Fractional Excretion Of Lithium Research Articles

Comparison of the renal effects of six sedating agents in rats

This study was designed to compare the renal effects of sedation with alphadolone-alphadolone, etomidate, propofol, midazolam, fentanyl-fluanisone, and thiopental in rats. The sedative dose was defined as the highest dose that abolished the escape response without affecting the righting reflex. Female Wistar rats were chronically catheterized with a jugular vein catheter, and urine flow rate and renal clearances of inulin (glomerular filtration rate = GFR), sodium, and lithium (used as an index of proximal tubular function) were measured in the conscious, unrestrained state ( n = 107 experiments). In a separate series ( n = 70 experiments), the effect of sedative doses of each drug on the nociceptive threshold was tested with the tail-flick test. Responses in sedated animals were compared to responses in animals infused with the vehicle. Fentanyl-fluanisone and thiopental had hypoalgesic actions in sedating doses. Propofol, fentanyl-fluanisone, and thiopental reduced GFR by 20–30%. Urine flow rate was significantly decreased by propofol (−24%) and thiopental (−48%). Propofol and fentanyl-fluanisone reduced fractional lithium excretion by 9–13%. Only alphadolone-alphadolone, etomidate, and midazolam produced sedation without affecting renal function in rats. Because midazolam produced the most consistent degree of sedation, we conclude that midazolam is the least confounding sedative agent for renal function studies in conscious rats.

Comparison of the Renal Effects of Six Sedating Agents in Rats

This study was designed to compare the renal effects of sedation with alphadolone-alphadolone, etomidate, propofol, midazolam, fentanyl-fluanisone, and thiopental in rats. The sedative dose was defined as the highest dose that abolished the escape response without affecting the righting reflex. Female Wistar rats were chronically catheterized with a jugular vein catheter, and urine flow rate and renal clearances of inulin (glomerular filtration rate = GFR), sodium, and lithium (used as an index of proximal tubular function) were measured in the conscious, unrestrained state (n = 107 experiments). In a separate series (n = 70 experiments), the effect of sedative doses of each drug on the nociceptive threshold was tested with the tail-flick test. Responses in sedated animals were compared to responses in animals infused with the vehicle. Fentanyl-fluanisone and thiopental had hypoalgesic actions in sedating doses. Propofol, fentanyl-fluanisone, and thiopental reduced GFR by 20–30%. Urine flow rate was significantly decreased by propofol (−24%) and thiopental (−48%). Propofol and fentanyl-fluanisone reduced fractional lithium excretion by 9–13%. Only alphadolone-alphadolone, etomidate, and midazolam produced sedation without affecting renal function in rats. Because midazolam produced the most consistent degree of sedation, we conclude that midazolam is the least confounding sedative agent for renal function studies in conscious rats.

Effect of meclofenamate or ketoconazole on the natriuretic response to increased pressure

Increases in renal interstitial hydrostatic pressure (RIHP) by direct renal interstitial volume expansion (DRIVE) decrease proximal sodium reabsorption and increase urinary fractional sodium excretion (FENa). This natriuretic response is blunted by inhibition of the cyclooxygenase pathway. However, complicating the interpretation of the effects of cyclooxygenase inhibition on sodium excretion are the following: (1) products of the other pathways of arachidonic acid metabolism, such as the cytochrome P-450 metabolites, may be attenuated when cyclooxygenase activity is reduced; (2) the proximal tubule has a high biosynthetic capacity for cytochrome P-450 metabolites of arachidonic acid. Therefore, the purpose of the present study was to compare blockade of the epoxygenase products of the cytochrome P-450 pathway with ketoconazole to blockade of the cyclooxygenase pathway with meclofenamate on the natriuretic response to increased RIHP during DRIVE. RIHP, fractional excretion of lithium (FELi), FENa, and glomerular filtration rate (GFR) were measured before and after DRIVE in control (n = 6), meclofenamate-treated (n = 6), and ketoconazole-treated (n = 5) rats. DRIVE was achieved by infusing 100 μI of 2.5% albumin solution directly into the renal interstitium. In control animals, DRIVE significantly increased RIHP (Δ2.8 ± 0.6 mm Hg), FELI (Δ13.4% ± 5.2%), and FENa (Δ1.29% ± 0.31%). In the ketoconazole-treated group, RIHP (Δ3.9 ± 0.8 mm Hg), FELi (Δ19.3% ± 2.0%), and FENa (Δ1.73% ± 0.43%) also significantly increased. However, the natriuretic response to DRIVE was blunted during cyclooxygenase blockade with meclofenamate when compared with control or ketoconazoletreated animals (FELi (Δ2.5% ± 1.4%, not significant) and FENa (Δ0.07% ± 0.18%, not significant)), even though the response of RIHP was intact (Δ4.5 ± 0.4 mm Hg, p < 0.001). These results suggest that the natriuretic response to increased RIHP is dependent on the presence of, but not necessarily the increased synthesis of, products of cyclooxygenase rather than the cytochrome P-450 epoxygenase pathway for arachidonic acid metabolism.

