A picture of macroscopic hematuria and mild proteinuria with normal creatinine levels, accompanied by an upper tract catarrhal picture, is very suggestive of IgA nephropathy (option 3 correct).

A picture of macroscopic hematuria and mild proteinuria with normal creatinine levels, accompanied by an upper tract catarrhal picture, is very suggestive of IgA nephropathy ([HIDDEN]).

A 22-year-old male presents to the emergency department with "almost black" urine for the past 12 hours. He has no past history of interest and is not taking any medications. He refers an upper respiratory catarrhal symptoms since 4-5 days ago for which he has taken paracetamol. Examination: temperature 37.3 ºC, BP 150/95, HR 85 bpm, slight pharyngeal erythema, the rest normal. Laboratory tests showed: Hb 12.8 g/dl, Hcto 39%, leukocytes 10,500/mm3 with normal formula, platelets 250,000/mm3, normal coagulation, urea 25 mg/dl, creatinine 0.8 mg/dl, ions, hepatic, lipid, albumin and total proteins normal. Normal autoimmunity study and negative viral serology. Urine 24 h with proteinuria of 0.75 g/24 h, sediment with 10 erythrocytes per field (90% dysmorphic), no leukocyturia. Renal ultrasound was normal. Which diagnosis do you think is more likely?

When Coke Is Not Hydrating: Cocaine-Induced Acute Interstitial Nephritis.

A 47-year-old African American man was admitted with 4 days of back pain, nausea and vomiting, and low urine output. There was no history of fever, dysuria, frequency, hesitancy, viral symptoms, trauma, rash, or constipation. Despite his past medical history of hypertension, diabetes mellitus, and hyperlipidemia he denied taking any medications for 18 months, including nonsteroidal anti-inflammatory drugs, acetaminophen, or antacids. He denied smoking and alcohol but admitted to cocaine use. No significant FH. Physical examination results were as follows: BP 235/125 mm Hg, heart rate 90 beats/min, temperature 98°F, O2 saturation normal; lungs and heart normal, abdomen soft but bilateral costovertebral angle tenderness. Neurological examination was normal. Laboratory tests yielded the following results: creatinine (Cr) 10.5 mg/dL (1.2 mg/dL in 2010), blood urea nitrogen 63 mg/dL, glucose 151 mg/dL, Ca 9.4 mg/dL, PO4 6.1 mg/dL, Hgb 15 g/dL, white blood cells (WBC) 9100, platelets 167 000, amylase/lipase normal, aspartate aminotransferase/alanine aminotransferase (AST/ALT) normal, bilirubin 1.4 mg/dL, alkaline phosphatase 39 IU/L, creatine phosphokinase 127 µg/L. Hepatic panel, C- and P-ANCA (cytoplasmic- and perinuclear-antineutrophil cytoplasm antibodies, respectively), anti-GBM (anti-glomerular basement membrane), antimyeloperoxidase, antinuclear antibody, and Helicobacter pylori were all negative. C3, C4 normal, urinalysis: 2+ blood, no white blood cells or eosinophils, no casts, no albumin, negative for nitrate/leukocyte esterase and bacteria. Imaging: chest radiograph, abdominal radiograph, computed tomography of the abdomen, electrocardiography, and transthoracic echocardiography were all normal. Course. The patient's urine output declined from 700 to 400 cm(3)/d and the on third day he required hemodialysis with Cr 14 mg/dL. Renal biopsy showed typical findings of interstitial nephritis. The patient was dialyzed for 10 days and responded to steroids and went home with an improving Cr of 3.5 mg/dL, back to baseline of 1.5 in 8 weeks. Discussion. Internists encounter patients with acute kidney injury (AKI) on a daily basis, most of which can be explained by prerenal azotemia, acute tubular necrosis (ATN), obstruction, or rhabdomyolysis among other etiologies. Cocaine is only rarely implicated as an etiology of AKI and if it is, usually the injury is due to ATN or pigment effects. Acute interstitial nephritis (AIN) caused by cocaine, on the other hand, has only been described in a handful of cases. AIN is a renal lesion that causes a decline in creatinine clearance and is characterized by an inflammatory infiltrate in the kidney interstitium and is most often associated with drug therapy. AIN can also be seen in autoimmune disorders like systemic lupus erythematosus, Sjögren's syndrome, or sarcoidosis; or with infections remote to the kidney like Legionella, leptospirosis, and streptococcal disease. Our case was very similar to the other reported cases of AIN due to cocaine in that all have occurred in middle-aged African American males and all have responded to steroids. This case reminds clinicians to consider AIN in patients with AKI and a history of cocaine abuse.

Cases from the Osler Medical Service at Johns Hopkins University. Antiglomerular basement membrane disease.

A 47-year-old Taiwanese man with no notable medical history was admitted with low-grade fevers and night sweats that had persisted for 5 to 6 weeks. An extensive investigation at another hospital could not determine the cause of the fevers, but documented acute renal failure with a blood urea nitrogen level of 60 mg/dL and a serum creatinine level of 5.6 mg/dL. He was admitted to the Johns Hopkins Hospital for further evaluation.The patient, who had been living in the United States for the past 20 years, reported no recent travel and no behaviors that are associated with transmission of human immunodeficiency virus. He was not taking any medications, and he denied using herbal or nutritional supplements. He had no recent weight loss. There were no specific complaints on review of systems. On physical examination, he was a thin, middle-aged man in no distress. Vital signs included a temperature of 37.5 degrees C, a blood pressure of 166/86 mm Hg, a pulse of 70 beats per minute, a respiratory rate of 16 breaths per minute, and 99% oxygen saturation on room air. Sclera were anicteric, and he had no palpable adenopathy. His lungs were clear, and his heart rate was regular without extra sounds. His abdomen was thin, nontender, and without masses or organomegaly. There was no edema or signs of embolism in the extremities. Laboratory studies revealed a white blood cell count of 14,200/mL(3), a hematocrit of 23.1%, and a platelet count of 456,000/mL(3). Blood chemistries were notable for a blood urea nitrogen level of 61 mg/dL and a serum creatinine level of 7.6 mg/dL. Levels of aminotransferases, total bilirubin, and alkaline phosphatase were within normal limits. Urinalysis revealed large hemoglobin, 1+ protein, numerous red blood cells, and 3 to 5 white blood cells. Numerous red blood cell casts were seen on microscopic examination of the urine sediment. The patient's erythrocyte sedimentation rate was >130 mm/h, and his C-reactive protein level was elevated at 12.6 mg/dL. Serologies were negative for antinuclear antibodies and antineutrophil cytoplasmic antibodies; serum complement levels were normal. What is the diagnosis?

[Rapidly progressive glomerulonephritis in a 68-year-old man].

A 68-year-old male with macroscopic hematuria and constitutional symptoms as fever and weight loss. There was nothing interesting in the anamnesis or in the physical exploration. The laboratory test had an elevation of creatinine of 4 mg/dL and ten days before it had been 1.4 mg/dL. In the urine analysis: proteinuria of 1.5 G/24 h, and hematuria. On the second day we made a renal biopsy where we could seen segmental glomerular necrosis and crescent fromation in 80% of the glomeruli. In the immune study c-ANCA anti-PR3 was positive. In the complementary studies we didn't find other organs affected. With the diagnosis of pauci-immune glomerulonephritis limited to the kidney we began treatment with corticosteroids and cyclophosphamide. As the renal function was severely affected the patient needed one dialysis session. We began with 1 g intravenous methylprednisolone daily for 3 days followed by oral prednisone 60 mg daily tapering to 10 mg daily by 3 months. This was combined with 150 mg oral cyclophosphamide daily. Seven plasma exchanges were performed. At the beginning of treatment creatinine was 7 mg/dL, it was decreasing rapidly and three week after cretinine was 3 mg/Dl and he was asymptomatic. One year after treatment, creatinine is 1.4 mg/dL and the urine analysis is normal, C-ANCA are negative.

Nephrotic syndrome

Along with obtaining a complete medical history, a series of biochemical tests are required in order to arrive at an accurate diagnosis that verifies the presence of the illness. In addition, imaging of the kidneys (for structure and presence of two kidneys) is sometimes carried out, and/or a biopsy of the kidneys. The first test will be a urinalysis to test for high levels of proteins, as a healthy subject excretes an insignificant amount of protein in their urine. The test will involve a 24-hour bedside urinary total protein estimation. The urine sample is tested for proteinuria (>3.5 g per 1.73 m2 per 24 hours). It is also examined for urinary casts, which are more a feature of active nephritis. Next a blood screen, comprehensive metabolic panel (CMP) will look for hypoalbuminemia: albumin levels of ≤2.5 g/dL (normal=3.5-5 g/dL). Then a Creatinine Clearance CCr test will evaluate kidney function particularly the glomerular filtration capacity. Creatinine formation is a result of

[Interstitial lupus nephritis].

A 17-year old-male presented with a 6-week history of weight loss, lassitude and calf pains. On examination he was very pale. Laboratory tests showed a very high erythrocyte sedimentation rate (155 mm in the first hour), anaemia (haemoglobin 10.1 g/dl), and a raised serum creatinine of 1.54 mg/dl. Microhaematuria (5-10 erythrocytes/microliter) and pronounced pyuria (500 leucocytes/microliter) were present, but the urine was sterile and there was no increase in albumin excretion. The serum IgG was raised to 75.7 g/l, suggesting an autoimmune disorder. Anti-nuclear antibodies (titre 1 : 1920) and anti-double-stranded DNA antibodies (31 U/ml) were present, while the serum complement C4 was decreased to 0.11 g/l. Renal histology showed an interstitial nephritis without glomerular involvement, while the bone marrow showed vasculitis accompanied by a prominent plasma-cell infiltrate. A diagnosis of interstitial nephritis associated with systemic lupus erythematosus was made, with asymptomatic cardiac and hepatic involvement. Renal function recovered rapidly with prednisolone therapy (initial dose 2 mg/kg.d). While glomerulonephritis is the most common lupus-associated renal disorder, isolated interstitial nephritis may occur in some cases, often with an absence of proteinuria.

