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The SARS-CoV-2 (Covid-19) has infected about 124 million people worldwide and the total amount of casualties now sits at a staggering 2.7 million. One enigmatic aspect of this disease is the protean nature of the clinical manifestations, ranging from total absence of symptoms to extremely severe cases with multiorgan failure and death. Chronic Kidney Disease (CKD) has emerged as the primary risk factor in the most severe patients, apart from age. Kidney disease and acute kidney injury have been correlated with a higher risk of death. Notably the Italian Society of Nephrology have reported a 10-fold increase in mortality in patients undergoing dialysis compared to the rest of the population, especially during the second phase of the pandemic (26% vs 2.4). These dramatic numbers require an immediate response. At the moment of writing, three Covid-19 vaccines are being administered already , two of which, Pfizer-BioNTech and Moderna, share the same mRNA mechanism and Vaxzevria (AstraZeneca) based on a more traditional approach. All of them are completely safe and reliable. The AIFA scientific commission has suggested that the mRNA vaccines should be administered to older and more fragile patients, while the Vaxzevria (AstraZeneca) vaccine should be reserved for younger subjects above the age of 18. The near future looks bright: there are tens of other vaccines undergoing clinical and preclinical validation, whose preliminary results look promising. The high mortality of CKD and dialysis patients contracting Covid-19 should mandate top priority for their vaccination.

Over the past two decades it has emerged that, in addition to erythropoietic activity, erythropoietin (EPO) has numerous other functions, including neuro-protective, anti-apoptotic, antioxidant, angiogenetic and immunomodulatory ones. EPO interacts with two different forms of its receptor (EPOR): a homodimer receptor, responsible for the erythropoietic effects, and a heterodimer receptor, responsible for the non-erythropoietic effects. The effects on the heterodimer receptor are responsible for EPO-induced prolongation of organ transplant survival in mice and humans. The development of new molecules that selectively target the heterodimer EPOR is allowing to test the effect of long-term treatments, without the possible complications related to the increased hematocrit., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Cardiovascular and renal diseases are one of the main health problems in all industrialized countries. Their incidence is constantly increasing due to the aging of the population and the greater prevalence of obesity and type 2 diabetes. Clinical evidence suggests that aldosterone and the activation of mineralocorticoid receptors (MR) have a role in the pathophysiology of cardiovascular and renal diseases. Moreover, clinical studies demonstrate the benefits of mineralocorticoid receptor antagonists (MRAs) on mortality and progression of heart and kidney disease. In addition to renal effects on body fluid homeostasis, aldosterone has multiple extrarenal effects including the induction of inflammation, vascular rigidity, collagen formation and stimulation of fibrosis. Given the fundamental role of MR activation in renal and cardiac fibrosis, effective and selective blocking of the signal with MRAs can be used in the clinical practice to prevent or slow down the progression of heart and kidney diseases. The aim of the present work is to review the role of MRAs in light of the new evidence as well as its potential use as an antifibrotic in chronic kidney disease (CKD). The initial clinical results suggest that MRAs are potentially useful in treating patients with chronic kidney disease, particularly in cases of diabetic nephropathy. We don't yet have efficacy and safety data on the progression of kidney disease up to the end stage (ESRD) and filling this gap represents an important target for future trials., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Hyperuricemia is one of the many metabolic changes that occur during the course of chronic kidney disease (CKD). Even though it is clear its genesis of high uric acid levels (decreased renal clearance, overproduction, summation of both factors), we do not know the significance with regard to its effects on the cardiovascular (CV) system. On the other hand, the exact role of hyperuricemia in the general population it is not even established . In the general population, many studies have shown a strong correlation between uric acid levels and CV morbidity and mortality. However there are many researches that suggest a role of innocent bystander of uric acid, even in presence of elevated serum levels. Recently, there is an accumulation of evidence that emphasize a close link between uric acid and CV disease, at least in the field of CKD. In the patient population participating to the PIRP project (Prevention of Progressive Renal Failure of the Emilia-Romagna Region), we have seen, even with multivariate analysis, an independent role of high levels of uric acid concerning both, the occurrence of CV events and CV mortality.

