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Urinary excretion of albumin and beta-2-microglobulin was measured in nine hypertensive and nine normotensive renal transplant recipients and 10 healthy control subjects before and after an oral water load of 20 ml (kg body weight)-1 (study 1) and in eight hypertensive and 11 normotensive renal transplant recipients and 11 healthy control subjects during 24-h water deprivation (study 2). In both studies 1 and 2 urinary albumin excretion was significantly higher (p less than 0.01) in the hypertensive renal transplant recipients that in the normotensive patients and the control subjects (levels before loading; hypertensives: 23.9 micrograms/min (median), range 7.5-58.7; normotensives: 3.4 micrograms/min, range 1.0-49.3; controls: 2.9 micrograms/min, range 1.3-10.3). Urinary albumin excretion was significantly positive correlated to both systolic, diastolic and mean blood pressure (for mean blood pressure: rho = 0.625, n = 18, p less than 0.01) in transplanted patients. Albumin excretion tended to increase after water loading and to decrease during water deprivation in all groups. Beta-2-microglobulin excretion was approximately the same in all groups in both studies 1 and 2 and was not correlated to blood pressure. During a follow-up period of at least 18 months, none of the renal transplant recipients developed signs of chronic graft failure. Increased urinary albumin excretion in hypertensive renal transplant recipients thus appears to be caused by increased glomerular permeability that may be due to glomerular damage induced by arterial hypertension corresponding to the findings in essential hypertension.

Forty-seven diabetic patients with duration of diabetes of 1 to 40 years and 31 normal subjects were investigated using classical renal clearance technique. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were significantly increased in patients with juvenile diabetes mellitus of short duration. There was no correlation between GFR and serum glucose concentration, or between GFR and serum sodium concentration. A significant decrease in both GFR and RPF was found with increasing duration of diabetes. If consistent proteinuria was not present in the long-term diabetics, no reduction could be demonstrated in GFR and RPF.

There is now circumstantial evidence indicating that initiation and progression of renal disease in diabetes is associated with the degree of metabolic control, although modifying factors, such as elevation of blood pressure and, possibly, dietary protein intake, are important. Further, there is differential susceptibility, and more studies are clearly needed to clarify why some patients develop nephropathy and others do not, despite similar metabolic control. Metabolic control, blood pressure level and protein intake are probably not only risk factors but are also involved in the pathogenesis of diabetic nephropathy. Thus, intervention by optimizing glycaemic control and blood pressure treatment and by low-protein diets appears possible and can be recommended as a prudent treatment programme. Early clinical detection of patients at risk for late nephropathy is already possible, since easy, rapid, inexpensive methods for detecting microalbuminuria are now available.

A method is described for measuring glomerular permeability by dextran clearance using Sephadex gel filtration technique. Clearance is shown to be a function of molecular size, decreasing with increasing molecular weight. At a mol. weight higher than 55,000, the clearance is very low and approximately zero, while it averages 95 ml per minute at a mol. weight of 15,000. If plotted in a log.log. graph, a linear relation is found between clearance and molecular weight. In a semilog. graph, however, with clearance plotted against log. Stokes radius, the relation is also linear, with a slight deflection in the high molecular part, however.

The unique findings from the HOPE (Heart Outcomes Prevention Evaluation) study strongly support extending the use of the angiotensin-converting enzyme (ACE) inhibitor ramipril as a preventive agent for patients at high risk of cardiovascular events with normal left ventricular function. In addition, ramipril provides significant benefit in diabetic patients. These findings will impact on how ramipril is used in primary care, where ACE inhibitors are currently underprescribed. Patients reflecting the inclusion criteria of the HOPE study should be considered as suitable candidates for long-term ramipril therapy as an addition to their existing drug regimen. Screening should include control of kidney function (by serum creatinine), particularly within the first two weeks of treatment, in addition to regular monitoring of serum potassium. However, the HOPE study shows that ramipril is well tolerated at high doses and over a long treatment period. The effectiveness of therapy should also be regularly reviewed and dose adjustments made where necessary. If concern remains, referral to a specialist--a cardiologist or a diabetologist--may ultimately be necessary.