Rhythms of electrolyte excretion in healthy people

The rhythms of urinary electrolyte excretion have been examined in normal subjects by following up every examinee for 72-120 hrs. Circadian rhythms have been detected in the predominant majority of the examinees. The mean values of other rhythm parameters (mesor, amplitude) have been established, that are suggested to be used as the reference values in the early diagnosis of abnormalities, with due consideration for the ecologic conditions and nutrition.     

Further studies on the mechanism of the natriuretic response to low-dose dopamine in man: effect on lithium clearance and nephrogenic cAMP formation

The effect of intravenous infusion of low-dose dopamine on electrolyte excretion, lithium clearance, nephrogenous cAMP formation and renal haemodynamics was investigated in healthy volunteers. Dopamine significantly increased the urine flow rate by 70.6% and urinary sodium excretion by 72%, but did not change creatinine clearance, PRA or plasma levels of AVP, ANP and cAMP. Renal plasma flow significantly increased by 48.6%; the glomerular filtration rate was not changed. Lithium per se increased basal PRA, but had no effect on the increments of urine flow rate, sodium excretion and renal blood flow induced by dopamine. Dopamine significantly increased the fractional excretion of lithium (representing fractional excretion of sodium at the proximal level). The increase in urinary sodium excretion during dopamine infusion, significantly correlated with the increase in fractional excretion of lithium (r = 0.94; P less than 0.01) and the increase in nephrogenous cAMP formation (r = 0.96; P less than 0.01). No correlation was found between the increase in urinary sodium excretion and the increase in renal blood flow. In conclusion, this study confirms that low-dose dopamine increases renal blood flow and urinary sodium excretion in healthy volunteers. This natriuretic response appears to be due to interaction with proximal tubular dopamine receptors, which are positively coupled to adenylate cyclase.     

Effects of angiotensin II and atrial natriuretic peptide alone and in combination on urinary water and electrolyte excretion in man

1. Atrial natriuretic peptide (ANP) has previously been shown to inhibit the renin-angiotensin-aldosterone system (RAAS) at several different levels. We have now investigated a further non-endocrine, renal interaction between ANP and the RAAS. 2. The effects of ANP and angiotensin II (ANG II) alone, and in combination, on urinary electrolyte and water excretion were studied in eight normal male subjects undergoing maximal water diuresis. 3. ANP caused a significant increase in urine flow and sodium excretion. ANG II alone was antidiuretic, antinatriuretic and antikaliuretic. When ANP was given against a background infusion of ANG II, urinary flow rate and electrolyte excretion increased from a new lower level to reach a value intermediate between that found with ANG II alone and ANP alone. 4. It is concluded that the renal effects of ANP are modified in the presence of simultaneously elevated levels of ANG II and that net water and electrolyte excretion reflect the sum of the opposing influences of each peptide. While this interplay may be non-specific, it is possible that ANP may exert some of its actions by specifically inhibiting the intrarenal effects of ANG II.     

A review on urinary proteins in outflow disease of the upper urinary tract

INYRODUCTION: No review articles on outflow disease of the upper urinary tract discuss urinary protein excretion. DISCUSSION: Following acute partial and/or complete ureteral obstruction (UO) or chronic partial UO, alpha-1-microglobulin excretion is significantly higher than in the reference population or patients with proven renal dilatation without obstruction, but is not found to be diagnostic for these conditions as such. Chronic partial UO is followed first by a destructive and then by a steady-state phase in renal damage. The observed increase in tubular proteinuria during the destructive phase correlates with the decrease in absolute dimercaptosuccinic acid (DMSA) uptake. If the destructive phase is not followed by a stable phase, a mixed tubular and glomerular proteinuria is seen. Urinary alpha-1-microglobulin excretion is found to be diagnostically useful in vesico-ureteral reflux (VUR) patients, increases with higher intravesical-intrapyelic pressure, correlates with the decrease in absolute DMSA uptake or with urinary epidermal growth factor excretion (both markers of the number of functioning nephrons) and predicts the outcome after treatment. CONCLUSION: alpha-1-Microglobulin is useful in the detection of renal tubular damage in patients with outflow disease of the upper tract, is diagnostic for VUR but is not so for ureteral obstruction.     

