk reduction). There was no significant between-group difference in the key secondary outcome (P=0.08 for superiority). Among patients receiving empagliflozin, there was an increased rate of genital infection but no increase in other adverse events. Conclusions Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care. (Funded by Boehringer Ingelheim and Eli Lilly; EMPA-REG OUTCOME ClinicalTrials.gov number, NCT01131676 .).
Inhibitors of SGLT2 (sodium-glucose cotransporter-2) inhibitors are hypoglycemic agents that have shown benefit in the management of heart failure in their capacity as potent osmotic diuretic through increased glycosuria.
In this study, Zinman et al show a benefit in all cause and cardiovascular mortality in patients at high cardiovascular risk due to T2DM.
It is intriguing that the only difference related to CVD ouitcomes is heart failure; all other causes of CVD death such as myocardial infractions or stokes dont seem different in those on SGLT2 inhibitors and placebos.
The only difference between the two groups seem to depend on a significant reduction in heart failure, related hsopitalisation and death.
This along with a reduction in weight and BP in the SGLT2 treated group that the beneficial effect is primarily related to the diuretic effect of this agent. Unfortunately, the placebo group did not incorporate additional diuretic therapy to match that of the two SGLT2 inhibitors arms.
The questions that warrant consideration is:
Is this agent with its protective effect on CVD death due to heart failure an expense diuretic...with considerable potential side effects including urosepsis (fourfold higher in this study in those treated with SGLT2 inhibitors compared to placebo), genital candidiasis, and even urogenital malignancies...and high cost, worth its use!?
Also, in this high risk group of patients with high CVD risk who are often on ACE inhibitors, is there an increased risk of AKI associated with the uise of excessive SGLT2 inhibition-induced diuresis?
Lancet. 2015 Sep 18. pii: S0140-6736(15)00257-3. doi: 10.1016/S0140-6736(15)00257-3. [Epub ahead of print]
Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial.
Optimal drug treatment for patients with resistant hypertension is undefined. We aimed to test the hypotheses that resistant hypertension is most often caused by excessive sodium retention, and that spironolactone would therefore be superior to non-diuretic add-on drugs at lowering blood pressure.
In this double-blind, placebo-controlled, crossover trial, we enrolled patients aged 18-79 years with seated clinic systolic blood pressure 140 mm Hg or greater (or ≥135 mm Hg for patients with diabetes) and home systolic blood pressure (18 readings over 4 days) 130 mm Hg or greater, despite treatment for at least 3 months with maximally tolerated doses of three drugs, from 12 secondary and two primary care sites in the UK. Patients rotated, in a preassigned, randomised order, through 12 weeks of once daily treatment with each of spironolactone (25-50 mg), bisoprolol (5-10 mg), doxazosin modified release (4-8 mg), and placebo, in addition to their baseline blood pressure drugs. Random assignment was done via a central computer system. Investigators and patients were masked to the identity of drugs, and to their sequence allocation. The dose was doubled after 6 weeks of each cycle. The hierarchical primary endpoints were the difference in averaged home systolic blood pressure between spironolactone and placebo, followed (if significant) by the difference in home systolic blood pressure between spironolactone and the average of the other two active drugs, followed by the difference in home systolic blood pressure between spironolactone and each of the other two drugs. Analysis was by intention to treat. The trial is registered with EudraCT number 2008-007149-30, and ClinicalTrials.gov number, NCT02369081.
Between May 15, 2009, and July 8, 2014, we screened 436 patients, of whom 335 were randomly assigned. After 21 were excluded, 285 patients received spironolactone, 282 doxazosin, 285 bisoprolol, and 274 placebo; 230 patients completed all treatment cycles. The average reduction in home systolic blood pressure by spironolactone was superior to placebo (-8·70 mm Hg [95% CI -9·72 to -7·69]; p<0·0001), superior to the mean of the other two active treatments (doxazosin and bisoprolol; -4·26 [-5·13 to -3·38]; p<0·0001), and superior when compared with the individual treatments; versus doxazosin (-4·03 [-5·04 to -3·02]; p<0·0001) and versus bisoprolol (-4·48 [-5·50 to -3·46]; p<0·0001). Spironolactone was the most effective blood pressure-lowering treatment, throughout the distribution of baseline plasma renin; but its margin of superiority and likelihood of being the best drug for the individual patient were many-fold greater in the lower than higher ends of the distribution. All treatments were well tolerated. In six of the 285 patients who received spironolactone, serum potassium exceeded 6·0 mmol/L on one occasion.
