Ocorrência de pessoas infectadas pelo HIV que realizam tratamento com antirretroviral em uma cidade do sul do Brasil: um desafio aos profissionais de saúde / Adherence of HIV-infected individuals to antiretroviral therapy in a municipality in southern Brazil: a challenge for health professionals

Introdução: A utilização da terapia com antirretroviral (TARV) é um dos maiores desafios para o sucesso do tratamento para HIV/AIDS, uma vez que é uma das ferramentas contra a pandemia, possibilitando a melhoria da qualidade de vida e longevidade da população infectada. O objetivo deste trabalho foi verificar a ocorrência de pessoas infectadas com o HIV que faziam tratamento com TARV. Métodos: O estudo foi realizado para verificar a ocorrência de pessoas infectadas com o HIV notificadas entre os anos de 2006 a 2016 que faziam tratamento com TARV, através das informações do Sistema Nacional de Informação de Agravos de Notificação (SINAN). Resultados: Dos 715 pacientes notificados desde o ano de 2006, 597 (83,5%) faziam o uso de TARV e 118 (16,5%) abandonaram a terapia. Com relação ao perfil dos infectados, o maior número de notificações de HIV eram do sexo masculino (54,83%), com idades entre 25 a 29 anos (56%) dos casos. Conclusão: Os dados apresentados no estudo mostram que algumas pessoas infectadas com HIV não dão continuidade ao tratamento, isso gera preocupação uma vez que mascara a realidade da infecção pelo vírus e diante deste cenário deve ocorrer o incentivo dos órgãos competentes para que registre os casos ocorrentes. Os profissionais de saúde nos seus mais diversos segmentos devem incentivar a utilização do TARV e notificar e acompanhar as pessoas que não retiram e não utilizam a medicação, e que sejam mais direcionadas as medidas de prevenção. (AU)

Introduction: Adherence to antiretroviral therapy (ART) is a major challenge to the success of HIV/AIDS treatment. It is a weapon against the pandemic, being capable of improving the quality of life and longevity of the infected population. The aim of this study was to ascertain the adherence to ART in HIV-infected individuals. Methods: The study assessed whether HIV-infected individuals with infection reported between 2006 and 2016 were receiving ART, using information from the National Information System for Notifiable Diseases (SINAN). Results: Of a sample of 715 patients, 597 (83.5%) were using ART and 118 (16.5%) discontinued treatment. Regarding the profile of HIV-infected individuals, most were male (54.83%), aged 25 to 29 years (56%). Conclusions: These data show that a significant proportion of HIV-infected individuals discontinue treatment, which causes concern because it conceals the reality of HIV infection. Thus, authorities should call for proper reporting. Health professionals from different areas should encourage the use of ART and follow individuals who fail to adhere to treatment, while national health policies should focus on prevention. (AU)

Plasma exchange in elderly patients.

Plasma exchange (PE) is an extracorporeal blood purification technique designed for the removal of large molecular weight substances from plasma. Data regarding the use of PE in elderly patients is lacking, so this study analyzes the database of the Department of Dialysis at the University Hospital Center Zagreb (634 patients, 6237 procedures) for indications and complications in patients aged 65 years or older who were submitted to PE during the period from 1982 to 2007. A total of 50 patients in this age group were submitted to PE; their median age was 69 years (range 65-83). This population underwent 323 episodes of PE, mostly with albumin solution as the replacement fluid (94.0%), and blood access was usually via peripheral veins (72.0%). The most common indication for therapy (76.0%) was neurological (e.g. myasthenia gravis and Guillain-Barré syndrome), which was more common than in the entire population (i.e. of all age groups) (60%). The second most common indications were hematological diseases, followed by intoxications and Goodpasture's syndrome. Ninety-four percent of patients showed improvement, two patients with Guillain-Barré syndrome died, and a patient with pemphigus vulgaris had no change in clinical status, compared with 75% of younger patients whose status improved after PE. Complications occurred during 11.5% of treatments, compared to 3.9% in the younger group. The most common complications were clotting (3.7%), blood access difficulties (1.5%), mild-to-moderate allergic reactions (1.5%), and precordial oppression (0.6%). Plasma exchange is rarely used in the elderly population; however, when carried out by experienced staff, it is a safe and efficient method that may significantly improve the outcome of elderly patients with appropriate indications.

