Tuesday, November 30, 2010

CONSULT ROUNDS: Propofol Infusion Syndrome

Why does a nephrologist care about Propofol infusion syndrome (PRIS)?
Its an important entity for us to know. It is a known cause of Rhabdomyolysis and hence AKI and also causes lactic acidosis. PRIS is a rare but fatal syndrome described in adults and children who get high dose propofol infusion(usually for CNS injury sedation or alcoholics). Usually >48 hours of infusion of 5mg/kg or higher.
Classic features: Rhabdomyolysis, hyperkalemia, hypocalcemia, elevated troponin, severe metabolic lactic acidosis, renal injury, high Triglycerides and features of SIRS without other real findings of Sepsis.  Usually these patients are neurological injuries and getting catecholamines as well or steroids. Tmax could be very high in such cases sometimes in 106-107F range. Cardiac features can include Bradycardia, hypotension, PEA, VT, Atrial Fibrillation and SVTs. Some of the cases described have been with concurrent severe infection as well. What happens at cellular level- this drug impairs free fatty acid utilization and mitochondrial activity leading to these findings?
In summary: Steroids, catecholamines and propofol alter energy production alter the SIRS and MODS syndrome and that leads to worsening rhabdomyolysis and cardiac failure that then leads to metabolic acidosis and acute renal injury. Cerebral Microdialysis can monitor brain energy related metabolites including lactate and pyruvate during head injury.  The cerebral lactate to pyruvate ratio is increased in PRIS. One way to monitor this syndrome.
Some people think that the term PRIS might be misleading and really it is a pathophysiologic state.  Critical illness of any kind is the priming factor and the propofol along with steroids or pressors can be triggering factors.  So really the name critical illness cardiac, renal failure and rhabdomyolysis associated with high dose propofol, steroids or pressors seems more appropriate.
In such cases where this risk is high, best is to use a different agent for sedation and remove propofol from the culprit.
Ref: 

Sirolimus - The negative aspects

A recent article in Kidney International discusses the negative and positive aspects of this interesting drug- sirolimus, mTOr inhibitor.  Initially designed to fight renal cancer, fast caught on to treat rejection and be used as an immunosuppression.
1. Six trials so far have randomized sirolimus vs a calcineurin inhibitor that were mentioned in this article. They all had more acute rejection episodes with sirolimus. So graft survival is a concern.
2. Renal toxicity has been described- from TMA to collapsing FSGS and severe proteinuria making it not as promising as CNI. But CNI have a more chronic toxicity to the kidney
3. Dyslipidemia has been noted as well more with this agent. - close to 60% of the patients getting mTor in clinical trials required lipid lowering agents
4. NODAT was also noted to be higher in this group; 25% more chance than CNI
5. Wound healing:- preventing the surgical wound healing or in future if patients need other surgeries makes it tough.
6. Other- mouth ulcers, myelosuppresion and infertility were more common in this agent as well.
7. Finally, they mention the new findings lately described pulmonary toxicities that are leading to a restrictive disease in the lung.

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/20703217

Monday, November 29, 2010

Nephsap review: Fluids Electrolytes

Interesting thing we learned at our Nephsap about why hypomagnesemia causing hypokalemia
1. Intracellular Mg has inhibitory effects on the K secretion of ROMK channels in the distal nephron.
2. A decrease in Intracellular Mg will release this inhibitory effect and cause Renal K excretion.
3. Also Low Mg can lead to increase distal Na delivery and increased aldo as well and K excretion increases.

Tuesday, November 23, 2010

CLINICAL CASE 29, ANSWERS AND SUMMARY

Which one of these is the most common renal manifestation of the drug "sunitinib"( Tyrosine kinase inhibitor)?

