Understanding Proteinuria and Nephrotic Syndrome in Children
School
Al Azhar University - Gaza**We aren't endorsed by this school
Course
MED 101
Subject
Nursing
Date
Dec 10, 2024
Pages
9
Uploaded by PresidentSeaLion4707
Approach to proteinuria & nephrotic syndrome Urinary protein excretion in normal child is lessthan 100 mg /m2/day or <4mg/m2 per hr or lessthan 150 mg protein per day . 50 % of normal protein excretion consist of Tamm Horsfall proteins(uromodulin) ,which are result of shedding of tubular epithelium . Other 50% of normally excreted protein consists of albumin, beta 2 macroglobulinand amino acidsAbnormal protein excretion is defined as urinary protein excretion morethan 100 mg /m2 per day or morethan 4 mg /m2 per hour . Nephrotic range proteinuria( heavy proteinuria ) is defined as urinary protein excretion : 1.≥ 1000 mg/m2/day2.> 40 mg/m2/hr3.UPr/Crgreater than 24.+3 - + 4 proteinuria 5.greater than 50 mg/kg per dayMEASUREMENT OF URINARY PROTEIN:Urine dipstick— The urinary dipstick measures albumin concentration via a colorimetric reaction between albumin and tetrabromophenol blue producing different shades of green according to the concentration of albumin in the sample.● Negative● Trace – between 15 and 30 mg/dL● 1+ – between 30 and 100 mg/dL● 2+ – between 100 and 300 mg/dL● 3+ – between 300 and 1000 mg/dL● 4+ – >1000 mg/dLDipstick testing will notdetect low molecular weight (LMW) proteins.it is not sufficiently sensitive for detecting albumin in the range of microalbuminuria (ie, albumin excretion of 30-300 mg/d in an adult). The threshold for transition from microalbuminuria to dipstick-detectable albuminuria (300 mg albumin excreted per day in an adult) corresponds to a concentration of 15 mg/dL if the daily urine volume is 2000 mL. This level gives only a trace result with the dipstick and is not sensitive for the detection and quantitation of microalbuminuria.
False-positiveresults may be obtained in samples that are very alkaline (ph > 8 ), or contaminated by antiseptic agents(such as chlorhexidine or benzalkonium chloride) or iodinated radiocontrast agents.Thus, the urine should not be tested for protein with the dipstick for at least 24 hours after a contrast study.dipstick result may be difficult to read if the urine is abnormally colored because of nitrofurantoin, riboflavin, azo-containing sulfonamide antimicrobials, or blood.Dilute urine, as may occur when a random urine specimen is tested in the middle of theday, may mask significant proteinuria. Conversely, highly concentrated urine may suggest clinically significant proteinuria when the actual degree of proteinuria is not severe. Sulfosalicylic acid test— In contrast to the urine dipstick, sulfosalicylic acid (SSA) detects all proteins in the urine including the LMW proteins that are not detected by the dipstick . The SSA test is performed by mixing one part urine supernatant (eg, 2.5 mL) with three parts 3% SSA, followed by assessment of the degree of turbidity. This testis infrequently necessary in children.Quantitative assessment— Children with persistent dipstick-positive proteinuria must undergo a quantitative measurement of protein excretion. Because of the difficulty of obtaining an accurate 24 hour collection, we prefer to use the quantitative measurement of thetotal protein/creatinine (Pr/Cr) ratioon a spot urine sample. In particular, it is difficult to obtain accurately time urine collection in young children and infants who are not toilet trained.Spot urine sample— The quantitative assessment is measurement of the total protein/creatinine ratio (Pr/Cr) on a spot urine sample is preferably performed on a first morning specimen . The normal value for this ratio is<0.2 mg protein/mgcreatinine (<20 mg protein/mmol creatinine) in children greater than two years of ageand <0.5mg protein/mgcreatinine (<50 mg protein/mmol creatinine) in infants and toddlers from 6 to 24 months .note, spot urine protein to creatinine ratio will overestimate the actual protein excretion in very dilute urine (ie, urine Cr <38.8 mg/dL [3.43 mmol/L]) or underestimate protein excretion for a concentratedsample (ie, urine Cr>61.5 mg/dL [5.44 mmol/L])Timed 24-hour urine collection— In children (except neonates),levels of urinary protein excretion higher than 100mg/m2per day (or 4mg/m2per hour) are abnormal. Proteinuria of greater than 40mg/m2per houris considered heavyor in the nephrotic range.
