Renal COPY Flashcards
Describe the 3 zones of the adrenals and what hormones they produce
Adrenal cortex (mnemonic GFR - ACD)
• Zona Glomerulosa (on outside): mineralocorticoids, mainly Aldosterone
• Zona Fasciculata (middle): glucocorticoids, mainly Cortisol
• Zona Reticularis (on inside): androgens, mainly Dehydroepiandrosterone (DHEA)
Describe the renin - angiotensin - aldosterone system
-Where is renin released from and why
-what does this do
-what happens to angiotensin and where does this take place
-what does this result in
-where is aldosterone released from and why
-what does this cause
Renin
• Released by JGA cells in kidney in response to ↓ renal perfusion, low sodium
• Hydrolyses angiotensinogen to form angiotensin I
Angiotensin
• ACE in lung converts angiotensin I → angiotensin II
• Vasoconstriction leads to raised BP
• Stimulates thirst
• Stimulates aldosterone and ADH release
Aldosterone
• Released by the zona glomerulosa in response to raised angiotensin II, potassium, and ACTH levels
• Causes retention of Na+ in exchange for K+/H+ in distal tubule
what factors stimulate renin secretion?
Factors stimulating renin secretion
• ↓ BP → ↓ renal prefusion
• Hyponatremia
• Sympathetic nerve stimulation
• Catecholamines
• Erect posture
what factors reduce renin secretion?
Factors reducing renin secretion
• β-blockers
• NSAIDS
what urinalysis is shown:
• Few RBCs (of normal morphology)
• Fine grandular cast or hyaline cast
or
-Dysmorphic RBCs
or
-WBCs+whitecellcast
or
• Red cell casts
Normal
• Few RBCs (of normal morphology)
• Fine grandular cast or hyaline cast
Glomerular Disease
-Dysmorphic RBCs
UTI and Pylonephritis
-WBCs+whitecellcast
Glomerulonephritis
• Red cell casts
what happens to:
Vit D
Phosphate
Calcium
Parathyroid hormone
in kidney disease
• Low vitamin D (1-α hydroxylation normally occurs in the kidneys)
• High phosphate due to ↓ execretion.
• Low calcium: due to lack of vitamin D,
high phosphate
• Secondary hyperparathyroidism: due to
low calcium, high phosphate and low vitamin D
What clinical manifestation may result from:
-hyperparathyroidism in kidney disease
Osteitis fibrosa cystica
o AKA hyperparathyroid bone disease
• Adynamic bone disease
o Reduction in cellular activity (both osteoblasts
and osteoclasts) in bone
oMay be due to over treatment with vitamin D
• Osteomalacia
o Due to low vitamin D
• Osteosclerosis
• Osteoporosis
describe the management of anaemia in CKD
-what level should ferritin be before starting EPO?
-what is the Hb target
-why should the Hb not be too high
-why should the Hb not be too low
Management:
• Correction o iron with IV if needed
• Ferritin should be > 200 ng/mL before starting EPO
• EPO is used to target Hb 10-12 (>11 or hematocrit >33%) reach the target within 4 months
• Corrected Hb of > 13.5 is associate with HTN crisis
• Hb < 10.5 ↑ risk of seizures.
what is EPO
-what does it do?
-what are it’s main uses?
Erythropoietin: (EPO) is a hematopoietic growth factor that stimulates the production of erythrocytes. The main uses of erythropoietin are to treat the anemia associated with chronic renal failure and that associated with cytotoxic therapy
what are the 8 side effects assoc with EPO
• HTN and HTN crisis, potentially → encephalopathy and seizures (BP ↑ in 25% of patients)
• EPO induced seizures occurs after 90 days from starting the treatment
• Bone aches
• Flu-like symptoms
• Skin rashes, urticaria
• Pure red cell aplasia* (due to antibodies against erythropoietin)
(*the risk is greatly ↓ with darbepoetin)
• Raised packed cell volume (PCV) =HCT → ↑ risk of thrombosis (e.g. Fistula)
• Iron deficiency 2nd to ↑ erythropoiesis
why may patients fail to respond with EPO?
• Iron deficiency
• Inadequate dose
• Concurrent infection/inflammation
• Hyperparathyroid bone disease
• Aluminum toxicity
how long can EPO be detected in urine until?
