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Understanding, Treating Chronic Kidney Disease - VetPracticeNews.com
Understanding, Treating Chronic Kidney Disease

By Wendy Bedwell-Wilson
For The Education Series

Posted: May 25, 2012, 7:30 p.m. EDT

Chronic kidney disease, one of the most common diseases among dogs and cats, involves the loss of functional renal tissue due to a prolonged, usually progressive process. But thanks to both traditional and cutting-edge methods for diagnosing and treating the condition, veterinarians have more options than ever for helping these animals enjoy longer lives.

Causes, Signs and Symptoms
In most cases of chronic kidney disease, the underlying cause is unknown, says Mark Acierno, DVM, Dipl. ACVIM, MBA, an associate professor and dialysis service coordinator at Louisiana State University’s School of Veterinary Medicine in Baton Rouge.

“It’s likely a combination of environmental and congenital factors, but we’re really not sure in most cases,” Dr. Acierno says. “Sometimes there’s a defining event, but often there isn’t.”

The causes can be categorized in different ways, adds Anthony Ishak, DVM, Dipl. ACVIM, of BluePearl Veterinary Partners in Tampa, Fla.

“There are acute insults that destroy enough renal parenchyma in an irreversible manner and result in decreased functional renal mass,” Dr. Ishak says, citing leptospirosis, pyelonephritis, lilly intoxication, ethylene glycol intoxication, hypovolemia/hypotension, pancreatitis and sepsis as examples. “There are also chronic diseases that result in progressive loss in renal function over time, such as interstitial nephritis, chronic partial ureteral obstructions and polycystic kidney disease.”

Chronic kidney disease looks different in cats and dogs, Acierno says. Cats can live with the disease for years and “do really well with it,” he says. In geriatric patients at referral institutions, chronic kidney disease affects up to 35 percent of cats, though the prevalence in the general population is likely lower. Dogs are another matter.

“It’s been estimated that chronic kidney disease will strike 10 percent of dogs over the age of 12,” Acierno says. “But they don’t do as well with it. Chronic kidney disease in dogs doesn’t seem to go for years and years as it does in cats.”

In general, however, chronic kidney disease tends to affect older animals, and it often smolders for months or years before it becomes clinically apparent. Dogs and cats come into the office looking “underweight, emaciated, anorectic, dehydrated and maybe vomiting,” Acierno says, noting that the vomiting is often one of the primary reasons owners bring in their pets. “A lot of these animals are also hypertensive.”

Dogs and cats affected by chronic kidney disease show other signs, too, Ishak says.

“Occasionally, more specific signs such as renal pain, pigmenturia, uremic stomatitis and anemia are present depending on disease severity and underlying etiology,” he says.

Clinical Findings and Diagnosis
Renal disease is typically diagnosed when azotemia becomes apparent on screening chemistry panels as animals age, Ishak says.
 
“Sometimes abnormalities are detected when routine urinalysis is done,” he says. “Earlier changes can be found with imaging such as radiographs or ultrasound and careful attention to blood pressure and urinalysis results, especially the presence of proteinuria, over time. A glomerular filtration rate is an ideal method of assessing decline in renal function over time.”

Usually, the earliest clinical signs commonly attributable to renal dysfunction are polydipsia and polyuria, which are not observed until the function of about two-thirds of the nephrons have been impaired.

As the disease progresses, anorexia, weight loss, dehydration, oral ulceration, vomiting and diarrhea fully manifest. In imaging studies and through physical examination, the animal’s kidneys also may appear abnormal, Acierno says.

“Classically, there is a non-concentrated urine,” he says. “Sometimes it may have protein in it, sometimes it may not. And in looking at the kidneys themselves, they tend to be small and irregular. Sometimes you can palpate that, but certainly with ultrasound and sometimes even X-ray, you can interrogate the kidneys and see that they’re not normal.” 
 
A combination of survey radiography, abdominal ultrasound, clinical pathology tests and blood pressure measurements will allow practitioners to evaluate the severity of the disease and establish a prognosis, Acierno says.

“Blood test, urinalysis and some sort of diagnostic imaging, such as an ultrasound, is the way to go,” he says.

