Renal function

Renal outcomes associated with invasive versus conservative management of acute coronary syndrome: propensity matched cohort study.

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Abstract

Objectives To examine the association of early invasive management of acute coronary syndrome with adverse renal outcomes and survival, and to determine whether the risks or benefits of early invasive management differ in people with pre-existing chronic kidney disease.

Design Propensity score matched cohort study.

Setting Acute care hospitals in Alberta, Canada, 2004-09.

Participants 10 516 adults with non-ST elevation acute coronary syndrome.

Interventions Participants were stratified by baseline estimated glomerular filtration rate and matched 1:1 on their propensity score for early invasive management (coronary catheterisation within two days of hospital admission).

Main outcome measures Risks of acute kidney injury, kidney injury requiring dialysis, progression to end stage renal disease, and all cause mortality were compared between those who received early invasive treatment versus conservative treatment.

Results Of 10 516 included participants, 4276 (40.7%) received early invasive management. After using propensity score methods to assemble a matched cohort of conservative management participants with characteristics similar to those who received early invasive management (n=6768), early invasive management was associated with an increased risk of acute kidney injury (10.3% v 8.7%, risk ratio 1.18, 95% confidence interval 1.03 to 1.36; P=0.019), but no difference in the risk of acute kidney injury requiring dialysis (0.4% v 0.3%, 1.20, 0.52 to 2.78; P=0.670). Over a median follow-up of 2.5 years, the risk of progression to end stage renal disease did not differ between the groups (0.3 v 0.4 events per 100 person years, hazard ratio 0.91, 95% confidence interval 0.55 to 1.49; P=0.712); however, early invasive management was associated with reduced long term mortality (2.4 v 3.4 events per 100 person years, 0.69, 0.58 to 0.82; P<0.001). These associations were consistent among people with pre-existing reduced estimated glomerular filtration rate and with alternate definitions for early invasive management.

Conclusions Compared with conservative management, early invasive management of acute coronary syndrome is associated with a small increase in risk of acute kidney injury but not dialysis or long term progression to end stage renal disease.

Discussion

In this cohort study, compared with people managed conservatively, people with otherwise similar characteristics who received early invasive management for non-ST segment elevation acute coronary syndrome were modestly more likely to develop acute kidney injury during admission to hospital. Despite this finding, early invasive management was not associated with a significant increase in short term risk of acute kidney injury requiring dialysis, or long term risk of end stage renal disease, but was associated with better long term survival. Similar findings were observed when people who received invasive procedures at any time during admission to hospital were compared with those managed medically, and when those who received coronary revascularisation were compared with those who received medical management alone. Although patients with lower estimated glomerular filtration rate at admission were less likely to receive invasive management and were at higher risk of adverse outcomes, the associations between invasive management and clinical outcomes remained consistent across varying levels of baseline estimated glomerular filtration rate. These finds suggest that the additional short term risks of acute kidney injury associated with invasive coronary procedures are fairly small and, when considered alongside other clinical outcomes, should not act as a deterrent to their use.

Data on the risk of adverse renal events from randomised trials of early invasive versus conservative treatment for acute coronary syndrome are limited, in part due to the exclusion of patients with moderate to severe renal insufficiency from trials. Among people with baseline serum creatinine concentrations <1.7 mg/dL (150 μmol/L) enrolled in the Fast Revascularization during InStability in Coronay artery disease (FRISC) trial, estimated glomerular filtration rate declined similarly in the early invasive and conservative management arms; however, the incidence of acute kidney injury, acute dialysis, and end stage renal disease was not reported.32 Several previous observational studies have shown a high incidence of acute kidney injury after coronary angiography and percutaneous coronary intervention in people with chronic kidney disease,10 11 and strong associations between acute kidney injury and death, major adverse cardiovascular events, and kidney failure requiring dialysis in this setting.12 1314 16 Although other studies have examined the links between acute kidney injury and mortality and end stage renal disease in people admitted to hospital with myocardial infarction treated with either invasive or medical management,18 33 these studies have not compared renal outcomes on the basis of treatment strategies.

Our findings show that acute kidney injury is a relatively common complication in people with non-ST elevation acute coronary syndrome and chronic kidney disease and increases substantially with lower baseline estimated glomerular filtration rate. However, the difference in the incidence of acute kidney injury between people who receive early invasive management and similar patients treated conservatively is relatively small. Importantly, despite the modestly higher risk of acute kidney injury associated with early invasive management at all levels of estimated glomerular filtration rate, our findings suggest that this strategy is not associated with higher risks of more clinically relevant renal outcomes (including acute dialysis or progression to end stage renal disease), which occurred much less often at all levels of baseline estimated glomerular filtration rate, regardless of treatment strategy. Since early invasive management seemed to be consistently associated with a long term survival advantage at all levels of baseline estimated glomerular filtration rate, these findings (interpreted in light of their consistency with results from randomised trials showing that early invasive management improves long term survival in high risk patients3 4) suggest that restricting or delaying access to invasive coronary procedures may not avoid most cases of clinically relevant acute kidney injury and could deny high risk individuals (including those with pre-existing chronic kidney disease) important benefits.