Uric acid is the end product of purine catabolism in humans. The plasma concentration is the result of an intricate and partially known process that regulates its synthesis and excretion. Plasma levels range from 3 to 7 mg/dl, and are influenced by diet rich in purines, cell turnover and reduced renal excretion. The kidney plays a pivotal role in acid uric homeostasis, and the pathogenesis of hyperuricemia often correlates with a reduction in the amount of renal excretion, as happens in chronic kidney failure or as a result of certain drugs. Physiologically, uric acid is freely filtered by glomerulus; along the proximal tubule it is reabsorbed and secreted, with a fractional excretion equal to 6-12%. During the last decades many efforts have led to a better understanding of the molecular basis of renal urate handling. The present study analyzes the most recent evidences that demonstrate the role of several proteins involved in urate transport. Understanding this physiological mechanisms had a great impact in clinical practice, providing advances in our knowledge of drug action and genetic associations in hyperuricemic patients; contextually it opened new avenues for drug development.

In the last decades, many progress has been made in our understanding of kidney metabolism and transport of a wide amount of solutes. The purpose of this review is to highlight some issues of kidney metabolism which are still not completely understood and that are nonetheless implicated in the pathophysiology of chronic kidney disease. These untold stories include the recently discovered ammonium transporter proteins Rh and the role of ammonium in causing kidney hypertrophy and renal damage; the role of the human kidney methionine metabolism on epigenetics and the effects of accelerated glucose reabsorption in the proximal tubule on tubulointerstitial damage in diabetic nephropathy. These issues have potential clinical applications and can be a starting point for future research in kidney disease.

Over the past 10 years, major progress has been made in the knowledge of urinary lithogenesis, including the potential pathogenetic role of Randall's plaques and renal tubular crystal retention. Urine supersaturation is the driving force of this process and can be induced by some risk factors, including low urine volume, high urinary excretion of calcium oxalate and uric acid and low urinary excretion of citrate. Primary hypercalciuria can be due to intestinal overabsorption renal leak and bone reabsorption of calcium. Prophilaxis is mainly conducted with thiazides and low calcium diet which is indicated only in the intestinal form. Primary hyperoxaluria is treated with pyridoxine and may require in the severe forms simultaneous renal and liver transplantation. Enteric hyperoxaluria is secondary to fatty acids malabsorption and requires diet, oral calcium and cholestiramine. Hyperuricosuria is caused by diet endogenous overproduction, mainly due to enzymatic defects or high renal excretion of uric acid. Urine alkalinization with K or K and Mg citrate can prevent stone formation even in idiopathic uric acid nephrolithiasis, in which a defect of urine acidification is supposed to be the main abnormality, and in hypocitraturic patients. Cystinuria is a rare inherited defect with an intense clinical impact. It can be classified in three forms and urinary stone formation is the role. Increased solubility and conversion of cystine in a more soluble form are the main goals of the prophylaxis which includes K citrate and thiol agents administration. Tiopronin is preferred to D-penicillamine due to its lower side effects.

Hydrogen sulfide, (H2S), is an endogenous gas which exerts a protective function in several biological processes, including those involved in inflammation, blood pressure regulation, and energy metabolism. The enzymes involved in H2S production are cysthationine -synthetase, cysthationine -lyase and 3-mercaptopyruvate sulfurtransferase. Low plasma H2S levels have been found in chronic renal failure (CRF) in both humans and animal models. The mechanisms leading to H2S deficiency in CRF are linked to reduced gene expression of cysthationine -lyase. Intense research is currently under way to discover the link between low H2S levels, CRF progression and the uremic syndrome and to determine whether therapeutic interventions aimed at increasing H2S levels might benefit these patients.