Treatment Options
With appropriate therapy, animals can survive for long periods with only a small fraction of functional renal tissue, perhaps 5 to 8 percent in dogs and cats. The key is managing it, says Acierno, and one way to do that is through diet.

Chronic kidney disease patients tend to be azotenic, acidotic, hyperphosphatemic, hypertensive, anemic and dehydrated. “That’s a lot of things to worry about,” Acierno says. “But we can control the azotemia, acidosis and elevated phosphate levels very often by just changing to an appropriately formulated renal failure diet. They tend to be low-protein, low-phosphate and bicarbonate balanced so they don’t promote acidosis.”

High phosphate levels that aren’t affected by diet can be managed with phosphate binders, such as aluminum hydroxide and other proprietary drugs, he says.

To manage the hypertension, which is a greater than 150 mm of mercury systolic blood pressure, practitioners should treat with calcium channel blockers and ACE inhibitors, Acierno says.

“In dogs, we usually start with an ACE inhibitor and then add a calcium channel blocker if we don’t get the appropriate response,” he says. “In cats, for physiologic reasons, we often do just the opposite.”

Careful blood pressure monitoring is critical, Acierno says.

“Hypertension can be caused by renal failure, and hypertension can cause renal failure,” he says. “So if you don’t get the blood pressure under control, you can find your patient spiraling downward very quickly.”

Anemia can be managed with recombinant erythropoietin and the human drug epogen, but animals can develop antibody response to the proteins. A newer—and more expensive—alternative is a synthetic form of erythropoietin called darbepoetin alfa.

“In it, the molecules are camouflaged with carbohydrate molecules,” Acierno says. “So when the body’s immune system sees it, it lets it go right by.”

And to manage the animals’ dehydration, Acierno recommends that owners give their pets at-home subcutaneous fluids.

“We’ll send our patients home with a bag of fluids, some needles and a drip line,” he says. “Basically, we stick a needle under the skin and create a fluid pocket that gets reabsorbed over a period of time to keep the animal hydrated.”

Other options include a wet diet, subcutaneous catheter or an esophagostomy tube, Acierno says.

Caring for dogs and cats with chronic kidney disease requires careful monitoring and owner education—and a skilled in-clinic team, Acierno says.

“Getting a blood pressure, client education and things like that are all billable events,” he says. “Some of our technicians are extremely well-skilled at getting blood pressures and educating clients about subcutaneous fluids, and we use those tools to our advantage.” 

This Education Series story was underwritten by Vétoquinol USA of Fort Worth, Texas.

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ChemoCentryx Presents Data on CCX168, an Orally Administered Small Molecule ... - Mesh Press (press release)

Source: www.globenewswire.com

MOUNTAIN VIEW, Calif., May 26, 2012 (GLOBE NEWSWIRE) — ChemoCentryx, Inc. (Nasdaq:CCXI), today announced the presentation of results from the Company’s development program for CCX168, an investigational orally administered inhibitor of the complement anaphylatoxin receptor known as C5aR. CCX168 is currently in a multinational, randomized, double-blind, placebo-controlled Phase II clinical trial for the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis, an inflammation of small blood vessels in the kidney. ANCA-associated renal vaculitis can lead to renal failure and a high mortality if untreated. As presented in two posters at the 49th European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) Congress in Paris, France, Phase I clinical trial results, supported by findings from preclinical in vivo studies, established the target dosing level for the Company’s ongoing Phase II clinical trial.

“CCX168 is a novel treatment approach to help patients with ANCA-associated renal vasculitis. Our CCX168 Phase II clinical program is evaluating the safety, tolerability, and early signs of treatment efficacy of CCX168 to reduce or possibly eliminate concomitant use of corticosteroids,” stated Thomas J. Schall, Ph.D., President and CEO, ChemoCentryx. ”ANCA vasculitis currently is treated with high-dose corticosteroids and cyclophosphamide, among other noxious treatment regimens in severe cases. Therefore, a novel medicine such as CCX168 could provide a more safe and tolerable treatment option for these patients.”

