Systems

Should All Patients with Hepatitis C Be Screened for Hepatocelluar Carcinoma?

July 3, 2007

Should patients with Hepatitis C (HCV) with no evidence of cirrhosis undergo screening for hepatocellular carcinoma (HCC)? Is there any reason to check for HCC when the liver associated enzymes (LAEs) are normal?

-Sandeep Mangalmurti, PGY-2

Commentary by Mike Poles MD, Associate Editor Clinical Correlations and Assistant Professor, Division of Gastroenterology

HCC continues to be one of the most common solid malignancies worldwide. Further, almost all cases of HCC occur in the background of a histologically-abnormal liver; approximately 90% of cases of HCC occur in the background of cirrhosis. It is important to note that cirrhosis due to any etiology can result in the development of HCC, though cirrhosis due to the viral hepatitides is the most common causes. In the Far East, where HBV is highly endemic, it is the most common cause of cirrhosis-related HCC. On the other hand, in the U.S. and Western Europe, HCV-related cirrhosis is more commonly associated with HCC development. As noted above, approximately 10% of patients with HCC do not have cirrhosis. Worldwide, the majority of those with HCC, but without cirrhosis, are infected with HBV, which is believed to be oncogenic, in part, by virtue of its ability to integrate its DNA into the human genome. HCV, on the other hand, is a RNA virus that is not capable of integration, but nonetheless can probably rarely cause HCC through its effect on hepatic inflammation and increased hepatocyte activation and proliferation. A recent article in the Annals of Internal Medicine (Ikeda K et al. Antibody to Hepatitis B Core Antigen and Risk for HCV-Related HCC: A Prospective Study. Ann Int Med. 2007;146(9):649-656) [http://www.annals.org/cgi/content/full/146/9/649]supports past studies that have shown that the development of HCC in HCV-infected patients may also be related to occult (latent) HBV infection in which the patient has been exposed to HBV and has integrated HBV in the liver, but no signs of infection in the periphery except for antibody against the HBV Core antigen. Thus, in HCV-infected patients without cirrhosis, the development of HCC may be related to co-existent HBV infection. So, is this risk of development of HCC in non-cirrhotic HCV patients enough to trigger us to perform surveillance for HCC? It is generally accepted that it is not cost-effective to screen for HCC if it is not expected to occur at a rate of greater than 0.2% per year (Di Bisceglie AM. Issues in Screening and Surveillance for Hepatocellular Carcinoma. Gastroenterology. 2004;127:S104-S107). This threshold is exceeded in patients with established cirrhosis, who have a rare of development of HCC at 1-4% per year. Since the risk of development of HCC in patients with chronic HCV, but without cirrhosis is very low (below 0.2% yearly), surveillance is not cost-effective in such patients. Whether this recommendation would be modified by the presence of anti HBV Core antibody requires more study.

In response to the second question, it is important to realize that patients with chronic HCV, but without abnormal LAEs can still have significantly abnormal liver histology, including development of cirrhosis, though the risk of development of significant liver damage is decreased in this population. Thus, evidence for the presence of cirrhosis is far more pertinent with regard to HCC risk than is the presence of abnormal LAEs.

How Do you Approach a Patient with Primary Hyperaldosteronism?

June 28, 2007

An 80 year old male with atrial fibrillation, hypertension, hypokalemia is diagnosed with hyperaldosteronism with an aldosterone to renin ratio of 34.5/0.15=230 . CT scan reveals a right adrenal 1 cm presumed adenoma

Questions:
1. How do you accurately diagnose primary hyperaldosteronism?
2. Do medications which the patient is taking influence the work-up?
3. Can you have primary hyperaldosteronism in the absence of hypokalemia?
4. Can the adrenal mass be incidental? Should the patient have additional testing?

-Anna Dvorak PGY-3

Commentary By: Stephen Richardson, MD Assistant Professor of Medicine, Divsion of Endocrinology

1. It is almost certain that primary hyperaldosteronism is responsible for the patient’s clinical and laboratory features of hypertension and hypokalemia with a very high aldosterone: plasma renin ratio. This test is performed in order to exclude other causes of hypertension with hypokalemia such as Cushing’s syndrome, renal artery stenosis or licorice ingestion. Patients should not be taking angiotensin blockers as they may interfere with the test results. A ratio of greater than 30:1 is suspicious for primary hyperaldosteronism, which is associated with hypokalemia in only about fifty percent of cases. Thus the lack of a low serum potassium does not exclude the diagnosis. Primary aldosteronism is under-diagnosed and should be suspected in young patients with hypertension and in those whose blood pressure is hard to control with multiple anti-hypertensive drugs.