Seasonal and circadian rhythms of the excretion of androgens and their fractions in peptic ulcer patients in the remission phase in the markedly continental climate of Transbaikalia

Seasonal rhythms of androgen excretion were studied in 247 normal subjects and 213 patients with peptic ulcer in the stage of remission. Circadian rhythms were examined in 84 patients and excretion of androgen fractions in 81 patients. The patients manifested changes in the seasonal rhythms of androgen excretion. In winter period, androgen excretion was higher in the patients with peptic ulcer but in spring, the normal subjects had a higher excretion than patients, whereas in summer the patients had a higher excretion than normal subjects. Despite the preservation of the rhythmical pattern the patients demonstrated changes in the rhythm expressed in the decreased amplitude of seasonal fluctuations and deformation of the seasonal rhythm. Circadian rhythms differed only at some seasons. The difference in excretion of androgens (dehydroandrosterone and androsterone) were revealed at individual seasons. Deformation of the rhythms in peptic ulcer patients can be corrected by application of early preventive measures aimed at normalization of the excretory rhythm and restoration of the rhythm characteristic of the regional climatic zone under consideration.     

Renal tubular action of prostaglandin E2 on water and electrolyte excretion in the nonanesthetized chicken

The tubular effects of prostaglandin (PG) E2 on electrolyte and water excretion were investigated in vitro in the nonanesthetized chicken by the Sperber technique. This technique allowed the administration of PGE2 directly into the peritubular space of one kidney by way of the venous portal circulation. When compared to the contralateral, noninfused kidney, PGE2 in the infused kidney (0.6-4.5 X 10(-10) mol/kg X min) induced a dose-dependent increase in urinary flow rate, a mild natriuresis and kaliuresis, with a concomitant decrease in urinary osmolality and an increase in free-water clearance. These effects occurred without changes in renal plasma flow or glomerular filtration rate. PGA2 (1.7-7.8 X 10(-10) mol/kg X min), another vasodepressor PG, did not modify electrolyte excretion. The tubular handling of PGE2 was observed by following the administration of [3H]PGE2. [3H] PGE2 was metabolized extensively during its renal tubular excretion. The 3H label was secreted actively into the urine by the organic anion transport system which was inhibited by novobiocin. Inhibition of the organic anion transport system did not modify the renal tubular effects of PGE2 on electrolyte and water excretion. These results indicate that PGE2 exerts a tubular inhibitory effect on sodium and water excretion, this action being located on the peritubular side.     

Urinary excretion of lysozyme and N-acetyl-beta-D-glucosaminidase in the diagnosis of renal allograft rejection.

The urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) has been claimed to be of high diagnostic value in indicating acute renal graft rejection. Similar claims have been made for the significance of urinary lysozyme excretion. Serial measurements of urinary lysozyme and NAG have been made in 35 patients after renal transplantation, and during 52 suspected rejection episodes. A close correlation has been found between these two parameters although they did not consistently change in parallel. The use of both assays may give a better indication of impending rejection than either assay alone.     

Loop diuretics alter the diurnal rhythm of endogenous parathyroid hormone secretion. A randomized-controlled study on the effects of loop- and thiazide-diuretics on the diurnal rhythms of calcitropic hormones and biochemical bone markers in postmenopausal women

