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Introduction: Peritoneal ultrafiltration (PUF) has been proposed as an additional therapeutic option for refractory congestive heart failure (RCHF) patients. Despite promising observational studies and/or case report results, limited clinical trial data exist, and so far, PUF solutions remain only indicated for chronic kidney diseases. In this article, we described a multicenter, randomized, controlled, unblinded, adaptive design clinical trial, about to start, investigating the effects of PolyCore™, an innovative PUF solution, in the treatment of RCHF patients., Methods: The Peritoneal Ultrafiltration in Cardiorenal Syndrome (PURE) study is a phase II, multicenter, randomized, controlled, unblinded, adaptive design clinical trial that aims to evaluate the safety and efficacy of PUF, using PolyCore™ as the investigational solution, in the treatment of RCHF patients who present with prominent right ventricular failure due to afterload mismatch, functional tricuspid regurgitation and enlarged cava vein consequent to intravascular fluid overload. Approximately 84 patients will be randomized 1:1 either to continue with their prescribed guideline-directed medical therapy or to add the PUF treatment on top of it. The primary objective is to evaluate if PUF treatment has an impact on the composite endpoint of the patient's mortality or worsening of the patient's condition such as hospitalization for cardiovascular causes, increasing the initial daily dose of loop diuretic or worsening of renal function. Statistical analysis for the primary endpoint will be standard survival analysis to estimate the failure rate at month 7 for each group via Kaplan-Meier curves. Sensitivity analysis and various secondary analyses, including a multiple events analysis, will be conducted to evaluate the robustness of the primary endpoint results. Safety will be evaluated for up to 12 months., Conclusion: The PURE study was designed to evaluate the safety and efficacy of peritoneal ultrafiltration with PolyCore™ on top of guideline-directed medical therapy in patients with RCHF, assuming a combined clinical endpoint of mortality or worsening patients' condition. If successful, the treatment should allow for an improvement of the RCHF symptoms, decreasing hospitalization rate of patients., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Cystinuria (CYS) is the most common monogenic kidney stone disease., Methods: Starting from an unusual case of CYS associated to primary sclerosing cholangitis, inflammatory bowel disease (IBD), and autoimmune hepatitis in a young male, we carefully review the literature and propose here a working hypothesis regarding the potential risk of cystinuric patients to develop conditions due to immune system dysregulation. To corroborate this hypothesis, we retrospectively evaluate the frequency of dysimmunity in a monocentric cohort including 36 cystinuric patients compared to healthy and disease controls., Results: CYS patients have an increased prevalence of atopic disease compared to disease controls (p = 0.03) and 16.7% of CYS subjects were diagnosed with allergic disease to a variety of antigens., Conclusion: Further studies are needed to define the relationship between proximal tubular transport defect of CYS and dysregulated immunity., (© 2024 S. Karger AG, Basel.)

