Friday, October 24, 2014

SEVERE CHRONIC HYPONATREMIA: A Pathophysiological Rumination (Part 3)


In my previous post concerning chronic severe hyponatremia, I explained how over corrections of serum sodium of large magnitude required a dilute large volume diuresis, often precipitated by resolution of a transient source of ADH secretion.  In this post I will discuss two phenomena which are particularly dangerous as they carry significant risk of producing large volume water diuresis.

1.  Subclinical Volume Depletion: As mentioned in my previous post, we noticed during our review of a large number of cases of severe hyponatremia treated with 3% saline that most of the patients whose serum sodium eventually overcorrected responded to small volumes of 3% saline as if they were volume depleted, with sudden emergence of water diuresis.  Interestingly, most of these patients were initially considered to be euvolemic by experienced nephrologists. 
This very interesting paper reviewed the literature concerning the value of physical examination in diagnosing volume depletion.  The conclusion, rather humbling, was that other than in cases of severe volume depletion our physical exam was quite inaccurate in diagnosing volume depletion.  This is especially concerning considering that establishing a patient's volume status forms the major decision point in the ubiquitous diagnostic algorithm for hyponatremia. 
According to the paper, reliable signs of volume depletion usually are visible with the loss of about 20% of the intravascular volume.  The ADH secretion and response to volume depletion starts with volume losses as low as 5-8% of the effective intravascular volume.  This implies that the patient may have significant ADH secretion, contributing to the relative excess water retention causing hyponatremia, while clinically appearing euvolemic.  It also means small volume bolus may switch off this ADH secretion, causing water diuresis and sudden rise in serum sodium.
Subclinical volume depletion as a contributor to hyponatremia should always be considered a possibility especially when starting therapy with 3% saline.

2.  Solute Depletion Hyponatremia: The so called "Tea and Toast Diet " hyponatremia and "Beer Potomania" are examples of solute depletion hyponatremia.  As nicely described by Dr. Berl, our solute intake limits our ability to excrete free water.  Even with a maximally dilute urine of around 50 mOsm/L, a person consuming a 300 mOsm/d diet can only excrete 6 L of urine (300/50=6).  Such a person will become hyponatremic with drinking more than 6 L of fluids a day because any water in excess of 6 L per day excretory capacity will be retained in the body.  It is important to note that this water retention is not due to ADH secretion.  ADH is often suppressed in such patients.  The renal danger of this pathophysiological mechanism is that whenever such patient is "presented" with solute (IV normal saline, high-protein meal which would generate BUN or even 3% saline!), without a high ADH level to prevent it, the added solute is used to rapidly excrete free water that has been "trapped" in the body. 
As an example, consider the case of the 26-year-old female that I briefly alluded to in the previous post.  She presented with a serum sodium of 108 mEq/L after being on an exclusively alcohol diet for the last 2 weeks.  She received 2 L of normal saline in the ER (154 mEq x2 = 308 mEq of Na). Using the Edelman equation (see figure) and an initial total body water of 32 L, if we do not account for urine output, that amount of added NaCl would have raised the serum sodium to about 111 mEq/L. But the actual rise of serum sodium was to 131 mEq/L in about 5 hours accompanied by almost 7 liters of dilute urine output. Her kidneys used the roughly 300 mEq of sodium in the NS bolus to excrete more than 6 liters of maximally dilute urine (300/50=6 L, remember the earlier calculation?) and almost perfectly accounts for the 23 mEq/L rise in serum sodium (by reducing the denominator, TBW).
This would have also happened if she had received the same amount of NaCl in the form of 3% saline as in such cases the volume of infusate matters less than the amount of solute delivered.
I hope this case illustrates how dangerous solute depletion hyponatremia can be and how easy it can be to precipitate an overcorrection of serum sodium in such patients. This raises a very important question: if even treatment with 3% saline is so unreliable in patients with chronic severe solute depletion hyponatremia, how can we safely treat such patients? That will be the subject of my next post.
In conclusion, subclinical volume depletion and solute depletion pose a particularly tricky challenge in the management of chronic hyponatremia as sudden rises in serum sodium level can happen rather easily in these patients with, what would otherwise seem to be, rather innocuous treatment with saline solutions.

