Nephrotic Syndrome

Definition
Nephrotic syndrome (NS) is an abnormal condition that is marked by a deficiency of
albumin in the blood and its excretion in the urine due to altered permeability of the
glomerular basement membranes.
Epidemiology
About two in every 10,000 people experience nephrotic syndrome. The prevalence is diffi
cult to establish in adults because the condition is usually a result of an underlying disease.
Nephrotic syndrome may occur at any age but is more prevalent in children than in adults. In
children, it is most common between the ages 1.5 and 4 years, and aff ects more males than
females.
Etiology
NS can occur with many diseases, such as primary glomerular disease. A number of diff erent
diseases can result in glomerular dysfunction, including many conditions with a variety of
genetic and environmental causes. It may be the direct result of a sclerotic disease such as
focal segmental glomerulosclerosis (FSGS) or diabetic nephropathy, or of an infection/drug
toxic to the kidneys. It also may result from autoimmune diseases such as IgA nephropathy
or systemic lupus erythematosus (SLE). Many diff erent kinds of diseases can cause swelling
or scarring of the glomerulus. Diabetic nephropathy is the leading cause of glomerular
disease and of chronic kidney disease in the United States, followed by membranous
nephropathy, the second most common cause of nephrotic syndrome.
Pathophysiology
As stated above, nephrotic syndrome is one of several conditions that are associated with
damage to the glomerulus. Previously in the review of anatomy and physiology, it was
discussed that the role of the glomerulus is to receive systemic blood flow for the initiation of
filtration. Nephrotic syndrome is characterized by proteinuria (urinary protein levels greater
than 3.5 g per 1.73 m2 of body surface area per day), hyperlipidemia, and hypoalbuminemia
<3.5 g/dL with edema. Proteinuria is thought to occur through a functional derangement in
the glomerular barrier that allows larger molecular weight proteins and sometimes red blood
cells to leak into the urine. Superficially, NS is like kwashiorkor or protein-energy
malnutrition. In both NS and kwashiorkor, albumin levels are low, plasma volume is
expanded, and albumin pools shift from the extravascular space to the vascular space. Muscle
wasting is common in those patients with massive and continual proteinuria and can often be
masked by edema.
An early sign of NS is frothy urine; this is primarily due to proteinuria. Other symptoms
include anorexia, malaise, puffy eyelids, abdominal pain, and muscle wasting. Anasarca with
ascites and pleural effusions may occur.
Depending on the degree of angiotensin II production, adults may have low, normal, or
elevated blood pressure. Oliguria or acute renal failure may develop because of hypovolemia

(a decrease in the volume of the circulating blood) and diminished renal perfusion.
Orthostatic hypotension and even shock can be seen in pediatric patients.
Protein losses in adults with NS average about 6 to 8 grams per day. Albumin is the principal
protein lost in urine, accounting for between 75% and 90% of urinary protein. Micronutrients
lost in the urine include those bound to plasma proteins such as zinc, copper, vitamin D, and
iron.
Hypoalbuminemia is common in NS due to an inadequate rate of hepatic albumin synthesis
in other words, the synthesis cannot compensate for the excessive urinary protein losses. In
adults, serum albumin levels may be less than 2 g/dL.
Edema is another hallmark of NS. Two mechanisms have been proposed. Th e first is the
classic explanation, also known as the underfi ll model. A decrease in plasma albumin leads
to a decrease in difference between interstitial and plasma oncotic pressure and thus plasma
volume contraction. Edema occurs when the amount of fluid flowing into the interstitium
exceeds maximal lymph fl ow. Th e second explanation suggests that renal disease creates
primary sodium and water retention, leading to plasma volume expansion and increased
capillary hydrostatic pressure. Focal edema may present as difficulty breathing (pleural
effusion or laryngeal edema), substernal chest pain (pericardial effusion), scrotal swelling,
swollen knees, and ascites. In children, signs of abdominal pain may be common due to
edema of the mesentery. Most often, the edema is mobile (e.g., detected in the eyelids in the
morning and in the ankles after ambulation).
