Renal failure

APPROACH to Cardiac Troponin Elevations in Patients With Renal Disease

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A 62-year-old male presented to the emergency department with chest pain radiating down his left arm that lasted 40 minutes and awakened him 3 hours prior to arrival. It was associated with shortness of breath, nausea, and diaphoresis. You note a history of hypertension and hypercholesterolemia controlled with hydrochlorothiazide and atorvastatin. In addition, he has chronic renal failure, for which he tells you that his doctor thinks he might soon require dialysis. His father had died of an acute myocardial infarction (AMI) at 70 years of age. Physical examination shows no acute distress. His blood pressure is 149/89 mmHg and heart rate is 86 bpm. On auscultation, both heart sounds are audible and normal, although you do notice a fourth heart sound and bibasilar rales on the chest posteriorly along with bilateral pedal edema to the level of the mid-shins and mild jugular venous distension. A 12-lead ECG suggests left ventricular hypertrophy (LVH) but is otherwise unremarkable, and his chest x-ray is normal. Upon reviewing his blood work you notice that his cardiac troponin (cTn) level drawn on admission was elevated and that his most recent estimated glomerular filtration rate (eGFR) is 23 mL/min. The resident with you concludes the elevated cTn can be explained by the patient’s renal failure and that his kidneys are no longer able to excrete it effectively. He goes on to state that, despite the patient’s highly suggestive report of chest pain and impressive risk factors, in the absence of ECG changes or “new” cTn elevations, this cannot be classified as an AMI. The patient is therefore not at high risk and so is not a candidate for an invasive strategy and can be managed with medical therapy alone.

Our approach

The resident is correct in recalling that the universal definition of AMI requires elevated biochemical markers of myocardial necrosis in addition to either symptoms of cardiac ischemia or ECG changes indicative of ischemia. In addition, he is correct in noting that elevated cTn levels related to cardiac ischemia are associated with an adverse prognosis and that these high-risk patients benefit from an early invasive strategy. However, the resident has made a number of errors as well. The cTn used here is a conventional assay and, with these, cTn is typically only elevated in patients with end-stage renal disease (ESRD). In this setting, raised levels increase progressively as the duration of dialysis increases and are associated with a poor prognosis. This patient may require renal replacement therapy soon, but, for the time being, his eGFR is not low enough to explain the elevated cTn. Even if it was low enough, there is no evidence that cTn is cleared renally. cTn may persist in the blood of patients with ESRD due to alternative cleavages involved in the degradation of the protein. This is also likely to be the reason why there are more elevations of cTnT than of cTnI, although both predict adverse long-term outcomes. Furthermore, concomitant changes such as LVH and other metabolic changes can often be attributed to cTn elevations.

This patient’s cTn may in fact be associated with a coronary event. A more diligent resident may have checked the patient’s chart for previous cTn levels, which, if in the normal range, would help to identify a rising pattern. The universal definition for AMI states that clinicians should look for a rising and/or falling pattern in cTn levels. This may not necessarily be synonymous with an AMI, but certainly indicates an acute event, which, along with a suggestive ECG or clinical history, should help to confirm the diagnosis of an AMI. Patients who present late (12–18 hours) after the onset of symptoms may not demonstrate a rising/falling pattern, so clinical judgment must be used. However, in this situation, the patient presented 3 hours after the onset of symptoms and one would expect a rising pattern associated with an acute coronary event. Thus, serial cTn levels should be drawn at 3 and 6 hours from the point of the patient’s arrival. A documented rising pattern in conjunction with the clinical history will confirm the diagnosis of AMI and trigger the decision for an early invasive approach, but the patient should receive full antiplatelet therapy in the meantime if suspicion of an acute coronary syndrome is high. If such a pattern is not present, alternative diagnoses should be sought. A presumptive diagnosis of AMI should not be made. This is particularly important among patients with ESRD whose cTn is elevated at baseline and who are at higher risk for bleeding as a result of their uremic state, and should not, therefore, be needlessly subjected to invasive procedures. In addition, the use of IV contrast during angiography may lead to worsening of already compromised renal function, further highlighting the need for appropriate case selection. A useful approach for these patients is to have cTn drawn routinely in outpatient settings, which can provide a baseline cTn level with which levels drawn during an acute presentation can be compared to help make a diagnosis.

Marked elevations in cTn tend to occur in only four situations: AMI, myocarditis, renal failure, and, on rare occasions, with an analytical error. Thus, serially drawn levels are still required, and a crucial facet of this problem is defining what degree of change in cTn is required. One such approach may be to define a level of change that exceeds the degree of analytical imprecision associated with a particular assay. This will vary from assay to assay and should be calculated and reported by laboratories. The changes required will be large on a percentage basis when the initial level is low, but, in ESRD where the baseline levels are elevated, lesser changes are required. Some have suggested a change of 50% when values are close to the 99% upper reference limit and 20% when they are above this.

