Refeeding syndrome as described in 1507 by Antonio Benivieni in Florence.

In 1981, Weinsier and Krumdieck described death resulting from overzealous total parenteral nutrition in two chronically malnourished, but stable, patients given aggressive total parenteral nutrition. This was the birth of what is now called the refeeding syndrome, a nutrition-related disorder associated with severe electrolyte disturbances. The purpose of this work is to demonstrate that refeeding syndrome was first described medically in Florence by Antonio Benivieni in 1507 in his book On Some Hidden and Remarkable Causes of Diseases and Cures. What we now know as refeeding syndrome was described in Report No. LVII of that book. The condition occurred as a result of the famine that affected Florence in 1496. The report documents (i) death due to starvation, (ii) death due to ingestion of deteriorated/toxic foods (inevitable in times of famine when healthy food is scarce), (iii) death caused by excessive food ingestion after forced, prolonged abstinence from food in adults, (iv) the death of breast-fed children and of their starved mothers eating to satiety and (v) the more favourable clinical outcome of those admitted to hospitals. It is possible that Benivieni was inspired by the description of the deaths of starved deserters in the book The Jewish War (70 AD) by the Romano-Jewish historian Flavius Josephus. Nevertheless, Benivieni wrote the first medical account of the central clinical features of refeeding syndrome. The main, broad clinical aspects of refeeding syndrome, described by Weinsier and Krumdieck in 1981, had been documented in medical literature four centuries earlier by Benivieni.

John XXI, the Pope Philosopher and Physician-Scientist of Portuguese Origins Died of Crush Syndrome in 1277.

The aim of this work is to refer on the death due to crush syndrome in 1277 of Pope John XXI, philosopher, logician, anatomist, physician scientist, university professor of medicine at the university of Siena and author of books adopted for nearly 4 centuries in universities in the Middle Ages. The Pope died crushed by the ceiling of his office which had been built in rush to meet his need for a quiet and warm place, his need of light and nature. There he attended to his duties of governing the church, studied fine theological questions, inspected the stars, made experiments and discussed with the renowned ophthalmologists who in those days made Viterbo the center of the study on vision. Following the fall of the ceiling of his apartment, John XXI was extracted alive from among the pieces of wood and stones. However, a few days after the disaster, he died in bad conditions (miserabiliter). He experienced a typical death due to crush syndrome which was described for the first time by Antonino D'Antona, following the Messina-Reggio Calabria 1908 earthquake. He was born (c. 1210-1220) in Lisbon as Pedro Hispano (Peter of Spain). He had regular trivium and quadrivium courses at the University of Paris under Albertus Magnus, a talented naturalist. He became Master of Arts, then studied medicine out of Paris (probably Montpellier or Salerno). He wrote three treatises (On the eye (De oculo), The Treasury of Medicines for the Poor (Thesaurus Pauperum) and Little Summaries of Logic (Summulae Logicales)) which were used in the European universities from the 13th to the beginning of the 18th century. Pedro Hispano was advisor of King Alphonso III for affairs inherent to the Church, bishop of Braga and then Cardinal Bishop of Tusculum and Pope as John XXI. He was buried in the Cathedral of Viterbo, the city where he had settled the seat of the Pontiff.

A decrease in aquaporin 2 excretion is associated with bed rest induced high calciuria.

BACKGROUND: Exposure to microgravity or immobilization results in alterations of renal function, fluid redistribution and bone loss, which couples to a rise of urinary calcium excretion. We recently demonstrated that high calcium delivery to the collecting duct reduces local Aquaporin-2 (AQP2) mediated water reabsorption under vasopressin action, thus limiting the maximal urinary concentration and reducing calcium saturation. To investigate renal water balance adaptation during bed rest, a model to mimic the effects of microgravity on earth, the effect of changes in urinary calcium on urinary AQP2 excretion were assessed. METHODS: Ten healthy men (aged 21-28 years) participated in the experiment. Study design included 7 days of adaptation and 35 days of continuous bed rest (days -6 to 0 and 1 to 35, respectively) under controlled diet. Food records and 24-hour urine samples were collected daily from day -3 to 35. Changes in blood hematocrit were used as an indirect index of plasma volume changes. AQP2 excretion was measured by ELISA. RESULTS: Bed rest induced bone demineralization and a transient increase in urinary calcium followed by transient decrease in AQP2 excretion, which can reduce the urine concentrating ability causing plasma volume reduction. The return of calciuria to baseline was followed by a recovery of AQP2 excretion, which allows for a partial restoration of plasma volume. CONCLUSIONS: These results further support the view that urinary calcium can modulate the vasopressin-dependent urine concentration through a down-regulation of AQP2 expression/trafficking. This mechanism could have a key role in the prevention of urine super-saturation due to hypercalciuria.

