Renal Volume in ADPKD Patient Evaluation.

The clinical manifestations of ADPKD are related to the growth of renal cysts. Renal volume has been recognised as the biomarker that is able to identify those patients at risk of complications (hypertension and haematuria) and at risk of progression to End Stage Renal Disease (ESRD). Recently, several scores have been introduced to predict the evolution of ADPKD. The Mayo Clinic Group developed a classification based on renal volume as measured by CT or MRI and corrected for age and height (Ht-TKV); this allowed predicting the evolution of the disease, but it has not been fully validated so far. In addition, it is used to identify patients labelled as "fast progressors" and eligible for Tolvaptan therapy according to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) recommendations. We studied 80 patients who underwent MRI and had been classified as ADPKD typical form (class 1A-1E). A significant correlation between renal volume, hypertension, and low GFR was found (p < 0.005). A progressive increase in disease severity has been found across the different Mayo classes; 41.2% were eligible for Tolvaptan therapy. The results demonstrate that the Mayo method is easy to perform and provides valid information in order to identify with rapidly progressing disease.

Nonvitamin K-dependent oral anticoagulants (NOACs) in chronic kidney disease patients with atrial fibrillation.

Atrial fibrillation (AF) represents the most common arrhythmia in patients with chronic kidney disease (CKD). As in the general population, in CKD patients AF is associated with an increased risk of thromboembolism and stroke. However, CKD patients, especially those on renal replacement therapy (RRT), also exhibit an increased risk of bleeding, especially from the gastrointestinal tract. Oral anticoagulation is the most effective form of thromboprophylaxis in patients with AF presenting increased risk of stroke. Limited evidence on efficacy, the increased risk of bleeding as well as some concern regarding the use of warfarin in CKD, has often resulted in the underuse of anticoagulation CKD patients. A large body of evidence suggests that non-vitamin K-dependent oral anticoagulant agents (NOACs) significantly reduce the risk of stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with vitamin K antagonist such as warfarin in normal renal function subjects. Hence, they are currently recommended for patients with atrial fibrillation at risk for stroke. However, NOACs metabolism is largely dependent on the kidneys for elimination and little is known in patients with creatinine clearance <25ml/min who were excluded from all pivotal phase 3 NOACs trials. This review focuses on the current pharmacokinetic, observational, and prospective data on NOACs in patients with moderate to advanced chronic kidney disease (creatinine clearance 15-49ml/min) and those on dialysis.

[Pharmacokinetic principles and drug-dosing adjustments during continuous renal replacement therapies (CRRT)]. / Principi di farmacocinetica e aggiustamento posologico dei farmaci nell terapie sostitutive renali continue (CRRT).

In the critically ill, acute renal failure (ARF) and "Multiple Organ Dysfunction Syndrome" (MODS) can be associated with significant modifications of many pharmacokinetic parameters, such as protein binding, volume of distribution and total body clearance. The start of renal replacement therapy (RRT) represents an additional variable to take in consideration for drug-dosing adjustments. Drugs significantly eliminated by the kidney are likely to be removed during RRT and a supplemental dose or further dosing adjustments are required if extracorporeal clearance is more than 25-30% of total body clearance. The impact of RRT on plasma drug concentrations can be substantially different in relation to the type of treatment (diffusive, convective or both), membrane characteristics (low-flux or high-flux), filter surface area and prescribed dialysis dose. The molecular weight cut-offs of high-flux membrane are much higher than the molecular weight of most drugs. Therefore, molecular size will not be a limitation for the removal of the unbound fraction of the drugs most commonly used in the critically ill undergoing continuous renal replacement therapy (CRRT). However, diffusive clearance could be significantly lower than convective clearance for drugs in the middle molecular weight range. In any case, the extracorporeal clearances report-ed with the use of high-volume CRRT (>50-60 L/2 h) are often surprisingly elevated and can lead to drug underdosing in clinical conditions where adequate antibiotic treatment is essential.

[Plasmapheresis combined with pharmacology in the treatment of lupus nephritis: a new therapeutic protocol]. / La plasmaferesi associata alla terapia farmacologica nel trattamento della nefrite lupica: nuovo protocollo terapeutico.

Systemic Lupus Erythematosus (SLE) is a pathology of unknown cause, characterized by tissue and cellular damage, secondary to production of autoantibodies and to deposition of immunocomplexes. Lupus nephritis is one of the most common complications of SLE. Our purpose is to propose a therapeutic protocol for patients suffering from Lupus nephritis. This consists of Plasmapheresis associated with pharmacological therapy so that dosage of immunosuppressors can be reduced and consequently also the side effects of the pharmacological therapy.

