Effects of Rheopheresis in dialysis patients with peripheral artery disease and diabetic foot ulcers: A multicentric Italian study.

BACKGROUND: Peripheral artery disease (PAD) in hemodialysis (HD) patients has a significant social impact due to its prevalence, poor response to standard therapy and dismal prognosis. Rheopheresis is indicated by guidelines for PAD treatment. MATERIALS AND METHODS: Twenty-five HD patients affected by PAD stage IV Lerichè-Fontaine and ischemic ulcer 1C or 2C according to the University of Texas Wound Classification System (UTWCS), without amelioration after traditional medical therapy and/or revascularization, were selected and underwent 12 Rheopheresis sessions in 10 weeks. Improvements in pain symptoms using Numerical Rating Scale (NRS), healing ulcers and laboratory hemorheological parameters have been evaluated. RESULTS: A clinically and statistically significant mean value reduction and of relative percentage differences between estimated marginal means (Δ), calculated at each visits, of NRS was observed, with a maximum value (-48.5%) between the first and last visit. At the end of the treatment period 14.3% of ulcers were completely healed, 46.4% downgraded, 53.6% were stable. Overall, no ulcers upgraded. A statistically significant reduction of the Δ, between the first and last visit, for fibrinogen (-16%) was also observed. CONCLUSION: Rheopheresis reduced overall painful symptoms; data suggest that it could heal or improve ulcers and hemorheological laboratory parameters in HD patients with PAD and ischemic ulcers resistant to standard therapies.

Therapeutic Plasmapheresis: a revision of literature.

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 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.

Regulation of urinary calcium excretion by vasopressin.

BACKGROUND: The antidiuretic hormone (ADH) or arginine vasopressin (AVP) regulates the body's water balance. Recently, modifications in AVP levels have been related to osteoporosis during ageing and microgravity/bed rest. Therefore the present study was devised to assess whether the absence of AVP, as in patients with central diabetes insipidus (CDI), modulates renal calcium excretion. METHODS: We retrospectively analysed data from 12 patients with CDI with measured 24-h urinary excretion levels of calcium. Data were available at the moment of the diagnosis when patients were drug-free and after therapy with dDAVP, an analog of AVP. Hypercalciuria was defined as 24-h urinary Ca2+ >275 mg/day in males and >250 mg/day in females and a urinary calcium (Ca):creatinine (Cr) ratio >0.20 mg/mg. RESULTS: Untreated CDI patients had a daily urinary Ca2+ excretion of 383 ± 47 mg/day and a urinary Ca:Cr ratio of 0.26 ± 0.38 mg/mg. The urine osmolarity significantly increased after the administration of dDAVP by 210% and the urinary flow decreased by 72%. Furthermore, the estimated glomerular filtration rate (eGFR) increased by 7%, which did not reach statistical significance. dDAVP treatment did not significantly modify the urinary Ca2+ concentration; however, the daily calcium excretion and the urinary Ca:Cr ratio were significantly decreased (160 ± 27 mg/day and 0.11 ± 0.02 mg/mg, respectively). CONCLUSIONS: Patients with CDI show hypercalciuria even though urine is more diluted than normal controls, and dDAVP reverses this effect. These data support the intriguing relationship between AVP and osteoporosis in ageing and microgravity/bed rest.

Diuretic Resistance in Cardio-Nephrology: Role of Pharmacokinetics, Hypochloremia, and Kidney Remodeling.

BACKGROUND: Diuretic resistance is among the most challenging problems that the cardio-nephrologist must address in daily clinical practice, with a considerable burden on hospital admissions and health care costs. Indeed, loop diuretics are the first-line therapy to overcome fluid overload in heart failure patients. The pathophysiological mechanisms of fluid and sodium retention are complex and depend on several neuro-hormonal signals mainly acting on sodium reabsorption along the renal tubule. Consequently, doses and administration modalities of diuretics must be carefully tailored to patients in order to overcome under- or overtreatment. The frequent and tricky development of diuretic resistance depends in part on post-diuretic sodium retention, reduced tubular secretion of the drug, and reduced sodium/chloride sensing. Sodium and chloride depletions have been recently shown to be major factors mediating these processes. Aquaretics and high-saline infusions have been recently suggested in cases of hyponatremic conditions. This review discusses the limitations and strengths of these approaches. SUMMARY: Long-term diuretic use may lead to diuretic resistance in cardio-renal syndromes. To overcome this complication intravenous administration of loop diuretics and a combination of different diuretic classes have been proposed. In the presence of hyponatremia, high-saline solutions in addition to loop diuretics might be beneficial, whereas aquaretics require caution to avoid overcorrection. Key Messages: Diuretic resistance is a central theme for cardio-renal syndromes. Hyponatremia and hypochloremia may be part of the mechanisms for diuretic resistance. Aquaretics and high-saline solutions have been proposed as possible new therapeutic solutions.