Background: Therapeutic plasmapheresis (TP) is an extracorporeal therapy that allows the removal of pathogens from plasma. The role of TP in immuno-mediated diseases and toxic conditions has been of interest for decades., Summary: We reviewed the recent literature on the application and the optimal choice of TP technique ranging from plasma exchange, double filtration plasmapheresis, rheopheresis, immunoadsorptions, plasma adsorption perfusion and lipidoapheresis. In addition, we report our experience in the application of TP for various diseases ranging in different medical specialties, following the American Society for Apheresis (ASFA) recommendations., Key Messages: Overall patients receiving TP showed an improvement in clinical and laboratory parameters. Our review and single-center experience suggest a benefit of the application of TP in multiple clinical disciplines., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Since the pandemic of COVID-19 started from December 2019, remarkable numbers of infections and deaths associated with COVID-19 have been recorded worldwide. End-stage kidney disease patients on dialysis are particularly at high risk of infections due to impairments in the innate and adaptive immune systems. Vaccination on dialysis patients (DP) still remains challenging because of the variable response and a low seroconversion rate compared with healthy participants (HP). Therefore, it is urgently necessary to establish a different vaccination strategy for DP, in terms of the dose and administration time., Methods: Here, we report an observational prospective cohort study in which the immunogenic efficacies of SARS-CoV-2 vaccine BNT162b2 on DP and HP were evaluated by absolute quantification of IgG levels in the blood., Results: DP showed a delayed seroconversion after two vaccine doses, with a low absolute IgG levels compared to HP. While HP reached complete seroconversion within 10 days from the administration of a second dose, only 76% of DP were seropositive. After the booster dose, DP had a strongly improved seroconversion rate as well as antibody levels, reaching 97% seropositivity and 50 times enhancement on antibody levels., Discussion/conclusion: These results prompt to suggest an additional vaccine dose in DP, reducing the interval of time from the second dose. Since limited data are available on immune response in DP overtime after three vaccine doses currently, our study is among the first reports demonstrating the improved seropositivity and IgG levels in DP after the booster vaccine dose., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Renal dysfunction is a frequent complication in patients suffering from β-thalassemia major (β-TM). The aim of this study was to analyze the renal function and urine metabolomic profile of β-TM patients undergoing transfusions and deferasirox (DFX) therapy, in order to better characterize and shed light on the pathogenesis of renal disease in this setting., Methods and Subjects: 40 patients affected by β-TM treated with DFX and 35 age- and gender-matched healthy controls were enrolled in the study. Renal function was assessed. Glomerular filtration rate (GFR) was estimated with CKD-EPI and Schwartz formula for adults and children, respectively. Renal tubular function and maximal urine concentration ability were tested. Urine specimens were analyzed by nuclear magnetic resonance spectroscopy to identify the urinary metabolite profiles., Results: The study of renal function in β-TM patients revealed normal estimated (e)GFR mean values and the albumin-to-creatinine ratio was <30 mg/g. The analysis of tubular function showed normal basal plasma electrolyte levels; 60% of patients presented hypercalciuria and many subjects showed defective urine concentration. Several amino acids, N-methyl compounds, and organic acids were overexcreted in the urine of thalassemic patients compared with controls., Discussion: The major finding of this work is that β-TM patients and controls exhibit different concentrations of some metabolites in the urine. Early recognition of urinary abnormalities may be useful to detect and prevent kidney damage., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Background: The outbreak of severe acute respiratory syndrome β-coronavirus 2 (SARS-CoV-2) has the potential to become a long-lasting global health crisis. The number of people infected with the novel coronavirus has surpassed 22 million globally, resulting in over 700,000 deaths with more than 15 million people having recovered (https://covid19.who.int). Enormous efforts are underway for rapid vaccine and treatment developments. Amongst the many ways of tackling the novel coronavirus disease 2019 (COVID-19) pandemic, extracellular vesicles (EVs) are emerging., Summary: EVs are lipid bilayer-enclosed structures secreted from all types of cells, including those lining the respiratory tract. They have established roles in lung immunity and are involved in the pathogenesis of various lung diseases, including viral infection. In this review, we point out the roles and possible contribution of EVs in viral infections, as well as ongoing EV-based approaches for the treatment of COVID-19, including clinical trials. Key Messages: EVs share structural similarities to viruses and recent findings demonstrate that viruses exploit EVs for cellular exit and EVs exploit viral entry mechanisms for cargo delivery. Moreover, EV-virus interplay could be exploited for future antiviral drug and vaccine development. EV-based therapies, especially the mesenchymal stem cell-derived EVs, are being intensively studied for the treatment of COVID-19., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Background: /Aims: Renal disease is a common cause of morbidity in patients with Bardet-Biedl syndrome (BBS), however the severity of kidney dysfunction is highly variable. To date, there is little information on the pathogenesis, the risk and predictor factors for poor renal outcome in this setting. The present study aims to analyze the spectrum of urinary proteins in BBS patients, in order to potentially identify 1) disease-specific proteomic profiles that may differentiate the patients from normal subjects; 2) urinary markers of renal dysfunction., Methods: Fourteen individuals (7 males and 7 females) with a clinical diagnosis of BBS have been selected in this study. A pool of 10 aged-matched males and 10 aged-matched females have been used as controls for proteomic analysis. The glomerular filtration rate (eGFR) has been estimated using the CKD-EPI formula. Variability of eGFR has been retrospectively assessed calculating average annual eGFR decline (ΔeGFR) in a mean follow-up period of 4 years (3-7)., Results: 42 proteins were significantly over- or under-represented in BBS patients compared with controls; the majority of these proteins are involved in fibrosis, cell adhesion and extracellular matrix organization. Statistic studies revealed a significant correlation between urine fibronectin (u-FN) (r2=0.28; p<0.05), CD44 antigen (r2 =0.35; p<0.03) and lysosomal alfa glucosidase ( r20.27; p<0.05) abundance with the eGFR. In addition, u-FN (r2 =0.2389; p<0.05) was significantly correlated with ΔeGFR., Conclusion: The present study demonstrates that urine proteome of BBS patients differs from that of normal subjects; in addition, kidney dysfunction correlated with urine abundance of known markers of renal fibrosis., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Current urate-lowering therapy (ULT) includes three direct acting drugs (allopurinol, febuxostat, Rasburicase) and at least four 'indirect' drugs with other important targets (canagliflozin, losartan, fenofibrate and sevelamer). Moreover, the alcalinization of urines using bicarbonate can be used to dissolve urate crystals and the clinician may discontinue several drugs are known to increase serum levels of uric acid, such as diuretics, aspirin, cyclosporine, theophylline, mycophenolate and ACE inhibitors. While there is a consensus to start ULT in cases of symptomatic hyperuricemia (gout, urate-nephrolithiasis), the very frequent conditions of asymptomatic hyperuricemia remains a major conundrum. The effect of asymptomatic hyperuricemia on kidney function has had fluctuating positions over decades. The conflicting results might indicate: (i) the presence of counterbalancing positive and negative effects on kidney function of both serum uric acid and urate-lowering agents, (ii) the presence of a subpopulation of patients, as yet unidentified, which could truly benefit from a urate-lowering therapy. Therefore, today the treatment of asymptomatic hyperuricemia is not recommended nor excluded by current guidelines. Here we suggest that a possible guide for the treatment of asymptomatic hyperuricemia might be the presence of urate crystals in the urine sediment and/or signs of asymptomatic articular damage by urates, identified by musculo-skeletal ultrasound. Moreover, a watchful analysis of the trend in creatinine/eGFR, proteinuria or urate levels might also guide the clinician. Initiation of ULT and follow-up in cases of asymptomatic hyperuricemia should consider urine sediment analysis, musculoskeletal ultrasound and trends in creatinine, proteinuria and serum urate levels., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Background/aims: Little information is available about the tubular functions and the renal adjustments that take place in obese subjects after a protein meal. How the excess fat may affect renal response to dietary proteins is currently only partially understood. This paper aims to address (i) whether severe obesity, in the absence of other comorbidities, is responsible of kidney dysfunction at either the glomerular or the tubular level and (ii) whether it compromises renal adaptations to a large protein meal., Methods: Twenty-eight obese subjects without albuminuria, along with 20 control subjects, age and gender matched, have been studied. The glomerular filtration rate (GFR; inulin clearance), renal plasma flow (p-aminohippurate clearance), the proximal tubular function (lithium clearance), the fractional excretion of sodium (FPRNa) have been measured at the basal level (steady state) and after a protein meal (perturbation)., Results: Under steady state conditions, filtration fraction, proximal tubular sodium handling and the FPRNa were not significantly different in non proteinuric obese subjects compared with controls. However, a protein meal led to a delayed glomerular hyperfiltration in obese patients compared with controls., Conclusion: This study shows that obese patients, in the absence of significant comorbidities, have a normal proximal tubule Na+ absorption at basal; conversely, these subjects showed a different response to a protein meal compared with normal subjects in terms of changes of GFR. Overall, these results suggest that the modified hemodynamic response to a protein meal might be the earliest hallmark of future kidney dysfunction in obese subjects., (© 2017 S. Karger AG, Basel.)

