Evidence for large intestinal control of potassium homoeostasis in uraemic patients undergoing long-term dialysis

1. The role of the large intestine in the maintenance of K+ balance in uraemic patients established on long-term dialysis was studied with a rectal dialysis technique in 14 normal subjects, ten normokalaemic patients undergoing chronic ambulatory peritoneal dialysis (CAPD), and seven patients undergoing haemodialysis. Dietary K+ intakes in the normal subjects, CAPD patients and haemodialysis patients were 80-100 mmol/24 h, 70-80 mmol/24 h and 60-70 mmol/24 h, respectively. 2. At an initial intraluminal K+ concentration of 45 mmol/l, rectal K+ secretion in the CAPD patients (2.4 +/- 0.4 mumol h-1 cm-2) was greater than in normal subjects (1.2 +/- 0.2 mumol h-1 cm-2, P less than 0.02). Under similar conditions, rectal K+ secretion was also greater in the haemodialysis patients than in normal subjects, both predialysis (3.7 +/- 0.4 mumol h-1 cm-2, P less than 0.001) and postdialysis (2.4 +/- 0.5 mumol h-1 cm-2, P less than 0.05), even though haemodialysis decreased plasma K+ concentration from 5.3 +/- 0.1 mmol/l to 3.5 +/- 0.2 mmol/l (P less than 0.001). 3. There were no significant differences in rectal Na+ absorption, rectal potential difference, plasma aldosterone concentration, or total body K+ content (measured by whole-body counting of 40K), between the normal subjects and either the CAPD or the haemodialysis patients. 4. These results indicate that K+ homoeostasis is maintained in uraemic patients undergoing long-term dialysis by a combination of K+ losses during dialysis, and enhanced large intestinal K+ excretion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanisms of leucocyte sodium influx in essential hypertension

1. Leucocyte Na+ influx in media containing 10 mmol/l Na+ was studied directly using a triple-isotope method for measuring initial 22Na uptake rates in 20 normal and 18 untreated hypertensive subjects. The effects of 1 mmol/l amiloride (a Na+-H+-antiport inhibitor) and 0.1 mmol/l bumetanide (a Na+,K+,Cl-symport inhibitor) were also examined. 2. The total, amiloride-sensitive and bumetanide-sensitive influx rates were raised in hypertensive compared with normotensive subjects [median (range): total 0.63 (0.25-1.82) vs 0.40 (0.09-0.65) mmol min-1 l-1, P less than 0.002; amiloride-sensitive 0.43 (0.18-1.56) vs 0.26 (0.04-0.48) mmol min-1 l-1, P less than 0.002; bumetanide-sensitive 0.12 (-0.03 to 0.83) vs 0.02 (-0.25 to 0.21) mmol min-1 l-1, P less than 0.005]. 3. We conclude that hypertensive patients have a raised leucocyte total Na+ influx when measured in media containing 10 mmol/l Na+ and that this is contributed mainly by amiloride-sensitive and bumetanide-sensitive Na+ influx mechanisms.     

Mechanism of alteration of sodium potassium pump of erythrocytes from patients with chronic renal failure.

