Albuminuria in non-primary renal disease: risk marker rather than risk factor

Abstract

The impact of an increased urinary albumin excretion in predicting future renal function loss in subjects with diabetes was emphasized already in the 1980s–1990s [1,2]. During these years, the terminology of ‘early diabetic nephropathy’ was introduced to indicate diabetic subjects with microalbuminuria. In this early phase of diabetic nephropathy, the glomerular filtration rate (GFR) is still generally well preserved. Early nephropathy contrasts with the later phase of overt nephropathy in which albuminuria increases into the macroalbuminuria range and the GFR falls below 60 ml/min to finally progress to the level of endstage renal disease (ESRD). The documentation of the early phase of kidney damage with microalbuminuria but still normal GFR helped to better understand the impact of albuminuria in the loss of renal function in diabetes. Moreover, it led to the demonstration that early intervention by interfering in the renin–angiotensin–aldosterone system (RAAS) [3,4] slows the progression of nephropathy in diabetic patients. Data on the impact of albuminuria on the progressive decline of renal function in non-diabetic renal disease received attention in the 1990s. The findings from large clinical trials, showing the beneficial effect of lowering albuminuria by using agents that interfere with the RAAS to (partially) prevent progression to ESRD [5,6], gave a boost to the concept of focussing the treatment in renal patients on albuminuria and not only on blood pressure [7]. These studies often focused on subjects with macroalbuminuria and a GFR in the range of Stage 3 or 4 chronic kidney disease (CKD) which was mostly due to glomerular disorders. Thus far, no trials have shown that the lowering of albuminuria in the early phase (which is the case in microalbuminuria with a GFR >60 ml/min, thus in Stage 1 or 2 CKD) slows the progressive decline of renal function. There is, however, some evidence that ACE inhibition in subjects with non-diabetic microalbuminuria may prevent future cardiovascular events [8]. In this issue of the journal, Lorenzo et al. nicely show the parallel impact of albuminuria on progressive loss of renal function in patients with diabetic and non-diabetic CKD [9]. In an observational cohort study, they followed the loss of GFR in diabetic and non-diabetic patients. Progression was faster in the diabetic compared to the nondiabetic group. The more rapid progression was, however, fully related to the higher albuminuria in the diabetic group: after adjustment for albuminuria, the progression in the diabetic group was comparable to that in the nondiabetic group. This led the authors to conclude that it is not the diabetes itself, but the albuminuria related to the underlying disease that best predicts progressive decline of renal function. Of particular interest is the underlying diagnosis of the CKD in non-diabetic subjects. These were mostly patients with ischaemic or vascular nephropathy. Interestingly, these causes of ESRD currently form the great majority of new ESRD cases and outweigh the number of subjects with ESRD due to the classical glomerular or interstitial renal diseases [10].