Urinary calcium, magnesium and citrate levels are important in promoting or inhibiting renal stone formation. Here we review current information on the tubular handling of these ions. Most filtered calcium is reabsorbed in the proximal tubule and the thick ascending limb (TAL) of the loop of Henle, largely paracellularly; most of the remainder is reabsorbed in the distal tubule, transcellularly. Calcium reabsorption in the TAL and distal tubule is stimulated by parathyroid hormone and vitamin D; other factors influencing its renal handling include extracellular volume status and acid-base balance. Little filtered magnesium is reabsorbed in the proximal tubule; the bulk is reabsorbed paracellularly in the TAL, while most of the remainder is reabsorbed transcellularly in the distal tubule. Dietary intake, peptide hormones and chronic potassium depletion can all influence magnesium reabsorption in the TAL and distal tubule. Most filtered citrate is taken up across the apical membrane of the proximal tubule via a sodium-dicarboxylate co-transporter (NaDC-1). It also enters proximal tubular cells across the basolateral membrane; citrate contributes to the cells' oxidative metabolism. Citrate excretion is affected by acid-base balance, acetazolamide treatment, chronic potassium depletion and urinary excretion of calcium and magnesium. Where possible, we have indicated the mechanisms of these complex interactions., (Copyright (c) 2004 S. Karger AG, Basel.)

Background/aims: Calbindin D28k has been reported to be involved in transcellular calcium transport along the rat distal convoluted tubule (DCT). It has also been shown that administration of bumetanide is associated with hypercalciuria. The experiments reported here were designed to verify whether chronic infusion of this diuretic affects the gene expression and protein abundance of calbindin D28k along rat kidney DCT., Methods: Bumetanide was subcutaneously infused by an osmotic minipump for 7 days at a rate of 1.5 mg x h(-1) x kg(-1). cDNA was synthesized from total RNA extracted from DCT microdissected from collagenase-treated kidneys., Results: Calbindin D28k mRNA abundance, quantified by competitive PCR, was found to be 13.7 +/- 1.9 amol x ng(-1) total RNA in DCT of control rats (n = 4) as compared to 24.2 +/- 2.4 amol x ng(-1) total RNA in DCT of bumetanide- treated rats (n = 5) (p < 0.01). This effect was associated with a 52% increase (p < 0.005) in calbindin D28k protein abundance, as detected by Western blot performed on tissue slices from renal cortex (n = 4)., Conclusion: These data not only demonstrate that bumetanide upregulates the mRNA and protein abundance of calbindin D28k in rat DCT, but also suggest that DCT calcium reabsorption is increased following the administration of this loop diuretic., (Copyright 2004 S. Karger AG, Basel)