[The role of nephrologist in treatment of multiple myeloma]. / Uloga nefrologa u lijecenju paraproteinemija.

Multiple myeloma (MM) is malignant disease caused by proliferation of malignant clone of terminally differentiated plasma-cells. Clinical features may include symptoms of bone disease, unexplained back-pain, fractures, anaemia, kidney failure, oedema, hypercalcaemia, bacterial infections, impaired hemostasis, peripheral neuropathy and hyperviscosity. Impairment of renal function occurs in 50% of patients with different forms of kidney disease. Majority of patients have precipitation of monoclonal immunoglobulins or their fragments in kidney. Hypercalcemia, dehydration, infections and nephrotoxic drugs contribute to development of kidney injury. Treatment consists of chemotherapy for primary disease, with plasma exchange in cases of hyperviscosity. Supportive treatment should include rehydration, treatment of hyperuricemia and hypercalcaemia. Patients with end-stage renal disease could be treated with peritoneal dialysis or haemodialysis. Renal transplantation is rarely offered to this group of patients.

[Arterial hypertension in renal transplant recipients]. / Hipertenzija nakon transplantacije bubrega.

Arterial hypertension develops in up to 80% of renal transplant recipients. Uncontrolled hypertension induces left ventricular hypertrophy, heart failure and death, but also promotes deterioration of allograft function. Cadaveric transplantation, delayed graft function, renal artery stenosis, presence of native kidneys, increased body weight and therapy with calcineurin inhibitors and steroids have been associated with an increased incidence of hypertension after kidney transplantation. Cyclosporine increases both systemic and renal vascular resistance, enhances sympathetic activation, endothelin production and, possibly, decreases vascular relaxation by decreasing the generation of nitric oxide. Tacrolimus has less pronounced prohypertensive role after renal transplantation. Corticosteroids contribute to the development of hypertension, since their withdrawal results in a significant decrease of blood pressure in the majority of patients. Renal artery stenosis occurs in almost 12% of hypertensive renal transplant recipients. It is a correctable cause of hypertension, and for this reason should be investigated in all suspected patients. Doppler ultrasonography is used as the screening method that is highly sensitive and specific in the hands of a well-experienced investigator. However, dependence of the method on the experience of the investigator is its major drawback. Magnetic resonance angiography and spinal computed tomography angiography are useful noninvasive methods, but arteriography remains a method for establishing the definitive diagnosis. Percutaneous balloon angioplasty, with or without placement of the stent, is successful in the majority of patients, but with a high incidence of restenoses (20%). Surgery is indicated for stenoses that cannot be treated with angioplasty or that recur. Auto-transplantation of the kidney with complex stenoses of graft arteries is useful in selected cases. Posttransplant hypertension should be aggressively treated to prevent the development of end-organ damage. Every effort should be invested in reducing immunosuppression when appropriate, together with salt restriction and weight reduction. Calcium channel blockers have good antihypertensive properties accompanied with minimization of cyclosporine-induced renal vasoconstriction. Angiotensin-converting enzyme inhibitors (ACEi) should be used in patients with proteinuria. Renal function should be carefully monitored after their introduction since they may cause transitory deterioration of glomerular filtration and/or hyperkaliemia. ACEi can induce anemia in renal transplant recipients, side effect that is often used in the treatment of posttransplant erythrocytosis. All other antihypertensive drugs could be used, with minoxidil being the most potent one. Patients with resistant hypertension should be investigated for the presence of renal artery stenosis. After exclusion of rejection, renal artery stenosis and recurrent disease, in cases of severe hypertension, native kidneys laparoscopic nephrectomy should be considered.

Treatment of thrombotic microangiopathies with plasma exchange.

