Nephrotic Syndrome Flashcards
What is the thing to remember about nephrotic syndrome?
The thing to remember for this one is massive proteinuria.
What does this massive proteinuria lead to in nephrotic pts?
hypoalbuminemia -they are peeing out albumin!
Why does hypoalbumemia result in edema?
the oncotic pressure in the blood goes down, and fluid leaks out of the vasculature into the surrounding tissue
What is the fourth feature of nephrotic syndrome (first three- massive prorteinuria, hypoalbuminemia, edema)?
Why does this occur?
hyperlipidemia/hyperlipiduria
Liver is trying to compensate for the loss of protein so its making lipids for this reason.
- Hemodynamic changes cause what kind of changes in the GFR?
- How does this manifest clinically? 2
- a decreased glomerular filtration rate
2. (manifested clinically as oliguria and azotemia).
The hypertension seen in nephritic syndrome is probably a result of what?
2
- fluid retention and
2. increased renin released from ischemic kidneys
Nephrotic Syndrome–Features
5
- Proteinuria—(>3.5 g in 24 hrs)
- Edema
- Hypoalbinemia—(less than 3.0)
- Usually: Hyperlipidemia/hyperlipiduria
- [Glomerulopathy—proteinuria without the rest]
What is the most common disease in nephrotic syndrome in children?
Primarily—Minimal Change Disease (MCD)
Nephritic Syndrome–Features
4
- Hematuria—RBC casts
- Oliguria
- Azotemia
- HTN
Nephrotic syndrome is Defined by the presence of?
5
- Heavy proteinuria** (albuminuria greater than 3.5 g/24 hours)
- Hypoalbuminemia** (less than 3.0 g/dL)
- Peripheral edema***
- Hyperlipidemia and thrombotic disease
- Few cells or casts in the urine
Etiologies in adults?
6
Adults
- Systemic diseases such as diabetes mellitus, amyloidosis, HIV and SLE [Lupus] (30%) in adults
- NSAIDs
- Minimal Change Disease (MCD)
- Segmental Focal
- Glomerulosclerosis (SFG)
- Membranous Nephropathy
Nephrotic Syndrome Pathophysiology
6 steps
- glomerular damage
- increased permeability of glomerular capillaries to protein
- Proteinuria leads to less protein in the blood
- Hypoproteinuria leads to increase in plasma oncotic pressure
- this decreases plasma volume, GFR
- Aldosterone is secreted and fluid is retained
Name the steps that must occur to reach nephrotic syndrome?
6
1. Massive proteinuria leads to 2. Decrease in plasma proteins leads to 3. Fluid shift leads to 4. decrease in plasma volume leads to 5. Decrease in GFR leads to 6. Increase aldosterone secretion which will also promote edema
What is the function of the glomerular capillary wall?
2
- Electrostatically prevents negatively charged proteins from passing through
- Podocyte intercellular junctions restrict the passage of proteins of certain molecular weight sizes
Most nephrotic disease there is damage to the GCW that results in?
2
- Loss of charge to prevent proteins from passing
2. Damage to podocyte structure so loss of selection due to size restriction
What is proteinuria?
Increased filtration of macromolecules across the glomerular capillary wall**
What proteins are lost? 5
This protein loss results in what? 3
- Albumin
- Clotting factors
- Transferrin
- Immunoglobulins
- Vitamin D binding Protein
- Results in decreased levels of
Vitamin D - This decreases serum calcium levels
- Which raises the level of PTH
- Hypoalbinemia is partially due to what?
- Also thought that albumin is catabolized where?
- The low oncotic pressure stimulates what?
- Partially due to loss of albumin through the glomeruli
- Also thought that albumin is catabolized in the proximal tubular cells of the kidney
- hepatic lipoprotein synthesis leading to hyperlipidemia
- How Does nephrotic syndrome affect LDL, TGC, HDL levels?
- How does nephrotic syndrome affect hepatic syntheis and peripheral metabolism?
- This all increases the risk of what?
- What will we find in the urine at this point? (what are these called?)
