IM MINI REVALIDA

CASE:GLOMERULONEPHRITIS
Prepared by: ​CC Peñalba, Kathy Mae & CC Peñamante, Fides Grace

DEFINITION

According to the National Kidney Foundation, glomerulonephritis is a group of diseases that injure the part of the kidney
that filters blood (called glomeruli). When the kidney is injured, it cannot get rid of wastes and extra fluid in the body. If
the illness continues, the kidneys may stop working completely, resulting in kidney failure.

EPIDEMIOLOGY

● In the US
○ GN: 10-15% of glomerular diseases
○ Variable incidence due to the sublicinal nature of disease
○ Decrease in PSGN due to better health care delivery and improved socioeconomic conditions
○ 25-30% of all cases of end-stage renal disease (ESRD)
○ Asymptomatic episodes of PSGN exceed symptomatic episodes by a ratio of 3-4:1.
● Worldwide
○ IgA Nephropathy (Berger disease) is the most common cause of GN
○ PSGN incidence decreased in developed countries
● Postinfectious GN can occur at any age but usually develops in children
○ aged 5-15 years
○ Only 10% >40 years old
● Acute GN predominantly affects males (2:1 male-to-female ratio)
● Postinfectious GN has no predilection for any racial or ethnic group
● A higher incidence (related to poor hygiene) may be observed in some socioeconomic groups.

ETIOLOGY/RISK FACTORS

Pathogenesis is variably linked to:

● Presence of genetic mutations
● Infection
○ Strep throat
○ Viral infections, such as HIV, hepatitis B and hepatitis C
● Toxin exposure
● Autoimmunity
● Atherosclerosis
● Hypertension
● Emboli
● Thrombosis
● Diabetes Mellitus
● Cancer
● Regularly taking more than the recommended dose of non-steroidal anti-inflammatory drugs (NSAIDs), such as
ibuprofen, aspirin or naproxen
● Immune diseases, such as lupus, Goodpasture syndrome and IgA nephropathy
● Vasculitis (a condition that causes irritation to your blood vessels)
● Idiopathic

PATHOPHYSIOLOGY

● Impairs the ability of the glomerulus to selectively filter substances

● May also damage the arterioles (e.g. immunologic reactions)
● There are many forms of glomerular disease with pathogenesis variably linked to the presence of genetic
mutations, infection, toxin exposure, autoimmunity, atherosclerosis, hypertension, emboli, thrombosis, or
diabetes mellitus. Even after careful study, however, the cause often remains unknown, and the lesion is called
idiopathic.

Progression of Glomerular Disease:

Efferent arterioles from inflamed glomeruli carry inflammatory mediators downstream interstitial nephritis and causing
fibrosis → Proteinuria (with activated cytokines and ROS) → Inflammation in and around epithelial cells of the tubules
→ T Lymphocyte macrophage infiltration in the interstitium → Interstitial fibrosis and tubular atrophy (IFTA)

CLINICAL MANIFESTATIONS

(include pertinent PE findings for the diagnosis and how to elicit)

Variable features include
● skin rash, arthralgias, sinusitis (AGBM disease)
● lung hemorrhage (AGBM, ANCA, lupus)
● recent skin infection or pharyngitis (poststreptococcal)
Below is a table that will help you differentiate if the symptoms of the patient is nephritic or nephrotic in origin:
Nephritic Nephrotic

● Hematuria ● Hyperproteinuria (>3g/24hr)

● Hypertension ● Edema
● Edema ● Hyperlipidemia
● Renal insufficiency/Oliguria ● Hypoalbuminemia
Proteinuria presents as bubbly urine that does not dissipate.

DIFFERENTIAL DIAGNOSIS

(identify at least 2 differential diagnoses, and bases)

Serum complement levels may be useful in differentiating the underlying etiology of glomerulonephritis; complement
levels are typically normal in anti-GBM disease and pauci-immune glomerulonephritis but low in immune
complex-mediated glomerulonephritis (with the exception of immunoglobulin A [IgA] nephropathy). However, in
practice, a kidney biopsy is almost always required to secure the diagnosis.

