Renal Flashcards
Renal disease can affect different sitdes of the nephron.
How can it be differentiated/ what different sites can be affected?
- Glomerulus
- Tubules and Interstitium
- Blood vessles
(Just one way of classyfiying renal disease, other things also can be different)
How does immune complex deposition in the kidney cause disease?
Generall immune complec is just combination of antibody and antigen
Can deposit in different and several sites of the nephron and therefore can cause different presentation
Can cause
1. Direct obstruction
2. driver further inflammatory responses and therefore cause damage
Recall the components of the normal glumerular filtration Barrier
3 Layers
- Fenestrated epithelium of capillaries
- Basement membrane (with charge)
- Podocytes
What are two different renal syndromes that can appear due to damage to the glomerulus?
What are the most common causes?
Nephrotic syndrome
Primary
- Minimal change disease
- Membranous glomerular disease
- Focal segmental glomerulosclerosis
Secondary
- e.g. diabetes, amyloidosis, SLE
Nephritic syndrome
- Acute post-infection
- IgA nephropathy
- Rapidly progressive glomerulonephritis
- Alport’s syndrome
- Thin basememnt membrane disease
What is Nephrotic syndrome?
(Definition)
Not a single disease but a constellation of features that can be achieved in several renal diseases
1. proteinuria (>3g/24h OR protein:createning ration >300mg/mmol) 2. hypoalbuminaemia (<30g/L), 3. oedema and
(+/- hypercholesterolaemia)
What is the pathophysiology of Nephrotic syndrome?
Damage to podocytes → structural damage of glomerular filtration barrier → massive renal loss of protein
Structural Damage to Glomuerular Filtration barrier leads to
1. Loss of charge of Filtration Barrier –> loss of selectivity of filtration barrier (particularly for albumin)
2. Podocyte damage –> non-selective proteinuria
What are the main primary causes of Nephrotic syndrome?
- Minimal change disease
- Membranous glomerular disease
- Focal segmental glomuerlosclerosis
What are some of the secondary causes of Nephrotic Syndrome?
Most commonly
1. Diabetes
2. SLE
3. Amyloidosis
What is Minimal Change disease?
What is the pathophysiology?
It is a primay glomerular disease usually presenting clinically with nephrotic syndrome (most common cause of nephrotic syndrome in Children)
Exact pathophysiology if know but thought that
1. T-cell release cytokines –> loss of podocytes foot processes–> loss of charge –> selective protienuria
Due to loss of charge.
BUT:
- No changes in light microscopy
- NO immune deposits
What is the aetology of Minimal change disease?
Usually idiopathic
But is associated with
1. recent allergic reaction
2. exzema, astham
What is the Epidemiology and clinical presentaiotn of Minimal Change disease?
75% are in children : most common cause of nephrotic syndrome in children
–> Presentation with
1. Frothy urine/ proteinuria
2. Swelling (periorbital in children)
How is the diagnosis of Nephrotic syndrome/ Minimal change disease usually made?
1. Diagnosis of nephrotic syndrome
- Urine dip: proteinuria, no haematuria
- Urine protein:creatinine ratio >300mg/mmol
- Serum albumin low
- total cholesterol high
- immunoglobulins low
2. Cause of nephrotic syndrome
- exclude other causes (complement levels, urine microscopy, Renal ultrasound)
- Renal biopsy (in adults, avoided in children)
What is the management and prognosis of minimal change disease?
Management: Immunosuppression
- Steroids (Prednisolone)
- Cyclosporin 2nd line
(as pathophysiology due to cytokine release)
Very good prognosis
- 90% respond well to steroids
- under 5% develop end-stage renal failure
What is Membranous glomerular disease?
What is the pathophysiology?
It is a form of Primary (or secondary) Glumoerular disease usually presenting with Nephrotic syndrome
Anti-phospholipase A2 receptor antibodies (anti-PLA2R antibodies)
- bind to PLA2R (an autoantigen in glomerular podocytes) and thereby form immune complexes that activate the complement system,
- leading to podocyte injury
What are the histological changes seen in Membranour glomerulonepthritis (membranous nephropathy)?
- Under Light Microscopy
- Electron microscopy
- and Immunofluorescens
Pathophysiology is due to deposition of antibodies between podocytes and the basal membrane
- On Light Microspy: Diffuse glomerular basement membrane thickening
- Electron Microscopy: subepithelial dense deposits (IgG and C3) with a spike and dome appearance
- Immune complex depositoin along entired Glomerular Basememet membrane
What is the Epidemiolgy and aetiology of Membranous nephropathy?