Since phosphorus plays a critical role in diverse biological processes, regulation of the phosphorus balance and homeostasis are critical to the well-being of the organism. Recent findings point to the presence of a phosphate-sensing mechanism in the various organs and the presence of novel intestinal effectors that alter the renal phosphate excretion after the ingestion of a phosphate-containing meal. Recent studies have provided strong evidence that the sodium-phosphate cotransporter NaPi-IIb is responsible for sodium-dependent phosphate absorption by the small intestine, and this protein might link changes in dietary phosphate to altered renal phosphate excretion in order to maintain the phosphate balance. It has been established that different regions of the small intestine respond differently to acute or chronic changes in dietary phosphate load and that phosphatonins inhibit both renal and intestinal phosphate transport.

Sodium, the most important extracellular fluid electrolyte, is the focus of several homeostatic mechanisms that regulate fluid and electrolyte balance. Hyponatremia is a common electrolyte abnormality caused by an actual sodium deficiency or extracellular compartment fluid excess. Clinical symptoms are related with acuity and speed with which this abnormality is established. The symptoms are mainly neurological and neuromuscular disorders (headache, confusion, stupor, seizures, coma) due to brain cells edema. Hyponatremia due to sodium deficiency is caused by sodium loss from kidney (nephritis, diuretics, mineralocorticoid deficiency) and / or extrarenal (vomiting, diarrhea, burns). Hyponatremia due to water excess seems to be the most common and it is attributable to cirrhosis, nephrotic syndrome, heart failure, infusion 5% glucose solutions and drugs that stimulate ADH secretion. It was recently highlighted the role of inflammation and IL-6 in the non-osmotic ADH release. Hyponatremia is considered also marker of phlogosis. Acute (<48 h) and severe (<125 mEq/ L) hyponatremia is a medical emergency that requires prompt correction. Patients with chronic hyponatremia have a high risk of osmotic demyelination syndrome if rapid correction of the plasmatic sodium occurs. In combination with conventional therapy, a new class of drugs, vasopressin receptors antagonists (AVP-R antagonists) would be able to increase the excretion of electrolyte-free water and the serum sodium concentration.

Hyperphosphatemia is pivotal in some complications secondary to kidney dysfunction. Current guidelines suggest that hyperphosphatemia due to kidney dysfunction develops only when kidney function is reduced to <50%. This paper deals with the relationship of age to phosphatemia and with the possible influences of this relationship on hyperphosphatemia due to kidney dysfunction. In pediatric age phosphatemia decreases during growth. A recent epidemiological study showed a decrease in phosphatemia with age among adults also. This decrease differs between men and women, being continuous in men but not women because of a transitory increase in phosphatemia during menopause. Data also show that age-associated differences in phosphatemia among adults are explained by differences in the maximum reabsorption of phosphate in the renal proximal tubule (TmP/GFR). Other studies suggest that the opposite influences on TmP/GFR of growth hormone (stimulation) and estrogens (inhibition) are the determinants of the changes in TmP/GFR and phosphatemia associated with age. The inverse relationship of age with phosphatemia leads to the hypothesis that, in the presence of a disorder increasing phosphatemia, the prevalence of hyperphosphatemia would be higher in young adults than in elderly people, who have lower phosphatemia in health. A large clinical study supports this hypothesis, showing that hyperphosphatemia secondary to kidney dysfunction is approximately four times higher at age <65 than at age >65 years. Data suggest that the relation between kidney function and phosphatemia should be re-evaluated considering possible confounding due to age.

Erythropoietin synthesis is one of the essential adaptive responses to a hypoxic environment. In mammals, a renal oxygen sensor capable of stimulating erythropoietic hormone synthesis through a transcriptional factor called HIF (hypoxia-inducible factor) has long been identified. Recent research has demonstrated that cerebral astrocytes and skin keratocytes can also produce erythropoietin as a response to different oxygen concentrations. Therefore, it is possible to hypothesize a skin-brain-kidney link which, through erythropoietin production, modulates the oxygen contribution to tissues. Moreover, the results are not so unambiguous and further research on the pleiotropic effects of erythropoetin would be opportune.