Diffuse Proliferative Glomerulonephritis -- Evaluation

A complete blood count showing possible anemia and low platelet count followed by renal function tests with elevated serum creatinine (0.4 mg/dl above the upper limit), blood urea nitrogen levels, and urine analysis positive for urine sediments: red blood cells and casts, white blood cells, granular casts are indicative of a glomerular pathology. For further confirmation, a 24 hours urine protein to creatinine ratio and 24 hours urine sample for protein levels can be done. A protein count of greater than 3.5 g/day is suggestive of nephrotic range proteinuria, which is associated with a worse prognosis. A 24-hour urine sample can be used to calculate creatinine clearance to estimate the eGFR. Renal ultrasound can be done to see the size and confirm the presence of two kidneys and the absence of any obstructive pathology resulting in hydronephrosis. Serum complement (C3 and C4) levels help determine the etiology; low levels are associated with the presence of SLE, cryoglobulinemia, and infectious etiology. [12]

An unusual manifestation of diabetes mellitus.

Type 2 diabetes mellitus for five years; unexplained 35-lb weight loss three years ago; Bell's palsy on right side many years ago. Glipizide, 10 mg/day. Father died of leukemia at age 65; mother has kidney stones; no diabetes or neuromuscular disease. Insurance salesman; heterosexual, promiscuous, uses condoms; smokes (25 pack years); does not drink. Well-nourished, well developed, not in acute distress; had difficulty rising from a sitting position because of right lower extremity weakness. Blood pressure, 154/74; pulse, 88; temperature, 36.6 degrees C; respiratory rate, 16. Head, eyes, ears, nose, and throat: normal. Neck: normal. Heart: S4. Lungs: clear. Abdomen: mildly obese. Extremities: no cyanosis, clubbing, or edema; atrophy and weakness of right thigh and both calves; wide-based gait; able to walk on toes but not heels. Neurologic responses: cranial nerves intact; deep tendon reflexes, 1 + symmetrically; plantar reflexes, flexor bilaterally. Skin: macular rash in sun-exposed areas. Hemoglobin, 13.2 gm/dL; mean corpuscular volume, 80 micron 3; white blood cell count, 7,200/mm3 (normal differential); platelet count, 137,000/mm3. Serum: electrolytes, normal; blood urea nitrogen, 18 mg/dL; creatinine, 0.8 mg/dL; glucose, 308 mg/dL; total protein, albumin, liver enzymes, and creatine kinase, normal. Urine: 1 + glucose. Venereal disease test: nonreactive; HIV test: negative. Dermatomyositis; heavy-metal poisoning; diabetic amyotrophy. The patient was given 50 mg/day of oral amitriptyline to alleviate the painful paresthesias and was switched to 20 U/day of subcutaneously injected neutral protamine Hagedorn (NPH) insulin to normalize the blood glucose level. Histologic studies of skin and muscle showed sun damage and neuropathic changes, respectively. There was no evidence of vasculitis. Screening for heavy-metal toxins produced negative results.

InternalMed_Harrison

AZOTEMIA Urinalysis and Renal ultrasound HydronephrosisRenal size parenchyma Urinalysis Urologic evaluation Relieve obstruction Small kidneys, thin cortex, bland sediment, isosthenuria <3.5 g protein/24 h Normal size kidneys Intact parenchyma Bacteria Pyelonephritis Chronic Renal Failure Symptomatic treatment delay progression If end-stage, prepare for dialysis Normal urinalysis with oliguria Abnormal urinalysis WBC, casts eosinophils Interstitial nephritis Red blood cells Renal artery or vein occlusion Urine electrolytes Muddy brown casts, amorphous sediment + protein RBC casts Proteinuria Angiogram FeNa <1% U osmolality > 500 mosmol FeNa >1% U osmolality < 350 mosmol Renal biopsy Prerenal Azotemia Volume contraction, cardiac failure, vasodilatation, drugs, sepsis, renal vasoconstriction, impaired autoregulation Acute Tubular Necrosis Glomerulonephritis or vasculitis Immune complex, anti-GBM disease Acute Renal Failure

Albuminuria

Causes of albuminuria can be discriminated between by the amount of protein excreted. The nephrotic syndrome usually results in the excretion of about 3.0 to 3.5 grams per 24 hours. Nephritic syndrome results in far less albuminuria. Microalbuminuria (between 30 and 300 mg/24h, mg/l of urine or μg/mg of creatinine) can be a forerunner of diabetic nephropathy. The term albuminuria is now preferred in Nephrology since there is not a "small albumin" (microalbuminuria) or a "big albumin" (macroalbuminuria). A1 represents normal to mildly increased urinary albumin/creatinine ratio (<30 mg/g or < 3 mg/mmmol); A2 represents moderately increased urinary albumin/creatinine ratio (30–300 mg/g or 3–30 mg/mmmol, previously known as microalbuminuria); and A3 reflects severely increased urinary albumin/creatinine ratio >300 mg/g or > 30 mg/mmol).

[Laboratory findings in patients with hemorrhagic fever with renal syndrome].

To examine the frequency and distribution of hematologic and biochemical laboratory findings in 94 patients with hemorrhagic fever with renal syndrome (HFRS) in the epidemic year 2002. The following laboratory findings were retrospectively analyzed: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin, hematocrit, leukocyte count and differential percentage (segmented neutrophils, band neutrophils, atypical lymphocytes), platelet count, coagulation tests, blood urea nitrogen (BUN), creatinine, urine, potassium, bilirubin (BIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GT), alkaline phosphatase (ALP), and serum protein electrophoresis. The study included 94 HFRS patients treated at the Dr Fran Mihaljević University Hospital for Infectious Diseases in Zagreb during 2002. ESR increase, mostly mild to moderate, was found in 86.2% of study patients. Increased CRP was recorded in 98.9% of study patients, however, one-fourth had CRP higher than 100 mg/L. Leukocytosis was recorded in 38.3% (10.1 +/- 4.2 x 10(9)/L), thrombocytopenia in 89.4% patients (68.2 +/- 48.3 x 10(9)/L), and severe thrombocytopenia (x 10(9)/L) in six patients. Three patients had abnormal coagulation tests. Increased values of BUN and creatinine were recorded in more than a half of patients, while only four patients had mild hyperkalemia. Only three patinets required hemodialysis. Mildly to moderately increased values of aminotransferases (AST, ALT, GT) were observed in more than 2/3; hypoalbuminaemia in nearly 1/3, and elevated alpha-2 fraction in more than 2/3 of patients. The majority of patients had pathologic urine findings. First laboratory abnormalities were usually found between day 5 and 7 of the disease (increased CRP level, thrombocytopenia, leukocytosis, and elevation of hemoglobin and hematocrit). Biochemical abnormalities(elevation of cratinine and urea, increased levels of aminotransferases) usually occurred at the beginning of the second week, and ESR increase in the second week of disease. The majority of our patients had laboratory findings characteristic of HFRS. Thrombocytopenia and increased level of CRP were the most common laboratory findings during the first week of the disease. Renal and liver impairment occurred at the beginning of the second week of the disease.

[Asymptomatic hematuria. Features of 11 observed cases].

The management of 11 cases of asymptomatic haematuria (E.A. in text) of which 1 macroscopic and 10 microscopic, involved a very accurate investigation on family medical history (focusing on haematuria, renal failure, deafness and atopy) as well as individual anamnesis (former events of E.A., concomitant and previous upper respiratory tract infections and allergic diseases) together with all laboratory and clinical tests on kidney functions. The first six months, the 24/hrs proteinuria, the "minute count" of urinary erythrocytes and the blood pressure were tested in all patients once a month, while, during the following 18 months, 3 tests only were carried out. All the subjects presented normal renal functions; for 2 of them the intravenous urography proved to be necessary because of a renal pain concomitant with haematuria while the audiogram was required for 1 subject only. After 2 years, the microscopic E.A. is still enduring in 3 patients: 2 of them recording haematuria in familial anamnesis and 1 suffering from similar episodes, long before we studied his case. None of them had to undergo the renal biopsy which the authors take into consideration only when E.A. is higher than 10,000.000 R.C./24 hrs and associated with high proteinuria and high complement decrease or when hereditary and concomitant to deafness (high frequences only).

Nephrotic syndrome

The main signs of nephrotic syndrome are: A proteinuria of greater than 3.5 g /24 h /1.73 m2 (between 3 and 3.5 g/24 h /1.73 m2 is considered to be proteinuria in the nephrotic range) or greater than 40 mg/h/m2 in children. The ratio between urinary concentrations of albumin and creatinine can be used in the absence of a 24-hour urine test for total protein. This coefficient will be greater than 200–400 mg/mmol in nephrotic syndrome. This pronounced loss of proteins is due to an increase in glomerular permeability that allows proteins to pass into the urine instead of being retained in the blood. Under normal conditions a 24-hour urine sample should not exceed 80 milligrams or 10 milligrams per decilitre. A hypoalbuminemia of less than 2.5 g/dL, that exceeds the liver clearance level, that is, protein synthesis in the liver is insufficient to increase the low blood protein levels.

InternalMed_Harrison

Fever >38.3°C (101°F) on at least two occasions 2. Illness duration of ≥3 weeks 3. 4. Diagnosis that remains uncertain after a thorough history-taking, physical examination, and the following obligatory investigations: determination of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level; platelet count; leukocyte count and differential; measurement of levels of hemoglobin, electrolytes, creatinine, total protein, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatine kinase, ferritin, antinuclear antibodies, and rheumatoid factor; protein electrophoresis; urinalysis; blood cultures (n = 3); urine culture; chest x-ray; abdominal ultrasonography; and tuberculin skin test (TST). The range of FUO etiologies has evolved over time as a result of changes in the spectrum of diseases causing FUO, the widespread Percentage of Cases Due to Indicated Cause

A child with spider bite and glomerulonephritis: a diagnostic challenge.

