BMP-7

Bone morphogenetic protein 7 (BMP-7) is a protein used to repair bone in humans. Recent research in mice indicates that BMP-7 may be able to repair damaged kidneys and even reverse kidney disease. No research on cats has taken place to date, but human recombinant BMP-7 was used to treat the mice in the recent research, with promising results.

BMP-7 is already approved by the FDA for the treatment of broken bones in humans in the USA, so these findings should lead to further research into the kidney angle and may eventually lead to a way of controlling and even curing CRF, although it is very early days as yet so please do not get your hopes up too much.

I regularly hear from people desperate to try BMP-7 on their cats. Unfortunately, this is not currently an option unless you are a millionaire. When used in orthopaedic surgery, BMP-7 is distributed in sponge form. However, for kidney treatment, this form is not usable; instead the pure protein form of BMP-7, suspended in a carrier liquid, is required, and this is infinitely more expensive. A couple of people I know looked into obtaining this form of BMP-7, only to discover it would cost in excess of US$142,000 a month to purchase the amount required for a 10 lb (4.5 kg) cat. The price may fall as BMP-7 is used for humans with kidney disease, but unfortunately this may well take some time. Since BMP-7 is a human product, it is also possible that a cat might develop antibodies to it.

Bone Morphogenetic Protein-7 improves renal fibrosis and accelerates the return of renal function (2002) Morrissey J, Hruska K, Guo G, Wang S, Chen Q & Klahr S Journal of the American Society of Nephrology 13 pp14-21 appears to show that that the use of BMP-7 may blunt the development of fibrosis, and preserve renal function.

BMP-7 reduces inflammation and improves blood flow in models of kidney disease (2002) is a report on the development of the treatment for use in kidney disease.

The bone morphogenetic proteins (BMPs). Their role in renal fibrosis and renal function (2003) Klahr S Journal of Nephrology 16 reports in detail on the use of BMP-7 in renal dysfunction.

Exploring the connection between chronic renal fibrosis and bone morphogenic protein-7 (2003) Kalluri R & Zeisberg M Histology and Histopathology 18 is another discussion of the possibilities for BMP-7.

BMP-7 counteracts TGF-߹-induced epithelial-to-mesenchymal transition and reverses chronic renal injury (2003) Zeisberg M, Hanai J, Sugimoto H, Mammoto T, Charytan D, Strutz F & Kalluri R Nature Medicine 9 reports on how BMP-7 may reverse kidney damage.

Eurekalert has a report on BMP-7 in layman's language.

BMP-7 signaling in renal development and disease (2005) Patel SR, Dressler GR Trends in Molecular Medicine 11(11) pp512-8 discusses how BMP-7 counteracts fibrosis in the kidneys.

Kielin/Chordin-Like Protein (KCP)

In a 2005 study (Kielin/chordin-like protein, a novel enhancer of BMP signaling, attenuates renal fibrotic disease (2005) Lin J, Patel SR, Cheng X, Cho EA, Levitan I, Ullenbruch M, Phan SH, Park JM, Dressler GR Natural Medicine 11(4) pp387-93), a new protein called kielin/chordin-like protein (KCP) was found in mice which appears to reduce the damage caused by CRF and acute renal failure (ARF). KCP seems to work by enhancing signals from bone morphogenic proteins such as BMP-7 which are essential to the normal functioning of healthy kidneys. The study indicates that KCP activity is also important in slowing the progression of kidney disease: mice who could not secrete this protein were more likely to develop renal problems and had more scarring on their kidneys than healthy mice who were able to secrete KCP.  Research is to be undertaken into what role KCP could play in helping humans with renal disease.

Eurekalert has a report on this study.

Renalase

It has long been known that the kidneys regulate blood pressure by producing a hormone called renin. Recent research has discovered renalase, a monoamine oxidase that breaks down catecholamines, such as adrenaline and dopamine, and which therefore appears to have a role in regulating heart contraction and blood pressure. Renalase is secreted by the kidneys and circulates in the blood. Patients with kidney disease have been found to have very low levels of renalase, presumably because the kidneys can no longer produce it efficiently. In human patients with end stage renal disease (ESRD), this probably plays a role in the build up of adrenaline, which in turn may then lead to heart disease, a common cause of death in humans with ESRD.

