Nephrotic syndrome (Nephrosis)

DEFINITION:

Nephrotic syndrome is a group of symptoms including protein in the urine (more than 3.5 grams per day), low blood protein levels, high cholesterol levels, high triglyceride levels, and swelling.

Autoimmune process leading to structural alteration of glomerular membrane that results in increased permeability to plasma proteins, particulary albumin.

Nephrotic syndrome is a disorder of the glomeruli (clusters of microscopic blood vessels in the kidneys that have small pores through which blood is filtered) in which excessive amounts of protein are excreted in the urine. This typically leads to accumulation of fluid in the body (edema) and low levels of the protein albumin and high levels of fats in the blood.

Nephrotic syndrome is not a specific glomerular disease but a cluster of clinical findings, including:Marked increase in protein (particularly albumin) in the urine (proteinuria), Decrease in albumin in the blood (hypoalbuminemia), Edema, High serum cholesterol and low-density lipoproteins (hyperlipidemia).

ANATOMY AND PHYSIOLOGY:

The organs, tubes, muscles, and nerves that work together to create, store, and carry urine are the urinary system. The urinary system includes two kidneys, two ureters, the bladder, two sphincter muscles, and the urethra.

Your body takes nutrients from food and uses them to maintain all bodily functions including energy and self-repair. After your body has taken what it needs from the food, waste products are left behind in the blood and in the bowel. The urinary system works with the lungs, skin, and intestines—all of which also excrete wastes—to keep the chemicals and water in your body balanced. Adults eliminate about a quart and a half of urine each day. The amount depends on many factors, especially the amounts of fluid and food a person consumes and how much fluid is lost through sweat and breathing. Certain types of medications can also affect the amount of urine eliminated.

The urinary system removes a type of waste called urea from your blood. Urea is produced when foods containing protein, such as meat, poultry, and certain vegetables, are broken down in the body. Urea is carried in the bloodstream to the kidneys.

The kidneys are bean-shaped organs about the size of your fists. They are near the middle of the back, just below the rib cage. The kidneys remove urea from the blood through tiny filtering units called nephrons. Each nephron consists of a ball formed of small blood capillaries, called a glomerulus, and a small tube called a renal tubule. Urea, together with water and other waste substances, forms the urine as it passes through the nephrons and down the renal tubules of the kidney.

From the kidneys, urine travels down two thin tubes called ureters to the bladder. The ureters are about 8 to 10 inches long. Muscles in the ureter walls constantly tighten and relax to force urine downward away from the kidneys. If urine is allowed to stand still, or back up, a kidney infection can develop. Small amounts of urine are emptied into the bladder from the ureters about every 10 to 15 seconds.

The bladder is a hollow muscular organ shaped like a balloon. It sits in your pelvis and is held in place by ligaments attached to other organs and the pelvic bones. The bladder stores urine until you are ready to go to the bathroom to empty it. It swells into a round shape when it is full and gets smaller when empty. If the urinary system is healthy, the bladder can hold up to 16 ounces (2 cups) of urine comfortably for 2 to 5 hours.

Circular muscles called sphincters help keep urine from leaking. The sphincter muscles close tightly like a rubber band around the opening of the bladder into the urethra, the tube that allows urine to pass outside the body.

Nerves in the bladder tell you when it is time to urinate, or empty your bladder. As the bladder first fills with urine, you may notice a feeling that you need to urinate. The sensation to urinate becomes stronger as the bladder continues to fill and reaches its limit. At that point, nerves from the bladder send a message to the brain that the bladder is full, and your urge to empty your bladder intensifies.

When you urinate, the brain signals the bladder muscles to tighten, squeezing urine out of the bladder. At the same time, the brain signals the sphincter muscles to relax. As these muscles relax, urine exits the bladder through the urethra. When all the signals occur in the correct order, normal urination occurs.

