Impact of angiotensin II-mediated stimulation of sodium transporters in the nephron assessed by computational modeling.

Angiotensin II (ANG II) raises blood pressure partly by stimulating tubular Na+ reabsorption. The effects of ANG II on tubular Na+ transporters (i.e., channels, pumps, cotransporters, and exchangers) vary between short-term and long-term exposure. To better understand the physiological impact, we used a computational model of transport along the rat nephron to predict the effects of short- and long-term ANG II-induced transporter activation on Na+ and K+ reabsorption/secretion, and to compare measured and calculated excretion rates. Three days of ANG II infusion at 200 ng·kg-1·min-1 is nonpressor, yet stimulates transporter accumulation. The increase in abundance of Na+/H+ exchanger 3 (NHE3) or activated Na+-K+-2Cl- cotransporter-2 (NKCC2-P) predicted significant reductions in urinary Na+ excretion, yet there was no observed change in urine Na+. The lack of antinatriuresis, despite Na+ transporter accumulation, was supported by Li+ and creatinine clearance measurements, leading to the conclusion that 3-day nonpressor ANG II increases transporter abundance without proportional activation. Fourteen days of ANG II infusion at 400 ng·kg-1·min-1 raises blood pressure and increases Na+ transporter abundance along the distal nephron; proximal tubule and medullary loop transporters are decreased and urine Na+ and volume output are increased, evidence for pressure natriuresis. Simulations indicate that decreases in NHE3 and NKCC2-P contribute significantly to reducing Na+ reabsorption along the nephron and to pressure natriuresis. Our results also suggest that differential regulation of medullary (decrease) and cortical (increase) NKCC2-P is important to preserve K+ while minimizing Na+ retention during ANG II infusion. Lastly, our model indicates that accumulation of active Na+-Cl- cotransporter counteracts epithelial Na+ channel-induced urinary K+ loss.

Is Capillary Electrophoresis a New Tool to Monitor Acute Lithium Poisoning in Human?†.

A 38-year-old man was admitted in the intensive care unit (ICU) after supposed ingestion of 504 sustained-release tablets of Theralithe™ corresponding ~200 g of lithium carbonate. At the admission, ~19.5 h after ingestion, the patient was conscious with trembling limbs, intense thirst, profuse sweats and vomiting and lithium serum concentration was 14.2 mmol/L. Toxicological screenings performed in urine and serum, were negative. Patient was treated with continuous extrarenal epuration by continue veno-venous hemodiafiltration starting (CCVHDF) 24 h post-admission and was carried on until 64 h. After 11 days in ICU, the patient was dismissed to the service without sequelae, and transferred to a psychiatric unit. To follow lithium concentrations in serum, urines and dialysates, we developed a simple, rapid and reliable method by capillary zone electrophoresis (CZE). Separation was achieved in 7 min. The method was linear between 0.14 and 1.44 mmol/L for serum samples, and between 0.07 and to 1.44 mmol/L for urines and dialysates. Limits of quantification were 0.15 mmol/L and 0.07 mmol/L for serum and others fluids, respectively. Intra- and inter-day precisions expressed as CV were systematically inferior to 12.1% for serum and 8.2% for other fluids. Results obtained regarding precision, accuracy, recovery and stability were satisfying, with recoveries ranging from 91.0 to 102.0%. Serum, urine and dialysate samples were measured using CZE and flame photometry. We observed a strong correlation between both methods as assessed by linear regression and Bland-Altman analysis. For the intoxicated patient, the assay was successfully applied to serum, urine and dialysates to determine the amount of lithium present in circulation and excreted. Lithium amounts in dialysates were estimated to correspond to 89% of total lithium excreted during CCVHF session while urine excretion account only for 11%.

Contribution of NHE3 and dietary phosphate to lithium pharmacokinetics.

Lithium is one of the mainstays for the treatment of bipolar disorder despite its side effects on the endocrine, neurological, and renal systems. Experimentally, lithium has been used as a measure to determine proximal tubule reabsorption based on the assumption that lithium and sodium transport go in parallel in the proximal tubule. However, the exact mechanism by which lithium is reabsorbed remains elusive. The majority of proximal tubule sodium reabsorption is directly or indirectly mediated by the sodium-hydrogen exchanger 3 (NHE3). In addition, sodium-phosphate cotransporters have been implicated in renal lithium reabsorption. In order to better understand the role of sodium-phosphate cotransporters involved in lithium (re)absorption, we studied lithium pharmacokinetics in: i) tubule-specific NHE3 knockout mice (NHE3loxloxPax8Cre), and ii) mice challenged with low or high phosphate diets. Intravenous or oral administration of lithium did not result in differences in lithium bioavailability, half-life, maximum plasma concentrations, area under the curve, lithium clearance, or urinary lithium/creatinine ratios between control and NHE3loxloxPax8Cre mice. After one week of dietary phosphate challenges, lithium bioavailability was ~30% lower on low versus high dietary phosphate, possibly the consequence of a smaller area under the curve after oral administration. This was associated with higher apparent lithium clearance after oral administration and lower urinary lithium/creatinine ratios on low versus high dietary phosphate. Collectively, renal NHE3 does not play a role in lithium pharmacokinetics; however, dietary phosphate could have an indirect effect on lithium bioavailability and lithium disposition.

Urinary reference ranges and exposure profile for lithium among an Italian paediatric population.

The aims of the present study were to establish reference values useful in monitoring Lithium (Li) treatment and to trace environmental Li exposure profiles in paediatric age. A cross-sectional study was conducted on a group of healthy Italian children aged 5-11. Data on possible predictors were assessed through a questionnaire, and Li levels in morning and evening urinary samples were determined by ICP-MS technique. The reference intervals for the evening and morning samples were respectively 3.8-51.9µgL-1 or 5.6-60.6µgg-1 creatinine and 4.8-71.7µgL-1 or 4.8-73.2µgg-1 creatinine. Urinary Li levels showed a significantly inverse correlation with age and a positive correlation with urinary creatinine in both the evening and morning samples. No other studied variables influenced Li urinary excretion. These results, obtained using a readily available matrix as urine, can be useful for both environmental research and Li treatment monitoring.

Nonlinear disposition of lithium in rats and saturation of its tubular reabsorption by the sodium-phosphate cotransporter as a cause.

We previously reported the contribution of sodium-phosphate cotransporter to the tubular reabsorption of lithium in rats. In the present study, the dose dependency of the renal handling of lithium was examined in rats. When lithium chloride at 1.25 mg/kg, 2.5 mg/kg and 25 mg/kg was intravenously injected as a bolus, the areas under the plasma concentration-time curve of lithium until 60 minutes were calculated to be 6.23 mEq·min/l, 8.77 mEq·min/l and 64.6 mEq·min/l, respectively. The renal clearance of lithium and its fractional excretion increased with increments in the dose administered. The renal clearance of lithium strongly correlated with the urinary excretion rate of phosphate in the 1.25 mg/kg group (r = 0.840) and 2.5 mg/kg group (r = 0.773), whereas this correlation was weak in the 25 mg/kg group (r = 0.306). The infusion of foscarnet, a typical inhibitor of sodium-phosphate cotransporter, decreased the fractional reabsorption of lithium in rats administered lithium chloride at 2.5 mg/kg, but did not affect it in rats administered 25 mg/kg. These results demonstrate the nonlinearity of the renal excretion of lithium in rats, with the saturation of lithium reabsorption by the sodium-phosphate cotransporter potentially being involved.

Doping control analysis of lithium in horse urine and plasma by inductively coupled plasma mass spectrometry.

Lithium salts are commonly prescribed to treat bipolar disorder in humans. They are effective for the treatment of acute mania and the prophylaxis of manic relapses through long-term use. Although there is no reported legitimate therapeutic use of lithium in horses, its potential mood-stabilizing effect, low cost, and ready availability make lithium salt a potential agent of abuse in equine sports, especially for equestrian competition horses. Lithium can be found in soil, plants, and water, as such it is naturally present in the equine body, thus a threshold is necessary to control its misuse in horses. This paper describes the validation of quantification methods for lithium in equine urine and plasma using inductively coupled plasma mass spectrometry (ICP-MS). Based on a population study of lithium in horse urine and an administration study using a single oral dose of lithium chloride (100 mg) to mimic the daily lithium intake from a diet rich in lithium, a urinary threshold of 5 µg/mL was proposed. Applying this urinary threshold to two other administration studies (a single oral dose of 65 g of lithium chloride, and a single intravenous dose of 2.54 g of lithium chloride), excessive lithium in urine could be detected for 8 days and 2.5 days respectively. The concentrations of lithium in plasma following these three lithium chloride administration trials were also studied. Copyright © 2017 John Wiley & Sons, Ltd.

Recent advances in understanding renal ammonia metabolism and transport.

PURPOSE OF REVIEW: The purpose of this review is to provide a succinct description of the recent findings that advance our understanding of the fundamental renal process of ammonia metabolism and transport in conditions relevant to the clinician. RECENT FINDINGS: Recent studies advance our understanding of renal ammonia metabolism. Mechanisms through which chronic kidney disease and altered dietary protein intake alter ammonia excretion have been identified. Lithium, although it can acutely cause distal renal tubular acidosis, was shown with long-term use to increase urinary ammonia excretion, and this appeared to be mediated, at least in part, by increased Rhcg expression. Gene deletion studies showed that the ammonia recycling enzyme, glutamine synthetase, has a critical role in normal-stimulated and acidosis-stimulated ammonia metabolism and that the proximal tubule basolateral bicarbonate transporter, NBCe1, is necessary for normal ammonia metabolism. Finally, our understanding of the molecular ammonia species, NH3 versus NH4, transported by Rh glycoproteins continues to be advanced. SUMMARY: Fundamental studies have been recently published that advance our understanding of the regulation of ammonia metabolism in clinically important circumstances, and our understanding of the mechanisms and regulation of proximal tubule ammonia generation, and the mechanisms through which Rh glycoproteins contribute to ammonia secretion.

Lack of Effect of Vortioxetine on the Pharmacokinetics and Pharmacodynamics of Ethanol, Diazepam, and Lithium.

INTRODUCTION: Because the multimodal antidepressant vortioxetine is likely to be coadministered with other central nervous system (CNS)-active drugs, potential drug-drug interactions warrant examination. OBJECTIVE: These studies evaluated whether there are pharmacokinetic and/or pharmacodynamic interactions between vortioxetine and ethanol, diazepam, or lithium. METHODS: This series of phase I studies included healthy men and women (only men in the lithium study) aged 18-45 years. The ethanol study was a randomized, double-blind, two-parallel group, four-period crossover study in which subjects received a single dose of vortioxetine (20 or 40 mg) or placebo with or without ethanol, and the diazepam study was a randomized, double-blind, placebo-controlled, two-sequence, two-period crossover study in which subjects received a single dose of diazepam following multiple doses of vortioxetine 10 mg/day or placebo. These two studies evaluated the effect of coadministration on standardized psychomotor parameters and on selected pharmacokinetic parameters of each drug. The lithium study was a single-blind, single-sequence study evaluating the effect of multiple doses of vortioxetine 10 mg/day on the steady-state pharmacokinetics of lithium. RESULTS: Concomitant administration of vortioxetine and single doses of either ethanol or diazepam had no significant effect on the psychomotor performance of subjects compared with administration of ethanol or diazepam alone. Vortioxetine had no significant effect on the pharmacokinetics of ethanol, diazepam, or lithium, and ethanol had no significant effect on the pharmacokinetics of vortioxetine. CONCLUSIONS: Concomitant administration of these agents with vortioxetine was generally well tolerated, with no clinically relevant drug-drug pharmacokinetic or pharmacodynamic interactions identified.

Exposure to lithium through drinking water and calcium homeostasis during pregnancy: A longitudinal study.

There is increasing evidence of adverse health effects due to elevated lithium exposure through drinking water but the impact on calcium homeostasis is unknown. This study aimed at elucidating if lithium exposure through drinking water during pregnancy may impair the maternal calcium homeostasis. In a population-based mother-child cohort in the Argentinean Andes (n=178), with elevated lithium concentrations in the drinking water (5-1660µg/L), blood lithium concentrations (correlating significantly with lithium in water, urine and plasma) were measured repeatedly during pregnancy by inductively coupled plasma mass spectrometry and used as exposure biomarker. Markers of calcium homeostasis included: plasma 25-hydroxyvitamin D3, serum parathyroid hormone (PTH), and calcium, phosphorus and magnesium concentrations in serum and urine. The median maternal blood lithium concentration was 25µg/L (range 1.9-145). In multivariable-adjusted mixed-effects linear regression models, blood lithium was inversely associated with 25-hydroxyvitamin D3 (-6.1nmol/L [95%CI -9.5; -2.6] for a 25µg/L increment in blood lithium). The estimate increased markedly with increasing percentiles of 25-hydroxyvitamin D3. In multivariable-adjusted mixed-effects logistic regression models, the odds ratio of having 25-hydroxyvitamin D3<30nmol/L (19% of the women) was 4.6 (95%CI 1.1; 19.3) for a 25µg/L increment in blood lithium. Blood lithium was also positively associated with serum magnesium, but not with serum calcium and PTH, and inversely associated with urinary calcium and magnesium. In conclusion, our study suggests that lithium exposure through drinking water during pregnancy may impair the calcium homeostasis, particularly vitamin D. The results reinforce the need for better control of lithium in drinking water, including bottled water.

Environmental exposure to lithium during pregnancy and fetal size: a longitudinal study in the Argentinean Andes.

BACKGROUND: Lithium, used for treating bipolar disease, crosses freely the placenta and is classified as teratogenic. It is unclear to what extent environmental lithium exposure may affect fetal growth and development. OBJECTIVES: To elucidate potential effects of lithium exposure through drinking water during pregnancy on fetal size. METHODS: We developed a prospective population-based mother-child cohort (N=194) in an area with highly varying drinking water lithium concentrations (5-1600 µg/L) in northern Argentinean Andes. Blood and urinary lithium concentrations (sampled repeatedly during pregnancy) were measured using inductively coupled plasma mass spectrometry. We measured fetal size by ultrasound in second and third trimesters, and weight, length and head circumference at birth. Multivariable models were used to examine associations between lithium exposure (continuous and in tertiles) and fetal size measures. RESULTS: Lithium in maternal blood (median 25; range 1.9-145 µg/L) and urine (1645; 105-4600 µg/L) was inversely associated (apparently linearly) with all fetal measures (body, head and femur) in the second trimester, and with birth length (ß -0.53 cm per 25 µg/L increase in blood lithium, 95%CI -1.0; -0.052). An increase of 100 µg/L in blood was associated with 2 cm shorter newborns (about one standard deviation). CONCLUSIONS: Lithium exposure through drinking water was associated with impaired fetal size and this seemed to be initiated in early gestation. Further studies are warranted to confirm causality and to understand the mechanisms. If confirmed, these findings have public health relevance and emphasize the need for more data on lithium concentrations in drinking water, including bottled water.

Kinetics of lithium as a lithium chloride dose suitable for conditioned taste aversion in lactating goats and dry sheep.

Lithium chloride (LiCl) is widely used for inducing conditioned taste aversion (CTA) so that livestock will reduce or avoid ingestion of toxic plants and graze groundcover mingled with valuable crops. However, pharmacokinetic studies of LiCl at effective CTA doses are lacking. With this aim, 6 Murciano-Grandina dairy does during late lactation and 6 dry Manchega dairy ewes were orally dosed with 200 and 225 mg LiCl/kg BW, respectively. Does were placed in metabolism cages whereas ewes were group fed in pens. Lithium was measured over 168 (does) and 192 h (ewes) at predefined intervals in plasma, urine, feces, and milk using flame atomic absorption spectroscopy. Plasma Li concentrations reached a maximum at 4 h in does (13.4 ± 1.35 mg Li/L) and 12 h in ewes (17.7 ± 0.8 mg Li/L). The calculated plasma half-lives were 40.3 ± 3.8 and 30.9 ± 2.1 h for does and ewes, respectively. In goats, all Li administered was recovered at 96 h (92 ± 4% in urine, 6.5 ± 1.3% in feces, and 2.8 ± 0.4% in milk); however, the estimated clearance time in feces was 11 and 9 d for does and ewes, respectively. Additionally, maximum Li excretion in doe milk was 15.6 ± 0.5 mg/L, which was approximately half of the calculated effective dose for a 5-kg BW sucking kid. In conclusion, Li kinetics in goats and sheep were similar to cattle and elimination took longer than in monogastric species. The low concentration of Li in feces, urine, and milk, as well as the complete elimination of Li from the body after 1.5 wk allows us to conclude that LiCl is safe and suitable for inducing CTA in ruminants.

Blood pressure in relation to interactions between sodium dietary intake and renal handling.

There is abundant evidence that sodium intake is related to blood pressure. However, the relationship varies between individuals and is probably determined by renal sodium handling. We investigated clinic and ambulatory blood pressure in relation to interactions between sodium dietary intake and renal handling, as assessed by 24-hour urinary sodium excretion and endogenous lithium clearance, respectively. We calculated fractional excretion of lithium and fractional distal reabsorption rate of sodium, as markers of proximal and distal sodium handling, respectively. The 766 subjects included 379 men and 478 ambulatory hypertensive patients. They were never treated (n=697) or did not take antihypertensive medication for ≥2 weeks (n=69). In adjusted analyses, none of the associations of urinary sodium excretion, fractional excretion of lithium, and fractional distal reabsorption rate of sodium with clinic or ambulatory blood pressure were statistically significant (P≥0.09). However, there was significant (P=0.01) interaction between urinary sodium excretion and fractional excretion of lithium in relation to nighttime diastolic blood pressure. In tertile 3 but not tertiles 1 and 2 of fractional excretion of lithium, nighttime diastolic pressure was positively associated with urinary sodium excretion (P=0.03). However, nighttime diastolic pressure was higher in tertile 1 than tertile 3 of fractional excretion of lithium (+2.0 mm Hg; P=0.01), especially in the bottom tertile of urinary sodium excretion (+4.9 mm Hg; P<0.001). Similar trends were observed for nighttime systolic pressure and clinic and 24-hour diastolic pressure. In conclusion, sodium dietary intake and proximal tubular handling interact to be associated with blood pressure.

Relationship between serum lithium, salivary lithium, and urinary lithium in patients on lithium therapy.

Lithium carbonate is used in the treatment of both psychiatric and nonpsychiatric disorders. The aim of this study was to explore the relationship between serum lithium, salivary lithium, and urinary lithium. Blood, saliva, and urine samples were collected from 50 patients, and estimation of serum, salivary, and urine lithium was done using an atomic absorption spectrophotometer. Mean serum lithium was 0.75 ± 0.25 mEq/L, mean salivary lithium was 1.91 ± 0.80 mEq/L, and mean urine lithium was 7.16 ± 4.84 mEq/L. A significant direct correlation was found between serum lithium and salivary lithium (r = 0.695, p < 0.001). This correlation was higher in females (r = 0.770, p < 0.001) when compared to males (r = 0.665, p < 0.001). Even though a significant correlation was found between serum and salivary lithium levels, more studies are needed in this domain to establish salivary therapeutic monitoring as a feasible option for patients on lithium carbonate therapy.