Increased proximal sodium reabsorption is associated with increased cardiovascular risk in men.

To explore the relationship between fractional lithium excretion (taken as an index of proximal sodium excretion), blood pressure and metabolic risk factors for coronary heart disease in a sample of a general white male population. A cross-sectional survey of a sample of a white male working population carried out as part of the Olivetti Heart Study. The Olivetti factory in Pozzuoli, a suburb of Naples, Italy. Five hundred and sixty-seven untreated white male workers aged 21-68 years. Anthropometry, blood pressure, a blood test to determine the lipid profile, electrolytes, glucose and uric acid levels, a detailed questionnaire and urinary measurements on a fasting timed urine sample after a 300 mg lithium carbonate capsule taken the night before the investigation. The fractional excretion of lithium was inversely associated with body weight, body mass index, diastolic blood pressure, serum triglycerides level and serum uric acid level whereas it was positively associated with serum high-density lipoprotein cholesterol level. The greater the percentage of filtered sodium reabsorbed at the proximal tubule the greater the overall metabolic cardiovascular risk. The association was consistent across tertiles of fractional excretion of lithium, was independent of age, smoking, alcohol consumption and sodium excretion (taken as an index of sodium intake) and persisted in multiple regression analysis. Men with high serum triglycerides, high serum uric acid and low serum high-density lipoprotein cholesterol levels and higher blood pressure had significantly lower fractional excretion of lithium (and thus enhanced proximal sodium reabsorption) than did men with a normal metabolic profile (21.8 +/- 5.6 versus 26.5 +/- 5.1%, p = 0.002). The independent association between a cluster of risk factors for cardiovascular disease suggestive of insulin resistance and increased proximal sodium reabsorption at the renal tubule indicates a new feature of the metabolic syndrome that, if causal, could be amenable to intervention.

Effect of vasopressin on renal lithium reabsorption: a micropuncture and microperfusion study.

Micropuncture techniques were used to investigate the nephron site(s) responsible for the vasopressin-induced reductions in lithium clearance and fractional lithium excretion (FELi) in anesthetized Brattleboro rats lacking endogenous vasopressin. In rats treated intravenously with the vasopressin analogue 1-desamino-8-D-arginine vasopressin (DDAVP; 40 pg/min), FELi was significantly lower than in untreated animals (0.23 +/- 0.01 vs. 0.28 +/- 0.02, P < 0.05). Free-flow micropuncture showed that fractional lithium delivery (FDLi) to late proximal convolutions was identical in the two groups, whereas at the early distal tubule both FDLi (0.28 +/- 0.02 vs. 0.33 +/- 0.01, P < 0.05) and the tubular fluid-to-plasma lithium concentration ratio (1.18 +/- 0.04 vs. 1.36 +/- 0.06, P < 0.05) were lower in the DDAVP-treated group. No differences between the groups with respect to lithium handling beyond the early distal tubule were observed. In rats subjected to in vivo microperfusion of loops of Henle, intravenous infusion of DDAVP (40 pg/min) increased fractional lithium reabsorption in the loop from 0.56 +/- 0.03 to 0.66 +/- 0.04 (P < 0.05) and from 0.39 +/- 0.02 to 0.45 +/- 0.02 (P < 0.05) at perfusion rates of 10 and 15 nl/min, respectively. We conclude that DDAVP stimulates lithium reabsorption in the loop of Henle and suggest that this results from an increased transepithelial potential difference in the thick ascending limb.