Nephrotic syndrome has also been associated with increased risk of atherosclerosis. This is
most likely due to altered lipid metabolism that is characterized by high levels of serum
cholesterol and triglycerides, increased low-density lipoprotein (LDL), and either normal or
low levels of high-density lipoprotein (HDL). The reduction of lipoprotein lipase, an enzyme
responsible for lipoprotein metabolism, is thought to be the reason for reduced clearance of
these lipids. Atherogenic lipoprotein and fibrinogen levels are also increased due to increased
hepatic synthesis, which raises cardiovascular risk in NS. Animal studies strongly suggest
that hyperlipidemia alone can impair renal function, and that reducing lipid levels can slow
down the progression of renal injury. Although clinical studies are less conclusive, evidence
suggests that this is also true in humans.
Treatment
Medical treatment of nephrotic syndrome focuses on identifying and treating the underlying
cause, if possible, and on reducing high cholesterol, blood pressure, and protein in the urine
through a protein-controlled diet, the use of angiotensinconverting enzyme (ACE) inhibitors,
or both. In diabetic patients with microalbuminuria, research has found that the use of ACE
therapy reduces proteinuria and slows down the progression of chronic kidney disease. As
renal disease progresses, nephrons are destroyed, and the remaining healthy nephrons must
compensate (hyperfi ltration) in order to maintain the bodys homeostasis. In addition, the
remaining nephrons GFR increase via dilation of the glomerular afferent arteriole. Th is

results in secondary injury to the glomerulus, increased proteinuria, and ultimately

destruction of the nephron. ACE inhibitor and angiotensin receptor blockers (ARBs) therapy,
including combination therapy, has been shown to reduce proteinuria in patients with diabetic
nephropathy and in those with idiopathic nephritic syndrome. Proteinuria may also be
decreased by lowering the patients mean arterial pressure to levels below 92 mm Hg,
independent of the class of antihypertensives used.75 Potassium levels should be checked in
those with moderate to severe renal dysfunction, because ACE inhibitors may exacerbate
hyperkalemia.
To minimize accelerated atherosclerosis, hyperlipidemia should be managed with HMG-CoA
reductase inhibitors or agents such as gemfi brozil in order to lower triglycerides and LDL
levels. These types of drugs should not be used at the same time due to the increased risk of
rhabdomyolysis.
Tekanan Onkotik plasma adalah tekanan osmotik yang ditimbulkan oleh larutan koloid
protein plasma. walaupun nilainya kecil (1,4msOsm/L (tekanan osmotik koloid plasma)
Tekanan Onkotik plasma adalah tekanan osmotik yang ditimbulkan oleh larutan koloid
protein plasma. Walaupun nilainya kecil (1,4msOsm/L atau kira-kira sama dnegan 25mmHg),
tekanan onkotik ini sangat penting dalam menjaga keseimbangan air antara cairan interstitial
dan cairan intravaskular
Protein-protein plasma, albumin dan globulin menentukan tinggi tekanan osmotik koloid
plasma (disebut juga tekanan onkotik).
Fungsi penting albumin:
- Alat pengikat dan transport
Salah satu yang membedakan albumin dengan koloid dan kristaloid adalah
kemampuan mengikat. Albumin berfungsi penting sebagai pengikat asam, basa dan
netral juga berfungsi penting sebagai transport lemak dan zat yang larut dalam lemak.
- Memelihara tekanan osmotik koloid plasma
Albumin bertanggungjawab untuk memelihara 75%-80% tekanan onkotik plasma. Penurunan
albumin plasma akan menurunkan 66% tekanan onkotik koloid. Dalam hal ini gradien
tekanan osmotik koloid lebih berperan penting daripada kadar absolutnya dalam plasma. Hal
ini akan membedakan hipoalbuminemia akibat kebocoran plasma dan hipoalbuminemia
akibat
defisiensi
albumin
dalam tubuh
Sindrom nefrotik
Nephrotic syndrome (NS) is an abnormal condition that is marked by a deficiency of
albumin in the blood and its excretion in the urine due to altered permeability of the
glomerular basement membranes.

Definisi
Sindrom nefrotik (NS) adalah kondisi abnormal yang ditandai dengan kekurangan albumin
dalam darah dan ekskresi albumin dalam urin karena perubahan permeabilitas dari membran
dasar glomerulus.
Epidemiology
About two in every 10,000 people experience nephrotic syndrome. The prevalence is diffi
cult to establish in adults because the condition is usually a result of an underlying disease.
