IN the NEWS: End of Fenoldopam in prevention of AKI following CT surgery

Fenoldopam has been advocated in prior studies to prevent AKI following surgery: specially studied the most in cardiac surgery.  The most recent issue of JAMA gives us the first randomized multi center placebo controlled trial on use of fenoldopam in CT surgery patients for prevention of AKI. 

Key points:

This study assigned >600 patients to placebo or fenoldopam that were admitted to CT ICU following cardiac surgery with early AKI.  30 day follow up was done.

The primary outcome was need for RRT and mortality was the secondary outcome/ rate of hypotension during infusion.

Patient characteristics appeared equal. There seemed to be more patients with A fib in treatment arm, more pulm HTN and MI in control arm.

Types of surgeries were equal in both( CABG, MVR, AVR, TVR, aorta surgery, and others)

CKD stages based patients were equal in both.  There was 13 CKD IV patients in control  and 19 CKD IV patients in fenoldopam arm.  But majority of them initially had GFR >90. 

Conclusions: Among patients with AKI after CT surgery, fenoldopam infusion compared to placebo showed no benefit in need for RRT or 30 day mortality.

In addition, the infusion caused some harm and led to hypotension episodes compared to placebo arm. 

A prior study had shown similar findings from AJKD.

Is this the end of fenoldopam in prevention of AKI in CT surgery?  Largest study, multi centered and good power showing harm more than benefit. I think we have our answer.  

Full article

http://jama.jamanetwork.com/article.aspx?articleid=1910563

Consult Rounds: Dialysis in the Acute Brain Injury patient

Standard hemodialysis can increase cerebral water content and lead to edema. The pressure in the brain or ICP shouldn’t have too many influences.  There is strong buffer system in the brain but if that fails- then the ICP can increase rapidly.  It has been noted that even small subclinical cerebral edema that occurs in IHD can slowly raise the ICP.  Why is that and how does the BP and acidosis make this possible?

A review by Davenport on this topic suggests few cautions:

1.      Drops in blood pressure or intradialytic hypotension can lead to ICP rises( Figure 1 from the Davenport review)

2.      Big fluctuations in urea shifting

3.      Intracellular acidosis in the brain as CO2 is removed in dialysis leads to paradoxical Co2 absorption in the brain and causing imbalance.

4.      Exogenous substances can enter brain ( albumin) during brain injury as BBB is broken and lead to worsening edema.

Above Figure from Davenport article.

Some key points regarding what should be done then?

1.         All standard intermittent therapies, hemofiltration, hemodialysis, and hemodiafiltration, will lead to increased cerebral swelling, and if the patient has suffered a severe injury and is unconscious, then most centers would deem continuous renal replacement or hybrid therapies as the preferred treatment. ICPs have shown to remain much more preserved and constant in CRRT forms rather than IHD forms of therapy.

2.         Treatment should be designed to both slow down the rate of change of serum urea and osmolality, and to maintain cardiovascular stability( so perhaps daily IHD might be needed to minimize BUN shifts and prevent edema from getting worse)

3.         Given breakdown of BBB, avoid heparin based dialysis in this setting

4.         If doing HD, would do daily and use a lower BFR and cooler dialysate( 35C), smaller dialyzer and high Na bath(≤10 mEq/L above serum sodium), bicarb of 30meq/l , higher K and calcium baths).

5.         Some might suggest keeping a pre dialysis BUN low( less osmotic shifts – close to 30 and keep on supplemental oxygen.

Interestingly, regarding cooled dialysis- a recent JASN 2014 article sheds some light on that as well. In total, 73 patients on incident hemodialysis starting within 6 months were randomized to dialyze with a dialysate temperature of either 37°C or 0.5°C below the core body temperature and followed up for 1 year. Cooled dialysate improved hemodynamic tolerability, and changes in brain white matter were associated with hemodynamic instability and patients who dialyzed at 0.5°C below core body temperature exhibited complete protection against white matter changes at 1 year.

Preventing hypotension and rapid osmotic shifts is essentially what is required. 

Nephrology physiology videos by a fellow in training

 John Roberts, a nephrology fellow at Duke, recently produced a collection of short (10-15min) videos on renal physiology to simplify nephrology. They are "khan academy" type videos.  Medical students, residents and fellows can benefit from this basic physiology review. 

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
Action of Diuretics

TOPIC DISCUSSION: Crystalglobulinemia and prarproteins and the kidney

Crystalglobulin induced nephropathy is a known complication of paraproteinemias.  A recent review In JASN focuses on this presentation of kidney damage from paraproteins. Monoclonal proteins can also deposit in the kidney as crystals and cause tissue damage. This happens in cases of  light chain proximal tubulopathy, crystal-storing histiocytosis, and crystalglobulinemia. Crystalglobulinemia is a rare complication of multiple myeloma that results from crystallization of monoclonal proteins in the systemic vasculature, leading to vascular injury, thrombosis, and occlusion. One can observe diffuse rectangular, rhomboid and sharp needle shaped hyaline-like  crystals depositing in multiple organ systems, including the kidneys, myocardium, coronary arteries, tricuspid and  pulmonary valves, lungs, bone marrow and other organs. Usually, this is a quick and drastic leading to AKI, and ESRD. The reason why this happens is unclear.  It is possible that it related to the abnormal glycosylation of light chains and their interactions with albumin.  IgG k and IgG lambda chains both have been reported to be involved. Heavy chains have also been reported.  Both cases of MM and MGRS have been reported to be present with crystalglobulinemia.