Most common cause of nephrotic syndrome in adults of European, Middle Eastern, or North African descent (30%)
It can be
1. Primary: Idiopathic (production of antibodies against Phospohlipase A2 receptors)
- Or Secondary: SLE, infections (Hepatitis, syphillis, Drugs, Malignancies
What is the treatment and prognosis of Membranous nephropathy?
1.Steroids (but usually poor response)
2.RAAS inhibitory (to control BP)
3.trial of other immunosuppressive therapies
40% will have end-stage renal failure after 2-20 years
What is Focal segmental Glomerulosclerosis?
What is the pathophysiology?
Primary glumerular disease, and the most common cause of Nephrotic syndrome in adults of afro-carribean descent
Sclerosis of glomeruli → damage and loss of podocytes
What is the aetiology of Focal Segmental glumerulosclerosis?
- Primary : usually idiopathic
can be secondary due ot obesity, HIV or drugs
What is the epidemiology of Focal segmental glomerulosclerosis?
Most common cause of nephrotic syndrome in adults, especially in African American and Hispanic populations
What are the histological changes in Focal segmental Glomerulosclerosis on
1. Light microscopy
2. Electronmicroscopy
3. Immunoflourescence
Pathophysiology: Sclerosis
- LM: Focal and segmental glomerular consulidation and scarring, hyalinosis
- EM: loss of podocyte foot processes
- No immune deposits
What is the management and prognosis of Focal Segmental Glumerulosclerosis?
- trial of immunosuppressants : Steroids (about 50% responsive), Calcineurin inhibitors 2nd line
ACEi, ARB to control BP
Prognosis
1. 50% will develop end-stage renal failure within 10 years
What are the epidemiology and the histopathological features of diabetic nephropathy?
- Leading cause of end-stage renal failure in high-income countries
Changes include
- Thickening of the glomerular basement membrane (increased permeability) (throughout)
- Eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson nodules) (yellow)
- Hyaline thickened arteriole (blue overlay)
What is the difference between Nephrotic and Nephritic syndrome?
Both, Nephrotic and Nephrotic syndromes are common clinical manifestations of glumerular diseases
They are defined by different characteristics (table) and have distinctive pathophyshiologies.
Most noticable differences
1. High Loss of proten = Nephrotic syndrome
2. Haematuria = Nephritic syndrome
What is Nephritic syndrome?
(Definitoin)
Manifestation of glumerular inflitration characteristed by
- Proteinuria (less thatn in Nephritc, under 3.5g/24h)
- Hamaturia (incl. acanthocytes and RBC casts in urine)
- Azotemia (high urea and creatinine)
- Oliguria
- Hypertension (due to salt-retenetion)
What is the pathophysiology of Nephritic syndrome?
Generally due to Glomerular inflammation (i.e. clinical manifestation of glomerulonephritis)
Inflammatory response within glomeruli → Glomerular BM disruption → loss of renally excreted RBCs (acanthocytes) and ↓ GFR → hematuria, oliguria, azotemia, and ↑ renin → edema and hypertension
What are some of the most common causes of nephritic syndrome?
- Acute post-infectious glomerulonephritis
- IgA Nephorpathy
- Rapidly progressive (crescentig) Glomerulonephritis
- Hereditary Nephritis (Alport’s syndrome)
- Thin Basement Membrane disease (Benign familial haematuria)
What is the aetiology and pathophysiolgy of post-streptococcal glomerulonephritis?
Acute Nephritic syndrome presenting 1-3 weeks post streptococcal throat infection or impetigo (usually group A alpha-haemolytic strep =strep pyogenes)
Immune complexes containing the streptococcal antigen deposit within the glomerular basement membrane (likely involves molecular mimicry) → complement activation (↑ consumption of complement factors) → destruction of the glomeruli → immune complex-mediated glomerulonephritis and nephritic syndrome
What is the clinical presentaiton of Acute post-infectious glomerulonephritis?
Approx. 50% of patients remain asymptomatic. Symptoms occur approximately 1–6 weeks following an acute infection.
Nephritic syndrome
- Hematuria: tea- or cola-colored urine
- Hypertension: can lead to headaches
- Edema (prominent facial edema)
- Oliguria
- Influenza-like symptoms
- Flank pain
How is acute post-streptococcal glomerulonephritis diagnosed?
1. Nephritic syndrome
- urine dip + microscorpy (proteinuria, hamaturia, RBC casts, pyuria)
2. Recent Group A strep infection
- Anti-streptotolysin O antibody (ASO) titres (increased)
- if active infection: throat/ wound swap
- Others: complement (C3+4). usually reduction in C3, normal C4
What is the prognosis and management of Post-streptococcal glomerulonephritis?
