ELECTROLYTE QUIZ

The answer is A. The patient has cardiotoxicity from hyperkalemia. Protection by calcium is needed immediately, followed by some approach to reduce plasma potassium. Kayexalate is contraindicated because of its effect on bowel - colonic necrosis and because it will take too long to work.

The Question
A 68 year old African American male patient on chronic dialysis comes into the hospital with nausea and vomiting that began 6 hours previously. The patient has mild abdominal bloating and some mild tenderness in the epigastrium and peri-umbilical area, but there is no guarding or rebound. No bowel sounds are heard. The patient has labs drawn and the serum potassium is 7.2 mEq/L. His electrocardiogram is shown below. All of the following would be reasonable next steps, except:

A.) Treatment with Kayexalate 30 grams with 30 cc's of sorbitol

B.) 10 mEq of calcium gluconate immediately

C.) Calcium gluconate and 10 units of soluble insulin and 50 grams of dextrose IV

D.) Medical treatment with calcium gluconate IV and immediate hemodialysis

Explanation: Management of hyperkalemia

1. If K>5.5 mEeq/L, do an ECG to look for cardiotoxicity of the hyperkalemia. If present: intravenous calcium.

2.) Enhance potassium uptake by cells.

a.) Insulin and dextrose.

b.) Beta-adrenergic agonists. In the United States, the most commonly used preparation is nebulized albuterol. The dose for treating hyperkalemia, 10 mg, is substantially higher than the usual dose for the treatment of bronchospasm and requires the assistance of a respiratory therapist.

3.) Increase potassium excretion from the body.

a.) Cation exchange resins. Sodium polystyrene sulfonate (SPS) or Kayexalate either orally or rectally (as a retention enema). The onset of action occurs <2 hours and is long lasting. However, note that Kayexalate should be avoided in patients with GI symptoms. Sterns in JASN: “In September 2009, the US Food and Drug Administration (FDA) posted safety labeling changes for Kayexalate powder on its web site. The warning reads, “Cases of colonic necrosis and other serious gastrointestinal adverse events (bleeding, ischemic colitis, perforation) have been reported in association with Kayexalate use. The majority of these cases reported the concomitant use of sorbitol. Concomitant administration of sorbitol is not recommended. At the same time, evidence has grown that mixtures of resin in sorbitol may be harmful. By 2005, the FDA had received 35 adverse event reports of serious bowel injuries associated with both oral and rectal administration of the mixture, many of them fatal. Extensive transmural infarction of the colon and ileum was observed with SPS crystals adherent to the mucosa and in luminal debris.”

b.) Emergency dialysis. Very effective especially in chronic dialysis patients.

Electrolyte Quiz

A 68 year old African American male patient on chronic dialysis comes into the hospital with nausea and vomiting that began 6 hours previously. The patient has mild abdominal bloating and some mild tenderness in the epigastrium and peri-umbilical area, but there is no guarding or rebound. No bowel sounds are heard. The patient has labs drawn and the serum potassium is 7.2 mEq/L. His electrocardiogram is shown below. All of the following would be reasonable next steps, except:

A.) Treatment with Kayexalate 30 grams with 30 cc's of sorbitol
B.) 10 mEq of calcium gluconate immediately
C.) Calcium gluconate and 10 units of soluble insulin and 50 grams of dextrose IV
D.) Medical treatment with calcium gluconate IV and immediate hemodialysis

Cases from the Brigham and Women's Hospital

The correct answer is D: Obtain renal arteriography. This is most likely bilateral disease due to fibrous dysplasia in a middle aged white woman. Arteriography is needed to establish the diagnosis and based upon these findings angioplasty attempted for improved blood pressure control. 