Protein intake and kidney function in the middle-age population: contrast between cross-sectional and longitudinal data.

BACKGROUND: Protein intake is considered a determinant of glomerular filtration rate (GFR). Urinary urea is an objective marker of protein intake. The population-based study investigated, cross-sectionally and longitudinally, the association of protein intake with GFR, indexed by estimated GFR (eGFR). METHODS: Data were collected on overnight urinary urea, serum creatinine (S-cr), eGFR and other variables in 1522 men and women aged 45-64 years who participated in the Gubbio study (baseline). S-Cr, eGFR and other variables were re-assessed in 1144 of the 1425 survivors after 12-year follow-up. RESULTS: At baseline, mean ± SD was 84.0 ± 11.4 mL/min × 1.73 m(2) for eGFR calculated by CKD-Epi equation and 1.34 ± 0.57 g/day per kg of ideal weight for protein intake assessed by measurements of overnight urine excretion of urea nitrogen. Cross-sectional analyses of baseline data indicated a positive correlation of protein intake with eGFR (R = 0.180, P < 0.001). In multi-variable regression, 1 g/day higher protein intake related to 4.7 mL/min × 1.73 m(2) higher eGFR [95% confidence interval (CI) = 3.7/5.7]. At follow-up, mean ± SD of 12-year eGFR change was -11.6 ± 9.0 mL/min × 1.73 m(2). Baseline protein intake correlated with more negative eGFR change (R = -0.251, P < 0.001). In multi-variable regression, 1 g/day higher protein intake related to -4.1 mL/min × 1.73 m(2) more negative eGFR change (95% CI = -5.1/-3.1) and to 1.78 risk for incidence of eGFR < 60 mL/min × 1.73 m(2) (95% CI = 1.15/2.78). CONCLUSIONS: In middle-aged adults, high protein intake is associated cross-sectionally with higher GFR but longitudinally with greater GFR decline over time.

The enlightenment kidney-nephrology in and about the eighteenth century.

The intellectual movement of inquiry by direct observation and inductive reasoning to acquire new knowledge matured in the Enlightenment. In medicine, personal observation as the prime mover of investigation began in anatomy, and gradually extended into studies of function, site of disease, and composition of body fluids. This led to the generation of new information on renal structure, function, and urine composition in health and to some extent in disease. Studies on the dissected, injected, and teased kidneys have left us with many of the eponymous renal structures described by Eustachio, Bellini, Malpighi, and Ferrein. Subsequent studies by Haller of the renal circulation and scrutiny of the separation of serous fluid from blood in the renal cortical glandular components established the beginnings of renal physiology. The movement to integrate chemistry into medicine championed by Boerhaave, which launched studies of urine composition in diabetes, urolithiasis, and gout led to the exploration of a chemical basis of other diseases. Albuminous precipitate in the urine of a dropsical case was described by Cotugno, but its association with kidney disease went unappreciated. Most of the new information on the kidney was communicated to and discussed in the increasing number of new scientific societies that were being formed, and transmitted to the eager members of the learned bourgeoisie of the period in the Encyclopédie of Diderot and d'Alembert.

Hyperhomocysteinemia in chronic renal failure: alternative therapeutic strategies.

