Treatment of Nephrotic Syndrome

Treatments of Nephrotic Syndrome
Treat the complications
Peripheral Edema
• frusemide, spironolactone as diuretics
• CIx – albumin serum level <1.5 g/dL (N-3.4 - 5.4 g/dL)
Protein Loss (Proteinuria)
• dietary protein intake should replace the daily urinary protein losses
• protein restriction to 0.6 - 0.8 g/kg/d shows mild benefit but great care must be taken so there is no malnutrition.
• ACE inhibitors or ARB. (Lisinopril | Losartan [for those unable tolerate ACE I - cough] )
o Reducing blood pressure by reducing intraglomerular pressure and direct action of podocytes (increasing their population)
Hyperlipidemia
• statin (Lovastatin)
• hyperlidpidemia always be there unless nephrotic syndrome is treated
Hypercoagulable State
• serum albumin < 2 g/dL can become hypercoagulable.
• taken by ppl prone to renal vein thrombosis and other tromboemboli but not as primary prevention.
Treat underlying cause
• Systemic Lupus Erythematosus [causes lupus nephritis, autoimmune disease]
o Immunomodulators
 Cyclophosphamide [prodrug - liver]
 Useful for relapse steroid sensitive nephrotic syndrome
• Minimal Change Nephropathy [histopathologic lesion in the glomerulus]
o Corticosteroids
 Prenidisone [prodrug - liver]
• Amyloidosis [extracellular tissue deposition of fibrils composed of fragments of serum amyloid A (SAA) protein.]

Glasgow Coma Scale

Glasgow Coma Scale(GCS)
Definition:
The Glasgow Coma Scale is the most widely used scoring system used in quantifying level of consciousness, especially after a head injury, in which scoring is determined by three factors: amount of eye opening, verbal responsiveness, and motor responsiveness. Graham Teasdale and Bryan J. Jennett first developed the Glasgow Coma Scale in 1974. At the University of Glasgow, these neurosurgery professors continued to develop important work in the field of head traumas, publishing Management of Head Injuries in 1981.
It is used primarily because it is simple, has a relatively high degree of interobserver(meaning different people scale it consistently) reliability and because it correlates well with outcome following severe brain injury.
There are limitations to its use. If the patient has an endotracheal tube in place, they cannot talk. For this reason, many prefer to document the score by its individual components; so a patient with a Glasgow Coma Score of 15 would be documented as follows: E4 V5 M6. An intubated patient would be scored as E4 Vt M6. Of these individual factors, the best motor response is probably the most significant.
Other factors which alter the patients level of consciousness interfere with the scale's ability to acurately reflect the severity of a traumatic brain injury. So, shock, hypoxemia, drug use, alcohol intoxication, metabolic disturbances may alter the GCS independently of the brain injury. Obviously, a patient with a spinal cord injury will make the motor scale invalid, and severe orbital trauma may make eye opening impossible to assess (Ec). The GCS also has limited utility in children, particularly those less than 36 months.
Consequently, both doctors and nurses regularly use the Glasgow Coma Scale multiple times on individual patients to determine their evolving needs and changing conditions.
E + M + V = 3 to 15
90% less than or equal to 8 are in coma
Less than or equal to 8 at 6 hours - 50% die
8 is the critical score
9-11 = moderate severity
Greater than or equal to 12 = minor injury
Coma is defined as: (1) not opening eyes, (2) not obeying commands, and (3) not uttering understandable words.
Mild (13-15)
Moderate Disability (9-12)
Severe Disability (3-8)
Vegetative State (Less Than 3):
Sleep wake cycles
Aruosal, but no interaction with environment
No localized response to pain
Persistent Vegetative State:
Vegetative state lasting longer than one month
Individual elements as well as the sum of the score are important. Hence, the score is expressed in the form "GCS 9 = E2 V4 M3 at 07:35".
The GCS has limited applicability to children, especially below the age of 36 months (where the verbal performance of even a healthy child would be expected to be poor). Consequently the Pediatric Glasgow Coma Scale, a separate yet closely related scale, was developed for assessing younger children.
Glasgow Coma Scale: While the 15 point scale is the predominant one in use, this is in fact a modification and is more correctly referred to as the Modified Glasgow Coma Scale. The original scale was a 14 point scale, omitting the category of ‘withdrawal to pain'. Some centres still use this older scale, but most (including the Glasgow unit where the original work was done) have adopted the modified one.
http://www.patient.co.uk/doctor/Glasgow-Coma-Scale-(GCS).htm

Complications of Nephrotic Syndrome

Hyperlipidemia
The occurrence of hyperlipidemia may be considered a typical feature of the nephrotic syndrome, rather than a mere complication. 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.
Some of the elevated serum lipoproteins are filtered at the glomerulus, leading to lipiduria and the classical findings of oval fat bodies and fatty casts in the urine sediment.

Atherosclerotic vascular disease appears to occur in greater frequency in subjects with nephrotic syndrome than in healthy subjects of the same age. The frequency and extent of coronary artery disease stenoses were greater in patients with nephrotic syndrome.

Complication of edema:

Pulmonary edema causing hypoxia and dyspnea and congestive heart failure

Other complications:

Acute renal failure: due to hypovolemia. Despite the excess of fluid in the tissues, there is less fluid in the vasculature.
Decreased blood flow to the kidneys causes them to shutdown. Thus it is a tricky task to get rid of excess fluid in the body while maintaining circulatory euvolemia.
Hypovolemia is generally observed only when the patient's serum albumin level is less than 1.5 g/dL. Symptoms include vomiting, abdominal pain, and diarrhea.
The signs include cold hands and feet, delayed capillary filling, oliguria, and tachycardia. Hypotension is a late feature.