Post-strep
- ABX for acute infection (not if not-acute infection) (penicillin V/ allergy erythromycin)
Otherwise supportive
- oedema: low sodium diet, fluid restriction and loop diuretics
- Antihypertensives: CCB (try to avoid RAAS modyfying agents initially)
Prognosis
Usually recovery within 6-8 weeks
- in children great recovery
- urine dip might remain abnormal for a while –> regular follow up until urine dip normal
What are the main 2 tubular disease changes that cause renal pathlogy?
- Acute Tubular necrosis/ injury
- Acute Tubulo-interstitial Nephritis
What is the most common cause of Acute Renal failure?
Acute tubular injury
Tubular epithelium damaged by
- Ischaemia
- toxins (contracs, haemoglobin, myoglobin)
- Drugs
What is Acute Tubular necrosis?
Pathophysiology?
Histopathology?
Differnt aetiologies lead to damage and necrosis of short segments of tubules (thick parts of proximal tubule and distal tubule) (Histo)
Necrotic proximal tubular cells fall into the tubular lumen → debris obstructs tubules → decreased GFR → sequence of pathophysiological events similar to prerenal failure
What are the most common aetiologies of Acute Tubular Necrosis?
Ischaemic
- hypovolaemia
- embolism
Toxic
- drugs (aminogylcosides, NSAIDS)
- contrast
- myoglobin/ haemoglobins
- heavy metals
What is Acute Tubulointerstitial Nephritis?
What is the pathophysiology?
Renal infalmmatory diseases that cause damge to renal tubules and interstitium
Immune-mediated tubulointerstitial damage (allergic interstitial nephritis) is the most widely accepted theory:
- Inflammatory infiltrates → tissue edema and tubular cell damage → compromised tubular flow
- Allergic interstitial nephritis: drugs act as allergens → type IV hypersensitivity reaction
OR:
Acute obstruction: crystals (from e.g., uric acid, medications) or proteins (e.g., light chains) obstruct tubules
What is the aetiology of acute Interstitial nephritis?
Most important: Drugs
- Antibiotics: β-lactams, sulfonamides, rifampin, fluoroquinolones
- NSAIDs
- Proton pump inhibitors and H2 blockers
- Loop diuretics and thiazides
- Anticonvulsants: phenytoin, valproate, carbamazepine, phenobarbital
- Bacteria
What is the usual clinical presentation of acute interstitial nephritis?
Usually begins days after drug exposure
1. AKI +/-
- fever,
- skin rash,
- haematuria,
- proteinuria, eosinophilia
Histology: inflammatory infiltrate with tubular injury, eosinophils & granulomas
What is the aetiology and pathophysiolgy of post-streptococcal glomerulonephritis?
Acute Nephritic syndrome presenting 1-3 weeks post streptococcal throat infection or impetigo (usually group A alpha-haemolytic strep =strep pyogenes)
Immune complexes containing the streptococcal antigen deposit within the glomerular basement membrane (likely involves molecular mimicry) → complement activation (↑ consumption of complement factors) → destruction of the glomeruli → immune complex-mediated glomerulonephritis and nephritic syndrome
What is the prognosis and management of Post-streptococcal glomerulonephritis?
Usually recovery within 6-8 weeks
* in children great recovery
* urine dip might remain abnormal for a while
What is the most commono glomerulonephritis worldwide?
IgA nephropathy (or Berger disease)
What is IgA Nephropathy (pathophysiology)?
Renal glomerular disease usually presenting with Nephritic syndrome
Usually presents 1-2 days after URTI with frank haematuria
increased number of defective, circulating IgA antibodies are synthesized (often triggered by mucosal infections, i.e., upper respiratory tract and gastrointestinal infections) → IgA antibodies form immune complexes that deposit in the kidney → glomerulonephritis (type III hypersensitivity reaction)
What is the main clinical presentation of IgA Nephropathy?
Classically presents in males in 2nd - 3rd decade of life (more common in asians)
- often asymptomatic (only microscopif haematuria)
Recurring episodes of:
- Gross or microscopic hematuria
- Flank pain
- Low-grade fever
- And/or nephritic syndrome (including hypertension)
- Usually during or immediately following a respiratory or gastrointestinal infection
- +/- vasculitic rash
How is IgA nephropathy investigated + diagnosed?
- Urinalysis: Nephritic syndrome and 50% recurring frank haematuria
- Labs: Serum IgA increase (in 50%), complement normal (C3 often changed in ohter types of glomerulonephritis)
Urine biopsy rarely indicated but includes
* IgA deposition in meangium
What is the prognosis and treatment of IgA Nephropathy?