Background: The use of cyclosporin A (CyA) is limited by its significant nephrotoxicity. Atrial natriuretic peptide (ANP) has been shown to ameliorate the reduction in glomerular filtration rate (GFR) induced by CyA, but its effect is transient. One explanation may be the rapid breakdown of this hormone by neutral endopeptidase (NEP) which is highly active in the kidney. In the present study, we examined the effect of the NEP inhibitor thiorphan on the acute fall in GFR induced by CyA., Methods: After a first set of experiments to investigate the renal hemodynamic effects of CyA (20 mg.kg(-1), i.v. bolus), we studied four additional conditions where acute CyA treatment was followed by the administration of: (2) ANP alone (10 microg.kg(-1) i.v. as bolus and a maintenance infusion of 1 microg. kg(-1).min(-1)); (3) thiorphan alone (5 mg.kg(-1) i.v. as bolus and a maintenance infusion of 0.5 mg.kg(-1). min(-1)); (4) ANP plus thiorphan (as in 2 and 3), and (5) an infusion of 0.9% saline, increased from 1.2 to 3 ml.h(-1). The GFR was measured as the clearance of (3)H-methoxyinulin (ml.min(-1).100 g(-1) body weight)., Results: The data show: (1) the GFR fell from 1.06 +/- 0.15 to 0.59 +/- 0.09 ml.min(-1).100 g(-1) (p < 0.01) 60 min after CyA and remained depressed for at least 2 h; (2) ANP caused a marked initial rise in GFR from 0.49 +/- 0.07 to 1.23 +/- 0.18 ml.min(-1).100 g(-1) (p < 0.005 vs. CyA) which declined rapidly to the value seen after CyA injection alone, despite continuing ANP infusion; (3) thiorphan caused a modest, but significant increase in GFR within 15 min from 0.48 +/- 0.04 to 0.69 +/- 0.10 ml.min(-1).100 g(-1) (p < 0.05 vs. CyA) which was sustained during infusion and for at least 30 min after stopping infusion; (4) ANP plus thiorphan produced a marked increase in GFR from 0.58 +/- 0.09 to 1.39 +/- 0.44 ml.min(-1).100 g(-1) (p < 0.05 vs. CyA) which then decreased, but remained above the post-CyA injection value, until infusion of both drugs ended; (5) more than doubling the saline infusion rate per se had no significant effect on the GFR response to CyA. The blood pressure decreased significantly during ANP infusion, but more so when combined with thiorphan., Conclusion: These data indicate that the inhibition of NEP by thiorphan is able to ameliorate partially the reduction in GFR induced by CyA and to enhance, and prolong, the vasodilator and diuretic effects of ANP., (Copyright 2000 S. Karger AG, Basel)

The work was devised to compare measurements of glomerular filtration rate (GFR) by technetium-99m-diethylenetriaminepentacetic acid (99mTc-DTPA) renogram to those by creatinine clearance (measured and predicted by Cockroft and Gault) and by inulin clearance. A total number of 65 individuals were enrolled: 15 healthy controls and 50 patients with renal disease. Compared to inulin clearance used as the gold standard, 99mTc-DTPA overestimated at low and underestimated at high GFRs. 99mTc-DTPA measurements were less precise than creatinine clearance except for individuals with GFR >100 ml/min x 1.73 m2. Measured creatinine clearance had the highest correlation coefficient with inulin clearance, 99mTc-DTPA clearance the lowest. In correlation analyses, 81.5% of the interindividual variability for measured creatinine clearance could be explained by true differences in inulin clearance; this value dropped to 59.1 and 57.4% for predicted creatinine clearance and 99mTc-DTPA, respectively. In patients with GFR <25 ml/min x 1.73 m2, all 99mTc-DTPA measurements were out of the 95% confidence interval for the inulin measurement. It can be inferred that 99mTc-DTPA clearance from the renogram is less precise than measured and predicted creatinine clearance.

Thyroid hormones affect the functions of several organs including the heart and kidney. Using isolated left papillary muscles we have investigated the action of thyroid hormones on the mechanical and electrical properties of the heart. We found that pure hypothyroidism causes a depression in contractile and electrical parameters, but we noticed that superimposed hypoparathyroidism accounts for the marked prolongation in contractile kinetics and action potential duration. At kidney level we have shown that thyroid hormones affect proximal tubular sodium transport and this effect is only partially mediated by the action of thyroid hormones on Na-K-ATPase activity. Using the micropuncture technique, we hypothesized that the early effect of thyroid hormone action is on the potassium permeability of proximal tubular cell membrane. This latter effect would explain the increase in isotonic fluid reabsorption through an increase in the driving force for sodium. Finally, hypothyroid patients have a decrease in glomerular filtration rate and renal plasma flow that are completely reversed by thyroxine administration. On the other hand, hyperthyroid subjects exhibit a significant increase in both parameters.