A previously healthy 7-year-old white boy presented to St. Louis Children's Hospital with a 1-day history of headache, malaise, temperature of 38.7 degrees C, and a progressively erythematous, tender calf with central dusky purpura. On the morning of admission, his mother noticed a 2-mm crust on the patient's right calf with a 3-cm x 3-cm area of surrounding erythema. No history of recent trauma or bite was obtained. He had suffered two episodes of nonbloody, nonbilious emesis during the last day. In addition, over the previous 12 h, he presented brown urine without dysuria. His mother and brother had suffered from gastroenteritis over the previous week without bloody diarrhea. On initial physical examination, there was a 6-cm x 11-cm macular tender purpuric plaque with a central punctum on the right inner calf, which was warm and tender to the touch, with erythematous streaking towards the popliteal fossa (Fig. 1). The inguinal area was also erythematous with tender lymphadenopathy and induration, but without fluctuance. Laboratory studies included an elevated white blood cell count of 20, 800/microL with 6% bands, 86% segs, and 7% lymphocytes, hemoglobin of 12.5 g/dL, hematocrit of 35.1%, and platelets of 282,000/microL. The prothrombin time/activated partial tissue thromboplastin was 10. 4/28.0 s (normal PT, 9.3-12.3 s; normal PTT, 21.3-33.7 s) and fibrinogen was 558 mg/dL (normal, 192-379 mg/dL). Urinalysis showed 1+ protein, 8-10 white blood cells, too numerous to count red blood cells, and no hemoglobinuria. His electrolytes, blood urea nitrogen (BUN), and creatine were normal. The urine culture was negative. Blood culture after 24 h showed one out of two bottles of coagulase negative Staphylococcus epidermidis. The patient's physical examination was highly suggestive of a brown recluse spider bite with surrounding purpura. Over the next 2 days, the surrounding rim of erythema expanded. The skin within the plaque cleared and peeled at the periphery. The coagulase negative staphylococci in the blood culture were considered to be a contaminant. Cefotaxime and oxacillin were given intravenously. His leg was elevated and cooled with ice packs. The patient's fever resolved within 24 h. The lesion became less erythematous and nontender with decreased warmth and lymphadenopathy. The child was discharged on Duricef for 10 days. Because the patient experienced hematuria rather than hemoglobinuria, nephritis was suggested. In this case, poststreptococcal glomerulonephritis was the most likely cause. His anti-streptolysin-O titer was elevated at 400 U (normal, <200 U) and C3 was 21.4 mg/dL (normal, 83-177 mg/dL). His urine lightened to yellow-brown in color. His blood pressure was normal. Renal ultrasound showed severe left hydronephrosis with cortical atrophy, probably secondary to chronic/congenital ureteropelvic junction obstruction. His right kidney was normal.

Minimal Change Disease -- Evaluation -- Basic labs:

Urine collection: A spot protein/creatinine ratio greater than 200 mg/mmol in children and protein/creatinine ratio>300-350mg/mmol in adults is consistent with nephrotic syndrome, as is a 24-hour urine collection that reveals a total protein greater than 3 to 3.5 g/24hour in adults. A report of measuring protein output as gms/m2/hr accounts for differences in body mass. A measurement of 40mg/m2/hour or greater (1gm/m2/24hour) is indicative of proteinuria consistent with nephrotic syndrome in children. Microscopic hematuria is present in 10% to 30% of adults. [13]

[Chronic renal failure: unexpected late sequela of pulmonary tuberculosis after 30 years].

Tuberculosis-related chronic granulomatous tubulointerstitial nephritis (GTN) and chronic renal dysfunction as a consequence of GTN is a rarely seen clinical condition, with a few case reports in the literature. In this report, a case with end stage renal failure as an unexpected late extrapulmonary sequela of tuberculosis has been presented. A 60 years old female patient was admitted to hospital with the complaints of fever, malaise and nausea. Her history revealed that she had pulmonary tuberculosis 30 years ago and received antituberculosis therapy for nine months. The laboratory results on admission were as follows: blood urea nitrogen 90 mg/dl, serum creatinine 9 mg/dl, sodium 116 mEq/L, potassium 6.6 mEq/L, albumine 2.9 g/dl, hemoglobin, 8.4 g/dl, white blood cell count 10.800/mm3, C-reactive protein 187 mg/L and erythrocyte sedimentation rate 110 mm/hour. Urinalysis showed 8.1 g/L protein, 10-12 leukocytes, 1-2 erythrocytes, while 24-hours urinalysis yielded proteinuria with 8 ml/minutes creatinine clearance value. Urine and blood cultures of the patient revealed neither bacteria or mycobacteria. PPD skin test was negative. Acid-resistant bacilli (ARB) were not detected in sequential urine samples obtained on three consecutive days. Since sputum samples could not be obtained, diagnostic procedures for sputum were not performed. Abdomen ultrasonography yielded bilateral edema and grade II echogenity in kidneys. Computed tomography of the chest showed bilateral pulmonary nodules, chronic sequela lesions, pleural scarring and calcifications, as well as minimal interstitial infiltrate. Transthoracic lung biopsy showed chronic inflammation and fibrosis, while amyloid was negative. Renal biopsy showed GTN with central caseified necrosis and granulomas, multinuclear giant cells, tubular atrophy and interstitial fibrosis. Amyloid was negative and ARB were not detected in renal biopsy sample. Definitive diagnosis was achieved by the demonstration of Mycobacterium tuberculosis nucleic acid in kidney biopsy by polymerase chain reaction (PCR). Antituberculosis therapy was not initiated since there were no signs of active tuberculosis. The patient became clinically stable following dialysis and was discharged, however, she has been undergoing hemodialysis three times a week. The aim of this case presentation was to emphasize that renal tuberculosis should be considered in the differential diagnosis of patients with end stage renal failure, especially in countries like Turkey where tuberculosis incidence is high.

[Glomerulonephritis and vasculitis as causes of arterial hypertension].

The various types of glomerulonephritis, including many forms of vasculitis, are responsible for about 15% of cases of end-stage renal disease (ESRD). Arterial hypertension represents a frequent finding in patients suffering from glomerulonephritis or vasculitis and hypertension also serves as an indicator for these severe types of diseases. In addition, there are symptoms and signs like hematuria, proteinuria and renal failure. Especially, rapidly progressive glomerulonephritis (RPGN) constitutes a medical emergency and must not be missed by treating physicians. This disease can either occur limited to the kidneys or in the context of a systemic inflammatory disorder, like a vasculitis. If left untreated, RPGN can lead to a necrotizing destruction of glomeruli causing irreversible kidney damage within several months or even weeks. With respect to the immunologically caused vasculitis, there are - depending upon the severity and type of organ involved - many clinical warning signs to be recognized, such as arterial hypertension, hemoptysis, arthalgias, muscle pain, palpable purpura, hematuria, proteinuria and renal failure. In addition, constitutional signs, such as fever and loss of body weight may occur concurrently. Investigations of glomerulonephritis or vasculitis must contain a careful and complete examination of family history and medications used by the respective patient. Thereafter, a thorough clinical examination must follow, including skin, joints and measurement of arterial blood pressure. In addition, a spectrum of laboratory analyses is required in blood, such as full blood screen, erythrocyte sedimentation rate, CRP, creatinine, urea and glucose, and in urine, including urinalysis looking for hematuria, red cell casts and proteinuria. Importantly, proteinuria needs to be quantified by the utilization of a random urine sample. Proteinuria > 3g/d is diagnostic for a glomerular damage. These basic tests are usually followed by more specialized analyses, such as a screening for infections, including search for HIV, hepatitis B or C and various bacteria, and for systemic inflammatory diseases, including tests for antibodies, such as ANA, anti-dsDNA, ANCA, anti-GBM and anti-CCP. In cases of membranous nephropathy, antibodies against phospholipase-A2-receptor need to be looked for. Depending upon the given clinical circumstances and the type of disease, a reasonable tumor screening must be performed, especially in cases of membranous and minimal-change nephropathy. Finally, radiological examinations will complete the initial work-up. In most cases, at least an ultrasound of the kidney is mandatory. Thereafter, in most cases a renal biopsy is required to establish a firm diagnosis to define all treatment options and their chance of success. The elimination of a specific cause for a given glomerulonephritis or vasculitis, such as an infection, a malignancy or a drug-related side-effect, remains the key principle in the management of these diseases. ACE-inhibitors, angiotensin receptor-blockers, aldosteron antagonists and renin-inhibitors remain the mainstay in the therapy of arterial hypertension with proteinuria. Only in cases of persistently high proteinuria, ACE-inhibitors and angiotensin receptor blockers can be prescribed in combination. Certain types of glomerulonephritis and essentially all forms of vasculitis require some form of more specific anti-inflammatory therapy. Respective immunosuppressive drug regimens contain traditionally medications, such as glucocorticoids (e. g. prednisone), cyclosporine A, mycophenolate mofetil, cyclophosphamide, and azathioprine. With respect to more severe forms of glomerulonephritis and vasculitis, the antibody rituximab represents a new and less toxic alternative to cyclophosphamide. Finally, in certain special cases, like Goodpasture's syndrome or severe ANCA-positive vasculitis, a plasma exchange will be useful and even required.

Behcet's disease and IgA nephropathy: report of this association in a patient from Brazil and literature review.

Behcet's disease (BD) is associated with renal involvement in about one-third of the cases and a variety of renal lesions have been reported. A 27-year-old man presented a history of recurrent oral and genital ulcers, associated with pseudofoliculitis and arthritis in his left knee. The first laboratory tests revealed: urea = 53mg/dL, creatinine = 1.8 mg/dL. The urinalysis showed leukocyturia. Initial treatment with ceftriaxone, thalidomide and prednisone was instituted. He became clinically stable, with normal renal function, but presenting hematuria and proteinuria. One year later the patient presented dark urine. The new laboratory tests showed urea=58 mg/dL, creatinine = 1.4 mg/dL, and mild proteinuria (500-1000 mg/24h). Two years later the proteinuria was 2230 mg/day. The renal biopsy showed one glomerulus with severe glomerular sclerosis, mild tubular atrophy, mild interstitial fibrosis and thickening of arterial walls. Treatment with captopril was started to decrease proteinuria. Two years later, the patient presented creatinine = 1.7 mg/dL and proteinuria = 2509 mg/day. A new renal biopsy evidenced proliferative crescentic glomerulonephritis, with diffuse granullary deposits of IgA, IgM and C3. It was instituted pulsotherapy with metilprednisolone, monthly endovenous cyclophosphamide and maintenance prednisone. The patient became clinically stable, with creatinine of 1.3 mg/dL and proteinuria of 500 mg/day. BD could be one of the various causes of secondary IgA nephritis. It is important to periodically perform renal function evaluation in patients with BD, through urinalysis and measurement of serum creatinine and its clearance, in order to detect any abnormality and provide an early adequate treatment.