Problems in the urinary system can be caused by aging, illness, or injury. As you get older, changes in the kidneys’ structure cause them to lose some of their ability to remove wastes from the blood. Also, the muscles in your ureters, bladder, and urethra tend to lose some of their strength. You may have more urinary infections because the bladder muscles do not tighten enough to empty your bladder completely. A decrease in strength of muscles of the sphincters and the pelvis can also cause incontinence, the unwanted leakage of urine. Illness or injury can also prevent the kidneys from filtering the blood completely or block the passage of urine.

PREDISPOSINGFACTOR RATIONALEAge Children ages 1 1⁄2 and 4 yr are predisposed in having nephrotic syndrome.Sex Males are more predisposed than males in acquiring nephrotic syndrome.Genetics People with family history of nephrotic syndrome increases likelihood of

developing nephrotic syndrome.

PRECIPITATINGFACTOR RATIONALEFocal segmentalglomerulosclerosis> HIV/AIDS> Nephrectomy

Most common cause of idiopathic NS among adults. May be secondary to HIV/AIDS infection or loss of nephrons.

Membranous nephropathy> Hepatitis B infection> SLE> Cancer

Deposition of immune complexes on the glomerular basement membrane causing it to thicken. It can be secondary to certain cancers, Hepatitis B infections and autoimmune disorders such as SLE.

Minimal change disease

Causes 80 to 90% of childhood nephrotic syndrome in children 4 to 8 years of age idiopathic in nature.

Diabetes Mellitus Prolonged elevated blood glucose levels alters glomerular base membranes thereby causing impaired renal function.

Drugs> Heroin> NSAID> Gold> Penicillamine

These drugs can contribute to the development of focal segmental glomerulosclerosis, membranous nephropathy and minimal change disease which in turn precipitate occurrence of nephrotic syndrome.

SYMPTOMSLEGEND SYMPTOM RATIONALES1 Albuminuria In nephrotic syndrome the podocytes are damaged and very

permeable allowing albumin from the blood to escape and be excreted out the body along with urine.

S2 Edema Edema is the result of fluid shifting from the intravascular space to the interstitial space due to the decrease intravascular pressure.

S3 Hyperlipidemia Results due to the increased production of lipoproteins by the liver in response to the low levels of albumin in the blood.

S4 Hypoalbuminemia In nephrotic syndrome the podocytes are damaged and very permeable allowing albumin from the blood to escape and be excreted out the body along with urine.

MEDICAL MANAGEMENT

1. fluid and sodium restriction, oral or intravenous diuretics, and angiotensin-converting enzyme inhibitors.

Fluid and sodium restrictions

Creating a negative sodium balance will help reduce edema, presumably as the underlying illness is treated or as renal inflammation slowly resolves. Patients should limit their sodium intake to 3 g per day, and may need to restrict fluid intake (to less than approximately 1.5 L per day). Large

doses (e.g., 80 to 120 mg of furosemide) are often required,14 and these drugs typically must be given intravenously because of the poor absorption of oral drugs caused by intestinal edema.3 Low serum albumin levels also limit diuretic effectiveness and necessitate higher doses. Thiazide diuretics, potassium-sparing diuretics, or metolazone (Zaroxolyn) may be useful as adjunctive or synergistic diuretics.

Diuretics

"Diuretics are the mainstay of medical management; however, there is no evidence to guide drug selection or dosage," Dr. Kodner writes. "Based on expert opinion, diuresis should aim for a target weight loss of 1 to 2 lb (0.5 to 1 kg) per day to avoid acute renal failure or electrolyte disorders. Loop diuretics, such as furosemide (Lasix) or bumetanide, are most commonly used."

Angiotensin-converting enzyme

In persons with nephrotic syndrome, angiotensin-converting enzyme inhibitors have been shown to decrease proteinuria and lower the risk for progression to renal disease.

Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce pro-teinuria and reduce the risk of progression to renal disease in persons with nephrotic syndrome.15,16 One study found no improvement in response when corticosteroid treatment was added to treatment with ACE inhibitors.17 The recommended dosage is unclear, and enalapril (Vasotec) dosages from 2.5 to 20 mg per day were used. Most persons with nephrotic syndrome should be started on ACE inhibitor treatment to reduce protein-uria, regardless of blood pressure.