Chronic renal failure and uremia represent states wherein high blood levels of homocysteine, a cardiovascular risk factor, are largely resistant to folate therapy. Indeed, normalization of homocysteine levels through vitamin administration is rarely achieved in this population, and this fact could explain, among other causes, the negative results of intervention trials designed to lower cardiovascular risk. Dialysis itself lowers homocysteine levels, albeit transitorily. N-acetylcysteine therapy could induce an additional decrease in homocysteine removal during dialysis, thus representing an alternative approach in the attempt to lower cardiovascular risk in these patients.

Therapy of hyperhomocysteinemia in hemodialysis patients: effects of folates and N-acetylcysteine.

OBJECTIVE: Uremia represents a state where hyperhomocysteinemia is resistant to folate therapy, thus undermining intervention trials' efficacy. N-acetylcysteine (NAC), an antioxidant, in addition to folates (5-methyltetrahydrofolate, MTHF), was tested in a population of hemodialysis patients. DESIGN: The study is an open, parallel, intervention study. SETTING: Ambulatory chronic hemodialysis patients. SUBJECTS: Clinically stable chronic hemodialysis patients, on hemodialysis since more than 3 months, undergoing a folate washout. Control group on standard therapy (n = 50). INTERVENTION: One group was treated with intravenous MTHF (MTHF group, n = 48). A second group was represented by patients treated with MTHF, and, during the course of 10 hemodialysis sessions, NAC was administered intravenous (MTHF + NAC group, n = 47). MAIN OUTCOME MEASURE: Plasma homocysteine measured before and after dialysis at the first and the last treatment. RESULTS: At the end of the study, there was a significant decrease in predialysis plasma homocysteine levels in the MTHF group and MTHF + NAC group, compared with the control group, but no significant difference between the MTHF group and MTHF + NAC group. A significant decrease in postdialysis plasma homocysteine levels in MTHF + NAC group (10.27 ± 0.94 µmol/L, 95% confidence interval: 8.37-12.17) compared with the MTHF group (16.23 ± 0.83, 95% confidence interval: 14.55-17.90) was present. In the MTHF + NAC group, 64% of patients reached a postdialysis homocysteine level <12 µmol/L, compared with 19% in the MTHF group and 16% in the control group. CONCLUSIONS: NAC therapy induces a significant additional decrease in homocysteine removal during dialysis. The advantage is limited to the time of administration.

Hydrogen sulfide, a toxic gas with cardiovascular properties in uremia: how harmful is it?

Hydrogen sulfide (H(2)S) is a poisonous gas which can be lethal. However, it is also produced endogenously, thus belonging to the family of gasotransmitters along with nitric oxide and carbon monoxide. H(2)S is in fact involved in mediating several signaling and cytoprotective functions, for example in the nervous, cardiovascular, and gastrointestinal systems, such as neuronal transmission, blood pressure regulation and insulin release, among others. When increased, it can mediate inflammation and apoptosis, with a role in shock. When decreased, it can be involved in atherosclerosis, hypertension, myocardial infarction, diabetes, sexual dysfunction, and gastric ulcer; it notably interacts with the other gaseous mediators. Cystathionine γ-lyase, cystathionine ß-synthase, and 3-mercaptopyruvate sulfurtransferase are the principal enzymes involved in H(2)S production. We have recently studied H(2)S metabolism in the plasma of chronic hemodialysis patients and reported that its levels are significantly decreased. The plausible mechanism lies in the transcription inhibition of the cystathionine γ-lyase gene. The finding could be of importance considering that hypertension and high cardiovascular mortality are characteristic in these patients.

The gasotransmitter hydrogen sulfide in hemodialysis patients.

Hydrogen sulfide, H2S, is the third endogenous gas with cardiovascular properties (the others are nitric oxide and carbon monoxide). In fact, among other important signaling functions, H2S plays a key role in regulating blood pressure. Cystathionine ß-synthase, cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase are the principal enzymes devoted to H2S formation. We have recently shown that H2S levels are decreased in patients on chronic hemodialysis through the transcriptional deregulation of the CSE gene, hinting at the possibility that a link exists between this finding and hypertension and the high cardiovascular mortality typical of these patients.

A longitudinal study of sleep disorders in early-stage chronic kidney disease.