EPO can be detected in urine for few weeks after the latest dose
what are 5 indications for urgent dialysis?
• Severe acidosis
• Pulmonary edema due to volume overload
• Hyperkalemia
• Uremic pericarditis
• Severe uremic symptoms: Encephalopathy/Vomiting
what is hyperacute graft rejection due to in renal transplantation?
-what antibody mediates this?
-is this common?
Hyperacute graft rejection is due to pre-existent antibodies to HLA antigens and is therefore IgG
mediated
• Due to antibodies against donor HLA type 1 antigens
• Rarely seen due to HLA matching
describe the 1 and 10 year survival rate for cadaveric transplants vs living-donar transplants
Graft survival
• 1 year = 90%, 10 years = 60% for cadaveric transplants
• 1 year = 95%, 10 years = 70% for living-donor transplants
what are 6 post-op problems up to 4 months post-op in renal transplant?
Post-op problems (can cause graft dysfunction) – up to 4 months post-op:
• Acute rejection: risk is great in 1st 2 weeks occurs in 30-50% of cases
• Ciclosporin toxicity
• ATN of graft
• Vascular thrombosis
• Urine leakage
• UTI
describe the management of acute graft failure <6mths
Management of acute graft failure (< 6 months)
• Acute rejection: give steroids, if resistant use monoclonal antibodies
what are 3 causes of chronic graft failure i.e. >6mths?
Causes of chronic graft failure (> 6 months)
• Chronic allograft nephropathy
• Ureteric obstruction
• Recurrence of original renal disease (Mesangiocapillary glomerulonephritis > IgA > Focal segmental glomerulosclerosis)
Autosomal dominant polycystic kidney disease:
-what 2 disease loci have been identified and what do these code for?
Autosomal Dominant Polycystic Kidney Disease: (ADPKD) is the most common inherited cause of kidney disease, affecting 1 in 1,000 Caucasians. Two disease loci have been identified, PKD1 and PKD2, which code for polycystin-1 and polycystin-2 respectively
Autosomal dominant polycystic kidney disease type 1:
-what percentage of cases
-which chromosome
-how does this present?
85% cases
chromosome 16
presents with renal failure early
Autosomal dominant polycystic kidney disease type 2:
-what percentage of cases
-which chromosome
15%
chromosome 4
what is the diagnosis of ADPKD?
• In < 20 yrs age, CT scan is not needed
• In < 20 yrs age, ultrasound gives false –ve
• 2 cysts, unilateral or bilateral, if aged < 30 years
• 2 cysts in both kidneys if aged 30-59 years
• 4 cysts in both kidneys if aged > 60 years
what are assoc. conditions with ADPKD:
Associated conditions:
• Colonic diverticula (with any related symptoms, screen by barium enema)
• Mitral Valve Prolapse (needs echo screening)
• Berry aneurysms
what is the management of adult polycystic kidney disease?
Management:
• Painkillers
• Urinary tract infections: → ABX
• ↑BP control
• End-stage renal disease → Transplantation
For select patients, tolvaptan (vasopressin receptor 2 antagonist) may be an option. NICE recommended it as an option for treating ADPKD in adults to slow the progression of cyst development and renal insufficiency only if:
they have chronic kidney disease stage 2 or 3 at the start of treatment
there is evidence of rapidly progressing disease and
the company provides it with the discount agreed in the patient access scheme
Autosomal Recessive Polycystic Kidney Disease (ARPKD):
-common?
-chromosome?
Autosomal Recessive Polycystic Kidney Disease (ARPKD) is much less common than autosomal dominant disease (ADPKD). It is due to a defect in a gene located on chromosome 6
what is the diagnosis of Autosomal Recessive Polycystic Kidney Disease
-what is the progression of disease?
-what other organ is typically involved?
Diagnosis may be made on prenatal ultrasound or in early infancy with abdominal masses and renal failure. End-stage renal failure develops in childhood. Patients also typically have liver involvement, for example portal and interlobular fibrosis
what is the triad of nephrotic syndrome?
What is nephritic syndrome?