- 1/3rd are asymptomatic –> regular monitoring or renal function
- 1/3rd develop CKD –> BP control (ACEi/ARB)
- 1/3rd develop progressive CKD requiring dialysis / transplantation
For severe/ progressive disease: steroids/ immunosuppression
What is Rapidly Progressive Glomerulonephritis?
How can it be further sub-devided?
What is the histopatholigcal hallmark?
Most Aggressive form of Glomerulonpehritis (presents with nephritic syndrome + oliguria and renal failure) due to extensive damange to glomerular basement membrane and Bowman’s capsule
It has 3 distinctive pathophysiolgical aetiologies
1. Anti-GBM antibodies (i.e. Goodpasture’s syndrome)
2. Immune-complex mediated (e.g. SLE, IgA nephropathy)
3. Pauci-immune (usually due to Vasculitis (c-ANCA and p-Anca associated)
Regardless of cause is characteried by crescentson Histology
What are the histological crescents characterising Rapidly progressive glomerulonephritis made of?
Damage to renal capillaries + inflammatioin –> leakage of cells into bowman’s space
Fibrin clots and proliferation of cells (e.g., macrophages, fibroblasts, neutrophils, epithelial cells) make up crescents and compress glomerulus –> renal destructioin
What is Goodpasture’s syndrome?
Pathophysiology?
Clinical manifestation?
rare Autoimmune disease with production of anti-Glomerular basement antibody against Collagen Type 4 (in renal and pulmonary basement membrane)
Leading to
1. Rapidly progressive Glomerulonephritis
2. Lung involvement: hamoptysis, cough, dyspnoea
What are the differnt aetiologies of Type 2 (Immune complex-mediated) rapidly progressive glomerulonephritis?
- SLE
- IgA nephropathy
- Post-infectious Glomerulonephritis
- Alport’s syndrome
What are the Clinical and laboratory finidngs of immune-complex mediated rapidly progresive glomerulonephritis?
Nephritic syndrome
usually few additional organ involvement but most causes have
- reduction in C3 complement levels
- additional serology depending on cause
When should you suspect rapidly-progressive glomerularnpehritis?
What investigations should you do?
Clinically
1. acute AKI and rapid increase in creatinine
Then order
1. Urinalysis + microscopy –> renal sediment
2. Urgent biopsy: Crescents + immunoflourescents
What is the management and prognosis of Rapidly progressive glomerulonepthritis?
Management:
Immunosuppression (glococorticoids and cyclophosphamides)
+ Plasma exchange for goodpastrues
Prognosis:
1. If early treatment >50% return to normal renal function
2. if not: poor prognosis and high mortality
What are some of the differentials of asymptomatic haematuria?
- THIN BASEMENT MEMBRANE DISEASE (Benign familial haematuria) (5% prevalence, weak collagen causing weak BM and asymptomatic microscopic haematuria)
- IgA NEPHROPATHY (Berger disease)
- ALPORT SYNDROME (mutation in collagen + sensorineural deafness + eye problem)
What are the main causes of renal disease mediated by Thrombotic Microangiopathies?
Mainly HUS and TTP
What is the most common renal malignancy?
What tissues does it originate from?
Renal cell cancers, in particular Clear cell carcinomas
Renal tubular epithelium
What is Adult Polycystic Kindey disease?
What is the mode of inheritance?
What is the epidemiology?
Relatively common: 1:500 people
Is a usually autosomal dominant condition characteristed by polcystic kidneys and other extra-renal manifestations
What are the genetic mutations associated with Polycystic kidney disease?
Autosomal dominant inherience with mutations in polycystin encoding genes:
1. 85% PKD1 (chromosome 16)
2. 15% PKD2 (chromosome 4)
Change Ca+ flow in cells and therefore abnormal cell-signaling
What is the prognosis of Adult polycystic kidney disease?
2/3 of patients will require renal replacement therapy
Accounts for 10% of cases of CKD
What are the exra-renal manifestations of autosomal dominant polycystic kidney disease?
- Liver Cysts
- Berry aneurism
- +/- mitral valve prolapse
What are the renal manifestations of polcystic kidney disease?
Cysts (number is age-dependant)
- 15-39: 3 or more
- 40-59 >2 cysts in each kidney
- > 60 >4 cysts in each kidney
–> Leading to **destruction of Renal parenchyma **
+ Resulting in clinical picture of
- Abdominal masses
- Infected cysts and hypertension
- Gros haematuria
- Stones
- polyuria and nocturia