BACKGROUND: Thiazide diuretics (TD) reduce urinary calcium, bone loss and fracture risk. Loop diuretics (LD) may have opposite effects. These effects could depend on induced rhythmic changes in bone and calcium homeostasis. DESIGN: After a run-in period of 7 days, we studied (in a factorial design) the diurnal rhythms of plasma levels of calcium, phosphate, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D and osteocalcin, as well as renal excretions rates of calcium, phosphate, and cross-linked N-terminal telopeptide of type 1 collagen (NTx) in 50 postmenopausal women randomized to treatment with either a thiazide diuretic (TD; bendroflumethiazide, n = 14), a loop diuretic (LD; bumetanide, n = 13), LD plus TD (bendroflumethiazide plus bumetanide, n = 11), or placebo (n = 12). RESULTS: In all four groups, all measured quantities showed a diurnal variation. LD caused a steep increase, with a subsequent decrease, in urinary calcium and plasma PTH. The mean 24 h plasma PTH concentration was increased (8.5 +/- 0.9 mmol L-1) compared with placebo (4.4 +/- 0.4 mmol L-1), whereas net 24 h renal calcium excretion did not differ from that of the placebo group due to a rebound hypocalciuria. Compared with placebo, diurnal rhythms of plasma phosphate and osteocalcin were changed with an increase during daytime and a decrease during the night. TD did not alter the diurnal rhythm of any of the measured quantities. However, the 24-h renal calcium excretion decreased, whereas the mean 24-h plasma calcium concentration increased without PTH suppression. LD plus TD caused changes similar to those observed with LD alone. CONCLUSION: One daily dose of LD increases parathyroid activity with alterations in the diurnal pattern of osteocalcin. This could indicate a potential anabolic effect of LD.     

Circadian rhythms of mineral-excreting kidney function in healthy persons and their changes in ischemic heart disease

Seventy normal persons and 100 patients with coronary disease were examined for circadian rhythms of urine and minerals excretion. The data obtained demonstrate that normal persons were characterized by circadian rhythms of urine and minerals excretion with a definite confidence interval of mesor and amplitude fluctuations. Angina pectoris of effort was marked by infradian rhythms of mineral excreting renal function. Monotherapy with beta-blockers or calcium antagonists given in courses entailed the recovery of the circadian rhythms of mineral-excreting renal function. Parameters of the rhythms of urine and minerals excretion in patients with angina pectoris of effort and rest noticeably differed from those in patients with angina pectoris of effort. In 30.7 percent of the persons, the use of the mathematic methods did not reveal any significant rhythms. The circadian range was found to predominate among the significant rhythms. Antianginal treatment did not produce any appreciable changes.     

Circadian renal rhythms influenced by implanted encapsulated hANP-producing cells in Goldblatt hypertensive rats

Renal excretion in experimental hypertensive rats implanted with encapsulated human atrial natriuretic peptide (hANP)-producing cells is circadian periodic. Chinese hamster ovary (CHO) cells transfected with the plasmid hANP-cDNA were encapsulated in biocompatible polycaprolactone capsules for intraperitoneal implantation into two-kidney, one-clip (2K1C) hypertensive rats. During a 12:12 light-dark cycle, as compared to control CHO cells, the implantation of encapsulated hANP-producing CHO cells was associated with an increase in the net excretion of water, sodium and potassium, and with a reversal of the advanced circadian phases related to renovascular hypertension in 2K1C rats. The increase in blood pressure postimplantation was delayed, and increases in renal blood flow, glomerular filtration rate, sodium output, urinary excretion and urinary cyclic GMP concentrations were also found. Implantation of encapsulated hANP-producing cells affects circadian rhythms in kidney excretion functions of 2K1C rats, and may be useful for the treatment of cardiovascular disease.     

Pharmacokinetics of synthetic atrial natriuretic peptides in normal men

The kinetics of atrial natriuretic peptides (ANP) and the kinetic profile of their effect on blood pressure and renal hemodynamic and electrolyte excretion were investigated in 20 salt-loaded healthy volunteers during and after constant rate infusion. At steady state, mean plasma concentrations of ANP were measured at 210, 430, and 2990 pg/ml and mean systemic clearance was 2.6, 2.5, and 1.7 L/min for ANP infusion rates of 0.5, 1, and 5 micrograms/min, respectively, which corresponds to the clearance rate of other vasoactive peptide hormones. The apparent volume of distribution averaged 17 L and the mean half-life was 4.5 minutes. ANP induced dose-related effects on systemic and renal hemodynamic, as well as urinary electrolyte excretion, albeit with a time lag between onset and full effect.     