The erythropoietin is produced by the kidney and other organs. EPO does not only affect erythroid cells, but also other blood cell lines, such as myeloid cells, lymphocytes and megakaryocytes. This hormone can also enhance phagocytes function of the polymorph nuclear cells and reduces the activation of macrophages, thus modulating the inflammatory process. Hematopoietic and endothelial cells probably have the same cellular origin, and the discovery of erythropoietin receptors also on mesangial and myocardial cells and smooth muscle fibro-cells has prompted the study of the pleiotropic actions of this hormone. Through its receptors, spread out over the body, it carries out many actions which range from the erythrogenesis after hypoxic stimuli to the tissue protection of the heart and the brain after ischemia. Erythropoietin also acts in the endothelial proliferation of new vessels involving the tumor genesis, but it opens new frontiers to the employment of rHuEPO in the Regenerative Medicine.

The wide distribution of the vitamin D receptor (VDR) suggests that its activators (VDRAs) are involved in diverse organ functions including the cardiovascular, immune, and reproductive systems. These actions are likely to be independent of PTH and calcium/phosphorus levels. Earlier studies had shown that calcitriol was able to favorably influence experimental nephritis, remnant kidney glomerulosclerosis, and interstitial fibrosis, mediated through inhibition of inflammatory cytokines. Recently, VDRAs were shown to inhibit the reninangiotensin system (RAS), acting directly on the renin gene promoter. This action is independent of the systemic RAS blockade. VDRAs also inhibit other important gene promoters including NF-kB and p65, which are known to foster inflammation and fibrogenesis. These multiple actions result in a decrease in macrophage infiltration, fibroblast activation, and endothelial mesenchymal transition in the kidney. These findings represent the rationale for the use of VDRAs, in association with RAS blocking agents, to counteract the progression of renal injury characterized by inflammation and neofibrogenesis. However, despite promising preliminary results, the human studies available to date do not allow to draw definitive conclusions on this matter.

Stem cells are a potential source for the regeneration of many tissues, including damaged kidneys. The present study describes the adoption of hyaluronic- butyric acid monoesters (HB) to induce expression of nephrogenic genes by mesenchymal cells isolated from human placental membranes. HB at a concentration of 1 mg/mL induces chromatin opening and increases the expression of the observed markers (cadherin 11, CD24, RAR-alpha, stearoyl-CoA desaturase 2, 14-3-3 0, Ewing sarcoma homolog.). These results open new routes toward cell regeneration after kidney injury.

Many parameters of biological functions, interesting different branches of medicine, have to be indexed by the same value for each other comparison between single individuals or between-within groups. Body Surface Area (BSA) and 1.73 m2 reference value are probably the most used tools for indexation, but a growing number of scientific papers emphasize the risk of under or over estimates of data by BSA indexation in overweight--obese or on the contrary underweight individuals. This study has been planned to evaluate this problem a) by a theoretical approach, indexing to 1.73 m2 the creatinine clearance (CtCl) in an ideal population and b) analysing and debating the doubts and problems about the indexation by BSA in many fields, the possibilities of indexation by other methods, or to use BSA with different approach, to reduce the risk of bias, evaluating the possibility of this target in a real population of 45 men and 84 women undergoing Peritoneal Dialysis (PD)--III--There is a lack of significative correlation between BSA and GFR, this one on the contrary significantly correlated with lean body mass and body water, possible alternatives to BSA. Researches performed to validate the indirect estimates of above variables by creatinine excretion and bioimpedance don't seem up till now to give sufficient evidences for a general acceptance. In conclusion, it would be advisable or to drop the indexing by BSA or, if necessary, to use it by different methods, as theoretically shown in this paper.