2. Theoretically, demonstration of lack of suppression of aldosterone by salt loading is needed to confirm the diagnosis of primary hyperaldosteronism. Pragmatically, this may induce heart failure in a patient with underlying cardiac disease so the physician has to be judicious in performing the test. A 24 hour urine aldosterone is measured after three days of oral salt loading. Aldosterone values of over 18 ug are diagnostic. Another alternative is parenteral salt loading. Urine sodium levels should also be checked in order to ensure that salt loading has been adequate.

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Meeting Perspectives-ASCO 2007

June 26, 2007

ASCOCommentary By: Theresa Ryan, M.D. Assistant Professor, Division of Oncology

During the first five days in June, the American Society of Clinical Oncology met in Chicago for their 43rd annual meeting. The theme of this meeting was “Translating Research into Practice,” emphasizing the society’s goal of enhancing patient care by creating a forum wherein the latest advances in translational and clinical cancer research are presented in the context of our current understanding of cancer biology. Many abstracts presented will lay the groundwork for further research. A number will likely have immediate impact. While I can not do justice to the scope of the meeting, I have highlighted a few of the presentations that I believe will have the greatest immediate impact on the practice of oncology as well as outline challenges for the future.

Abstract #1: “Randomized phase III trial of Sorafenib vs. placebo in patients with advanced hepatocellular carcinoma.” Results of the SHARP trial.

Importance: HCC is the 3rd cause of cancer death globally. HCC is expected to rise in incidence in the West. No standard therapy exists for advanced HCC.
Background: Sorafenib is a orally bioavailable multikinase inhibitor with anti-angiogenic, pro-apoptotic and Raf kinase inhibitory activity,
The Trial: A large, multicenter, randomized, placebo-controlled phase III trial evaluated the efficacy and safety of Sorafenib vs. placebo. This trial was stopped early as it met it pre-defined early stopping criteria. The HR for overall survival was 0.69 (95% CI: 0.55, 0.87; p=0.0006), representing a 44% improvement in overall survival vs. placebo. Median overall survival was 10.7 vs. 7.9 mos. Most frequent toxicities were diarrhea, hand-foot skin reaction, fatigue, and bleeding. The conclusions of the authors were that Sorafenib was well tolerated and is the first agent to demonstrate a statistically significant improvement in overall survival for patients with advanced HCC. This effect is clinically meaningful and establishes sorafenib as first-line treatment for these pts.
The editorial: While the improvement in overall survival is probably one only an oncologist could become excited about; this truly does represent a significant advance in our understanding and treatment of HCC. Traditional chemotherapy agents are essentially ineffective. This trial combined with the encouraging positive results of other (smaller) trials employing an “anti-angiogenic” strategy (bevacuzimab, sunitinib) provides a rationale upon which to develop future trials in HCC. Read more »

Meeting Perspectives: Digestive Disease Week (DDW) 2007

June 20, 2007

Commentary by Milini Sahu, MD Fellow, Division of Gastrotenterology, Gina Sam-DeRiggs, Fellow, Division of Gastroenterology, and Michael Poles MD,  Assistant Professor, NYU Division of Gastroenterology and Associate Editor, Clinical Correlations

Close to 17,000 gastroenterologists attended Digestive Disease Week (DDW) from May 19-24 in Washington DC. While I stayed behind (someone has to help with emergency endoscopies), the majority of NYU’s gastroenterology fellows and attendings were there for a week of learning, presenting, and making NYU proud.  Two of our fellows, Malini Sahu and Gina Sam-DeRiggs were there and have provided the majority of the information in this update.