Nephrotic syndrome and plasmapheresis.

We studied 15 patients suffering from nephrotic syndrome (NS) in bioptically-accertained primary and secondary glomerulopathies responding poorly to the common pharmacological treatment. They were monitored for one year by assessing their immunological and kidney functionality parameters, especially proteinuria. The patients underwent 3 apheretic sittings using the cascade double-filtration technique. After the third apheretic sitting the patients received metilprednisolone 300 mg/m2. This therapy was repeated every month for 6 months. At the end of the apheretic cycle it was shown that all patients had responded well to the therapy with a dramatic decrease in proteinuria, maintenance and/or recuperation of kidney functionality and improvement of lipidic asset; these data remained unchanged over time. Considering our preliminary results, we believe that therapeutic apheresis has a precise function in refractory nephrotic syndrome and, in particular, we propose the use of the cascade double-filtration technique.

[Holter monitoring of the arterial pressure in the follow up of a group of aged patients with chronic uremia]. / Follow-up della pressione arteriosa in un gruppo di uremici anziani cronici mediante monitoraggio Holter.

The cardiovascular complication represents the principal effect of death in patients uraemics cronics. The hypertension is one of most cause; for this, the control of hypertension is one important objective in this patients. The introduction of dynamic monitoring permit to estimate the adeguatesse of hypertension control or the appearance of extradialitic hypotension. The dynamic monitoring permit to value the difference in two groups, young and elderly and to conform the hypertension therapy.

[Plasmapheresis and mushroom poisoning:report of a case of Amanita phalloides poisoning]. / Plasmaferesi e avvelenamento da funghi: presentazione di un caso di intossicazione da Amanita phalloides.

A case of amanita phalloides which presented a typical picture of phalloides intossication has been treated at our Centre. The patient was submitted to four treatments of plasmaexchange (Plasmafiltration), exchanging from 70 to 80% of the plasmatic volume and using substitutive liquids 4% albumine and frozen plasma, using as filter Plasmaflo Asahi OP-O5 (1) and Plasmapheresis equipment SIFRA mod. 914. Already after the first treatment there was an improvement of the general condition with a stabilization of the renal and hepatic parameters at the end of the cycle.

[Comparative study of the modification of arterial pressure in adult and aged subjects treated with hemofiltration. Preliminary results]. / Studio comparativo delle modificazioni della pressione arteriosa in soggetti adulti ed anziani in trattamento dialitico con tecnica di emofiltrazione. Risultati preliminari.

Haemodynamics modifications in 49 patients divided in two groups consisting of 21 young people (average age 43 +/- 12 yrs.) and 28 elderly people (average age 72 +/- 7 yrs.) who have undergone at least three treatments with haemofiltration for congestive cardiac decompensation and chronic renal failure have been evaluated. Systolic and diastolic blood pressure and heart rate have been monitored for each patient in a length of time of iT, T30 min., T60 min., fT. The results show a statistically significant reduction of the systolic pressure during the time interval iT-T30 min. in subjects over 65, contrary to the control group. Such preliminary results can be justified by the haemodynamic modifications correlated to the elderly process. In any case the hypothesis cited by the authors need further testing even if confirming the indication of the dialytic treatment on patients over 65 through haemofiltration techniques.

[Efficacy of recombinant erythropoietin on the quality of life in patients over 60 years of age undergoing hemodialysis]. / Efficacia dell'eritropoietina ricombinante sulla qualità di vita in pazienti emodializzati ultrasessantenni.

We followed for a period of six months, 54 patients of over 60 years old, submitted to hemodialitic treatment. We gave human recombinant erythropoietin, average dosage 50 UI/Kg subcutaneously on alternative days, folic acid and iron supplements together with a proteic supply of 1.2 g/Kg/die (35 Kcal/Kg). The medullary response has been monitored with hematochemical tests; blood pressure and nutritional conditions have been evaluated. Furthermore, the patients were given a questionnaire to evaluate their quality of life. At the end of the follow up, 50 patients responded positively to therapy. These patients showed an increase of RBC (from 2,789,780 +/- 259,310 to 3,313,110 +/- 472,780 p < 0.001) of HCT (from 21.86% +/- 2.16% to 27.18 +/- 2.74% p < 0.0001) and of Hb (from 7.72 +/- 1.12 g/dl to 9.28 +/- 0.98 g/dl p < 0.006). Total protein and albumin increased too. Furthermore they showed a progressive increase of "performance status". Our results confirm efficacy of erythropoietin in the treatment of anemia in elderly hemodialized patients.

