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Biomedical subjects

K Lau

Publications and source records attributed to K Lau.

At least 91 records · Page 5Linked to original sources
PubMed1986

Low fractional excretion of sodium in acute renal failure: role of timing of the test and ischemia.

To evaluate the mechanisms for a low fractional excretion of Na (FENa less than or equal to 1.0) in acute renal failure (ARF) of a sustained nature, causes were determined independent of FENa in 41 patients without volume depletion, obstruction, vasculitis or glomerulonephritis. The 16 patients (39%) with low FENa had lower incidence of preexisting azotemia, lower peak serum creatinine, but higher incidence of renal ischemia and earlier testing (by 1.7 days). Seven of ten such patients converted to high FENa on repeat, whereas FENa remained high in 15 of 17 patients with initially high values. The initial FENa was a direct function of time from the onset of ARF. Low FENa in acute but sustained renal failure is therefore best explained by milder insults; earlier determinations, and/or super-imposed renal ischemia.

Acute Kidney Injury↗
PubMed1986

Evidence against the role of calcium deficiency in genetic hypertension.

Epidemiological studies suggest an association between reduced calcium uptake and hypertension, while clinical trials and rat experiments indicate a small but significant hypotensive effect with oral calcium supplements. These data imply that calcium deficiency has a role in genetic hypertension. We reasoned that if the hypothesis is correct, the hypertension should be aggravated by further reducing calcium balance but attenuated by augmenting calcium balance. We tested this hypothesis by evaluating the blood pressure response in spontaneously hypertensive rats (SHR) as calcium balance was decreased by dietary restriction of calcium or increased by supplementation with magnesium or 1 alpha, 25-dihydroxycholecalciferol (calcitriol). A low calcium diet within the physiological range did not accentuate the hypertension in SHR during the 11 weeks of treatment, even though calcium balance was reduced by half. Similar results were obtained with dietary calcium restriction in parathyroidectomized SHR, which excludes any offsetting effects of changes in parathyroid hormone levels. Conversely, 7 weeks of a high magnesium diet, which increased calcium balance without reducing PO4 balance, did not correct the hypertension of SHR. Similarly, long-term administration of calcitriol failed to reduce the blood pressure of parathyroidectomized SHR and normotensive Wistar-Kyoto (WKY) controls, despite the presence of increased serum calcium levels comparable to those produced by oral calcium loading. Finally, external calcium balance was measured directly in 25-day-old, prehypertensive SHR. As a result of the increased calcium absorption and reduced calcium excretion, SHR retained more calcium than did the normotensive WKY, which directly refutes the existence of calcium deficiency at this normotensive stage. These data do not support the role of calcium deficiency in genetic hypertension.

Animals↗
PubMed1986

Increased calcium absorption in prehypertensive spontaneously hypertensive rat. Role of serum 1,25-dihydroxyvitamin D3 levels and intestinal brush border membrane fluidity.

Changes in Ca absorption have been described in the spontaneously hypertensive rat (SHR) compared with Wistar-Kyoto (WKy) rats. In 3.5-wk-old SHR and age-matched WKy controls, we measured direct arterial blood pressure, Ca absorption, and serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels and small intestine brush border membrane (BBM) fluidity and lipid composition. The two objectives were (a) to define the nature of the absorptive changes before detectable hypertension and (b) to evaluate the potential mechanism(s). We found that even at this normotensive stage (106 +/- 4 vs. 107 +/- 2 torr for the female and 109 +/- 3 vs. 104 +/- 3 torr for the male), the SHR (a) absorbed more Ca (1.46 +/- 0.06 vs. 1.14 +/- 0.08 mmol/d and 1.53 +/- 0.06 vs. 1.28 +/- 0.06 mmol/d, respectively) and retained more Ca, (b) had higher serum 1,25(OH)2D3 levels (340 +/- 36 vs. 160 +/- 18 pg/ml and 230 +/- 25 vs. 150 +/- 16 pg/ml, respectively), and (c) possessed BBM with increased fluidity and with reduced fatty acyl saturation index owing to decreased stearic (32.2 +/- 2.6% vs. 38.2 +/- 0.9%) but increased linoleic acids (12.2 +/- 2.0% vs. 7.6 +/- 1.6%). These results demonstrate increased Ca absorption in prehypertensive SHR associated with increased serum 1,25(OH)2D3 levels, increased intestinal BBM fluidity, and reduced saturation index, which singly or in combination could produce the changes in intestinal Ca transport.

