Low Fractional Excretion Of Sodium Research Articles

Prolonged Controlled Oxygenated Rewarming Improves Immediate Tubular Function and Energetic Recovery of Porcine Kidneys During Normothermic Machine Perfusion.

Normothermic machine perfusion (NMP) is typically performed after a period of hypothermic preservation, which exposes the kidney to an abrupt increase in temperature and intravascular pressure. The resultant rewarming injury could be alleviated by gradual rewarming using controlled oxygenated rewarming (COR). This study aimed to establish which rewarming rate during COR results in the best protective effect on renal rewarming injury during subsequent NMP. Twenty-eight viable porcine kidneys (n = 7/group) were obtained from a slaughterhouse. After these kidneys had sustained 30 min of warm ischemia and 24 h of oxygenated HMP, they were either rewarmed abruptly from 4-8 °C to 37 °C by directly initiating NMP or gradually throughout 30, 60, or 120 min of COR (rate of increase in kidney temperature of 4.46%/min, 2.20%/min, or 1.10%/min) before NMP. Kidneys that were rewarmed during the course of 120 min (COR-120) had significantly lower fractional excretion of sodium and glucose at the start of NMP compared with rewarming durations of 30 min (COR-30) and 60 min (COR-60). Although COR-120 kidneys showed superior immediate tubular function at the start of normothermic perfusion, this difference disappeared during NMP. Furthermore, energetic recovery was significantly improved in COR-30 and COR-120 kidneys compared with abruptly rewarmed and COR-60 kidneys. This study suggests that a rewarming rate of 1.10%/min during COR-120 could result in superior immediate tubular function and energetic recovery during NMP. Therefore, it may provide the best protective effect against rewarming injury.

Renin-Angiotensin-Aldosterone System Activation and Diuretic Response in Ambulatory Patients With Heart Failure

Rationale & ObjectiveHeart failure treatment relies on loop diuretics to induce natriuresis and decongestion, but the therapy is often limited by diuretic resistance. We explored the association of renin-angiotensin-aldosterone system (RAAS) activation with diuretic response.Study DesignObservational cohort.Setting & PopulationEuvolemic ambulatory adults with chronic heart failure were administered torsemide in a monitored environment.PredictorsPlasma total renin, active renin, angiotensinogen, and aldosterone levels. Urine total renin and angiotensinogen levels.OutcomesSodium output per doubling of diuretic dose and fractional excretion of sodium per doubling of diuretic dose.Analytical ApproachRobust linear regression models estimated the associations of each RAAS intermediate with outcomes.ResultsThe analysis included 56 participants, and the median age was 65 years; 50% were women, and 41% were Black. The median home diuretic dose was 80-mg furosemide equivalents. In unadjusted and multivariable-adjusted models, higher levels of RAAS measures were generally associated with lower diuretic efficiency. Higher plasma total renin remained significantly associated with lower sodium output per doubling of diuretic dose (β = −0.41 [−0.76, −0.059] per SD change) with adjustment; higher plasma total and active renin were significantly associated with lower fractional excretion of sodium per doubling of diuretic dose (β = −0.48 [−0.83, −0.14] and β = −0.51 [−0.95, −0.08], respectively) in adjusted models. Stratification by RAAS inhibitor use did not substantially alter these associations.LimitationsSmall sample size; highly selected participants; associations may not be causal.ConclusionsAmong multiple measures of RAAS activation, higher plasma total and active renin levels were consistently associated with lower diuretic response. These findings highlight the potential drivers of diuretic resistance and underscore the need for high-quality trials of decongestive therapy enhanced by RAAS blockade.

47-Year-Old Woman With Bilateral Flank Pain

47-Year-Old Woman With Bilateral Flank Pain

High expression of a vascular stricture-related marker is predictive of an early response to tolvaptan, and a low fractional excretion of sodium is predictive of a poor long-term survival after tolvaptan administration for liver cirrhosis.