Many parameters of biological functions, interesting different branches of medicine, have to be indexed by the same value for each other comparison between single individuals or between-within groups. Body Surface Area (BSA) and 1.73 m2 reference value are probably the most used tools for indexation, but a growing number of scientific papers emphasize the risk of under or over estimates of data by BSA indexation in overweight--obese or on the contrary underweight individuals. This study has been planned to evaluate this problem: a) by a theoretical approach, indexing to 1.73 m2 the creatinine clearance (CtCl) in an ideal population and b) analysing and debating the doubts and problems about the indexation by BSA in many fields, the possibilities of indexation by other methods, or to use BSA with different approach, to reduce the risk of bias, evaluating the possibility of this target in a real population of 45 men and 84 women undergoing Peritoneal Dialysis (PD). The effects of indexing 1.73 m2, according different weights on the CtCl of the ideal population and on the values of BSA estimation according different formulae. Results, methods, and the problems due to abnormal fluctuation of weight compared to normal range of standard value according height are analyzed and discussed.

Mercury (Hg) exposure makes happen disease to humans and animals spreading in all body compartments, especially in liver and kidney. In these ones, copper, zinc, manganese and iron were investigated to assess perturbation of essential metals' homeostasis due to Hg chronic intoxication. Because L-arginine, is able to induce beneficial influence on immunologic functions on mice intoxicated with Hg, we also studied the efficiency of detoxification process before and after treatment with this aminoacid. Adding L-arginine to diet of the intoxicated mice we achieved a good restoration to normal homeostatic conditions.

Organic anion transporters (OATs), which are expressed in proximal tubule cells, mediate diuretic secretion into tubular fluid. Increased plasma levels of organic anions and urate and metabolic acidosis, i.e. two characteristic features of chronic renal insufficiency, could be factors contributing to diuretic resistance. These limitations demand increasing doses of diuretics up to a maximum level, or the use of a loop diuretic with non-renal metabolism. Diuretic responsiveness in nephrotic syndrome is limited by strong Na+ reabsorption in the distal nephron. Strategies to improve loop diuretic responsiveness include diuretic dosage and the combination of a loop diuretic with a distal acting diuretic. Strategies to limit protein excretion include the use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers and appropriate salt intake limitation.

Histopathological features of transplanted kidneys which gradually lose graft function have been traditionally reported with the term of chronic rejection (CR). In 1997 Banff's classification indicated the adoption of a new term for all these histological features, namely Chronic allograft nephropathy (CAN), recommending that the presence of morphological aspects suggestive of chronic rejection, such as chronic transplant glomerulopathy (CTG) and proliferative endoarteritis (PE), has to be specified. On the basis of these criteria we reviewed the renal biopsies of 92 patients who underwent kidney transplantation from 1999 to 2002. In all cases the biopsy had been performed 6 months after organ transplantation. In 30 of the 92 patients CTG and/or PE was evident supporting a diagnosis of CR; on the contrary, in 11 of the 92 patients the final diagnosis based on histological evidence was that of CAN. Clinical and laboratory tests revealed that the presence of proteinuria in patients with CR at the time of diagnosis was the single statistically significant difference between these two groups. In 7 of the 32 patients where the diagnosis of CR was based on the presence of early features of CTG, the treatment with ACE-I induced complete remission of the proteinuria. Cyclosporine-induced arteriolopathy (CSA) represents an additional histological finding which has been associated with graft loss in the transplanted kidney. The observation of arteriolopathy, similar to CSA in patients who did not receive calcineurine inhibitors, suggests some caution in the use of this diagnostic criteria.

Background: It was considered appropriate to update of the significance and use of the different mercury exposure indicators., Objective: The aim of the this paper was to correctly select biological media and sampling time and to understand the toxic kinetics of mercury for assessment of accurate biological monitoring., Results: It was confirmed that mercury in blood (B-Hg) is a good indicator of recent exposure, while urinary mercury (U-Hg) indicates current exposure when mercury reaches the renal steady state. B-Hg values are greatly influenced by fish consumption, while the variables influencing U-Hg values are amalgam fillings, commercial gamma-globulin preparations, vaccines, topical remedies, environmental pollution and hobbies, occupational exposure and, partly, fish consumption. The speciation of mercury (Hg0, Hg++, methylmercury and ethylmercury) in biological media, should provide additional and important information in evaluating mercury toxicity., Conclusion: It was stressed that the appropriate choice of exposure indicators has to take account of the different variability factors and the characteristics of the toxic kinetics of mercury. The results of biological monitoring must be compared with references values, which are generally in the order of several micrograms/g creatinine, and limit values such as ACGIH BEI (U-Hg 35 micrograms/g creatinine and B-Hg 15 micrograms/l) or the DFG BAT (U-Hg 100 micrograms/l and B-Hg 25 micrograms/l).