Monday, October 20, 2014

SEVERE CHRONIC HYPONATREMIA: A Pathophysiological Rumination (Part 2)

I mentioned in the previous post that severe hyponatremia is multifactorial and that the contributing etiological factors in any given case may be transient and reversible.  In this post I would like to stress the importance of closely monitoring the urine output of the patient in addition to frequent monitoring of the plasma sodium.  Urine output is an extremely important clinical parameter that needs to be monitored closely but is not really mentioned in textbooks and handbooks.
Overcorrection by more than 12 mEq/L in 24 hours is not easy to achieve if the patient has a stable state of antidiuresis.  In an anuric patient with total body water of 32 L and a starting serum sodium of 108 mEq/L would require an infusion of more than 750 mL of 3% saline: a prescription not many of us would order.  In fact, during our review of cases of severe hyponatremia we found that the very popular Adrogue-Madias equation grossly underestimated the sodium correction in the majority of patients.  Most of the patients' sodium corrected far in excess of what the equation predicted.
The reason for that is that these equations treat the patients as if they were beakers that we can add sodium to and watch the plasma sodium rise as predicted.  However, unless the patient is on dialysis or in oliguric renal failure, they also lose free water in the urine, a fact that the equation does not take into consideration.  In fact, in our case series every patient that had an overcorrection of sodium beyond the desire goals, and had adequate documentation of ins and outs, had a documented large volume dilute diuresis.  Invariably, such large-volume water diuresis emerged suddenly as if an ADH switch was turned off, suggesting resolution of a transient source of ADH secretion.
While small, sudden increases in serum sodium are certainly possible with the addition of too much sodium to the system, very large and dangerous increases require simultaneous loss of free water.  A very illustrative case is one of a 26-year-old female I managed a couple of years ago.  She presented with a serum sodium of 108 mEq/L and received the inescapable 2 L of normal saline bolus in the ER and about 5 hours later her serum sodium was 131 mEq/L. With an estimated total body water of 32 L (and using the Edelman equation, see figure), if we considered her oliguric and try to account for the rise in serum sodium slowly on the basis of addition of sodium chloride to the system, we would require about 1.9 L of 3% saline to be infused in a 5 hour period!  However it is perfectly explained by the almost 7 L of water diuresis that emerged with the 2 L saline bolus.  More on this case in a later post.

In conclusion, very close monitoring of urine output should be an important and integral part of the early management of severe hyponatremia.  The sudden emergence of water diuresis is often the earliest sign of a rising serum sodium and should prompt a stat plasma sodium check. I have often relied upon a well documented q2hr urine output in ICU setting more so than the q2-4hr sodium levels which are fraught with the issue of delayed venipuncture and delays in reporting.

Monday, October 13, 2014

SEVERE CHRONIC HYPONATREMIA: A Pathophysiological Rumination (Part 1)

Severe chronic hyponatremia (<120 mEq/L) remains the #1 reason nephrologists lose sleep on call nights and rightly so.  The fear of overcorrection and the risk of central pontine myelinolysis (CPM) or osmotic demyelination syndrome (ODS), however uncommon they actually might be, has been drilled into our brains since the beginning of medical school.
In this post and the few that follow, I will attempt to address some aspects of chronic severe hyponatremia which have traditionally not been included when hyponatremia is taught or written about or have only recently been backed by some evidence and have not yet made their way into the textbooks. The recently released guidelines also did not address some of these issues. While this is not, by any means, an exhaustive discussion of the topic, I hope that these posts will not only help the readers enhance their understanding of the pathophysiology of severe hyponatremia but also help them manage it more effectively with a lot less stress and mental anguish.

The Schrier-Berl algorithm for diagnosis of hyponatremia has been used successfully for decades for teaching, and for reasoning through the differential diagnosis at the bedside.  It is an integral part of every medicine textbook and pocket handbook. It takes us to our diagnosis through 3 decision points: Plasma osmolarity, volume status and urine sodium sequentially.  While the algorithm holds true for the garden variety mild to moderate hyponatremia, it almost invariably breaks down in case with very severe hyponatremia.

During our extensive review of cases of severe hyponatremia treated with 3% saline, we seldom came across a case in which there was only one isolated cause for hyponatremia.  Rather, they were almost always two or more possible etiologies.  In addition, many patients that were initially considered to be euvolemic by experienced nephrologists, responded to 3% saline as if they were volume depleted.  Lastly, the clinical course of these patients during the hospitalization seemed to suggest many of these causes of inappropriate release of ADH were transient and reversible (SSRIs, acute nausea, postop state etc.). The patients' physiology seemed to change from time to time, with overcorrection of sodium invariably accompanied by large-volume water diuresis as these transient sources of ADH were "switched off."
It was, however, the paper by Sood et al that finally looked at the possible different etiologies for cases of severe hyponatremia as shown in the table (see image), which I consider the single most important table in all of recent hyponatremia literature.  They showed for the first time for multiple etiologies and processes are at play, some fixed and some transient in generating severe hyponatremia.

