ELECTROLYTE QUIZ

A 35 year-old man with bipolar disorder treated on lithium, is referred to you for chronic polyuria and polydipsia. He complains that he has to void once every hour.

Laboratory studies:

Serum sodium                     146 mEq/L

Blood urea nitrogen               35 mg/dL

Serum creatinine                    1.9 mg/dL

Serum osmolality                 305 mOsm/kg

24-hr urine volume                  5 L

Urine sodium                         28 mEq/L

Urine osmolality                   190 mOsm/kg

Which of the following might be appropriate in the management of this patient?

(A)      Discontinue lithium

(B)      Demeclocycline

(C)      Vasopressin V2 receptor antagonist

(D)      Fluid restriction

(E)      Furosemide

Glomerulonephritis Quiz

The Answer

Membranous glomerulopathy: Light microscopy; details of basement membrane "spikes" by silver stain (Jones' silver methenamine stain)

The Question

The image below is a light micrograph of a segment of a glomerulus stained with a silver stain (Jones' silver methenamine stain). what do you see and what's the likely diagnosis?

Explanation

Membranous  glomerulonephritis (MGN) is the second most common cause of nephrotic syndrome in adults, with focal segmental glomerulosclerosis (FSGS) being the most common.

Classification

Primary/idiopathic

85% of MGN cases are classified as primary membranous glomerulonephritis -- i.e., the cause of the disease is idiopathic. One study has identified antibodies to an M-type phospholipase A₂ receptor in 70% (26 of 37) cases evaluated. Other studies have implicated neutral endopeptidase and cationic bovine serum albumin as antigens.

Secondary

The remainder of the causes of MGN are secondary:

- autoimmune conditions (e.g., systemic lupus erythematosus)

- infections (e.g., syphilis, malaria, hepatitis B)

- drugs (e.g., captopril, NSAIDs, penicillamine, probenecid).

- inorganic salts (e.g. gold, mercury).

- tumors, frequently solid tumors of the lung and colon; hematological malignancies such as chronic lymphocytic leukemia are less common.

The defining point of MGN is the presence of subepithelial immunoglobulin-containing deposits along the glomerular basement membrane (GBM).

Pathology

• By light microscopy, the basement membrane is observed to be diffusely thickened.
• Using Jones' stain, the GBM appears to have a "spiked" or "holey" appearance.
• On electron microscopy, subepithelial deposits that nestle against the glomerular basement membrane seems to be the cause of the thickening. Also, the podocytes lose their foot processes. As the disease progresses, the deposits will eventually be cleared, leaving cavities in the basement membrane. These cavities will later be filled with basement membrane-like material, and if the disease continues even further, the glomeruli will become sclerosed and finally hyalinized.
• Immunoflourescence microscopy will reveal typical granular deposition of immunoglobulins and complement along the basement membrane.
• (Source: click here)

Other examples of pathology (Courtesy Dr. Rennke):

A: Light microscopy (PAS stain) of a glomerulus with thickened GBM (compare with tubular basement membrane) in a stage II to III disease. The mesangium is slightly prominent. 

B: Immunofluorescence microscopy; the section was incubated with anti-IgG. Notice the fine granular fluorescence pattern along the peripheral capillary wall. The mesangial matrix is generally free of deposits. (anti-IgG-FITC)

C: This electron microscopy shows a classical stage II disease. Numerous, sometimes confluent electron dense deposits in the subepithelial space (asterisks)are separated from each other by "spikes" of matrix material that extend from the basement membrane toward the epithelial cells. This gives the appearance of the deposits being partially incorporated into the basement membrane.

D: Electron microscopy of an early, Stage I, disease.  This form of the disease in some patients has been reported to be associated with the use of drugs, in particular, NSAID.

Glomerulonephritis Quiz

The image below is a light micrograph of a segment of a glomerulus stained with a silver stain (Jones' silver methenamine stain). what do you see and what's the likely diagnosis?

Dialysis Unplugged: “It will be alright in the end”

This line, most recently used in the recent movie “Best Exotic Marigold Hotel”, is emblematic of some of what’s wrong with dialysis.

Take the following story from a patient I saw the other day.  She is a 76-year-old retired Armenian pediatric neurologist. She has stable chronic kidney disease and was seeing me after approximately 6 months. She told me that she had lost her husband a few months ago.