A 25 years old lady presented to our outpatient clinic complaining nicturia, polyuria and polydipsia. On the basis of clinical assessment and the results of a simple test, a diagnosis of Nephrogenic Diabetes Insipidus (NDI) was made. The diagnosis of NDI is often missed, and appropriate treatment therefore delayed, with severe consequences especially in elderly and bed restricted people.

Background: The aim of the study was to value the behaviour of systolic (S) and diastolic (D) arterial pressure (AP)/24 hrs in a group of diabetic patients insulin-dependent (IDDM) and non insulin-dependent (NIDDM) with preserved renal function., Methods: We examined 65 diabetic patients (aged 39.1 +/- 23.3), 33 IDDM (aged 18.2 +/- 7.5; years of diabetes: 5.8 +/- 4.9) and 32 NIDDM (aged 60.7 +/- 11.4; years of diabetes: 7.2 +/- 7.5). In all of them we computed BMI and determined creatinine clearance, glycosylated haemoglobin A, total and HDL-associated cholesterol, triglyceridemia, middle glycemia and microalbuminuria. AP measurement was performed by 24 hrs monitoring (periodicity 15') using a Takeda 2420 measurer. Chronobiological characteristics of AP were analysed by statistical method of cosinor according to Halberg, examining if there was or not a blood pressure circadian rhythm (PCR) (p < 0.05) and its characteristics represented by the mesor, the amplitude and the acrophase. Moreover the patients were subjected to a diet with fixed contents of sodium (130 mEq/day) and afterwards we drew (every 4 hours) renin (R), aldosterone (A1) and atrial natriuretic factor (ANF) which were analysed with cosinor's method. The purpose was not to compare the two populations, not homogeneous between them and not different only for the years of diabetes, but to study their blood pressure behaviour, the rhythm, the order of the indicated hormones for possible pathogenetic connections., Results: NIDDM presented higher blood pressure values (PAS 134.2 +/- 3.5 and PAD 80.9 +/- 2 mmHg) than IDDM (PAS 116.6 +/- 1 and PAD 66.4 +/- 1.7 mmHg), still in limits of substantial normality. The acrophase was in the midday for NIDDM (PAS 11:25', PAD 12:06') and in the early afternoon for IDDM (PAS 14:15', PAD 14:06'). Analysing the trend of the AP in the single cases, PCR was present in 70% and absent in 30% of IDDM while it was persistent in 56% and disappeared in 44% of NIDDM. IDDM without PCR differed from those with it in years of diabetes (p < 0.001), body weight (p < 0.02), BMI (p < 0.01), triglyceridemia (p < 0.05), all more elevated, as well as in higher PAS and PAD (p < 0.001) and in higher concentration of ANF (p < 0.05). The same comparison was done in NIDDM. Patients without PCR were older (p < 0.025), had higher PAS (p < 0.025) and PAD (p < 0.001) and also a more activated ANF (p < 0.001)., Conclusions: This hormonal anomaly may be ascribed to a lower excretion of sodium with consequent expansion of extracellular volume due to antinatriuretic action of insulin often found at high plasmatic levels particularly in NIDDM.

