Viral infections and the kidney

Hepatitis C and the kidney

Thanks to Dr. David Frost and Team 1 for presenting an interesting case in morning report today:

We discussed hepatitis C, and the various mechanisms of acute kidney injury specific to the infection. 

Our case had a sub-acute course of 6 weeks duration in which the creatinine increased from a baseline of 69 to 677 on the day of presentation.

We also discussed the importance of the physical exam, making sure to search for findings suggestive of fluid overload, which may push you towards dialysis, and also looking for specific findings of cryoglobulinemia (palpable purpura).  In any patient with acute renal failure, searching for findings that might lead to urgent dialysis is of high priority and so listening for pericardial rubs, and looking for signs of uremic encephalopathy (asterixis, decreased LOC) is important.

Investigations:

The initial investigations showed a normocytic anemia.  There was a non-anion gap metabolic acidosis with a normal potassium.  The liver enzymes and function tests were normal.  The blood film, looking for findings of HHS or TTP, did not show any schistocytes.

The urinalysis, also known as the physical exam of the kidney, showed 3+ protein, trace blood, and the microscopy showed heme-granular casts.  The urine sodium was 24.  The abdominal ultrasound did not show any hydronephrosis or ascites, and the kidneys were normal in size.

 

Viral infections and the kidney: HIV, hepatitis B, and hepatitis C. Appel, G. Cleveland Clinic Journal of Medicine. Volume 74. May 2007.

Discussion:

This interesting case brought up a differential diagnosis that is not commonly encountered, but general internists should have some idea of how to approach it, mainly the various renal manifestations of viral infections.

Many viruses can cause renal impairment, most notably HIV (HIVAN), Hepatitis B -membranous glomerulonephritis (GN), and Hepatitis C which causes a membranoproliferative GN (MPGN).

Viruses can damage the kidney through different mechanisms including immune complex deposition such as in the case of cryoglobulinemia, through direct cytotoxic effects, and also as a result of the antiviral medications themselves.

Hepatitis C and the kidney:

In the case of Hepatitis C, possibilities included MPGN, cryoglobulinemia, adverse effects of the medications, and in patients with cirrhosis then hepatorenal syndrome.

The treatment of MPGN related to cryoglobulinemia associated with Hepatitis C often involves plasmapheresis (PLEX) to remove the cryoglobulins, immunomodulatory medications (steroids), and treatment for the Hepatitis C virus itself (interferon, ribavirin).

As Dr. Frost nicely pointed out, the time honoured approach of pre-renal, renal, post-renal with regards to the diagnosis and management of acute kidney injury almost never fails.  I must admit, I was taught this approach by Dr. J. Bargman as a 2nd year medical student.  I use it to this day, and I believe it will still be taught well off into the future.

Please see the excellent paper below, which discusses various viruses and their effects on the kidney:

Reference:

Viral infections and the kidney: HIV, hepatitis B, and hepatitis C. Appel, G. Cleveland Clinic Journal of Medicine. Volume 74. May 2007.

Endocrine Morning Report - Euglycemic DKA in pregnancy

A devastating complication of pregnancy in type I diabetics

A special thank you to Dr. Robert Silver for leading our discussion of the case.

           Today we discussed an interesting case of a 29 year old G1P0 female who presented at 32 weeks gestation with a chief complaint of shortness of breath.

On her third day of admission in hospital, she developed worsening of her symptoms and her respiratory rate increased to 40 breaths per minute, with a normal oxygen saturation (98%) on room air.

Her capillary blood glucose registered a blood sugar of 10 mmol/L, and it was only after examining her arterial blood gas that a diagnosis of diabetic ketoacidosis (DKA) could be established.

Her arterial blood gas (ABG) showed a pH of 7.29 / pCO2 of 14 / pO2 of 120 / HCO3 of 6.  Her serum electrolytes showed an anion gap of 31, and alarmingly a serum potassium of 4.7 (in the context of insulin deficiency, this is worrisome).

The appropriate intervention, being transfer to the intensive care unit, potassium replacement via a central line, and aggressive fluid resuscitation were all initiated. She was started on an insulin infusion as well as IV D10W to maintain her blood sugar, and within 24 hours she was completely stable and back to her normal state of health.  

Table 1: The American Diabetes Association diagnostic criteria for DKA: triad of hyperglycemia, anion gap metabolic acidosis, and ketonemia.

Why do pregnant patient's decompensate into DKA at a lower glucose?

           There are a number of cases reported in the literature of euglycemic DKA in pregnant patients, and it is thought to be a rare but devastating complication of pregnancy in type 1 diabetics.  The frequency of occurrence is approximately 1% of all DKA's in pregnant patients (Guo, 2008).  It carries a high fetal mortality rate (30- 90%) and is often a missed diagnosis because of the falsely reassuring glucose readings (Guo, 2008).

Maternal Changes:
The pathophysiology of this process is  interesting.  The normal physiology of pregnancy results in a decrease in insulin sensitivity, and this is thought to be related to increased lipolysis and ketogenesis (Chico et. al, 2008).  Also, pregnant women have a baseline respiratory alkalosis due to pregnancy induced hyperventilation.  This results in a decreased serum bicarbonate and reduced buffering capacity (Chico et. al, 2008).

These normal physiologic changes reduce the body's ability to cope with acidosis, whether it be sepsis or DKA mediated.

Placental-Fetal Changes:
Furthermore, the growing placenta and fetus utilize large quantities of glucose and produce factors such as placental lactogen, progesterone and cortisol that further increase insulin resistance, especially towards the later stages of pregnancy.

