Correspondence

Expression of Renin in Glomerular Nonjuxtaglomerular Cells in a Child with a Hypertensive Bartter's-Like Syndrome

N Engl J Med 1998; 339:632-634August 27, 1998

Article

To the Editor:

Bartter's-like syndromes are characterized by hypokalemia, hypochloremia, metabolic alkalosis, and normal blood pressure despite hyperreninemia and hyperaldosteronism.1 We report on an infant with a Bartter's-like syndrome characterized by hypertension, hypercalcemia, and the ectopic expression of renin in glomerular nonjuxtaglomerular and adrenal vascular smooth-muscle cells.

The patient was a girl who was delivered at 30 weeks' gestation by cesarean section because of fetal tachycardia. The infant's maternal great-grandmother and maternal great-aunt had hypertension. She weighed 1620 g. The neonatal course was characterized by hyponatremia, hypochloremia, hypophosphatemia, metabolic acidosis, hypercalcemia, hypomagnesemia, and anemia. The blood urea nitrogen and serum creatinine concentrations were normal. The serum parathyroid hormone concentration was increased, but the concentrations of serum vitamin D metabolites were normal. Urinalysis revealed glycosuria, aminoaciduria, and increased urinary electrolyte, calcium, phosphorus, and bicarbonate excretion. The serum aldosterone concentration and plasma renin activity were elevated. Renal ultrasonography revealed nephrocalcinosis. Hypertension (blood pressure, approximately 125/95 mm Hg) was noted during the first week of life and treated with captopril (0.3 mg per kilogram of body weight per day). Failure to thrive developed, and the infant required nasogastric feeding and large supplements of sodium, potassium, and phosphate. At five months of age, she died after the development of aspiration pneumonia and sepsis. Relevant autopsy findings included parathyroid hyperplasia, biventricular hypertrophy of the heart, nodular hyperplasia of the adrenal cortex, nephrocalcinosis, hyperplasia of the juxtaglomerular apparatus, and a rickets-like lesion in the ribs.

Immunohistochemical studies of the distribution of renin were performed with a renin antibody in 4-μm paraffin-embedded renal-tissue sections, as described previously.2,3 In situ hybridization studies were performed with digoxigenin-labeled renin RNA probes (a gift from Dr. K. Murakami, University of Tsukuba, Tsukuba, Japan),4 with the use of a kit from Boehringer Mannheim Biochemica. In contrast to the findings in control sections of renal tissue from 14 children with conditions such as sepsis, congenital heart disease, renal-artery stenosis, adrenal insufficiency, the hemolytic–uremic syndrome, and human immunodeficiency virus–associated nephropathy, renin protein and messenger RNA were detected in the child's glomerular mesangial and endothelial cells (Figure 1AFigure 1Detection of Renin in Glomerular Nonjuxtaglomerular Cells in an Infant with a Hypertensive Bartter's-Like Syndrome., Figure 1B, Figure 1C, and Figure 1D) and in vascular smooth-muscle cells in the adrenal glands. This aberrant expression of renin has not been reported in other patients with Bartter's-like syndromes or renal disease.2,3,5 The ectopic production of renin and hypercalcemia may explain the presence of hypertension, cardiac hypertrophy, nephrocalcinosis, and failure to thrive in this infant. These findings suggest that the ectopic expression of renin in nonjuxtaglomerular cells may be involved in the pathogenesis of other neonatal forms of Bartter's-like syndromes associated with hypertension.

Patricio E. Ray, M.D.
Xue-Hui Liu, M.D., Ph.D.
Children's National Medical Center, Washington, DC 20010

Tadashi Inagami, Ph.D.
Vanderbilt University Medical Center, Nashville, TN 37232

Roma S. Chandra, M.D.
Children's National Medical Center, Washington, DC 20010

5 References

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