In a poster titled, “Clinical Dose Selection of the C5a Receptor Antagonist CCX168 for the Phase II ANCA-Associated Renal Vasculitis Clinical Trial (the CLEAR Trial),” the pharmacokinetic (PK) and pharmacodynamic (PD) profiles and therapeutic effectiveness achieved with CCX168 in an anti-myeloperoxidase antibody (anti-MPO IgG) preclinical model of ANCA nephropathy were presented.  In addition, the Phase I clinical trial PK/PD data were also shown. Analysis of these results led to the selection of the dosing regimen of 30 mg twice daily for the Company’s Phase II CLEAR (for C5aR inhibitor on Leukocytes Exploratory ANCA-associated Renal vasculitis) clinical trial in ANCA-associated renal vasculitis. Furthermore, the Phase I clinical trial demonstrated that CCX168 was well-tolerated and caused no serious adverse events.

Also presented at the ERA-EDTA Congress, a second poster titled, “Oral C5a Receptor Antagonist CCX168 in a Phase 2 Clinical Trial in ANCA Associated Renal Vasculitis,” outlined the clinical protocol for the CLEAR trial. In this study, eligible patients with ANCA-associated renal vasculitis are being randomized in a 1:2 ratio to receive either placebo or 30 mg CCX168 twice daily for a 12-week treatment period, with a 12-week follow-up period. The trial is assessing the safety and tolerability of CCX168, as well as the feasibility of reducing or eliminating the concomitant use of corticosteroids and evaluating the effect of CCX168 treatment on renal function and ANCA disease. To date, CCX168 has been well-tolerated in the Phase II clinical trial.

ABOUT C5aR AND CCX168

The complement system consists of a set of proteins that regulate certain types of inflammatory responses.  Fragments of complement proteins, including the chemoattractant complement fragment known as C5a, work to recruit inflammatory cells, including neutrophils, to sites of inflammation by means of its receptor (C5aR). Given molecular structure similarities between the C5aR and chemokine receptors, ChemoCentryx researchers successfully applied the Company’s proprietary drug discovery technologies to the design of small molecule C5aR inhibitors and selected CCX168 based on its potency, selectivity and favorable pharmacokinetics. CCX168 was discovered and is being developed by ChemoCentryx and is the final drug candidate subject to option under an alliance with GlaxoSmithKline (GSK).

ABOUT CHEMOCENTRYX

ChemoCentryx, Inc. is a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing orally-administered therapeutics that target the chemokine and chemoattractant systems in order to treat autoimmune diseases, inflammatory disorders and cancer. The chemokine system is a biological network that regulates inflammation via a collection of secreted chemokine molecules, or ligands, and their specific cell surface receptors. Based on its proprietary drug discovery and drug development platform, ChemoCentryx has generated multiple clinical and preclinical-stage programs, each targeting distinct chemokine and chemoattractant receptors with different small molecule compounds. ChemoCentryx’s most advanced drug candidate, vercirnon (also known as Traficet-EN, CCX282 or GSK1605786), a specific CCR9 inhibitor, completed a multi-national clinical trial, called PROTECT-1, in patients with moderate-to-severe Crohn’s disease, where it demonstrated the ability to induce a clinical response and to maintain clinical remission, and is now in Phase III clinical development. ChemoCentryx’s lead independent drug candidate, CCX140, a CCR2 inhibitor, has been shown to be safe and well tolerated while demonstrating clinical activity on glycemic indices in a Phase II clinical trial in type 2 diabetics, and is now in Phase II clinical development for the treatment of diabetic nephropathy. Other clinical programs include CCX354 (also known as GSK2941266), a CCR1 inhibitor which successfully completed a Phase II clinical trial for the treatment of rheumatoid arthritis, and CCX168, a C5aR inhibitor in Phase II clinical development for the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. ChemoCentryx also has several programs in advanced preclinical development.

FORWARD-LOOKING STATEMENTS

ChemoCentryx cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. Words such as “may,” “could,” “will,” “would,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “intend,” “predict,” “seek,” “contemplate,” “potential” or “continue” or the negative of these terms or other comparable terminology are intended to identify forward-looking statements. These statements are based on the Company’s current beliefs and expectations. The inclusion of forward-looking statements should not be regarded as a representation by ChemoCentryx that any of its plans will be achieved. Actual results may differ from those set forth in this release due to the risk and uncertainties inherent in the ChemoCentryx business and other risks described in the Company’s filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and ChemoCentryx undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. Further information regarding these and other risks is included under the heading “Risk Factors” in ChemoCentryx’s periodic reports filed with the Securities and Exchange Commission (“SEC”), including ChemoCentryx’s Annual Report on Form 10-K for the year ended December 31, 2011 and Quarterly Report on Form 10-Q for the three-month period ended March 31, 2012, which are available from the SEC’s website (www.sec.gov) and on ChemoCentryx’s website (www.ChemoCentryx.com) under the heading “Investors.” All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.

