Vanderbilt University researchers are coming to some surprising conclusions about abnormally low levels of oxygen in organs or tissues (hypoxia) and the effect on kidney disease. Hypoxia has been linked to inflammation in a number of ailments, including kidney disease, where it is also believed to cause kidney scarring or fibrosis. When hypoxia occurs, the body may adapt by producing hypoxia-inducible factors (HIF), transcription factors which signal a protective response.

The Vanderbilt scientists set out to discover how HIF behaves in kidney disease by experimenting with HIF-1 and HIF-2, HIF variants which are expressed in different cells of the kidney. They found that global activation of HIF suppressed inflammation and fibrosis in a mouse model of kidney injury; activation of HIF in the myeloid cells alone suppressed inflammation, but not fibrosis. Deleting HIF promoted inflammation. They also found that prolonged hypoxia suppressed the inflammatory response in healthy kidneys. The researchers hope to continue their studies to find out how HIF might be used to protect kidneys in chronic kidney disease.

Source:

Myeloid Cell-Derived Hypoxia-Inducible Factor Attenuates Inflammation in Unilateral Ureteral Obstruction-Induced Kidney Injury, The Journal of Immunology, April 6, 2012

Low Oxygen Could Protect Sick Kidneys, Vanderbilt University Medical Center, June 28, 2012

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In discovering the cause of a rare kidney disease, University of Michigan researchers have uncovered a new genetic mechanism behind renal fibrosis and chronic kidney disease. The scientists identified mutations of the damage repair gene FAN1 as a cause of karyomegalic interstitial nephritis or KIN. KIN causes kidney fibrosis or scarring, as well as nuclear changes in the tubule cells, glomeruli and blood vessels. This led the researchers to suspect that renal fibrosis and chronic kidney disease may be linked to DNA damage response signaling (DDR). They note that certain chemical compounds in the environment can trigger DNA damage and theorize that these “genotoxins” could also be involved in chronic kidney disease.

Source:

U-M Researchers Identify New Genetic Cause for Chronic Kidney Disease, University of Michigan Health System, July 8, 2012

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A new study from Cleveland Clinic Bariatric and Metabolic Institute suggests that weight loss surgery may improve kidney damage in obese patients with Type 2 diabetes. The researchers followed 52 patients with an average age of 51 years who had lived with diabetes for an average of almost nine years; more than a third of these patients had diabetic kidney disease before bariatric surgery. 84% had hypertension. Using the urine albumin-to-creatinine ratio test to determine kidney function, the researchers found that after five years, 58% percent no longer showed signs of protein in their urine or kidney damage. 42% experienced no change in microalbuminuria. 25% of the patients who had not had signs of kidney damage before surgery did go on to develop albuminuria.

Interestingly, 44% of patients experienced remission of their diabetes and were able to stop taking insulin and in some cases, blood pressure medications. 33% of the patients experienced significant improvement of their diabetes. The researchers determined that the remaining patients with no improvement or worsening of their disease had lost the least amount of weight and had suffered from diabetes for the longest period of time before surgery.

The researchers believe the positive effects of bariatric surgery on kidney health could be due to improvements in blood sugar control and insulin sensitivity as well as reversal of hypertension. According to one expert, a larger study comparing diabetics who did not undergo weight loss surgery is needed to confirm these findings.

Source:

Bariatric Surgery Yields Durable Results for Diabetic Nephropathy, Clinical Endocrinology News, July 9, 2012

Bariatric Surgery May Help Diabetic Kidney Diease, WebMD, June 21, 2012

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Researchers from the University of Alberta have found that patients with chronic kidney disease face the same risk for a coronary event as previous heart attack sufferers. The study followed 1.3 million Canadians with risk factors for coronary events, including patients who had already had a heart attack, those with CKD, diabetes or a combination of risk factors. According to lead researcher, Dr. Marco Tonelli, “The rate of death from heart disease among people with chronic kidney disease was similar to or higher than the rate of death among people with diabetes—in whom the value of preventive treatments is well known.” Although the study did not take medications or blood pressure readings from the patients into account, the findings suggest that early drug treatments and interventions could help prevent cardiac events in kidney patients.

Source:

Risk of Coronary Events in People with Chronic Kidney Disease Compared with Those of Diabetes: A Population-Level Cohort Study, The Lancet, June 19, 2012

Chronic Kidney Disease and Heart Attack Risk, Medical News Today, June 20, 2012

Kidney Disease May Be As Harmful to Heart As Heart Attack: Study, Medline Plus, June 19, 2012

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Japanese researchers have discovered that NT-proBNP, a biomarker used to detect heart failure, may also predict risk of progressive CKD as well as cardiac risk in patients with Type 2 diabetes. The study followed diabetic patients with stage 1 or stage 2 CKD for 5 years and found that those with a higher baseline of NT-proBNP were more likely to experience a new cardiac event and a 30% decrease in estimated glomerular filtration. The scientists need to conduct more research to confirm an optimal cutoff for levels of NT-proBNP. Because NT-proBNP is already used to test for cardiac risk, the researchers believe it could be an inexpensive and simple way to evaluate diabetic patients in hopes of preventing cardiovascular disease as well as progressive chronic kidney disease.

ADA: Cardiac Biomarker Good for Kidneys, Too, MedPage Today, June 14, 2012

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