Spironolactone was the most effective add-on drug for the treatment of resistant hypertension. The superiority of spironolactone supports a primary role of sodium retention in this condition.
The British Heart Foundation and National Institute for Health Research.
So called resistant hypertension is often the result of:
1. Inadequate treatment
2. Poor compliance
The PATHWAY-2 study by the British Hypertension Society highlights the importance of hyperaldosteronism, sodium retention and volume expansion in the pathogenesis of "Resistant Hypertension". It showed a significant improvement in BP control upon the addition of Spironolactone (a mineralcorticoid receptor antagonist).
Spironolactone was superior to a beta-blocker (Bisoprolol) or an alpha blocker (Doxazosin) or placebo as an add on treatment, over 3 months, to patients already on optimised/maximum (A [ACE inhibitor]+C [Calcium antagonist]+D [Diuretics]) treatment.
The question remains whether the observed benefit is due to:
a specific anti-aldosterone effect
More suitable controls would have been:
1. Either stricter dietary sodium restriction (known to optimise the anti-hypertensive effect of ACE inhibitors/ARBs)
2. an increase in the existent diuretic therapy (D), also previously shown to optimise treatment with RAS inhibitors.
Finally, a study of Hypertension control including patients aged:
18 to 79...
and GFR from normal to 45 ml/min...
calls for more analysis of subgroups response to the proposed therapeutic approach and raises questions as to whether all hypertensive are the same regardless or age and regardless of kidney function in terms of pathophysiology and response to therapy.
Nocturnal Dialysis May Provide Cardiovascular Benefits over Conventional Hemodialysis
Conversion from conventional hemodialysis (CHD) to in-center nocturnal hemodialysis (INHD) was associated with a 14.2 g reduction in left ventricular mass after 1 year as compared with continuation on CHD. Investigators also observed a trend toward larger reductions in systolic blood pressure (9.8 mm Hg) among INHD patients with fewer antihypertensive medications prescribed over time. Serum phosphate concentration declined by 0.40 mmol/L among INHD recipients, but there were no differences in patients’ requirements for phosphate binders. The Canadian Journal of Cardiology study included 67 prevalent CHD (4 hours/session, 3 times/week) recipients, of whom 37 converted to INHD (7–8 hours/session, 3 times/week).
Why go on about NOCTURNAL HD, versus daytime HD, and its benefits when all there is has been known since the 70s and 80s...LONGER HD is benefical...it improves ultrafiltration volume, improves BP control by reducing intravascular volume and ultimately reduces LVH (LVMI)...
This was also observed with FREQUENT HD (FHN Study) where all the benefits could be ascribed to LONGER dialysis time, with better UF, BP and LVMI...
IT IS HIGH TIME THOSE WHO PUBLISH THESE PAPERS STOP TRYING TO FOOL PUBLISHERS AND READERS...NEPHROLOGISTS BEWARE; TIME IS GOLDEN!
Urinary Sodium and Potassium Excretion and CKD Progression.
CKD is a major risk factor for ESRD, cardiovascular disease, and premature death. Whether dietary sodium and potassium intake affect CKD progression remains unclear. We prospectively studied the association of urinary sodium and potassium excretion with CKD progression and all-cause mortality among 3939 patients with CKD in the Chronic Renal Insufficiency Cohort Study. Urinary sodium and potassium excretion were measured using three 24-hour urine specimens, and CKD progression was defined as incident ESRD or halving of eGFR. During follow-up, 939 CKD progression events and 540 deaths occurred. Compared with the lowest quartile of urinary sodium excretion (<116.8 mmol/24 h), hazard ratios (95% confidence intervals) for the highest quartile of urinary sodium excretion (≥194.6 mmol/24 h) were 1.54 (1.23 to 1.92) for CKD progression, 1.45 (1.08 to 1.95) for all-cause mortality, and 1.43 (1.18 to 1.73) for the composite outcome of CKD progression and all-cause mortality after adjusting for multiple covariates, including baseline eGFR. Additionally, compared with the lowest quartile of urinary potassium excretion (<39.4 mmol/24 h), hazard ratios for the highest quartile of urinary potassium excretion (≥67.1 mmol/24 h) were 1.59 (1.25 to 2.03) for CKD progression, 0.98 (0.71 to 1.35) for all-cause mortality, and 1.42 (1.15 to 1.74) for the composite outcome. These data indicate that high urinary sodium and potassium excretion are associated with increased risk of CKD progression. Clinical trials are warranted to test the effect of sodium and potassium reduction on CKD progression.