“I lost my husband with whom I was married for 40 years. We loved each other every one of those great years and I miss him so much”.

I asked her how he died.

 “Well, you know, he was on dialysis, dialyzed three times a week. Around 4 am, on the night he died, he woke up suddenly complaining of an inability to breathe. He asked me to take him to the ER in the car rather than calling 911. But, as we were leaving the house he collapsed in the hallway and stopped breathing. I performed CPR on him, called 911, but we weren’t able to revive him.”

What was the cause of death?

“The autopsy didn’t really provide any answer; his heart was fine, but the lungs were filled with fluid. They said he died from pulmonary edema."

She went on: “He had stopped eating months before he died. He just lost his appetite. I think that the dialysis doctors didn’t realize that he had lost muscle. They just kept dialyzing him to the same weight, and I think he filled up with fluid until he couldn’t take it anymore”

As I reflect on this conversation, I am sad for my profession. In the 25 years I have been looking after dialysis patients our tools to assess the dry weight remain rudimentary. 

Establishing the patient’s dry weight is also usually done empirically by volume challenging the patient. It’s not easy to get the patient to their dry weight. There is a risk of hypotension and cramps, and I’ve seen patients pass out when we’ve been too aggressive. But the truth is that we don’t have a fancy assay like the BNP to tell us if a patient is wet or dry. We still rely on taking a history and performing a physical examination. Some of the signs of volume expansion are unreliable and a physical exam is usually hard to do in an open dialysis unit with patient’s hooked to a machine in a dialysis chair.

Here is an excerpt from a superb article by Jack Jaeger and Ravi Mehta in JASN from 1999.

“Missing Changes in Lean Body Mass. There is also the occasional patient who has achieved their so-called dry weight, but over time subtle negative changes in lean body mass occur due to inadequate dialysis prescription, inadequate dialysis delivery, comorbid illness, depression, or other causes. This change might not be reflected in serum albumin or urea kinetics studies, and failure to adjust dry weight results in a greater proportion of their body weight becoming ECF. An increase in BP with recognition of lean body mass change and consequent adjustment of dry weight may occur. Alternatively, there may be no BP response to this ECF expansion, a failure to adjust dry weight downward, and henceforth failure to identify this subtle change in nutritional status. Such small changes in nutritional status might be significant for the patient.”

They continue: “it is evident that contemporary management of fluid in the dialysis patient is largely dependent on a clinically derived estimate of dry weight. Clinical assessment of dry weight inevitably leads to both overestimation and underestimation of dry weight. Overestimation of dry weight leads to hypertension, stroke, and congestive heart failure, which are the main causes of excess death in dialysis. Underestimation leads to persistent hypotensive episodes, alienating dialysis patients from their caretakers, and affecting delivery of prescribed dialysis. Moreover, the current focus on Kt/V as an index for adequacy of dialysis in terms of solute removal ignores the contribution of volume as an independent factor influencing outcome.”

The bottom-line is that we need to develop better ways to assess dry weight. For the husband of my patient, it really wasn't alright in the end and for our patient's not knowing precisely their dry weight isn't good enough. 

Cases from the Brigham and Women's Hospital

The Case
42 year old doctor, body building fanatic, with history of mild hypertension, intermittent heavy NSAID use while playing college rugby, found to have elevated Cr to 1.4 to 1.7 since 2003.  Nonproteinuric.  Environmental exposures neg, denies drug or anabolic steroid use.  Medications – lisinopril 5 mg/d. BP  134/84 mmHg, HR 66. Rest of the examination normal. Patient is very keen to know the cause of his renal insufficiency. Would you perform the biopsy? What would it likely show?

The Answer
I declined to perform a kidney biopsy on the patient, arguing that the biopsy would not reveal a lesion for which I would change my treatment. My clinical diagnosis was chronic interstitial scarring from chronic NSAID use in the past, coupled with high protein consumption as part of his body-building routine, and a high lean body mass from muscle. I was reluctant to recommend a biopsy because his history was suggestive of an etiology, renal function had been stable for many years, and his urinalysis and sediment examination was benign. The patient self-referred himself to another nephrologist and a biopsy was done. There were no complications from the biopsy.

There is no correct answer here.