Reduced renal fractional excretion of lithium in cystic fibrosis.

We hypothesized that patients with cystic fibrosis would have abnormal lithium handling because the genetic defect in cystic fibrosis encodes an ion channel which causes a generalized electrolyte transport disorder in epithelial membranes. Eight patients with cystic fibrosis and eight age-sex matched healthy subjects ingested 600 mg lithium carbonate and had urine and serum lithium levels assessed 24 h later. Compared with healthy subjects, the patients with cystic fibrosis had higher serum lithium levels (0.071 +/- 0.038 vs 0.113 +/- 0.055 mmol l-1, P = 0.03) and had lower fractional renal excretion of lithium (27.5 +/- 14.8 vs 18.8 +/- 9.3%, P = 0.03). Caution should be used in prescribing standard doses of lithium to patients with cystic fibrosis until more definitive data are available.

Clinical assessment of renal proximal tubular function using lithium clearance method

Proximal and distal sodium reabsorption values were calculated from lithium clearance in 63 patients with renal diseases, 13 cirrhotic patients with ascites and 12 control subjects. In the patients with renal diseases, fractional excretion of lithium (FELi) and fractional proximal reabsorption of sodium (FPRNa) were not changed in patients whose glomerular filtration rate (GFR), was over 30 mL/min, but FELi was increased and FPRNa was decreased when the GFR was lower than 30 mL/min. Moreover, fractional distal reabsorption of sodium (FDRNa) was decreased in patients whose GFR was under 40 mL/min. These results indicate that proximal tubular function is well adapted to the degree of renal function even if the etiologies of renal diseases are different. Five patients with nephrotic syndrome (minimal change type) were subjected to lithium clearance method before and after steroid treatment. FPRNa in nephrotic patients was reduced after the treatment, though there was no significant difference in FDRNa. In cirrhotic patients, FELi, FPRNa and FDRNa did not differ from the values in the control subjects, which were not influenced by the decrease in GFR. Thus, the reduction of FPRNa with GFR which was observed in renal disease, was absent in liver cirrhosis. In conclusion, these data indicate that renal adjustment of sodium excretion in chronic renal disease at first takes place in the distal parts of the nephron and later in the proximal tubule, and in addition, that in appropriate reabsorption of sodium from the proximal tubule probably plays a role in ascites formation in cirrhotic patients.

Effect of prednisolone on amino acid-induced changes in renal haemodynamics and tubular function

The effect of oral prednisolone treatment on renal haemodynamics, tubular function and various hormones during amino acid infusion was studied in 14 normal men. A balanced amino acid solution was infused for 120 min, before and after 4 days of prednisolone treatment (40 mg day-1). During amino acid infusion before prednisolone glomerular filtration rate, renal plasma flow, urinary sodium excretion, fractional excretion of sodium, lithium clearance, fractional excretion of lithium, serum insulin (s-insulin), plasma glucagon (p-glucagon) and s-growth hormone increased, whereas p-atrial natriuretic peptide, p-aldosterone, p-vasopressin and s-insulin-like growth factor 1 were unchanged, and potassium excretion and fractional excretion of potassium fell. After prednisolone treatment the most important differences during amino acid infusion were a significantly lower fractional excretion of sodium after 120 min (before prednisolone 26%; after prednisolone-7%; p < 0.05), a more pronounced increase in s-insulin after 120 min (before 118%; after 200%; p < 0.05) and a lower s-potassium. In conclusion, amino acid infusion increased fractional sodium excretion in healthy men, and this increase was reduced by prednisolone due to increased reabsorption in the distal tubules. It is suggested that the more pronounced the increases in plasma insulin and the decrease in serum potassium are mediators of the increased distal tubular sodium reabsorption during amino acid infusion during prednisolone treatment.

