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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

Objective: To perform a comparative analysis of the results of arthroscopic surgical treatment of partial and complete rotator cuff (RC) injuries., Methods: Eighty-four shoulders with partial or complete RC tear that underwent arthroscopic repair were retrospectively evaluated using UCLA and Constant scores, assessment of strength, and range of motion. Fifty-seven shoulders with complete injuries and 27 with partial injuries were identified., Results: Age (p = 0.007) was higher in those with complete lesions (mean 61.4 ± 7.9 years), compared to those with partial lesions (mean 56.5 ± 7.1 years). The complete injuries group showed a higher elevation difference in relation to the contralateral shoulder compared to the partial injuries group (partial injuries: -1.1% vs complete injuries: -16.5%), statistically significant difference (p = 0.0004). In addition, complete lesions presented 96.5% of excellent and good results and a median of 35 in the UCLA score and partial lesions presented 84.6% of good/ excellent results and a median of 34. The Constant score showed 91.2% of satisfactory results in complete lesions and 77% in partial ones., Conclusion: Arthroscopic repair shows satisfactory functional results for both partial and complete rotator cuff injuries, with similar outcomes between groups. Level of Evidence III, Retrospective Comparative Study., Competing Interests: All authors declare no potential conflict of interest related to this article.

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., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 M. Galliani et al.)

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most frequent monogenic hereditary disease as well as the most studied inherited kidney disease. Two drugs have recently been authorized that can slow down the progression of the disease: Tolvaptan (vasopressin receptor antagonist) and Octreotide-LAR (long-acting somatostatin analogue); they both are able to reduce the activity of cyclic adenosine monophosphate (cAMP) and therefore have anti-proliferative and anti-secretory effects. This review analyzes the main trials published to date demonstrating the effects on disease progression in patients with ADPKD and illustrates the indications for identifying subjects eligible for therapy., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Autosomal dominant polycystic kidney disease affects over 12 million people in the world and is the fourth cause of ESRD. It is the main monogenic kidney disease and causes the progressive formation of cysts leading to renal failure after a few decades. The main manifestations of the disease are observed even at a young age. The early sign of ADPKD is impaired urinary concentrating capacity, due to medullary alteration by cysts, and resistance to vasopressin. These anatomical alterations determine hyperfiltration, altered ammonium transport, nephrolithiasis, and, above all, hypertension even in pediatric age. Activation of the renin-angiotensin-aldosterone system has been shown responsible for the maintenance of high pressure values as well as the growth of cysts and renal fibrosis. Arterial hypertension would be responsible for ventricular hypertrophy. Many recent studies have confirmed the role of pressure control, especially if rigorous, in decreasing the progression of renal disease, and the use of ACE inhibitors seems to have higher efficacy than other antihypertensive drugs. The progression of renal disease is evidenced by the reduction of glomerular filtration which may be minimal in the early years, due to hyperfiltration, but, then, may even exceed 5 ml / min per year, especially when the total kidney volume (TKV) exceeds 1500 ml. In more rapid progression forms, ESRD may appear at about 55 years of age. The main risk factors are age, genetic mutation, familiarity with ESRD, macrohematuria episodes, and early onset hypertension. Some authors have proposed both genetic and clinical scores that can provide guidance on the probability of rapid progression. Other renal manifestations include kidney pain, nephrolithiasis, urinary tract infections and cyst hemorrhage. Renal cell carcinoma is a very rare event., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: The need for prolonged anticoagulation and the occurrence of hypophosphatemia are well known drawbacks of continuous renal replacement therapies (CRRT). The aim was to evaluate the effects on acid-base status and serum phosphate of a regional citrate anticoagulation (RCA) protocol for continuous veno-venous hemofiltration (CVVH) combining the use of citrate with a phosphate-containing replacement fluid., Methods: In a small cohort of heart surgery patients undergoing CRRT for acute kidney injury, we adopted an RCA-CVVH protocol based on a commercially available citrate solution (18 mmol/l) combined with a recently introduced phosphate-containing replacement fluid (HCO3 -30 mmol/l, phosphate 1.2), aimed at preventing phosphate depletion., Results: In 10 high bleeding-risk patients, the RCA-CVVH protocol provided an adequate circuit lifetime (46.8 ± 30.3 h) despite the adoption of a low citrate dose and a higher than usual target circuit Ca2+ (≤0.5 mmol/l). Acid-base status was adequately maintained without the need for additional interventions on RCA-CVVH parameters and without indirect sign of citrate accumulation [(pH 7.43 (7.41-7.47), bicarbonate 24.4 mmol/l (23.2-25.6), BE 0 (-1.5 to 1.1), calcium ratio 1.97 (1.82-2.01); median (IQR)]. Serum phosphate was steadily maintained in a narrow range throughout RCA-CVVH days [1.1 mmol/l (0.9-1.4)]. A low amount of phosphorus supplementation (0.9 ± 2 g/day) was required in only 30% of patients., Conclusions: Although needing further evaluation, the proposed RCA-CVVH protocol ensured a safe and effective RCA without electrolyte and/or acid-base derangements. CRRT-induced hypophosphatemia was prevented in most of the patients by the adoption of a phosphate-containing replacement solution, minimizing phosphate supplementation needs.