The end product of both these maternal-fetal changes is that pregnant patients with T1DM are at an increased risk of developing DKA.  They also have a lower serum glucose threshold at which DKA will occur compared to non-pregnant women with T1DM (Guo, 2008).

The average glucose of pregnant patients with DKA was 16 mmol/L compared with 27 mmol/L in non-pregnant patients (Guo, 2008).

Take home message: In pregnant women with T1DM, a normal appearing glucose does not adequately rule out DKA and can have devastating consequences for both mother and the fetus.


Please see the video below about Dr. Ho Ping Kong and his best selling book "The Art of Medicine".

http://canadaam.ctvnews.ca/video?playlistId=1.1915992

References:

Guo, R.X., Yang, L.Z., Li, L.X., Zhao, X.P. Diabetic Ketoacidosis in pregnancy tends to occur at lower blood glucose levels: case-control study and a case report of euglycemic diabetic ketoacidosis in pregnancy. Journal of Obstetrical Gynaecology Research. 34(3):324-330. 2008.

Chico, M., Levine, S.N., Lewis, D.F. Normoglycemic diabetic ketoacidosis in pregnancy. Journal of Perinatology. 28(4): 310-2. 2008.

Welcome to the 2014-2015 Academic Year! Emergency Lecture Series - Upper GI Bleed

Firstly, I just wanted to thank the outgoing CMR's for all of their hardwork and dedication over the past year.  I look forward to continued friendship and working with you guys into the future.

Now we shall get to business...

Our first blog today is about the Emergency Management of an Upper GI Bleed:

We discussed at lunch rounds today that there are 5 essential questions that need to be answered by the Internist in the emergency management of any patient with an upper GI bleed (UGI bleed).

Question #1:  Is this truly an upper GI bleed, or is it something else (hemoptysis, a lower GI bleed):

From the JAMA rational clinical exam series, useful historical features to help you answer this question include whether they've had a previous UGI bleed (LR+ of 6.2), if their is a history of melena (LR+ 5.5), cirrhosis (LR+ 3.1) and if they have been taking any anti-coagulation (mainly warfarin, but can likely be extrapolated to the NOAC's) - LR+2.3.

The most useful feature on physical exam to determine if the patient has an UGI bleed would be the presence of melena on DRE (LR+ 25).

Question #2: How severe is this UGI bleed?

Again, from the same paper, key historical features that predict a more severe UGI bleed include a history of malignancy or cirrhosis (LR + 3.7), and a history of syncope (LR+ 3.0).  On the physical exam, abnormal vital signs, mainly tachycardia (HR>100) has a (LR+4.9) for a severe UGI bleed.  The presence of an orthostatic drop in the blood pressure also is suggestive of a more severe UGI bleed (LR+ 2.8).

Luckily, in the 21st century a clinician does not have to memorize these numbers and they have been nicely integrated into a clinical score (Glasgow-Blatchford Score) - which can be accessed at the following link

http://www.mdcalc.com/glasgow-blatchford-bleeding-score-gbs/  .

Question #3: Does this patient have a variceal bleed?

To assist with answering this question from a clinical perspective, the JAMA series again proves useful.  Mainly, once you have determined the patient is having an UGI bleed, the next step is to search for signs suggestive of cirrhosis.  If any features of cirrhosis are present, then the safest approach would be to presume the bleed is variceal in origin.  Unfortunately in determining whether a patient has cirrhosis, history does not prove very useful.  The physical exam and baseline laboratory investigations are however, very useful.  The presence of distended abdominal veins "caput medusae" is particularly helpful in ruling in cirrhosis (LR+ 11).  Other helpful clues include encephalopathy (LR+10), ascites (LR+ 7.2) and jaundice (LR+ 3.8).

From a laboratory perspective, the most helpful clues to making a diagnosis of cirrhosis include thrombocytopenia (LR+ 9.8) if the platelets are less than 110, a prolonged INR (LR+ 5.0), and a low albumin (LR+ 4.4).

Again, if one suspects a variceal bleed, it should be treated as such.

Question #4: Does this patient need ICU or urgent endoscopy?

To answer this question, if there is hemodynamic compromise such as shock (elevated lactate, etc.) or signs of organ hypoperfusion (demand ischemia), the threshold for calling help is quite low.  For severe UGI bleeds (based on Glasgow-Blatchford score), or those with high risk features (hypotension, tachycardia), urgent endoscopy and close monitoring is essential.  If there is the suspicion of a variceal bleed, then ICU and GI should be notified in most cases immediately to help expedite endoscopy.

Question #5: Is the patient on an anticoagulant, and what is the indication?

This should essentially prompt the internist to consider the risks and benefits of reversing the anticoagulation.  These decisions are on a case-by-case basis and almost always should include input from gastroenterology, cardiology (in the case of mechanical valves), and hematology (in the cases of DVT/PE).  With the newer anti-coagulants, a phone call to the blood bank and ICU is also necessary as currently their exists no anti-dote or reversal agent on the market.

Those are the key questions to consider in the emergency management of an UGI bleed from the intern, or internist's perspective.  Please see the below references for further details on the management of an UGI bleed.

That was a long tangent... Welcome to 2014-2015

(Thanks Lee)

Management of Acute Bleeding from a Peptic Ulcer. Gralnek, et. al. NEJM. 2008

Does this patient have a severe Upper Gastrointestinal Bleed. Srygley, et. al. JAMA. 2012.

Does this patient with liver disease have cirrhosis. Udell, et. al. JAMA. 2012