We examined intracellular electrolytes, K influx, and [3H]ouabain-binding capacity of erythrocytes from 32 normal subjects and 45 patients with end-stage renal failure on dialysis, including 16 with high intracellular Na (mean 17.3 +/- 3.9 mmol/liter cell water). The [3H]ouabain-binding capacity of erythrocytes with high cell Na was markedly reduced as compared with that of erythrocytes from normal subjects (274 +/- 52 vs. 455 +/- 59 sites/cell, P less than 0.001). The mean serum creatinine was higher in the uremic group with high cell Na. There was a significant linear correlation between intracellular Na and [3H]ouabain-binding in both normal and uremic subjects. Cross-incubation of normal cells with uremic plasma for 24 h failed to reduce [3H]ouabain-binding capacity of normal cells. In spite of a substantial increase in cell Na, K pump influx was not higher in uremic erythrocytes with high cell Na. When intracellular Na was altered with nystatin (cell Na equal to 120 mmol/liter cell water in both groups), K pump influx was proportional to the number of Na-K pump sites so that the ion turnover rate per pump site was similar in the two groups. Uremic plasma failed to depress K pump influx of normal erythrocytes. The passive net influx of Na in uremic cells with high intracellular Na was not different from that observed in erythrocytes from normal subjects. When erythrocytes were separated by age on Percoll density gradients, the number of Na-K pump sites of the youngest uremic cells was significantly lower than that of the youngest normal cells, suggesting that decreased synthesis of Na-K pump sites, rather than accelerated loss of Na-K pump sites during aging, was responsible for the decrease in [3H]ouabain-binding capacity of erythrocytes from uremic subjects. Taken together, these findings suggest that a decrease in the number of Na-K pump sites plays a major role in the abnormality of Na-K pump of erythrocytes from patients with chronic renal failure.     

Methylene blue dye spraying method in patients with ulcerative proctitis: a comparative study with morphological findings and functional capacity of the rectal epithelium.

Methylene Blue dye spraying method is currently used in the endoscopic assessment of the colonic mucosa of patients with chronic ulcerative proctocolitis. We have assessed the validity of this method in the evaluation of the functional capacity of the rectal mucosa in 17 patients with ulcerative proctitis and in 5 normal subjects. The ionic transmucosal fluxes of Na+ and K+ and the potential difference were used as parameters of the mucosal function. Our results indicate that methylene blue dye spraying method can be useful in the functional assessment of the rectal epithelium, especially for differentiating normal subjects and patients with mild ulcerative proctitis.     

Amelioration of metabolic acidosis by dietary potassium restriction in hyperkalemic patients with chronic renal insufficiency

Hyperkalemia has been implicated in the pathogenesis of metabolic acidosis in chronic renal insufficiency because acidosis is ameliorated after administration of medications that correct hyperkalemia: mineralocorticoids, diuretics, intestinal K+-binding agents. However, the acidosis-ameliorating effect of these medications may be a consequence not of their ability to correct hyperkalemia, but of their ability to directly stimulate renal or intestinal excretion of acid. To investigate the specific effect of correcting hyperkalemia, balance studies were performed wherein hyperkalemia was corrected solely by restriction of dietary K+ in three patients with moderate chronic renal insufficiency (Ccreat 36, 44, and 58 ml/min/1.73 m2, respectively). Reduction of K+ intake was effected by substitution of Na+ for K+ in the electrolyte supplement to a whole-food diet of low K+ content. This maneuver resulted in correction of hyperkalemia and sustained amelioration of metabolic acidosis in each patient. Net acid excretion increased only transiently, and not enough to fully account for the magnitude of the increment in plasma [HCO3-], suggesting that an extrarenal mechanism of HCO3- input to the systemic circulation was the major factor that ameliorated the systemic acidosis. Evidence of an extrarenal mechanism was obtained only during the phase of decreasing plasma [K+]. Subsequently, during sustained normokalemia, the increased plasma [HCO3-] was maintained as a consequence of a sustained increase in total renal H+ secretion, evidenced by complete reabsorption of the increased filtered load of HCO3- and no reduction in net acid excretion from control values. These results indicate that in some patients with moderate chronic renal insufficiency, metabolic acidosis is ameliorated when hyperkalemia is corrected by restriction of dietary K+ (Na+ substitution) without otherwise changing diet composition and without administration of medication. Amelioration of the acidosis is predominantly effected by extrarenal mechanisms, and is sustained by an increase in the set point at which plasma [HCO3-] is regulated by the kidney.     

