nephrotic and nephritic syndrome

1. Case Presentation
Generalized Edema
Dania Alsarheed
Fatima siddiqui
Seham abdulkader
Supervised by :fahad alobaid

2.  Case 1:
 A 19-year-old woman is evaluated for a 3-month history of
periorbital edema, ankle edema that worsens towards the end of
the day, and foamy urine. Medical history is unremarkable, and she
takes no medications.

3. What should we ask more ?
 SOB and/or chest pain (cardiopulmonary /Thromboemboli)
 Changes in urine output (renal)
 Abdominal discomfort and bloating (hepatic
congestion/ascites)
 Back pain or weight loss (malignancy)
 Changes in sodium intake (not typically cause oedema alone)
 long-standing diabetes
 Butterfly rash or arthralgia (SLE)
 Previously known kidney disease
 Medications (NSAIDs, lithium, gold, or penicillamine)

4.  On physical examination, temperature is normal, blood pressure is
112/70 mm Hg, pulse rate is 70/min, and respiration rate is 12/min.
There is 2+ bilateral pedal edema 4+ protein.

5.  laboratory studies:
 Serum creatinine 0.8 mg/dL (70.7 µmol/L)
 Urinalysis 4+ protein; no blood; no bacteria
 Urine protein-creatinine ratio 10 mg/mg

6. Further investigations
 CBC
 Coagulation profile
 Renal function ( BUN, creatinine, GFR)
 LFTs ( abnormalities in liver)
 Lipid profile
 Hg (decreased in malabsorption)
 Serum albumin (decreased with nephrotic syndrome, liver disease,
malabsorption and malnutrition)
 Renal US and biopsy ( to determine the cause of nephrotic syndrome
in adults)
 Echocardiography
 Liver biopsy
 Lymphangiography

7. Deferential diagnosis of edema
nephrotic syndrome include there causes:
• Minimal-change nephropathy
• Focal glomerulosclerosis
• Membranous nephropathy
• Hereditary nephropathies
Systemic disease
 SLE
 amylidosis
 DM

8. Kideny biopsy was done and shows..
 Electron microscopy of the specimen reveals diffuse foot
process effacement. Light microscopy is normal.
Immunofluorescence testing shows no immune complex deposits

9. Nephritic and nephrotic

10. Minimal change disease

12. Management of minimal change disease
 In patients who have minimal change disease (MCD) based on clinical and
laboratory findings, empiric therapy with oral prednisone is recommended to
avoid the renal biopsy.
 We start with oral prednisone at a dose of 60 mg/m2 per day (maximum of
60 mg/day). When proteinuria disappears, prednisone is continued at the
same daily dose for 30 days, followed by alternate day therapy (at the same
dose). Alternate day therapy is tapered over a one to two-month period.

13. Patients who are frequent relapsers and/or are steroid-dependent, often
develop evidence of steroid toxicity. In these patients, we recommend
treatment with a nonsteroidal agent to maintain remission while reducing
steroid dosing and toxicity.
The initial steroid-sparing agent of choice is levamisole, if it is available. If
not than, mycophenolate mofetil (MMF) is preferred drug for patients with
significant steroid toxicity.
Contd..

14. Management
 Other experts in the field have suggested the use of a 12-week course of
cyclophosphamide in patients with frequently relapsing NS, but do not
recommend this regimen in those with steroid-dependent NS, as the long-
term remission rate is much lower and does not warrant the significant
potential toxicity.
 Ten percent of children will fail to respond to steroid therapy. These children
with steroid-resistant NS are at increased risk for developing end-stage renal
disease.

15.  You have started the patient on the appropriate treatment and
1 week later she presented to emergency room with flank pain
and frank hematuria.
 What is the most likely cause of her current presentation?