Thrombotic microangiopathy (TMA) is a syndrome characterized by thrombocytopenia, microangiopathic hemolytic anemia, neurologic abnormalities, fever and renal dysfunction. This retrospective analysis sought to determine the clinical characteristics and outcome of patients with TMA treated with plasma exchange at the Department of Dialysis, University Hospital Zagreb. From 1982 to July 2005, 17 patients (10 male and 7 female, age ranging from 18 to 74 years) have been diagnosed with TMA. The most common presenting symptom was purpura in 76.5%, followed by neurologic disturbance in 70.5%, renal function abnormality in 41.1%, and fever in 29.4% of patients. Patients were treated with a daily plasma exchange, which was continued until the normalization of platelet count with minimal hemolysis. Plasma exchange treatment was first tapered and later discontinued with careful monitoring of laboratory parameters. Of the 17 patients, 13 achieved complete remission after 5-32 sessions, two had partial response, and two had no response and died of progressive disease. Four patients developed chronic relapsing TMA, and three of them progressed to end-stage renal disease. Survival at 1 year in our series exceeds 88%, but decreased with duration of follow-up. Overall, with the median follow up of 5 years, 6 patients died from consequences of TMA (35.3%); three with chronic TMA, and 2 in the acute phase of progressive disease. A 74-year old male who developed TMA after prostate cancer died from disseminated malignant disease. Our results demonstrate a high incidence of renal function abnormalities in patients with TMA at presentation, but also during long term follow-up. Development of end-stage renal disease was associated with poor prognosis. Further studies, long term follow-up and establishment of international registries are needed to clarify many dilemmas associated with the diagnosis, treatment and outcomes of patients with TMA.

[Cardiovascular diseases after kidney transplantation]. / Srcanozilne bolesti nakon transplantacije bubrega.

Cardiovascular complications represent the leading cause of mortality in renal transplant recipients, with ischemic heart disease accounting for more than 50% of deaths. Besides the well known risk factors that affect the general population, risk for development of atherosclerosis in renal transplant patients is further increased by previous uremia and dialysis, as well as by the use of immunosuppressive agents. Diabetes mellitus, arterial hypertension, dyslipidemia, smoking, hyperhomocysteinemia, hyperuricemia, coagulation abnormalities, increased expression of cell adhesion molecules, persistent inflammation, frequent infections and obesity all increase the risk for development of atherosclerosis in transplanted patients. There is a growing body of evidence suggesting that the risk of cardiovascular disease falls significantly with smoking cessation, reduction of alcohol consumption, reduction of excessive weight, and appropriate and aggressive control of blood pressure and dyslipidemia. Patients should be instructed, and every effort should be invested to increase their compliance with the modified lifestyle and drug adherence. Novel immunosuppressive regimens tend to decrease the risk of atherosclerosis by being individualized according to the characteristics of the particular patient.

[Anderson-Fabry disease]. / Anderson-Fabrijeva bolest.

Anderson-Fabry disease is a rare inherited X-linked lysosomal storage disease caused by deficiency of the enzyme alpha-galactosidase A. The deficiency of alpha-galactosidase activity leads to progressive, abnormal accumulation of neutral glycosphingolipids in the lysosome. With increasing age globotriaosylceramide (Gb3) progressively accumulates in different cells, tissues and organs throughout the body. The overall prevalence of Anderson-Fabry disease is 1:117.00 or 1: 40.000 in (male) population. Typically, the clinical onset of Anderson-Fabry disease occurs during childhood or adolescence, with early symptoms of neuropathic pain (recurrent episodes of severe pain in the extremities), angiokeratomas (characteristic cutaneous lesions), oedematous upper eyelids, peripheral vasospasm and ophthalmological abnormalities. The disease progresses through adulthood and by the age of 30-40 years several major organ systems may be affected; cardiac disease, renal insufficiency, cerebrovascular attacks and neurologic findings are common. Death usually occur secondary to renal, cardiac or cerebrovascular complications during the fourth or fifth decade of life. Enzyme replacement therapy is a major advance in the treatment of rare diseases. In 2001 two formulations have been approved by the European Medical Evaluation Agency, agalsidase alpha and agalsidase beta. Agalsidase alpha is produced on the human fibroblast cell line, and agalsidase beta from the Chinese hamster ovary cell line.

[Regulation of blood pressure in dialyzed patients]. / Regulacija krvnog tlaka u bolesnika na dijalizi.

