Doença De Lesão Mínima Flashcards
Doença de lesão mínima é mais comum em……
Achado laboratorial na glomerulonefrite por lesão mínima:
Quando deve ser feita a Bx renal em crianças com doença de lesão mínima?
Tto da glomerunefrite por lesão mínima:
lesao minima
the classical cause of the nephrotic syndrome in pediatric populations where it accounts for 90% of cases, accounts for only 10% of cases in adults.
The majority of cases are primary (idiopathic), although an appreciable number may be secondary to another process including; drugs, allergy, malignancy, and infection.
lesao minima
causas secundarias
non-steroidal anti-inflammatory (NSAIDs), antibiotics, lithium, d-penicillamine and pamidronate.
• Malignancies that may cause MCD are usually hematological, such as Hodgkin or non-Hodgkin lymphoma.
They are usually apparent at the time of the MCD diagnosis.
• A history of allergy may be noted in up to 30% of cases, and relapses may be triggered by an allergic reaction. •
MCD may rarely be associated with infectious etiologies such as syphilis, mycoplasma and tuberculosis.
Infections: Tuberculosis, syphilis, mycoplasma, ehrlichiosis, hepatitis C virus
Neoplasms: Hematologic malignancies, including leukemia, Hodgkin and non-Hodgkin lymphoma
Allergy: Bee and medusa stings, cat fur, fungi, poison ivy, ragweed pollen, house dust
Drugs: NSAIDs, lithium, antibiotics (ampicillin, cephalosporins), immunizations, and gamma interferon
Other glomerular diseases: Associated with IgA nephropathy, SLE, type 1 DM, and HIV
lesoes minimas
clinica
“nil disease” or “lipoid nephrosis.
: MCD is usually characterized by the abrupt onset of the nephrotic syndrome over a few days to a week,
The nephrotic syndrome itself is characterized by nephrotic range proteinuria (>3.5 g/day), edema, hypoalbuminemia and hyperlipidemia.
This relatively sudden onset is in contrast to the other major causes of nephrotic syndrome – membranous nephropathy and FSGS which are typically more subacute (with the notable exception of the glomerular tip variant of FSGS).
Patients may also have microscopic hematuria and can have a mild decrease in kidney function.
doenca lesoes minimas
FISIOPATOLOGIA
nephrotic syndrome characterized by an increased renal membrane permeability and loss of protein (primarily albumin) due to damage to the glomerular filtration barrier (GFB).
The GFB is composed of fenestrated endothelium (inner layer), the glomerular basement membrane (middle layer), and an outer epithelial layer composed of podocytes.
Podocytes are epithelial cells with large cell bodies and long foot processes that run parallel along the outside of glomerular capillaries. The space between foot processes is interspersed by cell-to-cell junctions called slit diaphragms.
Glomerular filtration is both size-specific and charge-specific. The actin cytoskeleton of podocytes provides support to the GBM and regulates flow across the basement membrane depending on hydrostatic pressures, molecular size, and molecular charge.
The apical and luminal membrane of the slit diaphragms and podocytes are coated with a sialoglycoprotein (podocalyxin) which contributes to repels negatively charged molecules such as albumin. The two outer layers of the glomerular basement membrane are composed of heparin sulfate proteoglycans that are also negatively charged and contribute to the charge selectivity of the barrier. Disruption of this barrier leads to the proteinuria seen in nephrotic syndrome.
The pathogenesis of MCD is not exactly known, but it is thought to be multifactorial. Several studies have focused on the integrity and biology of podocytes.
Because the actin cytoskeleton of podocytes maintains the integrity of the podocytes by supporting the cell body and foot processes, regulation of flow across the basement membrane is controlled by a series of interactions.
Some of the proposed theories published include T cell dysfunction/dysregulation that leads to cytokine release and upregulation of proteins, such as CD80 and C-mip that affects the integrity of podocytes, systemic circulating factors that disrupt podocyte function, and B- cell activation (suspected due to the efficacy of anti- CD-20 monoclonal antibodies, such as rituximab).
lesoes minimas
exame fisico
Patients with MCD commonly present with periorbital, scrotum, labia, and/or lower extremity edema. On exam, patients may demonstrate anasarca, pericardial or pleural effusion, ascites, and abdominal pain. An affected individual is an intravascularly volume depleted and maybe oliguric, which can lead to acute kidney injury, a finding most frequently noted in adults.
Children often present with severe infections (sepsis, pneumonia, and peritonitis) due to the depletion of immunoglobulin.
Minimal change disease in adults presents with hematuria, acute kidney injury, and hypertension
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quando biopsiar? crianca
In children, MCD is primarily a clinical diagnosis, and biopsy is only required in the presence of atypical clinical features:
Age of onset before 1 or after12 years old
Gross hematuria
Low serum C3
Marked Hypertension
Elevated creatinine
Renal failure without hypovolemia
Positive history or serology for secondary causes
Steroid resistance[2]
A successful response to steroids might be anticipated in children how to present with typical clinical findings of MCD and are:
Age 1-12 years old
Normotensive
Normal Renal Function
+/- Microscopic hematuria
dlm
avaliacao
Nephrotic syndrome is associated with heavy proteinuria, hypoalbuminemia, peripheral edema, hyperlipidemia, and thrombotic disease.
The fluid status in patients with nephrotic syndrome alternates between hypovolemia and hypervolemia.
