No abstract

The present study confirms that NH4Cl-induced acidosis causes disturbances in renal sodium handling. In addition, these findings demonstrate a sustained pre-stimuli activation of kidney MAPK/ERKs signalling pathways in the NH4Cl-treated rats that may correlate with an increased rate of kidney hypertrophy and a transient renal tubule inability to handle sodium. Thus, the altered renal electrolyte handling may result from a reciprocal relationship between the level of renal tubule metabolic activity and ion transport. In addition, the study shows that the appropriate regulation of tyrosine kinase protein phosphorylation, and its downstream signal transduction pathway, plays an important role on renal growth in the NH4Cl-treated rats.

Systemic metabolic acidosis is known to cause a decrease in salt and water reabsorption by the kidney. We have used renal lithium clearance to investigate the effect of chronic, NH 4 Cl-induced metabolic acidosis on the renal handling of Na + in male Wistar-Hannover rats (200-250 g). Chronic acidosis (pH 7.16 ± 0.13) caused a sustained increase in renal fractional Na + excretion (267.9 ± 36.4%), accompanied by an increase in fractional proximal (113.3 ± 3.6%) and postproximal (179.7 ± 20.2%) Na + and urinary K + (163.4 ± 5.6%) excretion when compared to control and pair-fed rats. These differences occurred in spite of an unchanged creatinine clearance and Na + filtered load. A lower final body weight was observed in the acidotic (232 ± 4.6 g) and pair-fed (225 ± 3.6 g) rats compared to the controls (258 ± 3.7 g). In contrast, there was a significant increase in the kidney weights of acidotic rats (1.73 ± 0.05 g) compared to the other experimental groups (control, 1.46 ± 0.05 g; pair-fed, 1.4 ± 0.05 g). We suggest that altered renal Na + and K + handling in acidotic rats may result from a reciprocal relationship between the level of metabolism in renal tubules and ion transport.

ABSTRACT

Bartter's syndrome is a disorder that has been linked to mutations in one of three ion transporter proteins: NKCC2 (type I), ROMK (type II) and CCLNKB (type III), which affects a final common pathway that participates in ion transport by thick ascending limb cells. We present an atypical case of mitochondriopathy combined with tubule functional disturbances compatible with Bartter's syndrome and definitive sensorineural blindness. Our patient had a peculiar clinical presentation with signs of salt and volume depletion, low blood pressure and secondary hyperaldosteronism, associated with hypokalemic metabolic alkalosis, hypocalcemia and severe hypomagnesemia, uncommon in genetic forms of Bartter's syndrome. The enhanced absolute and fractional sodium excretion in our patient compared to volunteers was accompanied by increased post-proximal sodium rejection, suggesting a striking ion transport dysfunction in these nephron segments. These findings lead to the Bartter's syndrome diagnosis, accompanied by a suppose mitochondrial tick ascending loop of Henle epithelium dysfunction that may reflect the high energy supplied by mitochondria electron transport chain, required for this nephron segment to maintain normal ion transport.