Glutamine is a non essential amino acid. Nevertheless it has to be considered a "conditionally essential" amino acid for several metabolic reactions in which it is involved. Glutamine is the most abundant amino acid in human plasma and muscle. Because glutamine is highly unsteady, it was never used for enteral and parenteral nutrition in the past. It appears to be a unique amino acid for rapidly proliferating cells serving as a preferred fuel compared to glucose. It seems to be essential for cellular replication such as a "nitrogen carrier" between the tissues. A deficiency state of glutamine causes morphology and functional changing and negative nitrogen metabolism. The need for glutamine is particularly high when metabolism is increased as in the critically ill (surgical stress, sepsis, inflammatory states, fasten, burns) especially in the tissues with a rapid cell turn-over. In these conditions the body requirements of glutamine appear to exceed the individual's muscle deposits (muscle is the most important place of synthesis and storage), causing an increased synthesis with a high energy waste and loss of muscle mass. Glutamine is essential for bowel mucosa trophism and its deficiency in all the catabolic states allows bacterial translocation. In these cases feeding is not sufficient to restore basal conditions. At present enteral or parenteral glutamine supplementations are of high interest for the feeding of critically ill patients.

Attempts to rationalise the treatment of hypertension on the basis of pathophysiological and clinical characteristics of patients, such as renin profile and age, have had minimal success in the past. More recently it has been found that the response to ACE inhibitors or calcium antagonists might be predicted on the basis of the ability of the kidney to produce kallikrein. Urinary excretion of active kallikrein is considered an index of the activity of the renal-kallikrein system and this system is thought to play an important role in modulating the effects of ACE inhibitors. In patients with low urinary kallikrein excretion the efficacy of ACE inhibitors is blunted and, on the contrary, that of calcium antagonists seems to be enhanced. Among ACE inhibitors the choice of a specific drug might also-based upon the effects of the molecule on the tissue renin-angiotensin system. In this regard lipophilic ACE inhibitors, such as ramipril, may produce a therapeutic effect at doses which are better tolerated due to greater tissue penetration.

We assessed the iron load content in 36 beta-thalassemia patients by NMR correlating the results with serum ferritin levels. 22 of them were affected by beta-thalassemia major on hyper-transfusional regimen (Group A), 4 by beta-thalassemia intermedia (Group B) and 10 by beta-thalassemia major, who had been previously bone marrow transplanted (Group C). In A and C Groups the liver showed the lowest signal intensity on spin echo images (p less than 0.01; p less than 0.06, respectively). A significant correlation between the summation of signals obtained from all the examined organs and serum ferritin levels was observed by evaluating both all the patients globally (r = 0.78; p less than 0.001) and the A and C Group patients. This correlation was confirmed only in the liver both in all the patients (r = 0.77; p less than 0.001) and in A and C Group patients, when the signals obtained from each organ were evaluated.

Renal clearances of transeferrin, IgG and C'3 were determined by the immunodiffusion method in 51 healthy children. Statistical elaboration shows the great dispersion around the mean values. The results of other Authors in healthy adults are confirmed.

Biosynthesis of prostaglandins of E series in BK virus-transformed rabbit-kidney cells (RKBK) and mouse hepatoma cells cultured in vitro with and without exogenous arachidonic acid was determined by radioimmunoassay. Elevated concentrations of prostaglandin E2 were observed in both cell types; moreover, tumor and transformed cells were capable to synthesize higher levels of prostaglandin E2 than normal cells. Mouse hepatoma cells produced more prostaglandins compared to RKBK cells; in addition they seemed less sensitive to inhibition by indomethacin. These data suggest that arachidonic acid metabolism may be another one of the intrinsic biochemical properties that differentiate tumor and virus transformed cells.

The effect of various concentrations of aflatoxin B1 (AB1) is studied "in vitro" on heart (HM) and kidney mitochondria of rabbit (KM). AB1 inhibits (4 x 10(-4)M) the respiratory rate up to a maximum 50-35% in HM and 28-35% in KM by glutamate and succinate as substrates respectively, but it does not uncouple oxidative phosphorylation nor does it inhibit site III (ascorbate + TMPD). The inhibited site appears to be between cytochromes b and c (c1). AB1 seems to be easily transported across heart mitochondrial membrane. The relevance of these findings to liver cell necrosis promoted by aflatoxin is discussed.

