IT is now more than 30 years since Addis suggested that protein intake be restricted in patients with chronic renal insufficiency.1 His aim was not to reduce uremic symptoms but rather to prevent a...

Dietary Protein Intake and the Progressive Nature of Kidney Disease: The Role of Hemodynamically Mediated Glomerular Injury in the Pathogenesis of Progressive Glomerular Sclerosis in Aging, Renal Ablation, and Intrinsic Renal Disease

The renal nerves are the communication link between the central nervous system and the kidney. In response to multiple peripheral and central inputs, efferent renal sympathetic nerve activity is altered so as to convey information to the major structural and functional components of the kidney, the vessels, glomeruli, and tubules, each of which is innervated. At the level of each of these individual components, information transfer occurs via interaction of the neurotransmitter released at the sympathetic nerve terminal-neuroeffector junction with specific postjunctional receptors coupled to defined intracellular signaling and effector systems. In response to normal physiological stimuli, changes in efferent renal sympathetic nerve activity contribute importantly to homeostatic regulation of renal blood flow, glomerular filtration rate, renal tubular epithelial cell solute and water transport, and hormonal release. Afferent input from sensory receptors located in the kidney participates in this reflex control system via renorenal reflexes that enable total renal function to be self-regulated and balanced between the two kidneys. In pathophysiological conditions, abnormal regulation of efferent renal sympathetic nerve activity contributes significantly to the associated abnormalities of renal function which, in turn, are of importance in the pathogenesis of the disease.

Neural Control Of Renal Function

https://www.kidney-international.org/article/S0085-2538(15)33553-5/pdf

Limitations of creatinine as a filtration marker in glomerulopathic patients

Heart failure is a major cause of cardiovascular mortality and morbidity, resulting in more than 1 million hospitalizations per year, and is the most common hospital-discharge diagnosis among patients older than 65 years.1 In recent years, much has been learned about the pathophysiology of heart failure, particularly in the area of fluid and electrolyte metabolism, and this will be the focus of the present review. Regulation of Body-Fluid Volume There is considerable evidence in support of a unifying hypothesis of the regulation of body-fluid volume that is applicable to patients with edematous disorders such as cardiac failure, to patients with . . .

Hormones and Hemodynamics in Heart Failure

The effects of insulin on the renal handling of sodium, potassium, calcium, and phosphate were studied in man while maintaining the blood glucose concentration at the fasting level by negative feedback servocontrol of a variable glucose infusion. In studies on six water-loaded normal subjects in a steady state of water diuresis, insulin was administered i.v. to raise the plasma insulin concentration to between 98 and 193 muU/ml and infused at a constant rate of 2 mU/kg body weight per min over a total period of 120 min. The blood glucose concentration was not significantly altered, and there was no change in the filtered load of glucose; glomerular filtration rate (CIN) and renal plasma flow (CPAH) were unchanged. Urinary sodium excretion (UNaV) decreased from 401 plus or minus 46 (SEM) to 213 plus or minus 18 mueq/min during insulin administration, the change becoming significant (P smaller than 0.02) within the 30-60 min collection period. Free water clearance (CH2O) increased from 10.6 plus or minus 0.6 to 13 plus or minus 0.5 ml/min (P smaller than 0.025); osmolar clearance decreased and urine flow was unchanged. There was no change in plasma aldosterone concentration, which was low throughout the studies, and a slight reduction was observed in plasma glucagon concentration. Urinary potassium (UKV) and phosphate (UPV) excretion were also both decreased during insulin administration; UKV decreased from 66 plus or minus 9 to 21 plus or minus 1 mueq/min (P smaller than 0.005), and tupv decreased from 504 plus or minus 93 to 230 plus or minus 43 mug/min (P smaller than 0.01). The change in UKV was associated with a significant reduction in plasma potassium concentration. There was also a statistically significant but small reduction in plasma phosphate concentration which was not considered sufficient alone to account for the large reduction in UPV. Urinary calcium excretion (UCaV) increased from 126 plus or minus 24 to 200 plus or minus 17 mug/min (P smaller than 0.01). These studies demonstrate a reduction in UNaV associated with insulin administration that occurs in the absence of changes in the filtered load of glucose, glomerular filtration rate, renal blood flow, and plasma aldosterone concentration. The effect of insulin on CH2O suggests that insulin's effect on sodium excretion is due to enhancement of sodium reabsorption in the diluting segment of the distal nephron.

/pdf/the-effect-of-insulin-on-renal-handling-of-sodium-potassium-5gvkrkmzp2.pdf

The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man.

The osmolality was determined of fluid collected by micropuncture from proximal and distal convolutions, loops of Henle, collecting ducts and vasa recta of kidneys of various rodents with and without osmotic diuresis. Proximal tubular fluid was isosmotic; in the presence of antidiuretic hormone, early distal fluid was hypo-osmotic due to the prior reabsorption of sodium chloride, and late distal fluid again isosmotic. The hyperosmotic concentration of the urine is established in the collecting ducts, apparently as a consequence, in part at least, of the hyperosmotic reabsorption of sodium chloride in the loops of Henle. Fluid from the bends of loops of Henle, and from collecting ducts and vasa recta at the same level were equally hyperosmotic, consistent with the hypothesis that the mammalian nephron functions as a countercurrent multiplier system. The vasa recta are believed to play an important role in the concentration of the urine by functioning as countercurrent diffusion exchangers.