Nephrotic
1. Proteinuria (> 3g/24hr) causing
2. Hypoalbuminemia (< 30g/L) and
3. Edema
Nephritic: haematuria, hypertension
In nephrotic syndrome:
-why does this predispose to thrombosis?
-what happens to thyroxin levels?
Loss of antithrombin-III (↑↑↑), proteins C and S and associated rise in fibrinogen levels
predispose to thrombosis. Loss of TBG lowers total, but not free thyroxin levels
what are the 4 main causes of nephrotic syndrome?
- Glomerulonephritis (GN, c. 80%)
• Minimal change GN (causes 75% in children, 25% in adults)
• Membranous GN
• Focal Segmental GlomeruloSclerosis - Systemic disease (c. 20%)
• Amyloidosis
• SLE - Drugs
• Gold (sodium aurothiomalate), penicillamine - Others
• Congenital
• Neoplasia: carcinoma, lymphoma, leukemia, myeloma
• Infection: bacterial endocarditis, hepatitis B, malaria
• Renal vein thrombosis
what are the 5 complications of nephrotic syndrome?
• ↑ risk of infection due to urinary immunoglobulin loss
• ↑ risk of thromboembolism related to loss of antithrombin III and plasminogen in the urine
• Hyperlipidemia
• Hypocalcemia (vitamin D and binding protein lost in urine)
• Acute renal failure could be due to thrombotic renal veins it comes with lion pain and
hematuria.
What is the disease?
• Presentation: proteinuria / nephrotic syndrome / CRF
• Cause: infections, rheumatoid drugs, malignancy
• 1/3 resolve, 1/3 respond to cytotoxics, 1/3 develop CRF
Membranous glomerulonephritis
What is the disease?
• Typically young adult with hematuria following an URTI
• Associated with Henoch-Schonlein purpura
• Mesangial hypercellularity (mesangioproliferative)
IgA nephropathy - AKA Berger’s disease, mesangioproliferative GN
what is the disease?
• Classical post-streptococcal glomerulonephritis in child
• Presents as nephritic syndrome / ARF
• Most common form of renal disease in SLE (IV)
- Diffuse proliferative glomerulonephritis
what is the disease?
• Typically a child with nephrotic syndrome (accounts for 80%)
• Causes: Hodgkin’s, NSAIDs
• Good response to steroids
- Minimal change disease
what is the disease?
• May be idiopathic or secondary to HIV, heroin
• Presentation: proteinuria / nephrotic syndrome / CRF
- Focal segmental glomerulosclerosis
what is the disease?
• Rapid onset, often presenting as ARF
• Causes include Goodpasture’s, ANCA positive vasculitis (e.g. Wegener’s granulomatosis)
- Rapidly progressive glomerulonephritis (RPGN) - AKA Crescentic Glomerulonephritis
what is the disease?
• Type 1: cryoglobulinemia, hepatitis C → associated with low C4
• Type 2: partial lipodystrophy → associated with low C3
- Mesangiocapillary glomerulonephritis (membranoproliferative)
what 4 diseases are assoc. with glomerulonephritis and low serum C3 levels?
• Post-streptococcal glomerulonephritis
• Subacute bacterial endocarditis
• Systemic lupus erythematosus
• Mesangiocapillary glomerulonephritis
how common is membranous glomerulonephritis?
-how does this usually present?
Membranous glomerulonephritis is the commonest type of glomerulonephritis in adults and is the third most common cause of end-stage renal failure (ESRF). It usually presents as nephrotic syndrome or proteinuria
what does renal biopsy show in membranous glomerulonephritis?
Renal biopsy demonstrates:
• Sub-epithelial immune complex (mainly IgG and C3) deposition in the glomerulus
• Electron microscopy: the basement membrane is thickened with sub-epithelial electron dense
deposits (IgG, C3)
what are the causes of membranous glomerulonephritis:
-infections?
-malignancies?
-drugs?
-autoimmune disease?
Causes
idiopathic: due to anti-phospholipase A2 antibodies
infections: hepatitis B, malaria, syphilis
malignancy (in 5-20%): prostate, lung, lymphoma, leukaemia
drugs: gold, penicillamine, NSAIDs
autoimmune diseases: systemic lupus erythematosus (class V disease), thyroiditis, rheumatoid
what is the prognosis for membranous glomerulonephritis?