Effects of sulindac on renal function and prostaglandin synthesis in patients with moderate chronic renal insufficiency

The renal effects of therapeutic doses of sulindac were studied in nine patients with stable renal insufficiency, mean creatinine clearance 37.0 +/- 2.2 ml min-1 1.73 m-2 (range 24.7-54.6 ml min-1 1.73 m-2). Nine days' treatment with sulindac produced a small, but significant, reduction in the mean creatinine clearance (37.0 +/- 2.2 to 34.7 +/- 2.2 ml min-1 1.73 m-2; P less than 0.02) and 99mTc diethylenetriaminepenta-acetate (DTPA) clearance (35.5 +/- 3.4 to 31.4 +/- 3.6 ml min-1 1.73 m-2; P less than 0.02) without altering body weight, effective renal plasma flow [131I]hippuran clearance), plasma renin activity (PRA), 24 h urinary volume or electrolyte excretion. After discontinuation of sulindac, creatinine clearance returned to pretreatment values. In five female patients, pretreatment urinary excretion of the 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), a stable breakdown product of prostacyclin (PGI2), was significantly reduced (P less than 0.02) when compared with four healthy controls, whereas prostaglandin E2 (PGE2) was unchanged. Administration of sulindac did not significantly alter the excretion rate of PGE2 or 6-ketoPGF1 alpha in this group of patients. In chronic renal disease with moderate renal impairment, reduced renal prostacyclin synthesis may be an important predisposing factor to the renal toxicity associated with the use of non-steroidal anti-inflammatory drugs (NSAID). Short term use of sulindac in therapeutic doses does not appear to influence the excretion of prostaglandins and produces only a minor reversible change in renal function; used cautiously it may have advantages over other NSAID in these patients.     

Effect of chronic and progressive hepatic outflow blockade on renal function in rats

Systemic and splanchnic hemodynamics, plasma concentration, and urinary excretion of several hormones and the changes in renal function induced by saline infusion were studied in rats with a chronic and progressive model of postsinusoidal hypertension by hepatic vein ligation (HVL) and in a control group. HVL rats showed no differences in systemic hemodynamics compared with control rats, with the exception of decreased renal blood flow and increased renal vascular resistance. HVL rats showed increased portal and intrahepatic pressure, without other differences in splanchnic hemodynamics or in portal-systemic shunts. Clearance studies revealed that under basal conditions, HVL rats showed lower glomerular filtration rate, renal plasma flow, urinary flow, and sodium, chloride, and potassium excretion than control rats. After saline infusion (3% body weight, 15 ml/hr) differences in glomerular filtration rate became nonsignificant, but urinary flow and electrolyte excretion remained lower in HVL than in control rats. Under basal conditions, plasma norepinephrine and dopamine concentrations were higher and urinary prostaglandin E2 (PGE2) and prostaglandin F2 alpha levels were lower in HVL than in control animals. These results demonstrate that chronic and progressive hepatic congestion results in impaired renal function with decreased water and electrolyte excretion, and suggest the involvement of a hepatorenal sympathetic reflex in these alterations. Renal effects could also be mediated by the low levels of PGE.     

Imbalances of the water and electrolyte status

Nutritional therapy can be impaired if imbalances in water and electrolyte status have led to gross disorders of the cardiovascular, pulmonary, renal, metabolic, and central nervous systems. Restauration and maintenance of the functional extracellular fluid volume is the primary therapeutic goal in water and electrolyte resuscitation. Hyper- and hypoosmolar disturbances are automatically corrected by intrinsic regulatory mechanisms. Potassium deficiency or overload, or potassium disequilibrium between the intracellular and extracellular space can lead to dangerous cardiac arrhythmias. Hyper- and hypokalemia usually develop within days or even weeks and should not be corrected within a few hours. If life threatening hyperkalemia develops during acute renal failure, 20 ml 10% calcium gluconate solution can be given intravenously in order to avoid ventricular fibrillation or cardiac arrest. The discrimination between prerenal disease, acute tubular necrosis and other causes of acute renal failure is based on special investigations, such as urinary osmolality, urinary sodium concentration, clearance of creatinine, osmolar solutes, free water, and fractional sodium excretion. The clinical examination of a patient should be the basis of assessing his water and electrolyte state. Laboratory findings which are in disagreement with the clinical state have to be repeated, critically interpreted, but not completely rejected. Third space losses make fluid balance difficult.     