Diurnal Pattern of Sodium Excretion in Dogs with and without Chronically Reduced Renal Perfusion Pressure

In 5 conscious dogs the diurnal patterns of urinary sodium excretion (UNaV) were investigated, initially during 1 control day and, thereafter, during 4 days of servo-controlled reduction of renal perfusion pressure (rRPP). The individual dog's mean arterial blood pressure was reduced to 80% of the blood pressure on the control day. This value was always found to be below the threshold for the pressure-dependent renin release. During the entire study period urine was collected in 4-hour intervals and blood samples were taken every 4 h. The dogs were kept on a standardized high sodium and high water intake and were fed once daily at 8.30 h. On the control day, UNaV, urinary flow rate (UV), fractional lithium excretion (FELi) and fractional sodium excretion (FENa) had similar diurnal patterns. They peaked 4-8 h after food intake and decreased to low values during the night. On day 1 of rRPP, UNaV and FENa were maintained at very low levels in all collection periods, whereas the patterns of UV and FELi were unaltered compared with the patterns on the control day. On days 2-4 of rRPP, a clear-cut maximum in the patterns of UNaV and FENa recurred, comparable with the patterns on the control day. However, compared with the control day this maximum was shifted by 4 h towards the night. In contrast, the patterns of UV and FELi remained unchanged compared with the control day. The results indicate that UNaV has a typical time course in conscious, sodium- and water-replete dogs fed once daily. Endogenous stimulation of sodium reabsorption by means of rRPP results in a characteristic 4-hour shift of UNaV and FENa towards the night during rRPP days 2-4. This delay in UNaV seems to be evoked by processes in the distal tubule.

Nitric oxide stimulates guanylate cyclase and regulates sodium transport in rabbit proximal tubule.

The proximal tubule contains the target for nitric oxide (NO), soluble guanylate cyclase, and has the capacity for NO production. Inhibition of renal NO synthesis reduces fractional excretion of lithium, suggesting an inhibitory effect of NO on proximal tubule Na+ transport. The present studies determined direct effects of donors of NO in rabbit proximal tubule. In both freshly isolated proximal tubule segments and in primary cultures of proximal tubule cells, sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) caused dose-dependent increases in guanosine 3',5'-cyclic monophosphate (cGMP). SNAP was more potent than SNP in stimulating cGMP; this was associated with an enhanced production of nitrite, the stable end-product of NO. In rabbit proximal tubule cells, SNP or SNAP (10(-3) M) significantly inhibited the activity of the apical Na+/H+ exchanger, determined by assay of amiloride-sensitive 22Na+ uptake (% inhibition: SNP, 34.90 +/- 5.52%, P < 0.001; SNAP, 30.77 +/- 8.20%, P < 0.002). To determine the role of cGMP in mediating these effects, proximal tubule cells were incubated with the membrane-permeable analogue, 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP). Na+/H+ exchange was significantly inhibited by 8-BrcGMP (10(3)M) (% inhibition: 32.40 +/- 9.06%: P < 0.05). The inhibitor of soluble guanylate cyclase, LY-83583, caused partial inhibition of SNP-stimulated cGMP generation and partly blocked the inhibitory effect of SNP on Na+/H+ exchange. Protein kinase A (PKA) activity was not stimulated by SNP, indicating that potential cross-activation of PKA by cGMP did not mediate the effects of NO donors. These data indicate that NO stimulates soluble guanylate cyclase in rabbit proximal tubule and causes inhibition of Na-/H+ exchange. This is at least partly mediated by generation of cGMP. We conclude that NO is an important autocrine or paracrine factor directly regulating Na+ transport in the proximal tubule.

Interactions between angiotensin and nitric oxide in the renal response to volume expansion.

This study examined, in anesthetized dogs, the possible interactions between nitric oxide (NO) and angiotensin II (ANG II) in mediating the renal response to an extracellular volume expansion (ECVE). It was found that the intrarenal maintenance of ANG II levels (group 1) or the intrarenal NO synthesis inhibition (group 2) did not induce changes in renal hemodynamics but reduced (P < 0.05) the ECVE-induced increments in sodium excretion and fractional lithium excretion (FeLi). In the third group, ANG II synthesis was inhibited during NO synthesis blockade. It was found in this group that the NO synthesis inhibition reduced the ECVE-induced increment in sodium excretion (P < 0.05) but did not modify the ECVE-induced increment in FeLi. These results suggest that the increase of proximal sodium reabsorption induced by the No synthesis inhibition is mediated by endogenous ANG II levels. In the fourth group, it was observed that NO synthesis inhibition, during the intrarenal maintenance of ANG II levels, induced a decrease of renal blood flow (P < 0.05) and reduced the natriuretic response to ECVE to a lower level (P < 0.05) than that observed in groups 1 and 2. The results of this group suggest that endogenous NO modulates the vasoconstrictor and antinatriuretic effects of ANG II during an ECVE. In summary, the results of this study suggest that there is an important interaction between NO and ANG II in mediating the renal response to an ECVE.

