W. Gordon Walker

Hypertension-related renal injury: a major contributor to end-stage renal disease.

The US Renal Data System Annual Report reveals that 57% of new cases and of end-stage renal disease are attributed to hypertensive nephropathy and diabetic nephropathy. Analyses of the data on serum creatinine from the Multiple Risk Factor Intervention Trial confirms that one in 20 of the hypertensive men exhibits a rate of decline in renal function that equals or exceeds 3% per year, the rate of loss being greater in older men, black men, and men with higher baseline blood pressure. Effective blood pressure treatment with maintenance of diastolic blood pressure below 95 mm Hg protected renal function in non-blacks but not in blacks, despite comparable blood pressure reduction in blacks. A longitudinal study of a diabetic cohort (n = 131) revealed that hypertension, plasma angiotensin II, and aldosterone are independent predictors of accelerated loss of renal function in diabetic nephropathy, possibly aggravated by diuretic usage as part of the antihypertensive regimen in diabetic nephropathy. No significant loss of renal function could be documented in those individuals whose blood pressure was adequately controlled (systolic blood pressure, < 140 mm Hg). These findings provide emphasis for the importance of adequate blood pressure control in both essential hypertension and hypertension associated with diabetes mellitus. They also provide support for the proposal that careful blood pressure control offers promise for reducing the incidence of end-stage renal disease in both hypertensive nephropathy and diabetic nephropathy.

TRANSIENT IDIOPATHIC HYPERAMMONAEMIA IN ADULTS

Transient severe hyperammonaemia developed in the absence of serious liver dysfunction in three patients being treated for acute leukaemia. The onset of the biochemical disturbance was abrupt and led rapidly to acute encephalopathy, fatal in two cases. In the third patient, prompt initiation of aggressive haemodialysis and intravenous sodium benzoate and sodium phenylacetate infusion successfully controlled plasma ammonium levels until they spontaneously resolved. The cause of the disorder remains to be determined, but urinary nitrogen partition studies suggest temporary impairment of ureagenesis in a catabolic setting as a major pathophysiological feature of this disorder. The absence of liver disease, the normal mitochondrial ultrastructure seen in two cases, and the plasma aminoacid profiles observed serve to distinguish this disorder from others such as Reyes syndrome.

A rapid extraction technique for atomic absorption determinations of kidney calcium

Abstract A simple method of extracting calcium from kidney tissue prior to atomic absorption measurements of calcium in experimental models of nephrocalcinosis is described. This technique results in substantial time savings over traditional ashing or acid-digestion techniques for monitoring the rate and extent of calcification of the kidney. Comparisons of calcium in the kidneys of mice maintained on regimens which produce both intra- and extracellular calcification by both extraction and ashing techniques produced statistically equivalent results. Brief sonication of the tissue in a butanol-HCl-lanthanum medium effectively extracted calcium allowing accurate determination of tissue calcium without ashing. This technique has proven very useful when numerous samples must be processed daily.

INDICATIONS AND CONTRAINDICATIONS FOR DIURETIC THERAPY

The rate at which edema fluid accumulates in disturbances of cardiac, hepatic and renal function is a reflection of the disparity between dietary sodium intake and sodium excretion produced by these disorders. When they are mild, dietary sodium restriction alone may suffice for control of edema formation. With increasing severity, the renal excretion of sodium becomes so impaired that restriction of sodium intake to levels that will prevent edema formation is impractical without the help of diuretic therapy. This obvious relation between salt intake and rate of accumulation of edema may occasionally be ignored in planning diuretic therapy, resulting in undesirable consequences to the patient. Most patients exhibiting their first symptoms of congestive failure, for example, respond dramatically to relatively small doses of any of a variety of diuretics and hence vigorous treatment with potent diuretic agents coupled with severe dietary sodium restriction may rapidly produce severe sodium depletion. These risks become greater as more potent diuretic agents are used. For this reason it is desirable to begin diuretic therapy at relatively low dosages and with relatively mild agents, with increases in dosage and potency being dictated by the patients response to therapy. Adverse drug reactions account for virtually all the specific contraindications to the use of diuretics and any given reaction is usually confined to a single drug or class of drugs. Drug hypersensitivity with skin eruptions is the most commonly occurring example of this type reaction and may occur with any of the drugs used as diuretic agents. Generalized maculopapular eruptions, petachial eruptions, erythema multiforme, vesicular erythema with photosensitivity, lichen planus, photoallergic reactions, and urticaria have been encountered in one or more of the diuretic agents currently available. Blood dyscrasias are occasionally enc~un te red .~ -~ In addition, reactions not clearly related to hypersensitivity have been observed, such as the pancreatitis and diabetes mellitus seen with some of the benzothiadiazines,l0>*l and renal tubular necrosis with therapeutic doses of mercurial diuretics in the presence of chronic renal impairment.I2 Fortunately, all these adverse reactions are relatively rare. More commonly, contraindicating to the use of certain diuretic agents or to the continuation of a particular diuretic regimen arise as a result of disturbances in electrolyte composition of the body fluids. Some of these disturbances are drug-induced and may be directly or indirectly attributable to the major pharmacologic actions of the diuretic agent. This group of disorders will almost certainly increase in frequency as more potent diuretics continue to he made available for clinical use. The electrolyte disturbances which may arise during the course of the underlying illness may also complicate therapy and require modifications in the treatment regimen. The diseases for which diuretic therapy is most useful are progressive diseases and with this progression, increasingly vigorous diuretic

Prevention of Phosphate Induced Progression of Experimental Uremia by 3-Phosphocitric Acid

Excess dietary phosphate produces progressive increase in calcium content of the kidney and also leads to progressive deterioration of renal function1–3. The important variables responsible for determination of both the rate of deposition of calcium and loss of renal function are the quantity of dietary phosphate, the amount of functioning renal tissue and the level of parathyroid activity3,4. Given sufficient reduction in the size of the functioning renal mass, progressive deposition of calcium can be demonstrated in the kidney of animals maintained on a diet of normal phosphate content5. The histologic changes associated with these progressive calcium deposits provide convincing evidence of the structural damage produced, apparently resulting from cellular damage associated with calcium phosphate deposition 3,6.