Few studies have addressed the problem of sleep disturbances in patients with early-stage chronic kidney disease (CKD). A total of 220 patients newly diagnosed with CKD and 220 patients newly diagnosed with chronic hepatitis C were studied within 1 month from the diagnosis. They were evaluated by using the Charlson Comorbidity Index, the Pittsburgh Sleep Quality Index, and the Beck Depression Inventory. Patients with CKD were followed up for 4 years. Sleep disturbances affected 59.5% of patients with chronic hepatitis C and 84.6% of patients with CKD. Sleeping disorders that were severe and peculiar in early CKD improved significantly over time. Beck Depression Inventory disclosed significant depression, which was ameliorated over time. Charlson Comorbidity Index was constant over time. Logistic regression analysis failed to detect significant correlations for putative factors emerging from studies in hemodialyzed patients, with the exception of depression.

The high prevalence of alexithymia in hemodialyzed patients with secondary hyperparathyroidism unsuppressed by medical therapy is cured by parathyroidectomy.

There are scanty data available on alexithymia in patients with end-stage renal disease, which point to an independent association with depression and social support. This study was devised to investigate the prevalence of alexithymia and sleep disorders in patients maintenance hemodialysis with insuppressible secondary hyperparathyroidism, who need parathyroidectomy (PTX), because previous data from our laboratories as well as those of others showed that this patient-group are the worst sleepers among hemodialysis patients with end-stage renal disease. A total of 40 patients needing PTX were enrolled and studied before the surgery. As for the control group, 80 patients on maintenance hemodialysis not needing PTX were enrolled. We measured alexithymia with the Toronto Alexithymia Score (TAS-20), sleep disorders with the Pittsburgh Sleep Quality Index (PSQI), and depression with Beck Depression Inventory (BDI), intact parathyroid hormone (iPTH), calcium, phosphate, use of antihypertensives, systolic and diastolic blood pressure, hemoglobin concentration, and albumin concentration. Patients needing PTX in comparison with those not needing PTX had significantly higher iPTH, calcium, and phosphate; they also had significantly higher systolic and diastolic blood pressure. They were more significantly alexithymic (P < .001), had more severe sleep disorders (P < .001), and were more depressed (P < .043). In multivariate analysis, BDI correlated significantly with iPTH concentration (r = 0.505, P < .001). A reduction of TAS-20 occurred after PTX which correlated with the number of patients on antihypertensive drugs, PSQI, BDI, hemoglobin concentration in the univariate and multivariate analysis. When TAS-20 and PSQI were adjusted for BDI (using analysis of variance) there was still a significant difference of TAS-20 and PSQI between patients needing PTX and not needing PTX (P < .001). This study confirms the high prevalence of sleep disorders in patients with unsuppressed secondary hyperparathyroidism and discloses a high prevalence of Alexithymia which is ameliorated by PTX. However, the correlation of Alexithymia with sleep disorders does not depend on depression.

Hydrogen sulfide, the third gaseous signaling molecule with cardiovascular properties, is decreased in hemodialysis patients.

Hydrogen sulfide, H(2)S, is the third endogenous gas with cardiovascular properties, after nitric oxide and carbon monoxide. H(2)S is a potent vasorelaxant, and its deficiency is implicated in the pathogenesis of hypertension and atherosclerosis. Cystathionine beta-synthase, cystathionine gamma-lyase, and 3-mercaptopyruvate sulfurtransferase catalyze H(2)S formation. Chronic kidney disease is characterized by high prevalence of hyperhomocysteinemia, hypertension, and high cardiovascular mortality, especially in hemodialysis patients. H(2)S levels are decreased in hemodialysis patients through transcriptional deregulation of genes encoding for the H(2)S-producing enzymes. Potential implications relate to the pathogenesis of the manifestations of the uremic syndrome, such as hypertension and atherosclerosis.

Glomerular filtration rate and serum phosphate: an inverse relationship diluted by age.

