Icm neph synd 234


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Icm neph synd 234

  1. 1. • Nephrotic Syndromnephrotic = proteinnephritic = blood- few RBC in nephrotic syndrome- nephritic syndrome: more than 1 gram means its nephrotic nephriticprotein in the urine= bad prognosis- means the kidney is sickINTRODUCTIONAMOUNTS OF PROTEINURIA — In normal subjects, low molecular weight proteinsand small amounts of albumin are filtered. no more than about 2 to 4 g of albumin perday are filtered normally, each day (with the bulk of this filtered albumin "reclaimed" inthe early proximal tubule). The filtered proteins enter the proximal tubule where theyare almost completely reabsorbed and then catabolized by the proximal tubular cells.Some of the catabolized proteins (including albumin) are excreted as peptides in theurine.. The net result is the normal daily protein excretion of less than 150 mg(usually 40 to 80 mg), of which approximately about 4 to 7 mg is intact,immunoreactive albumin.
  2. 2. TYPES OF PROTEINURIA — There are three basic types of proteinuria: — Glomerular — , tubular, — overflow Only glomerular proteinuria (ie, albuminuria) is identified on a urine dipstick Glomerular proteinuria — Glomerular proteinuria is due to increased filtration of macromolecules (such as albumin) across the glomerular capillary wall. The proteinuria associated with diabetic nephropathy and other glomerular diseases, as well as more benign causes such as orthostatic or exercise-induced proteinuria fall into this category. Tubular proteinuria — Low molecular weight proteins — such as ß2- microglobulin, immunoglobulin light chains, retinol-binding protein, and amino
  3. 3. acids — have a molecular weight that is generally under 25,000 in comparison to the 69,000 molecular weight of albumin. These smaller proteins can be filtered across the glomerulus and are then almost completely reabsorbed in the proximal tubule. Interference with proximal tubular reabsorption, due to a variety of tubulointerstitial diseases or even some primary glomerular diseases, can lead to increased excretion of these smaller proteins Tubular proteinuria is often not diagnosed clinically since the dipstick for protein does not detect proteins other than albumin and the quantity excreted is relatively smallOverflow proteinuria — Increased excretion of low molecular weight proteins canoccur with marked overproduction of a particular protein, leading to increasedglomerular filtration and excretion. This is almost always due to immunoglobulin lightchains in multiple myeloma, but may also be due to lysozyme (in acutemyelomonocytic leukemia), myoglobin (in rhabdomyolysis), or hemoglobin (inintravascular hemolysis) .In these settings, the filtered load is increased to a levelthat exceeds the normal proximal reabsorptive capacity.Patients with myeloma kidney also may develop a component of tubular proteinuria,since the excreted light chains may be toxic to the tubules, leading to diminishedreabsorption.In addition, patients with multiple myeloma and Bence Jones proteinuria canalso develop nephrotic syndrome due to AL (primary) amyloidosis.MEASUREMENT OF URINARY PROTEINStandard urine dipstick — The standard urine dipstick primarily detects albumin via acolorimetric reaction between albumin and tetrabromophenol blue producingdifferent shades of green according to the concentration of albumin in the sample.Proteinuria on the urine dipstick is graded from 1+ to 4+, which reflects progressiveincreases in the urine albumin concentration:
  4. 4. • Negative • Trace — between 15 and 30 mg/dL - 1500 cc = 300 mg/24h • 1+ — between 30 and 100 mg/dL –1500cc = 1.5gr/24h • 2+ — between 100 and 300 mg/dL – 1500cc= 4.5gr/24h • 3+ — between 300 and 1000 mg/dL –1500cc 3gr 10gr/24h • 4+ — >1000 mg/dL-1500cc >10gr/24hThe urine dipstick is highly specific, but not very sensitive for the detection of mildproteinuria; it becomes positive only when protein excretion exceeds 300 to 500mg/day Sulfosalicylic acid test — In contrast to the urine dipstick, which primarily detects albumin, sulfosalicylic acid (SSA) detects all proteins in the urine( light chains)in MM lyzozymes in AMN Leukemia ***the stick measures only albuminA concentrated urine will overestimate and dilute urine, for example, willunderestimate the degree of proteinuria. Measurement of quantitative protein excretion