As always, there is an immense amount of information presented at this meeting, where the world’s experts in gastroenterology present their most recent observations. A handful of important studies are presented below:

In a study examining the interaction between body weight and erosive esophagitis, Koo et al. performed a cross-sectional study. They enrolled 3801 patients in Korea who had routine EGD, of which 9.9% were found to have esophageal erosions. They found that BMI was higher in patients with esophageal erosions, though the average BMI of each group was less than 25. Waist circumference was also significantly higher in patients with erosive esophagitis. This study therefore suggests that, even in patients with fairly unimpressive BMIs, abdominal obesity is a risk factor for erosive esophagitis

As endoscopists, we are often faced with patients with melena for whom a diagnosis is not revealed by EGD and colonoscopy. A study examined 41 patients who received either capsule endoscopy or mesenteric angiogram as the next step in the diagnostic work-up. The authors showed that capsule endoscopy revealed the likely source of bleeding 55% of the time, while the angiogram only showed the source 9.5% of the time. A drawback of this study was the exclusion of further examination of the upper GI tract using enteroscopy, given that many lesions were found in the stomach (missed with the first endoscopy) and proximal small bowel (potentially within the reach of a longer endoscope). While therapy cannot be rendered with the capsule as opposed to angiography, it appears that it may be a important diagnostic modality in patients with obscure GI bleeding.

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Hyperparathyroidism in Chronic Kidney Disease

June 13, 2007

Commentary by Sarah Berry MD, PGY-3 and Joseph Weisstuch, MD Clinical Assistant Professor of Medicine, Divsion of Nephrology

Case: Mr. K is a 59 year old gentleman with a past medical history of hypertension, non-insulin dependent diabetes mellitus, dyslipidemia and worsening chronic kidney disease (CKD) over the last six years, despite compliance with his medications and optimized glucose and blood pressure control. His current medication regimen includes metoprolol, hydrochlorothiazide, aspirin, simvastatin, glyburide, and monopril. Mr. K’s most recent lab work indicates that his serum creatinine is 1.7mg/dl, potassium 4.6mmol/l, sodium 141mmol/l, magnesium 1.7mg/dl, calcium 9.4mg/dl, phosphate 3.5mg/dl, HgA1c 7.1%. His calculated GFR (via the Cockroft Gault formula) is 50ml/min, meeting the definition of Stage 3 CKD.

At a glance, Mr. K’s electrolytes look fine, with no apparent metabolic effects due to his chronic kidney disease as of yet. Are there any interventions to be made today?

The answer is yes. Abnormal phosphate retention is known to begin as early as Stage 2 (GFR 60-90ml/min). A compensatory elevation in serum intact parathyroid hormone (iPTH) initially prevents hyperphosphatemia by decreasing proximal tubule phosphate reabsorption. However, this physiologic compensation over time causes hyperplasia and hypertrophy of the parathyroid gland, setting the stage for secondary hyperparathyroidism and the wide array of metabolic, vascular, rheumatologic, and cardiac complications that accompany its onset.

Therefore, in patients with early stage CKD, measurement of serum iPTH is a better benchmark for action by physicians. This fact is emphasized in the K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease published in 2003. These guidelines specifically delineate goal iPTH values, varying by the severity of the CKD. In patients with Stage 3 CKD, such as Mr. K, goal iPTH is 35-70pg/ml. For patients with Stages 4 and 5 CKD, goal iPTH is 70-110pg/ml and 150-300pg/ml, respectively. [1]

On measurement, Mr. K’s iPTH level is 95pg/ml, significantly above the K/DOQI recommended value and an indication that he is progressing towards hyperparathyroidism. The K/DOQI guidelines also outline strict goals for serum phosphorus values: 2.7-4.6 for patients with stage 3 and 4 disease, and 3.5-5.5 for patients with Stage 5 CKD. How important is normalization of serum phosphorus? The evidence is mixed. In 2005, the data from 840 patients in the Modification of Diet in Renal Disease study showed that neither serum phosphate nor calcium-phosphate product were significantly associated with increased mortality in non-dialysis dependent patients. [2] However, a recent VA study of nearly 3490 veterans refuted those findings, showing that serum phosphate >3.5mg/dL in non-dialysis dependent patients was an independent marker for increased mortality at 2 years. Additionally, mortality increased linearly with each 0.5mg/dL increase in serum phosphate. [3]

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Clinical Commentary: The Travesty of Grinding Axes with Science: Rosiglitazone and Cardiac Risk

June 12, 2007

Welcome to our first blog commentary. One of the purposes of the blog is to generate discussion about issues in health care. This “Clinical Commentary” section is an invitation to our housestaff and faculty to submit their own thoughts and viewpoints on current issues. The views expressed in this section are soley those of the authors and do not necessarily represent the views of Clinical Correlations.