Micropuncture study of the mammalian urinary concentrating mechanism: evidence for the countercurrent hypothesis.

The renal responses to sympathetic nerve stimulation were studied in saline-expanded rats. The left kidney was partially denervated by crushing the left greater splanchnic nerve. Then the distal portion of the nerve was stimulated with square wave pulses of 0.5 ms duration, voltage twice threshold, and 1 or 2 Hz frequency while monitoring the compound action potential. Fibers with conduction speeds of 13-17 m-s-1 and of 0.7-1 m-s-1 were identified. Only stimulation of the latter appeared to produce changes in renal Na and water excretion. Whole kidney and individual nephron studies were performed alternating control and nerve stimulation periods. Nerve stimulation produced approximately a 25% reduction of the left kidney urine volume and sodium excretion. Glomerular filtration rate and renal plasma flow remained unchanged. Right kidney Na and water excretion, glomerular filtration rate, and renal plasma flow remained constant. In the left kidney, during nerve stimulation, the tubular fluid to plasma inulin concentration ratio increased significantly in the late proximal tubule. We conclude that the antidiuresis and antinatriuresis seen during sympathetic nerve stimulation were caused by increased sodium and water reabsorption in the proximal tubule, probably mediated by the stimulation of slowly conducting unmyelinated fibers. These responses appeared to be unrelated to systemic or intrarenal hemodynamic changes.

/pdf/effect-of-renal-sympathetic-nerve-stimulation-on-proximal-15kkwu32wl.pdf

Effect of renal sympathetic nerve stimulation on proximal water and sodium reabsorption.

Studies were undertaken to characterize the renal responses to acute unilateral renal denervation and the mechanisms involved in these responses. Denervation was produced in anesthetized nondiuretic rats by application of phenol to the left renal artery. Studies were also performed in sham-denervated nondiuretic rats. Whole kidney and individual nephron studies were performed before and after denervation or sham denervation. Denervation increased urine volume from the left kidney to about twice its control value (P less than 0.001) and increased urinary sodium excretion from 332 neq min minus -1 to 1,887 neq min minus -1 (P less than 0.001). Glomerular filtration rate (GFR) and renal plasma flow (RPF) remained unchanged in both kidneys after the procedure. The innervated right kidney showed no changes in urine volume or in sodium excretion. After denervation, late proximal ratio of tubular fluid inulin concentration to that of plasma [(F/P)In] decreased from 2.23 to 1.50 (P less than 0.001) while single nephron GFR remained unchanged. Absolute reabsorption decreased from 16.5 to 9.9 n. min minus -1 (P less than 0.001). (F/P)In ratios were also decreased in early distal (from 6.21 to 3.18, P less 0.001) and late distal convolutions (from 16.41 to 8.33, P less than 0.001) during the experimental period. (F/P)Na ratios remained unchanged in the early distal convolutions, but increased from 0.18 to 0.38 (P less than 0.01) in late distal convolutions after denervation. Absolute Na reabsorption after denervation increased in the loop of Henle, distal convolution, and collecting ducts. Any changes in intrarenal hydrostatic pressures after denervation were always small. There were no changes in GFR, RPF, urine volume, urinary sodium excretion, or late proximal (F/P)In after sham denervation. We conclude that the diuresis and natriuresis seen after acute renal denervation were caused by a marked depression of sodium and water reabsorption in the proximal tubule with partial compensation in more distal nephron segments. These responses appeared to be unrelated to systemic or intrarenal hemodynamic changes. The results demonstrate an effect of the renal nerves on proximal tubular function.

/pdf/effects-of-acute-unilateral-renal-denervation-in-the-rat-102expgbhx.pdf

Effects of acute unilateral renal denervation in the rat.

Methods are described for direct measurement of the hydrostatic pressure in the surface tubules and capillaries of the rat kidney. In fifty-six anesthetized rats intratubular pressure averaged 13.5...

Micropuncture study of pressures in proximal tubules and peritubular capillaries of the rat kidney and their relation to ureteral and renal venous pressures

Anesthetized, nondiuretic rats and hamsters were infused with C14-labeled inulin-carboxylic acid or urea, and fluid was subsequently collected by micropuncture from surface tubules in the rats and ...

Carl W. Gottschalk

Papers

Micropuncture study of the mammalian urinary concentrating mechanism: evidence for the countercurrent hypothesis.

Effect of renal sympathetic nerve stimulation on proximal water and sodium reabsorption.

Effects of acute unilateral renal denervation in the rat.

Micropuncture study of pressures in proximal tubules and peritubular capillaries of the rat kidney and their relation to ureteral and renal venous pressures

Micropuncture study of net transtubular movement of water and urea in nondiuretic mammalian kidney