Haemorheological changes in mixed cryoglobulinaemia during apheresis treatment.

Thirty-four patients affected by mixed cryoglobulinaemia have been submitted to treatment by apheresis (plasma exchange or double cascade filtration). The authors have monitored clinical, laboratory and, above all, haemorheological changes following therapy. The final results have shown mainly a reduction of plasma viscosity and consequently an improvement of the haemorheology of the affected organs. In conclusion, apheresis may be considered a successful therapy in patients with severe renal or neurological diseases due to mixed cryoglobulinaemia.

[Reinfusion ascites therapy: considerations after a year's experience]. / Terapia dell'ascite refrattaria: considerazioni dopo un anno di esperienza.

Ascites often appears as a complication of several illnesses. The therapy is essentially based on the use of low-sodium diet, plasma or albumin infusion, diuretics and low-dosed ACE-inhibitors. To use the simple paracentesis or special techniques as Rhodiascit or Lee Veen Shunt means not to resolve definitively the problem and sometimes to cause undesirable complications. The authors present a new therapeutic tactics that joins the use of technique of double filtration of ascitic fluid and reinfusion of concentrated proteins (DFAF) with the injection in the peritoneal cavity of beta-interferon and the venous infusion of ATIII. Twenty patients affected by hepatic cirrhosis with the presence of ascitic fluid not treatable with the usual therapy have been subjected to this treatment. All the patients showed an immediate improvement of the clinical situation. After one year of observation, we describe our results. Twelve patients needed a further treatment with the DFAF technique, two patients died for the original pathology and six patients just needed an adjustment of pharmacologic therapy.

Biocompatibility in hemapheresis: new materials.

The development of new technologies implying the use of semidialytic synthetic membranes in therapeutic apheresis, lays stress also on the problem of biocompatibility. The first alterations of plasma proteins and of the immune system are observable 15 minutes after the beginning of the apheretic session. This may suggest that the acute clinical reactions observed during apheresis are related to biocompatibility. However, the first chronic side effects, comparable to those observed in hemodialysis, do not occur before 10-20 sessions. It is known, in fact, that even when inactive materials, such as the last generation membrane, are used, plasma exchange affects the immune system and may determine plasma protein alterations (protein film, erythrocytic damage, ADP release, beginning of the coagulation process, complement consumption). The whole system or the type of membrane, the involucre, the potting glue and the lines affect the interactions. The contact of blood with a foreign surface initiates a number of local reaction, with subsequent reactivity of the organism. The activation of the complement system, coagulative system, fibrinolytic system and callicrein-kinin system is therefore responsible for the cell functional modifications. It is necessary to underline the role of the membrane surface used, in that the activation of the complement system, of the gathering of platelets and of the cell activity modification all increase with the increase in surface. Biocompatibility may be affected not only by the membranes, but also by the substitution fluids and by the anticoagulant used.

[Therapy of hypercholesterolemia and hypertriglyceridemia. Comparison of hypolipemic effects of lovastatin and gemfibrozil]. / Sulla terapia dell'ipercolesterolemia e dell'ipertigliceridemia. Confronto sull'effetto ipolipemizzante fra lovastatina e gemfibrozil.

The authors report the results of a comparative study of the effects of lovastatin and gemfibrozil on plasma cholesterol. Both drugs inhibit the enzyme systems responsible for cholesterol synthesis at the initial stages. The trial was conducted in 40 patients with nonfamilial hypercholesterolemia of whom 20 were treated with lovastatin and 20 with gemfibrozil. Throughout the trial, subjects took a dietary regime of about 1500 cal. Thirty days' before the start of the trial, patients received a placebo daily. Before and after the placebo period and at the end of 30 days treatment with either drug, cholesterol, esterified cholesterol, VLDL, LDL, and HDL cholesterol, apolipoprotein B, phospholipid, triglyceride and free fatty acid blood levels were tested, as well as the level of fatty acid saturation (iodine number), and the activities of lipase and plasma heparin. The results obtained showed both drugs to induce significant reductions of total, VLDL- and LDL-cholesterol and apolipoprotein B, and a relative increase in HDL-cholesterol. Triglyceride blood level was more markedly reduced in patients treated with gemfibrozil compared to those treated with lovastatin, a difference accounted for by the different levels at which the two drugs interfere with the enzymes of the initial stages of cholesterol synthesis. Plasma free fatty acids rose more markedly under gemfibrozil while plasma lipase and heparin activity did not show any appreciable changes under either drugs. The authors conclude by pointing out that the use of these drugs should be decided according to the type of metabolic disorder to be corrected.