Up to 90% of chronic haemodialysis patients have blood preasure (BP) greater than 140/90 mmHg. This suggests that only a minor number of the haemodialysis patients have adequate BP control. This is associated with significantly increased morbidity and mortality in haemodialysis population when compared with normal, healthy population. The main aim of antihypertensive treatment in hypertensive haemodialysis patients is to achieve BP values which should not differ from those recommended for general population. The most important factor in BP regulation in haemodialysis patients is adequate fluid volume regulation. Sympathetic nervous system and impaired vasodilatation with consequent changes in peripheral vascular resistance, secondary hyperparathyreoidism and its effects on calcium balance and consequent effects on cotractility of the smooth muscle cells of the vessel wall, correction of renal anemia in patients receiving human recombinant erythropoietin, regulation of salt intake, and frequency and duration of haemodialysis procedure have also a significant role in BP regulation in these patients. If dialysis procedure is not adequate, meaning that salt and water balance is not satisfyng, antihypertensive medications cannot alone control BP in haemodialysis patients.

Complications of therapeutic plasma exchange: experience with 4857 treatments.

Plasma exchange (PE) is a technique of extracorporeal blood purification which removes large molecular weight substances from plasma. The Department of Dialysis, Zagreb University Hospital Center's database, which includes data on 509 patients, or 4857 PE treatments, was retrospectively analyzed to test the safety of PE. A total of 231 adverse reactions were recorded (4.75% of treatments). The most common complications were paresthesias (2.7%), hematoma at the puncture site (2.4%), clotting (1.7%), mild to moderate allergic reactions (urticaria; 1.6%) and bleeding (0.06%). True anaphylactoid reactions were recorded in five procedures. The incidence of severe, potentially life-threatening adverse reactions was 0.12%. The prophylactic use of calcium and potassium was responsible for a low incidence of electrolyte disturbances. There was no lethal outcome associated with PE. When carried out by experienced staff, PE is a relatively safe procedure. The use of fresh frozen plasma is associated with a higher rate of adverse reactions.

[Biological adequacy--what does it mean?]. / Bioloska primjerenost--sto to znaci?

Appropriate initiation of dialysis is of an outstanding importance in the treatment of patients with end-stage renal disease. It prevents development of irreversible uremic complication and enables selection of the most appropriate dialysis modality for the individual patient. The major causes of morbidity and mortality in dialysis patients are cardiovascular diseases. Hypertension and hyperlipidemia are commonly found in dialysis patients as well as anemia, chronic inflammation and fluid overload, all of which are found to be risk factors for the development of cardiovascular diseases. Arterial hypertension is the main risk factor for left ventricular hypertrophy, and there is clear evidence that control of hypertension has a beneficial effect on left ventricular hypertrophy. It is best achieved by correction of overhydration and maintenance of dry weight. Modern dialysis machines are capable of changing electrolyte concentrations, which reduces intradialytic cardiovascular complications, incidence of cardiac arrhythmias and hypotension. Correction of anemia with erythropoietin results in regression of left ventricular hypertrophy and improvement of the quality of life and defense against microorganisms. Chronic inflammation can be prevented with the use of biocompatible high-flux dialysis membranes and sterile dialysate, which are also important for the prevention of oxidative stress involved in the increase of LDL oxygenation and incorporation into the intimal layer of the vessels. Low molecular weight heparins by their action on lipoprotein lipase serve as an additional factor that suppresses development of atherosclerotic plaque in dialysis patients. Optimal dialysis dose decreases the mortality and morbidity rates. High-flux membranes or prolongation of dialysis session are modalities for dialysis dose improvement. Individualized approach to preparation of dialysis solutions has resulted in better control of fluid overload and intradialytic hyper- or hypotension, reduction in the incidence of arrhythmias, improvement of hemodynamic stability, and delay of renal osteodystrophy. Malnutrition is a relatively common problem in dialysis patients that may be secondary to poor nutritional intake, inadequate amount of dialysis, lack of appetite, acidosis, associated disease, and/or increase in protein catabolism. The most appropriate approach includes individualization of dietary prescription according to the nutritionist's advice, increase of dialysis dose with biocompatible membranes, and use of sterile bicarbonate dialysate with glucose and erythropoietin. The major goal of adequate dialysis is not just improvement in survival of dialysis patients, but also improvement in the quality of their lives.

