Kidney Disease Research Updates
Spring/Summer 2007

NIDDK Explores Key Clinical Research Opportunities in Kidney Disease

With kidney disease continuing to take a rising toll on public health and medical costs, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) turned to the extramural research community for input on designing studies to help reverse the trend.

At a recent 2-day meeting of the researchers in Bethesda, MD, Robert Star, M.D., acting director of the NIDDK’s Division of Kidney, Urologic, and Hematologic Diseases, stressed the sizable public health burden of all forms of renal disease.

A study from the U.S. Renal Data System for the Centers for Medicare and Medicaid Services found that treatment for people with chronic kidney disease (CKD) accounted for 19 percent of Medicare expenditures in 2002; treatment for people with end-stage renal disease (ESRD) accounted for another 7.8 percent.

In 2004, ESRD cost Medicare $20 billion. The incidence of acute kidney injury (AKI) is increasing, according to Star, accelerating kidney function decline in some people with CKD. In addition, cardiovascular disease (CVD) accounts for half of all deaths among people with kidney failure.

With 10 large kidney studies scheduled to end between fiscal year 2007 and 2009, the NIDDK is seeking the most promising, compelling, and feasible opportunities that address what research is needed to reduce the morbidity and mortality of kidney disease.

In recommending topics for the NIDDK to study, participants were asked to consider if a concept addresses a profound public health concern in adults or children, will have a large potential economic impact, is answerable and feasible to start in 1 to 3 years, and is not likely to be addressed by others.

Meeting participants met in three groups to identify clinical research opportunities in key areas: AKI, CKD, and ESRD.

Acute Kidney Injury

The key challenges with AKI are identifying people at risk in order to carry out evaluation and undertake possible preventive measures; developing preventative and therapeutic agents; improving surveillance and care management of all patients, especially those who are high-risk; and gaining a better understanding of the natural history of AKI and how it accelerates CKD. The concepts participants recommended included

• studying treatment for patients with established AKI, involving, for example, careful volume resuscitation; and

• studying two observational cohorts to validate biomarkers with opportunities for targeted interventional studies to test new therapies. Patients would be studied with either timed AKI—for example, following cardiovascular surgery—or untimed injury, such as sepsis.

Chronic Kidney Disease

Although CKD rates have both improved and stabilized, awareness of CKD is low and implementation of secondary prevention is poor. The key challenges participants identified were the need for better diagnostic tests and use of current testing strategies, better understanding of group and individual variation, and testing new therapies targeting both progression of the renal disease itself as well as CVD.

The concepts recommended by the CKD group included

• determining whether treating systolic blood pressure to a lower goal than currently recommended reduces CVD illness and mortality in people who don’t have diabetes but have at least one CVD risk factor

• developing improved renal functional measurements to better monitor CKD as well as genetic tests to identify people who are at risk

• determining if a therapy that lowers nocturnal blood pressure reduces CKD progression and CVD mortality

• examining the efficacy of novel drugs such as anti-fibrotic or cytoprotective agents to slow progressive renal decline

• testing whether bicarbonate preserves muscle mass, limits bone disease, and slows CKD progression

End-Stage Renal Disease

The key challenge in treating ESRD is that mortality remains stubbornly high, especially in the first year of hemodialysis. Studies have failed to show that increased dialysis dose improves outcomes. While fistula use in dialysis is associated with lower morbidity, mortality, and cost, 25 to 50 percent of fistulas fail to mature, increasing the risk of sepsis from temporary catheters.

The ESRD group proposed

• determining if the mortality and cardiovascular event rate could be reduced by beta blockers and renin angiotensin system blockers

• conducting an observational study to identify determinants of fistula maturation

• assessing the need for the invasive pretransplant evaluation of CVD in transplant candidates with a randomized, controlled study

• conducting an observational study to determine the causes of the high mortality and morbidity in the first 90 days of dialysis

• developing optimal techniques to reduce the calcium-phosphorus product by dialysis and optimize use of vitamin D to reduce vascular calcification and CVD

• studying pediatric ESRD patients with a focus on adherence and neurocognitive function

The NIDDK will review, clarify, and further develop these concepts for potential incorporation into the Institute’s research agenda. For information about NIDDK clinical trials for kidney disease, visit www.kidney.niddk.nih.gov/clinicaltrials.

The large kidney studies scheduled to end between fiscal year 2007 and 2009 are the

• African American Study of Kidney Disease and Hypertension (AASK)

• Family Investigation of Nephropathy of Diabetes (FIND)

• Acute Renal Failure Trial Network (ATN) Dialysis Study

• Dialysis Access Clinical Trials Consortium (DAC)

• Frequent Hemodialysis Network (FHN)

• Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT)

• Focal Segmental Glomerulosclerosis (FSGS)

• Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR)

• Chronic Kidney Disease in Children Prospective Cohort Study (CKid)

• Chronic Renal Insufficiency Cohort (CRIC)

NIH Publication No. 07–4531
June 2007

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