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

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

Delay in Renal Hemodynamic Response to a Meat Meal in Severe Obesity.

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.

Disease of the kidney and of the urinary tract in De Medicina Methodica (Padua, 1611) of Prospero Alpini (1563-1616).

AIM: The study was devised to understand the contribution to nephrology ofDe Medicina Methodicaof Prospero Alpini published in 1511, at a time when the fame of the professor reached the azimuth. METHOD: We have analyzed the contents of chapters devoted to nephrology in that book of Prospero Alpini and the novelties of his message. RESULTS: Prospero Alpini (1563-1616) taught at the University of Padua (1594-1616), at the same time of Galileo Galilei, Santorio Santorio, and Girolamo Fabrizi dAcquapendente, when measurements (pulse, temperature, perspiration) were introduced into medicine. He was a travelling physician to whom we owe fundamental contributions to the use of urine to prognosticate life and death (De Praesagienda vita et morte aegrotantium libri septem, Venetiis, apud Haeredes Melchioris Sessae,1601). As prefect of the Botanical Garden - the first ever and a model in the world - he could turn the study of simples into cures(De Medicina Methodica Libri Tredecim. Patavi, apud Franciscum Bolzettam, 1611. Ex typographia Laurentij Pasquali, is anin foliovolume of XLVII + 424 pages, 54 lines per page), wherein Alpini aimed to rejuvenate antique medical Methodism. It is a testimony of the interest of medicine philosophers of the modern era for the corpuscular and atomic ideas (Nancy Siraisi). Methodists (2ndCentury BC) refused anatomy and physiology as unique guidelines to the interpretations of diseases and gave importance to the development of a pharmacological science and alternative medicine. The book begins with a 3 page letter to Francis Maria della Rovere Duke of Montefeltro, and a 2 page letter to the readers. We discuss the novelties of the chapters on renal colic (de dolorerenum), hematuria (de sanguinis profluvium), pyuria, anuria (de urina suppressa) and its cure, polyuria (de urina profluvio), renal abscesses, hydrops and its treatment by skin incisions. We also analyze the chapter on kidney and bladder stones (Book X, Chapter XVIII, pp. 354-356) - a masterpiece of scholarly teaching - encompassing localization of stones, their formation and shape, renal colic and its irradiation according to the site and gender, the best antalgic position to pass stones, the use of laxatives, cathartics, warm baths, the plants to be used, their preparation and quality, the waters to be drank and their quantity (up to 15 pounds a day), the removal of bladder stones without surgery (methods learned in Cairo and described in Aegyptyan Medicine), and lithotomy and its feasibility even in old people. CONCLUSION: De Medicina Methodicawas a modern monograph devoted to clinical medicine including urinary disease. The book reflected the polyhedral personality of the author, his experience as physician of the Republic of Venice at Cairo, and his capabilities as a director of the Botanical Garden of the University of Padua, a unique research centre in those times.

[DFPP in myasthenia gravis: case report]. / La filtrazione a cascata nel trattamento della miastenia grave: caso clinico.

INTRODUCTION: Myasthenia Gravis (MG) is a neuromuscular disease due to a decrease in the number of acetylcholine receptors (AChR) present at the level of the neuromuscular junction. It is characterized by weakness and muscle fatigue. The pathogenesis of MG would seem to be autoimmune (autoantibodies against AChR, Musk, Titin). The treatment of MG includes acetylcholinesterase inhibitors, immunosuppressants, intravenous human immunoglobulin, thymectomy and therapeutic apheresis. MATERIALS AND METHODS: We report a case of a 40-year-old woman, suffering from MG, subjected to thymectomy, in therapy with corticosteroids, azathioprine and antagonist of acetylcholinesterase. The patient came under our observation for the appearance of a severe acute worsening of neurological disease unresponsive to medical therapy. She underwent a series of four treatments, every other day, of double filtration plasmapheresis (DFPP). RESULTS AND DISCUSSION: The DFPP removed from the patient's blood high-molecular-weight substances. It showed a reduction of Immunoglobulins, Fibrinogen, C3 and C4 complement fractions and anti ACh-R Ab.The DFPP resulted in disappearance of symptoms with improvement in motor and sensory conduction parameters evaluated by electromyography. CONCLUSION: The DFPP quickly reduces the anti ACh-R Ab and anti Titin Ab, as well as the risk of infections and allergies, compared to Plasma Exchange. It improves clinical symptoms, therefore it is proved to be an effective therapy for the acute exacerbation of MG.