16. Complications of the disease
Complications in patients result from abnormalities directly related to
the nephrotic syndrome and secondarily from therapy used for its
treatment.
The five major complications directly related to the underlying
nephrotic syndrome are:
●Infection
●Thromboembolism
●Renal insufficiency
●Anasarca
●Hypovolemia

17. Complications
 INFECTION — patients with nephrotic syndrome are at
increased risk of infection. The following factors may
contribute to this problem:
 Reduced serum concentrations of immunoglobulin G (IgG)
 Impaired ability to make specific antibodies
 Decreased levels of the alternative complement pathway
factors
 Immunosuppressive therapy
 Bacterial infection — encapsulated bacteria.
 Varicella — Viral infections,

18. complication
 THROMBOEMBOLISM — Several factors contribute to an
increased risk of thromboembolic complications in patients
with nephrotic syndrome:
 The nephrotic syndrome is associated with a hypercoagulable
state due to thrombocytosis, and hemostatic abnormalities
including decreased levels of anti-thrombin III, free protein S,
and plasminogen (due to urinary losses), increased levels of
procoagulant proteins (fibrinogen, and factors V and VIII), and
increased platelet activation

19. Complications
 Both arterial and venous thromboses have been reported in
patients with nephrotic syndrome. The most common sites
include the pulmonary artery, renal vein, deep leg veins,
inferior vena cava, and femoral/iliac artery.
 ●Renal vein thrombosis: some patients develop acute
complete venous occlusion, which is characterized clinically by
the sudden onset of macroscopic hematuria, flank
pain and/or tenderness, and, in patients with bilateral disease,
acute renal failure.

20. How do you investigate the current
problem?

21. RVT
Doppler ultrasonography shows an increase in
kidney size and the absence of blood flow in the
renal vein.
 The gold standrded diagnostic test
 Selective renal venography
 Other less invasive tests
 Doppler ultrasound
 Spiral CT with contrast
 MRI

22. Management
 HYPERCOAGULABILITY — Nephrotic patients with severe
hypoalbuminemia are at risk for thromboembolic complications.
 Preventative measures include regular ambulation, avoidance of
hemoconcentration resulting from hypovolemia, avoidance of central venous
catheter if possible, and early treatment of sepsis or volume depletion.
 Treatment of venous thromboembolism — Anticoagulation with low
molecular weight heparin, such as enoxaparin, at a starting dose of
1 mg/kg given every 12 hours. It can be given subcutaneously.

23. Back to our case; follow up
 Patient was started with proper management and continued taking her
medication, Presented to follow up, this time the patient had a negative
dipstick but she has moon face, acne and swelling in the back of the
neck.
 What is the cause of her clinical finding?
 What are other complications?

24. Cushing Syndrome

26. Exogenous Cushing`s Syndrome
 HPA axis suppression — Both endogenous and exogenous
glucocorticoids exert negative feedback control on the hypothalamic-
pituitary-adrenal axis by suppressing hypothalamic corticotropin-releasing
hormone (CRH) production and pituitary corticotropin (ACTH) secretion.
This leads to adrenal atrophy and loss of cortisol secretory capability.
 suppression of hypothalamic-pituitary-adrenal function include:
 ●Anyone who has received more than 20 mg of prednisone a day for more
than three weeks.
 ●Any patient who has clinical Cushing's syndrome

27. Other Complications;

28. Complications
 Skin and soft tissues — skin thinning and purpura.
 Cushingoid appearance and weight gain — The development of Cushingoid
features (redistribution of body fat with truncal obesity, buffalo hump, and moon
face) and weight gain
 Eye — The risk of both cataracts and glaucoma is increased in patients on
glucocorticoids and is dose-related.
 Cardiovascular disease — Glucocorticoid use is associated with an increased
risk of serious adverse cardiovascular events, particularly ischemic heart disease
and heart failure
 Lipids — The effect of glucocorticoids on atherosclerotic vascular disease