* Although corticosteroid treatment may benefit some adults with nephrotic syndrome, research evidence supporting this therapy is limited. At present, intravenous albumin, prophylactic antibiotics, and prophylactic anticoagulation are not advised.

ALBUMIN

Intravenous albumin has been proposed to aid diuresis, because edema may be caused by hypoalbuminemia and resulting oncotic pressures. However, there is no evidence to indicate benefit from treatment with albumin,18 and adverse effects, such as hypertension or pulmonary edema, as well as high cost, limit its use.

CORTICOSTEROIDS

Treatment with corticosteroids remains controversial in the management of nephrotic syndrome in adults. It has no proven benefit, but is recommended in some persons who do not respond to conservative treatment.19,20 Treatment of children with nephrotic syndrome is different, and it is more clearly established that children respond well to corticosteroid treatment.21 Classically, minimal change disease responds better to corticosteroids than FSGS; however, this difference is

found primarily in children with nephrotic syndrome. One older study found that corticosteroid treatment improved proteinuria and renal function in persons with minimal change disease, but not membranous nephropathy or proliferative glomerulonephritis.22 Another small older study found that persons with less severe glomerular changes responded well to corticosteroids.23 One case series in black persons with FSGS found no benefit from corti-costeroid treatment.19 Two Cochrane reviews on the treatment of nephrotic syndrome in adults found no benefit for mortality or need for dialysis with corticosteroid therapy for membranous nephropathy or minimal change disease, but found a weak benefit for disease remission and proteinuria in persons with membranous nephropathy.20,24 However, the findings for minimal change disease were based on only one randomized trial, and the role of corticosteroid treatment remains unclear. Many experts recommend the use of corticosteroids, particularly for persons with minimal change disease1; however, adverse effects from corticosteroids often lead to discontinuation.

Family physicians should discuss with patients and consulting nephrologists whether treatment with corticosteroids is advisable, weighing the uncertain benefits and possibility of adverse effects. Alkylating agents (e.g., cyclophosphamide [Cytoxan]) also have weak evidence for improving disease remission and reducing proteinuria, but may be considered for persons with severe or resistant disease who do not respond to corticosteroids.

LIPID-LOWERING TREATMENT

A Cochrane review is underway to investigate the benefits and harms of lipid-lowering agents in nephrotic syndrome.25 Some evidence suggests an increased risk of athero-genesis or myocardial infarction in persons with nephrotic syndrome, possibly related to increased lipid levels.25 However, the role of treatment for increased lipids is unknown and, at present, the decision to start lipid-lowering therapy in persons with nephrotic syndrome should be made on the same basis as in other patients.

ANTIBIOTICS

There are no data from prospective clinical trials about treatment and prevention of infection in adults with nephrotic syndrome. Given the uncertain risks of infection in adults with nephrotic syndrome in the United States, there are currently no indications for antibiotics or other interventions to prevent infection in this population. Persons who are appropriate candidates should receive pneumococcal vaccination.

ANTICOAGULATION THERAPY

There are currently no recommendations for prophylactic anticoagulation to prevent thromboembolic events in persons with nephrotic syndrome who have not had previous thrombotic events, and clinical practice varies. A Cochrane review is in process.26 Physicians should remain alert for signs or symptoms suggesting thromboembolism and, if it is diagnosed, these events should be treated as in other patients. Persons who are otherwise at high risk of thromboembolism (e.g., based on previous events, known coag-ulopathy) should be considered for prophy-lactic anticoagulation while they have active nephrotic syndrome.

LABORATORY EXAM

1. Proteinuria (predominately albumin) exceeding 3.5 g/day is the hallmark of the diagnosis of nephrotic syndrome.

2. A needle biopsy of the kidney may be performed for histologic examination of renal tissue to confirm the diagnosis.

3. Recent studies have confirmed the usefulness of serum markers as a means of assessing the disease process. Anti-C1q antibodies are the most reliable markers for assessing disease activity.