Renal Handling of Lithium and the Effects of Mannitol and Arginine Vasopressin in man

1. A study has been undertaken in six healthy male subjects to clarify whether post-proximal segments of the nephron contribute to the renal handling of lithium under conditions of maximal forced osmotic load diuresis and arginine vasopressin-induced antidiuresis. Increments in the fractional clearance of free water, as a measure of effect at the proximal tubule, were positively correlated with incremental changes in flow rate, factored for glomerular filtration rate (mean r = 0.80 +/- 0.12, P < 0.001), and fractional excretion of lithium (mean r = 0.84 +/- 0.06, P < 0.001). Changes in flow rate and fractional excretion of lithium were also closely correlated with one another (mean r = 0.81 +/- 0.06, P < 0.001), and the mean slope of these regression lines was not significantly different from unity (1.18; 95% confidence interval 0.76-1.59). These results show that, under conditions of maximal hydration, mannitol-induced changes in proximal tubular function were closely correlated with induced changes in the fractional excretion of lithium. 2. Infusion of arginine vasopressin alone (0.5 m-units/min) caused a marked reduction in both fractional clearance of free water (10.7% +/- 1.2% to -1.2% +/- 0.2%, P < 0.001) and flow rate factored for glomerular filtration rate (14.0 +/- 1.5 to 0.8 +/- 0.2%; P < 0.001) while the fractional excretion of lithium showed only a small non-significant decrease (25.3% +/- 2.0% to 23.3% +/- 2.2%). A similar dissociation was noted between fluid and lithium excretion when arginine vasopressin was superimposed on mannitol infusion with reductions in the fractional clearance of free water (12.7% +/- 1.0% to -0.9% +/- 0.7%, P < 0.001) and flow rate (18.6% +/- 1.5% to 5.7% +/- 1.0%; P < 0.001), while the fractional excretion of lithium showed a significant increase (28.4% +/- 1.7% to 33.1% +/- 2.4%; P < 0.05). The lack of correlation between fluid and lithium excretion, in the presence of arginine vasopressin with or without mannitol, indicates that the late distal tubule and collecting duct have little or no significant capacity to reabsorb lithium. 3. These findings, taken as a whole, strengthen the view that renal tubular handling of lithium is primarily a proximal event.

Renal sodium handling with cyclosporin A and FK506 after orthotopic liver transplantation.

Hypertension is common after orthotopic liver transplantation and may be due, in part, to cyclosporin A-induced renal dysfunction and/or enhanced proximal tubular sodium reabsorption. To determine whether enhanced proximal tubular sodium reabsorption is central to the development of posttransplant hypertension, measurements of renal hemodynamics and fractional clearances of lithium and sodium were compared 1 month after orthotopic liver transplantation in previously normotensive patients receiving either cyclosporin A (N = 24) or FK506 (N = 18), an immunosuppressive agent that is structurally unlike cyclosporin A and that has a lower reported incidence of hypertension. Median prednisone doses were 20 and 13 mg/day in the cyclosporin A and FK506 groups, respectively (P < 0.05). At 1 month, mean arterial blood pressure was higher in the cyclosporin A versus the FK506 group: 108 +/- 2 versus 95 +/- 3 mm Hg (P < 0.05). GFR, RBF, and renal vascular resistance were not different between the two groups: 59 +/- 4 and 53 +/- 5 mL/min per 1.73 m2, 439 +/- 28 and 440 +/- 41 mL/min per 1.73 m2, and 22,429 +/- 1,822 and 22,977 +/- 3,506 dyne s/cm5 per 1.73 m2, respectively. Fractional lithium excretion was similar in the cyclosporin A and FK506 groups: 19.9 +/- 2.2 and 19.4 +/- 2.0% (P = not significant) although both values were lower than those of normal controls (25.5 +/- 1.1%) (P < 0.05). Fractional sodium excretion was 2.7 +/- 0.3 and 2.3 +/- 0.4% in the cyclosporin A and FK506 groups, respectively (P = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Enalapril reduces the albuminuria of patients with sickle cell disease