29. Complications

Gastrointestinal tract — Glucocorticoids independently increase the risk for a
number of adverse gastrointestinal events, such as gastritis, ulcer formation, and
gastrointestinal bleeding.
 Pancreatitis — The role of glucocorticoids in causing acute pancreatitis is uncertain.
 Kidney and systemic hemodynamics
Higher-dose glucocorticoids commonly promote fluid retention,
 Glucocorticoid therapy can raise the blood pressure in both normotensive and
hypertensive subjects.
 Genitourinary system — High doses of glucocorticoids can cause menstrual
irregularities in women and can lower fertility in both men and women.
 Pregnancy — Glucocorticoid use in pregnancy may increase the risk of cleft palate
in offspring

30.  Musculoskeletal
 Osteoporosis — One of the more serious glucocorticoid-induced AEs is
osteoporosis, which is discussed in detail elsewhere
 Vertebral fractures —
 Osteonecrosis — Osteonecrosis (avascular or ischemic necrosis of bone)
 Growth in children — Growth impairment is commonly seen in children
receiving glucocorticoids. The effect is most pronounced with daily therapy.
 Muscle weakness —It typically presents as proximal motor weakness in both
the upper and lower extremities.
 Central nervous system — emotional lability, depression, psychosis, delirium,
confusion, and cognitive changes including. memory deficits may occur.

31. 
Glucose metabolism — Glucocorticoids cause a dose-dependent, usually mild
increase in fasting glucose levels and a greater increase in postprandial values in
patients without preexisting diabetes mellitus,
 infection and immune response — Systemic glucocorticoids have many effects
upon innate and acquired immunity that predispose to infection, resulting in a dose-
dependent increase in the risk of infection, especially with common bacterial, viral,
and fungal pathogens.
 Neutrophilia — Pharmacologic doses of glucocorticoids often result in an increased
white blood cell count (leukocytosis) that is due primarily to an increase in neutrophils
(neutrophilia). This phenomenon is due to a decreased proportion of neutrophils that
are adhering to the endothelium.

32. Management:
MINIMIZING GLUCOCORTICOID SIDE EFFECTS —
In addition to minimizing the exposure to glucocorticoids,
certain measures may decrease their undesirable side effects.
●Exercise programs may reduce the risk of myopathy and
osteoporosis.
●Exercise, calcium, vitamin D, bisphosphonates and, in
postmenopausal women, estrogen therapy, may minimize
glucocorticoid-induced lumbar vertebral bone mineral loss, but
none of these treatments appear to prevent loss from the
femoral neck or distal radius.

33. Case 2

34. History and physical
 A 19-year-old man is evaluated for red urine sudden-onset
periorbital and pretibial edema. Three weeks ago, he was
diagnosed with tonsillitis that has since resolved.
 On physical examination, blood pressure is 150/100 mm Hg.
Cardiac examination reveals a normal S1 to S2. There are crackles
in both lung bases. There is bilateral pitting tibial edema. There are
no rashes.
 Laboratory studies Urine analysis 1+ protein
 several dysmorphic erythrocytes
 erythrocyte casts/hpf.

35. What is the most likely cause of the patient
presentation?
Nephritic
Syndrome
Renal salt &
water
retention
Sudden
hematuria
Proteinuria
>3.5 gday
RBC casts
Hypertensio
n
Edema
Azotemia
oliguria
<GFR

36. DDx
 Poststreptococcal Glomerulonephritis
 IgA Nephopathy
 MPGN
Back to the patient's story:
 Three weeks ago He was diagnosed with tonsillitis!
INFECTION RELATED GLOMUERULONEPHRITIS
 Most common organism
Group A B-hemolytic streptococci
Other causes :
Bacterial :pnemococcal pnemonia, Salmonella , E-coli.
Viral : Hep b&c ,mumps , HIV (FSGS)
Parasitic : malaria, Schistosoma.