It is of paramount importance, that in the workup of hyponatremia, especially severe cases, we do not limit our reasoning through the differential diagnosis to comply with the algorithm that we have so familiar with but constantly look for multiple etiologies and transient causes of SIADH, especially subclinical volume depletion (low urinary sodium can be helpful here), as often it is the resolution of these causes that leads to the large-volume water diuresis and overcorrection. 
Posted by Hashim Mohmand

Wednesday, October 8, 2014

No more folic acid

Although tangetial to nephrology in some ways, I believe a recent study published in JAMA Internal Medicine has important lessons for anyone involved in clinical medicine and should make us think about the things that we do reflexively without really thinking about the reasons.

In 1998, the US government mandated that all cereals be fortified with folic acid. Prior to this point, folate deficiency was a real problem. Now, not so much. In fact, folate deficiency has pretty much disappeared as an important clinical problem. Researchers at the Beth Israel Hospital in Boston examined their clinical database to see whether or not this change had lead to any difference in the number of folic acid tests performed and if the number of low serum folate diagnoses was substantial. The results are fascinating. There was no change in the pattern of ordering this test over the 11 year period covered by the paper. In total, 84,000 tests were performed of which 47 (0.056%) were low. The cost if this test to the institution is $2, the charge is $128 while medicare reimburses $20 per test. Thus, the cost per positive result was $35,800.

It is clear based on this that routine testing of folic acid levels is inappropriate and yet it is still often ordered as a routine test in working up individuals with anemia, dementia and neuropathies. Alan Wu, in an accompanying editorial suggests that clinical laboratories should retire this test and in fact his institution, San Francisco General, now includes this as a send-out only that has to be clinically justified.

The reflexive ordering of laboratory and other tests is a problem that has only gotten worse with computerization. When I started working, as interns we had to write individual lab requests on paper and leave them on patient's wards. There was an explosion in testing when interns were finally able to order labs with just a click of a button. I wonder what tests in particular in nephrology we should be ridding ourselves of or at least ordering far less often?

Thursday, September 25, 2014

Renal Physiology PenCasts

Improving preclinical nephrology education during medical school is a hot topic in nephrology these days. John Roberts, a nephrology fellow at Duke, recently produced a collection of short (10-15min) videos on renal physiology in an effort to do just this. These videos are geared towards 1st year medical students and are meant to compliment other learning styles such as book reading, group learning or standard didactic lectures. Take a look at the videos and offer any comments or suggestions. These are fantastic videos that really break down the essence of basic renal physiology that is the foundation of our field. Kudos to John for taking on this project. They look great! Mike Berkoben of Duke Nephrology makes an appearance as well.

Tubular Transport 1 
Tubular Transport 2
Regulation of Body Fluid Osm 1 
Regulation of Body Fluid Osm 2 
Body Fluid Compartments: Regulation of ECFV 1 
Body Fluid Compartments: Regulation of ECFV 2 
Potassium 1
Potassium 2
Acid Base Physiology 1 
Acid Base Physiology 2 
Acid Base Physiology 3

Link to all of the videos

Tuesday, September 16, 2014

NephroCheck®—can we predict AKI in the ICU? And then what?

Nephrologists have been looking for sensitive biomarkers to predict AKI. Efforts have been made and the idea of “renal angina” was proposed by Goldstein and Chawla in 2010, but still there has been no reliable biomarker commercially available to detect AKI early enough. 
Well, the FDA has just approved a point-of-care biomarker assay, NephroCheck®, for predicting risk of AKI. Interestingly, none of the most studied biomarkers such as KIM1 and NGAL are included. NephroCheck® uses two urinary biomarkers : insulin-like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases (TIMP-2).

IGFBP7 and TIMP-2 were selected as biomarkers to predict AKI using a 522-patient cohort (median age 64, 91% Caucasian) of critically ill patients admitted with sepsis, shock, major surgery and trauma—though inclusion criteria differed based on the facilities (Crit Care 2013). Over 340 biomarkers were screened, including urine kidney injury molecule-1 (KIM-1), plasma and urine neutrophil gelatinase-associated lipocalin (NGAL), plasma cystatin-C, urine interleukin-18 (IL-18), urine pi-glutathione S-transferase (pi-GST) and urine liver fatty acid-binding protein (LFABP).