MPGN
  2 (6%)
TMA
  16 (48%)
FSGS
  4 (12%)
AIN
  5 (15%)
ATN
  6 (18%)




Most of you got it right. Dr.Tamim Naber actually gave out the answer in the last post on Onco Nephrology. The Tyrosine Kinase inhibitors have been lately the life saving drugs in kidney cancer. The outcomes with these agents are really good. Since they act downstream of VEGF, there side effects will be similar to the side effects of Anti VEGF agents or " like pre eclampsia".  Hence the most common pathology and clinical finding that we encounter is TMA. Cases of Nephrotic syndrome without biopsy have been described.  AIN has also been shown by biopsy proven cases. Initially, you see HTN, with some non nephrotic proteinuria, slightly low platelets, elevated LDH, lower than usual haptoglobin and slight increase in Crt.  Its not a full blown TTP or HUS but rather a spectrum of TMA as the constellation of findings.

Ref:


Monday, November 22, 2010

ASN 2010 - Live update: "Onco Nephrology"

Onco Nephrology is one of the many interesting fields in nephrology that's growing; as treatment becomes more sophisticated and efficient, so do the renal complications. Key points are: "Dr Larson, R., Glezerman, I"

1- Tumor Lysis Syndrome "TLS":
-Expected within 3 days before and 7 days after starting therapy
-High risk factors to develop TLS: Highly proliferative tumors (ALL, AML, NHL, lymphoblastic or Burkhitt's lymphoma), high tumor load, and those tumors most susceptible to therapy.
-Low risk for TLS: Solid tumors in general, MM, AML, CLL, and Hodgkin's
-Best management is prevention with hydration "Maintain U/O 150-200 ml/hr", Close F/U for complications
-Bicarb shown not much helpful and it carries many potential complications including increase chance for phosphate to precipitate in tubules in the alkaline media. Also, Bicarb can increase total body volume "risk for CHF". Best Hydration fluid is 0.9% NS
-start allopurinol early before therapy.
-If uric acid already high, then Rasburicase is indicated "absolute contra-indicated in G6PD!"
Kayexalate for hyperkalemia "remember: 1gm kayexalate binds 1meq of K+"

2-Tubulo-interstitial disease "2ry to chemotherapy":
a- Cisplatin:
-Dose dependent, highly concentrated in urine
-causes: non-oliguric bland urine, SIADH, HUS, salt wasting, low Mg and high Na in Urine electrolytes analysis!
-Before starting cisplatin, make sure patient is euvolemc and normal GFR

b- I-Phosphamide:
-Dose dependent, and children 3-5 years are more susceptible!
-can develop CKd in up to 50% of cases of AKI
-Causes proximal tubular injury/Fanconi's syndrome

c-Methotrexate:
-95% excreted in urine
-AKI due to crystal deposits/ tubular obstruction, and usually non-oliguric
-treatment: maintain U/O >3 L/day, urine PH >6.5. Leucovorin rescue therapy showed benefit

3- Glomerular toxicity:
a- Gemcitabine:
-can cause Thrombotic Micro Angiopathic syndrome "TMA", as well as worsening HTN
-No evidence for benefit of using plasma exchange therapy for TMA here. Best is withdrawing therapy.

b- Anti VEGF therapy "Sunitinib, Bivacizumab, etc.."
-TMA, proteinurea "some develops nephrotic syndrome", HTN
-AIN; been described by Dr Jhaveri, Kenar in his case series review of a single center experience of 3 cases developed AIN after introducing Sunitinib.

c- Metamycin
-Dose dependent TMA "20% develops TMA for dose >100mg/m2 in contrast to 1% only for dose<50mg/m2!"

Video: The Treatment of Resistant Nephrotic Syndrome with Acthar Gel (ACTH) - Renal and Urology News

Video: The Treatment of Resistant Nephrotic Syndrome with Acthar Gel (ACTH) - Renal and Urology News

ASN 2010 Live Update - Late Breaking Trials

Please refer to Nephrology now for this excellent summary of late breakers!
http://www.nephrologynow.com/publications/asn-2010-late-breaking-clinical-trial-results-sharp-preclot-more

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