37. Investigations
 Urinalysis ( test of choice)
 Serology
 Biopsy ( most accurate but not routinely done)
 Light microscopy
 Immunofluorescence
 Other tests should include the following:
 Complete blood count (CBC)
 Blood urea nitrogen (BUN), serum creatinine, and serum
electrolytes (especially serum potassium)
 Erythrocyte sedimentation rate (ESR)
 Complement levels (C3, C4, CH50)

38. Urinalysis and chemistry
 In a nephritic syndrome patient, UA will show:
Dysmorphic RBCs,
RBCs casts
Proteinuria
 Urine electrolyte, urine sodium, and fractional excretion of sodium
(FENa) assays are needed to assess salt avidity, rise in serum
creatinine

39. Serology
 Elevated titers of antibodies to extracellular streptococcal products is evidence
of a recent GAS infection:
The Streptozyme test includes the following antibodies:
Anti-streptolysin (ASO)
Anti-DNAse B antibodies
Anti-hyaluronidase (AHase)
Anti-streptokinase (ASKase)
Anti-nicotinamide-adenine dinucleotidase (anti-NAD)

40. Renal biopsy

41. Light microscopy
 Diffuse proliferative
glomerulonephritis with prominent
endocapillary proliferation and
numerous neutrophils
 Trichrome stain may show small
sub-epithelial hump-shaped
deposits
  Endocapillary hypercellularity
with numerous neutrophils –
HYPERCELLULAR GLOMERULI

42. Immunofluorescence
 Deposition of immunoglobulin
G (IgG) and C3 distributed in a
diffuse granular pattern within
the mesangium and glomerular
capillary walls.
 Other immune reactants (eg,
IgM, IgA, fibrin, and other
complement components) may
also be detected.
Starry sky pattern: coarse granular
pattern of staining (mesangial
subepithelial and subendothelial
deposits).

43. Electron microscopy

44. Management
 There is no specific therapy for poststreptococcal
glomerulonephritis (PSGN). There is no evidence that
aggressive immunosuppressive therapy has a beneficial
effect in patients with rapidly progressive crescentic disease.
However, patients with more than 30 percent crescents on
renal biopsy are often treated with methylprednisolone pulses.
 Management is supportive and is focused on treating the
clinical manifestations of the disease, particularly
complications due to volume overload. These include
hypertension and, less commonly, pulmonary edema. General
measures include sodium and water restriction and loop
diuretics.

45. Management
 Loop diuretics generally provide a prompt diuresis with
reduction of blood pressure and edema. In our practice,
intravenous furosemide is given at an initial dose of
1mg/kg (maximum 40 mg).
 Infrequently, patients have hypertensive encephalopathy due
to severe hypertension. These patients should be treated
emergently to reduce their blood pressure. Oral nifedipine or
parenteral nicardipine are effective, while angiotensin-
converting enzyme inhibitors should be used with caution due
to the risk of hyperkalemia

46. Complication
 Patients with PSGN have variable reductions in renal
function, and some patients require dialysis during the acute
episode.
 Patients with evidence of persistent group A streptococcal
infection should be given a course of antibiotic therapy.
 In severe cases with nephrotic range proteinuria, this degree
of proteinuria may persist for six months or more, long after
the hematuria has disappeared.
 Recurrence — Recurrent episodes of PSGN are rare. This
may be due to the long-term persistence of antibodies to
nephritis-associated streptococcal antigens

47. Complication
 These late renal complications are associated with
glomerulosclerosis on renal biopsy, which is thought to be
hemodynamically mediated.
 It is possible that, in those patients who develop
glomerulosclerosis, renal damage can be prevented by
antihypertensive therapy (preferentially with an angiotensin-
converting enzyme inhibitor).
 Acute PSGN is prevented by early antibiotic treatment, and the
spread of nephritis-associated streptococcal infection is contained
by prophylactic antibiotic treatment to individuals at risk.

48. Prognosis
 PROGNOSIS — Most patients, particularly children, have an
excellent outcome. This is true even in patients who present
with acute renal failure and may have crescents on the initial
renal biopsy.
 However, the long-term prognosis of PSGN is not always
benign. Some patients, particularly adults, develop
hypertension, recurrent proteinuria (with a relatively normal
urine sediment), and renal insufficiency as long as 10 to 40
years after the initial illness.