Mineralocorticoid hypertension and hypokalemia.

Mineralocorticoid hypertension is hypertension associated with the presence of hypokalemia, metabolic alkalosis, and suppression of plasma renin. Mineralocorticoid hypertension represents only 10% of patients with essential hypertension. However, its recognition is important because it is a potentially reversible cause of hypertension. Primary hyperaldosteronism is the most common form of mineralocorticoid hypertension. It is current clinical practice to use the plasma aldosterone-renin ratio and the absolute plasma aldosterone level as screening tests. Confirmatory suppression tests and adrenal imaging are performed in appropriate patients. Three monogenic forms of mineralocorticoid hypertension have been identified including Liddle's syndrome, glucocorticoid-remediable hypertension, and apparent mineralocorticoid excess. In a number of patients with mineralocorticoid hypertension, hypokalemia can be a variable finding. This review highlights mineralocorticoid biology and important features of primary hyperaldosteronism and monogenic hypertension.

Predicting the development of diabetic nephropathy and its progression.

Diabetes remains the number one cause of end-stage renal disease worldwide. Only about one third of diabetic patients develop nephropathy, and the risk appears to be, in part, genetically determined. In this article, we review clinical and genetic markers for the development and progression of diabetic nephropathy. Microalbuminuria remains the best available predictor of the subsequent development of nephropathy, even though in recent years it has become clear that less than 50% of individuals with type 1 diabetes progress to overt proteinuria over a period of less than 10 years. It is of great interest for early recognition of risk of nephropathy that small elevations in nighttime blood pressure predict microalbuminuria in type 1 diabetes. Genetic markers for diabetic nephropathy have not been conclusively identified. The occurrence of renal events in diabetic patients, however, appears to be influenced by the angiotensin-converting enzyme (ACE) genotype, with a dominant deleterious effect of the D allele (D/D or I/D) versus I/I genotype. Some patients with the DD genotype also appear less susceptible to the renoprotective effects of conventional doses of ACE inhibitors, suggesting that ACE genotyping might be useful in selecting those patients that could benefit from higher doses of ACE inhibitors and more aggressive treatment to prevent or delay disease progression.

Nocturnal hypertension: will control of nighttime blood pressure prevent progression of diabetic renal disease?

Patients with type 1 and 2 diabetes and nephropathy frequently have a blunted fall in nighttime arterial blood pressure. This abnormality is already seen in subjects with type 1 diabetes who are in the microalbuminuric phase of the disease, and we have also shown that an increase in nighttime systolic blood pressure precedes the development of microalbuminuria. These studies suggest that nocturnal hypertension may be an important early predictor of diabetic nephropathy. Various drugs have different effects on nocturnal blood pressure, and chronotherapy may be key in determining clinical outcomes. There is a compelling need for studies showing that treating nocturnal hypertension in diabetes can prevent renal disease progression.

Circadian changes in blood pressure and their relationships to the development of microalbuminuria in type 1 diabetic patients.

Diabetic nephropathy in type I diabetic patients, as it is currently understood, progresses in a stepwise fashion from normoalbuminuria to microalbuminuria, then to overt proteinuria and progression to chronic renal failure, and ultimately to end-stage renal disease. The role of early blood pressure changes in relation to diabetic nephropathy is now better understood in light of recent data using ambulatory blood pressure monitoring as a means to monitor blood pressure changes noninvasively throughout the day. Cross-sectional studies with type I diabetic patients with microalbuminuria have shown that the normal nocturnal blood pressure often fails to fall normally during sleep. The question of which comes first, microalbuminuria or a rise in blood pressure in patients with type I diabetes, was recently addressed in a prospective study. An increase in systolic blood pressure during sleep precedes the development of microalbuminuria and may play a causative role in its development.