There are several potential mechanisms for the higher risk of acute kidney injury associated with early invasive management. People who received early invasive management were more likely to receive coronary angiography, percutaneous coronary intervention, coronary artery bypass grafting surgery, and angiotensin converting enzyme inhibitors or angiotensin receptor blockers, placing them at risk of acute kidney injury from contrast exposure, perioperative ischaemia, and haemodynamic effects. Furthermore, patients who received invasive management had a longer hospital stay and more measurements of creatinine during follow-up, which may have increased the probability that acute kidney injury would be ascertained. However, the magnitude of the increased risk associated with invasive management strategies was small, suggesting that patients’ characteristics such as age, comorbidity, pre-existing chronic kidney disease, drug use (including diuretics and inhibitors of the renin angiotensin system), and haemodynamic instability are more important contributors to the risk of acute kidney injury in patients with acute coronary syndrome than whether or not they are managed invasively or medically.

The better survival associated with early invasive management of non-ST elevation acute coronary syndrome in this cohort are in keeping with the clinical benefits of angiography and revascularisation reported in clinical trials, including subgroups with pre-existing chronic kidney disease.2 3 4 Although episodes of acute kidney injury have been linked to an increased risk of end stage renal disease,18 19 34 we did not observe a higher risk of end stage renal disease in people with otherwise similar characteristics who received early angiography despite the higher risk of acute kidney injury, even among strata with lower baseline estimated glomerular filtration rate. Radiocontrast associated acute kidney injury is typically manifested by a small change in serum creatinine levels, rarely leads to acute dialysis, and is usually reversible.10 Our findings suggest that the majority of such additional episodes of acute kidney injury associated with invasive procedures may confer relatively low risks of progression to end stage renal disease, although further studies are needed to help predict those at risk of progressive chronic kidney disease after acute kidney injury.

Conclusion

In conclusion, early invasive management of non-ST elevation acute coronary syndrome is associated with a small increase in the risk of acute kidney injury compared with a conservative management approach but is not associated with higher risks of in-hospital acute kidney injury requiring dialysis or long term risk of end stage renal disease. Given the improvement in cardiovascular outcomes and long term survival observed with early invasive management, these results suggest that invasive treatments should not be withheld solely because of concern they might increase the risk of kidney injury.

What is already known on this topic

  • Acute kidney injury after invasive coronary procedures is associated with adverse outcomes, including end stage renal disease and death
  • Fear of precipitating contrast induced acute kidney injury possibly contributes to underuse of invasive treatments for acute coronary syndrome in people at high risk of kidney disease
  • Comparisons of renal outcomes between people treated with invasive versus conservative management are lacking
  • People who received early invasive management for non-ST segment elevation acute coronary syndrome were modestly more likely to develop acute kidney injury
  • After early invasive management the risks of requiring dialysis and long term risk of end stage renal disease were similar, and patients had better long term survival than those treated conservatively
  • These findings were consistent across varying levels of baseline kidney function, suggesting similar relative risks and benefits of early invasive management in people with and without pre-existing kidney disease

What this study adds

 

Source: BMJ

 

Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic–Uremic Syndrome.

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BACKGROUND

Atypical hemolytic–uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease.

METHODS

We conducted two prospective phase 2 trials in which patients with atypical hemolytic–uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases. Patients with low platelet counts and renal damage (in trial 1) and those with renal damage but no decrease in the platelet count of more than 25% for at least 8 weeks during plasma exchange or infusion (in trial 2) were recruited. The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event–free status (no decrease in the platelet count of >25%, no plasma exchange or infusion, and no initiation of dialysis) (in trial 2).

RESULTS

A total of 37 patients (17 in trial 1 and 20 in trial 2) received eculizumab for a median of 64 and 62 weeks, respectively. Eculizumab resulted in increases in the platelet count; in trial 1, the mean increase in the count from baseline to week 26 was 73×109 per liter (P<0.001). In trial 2, 80% of the patients had thrombotic microangiopathy event–free status. Eculizumab was associated with significant improvement in all secondary end points, with continuous, time-dependent increases in the estimated glomerular filtration rate (GFR). In trial 1, dialysis was discontinued in 4 of 5 patients. Earlier intervention with eculizumab was associated with significantly greater improvement in the estimated GFR. Eculizumab was also associated with improvement in health-related quality of life. No cumulative toxicity of therapy or serious infection-related adverse events, including meningococcal infections, were observed through the extension period.

CONCLUSIONS

Eculizumab inhibited complement-mediated thrombotic microangiopathy and was associated with significant time-dependent improvement in renal function in patients with atypical hemolytic–uremic syndrome.

 

Source: NEJM

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

 

Fibrates and estimated glomerular filtration rate: observations from an outpatient clinic setting and clinical implications.

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Previous studies have demonstrated that fibrates have an effect on creatinine concentrations. The pattern of change with fibrates in estimated glomerular filtration rate (eGFR), widely used in clinical practice, has not been previously described.

Methods Data was retrospectively collected from 132 consecutive case notes of patients started on fibrates in a lipid clinic between 2002 and 2008. Pre- and post-fibrate creatinine concentrations were measured and eGFR measurements were obtained.

Results Of the 79 patients with both pre and post-treatment eGFR values <90 ml/min/1.73 m2, a significant mean eGFR reduction of 8.2 ml/min/1.73 m2 was noted. Of these patients, 50% demonstrated a reduction in eGFR >8 ml/min/1.73 m2, 25% demonstrated a reduction >16 ml/min/1.73 m2, and 10% demonstrated a reduction >21 ml/min/1.73 m2.

Conclusions The authors demonstrate a significant effect of fibrates on eGFR in clinical practice. Awareness of the pattern of eGFR change is important for decisions regarding the continued use of fibrate therapy and/or commonly co-prescribed diabetic drugs and renal specialist referrals.

Source: PMJ/BMJ