Tolvaptan is a newly available diuretic that has a specific function in water reabsorption inhibition. Given that spironolactone or furosemide induces the aggravation of cirrhotic hyponatremia and dehydration, tolvaptan affects the management strategy of liver cirrhosis. Representative predictive markers of its response include renal function-related markers such as urea nitrogen or creatinine. However, vascular function-related markers have not been well investigated. We investigated the effect of the vascular function-related marker asymmetric dimethylarginine (ADMA) and the effective arterial blood volume (EABV) marker, fractional excretion of sodium (FENa), on the early tolvaptan response and survival in liver cirrhosis. We prospectively recruited 49 patients who required add-on tolvaptan for refractory ascites or edema. Laboratory data were obtained immediately before and 1day after tolvaptan administration. Patients exhibiting >1.5kg weight loss after 1week were categorized as early responders to tolvaptan. Patients were followed for a median of 200days and were assessed for survival. Early responders showed lower creatinine levels (<1.0mg/dL), and higher ADMA levels (≥0.61nmol/mL) than others in a multivariate analysis. Patients with a shorter survival were positive for hepatocellular carcinoma and had a low FENa (<0.35%). Early responders showed higher ADMA levels reflecting vascular stricture, suggesting that higher vascular tonus is required for a tolvaptan early response. Patients with a shorter survival showed a lower FENa, reflecting a lower EABV and suggesting that adequate EABV is required for the prolonged survival after tolvaptan administration.

Hepatic and renal protective effects of quercetin in ferrous sulfateinduced toxicity.

Iron is a vitally important element for the maintenance of health in living organisms. But, iron overload can be toxic. This study investigated the protective efficacy of quercetin against ferrous sulfate-induced oxidative stress, hepato- and nephrotoxicity in rats. There were five experimental groups (n = 7): Sham (distilled water, 1 ml/day for 14 days, i.p.), Quer (quercetin, 50 mg/kg/day for 14 days, i.p.), DMSO (dimethyl sulfoxide 1%, 1 ml i.p.), Fe (ferrous sulfate, 30 mg/kg/day for 14 days, i.p.), Fe+Quer (ferrous sulfate, 30 mg/kg/day for 14 days; quercetin, 50 mg/kg/day for 11 days from fourth day of ferrous sulfate injection). Blood, 24-h urine and tissue samples were collected at the end of experiment. Quercetin prevented ferrous sulfate-induced hepatotoxicity and nephrotoxicity as indicated by decreased activities of serum hepatic marker enzymes and decreased serum bilirubin concentration, higher levels of serum triglyceride, cholesterol, glucose, albumin and total protein, as well as higher creatinine clearance and lower fractional excretion of sodium. Besides, quercetin decreased malondialdehyde levels and histological damages in the liver and kidney of Fe group as compared with sham, DMSO and Quer groups. The protective effect of quercetin relies, at least partially, on its antioxidative effect which leads to decreased lipid peroxidation as well as iron-chelating property.

Urinary output and fractional excretion of sodium and urea as indicators of transient versus intrinsic acute kidney injury during early sepsis

IntroductionThe pathophysiology of acute kidney injury (AKI) in sepsis is ill defined. We investigated parameters associated with low glomerular filtration, and their predictive value to discriminate transient from intrinsic septic AKI.MethodsIn 107 sepsis patients, AKI was defined by the Risk, Injury, Failure, Loss of Kidney Function, End-stage renal disease (RIFLE) urinary output or serum creatinine criterion, or both. Transient AKI (TAKI) versus intrinsic AKI was defined as RIFLE R, I, or F on the first day evolving to no AKI or not, respectively, over the following 5 days. Fractional excretion of sodium (FENa), urea (FEUrea), and NGAL (FENGAL) at admission (d0t0), 4 (d0t4), and 24 hours (d1) was determined.ResultsIncluding versus not including the urinary-output criterion of RIFLE increased AKI from 43% to 64.5%. Median uNGAL levels and FENGAL were lower in no AKI versus transient AKI when AKI was defined based on creatinine (P = 0.002 and P = 0.04, respectively), but not when based on urinary output (P = 0.9 and P = 0.49, respectively). FENa < 1% and FEUrea <35% was present in 77.3% and 63.2% of patients. Urinary NGAL was higher (P < 0.001) in those with high versus low fractional sodium excretion, but this was only in patients with transient or intrinsic AKI (P < 0.001 in subgroups), and not in patients without AKI. The negative predictive value for either intrinsic AKI or not restoring diuresis in patients with FENa > 0.36% and FEUrea > 31.5% was 92% and 94.5% respectively.ConclusionsA low FENa and FEUrea is highly prevalent in the first hours of sepsis. In sepsis, oliguria is an earlier sign of impending AKI than increase in serum creatinine. A combination of a high FENa and a low FEUrea is associated with intrinsic AKI, whereas a combined high FENa and FEUrea is strongly predictive of transient AKI.