  5. 5. Normal rate (albumin): up to 30mg/24hMicroalbuminuria : between 30 and 300 mg/day Proteinuria : >300mg/24h more than 3.5 grams per day = NEPHROTIC SYNDROME - diabetics: disease that cause proteinuria- usually for first 10 yrs- doesnt matter waht type- will have microalbuminuria- then will go to proteinuria,and then nephrotic syndrome (more than 3.5 g /day) - microalbuminuria: bad prognostic sign- we are about albumin- not total proteinuria (unless pt has myeloma)24-hour collection — The traditional method requires a 24-hour urine collection todirectly determine the daily total protein or albumin excretion. An extra benefit of thisapproach, if creatinine is also measured, is that it provides the information necessaryto estimate the glomerular filtration rate (GFR) from the creatinine clearance.Protein/creatinine ratioAn alternative method requires only a random urine specimen to estimate the degreeof proteinuria [9-12]. This test calculates the total protein-to-creatinine ratio (mg/mg).This ratio correlates with daily protein excretion expressed in terms of g per 1.73m2 ofbody surface area (figure 1). Thus, a ratio of 4.9 (as with respective urinary proteinand creatinine concentrations of 210 and 43 mg/dL) represents a daily proteinexcretion of approximately 4.9 g per 1.73.Thus, a ratio of 4.9 represents a daily protein excretion of approximately 4.9 g/24h - most imp test to detect early stage of renal disease: especially in diabetics ACR Urine albumin to creatinine ratio — The urine albumin:creatinine ratio (ACR), like the PC ratio, is measured using a random "spot" urine specimen. The K/DOQI guidelines note that the relative merits of measuring and monitoring the total protein-to-creatinine ratio versus the albumin-to-creatinine ratio to detect and monitor kidney damage are unclear. However, given that albuminuria is a more
  6. 6. sensitive marker than total protein for chronic kidney disease due to diabetes, hypertension, and glomerular diseases, they recommend, in adults, that the ratio in spot urine samples should be measured with the albumin-to-creatinine ratio. If the albumin-to-creatinine ratio is high (>500 to 1000 mg/g, which corresponds to urinary albumin excretion of >500 to 1000 mg/day), they state that total protein-to-creatinine ratio is also acceptable. Types of proteinuria Isolated proteinuria Proteinuria may be associated with a renal or systemic disease, or it may be isolated. The latter occurs in asymptomatic patients without evidence of any disease or abnormality of the urine sediment.it has, with a favorable-to-excellent prognosis Most patients with benign causes of isolated proteinuria excrete less than 1 to 2 g/day. Proteinuria in pregnancy In non-pregnant individuals, abnormal total protein excretion is typically defined as greater than 150 mg daily. In normal pregnancy, urinary protein excretion increases substantially, due to a combination of increased glomerular filtration rate and increased permeability of the glomerular basement membrane Hence, total protein excretion is considered abnormal in pregnant women when it exceeds 300 mg/ 24 hours. Preeclampsia is the most common cause of proteinuria in pregnancy and must be excluded in all women with proteinuria first identified after 20 weeks of gestation. If preeclampsia is excluded, then the presence of primary or secondary renal disease should be consideredorthostatic or postural proteinuria In this disorder, which is primarily a diseaseof adolescents, protein excretion is increased in the upright position but is normal whenthe patient is supine. Thus, since the results of a random specimen vary markedly withposture, a first morning spot urine can be obtained to help avoid thisconfounding effect. A normal value in the first morning spot urine and dipstick-