Absorption↗
PubMed1986

Effects of high-calcium and/or high-sodium diet on basal and angiotensin II-stimulated blood pressure in the spontaneously hypertensive rat.

Direct conscious blood pressure (BP) was measured via indwelling femoral cannula to evaluate the effects of chronic diet supplements with Na, Ca or both, offered to 3-week-old weanling spontaneously hypertensive rats (SHR). Despite similar food intakes, body weights were reduced within 1-2 weeks on high-Ca diets. Blood pressure was unchanged by 5.5 weeks of diet treatments. However, irrespective of concomitant Na supplement, more prolonged treatment with the high-Ca diet completely abolished the further increase in BP between the 9th and 12th weeks of age, which was noted in the rats fed the normal or high-Na diets. Angiotensin-stimulated BP was attenuated by high-Ca diets regardless of diet Na, similar to basal readings. These weight and pressure effects of Ca were not reproduced by high-Na diet alone. For all four groups, BP was directly and significantly correlated with body weight, both at 9 and 12 weeks of age. These studies demonstrate the potential role of growth retardation in the antihypertensive action of oral Ca loading in young rats.

Angiotensin II↗
PubMed1986

Nature and metabolic consequence of hypophosphaturia in spontaneously hypertensive rats.

Previous studies suggest abnormalities in PO4 and perhaps vitamin D metabolism in the spontaneously hypertensive rat (SHR) compared with normotensive Wistar-Kyoto (WKY) control rats. The mechanism for the hypophosphaturia obscure, but intestinal malabsorption of P and/or the possibility of linkage to renal Na avidity has not been evaluated. Furthermore, if sustained, the potential effects of the hypophosphaturia on P balance are not known. The present investigation examined these issues. We found that the reduced P excretion occurs as early as age 22 days, the second day after weaning in the SHR, well before the onset of detectable hypertension. This phenomenon is dissociable from renal Na avidity, and sustained through the 12th week of age, the last week of our studies. Since P absorption is normal, external P balance is increased relative to the WKY control rats. The greater cumulative P retention from infancy to adulthood may explain the age-dependent fall in serum 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] reported in the SHR by some investigators.

Aging↗
PubMed1986

The nature and role of disturbances in calcium metabolism in genetic hypertension.

Abnormalities in Ca metabolism in genetic hypertension have been suggested by studies of the spontaneously hypertensive rat and of humans with essential hypertension. A state of relative Ca deficiency in genetic hypertension was previously hypothesized to explain the reduced serum ionized Ca, increased serum parathyroid hormone levels, and the association between oral Ca loading and mild reduction in blood pressure. Renal Ca leak, reduced intestinal Ca absorption, and diminished Ca intake were further postulated to account for the Ca deficient state. This hypothesis, however, is not supported by the following lines of evidence in genetic hypertension: the absence of fasting hypercalciuria owing to intrinsic tubular defects, increased net Ca absorption in vivo despite greater Ca retention before and during established hypertension, increased intracellular free Ca concentrations, the failure to aggravate the hypertension by 50% reduction in dietary Ca intake, and the failure to ameliorate the hypertension by maneuvers that augment Ca balance (parenteral Ca administration, a high Mg diet, and 1,25-dihydroxyvitamin D3 injections). The available literature may be explained by the alternative hypothesis that genetic hypertension is characterized by generalized membrane defects in Ca regulation, resulting in a relative increase in cytosolic free Ca. The mechanism (or mechanisms) and physiological consequences of the disturbances in Ca homeostasis, however, remain to be defined.

Animals↗
PubMed1985

Renal handling of aluminum in the rat: clearance and micropuncture studies.