IGFBP7 and TIMP-2 are both inducers of G1 cell cycle arrest and showed the highest AUCs on the above cohort (0.76 and 0.79 respectively, and 0.80 when combined). The results were then validated using another 722-patient cohort, without evidence of AKI on admission. Primary outcome was AKI stage 2-3 (KDIGO) within 12-18 hours post-test. There was also another validation study published earlier this year (AJRCCM 2014), using 420 patient from 23 facilities in the US, demonstrating sensitivity of 92% (95% CI 85-98), and specificity of 46% (95% CI 41-52) with cut-off value of 0.3 (ng/ml)2/1000. AUC was 0.82 (0.76-0.88).
Although NephroCheck may have potential advantage to rapid response to developing AKI, still there is substantial limitations of the study including: heterogeneity of the validating cohorts, Caucasian racial predominance, focusing on septic AKI and reflecting more ischemic/hemodynamic-related AKI/ATN.
 So, what should we do next, based on the early detection/ risk prediction of AKI? What interventions or drugs could we use to prevent AKI development in those high-risk patients? Specific treatment strategies for AKI are now warranted for this biomarker to be in full use in the fight against AKI.
Figure from Crit Care 2013 paper: Proposed mechanistic involvement of the novel biomarkers in AKI.

Naoka Murakami

Monday, September 8, 2014

CJASN Activities

Two ASN-related activities to mention happening in the next couple of months. First, CJASN eJC will be hosting a twitter conversation about the recently published commentary "Training the Next Generation's Nephrology Workforce. This will be hosted by Amar Bansal, a fellow at UPenn who is the author of the article. It will take place on September 10th at 9pm and the hastag is #CJASNeJC.

The second event is a fellows luncheon at the ASN annual meeting on November 13th from 12.45 to 1.45pm. This is titled "Improving the journal club experience for fellows" and will be moderated by Drs Gary Curhan and David Goldfarb. An email will be sent in September/October to all registered fellows with the ASN.

Thursday, August 28, 2014

Kidney Organ Allocation in the USA - Upcoming Changes!

This is a short video describing the current and new policies regarding deceased donor kidney allocation in the USA. These policies may significantly affect certain groups of patients and physicians must be aware of those in order to best represent their patients. For more details, also check prior blog.

Link for the video here

Hypokalemic Periodic Paralysis

A recent renal consult I encountered was a Cantonese gentleman with a classical symptomatic history for Hypokalemic Periodic Paralysis (HPP). He presented with a serum K of 1.4 mmol/l and profound weakness. Initially beginning in his teenage years, he had intermittent attacks of weakness lasting hours and affecting proximal muscle groups. Emergency department admissions invariably revealed low serum K.
Many of us will know the classical features to look for in the history:
  • High risk Asian and Hispanic population groups, particularly males less than 20 years old.
  • High carbohydrate meals triggering insulin release or  B-adrenergic surge from exercise or volume depletion.
  • Thyrotoxicosis: A major subgroup of patients, usually men. The mechanism is thought to involve a combination of up regulation of Na-K-ATPase, loss of function of the inward potassium rectifying channel Kir2.6, and a feed forward effect in certain variants of the sulphonylurea receptor 1, culminating in dramatic intracellular potassium shifts. It is important to note is that rarely the paralytic episodes can predate the thyroid disease by many years.
The genetics of hypokalemic periodic paralysis have been discussed previously on Renal Fellow Network.