Interaction of renal prostaglandins with the renin-angiotensin and renal adrenergic nervous systems in healthy subjects during dietary changes in sodium intake

In six healthy subjects the role of renal prostaglandins (PG) in modulating the actions of the renin-angiotensin and renal adrenergic nervous systems on renal function was investigated. During high dietary sodium intake (350 mmol/day) for 4 days no changes in urinary excretion of PGE2, PGF2 alpha, noradrenaline or adrenaline were noted, whereas plasma renin activity (PRA) and urinary aldosterone excretion were suppressed. After 4 days of low sodium intake (35 mmol/day) urinary excretion of PGE2, aldosterone and noradrenaline, as well as PRA, had significantly increased. Inhibition of PG synthesis with indomethacin (2 mg/kg body weight) had no effects on renal function on day 5 of high sodium intake. Despite suppression of PRA and urinary aldosterone, indomethacin significantly reduced p-aminohippurate (PAH) clearance, glomerular filtration rate (GFR) and urinary sodium excretion on day 5 of low sodium intake, when urinary noradrenaline excretion remained high. The results point to the crucial role of the renal adrenergic nervous system in controlling renal vascular resistance and sodium conservation in healthy subjects during low sodium intake, which is unmasked when renal PG synthesis is blocked by indomethacin. Enhanced renal PG synthesis during sodium restriction therefore not only attenuates the vascular and tubular effects of the renin-angiotensin system but, more importantly, also those of the highly stimulated renal adrenergic nervous system.     

Compensatory adaptation of bicarbonate excretion following acute contralateral kidney exclusion in the dog.

Changes in the excretion of bicarbonate, sodium and potassium in one kidney after exclusion (complete sudden ligation of renal pedicle) of its partner have been studied in 16 dogs undergoing bicarbonate diuresis. Fluid balance, haematocrit, plasma electrolyte and protein concentrations were maintained constant throughout the experiment. Acute contralateral renal pedicle ligation lead to an immediate increase in bicarbonate as well as water, sodium and potassium excretion by the remaining kidney. The rapid and immediate increase in the fractional and absolute rates of bicarbonate excretion was observed at varying levels of bicarbonate loading, with the greatest response occurring at the highest infusion rate. Sodium, potassium and water excretion also increased in parallel with urinary bicarbonate loss. The increase in bicarbonate exposition, glomerular filtration rate, effective renal plasma flow, aldosterone and vasopressin. In 8 sham-operated animals, no abrupt increase in sodium and bicarbonate excretion occurred despite similar continued infusion of sodium bicarbonate. It was concluded that exclusion of one kidney induces immediate adaptive excretory changes for sodium and bicarbonate in the remaining kidney, and that these changes are not accounted for by any of the known factors normally regulating sodium and bicarbonate excretion.     

Changes in the rhythms of urinary sodium, potassium and chlorine excretion in patients with circulatory failure

Measurements were made of the parameters (period, mesor, amplitude) of the rhythms of sodium, potassium and chlorine excretion with urine in patients with different stages of circulatory failure (CF). It has been shown that revelation of the status of neorhythmostasis is an early and sensitive criterion for estimating functions of electrolyte excretion by the kidneys in different CF stages. Dysrhythmostasis that increases depending on the stage of pathology attains maximum during stage IIB CF. In patients with stage IIB CF, there was an appreciable decrease of chlorine excretion mesor. This indicates that in solving the problem of deviation from normal, the parameters of the rhythm were not equally informative. The period turned out the most sensitive parameter of the rhythm. Determination of the time organization of functions and processes provides an undoubtedly more complete idea of the body on the whole.     