The patient decided to see another nephrologist and persuaded him to perform a kidney biopsy. The result is below:

Cases from the Brigham and Women's Hospital

42 year old doctor, body building fanatic, with history of mild hypertension, intermittent heavy NSAID use while playing college rugby, found to have elevated Cr to 1.4 to 1.7 since 2003.  Nonproteinuric.  Environmental exposures neg, denies drug or anabolic steroid use.  Medications – lisinopril 5 mg/d. BP  134/84 mmHg, HR 66. Rest of the examination normal. Patient is very keen to know the cause of his renal insufficiency. Would you perform the biopsy? What would it likely show?

iSEDIMENT

The answers are:

1. A, 2D, 3 B, 4. F, 5. E, 6.C

The Question

Identify the crystal

1. Struvite 2. Uric acid 3. Calcium phosphate 4. Cystine 5. Ammonium biurate 6. Calcium oxalate

iSEDIMENT

Identify the crystal

1. Struvite 2. Uric acid 3. Calcium phosphate 4. Cystine 5. Ammonium biurate 6. Calcium oxalate

Journal Club: Should diuretics be used to treat AKI?

The KDIGO AKI guidelines were recently published as a supplement to Kidney International. I have already discussed the guidelines briefly, but wanted to now focus on the specific guideline recommendation.

KDIGO’s recommended position on the use diuretics in AKI caught my eye. Chapter 3.4, pages 47-49, reviews the data for the use of diuretics. The recommendations are as follows:

3.4.1: We recommend not using diuretics to prevent AKI. (1B)
3.4.2: We suggest not using diuretics to treat AKI, except in the management of volume overload. (2C)

The KDIGO panel cite some of the potential benefits of loop diuretic therapy, including reducing oxygen consumption in the loop of Henle by inhibiting active sodium transport - therefore potentially reducing ischemic injury; inducing the loss of the high medullary osmolality by inhibiting the Na-K-2Cl cotransporter – decreasing the ability to reabsorb water; increase intratubular pressure and thereby push out necrotic debris blocking tubules; inhibiting prostaglandin dehydrogenase which reduces renovascular resistance and increases renal blood flow.

The panel then goes on to say: “There is no evidence that the use of diuretics reduces the incidence or severity of AKI. Ho et al conducted two comprehensive systematic reviews on the use of the loop diuretic furosemide (furosemide) to prevent or treat AKI. Furosemide had no significant effect on in-hospital mortality, risk for requiring RRT, number of dialysis sessions, or even the proportion of patients with persistent oliguria."

The question: why is there continued use of loop diuretics in the management of AKI given the lack of evidence and in light of KDIGO guidelines? In an informal survey of my colleagues at the Brigham there was a uniform opinion that a trial of loop diuretics is useful in managing patients with AKI. So what gives?

The quick answer is that there have been very few studies in this area and in each of the studies the sample size has been quite limited – in the 50 to 100 range, and the trials are flawed - some severely, so there is really no basis for making a recommendation either way. The role of diuretics to treat AKI has really not been adequately tested. 

To give you a flavor of the type of evidence there is, KDIGO cite a study by Félix Cantarovich and co-workers on behalf of the High-Dose Furosemide in Acute Renal Failure Study Group, a French consortium as evidence to support the recommendation of no benefit of loop diuretics. The study published in AJKD is unfortunately unavailable open access (Vol 44, No 3 (September), 2004: pp 402-409).

Cantarovich et al enrolled 338 consecutive subjects with ARF [AKI] requiring RRT in a prospective, randomized, double-blind, placebo-controlled, multicenter trial. The design of the study was complicated – they had a screening phase where they treated patients with very high dose of furosemide 15 mg/Kg IV over 4 hours (for a 60 Kg patient that is 900 mg of furosemide over 4 hours!) and if they had a further increase in serum creatinine they were randomized to either furosemide 25 mg/kg/d IV (maximum, 2 g/d,), or matched placebo. They also stratified patient’s severity using a Simplified Acute Physiology Scores (SAPS) score. After randomization, patients could enter an optional predialysis period (phase I) for a maximum of 48 hours (days 1 and 2) or a dialysis period (phase II), which began either immediately after the screening period or after phase I, according to the urgency of dialysis requirements. Intermittent or continuous RRT could be performed. RRT modalities differed between intensive care units and nephrology wards and included continuous hemofiltration or hemodiafiltration, when possible, as well as hemodialysis daily or on alternate days.

