Julio E. Benabe

Role of macula densa in diuretics-induced renin release.

Diuretic therapy may enhance renin release by various mechanisms, principally contraction of extracellular fluid volume and its effects, including a fall in arterial pressure. Awake hydropenic or volume-expanded rats received diuretics (amiloride and hydrochlorothiazide) that are known inhibitors of NaCl transport beyond the macula densa; also the well-known Na(+)-K(+)-2 Cl- transport system inhibitor furosemide was administered. We also evaluated the effect of a dose of ethacrynic acid (a drug that shares the same mechanism of action as furosemide but is not diuretic in the rat). The direct action of the diuretics on renin-producing cells was examined in isolated glomeruli; a rise in renin release was observed with the calmodulin inhibitor trifluoperazine (10(-5) M). Renin release in intact hydropenic rats was not altered by diuretic therapy, but furosemide increased plasma renin activity in hydropenic as well as in volume-expanded rats. This demonstrates the importance of furosemide inhibition of transport in the macula densa for its renin secretory action. None of the diuretics (amiloride, hydrochlorothiazide, ethacrynic acid, or furosemide) elicited changes in renin release from glomeruli (10(-6) to 10(-3) M); amiloride and hydrochlorothiazide (10(-4) to 10(-3) M) did not change renin release from slices, but 10(-3) M ethacrynic acid and furosemide increased renin secretion in this preparation. This suggests that an effect on the macula densa is essential in loop diuretic-mediated renin release.(ABSTRACT TRUNCATED AT 250 WORDS)

The Impact of Malnutrition on Kidney Function

Malnutrition is the most common cause of mortality in the world. It affects underdeveloped as well as industrialized societies, in the latter demonstrating a prevalence in hospitalized patients of between 30 and 50%. Although the prevalence has decreased in recent studies, the problem is still significant among a selected group of patients. The clinical manifestations of malnutrition may be evident on physical examination but alterations in renal function may not show up at the initial exam. Clinical and experimental models of protein-calorie malnutrition have confirmed significant alterations in renal hemodynamics, renal concentration capacity, and renal acid excretion. Children and adults with malnutrition have been shown to have a decreased glomerular filtration rate and renal plasma flow (RPF), as well as a lowered capacity to concentrate the urine and excrete an acid load. Moreover, clinical and experimental models of protein-calorie malnutrition have unravelled the roles of the renin-angiotensin system, renal prostaglandins, and urea production in the renal function changes associated with malnutrition. We have reviewed the most pertinent and recent studies from our and other laboratories which have improved our understanding of renal functional alterations in malnutrition.

Renal and hemodynamic effects of atrial natriuretic peptide in patients with cirrhosis

The effects of anaritide, a 25-amino-acid synthetic analogue of ANP, were evaluated in 28 patients with cirrhosis complicated by ascites and/or edema. Each patient received two doses of the agent, as well as an infusion of placebo. Six different doses were tested ranging from 0.015-0.300 microgram/kg/min. The infusions lasted for 2 hours and were flanked by both baseline and recovery periods. There was a significant effect of placebo on urinary sodium and chloride excretion rates but no effect on urine flow rate. In response to anaritide, the urine flow rate increased at 0.03, 0.06, 0.075, and 0.100 microgram/kg/min. The sodium and chloride excretion rates increased at all doses except the highest dose. There was no definite effect of anaritide on urinary potassium, calcium, and phosphate excretion rates. There was also no significant effect on creatinine clearance. The mean arterial pressure decreased in response to the 0.060, 0.075, and 0.100 microgram/kg/min doses. In addition, five of the patients receiving the highest dose (0.300 microgram/kg/min) had decreases in their systolic pressures to 90 mm Hg or less. In conclusion, anaritide is natriuretic and diuretic in patients with cirrhosis complicated by ascites and/or edema. Its effect, however, on arterial pressure may limit its therapeutic potential in this patient population.

Some characteristics of recurrent calcium stone formers in Puerto Rico.

We have studied 83 patients with recurrent calcium stone formation in an attempt to determine an approximate incidence of metabolic disturbances associated with stone disease. Male veterans (n = 42), male non-veterans (n = 13), and women (n = 28) composed the group. We divided the groups in such fashion because they represented generally two distinct socioeconomic groups. Primary hyperparathyroidism was present in 19 per cent of the subjects; a marked predominance of women (15/16) was noted. Hypercalciuria of renal or intestinal origin was present in 23 per cent of the group. Of interest was a group of male veterans (17/83) in whom normocalciuria, normocalcemia, and normal serum phosphate were associated with high values of immunoreactive parathyroid hormone. These subjects had low urine phosphate. This set of findings indicates that these patients may be a new subgroup of stone-forming patients. Metabolic abnormalities could not be detected in 38 per cent of the patients. Classification of stone subjects is essential for rational management.

Congenital Disorders of the Kidneys and Tumors

In 1902, Guthrie1 described the unusual occurrence of renal disease in 12 members of a family. In 1927, Alport observed the association of deafness with renal failure in the same family.2 Over the next few decades, the finding of several other families in whom progressive hereditary nephritis coexisted with deafness clearly suggested that this association was indeed a distinct form of hereditary nephritis.3–8 Williamson named the entity Alport’s syndrome in 1961.9 More recent reports have expanded the classic dyad of aural and renal defects to include other abnormalities, including ocular defects, thrombocytopathia, hypoparathyroidism, and others.10–21 Renal disease, however, is the hallmark of Alport’s hereditary nephritis.

Congenital Renal Disorders and Kidney Tumors

This chapter reviews the literature until May 1986. The first part covers the anatomic and functional correlates of autosomal dominant polycystic kidney disease (ADPKD) and aspects of renal cell carcinoma that will be of interest to nephrologists. Several other tumors that produce symptomatology that is likely to result in nephrologic consultation, such as those seen with acquired cystic disease of dialysis and hemangiopericytoma, are also discussed.

Importance of Calcium in the Renal Hemodynamic Changes Induced by Vanadate

Vanadate has been recognized as an inhibitor of (Na+, K+)-ATPase (1, 5). Several groups have emphasized it’s potential role as a regulator of the enzyme in the kidney (6), an organ where vanadium tends to accumulate (7). In the dog, intraarterial infusion of vanadate produces a marked vasoconstriction, a decrease in renal blood flow and glomerular filtration rate as well as a decrease in urine flow and sodium excretion (8, 9). In addition to the hemodynamic changes there is also a decrease in renin secretion (10, 11), suggesting that the vasoconstriction is a direct result of the inhibition of the vascular ATPase system. Inhibition by vanadate of sodium or calcium pumps may increase the influx of Ca++ or reduce its efflux from the cytoplasm of muscle cell. This increase in cytoplasmic Ca++ may serve as a stimulus for vasoconstriction.