Factors affecting potassium balance during frusemide administration

We investigated the effects of Na+ intake, the renin-angiotensin-aldosterone system and anti-diuretic hormone (ADH) on K+ balance during 3 days of frusemide administration to six normal subjects. Subjects received 40 mg of frusemide for 3 days during three different protocols: Na+ intake 270 mmol/day (high salt); Na+ intake 20 mmol/day to stimulate the renin-angiotensin-aldosterone system (low salt); Na+ intake 270 mmol/day plus captopril (25 mg/6 h) to prevent activation of the renin-angiotensin-aldosterone system. In a fourth protocol, a water load was given during high salt intake to prevent ADH release and then frusemide was given. During high salt intake, frusemide increased K+ excretion (UKV) over 3 h, but the loss was counterbalanced by subsequent renal K+ retention so that daily K+ balance was neutral. During low salt intake, the magnitude of the acute kaliuresis following the first dose of frusemide and the slope of the linear relationship between UKV and the log of frusemide excretion were increased compared with that found during the high salt intake. In addition, low salt intake abolished the compensatory renal retention of K+ after frusemide and cumulative K+ balance over 3 days of diuretic administration was uniformly negative (-86 +/- 7 mmol/3 days; P less than 0.001). Captopril abolished the rise in plasma aldosterone concentration induced by frusemide. The acute kaliuresis after frusemide was unchanged compared with that observed during high salt intake. The compensatory reduction in UKV occurring after the diuretic was slightly potentiated. In fact, captopril given without the diuretic induced a small positive K+ balance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Investigations on the Na+, K+-pump in erythrocytes of patients with renal hypertension

The ouabain-sensitive 42K+ flux from an artificial medium into erythrocytes was measured in 29 control subjects, 66 patients with chronic parenchymatous renal disease and in 32 subjects with primary hypertension. The ouabain-sensitive 42K+ influx was reduced in subjects with chronic renal disease by about 20%, even when they were normotensive. The reduction in these patients was greater than that in patients with essential hypertension. The changes in 42K+ influx and Na+ content with a decrease in the 42K+ influx/Na+ content ratio suggest an inhibition of the Na+ pump in the patients with chronic renal disease. The inhibition of the Na+ pump may be secondary to the hypervolaemia which we suggest is the initial event leading to renal hypertension.     

Are sodium bicarbonate and potassium bicarbonate fully dissociated under physiological conditions?

In solutions containing 160 mmol/l Na+ and K+, respectively, measurements with an ion-selective electrode system (KNA1, Radiometer), showed apparent falls in the respective Na+ and K+ concentrations when C1- was replaced by HCO3-. After correction for the change in liquid junction potential, the fall was 9.2 mmol/l for Na+ and 7.3 mmol/l for K+. On the basis of these findings we conclude that sodium bicarbonate and potassium bicarbonate are not fully dissociated in solution, and that NaHCO3(0) and KHCO3(0) do exist as chemical components with association constants of 0.72 and 0.55, respectively. Using these association constants, normal plasma will contain 1.2 mmol/l NaHCO3(0) and 0.03 mmol/l KHCO3(0). Thus NaHCO3(0) accounts for virtually the same amount of CO2 as the physically dissolved fraction. A review of all the currently known CO2 species in plasma suggests that there may be a residue of about 2 mmol/l of unknown CO2 species in normal plasma.     

Influence of angiotensin converting enzyme inhibitor (captopril) on kidney epithelial cells in vitro: studies on potassium (86Rb) influx and cellular proliferation

The effects of captopril on potassium influx and cellular proliferation in a dog kidney epithelial cell line (Madin-Darby canine kidney cells, MDCK) were studied. Na+K(+)-ATPase activity and the loop diuretic sensitive Na/K/2Cl- cotransport were measured using 86Rb as tracer substance. Cells were incubated with various concentrations of captopril (1-10 mmol/l). The furosemide sensitive Na/K/2Cl- cotransport was significantly decreased from 1 mmol/l onwards. Na+/K(+)-ATPase activity was lowered only when high amounts (10 mmol/l) of the drug were used. Cell proliferation was measured via [3H]thymidine incorporation. After incubation with 1 mmol/l captopril proliferation was strongly decreased (greater than 50%). Higher amounts (5-10 mmol/l) did not further suppress cell proliferation. The data suggest that natriuresis following ACE inhibition in vivo does not involve a direct effect of captopril on Na+K(+)-ATPase. However, the effect on cell proliferation may be of clinical relevance in respect to a possible mitogenic effect of angiotensin II.     