The trial had many limitations. The most important were:

1. The sample comprised of quite severe AKI. This is because they only enrolled the patient’s if they needed RRT. RRT was defined according to French practice guidelines at the time: a progressive increase in plasma urea levels greater than 180 mg/dL (>30 mmol/L), oligoanuria for 48 hours, or uremic syndrome.

2. The complicated design – with a screening period, stratification, 2 different phases, different dialysis modalities by center. 

3. They did not use the “intention to treat” principle because of 338 subjects enrolled and randomized, they excluded 8 subjects because “they did not meet inclusion criteria”. But in actuality these subjects 2 patients in the furosemide group and 6 patients in the placebo group, showed a spontaneous recovery in renal function during predialysis phase I. Notably, though, these excluded patients had all been treated with furosemide at a high dose already. The recovery was not really spontaneous!

4. The randomization was not balanced. Patients randomized to the furosemide versus the placebo arm had worse kidney function at baseline (4.87 +/- 2.61 versus 4.31 +/- 2.78, P=0.013, respectively). Likewise, there was imbalance for BUN at baseline between the 2 arms. Staggeringly, 33 of 166 versus 13 of 164 subjects had diabetes in the furosemide versus placebo arms. One imbalance went in the other direction with more subjects with sepsis and sepsis/shock in the placebo versus furosemide arm, respectively.

5. The surprising use of “death” and “death at the end of the study”. They assumed a 45% baseline value and they observed a 33% rate. They also assumed that they would need to see a 15% effect size for 80% power. Pretty ambitious! Clearly, the study was underpowered.

Despite all of these limitations, the authors report that “More patients in the furosemide group achieved a diuresis of 2 L/d and in a shorter period compared with the placebo group.”

The bottom-line is that KDIGO went on a limb to make the assertion recommending against diuretics in AKI. The evidence is simply not there to make such a statement. The largest randomized trial is deeply flawed but even this showed minimal evidence for harm and a potential benefit. So, I will continue to use diuretics in the treatment of AKI until there is additional data to suggest otherwise.

GLOMERULONEPHRITIS QUIZ

The answer to the GN Quiz June 21, 2012: the biopsy showed anti-GBM nephritis (see images, CLICK OVER IMAGE TO ENLARGE).

The Question

73-year-old woman presents with hematuria and ARF. Serum creatinine is 10.2 mg/dl.  BP 160/62.  P-ANCA positive. She gives history of hemoptysis in 2005.  What will the renal biopsy show?

ANCA+ with anti-myeloperoxidase titers:

6/14/05        26 units

8/17/05        5.4 units

10/18/05      1.3 units

12/13/05      <1.0 units

11/07/06      1.3 units

05/08/07      2.3 units

08/14/07      16 units

11/25/08      155 units

02/10/09      26 units

05/15/09      15 units, two days after the biopsy   

Discussion

• All patients with anti-GBM antibody nephritis should be tested for ANCA.
• 20–25% of patients with anti-GBM nephritis also have ANCA antibodies known as WHO type IV crescentic disease.
• The majority of reported cases with dual antibodies are 50 to 80 years of age, which corresponds to the typical age of patients with ANCA-associated disease.
• In contrast, anti-GBM nephritis has a bimodal distribution, typically occurring in males in their 20 s and women >80 years old.
• Previous studies have noticed a prevalence of anti-GBM antibodies in 5% of ANCA vasculitis cases. Therefore, it is possible that many elderly patients with anti-GBM nephritis (second peak of bimodal curve) may in fact have ANCA vasculitis with superimposed anti-GBM antibody nephritis, as ANCA vasculitis is signficantly more common.
• One pathophysiological hypothesis regarding anti-GBM antibody formation is the p-ANCA injures of the glomerular basement membrane during crescent formation, exposing de novo basement membrane antigens and initiating development of an anti-GBM antibody.
• In vivo experiments have demonstrated that MPO-ANCA can severely aggravate subclinical anti-GBM glomerular disease in rats.
• It is unknown why only a small percentage of ANCA vasculitis patients develop anti-GBM antibodies, but this may relate to associated factors including the presence of underlying renal disease, smoking, infection, or environmental and genetic factors.
• Patients with dual antibodies may have an atypical presentation, which may cause delay in the correct diagnosis and initiation of treatment.
• Some clinical features of vasculitis including arthralgias, rash, malaise, and fever may occur in these patients, while typically are absent in classic anti-GBM nephritis.
• Patients with persistence of ANCA after resolution of the initial symptoms have a higher incidence of recurrence and need close monitoring of ANCA levels.
• Unlike classic anti-GBM cases, such patients should be treated with long-term maintenance immunosuppression such as azathioprine, methotrexate, or low-dose prednisone. 