To visualize superficial and accessible renal tubule cells functioning in situ and to relate what we can 'see' to what we know of their function from more invasive in vivo or less direct in vitro studies means applying and adapting recent advances in epifluorescence and confocal microscopy to improve image resolution and to combine this with the use of fluorescent labels to monitor the handling of specific molecules by the proximal and distal renal tubule cells in vivo. Doing this in living tissue is novel, especially in the kidney. Application of confocal microscopy to the imaging of living tissue, as opposed to isolated cells, has not been widely reported. The kidney surface has been imaged before using the confocal microscope and in preliminary studies we have extended this by using a different confocal system with and without fluorescence. While the studies published up to now have been morphological, comparing standard renal (structural) histology of surface glomeruli and renal tubules with the corresponding in vivo confocal images, more dynamic, real-time studies have been limited. Individual red blood cells can be seen flowing around the peritubule capillary network and nucleated white blood cells can also be distinguished. Tubule cells, endothelial cells, the proximal tubule cell brush border and cell mitochondria can be visualized. Filtration and secretion can be observed, and the early and late parts of the proximal tubule distinguished, and the distal tubule recognized. Localization of fluorescently labeled insulin to the luminal brush border and progressive uptake of label and distribution within proximal tubule cells toward the basolateral (blood side) membrane can be demonstrated. The possibility of monitoring hemodynamic changes and tracking the filtration, uptake, secretion and absorption of fluorescently tagged molecules, as well as intracellular fluorescence, e.g. calcium or pH, is an exciting prospect and is ripe for detailed exploration.

The kidney plays a major role in the regulation of acid-base balance. This process is mainly dependent on H+ secretion in the tubular lumen. Two acid extruder proteins are involved: the Na+/H+ exchanger and H(+)-ATPase. Studies using in vivo and in vitro microperfusion and isolated membrane vesicles have clearly demonstrated that the Na+/H+ exchanger is the main mechanism regulating H+ secretion/HCO3- reabsorption along the proximal nephron. Moreover, several reports indicate that this protein is involved in intracellular pH (pHi) regulation. Newer studies using molecular biology techniques have identified at least five isoforms of the Na+/H+ exchanger: NHE-1 is the housekeeping isoform, while NHE-3 seems to be implicated in transepithelial acid-base transport, although other isoforms could be involved too. H(+)-ATPase is the major acid extruder protein along the distal nephron, but it is also expressed along the proximal tubule, where a Na(+)-independent bicarbonate reabsorption has been described. There are a few studies indicating that the proton pump participates in pHi regulation, particularly in the presence of a large acid load. Its absence along the distal nephron may be one of the causes of distal tubular acidosis.

This study was carried out to examine the renal hemodynamic response in adult patients with single kidneys born with unilateral renal agenesis. A group of 21 patients with unilateral renal agenesis were divided into three groups according to their glomerular filtration rate (GFR): 112 +/- 3 ml/min x 1.73 m2 in group A, 68 +/- 3.2 ml/min x 1.73 m2 in group B, and 40.7 +/- 3.3 ml/min x 1.73 m2 in group C. Mean arterial blood pressure was significantly higher in the patients of group C who were also proteinuric. The renal hemodynamic response to an oral protein load (2 g/kg of protein as beefsteak) was normal in all groups and unrelated to hyperfiltration or to renal failure and proteinuria. The study indicates that in patients with renal agenesis, the hemodynamic response to a protein challenge is similar to that of kidney donors, renal transplant recipients and uninephrectomized patients. The paper also demonstrates that the renal response to a protein challenge is inadequate to identify patients with renal agenesis who are at risk of developing renal disease. Finally, in renal agenesis with renal disease, creatinine clearance overestimated the GFR by an average of 32.7%.

The study was devised to explore the effects of an acute oral protein load on renal hemodynamic response in patients with IgA nephropathy (IgAN). The study was performed in 10 proteinuric IgAN patients (800 +/- 300 mg/day) and in 20 healthy controls (matched by sex, age, BMI, BSA, plasma creatinine, plasma urea, urinary urea and protein intake). Blood pressure and creatinine clearance were nearly identical in the two groups. GFR and RPF, measured as the clearance of inulin and of p-aminohippurate (PAH) were studied before and after a meat meal which provided 2 g of protein/kg BW. Following the protein load, renal reserve, percent renal reserve and postmeal cumulative changes of GFR were not significantly different in IgAN and controls. Filtration fraction (FF) at baseline was significantly higher (p < 0.01) in IgAN than in controls (25.5 +/- 1.41 vs. 19 +/- 2%). Postmeal hyperemia and hyperfiltration did not affect FF in either group. Filtration capacity in IgAN was lower (p<0.02) than in controls (117 +/- 5.6 vs. 137.9 +/- 7.0 ml/min x 1.73 m2), whereas the percent of filtration capacity utilized at rest was identical in controls and in IgAN. Creatinine clearance overestimated GFR in IgAN. The data indicate that renal hemodynamic response to proteins in IgAN is normal.

The availability of cloned transport molecules achieved by efforts in expression cloning has allowed their electrophysiological analysis in the Xenopus oocyte expression system. We describe the electrogenic uptake of various substrates by their corresponding transport molecules originally expressed in brush border membranes of proximal tubules. The functional properties of the following transport molecules are discussed: the sodium-coupled glucose transporter, the sodium-coupled phosphate transporter, the sodium-coupled sulfate transporter and the sodium-independent transporter of neutral and dibasic amino acids. Additionally, functional consequences of naturally occurring disease-causing mutations in some of these transport molecules are described.