Fractional Excretion of Uric Acid as a Predictor for Saline Responsiveness in Long-Term Kidney Transplant Patients

Background/Aims: Subclinical hypovolemia may contribute to allograft dysfunction in long-term kidney transplant (KT) patients. In order to predict responsiveness to saline hydration, indices for tubular transport were investigated. Methods: Fifty-four clinically euvolemic long-term KT patients with recently aggravated azotemia were given intravenous hydration as follows: 0.9% saline 5 ml/kg over 1 h, followed by 0.9% saline 1 ml/kg/h over 12 h and 1 liter of 0.45% saline over the next 24 h. Serum and urine data were collected and analyzed to assess responses. Results: In all patients, saline hydration relieved azotemia, as shown by blood urea nitrogen (46.9 ± 17.2 vs. 39.3 ± 15.4 mg/dl; p < 0.01) and serum creatinine levels (2.9 ± 1.1 vs. 2.5 ± 1.1 mg/dl; p < 0.01) on day 0 versus day 2. In 38 patients, serum creatinine did not increase in the following month (70% responders). Compared with the nonresponders, the responders had a higher urine-to-plasma creatinine ratio and lower fractional excretion of sodium, uric acid and urea at admission. Multivariate logistic regression analysis revealed that responsiveness to saline hydration was independently associated with lower fractional excretion of uric acid. Conclusion: Subclinical hypovolemia should be considered in long-term KT patients with azotemia of unexplainable causes. Fractional excretion of uric acid may predict responsiveness to saline hydration.

Glomeruloid haemangiomas associated with generalized oedema in a patient with atypical POEMS syndrome.

A 55-year-old woman was admitted for evaluation of progressive generalized oedema and mild kidney dysfunction (serum creatinine 1.12 mg/dL; blood urea nitrogen 45 mg/dL). On admission, generalized oedema, transudative pleural effusion, collapsed inferior vena cava and low fractional excretion of sodium (0.14%) suggested severe volume depletion due to plasma extravasation; however, its aetiology could not be attributed to decreased colloid osmotic pressure (serum total protein 6.4 g/dL). Further examination of the patient revealed hepatosplenomegaly, slowing of nerve conduction velocities, albuminocytological dissociation in the cerebrospinal fluid, and multiple cherry-red papules on the neck and chest (Figure 1). These features were suggestive of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome, also called osteosclerotic myeloma or Crow–Fukase syndrome. However, this case did not entirely fulfil the diagnostic criteria because monoclonal plasma cell disorders were not detected [1]. The skin biopsy revealed lesions consistent with glomeruloid haemangiomas (Figure 2), which is considered to be a specific marker for POEMS syndrome [2]. Furthermore, the serum level of vascular endothelial growth factor (VEGF), which is involved in the pathogenesis of POEMS syndrome [1], was extremely elevated to 16 300 pg/mL. These findings led us to make a diagnosis of atypical POEMS syndrome and speculate that microvascular hyperpermeability induced by excess VEGF resulted in generalized oedema and effusions associated with severe volume depletion [3,4]. In patients with oedema and effusions of unknown cause, one should consider the possibility of disorders associated with VEGF overproduction including POEMS syndrome. Fig. 1 Multiple eruptive cherry-red papules on the neck. Fig. 2 (a) Dermal lesions showing vascular structures with capillary loops, resembling renal glomeruli (haematoxylin–eosin stain). (b) Endothelial cells stained for CD 31.

Effect of acute hyperglycaemia on selected plasma and urinary cytokine antagonists in Type 1 diabetes mellitus.