BACKGROUND: Available data indicate that serum phosphate increases only when glomerular filtration rate (GFR) falls into the low range (<60 mL/min x 1.73 m(2)). GFR and serum phosphate decrease with ageing. This population-based study investigated by age-controlled analyses the relationship of GFR with serum phosphate in adults with GFR above the low range. METHODS: Data were collected on age, sex, menstrual status, anthropometry, overnight urinary creatinine, dietary protein (overnight urinary urea), reported intake of milk/yogurt, serum creatinine, phosphate, calcium and total protein in 4034 adults (age 18-91 years) with GFR >or=60 mL/min x 1.73 m(2) as assessed by estimated GFR (eGFR, simplified MDRD equation) and creatinine clearance (overnight urinary creatinine/serum creatinine). RESULTS: The relationship of eGFR with serum phosphate was positive in men and null in women in univariate analyses (P = 0.001 and 0.148), negative in both sexes with age adjustment (P < 0.001). Age-adjusted results did not depend on colinearity between age and eGFR because the relationship was inverse also replacing eGFR with creatinine clearance (P < 0.001 in both sexes). In univariate regression analysis done separately by gender and six age-strata (18-24, 25-34, 35-44, 45-54, 55-64 and >or=65), the line of serum phosphate over eGFR was constantly inverse (range of P = 0.010/0.089) with the progressively lower y-axis intercept from young to older ages. The inverse relationship of eGFR or creatinine clearance with serum phosphate was significantly inverse also controlling for other variables (P < 0.01). CONCLUSIONS: GFR differences in the range >or=60 mL/min x 1.73 m(2) are inversely and independently related to serum phosphate. The relationship is undetectable without age-controlled procedures because, for serum phosphate, the effect of GFR differences above >or=60 mL/min x 1.73 m(2) is much smaller than the effect of age.

Hydrogen sulphide-generating pathways in haemodialysis patients: a study on relevant metabolites and transcriptional regulation of genes encoding for key enzymes.

BACKGROUND: Hydrogen sulphide, H(2)S, is the third endogenous gas with putative cardiovascular properties, after nitric oxide and carbon monoxide. H(2)S is a vasorelaxant, while H(2)S deficiency is implicated in the pathogenesis of hypertension and atherosclerosis. Cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CSE) and 3-mercaptopyruvate sulphurtransferase (MPS) catalyze H(2)S formation, with different relative efficiencies. Chronic kidney disease (CKD) is characterized by elevation of both plasma homocysteine and cysteine, which are substrates of these enzymes, and by a high prevalence of hypertension and cardiovascular mortality, particularly in the haemodialysis stage. It is possible that the H(2)S-generating pathways are altered as well in this patient population. METHODS: Plasma H(2)S levels were measured with a common spectrophotometric method. This method detects various forms of H(2)S, protein-bound and non-protein-bound. Blood sulphaemoglobin, a marker of chronic exposure to H(2)S, was also measured, as well as related sulphur amino acids, vitamins and transcriptional levels of relevant genes, in haemodialysis patients and compared to healthy controls. RESULTS: Applying the above-mentioned methodology, H(2)S levels were found to be decreased in patients. Sulphaemoglobin levels were significantly lower as well. Plasma homocysteine and cysteine were significantly higher; vitamin B(6), a cofactor in H(2)S biosynthesis, was not different. H(2)S correlated negatively with cysteine levels. CSE expression was significantly downregulated in haemodialysis patients. CONCLUSIONS: Transcriptional deregulation of genes encoding for H(2)S-producing enzymes is present in uraemia. Although the specificity of the method employed for H(2)S detection is low, the finding that H(2)S is decreased is complemented by the lower sulphhaemoglobin levels. Potential implications of this study relate to the pathogenesis of the uraemic syndrome manifestations, such as hypertension and atherosclerosis.

Hyperhomocysteinemia in uremia--a red flag in a disrupted circuit.