The Case and Question A 42-year old white woman who has had hypertension for three years is referred to you because her blood pressure has become increasingly difficult to control. Family history is notable for hypertension. Her current medications are hydrochlorothiazide, 12.5 mg daily; atenolol, 100 mg daily; and extended-release diltiazem, 240 mg daily, which recently was added to her regimen. Blood pressure is 160/110 mm Hg supine and 159/102 mm Hg standing. Funduscopic examination reveals sharp disc margins with mild arteriolar narrowing. No carotid bruits are noted. Heart rate and rhythm are normal; no S4 is heard, and the cardiac impulse is not displaced. A soft abdominal bruit is heard over the left periumbilical area. No peripheral edema is present.

Laboratory Studies

BUN: 10 mg/dL

Serum creatinine: 1.2 mg/dL

Serum electrolytes:

Sodium 140 mEq/L

Potassium 3.6 mEq/L

Chloride 103 mEq/L

Bicarbonate: 27 mEq/L

Urinalysis: Specific gravity 1.015; pH 6.0; trace protein and blood, no glucose; occasional granular and hyaline casts

Duplex Doppler ultrasound reveals features consistent with renal artery stenosis. Acceleration times are normal, and resistive indices are 0.71 on the right and 0.74 on the left.

Based on the ultrasound findings, which of the following should you do next?

A. Order kidney scintigraphy, with and without captopril

B. Add benazepril, 5 mg daily

C. Add irbesartan, 75 mg daily

D. Schedule renal artery angiography

E. Refer for renal artery bypass surgery

(Source: Dr. Brad Denker, Chief of Nephrology, Harvard Vanguard Medical Associates, Nephrology Staff, Beth Israel Deaconess Medical Center and Associate Professor of Medicine, Harvard Medical School)

Explanation

1. FMD definition: Nonatherosclerotic, noninflammatory disease

2. Epidemiology

• More common in women and younger individuals
• The incidence of FMD in children is unknown.
• Described in almost every vascular bed
• Renal arteries (60-75%)

• Cervicocranial arteries (25-30%)

• Non-renal visceral arteries (9%)
• Arteries in the extremities (5%)

•  Others including pulmonary and coronary arteries
• Multiple vascular beds in 28% of patients

3. Classification

• Intimal fibroplasia (less than 10%)
• Medial dysplasia
• Medial fibroplasia (80%)
• Perimedial fibroplasia (10-15%)
• Medial hyperplasia (1-2%)
• Adventitial (periarterial) fibroplasia 

Intimal fibroplasia

• Children and young adults
• Circumferential deposition of collagen in the intima, often projecting into lumina
• Internal elastic lamina may be duplicated or disrupted but can be identified
• Long, irregular (tubular) or focal, smooth (concentric band) stenosis

Medial dysplasia

• 25-50 year old women
• Thickened media alternating with thinned media  aneurysmal dilatation 
– “String of beads”
• Thickened media is replaced by collagen
• Internal elastic lamina may be thinned or fragmented – May lead to macroaneurysm formation1
• Frequently affects the renal arteries bilaterally

Perimedial fibroplasia

• 15- 30 year old women
• Collagen deposition in the outer half of the media replacing the external elastic lamina; intact adventitial connective tissue
• “String of beads”
– can result in severe stenosis
• Often associated with collateral circulation
• Preferentially affects the renal artery (mid portion)

Adventitial (periarterial) fibroplasia

•  Very rare
• Collagen replaces the fibrous adventitia
• May extend beyond artery

4. Etiology

• Genetic
• Autosomal dominant with variable penetrance in 60% of cases based on “clinical symptoms”
• 11% prevalence angiographically
• Hormonal
• No difference in gravidity or parity rates, effect on disease progression
• Oral contraceptive pill use?