Several cytokines have been implicated in the pathogenesis of diabetic nephropathy. Their ability to generate a biological response in vivo is modulated by specific antagonists and soluble receptors. The aims of the study were firstly, to measure the interleukin 1 receptor antagonist (IL-1ra) and tumour necrosis factor alpha soluble receptors p55 (TNFsr1) and p75 (TNFsr2) in plasma and urine, and secondly to test their response to acutely induced hyperglycaemia in Type 1 diabetes mellitus (DM 1). Plasma concentrations and urinary excretions of IL-1ra, TNFsr1 and TNFsr2 were measured in two 90-min periods of glycaemic clamp-induced normoglycaemia and hyperglycaemia (5 and 12 mmol/l; study 1) and during time-controlled normoglycaemia (5 and 5 mmol/l; study 2) in 20 Type 1 diabetic patients with normal albumin excretion and normal glomerular filtration rate, and in 11 weight-, age- and sex-matched healthy control subjects. The plasma concentrations of IL-1ra, TNFsr1 and TNFsr2 were comparable in Type 1 diabetic patients and control subjects, and no significant changes during study 1 and study 2 were found. Urinary IL-1ra excretion measured during normoglycaemia was higher in Type 1 diabetic patients compared to control subjects ( p<0.05). In diabetic patients, it decreased in study 1 compared to study 2 ( p<0.05), while it did not change in control subjects. The urinary excretions of TNFsr1 and TNFsr2 during normoglycaemia were comparable in diabetic patients and controls. In diabetic patients, hyperglycaemia decreased TNFsr1 excretion (study 1 vs study 2; p<0.01), while TNFsr1 excretion did not change in control subjects. Hyperglycaemia did not affect TNFsr2 excretion in diabetic patients, while it led to an increase in TNFsr2 excretion in control subjects (study 1 vs study 2; p<0.05). Despite comparable renal haemodynamics, diabetic patients had lower fractional excretion of sodium compared to control subjects ( p<0.01). No significant relationships between cytokine antagonists and renal functions have been found. Type 1 diabetic patients with normal renal haemodynamics are associated with impaired regulation of renal IL-1ra, TNFsr1 and TNFsr2 production with a potential impact on local control of cytokine activity in the kidneys.

Effects of immunosuppressant FTY720 on renal and hepatic hemodynamics in the rat.

FTY720 is a novel immunomodulator that may provide an opportunity for a reduction in calcineurin inhibitor dosage in transplant recipients with renal/hepatic side effects. However, the effects of FTY720 on renal or hepatic hemodynamics are unknown. The aim of this study was to establish the hemodynamic and renal actions of FTY720 at therapeutically relevant dosages. The effects of acute and repeat oral administration of FTY720 on systemic, renal, and hepatic hemodynamics were investigated in the anesthetized male Lewis rat. Renal function and renal tubular parameters were examined in animals that received repeat high dosage of FTY720. Seven-day oral administration of FTY720 did not cause any significant changes in markers of hepatocyte injury, nor did it cause any reduction in renal function (elevated urea and creatinine). Histological examination of liver and kidney from animals treated with repeat FTY720 for 1 or 3 weeks did not reveal any sclerosis, tubular changes, infiltrates, or fibrosis. Hepatocyte, vascular, and biliary structures were normal. Compared with the vehicle (saline), oral administration of FTY720 at dosages up to 5 mg/kg/day for 1 week did not have any significant effects on systemic, hepatic, or renal hemodynamics. Five min after intravenous FTY720 administration (1 mg/kg), mean arterial pressure (MAP) rose to 114+/-3.3% of baseline (P <0.01) before returning to the normal range within 30-45 min. Lower doses of FTY720 (0.3 and 0.5 mg/kg, i.v.) did not affect MAP. Renal cortical perfusion, renal artery blood flow, and renal vascular resistance were not altered by FTY720 at i.v. doses up to 1 mg/kg. Animals that received FTY720 (5 mg/kg/day) for 3 weeks showed a significant reduction in body weight (-4.8+/-1% of baseline at 3 weeks, P <0.001); however, weight-adjusted creatinine clearance, 24 h urine production, and urine osmolality were not different from those in control animals (0.71+/-0.1 vs. 0.74+/-0.1 ml/min/100 g, 2.63+/-0.2 vs. 3.12+/-0.2 ml/100 g, and 2003+/-33 vs. 1966+/-56 mOsm/kg, respectively). FTY720 at the same repeat oral dosage was, nevertheless, associated with a significantly lower 24 h sodium excretion and a significantly lower fractional excretion of sodium compared with those in control animals (223.4+/-35 vs. 304.5+/-50 micromol/100 g and 1.75+/-0.3 vs. 2.23+/-0.3%, respectively; P <0.05). Our data indicate that, at least in the short term, oral FTY720 does not cause any significant adverse effects on renal or hepatic hemodynamics, nor does it cause any reduction in glomerular perfusion and thus may provide reasonable rescue/add-on therapy in calcineurin-inhibitor treated transplant recipients. At high repeat oral dosages, however, FTY720 may alter renal handling of sodium.