Thrombotic microangiopathy (TMA​)

● In patients with an acute presentation of microangiopathic hemolytic anemia, thrombocytopenia, and kidney
failure, the diagnosis of ​thrombotic microangiopathy (TMA)​ is a clinical one
● Do not need a kidney biopsy to secure the diagnosis. However, patients with subacute and chronic TMA may
exhibit minimal or no hematological or systemic abnormalities but present with progressive kidney failure with or
without proteinuria and hematuria (eg, in drug-induced TMA). Such patients do need to be biopsied to secure
the diagnosis.

Isolated glomerular hematuria

● Persistent glomerular hematuria is distinguished from transient hematuria by repeating the urinalysis over a
period of weeks to months.
● Persistent glomerular hematuria​ is isolated if the patient is asymptomatic (ie, the systemic findings
mentioned above are all absent) and has a normal urine albumin excretion rate, a normal glomerular filtration
rate, normal blood pressure, and if the laboratory tests that are typically obtained to evaluate glomerulonephritis
are all negative.
● Transient hematuria​ is a relatively common finding over time in adults and may be induced by factors such as
exercise or infection.
● Evaluation of isolated glomerular hematuria — In such patients, a careful workup for extrarenal etiologies
should be undertaken, which may include imaging of the upper and lower urinary tract, cystoscopy, and
evaluation for sickle cell disease or trait in appropriate patients. A kidney biopsy is usually not performed in the
absence of proteinuria and/or reduced kidney function, especially if there is a strong family history of hematuria
or kidney disease.

Poststreptococcal Glomerulonephritis
● GN following a streptococcal infection characterized by the sudden appearance of hematuria, proteinuria, red
blood cell casts in the urine, edema, and hypertension with or without oliguria
● Common in children and males
● From infection with nephritogenic streptococcus strain wherein immune complexes containing a streptococcal
antigen is deposited in the affected glomeruli.
● Manifestations:
○ 2-6 weeks after skin infections/Impetigo
○ 1-3 weeks after Pharyngitis
○ Gross Hematuria lasts up to 3 weeks
○ Proteinuria may last up to 6 months
○ Presence of RBC casts
○ Edema
○ HTN that lasts up to 3 weeks
○ Low C3 complement levels for 6 to 8 weeks.
● Diagnosis is usually clinical, renal biopsy rarely required,
○ ASO – for pharyngitis
○ Anti-DNase – for skin infections

IgA Nephropathy (Berger Disease)

● Most common form of glomerulonephritis worldwide
● Male predominance, peak incidence 2nd and 3rd decade of life, rare familial clustering.
● Immune-complex mediated glomerulonephritis characterized by recurrent episodes of hematuria with
mesangial IgA deposits
● Recurrent episodes of macroscopic hematuria during or​ immediately​ following a Respiratory Tract Infection,
persistent asymptomatic microscopic hematuria
● “Synpharyngitic”: Gross hematuria often occurs within 1-2 days of onset of an upper respiratory or
gastrointestinal infection, in contrast with the longer latency period observed in acute postinfectious
 glomerulonephritis

Lupus Nephritis
● Common and serious complication of systemic lupus erythematosus (SLE)
● Genetic predisposition plays in important role, common in females and Asians
● Results from deposition of circulating immune complexes or in situ immune complex formation
● Manifestations: Proteinuria – most common, Hematuria, Casts/sediments, HTN, Renal failure,
Hypocomplementemia

DIAGNOSTIC PLAN

(​Bases of each test, expected findings with normal/reference values)

Urinalysis
● In order to identify hematuria, proteinuria, presence of RBC casts
● R/o possible UTI
○ Check for bacteria, nitrites, leukocyte esterases
● At least 3-5 RBC
● Acute Nephritic Syndrome: 1-2g/24h proteinuria
● Dysmorphic RBC + RBC cast → glomerular injury
○ Isomorphic → extraglomerula (trauma, infection, obstruction, mass)

Blood urea nitrogen (BUN), serum creatinine,

● If elevated: may indicate a degree of renal compromise

Serum electrolytes
● Potassium levels may be elevated in patients with significant renal functional impairment