Interesting and not surprising observation linking a high urinary sodium excretion with CKD progression. The association seemd to be affected by the level of albuminuria that also correlated with the rate of CKD progression.
The authors showed the association to be independent of presence or absence of hypertension, type of anti-hypertensive agent or systolic blood pressure...
the association between high urinary sodium excretion, most likely the reflection of high dietary sodium intake, is most liley the refelction of poorly controlled hypertension...
the authors overlook the fact that a casual, occasional, single blood poressure recording is meaningless and doesnt ascertian whether individuals are hypertensive or not and/or controlled or not...
WHEN WILL NEPHROLOGISTS LEARN THAT CASUAL, SINGLE, BP READING DOESNT INFORM ON HYPERTENSION, ITS PRESENCE OR THE QUALITY OF ITS CONTROL...
This whole paper is likely to tell us that a high sodium diet, associated with a high urinary sodium excretion, increases BP, that in turn affects both albuminuria and the rate of CKD progression...no more or less!
On the 17th of September the New York Times published a well balanced account of the issue of kidney dysfunction in the growing elderly population, it was entitled:
Chronic Kidney Disease Can Be Dubious Diagnosis
and it highlighted the debate that rages amongst Nephrologists with on one hand those claiming an alarming rise in those affecetd by CKD; mostly the elderly population, and on the other hand those calling for moderation and consideration that such a high prevalence of "CKD" merely reflects the decline in kidney function with ageing and arguing against the medicalisation of old age...
The artilce received many congratulations and acclaims for its fair and balanced display of the two prevailing views.
The story doesnt stop here...with a fair and well reported medical item by a major newspaper of international repute and acclaim...
Pressure was brought to bear on the author of this excellent article by those who saw in the above title a bias...favoring those doubting the label of CKD in th eelderly population...leading her to change the title in subsequent editions to:
For Older Adults, Questioning a Diagnosis of Chronic Kidney Disease
whilst this is in itself surprising and disappointing, it highlights alarming facts:
1. The Press, even in the most advanced of democracies, gives in to lobbies and pressure...
2. The Press is not free to express its views and biases, unchecked by those who hold differing views...
3. The general and medical Press is hostage to pressure and lobbies that curtails its freedom of expression.
I though this was the domain of politics and political lobbies, this incident highlighted to me that medical reproting is equally hostage to pressure and gives in equally to lobbies and censure.
A VERY SAD DAY FOR MEDICAL REPORTING!
International guidelines adopted in 2012 make it seem that way. They define the disease in terms of how efficiently kidneys filter the waste from our blood, a measure called the glomerular filtration rate. Healthy young people commonly have G.F.R.s of about 120. A G.F.R. lower than 60 or another marker of kidney damage (such as protein in the urine) for more than three months means chronic kidney disease.
At which point, patients become scared. “When you’re told you have a disease, that’s a bad day,” said Dr. Ann O’Hare, a nephrologist at the University of Washington in Seattle who specializes in treating older adults. “Patients worry about dialysis, because that’s what they associate with kidney disease.”
Chronic kidney disease causes no symptoms until its later stages, and most seniors with the diagnosis are told they’re at Stage 3, of five — sudden, unwelcome news. Because Medicare uses these benchmarks for billing and reimbursement, they’ve become, in effect, the official definition of the disease for older Americans.
But wait a minute. Kidney function declines with age in almost everyone, and the proportion of older people with G.F.R. readings below 60 approaches 50 percent, studies have found. As the older adult population grows, the prevalence may rise even higher.
Yet the proportion of older people who will ever reach kidney failure, and thus need dialysis or a transplant, remains very low. People don’t turn to dialysis until their G.F.R. sinks much further, to about 10. In the great majority of older adults, that will never happen.
