Case Presentation Generalized EdemaDania Alsarheed Fatima siddiquiSeham abdulkader Supervised by :fahad alobaid

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.

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)

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.

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

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

Deferential diagnosis of edema

nephrotic syndrome include there causes:• Minimal-change nephropathy • Focal glomerulosclerosis • Membranous nephropathy • Hereditary nephropathiesSystemic disease SLE amylidosis DM

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

Nephritic and nephrotic

Minimal change disease

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.

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..

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.

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?

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

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,

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

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.

How do you investigate the current problem?

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

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.

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?

Cushing Syndrome

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

Other Complications;

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 

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 hemodynamicsHigher-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

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.

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.

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.

Case 2

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.

What is the most likely cause of the patient presentation?

Nephritic Syndrome

Renal salt & water

retentionSudden

hematuria

Proteinuria >3.5 g\day

RBC castsHypertension

Edema

Azotemia \ oliguria

<GFR

DDx Poststreptococcal Glomerulonephritis IgA Nephopathy MPGNBack 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.

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)

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

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)

Renal biopsy

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

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).

Electron microscopy

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.

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

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 

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.

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.