(Source for discussion Tariq Javed Case Reports in Nephrology 2012 (2012),doi:10.1155/2012/132085)

Glomerulonephritis Quiz

73-year-old woman presents with hematuria and ARF. Serum creatinine is 10.2 mg/dl.  BP 160/62.  P-ANCA positive. She gives history of hemoptysis in 2005.  What will the renal biopsy show?

ANCA+ with anti-myeloperoxidase titers:

6/14/05        26 units

8/17/05        5.4 units

10/18/05      1.3 units

12/13/05      <1.0 units

11/07/06      1.3 units

05/08/07      2.3 units

08/14/07      16 units

11/25/08      155 units

02/10/09      26 units

05/15/09      15 units          two days after the biopsy   

Commentary: CKD in the elderly

This past week I had a referral of a 78 year old patient with mildly reduced eGFR (down to 58 ml/min/1.73 m2) for "management of kidney disease". The patient was otherwise healthy, except for controlled hypertension that he had had for the past 20 years. However, he was quite distressed that he might need dialysis some time in the future.

After the history and physical examination, I checked his urinalysis - he had no albuminuria or hematuria on dipstick - and on microscopy his sediment was bland. I checked labs - his BUN was 28 and his serum creatinine 1.3 mg/dL with an eGFR of 58. His urine albumin to creatinine ratio (UACR) showed 190 mg of albumin per gram of creatinine. The renal ultrasound showed normal sized kidneys. My diagnosis - microvascular disease from long-standing hypertension. Does he have CKD? Yes, but mild and of low-risk.

The patient above reminds me of a thoughtful editorial published in JAMA by Dick Glassock March 24, 2010. It is available open access. Dr. Glassock has been a staunch critic of the use of eGFR equations for CKD classification, particularly among the elderly. He writes: "referral to nephrologists for evaluation based on a possible risk of adverse outcomes is not appropriate for older patients with an estimated GFR of 45 mL /min/1.73 m or greater unless concomitant overt proteinuria or other findings are present (such as hematuria, abnormal imaging, a family history of renal disease, or significant comorbidity) [and]... a “one size fits all” approach to classifying CKD is not appropriate."

The Glassock view is shared by many nephrologists - my patient would not have been referred to me if one used his criteria. Perhaps he would have been reassured by his internist that "his labs are fine". Glassock goes onto write: "The current estimated GFR–dominant formulation for defining and classifying generic CKD requires an urgent overhaul, routine reporting of estimated GFR needs reconsideration (regardless of the formula used), and primary care physicians and nephrologists should work together to ensure that referrals for subspecialty care are timely and appropriate....Much work still needs to be done to achieve the proper balance between efficiently identifying the problem of actual CKD and minimizing the nuisance of both mislabeling CKD and unnecessary referral to a subspecialist."

Global Nephrology: Nocturnal Dialysis in India

While many western countries are still struggling to figure out whether frequent daily dialysis or nocturnal dialysis or even quotidian dialysis can emerge as a viable therapy, centers around the world are starting to do nocturnal dialysis. But, globally nocturnal dialysis is not what we think of in either North America or Europe. It is simply dialysis at night administered slowly and for several hours each time, and not frequent or daily nocturnal dialysis.

There are several news reports of centers offering nocturnal dialysis in India but there is little data on how prevalent the practice is, how many centers are doing nocturnal dialysis and the numbers of patient’s receiving nocturnal dialysis. Still, the fact that countries around the world appreciate the potential benefits for patients and have ramped up to offer it is encouraging.

Take the example of Nephroplus a for-profit dialysis chain in India.

Dr Krishna a medical director of Nephroplus is quoted in the article:  “Nocturnal dialysis helps reduce stress level among patients. It is popular among corporate executives and young kidney patients, who have hectic professional life. It is a slow, gentle and lengthy process compared to normal hemodialysis as it purifies the blood better.”


Other centers, like the dialysis unit at Vadamalayan Hospitals in Madurai featured in a recent news report is also embarking on night-time dialysis.