The lifetime risk of kidney failure in the United States is 3.6 percent for whites and 8 percent for African-Americans, one widely cited study found.
“Probably a majority of older patients we see have some degree of impaired renal function,” said Dr. Michael Steinman, a geriatrician at the University of California, San Francisco. “The chances are far and away that they’ll die of something else, and their kidneys will never be a problem.
“Why are we even thinking about this as a disease?”
Indeed, a small but spirited cadre of physicians and researchers are arguing — most recently in JAMA — that the guidelines should be recalibrated by age.
By using the same standards for everyone, ”We’re labeling and medicalizing and victimizing a substantial fraction of the elderly population,” said Dr. Richard Glassock, an author of the article and a nephrologist at the University of California, Los Angeles.
Instead, Dr. Glassock and others propose that in people older than 65, the diagnosis should require a G.F.R. reading less than 45. At that lower threshold, they estimate, a third to half of the chronic kidney disease diagnosed in older patients would suddenly disappear.
These patients should just be considered … old, the researchers say, with lower kidney function normal for their ages.
When it comes to kidney decline, Dr. O’Hare said, a G.F.R. below 60 would cause great concern in a 20-year-old. At older ages, “it’s a gray zone.”
Most G.F.R. readings that fall below 60 in older adults remain in the 45 to 59 range, considered a modest reduction in kidney function. Most of these seniors will not have protein in their urine or other evidence of kidney damage. “People are being told they have a condition and it doesn’t really mean anything,” Dr. O’Hare said.
In the same JAMA issue, though, another group of physician researcherswarned against changing the guidelines.
“Having chronic kidney disease increases the risk of death from any cause, but particularly cardiovascular disease,” a co-author, Dr. Andrew Levey, the chief of nephrology at Tufts Medical Center, said in an interview. “People with kidney disease shouldn’t be treated the same as people without it.”
Regarding kidney disease as part of normal aging offends researchers like Dr. Levey. They point out that although the relative risk of dying is actually higher in younger people with chronic kidney disease, the absolute risk — the numbers of people who die from it — is higher at older ages.
Moreover, they argue, an older person with low G.F.R. and protein in his urine (called proteinuria or albuminuria) can take some steps to reduce the risk of eventual kidney failure, even if that’s already extremely low. Certainblood pressure medications with tongue-tangling names may protect the kidneys, for instance, though their effect on older adults is also a matter of debate.
A diagnosis can also help patients avoid drugs that can harm kidneys, said Dr. Levey and the co-author Dr. Josef Coresh, an epidemiologist at Johns Hopkins Bloomberg School of Public Health. (Both were part of the working group that developed the guidelines.) Doctors can modify medication dosages and warn older patients away from drugs that can impair kidney function, like ibuprofen, certain injected antibiotics, and the contrast dyes used in CT scans.
Generally, though, what a doctor tells an older patient found to have chronic kidney disease is fairly standard counsel: Control your blood pressure, which exacerbates kidney disease and vice versa, and yourcholesterol. Manage your diabetes. Keep track of drugs.
“That’s just sensible, healthy living, whether you have kidney disease or not,” Dr. Glassock said. So he questions whether we should even call somewhat reduced kidney function at older ages a disease.
It may amount to more than semantics. Along with fears of sitting in a dialysis center three days a week for the rest of one’s life come the costs of additional tests, appointments and referrals to specialists. “It pulls people into further engagement with the health care system,” Dr. O’Hare said. Most older adults face plenty of that already.
Still, here’s the reality: Revising the international guidelines, a protracted and complicated undertaking, doesn’t appear to be in the cards. The definition we have is the one we’re going to have for years, maybe for good. Many older people are likely at some point to hear a physician say they have chronic kidney disease.
How should they respond?
No special screening is required to learn one’s glomerular filtration rate. It’s part of the common basic metabolic panel. Most of us have it in our records somewhere.
One thing the kidney disease combatants agree on is that a G.F.R. less than 60 should prompt a conversation, before any prescription or advice. Doctors need to put these numbers in perspective, to explain that kidneys age with the rest of us.
It makes sense to repeat the test to see if the G.F.R. remains stable or continues to fall; it also makes sense to test the urine for protein. Physicians can use risk predictors —some exist, more are coming — to help determine an individual’s odds of kidney failure.