Rapid and simple pretreatment of human body fluids using electromembrane extraction across supported liquid membrane for capillary electrophoretic determination of lithium.

Electromembrane extraction was used for simultaneous sample cleanup and preconcentration of lithium from untreated human body fluids. The sample of a body fluid was diluted 100 times with 0.5 mM Tris solution and lithium was extracted by electromigration through a supported liquid membrane composed of 1-octanol into 100 mM acetic acid acceptor solution. Matrix compounds, such as proteins, red blood cells, and other high-molecular-weight compounds were efficiently retained on the supported liquid membrane. The liquid membrane was anchored in pores of a short segment of a polypropylene hollow fiber, which represented a low cost, single use, disposable extraction unit and was discarded after each use. Acceptor solutions were analyzed using capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C(4) D) and baseline separation of lithium was achieved in a background electrolyte solution consisting of 18 mM L-histidine and 40 mM acetic acid at pH 4.6. Repeatability of the electromembrane extraction-CE-C(4) D method was evaluated for the determination of lithium in standard solutions and real samples and was better than 0.6 and 8.2% for migration times and peak areas, respectively. The concentration limit of detection of 9 nM was achieved. The developed method was applied to the determination of lithium in urine, blood serum, blood plasma, and whole blood at both endogenous and therapeutic concentration levels.

Lithium in drinking water and thyroid function.

BACKGROUND: High concentrations of lithium in drinking water were previously discovered in the Argentinean Andes Mountains. Lithium is used worldwide for treatment of bipolar disorder and treatment-resistant depression. One known side effect is altered thyroid function. OBJECTIVES: We assessed associations between exposure to lithium from drinking water and other environmental sources and thyroid function. METHODS: Women (n=202) were recruited in four Andean villages in northern Argentina. Lithium exposure was assessed based on concentrations in spot urine samples, measured by inductively coupled plasma mass spectrometry. Thyroid function was evaluated by plasma free thyroxine (T4) and pituitary gland thyroid-stimulating hormone (TSH), analyzed by routine immunometric methods. RESULTS: The median urinary lithium concentration was 3,910 µg/L (5th, 95th percentiles, 270 µg/L, 10,400 µg/L). Median plasma concentrations (5th, 95th percentiles) of T4 and TSH were 17 pmol/L (13 pmol/L, 21 pmol/L) and 1.9 mIU/L, (0.68 mIU/L, 4.9 mIU/L), respectively. Urine lithium was inversely associated with T4 [ß for a 1,000-µg/L increase=-0.19; 95% confidence interval (CI), -0.31 to -0.068; p=0.002] and positively associated with TSH (ß=0.096; 95% CI, 0.033 to 0.16; p=0.003). Both associations persisted after adjustment (for T4, ß=-0.17; 95% CI, -0.32 to -0.015; p=0.032; for TSH: ß=0.089; 95% CI, 0.024 to 0.15; p=0.007). Urine selenium was positively associated with T4 (adjusted T4 for a 1 µg/L increase: ß=0.041; 95% CI, 0.012 to 0.071; p=0.006). CONCLUSIONS: Exposure to lithium via drinking water and other environmental sources may affect thyroid function, consistent with known side effects of medical treatment with lithium. This stresses the need to screen for lithium in all drinking water sources.

High-level exposure to lithium, boron, cesium, and arsenic via drinking water in the Andes of northern Argentina.

