Clinical Case 68 : Answers and Summary

67 Y OLD MALE POST CABG -NOTED TO HAVE A SERUM CREATININE OF 1.4MG/DL. HIS SERUM CREATININE PRE-OP WAS 1.0MG/DL. HIS RENAL FUNCTION RESOLVES TO BASELINE AFTER 2 DAYS. HIS MORTALITY IS....

The three surgical procedures with highest renal injury risk are: cardiac surgery, AAA and post obstructive jaundice gall bladder operation. Incidence of AKI ranges from 1-30% in patients with cardiac surgery and typical CABG is around 2.5%, valvular surgery 2.8% and both combined is 4.6% and risk increases in each category with AKI with need for dialysis. One study showed that even a small minute change in serum creatinine during the post op period after cardiac surgery, increased the mortality significantly. 

Consult Rounds: Zoledronic Acid and Kidney Diseases

1. Bisphosphonates, in particular zoledronate(ZA), have been associated with renal toxicity manifested as deterioration in renal function and potential renal failure. Biopsy findings have suggested ATN. Pamidronate on the other hand leads to a more glomerular pathology namely collapsing FSGS. 
2.  In clinical trials, the risk for renal function deterioration was significantly increased in patients receiving ZA infusion over 5 minutes compared with those receiving the same dose over 15 minutes. An abstract presented at ASCO found via an FDA AERS,  480 cases of bisphosphonate-associated acute kidney injury in cancer patients. Patients were mostly female 298 (56%), mean age 66 with most common cancer being myeloma. Associated agents included ZA (n=411, 87.5%), pamidronate (n=8, 17%), and alendronate (n=36, 2%). 
3. The American Society ofClinical Oncology 2007 Clinical Practice Guideline Update recommends that pamidronate (90mg over no less than 2h) and zoledronate (4mg over 15min) be employed for patients with normal kidney function. In patients with mild-to-moderate kidney disease (estimated CrCl 30-60cc/min), the dose of zoledronate should be reduced with no change in pamidronate, although the committee suggests that clinicians 'consider reducing the initial dose of pamidronate'. For more severe kidney disease (estimated CrCl <30cc/min), zoledronate is not recommended whereas the infusion time for pamidronate should be increased to 4-6h, again with a consideration for reducing the dose. Serum creatinine should be monitored before each dose of bisphosphonate and the drug withheld in patients who develop an otherwise unexplained increase in serum creatinine concentration. 
4. A case of Fanconi syndrome has also been described in ZA use. 

IN the NEWS: Peginesatide for Anemia of Kidney Diseases( PEARLS and EMERALDS)

Anemia treatment in both CKD patients and ESRD patients is challenging. Partial correction is what is recommended at this point. In the past decade, we have seen the rise of erythropoietin and darbopoietin as the major agents used to help manage this condition. Peginesatide was FDA approved in 2012 for use of anemia of kidney disease in dialysis patients. It is a "epomimetic" agents as the authors of the recent four trials published in NEJM suggest. Perhaps a "sensipar" of the anemia world.
Four trails and two manuscripts published in the same issue of Jan 2013 in NEJM this week re the use of this agent in anemia of both ESRD and CKD patients.

Major points: 
1. PEARL 1 and 2( use of this agent randomized comparison to darbopoietin) in CKD patients and EMERALD 1 and 2( use of this agent randomized comparison to erythropoietin) in ESRD patients.
2. Both studies showed non inferiority in terms of Hgb control of 10-12 goal as set by the investigators.
3. Cardiovascular end points of MI, Stroke and other cardiac outcomes were similar in both groups in the ESRD study( EMERALD)
4. In the CKD study( PEARL), there were more significant cardiovascular events in the peginesatide arm. 
5. AKI and unexplained back pain was also noted more in the CKD group peginesatide arm.
6. Neither the two articles nor the editorial could explain the reason for the increased cardiac events or AKI or back pain with the agent( hgb levels were similar and doses in HD were higher than CKD patients)
7. Benefits of using this agent:- once a month as oppose to more frequent dosing in HD patients
8. Caution: new agent, cost and at this point perhaps not recommended in CKD patients.