Contact Information:

Susan M. Kanaya
         Senior Vice President, Finance and
         Chief Financial Officer or
         Markus J. Cappel, Ph.D.
         Chief Business Officer
         650-210-2900
         
 This e-mail address is being protected from spambots. You need JavaScript enabled to view it
 

         Burns McClellan
         Media Inquiries
         Justin Jackson
         212-213-0006
         
 This e-mail address is being protected from spambots. You need JavaScript enabled to view it
 

 

 

 

 

...

 
ChemoCentryx Presents Data on CCX168, an Orally Administered Small Molecule ... - GlobeNewsWire (press release)
GlobeNewsWire (press release)
CCX168 is currently in a multinational, randomized, double-blind, placebo-controlled Phase II clinical trial for the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis, an inflammation of small blood vessels in the

...

 
ChemoCentryx Presents Data on CCX168, an Orally Administered Small Molecule ... - MarketWatch (press release)

MOUNTAIN VIEW, Calif., May 26, 2012 (GlobeNewswire via COMTEX) -- ChemoCentryx, Inc. /quotes/zigman/8663976/quotes/nls/ccxi CCXI -0.83% , today announced the presentation of results from the Company's development program for CCX168, an investigational orally administered inhibitor of the complement anaphylatoxin receptor known as C5aR. CCX168 is currently in a multinational, randomized, double-blind, placebo-controlled Phase II clinical trial for the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis, an inflammation of small blood vessels in the kidney. ANCA-associated renal vaculitis can lead to renal failure and a high mortality if untreated. As presented in two posters at the 49th European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) Congress in Paris, France, Phase I clinical trial results, supported by findings from preclinical in vivo studies, established the target dosing level for the Company's ongoing Phase II clinical trial.

"CCX168 is a novel treatment approach to help patients with ANCA-associated renal vasculitis. Our CCX168 Phase II clinical program is evaluating the safety, tolerability, and early signs of treatment efficacy of CCX168 to reduce or possibly eliminate concomitant use of corticosteroids," stated Thomas J. Schall, Ph.D., President and CEO, ChemoCentryx. "ANCA vasculitis currently is treated with high-dose corticosteroids and cyclophosphamide, among other noxious treatment regimens in severe cases. Therefore, a novel medicine such as CCX168 could provide a more safe and tolerable treatment option for these patients."

In a poster titled, "Clinical Dose Selection of the C5a Receptor Antagonist CCX168 for the Phase II ANCA-Associated Renal Vasculitis Clinical Trial (the CLEAR Trial)," the pharmacokinetic (PK) and pharmacodynamic (PD) profiles and therapeutic effectiveness achieved with CCX168 in an anti-myeloperoxidase antibody (anti-MPO IgG) preclinical model of ANCA nephropathy were presented. In addition, the Phase I clinical trial PK/PD data were also shown. Analysis of these results led to the selection of the dosing regimen of 30 mg twice daily for the Company's Phase II CLEAR (for C5aR inhibitor on Leukocytes Exploratory ANCA-associated Renal vasculitis) clinical trial in ANCA-associated renal vasculitis. Furthermore, the Phase I clinical trial demonstrated that CCX168 was well-tolerated and caused no serious adverse events.

Also presented at the ERA-EDTA Congress, a second poster titled, "Oral C5a Receptor Antagonist CCX168 in a Phase 2 Clinical Trial in ANCA Associated Renal Vasculitis," outlined the clinical protocol for the CLEAR trial. In this study, eligible patients with ANCA-associated renal vasculitis are being randomized in a 1:2 ratio to receive either placebo or 30 mg CCX168 twice daily for a 12-week treatment period, with a 12-week follow-up period. The trial is assessing the safety and tolerability of CCX168, as well as the feasibility of reducing or eliminating the concomitant use of corticosteroids and evaluating the effect of CCX168 treatment on renal function and ANCA disease. To date, CCX168 has been well-tolerated in the Phase II clinical trial.