Elevated concentrations of arsenic in drinking water are common worldwide, however, little is known about the presence of other potentially toxic elements. We analyzed 31 different elements in drinking water collected in San Antonio de los Cobres and five surrounding Andean villages in Argentina, and in urine of the inhabitants, using ICP-MS. Besides confirmation of elevated arsenic concentrations in the drinking water (up to 210 microg/L), we found remarkably high concentrations of lithium (highest 1000 microg/L), cesium (320 microg/L), rubidium (47 microg/L), and boron (5950 microg/L). Similarly elevated concentrations of arsenic, lithium, cesium, and boron were found in urine of the studied women (N=198): village median values ranged from 26 to 266 microg/L of arsenic, 340 to 4550 microg/L of lithium, 34 to 531 microg/L of cesium, and 2980 to 16,560 microg/L of boron. There is an apparent risk of toxic effects of long-term exposure to several of the elements, and studies on associations with adverse human health effects are warranted, particularly considering the combined, life-long exposure. Because of the observed wide range of concentrations, all water sources used for drinking water should be screened for a large number of elements; obviously, this applies to all drinking water sources globally.

Dietary sodium intake in a sample of adult male population in southern Italy: results of the Olivetti Heart Study.

BACKGROUND/OBJECTIVES: To assess dietary habitual sodium intake and the association between daily sodium intake and anthropometric indices, food habits and hypertension in the sample of adult male population participating in the Olivetti Heart Study. SUBJECTS/METHODS: The study population was composed of 940 men participating in the 2002-2004 follow-up examination of the Olivetti Heart Study. Blood pressure, anthropometric indices, biochemical parameters and sodium excretion in a 24-h urine collection were measured. The frequency of consumption of selected foods was estimated by a food frequency questionnaire (FFQ) capturing the previous year data. In a subgroup of the study population (n=138), the fractional excretion of sodium was estimated by endogenous lithium clearance. RESULTS: Dietary sodium intake estimated by 24 h urinary excretion was 203+/-70 mmol/day. Sodium excretion was significantly lower in treated hypertensive patients and higher in overweight/obese participants when compared with normotensive and normal-weight individuals, respectively. In addition, the inverse correlation detected in normal-weight individuals (r=-0.321; P<0.05) between fractional proximal tubular sodium reabsorption and dietary sodium intake was disrupted in overweight/obese individuals (r=0.058; P=NS). The independent determinants of 24 h urinary sodium excretion were body mass index (BMI), the occurrence of antihypertensive treatment, and frequency of consumption of pasta and cold cuts. CONCLUSIONS: Habitual salt intake in this sample of male adult population in southern Italy was well above the recommended amounts. A higher salt intake and an altered renal sodium handling were observed in overweight and obese participants. Sodium intake was only slightly reduced in hypertensive participants on pharmacological therapy.

Glomerular hyperfiltration and increased proximal sodium reabsorption in subjects with type 2 diabetes or impaired fasting glucose in a population of the African region.

BACKGROUND. Glomerular hyperfiltration (GHF) is a well-recognized early renal alteration in diabetic patients. As the prevalence of GHF is largely unknown in populations in the African region with respect to normal fasting glucose (NFG), impaired fasting glucose (IFG) and type 2 diabetes [diabetes mellitus (DM)], we conducted a cross-sectional study in the Seychelles islands among families including at least one member with hypertension. METHODS. The glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and proximal tubular sodium reabsorption were measured using inulin, p-aminohippurate (PAH) and endogenous lithium clearance, respectively. Twenty-four-hour urine was collected on the preceding day. RESULTS. Of the 363 participants (mean age 44.7 years), 6.6% had IFG, 9.9% had DM and 63.3% had hypertension. The prevalence of GHF, defined as a GFR >140 ml/min, was 17.2%, 29.2% and 52.8% in NFG, IFG and DM, respectively (P trend <0.001). Compared to NFG, the adjusted odds ratio for GHF was 1.99 [95% confidence interval (CI) 0.73-5.44] for IFG and 5.88 (2.39-14.45) for DM. Lithium clearance and fractional excretion of lithium were lower in DM and IFG than NFG (P < 0.001). CONCLUSION. In this population of African descent, subjects with impaired fasting glucose or type 2 diabetes had a high prevalence of GHF and enhanced proximal sodium reabsorption. These findings provide further insight on the elevated incidence of nephropathy reported among African diabetic individuals.