To evaluate the effects of enalapril, an angiotensin-converting enzyme inhibitor, on albuminuria associated with sickle cell anemia. Two males and 6 females, mean age 22.8 +/- 5.5 years, with sickle cell anemia and albuminuria, received enalapril for 6 months. Before entry into the study, all had a urinary albumin concentration above 30 mg/L as determined by radioimmunoassay documented on three separate occasions at intervals of 15 to 30 days. Samples were collected before 10 AM after an oral water load of 10 mL/kg. Enalapril reduced 6 patients' pretreatment hyperalbuminuria to normal. One patient whose levels did not reach normal values experienced a reduction of 70%. Fractional excretion of sodium, potassium, and lithium did not change during the treatment. Mean arterial pressure decreased by 8.6 +/- 0.42 mm Hg. Two years after enalapril was discontinued, there were no changes in sodium, potassium, or creatinine levels of 7 patients who had received enalapril or in their mean arterial pressures. Urinary albumin concentration increased relative to pretreatment levels in 2 individuals, returned to pretreatment levels in 2, and remained below 30 mg/L in 2. Our results demonstrate that enalapril reduces albuminuria in patients with sickle cell anemia. After discontinuation of the drug, however, the albuminuria may increase to pretreatment levels or higher. Whether the reduction in urinary albumin concentration by angiotensin-converting enzyme inhibitors can delay the development of progressive renal failure in sickle cell anemia patients remains to be established.

Clearance of endogenous lithium in humans: altered dietary salt intake and comparison with exogenous lithium clearance

We compared endogenous with exogenous lithium clearance (CLi) and studied the effects of dietary salt intake on endogenous CLi in healthy volunteers. Lithium was detectable within a narrow fourfold range in serum and in urine in all 25 subjects studied [serum (n = 25), mean 0.27 +/- 0.02 mumol/l, range 0.13-0.55 mumol/l; urine (n = 20), range 1.49-7.32, mean 4.09 +/- 0.36 mumol/24 h]. Mean clearance and fractional excretion of endogenous lithium were lower (15.2 +/- 2.0 ml/min and 16.4 +/- 2.1%, respectively) compared with results obtained using the exogenous CLi technique (25.5 +/- 1.7 ml/min and 27.9 +/- 2.1%; P < 0.01 and P < 0.05, respectively; n = 17). In a separate group of six normal subjects, absolute (8.7 +/- 2.9 vs. 20.7 +/- 3.8 ml/min) and fractional excretion of lithium (8.3 +/- 2.9 vs. 18.0 +/- 5.1%) were significantly lower on 5 days of low (31 +/- 10 mmol/day) vs. high sodium intake (357 +/- 78 mmol/day; P < 0.05). Use of endogenous CLi precludes the need for lithium tablets. This could be a particular advantage in population studies and permits serial measurement of CLi on different days. Our results show that it is important to take dietary sodium intake into account in studies of endogenous CLi. Lower values for endogenous compared with exogenous CLi could reflect differences in renal handling depending on the plasma lithium concentration. This clearly requires further study.

A micropuncture study of renal tubular lithium reabsorption in sodium-depleted rats.