ABOUT C5aR AND CCX168

The complement system consists of a set of proteins that regulate certain types of inflammatory responses. Fragments of complement proteins, including the chemoattractant complement fragment known as C5a, work to recruit inflammatory cells, including neutrophils, to sites of inflammation by means of its receptor (C5aR). Given molecular structure similarities between the C5aR and chemokine receptors, ChemoCentryx researchers successfully applied the Company's proprietary drug discovery technologies to the design of small molecule C5aR inhibitors and selected CCX168 based on its potency, selectivity and favorable pharmacokinetics. CCX168 was discovered and is being developed by ChemoCentryx and is the final drug candidate subject to option under an alliance with GlaxoSmithKline (GSK).

ABOUT CHEMOCENTRYX

ChemoCentryx, Inc. is a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing orally-administered therapeutics that target the chemokine and chemoattractant systems in order to treat autoimmune diseases, inflammatory disorders and cancer. The chemokine system is a biological network that regulates inflammation via a collection of secreted chemokine molecules, or ligands, and their specific cell surface receptors. Based on its proprietary drug discovery and drug development platform, ChemoCentryx has generated multiple clinical and preclinical-stage programs, each targeting distinct chemokine and chemoattractant receptors with different small molecule compounds. ChemoCentryx's most advanced drug candidate, vercirnon (also known as Traficet-EN, CCX282 or GSK1605786), a specific CCR9 inhibitor, completed a multi-national clinical trial, called PROTECT-1, in patients with moderate-to-severe Crohn's disease, where it demonstrated the ability to induce a clinical response and to maintain clinical remission, and is now in Phase III clinical development. ChemoCentryx's lead independent drug candidate, CCX140, a CCR2 inhibitor, has been shown to be safe and well tolerated while demonstrating clinical activity on glycemic indices in a Phase II clinical trial in type 2 diabetics, and is now in Phase II clinical development for the treatment of diabetic nephropathy. Other clinical programs include CCX354 (also known as GSK2941266), a CCR1 inhibitor which successfully completed a Phase II clinical trial for the treatment of rheumatoid arthritis, and CCX168, a C5aR inhibitor in Phase II clinical development for the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. ChemoCentryx also has several programs in advanced preclinical development.

FORWARD-LOOKING STATEMENTS

ChemoCentryx cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. Words such as "may," "could," "will," "would," "should," "expect," "plan," "anticipate," "believe," "estimate," "intend," "predict," "seek," "contemplate," "potential" or "continue" or the negative of these terms or other comparable terminology are intended to identify forward-looking statements. These statements are based on the Company's current beliefs and expectations. The inclusion of forward-looking statements should not be regarded as a representation by ChemoCentryx that any of its plans will be achieved. Actual results may differ from those set forth in this release due to the risk and uncertainties inherent in the ChemoCentryx business and other risks described in the Company's filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and ChemoCentryx undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. Further information regarding these and other risks is included under the heading "Risk Factors" in ChemoCentryx's periodic reports filed with the Securities and Exchange Commission ("SEC"), including ChemoCentryx's Annual Report on Form 10-K for the year ended December 31, 2011 and Quarterly Report on Form 10-Q for the three-month period ended March 31, 2012, which are available from the SEC's website ( www.sec.gov ) and on ChemoCentryx's website ( www.ChemoCentryx.com ) under the heading "Investors." All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.

CCXI -- G

This news release was distributed by GlobeNewswire, www.globenewswire.com

SOURCE: Burns McClellan




        CONTACT: Susan M. Kanaya
        Senior Vice President, Finance and
        Chief Financial Officer or
        Markus J. Cappel, Ph.D.
        Chief Business Officer
        650-210-2900
        
 This e-mail address is being protected from spambots. You need JavaScript enabled to view it
 
        Burns McClellan
        Media Inquiries
        Justin Jackson
        212-213-0006
        
 This e-mail address is being protected from spambots. You need JavaScript enabled to view it
 
        



(C) Copyright 2010 GlobeNewswire, Inc. All rights reserved.

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Pfizer says EU recommends approval of Inlyta - CBS News
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