Bartter’s and Gitelman’s syndromes are characterized by hypokalemia, normal to low blood pressure and hypochloremic metabolic alkalosis. Recently, investigators have been able to demonstrate mutations of six genes encoding several renal tubular transporters and ion channels that can be held responsible for Bartter’s and Gitelman’s syndromes. Neonatal Bartter’s syndrome is caused by mutations of NKCC2 or ROMK, classic Bartter’s syndrome by mutations of ClC-Kb, Bartter’s syndrome associated with sensorineural deafness is due to mutations of BSND, Gitelman’s syndrome to mutations of NCCT and Bartter’s syndrome associated with autosomal dominant hypocalcemia is linked to mutations of CASR. We review the pathophysiology of these syndromes in relation to their clinical presentation.

During treatment with indomethacin in a patient with Bartter's syndrome, hypokalemia, high plasma renin concentration, hyperaldosteronism and decreased sensitivity to angiotensin infusion were corrected. A particular finding in the renal biopsy specimen was a marked hyperplasia of renomedullary interstitial cells which had characteristics similar to the cells known to produce renal prostaglandins. The hypothesis is formultated that the primary defect in this syndrome is related to hyperplasia of renomedullary interstitial cells and inappropriate release of renal prostaglandins giving rise to decreased sodium reabsorption, volume depletion and hypersecretion of renin and aldosterone.

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An acute rise or decrease in parathyroid hormone (PTH) secretion was found in 30 patients, dialyzed with, respectively, low (5 mg/100 ml) or high (7.5 mg/100 ml) calcium concentration. The percentage changes were, respectively, +35% and -47% when a N-terminal antiserum measuring predominantly the glandular PTH was used. Only relatively small changes, respectively, +3% and -17%, were found using a C-terminal antiserum which detects preferentially smaller PTH fragments. Predialysis serum PTH concentration increases significantly with increasing duration of repetitive hemodialysis treatment using an intermediate (6 and 6.4 mg/100 ml) concentration of calcium in the dialysate. No such increase could be found in two other groups of patients treated with high-calcium (7.5 mg/100 ml) dialysis. Moreover, a significant but temporary decrease in predialysis serum PTH concentration occurred two months after a rise in dialysate calcium concentration from 6 to 7.5 mg/100 ml. Treatment with pharmacologic doses of vitamin D3 in selected patients (renal osterdystrophy or children) always resulted in a definite suppression of serum PTH concentration during 14 treatment periods in ten patients. After cessation of vitamin D3 treatment, serum PTH concentration returned to high levels in four out of five patients. These data fail to confirm the long-term involution of secondary hyperparathyroidism using high-calcium dialysis. Vitamin D treatment, however, results in a much more pronounced decrease in serum PTH concentrations, but sustained therapy is necessary.

In six healthy male volunteers we studied the effect of indomethacin on the renal hemodynamic adaptations to an acute oral protein load. Control and protein loading studies without and with indomethacin were performed under sustained water diuresis. In the control studies without indomethacin, creatinine (CCr) and inulin clearance (CIn) remained stable and p-aminohippurate (PAH) clearance (CPAH) and kaliuresis slightly decreased while natriuresis progressively increased. Urinary prostaglandin E2 (PGE2) excretion remained stable. Indomethacin had no effect on these control values except on natriuresis and PGE2 excretion. After protein loading CCr, CIn, and CPAH progressively increased to reach a peak 2 h after protein intake. Natriuresis, kaliuresis, and urinary PGE2 excretion also increased significantly. After indomethacin the peak increase of CCr, CIn, and CPAH during the 2nd h was significantly blunted. Indomethacin had no effect on the increased sodium and potassium excretion. The increase of PGE2 excretion was significantly attenuated by indomethacin. The results presented suggest that renal prostaglandins play at least a partial role in the renal hemodynamic adaptations to protein loading.