That way, Dr. Levey said, “we’re identifying the patients at risk for the worst outcomes and reassuring the others.”
But reassurance should be by far the more common response, whether a physician uses the D-word or not.
“I don’t think this is something to lose sleep over,” Dr. O’Hare tells patients with modestly lower but stable G.F.R., and no other indications of kidney damage. “That’s often a huge relief.”
Those who argue that patients should be labelled as "DISEASED" to adjust medication dosage or to avoid another disease such as AKI...fly in the face of reality and commion sense.
Our job as doctors is to avoid and prevent diseases...NOT to mislabel people in the community as DISEASED...for the sake of PROTECTING THEM...
if this held true then, EVERYBODY OVER THE AGE OF 65 WOULD BE SOMEHOW "DISEASED"...weather it is lung "disease" due to reduced lung vital capacity..., heart "disease" due to reduced diastolic function.., Bone "disease" due to reduced bone mineral density, not to mention visual and hearing diseases...due to age-related reduced visual and hearing acuity...
IT IS HIGH TIME THE MEDICALISATION OF OLD AGE IS STOPPED NO MATTER HOW LUCRATIVE THIS MAY BE TO SOME...
CKD DEFINITION, CLASSIFICATION AND EPIDEMIOLOGY; IS IT ALL ABOUT MONEY...?!
In the US, labelling older people as suffering from CKD 3a (age related decline in kidney function) leads under the Medicare Advantage plans to enhanced reimbursements to large private medical groups; Defining and labelling older people as suffering from "CKD" leads under the HCC system to increased reimbursement.
All too often an older patient with years of stable eGFRs of let say 59ml/min gets suddenly labeled as “CKD stage 3a” to increase his healthcare provider's income...at the expense of burdening the patient with an unnecessary and unjustified diagnosis of "CKD".
THIS MUST STOP!
The CKD classification has to be revised to spare millions the mislabelling of "CKD" even if it costs millions to private healthcare providers in the US...
A new age-sensitive classification has to be adopted.
IT IS HIGH TIME WE STOP MIXING CKD AND BUSINESS...
5 year mortality predictors in 498 103 UK Biobank participants: a prospective population-based study.
To our knowledge, a systematic comparison of predictors of mortality in middle-aged to elderly individuals has not yet been done. We investigated predictors of mortality in UK Biobank participants during a 5 year period. We aimed to investigate the associations between most of the available measurements and 5 year all-cause and cause-specific mortality, and to develop and validate a prediction score for 5 year mortality using only self-reported information.
Participants were enrolled in the UK Biobank from April, 2007, to July, 2010, from 21 assessment centres across England, Wales, and Scotland with standardised procedures. In this prospective population-based study, we assessed sex-specific associations of 655 measurements of demographics, health, and lifestyle with all-cause mortality and six cause-specific mortality categories in UK Biobank participants using the Cox proportional hazard model. We excluded variables that were missing in more than 80% of the participants and all cardiorespiratory fitness test measurements because summary data were not available. Validation of the prediction score was done in participants enrolled at the Scottish centres. UK life tables and census information were used to calibrate the score to the overall UK population.
About 500 000 participants were included in the UK Biobank. We excluded participants with more than 80% variables missing (n=746). Of 498 103 UK Biobank participants included (54% of whom were women) aged 37-73 years, 8532 (39% of whom were women) died during a median follow-up of 4·9 years (IQR 4·33-5·22). Self-reported health (C-index including age 0·74 [95% CI 0·73-0·75]) was the strongest predictor of all-cause mortality in men and a previous cancer diagnosis (0·73 [0·72-0·74]) was the strongest predictor of all-cause mortality in women. When excluding individuals with major diseases or disorders (Charlson comorbidity index >0; n=355 043), measures of smoking habits were the strongest predictors of all-cause mortality. The prognostic score including 13 self-reported predictors for men and 11 for women achieved good discrimination (0·80 [0·77-0·83] for men and 0·79 [0·76-0·83] for women) and significantly outperformed the Charlson comorbidity index (p<0·0001 in men and p=0·0007 in women). A dedicated website allows the interactive exploration of all results along with calculation of individual risk through an online questionnaire.