Complete blood count (CBC)

● Determine presence of infectious pathology

Erythrocyte sedimentation rate (ESR)

● Increased in infectious pathology

Complement levels (C3, C4, CH50)

● May be useful in narrowing specific disease etiology
● Low serum complement levels suggest the following systemic diseases: cryoglobulinemia, systemic lupus
erythematosus (SLE), bacterial endocarditis, and shunt nephritis. Under the same conditions, renal diseases
characteristic of membranoproliferative GN (MPGN) or poststreptococcal GN (PSGN) also may be considered.
● Normal serum complement levels suggest a visceral abscess, polyarteritis nodosa, Goodpasture syndrome, or
Henoch-Schönlein purpura. In addition, normal complement levels suggest renal diseases such as immune
complex disease, idiopathic rapidly progressive GN, and immunoglobulin G (IgG) or immunoglobulin A (IgA)
nephropathy.

ANA, ANCA, AGBM antibody, hepatitis serologies, cryoglobulins, blood culture, decreased complement levels, ASO
titer (abnormalities of these tests depending on etiology)

Kidney/Renal biopsy
● Quickly identifies the type of glomerular injury and often suggests a course of treatment
● Most accurate method to find out specific cause of the glomerulonephritis
● Done after confirmation of albuminuria and hematuria to know the cause
● Ideal specimen: at least 10 glomeruli
● Specimen will be processed for light microscopy, immunofluorescence, electron microscopy
● Contraindications
○ Small hyperechoic kidneys (generally indicative of chronic irreversible disease)
○ Solitary native kidney (relative contraindication)
○ Multiple, bilateral cysts or a kidney tumor (relative contraindication)
○ Uncorrectable bleeding diathesis
○ Severe hypertension (that cannot be controlled with antihypertensive medications)
○ Hydronephrosis
○ Active renal or perirenal infection
○ Anatomic abnormalities of the kidney that may increase risk (such as polycystic kidney disease or
horseshoe kidney)
○ Skin infection over the biopsy site
○ An uncooperative patient
○ When a skilled operator (nephrologist or interventional radiologist, experienced in performance of the
procedure) or appropriate pathology support is not available

MANAGEMENT

PHARMACOLOGIC ​(include Dosage, Route of Administration)

Acute Glomerulonephritis:
Treatment of acute poststreptococcal glomerulonephritis (PSGN) is mainly supportive, because there is no specific
therapy for renal disease. When acute glomerulonephritis (GN) is associated with chronic infections, the underlying
infections must be treated.

Chronic Glomerulonephritis:
● Blood pressure management
○ The target blood pressure for patients with proteinuria in excess of 1 g/day is less than 125/75 mm Hg;
for patients with proteinuria of less than 1 g/day, the target pressure is less than 130/80 mm Hg.
○ Angiotensin-converting enzyme inhibitors (ACEIs) are commonly used and are usually the first choice
for treatment of hypertension in patients with chronic kidney disease (CKD). ACEIs are renoprotective
agents that have additional benefits beyond lowering pressure. They effectively reduce proteinuria, in
part by reducing the efferent arteriolar vascular tone, thereby decreasing intraglomerular hypertension.
● Fibrosis inhibition
○ Because progressive fibrosis is the hallmark of chronic glomerulonephritis, some investigators have
focused on finding inhibitors of fibrosis in an attempt to slow progression. Of the many compounds that
have been considered, pirfenidone, an inhibitor of transforming growth factor beta and hence of
collagen synthesis, has emerged as the best candidate.
● Role of antioxidants
○ Cells have the ability to produce antioxidants, anti-inflammatory and detoxifying enzymes that are
useful for cell viability, but this pathway is constantly being inhibited by an enzyme called KEAP.
Inhibition of KEAP may therefore improve the antioxidant activity of cells and promote cell viability.
Bardoxolone, an oleanolic acid derivative, blocks Keap and has been postulated as a potential
mechanism to retard progression of CKD.
● Role of sodium bicarbonate
○ Sodium bicarbonate has been shown to reduce tubulointerstitial injury and endothelin production with
substantial benefits in slowing progressive kidney damage.
● Role of direct renin inhibitor
○ Preliminary studies using aliskiren, a direct renin inhibitor, show reductions in proteinuria over 6
months, but larger studies did not show benefit.

NON-PHARMACOLOGIC ​(include Diet)

● Restrict salt intake to prevent or minimize fluid retention, swelling and hypertension
● Consume less protein and potassium to slow the buildup of wastes in blood
● Maintain a healthy weight
● Control blood sugar level if patient has diabetes
● Quit smoking

TREATMENT RESPONSE AND COMPLICATIONS ​ (State anticipated treatment response and complications)
Possible complications of glomerulonephritis include:
● Acute kidney failure
○ Loss of function in the filtering part of the nephron can result in rapid accumulation of waste products.
Patients might need emergency dialysis — an artificial means of removing extra fluids and waste from
the blood — typically by an artificial kidney machine.
● Chronic kidney disease
○ The kidneys gradually lose their filtering ability. Kidney function that deteriorates to less than 10 percent
of normal capacity results in end-stage kidney disease, which requires dialysis or a kidney transplant to
sustain life.
● High blood pressure.
○ Damage to the kidneys and the resulting buildup of wastes in the bloodstream can raise your blood
pressure.
● Nephrotic syndrome.
○ With this syndrome, too much protein in the urine results in too little protein in your blood. Nephrotic
syndrome can be associated with high blood cholesterol and swelling (edema) of the eyelids, feet and
abdomen.

PREVENTIVE
● Seek prompt treatment of a strep infection with a sore throat or impetigo.
● To prevent infections that can lead to some forms of glomerulonephritis, such as HIV and hepatitis, follow
safe-sex guidelines and avoid intravenous drug use.
● Control high blood pressure, which lessens the likelihood of damage to kidneys from hypertension.
● Control blood sugar to help prevent diabetic nephropathy.

PROGNOSIS

Most epidemic cases follow a course ending in complete recovery of the patient.
The mortality of acute GN in pediatric patients has been reported at 0-7%.
Sporadic cases of acute nephritis often progress to a chronic form. This progression occurs in as many as 30% of adult
patients and 10% of pediatric patients.
GN is the most common cause of chronic renal failure (25%).
Acute poststreptococcal glomerulonephritis resolves completely in most cases, especially in children. About 1% of
children and 10% of adults develop chronic kidney disease.
 APPENDIX

Overview of the evaluation and differential diagnosis of glomerular disease

Links to References:
- Harrisons:
https://drive.google.com/file/d/1h_OYEl6qPYqW9UY01Xgln7WqSiX35Vs0/view?usp=sharing
- KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines—application to the
individual patient :
https://www.kidney-international.org/action/showPdf?pii=S0085-2538%2815%2955654-8
- KDIGO CLINICAL PRACTICE GUIDELINE ON GLOMERULAR DISEASES:
https://kdigo.org/wp-content/uploads/2017/02/KDIGO-GN-GL-Public-Review-Draft_1-June-2020.pdf
- https://drive.google.com/file/d/1hW-VqUiEealvip0Ta0SMqQC21BJexFcc/view?usp=sharing
- Include links to sample cases/case vignettes
- Include links to videos for History/PE
- Include links to CPGs pertinent to the case
- https://www.mayoclinic.org/diseases-conditions/glomerulonephritis/symptoms-causes/syc-20355705
- https://www.mayoclinic.org/diseases-conditions/glomerulonephritis/diagnosis-treatment/drc-20355710
- https://emedicine.medscape.com/article/239278-overview
- https://www.uptodate.com/contents/glomerular-disease-evaluation-and-differential-diagnosis-in-adults?
search=glomerulonephritis&source=search_result&selectedTitle=1~150&usage_type=default&display_r
ank=1#H1292164380
- https://www.uptodate.com/contents/glomerular-disease-evaluation-and-differential-diagnosis-in-adults#
H2303960309
- https://emedicine.medscape.com/article/239392-treatment#d9
- https://emedicine.medscape.com/article/239278-treatment