​Kembara Xtra - Medicine - Proteinuria

​Kembara Xtra - Medicine - Proteinuria 
Nephrotic-range proteinuria, often known as heavy proteinuria, is defined as urine protein excretion of greater than 150 mg per day.
Three pathogenic kinds include:
Protein permeability across the glomerular capillary membrane is elevated in glomerular proteinuria. Protein reabsorption in the proximal tubule is diminished in tubular proteinuria.
- Increased synthesis of low-molecular-weight proteins in overflow proteinuria


Child Safety Considerations

Proteinuria: Excretion of up to 100 mg/m2 (body surface area) per day is considered normal.
Proteinuria of the nephrotic range is defined as >1,000 mg/m2 (body surface area) per day excretion.

pregnant women's issues

Proteinuria in pregnancy after 20 weeks of gestation is a sign of pre- or eclampsia and necessitates additional testing.
Prior to 20 weeks of pregnancy, proteinuria is suggestive of underlying renal illness.


Pathophysiology and Etiology 

Glomerular proteinuria is caused by: higher filtration; bigger proteins (albumin); and
- The size of glomerular basement membrane holes has increased, and
Negative proteoglycan charge barrier loss
Tubular proteinuria: Tubulointerstitial disease prohibits smaller proteins (2-microglobulin, immunoglobulin [Ig] light chains, retinolbinding protein, amino acids) from being reabsorbable in the proximal tubule.
Overflow proteinuria is caused by excessive production of smaller proteins, which overwhelms proximal tubular reabsorption.
Primary glomerulonephropathy and glomerular proteinuria
Small-change illness
IgA nephropathy - Secondary Glomerulonephritis Idiopathic/Primary Membranous Glomerulonephritis Focal Segmental Glomerulonephritis Membranoproliferative Glomerulonephritis
diabetic kidney disease
 Vascular autoimmune/collagen disorders (such as Goodpasture syndrome, lupus nephritis)
Amyloidosis, preeclampsia, infections (HIV, hepatitis B and C, poststreptococcal, endocarditis, syphilis, malaria), malignancies (gastrointestinal, lung, lymphoma), and rejection of a kidney transplant are among the conditions that can occur.
Structural (polycystic kidney disease, reflux nephropathy)
 Substance-induced (heroin, lithium, heavy metals, NSAIDs, penicillamine, and other drugs),
Tubular proteinuria, hypertensive nephrosclerosis, tubulointerstitial disease (Fanconi syndrome, heavy metals, sickle cell disease, NSAIDs, antibiotics), hypersensitivity, interstitial nephritis, and
Chronic tubular necrosis
Multiple myeloma (light chains; also tubulotoxic) overflow proteinuria
- Myoglobinuria (in rhabdomyolysis) - Hemoglobinuria
Lysozyme is used to treat acute monocytic leukemia.
 Functional benign proteinuria (fever, exercise, exposure to cold, stress, CHF)
- Transient idiopathic
- Postural orthostasis
Genetics
No genetic pattern is known.

Risk factors include diabetes, obesity, strenuous activity, hypertension, UTI, and fever.

Basic Prevention 

Proteinuria is less likely when weight, blood pressure, and blood sugar are under control.


Preeclampsia, multiple myeloma, hypertension, diabetes mellitus (DM), and DM are all associated conditions.


A systemic illness such as diabetes, heart failure, autoimmune disease, or poststreptococcal infection should be ruled out. Diagnosis: Frothy/foamy urine; change in urine output; urine that is red or cola-colored; recent weight change; swelling.

Clinical examination, blood pressure, weight, periorbital and facial edema, ascites, kidney palpation, and a lookout for CHF symptoms in the heart and lungs.

Multiple Diagnoses 


Laboratory Results 

All persons with CKD risk factors should be evaluated for proteinuria using a random urine sample analysis and serum creatine measurement to estimate GFR.


Initial examinations (lab, imaging)
Urinalysis (UA) provides a quantitative assessment of proteinuria:
- Only sensitive to albumin; ineffective in detecting smaller proteins associated with overflow or tubular etiologies.
- False-positive result if urine contains leukocytes, iodinated contrast agents, penicillin analogues, sulfonamide metabolites, gross hematuria, specific gravity [SG] >1.015, and pH >7
- False-negative result if albumin excretion is less than 20 to 30 mg/dL and the protein is nonalbumin in the urine (SG 1.005).
- Specificity: 97-100%; sensitivity: 32-46%
- Additionally, sulfosalicylic acid testing can be done to find nonalbumin protein.
- The initial timed 24-hour urine test is not advised due to poor specimen collection and patient annoyance.
- Sensitive to high levels of proteinuria >300 mg/24 hours (may miss 30 to 300 mg)
Perform urine microscopy if the UA test is positive. If you notice any evidence of glomerular disease, consult a nephrologist.
 Rule out transient proteinuria with repeat UA at another visit if UA indicates trace to 2+ protein:
- More frequent than persistent proteinuria - Causes include cold exposure, exertion, fever, CHF, and other illnesses.
- Assure the patient that temporary proteinuria is benign and won't need any additional testing.
To confirm nephroticrange proteinuria, spot urine protein-to-creatine ratio should be used rather than 24-hour urine collection.
Measure creatinine clearance and quantify proteinuria using 24-hour urine collection (gold standard) or spot urine protein-to-creatinine (P/C) ratio (acceptable practice) if first UA indicates 3+ to 4+ protein or repeat UA is positive:
- Numerical P/C ratios are correlated with the amount of total protein excreted in grams per day (a ratio of 0.2 is correlated with 0.2 g over the course of a 24-hour collection, for example).
- Orthostatic proteinuria should be checked in patients under 30 years of age who have 24-hour urine output of less than 2 g/day and normal creatinine clearance:
 Between 2 and 5% of teenagers have a benign ailment.
 Found to have a normal urine P/C ratio in the morning void and an increased urine P/C ratio in a subsequent sample collected after standing for a while.
If protein excretion exceeds 2 g/day, consider referring the patient to a nephrologist and start the systemic/renal disease workup.
To rule out structural abnormalities (such as polycystic kidney and reflux nephropathy), renal ultrasonography should be performed on patients whose chronic proteinuria is not explained by orthostatic alterations.