Measures that can simply be obtained by questionnaires and without physical examination were the strongest predictors of all-cause mortality in the UK Biobank population. The prediction score we have developed accurately predicts 5 year all-cause mortality and can be used by individuals to improve health awareness, and by health professionals and organisations to identify high-risk individuals and guide public policy.
Knut and Alice Wallenberg Foundation and the Swedish Research Council.
This is one of the first report from the UK Biobank project including around 500,000 individual between 40-70 years followed up so far around 5 years. The participants provided health details through questionnaires, had a physical examination and gave bood and urine for biological measurements.
In this report the authors report on a Prediction Score for mortality derived from 13 self-reported predictors. In fact, all it shows is that if you ASK YOUR PATIENTS 4 SIMPLE QUESTIONS, you get most of the mortality prediction:
1. How old are you?...Age being the highest predictor of death...(surprise, surprise..!!!)
2. What gender?...men have a higher age-adjusted mortality than women...
3. Do you smoke? smoking is bad news...
4. Do you have difficulty walking?...if YES, thats bad news as you are not fit...
and thats it...
AGE + GENDER PREDICT ~70% of MORTALITY, the rest adds little!
Once more, that is the problem with mortality prediction scores: AGE+GENDER tells you most of what you need to know...
Lets hope the UK Biobank future results will prove more exciting...time will tell!
Despite the plethora of publications regarding kidney transplantation outcomes, immunosuppression remains remarkable similar in most centres. CNIs (usually tacrolimus), anti-metabolites (usually) MMF and steroids with IL2-receptor antagonism remaining the cornerstone of immunosuppression for most transplant centres. Of course there are variations on this (some centres maybe steroid free, others may use ATG induction) but broadly speaking graft outcomes are similar across most large transplant centres. Consequently there have been few interventions that have made any difference to graft outcomes in that last 10 years. Recently there has been increasing interest in donor interventions than can impact on graft outcomes - e.g. machine perfusion of kidneys from deceased donors has been shown to reduce delayed graft function (DGF -defined as the need for dialysis within the week after transplant) and possibly improve allograft function at one year.
In this weeks NEJM, Niemann and colleagues publish data looking at the effect of therapeutic hypothermia in patients transplanted in California and Nevada. In essence donors who had been declared brain dead according to neurological criteria were randomised to two target temperatures: hypothermia (34-35 C) or normothermia (36.5-37.5 C). Hypothermia was achieved either by not actively warming patients or through the use of ‘forced air-systems or passive cooling devices’ ( there is no further detail on what this actually is in practice).
The headline figures show that the trial was terminated early after the independent safety board saw a clear benefit of induced hypothermia. A total of 572 patients received a kidney from 370 donors. DGF developed in 28% of the hypothermia group and 39% of normothermia group - there was a significant difference (p=0.02). This was based on a multivariable analysis that accounted for variables that can influence DGF such as donor type (expanded vs standard-criteria), donor creatinine and age and cold ischaemia time. The beneficial effect of hypothermia was particularly striking in the expanded criteria donors (adjusted odds ratio 0.31;CI 0.15-0.68; p=0.003) whereas in the standard criteria group although hypothermia reduced DGF this did not reach statistical significance. The authors reasonably conclude that this may reflect the benefit of hypothermia is via mitigation of ischaemia-reperfusion injury.
As well as normothermia other statistically significant factors assocaied with an increased risk of DGF included donor age, cold ischaemia time, donor creatinine and donor age.
A few things worth pointing out. As the investigators could not control all donor variables it is worth noting that the cold ischaemia time in the hypothermia group was slightly (but significantly) less than in the normothermia group. This may of course skew the data in favour of hypothermia but it was accounted for in the multi-variate analysis. Furthermore although there were no safety signals, no long term data is presented so we don’t know whether this reduction in DGF translates into graft function at 1 year or any other longterm meaninful outcome. Finally there is little information presented on how hypothermia was achieved so I’m not quite clear how costly such an intervention would be.
In summary this is a really interesting study that suggests a relatively safe and presumably easy to deliver intervention (hypothermia) can have a meaningful impact graft outcomes particular in kidneys from expanded criteria donors. It will be interesting to see how quickly this intervention is taken up by the broader transplant community
THE WINNING RAMADAN BLOG BY Dr MOHAMED ESSAM: