Genesis and evolution of proteinuria in diabetes mellitus

International Journal of Clinical and Laboratory Research - 1985
Martin J. Wiseman1, Giangarlo Viberti1
1Unit for Metabolic Medicine Department of Medicine, Guy’s Hospital Medical School, London Bridge, Great Britain

Tóm tắt

Approximately 40–45% of insulin-dependent diabetic (IDD) patients will develop, with time, clinical proteinuria, a forerunner of certain renal failure. Before this, however, up to 45% of IDD patients excrete supranormal amounts of protein in the urine, though still undetectable by dipstix test. This microproteinuria appears to be glomerular in origin, consists mainly of albumin and IgG, and is associated with poor glycemic control and marginal elevation of arterial pressure. Glomerular hemodynamic disturbances, and loss of charge selectivity of the glomerular membrane, are probably responsible for this microproteinuria, which appears reversible by correction of hyperglycemia and raised blood pressure. Once the dipstix test becomes positive (i.e. total urinary protein excretion exceeds 0.5 g/24h) and blood pressure rises into the hypertensive range, glomerular filtration rate (GFR) falls relentlessly. By the time GFR is as low as 20 ml/min/1.73 m2, more IgG relative to albumin is being filtered, giving rise to a low selectivity proteinuria, a condition consistent with changes in the size selectivity properties of the glomerular filtre. Glycemic control does not affect the decline in GFR, although blood pressure control and low protein diet can slow it, presumably by altering the self-perpetuating hemodynamic disturbances that occur in surviving glomeruli. The recent demonstration that IDD patients with microalbuminuria in excess of 30 µg/min have approximatley a 20-fold increase in risk of developing persistent detectable proteinuria has provided a link between these two phases of diabetic nephropathy. The reversibility of the early microalbuminuria heralds a real chance of preventing the later irreversible phase of end-stage renal failure.

Từ khóa


Tài liệu tham khảo

Andersen A. R., Christiansen J. S., Andersen J. K., Kreiner S., Deckert T.: Diabetic nephropathy in type I (insulin-dependent) diabetes: an epidemiological study — Diabetologia25, 496, 1983.

Brenner B. M.: Progression of renal disease. In: Proceedings IX Int. Congr. of Nephrology. Los Angeles, 1984; p. 6A.

Brenner B. M., Meyer T. W., Hostetter T. H.: Dietary protein intake and progressive nature of kidney disease: the role of haemodynamically-mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation and intrinsic renal disease — New Engl. J. Med.307, 652, 1982.

Giovannetti S., Maggiore Q.: A low nitrogen diet with a protein of high biological value for severe chronic uraemia — Lanceti, 1000, 1964

Hostetter T. H., Troy J. L., Brenner B. M.: Glomerular haemodynamics in experimental diabetes mellitus — Kidney int.19, 401, 1981.

Jones R. H., Hayakawa H., Mackay J. D., Parsons V., Watkins P. J.: Progression of diabetic nephropathy — Lanceti, 1105, 1974.

Keen H., Chlouverakis C.: An immunoassay method for urinary albumin at low concentrations — Lancetii, 913, 1963.

Keen H., Chlouverakis C., Fuller J., Jarrett R. J.: The concomitants of raised blood sugar: studies in newly detected hyperglycemics. II. Urinary albumin excretion, blood sugar levels — Guy’s Hosp. Rep.118, 247, 1969.

Maschio G., Oldrizzi L., Tessitore N., D’Angelo A., Valvo E., Lupo A., Loschiavo C., Fabri S. A., Gammaro L., Rugiu C., Panzetta G.: Effects of dietary protein and phosphorus restriction in the progression of early renal failure — Kidney int.22, 371, 1982.

Mathiesen E. R., Oxenbøll D., Johnsen K., Svendsen P. Aa., Deckert T.: Incipient nephropathy in type I (insulin-dependent) diabetes — Diabetologia26, 406, 1984.

Mogensen C. E.: Renal function changes in diabetes — Diabetes25, 872, 1976.

Mogensen C. E.: Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy — Brit. med. J.285, 685, 1982.