Nephrotic syndrome may occur at any age but is more prevalent in children than in adults. In
children, it is most common between the ages 1.5 and 4 years, and aff ects more males than
females.
Epidemiologi
Sekitar dua di setiap 10.000 orang mengalami sindrom nefrotik. Prevalensi sulit terjadi pada
orang dewasa karena kondisi ini biasanya akibat dari penyakit yang mendasari. Sindrom
nefrotik dapat terjadi pada semua usia tetapi lebih umum pada anak-anak dibandingkan pada
orang dewasa. Pada anak-anak, adalah yang paling umum antara usia 1,5 dan 4 tahun, dan
lebih berpengaruh pada laki-laki daripada perempuan.
Etiology
NS can occur with many diseases, such as primary glomerular disease. A number of diff erent
diseases can result in glomerular dysfunction, including many conditions with a variety of
genetic and environmental causes. It may be the direct result of a sclerotic disease such as
focal segmental glomerulosclerosis (FSGS) or diabetic nephropathy, or of an infection/drug
toxic to the kidneys. It also may result from autoimmune diseases such as IgA nephropathy
or systemic lupus erythematosus (SLE). Many diff erent kinds of diseases can cause swelling
or scarring of the glomerulus. Diabetic nephropathy is the leading cause of glomerular
disease and of chronic kidney disease in the United States, followed by membranous
nephropathy, the second most common cause of nephrotic syndrome.
Etiologi
NS dapat terjadi karena berbagai penyakit, seperti penyakit glomerular primer. Sejumlah
penyakit yang berbeda dapat mengakibatkan disfungsi glomerulus, termasuk berbagai kondisi
dengan berbagai penyebab genetik dan lingkungan. Ini mungkin akibat langsung dari
penyakit sklerotik seperti focal segmental glomerulosklerosis (FSGS) atau nefropati
diabetik, atau infeksi / obat beracun ke ginjal. Hal ini juga hasil dari penyakit autoimun
seperti IgA nefropati atau lupus eritematosus sistemik (SLE). Berbagai macam penyakit
dapat menyebabkan pembengkakan atau jaringan parut dari glomerulus. Nefropati diabetik
adalah penyebab utama penyakit glomerulus dan penyakit ginjal kronis di Amerika
Serikat, diikuti oleh nefropati membranosa, penyebab paling umum kedua sindrom
nefrotik.

Pathophysiology
As stated above, nephrotic syndrome is one of several conditions that are associated with
damage to the glomerulus. Previously in the review of anatomy and physiology, it was
discussed that the role of the glomerulus is to receive systemic blood flow for the initiation of
filtration. Nephrotic syndrome is characterized by proteinuria (urinary protein levels greater
than 3.5 g per 1.73 m2 of body surface area per day), hyperlipidemia, and hypoalbuminemia
<3.5 g/dL with edema. Proteinuria is thought to occur through a functional derangement in
the glomerular barrier that allows larger molecular weight proteins and sometimes red blood
cells to leak into the urine. Superficially, NS is like kwashiorkor or protein-energy
malnutrition. In both NS and kwashiorkor, albumin levels are low, plasma volume is
expanded, and albumin pools shift from the extravascular space to the vascular space. Muscle
wasting is common in those patients with massive and continual proteinuria and can often be
masked by edema.
Patofisiologi
Sebagaimana dinyatakan di atas, sindrom nefrotik adalah salah satu dari beberapa kondisi
yang berhubungan dengan kerusakan glomerulus. Sebelumnya dalam review anatomi dan
fisiologi, hal ini dibahas bahwa peran glomerulus adalah untuk menerima aliran darah
sistemik untuk inisiasi penyaringan. Sindrom nefrotik ditandai oleh proteinuria (tingkat
protein urin lebih besar dari 3,5 g per 1,73 m2 luas permukaan tubuh per hari),
hiperlipidemia, dan hipoalbuminemia <3,5 g / dL dengan edema. Proteinuria diduga terjadi
gangguan fungsional dalam membran glomerular yang memungkinkan protein berat molekul
yang lebih besar dan tekadang sel darah merah untuk masuk ke dalam urin. Sederhananya,
NS seperti kwashiorkor atau protein-energi malnutrisi. NS dan kwashiorkor, memiliki tingkat
albumin yang rendah, volume plasma diperluas, dan albumin bergeser dari ruang
ekstravaskuler ke ruang vaskuler. Pengecilan otot umum pada pasien yang dalam jumlah
besar dan terus-menerus terjadi proteinuria dan sering dapat ditutupi oleh edema.