Classifications of proteinuria : Generally , proteinuria is divided into three categories :1-Transient proteinuria: the most commontype (90%) and usually due to several factors includingfever,stress,excersie,seizures etc…Transient, low-grade proteinuria may occur in a child with fever or when urine is tested shortly after strenuous physical activity. In these instances, the urine should be tested again after fever subsides, or, if the urine was positive for protein shortly after sports participation, it should be tested again 2-3 days later.2-Orthostatic ( postural ) proteinuria: defined as increasedprotein excretion in the upright position which returns to normalwhen the patient is recumbent. It is confirmed if the recumbenturine sample has a normal Pr/Crratio and the upright sample has an elevatedratio. The easiest recumbent sample to obtain is the first morning void.The patient should void completely just before going to sleep and collect a morning sample as soon as arising. A second sample is then collected after at least an hour of being upright and moving around normally. It is a common cause of proteinuria, especially in adolescent males it is a benign condition without clinical significance and usually resolves spontaneouslyA healthy child with orthostatic proteinuria may have a considerable quantity of protein in a 24-hour urine collection, perhaps up to 1000 mg, and may be falsely identified as having kidney disease. Alternatively, if a random urine sample is tested, the protein-to-creatinine ratio may even be in the nephrotic range Annual testing is prudent . The "nutcracker syndrome" (left renal vein entrapment), demonstrated by ultrasonic imaging and Dopplerflow scanning, appears to be a common cause of postural proteinuria . 3-Persistent (fixed) proteinuria: Persistent proteinuria should be more fully evaluated for underlying renaldisease.Persistent proteinuria is divided according to the underlying pathology:
Primary cause(90%) like- minimal change glomerulonephritis(80%) m:f >2:1 (2-6yrs )effacement of epithelial cell foot processes on electronic microscopy >95% responsive to steroid treatment -focal segmental glomerulosclerosis (10%)>>could progress from MCD or be separate Only 20% respond to steroid treatment mesangial prolifiration +sigmental scaring Think of other dx than MCD when: Age <1 yr or > 8 yr , family hx of kidney dz , extrarenal findings , htn,pulmonary edema , renal insuffeciency, hematuria Secondary cause (10%): DM , sle , amyloidosis etc. Membranous>hepatitis b or c , syphilis malaria gold salts penecillamin membranoprolifirative > lupus ,HSP , PSGNCongenital cause( less than 1%) likefinish type(AR, proteinuria detectable inutero(increased a phetoprotein ,large placenta and marked edema ,very bad prognosis ,usually the child die at age less than 5 years ) denys drash syndrome >(defuse mesangial sclerosis , >progressive sclerosis of the glomerular mesangiun , wilms tumor (mutation on wt gene ch11 ), male pseudohermaphroditism What is the criteria to diagnose nephrotic syndrome ? 1-Nephrotic range proteinuria (mainly albuminuria)2-Hypoalbuminemia ( serum albumin less than 2.5mg/dl)3-Generalized edema 4-Hyperlipidemia( mainly hypercholesterolemia more than 250 mg /dl )
Our approach to a child presenting with puffy eyes (edema) 1-History 2-Physical examination 3-Investigation and management History: 1-Personal data : name ,age ,gender ,etc ..2-Chief compliant : puffy eyes ,periorbital swelling with its duration ..3-History of presenting illness : Onset of edema whether sudden or gradualDuration and time course of the edema: Congenital or started later on (ask about child’s age at time of onset)Does the swelling(edema) , increaseor decrease at certain times during day ( in case of nephrotic syndrome ,periorbital puffiness appear at the morning and decrease during the day especially at the evening ) .Course of the edema or swelling , it is persistent or intermittent. Character of the edema including its progression to involve another sites, like( ankles ,sacrum ,abdomen ),Weight gain, difficulty putting shoes on, and tight-fitting clothes suggesting generalized edemaHistory of insect bite ,trauma or burnAssociated symptoms :Ask about previous history of upper respiratory tract illness 2-3 week or impetigo 3-6 wk before onset of edema which suggest post-streptococcal glomerulonephritis .Ask about symptoms of recurrent pyelonephritis (fever, flank pain ,..) which along with periorbital edema suggest renal scarring and renal failure .URTI + HEMATURIA+PERIORBITAL EDEMA suggest PSGN Ask about joint pain ,skin rash ,hair loss ,which suggest SLEAsk about dyspnea ,chest pain ,cough which suggest pulmonary edema as a complication of nephrotic syndrome Ask about CNS manifestations including headache ,altered level of consciousness ,seizure which suggest encephalopathy ( brain edema, cerebral vein thrombosis) as a complication of nephrotic syndrome . 4-Ask about drug history including corticosteroid , antihypertensives, ACEI inhibitors, CCB and drug allergy .. 5-Ask about birth history including maternal nutrition , maternal exposure to hepatitis B neonatal problems that may indicate renal problems.6-Past medical and surgical problems including ,renal disease, heart diseases ,gastrointestinal diseases ,liver disease ,sickle cell anemia, malignancies, ..7-Feeding or dietary history including poor feeding ,feeding difficulties , poor protein intake (kwashiorkor),allergic reaction to foods ( cows milk) , excess salt intake in diet ( may contribute to edema) ,dietary changes .