[Uremic polyneuropathy]. / Uremijska polineuropatija.

Uremic polyneuropathy is probably the most common complication of chronic renal failure. About 70 percent of dialysis patients regularly have uremic polyneuropathy, in 30 percent the neuropathy is moderate or severe. Coexistence of muscle weakness and atrophy, areflexia, sensory loss and graded distribution of neurologic deficit in a patient with renal disease suggests the presence of uremic polyneuropathy. During longterm hemodialysis, the symptoms of polyneuropathy stabilize, but they improve only in relatively few patients. Complete recovery, occurring over a period of 6 to 12 months, usually follows successful renal transplantation.

[Importance of plasmapheresis in the treatment of paraneoplastic cerebellar degeneration]. / Znacenje plazmafereze u lijecenju paraneoplasticne cerebelarne degeneracije.

Paraneoplastic neurologic syndromes are disorders of the nervous system function caused by cancer but not due to metastatic disease, vascular or metabolic deficits, infections, nutritive deficiency, nor side effects of antineoplastic drugs or irradiation. Immunologic factors probably play the crucial role in the pathogenesis of paraneoplastic neurologic syndromes, but nonimmunologic mechanisms that include metabolic abnormalities and competition for substrate are also involved. Paraneoplastic cerebellar degeneration most commonly occurs in the setting of gynecologic cancers, but it accompanies the small-cell lung cancer too. Other tumors are infrequently associated with cerebellar degeneration. Several paraneoplastic antibodies have been identified in patients with paraneoplastic cerebellar degeneration. Their association with particular cancers may help identify an occult lesion. Anti-Yo antibodies are directed against Purkinje cell antigens and occur in patients with cerebellar degeneration who have breast cancer or gynecologic tumors. A target antigen of anti-Yo antibody is CDR2 protein that is normally expressed only in the brain and testis. Patients with paraneoplastic cerebellar degeneration present with dizziness, nausea and vomiting followed by gait instability, diplopia, gait and appendicular ataxia, dysarthria and dysphagia. Therapeutic options include tumor excision, chemotherapy and/or irradiation, and adjuvant therapy with glucocorticoids, immunoglobulins and plasmapheresis. The role of plasmapheresis in the treatment of paraneoplastic cerebellar degeneration is still uncertain. Reports of its efficacy are anecdotal. We present patient with paraneoplastic cerebellar degeneration with positive anti-Yo antibodies and tumor of the ovaries whose neurologic status significantly improved after four daily plasmaphereses, which was accompanied by a fourfold decrease in the anti-Yo antibodies titer. Further investigations are needed to define a protocol for plasmapheresis in the treatment of patients with paraneoplastic syndromes.

[Continuous venovenous hemofiltration as a bridge to heart transplantation in a patient with congestive heart failure and acute renal failure]. / Premostenje razdoblja do transplantacije srca kontinuiranom venovenskom hemofiltracijom u bolesnika sa zavrsnim stupnjem zatajenja srca i akutnim zatajenjem bubrega.

Continuous venovenous hemofiltration effectively controls volume overload in cases of severe congestive heart failure accompanied by acute renal failure that could not be medicamentously controlled. A patient with severe ischemic dilated cardiomyopathy who developed acute renal failure while waiting for urgent heart transplantation is described. He was treated with CVVH for three days when the occasion for heart transplantation appeared. At the time of transplantation laboratory markers of renal function were within the normal range with stable hemodynamic parameters. After successful transplantation the patient spontaneously and completely recovered his renal function.

[Indications for continuous renal function replacement therapy]. / Indikacije za kontinuirano nadomjestanje bubrezne funkcije.

