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1.  Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy 
Six men aged 26-35 years with proteinuria due to insulindependent juvenile-onset diabetes were treated for moderate hypertension (mean blood pressure 162/103 mm Hg) and studied for a mean of 73 months for the effect on the progression of nephropathy. All patients were of normal weight. During a mean control period of 28 months before treatment the mean glomerular filtration rate (three or four measurements) was 86·1 ml/min and mean 24-hour urinary albumin excretion (also three or four measurements) 3·9 g (range 0·5-8·8 g).
During antihypertensive treatment the mean systolic blood pressure fell to 144 mm Hg and mean diastolic pressure to 95 mm Hg. In the control period five patients had shown a mean monthly decline in glomerular filtration rate of 1·23 ml/min; with antihypertensive treatment, however, this decline fell to 0·49 ml/min (2p=0·042). In the remaining patient the glomerular filtration rate was 137 ml/min before treatment and 135 ml/min at the end of the treatment period. In all patients the mean yearly increase in albumin clearance (expressed as a percentage of the glomerular filtration rate) fell from 107% before treatment to 5% during treatment (2p=0·0099).
This small study indicates that antihypertensive treatment slows the decline in renal function in diabetic nephropathy. Clinical trials beginning treatment in the incipient phase of diabetic nephropathy will define the optimal modality of treatment in this large patient population.
PMCID: PMC1499854  PMID: 6809187
2.  Relation between plasma amino-terminal propeptide of procollagen type III and left ventricular longitudinal strain in essential hypertension 
Heart  2005;91(5):624-629.
Objective: To investigate whether myocardial fibrosis assessed non-invasively is related to left ventricular (LV) longitudinal systolic function in patients with essential hypertension.
Design: The study consisted of 30 control subjects and 40 patients with hypertension with normal LV ejection fraction. Tissue Doppler echocardiography was performed to assess LV longitudinal systolic strain from the apical views. Mean strain was calculated from the basal and mid segments. Plasma concentrations of the amino-terminal propeptide of type III procollagen (PIIINP) were measured.
Results: In the hypertension group, mean strain was significantly reduced (mean (SD) 13 (6)% v 21 (6)%, p < 0.01) and plasma PIIINP were increased compared with controls (3.0 (0.7) μg/l v 2.1 (0.3) μg/l, p < 0.001). A significant correlation was found between mean strain and PIIINP (r  =  −0.56, p < 0.001). In patients with abnormal diastolic filling (n  =  21) mean strain was reduced compared with patients with normal LV filling (n  =  19) (10 (6)% v 15 (6)%, p < 0.01) and the serological marker PIIINP was increased (3.5 (0.6) μg/l v 2.5 (0.5) μg/l, p < 0.001).
Conclusions: There is a significant association between the extent of myocardial fibrosis and reduced LV longitudinal contractility.
doi:10.1136/hrt.2003.029702
PMCID: PMC1768864  PMID: 15831647
hypertension; systole; diastole; strain; fibrosis
3.  Danish general practitioners' estimation of urinary albumin concentration in the detection of proteinuria and microalbuminuria. 
BACKGROUND. Microalbuminuria may predict proteinuria and increased mortality in non-insulin dependent diabetic patients. Early detection of microalbuminuria may therefore be essential. AIM. The primary objective of this study was to describe the association between the presence of albuminuria in diabetic patients as detected by general practitioners using conventional reagent strip dipstick tests for albumin, and the urinary albumin concentration as measured in a hospital laboratory. METHOD. A total of 675 newly diagnosed diabetic patients aged 40 years or over were included in the Danish study, diabetes care in general practice. Data for urinary albumin concentration from a morning urine sample and the results of three consecutive dipstick tests for albumin were collected for 417 patients. RESULTS. When defining elevated urinary albumin concentration as 200 mg l-1 or more (proteinuria) the finding of at least one positive test out of the three dipstick tests for albumin had a diagnostic sensitivity of 73% and a specificity of 89%. When the microalbuminuric range (15.0 to 199.9 mg l-1) was added to the definition of renal involvement, the sensitivity of the dipstick test became as low as 28% with a specificity of 96%. CONCLUSION. It is essential for general practitioners to be able to identify proteinuric patients. To achieve this by means of the conventional dipstick test, general practice procedures need to be improved. As it is becoming increasingly well-documented that microalbuminuric non-insulin dependent diabetic patients may benefit from pharmacological treatment of even slight arterial hypertension and heart failure, it seems reasonable to suggest that the use of dipsticks for albumin in general practice be replaced by laboratory quantitative determination of urinary albumin concentration in a morning urine sample.