When you pubmed the drug name " peginesatide" only 27 articles appear ( 2 are listed above). What do they say regarding this agent? One question that comes up is regarding the clearance, distribution and metabolism of this agent. It seems that pharmcology related studies suggest that this agent is cleared via the kidneys and primarily localized to the hematopoetic sites as concentrations of this agent build up. The molecule is 45kDa molecular weight and low volume of distribution. The mean half-life is 25.0 ± 7.6 hours following intravenous administration and 53.0 ± 17.7 hours following subcutaneous administration in healthy subjects. The mean half-life in dialysis patients is 47.9 ± 16.5 hours following intravenous administration. Mean systemic clearance is 0.5 ± 0.2 mL/hr·kg and mean volume of distribution is 34.9 ± 13.8 mL/kg following intravenous administration in dialysis patients. No accumulation is observed following administration every 4 weeks following intravenous or subcutaneous administration( source: Rxlist.com). The pharmacokinetics of peginesatide in patients with CKD on dialysis are not altered by age, gender or race based on population pharmacokinetic analyses. There is something about dialysis or ESRD that less likely balances out the negative effects of this agent found in CKD patients in terms of cardiovascular mortality. 

New Nephrology Journal with cases to learn from images

The Open Urology and Nephrology Journal(TOUNJ) has an entire section on "Learning from Images"- all open access.

http://benthamscience.com/open/tounj/articles/V005/28TOUNJ.pdf

http://benthamscience.com/open/tounj/articles/V005/33TOUNJ.pdf

http://benthamscience.com/open/tounj/articles/V005/48TOUNJ.pdf

http://benthamscience.com/open/tounj/articles/V005/50TOUNJ.pdf

Urine dipstick screening

Early awareness of chronic kidney disease and prevention strategies have led to the mass screening at many places of urine dipstick for albuminuria in the general population. While in diabetics and hypertensives, this might be a very prudent approach, does mass screening really change outcomes? A recent commentary in CJASN discusses the screening concerns from a primary care's perspective. Some key points the authors make are:
1. Based on what a good screening test should be, urine dipstick doesn't cut it. The seven criteria for a good screening test are: target disease is prevalent, morbid; the screening test has to be low risk, cost effective and accurate and acceptable to patients; and we should have the ability to change the outcomes.
2. Many false positives are generate requiring not required follow ups ( especially in a time when we might not have that many nephrologists in near future)
3. Interestingly, are we really changing outcomes. Are we preventing them from getting to ESRD?

This might be a tide changer for many but some points they make are critical to look at. The threshold for screening needs to be higher ( DM, HTN, FMHx, edema - anything that raises the possibility of proteinuria) but as a routine screen for unselected people with no identified risk, the test (which is semi-quantitative and variable at best) probably cause more problems than it solves.  Generating inappropriate work up and referrals from a positive dipstick might be interesting to look at closely. Indication is most important in most cases.

International Conference on Glomerular Diseases

We are hosting an international conference on glomerular diseases(ISN and NKF endorsed) as part of our division with exceptional speakers. All interested in learning about the conference and to register, can see the entire brochure online at the listed website of NSLIJ CME. Online registration is offered.

An International Update on Glomerular Diseases

Saturday, April 27, 2013

North Shore University Hospital

Rust Auditorium

300 Community Drive

Manhasset, NY 11030

Program of the Day | April 27, 2013 • 7:30 am - 4:00 pm
7:30 am Registration, Continental Breakfast and Exhibitors
8:00 am Welcome and Introduction to Glomerular Diseases
Kenar D. Jhaveri, MD and
Steven Fishbane, MD
8:15 am Minimal Change Disease and FSGS: An Update
Daniel Cattran, MD
8:45 am Clinical Approach to Membranous Nephropathy
Claudio Ponticelli, MD
9:45 am MPGN: The New Classification and Emergence of C3 Nephropathy
Naveed Masani, MD
10:15 am BREAK AND EXHIBITORS
10:30 am HIV Associated Glomerular Diseases
Pravin C. Singhal, MD
11:00 am Treatment of ANCA Associated Vasculitis
Fernando Fervenza, MD, PhD
11:30 am Cancer and Glomerular Diseases
Hitesh H. Shah, MD
12:00 pm LUNCH
1:00 pm Lupus Nephritis: Lessons Learned From Clinical Trials
Richard Furie, MD
1:30 pm Paraproteins and Glomerular Disease
Kenar D. Jhaveri, MD
2:00 pm New Diagnostic Tests and Therapies of IgA Nephropathy
Gerald Appel, MD
2:30 pm Pathology-Based Case Discussion
Glen Markowitz, MD and Panel
4:00 pm Closing Remarks and Adjourn
Kenar D. Jhaveri, MD and Steven Fishbane, MD