[Comparison of the lowering effect on blood cholesterol of clofibrate and simvastatin]. / Confronto sull'effetto ipocolesterolemizzante fra clofibrato e simvastatina.

The authors report the results obtained in a comparative study of effects of clofibrate and simvastatin. The investigation was carried out on 44 patients with type IIB hypercholesterolemia subdivided into two groups. Throughout the study, patients observed a diet of about 1500 Kcal daily. Thirty days before starting drug treatment, all patients were given a placebo daily, either of the two drugs being administered during the subsequent 30 days. Plasma cholesterol level was examined before starting placebo and before drug treatment and every five days throughout drug treatment. The results obtained showed that both drugs reduced cholesterol plasma level significantly but the reduction obtained with simvastatin was greater than that obtained with clofibrate. The specificity of the use of these drugs in the management of hypercholesterolemia is stressed.

[Therapy of hypercholesterolemia and hypertriglyceridemia. Comparison of the lipid-lowering effect of simvastatin and tiadenol]. / Sulla terapia dell'ipercolesterolemia e dell'ipertrigliceridemia. Confronto sull'effetto ipolipemizzante fra simvastatina e tiadenolo.

A comparative trial was carried out on the effect on lipid metabolism of two drugs which inhibit the enzyme systems involved in cholesterol synthesis: tiadenol and simvastatin. The trial was performed in 40 patients with non familial and non secondary hypercholesterolemia. Subjects were divided into two groups of 20 patients each, one to be treated with tiadenol, the other with simvastatin. During the study period all patients followed a dietary regime of about 1500 cal daily. Thirty days before the trial, patients were given a placebo daily, and this was followed by thirty days with the drugs studied. Prior to the placebo period and at the end of the experimental period, blood was drawn for the assessment of total cholesterol, esterified cholesterol, VLDL-, LDL- and HDL-cholesterol, apolipoprotein B, phospholipids, and triglycerides. Both drugs were found to induce significant reductions of total cholesterol, VLDL, and LDL, a relative increase of HDL, and reduction of apolipoprotein B. Triglyceride blood level was markedly reduced in tiadenol-treated subjects, and to a lesser extent also in simvastatin-treated ones. This difference is attributed to the different levels at which the drugs interfere with the early steps of cholesterol synthesis. The authors conclude by pointing out that the two drugs should be used selectively according to the type of metabolic disorder prevalent in the individual patient.

[Preliminary results of an open study on the effects of DEAE-dextran on various lipid metabolism parameters in dyslipidemic subjects]. / Prime osservazioni di uno studio aperto sugli effetti del DEAE-destrano su alcuni parametri lipometabolici di soggetti dislipidemici.

The authors report the results of a study of 1963 patients treated with daily doses of 2 g DEAE-dextran. This was an open trial intended to evaluate the evolution of several biohumoral parameters under treatment for dyslipidemias. Statistically significant results were obtained for cholesterol blood level, triglycerides and body weight, as well as a favorable trend for HDL-cholesterol. Side effects or untoward reactions to DEAE-dextran were not observed.

Plasma cortisol and testosterone in hypercholesterolaemia treated with clofibrate and lovastatin.

Plasma testosterone and cortisol concentrations were measured in 32 familial heterozygous hypercholesterolaemic subjects, aged 40-45 years. The subjects were divided into two groups of 16, each containing eight men and eight women. The women had normal menstrual cycles. After a period on placebo, one group of patients was given 40 mg/day lovastatin and the other was given 1500 mg/day clofibrate. Both drugs significantly reduced the plasma cholesterol concentration, however, unlike clofibrate, lovastatin did not decrease plasma levels of testosterone and cortisol. The response to stimulation by adrenocorticotrophic hormone of plasma cortisol and urinary 17-hydroxy levels was significantly reduced by treatment with clofibrate, but unchanged by lovastatin. The different effects produced by the two drugs probably reflect different mechanisms and sites of action.

[Proposal for the nosographic classification of 2 integrated systems. Interrelations of the cutaneous and renal systems]. / Proposta di inquadramento nosografico di due sistemi integrati. Interrelazioni tra sistema cutaneo e sistema renale.

Having briefly recalled the close functional interaction of diseases which often involve both syplay between skin and kidney, the authors suggest a new model for the nosographic classificastems and are at present observed with increasing frequency.