  7. 7. positive proteinuria on an upright specimen is strongly suggestive of orthostaticproteinuria • Nephrotic Syndrome • Definition • protein excretion greater than 3.5 g/24 hours), • hypoalbuminemia (less than 3.0 g/dL), • peripheral edema. • HyperlipidemiaIsolated heavy proteinuria without edema or other features of the nephrotic syndromeis suggestive of a glomerulopathy (with the same etiologies as the nephroticsyndrome), but is not necessarily associated with the multiple clinical and managementproblems characteristic of the nephrotic syndrome. This is an important clinicaldistinction because heavy proteinuria in patients without edema or hypoalbuminemia ismore likely to be due to secondary focal segmental glomerulosclerosisETIOLOGY — Heavy proteinuria and the nephrotic syndrome may occur in associationwith a wide variety of primary and systemic diseases. Minimal change disease is thepredominant cause in children. In adults, approximately 30 percent have asystemic disease such as diabetes mellitus, amyloidosis, or systemic lupuserythematosus; the remaining cases are usually due to primary renal disorders suchas membranous nephropathy minimal change disease, focal segmentalglomerulosclerosis.A study of 233 renal biopsies performed between 1995 and 1997 at the University ofChicago in adults with full-blown nephrotic syndrome (in the absence of an obviousunderlying disease such as diabetes mellitus or lupus) found the major causes to be1.membranous nephropathy and focal segmental glomerulosclerosis (33 percenteach),2.minimal change disease (15 percent),3. amyloidosis (4 percent overall, but 10 percent in patients over age 44)Over time, the relative frequency of membranous nephropathy fell from 38 to 15percent, while the frequency of focal segmental glomerulosclerosis increased from14 to 25 percent overall; this increase was primarily seen in black and Hispanicpatients.Primary causes of nephrotic syndrome include the following, inapproximate order of frequency: • Minimal-change nephropathy • Focal Segmental glomerulosclerosis ( FSGS) • Membranous nephropathySecondary causes include the following, again in order of approximatefrequency:
  8. 8. • Diabetes mellitus • Lupus erythematosus • Amyloidosis and paraproteinemias (MM) • Viral infections (eg, hepatitis B, hepatitis C, human immunodeficiency virus [HIV] ) • PreeclampsiaMetabolic consequences of proteinuriaMetabolic consequences of the nephrotic syndrome include the following: Infection Urinary immunoglobulin losses • Edema fluid acting as a culture medium • Protein deficiency • Decreased bactericidal activity of the leukocytes • Immunosuppressive therapy • Decreased perfusion of the spleen caused by hypovolemia • Urinary loss of a complement factor (properdin factor B) that opsonizes certain bacteria • • Hyperlipidemia and atherosclerosis • It is related to the hypoproteinemia and low serum oncotic pressure of nephrotic syndrome, which then leads to reactive hepatic protein synthesis, including of lipoproteins.[7] In addition, reduced plasma levels of lipoprotein lipase results in diminution of lipid catabolism • Hypocalcemia and bone abnormalities •Hypocalcemia is common in the nephrotic syndrome, but rather thanbeing a true hypocalcemia, it is usually caused by a low serumalbumin level. Nonetheless, low bone density and abnormal bone histology are reportedin association with nephrotic syndrome. This could be caused by urinary
  9. 9. losses of vitamin D–binding proteins, with consequent hypovitaminosis Dand, as a result, reduced intestinal calcium absorption.[9] • • HypercoagulabilityVenous thrombosis and pulmonary embolism are well-knowncomplications of the nephrotic syndrome. Hypercoagulability in thesecases appears to derive from urinary loss of anticoagulant proteins, such asantithrombin III and plasminogen, along with the simultaneous increasein clotting factors, especially factors I, VII, VIII, and X. • • Hypovolemia • • Hypovolemia occurs when hypoalbuminemia decreases the plasma oncotic pressure, resulting in a loss of plasma water into the interstitium and causing a decrease in circulating blood volume. Hypovolemia is generally observed only when the patients serum albumin level is less than 1.5 g/dL