It is therefore hypothesised that injecting renalase might help those with kidney disease by replacing the missing renalase. Researchers compared this to giving erythropoietin to those whose kidneys can no longer produce it. It is possible that Renalase might also be of use in treating heart disease.

Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure (2005) Xu J, Li G, Wang P, Velazquez H, Yao X, Li Y, Wu Y, Peixoto A, Crowley S, Desir GV is the study in question.

Renalase, a catecholamine-metabolizing hormone from the kidney (2005) Luft FC Cell Metabolism 1 (6) pp358-360 briefly discusses the discovery of renalase.

Stem Cell Research

A 2004 study demonstrated that adult stem cells may assist with repairing damaged kidneys in mice. Adult stem cells were taken from the muscle tissue of healthy mice and cultured. Following implantation into mice with damaged kidneys, the cells formed new blood vessels and appeared to improve kidney function.

Adult skeletal muscle stem cells differentiate into endothelial lineage and ameliorate renal dysfunction after acute ischemia (2004) Arriero M, Brodsky SV, Gealekman O, Lucas PA, Goligorsky MS. American Journal of Physiology & Renal Physiology 287(4) ppF621-7

The Winn Feline Foundation is funding further study into stem cell research for the treatment of CRF in cats. The stem cells will be grown from bone marrow provided by each cat in the study, and will be injected directly into that cat's kidneys.

L-Arginine Supplementation

L-arginine is an amino acid which is used to make nitrous oxide in the kidneys. It is thought that nitrous oxide plays a critical role in regulating blood flow through the kidneys, and it is known that the amount of blood flowing through the kidneys can affect kidney function. L-arginine levels are often very low in CRF cats, so it is possible that supplementing this might increase nitrous oxide levels and thus help kidney function.

Safety and bioavailability of oral L-arginine supplementation in cats with naturally occurring chronic renal failure (2008) is a current study by Dr M Miles to see if L-arginine supplementation will help cats with CRF.

Acute Renal Failure Research

Neutrophil Gelatinase-Associated Lipocalin (Ngal)

Research on mice indicates that a protein called neutrophil gelatinase-associated lipocalin (Ngal) may be of use against acute renal failure. Large amounts of Ngal are found in blood, urine and kidney tissue at the onset of acute renal failure, which could make it helpful for diagnosing ARF at an early stage.

It is thought that Ngal is produced by the body during ARF in an attempt to protect the kidneys, but in many cases it is produced too late to prevent damage. If the Ngal were to be injected earlier, it might be able to prevent damage from occurring. It is expected that human trials of Ngal will begin shortly.

Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury (2005) Mori K, Lee HT, Rapoport D, Drexler IR, Foster K, Yang J, Schmidt-Ott KM, Chen X, Li JY, Weiss S, Mishra J, Cheema FH, Markowitz G, Suganami T, Sawai K, Mukoyama M, Kunis C, D'Agati V, Devarajan P, Barasch J Journal of Clinical Investigation 115(3) pp610-21 is the latest study.

Columbia University Medical Center has a report on the study.

Fenoldopam
A study at Auburn University indicates that a drug called fenoldopam may be of some use in treating cats with acute renal failure (ARF). Cats suffering from acute renal failure may exhibit oliguria (limited urine output). Dogs and humans with this problem are usually treated with a drug called dopamine, but this has not been particularly effective in cats because they have fewer receptors for this drug. Fenoldopam, which is normally used to treat severe hypertension in humans, appears to increase blood flow and urine output in healthy cats. Further studies are needed to see if it has the same effect on cats suffering from ARF.

Renal effects and characteristics of a newly identified dopamine-1 receptor in the cat kidney (2005) is a report on the work at Auburn University by Dr James Wohl (scroll down a little).

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