With a high-sensitivity troponin assay, a higher proportion of elevated levels will be appreciated and will often be associated with abnormal renal function, even when it is mild. As with conventional assays, these elevations also predict poor outcomes. These observations clarify to some extent the relationship between renal dysfunction and troponin, but also create the clinical challenge of discriminating elevations related to an acute cardiac event from other pathologies.

Ultimately, an understanding of cTn testing in conjunction with Bayesian principles of diagnostic testing must inform the decision-making process. This patient’s risk factors (including the fact that he has chronic renal failure) and clinical presentation give rise to a high pretest probability of disease. The isolated elevation in cTn determined using a conventional assay is unlikely to be related to his renal failure but cannot be immediately attributed to AMI until a changing pattern is observed, at which point his post-test probability of disease will justify an early invasive approach. When in doubt, clinical judgment must be used. Lastly, but of equal importance, is the fact that the elevation is associated with an adverse prognosis. Thus, our astute resident should investigate whether there is good control of blood pressure, volume, and lipids and institute preventative pharmacotherapy as appropriate.

Reduced Kidney Function Linked With Higher Risk Of Kidney And Urothelial Cancers.

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Individuals with poor kidney function may require more intensive screening for these cancer types

Reduced kidney function may increase the risk of developing kidney and urothelial cancers, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). The findings suggest that patients with kidney disease may benefit from more intensive screenings for these types of cancer.

Chronic kidney disease and cancer are both major and growing public health problems. “While multiple studies have observed higher risks of cancer in persons with end-stage renal disease, the association of less severe kidney disease with cancer remains poorly understood,” said Alan Go, MD (Kaiser Permanente Northern California).

To investigate, Dr. Go and his colleagues analyzed information from nearly 1.2 million adult members of Kaiser Permanente in Northern California who were at least 40 years of age and who had no history of cancer, dialysis, or kidney transplantation. Kidney function was measured by estimated glomerular filtration rate (eGFR), with normal kidney function being over 60 ml/min/1.73m2 and kidney failure being below 15 ml/min/1.73m2.

During more than 6 million person-years of follow-up, 72,875 individuals developed cancer. (A person-year is the number of years of follow-up multiplied by the number of people in the study.) Among the major findings during follow-up:

Individuals with an eGFR of 45 to 59 had a 39% increased risk of kidney cancer (or renal cell carcinoma).
Individuals with an eGFR of 30 to 44 had an 81% increased risk of kidney cancer.
Individuals with an eGFR below 30 had a 100% (or a 2-fold) increased risk of kidney cancer.
Individuals with an eGFR below 30 had a 48% increased risk of urothelial cancer, which includes tumors in the bladder and ureters.
There were no significant links between eGFR and other cancer types such as prostate, breast, lung, and colorectal cancers.

The researchers noted that various biologic mechanisms may help to explain the links observed in this study. For example, kidney dysfunction causes a state of chronic inflammation and oxidative stress. “These and other mechanisms deserve further study in order to better define the link between kidney function and site-specific cancer risk,” said lead author Will Lowrance, MD, MPH (University of Utah).

In an accompanying editorial, Jonathan Hofmann, PhD and Mark Purdue, PhD (National Cancer Institute) noted that the study is “an important step forward in characterizing the relationship between chronic kidney disease and risk of renal cell carcinoma and other malignancies. Studies such as this further support an etiologic role of impaired renal function in the development of renal cell carcinoma.”

 

Source: American Society of Nephrology

 

IV thrombolysis and renal function.

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Abstract

Objective: To investigate the association of renal impairment on functional outcome and complications in stroke patients treated with IV thrombolysis (IVT).

Methods: In this observational study, we compared the estimated glomerular filtration rate (GFR) with poor 3-month outcome (modified Rankin Scale scores 3–6), death, and symptomatic intracranial hemorrhage (sICH) based on the criteria of the European Cooperative Acute Stroke Study II trial. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Patients without IVT treatment served as a comparison group.