Hyperhomocysteinemia is an independent cardiovascular risk factor, according to most observational studies and to studies using the Mendelian randomization approach, utilizing the common polymorphism C677T of methylene tetrahydrofolate reductase. In contrast, the most recent secondary preventive intervention studies, in the general population and in chronic kidney disease (CKD) and uremia, which are all negative (with the possible notable exception of stroke), point to other directions. However, all trials use folic acid in various dosages as a means to reduce homocysteine levels, with the addition of vitamins B6 and B12. It is possible that folic acid has negative effects, which offset the benefits; alternatively, homocysteine could be an innocent by-stander, or a surrogate of the real culprit. The latter possibility leads us to the search for potential candidates. First, the accumulation of homocysteine in blood leads to an intracellular increase of S-adenosylhomocysteine (AdoHcy), a powerful competitive methyltransferase inhibitor, which by itself is considered a predictor of cardiovascular events. DNA methyltransferases are among the principal targets of hyperhomocysteinemia, as studies in several cell culture and animal models, as well as in humans, show. In CKD and in uremia, hyperhomocysteinemia and high intracellular AdoHcy are present and are associated with abnormal allelic expression of genes regulated through methylation, such as imprinted genes, and pseudoautosomal genes, thus pointing to epigenetic dysregulation. These alterations are susceptible to reversal upon homocysteine-lowering therapy obtained through folate administration. Second, it has to be kept in mind that homocysteine is mainly protein-bound, and its effects could be linked therefore to protein homocysteinylation. In this respect, increased protein homocysteinylation has been found in uremia, leading to alterations in protein function.

Klaus Hierholzer (1929-2007) and his impact on our understanding of the renal effects of steroid hormones.

Klaus Hierholzer (1929-2007) dissected various functions influenced by steroids in the distal tubule and showed that aldosterone in low doses reversed the sodium and potassium transport defect in adrenalectomized rats, through a rapid activation of Na+,K+-ATPase. Subsequent studies addressed the role of 11-beta-hydroxysteroid oxidoreductase (11-HSD) and showed that the undisturbed functioning of 11-HSD is a prerequisite for selective mineralocorticosteroid regulation of epithelial transport. Another set of original experiments showed that 11-HSD was equally important in the distal colon, thus establishing that the large intestine acts in parallel with the distal nephron. Hierholzer, born in Konstanz on June 8, 1929, was laureated in medicine on May 25, 1954. Subsequently he worked at the Department of Pharmacology of the University of Freiburg, Cornell University with J. F. Pitts, the Department of Medicine of the University of Frankfurt-am-Main, the University of Copenhagen with H. H. Ussing, and the Institute of Physiology of the Freie Universitaet in Berlin where he became full professor and head of the Institute of Clinical Physiology in 1968. He held that position until 1998. He died in Allensbach in the family house on February 27, 2007. Hierholzer was a member of the Naturforscher Leopoldina Academy and of many other scientific societies, including the Academy of Science and Technology in Berlin, and received various awards including an honorary professorship at the University of Naples, the Bezold Medal, the Volhard Medal, the Schoeller/Junkman Award, and the Malpighi Medal (in memoriam). He published nearly 300 papers including various seminal books. Noteworthy also are his papers on the history of physiology of the kidney and acid-base balance. A total of 26 scientists who trained in his laboratory became professors.

The nature of water: Thales' arkhe.

Thales was born into a noble family of Phoenician origin at the time of the 25th Olympiad (floruit 585 bc; he was 40 in the year of the solar eclipse. He had no teachers but had occasion to learn from Egyptian priests. He developed into a scholar and politician very much appreciated by Heraclitus, Herodotus and Democritus, and was always considered a man of practical wisdom. He was probably the first to speak about the immortality of the soul. He is listed as the first of many unmarried men who paved the road for philosophy. For Diogenes Laertius (Lives and Opinions of Eminent Philosophers), he was the instructor of Anaximander. Thales, the man who first discovered how to draw a right-angle triangle in a circle, was the first philosopher of nature (physis). "Philosophy begins with Thales," pointed out Bertrand Russell in 1961. This honor had been conceded also by Aristotle: "Anaximander, Thales' pupil, founded the Ionian tradition of philosophy." Many explanations may be given for the importance of water, including its importance for living processes, the economic role of the Nile, the importance of the port for Miletus and the fact that Ocean and Thetys were in Homer's tradition progenitors of the world.