Drug-induced acute interstitial nephritis

Drug-induced acute interstitial nephritis

Renal sodium handling in preascitic cirrhosis

Editor,—We read with interest the commentary by Clària and Rodés ((1999) Gut 45:639–639; [OpenUrl][1][Abstract/FREE Full Text][2]) on our paper published in Gut which re-examined the mechanisms of renal sodium retention in patients with preascitic cirrhosis.1 In summary, in our patients we observed indirect evidence of expanded central vascular fluid volume compared with healthy controls and thought this physiopathological alteration was due to slightly reduced values of glomerular filtration rate (measured as creatinine clearance) and, mainly, to increased distal tubular retention of sodium when expressed as a fraction of the filtered sodium load that is reabsorbed by the distal nephron (26.9 (6.7)% v 12.5 (3.4)%, respectively; p<0.05).1 Clària and Rodés advanced two criticisms and affirmed that our results, obtained by means of the lithium clearance and fractional excretion technique, may be influenced by two fundamental flaws. Firstly, the reliability of lithium clearance as a marker of distal fluid delivery in clinical conditions characterised by low fractional sodium excretion (below 0.40%) has not been proved due to possible lithium reabsorption in the distal nephron.2 Secondly, in … Professor J Rodés, Liver Unit, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain.rodes{at}medicina.ub.es [1]: {openurl}?query=rft.jtitle%253DGut%26rft.stitle%253DGut%26rft.aulast%253DBortolotti%26rft.auinit1%253DF%26rft.volume%253D46%26rft.issue%253D5%26rft.spage%253D715%26rft.epage%253D718%26rft.atitle%253DLong%2Bterm%2Beffect%2Bof%2Balpha%2Binterferon%2Bin%2Bchildren%2Bwith%2Bchronic%2Bhepatitis%2BB%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fgut.46.5.715%26rft_id%253Dinfo%253Apmid%252F10764718%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=gutjnl&resid=46/5/715&atom=%2Fgutjnl%2F48%2F5%2F740.2.atom

Renal sodium handling in pre-ascitic cirrhosis

Editor,—We read with interest the commentary by Claria and Rodes ( (1999) Gut 45:639–639; [OpenUrl][1][Abstract/FREE Full Text][2] ) on our paper published in Gut which re-examined the mechanisms of renal...

Exertional rhabdomyolysis in quarter horses and thoroughbreds: one syndrome, multiple aetiologies.

The purpose of this study was to determine if chronic exertional rhabdomyolysis (ER) in Quarter Horses and Thoroughbreds represents one or several distinct myopathies. Eighteen Quarter Horses and 18 Thoroughbreds with ER were selected from cases presented to the Veterinary Hospital on the basis of a history of ER, assessment of muscle histopathology, and serum CK activity before and 4 h post exercise. In addition, 2 of 3 of the following parameters were evaluated: muscle glycogen concentrations, thyroid hormones (T3, T4), fractional excretion (FE) of sodium, potassium and chloride. The CK response to training, the metabolic response to a near maximal standardised exercise test (SET), blood glucose concentrations after an i.v. glucose challenge and a skeletal muscle in vitro caffeine contracture test were performed on 5 of the Quarter Horses, selected because of polysaccharide storage myopathy (PSSM), and 5 of the Thoroughbreds. Serum T3 and T4 were all within normal limits. Low FE of sodium and potassium were seen in < 20% of Quarter Horses and Thoroughbreds. Four hours post exercise, CK was increased in 77% of Quarter Horses and 72% of Thoroughbreds with ER. Muscle glycogen concentrations in Quarter Horses with ER were significantly higher than in normal Quarter Horses and Thoroughbreds with ER. No Thoroughbreds, but 15/18 Quarter Horses with ER had abnormal polysaccharide accumulation in muscle biopsies consistent with a diagnosis of PSSM. PSSM Quarter Horses had higher CK activity during training than Thoroughbreds and higher glycogen utilisation with the SET. PSSM Quarter Horses also had significantly enhanced glucose clearance compared to normal Quarter Horses and Thoroughbreds with ER. Thoroughbreds with ER had significantly lower thresholds for caffeine-induced contracture than normal horses and PSSM Quarter Horses. It was concluded that there are multiple causes for exertional rhabdomyolysis. In Quarter Horses, rhabdomyolysis is commonly due to a glycogen storage disorder, PSSM, and is readily expressed in untrained horses. In Thoroughbreds, ER is commonly due to an underlying abnormality of muscle contraction. Rhabdomyolysis in Thoroughbreds, however, is only expressed intermittently when key stressors are present.