A new recombinant MnSOD prevents the cyclosporine A-induced renal impairment.

BACKGROUND: Cyclosporine A (CsA) is one of the most frequently used anticalcineurinic drugs for preventing graft rejection and autoimmune disease. Its use is hampered by nephrotoxic effects, namely an impairment of the glomerular filtration rate (GFR) and hypertension. Evidence suggests that reactive oxygen species (ROS) play a causal role in the nephrotoxicity. The present study aims to investigate in vivo the effects of a new recombinant mitochondrial manganese-containing superoxide dismutase (rMnSOD), a strong antioxidant, on the CsA-induced nephotoxicity. METHODS: Rats were treated with CsA (25 mg/kg/day) alone or in combination with rMnSOD (10 µg/kg/day) for 7 days. At the end of the treatment, GFR was estimated by inulin clearance (mL/min/100 g b.w.) and the mean arterial pressure (MAP) was recorded through a catheter inserted in the carotid artery. Superoxide concentration within the cells of the abdominal aorta was quantified from the oxidation of dihydroethidium (DHE). In kidney tissues, ROS levels were measured by the 2'7' dichloroflurescin diacetate assay. Renal morphology was examined at the histochemistry level. RESULTS: CsA-treated rats showed a severe decrease in GFR (0.34 ± 0.17 versus 0.94 ± 0.10 in control, P < 0.001) which was prevented by rMnSOD co-administration (0.77 ± 0.10). CsA-injected animals presented with higher blood pressure which was unaffected by rMnSOD. ROS levels both in the aorta and in renal tissue were significantly increased by CsA treatment, and normalized by the co-administration with rMnSOD. This effect was, partly, paralleled by the recovery from CsA-induced morphological lesions. CONCLUSIONS: Administration of rMnSOD prevents CsA-mediated impairment of the GFR along with morphological alteration. This effect could be related to the inhibition of ROS.

A case of valproic acid-induced acute pancreatitis in tuberous sclerosis coexisting with end-stage renal disease.

Tuberous sclerosis complex (TCS) is a genetic disorder with a variable clinical presentation. It is commonly characterized by seizures, mental retardation and cutaneous angiofibromas. Renal manifestations frequently include angiomyolipomas and cysts which lead to chronic kidney disease. We report a case of valproic acid-induced acute pancreatitis in a dialysis patient affected by TCS. The case demonstrates the importance of assessing antiepileptic drug treatment in dialysis patients.

[Voriconazole compromises renal function in an elderly CDK patient with Candida albicans infection]. / Aggravamento della funzione renale da Voriconazolo in paziente anziano con nefropatia cronica affetto da infezione da Candida albicans.

There has been a progressive increase in the number of intensive care patients being transferred to nephrology units because of improper dosage of drugs, especially patients with chronic kidney disease (CKD). Voriconazole is a new synthetic triazole derivative with stronger therapeutic activity against fungal infections than fluconazole or itraconazole. Its effectiveness is associated with high nephrotoxicity, affecting patients with CKD in particular. The adverse effects of voriconazole involve several segments of the nephron, particularly the proximal tubule, medullary thick ascending limb, and collecting duct, causing loss of potassium and magnesium and backdiffusion of hydrogen ions. We report the case of an 86-year-old man with moderate CKD who developed acute renal failure as a result of inadequate dosage of voriconazole. He developed oliguria, electrolyte imbalance and fluid overload requiring hemodialysis. Vericonazole withdrawal associated with short daily hemodialysis treatment led to the recovery of diuresis, kidney function, and electrolyte balance. In conclusion, in elderly patients with liver disease and moderate CKD, thorough evaluation is needed before the administration of voriconazole in order to establish the most appropriate dose.

The nature of water: excerpts from Pythagoras, Xenophanes, Heraclitus and Parmenides.

Water was a prominent substance with Pythagoras, Xenophanes, Heraclitus and Parmenides, who flourished in the years 530-490 bc. The basic Pythagorean elements were earth and fire, and between them there were 2 intermediate entities (water and air), which were instrumental and indispensable components of specific solids. All things are a blend of different elements. For Xenophanes, "All things that come into being and grow are earth and water," "We all originated from earth and water" and "And in certain caves water drips down."For Heraclitus water is an ambivalent substance: "One cannot bathe in the same river on two occasions." "The sea is the safest and the most polluted water, for fish it is healthy and gives life, for men it is unhealthy and causes death." "Fire experiences the death of earth, air experiences that of fire, water experiences the death of air and the earth that of water." Parmenides was a man who sought the truth through reasoning and was, according to Hegel, the founder of Western philosophy. He built a dualist theory of the cosmos based on heat and cold, fire and earth - the former as a cause, the latter as substrate. The former unified, the latter separated. According to Aristotle, Parmenides considered air and water as mixtures of earth and fire.