Previous uncertainty regarding glomerular ultrafilterability (UF) of aluminum has limited the definition of renal Al handling. Glomerular micropuncture was therefore performed in hydropenic Munich-Wistar rats infused with AlCl3 to achieve plasma (P) Al levels between 2 and 10 mg/liter. Glomerular fluid, P, and urine Al concentrations were measured by flameless atomic-absorption spectrophotometry. UFA1 was inversely correlated with PA1 [%UFA1 = 10.3 - 8.4 (log PA1), r = -0.90, P less than 0.01]. When this equation was used to calculate the filtered load (FLA1), A1 excretion (UA1V, ng/min) in simultaneously collected samples was found to be a direct function of FLA1 [UA1V = 5.7 + 0.37 (FLA1), r = 0.93, P less than 0.01]. Fractional excretion (FE) of A1 was 39.4 +/- 4.2% in these hydropenic experiments (FENa = 0.3 +/- 0.1%). We next evaluated the tubular handling of A1 (using these UF data) during step-wise extracellular fluid volume expansion with isotonic saline (2.5, 5.0, 7.0, and 7.0% body wt) and during the infusion of increasing doses (2.7, 5.3, 8.0, and 8.0 mg X kg-1 X h-1) of furosemide as urinary losses were quantitatively replaced. The natriuresis produced by volume expansion (FENa = 1.0, 3.0, 8.4, and 7.9%) and furosemide (FENa = 4.2, 6.0, 6.6, and 6.7%) were comparable. At similar FLA1, 7% volume expansion but not furosemide (at any dose) increased UA1V (240 and 95 ng/min, respectively, vs. 116 ng/min in hydropenia) and FEA1 (84.5 and 29.4 vs. 37.4%, respectively). These data indicate that at pharmacological PA1 levels, less than 8.4% of PA1 is ultrafilterable, suggesting extensive plasma protein binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1985

Pathophysiology of spontaneous hypercalciuria in laboratory rats. Role of deranged vitamin D metabolism.

Recent data suggest a causal role of deranged 1,25(OH)2D metabolism in the syndrome of idiopathic hypercalciuria. To test this hypothesis, we evaluated if vitamin D availability and/or increased serum 1,25(OH)2D were critical for the expression of hypercalciuria in laboratory rats. Ca balance, serum 25OHD3, and 1,25(OH)2D3 were studied in D-deprived (-D) and D-repleted (+D) male progeny (p) born to normocalciuric (NC) and spontaneously hypercalciuric (SH) rats. 7 of the 14 pSH and 2 of 21 pNC had SH, which was defined as urinary Ca greater than two standard deviations above the mean of values for control animals on days 5 and 6 of a low Ca +D diet (1.19 vs. 0.58 mg/d, P less than 0.001). Fasting serum Ca and 25OHD3 were similar to control. Serum 1,25(OH)2D3 was elevated in these nine SH rats (232 vs. 145 pg/ml, P less than 0.005). However, during vitamin D deprivation, their Ca excretion was also increased (1.53 vs. 0.45 mg/d, P less than 0.001), despite comparably reduced serum 1,25(OH)2D3 (102 vs. 106 pg/ml) and undetectable serum 25OHD3. Net intestinal Ca absorption on a low Ca diet was comparable during D repletion (-0.75 vs. -0.82 mg/d) or D deprivation (-0.80 vs. -2.15 mg/d), excluding primary hyperabsorption as the mediator of the hypercalciuria. Mild hypophosphatemia was present in SH on +D (5.8 vs. 6.9 mg/dl, P less than 0.005) and -D diets (6.2 vs. 7.9 mg/dl, P less than 0.005), and was associated with higher rates of cyclic adenosine monophosphate excretion (32.8 vs. 26.9 and 48.5 vs. 41.0 nmol/mg of creatinine, respectively). Spontaneous hypercalciuria is therefore dissociable from increased Ca absorption, serum levels of 25OHD3, or 1,25(OH)2D3. The data are most compatible with the hypothesis of a renal Ca leak which stimulates parathyroid hormone activity and increases serum 1,25(OH)2D3, if provided adequate 25OHD3 as substrate.

Animals↗
PubMed1984

Evidence for an intestinal mechanism in hypercalciuria of spontaneously hypertensive rats.