Fig 1: Crystals in urinary space

Fig 2: Intracardiac crystalline deposits 

Telenephrology: Is this the answer?

Chronic kidney disease (CKD) is a common medical condition, affecting approximately 26 million adults in the U.S. Parallel to the increasing prevalence of CKD, a record number of patients now have end stage renal disease (ESRD). In 2007, 368 544 patients were on dialysis—a striking 54% increase from one decade earlier. Meanwhile, mortality rates for dialysis patients have declined, and approximately 775 000 people are expected to be alive with ESRD in the year 2020.

The nephrologist—a central provider for patients with CKD, ESRD, or kidney transplants—assumes a critical role in addressing the primary care needs of these patients, who tend to require frequent follow-ups. To meet the projected need for nephrologists inthe United States, fellowship programs should have produced an estimated 436new nephrologists each year since 2000. During the past decade, however, the American Board of Internal Medicine (ABIM) only certified an annual average of 382 nephrologists. This is despite the organizations many efforts and initiatives to recruit physicians to the field of nephrology.  If you do the math, the deficit is alarming.

Telemedicine is the practice of medicine using modern communication technologies when the physician and the patient are separated by distance. The modern communication technologies involved are nothing more intimidating than the telephone, e-mail and videoconferencing. Formally defined by the American Telemedicine Association, telemedicine is the use of medical information exchanged from one site to another via electronic communications to improve a patient’s clinical health status. It has been applied to other specialties, particularly neurology, radiology, psychiatry, ophthalmology, and high-risk obstetrics but nephrology has been a slow starter. Indeed, as a specialty, nephrology may be very suitable for this type of medicine. 

Nephrology is a visual and auditory rather than tactile subject – the skill is in recognizing diseases principally from a history, backed up by demonstrating basic physical signs in an examination and established by laboratory tests. So, if nephrologists based in urban centers can deal with renal patients in distant parts of the country, or even different countries, by means of communication technology, then the problem of reduced access to specialist care may be lessened, if not solved.

Post By Judy K. Tan MD

Mount Sinai Medical Center, New York, New York

Twice weekly, three times weekly or daily dialysis- where do we stand?

While observational trials had shown that there is much more benefit in daily dialysis (improved phos control, better HTN control, anemia), the FHN trial in NEJM proved some of the hunch that more dialysis was better in terms of cardiac remodeling and quality of life. This study compared in center patients to standard HD vs daily dialysis.  These were prevalent patients and not incident patients with some residual renal function.  

A recent editorial in AJKD sheds some light on residual renal function as an important predictor of renal survival.  The authors suggest that thrice weekly might rapidly decline renal function compared to perhaps twice a weekly dialysis sessions. But does that matter compared to cardiac outcomes.  The second FHN trial in Kidney international showed that the more intensive nocturnal HD group failed to show benefit compared to the three times a week dialysis.  Interestingly, this was in all incident patients with residual renal function.  The study found that the more intensive HD group lost residual renal function faster and in addition no difference in cardiac remodeling and quality of life. More vascular interventions were also performed in the more intensive arm. 

Finally, the most recent AJN article published this week, a single center study from China shows that twice a week HD preserves residual renal function.  They examined 85 HD patients; 30 of them were initiated with twice-weekly HD for 6 months or longer and 55 patients were started and maintained on thrice-weekly HD treatment. Then a subcohort study in 48 incident HD patients was implemented to assess the independent risk factors responsible for RKF decline during the first year of HD therapy. Clinical outcomes were the same in both groups. The multivariate analysis showed that factors such as the male gender, HD frequency, URR and intradialytic hypotension episode were associated with residual renal function loss. This study’s main outcome was residual renal function and not mortality.  It will be interesting to see and follow these patients to see the mortality data regarding this.

What does this lead us to believe? One size DOES NOT fit all. Perhaps initially, HD should be catered to preserving residual renal function and start slowly. Some patients might require twice a week HD, some three times a week and some perhaps more such as 4-6 times a week.  Should we be doing HD just as we do PD? When we calculate PD related CRCL, we use the residual renal function clearance and then the peritoneal clearance and add them to get to our expected/desired kt/v.  Why shouldn’t we do that in HD as well?  Incident patients might benefit from less intensive HD and prevalent patients who have lost residual renal function, might benefit from more intensive HD.  More studies are needed to answer these questions that the FHN and other studies have raise. 

Nephrology Crosswords: Obstetric nephrology

Check out the next installment of Nephrology Crosswords in Kidney International on
Obstetric nephrology