Commentary by Gregory Mints MD and Nirav Shah MD, MPH

The meta-analysis of Rosiglitazone’s effect on cardiovascular events by Nissen(1) had the effect of an exploding bomb in both the lay and medical media. Unfortunately, much of the ensuing discussion had relatively little to do with the quality of the paper itself (2), with disproportionate attention to the failure of drug safety oversight in general and to the attempts at assigning blame for it on the manufacturer of Rosiglitazone and/or the FDA(3, 4). It thus appears that the paper has become a political leverage tool in the fight over the future direction of drug oversight in this country. We contend that the concerns about the medication approval process in the U.S. and the impact of drug manufacturers on that process, however important and acute, should not interfere with objective analysis of the presented studies. We do not believe that the ends justify the means (i.e. wrong arguments are o.k. for the right reasons), but also think that politicizing the data interpretation is harmful to the cause of reforming the relationships among the FDA, the pharmaceutical companies and the consumers. Most of our thoughts on this issue came about in the discussions we had with the two other members of our faculty: Drs. Natalie Levy and Tanping Wong. It is our opinion that the meta-analysis in question is of extremely poor methodological quality, which precludes any meaningful interpretation of the data. We therefore believe that no change in current existing practice is warranted, a conclusion supported by a recent editorial in the Lancet (5).

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Can you switch a patient from insulin to oral agents?

June 6, 2007

  A 48 year old male is diagnosed with type 2 Diabetes Mellitus after presenting to the emergency room with symptoms of hyperglycemia. He was immediately started on insulin and has been very compliant with his regimen. His initial Hemoglobin A1C at the time of diagnosis was 15.  However, over the past few months, due to hypoglycemia, his insulin dosage has been titrated down. He is currently on low doses of NPH and aspart, with an A1C of 6.6. Would it be possible to convert this patient to oral agents, and, if  so, what is the best way to transition to an oral regimen?

Commentary by Terry Seltzer MD, Department of Endocrinology

Before deciding to convert the patient from insulin to an oral agent, one must first be certain that he is a Type 2 Diabetic. Thus the lean 20 year old patient should be considered a possible Type 1 Diabetic, even though thus far he phenotypically appears to be a Type 2.  In such patients consider obtaining an anti-glutamic acid decarboxylase antibody (Anti-GAD Ab) – if positive this would strongly suggest Type 1 Diabetes and I would suggest continuing the patient on insulin.

Once we have established that the patient is a Type 2 Diabetic, one must weigh the risks and benefits of continuing the insulin versus a trial of an oral agent.  Since the patient is already well controlled and presumably well adjusted to the insulin, any change is likely to at least temporarily disrupt his control.  On the other hand, insulin is known to promote weight gain.  Patients almost universally prefer oral agents to insulin because of its ease of administration, but also because they perceive their illness to be less serious when on oral agents.  Certain oral agents also offer some additional benefits.  Metformin was shown in the UKPDS study to reduce the risk of a myocardial infarction by about 40% over a five-year period in obese Type 2 Diabetics.  The thiazoladinediones, pioglitazone and rosiglitazone, may prevent progressive islet cell burnout.  In general, I would usually attempt to change the insulin to an oral agent after several weeks.  One exception is the woman who is contemplating pregnancy in the near future – she should be continued on insulin.

Which oral agent to choose?   First one must consider the patient’s comorbidities.  Certain agents may be ruled out after such consideration.  If the patient has renal insufficiency, metformin must not be used, and sulfonylureas carry a greater risk of hypoglycemia.  In congestive heart failure and in chronic liver disease, both metformin and the thiazoladinediones are contraindicated.  In the frail and/or elderly patient, it may be desirable to avoid the risk of hypoglycemia associated with the sulfonylureas and repaglinide.