Prognosis - rule of thirds
• One-third: spontaneous remission
• One-third: remain proteinuric
• One-third: develop ESRF
describe the management in membranous glomerulonephritis?
Management
all patients should receive an ACE inhibitor or an angiotensin II receptor blocker (ARB):
these have been shown to reduce proteinuria and improve prognosis
immunosuppression
as many patients spontaneously improve only patient with severe or progressive disease require immunosuppression
corticosteroids alone have not been shown to be effective. A combination of corticosteroid + another agent such as cyclophosphamide is often used
consider anticoagulation for high-risk patients
IgA nephropathy:
-AKA?
-common?
-what is the pathogenesis?
-what is seen on histology?
• Also called Berger’s disease or mesangioproliferative glomerulonephritis
• Commonest cause of glomerulonephritis worldwide
• Pathogenesis unknown, ?Mesangial deposition of IgA immune complexes
• Histology: mesangial hypercellularity, positive immunofluorescence for IgA & C3
differentiating between IgA nephropathy and post-streptococcal glomerulonephritis (diffuse proliferative)
-complement level
-main symptom
-what precedes renal problems?
• Post-streptococcal glomerulonephritis is associated with low complement levels
• Main symptom in post-streptococcal glomerulonephritis is proteinuria (although hematuria can
occur)
• There is typically an interval between URTI and the onset of renal problems in post-
streptococcal glomerulonephritis
what are the main features of IgA nephropathy:
-what age of patients are affected?
-what is seen in the urine?
-what is this typically assoc. with?
-is there proteinuria?
• Young ♂, recurrent episodes of Hematuria, usually painless (sometimes with no renal impairment)
• Typically associated with mucosal infections e.g., URTI
• Nephrotic range proteinuria is rare, presents as nephritic syndrome
• Renal failure
what conditions are assoc. with IgA nephropathy?
Associated conditions
• Alcoholic cirrhosis
• Celiac disease/dermatitis herpetiformis
what is the management for IgA nephropathy?
Management
• Steroids/immunosuppressants have not shown to be useful
what is the prognosis of IgA Nephropathy?
-what are good prognostic indicators?
-what are poor prognostic indicators?
• 25% of patients develop ESRF
• Markers of good prognosis: frank hematuria
• Markers of poor prognosis: ♂ gender, proteinuria (especially > 2 g/day), hypertension,
smoking, hyperlipidemia, ACE genotype DD
how does minimal change glomerulonephritis present? is this common?
Minimal Change Glomerulonephritis nearly always presents as nephrotic syndrome, accounting for 75% of cases in children and 25% in adults
what are the different causes of minimal change glomerulonephritis?
Causes: majority of cases are idiopathic, but in around 10-20% a cause is found:
• Drugs: NSAIDs, rifampicin
• Hodgkin’s lymphoma, NHL and thymoma
• Infectious mononucleosis
what are 5 features of minimal change glomerulonephritis?
Features
• Nephrotic syndrome
• Normotension - hypertension is rare
• Hematuria is very rare
• Highly selective proteinuria*
(*only intermediate-sized proteins such as albumin and transferrin leak through the glomerulus)
• Renal biopsy: electron microscopy shows fusion of podocytes
what 2 conditions is podocyte fusion seen in?
Podocyte fusion is seen in minimal change glomerulonephritis but may occasionally be a feature
of focal segmental glomerulosclerosis as well. Minimal change however is far more common
what is included in the management of minimal change glomerulonephritis?
Management
• Majority of cases (80%) are steroid responsive (prednisolone)
• Cyclophosphamide is the next step for steroid resistant cases
ACE inhibitors may be used to ↓ proteinuria in patients with heavy proteinuria or who have a slow response to prednisolone
what is the prognosis of minimal change glomerulonephritis?
Prognosis is overall good, although relapse is common. Roughly:
• 1/3 have just one episode
• 2/3 have relapses:
o 1/3 have infrequent relapses
o 1/3 have frequent relapses which stop before adulthood
Mesangiocapillary Glomerulonephritis:
-what is this AKA?
-how may this present?
