Early glomerular hyperfiltration and the development of late nephropathy in Type 1 (insulin-dependent) diabetes mellitus

Lervang, Hans-Henrik; Jensen, Søren Buus; Brøchner‐Mortensen, Jens; Ditzel, Jørn

doi:10.1007/bf00274773

Cited by 82 publications

(42 citation statements)

References 32 publications

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“…One initially included report was subsequently removed from the analysis because it comprised patients with type 2 diabetes only, and as such was felt to be not comparable to the other studies [21]. In the end, ten cohort studies from six countries following 780 patients were included in this meta-analysis [22][23][24][25][26][27][28][29][30][31]. The publication years spanned three decades from 1984 to 2006 and all studies were of type 1 diabetic patients.…”

Section: Resultsmentioning

confidence: 99%

“…It would therefore be essential to compare duration of diabetes at entry into the study, as patients with shorter disease duration are more likely to have hyperfiltration. The mean duration of diabetes at entry into the studies analysed was 8.1 years, but this ranged from 3.4 to 12.6 years [22,23]. Patients should therefore have been on established glycaemic therapy even in the studies with the shortest disease duration at baseline.…”

Section: Discussionmentioning

confidence: 99%

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Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis

et al. 2009

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Aims/hypothesis Glomerular hyperfiltration is a wellestablished phenomenon occurring early in some patients with type 1 diabetes. However, there is no consistent answer regarding whether hyperfiltration predicts later development of nephropathy. We performed a systematic review and meta-analysis of observational studies that compared the risk of developing diabetic nephropathy in patients with and without glomerular hyperfiltration and also explored the impact of baseline GFR. Methods A systematic review and meta-analysis was carried out. Cohort studies in type 1 diabetic participants were included if they contained data on the development of incipient or overt nephropathy with baseline measurement of GFR and presence or absence of hyperfiltration. Results We included ten cohort studies following 780 patients. After a study median follow-up of 11.2 years, 130 patients had developed nephropathy. Using a random effects model, the pooled odds of progression to a minimum of microalbuminuria in patients with hyperfiltration was 2.71 (95% CI 1.20-6.11) times that of patients with normofiltration. There was moderate heterogeneity (heterogeneity test p=0.05, measure of degree of inconsistency= 48%) and some evidence of funnel plot asymmetry, possibly due to publication bias. The pooled weighted mean difference in baseline GFR was 13.8 ml min −1 1.73 m −2 (95% CI 5.0-22.7) greater in the group progressing to nephropathy than in those not progressing (heterogeneity test p<0.01). Conclusions/interpretation In published studies, individuals with glomerular hyperfiltration were at increased risk of progression to diabetic nephropathy using study level data. Further larger studies are required to explore this relationship and the role of potential confounding variables.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis

et al. 2009

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“…Three of these four studies [3,11,16] reported a significant odds ratio for the association between baseline hyperfiltration and subsequent progression to at least microalbuminuria [7]. By contrast none of the remaining six studies [2,4,9,10,15,72] in the meta-analysis that used the conventional definition of microalbuminuria demonstrated a significant odds ratio. It is, therefore, possible that differences in the definition of microalbuminuria contributed to the significant relationship between hyperfiltration and progression of AER in the meta-analysis.…”

Section: Resolution Of Hyperfiltration In Clinical Trialsmentioning

confidence: 97%

“…Although patients with newly diagnosed type 1 diabetes may have increased AER at presentation, hyperfiltration usually precedes changes in albuminuria by several years [2]. However, it remains uncertain whether hyperfiltration is merely a marker of glycaemic control or whether it exerts a pathogenetic role in human diabetic nephropathy, independently of factors such as HbA 1c , blood pressure, age and pubertal status, duration of diabetes, AER and smoking [3,4]. Experimental models of hyperfiltration include hyperfiltration at the single-nephron level, in the whole kidney in the intact animal and in the remnant kidney after subtotal nephrectomy [5,6].…”