Abnormal Na+K+ cotransport function in a group of patients with essential hypertension

In 50 normotensive controls, the increase in erythrocyte Na+ concentration up to 12.4 +/- 2.0 mmol/l cells (mean +/- SD) ensures half-maximal stimulation of outward Na+,K+ cotransport fluxes. Forty-six out of sixty-five patients with essential hypertension required more than 16 mmol/l cells of internal Na+ concentration to obtain a similar effect, strongly suggesting an abnormal cotransport function. Seven out of fourteen hypertensive patients with normal Na,K cotransport function showed Na+,Li+ countertransport fluxes higher than the normal upper limit of 220 mumol (1 cells h)-1. Conversely, countertransport fluxes were normal in fourteen hypertensives with abnormal cotransport function. The above results indicate that the total population of patients with essential hypertension is heterogeneous and includes one subgroup of subjects with abnormal Na+,K+ cotransport function, and another with increased Na+,Li+ countertransport fluxes.     

Clinical application of sodium-23 nuclear magnetic resonance for measurement of red cell sodium concentrations

Red cell sodium (RBC-Na+) concentrations were measured using 23Na nuclear magnetic resonance (NMR), without the destruction of erythrocyte membranes. Subjects were categorized into four groups: 20 normotensive subjects (NT group), 20 age-matched essential hypertensive patients (EHT group), 10 patients with primary aldosteronism (PA group), and 18 patients treated with digoxin (DIG group). Although RBC-Na+ concentrations were similar between the NT group (6.14 +/- 0.80 (Mean +/- SD) mmol/l) and the EHT group (5.92 +/- 0.99), they were significantly higher in both the PA group (7.55 +/- 0.88, p less than 0.001) and the DIG group (8.43 +/- 3.81, p less than 0.02). In the PA group, RBC-Na+ concentrations decreased significantly after resection of the adenoma, and there was an inverse relationship between serum potassium and RBC-Na+ concentrations (r = -0.65, p less than 0.01). In the DIG group, RBC-Na+ concentrations tended to increase in proportion to serum digoxin levels (r = 0.53, p less than 0.05). These results support the view that RBC-Na+ concentrations are determined primarily by Na+/K+-pump activity of red cell membranes. This study showed also that Na+ NMR is an useful method determining intracellular Na+ concentrations.     

On the mechanism of growth hormone-induced stimulation of renal acidification in humans: effect of dietary NaCl

Sustained administration of growth hormone (GH) to human subjects with NH(4)Cl-induced chronic metabolic acidosis (CMA) results in a large (4.5+/-0.5 mmol/l) increase in the plasma HCO(3-) concentration, as mediated by a large increase in renal net acid excretion. The renal mechanism(s) responsible for the potent stimulation of renal hydrogen ion secretion by GH remain to be elucidated. Accordingly, we have assessed the Na(+) dependence of prolonged GH-stimulated renal acidification in four normal NaCl-restricted subjects (Na(+) intake 0.3 mmol x kg(-1) x day(-1)) during CMA (4.2 mmol of NH(4)Cl x kg(-1) x day(-1) for 7 days), CMA plus GH (0.1 unit/kg every 12 h for 5 days) and then CMA plus GH plus NaCl (1.7 mmol x kg(-1) x day(-1) for 6 days). During CMA, urine Na(+) excretion averaged 22.4+/-4.1 mmol/24 h. In response to GH administration, urinary net acid excretion was essentially unchanged, and the accumulated increment over 5 days of GH treatment was not different from zero (14+/-12 mmol; not significant). The plasma HCO(3)(-) concentration increased only slightly, from 14.2+/-0.8 to 15.0+/-1.1 mmol/l (P<0.05). Despite the constraint on net acid excretion imposed by NaCl restriction, renal ammonia production increased, as suggested by increases in urine pH from 5.58+/-0.05 to 5.82+/-0.04 (P<0.005) and unchanged NH(4)(+) excretion (202+/-17 to 211+/-19 mmol/24 h; not significant). In response to dietary NaCl, urine pH decreased to 5.27+/-0.1 (P<0.001) and a large increment in net acid excretion accumulated (233+/-20 mmol; P<0.05), in association with an increase in plasma HCO(3-) to 18.7+/-1.3 mmol/l (P<0.001), a plasma HCO(3-) value similar to that reported previously in salt-replete, NH(4)Cl- fed subjects. These results demonstrate for the first time in any species that the acid excretory effect of GH administration is critically dependent on the availability of a surfeit of Na(+) for tubular reabsorption. GH and/or insulin-like growth factor-1 affect renal acid excretion proximally (by stimulation of NH(3) production) and by a Na(+)-transport-dependent mechanism in the collecting duct (voltage-driven acidification) in humans. The present results indicate that an isolated increase in renal NH(3) production is insufficient to obligate an increase in net acid excretion.     