5. Indications for intervention:

• Blood pressure cannot be controlled despite three antihypertensive medications at maximal doses
• The individual is intolerant to the medications
• Compliance is an issue
• An alternative to lifelong dependency on a medication in a relatively young individual

Source: www.fmdsa.org/

Cases from the Brigham and Women's Hospital

A 42-year old white woman who has had hypertension for three years is referred to you because her blood pressure has become increasingly difficult to control. Family history is notable for hypertension. Her current medications are hydrochlorothiazide, 12.5 mg daily; atenolol, 100 mg daily; and extended-release diltiazem, 240 mg daily, which recently was added to her regimen. Blood pressure is 160/110 mm Hg supine and 159/102 mm Hg standing. Funduscopic examination reveals sharp disc margins with mild arteriolar narrowing. No carotid bruits are noted. Heart rate and rhythm are normal; no S4 is heard, and the cardiac impulse is not displaced. A soft abdominal bruit is heard over the left periumbilical area. No peripheral edema is present.

Laboratory Studies

BUN: 10 mg/dL

Serum creatinine: 1.2 mg/dL

Serum electrolytes:

Sodium 140 mEq/L

Potassium 3.6 mEq/L

Chloride 103 mEq/L

Bicarbonate: 27 mEq/L

Urinalysis: Specific gravity 1.015; pH 6.0; trace protein and blood, no glucose; occasional granular and hyaline casts

Duplex Doppler ultrasound reveals features consistent with renal artery stenosis. Acceleration times are normal, and resistive indices are 0.71 on the right and 0.74 on the left.

Based on the ultrasound findings, which of the following should you do next?

A. Order kidney scintigraphy, with and without captopril

B. Add benazepril, 5 mg daily

C. Add irbesartan, 75 mg daily

D. Schedule renal artery angiography

E. Refer for renal artery bypass surgery

(Source: Dr. Brad Denker, Chief of Nephrology, Harvard Vanguard Medical Associates, Nephrology Staff, Beth Israel Deaconess Medical Center and Associate Professor of Medicine, Harvard Medical School)

Dialysis Unplugged: Conventional Dialysis - Should we be Leaving the Chair Empty?

The article by Hui Zhang and co-workers from Ann Arbor published in KI examining the DOPPS data represents additional evidence that the days of conventional dialysis should be numbered.

The paper is observational and although the authors adjust for known confounders the effect of residual confounding can’t be excluded.  The other major limitations of the study acknowledged by the authors are that dialysis schedule was not directly ascertained but inferred indirectly from when the dose of dialysis was reported. Direct information about the dialysis schedule was not available. Therefore there is a possibility of measurement error. As well, information about death – the exact time, its relationship to dialysis schedule, and the fact that it occurred in hospital where the possibility that patients may not have been on their outpatient dialysis schedule raises concerns. 

Nevertheless, despite these limitations, the study adds more weight to many other studies suggesting that our current way of dialyzing patients is simply not good enough. Here are a couple of paragraphs from the discussion in the paper:

“Despite its proven value as a life-saving therapy, HD [hemodialysis] remains an intermittent intervention, most typically administered three times a week. Harmful waste products and fluid accumulated over the extended weekend interval may therefore put patients at a higher risk of death on certain days. Our results from the DOPPS in the US, European, and Japanese patients indicate that, in all three regions, HD patients have a higher risk of all-cause death on Mondays if they are on a MWF schedule, or Tuesdays if they are on a TTS schedule. Thus, findings from prior reports are corroborated and expanded upon here. This day-of-week effect tends to be stronger for CVD than non-CVD death overall.”

They go on:
“Our results imply that there may be an advantage to a more frequent dialysis schedule in Europe, the United States, and potentially Japan. This is supported by the relatively low rates of mortality for patients receiving ‘daily dialysis’ based on various reports. One could hypothesize that more frequent dialysis would reduce or eliminate the day-of-week effect and, therefore, lower mortality on HD. Many previous reports have found that daily dialysis is beneficial.” 

IMAGE QUIZ

The answer is renal vein thrombosis (RVT). Aheed Siddiqi has a nice article on imaging in renal vein thrombosis in emedicine. He describes the CT findings as including: decreased nephrographic attenuation, loss of corticomedullary differentiation, a low-attenuating thrombus in the renal vein, renal enlargement with persistent parenchymal opacification, and renal vein enlargement. The acute stage of RVT is characterized by capsular venous collaterals, thickening of the Gerota fascia, and pericapsular whiskering.