Consult Rounds:Acute Anuria

What is your differential diagnosis when you have anuria?

An article in NEJM in the 1990s mentioned that when there is acute renal injury with anuria, obstruction has to be ruled out. Once that is ruled out, acute cortical necrosis or necrotizing glomerular nephritis are the more likely culprits. An editorial in the same issue by Goodkin et al suggested that acute tubular necrosis and vascular complications should be highly considered in the differential diagnosis. The authors replied back suggesting that ATN should rarely present with no urine output and anuria.  Clearly, acute cortical necrosis, obstruction, and renal vein thrombosis( bilateral) in some cases and renal arterial occlusions/tears ( sometimes seen in solitary kidneys and transplant kidneys more) might be causes high on the differential. Severe ATN and AIN have been found to have anuric AKI and perhaps cases of crystalluria as well. PAN as been noted to present such ways as well. Finally, papillary necrosis is another rare finding associated with anuria. 

There is an interesting condition called reflex anuria that occurs following certain surgeries. It is defined as cessation of urine output due to irritation of one or both kidneys due to trauma to painful stimuli leading to vasoconstriction. No obvious obstruction is found but ureteric manipulation was done perhaps in pelvic surgery. Its due to arterial vasospasm and ureteral spasm.

In general, Anuric renal disease: think obstruction; vascular catastrophe and cortical necrosis as the three most likely causes. 

ISN Education: New frontier

Surfing via ISN website, ISN education site is truly amazing now and has some features that are very educational.

The highlights are:
Guidelines KDIGO all in one area.
Editor's picks from KI and Nature Nephrology

Great beginning and more comprehensive.

NephSap: Onco-nephrology

This month, the ASN Nephsap is on my favorite topic of "onco-nephrology". Interestingly, its a nice case based approach with a lot of pictures. It highlights AKI in cancer patients, AKI with HSCT diseases and glomerular diseases with GVHD and HSCT, TMA and ends with chemotherapy in cancer patients and dosing in CKD and ESRD. Electrolyte disorders has been also discussed. Have a look at the entire nephsap, worth a complete read and much easier to read than other nephsaps. An editorial in JASN also summarizes this rising field in nephrology.

Nephrology match update 2013

The fellowship match this year was tough. Many centers didn't get their spots filled. 148 centers participate in match, 23% not filled this year. There are 400 positions in match, 11% did not fill.
25% were US medical graduates that matched, and most of the remainder are all international medical graduates. Interestingly, 6% USMG did not match. A podcast from Dr Berns on medscape shares his concern from one of the largest fellowship programs in the country. A twitter feed started by Dr.Topf has sparked some discussion.

Clearly, this is a problem in many fields in medicine and we are one part of the bigger puzzle. While the workforce committee of the ASN is working on trying to come up with ways to increase interest in nephrology, what do you all think? What are your suggestions- please share and comment on how we can get more of the medical students and residents interested.

Clinical Case 67: Answers and Summary

WHICH TRANSPLANTED ORGAN HAD THE FIRST EVER CONSENSUS CLASSIFICATION ON ORGAN REJECTION AND PATHOLOGY ?

Pancreas

  0 (0%)

Kidney

  15 (65%)

 

Heart

  2 (8%)

 

Lung

  1 (4%)

 

Liver

  1 (4%)

 

Skin

  4 (17%)

 

Most of you said "Kidney". Perhaps we shouldn't be that "nephrocentric". In a recent history related paper in Kidney International, Dr.Kim Solez et al discuss the history of the Banff classification and how it came about. 