To define the mechanism for the hypercalciuria in spontaneously hypertensive rats (SHR), Ca clearance was evaluated in fasted 23-wk-old SHR and normotensive Wistar Kyoto (WKy) controls. There was no exaggerated calciuria before or after parathyroidectomy. Ca balance was therefore measured in the nonfasted animals, which revealed hyperabsorption in SHR of both sexes with increments 10-fold that of Ca excretion, supporting the primacy of intestinal hyperabsorption. In situ duodenal Ca uptake was also increased in the SHR. Parathyroidectomy did not affect the hyperabsorption. Hypercalcemia (total and ionized) and hypercalciuria in SHR associated with reduced adenosine 3',5'-cyclic monophosphate excretion, were abolished by fasting. Correction of hypertension for 6 mo failed to abolish the hypercalciuria. Bone Ca deposits were increased in 1-yr-old SHR. Ten-week-old SHR, in contrast, displayed mild malabsorption. Our data do not support the "renal leak" hypothesis. Instead, the adult SHR is characterized by increased Ca retention due to primary hyperabsorption, absorptive hypercalciuria, and increased bone Ca deposition. These phenomena are independent of sex, parathyroid hormone, and treatment of the established hypertension.

Age Factors↗
PubMed1984

Evidence for the role of PO4 deficiency in antihypertensive action of a high-Ca diet.

Previous studies indicated a salutary effect of a high-Ca diet on high blood pressure (BP). The mechanism, however, is obscure. With balance and clearance techniques, the role of parathyroid hormone (PTH), volume contraction, hypercalcemia, and PO4 deficiency was evaluated in female spontaneous hypertensive rats (SHR). The antihypertensive effects of a high (4.3%) Ca diet in intact animals (groups I and II) could be reproduced in both 9- and 22-wk-old chronic stable parathyroidectomized (PTX) rats (groups III and IV), when compared with a low (0.22%) or normal (1.2%) CA diet. In both short (7 days) and long (12 wk) term exposure to the high-Ca diet, evidence for volume contraction could not be documented despite hypercalcemia sustained through the 12th wk (10.8 vs. 9.7 mg/100 ml, group I control, P less than 0.02). When produced by ip injections, chronic hypercalcemia of similar magnitudes as oral Ca supplements failed to reduce BP in either intact (group VI) or PTX (group IV) rats. Rats in group IV fed the high-Ca diet displayed marked hypophosphatemia (3.2 vs. 6.9 mg/100 ml), hypophosphaturia (0.15 vs. 15 mg/day), hypermagnesiuria (11 vs. 7.7 mg/day), and drastically reduced net intestinal PO4 absorption (13.3 +/- 7.5 vs. 66.8 +/- 7.5 mg/day) compared with rats fed 1.2% Ca diet. To test the PO4-deficiency hypothesis, additional SHR (group V) were fed either 1.2% Ca diet and injected ip with NaCl or fed 4.3% Ca diet, with half of these animals injected with neutral NaPO4 and half with NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Renal calculi associated with incomplete distal renal tubular acidosis.

We report 5 cases of renal calculi associated with incomplete type I renal tubular acidosis. The patients presented with a history of recurrent calculi and demonstrated bilateral calculi with corticomedullary junction calcification on x-ray. Stone analysis revealed primarily calcium phosphate stones and metabolic studies demonstrated hypercalciuria, mild depression of serum bicarbonate and inability to lower the pH of a fasting morning urine to less than 5.8. The 24-hour urinary citrate excretion was depressed markedly. The diagnosis was confirmed by an ammonium chloride loading test. Treatment consisted of alkalization of the patients, which corrects the hypercalciuria and increases the urinary citrate level and should decrease the tendency to form stones. The diagnosis of incomplete type I renal tubular acidosis should be considered in patients with recurrent renal calculi.

Acidosis, Renal Tubular↗
PubMed1982

Mechanism for the phosphaturia of NH4Cl: dependence on acidemia but not on diet PO4 or PTH.