Background: Recent guidelines suggest the adoption of regional citrate anticoagulation (RCA) as first choice CRRT anticoagulation modality in patients without contraindications for citrate. Regardless of the anticoagulation protocol, hypophosphatemia represents a potential drawback of CRRT which could be prevented by the adoption of phosphate-containing CRRT solutions. The aim was to evaluate the effects on acid-base status and phosphate supplementation needs of a new RCA protocol for Continuous Venovenous Hemodiafiltration (CVVHDF) combining the use of citrate with a phosphate-containing CRRT solution., Methods: To refine our routine RCA-CVVH protocol (12 mmol/l citrate, HCO3- 32 mmol/l replacement fluid) (protocol A) and to prevent CRRT-related hypophosphatemia, we introduced a new RCA-CVVHDF protocol (protocol B) combining an 18 mmol/l citrate solution with a phosphate-containing dialysate/replacement fluid (HCO3- 30 mmol/l, Phosphate 1.2). A low citrate dose (2.5-3 mmol/l) and a higher than usual target circuit-Ca(2+) (≤ 0.5 mmol/l) have been adopted., Results: Two historical groups of heart surgery patients (n = 40) underwent RCA-CRRT with protocol A (n = 20, 102 circuits, total running time 5283 hours) or protocol B (n = 20, 138 circuits, total running time 7308 hours). Despite higher circuit-Ca(2+) in protocol B (0.37 vs 0.42 mmol/l, p < 0.001), circuit life was comparable (51.8 ± 36.5 vs 53 ± 32.6 hours). Protocol A required additional bicarbonate supplementation (6 ± 6.4 mmol/h) in 90% of patients while protocol B ensured appropriate acid-base balance without additional interventions: pH 7.43 (7.40-7.46), Bicarbonate 25.3 (23.8-26.6) mmol/l, BE 0.9 (-0.8 to +2.4); median (IQR). No episodes of clinically relevant metabolic alkalosis, requiring modifications of RCA-CRRT settings, were observed. Phosphate supplementation was needed in all group A patients (3.4 ± 2.4 g/day) and in only 30% of group B patients (0.5 ± 1.5 g/day). Hypophosphatemia developed in 75% and 30% of group A and group B patients, respectively. Serum phosphate was significantly higher in protocol B patients (P < 0.001) and, differently to protocol A, appeared to be steadily maintained in near normal range (0.97-1.45 mmol/l, IQR)., Conclusions: The proposed RCA-CVVHDF protocol ensured appropriate acid-base balance without additional interventions, providing prolonged filter life despite adoption of a higher target circuit-Ca(2+). The introduction of a phosphate-containing solution, in the setting of RCA, significantly reduced CRRT-related phosphate depletion.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Attention is drawn to the relationship between information and biological models in the study of problems of human physiology and physiopathology. The biomathematical principles, to which reference must be made for the elaboration of the expert systems, necessary in evaluating biological feedback in particular are analyzed.

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.

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.

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.