The association between renal vein thrombosis(RVT) and nephrotic syndrome was first described by Rayer in 1840. Membranous glomerulopathy is the commonest cause of NS associated with RVT. The presentation can be clinically silent (common), versus flank pain and macroscopic hematuria (less common and in younger patients). Anticoagulation with warfarin is done to prevent pulmonary embolism.

The Question

A 65 year old patient with new onset nephrotic syndrome approximately 5 months after the diagnosis of CLL. He has 6 grams of albuminuria. What's the diagnosis on this CT of the kidneys?

IMAGE QUIZ

A 65 year old patient with new onset nephrotic syndrome approximately 5 months after the diagnosis of CLL. He has 6 grams of albuminuria. What's the diagnosis on this CT of the kidneys?

PSA Screening - "Goodbye to You My Trusted Friend"

Terry Jacks a singer-songwriter is best known for his song "Seasons in the Sun". It is about saying goodbye to a friend. The song was originally written by Jacques Brel a Belgian singer-songwriter who died from lung cancer in October 1978. "Seasons in the Sun" was originally named  "Le Moribond" ("The Dying Man"), and written and performed in French by Brel in 1961. Seasons in the Sun was one of my favorite songs growing up.

At any rate, what's this got to do with anything? Well, this week might mark the beginning of the end for another metaphorically trusted friend: the PSA. For many years, men have been screened for prostate cancer, but based on new widely publicized guidelines this may end.

The U.S. Preventive Services Task Force (USPSTF) has just ratified it's draft recommendations . That's the "D" grade (more harm than good) with respect to PSA screening in men as a preventive strategy for prostate cancer (Moyer et al, Annals May 21 issue). A recommendation against PSA-based screening for men of any age. This despite the fact that prostate cancer is the second commonest cause of death (after lung cancer) among men in the United States. In 2010, an estimated 217 730 men were diagnosed with the disease and 32 050 died from it.

By giving PSA a thumbs down it is quite possible - perhaps probable and inevitable - that Medicare and many third-party insurers will stop paying for routine PSA screening. Many men will be denied the option of having a PSA measured.
The current issue of the Annals of Internal Medicine has a series of articles that I would highly recommend. As someone who initially had my doubts about PSA screening, I now favor it after having read the primary literature, talked with urologists, and thought about this after managing a couple of patients who had cancers detected after elevated PSA's. I favor allowing the patient-doctor discussion over risks and benefits to prevail in the decision to screen or not to screen. As well, I very much agree with the commentary by Catalona and colleagues, which points out flaws in the evidence on which the USPSTF guideline is based. 

Aside from pointing out that the USPTSF did not include urologists or cancer specialists as a part of their panel, Catalona et al also point to flaws in the design and results of the US PLCO study and the [European] ERSPC study, especially the US PLCO study. These are the 2 major studies. They point to contamination (by non-protocol checking of PSAs) in the unscreened group as a key problem. They also point out that the follow-up in these studies is not sufficiently long - a median follow-up of about 10 years - not long enough, they argue, for evaluating outcomes in a cancer that may grow slowly but have devastating effects in its advanced form.

Frankly, I found the arguments by Catalona et al quite persuasive. The counter view - by Otis Brawley - focuses on the perils of mass screening and over-diagnosis but really doesn't address whether the arguments made by the USPTSF are on solid ground scientifically, despite I should add, his suggestion that "We need to practice medicine on the basis of evidence and not on the basis of faith." Dr. Brawley suggests that "physicians have a special obligation to ensure that the patient understands the proven risks and the unproven benefits of PSA-based screening." Is Dr. Brawley being naive?  Does he really believe that insurers will give doctors this luxury? Rather, it is more likely that insurers will stop paying for PSA's.

Bottom-line: I plan to ask my general internist to continue to check my PSA. My views may not be as extreme as some, but I'd rather struggle with figuring out how to deal with an increased PSA level as an individualized decision.

iSEDIMENT

The answer to the iSEDIMENT quiz from May 23, 2012 is: 1C, 2A, 3B.