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.

Combined fractional excretion of sodium and urea better predicts response to saline in hyponatremia than do usual clinical and biochemical parameters

The treatment of hyponatremic patients requires physicians to make a therapeutic choice between saline infusion and water restriction. Therefore, they need readily available and reliable parameters to facilitate making that choice. This study was designed to determine whether the use of clearance ratios can help clinicians recognize saline-responding hyponatremic patients. Thirty-five nonedematous, hospitalized, hyponatremic patients were classified according to their history and saline response into four groups: diuretic-taking patients, polydipsic patients, saline responders, and saline nonresponders. Within these four groups, clinical and biochemical volume-related parameters, including clearance ratios, were prospectively evaluated before infusion of 2 L isotonic saline. Clearance ratios as well as usual clinical and biochemical parameters were tested for their accuracy in predicting saline responsiveness. Both positive (70%) and negative (54.5%) predictive values for hypovolemia were unsatisfactory; clinical prediction of hypovolemia was also characterized by low sensitivity (41.1%), but acceptable specificity (80%). In the polydipsia and saline-nonresponder groups, plasma urea and uric acid values tended to be lower than in the diuretic and saline-responder groups. However, the usefulness of these parameters was limited by too large an overlap among the different groups. In both polydipsic patients and saline responders, urinary sodium concentration was low. The combined amount of urinary sodium and potassium in relation to plasma sodium did not discriminate among the different groups. Most helpful in distinguishing among the groups was a combination of several clearance ratios (fractional excretions of sodium, potassium, urea, and uric acid), since the predictive use of each parameter on its own was restricted. The best indicator of saline responsiveness was a low fractional excretion of filtered sodium (< 0.5%) combined with a low fractional excretion of urea (< 55%). The accuracy of clinical evaluation for predicting the state of extracellular fluid volume in hyponatremia is low. The combination of low fractional sodium excretion (< 0.5%) and low fractional urea excretion (< 55%) is the best biochemical way to predict saline response, whereas high fractional potassium excretion (> 20%) indicates diuretic intake.

Low-dose dopamine induces early recovery of recombinant interleukin-2—Impaired renal function

Recombinant interleukin-2 (rIL-2) can produce impairment of renal function with hypotension, fluid retention, elevated blood urea nitrogen, oliguria and low fractional sodium excretion; these side-effects are a common cause of reduction or interruption of rIL-2 infusion. The aim of this study was to investigate the control and treatment of renal toxicity induced by rIL-2 therapy. Here we show that dopamine, at a low dose of 2 micrograms/kg/min, completely prevented renal toxicity induced by rIL-2. While continuing rIL-2 therapy, 24-h continuous infusion of low-dose dopamine produced a rapid normalisation of urine output and a significant decrease in serum creatinine levels and body weight (P < 0.01), with an early and complete recovery of the rIL-2--impaired renal function: mean recovery time of renal function in patients treated with dopamine was significantly lower (P < 0.05) than in nontreated patients (4.8 days vs. 10 days, respectively).

Prostaglandins protect kidneys against ischemic and toxic injury by a cellular effect