Oestradiol-induced hypotension in spontaneously hypertensive rats: putative role for intracellular cations, sodium-potassium flux and prostanoids.

1. The effect of oestradiol alone and in combination with indomethacin on blood pressure, erythrocyte cation concentration and Na(+)-K+ flux has been studied in adult female normotensive and spontaneously hypertensive rats. 2. Oestradiol alone resulted in a significant decrease in blood pressure in spontaneously hypertensive rats (from 165.3 +/- 3.9 to 146.4 +/- 2.7 mmHg, P less than 0.001), whereas it induced a significant increase in normotensive rats (from 111.8 +/- 1.8 to 124.1 +/- 3.6 mmHg, P less than 0.001). When indomethacin and oestradiol were administered simultaneously or when indomethacin was given alone, no change in blood pressure occurred in spontaneously hypertensive rats (158.6 +/- 6.9 and 159.8 +/- 6.2 mmHg, respectively). 3. The fall in blood pressure induced by oestradiol in spontaneously hypertensive rats was associated with significant reductions in erythrocyte K+ concentration (from 127.4 +/- 1.2 to 116.9 +/- 1.7 mmol/l of cells, P less than 0.001), in erythrocyte Na+ concentration (from 14.3 +/- 0.8 to 13.0 +/- 0.6 mmol/l of cells, P less than 0.02), in ouabain-sensitive erythrocyte Na+ flux (from 17.8 +/- 0.3 to 16.0 +/- 0.4 mmol h-1 (l of cells)-1, P less than 0.01) and in ouabain-sensitive erythrocyte K+ flux (from 11.4 +/- 0.2 to 10.4 +/- 0.2 mmol h-1 (l of cells)-1, P less than 0.01). No change in blood pressure, erythrocyte cation concentration or Na(+)-K+ flux occurred when oestradiol and indomethacin were given together or when indomethacin was administered alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reliability of the Hitachi sodium and potassium electrodes assessed

We compared the Hitachi 705 E sodium/potassium electrode system with the Radiometer flame photometer for measuring concentrations of sodium and potassium ions in serum and plasma. Our data show that the Hitachi results are slightly but significantly (less than 0.001) lower than the flame photometer results: Na+ 1.33 mmol/L for serum and 2.24 mmol/L for plasma; K+ 0.062 mmol/L for serum and 0.082 mmol/L for plasma. The magnitude of the bias varied considerably from day to day, ranging from -0.10 to 2.33 mmol/L for Na+ in serum and from 0.00 to 0.11 mmol/L for serum K+; for plasma specimens the corresponding ranges were -0.03 to 5.97 mmol/L and 0.00 to 0.17 mmol/L. These variations probably reflected difficulties in reproducing the calibration from day to day, because the daily means for a serum pool varied in parallel. We occasionally encountered serious problems with reproducibility.     