- Elevated levels of LDL and triglycerides (HDL usually normal)
- Increased hepatic synthesis and decreased peripheral metabolism
- Increases risk of cardiovascular disease*
- Lipiduria (presence of oval fat bodies in urine)
Minimal Change Disease:
1. Can occur in adults secondary to use of what?
- What will you find in Minimal change that is different from other forms of Nephrotic syndrome? 3
- NSAIDS
- Find only mild mesangial cell proliferation
- No immune deposits
- Flattened podocytes
Etiologies of MCD
5
- Infections
- Drugs
- Tumors
- Allergies
- Other diseases
- What drugs can cause MCD? 3
- What kind of tumors can cause MCD? 2
- What kind of allergies can cause MCD? 3
- WHta other diseases can cause MCD? 2
- NSAIDS
- Lithium
- Ampicilln
- Hodgkin’s
- Leukemia
- food
- bee stings
- pollens
- Following allogenic stem cell for leukemia
- Following hematopoietic cell transplantation
Treatment for MCD?
steriods/prednisone
- Most common lesion found in those with idiopathic nephrotic syndrome 35% of the time [Blacks—50%] is what?
- What is this disease characterized by? 2
- What are the two forms?
- Focal Segmental Glomerulosclerosis (FSGS):
- Characterized by the presence in SOME glomeruli of segmental areas of
- mesangial collapse and
- SCLEROSIS - Can be primary and secondary forms
Secondary Causes of FSGS
6
- HIV infection
- Obesity
- Lupus
- Diabetes
- Chemicals that harm the kidneys
- Meds
Most common cause of nephrotic syndrome in adults?
Membranous Nephropathy
Membranous Nephropathy Characterized by: 3
-What is this caused by primarily?
- Basement membrane thickening w/ little infiltration
- Deposition of immune complexes on the basement membrane
- Electron dense deposits along the basement membrane
-Primarily idiopathic may be due to autoantibodies
Secondary causes of membranous nephropathy?
5
- Hep B antigenemia and also Hep C
- Autoimmune diseases such as 3. Lupus
- Cancer
- Drugs
What drugs could cause secondary membranous nephropathy? 3
- Gold
- Captopril
- NSAIDS
Why is the glomerular basement membrane thickened in membranous nephropathy?
immune complex deposition
Nephrotic Syndrome–Complications
(two most important to think about)
9
- Hypovolemia** (fluid in the third space and not the vasculature)
- Infection*** (biggest source of complications and death-immunocomprimised)
- Edema
- Hypertension
- Acute renal failure
- Protein malnutrition
- Thromboembolism
- Deficiency of vitamin D and hypocalcemia
- Increased risk for development of atherosclerosis
Nephrotic Syndrome diagnosis?
3
- 24 hour urine (Excreting more than 3.5 g/24 hrs.)
- Renal biopsy—for definitive diagnosis!
- MAY want to do serologic studies
Contraindications to renal biopsy:
for nephrotic syndrome?
7
- Uncorrectable bleeding diathesis
- Small kidneys (indicate chronic irreversible disease)
- Uncontrolled, severe HTN
- Bilateral cystic kidneys or renal tumor
- Hydronephrosis
- Renal or peri-renal infection
- Uncooperative patient
For a nephrotic syndrome diagnosis, name some Serologic studies (that MAY be run)?
7
- ANA
- Complement
- Serum or urine protein electrophoresis
- Syphilis
- Hep B and C serology’s
- Measurement of cryoglobulins
- Antistreptococcal antibodies
Treatment of proteinuria in Nephrotic syndrome pts? 2
What needs to be monitored for this?
Why do these things need to be monitored?
- ACE inhibitors/ARBs (best first step)
- Protein restriction NOT recommended as evidence is unclear about usefulness and because protein losses are so heavy the patient may have malnutrition
- Serum Cr and K+ level should be carefully monitored
- These decrease the intraglomerular pressure
How would we treat edema in nephrotic syndrome pts? 2
On what kind of timeline do we want to reverse edema? Why?
- Dietary sodium restriction
- Loop diuretics
Edema should be reversed slowly to prevent acute hypovolemia!