In patients with the metabolic syndrome (abdominal obesity, hypertension, high LDL cholesterol, low HDL cholesterol, and high triglycerides associated with a severe insulin resistance), a trial of a thiazoladinedione addresses the underlying pathology most directly and might be considered the agent of choice.  However, the recent meta-analysis suggesting a 43% higher incidence of myocardial infarctions in patients treated with rosiglitazone calls this into question.  More data is needed to address this question.

For most other patients, I believe metformin is the first choice because of its beneficial effect on the risk of atherosclerotic heart disease and weight reduction.  The usual starting dose of metformin is 500 mg before breakfast and dinner. In general, I try to avoid the sulfonylureas because of the risk of severe hypoglycemia, and its negative effect on beta cell survival.  Whatever oral agent is chosen, the patient must be followed carefully when insulin is discontinued.  Often, the patient will be instructed to use a sliding scale of a rapidly acting insulin temporarily until the effectiveness of the oral agent can be determinined.  One reasonable sliding scale would be: 3 units for a glucose of 180 to 240, 5 units for 241 to 320, 8 units for 321 to 400, and 10 units for more than 400, but the dosage should be individualized for each patient.  The patient and physician must be in frequent communication during this time.

Image of insulin molecule, courtesy of Wikimedia Commons.

Meeting Perspectives: 2007 American Thoracic Society International Conference

June 5, 2007

Commentary by Doreen Addrizzo-Harris MD, Associate Professor, Division of Pulmonary and Critical Care Medicine

The 2007 American Thoracic Society (ATS) meeting took place between May18-23 in San Francisco, California at the Moscone Conference center.  There were more than 400 sessions, 800 speakers and 5,500 original research abstracts.  The meeting is concentrated in the areas of pulmonary, critical care and sleep medicine.

The NYU Division of Pulmonary and Critical Care medicine, under the direction of Dr. William N. Rom, presented more than 30 original research abstracts and symposium in areas such as tuberculosis, asthma, lung cancer, WTC exposure, sleep medicine, interventional bronchoscopy and sepsis to name a few.  Fellow Pablo Herscovici, under the mentorship of Dr. David Steiger, was one of 14 chosen to present a case report at the fellow’s forum titled “Follicular Bronchiolitis in a Patient With Behcet;s Disease.”

Several faculty chaired symposium – Dr. David Rapoport- “Pathophysiology of Obstructive Sleep Apnea”; Dr. Joan Reibman – ” Upper respiratory Tract Disorders after the WTC collapse”; Dr. William Rom – ” Air Pollution: From Science to Policy;” and Dr. David Ost – ” Practical Interventional Pulmonology” and “Healthcare Associated Pneumonia Update.”

Dr. Doreen Addrizzo-Harris, president of the Association of Pulmonary and Critical Care Medicine Program Directors, and member of the ATS training committee, chaired the annual business meeting with updates on the new web-based pulmonary/ critical care medicine in-service exam which began his year.  The ATS will now allow free membership for fellows in their first year of training.  They have also made available on the ATS website (wwww.thoracic.org) an extensive ATS reading list on important publications in pulmonary, critical care and sleep medicine.

Some highlights of the meeting included a presentation by Dr. David Schwartz, director of the National Institute of Environmental Health Sciences, at a town hall meeting on changes in grant funding from the NIH and NIEHS.  More flexibility in grant funding and more assistance with regulatory barriers are planned for change. A scientific symposium chaired by Dr. Talmadge King addressed the difficult clinical situation of idiopathic pulmonary fibrosis and when to treat these patients.  A new NIH sponsored trial will evaluation the role of treatment in this group with a randomized control trial of three groups of patients; those being treated with prednisone, azathioprine and N-acetylcystine; those on N-acetylcystine alone and those on placebo.  The results of this trial are extremely important in the treatment of patient with IPF as there has been no significant reduction in mortality with any current therapy except for lung transplant.

A popular session on lung cancer chaired by Dr. Charles Powell from Columbia University and Dr. James Jett from Mayo Clinic highlighted the difficulties of following patients with pulmonary nodules detected on CT.  More than 99% of nodules detected that were less than 7mm in size were determined to be benign over time.  As nodule size increased the concern for malignancy increased as well.  Complex nodules, those with both solid and ground glass features, were the most likely nodules to be malignant with evidence of invasive adenocarcinoma.  Multiple genetic markers may play a key role in determining which carcinomas will progress and respond to treatment.