The bottom-line is that nocturnal dialysis in India serves “the haves” - the middle class who can afford night-time dialysis, but it represents another example of the inequity in health care that is rampant in India.


(correction posted June 23, 2012)

ELECTROLYTE QUIZ

The answer to the electrolyte quiz of June 17, 2012 is  C.

An 18-year-old female with anorexia nervosa is found on routine laboratory examination to be hypokalemic.

Laboratory Studies

Serum sodium 134 mEq/L

Serum potassium 3.1 mEq/L

Serum chloride 92 mEq/L

Serum bicarbonate 31 mEq/L

Blood urea nitrogen 5 mg/dL

Serum creatinine 0.7 mg/dL

Urine chloride 42 mEq/L

24 hour urine calcium 310 mg

Which of the following is the most likely cause of this patient’s laboratory findings:

A. Laxative abuse

B. Gitelman syndrome

C. Loop diuretic abuse

D. Surreptitious vomiting

E. Thiazide diuretic abuse

Explanation

This patient also has hypokalemic metabolic alkalosis with high urine chloride. The additional finding of hypercalciuria (>250 mg/d in females) narrows the differential diagnosis down to Bartter (usually presents in infancy or early childhood) and loop diuretic abuse (common in anorexics).


(Source: Dr. Alan Yu, Professor of Medicine, The Kidney Institute, UKMC, Kansas)

ElECTROLYTE QUIZ

An 18-year-old female with anorexia nervosa is found on routine laboratory examination to be hypokalemic.

Laboratory Studies

Serum sodium 134 mEq/L

Serum potassium 3.1 mEq/L

Serum chloride 92 mEq/L

Serum bicarbonate 31 mEq/L

Blood urea nitrogen 5 mg/dL

Serum creatinine 0.7 mg/dL

Urine chloride 42 mEq/L

24 hour urine calcium 310 mg

Which of the following is the most likely cause of this patient’s laboratory findings:

A. Laxative abuse

B. Gitelman syndrome

C. Loop diuretic abuse

D. Surreptitious vomiting

E. Thiazide diuretic abuse

ELECTROLYTE QUIZ

The answers to the electrolyte quiz for June 14, 2012 are 1. A, 2. D, 3. C, 4. B, 

The Questions

For each patient with hyperkalemia described below, select the best option (A-E) for treatment of their serum potassium.

A. Thiazide diuretic

B. Hydrocortisone

C. Insulin

D. Hemodialysis

E. Sodium polystyrene sulfonate

1. 43-year-old man with Type II diabetes mellitus, hypertension, congestive cardiac failure, nephrotic-range proteinuria, and a serum creatinine of 1.6 mg/dL. His serum potassium has been in the range of 5.6-5.9 mEq/L since starting captopril, despite adhering to a potassiumrestricted diet.

2. 88-year-old woman who had partial colectomy for perforated diverticular abscess and septicemia two days previously, and has been anuric since the operation. Her serum potassium is 6 mg/dL.

3. 18-year-old man with no prior medical history who presents with one week of polyuria and polydipsia.

Laboratory Studies

Serum sodium 132 mEq/L

Serum potassium 5.9 mEq/L

Serum chloride 91 mEq/L

Serum bicarbonate 16 mEq/L

Blood urea nitrogen 56 mg/dL

Serum creatinine 2.2 mg/dL

Serum glucose 330 mg/dL

4. 26-year-old woman with acquired immune deficiency syndrome, fatigue, weight loss, lowgrade fever, and orthostatic hypotension.

Serum cortisol level:

Baseline at 8 AM7 mcg/dL 

(nL 5-24 mcg/dL)

30 minutes after 250 10 mcg/dL mcg cosyntropin i.m.

60 minutes after 250.11 mcg/dL mcg cosyntropin i.m.