8-Ask about family history including previous similar attacks , history of renal diseases ,cystic fibrosis , sle , Alport syndrome , recurrent angioedema or atopy .. etc 9-Ask about social history : including risk of malnutrition ,exposure to toxins.10-Systemic review : inching ,angioedema ( allergy ) ,cardiovascular symptoms ( cough, diaphoresis, poor exercise tolerance , poor feeding indicate possible heart failure ), anorexia , chronic diarrhea ( protein losingenteropathy ) , jaundice , prior exposure to hepatitis b, hepatomegaly ( liver cirrhosis ) and so on ..Clinical examination : General lookincluding the appearance of the child ( ill-looking ,lethargic, drowsy ,seizing) child indicate serious condition e.g. (encephalopathy due to cerebral vein thrombosis , brain edema as a complication of nephrotic syndrome )Growth parametersaltered growth parameters seen in chronic illnesses including (chronic kidney disease from GN, heart failure , nephrotic syndrome , protein loosing enteropathy ,etcVital signs: Findings of tachycardia, tachypnea, gallop, rales, or hepatomegaly are seen in patients with heart failurewhereas tachypnea and rales alone may be indicative of pulmonary edema.Increased blood pressure (BP) levels may reflect hypervolemia resulting from acute/chronic renal failure or glomerulonephritis . Characterizing the edemaas localized or generalized, and assessing the extent of edema.Generalized edema– If generalized edema is present, the child should be evaluated for pleural effusion, pulmonary edema, ascites, scrotal/labial edema, or evidence of skin breakdown in regions of edema.Pulmonary findingsof decreased breath sounds and dullness to percussion are consistent with pleural effusion, although pulmonary edema is suggested by adventitial sounds such as rales.Ascites is associated with abdominal distention, and shifting dullness and a fluid wave on percussion of the abdomen.Patients with the nephrotic syndromealso may have prominent periorbital edemabecause of the low tissue hydrostatic pressure in this area; this finding is usually worse in the morning and improves with ambulation due to the dependent nature of this type of edema.Localized edema– With regional edema, the clinician should localize the area of swelling to help deduce where a region of venous or lymphatic obstruction is likely to be present, or if localized allergen exposure has occurred. Because cellulitis also can manifest with regional edema, assessment of the patient for fever and local signs of inflammation is important. If the edema is localized to the face, the child also should be carefully evaluated for concurrent airway involvement, which can be life-threatening.Some Clues and examples —The child with edema must be assessed for associated symptoms or other medical conditions that may help suggest the underlying etiology. The following are groupings of signs and symptoms found in a variety of diseases that cause edema in children:
A child with diaphoresis, dyspnea on exertion, and/or a history of heart disease may have edema secondary to cardiac failure. Findings on clinical examination include tachycardia, tachypnea, rales, hepatomegaly, and/or gallop.A child with a history of food allergiesmay present acutely with urticaria and angioedema after allergen exposure. If there is airway involvement, this is a medical emergency and requires emergent therapy. A history of jaundice, failure to thrive, steatorrhea, or abdominal pain should point the clinician toward a diagnosis of chronic liver diseaseor possibly a protein-losingenteropathy A child with progressive anasarca with a significant periorbital component, but minimal systemic complaints, may have nephrotic syndrome.Cola-colored urine with either generalized or facial edema strongly suggests acute glomerulonephritis. These patients also may have hypertension.Edema, anorexia, and growth impairment can be seen in a child with chronic renal failure.Family history of angioedema favors a diagnosis of hereditary angioedema.A newborn girl with edema of the hands and feet, webbed neck, nail dysplasia, high palate, and short fourth metacarpal may have Turner syndrome.Investigations: Lab investigations : 1-CBC : to look for leukocytosis as a sign of infection ( complication of nephrotic syndrome ) ,anemia ( hemolytic disease of newborn )2-KFT(serum creatinine and urea )3-Serum electrolyte 4-Albumin( nephrotic syndrome ,liver disease, protein losing enteropathy) 5-Liver function test( sign of liver cirrhosis )6-ANA,C3,C4, ANTI DNASE , ASOT 7-Urine analysisand culture8-Moring spot urine samplefor protein/creat ratio9-Others( stool level for a1-anti trypsin , when angioedema is suspected, plasma levels of the complement components, C1q, C4, C2, and C1 inhibitor may help diagnose inherited or acquired C1 inhibitor deficiency. With the inherited forms, C4 and C2 levels are chronically low in the majority of patients .