InternalMed_Harrison

Fever ˜38.3° C (101° F) and illness lasting ˜3 weeks and no known immunocompromised state History and physical examination Stop antibiotic treatment and glucocorticoids Obligatory investigations: ESR and CRP, hemoglobin, platelet count, leukocyte count and differential, electrolytes, creatinine, total protein, protein electrophoresis, alkaline phosphatase, AST, ALT, LDH, creatine kinase, antinuclear antibodies, rheumatoid factor, urinalysis, blood cultures (n=3), urine culture, chest x-ray, abdominal ultrasonography, and tuberculin skin test

Reversible acute renal failure and nephrotic syndrome in a Type 1 diabetic patient.

Nephrotic syndrome is a condition commonly associated with end-stage renal disease secondary to diabetic nephropathy. It is usually associated with long-standing renal insufficiency, microalbuminuria, and overt proteinuria. We present a diabetic patient with acute oliguric renal failure and nephrotic syndrome. At presentation, he had a serum creatinine of 2.3 mg/dl, blood urea nitrogen (BUN) of 69 mg/dl, urinary protein excretion of 10.5 g/24 h, serum albumin of 1.3 g/dl, and a urine output < 400 cc/24 h. A renal biopsy was done and the renal pathology was compatible with early diabetic nephropathy. Despite intense diuretic therapy, the patient's renal condition did not improve, and peritoneal dialysis was started several months after diagnosis. After 8 months of dialysis therapy, the patient's renal parameters and urinary output spontaneously restored to normal limits (serum creatinine was 1.1 mg/dl, urinary albumin excretion was 411 mg/24 h, serum albumin was 4.3 g/dl, and normal urine output) and dialysis was discontinued. His renal function did not deteriorate after discontinuation of dialysis. We conclude that this patient's reversible acute renal failure and nephrotic syndrome were associated with minimal change disease and not due to diabetic nephropathy.

[Clinical studies of the prognosis in cases of chance proteinuria and/or hematuria].

A total of 174 cases that consulted due to chance proteinuria and/or hematuria (CPH) were studied as to its clinical course, in particular patients' prognosis. They were selected from 311 patients on whom renal biopsy was performed from December, 1975 to December, 1985 in our institute. Furthermore, IgA nephropathy which occupied the major part of the CPH group was also studied as a prognostic factor. The CPH group showed 81% of disease stabilizing rate in 10 years' follow-up. In various data such as chemical analysis of blood and urine, immunoglobulin levels, and renal function at the time of biopsy, daily urinary protein excretion (greater than 1 g/day) statistically showed a significant correlation to deterioration of the renal function during the follow up. However, hematuria was not found correlated. Of CPH group, 48% was diagnosed to be with IgA nephropathy. The patients with IgA nephropathy with CPH, comparing with the cases without CPH, were younger and had better renal function and milder change of renal mesangial proliferation. The 10 years-disease stabilizing rates of the disease were 81% in CPH and 63% in non CHP group. In conclusion, prognostic factors affecting renal function in the CPH group was found to be daily urinary protein excretion and, if diagnosed as IgA nephropathy by biopsy, pathological changes were also shown to be prognostic factors. Therefore, CPH patients having proteinuria over 1 g/day must be examined by renal biopsy and when IgA nephropathy is diagnosed, long time follow-up is necessary and re-biopsy for examination of pathological change during the interval is recommended.

Urine test strip

Of the routine chemical tests performed on urine, the most indicative of renal disease is the protein determination. Proteinuria is often associated with early renal disease, making the urinary protein test an important part of any physical examination. Normal urine contains very little protein, usually less than 100–300 mg/L or 100 mg per 24 hours is excreted. This protein consists primarily of low-molecular-weight serum proteins that have been filtered by the glomerulus and proteins produced in the genitourinary tract. Due to its low molecular weight, albumin is the major serum protein found in the plasma, the normal urinary albumin content is low because the majority of albumin presented in the glomerulus is not filtered, and much of the filtered albumin is reabsorbed by the tubules. Other proteins include small amounts of serum and tubular microglobulins. Uromodulin produced by the renal tubular epithelial cells and proteins from prostatic, seminal, and vaginal secretions.

Nephrology

Diagnosis History and physical examination are central to the diagnostic workup in nephrology. The history typically includes the present illness, family history, general medical history, diet, medication use, drug use and occupation. The physical examination typically includes an assessment of volume state, blood pressure, heart, lungs, peripheral arteries, joints, abdomen and flank. A rash may be relevant too, especially as an indicator of autoimmune disease. Examination of the urine (urinalysis) allows a direct assessment for possible kidney problems, which may be suggested by appearance of blood in the urine (hematuria), protein in the urine (proteinuria), pus cells in the urine (pyuria) or cancer cells in the urine. A 24-hour urine collection used to be used to quantify daily protein loss (see proteinuria), urine output, creatinine clearance or electrolyte handling by the renal tubules. It is now more common to measure protein loss from a small random sample of urine.

Acute renal failure associated with diphosphonic acid (HEDP): a case report.

A 26-year-old man with no significant past medical history presented to emergency department 1 hr after ingesting approximately 200 ml of HEDP 2010 organophosphoric acid corrosion inhibitor. He had normal vital signs, physical examination and biochemical parameters. After 24 hr, he developed nausea with a decreased urine output. While his blood urea nitrogen, creatinine and uric acid levels increased to 36 mg/dl, 3.87 mg/dl, and 8.4 mg/dl, respectively; his serum calcium and phosphorus levels decreased to 7.4 mg/dl and 1.4 mg/dl, respectively. He had proteinuria, glucosuria, leukocyturia and high phosphorus excretion in the urine. On ultrasonographic examination, the kidneys were slightly enlarged and edematous. On the third day of hospitalization, creatinine level increased to 8.81 mg/dl and metabolic acidosis developed. He underwent to hemodialysis therapy and renal functions improved uneventfully. This case represents an example of acute renal failure developed and recovering uneventfully after unintentionally ingestion of a bisphosphonate used in industry.

Manifestation of paroxysmal nocturnal hemoglobinuria as repeated acute kidney injury.

The triad of hemolytic anemia, pancytopenia, and thrombosis makes paroxysmal nocturnal hemoglobinuria (PNH) a truly unique clinical syndrome. Intravascular hemolysis in PNH can lead to a severe hemolytic episode with massive hemoglobinuria which can cause acute kidney injury (AKI) probably from acute tubular necrosis (ATN). A 15 -year-old girl was admitted with history of fever, diarrhea, vomiting followed by decreased urine output since 3 days. Urinalysis showed nil protein, no red blood cells (RBCs) on microscopy. Plasma hemoglobin level, total leukocyte count, platelet count, and serum creatinine were 6.5 gm/dl, 6440/μl, 205 000/μl, and 3.1 mg/dl, respectively. She received 3 units of packed red blood cells and the patient was discharged with normal renal function test with a diagnosis of acute gastroenteritis with recovered AKI. After 8 months she again had fever, vomiting, nausea with decreased urine output since 3 days. Laboratory investigations showed hemoglobin - 5.5 gm/dl, total leukocyte count - 1550/ μl, platelet count - 165000/μl, and serum creatinine - 4.89 mg/dl. Serum LDH level was 2188 U/l. She was managed conservatively with steroids, antibiotics and she recovered her kidney functions to normal in a week. Presentation of repeated AKI with hemolytic anemia in a short span after fever led us to perform flow cytometric analysis of peripheral blood granulocytes which revealed the presence of PNH clone. PNH may present with renal disease and anemia only even without classical history of hematuria or venous thrombosis. Thus it needs high index of suspicion as early diagnosis and treatment will help in preventing repeated episodes of AKI and thus chronic kidney disease.

Methimazole-Induced ANCA Vasculitis: A Case Report.

Rapidly progressive glomerulonephritis (RPGN) is a syndrome which presents rapid loss of renal function. Vasculitis represents one of the major causes, often related to anti-neutrophil cytoplasmic antibodies (ANCA). Herein, we report a case of methimazole-induced ANCA-associated vasculitis. A 35-year-old woman complained of weight loss and fatigue for 2 weeks and attended the emergency room with alveolar hemorrhage. She had been diagnosed with Graves' disease and had been taking methimazole in the past 6 months. Her physical examination showed pulmonary wheezing, hypertension and signs of respiratory failure. Laboratory tests revealed urea 72 mg/dL, creatinine 2.65 mg/dL (eGFR CKD-EPI: 20 mL/min/1.73 m<sup2</sup), urine analysis with >100 red blood cells per high-power field, 24 h-proteinuria: 1.3 g, hemoglobin 6.6 g/dL, white-cell count 7700/mm<sup3</sup, platelets 238,000/mm<sup3</sup, complement within the normal range, negative viral serological tests and ANCA positive 1:80 myeloperoxidase pattern. Chest tomography showed bilateral and diffuse ground-glass opacities, and bronchial washing confirming alveolar hemorrhage. A renal biopsy using light microscopy identified 27 glomeruli (11 with cellular crescentic lesions), focal disruption in glomerular basement membrane and fibrinoid necrosis areas, tubulitis and mild interstitial fibrosis. Immunofluorescence microscopy showed IgG +2/+3, C3 +3/+3 and Fibrinogen +3/+3 in fibrinoid necrosis sites. She was subsequently diagnosed with crescentic pauci-immune glomerulonephritis, mixed class, in the setting of a methimazole-induced ANCA vasculitis. The patient was treated with methimazole withdrawal and immunosuppressed with steroids and cyclophosphamide. Four years after the initial diagnosis, she is currently being treated with azathioprine, and her exams show creatinine 1.30 mg/dL (eGFR CKD-EPI: 52 mL/min/1.73 m<sup2</sup) and negative p-ANCA.

Chronic overexposure to cadmium fumes associated with IgA mesangial glomerulonephritis.