1. The marked reduction in fractional lithium excretion (FELi) which accompanies chronic sodium depletion was investigated using free-flow micropuncture in anaesthetized rats which had been maintained in a sodium-depleted state for 8-10 days. 2. Compared with previous values in sodium-replete rats, sodium depletion was associated with small reductions in total and superficial nephron glomerular filtration rate and enhanced fractional reabsorption of water, sodium and lithium in the proximal convoluted tubule. 3. In untreated (sodium-depleted) rats, fractional deliveries of lithium (FDLi) to the late proximal convoluted tubule, early distal tubule and late distal tubule were 0.41 +/- 0.02, 0.20 +/- 0.01 and 0.18 +/- 0.02 (means +/- S.E.M.), respectively. Fractional lithium excretion (0.08 +/- 0.01) was significantly lower than late distal FDLi (P < 0.001). 4. Treatment with amiloride did not affect segmental lithium handling up to the late distal tubule. Frusemide had no effect on lithium reabsorption in the proximal convoluted tubule, but early distal FDLi (0.30 +/- 0.01) was raised compared with the untreated group (P < 0.001). Both diuretics eliminated the difference between late distal FDLi and FELi, respective values being 0.17 +/- 0.02 and 0.15 +/- 0.01 (amiloride-treated rats) and 0.31 +/- 0.02 and 0.34 +/- 0.02 (frusemide-treated rats). 5. These data indicate that part of the reduction in FELi in chronic sodium depletion is due to enhanced fractional fluid (and lithium) reabsorption in the proximal convoluted tubule. In addition, however, they provide direct evidence for amiloride-sensitive lithium reabsorption in the collecting ducts.(ABSTRACT TRUNCATED AT 250 WORDS)

Functional and Histologic Alterations in Growing Solitary Rat Kidney as Result of Extracorporeal Shockwaves

The long-term effects of extracorporeal shockwave lithotripsy (SWL) on children treated for renal calculi are unclear. To study the effects on the immature animal, we evaluated 31 Wistar white rats that underwent right nephrectomy at 30 days of age. At 40 days of age they were divided into three groups: a control group of 10 rats that received no shockwaves; Group I (9 rats) that received 1000 shockwaves at 16.0 kV, and Group II (12 animals) that received 1000 shock waves at 17.2 kV. Six months later at maturity (7 months and 10 days of age), the following parameters were measured: (1) body and renal weight; (2) blood lithium, sodium, potassium, and creatinine; (3) fractional lithium, sodium, and potassium excretion; and (4) clearances of lithium and creatinine. The kidneys were studied grossly and histologically. We found no significant changes in overall animal and renal growth between the post-SWL and control groups. However, there were significant changes in renal function. The animals in Groups I and II presented significant increases in blood potassium compared with the control group. Furthermore, the 1000 x 17.2 kV group showed permanent histologic renal changes, including red cells in Bowman's capsule and glomerular congestion. The disorders caused by SWL are compatible with hyporeninemic hypoaldosteronism, inappropriately low plasma renin activity, and aldosterone deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Considerations on the sodium retention in nephrotic syndrome.

Renin-angiotensin-aldosterone system, plasma atrial natriuretic peptide (PANP), and blood volume (BV) have been investigated in 20 nephrotic patients with normal renal function and with (group 1; n = 12) or without (group 2; n = 8) sodium retention. Patients of group 1 had a plasma albumin (PALB) concentration < 1.7 g/dl, low BV and PANP levels, a reduced fractional excretion of lithium (FELi), and high plasma angiotensin II levels. Patients of group 2 had PALB > 1.7 g/dl, and the other parameters were normal. The spontaneous intake of dietary sodium was lower in group 1 than in group 2. In all patients the BV was directly correlated with PALB, and the plasma renin activity (PRA) was inversely correlated with both BV and PALB. A nonlinear inverse relationship was present between plasma aldosterone (PALD) levels and fractional excretion of sodium (FENa). The acute expansion of the BV in patients of group 1 normalized PRA, PALD, PAII, FENa, and FELi and increased PANP. The administration of spironolactone to the patients of both groups had variable effects on FENa, did not modify PRA and PALD, and reduced body weight, PANP, and FELi, thus suggesting that the reduction of BV induced by the drug increased the proximal reabsorption of sodium. Three additional patients who had sodium retention, PALB of 2.3-2.4 g/dl, normal PRA and PALD, elevated urinary excretion of aldosterone, and a slightly low PANP showed a spontaneous normalization of urinary aldosterone and PANP associated with natriuresis and weight loss, but thereafter urinary aldosterone increased, PANP decreased, and the sodium retention began again. Our data suggest that in nephrotic patients with severe hypoalbuminemia, contraction of BV plays a major role in promoting the sodium retention through the activation of compensatory hormonal mechanisms. On the other hand, when PALB is not severely reduced, the patients have normal BV, but they are very sensitive to small changes of BV which are better evidenced by modifications of the urinary excretion of aldosterone and PANP rather than by the profiles of PRA and PALD.