Effect of high salt intake on sodium, potassium-dependent adenosine triphosphatase activity in the erythrocytes of normotensive men

1. We measured ouabain-insensitive adenosine triphosphatase (ATPase), sodium, potassium-dependent adenosine triphosphatase (Na+,K+-ATPase) and intracellular Na+ and K+ in the erythrocytes of 19 healthy volunteers, before and after supplementation of their normal diet was 6.0-8.9 g of salt (102-137 mmol of NaCl) per day, for 5 days. 2. The subjects had a small but significant gain in weight. Mean plasma renin activity decreased from 1.57 to 0.73 pmol of angiotensin 1 h-1 ml-1 and plasma aldosterone from 0.46 to 0.24 nmol/l. 3. Total ATPase activity fell from 197.9 nmol of inorganic phosphate h-1 mg-1 during the control period to 173.5 during the high-salt period (P less than 0.0125). Na+, K+-ATPase activity fell from 162.2 to 141.4 nmol of inorganic phosphate h-1 mg-1 (P less than 0.05). Intracellular Na+ and intracellular K+ did not change. 4. These results are consistent with the hypothesis that salt-induced volume expansion causes the release of a factor inhibitory to the Na+ pump.     

Intracellular chloride in essential hypertension

In 25 patients with untreated essential hypertension and 25 healthy controls, erythrocyte intracellular Cl- concentration and activity as well as Na+ activity were measured. Intracellular Cl- concentration in essential hypertensive patients was 70.6 +/- 11.3 as compared with 84.4 +/- 9.5 mmol/l in the controls (P less than 0.001). Intracellular Cl- activity was 77.5 +/- 13.0 mmol/l of cell water in hypertensive patients, the control value being 100.8 +/- 11.0 mmol/l of cell water (P less than 0.001). In the hypertensive group intracellular Na+ activity was 14.3 +/- 4.1 as compared with 7.1 +/- 1.8 mmol/l of cell water in the normotensive group (P less than 0.01). From these results it is suggested that in essential hypertension not only disturbances of cation metabolism, but also of anion metabolism, occur. Possibly the Cl- changes reflect a decreased Cl- inward transport due to an altered Na-K cotransport.     

Production of methylguanidine in dogs with acute and chronic renal failure

1. Methylguanidine is a suspected uraemic toxin that accumulates in renal failure. 2. We measured methylguanidine in the plasma of dogs with acute ischaemic-induced renal failure and in the plasma and urine of dogs with spontaneous chronic renal insufficiency, using a highly sensitive method involving solid-phase extraction followed by h.p.l.c. with post-column fluorescence detection. 3. Constriction of the remaining renal artery of four uninephrectomized dogs for 90 min resulted in a significant (P less than 0.01) increase in plasma creatinine concentration after 24 h (from 113 +/- 3 to 303 +/- 50 mumol/l; mean +/- SEM). Over the next 14 days, plasma creatinine fell towards baseline concentrations. Plasma methylguanidine also increased significantly (P less than 0.05) 24 h after renal occlusion (from 0.16 +/- 0.04 to 0.86 +/- 0.32 mumol/l) and showed a similar pattern to the plasma creatinine concentration. 4. In a further four dogs, administration of mannitol (2 g/kg) at the time of reperfusion significantly attenuated these responses. 5. Dogs with chronic renal failure demonstrated increased plasma concentrations and urinary excretion of methylguanidine, and the levels appeared to be related to the severity of renal insufficiency. Thus, the dogs with the highest plasma creatinine concentrations and lowest creatinine clearances had the highest plasma methylguanidine concentrations. The clearance of methylguanidine exceeded that of creatinine, indicating that the toxin undergoes renal tubular secretion.     