Cadmium is a metal used in the zinc, copper and steel industries, and in the manufacture of electric batteries and solar cells. Acute cadmium poisoning is characterized by irritation of the respiratory tract, while in chronic poisoning the main target organ is the renal tubule. We report a patient with chronic work overexposure to cadmium, who presented a IgA mesangial glomerulonephritis with no respiratory or renal tubule involvement. Case report A 39-year-old patient was referred to our hospital for evaluation of a glomerular nephropathy. For the past 12 years he had worked as a welder, using cadmium electrodes. The patient had no respiratory symptoms and the chest X-ray was normal. Tests showed a proteinuria of 2 g in 24 h with microhaematuria [150 red blood cells/high power field (rbc/hpf)], with preservation of the renal function (creatinine clearance of 137 ml/min). The concentrations of cadmium in blood and urine were 45 micro g/l and 25 micro g/g creatinine, and an environmental study showed that levels of cadmium in the workplace were 52 micro g/m(3). A renal biopsy showed an IgA mesangial glomerulonephritis. The patient ceased to work with cadmium, and 1 year later cadmium levels had decreased and renal function was found to be stable. IgA mesangial glomerulonephritis is a disease of unknown aetiology which has been associated with other diseases. Chronic overexposure to cadmium may contribute to the development of this nephrophathy.

Microscopic Polyangiitis -- Evaluation

Lab Evaluation: It  involves routine complete blood count (CBC), electrolytes, and measurement of serum titers of MPO and PR3 antibodies, which may be seen in most cases. However, low serum levels cannot be used to rule out AAV reliably. The complete blood cell count (CBC) shows leukocytosis and anemia. The erythrocyte sedimentation rate (ESR) is elevated. Blood urea nitrogen (BUN) and serum creatinine levels are elevated. Abnormal urine sediments, proteinuria, hematuria, leukocyturia, and erythrocyte casts are found on urine examination. The antineutrophil cytoplasmic antibody (ANCA) test is positive in 80% of cases. Among these, perinuclear ANCA, related to myeloperoxidase, is present in 60%, while cytoplasmic ANCA, related to proteinase-3 ANCA, is present in 40%. Blood cultures may be performed to rule out bacterial endocarditis. On complement testing, C3 and C4 levels are normal.

Safety of megadose of vitamin D in patients with nephrolithiasis.

This article describes two patients with renal lithiasis who received a megadose of 25-hydroxy vitamin D (25[OH]D) and had a good outcome. The first case reports a 74-year-old man with a long-term history of renal lithiasis and about four episodes of renal crisis. He was treated once with extracorporeal shock wave lithotripsy. He also had a history of dyslipidemia, myocardial infarction, and stroke. Laboratory tests demonstrated 25(OH)D of 28 ng/mL (normal range (nr): >30 ng/mL), normal lipid levels, creatinine of 1.1 mg/dL, and homocysteine of 26.6 mcmol/L (nr: 5-15 mcmol/L); parathyroid hormone (PTH) was high at 67.3 pg/mL (nr: 10-65 pg/mL), serum total calcium was 8.6 mg/dL, 24-h urinary calcium was 139 mg/d (normal range 100-300 mg/d), and urinary sediment was normal. He received 50 000 IU per week of vitamin D for 3 mo, and 25(OH)D increased to 36.6 ng/mL. Urinary calcium was 142 mg/d, PTH was 46.7 pg/mL, and serum calcium was 9.6 mg/dL. No renal crisis was perceived. He asked for an alternative form of medication since he usually would forget to take drugs. Vitamin D in a single dose of 600 000 IU intramuscular was prescribed. He was asked to increase water intake to 2 to 3 L/d. After 3 mo his 25(OH)D was 75.0 ng/mL, serum calcium was 9.2 mg/dL, urinary calcium was 148 mg/d, and PTH was 38.7 pg/mL. He had no episodes of lithiasis renal crisis. Folic acid and methylcobalamin were added, and homocysteine normalized. At follow-up 3 y later, the patient was asymptomatic, cardiologic evaluation was stable without any other renal lithiasis crises, 25(OH)D continued to be normal at 62 ng/mL, and he received a megadose of vitamin D every 6 mo. Renal ultrasound revealed only microlithiasis. The second case reports a 52-year-old man with a long-term history of renal lithiasis experienced since he was 30 y old, with three renal crisis episodes. He was treated with an extracorporeal shock wave three times. Laboratory tests demonstrated 25(OH)D 18 ng/mL, normal biochemistry, total serum calcium of 10.2 mg/dL, 24-h urinary calcium of 154 mg/d, and normal urinary sediment. He received 50 000 IU per week of 25(OH)D for 3 mo, and 25(OH)D increased to 40.3 ng/mL. Urinary calcium was 167 mg/d, PTH was 35.3 pg/mL, and serum calcium was 10.1 mg/dL. No renal crisis was perceived. He asked for an alternative form of medication, and vitamin D in a single dose of 600 000 IU intramuscular was prescribed. He was asked to increase water intake to 2 to 3 L/d. After 3 mo, his 25(OH)D was 82.0 ng/mL, serum calcium was 9.6 mg/dL, urinary calcium was 175 mg/d, and PTH was 35.3 pg/mL. The renal ultrasound was unchanged. He had no episodes of lithiasis renal crisis. At follow-up 4 y later, the patient was asymptomatic without any other renal lithiasis crises, a renal ultrasound revealed a reduction of calculi size to microlithiasis, 25(OH)D continues normal, and he received a megadose of this vitamin every 4 mo. To the best of our knowledge, this is the first description of a megadose of vitamin D used in patients with nephrolithiasis. Furthermore, this shows the safety of this strategy in patients without hypercalciuria.

Clinicopathological characteristics and outcome of adult patients with hematuria and/or proteinuria found during routine examination.

Patients with hematuria and/or proteinuria found during routine examination are commonly encountered. To define the clinicopathological characteristics and outcome of these patients, 142 patients with definite pathological diagnosis were studied retrospectively. All the 142 patients were divided into three groups: pure hematuria (HU, n = 13), concomitant hematuria and proteinuria (HUPU, n = 79), and proteinuria alone (PU, n = 50). At the time of renal biopsy, 26% of the patients had renal insufficiency and 48% of the patients had hypertension. Pathologically, IgA nephropathy (n = 67) was the most common. A total of 51 patients were enrolled into the follow-up group. Finally, urinary abnormalities disappeared in 18% of the patients, 22% of HU developed proteinuria, 21% of HUPU and 23% of PU appeared to have a distinct increase of proteinuria, and 15% of PU developed hematuria. Seven patients with normal blood pressure before became hypertensive and 6% of the patients with normal renal function initially developed renal insufficiency. The renal outcome was associated with proteinuria and tubulointerstitial lesions. Because renal pathologic change does not always coincide with clinical manifestations, patients with hematuria and/or proteinuria found during routine examination do not necessarily imply a favorable outcome, so renal biopsy is quite important. Besides, early treatment and careful follow-up are helpful in these patients.

InternalMed_Harrison

Laboratory studies should include a complete blood count to assess both the hematocrit and the platelet count as well as coagulation studies. Renal function should be evaluated and urinalysis conducted because of the possibility of pulmonary-renal syndromes presenting with hemoptysis. The documentation of acute renal insufficiency or the detection of red blood cells or their casts on urinalysis should elevate suspicion of small-vessel vasculitis, and studies such as antineutrophil cytoplasmic antibody, antiglomerular basement membrane antibody, and antinuclear antibody should be considered. If a patient is producing sputum, Gram’s and acid-fast staining as well as culture should be undertaken. If all of these studies are unrevealing, bronchoscopy should be considered. In any patient with a history of cigarette smoking, airway inspection should be part of the evaluation of new-onset hemoptysis as endobronchial lesions are not reliably visualized on CT.

UPCR

The difference between urine protein/creatinine ratio and 24-hour urine collection is that former requires a urine sample to be collected only once at any time. [Creatinine(U)] is taken into account due to the notion that creatinine is normally released into the urine at a constant rate. Scientists found that the ratio of protein to creatinine roughly estimates the actual value gained from the 24-hour urine protein test. The normal urine protein/creatinine ratio is not more than 200 mg/g. References Abnormal clinical and laboratory findings for urine


Treatment with diuretics should be started at high doses.

A 60-year-old man with a history of hypertension and dyslipidemia has recently been diagnosed with heart failure. After performing the relevant tests, it was found that the left ventricular ejection fraction was preserved (>50%). With regard to treatment, indicate the CORRECT answer:

Initial treatment should be directed to the underlying pathological process.

If nitrate treatment is required, it should be started at low doses.

Dyspnea can be treated by reducing neurohormonal activation with angiotensin converting enzyme inhibitors or angiotensin receptor antagonists.

Chronic Heart Failure.

Physicians must aggressively treat heart failure in the early stages to prevent disease progression and improve survival. Early treatment implies early diagnosis of left ventricular (LV) dysfunction, before the onset of symptoms. Patients with risk factors for the development of heart failure, especially coronary disease or hypertension, should undergo echocardiography to evaluate LV function. Patients with LV systolic dysfunction should be further evaluated to determine the type of cardiac dysfunction, uncover correctable etiologic factors, determine prognosis, and guide treatment. Angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic blocking drugs improve survival and are integral to the treatment plan. Physicians should prescribe an ACE inhibitor as initial therapy for all patients with LV systolic dysfunction unless there are specific contraindications. The combination of hydralazine and isosorbide dinitrate is an acceptable alternative therapy for patients who cannot take ACE inhibitors. Diuretics should be used if there are signs or symptoms of volume overload. Beta-adrenergic blocking drugs should be added to therapy in stable patients with mild to moderate heart failure after optimal treatment with ACE inhibitors, diuretics, or other vasodilators. Digoxin should be used routinely in patients with severe heart failure and should be added to therapy in patients with mild to moderate heart failure who remain symptomatic despite optimal doses of ACE inhibitors and diuretics. Spironolactone should be added, but electrolytes should be closely monitored. Warfarin anticoagulation should be considered in patients with a left ventricular ejection fraction (LVEF) of 35% or less. Until survival data exist, angiotensin receptor blockers (ARBs) should not be used as initial therapy or as sole therapy but can be used for ACE-intolerant patients or can be added to standard heart failure therapy. Outpatient use of intravenous inotropic therapy should be avoided. Patients with severe heart failure should have peak oxygen consumption measured to quantify functional impairment, determine prognosis, and identify the need for advanced heart failure therapy. Patients who remain symptomatic while receiving optimal standard therapy should be referred early to a specialized heart failure center.