Thrombotic episodes: leakage of anti-thrombin 3 which prevents thrombosis. oral anticoagulants can treat this (but not heparin as heparin acts via anti-thrombin 3)

Infections:due to leakage of immunoglobulins, encapsulated bacteria such as Haemophilus influenzae and Streptococcus pneumoniae can cause infection.

Growth retardation: does not occur in MCNS.It occurs in cases of relapses or resistance to therapy. Causes of growth retardation are protein deficiency from the loss of protein in urine, anorexia (reduced protein intake), and steroid therapy (catabolism).

Vitamin D deficiency can occur. Thyroxine is reduced due to decreased thyroid binding globulin. Maybe also a reduced ability of the kidneys to convert calcidiol to its active form.

Hypocalcemia can occur as a result of Nephrotic Syndrome. Hypocalcemia is common in the nephrotic syndrome, but rather than being a true hypocalcemia, it is usually caused by a low serum albumin level.
Nonetheless, low bone density and abnormal bone histology are reported in association with nephrotic syndrome.
This could be caused by urinary losses of vitamin D – binding proteins, with consequent hypovitaminosis D and, as a result, reduced intestinal calcium absorption.

Microcytic hypochromic anaemia is typical. It is iron-therapy resistant.

Investigation of Nephrotic Syndrome (NS)

Investigation of Nephrotic Syndrome (NS)

Laboratory Tests

1. Urine Tests*

a. Physical colour and appearance

b. Urine specific gravity

i. Concentration of all chemical particles in the urine

c. Microscopic appearance

i. Look at cells, urine crystals, mucus, etc

ii. Identify bacteria or other microorganisms

d. Chemical appearance

i. Dipstick tests

e. Normal results

i. Colour: colourless to dark yellow

ii. USUALLY, glucose, ketones, proteins, bilirubin are not detectable

iii. Hemoglobin, nitrites, RBC, WBC are not normally found in urine

f. NS results

i. Protein in urine > 100mg/dL (value as high as 1000mg/L are common)

ii. Blood in urine

2. Blood Tests

a. Low levels of the protein albumin (hypoalbuminemia)

i. Below normal range of 3.5~4.5 g/dL

b. Decreased levels of blood protein overall

i. Cause an increase in blood cholesterol & triglycerides

c. Serum creatinine and blood urea nitrogen (BUN)

i. Assess overall kidney function

ii. Normal adult serum creatinine level is ~ 1mg/dL

3. Kidney biopsy

a. Detects underlying cause and extent of disease

Imaging studies (no routine imaging for patients with NS)

1. Ultrasound

a. Normal to slightly enlarged kidney

b. Determine whether patient possesses 2 kidneys

i. 1 kidney à prone to developing focal glomerulosclerosis

ii. Contraindication to kidney biopsy

c. Demonstrate their echogenicity

i. Increased echogenicity à intrarenal fibrosis (chronic disease with reduced kidney function)

Other tests

1. Infants with NS, genetic testing for NPHS1 & NPHS2 mutation

2. In adults, tests for hepatitis B, C, HIV, or sysphilis

References:

http://www.mayoclinic.com/health/nephrotic-syndrome/DS01047/DSECTION=tests-and-diagnosis

http://emedicine.medscape.com/article/244631-diagnosis

http://www.nlm.nih.gov/medlineplus/ency/article/000490.htm

http://www.nephroticsyndrome.com/app/investigations.asp

Prognosis of Nephrotic Syndrome

Prognosis

• The prognosis for patients with primary nephrotic syndrome depends on its cause.
• The prognosis with congenital nephrotic syndrome is bad. Survival beyond several months is possible only with dialysis and kidney transplantation.
• Only approximately 20% of patients with focal glomerulosclerosis undergo remission of proteinuria; an additional 10% improve but remain proteinuric. Many patients experience frequent relapses, become steroid-dependent, or become steroid-resistant. End-stage renal disease develops in 25-30% of patients with FSGS by 5 years and in 30-40% of these patients by 10 years.
• The prognosis for children with minimal-change nephropathy is very good.
• Most children respond to steroid therapy; still, about 50% of children have 1 or 2 relapses within 5 years and approximately 20% of them continue to relapse 10 years after diagnosis. Only 30% of children never have a relapse after the initial episode. Approximately 3% of patients who initially respond to steroids become steroid-resistant.
• Poor patient response to steroid therapy may predict a poor outcome, and children who present with hematuria and hypertension are more likely to be steroid-resistant and have a poorer prognosis than are those who do not present with these conditions.
• In adult nephrotic syndrome, there is a similar variability according to the underlying cause.
• In adult minimal-change nephropathy, there is a burden of relapse similar to that of children. However, the long-term prognosis for kidney function in patients with this disease is excellent, with little risk of renal failure.
• As noted, the prognosis of membranous nephropathy is good in terms of patient survival, being the same as that of the unaffected population.
• In diabetic nephropathy with nephrotic syndrome, there is usually a good response to angiotensin blockade, with reduction of proteinuria to low, sub-nephrotic levels. However, true remission is uncommon. Cardiovascular morbidity and mortality increase as kidney function declines, and some subjects will eventually need dialysis or a kidney transplant.
• In primary amyloidosis, prognosis is not good, even with intensive chemotherapy. In secondary amyloidosis, remission of the underlying cause, such as rheumatoid arthritis, is followed by remission of the amyloidosis and its associated nephrotic syndrome.