24 December 2020
14:25
Haematuria
The management of patients with haematuria is often difficult due to the absence of widely followed guidelines. It is sometimes unclear whether patients are best managed in primary care, by urologists or by nephrologists.
The terminology surrounding haematuria is changing. Microscopic or dipstick positive haematuria is increasingly termed non-visible haematuria whilst macroscopic haematuria is termed visible haematuria. Non-visible haematuria is found in around 2.5% of the population.
Causes of transient or spurious non-visible haematuria
· urinary tract infection
· menstruation
· vigorous exercise (this normally settles after around 3 days)
· sexual intercourse
Causes of persistent non-visible haematuria
· cancer (bladder, renal, prostate)
· stones
· benign prostatic hyperplasia
· prostatitis
· urethritis e.g. Chlamydia
· renal causes: IgA nephropathy, thin basement membrane disease
Spurious causes - red/orange urine, where blood is not present on dipstick
· foods: beetroot, rhubarb
· drugs: rifampicin, doxorubicin
Management
Current evidence does not support screening for haematuria. The incidence of non-visible haematuria is similar in patients taking aspirin/warfarin to the general population hence these patients should also be investigated.
Testing
· urine dipstick is the test of choice for detecting haematuria
· persistent non-visible haematuria is often defined as blood being present in 2 out of 3 samples tested 2-3 weeks apart
· renal function, albumin:creatinine (ACR) or protein:creatinine ratio (PCR) and blood pressure should also be checked
· urine microscopy may be used but time to analysis significantly affects the number of red blood cells detected
NICE urgent cancer referral guidelines were updated in 2015.
Urgent referral (i.e. within 2 weeks)
Aged >= 45 years AND:
· unexplained visible haematuria without urinary tract infection, or
· visible haematuria that persists or recurs after successful treatment of urinary tract infection
Aged >= 60 years AND have unexplained nonvisible haematuria and either dysuria or a raised white cell count on a blood test
Non-urgent referral
Aged 60 >= 60 years with recurrent or persistent unexplained urinary tract infection
Since the investigation (or not) of non-visible haematuria is such as a common dilemma a number of guidelines have been published. They generally agree with NICE guidance, of note:
· patients under the age of 40 years with normal renal function, no proteinuria and who are normotensive do not need to be referred and may be managed in primary care
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:25
Hyperkalaemia: management
Untreated hyperkalaemia may cause life-threatening arrhythmias. Precipitating factors should be addressed (e.g. acute renal failure) and aggravating drugs stopped (e.g. ACE inhibitors). Management may be categorised by the aims of treatment
Stabilisation of the cardiac membrane
· intravenous calcium gluconate
o does NOT lower serum potassium levels
Short-term shift in potassium from extracellular to intracellular fluid compartment
· combined insulin/dextrose infusion
· nebulised salbutamol
Removal of potassium from the body
· calcium resonium (orally or enema)
o enemas are more effective than oral as potassium is secreted by the rectum
· loop diuretics
· dialysis
o haemofiltration/haemodialysis should be considered for patients with AKI with persistent hyperkalaemia
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:25
Diabetes insipidus
Diabetes insipidus (DI) is a condition characterised by either a deficiency of antidiuretic hormone, ADH, (cranial DI) or an insensitivity to antidiuretic hormone (nephrogenic DI).
Causes of cranial DI
· idiopathic
· post head injury
· pituitary surgery
· craniopharyngiomas
· histiocytosis X
· DIDMOAD is the association of cranial Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness (also known as Wolfram's syndrome)
· haemochromatosis
Causes of nephrogenic DI
· genetic: the more common form affects the vasopression (ADH) receptor, the less common form results from a mutation in the gene that encodes the aquaporin 2 channel
· electrolytes: hypercalcaemia, hypokalaemia
· drugs: demeclocycline, lithium
· tubulo-interstitial disease: obstruction, sickle-cell, pyelonephritis
Features
· polyuria
· polydipsia
Investigation
· high plasma osmolality, low urine osmolality
· a urine osmolality of >700 mOsm/kg excludes diabetes insipidus
· water deprivation test
Management
· nephrogenic diabetes insipidus: thiazides, low salt/protein diet
- central diabetes insipidus can be treated with desmopressin
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:25
Haemolytic uraemic syndrome
Haemolytic uraemic syndrome is generally seen in young children and produces a triad of:
· acute kidney injury
· microangiopathic haemolytic anaemia
· thrombocytopenia
Most cases are secondary (termed 'typical HUS'):
· classically Shiga toxin-producing Escherichia coli (STEC) 0157:H7 ('verotoxigenic', 'enterohaemorrhagic'). This is the most common cause in children, accounting for over 90% of cases
· pneumococcal infection
· HIV
· rare: systemic lupus erythematosus, drugs, cancer
Primary HUS ('atypical') is due to complement dysregulation.