Treatment of heart failure with normal left ventricular ejection fraction.

Underlying causes and precipitating causes of heart failure (HF) should be treated when possible. Persons with HF and normal left ventricular ejection fraction (LVEF) should have maintenance of sinus rhythm, treatment of hypertension, myocardial ischemia, dyslipidemia, and anemia, slowing of the ventricular rate below 90 bpm, and reduction of salt overload. First-line drug treatment in the management of these persons is the use of loop diuretics combined with beta blockers and angiotensin-converting enzyme (ACE) inhibitors. If persons are unable to tolerate ACE inhibitors because of cough, angioneurotic edema, rash, or altered taste sensation, angiotensin II type I receptor antagonists (ARBs) should be given. If HF persists despite diuretics, beta blockers, and ACE inhibitors or ARBs, isosorbide dinitrate plus hydralazine should be administered. Beta blockers, verapamil, diltiazem, and digoxin may be used to slow a rapid ventricular rate in persons with supraventricular tachyarrhythmias. Digoxin should not be used in persons with HF in sinus rhythm with normal LVEF. Exercise training should be encouraged in persons with mild to moderate HF to improve functional status and to decrease symptoms.

[Modern therapy of cardiac insufficiency].

Heart failure is a lethal, end-stage cardiovascular disease. Recent decrease in mortality rates from cardiovascular diseases has not been accompanied by a reduced mortality from heart failure. Survival, once the heart has used up all its reserves and compensatory mechanisms, is a little better than in cancer. That makes heart failure one of the most important world health problems. This paper briefly reviews history, present and future of heart failure therapy, as a worldwide problem. Definition and diagnosis of heart failure, mechanism of deterioration of heart function, clinical use of present drugs in heart failure therapy and need for prevention of heart failure are, briefly pointed out. Results of clinical studies are presented, as well as the recommended indication for drug use. Heart failure is not readily identified, defined and evaluated. There is an absence of clear definition. To find a new definition which complies best with clinical practice is an important challenge cardiologists must face. Heart failure is a progressive disease and once the process has started it continues with further deterioration of cardiac function or ends in sudden death. In many patients changes within heart develop long before clinical symptoms occur. The left ventricle goes through a number of adaptations remodeling to compensate increased pressure or volume load or subsequent myocardial infarction. For decades therapy has been focused on relieving symptoms, whereas preventive aspects and prolonging survival received less attention. Conventional therapy with diuretics and cardiotonic glycosides causes regression of symptoms and signs of heart failure, but there is no evidence that these drugs slow down the progression of the disease and reduce mortality. Currently, angiotensin-converting enzyme inhibitors plus diuretics are considered first line therapy for all degrees of heart failure, except for heart failure with atrial fibrillation and a rapid ventricular rate. They are, currently, the only agents with proven ability to decrease mortality. There is evidence about the efficacy of angiotensin-converting enzyme inhibitors in asymptomatic left ventricular dysfunction. It is likely that not only patients with significant reduction of systolic function but also other signs of impaired left ventricular dysfunction will benefit from treatment with ACE inhibitors. However, only preventive treatment may decrease the number of patients with new onset of clinical heart failure. Therefore treatment should be introduced early, rather than waiting for heart failure to progress to a more severe stage. Based on these facts ACE inhibitors should be considered as treatment of choice, a first line therapy in most cases of heart failure. A substantial reduction in cardiovascular mortality requires detection and correction of presymptomatic left ventricular dysfunction and risk factors, which predispose to its occurrence. Major contributors to the development of cardiac failure have been delineated and quantified. Identification of high-risk individuals is difficult since signs and symptoms of heart failure are often lacking. A strategy to find these patients must use objective methods to characterize the state of the left ventricle. Despite this, methods for efficient identification presymptomatic candidates for cardiac failure for preventive measures have been developed. High-risk candidates can now be costly-effectively targeted for treatment to delay failure. Early diagnosis and subsequent aggressive medical or surgical treatment are therefore fundamental to improve adverse outcome of heart failure. It is necessary to allow a rational approach to the clinician, indicating the effectiveness of these drugs in patients with evidence of impaired ventricular function. Further reduction of morbidity and mortality from heart failure and diseases associated with heart failure is to be expected by early

Left ventricular diastolic heart failure with normal left ventricular systolic function in older persons.

Underlying causes and precipitating causes of congestive heart failure (CHF) should be treated when possible. Older persons with CHF and normal left ventricular (LV) ejection fraction should have maintenance of sinus rhythm, treatment of hypertension and myocardial ischemia, slowing of the ventricular rate below 90 beats/minute, and reduction of salt overload. First-line drug treatment in the management of these persons is the use of loop diuretics combined with beta blockers as tolerated. Angiotensin-converting enzyme (ACE) inhibitors should be administered if CHF persists despite diuretics and beta blockers. If persons are unable to tolerate ACE inhibitors because of cough, rash, or altered taste sensation, angiotensin II type 1 receptor antagonists should be given. If CHF persists despite diuretics, beta blockers, and ACE inhibitors or the person is unable to tolerate beta blockers, ACE inhibitors, and angiotensin II type 1 receptor antagonists, isosorbide dinitrate plus hydralazine should be administered. Calcium channel blockers should be used if CHF persists despite administration of diuretics and the person is unable to tolerate beta blockers, ACE inhibitors, angiotensin II type 1 receptor antagonists, and isosorbide dinitrate plus hydralazine. Digoxin, beta blockers, verapamil, and diltiazem may be used to slow a rapid ventricular rate in persons with supraventricular tachyarrhythmias. Digoxin should not be used in persons with CHF in sinus rhythm with normal LV ejection fraction.

[Dyspnea in left-sided heart disease].

Shortness of breath (dyspnea) is a common symptom in left-sided heart disease but clinically, patient symptoms show a high variability. Echocardiography is the mainstay for evaluating whether left-sided heart disease is the cause of dyspnea. If left-sided heart failure is diagnosed, this symptom complex must then be subjected to further etiological evaluation. Hypertensive, ischemic and valvular heart diseases are common, as well as atrial fibrillation. If the patient does not have angina pectoris, testing for ischemic heart disease should be done non-invasively by coronary computed tomography or testing for regional myocardial ischemia. Coronary revascularization is indicated only when a prognostically relevant ischemia of more than 10 % of the left ventricle is diagnosed. Diuretics are important for the relief of dyspnea but do not improve the prognosis of patients. In patients with reduced left ventricular function, combination therapy with angiotensin-converting enzyme (ACE) inhibitors, beta blockers and aldosterone antagonists improve the symptoms and prognosis. For treatment of heart failure with preserved ejection fraction evidence-based measures are still lacking. In this case the recommended therapy consists of optimal treatment of comorbidities, regulation of heart rate and blood pressure and participation in structured exercise programs. Angiotensin receptor blockers and aldosterone antagonists can be given in patients with more severe symptoms even though the available data are very sparse.

Myocardial infarction

ACE inhibitor therapy should be started within 24 hours, and continued indefinitely at the highest tolerated dose. This is provided there is no evidence of worsening kidney failure, high potassium, low blood pressure, or known narrowing of the renal arteries. Those who cannot tolerate ACE inhibitors may be treated with an angiotensin II receptor antagonist. Statin therapy has been shown to reduce mortality and subsequent cardiac events and should be commenced to lower LDL cholesterol. Other medications, such as ezetimibe, may also be added with this goal in mind. Aldosterone antagonists (spironolactone or eplerenone) may be used if there is evidence of left ventricular dysfunction after an MI, ideally after beginning treatment with an ACE inhibitor.

Left axis deviation

Treatment Left axis deviation per se does not require treatment, however the underlying cause can be treated. If left ventricular hypertrophy is the cause of LAD, treatment depends on the underlying cause of the hypertrophy. If high blood pressure is the cause of LVH, then treatment is targeted at lowering blood pressure and preventing further enlargement of the left ventricle by using medications such as angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin receptor blockers (ARBs), calcium channel blockers, diuretics, and beta-blockers. If LVH is due to valvular issues such as aortic valve stenosis, surgical repair of the valve or replacement of the valve is required. See also Right axis deviation References Cardiovascular physiology

[ANMCO Position paper: Double, triple or quadruple therapy for heart failure with reduced ejection fraction. Current evidence and new strategies].

The triple therapy (angiotensin-converting enzyme [ACE] inhibitors or angiotensin receptor blockers, beta-blockers, mineralocorticoid receptor antagonists) certificated by the 2012 guidelines for symptomatic patients with heart failure and reduced ejection fraction, reaffirmed in the following document of 2016 with the introduction of angiotensin receptor-neprilysin inhibitors (ARNI), has not yet reached an adequate implementation in clinical practice (where the majority of patients is only treated with the double treatment of ACE-inhibitors or angiotensin receptor blockers and beta-blockers). Among the reasons for this general failure, we should consider the enrollment of unselected cases from the real world, without exclusion criteria for age, comorbidity and stage of the disease, the therapeutic inertia of many cardiologists and not least the clinical and organizational complexity of the conventional scheme of implementation of therapy indicated by the guidelines. Not only the prescription of triple therapy is inadequate, but also the "target doses" defined by the large randomized controlled trials should be considered unrealistic in the majority of patients, who often achieve a therapeutic effect at lower doses, generally better tolerated ("target effect"). The new guidelines forthcoming will certify a further step forward with the quadruple therapy (sodium-glucose co-transporter 2 inhibitors, ARNI, beta-blockers and mineralocorticoid receptor antagonists), underlining how a fourfold intervention with different pharmacological mechanisms is able to determine the greatest benefits in patients with systolic heart failure. The discussion is open on the possibility of simplifying and speeding up the conventional implementation scheme of treatment, exploiting the ability of all these pharmacological principles to exert a significant and rapid favorable effect on prognosis already at a low dose in the first 4-8 weeks of treatment.