Effect of potassium depletion on renal tubular function in the rat

1. In order to investigate the effects of K+ depletion on renal function, micropuncture studies were performed on anaesthetized rats which had been kept on a K+-deficient diet for 2 weeks; results were compared with those from control animals. 2. In the K+-depleted animals, values for total glomerular filtration rate and single-nephron filtration rate were significantly lower than in controls. Urine osmolality was also reduced; this was associated with reductions in the osmolality, Na+ concentration and K+ concentration of papillary interstitial fluid. No significant difference between urine and papillary osmolality was observed. 3. Fractional reabsorption by the proximal convoluted tubule was enhanced in the K+-depleted animals; end-proximal fluid delivery was markedly reduced. 4. Absolute, but not fractional, delivery of K+ to the beginning of the distal tubule was reduced in the K+-depleted animals. In contrast to observations in control rats, no net secretion of K+ into the distal tubule occurred and there was indirect evidence of K+ reabsorption in the collecting duct. 5. K+ depletion was associated with reductions in the delivery of Na+ and water to early and late regions of the distal tubule, whereas excretion rates of Na+ and water were unaffected. 6. It is suggested that the reduction in Na+ delivery to the loop of Henle (arising from the changes in filtration rate and proximal tubular reabsorption) might contribute to the reduced medullary osmotic concentration observed during K+ depletion. Reductions in fractional reabsorption of Na+ and water in the collecting duct might result from lowered plasma aldosterone levels and the reduced medullary osmolality.     

Hepatic metabolism of aminopyrine in patients with chronic renal failure

1. To evaluate potential alterations in hepatic metabolism of drugs occurring in patients with renal insufficiency the fate of aminopyrine was studied in 17 patients with chronic renal failure and in 27 normal subjects. 2. Although patients with chronic renal failure exhibited large variations, their aminopyrine plasma disappearance times (mean 0.62 +/- SD 0.24 h-1) were significantly higher than those found in normal subjects (0.30 +/- 0.07 h-1, P less than 0.002). 3. 14CO2 derived from [dimethylamine-14C]aminopyrine disappeared from breath more rapidly in patients with chronic renal failure and a history of analgesic abuse (0.40 +/- 0.04 h-1) than in control subjects (0.22 +/- 0.03 h-1, P less than 0.01) and in other patients with chronic renal failure (0.24 +/- 0.04 h-1). 4. Dialysis treatment and serum creatinine concentrations were not correlated with the rates of aminopyrine metabolism. Two additional patients, however, with combined renal and hepatic disease, exhibited markedly slowed rates of aminopyrine demethylation. 5. Although chronic renal failure by itself might not alter microsomal drug metabolism it is concluded that, in patients with a history of abuse of phenacetin-containing analgesics, marked acceleration in aminopyrine N-demethylation may be observed.     

Possible mechanisms of polyuria in progressive chronic renal failure

AIM: Elucidation of the role of saluresis and osmotic diuresis in renal function of patients with chronic renal failure. MATERIAL AND METHODS: The trial included 68 subjects, among them 25 patients with chronic renal failure (CRF) of the third and fourth degree aged 16 to 72 years. Enzyme immunoassay was used to measure osmolality, sodium, potassium, magnesium, calcium and creatinine concentrations in the serum and urine as well as urine prostaglandin E2. RESULTS: Renal function was studied in CRF patients with a 75-90% fall of glomerular filtration rate. Creatinine clearance was 19.9 +/- 0.96, it varied in different patients from 10.6 to 29.7 ml/min. It is shown that diuresis does not correlate with the total ion excretion (Na+ plus K+)(r = 0.946, p < 0.0001). A correlation was found between excretion of these ions and Mg2+ ions this indicating location of reabsorption reduction in the thick ascending limb of Henle loop. In CRF patients (Na+ plus K+) excretion correlated with PGE2 excretion (r = 0.65, p < 0.0001). CONCLUSION: It is suggested that at this stage of chronic renal failure the mechanism of a diuresis increase is not due to osmotic diuresis but rather to secretion of prostaglandin E2 which inhibits cation reabsorption and stimulates diuresis. Differences are considered between osmotic diuresis and different types of saluresis; their possible mechanisms are discussed.