Explanation

The 43-year-old man likely has diabetic nephropathy and hyporeninemic hypoaldosteronism. He is volume-expanded and loop or thiazide diuretics are a useful way to correct his potassium and volume simultaneously. The 88-year-old with postoperative anuric acute renal failure requires dialysis. Enteral administration of a potassium-binding resin is contraindicated, and no other measure will remove potassium from her body. The 18-year-old man has newly-diagnosed diabetes and diabetic ketoacidosis. The hyperkalemia is due to shift of potassium from the intracellular to extracellular space, which can be readily reversed with insulin, and his renal failure is largely due to hypovolemia and may be reversible with fluid replacement. His whole body potassium content is actually reduced and any measures that remove potassium from the body would risk subsequent development of hypokalemia once insulin therapy is initiated. The 26-year-old woman has primary adrenal insufficiency, which can occur in patients with acquired immunodeficiency syndrome due to infectious agents such as cytomegalovirus or mycobacteria, and drugs such as ketoconazole and rifampin. Although her baseline serum cortisol level is normal, it fails to rise appropriately (increment from baseline > 7 mcg/dL, or 30 minute level > 15 mcg/dL) after administration of cosyntropin. Replacement with hydrocortisone is therefore indicated.

(Courtesy of Dr. Alan Yu, Professor of Medicine, University of Kansas Medical Center) 

ELECTROLYTE QUIZ

For each patient with hyperkalemia described below, select the best option (A-E) for treatment of their serum potassium.

A. Thiazide diuretic

B. Hydrocortisone

C. Insulin

D. Hemodialysis

E. Sodium polystyrene sulfonate

1. 43-year-old man with Type II diabetes mellitus, hypertension, congestive cardiac failure, nephrotic-range proteinuria, and a serum creatinine of 1.6 mg/dL. His serum potassium has been in the range of 5.6-5.9 mEq/L since starting captopril, despite adhering to a potassiumrestricted diet.

2. 88-year-old woman who had partial colectomy for perforated diverticular abscess and septicemia two days previously, and has been anuric since the operation. Her serum potassium is 6 mg/dL.

3. 18-year-old man with no prior medical history who presents with one week of polyuria and polydipsia.

Laboratory Studies

Serum sodium 132 mEq/L

Serum potassium 5.9 mEq/L

Serum chloride 91 mEq/L

Serum bicarbonate 16 mEq/L

Blood urea nitrogen 56 mg/dL

Serum creatinine 2.2 mg/dL

Serum glucose 330 mg/dL

4. 26-year-old woman with acquired immune deficiency syndrome, fatigue, weight loss, lowgrade fever, and orthostatic hypotension.

Serum cortisol level:

Baseline at 8 AM7 mcg/dL 

(nL 5-24 mcg/dL)

30 minutes after 250 10 mcg/dL mcg cosyntropin i.m.

60 minutes after 250.11 mcg/dL mcg cosyntropin i.m.

On Being a Doctor: "Please Stop Interrupting"

Here's an interesting piece by Juliet Mavromatis who is a general internist based in Atlanta, Georgia in the Health Care Blog. It's titled “Why Doctors Interrupt”.

The article describes an interaction between Dr. Mavromatis and a neurosurgeon about a patient’s headaches. Only a few sentences into her opening description about the patient the neurosurgeon interrupts. Dr. Mavromatis persists tenaciously despite the neurosurgeon’s interruption with her story but describes the interaction leaving her with unease. She writes:

“Interruption is a pervasive communication style with doctors.  In a well known study by Beckman and Frankel patients were allowed to complete their opening statement expressing their agenda in its entirety in only 23% of physician interviews.  The average time to interruption was 18 seconds.  This study’s findings have been replicated by several others.  In a more recent study of primary care residents, patients were allowed to speak for only 12 seconds on average before they were interrupted.  Female patients experience interruption more frequently than males. In contrast, studies have suggested higher rates of patient satisfaction with physician visits during which patients and doctors interrupt at similar frequency and also with visits in which there is more “reflective” silent time during the conversation.  Perhaps the tendency to interrupt extends to all physician derived professional communications, as in my case with the neurosurgeon on the phone.

Why do physicians interrupt?  In practical terms, throughout the course of a given day a physician may be tasked with listening to twenty to thirty patient derived histories and with solving difficult problems for each of these patients in a matter of ten to fifteen minutes. This is a tough, if not impossible job.  Consequently, once a physician believes that the meat of the story is out there, he or she may respond and interrupt before hearing details that the patient (or colleague) feels are important.  In more abstract terms interruption is a communication strategy that reinforces physician dominance in the hierarchy of the patient-physician relationship.

The most frequent complaint that I hear from patients about other physicians is that a physician did not “listen,” or did not “seem to care” about their problem.  My advice to physicians and medical trainees: sit down, bite your tongue and wait. If you do interrupt, do so with brief questions allowing your patient to return to his or her agenda.  You might be surprised and learn something, and no doubt you’ll certainly have happier patients (and colleagues).”