Low salt diet and treatment of hypertension: an old story.

A relatively low salt intake is nowadays considered one of the characteristics of a healthy diet in the Western world because several disorders appear to be unfavorably affected by excessive salt intake with the diet. The first notion about a relation between salt intake and blood pressure traces back to 2500 bc in an ancient Chinese medical textbook. This paper focuses on studies about salt and hypertension in the first half of the 20th century. The first papers in this field were published from the beginning of the century, but due to a modest scientific content were still not considered in the 1940s to provide sufficient evidence in favor of a salt restriction in hypertensive patients. A major practical contribution came from the Kempner rice diet, an effective antihypertensive dietary treatment which included a severe restriction of salt intake. After that, several studies in animals and humans showed that, with regard to the antihypertensive effect, the key element of the Kempner diet was the low salt content. By the first years of the 1950s, the evidence was already available that salt restriction is an effective antihypertensive treatment and that adherence to the treatment should be assessed by monitoring urinary electrolytes.

Definition of kidney dysfunction as a cardiovascular risk factor: use of urinary albumin excretion and estimated glomerular filtration rate.

BACKGROUND: Urinary albumin excretion (UAE) and estimated glomerular filtration rate (eGFR) have been used separately to provide information about cardiovascular risk. We analyzed whether UAE and eGFR used together provide complementary information. METHODS: We analyzed UAE, eGFR, cardiovascular risk factors, and incidence of cardiovascular disease in 1665 men and women of the Gubbio Population Study (aged 45-64 years). We designated UAE in the highest decile as high (>or= 18.6 microg/min in men and >or= 15.7 microg/min in women) and eGFR in the lowest decile as low (<64.20 mL/min/1.73 m(2) in men and <57.90 mL/min/1.73 m(2) in women). RESULTS: Kidney dysfunction defined using both markers was more frequent than using 1 marker (UAE alone or eGFR alone) (P< .001) because high UAE and low eGFR clustered in different individuals and were weakly associated with each other (P= .12). The hazard ratio (HR) for incident cardiovascular disease was elevated for both markers, independently of each other (HR for high UAE, 2.15; 95% confidence interval [CI], 1.33-3.49; HR for low eGFR, 2.14; 95% CI, 1.32-3.48). Kidney dysfunction defined by both markers predicted cardiovascular disease independently of sex, age, hypertension, hypercholesterolemia, smoking, diabetes mellitus, prior cardiovascular disease, left ventricular hypertrophy, and obesity (HR, 1.50; 95% CI, 1.05-2.14). The discriminant power of dysfunction defined by both markers was statistically significant (area under the receiver operating characteristic curve, 0.569 [P= .02]) and slightly higher than what was found with 1 marker of diabetes mellitus, prior cardiovascular disease, left ventricular hypertrophy, and obesity. CONCLUSIONS: High UAE and low eGFR provide complementary information in defining kidney dysfunction because they cluster in different individuals. Concomitant evaluation of both markers should be considered to adequately assess kidney dysfunction and cardiovascular risk.

Renal response to an oral protein load in patients with central diabetes insipidus before and after treatment with vasopressin.

AIM: Different factors have been hypothesized to play a role in the cascade of events associated with the protein-induced glomerular response. However, scant data are available on the possible functional effect of vasopressin (VP) on the glomerular filtration rate (GFR) in humans with central diabetes insipidus (CDI), which was the aim of the present study. METHOD: Renal function was studied under fasting conditions (baseline) and after a meat meal in 16 patients with CDI before and after treatment with desmopressin (DDAVP) and in 16 control subjects. GFR was measured by the inulin method. RESULTS: At baseline, the GFR was lower in patients with CDI. Treatment with DDAVP resulted in an insignificant increase in GFR, which was not statistically different from untreated patients. After an acute oral protein load, the GFR increased, peaking at 45 min post meal in controls, and at 135 min post meal in treated and untreated CDI patients. CONCLUSION: After a meat meal, the peak GFR response is delayed in CDI patients suggesting that VP might indirectly affect tubule-glomerular feedback.