Possible Role Of Hyperfiltration As A Risk Marker For Diabetic Nephropathy

In certain IDDM patients, glomerular hyperfiltration is especially marked and sustained during many years, and it has been suggested that such hyperfiltration represents a pathogenetic factor for later development of diabetic nephropathy. This suspicion is supported by the apparent analogy between the characteristic early renal hemodynamic changes in human IDDM and in animal models of diabetes. Thus, in experimental diabetes a normalisation of the high GFR or the high intraglomerular hydraulic pressure by pharmacological or dietary means, has attenuated progression of renal disease [71]. In human diabetes retrospective data has suggested that marked hyperfiltration is associated with later nephropathy [12,72]. Two studies later questioned these early observations (75,76), but long-term prospective studies have confirmed an associations between glomerular hyperfiltration and later development of nephropathy. In a swedish cohort of normoalbuminuric adolescent patients multiple regression analysis after 8 years identified glomerular hyperfiltration as a strong independent predictor for nephropathy (73). The same cohort of diabetic patients has recently been studied after another 8-10 years ie. 16-18 years after baseline examination (diabetes duration 29±3 years) [103]. Of 75 patients included at baseline, 60 patients participated in the recent follow-up study. It was found that 32% of the patients had developed either persistent micro- or macroalbuminuria. It is noteworthy that 6 out of 7 patients with persistent macroalbuminuria and 10 of 12 with persistent microalbuminuria had an increased GFR at baseline. Approximately half of the patients with initial glomerular hyperfiltration showed progression to micro- or macroalbuminuria. When adjusted for duration of diabetes increased baseline GFR represented a risk factor for later development of micro- or macroalbuminuria with odds ratio 5.44. Also in a group of diabetic children, studied during 10 years, hyperfiltration was found to predict later development of microalbuminuria [74].

Concerning a possible association between hyperfiltration and development of morphological renal abnormalities, this was recently investigated in a follow-up study in adolescent IDDM patients before the stage of microalbuminuria [98]. This biopsy study reported a positive correlation between mesangial matrix volume fraction and the filtration fraction measured repeatedly during years before the biopsy. Filtration fraction also correlated to basement membrane thickness.

Indirect evidence for a pathogenetic role of abnormal renal hemodynamics is found in the marked slowing of early renal disease observed during antihypertensive treatment. This especially applies for ACE-inhibitors, which are considered to reduce intraglomerular pressure more specifically than other antihypertensives [78]. In a pilot study treatment with an ACE-inhibitor reduced both albumin excretion and kidney volume in microalbuminuric, normotensive IDDM patients [79].

Addressing kidney hypertrophy rather than hemodynamic parameters, a recent sonographic study in IDDM patients has indicated that large kidneys may be a morphological marker for later diabetic nephropathy [99].

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