The 2008 ATS will take place in Toronto, Canada next year. 

Recent Developments in the Treatment of Renal Cell Carcinoma

May 31, 2007

Commentary by Michael Seidman MD, Chief Oncology Fellow

New treatment options for both early and advanced Renal Cell Cancer have recently been published. Traditionally, treatment for early stage disease was partial or radical nephrectomy. In the metastatic setting, treatment options were limited to toxic cytokine therapy with IFN or IL-2.

Some recent literature has suggested that small, incidentally found renal tumors can safely be watched without the need for invasive surgery. Remzi et al [1] retrospectively reviewed 287 tumor bearing kidneys 4cm or less detected by imaging and surgically removed. High grade (poorer prognostic) tumors were seen in 4.2%, 5%, and 25.5% of tumors measuring 2 cm or less, 2.1-3.0 cm, and 3.1 to 4.0 cm respectively. Distant metastases were seen in 2.4% of tumors 3.0 cm or less compared to 10.8% of tumors 3.1-4.0 cm.

Schlomer et al [2] examined 349 renal masses form 331 patients. Malignant tumors were seen in 72.1% of tumors less than 2 cm compared to 93.7% of tumors greater than 7cm. The mean size of tumors in patients with symptoms at the time of diagnosis was 6.2cm compared to 3.7cm for tumors discovered incidentally. High grade histology was more common in larger tumors, occurring in 52 % of tumors >4cm compared to 7% and 29% in tumors measuring <2.0 cm and 2-4cm respectively.

These recent reports support the notion that most small renal tumors, especially those <3.0 cm are indolent in nature. In older patients, and those with multiple comorbidities, watchful waiting is an option. Newer technologies, specifically cryoablation and radiofrequency ablation, can provide good disease control with a less invasive procedure than nephrectomy. Matin et al [3] reported on 616 patients who underwent RFA and cryoablation. 10% of the patients had residual or recurrent disease after primary therapy. After salvage ablative therapy, failure was seen in only 4.2% of patients treated. 2 yr overall survival in patients with recurrent or residual disease was 82.5% with a 97.4% 2-year metastasis-free survival.

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New Guidelines on the Management of Intracerebral Hemorrhage

May 30, 2007

Commentary by Dr. Daniel Labovitz, Director of the NYU Stroke Center

After an 8-year hiatus, the American Heart Association/American Stroke Association has at last published a fresh set of guidelines on the management of acute spontaneous intracerebral hemorrhage (ICH) [Stroke 2007: DOI: 10.1161/STROKEAHA.107.183689]. ICH represents between 10 and 20% of all first strokes, depending on the population, but carries a mortality rate of 35% to 50%, with hemorrhage volume, hemorrhage location, intraventricular extension and age all contributing independently to the risk of death. Unfortunately, our therapeutic options have not changed substantially since the last set of guidelines came out in 1999. However, the new guidelines do provide a succinct overview of the literature and reflect evolving expert opinion based on pilot studies and observational studies. The paragraphs below describe some highlights.

Since the last set of guidelines was published there have been only two phase 3 clinical trials for acute hemorrhage management and both were negative. The STICH trial [Lancet 2005;365:387-397] showed no benefit for early surgical hemorrhage evacuation (within 24 hours of enrollment) as compared to routine care (including later surgical evacuation); however secondary analysis suggested there might be a benefit to early evacuation if the hematoma is <1 cm from the surface. The results of the phase 3 FAST trial of factor VII for acute ICH were not available for discussion in the guidelines but the phase 2 trial is discussed. We now know that the phase 3 trial was negative (unpublished except for a February 2007 press release), showing no benefit for disability or mortality at 3 months, although hemorrhage size was significantly reduced.

Although no important trials on blood pressure management in acute ICH have been published since the last set of guidelines came out, the discussion of blood pressure management is substantially expanded and the recommendations are slightly more nuanced. A series of studies have shown that some hematomas continue to expand in the first hours after onset, although expansion doesn’t continue beyond 24 hours in the absence of a coagulopathy. Theoretically, aggressive blood pressure reduction might reduce the risk of hematoma expansion; on the other hand, blood pressure reduction might lead to infarction of tissue with reduced circulation due severe local mass effect (although no such “penumbra” of tissue has been demonstrated on PET). The original guidelines recommended keeping the MAP <130 in acute ICH patients based on such reasoning. The new guidelines are effectively no different, recommending MAP <130 or SBP <180 and, for the first time, suggesting that pressure should be maintained high enough to maintain a cerebral perfusion pressure >60. The guidelines do not address how long the parameters should apply.