The medical history of salt begins in ancient times and is closely related to different aspects of human history. Salt may be extracted from sea water, mineral deposits, surface encrustations, saline lakes and brine springs. In many inland areas, wood was used as a fuel source for evaporation of brine and this practice led to major deafforestation in central Europe. Salt played a central role in the economies of many regions, and is often reflected in place names. Salt was also used as a basis for population censuses and taxation, and salt monopolies were practised in many states. Salt was sometimes implicated in the outbreak of conflict, e.g. the French Revolution and the Indian War of Independence. Salt has also been invested with many cultural and religious meanings, from the ancient Egyptians to the Middle Ages. Man's innate appetite for salt may be related to his evolution from predominantly vegetarian anthropoids, and it is noteworthy that those people who live mainly on protein and milk or who drink salty water do not generally salt their food, whereas those who live mainly on vegetables, rice and cereals use much more salt. Medicinal use tended to emphasize the positive aspects of salt, e.g. prevention of putrefaction, reduction of tissue swelling, treatment of diarrhea. Evidence was also available to ancient peoples of its relationship to fertility, particularly in domestic animals. The history of salt thus represents a unique example for studying the impact of a widely used dietary substance on different important aspects of man's life, including medical philosophy.

The study was devised to establish the role of prostaglandin E2, prostaglandin1 alpha and thromboxane A2 in the genesis of glomerular hyperfiltration response to a meat meal in healthy humans. To this end, a group of 8 healthy women was studied 4 times: in the control state (study 1), after a meat meal (study 2), following a meat meal associated with intravenous aspirin (study 3) and finally after a meat meal associated with intravenous aspirin following 2-day pretreatment with oral aspirin (study 4). Urinary excretion of prostaglandins and thromboxane increased during the glomerular hyperfiltration response to a meat meal and was suppressed by aspirin administration which did not suppress the renal hemodynamic response to the meat meal. The data do not support a causal role for prostaglandins and thromboxane A2 in the hemodynamic response to acute protein loading.

Joseph Jacob Plenck (1735-1807) is considered to be the forerunner of modern European dermatology, who also compiled a list of about 800 plants with medicinal uses. Of these about 115 have diuretic properties and are currently included in various pharmacopeias. They were traditionally used to cure ascites of various causes, in urolithiasis, nephritis, cystitis, bladder ulcers, strangury, urinary retention and incontinence. Few of these plants have been fully investigated by modern medicinal chemists, and many are worthy of further study.

The study was devised to assess the effects of a protein load (2 g/kg BW) on urinary prostaglandin E2 (PGE2), 6-keto-PGF1 alpha and thromboxane A2 (TxA2) in patients with renal failure of glomerular origin. To this end, 8 women with a glomerular filtration rate of 55 +/- 12 ml/min x 1.73 m2 underwent the following studies: study 1: control; study 2: meat meal; study 3: meat meal+intravenous aspirin; study 4: pretreatment with oral aspirin for 2 days+protocol in study 3. Glomerular hyperfiltration was seen after the meat meal (study 2) and was not suppressed by aspirin (studies 3 and 4). Urinary PGE2, 6-keto-PGF1 alpha and TxA2 increased after the meat meal in study 2 and were suppressed by aspirin in studies 3 and 4. The ratio between vasodilative (PGE2 + 6-keto-PGF1 alpha) and vasoconstrictive (TxA2) autacoids increased during the meat meal (study 2) and was suppressed when aspirin was injected at the time of the oral protein load, thus, the effect of aspirin was much greater for PGE2 and PGF1 alpha than for TxA2. These data do not support that urinary prostaglandin and TxA2 have a direct role in renal hyperfiltration due to an acute protein load.

This investigation was designed to study (1) renal sodium handling after an oral protein load and (2) its relationship to some known determinants of the hemodynamic response (glucagon, insulin, growth hormone, renin, aldosterone, and plasma amino acid concentration). To this end of group of 8 adult subjects was studied before (three 30-min clearances) and after a meat meal (MM; five 30-min clearances at 30, 60, 90, 120 and 180 min). The MM provided 2 g/kg BW of protein. Within 30 min from the MM an hyperfiltration response was seen, which was paralleled by a 2-fold increase in plasma alanine concentration while total plasma amino acid concentration was not different from the baseline values. The hemodynamic response was associated with a normally operating tubuloglomerular feedback mechanism independent of renin-aldosterone activity, but possibly associated with an early increase in plasma glucagon concentration and later on with a modest increase in postmeal plasma insuling concentration.

Urinary urea was measured, under normal living conditions, in children aged 3-16 years, from Cimitile, a small town near Naples in Southern Italy. Urinary urea correlated with age, height, weight, body mass index and body surface area, and was independent from sex. Urinary urea also correlated with urinary creatinine, uric acid, oxalate, sodium and phosphate. Protein intake assessed from urea excretion was 2.66 +/- 0.66 g/kg at 3 years of age and 1.49 +/- 0.31 g/kg at 16 years, and exceeded Italian standards for recommended intake. Also, the height and weight of the children living in Cimitile, with few exceptions, were in excess of national reference standards.