The need was as early as 1991 when the classification began.  Kidney transplant pathology had no mentors and no classifications. The first consensus guidelines that came for any organ was heart allograft rejection and that served as a model for the Banff Kidney transplant classification.  There began the history of pathology behind the kidney transplant.  So the historically accurate answer is the "heart". 

ESRD and Solid tumors

There is some data that certain cancers have a higher rate in ESRD patients. The largest series that was studied was a cohort of 831,804 patients. 

The highest risks are observed in

Kidney Cancer

Bladder Cancer

Thyroid Cancer

and other endocrine cancers.

Suggested mechanisms: Viral etiology from underlying immunosuppressed state as being ESRD. 

Acquired cystic disease perhaps leads to the increased risk of renal cancer

Loss of renal function or having kidney disease was also proposed as a mechanism( inflammation?)

Renal List serve- what it taught us as educators?

As a call for the workforce committee at ASN, a renal educators list serve was started. A survey was conducted via the list serve to the pre clinical kidney physiology and pathophysiology courses at US medical schools re methods of teaching, content and resources and in addition also how valuable the "educator" felt re their teaching versus their publications in terms of their medical school.
Some interesting findings:
1. Most of these educators were nephrologists compared to physiologists
2. 60% of course directors noted that their lectures were videotaped resulting in decreased pupils showing up to class.
3. Most common resource used: Audience response system, followed by others such as flash animations, virtual microscopy and simulation centers and others
4. NONE used social media( hard to believe)
5. Close to 70% received no full time equivalent for their efforts and 50% received no renumeration.
6. Most common method used was small groups problem based learning.
7. The most common textbook preferred by educators was Rennke and Denker's Renal Pathophysiology.
8. Harrison's came on the bottom of the list ( no kidding).
9. Most students found Water homeostasis, acid base disorders and glomerular diseases topics most difficult.
10. The renal list serve for educators is serving as a major communication tool to enhance tools and share tools with each other to improve the medical school experience.

Check out the full article at CJASN 

This is valuable information but what will be even more important will be getting more feedback from students as to what they find to be the most effective teaching methods for renal pathophysiology. No course director used social media to facilitate learning is an interesting finding in medical student education. While social media has risen in post graduate education in nephrology, there is still room for change in undergraduate medical education. 

IV contrast medium and ESRD

Radiologist: Please arrange for nephrology to comment on allowing us to give IV contrast to this dialysis patient. Right after the CT with IV contrast, dialysis has to be arranged.
Nephrology fellow: Why? the patient is anuric and what's the data on volume overload and needing of emergent dialysis after IV contrast dye.
Radiologist: Hmmm, good question. Lets look at it together.
Nephrology fellow: Look at this, its from the American College of Radiology Drug and Contrast Media 2012 update. 
"Renal Dialysis Patients and the Use of Iodinated Contrast Medium"
Patients with anuric end-stage chronic kidney disease can receive intravascular iodinated contrast medium without risk of further renal damage because their kidneys are no longer functioning. However, there is a theoretical risk of converting an oliguric dialysis patient to an anuric dialysis patient by exposing him or her to intravascular iodinated contrast medium. This remains speculative, as there are no conclusive outcome data in oliguric dialysis patients in this setting.
Patients receiving dialysis are also at theoretical risk from the osmotic load imposed by intravascular iodinated contrast medium because they cannot clear the excess intravascular volume. This osmotic load can theoretically result in pulmonary edema and anasarca. To mitigate this possible risk, contrast medium dosing should be as low as necessary to achieve a diagnostic result (as in all patients). However, complications were not observed in a study of dialysis patients who received intravascular nonionic iodinated contrast medium, though the number of patients was small.
Contrast agents are not protein-bound, have relatively low molecular weights, and are readily cleared by dialysis. Unless an unusually large volume of contrast medium is administered or there is substantial underlying cardiac dysfunction, there is no need for urgent dialysis after intravascular iodinated contrast medium administration.

Radiologist: I guess we rest that case.
Nephrology fellow: The guidelines by ACR have good information on MRI and CT scan and AKI and ESRD patients.