Hyperlipidemia treatment in nephrotic syndrome? 2
- Lipid abnormalities reverse with resolution of the disease
- Statins are used initially
- Hypercoagulability
treatment in nephrotic syndrome? - What if the patient does develop thrombosis?
- Not presently recommended to anticoagulate prophylactically
- Heparin bridging therapy with Warfarin. Until their INR is 2-3
Nephrotic Disease from Systemic Disorders
9
- Amyloidosis
- Diabetic Nephropathy
- HIV Associated Nephropathy
- Systemic Lupus Erythematosus (SLE)
- Hepatitis C
- Multiple Myeloma
- Sickle cell disease
- TB
- Gout
What is amyloidosis?
A group of diseases characterized by the deposition of proteins (amyloid) in organs leading to their destruction and ultimately the death of the patient
Renal amyloidosis:
What causes the Primary type? 2
What causes the Secondary type? 2
Primary:
- Deposition of light chain Ig—AL
- Deposition of heavy chain Ig—AH
Secondary—AA
- Primarily autoimmune disorders
- Some cancers
Pathophysiology of amyloidosis?
amyloid deposition in the mesangium then the capillary loops
- Treatment of amyloidosis? 2
- Remissions can happen if the inciting agent is removed in in what kind of amyloidois?
- Primary progresses to ESRD in how many years?
- What is the five year surivival rate?
- Dialysis
- Treat w/ mephalan (destroy bone marrow) then autologous hematopoietic cell transplantation (If eligible)
- Secondary AA
- 2-3 years
- FIVE-YEAR SURVIVAL is less than 20%
Is the risk higher in for nephropathy in Type 1 or Type 2?
Type II—risk is equal to that in Type I w/ current therapy
Initial screening of diabetics should always include urine screening for what?
Microalbumemia
Microalbumemia is defined as?
How do we collect this? 2
- Defined as 30 – 300 mg/day
- 24 hour urine collection is the accepted standard to confirm
- Special testing strips to detect microalbuminuria
Risk Factors for diabetic nephropathy?
9
- Genetic susceptibility
- Age
- Blood pressure
- GFR
- Race—higher in Blacks and
- Native Americans
- Glycemic control
- Obesity
- Smoking
Diabetic Nephropathy–Pathophysiology
- What causes the glomerularsclerosis? 2
- Hyperglycemia can induce what? How?
- What do we get as a result?
- Production of what adds to the sclerosis? 2
- Intraglomerular HTN
- ischemic injury
- directly mesangial expansion and damage—in part by glycation of matrix proteins
- Circulating advanced glycation end products
- Production of
- cytokines,
- inflammation and endothelial growth factors
Diabetic Nephropathy—Not always do to the diabetes!
Albuminuria in diabetes mellitus is occasionally due to a what? 2
- glomerular disease other than diabetic nephropathy, or to
- nephrosclerosis (from HTN)
The major clinical clues suggesting nondiabetic glomerular disease:
5
- Onset of proteinuria less than five years from the documented onset of type 1 diabetes
- Acute onset of renal disease
- Presence of an active urine sediment containing red cells and cellular casts
- Signs and/or symptoms of another systemic disease
- Significant reduction in the glomerular filtration rate (>30 percent) within two to three months after the administration of ACE inhibitors or ARBS (renal stenosis)
Treatment of Diabetic Nephropathy
5
- Tight glycemic control
- Good BP control with an ACEI or ARB (not both together*)
- Sometimes Na+ restriction/addition of a diuretic
- Weight loss if obese
- Control of hyperlipidemia
HIV Associated Nephropathy
1. What is VERY important in order to confirm this?
- WHat does the pathology show?
- Treatment?
- What treatment has showed variable success? 3
- NEED renal biopsy to confirm
- Pathology shows focal segmental glomerulosclerosis
- Highly active retroantiviral therapy [HAART] for prolonged course has been shown to slow progression
- Steroids with cyclosporine and ACEI have been used with variable success
Systemic Lupus (SLE) 1. There are a variety of renal presentations in SLE but what is the most common?
- What should we monitor this with? 2 And if we have positive findings what should we do?
- Variety of presentations—usually the nephritic type
2. Need to monitor with UA’s and chem panels and if positive findings do a renal biopsy
Systemic Lupus WHO Classification
Describe Type I through V?