The Question

Name those worms - those dreadful awful creepy parasites. 3 pictures, 3 choices.

1. Schistosoma hematobium (haematobium) egg.

2. Strongyloides stercoralis

3. Hookworm

iSEDIMENT

Name those worms - those dreadful awful creepy parasites. 3 pictures, 3 choices.
1. Schistosoma hematobium (haematobium) egg.
2. Strongyloides stercoralis
3. Hookworm

IMAGE QUIZ

The Answers to the image quiz from May 21, 2012:

A. Diffuse proliferative glomerulonephritis: higher power EM showing details of the glomerular capillary wall with subepithelial humps (A2-white asterisks),  and a large, confluent subendothelial electron dense deposit (A1-arrows).

B. Diffuse proliferative glomerulonephritis: This electron micrograph shows a subepithelial "hump“ (B1- D) and a portion of one neutrophil (PMN) in the lumen.  Notice the close contact between the endothelial cell and the inflammatory cell.  There is prominent effacement of the foot processes of the epithelium overlying the deposit, with dense condensation of microfilaments in the cytoplasm in this area.

C. Mesangioproliferative glomerulonephritis (e.g., IgA nephropathy). There is preservation of the peripheral capillary wall.  The mesangium shows large electron dense deposits (C.1-arrows).

The Questions

Name the deposits is the purpose of the quiz. You have 3 pictures, A, B, and C. The deposits are labelled by numbers in red. Name the type/location of deposit (e.g., subsendothelial versus mesangial deposit).

A1, A2, B1, C1

IMAGE QUIZ

Name the deposits is the purpose of the quiz. You have 3 pictures, A, B, and C. The deposits are labelled by numbers in red. Name the type/location of deposit (e.g., subsendothelial versus mesangial deposit).
A1, A2, B1, C1

Catheter Based Renal Sympathetic Denervation - A New Treatment for Resistant Hypertension

The Joint National Committee 7 defines resistant hypertension (RHTN) as:"a failure to achieve goal BP (<140/90 mm Hg for the overall population and <130/80 mm Hg for those with diabetes mellitus or chronic kidney disease) when a patient adheres to maximum tolerated doses of 3 antihypertensive drugs including a diuretic". In the AHA Scientific Statement: Resistent Hypertension: Diagnosis, Evaluation, and Treatment , Calhoun and colleagues define it as “high blood pressure (BP) requiring >4 antihypertensive medications, whether controlled or uncontrolled”. [see an earlier post here]

Using the AHA definition of RHTN, estimates are that ≈ 9% of patients have RHTN, although clinical trials suggest the prevalence of RHTN may be 20-30%. So far, the treatment of RHTN includes, the identification and reversal of lifestyle factors contributing to treatment resistance; the diagnosis and appropriate treatment of secondary causes of hypertension; and the use of effective multidrug regimens.

A paper published May 17 in JASN Hering and co-workers adds renal denervation as a new dimension to the treatment of RHTN. In an article in heart.org, renal denervation is "poised to depose transcatheter aortic-valve implantation (TAVI) as the hottest thing in interventional cardiology."

Hering et al performed renal denervation in 15 patients with hypertension and CKD. They enrolled patients with an eGFR of < 45 ml/min per 1.73 m².  Blood pressure at baseline, on average, was 174/91 mmHg despite taking numerous antihypertensive drugs. With denervation, blood pressure readings dropped considerably at one, three, six, and 12 months after the procedure (-34/-14, -25/-11, -32/-15, and -33/-19 mmHg, respectively). They report that renal denervation did not worsen patients' kidney function, indicating that at least on the basis of this study it is safe even when CKD is present.

According to the the heart.org article over 20 companies are working on renal denervation technology. The leading system "Symplicity" is from Medtronic. In the SYMPLICITY HTN 2 trials 84% of patients had a >10 mmHg drop in systolic BP from baseline.