Tests in the Future & Special Considerations
Workup for renal/systemic diseases may involve the following:
Electrolytes, LFTs, a lipid profile (preferably, fasting), ferritin, ESR, and serum iron.
 International normalized ratio of prothrombin time
Antiphospholipase A2 receptor antibody positivity is found in about 70% of cases of primary membranous nephropathy; antinuclear antibodies are elevated in lupus; antistreptolysin O titers are elevated after streptococcal glomerulonephritis; complement C3/C4 levels are low in most cases of glomerulonephritis; and HIV, syphilis, and hepatitis ser
 Multiple myeloma causes abnormal serum and urine protein electrophoresis results.
Patients with nephrotic-range proteinuria (25% of adult patients) have an elevated risk of hypercholesterolemia and thromboembolic events, with membranous nephropathy having the highest risk. Although the ideal time frame for preventive anticoagulation is unknown, it may last throughout the nephrotic condition.
Beyond 20 weeks' gestation, proteinuric pregnant women should be checked for other preeclampsia symptoms, such as hypertension, thrombocytopenia, and increased liver transaminases.

Management 
Adults with and without diabetes should aim for blood pressure of 140/90 mm Hg.
Goal for proteinuria is 0.5 g per day.
For patients with normal urine albumin concentrations, the target blood pressure is 130/80 mm Hg.
 A BP target of 125/75 mm Hg for patients with a proteinuria level of more than or equal to 1 g/24 hours.


General Actions 

In persons with diabetes mellitus (DM) or without DM and glomerular filtration rate (GFR) 30 mL/min/1.73 m2, limit protein consumption to 0.8 g/kg/day. The soy protein may protect the kidneys.
Utilize 24-hour urine urea excretion to keep track of protein intake.
To get the most out of your antiproteinuric drugs, keep your sodium chloride consumption to under 2 g per day.
The impact on BP is additionally protective.
Limit fluid intake to achieve a daily urine output goal of 2 L. Greater proteinuria and a later GFR decline are linked to larger urine volumes.
 Giving up smoking: Smoking is linked to an increase in proteinuria and a quicker progression of renal disease.
Encourage supine position (reduction of up to 50% compared to upright).
Encourage moderate exercise.
Promote weight loss.


First Line of Medicine
The use of ACE inhibitors, ARBs, or loop diuretics is a conservative therapeutic strategy for nephrotic syndrome.
ACE inhibitors are recommended as a first line of treatment; use only the highest doses that are tolerable.
Angiotensin receptor blockers (ARBs) are the first choice if ACE inhibitors are intolerable because they have been shown to be antiproteinuric and renoprotective.
It is not advisable to use an ACE inhibitor and an ARB together.
Despite having been found to lower proteinuria, the combination does not improve CV outcomes and raises the risk of negative drug reactions.
Next Line
Antiproteinuric and cardioprotective blockersNon-DHCCB: antiproteinuric; may be renoprotective; dihydropyridine calcium channel blockers (DHCCBs): should be avoided unless necessary for blood pressure managementAldosterone antagonists: antiproteinuric without affecting blood pressure
NSAIDs should generally be avoided since they are nephrotoxic and antiproteinuric.

Referral 
If you have impaired creatinine clearance, nephrotic-range proteinuria, or an unknown etiology, you should think about seeing a nephrologist for a potential renal biopsy.

Alternative Therapies 

 Corticosteroids: Although steroids are advised in some patients who do not respond to conservative treatment, there is no evidence that they reduce mortality or the requirement for renal replacement in adults with nephrotic syndrome. The nephrotic syndrome typically affects children more than adults, especially those with minimal change illness.
NS may have some advantages over corticosteroids and other immunosuppressive medications. possess high potential dangers. There is no proof or recommendation that all patients with nephrotic syndrome should take these medications.
In premenopausal women, estrogen/progesterone replacement therapy may be renoprotective, but it should be avoided in postmenopausal women.In diabetic nephropathy, antioxidant therapy may be antiproteinuric.Sodium bicarbonate: while not a proteinuric, it may prevent tubular damage brought on by proteinuria. In addition, addressing metabolic acidosis may reduce protein catabolism.
Avoid consuming too much coffee; it reduces proteinuria in diabetic rat models.
Don't take in too much iron.
Pentoxifylline, by unknown mechanisms, slows the progression of renal disease.
Mycophenolate mofetil is renoprotective and antiproteinuric in animal studies.

Patient Follow-Up Monitoring
Serial blood pressure checks, urine analyses, and renal function testing should be performed on all patients with chronic proteinuria in an outpatient setting. The intervals vary on the underlying cause.

Orthostatic proteinuria and transient proteinuria are benign diseases with good prognoses.
Depending on the underlying etiology, chronic proteinuria's clinical relevance can vary substantially.
 Independent of GFR, higher levels of proteinuria probably represent an increased risk of death, myocardial infarction, and progression to renal failure. Degree of proteinuria is connected with disease progression in chronic kidney disease.

Complications include: progression to chronic renal failure, which necessitates dialysis or a kidney transplant; hypercholesterolemia; hypercoagulable state; increased risk of infection for patients with nephrotic syndrome; and second dose of PPSV23, which should be given 5 years after the first PPSV.