Dialysis may improve outcomes in patients suffering from treatment-resistant congestive heart failure (CHF) accompanied by severe renal insufficiency, new findings suggest.

Trijntje T. Cnossen, MD, PhD, of the Maastricht University Medical Center in Maastricht, The Netherlands, prospectively studied 23 hypervolemic patients with CHF complicated by progressive and permanent chronic renal insufficiency. The patients were classified as having cardiorenal syndrome (CRS) Type 2. All subjects had failed treatment with high-dose intravenous diuretics.

Twelve patients were treated with peritoneal dialysis (PD) and 11 were treated with intermittent hemodialysis (IHD). The median survival time after the start of dialysis was 16 months. Hospitalizations for cardiovascular causes decreased significantly from 1.4 days/patient/month pre-dialysis to 0.4 days/patient/month post-dialysis, the researchers reported online ahead of print in Nephrology Dialysis Transplantation. The investigators observed no significant change in hospitalizations for all causes. The authors noted that “hospitalizations for non-cardiovascular causes appeared to be especially pronounced in patients who were already hospitalized at the start of dialysis and were in general not related to complications of the treatment.”

In addition, New York Heart Association class improved significantly from 3.8 at the start of dialysis to 2.4 after eight months. Dr. Cnossen's team observed no significant change in left ventricular ejection fraction. The investigators reported a relatively high number of technical complications associated with dialysis.

The finding of a reduction in hospitalization for cardiovascular causes after starting dialysis is consistent with early published studies, including a retrospective study by Dr. Cnossen and colleagues. That study, which was published in Blood Purification (2010;30:146-152), included 24 patients with CRS Type 2 treated with PD. The number of hospitalizations for cardiovascular causes decreased significantly from 13.7 days/patient/month pre-dialysis to 3.5 days/patient/month post-dialysis. The study population had a median survival of one year, but 12 patients who survived longer also had a significantly decreased number of hospitalizations for all causes (from 3.7 to 1.4 days/patient/month).

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When using erythropoiesis-stimulating agents (ESAs) to correct anemia in patients with chronic kidney disease, focus less on hitting a given hemoglobin target and more on improving patient-perceived quality of life in such areas as fatigue, weakness, and shortness of breath, advises Alan S. Kliger, MD, Chief Medical Officer and Chief Quality Officer for the Saint Raphael Healthcare System in New Haven, Conn.

In an editorial published in the February issue of the Clinical Journal of the American Society of Nephrology (2012;7:354-357), you and your colleagues contend that patients and their physicians should tailor the use of ESAs within the context of the patient's perceived quality of life. What experiences in your practice brought you to this conclusion?

Several studies of patients with CKD and those on dialysis have shown the dangers of treating anemia of CKD to goal hemoglobin (Hb) of 13 g/dL or higher. For decades, we have prescribed ESAs to achieve goal Hb levels, as if the Hb level itself is the important outcome.

However, our patients tell us a different story. For some, the Hb level appears to make no difference to their health, as long as they do not have profound anemia. For others, symptoms develop and change lives at different Hb levels. Since each of our patients is different, a single goal Hb level does not work, particularly when we know that there is potential harm to set goal Hb at 13 or higher, and we do not know if that harm extends to goals below 13.

Do you endorse this practice for any specific subgroup of patients—for example, the sickest patients who are more likely to succumb to ESRD than to the cardiovascular side effects of ESAs—or would you like to see it applied across the spectrum of all CKD patients with anemia?

I believe the practice of individualizing anemia treatment should be done for all patients. For each patient, we must consider the balance between the benefits and the risks of ESA treatment. That balance will not be the same for all.

For example, a minority of patients with ischemic heart disease develop increased angina and other symptoms when they become more anemic. For these patients, the benefits of ESAs, iron, or blood transfusions likely outweigh the risks, even if their achieved Hb levels to eliminate angina are in the range of 13 g/dL. For other patients, anemia appears to have no effect on their health, even when Hb levels are below 10 g/dL. For these patients, the risks of treating anemia outweigh the benefits, and ESAs should not be used.

What is your opinion of the FDA recommendations for more conservative dosing of ESAs in patients with CKD? To accommodate the FDA, ESA labels now recommend that physicians consider starting ESA treatment when Hb level is less than 10 g/dL, without defining how far below 10 g/dL is appropriate for initiation and without recommending a goal of 10 g/dL or higher.