It's worth briefly recalling that the initial report of catheter-based renal sympathetic denervation for RHTN was published by Henry Krum and colleagues in the Lancet in 2009. This was a "first-in-man" non-randomized study of 45 patients with RHTN (SBP>160 mmHg on >3 anti-HTN drugs including a diuretic with an eGFR by MDRD of >45 ml/min/1.73m2). The mean BP at baseline was 177/101 mmHg and office Bps after the procedure were reduced by −14/−10, −21/−10, −22/−11, −24/−11, and −27/−17 mm Hg at 1, 3, 6, 9, and 12 months, respectively.

Subsequent reports summarized in a powerpoint on the web - Symplicity HTN-1 and Symplicity HTN-2 have enlarged the sample size and increased the follow-up. The data continue to be very promising. In the Symplicity HTN-1 study that Sievert et al presented at the European Society of Cardiology in 2010, patients tolerated the procedure very well both in the short and long-term. In their hands, the median procedure time is 38 minutes with an average of 4 ablations per renal artery. Intravenous narcotics and analgesics are used to manage the pain during the delivery of the radio frequency energy. They report no major complications. Only 4 of 153 in Symplicity HTN-1 had minor complications - one renal artery dissection during catheter delivery prior to the ablation and in three there were access complications. Long-term complications were also minimal both structurally to the renal artery and in terms of renal function. 

Symplicity HTN-2 published in the Lancet,  was a relatively small RCT of 106 patients who were randomly allocated to renal denervation (n=52) or control (n=54). "Office-based blood pressure measurements in the renal denervation group reduced by 32/12 mm Hg (SD 23/11, baseline of 178/96 mm Hg, p<0·0001), whereas they did not differ from baseline in the control group (change of 1/0 mm Hg [21/10], baseline of 178/97 mm Hg, p=0·77 systolic and p=0·83 diastolic). Between-group differences in blood pressure at 6 months were 33/11 mm Hg (p<0·0001). At 6 months, 41 (84%) of 49 patients who underwent renal denervation had a reduction in systolic blood pressure of 10 mm Hg or more, compared with 18 (35%) of 51 controls (p<0·0001). We noted no serious procedure-related or device-related complications and occurrence of adverse events did not differ between groups; one patient who had renal denervation had possible progression of an underlying atherosclerotic lesion, but required no treatment."

Bottom-line: Renal denervation is emerging to be a very promising option for management of resistant hypertension. Fasten your seat-belts!

Image Quiz

The answer to the image quiz dated May 18 is: 1. Panel A, FSGS, primary; 2. Panel B, FSGS, secondary. 2. The patient in Panel B will typically present with only modest albuminuria ≈ 1-2 g/d, whereas the patient in Panel A will have albuminuria that typically exceeds 3 g/d.

The Question

The composite picture shows the pathology (LM and EM) from two patients (Panels A and B, respectively). What is the diagnosis for each and how would the clinical presentations differ?

(Click over pic to enlarge)

Explanation

Panel A: Idiopathic FSGS, focal and segmental lesion by light microscopy (top) but diffuse lesion by electron microscopy (bottom). This patient is nephrotic.

Panel B: secondary or adaptive FSGS in a patient with morbid obesity and sleep apnea. Also here the light microscopy lesion is focal and segmental (top) and indistinguishable form the idiopathic variant in panel A, top, however, the electron microscopy reveals preservation of foot processes in most capillaries of most glomeruli (panel B, bottom).  This patient has albuminuria without the full nephrotic syndrome. The other feature in secondary FSGS that is not shown here is the typically enlarged glomeruli. It is also important to note that distinguishing primary from secondary FSGS is important therapeutically - primary FSGS frequently requires treatment with steroids and/or CNIs (calcineurin inhibitors), whereas secondary FSGS can be managed conservatively with angiotensin blockade, treatment of BP, and management of the underlying cause (e.g., obesity).