Heart failure with preserved ejection fraction

Beta-blockers are the first-line therapy: they lower the heart rate and thus give more time for ventricles to fill. They may also improve survival. There is some evidence that calcium channel blockers may be of benefit in reducing ventricular stiffness. In some cases, (verapamil has the benefit lowering the heart rate). Angiotensin converting enzyme (ACE) inhibitors Likewise, treatment with angiotensin converting enzyme inhibitors, such as enalapril, ramipril, and many others, may be of benefit due to their effect on preventing ventricular remodeling but under control to avoid hypotension. ACE inhibitors do not appear to improve morbidity or mortality associated with HFpEF alone. However, they are important in the management of hypertension, a significant player in the pathophysiology of HFpEF. Angiotensin II receptor blockers (ARBs) ARB treatment results in an improvement in diastolic dysfunction and hypertension that is comparable to other anti-hypertensive medication.

Valsartan

Valsartan was patented in 1990, and came into medical use in 1996. It is available as a generic medication. In 2019, it was the 154th most commonly prescribed medication in the United States, with more than 4million prescriptions. Medical uses Valsartan is used to treat high blood pressure, heart failure, and to reduce death for people with left ventricular dysfunction after having a heart attack. High blood pressure It is a reasonable initial treatment for high blood pressure as are ACE inhibitors, calcium-channel blockers, and thiazide diuretics. Heart failure There is contradictory evidence with regard to treating people with heart failure with a combination of an angiotensin receptor blocker like valsartan and an angiotensin-converting enzyme inhibitor, with two major clinical trials showing a reduction in death, and two others showing no benefits, and more adverse effects including heart attacks, hypotension, and renal dysfunction.

Treatment of congestive heart failure in older persons.

To review the management of congestive heart failure (CHF), with emphasis on older adults. A computer-assisted search of the English language literature (MEDLINE database) followed by a manual search of the bibliographies of pertinent articles. Studies on the management of CHF were screened for review. Studies in older people and recent studies were emphasized. Pertinent data were extracted from the reviewed articles. Emphasis was on studies involving the older persons. Relevant articles were reviewed in depth. Available data about the management of CHF, with emphasis on studies involving older people, were summarized. Left ventricular ejection fraction (LVEF) should be measured in all older persons with CHF. Underlying causes of CHF should be treated when possible. Precipitating causes of CHF should be treated. Older persons with CHF associated with an abnormal LVEF should be treated with a low sodium diet and with diuretics plus angiotensin-converting enzyme (ACE) inhibitors. If CHF persists, digoxin should be added to the therapeutic regimen. If CHF still persists, isosorbide dinitrate plus hydralazine should be added. If CHF still persists, a beta blocker should also be used. Calcium channel blockers should not be used. Older persons with CHF associated with a normal LVEF should be treated with a low sodium diet and with diuretics plus ACE inhibitors. If CHF persists, a beta blocker or isosorbide dinitrate plus hydralazine or a calcium channel blocker should be added to the therapeutic regimen. If sinus rhythm is present, digoxin should not be used. The role of angiotensin II receptor antagonists such as losartan in the treatment of CHF is under investigation.

[Diastolic heart failure. Treatment].

Many therapeutic options are proposed for the treatment of diastolic heart failure although no consensus has been established. In experimental trials, several drugs have demonstrated a potentially beneficial effect on ventricular diastolic dysfunction and could be used for diastolic heart failure: nitrate derivatives, converting enzyme inhibitors, angiotensin II antagonists, spirolactones and bradycardia agents. CLINICAL PRACTICE: In everyday clinical practice, low-dose diuretics and treatments aimed at reducing the triggering factor leading to episodes of heart failure are used alone or in combination with treatments aimed at the underlying cause of the diastolic dysfunction: betablockers, calcium inhibitors or nitrate derivatives for ischemic heart disease, drug therapy for hypertension, anti-diabetes agents, anti-arrhythmic agents for atrial fibrillation. Digitalics are not indicated. In experimental trials, converting enzyme inhibitors and angiotensin II antagonists have demonstrated interesting properties for the left ventricle but to date are not warranted for diastolic heart failure. TREATMENT OF THE CAUSE: Due to the lack of consensus on the optimal treatment for diastolic heart failure, most clinicians rely on treating the underlying heart disease and triggering factors.

Aortic regurgitation

Medical treatment Medical therapy of chronic aortic regurgitation that is stable and asymptomatic involves the use of vasodilators. Trials have shown a short-term benefit in the use of ACE inhibitors or angiotensin II receptor antagonists, nifedipine, and hydralazine in improving left ventricular wall stress, ejection fraction, and mass. The goal in using these pharmacologic agents is to decrease the afterload so that the left ventricle is somewhat spared. The regurgitant fraction may not change significantly, since the gradient between the aortic and left ventricular pressures is usually fairly low at the initiation of treatment. Other rather conservative medical treatments for stable and asymptomatic cases include low sodium diet, diuretics, digoxin, calcium blockers and avoiding very strenuous activity.

[Drug treatment for chronic heart failure with reduced ejection fraction].

Based on multiple randomized controlled trials performed in the last 20 years, drugs form the basis of treatment for heart failure with reduced ejection fraction (HFREF). Despite solid evidence for their efficacy and safety and publication of detailed national and international guidelines many patients with HFREF remain, who are not at all or only insufficiently treated. Treatment goals include reduction of mortality and hospitalizations, improvement of symptoms and exercise tolerance as well as prevention of disease progression. ACE-inhibitors and beta-adrenergic receptor blockers exert beneficial effects on all treatment goals and are therefore indicated in all patients with HFREF if tolerated. Diuretics allow control of fluid retention and maintenance of "euvolemia". Low-dose spironolactone can be considered in persistent moderate to severe (NYHA 3 - 4) HFREF despite treatment. Angiotensin receptor blockers are indicated for ACE-inhibitor intolerance or in addition to ACE-inhibitors and beta-adrenergic receptor blockers in case of persistent symptoms. Triple combination of ACE-inhibitors, angiotensin receptor blockers and aldosterone antagonists should be avoided in view of the substantial risk of hyperkalemia. In current praxis digoxin is mainly used as an adjunctive agent for rate control of atrial fibrillation in combination with beta-adrenergic receptor blockers. Titration and maintenance of heart failure treatment requires continuous control of clinical parameters, renal function and electrolytes. It is recommended to use drugs and dosest hat have been shown to be effective in clinial trials. Despite the fact that heart failure is mainly a disease of the elderly, this population is underrepresented in clinical trials. The risk of side effects and drug-drug interactions is increased in elderly patients because of physiologic changes with age and frequent comorbidities with resultant polypharmacy.

Heart failure

Treatment depends on the severity and cause of the disease. In people with chronic stable mild heart failure, treatment commonly consists of lifestyle modifications such as stopping smoking, physical exercise, and dietary changes, as well as medications. In those with heart failure due to left ventricular dysfunction, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or valsartan/sacubitril along with beta blockers are recommended. For those with severe disease, aldosterone antagonists, or hydralazine with a nitrate may be used. Diuretics are useful for preventing fluid retention and the resulting shortness of breath. Sometimes, depending on the cause, an implanted device such as a pacemaker or an implantable cardiac defibrillator may be recommended. In some moderate or severe cases, cardiac resynchronization therapy (CRT) or cardiac contractility modulation may be of benefit. A ventricular assist device (for the left, right, or both ventricles), or

Amiloride

Amiloride may be used in combination with a thiazide diuretic for treatment of high blood pressure or (less commonly) in combination with a loop diuretic for treatment of heart failure. The potassium-sparing effects of amiloride offset the low blood potassium (hypokalemia) that is often induced by thiazides or loop diuretics, which is of particular importance in people for whom maintaining a normal level of potassium is critically important. For example, people that are taking Digitalis (i.e. digoxin) are at higher risk for changes in heart rhythm if their potassium levels get too high. The 2017 clinical practice guidelines of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines list amiloride as a "secondary" oral antihypertensive, with minimal efficacy. For people with resistant hypertension, already taking a thiazide diuretic, an angiotensin converting enzyme inhibitor (ACE-i) or an angiotensin II receptor blocker (ARB), and a

Antihypertensive drug

However, ACE inhibitors (and angiotensin II receptor antagonists) should not be a first-line treatment for black hypertensives without chronic kidney disease. Results from the ALLHAT trial showed that thiazide-type diuretics and calcium channel blockers were both more effective as monotherapy in improving cardiovascular outcomes compared to ACE inhibitors for this subgroup. Furthermore, ACE inhibitors were less effective in reducing blood pressure and had a 51% higher risk of stroke in black hypertensives when used as initial therapy compared to a calcium channel blocker. There are fixed-dose combination drugs, such as ACE inhibitor and thiazide combinations. Notable side effects of ACE inhibitors include dry cough, high blood levels of potassium, fatigue, dizziness, headaches, loss of taste and a risk for angioedema. Angiotensin II receptor antagonists

Pharmacologic therapy Indications Management of HFpEF is primarily dependent on the treatment of symptoms and exacerbating conditions. The role of specific treatments for diastolic dysfunction per se is as yet unclear. Benefit Currently treatment with ACE inhibitors, calcium channel blockers, beta blockers, and angiotensin receptor blockers are employed but do not have a proven benefit in HFpEF patients. Additionally, use of diuretics or other therapies that can alter loading conditions or blood pressure should be used with caution. It is not recommended that patients be treated with phosphodiesterase-5-inhibitors or digoxin. Agents

Antihypertensive drug

Sodium nitroprusside, a very potent, short-acting vasodilator, is most commonly used for the quick, temporary reduction of blood pressure in emergencies (such as malignant hypertension or aortic dissection). Hydralazine and its derivatives are also used in the treatment of severe hypertension, although they should be avoided in emergencies. They are no longer indicated as first-line therapy for high blood pressure due to side effects and safety concerns, but hydralazine remains a drug of choice in gestational hypertension. Renin inhibitors Renin comes one level higher than angiotensin converting enzyme (ACE) in the renin–angiotensin system. Renin inhibitors can therefore effectively reduce hypertension. Aliskiren (developed by Novartis) is a renin inhibitor which has been approved by the U.S. FDA for the treatment of hypertension. Aldosterone receptor antagonist Aldosterone receptor antagonists: eplerenone spironolactone

First-dose phenomenon

The cause is not clear. It occurs more commonly in patients who are salt and fluid volume depleted (as happens due to the use of diuretics), or were using beta blockers. Diuretics and beta blockers are frequently used to control hypertension. For this reason, treatment with prazosin (Minipress) should always be initiated with a low dose and should be taken at bedtime to avoid standing position. Other drug classes with observed first dose hypotension This effect is also observed after the administration of the first dose of drugs in the ACEi class (angiotensin-converting enzyme inhibitor). This may occur with the class's better known side effect of dry cough (due to decreased breakdown of bradykinin), though there is no clear relationship between the two side effects. The first dose phenomenon in ACEi is reduced and made safer by avoiding diuretics for 24 hours prior to first dose, taking first dose at night (so avoiding falls, etc) and starting on low doses and titrating upwards.