Investigations
· full blood count: anaemia, thrombocytopaenia, fragmented blood film
· U&E: acute kidney injury
· stool culture
o looking for evidence of STEC infection
o PCR for Shiga toxins
Management
· treatment is supportive e.g. Fluids, blood transfusion and dialysis if required
· there is no role for antibiotics, despite the preceding diarrhoeal illness in many patients
· the indications for plasma exchange in HUS are complicated. As a general rule plasma exchange is reserved for severe cases of HUS not associated with diarrhoea
· eculizumab (a C5 inhibitor monoclonal antibody) has evidence of greater efficiency than plasma exchange alone in the treatment of adult atypical HUS
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:25
Minimal change disease
Minimal change disease nearly always presents as nephrotic syndrome, accounting for 75% of cases in children and 25% in adults.
The majority of cases are idiopathic, but in around 10-20% a cause is found:
· drugs: NSAIDs, rifampicin
· Hodgkin's lymphoma, thymoma
· infectious mononucleosis
Pathophysiology
· T-cell and cytokine-mediated damage to the glomerular basement membrane → polyanion loss
· the resultant reduction of electrostatic charge → increased glomerular permeability to serum albumin
Features
· nephrotic syndrome
· normotension - hypertension is rare
· highly selective proteinuria
o only intermediate-sized proteins such as albumin and transferrin leak through the glomerulus
· renal biopsy
o normal glomeruli on light microscopy
o electron microscopy shows fusion of podocytes and effacement of foot processes
Management
· majority of cases (80%) are steroid-responsive
· cyclophosphamide is the next step for steroid-resistant cases
Prognosis is overall good, although relapse is common. Roughly:
· 1/3 have just one episode
· 1/3 have infrequent relapses
· 1/3 have frequent relapses which stop before adulthood
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:25
Renal transplant: HLA typing and graft failure
The human leucocyte antigen (HLA) system is the name given to the major histocompatibility complex (MHC) in humans. It is coded for on chromosome 6.
Some basic points on the HLA system
· class 1 antigens include A, B and C. Class 2 antigens include DP,DQ and DR
· when HLA matching for a renal transplant the relative importance of the HLA antigens are as follows DR > B > A
Graft survival
· 1 year = 90%, 10 years = 60% for cadaveric transplants
· 1 year = 95%, 10 years = 70% for living-donor transplants
Post-op problems
· ATN of graft
· vascular thrombosis
· urine leakage
· UTI
Hyperacute rejection (minutes to hours)
· due to pre-existing antibodies against ABO or HLA antigens
· an example of a type II hypersensitivity reaction
· leads to widespread thrombosis of graft vessels → ischaemia and necrosis of the transplanted organ
· no treatment is possible and the graft must be removed
Acute graft failure (< 6 months)
· usually due to mismatched HLA. Cell-mediated (cytotoxic T cells)
· other causes include cytomegalovirus infection
· may be reversible with steroids and immunosuppressants
Causes of chronic graft failure (> 6 months)
· both antibody and cell mediated mechanisms cause fibrosis to the transplanted kidney (chronic allograft nephropathy)
· recurrence of original renal disease (MCGN > IgA > FSGS)
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:25
Acute interstitial nephritis
Acute interstitial nephritis accounts for 25% of drug-induced acute kidney injury.