Prophylaxis against venous thrombo-embolism is addressed. The old guidelines simply stated that pneumatic compression devices reduce the risk of pulmonary embolism but made no formal recommendation. Now pneumatic compression devices are a class 1 recommendation; furthermore, subcutaneous heparin “may be considered…3-4 days from onset.”

Image of human brain from NIH, courtesy of Wikimedia Commons.

 

How should you approach a pregnant patient with chronic kidney disease?

May 25, 2007

A 31 year old female with hypertension and proteinuria secondary to IgA nephropathy, currently treated with an ARB, presents to clinic stating that she would like to become pregnant.

What is the risk of fetal morbidity in the setting of ARBs/ACE-inhibitors? What antihypertensive medications are used during pregnancy? At what point would you switch a patient’s medications if she is trying to become pregnant? What is the natural course of IgA nephropathy during pregnancy?

-Minisha Sood MD, PGY-3

Pregnancy and Chronic Kidney Disease
Commentary by Sergio Obligado MD, Renal Fellow

Chronic kidney disease (CKD) carries significant risks to the mother and fetus in pregnancy. Diseases such as IgA nephropathy (which frequently occurs in the second and third decades of life) and diabetic glomerulosclerosis, are sufficiently common that reproductive-age women with these diseases present to their primary care doctors. The overall incidence of pregnancy and CKD has been estimated to be in the range of .03 to .12% in different populations. 1

During the first trimester, the physiology of normal pregnancy is characterized by decreased blood pressure, increased glomerular filtration rate and renal plasma flow, and sodium and water retention.1 Although normal pregnant woman will achieve this increased GFR without an increase in glomerular capillary pressure, women with renal disease tend to have increases in proteinuria, even during early stages of pregnancy. During the second and third trimesters, when blood pressure starts to rise and GFR falls in normal women, women with kidney disease can manifest dangerous elevations in blood pressure and dramatic increases in proteinuria.2

Although systemic diseases can significantly influence the maternal and fetal outcomes (i.e. diabetes, SLE), there isn’t any strong evidence that the type of glomerular disease independently effects pregnancy outcomes.3, 4 However, most retrospective and observational studies written on pregnancy and CKD clearly document that the risks are inversely related to GFR at onset of pregnancy. Women with creatinine < 1.3 seem to do quite well, with relatively insignificant changes in GFR and proteinuria.1 A study in the NEJM in 1996 followed 86 pregnancies in women with moderate to severe non-diabetic renal disease (creatinine > 1.4).5 They found that the mean creatinine rise was 1.9 to 2.6, and 20% of women had worsening hypertension and severe proteinuria by the third trimester. 8 of the women required dialysis by 1 year post-partum. The vast majority of the maternal morbidity occurred in the women who had a creatinine > 1.9 at initiation of pregnancy. The remaining small studies show similar outcomes; a third of women with creatinine > 1.5 have irreversible renal decline. Certainly, complications of pregnancy are more frequent as well. Preeclampsia has been reported to occur in up to 40% of women with CKD; although the definition of preeclampsia in a woman who begins a pregnancy with hypertension and proteinuria, in my opinion, is somewhat arbitrary.

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FDA Black Box Warning on Gadolinium

May 24, 2007

Back in December we reported on the FDA cautioning practioners about the use of gadolinium (an mri contrast agent) in patients with chronic kidney disease.  The FDA is now requesting a black box warning  stating “that patients with severe kidney insufficiency who receive gadolinium-based agents are at risk for developing a debilitating, and a potentially fatal disease known as nephrogenic systemic fibrosis (NSF). In addition, it would state that patients just before or just after liver transplantation, or those with chronic liver disease, are also at risk for developing NSF if they are experiencing kidney insufficiency of any severity.” 

Prior 12/06 post discussing NSF

FDA Request