Type I Normal Type II Mesangial proliferative Type III Focal and segmental Type IV Diffuse proliferative Type V Membranous nephoprathy
Hepatitis C:
- 3 clinicopathological syndromes associated, but most common is what?
- Clinical manifestations? 4
- What may they exhibit?
- Many have elevated what? 2
- What is a very common finding?
- type I membranoproliferative glomerulonephritis (MPGN)
- Hematuria,
- proteinuria,
- hypertension
- anemia
- May exhibit the nephrotic syndrome
- Many have
- elevated serum transaminases
- RF - Hypocomplementemia very common
Hepatitis C: Treatment: Main indications for therapy
5
Interferon may result in suppression of viremia and improvement in hepatic function:
Renal function rarely improves unless what occurs?
- Poor renal function
- Nephrotic syndrome
- New or worsening hypertension
- Fibrosis on biopsy
- Progressive disease
viral suppression occurs
- Multiple Myeloma is what?
- What % of pts have renal involvement?
- What is a myeloma kidney?
- These cause?
- Where do they precipitate?
- What are they not detected by? - Earliest tubular damage causes what?
- What two metabolic imbalances are commonly seen?
- Malignancy of plasma cells
- Renal involvement in 25% of all patients
- “Myeloma Kidney”:
The presence of light chain immunoglobulins (Bence-Jones protein) in the urine:
-Cause renal toxicity
-Precipitates in the tubules and causes tubular obstruction
-Are NOT detected by dip-sticks for protein - Earliest tubular damage causes Fanconi’s Syndrome (a type II proximal renal tubular acidosis)
- Hypercalcemia and hyperuricemia frequently seen
Other conditions resulting in renal dysfunction may occur in MM pts such as? 2
Therapy? 3
- Plasma cell infiltration of the renal parenchyma
- Hyperviscosity syndrome compromises renal blood flow
- Correction of hypercalcemia
- Volume repletion
- Chemotherapy to treat underlying malignancy
Plasmapheresis does not provide any renal benefit
- Sickle Cell Disease affects the kidney how?
- Congestion and stasis lead to what? 3
- WHat is common? 2
- What kind of damage will we see in the kidney?
- Primary clinical manifestation is what?
- What does treatment require? 2
- Renal dysfunction due to sickling of RBCs in renal medulla
- hemorrhage
- interstitial inflammation
- papillary infarcts
- Hematuria is common
- Isothenuria (urine osmolality equal to that of serum) is routine—patients become easily dehydrated
- Papillary necrosis
- proteinuria
- Treatment require adequate hydration and control of the sickle cell disease
Tuberculosis
1. Classic renal manifestation of TB is the presence of what?
- What are the gold standard for diagnosing this? (how should this be accomplished?)
- WHat are two signs that may occur but are less frequent?
- Renal manifestations resolve with what?
- microscopic pyuria with a sterile urine culture – STERILE PYURIA
- Urine cultures are the “gold standard”
- Do first-morning, mid-stream voided specimens for 3-6 cultures - Papillary necrosis
- cavitation of the renal parenchyma occur less frequently
- adequate drug therapy for the TB
Gout
- Why is the kidney affected in gout so much?
- Patients with proximal tubular dysfunction have what problems with uric acid?
- Deposition of crystals can occur where? 3
- What are the two “pathologies” of the disease that this is seen in?
- Kidney is the primary organ for excretion of uric acid
- decreased excretion of uric acid and are more prone to gouty attacks
- in the tubules,
- interstitium
- urinary tract
- Disorder seen in both “overproducers” and “underexcretors” of uric acid
Treatment for kidneys affected by gout?
3
(two drugs)
- Avoid foods and drugs that cause hyperuricemia
- Aggressive hydration
- Pharmacotherapy aimed at reducing serum uric acid levels
- Allopurinol,
- colchicine
What foods cause hyperuricemia? 6
Drugs that cause hyperurecemia? 3
- Bacon,
- sardines,
- liver,
- sweetbreads,
5, bread, - wine
- Diuretics,
- theophylline,
- ascorbic acid
