conference overview

The incidence and prevalence of diabetes mellitus continue to grow dramatically throughout the world, due primarily to the increase in type 2 diabetes (T2DM), which in turn is largely related to the increase in obesity (1). This increase in T2DM disproportionately affects less developed countries, which also have fewer resources to deal with such patients. Although improvements in diabetes and hypertension management have reduced the proportion of diabetic individuals who develop chronic kidney disease (CKD) and who progress to ESRD, the sheer increase in the numbers developing diabetes will perforce have a major impact on dialysis and transplant needs. The competing outcome of cardiovascular disease (CVD) mortality is also of tremendous importance.

Because of this dramatic increase in the number of individuals developing diabetes, it is important to develop cost-effective strategies at every step: (1) prevention of obesity; (2) screening for and prevention of diabetes in an at-risk population; (3) glycemic control once diabetes develops; (4) blood pressure control once hypertension develops; (5) screening for diabetic CKD; (6) use of renin angiotensin aldosterone system (RAAS) inhibition/blockade in those with diabetic CKD; and (7) control of other cardiovascular risk factors such as management of LDL cholesterol.

The relationship of CKD to CVD remains complex. Increased urinary albumin excretion rates and decreased GFR are both associated with an increase in all-cause and CVD mortality independent of each other and of other CVD risk factors in general and high-risk populations (3-5). The relationship between the presence of microalbuminuria and CVD mortality in diabetic individuals has been known for over 25 years and the interrelationship between AER, GFR and CVD mortality has been well-studied in diabetic individuals . However, treatments that affect progression of CKD may not always have the same effect on the development/progression of CVD. Similarly, there may be differences in how interventions affect urinary AER vs. GFR. In patients with diabetes, there appear to be differences in the rate of progression of the fall in GFR that are related to the presence or absence of increased AER.

Studies in both T1DM and T2DM have shown that glycemic control can decrease the initial development of micro- and macroalbuminuria, but data documenting an effect on GFR are sparse. Recent data suggest that perhaps there should be different hemoglobin A1c (HbA1c) targets for CKD and CVD, as HbA1c levels below 7% continue to show benefit in preventing the development of microalbuminuria but show no benefit and perhaps harm with respect to CVD. Although there may be only a minimal effect of lower HbA1c levels on CKD as it progresses towards Stage 5, other complications of DM, such as retinopathy and neuropathy may benefit from such control.

Similarly, the blood pressure targets for CKD and CVD may be different. While it is recognized that blood pressure control is very important in slowing the rate of fall of GFR, at this point, the optimal blood pressure to benefit all outcomes is controversial. Similar to the effects of glycemic control, systolic BP (SBP) lower than 120 mmHg may be of further benefit for CKD progression (23), but may be associated with worsened CVD outcomes.

The role of RAAS blockade in the development and progression of diabetic CKD over and above BP control needs reevaluation. Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are not able to prevent the development of microalbuminuria in normotensive individuals with either T1DM or T2DM and their role in normotensive individuals with low levels of microalbuminuria is unclear. The relative benefits of ACE inhibitors vs. ARBs vs. direct renin inhibitors in T1DM and T2DM patients with hypertension and albuminuria remain to be determined. Similarly, the role of combinations of drugs acting in the RAAS remains controversial. Finally, whether RAAS blocking drugs have an effect over and above blood pressure reduction in decreasing the rate of CKD progression in those without increased AER is not clear.

Many other controversies exist in the management of diabetic CKD. Although statins likely decrease CVD in those with Stages I-IV CKD, proof that they are effective in patients on dialysis is lacking. Should statins be stopped when patients go on dialysis? Are there any data for other cholesterol-lowering medications in patients with diabetic CKD?

Another controversial issue is the use of metformin to control hyperglycemia in patients with decreased GFR. Although lactic acidosis is a potential problem in such patients, the risk appears to be small. Whether the current guidelines are too strict deserves a reanalysis.

To address these and other issues, KDIGO held a Controversies Conference on Diabetic Kidney Disease on 16-18 March, 2012 in New Delhi, India. Drs. Carl Erik Mogensen and Mark Molitch co-chaired this conference, which attempted to define the current state of our knowledge in the management of diabetic kidney disease. Topic areas covered included: 1) epidemiology, 2) albuminuria, 3) glycemic control, 4) RAAS blockade, 5) management of hypertension, and 6) role of statins.





Plenary session presentations

Advanced Renal Disease

Presenter: Eberhard Ritz

Disease Progression: Albuminuria versus eGFR

Presenter: Richard MacIsaac

Albuminuria as a Target for Treatment

Presenter: Michel Marre

Type 1 Diabetes

Presenter: Mark Molitch

Combination Therapy

Presenter: George Bakris

ACES vs ARBS

Presenter: Johannes Mann

Is there a Role for Direct Renin Inhibitors?

Presenter: Frederik Persson

Statins

Presenter: Christoph Wanner

Aspirin

Presenter: Alberto Zanchetti