Renal functional reserve in cyclosporin-treated recipients of kidney transplant

The aims of this study were to determine whether renal functional reserve (RFR) is still present in cyclosporin-treated renal transplant recipients, and to examine the relationship between RFR and proximal reabsorption. A serial study was carried out in 12 renal allograft recipients (R) with good renal graft function at 20 +/- 2.5 days (S1) and at 7.6 +/- 0.4 months (S2) post-transplantation, and the results were compared to those in eight subjects who had undergone unine-phrectomy (one-kidney controls: UNx.C) and in 12 healthy volunteers (two-kidney controls: 2K.C). R and C were in similar sodium and protein balance and with similar plasma renin and aldosterone levels. R had normal serum creatinine level on moderate doses of cyclosporin (whole blood cyclosporin concentration: 212 +/- 20 and 125 +/- 20 ng/ml at S1 and S2, respectively). Eight one-hour clearance periods were performed prior to, during and following a three-hour i.v. infusion of a mixture of 20 l-amino acids (Azonutril 25, 4.5 mg amino acids/kg/min). Baseline glomerular filtration rate (GFR) was lower in recipients at S1 and S2 (55 +/- 5 and 54 +/- 4 ml/min/1.73 m2, respectively) than in UNx.C and 2K.C (72 +/- 4 and 113 +/- 4 ml/min/1.73 m2, respectively, P < 0.05 and 0.001). Amino acid infusion elicited significant GFR increases in controls as well as in recipients in spite of higher renal vascular resistances (RVR). The greater measured increase in GFR, which represented RFR, was 18 +/- 3 and 28 +/- 2 ml/min/1.73 m2 in UNx.C and 2K.C, respectively (P < 0.001), and 17 +/- 3 ml/min/1.73 m2 in R at both S1 and S2 (P < 0.001). Contrary to both UNx and 2K controls, the acute hyperfiltration in R at S1 and S2 occurred with a significant increase in effective renal plasma flow, no alteration in filtration fraction and a large decrease (approximately 20 and 17%) in RVR while no correlation could be detected between the RFR and baseline GFR. Baseline lithium clearance, used as a marker of overall proximal fluid delivery (CLi), was significantly lower, whereas baseline fractional excretion of lithium (FELi) was significantly higher in R at S1 and S2 and in UNx.C (41 +/- 4, 40 +/- 3 and 38 +/- 3%, respectively) than in 2K.C (31 +/- 2%, P < 0.05). Consistent and significant increase in CLi, FELi and absolute proximal reabsorption occurred both in R at S1 and S2 and in UNx and 2K controls during elicitation of RFR.(ABSTRACT TRUNCATED AT 400 WORDS)

Endogenous lithium clearance as a probable measure of end-proximal fluid delivery in the amphibian kidneys: A study of renal water and Na+ reabsorption in the hydrated and dehydrated frog Rana temporaria

In fully hydrated frogs (R. temporaria) a clearance of endogenous lithium (CLi) coincides with the glomerular filtration rate (CCoEDTA) which is on average 32 ml/kg/hr, i.e. fractional lithium excretion (FELi) is close to unity, and urine to plasma concentration ratios (U/P) of Li+ and 27Co-EDTA are about 1.4. On average, in severely dehydrated frogs CCoEDTA decreases to 6.2 ml/kg/hr, CLi to 2.4 ml/kg/hr, and (U/P)CoEDTA and (U/P)Li rise to 8.4 (max = 15.2) and 3.2 (max = 5.5), respectively. FELi makes about 0.4, i.e. in these animals, rather than in well hydrated ones, a noticeable lithium reabsorption in the kidney-urinary bladder complex is observed. Obtained data are discussed from the point of view that in amphibian kidneys (as in mammalian ones) the lithium clearance may serve as a measure of end-proximal fluid delivery and observed reabsorption of Li+ in the total kidney-urinary bladder complex in fact characterizes the reabsorption of Na+ and H2O in the proximal tubule.