With the aim of disclosing a possibility for gastrin and bombesin to participate in the postprandial regulation of the renal hemodynamic response, 10 healthy males were studied before and after a meat meal (2 g/kg BW of proteins as cooked red meat). We evaluated the time course changes of glomerular filtration rate (GFR) renal plasma flow (RPF), and the plasma concentrations of gastrin, bombesin, glucagon, and total amino acids. After the meat meal a significant increase in GFR and RPF was seen, within 30 min, along with an increase in plasma gastrin and glucagon. Bombesin and amino acid concentrations increased at a later time. The data suggest but cannot demonstrate a causal role for gastrin and glucagon in the genesis of the hyperfiltration response to acute protein administration.

Tubular function was measured by lithium clearance (CLi) and by its derived formulae before and after the transient increase (lasting 90 min) in glomerular filtration rate (GFR) following a meat meal (2g protein/kg body weight) in 12 normal children. Three baseline and 4 clearances after the meal were obtained, each lasting 30 min. The mean baseline CLi was 23.1 +/- 1.64 ml/min/1.73 m2. At peak GFR response (60 min from starting the meal), CLi averaged 27.6 +/- 2.4 ml/min/1.73 m2 (p less than 0.025 vs. baseline) and it was further increased (32.2 +/- 5.04 ml/min/1.73 m2, p less than 0.01 vs. baseline) 120 min after starting the meal, while GFR returned to baseline values. Fractional lithium excretion averaged 0.23 +/- 0.04 at baseline and increased continuously after the meat meal and, at completion of the study, it averaged 0.38 +/- 0.07 (p less than 0.025 vs. baseline). The distal absolute and fractional sodium reabsorption increased throughout the studies following the meal and peaked at 120 min. The functional changes were associated with a statistically significant increase in the plasma concentration of insulin, glucagon, and total amino acids after the meal. The latter at the end of the study was almost doubled (5,600 +/- 780 versus 3,200 microM at baseline, p less than 0.01). The data indicate that the tubulo glomerular feedback mechanism operates normally after a meat meal. The finding on increased distal sodium reabsorption might point to the existence of an insulin-dependent mechanism.

The work was designed to assess the suitability of both measured endogenous creatinine clearance (CCR) and predicted creatinine clearance (P-CCR) to evaluate GFR in chronic renal disease (CRD) by utilizing the renal clearance of inulin (CIN) as gold standard. A total of 124 subjects were studied (62 healthy, 62 with CRF). CCR significantly overestimated GFR in healthy subjects as well as in CRF, whereas P-CCR was identical to GFR. The CCR/CIN ratio which calculates the fractional creatinine clearance and provides a rough estimation of the contribution of creatinine secretion in explaining the differences between CCR and GFR was increased in CRD and especially in CRD of glomerular origin. The ration P-CCR/CIN was significantly lower than CCR/CIN in healthy subjects and in patients with CRD of glomerular origin. The data are against the use of CCR in assessing GFR in healthy subjects and in patients with CRD.

To explore the age-related changes in tubular function and in the renal reserve (RR) a total of 98 healthy subjects were studied while on free living conditions. Enrolled people were divided into 3 groups: group A (n = 40, age range 5-18 years, Na intake 80 +/- 20 mM/day, protein intake 1.30 +/- 0.76 g/kg BW); group B (n = 34, age range 19-60 years, Na intake 110 +/- 12 mM/day, protein intake 1.32 +/- 0.75 g/kg BW), and group C (n = 24, age range 61-89 years, Na intake 159 +/- 12 mM/day (p less than 0.01 vs. A and B), protein intake 1.26 +/- 0.23). Glomerular filtration rate (GFR) (inulin), renal plasma flow (p-aminohippurate), the amount of filtrate and sodium delivered from the proximal tubule (lithium clearance), endogenous creatinine clearance, and predicted creatinine clearance were measured. The RR was evaluated after a meat meal (providing 2 g/kg BW of proteins) by subtracting baseline GFR from the peaking postprandial GFR. GFR was age-related and was identical in groups A and B and significantly lower in group C (p less than 0.0001). The drop in GFR averaged 7% per decade in the age range 61-89 years. The RR was not statistically different in groups A and B and increased significantly in group C (p less than 0.0001). In groups A and B the filtration fraction was constant after the meat meal and significantly increased over baseline GFR in group C (p less than 0.01), while the percentage of filtration capacity utilized at rest was lower in group C (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Lithium clearance (CLi) was studied in the healthy subjects (H) and in patients with chronic renal failure (CRF) with a mean GFR of 36.08 +/- 3.8 ml/min x 1.73 m2 in order to evaluate (1) the variability of CLi measurements; (2) the changes of CLi during the hyperfiltration response to a meat meal (2 g/kg b.w. of protein), and (3) the effects on CLi of different protein intakes. CLi correlated with GFR and with urinary sodium, FeLi correlated with FeNa in H and CRF. The intraindividual standard deviation (IISD) of GRF, CLi and FeLi assessed in triplicate studies in the course of a single experiment averaged 4.70, 7.15 and 10.69% in CRF and 1.77, 4.09 and 4.61% in H. When IISD for GFR, CLi, and FeLi was assessed in triplicate measurements in the course of 3 studies performed at 1-week intervals (day 1, day 8, day 15), it averaged 7.36, 9.21 and 15.72% in CRF and 1.83, 5.08 and 5% in H. During the hyperfiltration response to a meat meal, CLi and FeLi did not change in CRF and increased significantly in H. In 10 patients with CRF who were switched for 3 weeks from a protein intake of 0.85 g/kg to a protein intake of 0.60 g/kg, GFR was significantly (p less than 0.001) reduced by 29%, while CLi was stable. The data indicate that because of its variability, CLi is of little use in experiments designed to study subtle changes in renal Na transport.