• AKA membranoproliferative glomerulonephritis
• Mixed nephritic/nephrotic presentation
• Poor prognosis
what 3 types of mesangiocapillary glomerulonephritis exist?
-what are the causes of each one?
Type 1:
• Subendothelial immune deposits
• Cause: Cryoglobulinemia (with low C4), hepatitis C
Type 2 ‘dense deposit disease’:
• Intramembranous deposits of electron dense material • Causes: partial lipodystrophy, factor H deficiency • ↓ serum complement
• C3b nephritic factor (an antibody against C3bbb)
found in 70% (low C3)
Type 3
• Causes: hepatitis B and C
what is the management of mesangiocapillary glomerulonephritis?
Management
• Steroids may be effective
Focal segmental glomerulosclerosis
how does this present?
name 6 causes?
when does this have a high recurrence rate?
nephrotic syndrome
Causes
• Idiopathic
• Secondary to other renal pathology e.g. IgA nephropathy, reflux nephropathy
• HIV
• Heroin
• Alport’s syndrome
• Sickle-cell
Focal segmental glomerulosclerosis is noted for having a high recurrence rate in renal transplants
How is alport’s syndrome inherited?
-what is the due to?
-is this more severe in males or females?
Alport’s Syndrome is usually inherited in an X-linked dominant pattern*. It is due to a defect in the gene which codes for type IV collagen resulting in an abnormal glomerular-basement membrane (GBM). The disease is more severe in ♂s with ♀s rarely developing renal failure
*in around 85% of cases - 10-15% of cases are inherited in an autosomal recessive fashion with rare autosomal dominant variants existing
Give 7 risk factors for renal stones
Risk factors
• Dehydration
• Hypercalciuria, hyperparathyroidism, hypercalcemia
• Cystinuria NOT CYSTINOSIS
• High dietary oxalate
• Renal tubular acidosis
• Medullary sponge kidney, polycystic kidney disease
• Beryllium or cadmium exposure
give 2 risk factors for urate renal stones
Risk factors for urate stones
• Gout
• Ileostomy: loss of bicarbonate and fluid results in acidic urine, causing the precipitation of uric acid
give 2 drug causes of renal stones
Drug causes
• Drugs that promote calcium stones: loop diuretics, steroids, acetazolamide, theophylline
• Thiazides can prevent calcium stones (↑ distal tubular calcium resorption)
Give the frequency and radiograph appearance of:
-Calcium oxalate stones
-Mixed calcium oxalate/phosphate stones
-Triple phosphate stones
-Calcium phosphate
-Urate stones
-Cystine stones
-Xanthine stones
Calcium oxalate, 40%, Opaque
Mixed calcium oxalate/phosphate stones, 25%, Opaque
Triple phosphate stones, 10%, Opaque
Calcium phosphate, 10%, Opaque
Urate stones, 5-10%, Radio-lucent
Cystine stones 1% Semi-opaque, ‘ground-glass’ appearance
Xanthine stones, <1%, Radio-lucent
what is a staghorn calculus?
-what do they involve?
-what pH urine do they develop in?
-what predisposes to their formation?
stag-horn calculi involve the renal pelvis and extend into at least 2 calyces. They develop in alkaline urine and are composed of struvite (ammonium magnesium phosphate, triple phosphate). Ureaplasma urealyticum and Proteus infections predispose to their formation
what analgesia is given for renal colic?
Acute management of renal colic
Diclofenac 75 mg by intramuscular injection is the analgesia of choice for renal colic. A second dose can be given after 30 minutes if necessary. (PR diclofenac is an alternative)
what can be done in the prevention of calcium stones?
Calcium stones
• High fluid intake
• Low animal protein, low salt diet (a low calcium diet has not been shown to be superior to a
normocalcemic diet)
• Thiazide diuretics (↑ distal tubular calcium resorption)
• Stones < 5 mm will usually pass spontaneously
• Lithotripsy, nephrolithotomy may be required
what can be done in the prevention of oxolate stones?
• Cholestyramine ↓ urinary oxalate secretion
• Pyridoxine ↓ urinary oxalate secretion
what can be done in the prevention of urate stones?
• Allopurinol
• Urinary alkalinization e.g. Oral bicarbonate