Imaging modalities : 1-Renal ultrasound : An edematous newborn male with bilateral hydronephrosis may have obstructive uropathy from posterior urethral valves (PUV).A teenager with renal failure and small shrunken kidneys may have congenital renal hypoplasia, scarring from reflux nephropathy, or simply chronic renal failure of any cause.2-Doppler ultrasonography : is indicated in the child with suspected venous thrombosis . 3-Chest radiography— Chest radiography is helpful in detecting cardiac failure, pulmonary edema and pleural effusions.4-Echocardiography— Echocardiography can evaluate ventricular function, assess for the presence of a pericardial effusion, and aid in the diagnosis of cardiac disease in the child suspected of having heart failure.5-Renal biopsy: A child with presumed idiopathic nephrotic syndrome is nottypically biopsied at the outset of the disease. A trial of corticosteroid treatment is typically offered, with a renal biopsy reserved for steroid-resistant patients.TREATMENTmore than 80% of children 1 to 7 years old with typical MCNS respond to corticosteroids, Specific therapy for MCNS is prednisone, 2 mg/kg/day divided into 2-4 doses per day. respond to steroids do so within 4 weeks. continue to 6 wks then alternate days till 8thwk then reduce the dose The optimal duration of steroid therapy for responders is 12 weeks. If not respond to daily prednisone therapyrenal biopsy is indicated because steroid resistance greatly increases the chance for something other than MCNS. Frequent relapses or steroid resistance in MCNS immuno-suppressive therapy. REMISSION: URINE NEG/TRACE FOR PROTEIN FOR 3 CONSEQ DAYS . RELAPSE: 3+PROTEINURIA FOR 3 CONSEQUTIVE DAYS DURING REMISSIONFREQUENT RELAPSER: >2 RELAPSES IN 6 MONTH; >3 IN 1 YRSTEROID RESPONDER: REMISSION WITHIN 6 WEEKS OF STEROID RxSTEROID RESISTANCE: NO REMISSION FOR 8 WEEKS
STEROID DEPENDENT: RELAPSE WITHIN 2 WK OF STEROID DISCONTINUATION More than 80% of patients with FSGS do not respond to corticosteroid therapy. ggressive medical therapy of familial congenital nephrotic syndrome, with early nephrectomy, dialysis, and subsequent transplantation, is the only effective approach to this syndrome.Edema is treated with restriction of salt intake & use of diuretic therapy.if ineffective in alleviating severe edema:25% albumin (0.5 g/kg intravenously over 1 to 2 hours) IV loop diuretic (furosemide) during or after albumin results in diuresis. Acute hypertension is treated with β-blockers or calcium channel blockers.Persistent hypertension is often responsive to angiotensin-converting enzyme inhibitors.COMPLICATIONSInfection is a major complication in children with the nephrotic syndrome of any type. Bacteremiaand peritonitis, particularly Streptococcus pneumoniaeor Escherichia coli.Hypovolemia result of diarrhea or use of diuretics.The loss of proteins hypercoagulable state with a risk of thromboembolism. (Warfarin & low dose aspirinminimize the risk of clots)Most children with nephrotic syndrome eventually go into remission.80%of MCNS experience a relapse of the proteinuria at some point (as heavy proteinuria that persists for 3to 5 days). Transient (1 to 2 days) proteinuria in children with MCNS with an intercurrent infection, not a relapse. Steroid therapy is rapidly effective for a true relapse. Patients with FSGS may be initially responsive to steroids, but become late nonresponders. Manychildren with FSGS progress to end-stage kidney failure. Recurrence of FSGS occurs in 30%of children who undergo renal transplantation.