The ability of prostaglandins to protect the kidney against ischemic and toxic renal injury was evaluated by in vivo and in vitro models of renal ischemia. The prostaglandin E1 analogue, misoprostol, was found to provide significant protection against ischemia-induced renal dysfunction in rats subjected to 40 minutes of renal artery occlusion. Misoprostol-treated rats had glomerular filtration rates almost threefold greater than control animals, although renal blood flow and renal vascular resistance were not significantly different. Improved tubular function was reflected in a lower fractional excretion of sodium and a higher urine-to-plasma creatinine ratio. Misoprostol also provided similar protection in a model of toxic renal injury produced by mercuric chloride. In an in vitro model employing primary cultures of proximal tubule epithelial cells subjected to hypoxia and reoxygenation, misoprostol limited cell death. Posthypoxic cells had apical membrane disruption and loss of microvilli when examined by transmission electron microscopy. These changes were not seen in misoprostol-treated cells. The "cytoprotective" effect was also produced by prostaglandin E2 and prostacyclin. The ability of prostaglandin E to protect against toxic and ischemic renal injury did not appear to be due to an antioxidant effect because misoprostol did not limit lipid peroxidation in vivo and did not protect against oxidant injury by tert-butyl hydroperoxide in vitro. Although the exact mechanism of prostaglandin protection was not revealed, these studies demonstrate that prostaglandins protect renal tubule epithelial cells from hypoxic injury at the cellular level independent of hemodynamic factors or inflammatory responses. Such a "cytoprotective" effect of prostaglandins may be a generalized phenomenon since it has also been demonstrated in gastrointestinal epithelium.

Effects of amiloride on renal lithium handling in nonazotemic ascitic cirrhotic patients with avid sodium retention.

The reliability of lithium clearance as an index of distal fluid delivery in cirrhosis with ascites and in other clinical conditions characterized by low fractional sodium excretion has not yet been proven. In particular, lithium reabsorption in the amiloride-sensitive segment of the distal tubule, as evidenced in experimental studies, has not been excluded in such clinical conditions. Thus the acute effect of amiloride on renal lithium handling in 15 nonazotemic ascitic cirrhotic patients with avid sodium retention was evaluated after at least 5 days of controlled sodium intake. Renal plasma flow, glomerular filtration rate, fractional sodium excretion, fractional lithium excretion, fractional potassium excretion, fractional excretion of uric acid, plasma renin activity, plasma aldosterone and human atrial natriuretic peptide were evaluated before and for 6 hr after the administration of amiloride (20 mg/os). After amiloride administration a volume replacement scheme was enacted with intravenous amounts of saline solution, determined by the diuretic and natriuretic effect of the drug, to avoid volume depletion. Amiloride induced a prompt and sustained increase in fractional sodium excretion (from 0.28% +/- 0.09% to 1.0% +/- 0.41%, p less than 0.001) and a decrease in fractional potassium excretion (from 9.38% +/- 5.98% to 3.28% +/- 2.24%, p less than 0.0025), whereas it did not affect fractional lithium excretion and fractional excretion of uric acid. No change was observed in renal plasma flow, glomerular filtration rate, plasma renin activity, plasma aldosterone and human atrial natriuretic peptide. It was concluded that lithium is not reabsorbed in the amiloride-sensitive segment of the distal tubule in nonazotemic ascitic cirrhotic patients with avid sodium retention.

Renal effects of continuous infusion of recombinant interleukin-2 in children

Recombinant interleukin-2 (rIL-2) is a new promising treatment for cancer, but is associated with severe renal toxicity. This study is the first to analyse the renal effects of rIL-2 in children. Twenty-one cycles of continuous rIL-2 infusion were studied in 15 patients; mean age was 6.9 years and average weight 18.9 kg. Interstitial fluid retention and oliguria (baseline, 1.7 ml/kg per hour; nadir, 0.5 mg/kg per hour) were associated with hypotension (baseline, 101/56 mm Hg; nadir, 85/43 mm Hg) and decreased intravascular volume (plasma renin activity increased x 10). Weight gain (+7.9%) was observed in 13 cycles whereas weight loss (-6.3%) was shown in 8 cycles because of digestive and cutaneous losses, mainly in the youngest patients. This prerenal azotaemia was characterized by a decrease in creatinine clearance (from 101 to 36 ml/min per 1.73 m2) and a low fractional excretion of sodium (FENa) (from 0.70% to 0.09%). Hypotension and hypovolaemia needed vascular filling (n = 12), dopamine (n = 7) and interruption of rIL-2 (n = 2). Most abnormalities occurred as early as day 2 of therapy and were always reversible after a short period with sodium leakage (diuresis = 2.2 ml/kg per hour, FENa = 2.01%). Hypophosphataemia was associated with low urinary excretion of phosphorus, suggesting an increased uptake of inorganic phosphorus by rapidly proliferating lymphoid cells.