Hypovolemic patients may be referred to as “underfilled” due to the loss of albumin through proteinuria. Hypoalbuminemia leads to decreased oncotic pressure and fluid sequestration in the interstitial space. Hypoalbuminemia and low oncotic pressure induce reflexes through the juxtaglomerular apparatus to compensate for intravascular fluid losses by increasing sodium absorption and water retention. Patients with MCD are commonly hypovolemic (underfilled).
Hypervolemia (overfill) associated with nephrotic syndrome is due to tubular dysregulation, which increases sodium absorption and water retention. In these patients, hypoalbuminemia and decreased oncotic pressure are not the cause of edema. Therefore, it is important to understand each patient’s volume status before initiating therapy that addresses edema.
In children, MCD is the most common cause of idiopathic nephrotic syndrome. Minimal change disease is the third most common cause of idiopathic nephrotic syndrome in adults after focal segmental glomerular sclerosis and membranous nephropathy. An early kidney biopsy is crucial to making the diagnosis of MCD in adults.[1]
doença lesao minima
dlm no lupus
LES em atividade, e que se apresentam com proteinúria nefrótica, e por vezes sub-nefrótica, sem hematúria e sem hipertensão e que a biópsia renal mostra MO normal e ME com fusão podocitária (padrão de lesões mínimas), ou mesmo glomeruloesclerose segmentar e focal. Em nosso serviço, nos últimos três anos, já temos pelo menos 10 pacientes com LES e esse diagnóstico, confirmado por biópsia renal, com IF negativa e microscopia eletrônica característica de glomerulopatia podocitária.
O diagnóstico diferencial é muito importante, tendo em vista a diferença na resposta terapêutica entre essa entidade e a nefrite lúpica classes IV e V. A podocitopatia associada ao lúpus em geral responde muito bem a corticoterapia e não necessita de outros esquemas de imunossupressão. Sendo assim, é fundamental que os nefrologistas reconheçam essa possibilidade diagnóstica e realizem biópsia dos pacientes lúpicos com síndrome nefrótica, já que não existe um dado clínico que consiga diferenciar com clareza entre as lesões histológicas possíveis.
lab para excluir causa secundaria
Antinuclear antibodies
Hepatitis B and C serologic tests
Serologic test for syphilis (e.g., rapid plasma reagin)
HIV antibody test
Complement levels (CH50, C3, C4)
lab basico
Urinalysis/ Urine microscopy: Dipstick will show 3+/4+ proteinuria. A urine dipstick and urinalysis (UA) are often the initial tests obtained to screen for MCD. In MCD, the urine typically looks frothy secondary to proteinuria, and the microscopy shows oval fat bodies and fatty casts.
Dysmorphic RBCs, acanthocytes, abnormal casts, and proteinuria are findings suggestive of glomerular injury not frequently seen in MCD.
False-positive test results are noted in the presence of mucus, blood, pus, alkalinity, or concentration.A 24-hour urine collection is required to quantitate urinary protein.
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. Microscopic hematuria is present in 10% to 30% of adults.
Complete metabolic panel (CMP): CMP demonstrates a low total protein, low albumin (frequently <2.5 g/dl), and low total calcium (ionized calcium binds to albumin, and albumin is low).
Complete blood count (CBC): CBC will show hemoconcentration and thrombocytosis. This is seen due to the intravascular volume contraction from fluid sequestration into the interstitial space.
Total cholesterol and triglyceride levels: These are increased due to an increase in hepatic lipoprotein synthesis as a result of low oncotic pressures
tratamento dlm
CORTICOIDE
. Children frequently achieve remission with steroids within 4 weeks vs. adults who achieve remission in two months or more
. The incidence of relapse is high in children and adults.
Children
Initial prednisone therapy is 60 mg/m2(or 2 mg/kg) administered daily for 4-6 weeks (maximum dose, 60 mg/day), or 40 mg/m2/(or 1.5 mg/kg) on alternate days for 2-5 months taper. Reduce the dose by 5 mg/m2 to 10 mg/m2 each week for another four weeks, then stop, with a minimum duration of 12 weeks [14].
Adults
Initial prednisone treatment is 1mg/kg per day or 2 mg/kg/kg every other day (max 80mg/day or 120 mg every other day) for 4-16 weeks. Taper slowly over a course of 6 months after remission
• Prednisolone at a dose of 1 mg/kg (to a maximum of 80 mg) is given daily. This dose is usually continued for eight weeks. For those who have not responded by eight weeks, prednisolone tapering is commenced two weeks after the attainment of remission. • Tapering then occurs slowly, with a total duration of therapy being approximately six months.
Pacientes que relapsam
Steroid resistance is noted as the persistence of proteinuria in children after 4 weeks of prednisone and after 16 weeks for adults.
Frequent relapses occur, which are defined as two or more relapses in the first six months of presentation or four or more relapses within any 12 months
Relapse is not uncommon, with around 50 to 75% of glucocorticoid responsive patients suffering from a relapse at some point in their disease. Frequent relapses occur in up to 25%. Dependence on steroids to maintain a remission may be seen in up to 30%. Relapses may be triggered by allergic reactions or infections. They typically occur within a year of discontinuation of therapy, but can occur multiple years later.
Steroid dependency is defined as relapses that occur during the tapering phase of steroid therapy or less than two weeks after discontinuing steroids
Relapse nephrosis - > 2+ proteinuria on 3 consecutive days
Prednisolone should be restarted if there is a relapse: 2 mg/kg daily (maximum 60 mg) until in remission for 3 days, then 1.5 mg/kg alternate days for 4 weeks, then stop or taper the dose over 4-8 weeks
