G Colussi — Page 5 | PubMed Health

PubMedDate not supplied

Evaluation of the tubuloglomerular feedback system in human subjects.

It has been shown in animals that GFR decreases after administration of a carbonic anhydrase inhibitor (CAI) because of activation of the tubuloglomerular feedback. However, the magnitude of this response has never been studied in healthy subjects, nor has the possibility of inhibiting tubuloglomerular feedback with frusemide (FRU). Changes in CCr, V, CNa, CCl, CH2O, CLi were studied before and after acute administration of acetazolamide (ACZ) to 11 normal subjects or FRU to 9 normal subjects. Both ACZ and FRU increased V, CNa, CCl and CLi. Only FRU decreased CH2O. ACZ but not FRU decreased CCr, despite lesser increases of V, CLi and CH2O+CCl (rough indexes of distal delivery). The magnitude of the GFR decrease after comparable increases in distal delivery varied greatly between subjects. There was a tendency for the subjects with lower basal GFRs to show tubuloglomerular feedback responses of lesser magnitude than those with higher GFRs. These results show that it is possible to study tubuloglomerular feedback and its sensitivity in humans using CAIs. FRU blocks the tubuloglomerular feedback response. Its sensitivity appears to vary widely in normal subjects.

Acetazolamide↗

PubMedDate not supplied

Genotype-phenotype correlations in normotensive patients with primary renal tubular hypokalemic metabolic alkalosis.

Among the different forms of hereditary renal tubulopathies associated with hypokalemia, metabolic alkalosis and normotension, two main types of disorders have been identified: Gitelman disease, which appears to be a homogeneous post-Henle's loop disorder, and Bartter syndrome, a heterogeneous Henle loop disorder. A specific gene has been found responsible for Gitelman disease, encoding the thiazide-sensitive Na-Cl cotransporter (TSC) of the distal convoluted tubule. From a phenotypic point of view the characteristic findings of this disease are hypocalciuria, hypomagnesemia and tetanic crises appearing during childhood or later. Many subjects are asymptomatic. At least three different genes have been shown to be responsible for Bartter syndrome, characterized by mutations in the proteins encoding respectively the bumetanide-sensitive Na-K-2Cl cotransporter, the inwardly-rectifying renal potassium channel and a renal chloride channel, all protein transports located in the ascending limb of Henle's loop. Mutations in the first two transport proteins have been demonstrated in patients with the hypercalciuric forms of Bartter syndrome associated with nephrocalcinosis (respectively Bartter syndrome type I and II), who were often born after pregnancies complicated by polyhydramnios and premature delivery. Mutations in the gene encoding a renal chloride channel were recently recognized in patients with a Henle tubular defect not associated with nephrocalcinosis (Bartter syndrome type III). Most of the latter group of patients were normo-hypercalciuric and presented dehydration and life-threatening hypotension in the first year of life. However, these three genes do not explain all the patients with Bartter syndrome which unlike Gitelman disease, appears to be a very heterogeneous disorder. Clearance studies, especially if done during furosemide and/or hydrochlorothiazide administration, have been helpful in identifying the site of tubular involvement. Considering both phenotypic and genotypic data, we propose a clinical-pathophysiological and molecular approach to diagnose the different tubulopathies associated with hypokalemic metabolic alkalosis.

Alkalosis↗