To survive is not enough. Quality of life in CKD--the need for a new generation of health-oriented economists.

CKD is utilized as a paradigm, a chronic disease which allows decades of life conquered with great effort through a machine, a life with many losses and many dependencies. We must understand the patient's needs, which are not related to availability of drugs and machines and hospitals. We cannot provide good medical care with the limited amount of national product devoted to health care. Society is much older than ever before. We need a new cadre of economists working on health care with vision and ability, keeping in mind that there are no resources and there are no expenses which can be cut in medical care nowadays. We have to switch from curative medicine towards prevention, by implementing clinical research, bearing in mind that in the Western world, democracy was granted through the correct allocation of resources. The search for happiness and good quality of life are old concepts born in the Mediterranean area over the centuries, starting with Hesiod and Homer, and sleep and dreams were being investigated centuries before Freud was born.

The history of von Hippel-Lindau disease.

von Hippel-Lindau (vHL) disease is a heritable multisystem cancer syndrome that is associated with a germ line mutation of the vHL tumor suppressor gene on the short arm of chromosome 3. Affected individuals are at risk of developing various benign and malignant tumors of the central nervous system, kidneys, adrenal glands, pancreas, and epididymis. The name of this disease derives from two prestigious European physicians, Eugen von Hippel and Arvid Lindau, but many others played an important part in the description of the disorder. vHL disease has an old and modern history, thanks to the advent of new radiology and molecular biology diagnostic techniques.

The kidney in heart failure.

Renal dysfunction is a constant feature of congestive heart failure and is a stronger predictor of mortality than left ventricular ejection fraction or New York Heart Association classification. In heart failure, a reduction of glomerular filtration rate and renal plasma flow occurs, although the filtration fraction increases. There are many reason for this pattern. A reduction in effective circulating volume stimulates sympathetic activity and the renin-angiotensin-aldosterone system, and it is associated with increased concentrations of atrial natriuretic peptide, brain natriuretic peptide, and tumor necrosis factor alpha. Because in chronic kidney disease heart dysfunction commonly is present, an efficient cardiologist-nephrologist interaction should be promoted.

Creatinine clearance and hemoglobin concentration before and after heart transplantation.

Clinical studies indicate that indices of glomerular filtration rate (GFR) as serum creatinine or creatinine clearance can predict the risk of death in congestive heart failure (CHF) and in heart transplantation. The study reports data on creatinine clearance before and after heart transplantation in 160 patients followed-up for 5 years at our Unit. Pre-transplant creatinine clearance averaged 83.5+/-32 mL/min x 1.73 m(2) and was not significantly associated with 5-year mortality. Creatinine clearance significantly decreased after heart transplantation with a linear trend up to 3 years for patients with complete follow-up. Data suggest that the relation between kidney function and mortality after heart transplantation is affected by several confounders with inclusion of cause of heart disease, co-morbidity, anemia, and post-transplant decrease in kidney function.

The effect of oral protein loading on renal acidification in patients with heart failure.

BACKGROUND: The purpose of this study was to explore the renal acid-base response to acute protein load in patients with heart failure (HF). It was prompted by the fact that there are no data available regarding the role of renal tubules in maintaining acid-base balance following protein loading in HF patients. METHODS AND RESULTS: Nine male patients with HF and 12 healthy subjects (controls) were enrolled in this study. In the HF patients, average blood pH was 7.42 (0.03), average pCO2 was 36.6 mmHg (6.3) and average bicarbonate was 24.2 mmol/L (4.3). The acid-base status of patients was unaffected by meat ingestion. The values at peak glomerular filtration rate (GFR) did not differ significantly from baseline levels. An oral protein load did not influence the urinary pH, titratable acidity (TA) and ammonium excretion in the patients with HF, contrary to the findings in the controls. On the other hand, ammonium excretion in patients with HF reduced significantly compared with values from controls at baseline and following oral protein loading. Filtered and reabsorbed bicarbonate increased significantly in HF patients following meat ingestion, whereas there was no change in absolute and fractional bicarbonate excretion and fractional bicarbonate reabsorbed. CONCLUSIONS: This study demonstrated that in patients with HF, bicarbonate reabsorption increases following an oral protein load without a significant enhancement in bicarbonate excretion. The difference can be explained by the presence of respiratory alkalosis leading to bicarbonate conservation.