NURSING DIAGNOSIS Excess fluid volume related to compromised regulatory mechanism with changes in hydrostatic

or oncotic vascular pressure and increased activation of RAAS

Imbalanced nutrition: Less than body requirements related to anorexia, nausea, vomiting, protein catabolism, dietary restrictions and altered oral mucous membranes

Decreased cardiac output related to fluid imbalances affecting circulating volume, myocardial workload and systemic vascular resistance

Risk for infection depression of immunologic defenses

Disturbed body image related to changes in physical appearance

Risk for injury

NURSING MANAGEMENT

Assess and document the location and character of the patient's edema.

Weigh the patient each morning after he voids and before he eats, make sure he's wearing the

same amount of clothing each time you weigh him.

Measure blood pressure with the patient lying down and standing. Immediately report a decrease

in systolic or diastolic pressure exceeding 20 mm Hg.

Monitor intake and output

Ask the dietitian to plan a low-sodium diet with moderate amounts of protein.

Frequently check urine for protein

Provide meticulous skin care to combat the edema that usually occurs with nephrotic syndrome

Use a reduced-pressure mattress or padding to help prevent pressure ulcers.

To prevent the occurrence of thrombophlebitis, encourage activity and exercise, and provide

antiembolism stockings as ordered

Give the patient and family reassurance and support, especially during the acute phase, when

edema is severe and the patient's body image changes

PROGNOSIS

The prognosis varies depending on the cause of the nephrotic syndrome, the person's age, and the type and degree of kidney damage. Symptoms may disappear completely if the nephrotic syndrome is caused by a treatable disorder, such as an infection, cancer, or drugs. This situation occurs in about half the cases in children but less often in adults. If the underlying disorder responds to corticosteroids, sometimes progression of the disease is halted, and less often the condition partially or, rarely, completely reverses. When the syndrome is caused by HIV infection, it usually progresses relentlessly, often resulting in complete kidney failure in 3 or 4 months. Children born with the nephrotic syndrome rarely live beyond their first birthday, although a few have survived by means of dialysis treatments or a kidney transplant.

When the cause is systemic lupus erythematosus or diabetes mellitus, drug treatment often stabilizes or decreases the amount of protein in the urine. However, some people do not respond to drug treatment and develop progressive kidney failure within a few years.

In cases of nephrotic syndrome resulting from conditions such as an infection, allergy, or intravenous heroin use, the prognosis varies, depending on how early and effectively the underlying condition is treated.

Nephrotic syndrome may go away once the underlying cause, if known, has been treated. In children, 80 percent of nephrotic syndrome cases are caused by minimal change disease, which can be successfully treated with prednisone. However, in adults most of the time a kidney disease is the underlying cause, and these diseases cannot be cured.

Good – Fair – Poor Prognosis

Pathophysiology

RAAS – Renin Angiotensin Aldosterone SystemARF – Acute Renal FailureCRF – Chronic Renal FailureESRD – End Stage Renal DiseaseCAD – Coronary Artery DiseaseCVD – CardioVascular Disease

YOU MAY WONDER >>> Q. HOW DOES RAAS LEAD TO ARF???

A. RAAS will eventually be exhausted. Moreover, the RAAS cannot increase vascular volume since there is no albumin to hold the water within the vascular space. Thus the water and sodium reabsorbed will shift into the interstitial space. RAAS will only exacerbate the edema and make the patient more edematous. xD If left untreated then the blood flow to the kidneys(due to decreased intravascular volume) will be compromised causing acute trauma and injury to the nephrons ultimately causing ARF. =) hope this helps.

Damages podocytes

Podocyte pores/slits increase in diameter

Increased permeability of podocytes

Albumin passes through pores

Circulating albumin decreases

Fluid shifts from the vascular to the interstitial spaces

Reduced intravascular pressure

Plasma volume decreases

RAAS

ARF

CRF

ESRD

Pulmonary congestion

Stimulates production of albumin and lipoprotein synthesis

CAD

CVD

Cardiac arrest

Respiratory Arrest

S2

S1

S4 S3

DEATH

PRECIPITATING

PREDISPOSING