The article by Juliet Mavromatis resonates with me because, as I reflect on my own clinical practice, I agree it’s quite easy to interrupt a patient just to keep to the designated time for a follow-up versus new patient visit. After reading this article I am going to try in stop interrupting a patient.  

"Today is the Day We Start Making Excuses" - Blue Cross Blue Shield of Minnesota and Kidney Donation

A story June 11 in the New York Times strains credulity. Blue Cross Blue Shield (BCBS) of Minnesota refuses to insure Radburn Royer after donating a kidney to his daughter after she developed renal failure. Here is an excerpt of the story:

“When Erika Royer’s lupus led to kidney failure four years ago, her father, Radburn, was able to give her an extraordinary gift: a kidney.

Radburn Royer (Source: NY Times)

Ms. Royer, now 31, regained her kidney function, no longer needs dialysis and has been able to return to work. But because of his donation, her father, a physically active 53-year-old, has been unable to obtain private health insurance.

Like most other kidney donors, Mr. Royer, a retired teacher in Eveleth, Minn., was carefully screened and is in good health. But Blue Cross and Blue Shield of Minnesota rejected his application for coverage last year, as well as his appeals, on the grounds that he has chronic kidney disease, even though many people live with one kidney and his nephrologist testified that his kidney is healthy. Mr. Royer was also unable to purchase life insurance.”

The story goes on:

 “Mr. Royer said he is baffled by the denial. “From my perspective, I’d be a good risk,” he said. “I’d just be putting in premiums and helping balance the system out.”

There is little data on how often kidney donors have trouble obtaining insurance, but advocates say the fear of being uninsurable may be a powerful deterrent to donation. A 2006 study done by an advocacy organization for transplant professionals found that 39 percent of transplant centers reported that they had had eligible donors who declined to donate because they feared having future insurance problems.”

There are a couple of things that surprise me. First, someone needs to explain to the insurer that just because the patient donated a kidney doesn’t mean that he has chronic kidney disease. Indeed, even if his serum creatinine hasn’t normalized he doesn’t have a disease per se. And second, whatever happened to Obamacare’s goal of ridding the US of the “pre-existing clause”? Surely, the insurer shouldn’t be able to exclude coverage if someone has a medical problem.

Minnesota’s BCBS shouldn’t be allowed to get away with this. The transplant community should pile on and make sure that BCBS’s position is revered. 

The results from EVOLVE: Treatment with cinacalcet does not improve hard outcomes in dialysis patients.

The announcement by Amgen of the top-line results of EVOLVE today caught me by surprise - or maybe not. Still another RCT showing that should have worked based on observational data turns out to be negative.

EVOLVE (EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events) is a Phase 3 trial, which evaluated cinacalcet (Sensipar) for the reduction of the risk of mortality and cardiovascular (CV) events among 3,883 patients with secondary hyperparathyroidism (HPT) and chronic kidney disease (CKD) receiving dialysis.

EVOLVE is a randomized, double-blind, placebo-controlled Phase 3 study of 3,883 patients from 22 countries with secondary HPT and CKD receiving dialysis. The trial was event driven. The PI is Dr. Glenn Chertow from Stanford. The trial was designed to determine if treatment with cinacalcet compared to placebo decreases the risk of all-cause mortality and CV morbidity. The trial consisted of a 30-day screening phase, a titration phase with visits every 2 weeks, and a follow-up phase with visits every 8 weeks. The cinacalcet dose in the treatment arm could be escalated sequentially from 30 to 180 mg/d. Following the screening phase, patients were randomized to the cinacalcet or placebo. A paper in CJASN in 2007 provides details on study design.

The key result of this study is that it was negative, i.e., was null for the primary composite primary events time to the composite event comprising all-cause mortality or first non-fatal cardiovascular event, including myocardial infarction, hospitalization for unstable angina, heart failure or peripheral vascular event.

The most frequently reported adverse events in the cinacalcet arm of the trial were nausea, vomiting and hypocalcemia.

The bottom-line is that treatment targeted at reducing PTH with cinacalcet does not result in improved hard endpoints such as death and cardiovascular complications. This study reinforces the importance of assessing hard endpoints in large well designed and adequately powered RCTs rather than relying on observational studies to determine the role of interventions.. and before spending billions of dollars.