PRA, plasma and urine aldosterone levels and plasma digoxin were measured in rats in which digoxin had been administered under conditions of high PRA and high aldosterone levels experimentally induced by administering distilled water load and in rats in which digoxin had been administered without distilled water load. Results show that under conditions of high PRA and high aldosterone levels, plasma digoxin concentrations as measured 6 h after treatment were higher (45,3%) than in rats having received digoxin without water load. In assays carried out on rats sacrificed 12 h after digoxin treatment (with or without water load) all values approach basic levels again, thus suggesting that in rats too aldosterone might compete with digoxin at the level of tubular excretion.

In 14 patients the kinetics has been studied of two contrast media labelled with 131I, and namely of MGM diatrizoate and of diatrizoate of sodium and MGM. The clearance was determined both at basal concentrations and in double concentration by means of external counting. The results were statistically studied by means of the linear regression method. The authors conclude that the MGM diatrizoate is exclusively eliminated through the glomeruli both in basal and double concentration. The diatrizoate of sodium and MGM is eliminated in low concentration through the glomeruli, while in double concentration it is partially eliminated through the tubuli.

Density gradient centrifugation analysis has been used to study rat kidney receptors for dexamethasone. Density gradients performed with cytosol incubated with 3H-dexamethasone in a Tris 10 mM, EDTA 1.5 mM, glycerol 5%, monothioglycerol 12 mM (pH 7.5) buffer never gave any good evidence of a 85 radioactivity peak probably due to instability of the complex. The stability of the complex for at least 30 h was achieved by homogenizing the tissue and incubating cytosol in a distilled water, glycerol 5% monothioglycerol 12 mM solution. Density gradient centrifugation analysis in this way showed radioactivity peak at the bottom of the tube probably due to the aggregation of the complex. Since this drawback is inherent in the technique it must be concluded that density gradient centrifugation analysis cannot be used to study the dexamethasone-receptor complex of the kidney.

Aminoglycoside antibiotics are characterized by a quick fall of blood levels (half-life 2-3 hours) and by a very slow urinary excretion (they can be detected in the urine up to 10-20 days after therapy is discontinued). This peculiar pharmacokinetic feature of these antibiotics may be attributed to some rapid steps of their pharmacokinetics (glomerular filtration, tubular reabsorption or uptake, storage in the renal cells) followed by a very slow step (transfer from these cells to tubular lumen with following urinary excretion). The aminoglycosides are very polar compounds and their uptake by tubular cells is mediated by an active transport. The uptake is responsible for the storage in the corticorenal cells. It is generally held that the storage, because of its long duration, is responsible for the nephrotoxicity, although the correlation between storage and nephrotoxicity is denied by some authors. Some practical implications of aminoglycoside pharmacokinetics could be: a) Kidney damage by aminoglycosides is often reversible, but the potential risk of nephrotoxicity must be considered to be still present at the time of the interruption of therapy. Therefore the measures during aminoglycoside therapy (prophylaxis of risk factors, monitoring of renal function, etc.) are to be continued also in the period immediately after the interruption of therapy. b) In animals some factors (high-calcium diet, calcium blockers, ACE inhibitors) are able to reduce aminoglycoside nephrotoxicity; some of them are operating through inhibition of uptake. It would be desirable to test the possible ability of these factors to reduce aminoglycoside nephrotoxicity in humans.

The literature on glycide-induced lipidogenesis is reviewed. This is an important question also because of its relation to the pathogenesis of pathological conditions such as ketoacidosis, obesity and hypertriglyceridaemia. Doubt is expressed concerning the interpretation of some experimental procedures used in determining the extent of lipidogenesis in man. The questions raised are fully discussed. Their solution is sought via an experiment on the rat involving the comparison of tissue and plasma lipid metabolites values following infusion of a labelled glucose bolus. Little correlation was noted, low plasma levels being found with high tissue radioactivity. It is emphasized that it is very difficult to ideate a valid experimental approach in order to investigate the extent of lipidogenesis in man in vivo: in this respect, the long term risk arising from the use of tracers with a very long half-life (e.g. 14C) in man must be carefully valuated.