The available data on renal reserve and on the fraction of filtration capacity utilized at rest in childhood are analyzed both in healthy state and in renal disease. The methodological problems which might have biased available information are also discussed.

The renal hemodynamic response to a meat meal (2 g/kg BW) was studied in 11 healthy children and in 10 children with a mean plasma creatinine concentration of 2.6 +/- 0.1 mg/dl due to chronic renal failure (CRF) of various etiologies. In the healthy status, after a meat meal, the glomerular filtration rate (GFR) increased significantly from a baseline value of 119.0 +/- 5.0 to a peak of 159 +/- 5.8 ml/min x 1.73 m2; in CRF baseline GFR averaged 49 +/- 4.0 and at peak 76.6 +/- 7.2 ml/min x 1.73 m2 (p less than 0.005). The peak GFR response was reached earlier in healthy subjects than in CRF (p less than 0.05) and did not correlate with age or with baseline GFR. Renal plasma flow (RPF) in healthy controls increased from 532 +/- 32 at baseline to 646 +/- 42.9 ml/min x 1.73 m2 after the meal (p less than 0.005). Also in CRF after a meat meal there was a significant increase in RPF from 278 +/- 51 to 65 +/- 66 ml/min x 1.73 m2 (p less than 0.005). The filtration fraction was not affected. The percent increase over baseline values of GFR and RPF at the peak was significantly higher in diseased children. Renal reserve averaged 28.1 +/- 5.3 ml/min in diseased children and 39.7 +/- 5.2 ml/min (p less than 0.01). The data indicate that (1) a meat meal is a suitable method to recruit renal reserve in normal children and in children with chronic renal failure, and (2) the renal reserve is normal in chronic renal failure.

Renal morphology was evaluated in 2 siblings with Wiskott-Aldrich syndrome (WAS) aged 12 and 4 years. They gave a typical history of recurrent episodes of respiratory infection and presented with microhematuria of glomerular origin and proteinuria. The study disclosed a membranoproliferative glomerulonephritis with IgA mesangial deposition in the elder child, while immunofluorescence was negative in the younger. The data indicate that (1) a specific nephropathy does not exist in WAS and (2) the IgA nephropathy is the result of recurrent infections and of related formation of IgA immune complexes scarcely removed by a deficient reticuloendothelial system. This view is consistent with presenting features in WAS (microhematuria, episodes of macrohematuria, proteinuria, Henoch-Schönlein syndrome) and with the fact that it takes years to develop as indicated by the negativity of immunofluorescence in the younger patient.

A population-based study on daily and overnight urine excretion of Ca and Mg was performed in 220 children aged 4-15 years living in Cimitile, Campania Region, Southern Italy. The Ca/creatinine and the Mg/creatinine ratio in overnight urine were significantly higher than in daily urine (p less than 0.01). This finding was also confirmed in hypercalciuric children. The Mg/Ca ratio in the general population was identical in daily and overnight urine while in the hypercalciuric group Mg/Ca in overnight urine was significantly higher (p less than 0.01) than in daily urine. The data point to the existence of a circadian rhythm with a peak at night for urine Ca and Mg excretion in children living in Cimitile and studied while attending to their everyday life.

The organometal cisplatin has potent antitumor properties. However, its use is sometimes complicated by significant nephrotoxicity. This is characterized by tubular necrosis and impairment of the glomerular filtration rate (GFR). On the other hand, it has been demonstrated that atrial natriuretic factor (ANF) increases GFR in normal euvolemic rats. In the present study, we have therefore tested if this new potent natriuretic compound could restore some of the renal parameters affected by cisplatin. To investigate this issue, acute renal failure was induced in 9 rats by intraperitoneal injection of cisplatin 10 mg/kg body weight (b.w.). Renal function was studied 72 h later using the 3H-inulin clearance method and was compared with the renal function of 5 normal euvolemic rats. The cisplatin-treated rats showed high blood urea nitrogen levels, a 74% reduction of whole kidney GFR (0.308 +/- 0.047 vs. 1.17 +/- 0.08 ml/min/100 g b.w.) and a significant increase in the fractional excretion of urine, sodium and potassium. After 2 control clearances, synthetic ANF was administered intravenously as a prime (12 micrograms/kg b.w.) and then as a constant infusion (1 microgram/kg/min) to 6 cisplatin-treated rats. This promptly doubled the GFR (0.603 +/- 0.113 ml/min/100 g b.w.) and induced a significant increase in the excretion rate of urine, sodium and potassium. These results demonstrate that the administration of ANF has a beneficial effect on the experimental model of acute renal failure induced by cisplatin.