Results: Among 4,780 IVT-treated patients, 1,217 (25.5%) had a low GFR (<60 mL/min/1.73 m2). A GFR decrease by 10 mL/min/1.73 m2 increased the risk of poor outcome (OR [95% CI]): (ORunadjusted 1.20 [1.17–1.24]; ORadjusted 1.05 [1.01–1.09]), death (ORunadjusted 1.33 [1.28–1.38]; ORadjusted 1.18 [1.11–1.249]), and sICH (ORunadjusted 1.15 [1.01–1.22]; ORadjusted 1.11 [1.04–1.20]). Low GFR was independently associated with poor 3-month outcome (ORadjusted 1.32 [1.10–1.58]), death (ORadjusted 1.73 [1.39–2.14]), and sICH (ORadjusted 1.64 [1.21–2.23]) compared with normal GFR (60–120 mL/min/1.73 m2). Low GFR (ORadjusted 1.64 [1.21–2.23]) and stroke severity (ORadjusted 1.05 [1.03–1.07]) independently determined sICH. Compared with patients who did not receive IVT, treatment with IVT in patients with low GFR was associated with poor outcome (ORadjusted 1.79 [1.41–2.25]), and with favorable outcome in those with normal GFR (ORadjusted 0.77 [0.63–0.94]).

Conclusion: Renal function significantly modified outcome and complication rates in IVT-treated stroke patients. Lower GFR might be a better risk indicator for sICH than age. A decrease of GFR by 10 mL/min/1.73 m2 seems to have a similar impact on the risk of death or sICH as a 1-point-higher NIH Stroke Scale score measuring stroke severity.

Higher creatinine can occur after CT — even without contrast.

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Contrast media is often blamed for what appears to be contrast-induced nephropathy (CIN) in patients getting CT scans. But Chinese researchers have found that elevated rates of serum creatinine — a marker for CIN — can occur after CT even in

There are lots of reasons why patients could have higher serum creatinine levels after CT exams, according to two studies presented by researchers from Peking University First Hospital in Beijing at the 2013 International Symposium on Multidetector-Row CT. Clarifying those reasons is critical, according to the group.

“There are many factors affecting creatinine levels, especially among inpatients,” said Dr. Xiaoying Wang in her presentation. “Many patients have severe diseases where, due to the disease, doctors find it is not appropriate for them to have contrast-enhanced CT.”

Nailing down renal impairment

The findings don’t necessarily fit with conventional wisdom on contrast-induced nephropathy; however, they do highlight the multifactorial nature of impaired renal function and remind clinicians that several factors must be present for a CIN diagnosis, Wang said.

“The definition of CIN is clear and simple, but in practice it’s not easy to define,” she said. CIN requires an absolute or relative increase in serum creatinine (SCr) compared to baseline values, a temporal relationship between the rise in SCr and exposure to a contrast agent, and the exclusion of alternative explanations for renal impairment — which means looking for these explanations.

“Generally, as radiologists it is easy for us to detect an increase in serum creatinine, but it is not very easy for us — sometimes not even easy for nephrologists — to exclude alternative reasons for renal impairment,” Wang said.

In an effort to identify at-risk patients, in Wang’s practice, patients making appointments for contrast-enhanced CT are asked about a range of factors suggestive of CIN risk. The literature shows higher levels of risk for patients with a history of diabetes mellitus, hypertension, renal impairment, liver disease, renal-toxic medications, and a few other circumstances, though the studies used to identify the risk factors involved intra-arterial injection of contrast agents, Wang said.

Study 1: Are at-risk patients really more at risk for CIN?

For patients undergoing contrast-enhanced CT between 2010 and 2012, her group analyzed the association between risk factors and the subsequent development of CIN. The researchers examined a total of 2,556 patients, of whom 1,243 formed an observation group. The patients were measured for SCr before contrast-enhanced CT as well as 48 to 72 hours after CT; if SCr levels rose by the second test, the patient was referred to a nephrologist, and SCr was measured again seven to 10 days later.

In all, 68 (5.5%) of the 1,243 patients were diagnosed with CIN, including 12 with acute renal failure. (Fifty-one patients recovered and five were lost to follow-up.) However, the study showed no statistically significant difference in the development of CIN between the patients with risk factors and those without.

Of the patients who were not at risk, 4.5% (17/375) developed CIN, while in the at-risk group, 5.9% (51/868) developed the condition (p = 0.21). Among patients with no history of chronic kidney disease, only female gender (p = 0.03) and the use of low-osmolar contrast media (p = 0.03) were associated with a significantly increased risk of CIN.

Logistic regression analysis of risk factors showed several that increased the odds of CIN, including a history of diabetes mellitus (odds ratio [OR] = 1.83), history of tumor (OR = 1.54), use of nephrotoxic drugs (OR = 1.69), frequent use of contrast media (OR = 1.13), and use of low-osmolarity contrast media (OR = 2.28). In addition, women had an odds ratio of 1.69, and those older than 75 had an odds ratio of 1.26. The difference was only statistically significant in women (p = 0.04), however.