Compensatory Adaptation of Bicarbonate Excretion Following Acute Contralateral Kidney Exclusion in the Dog

Changes in the excretion of bicarbonate, sodium and potassium in one kidney after exclusion (complete sudden ligation of renal pedicle) of its partner have been studied in 16 dogs undergoing bicarbonate diuresis. Fluid balance, haematocrit, plasma electrolyte and protein concentrations were maintained constant throughout the experiment. Acute contralateral renal pedicle ligation lead to an immediate increase in bicarbonate as well as water, sodium and potassium excretion by the remaining kidney. The rapid and immediate increase in the fractional and absolute rates of bicarbonate excretion was observed at varying levels of bicarbonate loading, with the greatest response occurring at the highest infusion rate. Sodium, potassium and water excretion also increased in parallel with urinary bicarbonate loss. The increase in bicarbonate excretion was not accounted for by changes in extracellular fluid volume, plasma composition, glomerular filtration rate, effective renal plasma flow, aldosterone and vasopressin. In 8 sham-operated animals, no abrupt increase in sodium and bicarbonate excretion occurred despite similar continued infusion of sodium bicarbonate. It was concluded that exclusion of one kidney induces immediate adaptive excretory changes for sodium and bicarbonate in the remaining kidney, and that these changes are not accounted for by any of the known factors normally regulating sodium and bicarbonate excretion.     

Is apalcillin nephrotoxic?

Apalcillin is a new semisynthetic penicillin used as a sodium salt. More than 4,000 patients have been treated with this antibiotic, but increased serum creatinine levels were noted in 18 cases. In 5 of these cases, apalcillin was possibly responsible, and in 13 it was doubtful. We decided to study renal function of normal volunteers treated with 4 g of apalcillin. Three periods were studied: a pretreatment control period of 80 min followed by a treatment period of 60 min and a posttreatment period of 40 min. Inulin and p-aminohippurate (PAH) infusion were continued during all three periods. At the beginning of the treatment period, 2 g of apalcillin was injected as a bolus, followed by infusion of 2 g of apalcillin over 1 h. Urinary volume was measured every 20 min. Creatinine, insulin, and PAH clearances and urinary excretion of sodium, potassium, calcium, and magnesium were calculated for each period. Urinary beta-2-microglobulin excretion was also assessed. Analysis of variance was done. We observed no variation in clearances of creatinine or inulin or in urinary electrolyte output. PAH clearance was significantly decreased during apalcillin infusion. Apalcillin appeared to compete with PAH for proximal tubular secretion but induced no further renal dysfunction.     

Acute effects of high-dose furosemide on residual renal function in CAPD patients.

BACKGROUND: High doses of furosemide can increase urine volume in chronic peritoneal dialysis (CAPD) patients. However, no information is available about effects on urinary solute excretion in relation to residual glomerular filtration rate (GFR), urinary furosemide excretion, and peritoneal solute kinetics. METHODS: Diuretic response and the effect on peritoneal fluid and solute transport parameters were investigated in 7 stable CAPD patients with residual renal function (median urine volume 350 mL/24 hours, range 140- 1900 mL/24 hours). Comparisons were made during two clearance periods of 24 hours: one without (P1) and one during 2 g furosemide (P2). RESULTS: The median increase in urine volume was 400 mL (range 270 - 910 mL, p < 0.02) and the increase in sodium excretion was 54 mmol (range 25 - 118 mmol, p < 0.02). No change in GFR was found between P1 (2.4 mL/ minute, range 0.6 - 5.7 mL/min) and P2 (2.0 mL/min, range 1.0 - 4.8 mL/min). An increase in fractional clearance was found for volume, sodium, potassium, and osmolality (p < 0.02). No change was found in the fractional clearance of urea and electrolyte-free water. Furosemide excretion in urine was 8.7 mg/24 hours (range 2.1 - 38 mg/24 hours) and in dialysate 4.9 mg/24 hours (range 1.9 - 7.8 mg/ 24 hours). Plasma furosemide concentration was 29.5 mg/L (range 6.2 - 43.9 mg/L). A positive correlation was found between residual GFR and total urine furosemide excretion (r = 0.93, p < 0.005). Efficiency, expressed as the increase in fractional sodium clearance (percent) per milligram of furosemide excreted per 24 hours, was 1.2%/mg (range 0.3% - 11.3%/mg). CONCLUSION: High-dose furosemide is effective in CAPD patients in increasing urine volume and electrolyte excretion without affecting urea and creatinine clearance. In CAPD patients, the individual response to an identical high dose of furosemide is dependent on the magnitude of residual GFR.