NaCl transport deficiencies – hemodynamics to the rescue

Abstract

Hereditary defects in the renal handling of filtered NaCl and water have important implications for understanding the physiological mechanisms that enable the kidney to optimize the match between glomerular filtration rate and tubular reabsorption. Null mutations in the water channel aquaporin 1 (AQP1) or the Na/H exchanger NHE3, two major fluid transporters in the proximal tubule, are states in which a reduction in proximal fluid absorption is accompanied by proportionate decrements in glomerular filtration rate. Compensation of the transport defect by a reduction in filtered load is so efficient that clinically symptomatic Na losses are not observed in either AQPI or NHE3 deficiency. On the other hand, severe syndromes of salt wasting are caused by transport deficiencies in the thick ascending limb or the collecting duct, indicating that the severity of Na dysregulation is unrelated to the basal absorption of NaCl in a given nephron segment. Loss of function of the Na,K,2Cl-cotransporter (NKCC2) or of the epithelial Na channel (ENaC) reduces Na absorption in thick ascending limbs or collecting ducts. In these states, the increased delivery of Na to downstream segments is not monitored by a sensor linked to the site of filtrate formation. In the absence of adaptations in the filtered load, intrarenal compensation of a circumscribed NaCl malabsorption by adjustment of NaCl transport in other nephron segments is remarkably insufficient, particularly in the immature kidney of the newborn.

Fluid reabsorption in proximal convoluted tubules of mice with gene deletions of claudin-2 and/or aquaporin1

“…Nevertheless, our observations are fully in agreement with earlier evidence for a link between an inhibition of proximal fluid transport and a reduction of GFR in both rats and mice (17,21,26,33,41). Reductions of the tubular fluid load are a highly effective way to limit nonhomeostatic renal fluid loss in states of proximal malabsorption (38). In the present experiments, absolute reabsorption in the mutant mice decreased by about 50% due to the fact that filtration rate and, therefore, filtered fluid load fell, whereas fractional reabsorption was reduced only by ϳ20 -25%.…”

New Treatment Options for Bartter's Syndrome

“…Only half or fewer of the surviving patients had a durable benefit one year after splenectomy. These data are consistent with those of earlier reports [1][2][3][4] and confirm that splenectomy in patients with myeloid metaplasia is a procedure of uncertain benefit and one that carries substantial risk.…”

“…First, the median survival in the subgroup of young patients with two or more favorable prognostic determinants (hemoglobin level, »10 g per deciliter; absence of constitutional symptoms; and <1 percent circulating blasts) may approach 15 years, and the risk of transplantation-related mortality and morbidity in these particular patients may not be justified. 1 Second, the results of allogeneic stem-cell transplantation in young patients with unfavorable prognostic factors remain suboptimal (five-year survival, 31 to 43 percent) 2 and some "successfully treated" patients may have 660 · August 31, 2000…”

“…[1][2][3][4] Interestingly, patients with early-stage disease were more likely to have a response to prone positioning than patients in the later, fibrotic stage of the acute respiratory distress syndrome. 4 However, no conclusions can be drawn from these small, short-term, observational studies about the influence of long-term prone positioning on outcomes such as mortality or the duration of mechanical ventilation.…”

Developmental programming of a reduced nephron endowment: more than just a baby's birth weight

“…However, under pathological conditions, this system can also be reset, with inappropriate salt and water retention leading to hypertension and cardiovascular disease. Perturbations in TGF are a primary factor in the development of renal dysfunction and hypertension (15,24,63,83,91). A preliminary report in lambs from dexamethasone-treated sheep demonstrates that TGF sensitivity is enhanced before arterial pressure increases and, thus, might contribute to the development of hypertension in this model (101).…”