An early sign of NS is frothy urine; this is primarily due to proteinuria. Other symptoms
include anorexia, malaise, puffy eyelids, abdominal pain, and muscle wasting. Anasarca with
ascites and pleural effusions may occur.
Depending on the degree of angiotensin II production, adults may have low, normal, or
elevated blood pressure. Oliguria or acute renal failure may develop because of hypovolemia
(a decrease in the volume of the circulating blood) and diminished renal perfusion.
Orthostatic hypotension and even shock can be seen in pediatric patients.
Protein losses in adults with NS average about 6 to 8 grams per day. Albumin is the principal
protein lost in urine, accounting for between 75% and 90% of urinary protein. Micronutrients
lost in the urine include those bound to plasma proteins such as zinc, copper, vitamin D, and
iron.
Hypoalbuminemia is common in NS due to an inadequate rate of hepatic albumin synthesis
in other words, the synthesis cannot compensate for the excessive urinary protein losses. In
adults, serum albumin levels may be less than 2 g/dL.

Tanda awal NS adalah urine berbusa; ini terutama disebabkan oleh proteinuria. Gejala lain
termasuk anoreksia, malaise, kelopak mata bengkak, nyeri perut, dan atrofi otot. Anasarca
dengan asites dan efusi pleura dapat terjadi.
Tergantung pada tingkat produksi angiotensin II, orang dewasa mungkin memiliki tekanan
darah rendah, normal, atau tinggi. Oliguria atau gagal ginjal akut dapat berkembang karena
hipovolemia (penurunan volume darah yang beredar) dan perfusi ginjal berkurang. Hipotensi
ortostatik dan bahkan syok dapat dilihat pada pasien anak.
Kehilangan protein pada orang dewasa dengan NS rata-rata sekitar 6 sampai 8 gram per hari.
Albumin adalah protein utama yang hilang dalam urin, terhitung antara 75% dan 90% dari
protein urin. Mikronutrien hilang dalam urin termasuk yang terikat dengan protein plasma
seperti seng, tembaga, vitamin D, dan zat besi.
Hipoalbuminemia umum di NS karena sintesis albumin hati sintesis yang tidak memadai,
dengan kata lain sintesis tidak dapat mengkompensasi kehilangan protein urin yang berlebih.
Pada orang dewasa, tingkat serum albumin mungkin kurang dari 2 g / dL.
Edema is another hallmark of NS. Two mechanisms have been proposed. Th e first is the
classic explanation, also known as the underfi ll model. A decrease in plasma albumin leads
to a decrease in difference between interstitial and plasma oncotic pressure and thus plasma
volume contraction. Edema occurs when the amount of fluid flowing into the interstitium
exceeds maximal lymph fl ow. Th e second explanation suggests that renal disease creates
primary sodium and water retention, leading to plasma volume expansion and increased
capillary hydrostatic pressure. Focal edema may present as difficulty breathing (pleural
effusion or laryngeal edema), substernal chest pain (pericardial effusion), scrotal swelling,
swollen knees, and ascites. In children, signs of abdominal pain may be common due to
edema of the mesentery. Most often, the edema is mobile (e.g., detected in the eyelids in the
morning and in the ankles after ambulation).
Edema merupakan ciri lain NS. Dua mekanisme telah diusulkan. Yang pertama adalah
penjelasan klasik, juga dikenal sebagai "underfill" model. Penurunan albumin plasma
menyebabkan penurunan perbedaan antara interstitial dan tekanan onkotik plasma sehingga
volume plasma kontraksi. Edema terjadi ketika jumlah cairan yang mengalir ke interstitium
melebihi aliran getah bening maksimal. Penjelasan kedua menunjukkan bahwa penyakit
ginjal menciptakan natrium primer dan retensi air, yang menyebabkan ekspansi volume
plasma dan peningkatan tekanan hidrostatik kapiler. Edema fokal dapat hadir sebagai
kesulitan bernapas (efusi pleura atau edema laring), nyeri dada substernal (efusi perikardial),
pembengkakan skrotum, lutut bengkak, dan ascites. Pada anak-anak, tanda-tanda dari nyeri
perut mungkin umum karena edema dari mesenterium. Paling sering, edema adalah yang
dapat berpindah dengan mudah dari satu sisi ke sisi lain (misalnya, terdeteksi di kelopak mata
di pagi hari dan di pergelangan kaki setelah ambulasi).