Section: Introductionmentioning

confidence: 99%

The clinical significance of hyperfiltration in diabetes

et al. 2010

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Glomerular filtration rate is commonly elevated in early diabetes and patients with this symptom are arbitrarily considered to have hyperfiltration. The prevalence of hyperfiltration in type 1 diabetes varies from less than 25% to more than 75%. The corresponding figures in type 2 diabetes are significantly lower, ranging between 0% and more than 40%. Several factors, methodological and biological, may contribute to the wide variation in estimates of hyperfiltration prevalence. Methodological differences in measurement and evaluation of GFR apply in particular to the handling of plasma disappearance curves of filtration markers. Biological factors that may influence GFR in the hyperfiltration range include glycaemic control, diabetes duration, BMI, sex, pubertal status in type 1 diabetes and age in type 2 diabetes. Hyperglycaemia may influence GFR and albuminuria, and may therefore confound the evaluation of hyperfiltration as an independent risk factor for diabetic nephropathy. Adequate assessment of the relationship between glycaemic control, GFR and AER therefore requires serial measurements of all three variables followed by multivariate analysis. A recent meta-analysis of ten type 1 diabetes studies concluded that the presence of hyperfiltration at baseline more than doubled the risk of developing micro-or macroalbuminuria at follow-up. However, not all studies allowed for confounding factors or regression dilution bias. Future studies will therefore need to address the independent role of hyperfiltration, not only in the evolution of albuminuria, but also in the subsequent decline of GFR.

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“…Prospective studies in type 1 and type 2 diabetic patients generally support the concept that normoalbuminuric and MA patients who progress have significantly higher baseline levels of blood pressure (25,39,43,44,47,(75)(76)(77) and HbA 1c (14,21,22,25,39,40,(43)(44)(45)47,(77)(78)(79) compared with patients that do not progress. However, there is still controversy as to whether increased baseline GFR is a predictor of progression (9,24,(80)(81)(82)(83)(84)(85). Preliminary results of our prospective study in normoalbuminuric type 1 diabetic patients have shown that patients who progress to MA or proteinuria have worse baseline glomerular lesions, lower GFR, and are more frequently hypertensive than patients remaining normoalbuminuric (33).…”

Section: Need For New Markers and Predictors Of Diabetic Nephropathy mentioning

confidence: 99%

The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient?

2000

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Initial studies showing an ~80% rate of progression from microalbuminuria (MA) to proteinuria in type 1 diabetic patients led to the broad acceptance of MA as a useful clinical predictor of increased diabetic nephropathy (DN) risk. Some MA patients, however, have quite advanced renal structural changes, and MA may, in these cases, be a marker rather than a predictor of DN. More recent studies have observed only about a 30-45% risk of progression of MA to proteinuria over 10 years, while about 30% of type 1 diabetic patients with MA became normoalbuminuric and the rest remained microalbuminuric. The finding that some MA patients have only mild diabetic renal lesions is consistent with the lower than originally estimated risk of progression from MA to proteinuria and with the notion that some MA patients revert to normoalbuminuria. To increase the complexity of the scenario, some normoalbuminuric long-standing type 1 diabetic patients have well-established DN lesions and ~40% of all patients destined to progress to proteinuria are normoalbuminuric at initial screening, despite many years of diabetes. A similar picture is emerging in type 2 diabetic patients, although fewer studies have been conducted. Thus, the predictive precision for MA to progress to overt nephropathy over the subsequent decade or so is considerably less than originally described. It is unclear whether this is due to changes in the natural history of DN resulting from improved glycemia and blood pressure control, or whether there were overestimates of risk in the original studies due to the small sample sizes, post hoc analyses, and variable MA definitions. Albumin excretion rate (AER) remains the best available noninvasive predictor of DN risk and should be regularly measured according to established guidelines. However, AER may be unable to define patients who are safe from or at risk of DN with an accuracy that is adequate for optimal clinical decision making or for the design of certain clinical trials. Investigations into new risk markers or into the combined use of several currently available predictive parameters are needed.

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Early glomerular hyperfiltration and the development of late nephropathy in Type 1 (insulin-dependent) diabetes mellitus

Cited by 82 publications

References 32 publications

Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis

Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis

The clinical significance of hyperfiltration in diabetes

The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient?

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