Nephron Physiology最新文献

Disorders of water balance lead either to dehydration or overhydration. Because there is an intimate relationship between water and sodium concentration (water generally following salt), one can distinguish hypotonic, isotonic and hypertonic dehydration and the same for overhydration. The vast majority of water balance disorders are acquired. In this article, the focus is on the inherited disorders both of water (nephrogenic diabetes insipidus) and acid-base balance. Both acidosis and alkalosis can arise from primary tubular ion transport abnormalities. The alkaloses are usually secondary to salt handling problems, whereas the renal tubular acidoses are often a consequence of primary abnormalities of acid-base transporters.

Although hyponatremia is a recognized complication of several inflammatory diseases, its pathophysiology in this setting has remained elusive until recently. A growing body of evidence now points to an important role for interleukin-6 in the non-osmotic release of vasopressin. Here, we review this evidence by exploring the immuno-neuroendocrine pathways connecting interleukin-6 with vasopressin. The importance of these connections extends to several clinical scenarios of hyponatremia and inflammation, including hospital-acquired hyponatremia, postoperative hyponatremia, exercise-associated hyponatremia, and hyponatremia in the elderly. Besides insights in pathophysiology, the recognition of the propensity for antidiuresis during inflammation is also important with regard to monitoring patients and selecting the appropriate intravenous fluid regimen, for which recommendations are provided.

Amelogenesis imperfecta (AI) is a group of hereditary disorders that affect the quality and/or quantity of dental enamel. This paper describes the clinicopathological features of a patient who was born of consanguineous parents and who presented with oral alterations, including yellow and misshapen teeth, intrapulpal calcifications, delayed tooth eruption, and gum enlargement. Scanning electron microscopy of the teeth revealed hypoplastic enamel, and a renal ultrasound detected bilateral nephrocalcinosis, leading to a diagnosis of AI and nephrocalcinosis syndrome. Since nephrocalcinosis is often asymptomatic and can be associated with impaired renal function, dentists who see children with generalized and thin hypoplastic AI should consider a renal ultrasound scan and referral to a nephrologist, if appropriate. Children with nephrocalcinosis should also be considered for a dental check.

Background: Although it is known that moderate-to-high doses of the neurohypophysial hormones oxytocin and vasopressin are natriuretic, doubts remain over the identity of the receptors responsible. To address this issue, we have used highly selective antagonists of oxytocin and vasopressin receptors in animals with elevated endogenous circulating levels of the 2 hormones.

Methods: Rats were anaesthetised and prepared surgically for clearance studies, thereby raising plasma oxytocin and vasopressin concentrations. Sodium excretion, glomerular filtration rate and lithium clearance (an index of end-proximal fluid delivery) were measured: first during a control period, then after administration of the selective oxytocin receptor antagonist desGly-NH(2),d(CH(2))(5)[D-Trp(2),Thr(4),Dap(5)]OVT, the selective vasopressin V(1a) receptor antagonist d(CH(2))(5)[Tyr(Me)(2),Dab(5)]AVP, or vehicle alone.

Results: Absolute and fractional sodium excretion fell in rats given the oxytocin antagonist (by 32 and 27%, respectively, compared with corresponding values in vehicle-infused rats), but not in those given the V(1a) antagonist or vehicle. Antinatriuresis was associated with a small reduction in the ratio of sodium clearance to lithium clearance (an index of the fraction of distally delivered sodium that escapes reabsorption in the distal nephron).

Conclusions: These results corroborate previous studies showing that activation of oxytocin receptors increases sodium excretion and imply that the natriuretic effect of elevated plasma vasopressin concentrations results from stimulation of oxytocin receptors.

Following glomerular filtration, the bulk of solutes are reabsorbed in the proximal tubule to prevent excessive losses of vital metabolites. In this nephron segment, reabsorption is largely active via dedicated transporters. Hereditary defects in proximal tubular function are characterized by malabsorption affecting amino acids, glucose, potassium, phosphate, bicarbonate, low-molecular-weight proteins and other solutes handled by this nephron segment. Dysfunction may be isolated or generalized (Fanconi syndrome). Defects in specific transporters lead to increased urinary excretion of substrates, which are often diagnostic. In others, extrarenal gene expression causes a multisystem phenotype. In this review, we will give a short overview of the molecular genetics, clinical picture, pathophysiology and treatment of genetically defined proximal tubulopathies.

In addition to the structural changes in the kidney associated with aging, physiological changes in renal function are also found in older adults, such as decreased glomerular filtration rate, vascular dysautonomia, altered tubular handling of creatinine, reduction in sodium reabsorption and potassium secretion, and diminished renal reserve. These alterations make aged individuals susceptible to the development of clinical conditions in response to usual stimuli that would otherwise be compensated for in younger individuals, including acute kidney injury, volume depletion and overload, disorders of serum sodium and potassium concentration, and toxic reactions to water-soluble drugs excreted by the kidneys. Additionally, the preservation with aging of a normal urinalysis, normal serum urea and creatinine values, erythropoietin synthesis, and normal phosphorus, calcium and magnesium tubular handling distinguishes decreased GFR due to normal aging from that due to chronic kidney disease.

Background and aims: Untreated renal tubular acidosis (RTA) can result in severe complications. We reviewed the clinical features of patients with mutations in two genes causing RTA and evaluated their developmental expression assuming that timing, symptom severity and complications may be related to its occurrence.

Methods: Clinical data from 16 patients with RTA due to mutations in either ATP6V1B1 or CAII were retrospectively reviewed. Both genes' localization and expression pattern in the developing human kidney were analyzed by real-time polymerase chain reaction and immunostaining.

Results: RTA-presenting symptoms were non-specific. Patients with mutations in ATP6V1B1 had earlier presentation (4.9 vs. 11 months, p < 0.041) and longer time to diagnosis than patients with CAII mutations (5.8 vs. 57 months, p < 0.01). Patients with ATP6V1B1 mutations were more likely to develop chronic kidney disease than those with CAII mutations (follow-up GFR values: 89 vs. 110 ml/min/1.73 m2, respectively, p < 0.017), probably secondary to nephrocalcinosis. Both ATP6V1B1 and CAII were expressed early during human nephrogenesis, with relatively higher transcript levels of ATP6V1B1.

Conclusions: There is considerable delay in establishing a diagnosis of both types of RTA, supporting the need for earlier biochemical investigation. RTA due to ATP6V1B1 mutations is associated with mild progressive loss of kidney function.

The distal convoluted tubule (DCT) reabsorbs 5-10% of filtered Na, and is an important site for regulation of Na balance. Additionally, the amount and composition of the tubular fluid that leaves the DCT affects H and K secretion in more distal nephrin segments. Mutations in five genes whose products are expressed in the DCT demonstrate these points and help to define the mechanisms by which the DCT contributes to control of electrolyte balance and volume. Loss of function mutations in the apical thiazide-sensitive NaCl cotransporter and the basolateral K channel Kir4.1, and activating mutations in the Ca-sensing receptor cause a phenotypically similar salt wasting syndrome. Mutation in two recently identified kinases, WNK1 and WNK4 cause a salt-retaining syndrome through increased apical expression of NaCl cotransporter. Recent studies indicate that these genes are important not only for understanding the physiology of the distal nephron, but that they and others may also contribute to blood pressure variation in the general population.