Management: More Questions than Answers
Acute management is relativity straightforward – administration of K, either IV or orally. Case control series demonstrate up to 70% of patients having rebound hyperkalemia of >5mmol/l if  KCl doses of over 90mmol/ are administered. Lower doses may potentially be used if concomitant B-blockade is deployed in conjunction. Oral KCl rescue is more suitable for home use.  As a rule of thumb, 40 to 60 mmol/l of oral  Kraises plasma potassium concentration by 1.0 to 1.5 mmol/L, and 135 to 160 mmol/l Kraises plasma potassium by 2.5 to 3.5 mmol/l.
Besides avoiding obvious environmental triggers, therapeutic interventions and prophylaxis are more unclear. Patients have normal total body potassium with no chronic GI or renal loss, thus the drop in serum levels is mediated via a transcellular shift. Despite this, prophylactic K supplementation remains a traditional cornerstone of therapy, although one would imagine a normally functioning cortical collecting duct should excrete this quite rapidly, particularly with chronic dosing regimens.
The “highest quality” of evidence comes from a Cochrane review of 3 very small studies, the largest examining the utility of dichlorphenamide, a carbonic anhydrase inhibitor, in 34 patients. Self-reported quality of life improved in 15 patients, and attack frequency dropped. This is in line with a more recent study in 2011 which quote a 50% improvement in symptoms in a larger group of patients on dichlorphenamide. This is unusual as the additional HCO3 in the collecting duct should increase intraluminal negative charge, and encourage potassium excretion, as should the volume depletion and increased RAAS activity. Furthermore, volume depletion could theoretically induce increase sympathetic output, worsening K loss. The most plausible explanation I found was a paper from 1975 suggesting the metabolic acidosis induced by the carbonic anhydrase inhibitor buffers the transcellular shift of K+.
Despite aldosterone levels being normal during attacks, reports suggest aldosterone antagonists may benefit patients as a second line therapy via their K+ retaining effects, although their action appears to be opposite to that of dichlorphenamide. It is curious these agents with supposed diametric effects on renal K handling both have positive effects on K balance in HPP.

The most intuitive treatment is B-blockade, demonstrated in a number of series to be effective, but almost always in those whose HPP occurs in association with thyrotoxicosis.

Authored by Eoin O'Sullivan

Sunday, August 24, 2014

mTOR Pathway in Anti-phospholipid Syndrome

Antiphospholipid syndrome (APS) is an autoimmune hypercoagulable disorder characterized by small-to-large vascular (both arterial and venous) thrombosis with end-organ damages, in presence of circulating antibodies against phospholipid binding proteins.

Kidney transplantation in patients with APS is challenging because  post-transplant thrombosis, vascular complications and requirement of anticoagulation during peripoperative period. Let’s start with a brief review of recent advances in transplantation in APS.

For post-transplant TMA due to recurrent APS nephropathy, Canaud et al. recently explored the use of eculizumab. Eculizumab, a humanized mAb that binds C5, prevents cleavage of C5 into C5a and C5b, thereby preventing generation of the membrane attack complex (MAC). At a molecular level, the pathogenesis of endothelial damage in APS is in part via complement activation; C5b-9 MAC deposition on endothelium, leading to cell lysis and/or activation of other proinflammatory pathways, so the use of eculizumab is reasonable. Three patients, maintained with steroids, CNI and MMF, were treated with eculizumab for posttransplant TMA with robust improvement of allograft functions after several doses, and all three patients were successfully withdrawn from maintenance eculizumab treatment after 3-12 months of initial dose. Interestingly, although biopsy showed improved TMA lesions, C5b-9 depositions were persistent for as long as 3 months as “foot prints”. The authors also noticed that eculizumab treatment did not prevent the chronic vascular lesions seen in 12-month protocol biopsies.

Preemptive use of eculizumab in kidney transplant in APS-related ESRD was also attempted in another case series. Three patients, two with CAPS (catastrophic APS), received 1,200 mg of Eculizumab on day 0, 900 mg on POD 1, and weekly thereafter until week 4. After week 5, they received 1200 mg every 2 week. Despite one  biopsy proven cellular rejection successfully treated with pulse steroid, graft function and survival was acceptable without recurrence of APS during follow-up of 6 months to 4 years. In the setting of no specific treatment other than systemic anticoagulation, eculizumab seems potentially promising treatment, however, the sufficient treatment length of this drug needs to be optimized, especially due to high cost. Also, there is no description of immunosuppressive regimen either for induction nor maintenance, and it is unclear these patients were on sirolimus or not.

 In a recent NEJM article, Canaud et al.  indicated the beneficial effect of sirolimus in proliferative vascular changes associated with APS and CAPS, which were not reversed by eculizumab in their previous study. They demonstrated that the chronic vascular changes in APS patients were induced by activation of mTORC via phosphorylation of Akt-S6K pathway, using immunohistochemistry of renal biopsy samples and in vitro signaling studies with HIMEC-1, a human microvascular endothelial cell line, as well as autopsy samples of CAPS. Furthermore, using a cohort of kidney transplant patients with APS (10 treated with steroids+sirolimus+purine inhibitor and 27 with steroids+CNI+purine inhibitor), their nested-case-control study demonstrated that posttransplant allograft functions were better preserved at 144 months post transplant in the sirolimus group compared with CNI group (7 of 10 vs 3 of 27 patients with functioning grafts) and this effect was observed only in patients with APS and not in patients without APS. Other variables including cold ischemia time and immunologic risk profile were comparable between sirolimus and CNI groups. Although this is a relatively small case-controlled study, the use of mTOR inhibitors for the prevention of APS post-transplant seems very promising.