One of the most important achievements in the contemporary intensive care management is introduction of continuous renal replacement therapy (CRRT). The most common indications for CRRT are acute renal failure complicated with heart failure, volume overload, hypercatabolism, acute or chronic liver failure, and/or brain swelling. Less common indications include systemic inflammatory response (SIRS), sepsis, multiorgan failure (MOF), adult respiratory distress syndrome, crush syndrome, tumor lysis syndrome, lactacidosis, and chronic heart failure. Methods of CRRT could be used during or after open heart operations, heart, lung or/and liver transplantation in adults and children. Modern approach to treatment of acute renal failure introduces dialysis early in the course of disease in order to avoid complications on other organs. Sepsis, SIRS and septic shock are still major therapeutic problems in intensive care units with a mortality rate over 50%. Numerous uncontrolled and several controlled clinical studies have demonstrated that CRRT could remove inflammatory substances including cytokines, activated components of the complement, and derivatives of the arachidonic acid. Hemodynamic stability and gas exchange in the lungs were significantly improved. These is due not only to removal of inflammatory substances but also to other nonspecific hemodynamic effects (control of body temperature, fluid and metabolic balance). Besides the convection, cytokines could be removed from the plasma with adsorption on the membrane of dialyzer or hemofilter. Prophylactic use of CCRT in patients with normal renal function, without disturbances in fluid excretion and with normal hemodynamics is still controversial, while the possible benefit is not higher than the risks of invasive therapeutic method, and there is no evidence that prophylactic CCRT could prevent development of acute renal failure in these patients. However, current knowledge of MOF pathophysiology justifies the use of CRRT in patients with signs of heart failure, disturbances in metabolic and fluid homeostasis and sepsis, and in patients with the risk of developing acute respiratory failure or MOF, despite the mild impairment of renal function according to laboratory results.

[Should anemia be completely corrected in patients with chronic renal failure?]. / Treba li potpuno ispraviti anemiju u bolesnika s kronicnim zatajenjem bubrega?

The optimal target hemoglobin (Hb) for the correction of renal anemia by recombinant human erythropoietin therapy is discussed controversially. Normalization of Hb that could lead to a further improvement of the patient's status is often rejected, because of possible effects as a result of an increase in blood viscosity. However, recent studies demonstrated that the higher the Hb level, the better the quality of life and the lower the incidence of cardiovascular morbidity and mortality, as well as hospitalisation. These correlations tend to persist up to normal Hb levels.

[Lipoprotein disorders in chronic kidney failure, nephrotic syndrome and dialysis]. / Poremecaji lipoproteina u kronicnom zatajenju bubrega, nefrotskom sindromu i dijalizi.

Cardiovascular, cerebrovascular and peripheral vascular diseases are the largest cause-specific reason for morbidity and mortality in end-stage renal disease (ESRD) patients. High prevalence of cardio- and cerebrovascular death may be explained by multiple factors present in patients with progressive renal disease, including hypertension, hyprelipidemia, hyperhomocysteinemia, diabetes mellitus, and hyperparathyroidism. Experimental studies have provided in vivo and in vitro data to support the notion that lipid abnormalities contribute to glomerular and interstitial injury of the renal parenchyma. Hypercholesterolemia and increased low-density lipoprotein (LDL) cholesterol are prevalent in patients with the nephrotic syndrome. Plasma high-density lipoprotein (HDL) cholesterol is decreased, and reverse cholesterol transport is impaired in hemodialysis (HD) and pre-ESRD patients. Chronic renal failure patients treated with HD have an increased prevalence of intermediate-density lipoprotein (IDL), and lipoprotein(a). The findings in the diabetic patients corresponded to those in non-diabetic patients with renal failure, but diabetic patients have higher apolipoprotein C-III and apolipoprotein E concentrations. Impaired lipid metabolism is common in patients receiving peritoneal dialysis (PD). In the most of the ESRD patients treated with peritoneal dialysis hypercholesterolemia and hypertriglyceridemia are found. Wide panels of therapeutic interventions aimed at correcting the lipid abnormalities that may develop in chronic renal patients, as well as in ESRD patients are currently available. Although some novel pharmacological agents are remarkably effective for returning the lipid abnormalities to normal, there is still no convincing evidence based on long-term prospective studies which clearly demonstrate a significant reduction in cardiovascular morbidity and mortality of ESRD patients. The therapeutic approaches, which may be considered, include mainly dietary and life-style modifications, selective use of some technical components of dialysis systems, and the judicious prescriptions of lipid-lowering drugs.