Management of hypertension

The best first-line medication is disputed, but the Cochrane collaboration, World Health Organization, and US guidelines support low-dose thiazide-based diuretic as first-line treatment. The UK guidelines emphasise calcium channel blockers (CCB) in preference for people over the age of 55 years or people of African or Caribbean descent, with angiotensin-converting enzyme inhibitors (ACE-I) used as a first line for younger people. In Japan, starting with any one of six classes of medications, including CCB, ACEI/ARB, thiazide diuretics, beta-blockers, and alpha-blockers, is deemed reasonable, while in Canada and Europe all of these except alpha-blockers are recommended as options. Compared to placebo, beta-blockers have a greater benefit in stroke reduction, but no difference on coronary heart disease or all-cause mortality. However, three-quarters of active beta-blocker treatments in the randomised controlled trials included in the review used atenolol, and none used the newer

Management of hypertension

Unacceptable combinations are non-dihydropyridine calcium blockers (such as verapamil or diltiazem) and beta-blockers, dual renin–angiotensin system blockade (e.g., angiotensin converting enzyme inhibitor + angiotensin receptor blocker), renin–angiotensin system blockers and beta-blockers, and beta-blockers and centrally acting medications. Combinations of an ACE-inhibitor or angiotensin II–receptor antagonist, a diuretic, and an NSAID (including selective COX-2 inhibitors and non-prescribed medications such as ibuprofen) should be avoided whenever possible due to a high documented risk of acute kidney failure. The combination is known colloquially as a "triple whammy" in the Australian health industry. Tablets containing fixed combinations of two classes of medications are available and, while convenient, may be best reserved for those who have been established on the individual components. Additionally, the use of treatments with vasoactive agents for people with pulmonary

Angiotensin II receptor blocker

Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals that bind to and inhibit the angiotensin II receptor type 1 (AT1) and thereby block the arteriolar contraction and sodium retention effects of renin–angiotensin system. Their main uses are in the treatment of hypertension (high blood pressure), diabetic nephropathy (kidney damage due to diabetes) and congestive heart failure. They selectively block the activation of the AT1 receptor, preventing the binding of angiotensin II compared to ACE inhibitors. ARBs and the similar-attributed ACE inhibitors are both indicated as the first-line antihypertensives in patients developing hypertension along with left-sided heart failure. However, ARBs appear to produce less adverse effects compared to ACE inhibitors.

Heart failure

Vasopressin receptor antagonists can also be used to treat heart failure. Conivaptan is the first medication approved by US Food and Drug Administration for the treatment of euvolemic hyponatremia in those with heart failure. In rare cases hypertonic 3% saline together with diuretics may be used to correct hyponatremia. Ivabradine is recommended for people with symptomatic heart failure with reduced left ventricular ejection fraction who are receiving optimized guideline-directed therapy (as above) including the maximum tolerated dose of beta-blocker, have a normal heart rhythm and continue to have a resting heart rate above 70 beats per minute. Ivabradine has been found to reduce the risk of hospitalization for heart failure exacerbations in this subgroup of people with heart failure.

Hypertension

Medications Several classes of medications, collectively referred to as antihypertensive medications, are available for treating hypertension. First-line medications for hypertension include thiazide-diuretics, calcium channel blockers, angiotensin converting enzyme inhibitors (ACE inhibitors), and angiotensin receptor blockers (ARBs). These medications may be used alone or in combination (ACE inhibitors and ARBs are not recommended for use in combination); the latter option may serve to minimize counter-regulatory mechanisms that act to restore blood pressure values to pre-treatment levels. Most people require more than one medication to control their hypertension. Medications for blood pressure control should be implemented by a stepped care approach when target levels are not reached.

Angiotensin II receptor blockers (ARBs) ARB treatment results in an improvement in diastolic dysfunction and hypertension that is comparable to other anti-hypertensive medication. Diuretics Diuretics can be useful if significant congestion develops, but patients must be monitored because they frequently develop low blood pressure. Experimental The use of a self-expanding device that attaches to the external surface of the left ventricle has been suggested, yet still awaits FDA approval. When the heart muscle squeezes, energy is loaded into the device, which absorbs the energy and releases it to the left ventricle in the diastolic phase. This helps retain muscle elasticity.

Alpha blocker

Contraindications There is only one compelling indication for alpha blockers, which is for benign prostatic hyperplasia. Patients who need alpha blockers for BPH, but have a history of hypotension or postural heart failure, should use these drugs with caution, as it may result in an even greater decrease in blood pressure or make heart failure even worse. The most compelling contraindication is urinary incontinence and overall fluid retention. To combat such fluid retention, patients can take a diuretic in combination with the alpha-blocker. In the absence of compelling indications or contraindications, patients should take alpha blockers as a step 4 therapy to reduce blood pressure, but only if the use of ACE inhibitors, angiotensin-II receptor blockers, calcium channel blockers, or thazide diuretics (in full dose or in combinations) have not been efficacious.

Thiazide

Clinical practice guidelines regarding the use of thiazides vary by geographic region. Guidelines in the United States recommend thiazides as a first-line treatment for hypertension (JNC VIII). A systematic review by the Cochrane Collaboration specifically recommended that low-dose thiazides be used as the initial pharmacological therapy for high blood pressure. Low-dose thiazides are more effective at treating hypertension than beta blockers and are similar to angiotensin-converting enzyme (ACE) inhibitors. Thiazides are a recommended treatment for hypertension in Europe (ESC/ESH). However, the UK National Institute for Health and Clinical Excellence recommends ACE inhibitor and calcium channel blockers for first-line treatment of hypertension in adults (CG127). Thiazides should be considered as initial treatment if the patient has a high risk of developing heart failure. Thiazides have also been replaced by ACE inhibitors in Australia due to the association between thaizide use

[Changes in medical treatment of heart failure in the light of large clinical trials].

In the last years, the treatment of heart failure has radically changed, as has knowledge of this complex and heterogeneous clinical syndrome. This is largely due to the results of several multicenter clinical trials, which have been undertaken since the late 80's. These trials have not only contributed to the elaboration of present-day treatment protocols, but also to a better understanding of the pathophysiologic mechanisms involved in heart failure. In the past, heart failure was generally interpreted on the basis of pathophysiologic models according to which hemodynamic abnormalities played a very important role in determining the clinical presentation and evolution of the disease. This led to the use of digitalis, diuretics, inotropic drugs and vasodilators for the treatment of heart failure. More recently, improved knowledge of the pathophysiologic mechanisms involved in the progression of this disease has highlighted the central role and the complexity of various neurohormonal mechanisms. Antagonism of these systems has proved to be the only strategy which favorably modifies the natural history of heart failure. The proved effectiveness of ACE-inhibitors and particularly of beta-blockers in patients with heart failure and left ventricular systolic dysfunction was the most convincing demonstration of the validity of this model. However, the evolution and updating of the guidelines on the treatment of heart failure should only be considered as the first step in the development of strategies aimed at extending these principles to daily clinical practice and in particular to the real patient who is different from patients typically enrolled in heart failure trials. Moreover, the development of new effective models for the management of the ever-growing number of patients with heart failure is of utmost urgency.

Antihypertensive drug

If lifestyle changes are ineffective, then drug therapy is initiated, often requiring more than one agent to effectively lower hypertension. Which type of many medications should be used initially for hypertension has been the subject of several large studies and various national guidelines. Considerations include factors such as age, race, and other medical conditions. In the United States, JNC8 (2014) recommends any drug from one of the four following classes to be a good choice as either initial therapy or as an add-on treatment: thiazide-type diuretics, calcium channel blockers, ACE inhibitors, or angiotensin II receptor antagonists.

ACE inhibitor and thiazide combination

An ACE inhibitor and thiazide combination is a drug combination used to treat hypertension (high blood pressure). They are given by mouth. ACE inhibitors reduce the activity of angiotensin-converting enzyme (ACE) which produces angiotensin II, a hormone that constricts blood vessels. Thiazides are a class of diuretics that inhibit the thiazide receptor, thereby increasing urine production and reducing excess water and salt in the body. Several organizations recommend combination therapy for hypertension in cases of failure of a single drug to achieve target blood pressure, or even as a first line treatment for some patients. Examples Enalapril/hydrochlorothiazide (trade name Enalapril comp), wherein enalapril is the ACE inhibitor and hydrochlorothiazide is the thiazide. Quinapril/hydrochlorothiazide (trade name Accuretic) Lisinopril/hydrochlorothiazide is marketed as Prinzide, Zestoretic, and many others. Fosinopril/hydrochlorothiazide

Candesartan

Candesartan is an angiotensin receptor blocker used mainly for the treatment of high blood pressure and congestive heart failure. Candesartan has a very low maintenance dose. The metabolism for the drug is unique as it is a cascading pro-drug. Candesartan has good bioavailibility and is more potent among the AT-1 receptor antagonists. It was patented in 1990 and approved for medical use in 1997. Medical uses Hypertension As with other angiotensin II receptor antagonists, candesartan is indicated for the treatment of hypertension. Candesartan has an additive hypertensive effect when combined with a diuretic, such as chlorthalidone. It is available in a fixed-combination formulation with a low dose of the thiazide diuretic hydrochlorothiazide. Candesartan/hydrochlorothiazide combination preparations are marketed under various trade names including Atacand Plus, Hytacand, Blopress Plus, Advantec and Ratacand Plus.