Nephrotic syndrome has also been associated with increased risk of atherosclerosis. This is
most likely due to altered lipid metabolism that is characterized by high levels of serum
cholesterol and triglycerides, increased low-density lipoprotein (LDL), and either normal or
low levels of high-density lipoprotein (HDL). The reduction of lipoprotein lipase, an enzyme
responsible for lipoprotein metabolism, is thought to be the reason for reduced clearance of
these lipids. Atherogenic lipoprotein and fibrinogen levels are also increased due to increased
hepatic synthesis, which raises cardiovascular risk in NS. Animal studies strongly suggest
that hyperlipidemia alone can impair renal function, and that reducing lipid levels can slow
down the progression of renal injury. Although clinical studies are less conclusive, evidence
suggests that this is also true in humans.
Sindrom nefrotik juga telah dikaitkan dengan peningkatan risiko aterosklerosis. Hal ini
kemungkinan besar karena perubahan metabolisme lipid yang ditandai oleh tingginya tingkat
kolesterol serum dan trigliserida, meningkatkan low-density lipoprotein (LDL), dan tingkat
normal atau rendah dari high-density lipoprotein (HDL). Pengurangan lipoprotein lipase,
enzim yang bertanggung jawab untuk metabolisme lipoprotein, diduga menjadi alasan untuk
mengurangi membersihkan lipid ini. Lipoprotein aterogenik dan tingkat fibrinogen juga
meningkat karena peningkatan sintesis hati, yang meningkatkan risiko kardiovaskular pada
NS. Penelitian pada hewan sangat menyarankan bahwa hiperlipidemia saja dapat merusak
fungsi ginjal, dan bahwa tingkat pengurangan lipid dapat memperlambat perkembangan
kerusakan ginjal. Meskipun studi klinis kurang meyakinkan, bukti menunjukkan bahwa ini
juga berlaku pada manusia.
Pengobatan
Pengobatan sindrom nefrotik berfokus pada mengidentifikasi dan mengobati penyebab yang
mendasari, jika mungkin, dan mengurangi kolesterol tinggi, tekanan darah, dan protein dalam
urin melalui diet protein-dikendalikan, penggunaan enzim angiotensinconverting (ACE)
inhibitor, atau keduanya . Pada pasien diabetes dengan mikroalbuminuria, penelitian telah
menemukan bahwa penggunaan terapi ACE mengurangi proteinuria dan memperlambat
perkembangan penyakit ginjal kronis. Sebagai penyakit ginjal berlangsung, nefron hancur,
dan nefron yang sehat yang tersisa harus mengkompensasi (hyperfi filtrasi) untuk
mempertahankan homeostasis tubuh. Selain itu, GFR meningkat nefron yang tersisa 'melalui
pelebaran arteriol aferen glomerulus. Th adalah hasil cedera sekunder untuk glomerulus,
peningkatan proteinuria, dan akhirnya kehancuran nefron. ACE inhibitor dan angiotensin
receptor blocker (ARB) terapi, termasuk terapi kombinasi, telah terbukti mengurangi
proteinuria pada pasien dengan nefropati diabetik dan pada mereka dengan sindrom nefritik
idiopatik. Proteinuria juga dapat dikurangi dengan menurunkan tekanan berarti arteri pasien
ke tingkat bawah 92 mm Hg, independen dari kelas antihipertensi used.75 tingkat kalium
harus diperiksa pada mereka dengan moderat untuk disfungsi ginjal berat, karena inhibitor
ACE dapat memperburuk hiperkalemia.
Untuk meminimalkan percepatan aterosklerosis, hiperlipidemia harus dikelola dengan HMGCoA reductase inhibitors atau agen seperti gemfi brozil untuk menurunkan trigliserida dan
kadar LDL. Jenis obat tidak boleh digunakan pada saat yang sama karena peningkatan risiko
rhabdomyolysis.