PMCID: PMC1239138  PMID: 7702885
4.  Glomerular Filtration Rate and Renal Plasma Flow in Long-term Juvenile Diabetics without Proteinuria 
British Medical Journal  1972;4(5835):257-259.
Glomerular filtration rate and renal plasma flow were examined in 16 young male non-proteinuric diabetics (mean age 28·4 years) with a duration of diabetes of over 15 years (mean duration 21·5 years.) In this selected group of long-term diabetics the glomerular filtration rate was clearly increased, the mean being 136 ml/min (±S.D. 11·8) (normal value 114 ml/min (±14·1), being comparable to that found earlier in short-term diabetics. There was no change in renal plasma flow. It is concluded that kidney function is generally well preserved in long-term diabetics who have not developed proteinuria.
PMCID: PMC1788792  PMID: 5083884
5.  Is screening and intervention for microalbuminuria worthwhile in patients with insulin dependent diabetes? 
BMJ : British Medical Journal  1993;306(6894):1722-1725.
OBJECTIVE--To analyse the cost-benefit of screening for and antihypertensive treatment of early renal disease indicated by microalbuminuria in patients with insulin dependent diabetes mellitus. DESIGN--Previously published data were used to estimate transition probabilities for each step from normoalbuminuria until death. The effect of intervention on urinary albumin excretion rate by antihypertensive treatment was arbitrarily set at three different levels. All direct costs (screening, antihypertensive treatment, treatment of end stage renal failure) were included in the cost-benefit analysis by using real discount rates of 2.5% and 6%. SETTING--Computer simulation. SUBJECTS--Simulated cohort of 8000 patients. MAIN OUTCOME MEASURES--Mortality, incidence of diabetic nephropathy, incidence of end stage renal failure, and costs versus savings. RESULTS--Assuming treatment effects of 33% and 67% median life expectancy increased by four to 14 years, respectively, and the need for dialysis or transplantation decreased by 21% to 63%. Costs and savings would balance if the annual rate of increase of albuminuria was decreased from 20% to 18% a year. CONCLUSIONS--Screening and intervention programmes are likely to have life saving effects and lead to considerable economic savings.
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PMCID: PMC1678304  PMID: 8343628
9.  Microalbuminuria as predictor of increased mortality in elderly people. 
BMJ : British Medical Journal  1990;300(6720):297-300.
OBJECTIVE--Correlation of the urinary albumin excretion rate and the risk of death among elderly subjects. DESIGN--216 Subjects aged 60-74 whose urinary albumin excretion rate had been determined were followed up 62-83 months later. SETTING--Municipality of Fredericia, Denmark. SUBJECTS--223 People who had been selected as control subjects for diabetics found during a systematic screening for diabetes of all people aged 60-74 living in the municipality of Fredericia, Denmark. Of these subjects, 216 had an extensive clinical and biochemical examination within a few weeks of selection. MAIN OUTCOME MEASURE--Death. RESULTS--The median urinary albumin excretion rate was 7.52 micrograms/min. Eight of those with a rate below the median died compared with 23 with a rate equal to or greater than the median (p = 0.0078). The median albumin excretion rate in the 31 who died was 15.00 micrograms/min. Cardiovascular disease was the most common cause of death in both groups. A multivariate regression analysis of survival data was performed using the proportional hazards model. Besides albumin excretion rate, male sex, serum creatinine concentration, and hypertension were found to be of prognostic value. CONCLUSIONS--The association between the albumin excretion rate and mortality that has been described in recent years in patients with diabetes mellitus may be present in elderly people in general, even when other known risk factors are taken into account.
PMCID: PMC1661920  PMID: 2106959

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