Naoka Murakami

Thursday, August 21, 2014

Renal Function after Off- or On-Pump CABG: CORONARY Trial is next #NephJC

The next Nephrology online journal club (#NephJC) will discuss the results of the CORONARY Trial, presented at the late breaking session at the ASN and published this year in JAMA. The trial compared patients undergoing their first coronary artery bypass graft (CABG) surgery using an off- or on-pump technique. The main study published previously revealed no difference with respect to the composite outcome of 30-day mortality, myocardial infarction, stroke or acute kidney injury (AKI) requiring dialysis. The renal function trial was a prespecified substudy involving 2975 (of a total 4752) consecutive patients enrolled in CORONARY with baseline and post-operative serum creatinine data. The renal substudy patients had similar characteristics to the overall CORONARY population.

Outcomes of Interest:
  • Post-operative AKI was defined as a 50% increase in the serum creatinine concentration within 30 days of surgery (highest creatinine within 30 days was used).
  • Loss of renal function at 1 year = 20% loss in eGFR (using CKD-EPI).
  • Worldwide enrolment with 42% from Asia and the remainder mostly from Europe (21%) and the Americas (<1% were African American).
  • Baseline characteristics of note were a mean age of 68 years, BMI 27, >80% male, almost half were diabetic and a similar number of ‘urgent’ cases between the groups.
  • Almost a quarter had CKD (eGFR <60mls/min) and the mean eGFR was 74-75mls/min in the 2 groups.
  • There were 561 AKI events (median time of 2 days post-op to peak creatinine) with a reduced rate with off-pump (17.5%) V. on-pump (20.8%) surgery (adjusted RR 0.83 [CI 0.72-0.97]; p = 0.01).
  • Mean eGFR at 1 year was 72 mL/min with off-pump and 73 mL/min with on-pump.
  • No significant difference in loss of eGFR at 1 year between off-pump (17.1%) V. on-pump (15.3%) surgery (P = 0.23).
  • Those with CKD derived a greater benefit in reduced AKI with off-pump surgery but eGFR loss at 1 year remained insignificant.
  • Over 200 patients crossed over between the groups (evenly split) and results of the intention to treat were similar to as-treated analysis.
  • Multiple alternative definitions of AKI & loss of kidney function did not alter the main results.
Dialysis requiring AKI has detrimental effects on long-term kidney function. Less severe AKI is more common with major cardiac surgery (only just >1% had AKI requiring dialysis in the original CORONARY trial). It is less clear what effect these more subtle derangements have on long-term function. This study suggests that these ‘mild’ AKI events may not have much longer-term significance, contrary to observational studies [ref, ref]. As pointed out by the authors, this finding has implications for other interventions in mild AKI such as for contrast nephropathy. Does preventing a subtle GFR dip in this scenario have a long-term benefit? The study is limited somewhat by the unique situation studied in the trial (although cardiac surgery provides a very ‘convenient’ insult in which to study AKI). Also, we are relying on serum creatinine and all its limitation to assess kidney function. Moreover, not all eligible patients had creatinine values measured and single measurements and imputed values were often used for the analysis.

This study provides good evidence that off-pump CABG decreases the rate of non-severe AKI but that this does not appear to translate into better renal function at 1 year. When I first heard the results of this study at the ASN (a somewhat deflating session along with lots of other negative/inconclusive Nephrology studies), I was disappointed with the small magnitude of the AKI decrease with off-pump surgery. I had expected the toxic milieu associated with on-pump surgery (aortic cross clamping, exposure to bypass circuit, changes in blood pulsatility) to be associated with much higher rates of AKI, compared to off-pump. The study also questions my preheld assumption that acute drops in GFR, from mild to severe, had a continuous magnitude of impact on long term renal function.
Feel free to get involved by joining the live Twitter chat on Tuesday 26th August at 9pm Eastern using #NephJC. Also, check out for more background and past journal clubs.