Since several studies in recent years have been published showing the increased incidence of complications—some life-threatening—associated with using ESAs to goal Hb at 13 g/dL or higher, the FDA has responded appropriately to change the label for ESA use to reflect these dangers. The challenge is that there are no studies that show what the danger is when Hb goals are less than 13 g/dL. Is it safe to set goal Hb at 10 or 9 g/dL or higher? We do not know.

If a single goal Hb level is not appropriate for all patients, I think it is wiser to craft individualized therapy rather than seeking to find the single goal best for all. This does mean that each patient and his or her doctor must consider the relative risks and benefits of treatment to the best of their ability, and not simply depend on the FDA “black box” warning to prescribe a dose of ESA.

Your editorial accompanied another editorial in the same issue (pp.348-353) in which the authors thought the FDA should have been even more specific about the use of ESAs. That team suggested that instead of the FDA advising nephrologists to individualize dosing and reduce it when Hb exceeds 11 g/dL in dialysis patients and 10 g/dL in CKD patients not on dialysis, the agency perhaps should have recommended targeting Hb ranges of 9 to 11 g/dL in dialysis patients and 9 to 10 g/dL in nondialysis patients. Is there any benefit to giving nephrologists such target ranges, or would such recommendations restrict the nephrologist's inclination to customize treatment?

In the absence of clear studies showing the risks of targeting Hb at 9 or 10 g/dL, I think the FDA becomes a fortune teller rather than a responsible scientific body were it to recommend targeting Hb levels to 9 or 10. I believe the FDA should say we have insufficient data to determine the risk of targeting Hb less than 13, and direct patients and their physicians to consider the risks and benefits as best the data allow on an individual basis.

How can nephrologists reconcile the cardiovascular risks of ESAs with following your approach if it means bringing the patient into a high hemoglobin range, perhaps above 11 g/dL or even above 13 g/dL?

The whole art of medicine is the skill of reconciling the risks and benefits of any treatment when the data are incomplete and those risks are in part unknown. The dilemma posed by ESA treatment urges us all to step back and examine carefully the model of care we have used. We have treated anemia to goal Hb levels, with little evidence that this model improves patients' health. We believe that individualizing anemia care by using patient-reported outcomes, within the context of monitoring their Hb levels, may prove to be a more effective model of care.

Do you have any experiences to share about patients you have maintained at particularly high or particularly low hemoglobin levels through ESA use?

I cared for a 50-year-old man with stage IV CKD whose life was affected profoundly whenever his Hb level fell below 12 g/dL. In truth, I did not need to get a laboratory test to measure his Hb level; he came to the office and said, “I feel fine,” or at other times said, “I can't walk up stairs,” or, “I get breathless walking more than a block, and I know my anemia needs better treatment.” At these times, the Hb level was always less than 12.

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(HealthDay News) -- The potent, selective vascular endothelial growth factor receptor-1, -2, and -3 inhibitor, tivozanib, demonstrates antitumor activity and is well tolerated in patients with advanced/metastatic renal cell carcinoma (RCC), according to research published online April 9 in the Journal of Clinical Oncology.

Dmitry A. Nosov, M.D., Ph.D., of the Blokhin Oncology Research Center in Moscow, and colleagues conducted a phase II randomized discontinuation trial (RDT) involving 272 patients with advanced or metastatic RCC to evaluate the antitumor activity and safety of tivozanib. Patients were given 1.5 mg/d orally for 16 weeks, where one cycle was defined as three treatment weeks followed by a one-week break. During the first open-label phase of the trial, patients who experienced 25 percent or more tumor shrinkage continued to take tivozanib, while those with less than 25 percent shrinkage progressed to the second 12-week, double-blind phase and were randomized to receive either tivozanib or placebo. If patients experienced 25 percent or more tumor growth, they were discontinued from the trial. Safety, objective response rate (ORR) at 16 weeks, and percentage of patients who were progression free after 12 weeks of double-blind treatment were primary end points, and progression-free survival was a secondary end point.

The researchers found that, overall, 83 percent of participants had tumors with clear-cell histology, 73 percent had undergone nephrectomy, and 54 percent were treatment naive. In the 16-week open-label phase, the ORR was 18 percent. Among the 118 patients randomized to treatment with tivozanib or placebo, a statistically significant between-group difference in the percentage of patients who remained progression free after 12 weeks was observed (49 and 21 percent, respectively). Grade 3 and 4 hypertension was the most common treatment-related adverse event.

"Results from this RDT demonstrated promising activity and an acceptable safety and tolerability profile for tivozanib in advanced/metastatic RCC," the authors write.

The study was supported by AVEO Pharmaceuticals; several authors disclosed financial relationships (including employment) with AVEO.

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