The effects of metabolic acidosis on renal PO4 handling are controversial. Clearance experiments, therefore, were performed in fasted parathyroidectomized rats 1) to test the thesis that NH4Cl per se alters PO4 reabsorption, 2) to characterize the mechanisms responsible for these changes, and 3) to define the interaction of NH4Cl with parathyroid hormone (PTH) in PO4 deprivation. NH4Cl increased the clearance and fractional excretion of PO4 (FEPO4) without altering plasma PO4. Lactic acid and HCl, but not saline loading. NH4HCO3, or glutamine, produced similar effects. At steady-state phosphaturic effects of NH4Cl, neutralization of the acidemia by NaHCO3 abolished the increment. PTH (3.3 U.kg-1.h-1), superimposed on the maximal effective dose of NH4Cl (5.7 mmol.kg-1.h-1), further augmented FEPO4 (from 24.3 to 46.9%). The effects of NH4Cl (delta FEPO4 = 23 vs. 21%) and the synergism with PTH were not affected by PO4 deprivation. In both PO4 repletion and deprivation, NH4Cl increased basal and PTH-stimulated cAMP excretion, but the changes were poorly correlated with FEPO4. We conclude that NH4Cl inhibits PO4 reabsorption independent of PTH, extracellular fluid volume, natriuresis, NH4+ ion, plasma PO4, or the status of PO4 balance. The effects are mediated by mechanisms dependent on acidemia but are quite distinct from those of PTH. Our findings on cAMP are most compatible with the hypothesis that biochemical events beyond cAMP generation mediate both the phosphaturia of NH4Cl and its ability to restore PTH sensitivity in PO4 deprivation.

Ammonia↗
PubMed1982

Tubular mechanism for the spontaneous hypercalciuria in laboratory rat.

Recently it has been observed that Ca excretion in laboratory rats does not follow a Gaussian distribution, with approximately 10% of them excreting Ca at a rate of 2 SD above the group mean. This phenomenon has been described as spontaneous hypercalciuria (SH). Our studies were designed to define its mechanism. 48 Wistar rats were subjected to metabolic studies to identify SH, prospectively defined as Ca excretion 2 SD above the group mean during 7 d of dietary Ca deprivation (</=0.03% by analysis), in the absence of hypercalcemia, PO(4) depletion, or exaggerated natriuresis. Progenies from SH rats were found to have significantly higher urine Ca/creatinine (micrograms per milligram) (male = 38 vs. 23, P < 0.05; female = 79 vs. 60, P < 0.005) with 7/20 males and 9/26 females having values 2 SD above the means of normal. After a 12-h fast and during 10% volume expansion with saline, clearance and micropuncture studies were performed on three groups of acutely parathyroidectomized female rats; (a) normocalciuric (N) progenies from the normal, (b) normocalciuric (NC) progenies from SH, and (c) hypercalciuric (HC) progenies from SH rats. Among these groups, there was no significant difference in body weights, glomerular filtration rate, plasma ultrafiltrable Ca (4.5, 4.6 vs. 4.7 mg/100 g), PO(4), and the fractional excretion (FE) of Na or FE(PO4). FE Ca was significantly higher in HC rats (13.9%) than N (10.1%) and NC (10.7%). Segmental reabsorption of fluid and Na was comparable among the three groups. Fractional delivery (FD) of Ca was, however, significantly increased in the late proximal tubule of HC rats (62 vs. 49 and 46%, P < 0.05). The increased FDCa was no longer apparent in early or late distal tubule (6.9 vs. 6.9 and 7.6%, P = NS). Although FECa exceeded late distal FDCa in all three groups, the increment was significantly greater in HC rats (7.02%) than both N (3.4, P < 0.05) and NC rats (3.05, P < 0.02). The effects of chlorothiazide (27.5 mg/kg/d, i.p. x 7 d) were evaluated in the female offsprings of the SH rats. Before chlorothiazide, average urine Ca/creatinine (253 vs. 77.2) and cyclic AMP (26.6 vs. 13.4 mumol/mg creatinine, P < 0.001) on days 7 and 8 of the Ca-deprived diet were higher than the normal. On days 6 and 7 of chlorothiazide, average cyclic AMP (cAMP) excretion fell to normal range (11.7 vs. 12.7 mumol/mg creatinine) as Ca excretion was reduced to normal (62 vs. 59.4 mug Ca/mg creatinine). WE CONCLUDE: (a) SH, as defined in this study, is an inheritable biochemical marker and renal in origin. (b) The hypercalciuria is independent of parathyroid hormone, changes in plasma Ca and tubular handling of Na. (c) As studied in the PTX and volume expanded conditions of our experiments, decreased Ca reabsorption in superficial proximal convoluted tubule is demonstrable, but the hypercalciuria is probably mediated by diminished Ca transport by the deep nephron. The unlikely possibility of increased secretion by the terminal nephron, however, remains to be excluded. (d) In normal rats, there is internephron heterogeneity in regard to Ca transport during saline loading.

Animals↗