“These [risk] factors are not very strong to [predict] the incidence of CIN,” Wang said.

Study 2: Is ‘CIN’ risk really higher after noncontrast CT?

To continue to refine risk-factor prediction, the group recently completed a prospective cohort study of 623 patients who underwent CT with and without contrast. Of the 623 patients, 171 formed an observation group that received multiple SCr tests to allow the nephrologist to confirm a temporal association between increased SCr and contrast administration.

Among these 171 patients, 99 underwent contrast-enhanced CT and 72 had CT without contrast. There was no statistically significant difference in demographics and CIN-related risk factors between the 171 patients and the remaining 452, Wang said.

In all, 17 (9.9%) of the 171 patients developed what appeared to be CIN. Dividing up the patients between those who received contrast and those who did not, seven (7.1%) of the 99 who got contrast developed CIN. Meanwhile, 10 (13.9%) of the 72 patients who did not receive contrast developed “CIN.” Again, the difference in CIN rates between those who did and did not receive contrast was not statistically significant (p = 1.414).

Many factors affect creatinine levels, especially among those like the inpatients in this study, who have a wide range of medical conditions and are prescribed a variety of medications, Wang concluded. Even factors ranging from higher muscle mass to recent ingestion of cooked meat can result in higher SCr levels.

“That’s how we explain the higher SCr levels among noncontrast CT patients,” she said. “The increase of serum creatinine level after CT examination may occur without iodine contrast administration.”

She cautioned, though, that the sample sizes were small in both studies.

Excluding alternative explanations for renal impairment is crucial for diagnosing CIN, Wang concluded, and large, prospective cohort studies are needed to determine the true incidence of CIN in contrast-enhanced CT.

Source: auntminnie.com

FDA Warns That Opana Abusers Risk Blood Disorder .

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The extended-release formulation of the opioid Opana (oxymorphone) can cause thrombotic thrombocytopenic purpura if the pills are crushed and injected intravenously, the FDA warned on Thursday.

The complication can lead to kidney failure, brain damage, or stroke. Injecting Opana has resulted in at least one death.

Abuse of this painkiller has been on the rise since 2010, when Oxycontin (oxycodone) was made more difficult to inject or snort, according to Reuters. A crush-resistant formulation of Opana was announced by the manufacturer last month.

Source: FDA

Renal Safety of Treatment for Chronic HBV Infection.

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Nephrotoxicity was similar with tenofovir or entecavir.

Both tenofovir and entecavir are considered first-line oral antiviral agents for chronic hepatitis B virus (HBV) infection. In previous studies, nephrotoxicity has been observed with tenofovir therapy in patients coinfected with HBV and HIV. However, whether similar renal toxicity is present during tenofovir therapy in patients with HBV monoinfection is unclear.

This community-based, retrospective study compared nephrotoxicity in 80 patients with HBV infection who were treated with tenofovir (300 mg with varying frequency) — alone or in combination with another antiviral — and in 80 age- and sex-matched patients treated with entecavir alone (0.5 mg or 1 mg with varying frequency). Nephrotoxicity was defined as an incidence of serum creatinine (SCr) 2.5 mg/dL, an increase in SCr of 0.2 mg/dL, a drop in the estimated glomerular filtration rate (eGFR) to <60 mL/min, or an adjustment in medication dosage. The tenofovir and entecavir groups were similar in proportions of patients with diabetes mellitus (20% in each group), history of kidney or liver transplant (20% and 16%), and preexisting renal insufficiency (19% and 13%).

During treatment (mean duration, 80 weeks with tenofovir and 111 weeks with entecavir), more patients in the tenofovir versus the entecavir group had an eGFR <60 mL/min (15 vs. 6; P=0.022) and required medication dose adjustment (13 vs. 4; P=0.021). However, more patients in the entecavir versus the tenofovir group developed a SCr 2.5 mg/dL (6 vs. 1; P=0.053). Of note, in multivariate analysis, therapy assignment was not associated with an increase in SCr of 0.2 mg/dL or in eGFR <60 mL/min. Only history of organ transplant and preexisting renal insufficiency were associated with an increase in SCr of 0.2 mg/dL.

Comment: Renal adverse events were similar in patients receiving either tenofovir or entecavir for treatment of HBV infection. These findings are similar to those of long-term safety studies for both agents based on the treatment cohorts in their phase III registration trials. Clinicians should keep in mind that other patient factors, such as preexisting renal insufficiency, also increase the risk for renal adverse events.

Source: Journal Watch Gastroenterology