Mogensen C. E., Christiansen C. K.: Predicting diabetic nephropathy in insulin-dependent diabetes — New Engl. J. Med.311, 89, 1984.

Mogensen C. E., Steffes M. W., Deckert T., Christiansen J. S.: Functional and morphological renal manifestations in diabetes mellitus — Diabetologia21, 89, 1981.

Myers B. D., Winetz J. A., Chui F., Michaels A. S.: Mechanisms of proteinuria in diabetic nephropathy: a study of glomerular barrier function — Kidney int.21, 633, 1982.

Parthasarathy N., Spiro R. G.: Effects of diabetes on the glycosaminoglycan component of the human glomerular basement membrane — Diabetes31, 738, 1982.

Parving H. H., Andersen A. R., Smidt U. M., Svendsen P. Aa.: Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy — Lanceti, 1175, 1983.

Parving H. H., Oxenbøll D., Svendsen P. Aa., Christiansen J. S., Andersen A. R.: Early detection of patients at risk of developing diabetic nephropathy. A longitudinal study of urinary albumin excretion — Acta endocrinol. (Kbh.)100, 550, 1982.

Parving H. H., Jensen H. A., Mogensen C. E., Evrin P.-E.: Increased urinary albumin excretion rate in benign essential hypertension — Lanceti, 1190, 1974.

The Kroc Collaborative Study Group: Blood glucose control and the evolution of diabetic retinopathy and albuminuria: a multicentre randomized feasibility trial — New Engl. J. Med.311, 365, 1984.

Viberti G. C.: Early functional and morphological changes in diabetic nephropathy — Clin. Nephrol.12, 47, 1979.

Viberti G. C., Bilous R. W., Mackintosh D., Bending J. J., Keen H.: Long-term correction of hyperglycemia and progression of renal failure in insulin-dependent diabetics — Brit. med. J.286, 598, 1983.

Viberti G. C., Bilous R. W., Mackintosh D., Keen H.: Monitoring glomerular function in diabetic nephropathy: a prospective study — Amer. J. Med.74, 256, 1983.

Viberti G. C., Hill R. D., Jarrett R. J., Argyropoulos A., Mahmud U., Keen H.: Microalbuminuria as predictor of clinical nephropathy in insulin-dependent diabetes mellitus — Lanceti, 1430, 1982.

Viberti G. C., Jarrett R. J., McCartney P., Keen H.: Increased glomerular permeability to albumin induced by exercise in diabetic subjects — Diabetologia14, 293, 1978.

Viberti G. C., Keen H.: The patterns of proteinuria in diabetes mellitus — Diabetes33, 686, 1984.

Viberti G. C., Mackintosh D., Bilous R. W., Pickup J. C., Keen H.: Proteinuria in diabetes mellitus: role of spontaneous and experimental variation of glycaemia — Kidney int.21, 714, 1982.

Viberti G. C., Mackintosh D., Keen H.: Determinants of the penetration of protein through the glomerular barrier in insulin-dependent diabetes mellitus — Diabetes32 (Suppl. 2), 92, 1983.

Viberti G. C., Pickup J. C., Jarrett R. J., Keen H.: Effect of control of blood glucose on urinary excretion of albumin and β2-microglobulin in insulin-dependent diabetics — New Engl. J. Med.300, 638, 1974.

Viberti G. C.,Wiseman M. J.,Bending J. J.: Diabetic nephropathy: a preventable complictation? In: Proceedings of 21st Congr. of the EDTA European Renal Association. Florence, 23rd–26th September, 1984.

Vittinghus E., Mogensen C. E.: Albumin excretion and renal hemodynamic response to physical exercise in normal and diabetic man — Scand. J. clin. Lab. Invest.41, 627, 1981.

Wiseman M. J., Viberti G. C., Jarrett R. J., Keen H.: Glycaemia, arterial pressure and microalbuminuria in type I (insulin-dependent) diabetes mellitus — Diabetologia26, 401, 1984.

Thông tin
Thông tin xuất bản

International Journal of Clinical and Laboratory Research

Thông tin tác giả