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

encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant ne-phrotic syndrome. Nat Genet 2000; 24: 349–354 9. Hinkes B, Vlangos C, Heeringa S et al. Specific podocin mutations correlate with age of onset in steroid-resistant nephrotic syndrome. A, Le TC et al. NPHS2 mutations in late-onset focal segmental glomerulosclerosis: R229Q is a common disease-associated allele. et al. ACTN4 gene mutations and single nucleotide polymorphisms in idiopathic focal segmental glomerulosclero-sis. et al. Focal and segmental glo-merulosclerosis in mice with podocyte-specific expression of mutant alpha-actinin-4. Analysis of mutations in alpha-actinin 4 and podocin genes of patients with chronic renal failure due to sporadic focal segmental glomerulosclerosis. Alpha-actinin-4-mediated FSGS: an inherited kidney disease caused by an aggregated and rapidly degraded cytoskeletal protein. PLoS Biol 2004; 2: e167 20. Ruf RG, Lichtenberger A, Karle SM et al. Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome. 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 ne-phropathy' was introduced to indicate diabetic subjects with microalbuminuria. In this early phase of diabetic ne-phropathy, 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 end-stage 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 al-buminuria 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 pa