Causes
· drugs: the most common cause, particularly antibiotics
o penicillin
o rifampicin
o NSAIDs
o allopurinol
o furosemide
· systemic disease: SLE, sarcoidosis, and Sjögren's syndrome
· infection: Hanta virus , staphylococci
Pathophysiology
· histology: marked interstitial oedema and interstitial infiltrate in the connective tissue between renal tubules
Features
· fever, rash, arthralgia
· eosinophilia
· mild renal impairment
· hypertension
Investigations
· sterile pyuria
· white cell casts
Tubulointerstitial nephritis with uveitis
Tubulointerstitial nephritis with uveitis (TINU) usually occurs in young females. Symptoms include fever, weight loss and painful, red eyes. Urinalysis is positive for leukocytes and protein.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:25
Acute kidney injury: acute tubular necrosis vs. prerenal uraemia
| Pre-renal uraemia ('azotemia') | Acute tubular necrosis | |
| Urine sodium | < 20 mmol/L | > 40 mmol/L |
| Urine osmolality | > 500 mOsm/kg | < 350 mOsm/kg |
| Fractional sodium excretion* | < 1% | > 1% |
| Response to fluid challenge | Good | Poor |
| Serum urea:creatinine ratio | Raised | Normal |
| Fractional urea excretion** | < 35% | >35% |
| Urine:plasma osmolality | > 1.5 | < 1.1 |
| Urine:plasma urea | > 10:1 | < 8:1 |
| Specific gravity | > 1020 | < 1010 |
| Urine | Normal/ 'bland' sediment | Brown granular casts |
Prerenal uraemia - kidneys hold on to sodium to preserve volume
*fractional sodium excretion = (urine sodium/plasma sodium) / (urine creatinine/plasma creatinine) x 100
**fractional urea excretion = (urine urea /blood urea ) / (urine creatinine/plasma creatinine) x 100
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:25
ADPKD: features
Features
· hypertension
· recurrent UTIs
· abdominal pain
· renal stones
· haematuria
· chronic kidney disease
Extra-renal manifestations
· liver cysts (70% - the commonest extra-renal manifestation): may cause hepatomegaly
· berry aneurysms (8%): rupture can cause subarachnoid haemorrhage
· cardiovascular system: mitral valve prolapse, mitral/tricuspid incompetence, aortic root dilation, aortic dissection
· cysts in other organs: pancreas, spleen; very rarely: thyroid, oesophagus, ovary
| | |
| © Image used on license from PathoPic | |
Extensive cysts are seen in an enlarged kidney
| | |
| © Image used on license from Radiopaedia | |
CT of the abdomen demonstrates both kidneys to be markedly enlarged by innumerable cysts ranging in size from a few millimeters to multiple centimeters with cysts also present in the liver
| | |
| © Image used on license from Radiopaedia | |
CT showing multiple cysts of varying sizes in the liver, and bilateral kidneys with little remaining normal renal parenchyma.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:25
Chronic kidney disease: mineral bone disease management
Pathophysiology
Basic problems in chronic kidney disease (CKD):
· 1-alpha hydroxylation normally occurs in the kidneys → CKD leads to low vitamin D
· the kidneys normally excrete phosphate → CKD leads to high phosphate
This, in turn, causes other problems:
· the high phosphate level 'drags' calcium from the bones, resulting in osteomalacia
· low calcium: due to lack of vitamin D, high phosphate
· secondary hyperparathyroidism: due to low calcium, high phosphate and low vitamin D
Management
The aim is to reduce phosphate and parathyroid hormone levels.
Overview
· reduced dietary intake of phosphate is the first-line management
· phosphate binders
· vitamin D: alfacalcidol, calcitriol
· parathyroidectomy may be needed in some cases
Phosphate binders
· aluminium-based binders are less commonly used now
· calcium-based binders
o problems include hypercalcemia and vascular calcification
· sevelamer
o a non-calcium based binder that is now increasingly used
o binds to dietary phosphate and prevents its absorption
o also appears to have other beneficial effects including reducing uric acid levels and improving the lipid profiles of patients with chronic kidney disease
| | |
| © Image used on license from Radiopaedia | |
X-ray of a Brown tumour caused by secondary hyperparathyroidism in a young female with chronic kidney disease
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:26
Erythropoietin
Erythropoietin is a haematopoietic growth factor that stimulates the production of erythrocytes. Erythropoietin is secreted by the kidney in response to cellular hypoxia. The main uses of erythropoietin are to treat the anaemia associated with chronic kidney disease and that associated with cytotoxic therapy.
Side-effects of erythropoietin
· accelerated hypertension potentially leading to encephalopathy and seizures (blood pressure increases in 25% of patients)
· bone aches
· flu-like symptoms
· skin rashes, urticaria
· pure red cell aplasia* (due to antibodies against erythropoietin)
· raised PCV increases risk of thrombosis (e.g. Fistula)
· iron deficiency 2nd to increased erythropoiesis
There are a number of reasons why patients may fail to respond to erythropoietin therapy:
· iron deficiency
· inadequate dose
· concurrent infection/inflammation
· hyperparathyroid bone disease
· aluminium toxicity
*the risk is greatly reduced with darbepoetin
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:26
Acid - base disorders
Metabolic acidosis
Metabolic acidosis is commonly classified according to the anion gap.
Normal anion gap ( = hyperchloraemic metabolic acidosis)
· gastrointestinal bicarbonate loss: diarrhoea, ureterosigmoidostomy, fistula
· renal tubular acidosis
· drugs: e.g. acetazolamide
· ammonium chloride injection
· Addison's disease
Raised anion gap
· lactate: shock, hypoxia
· ketones: diabetic ketoacidosis, alcohol
· urate: renal failure
· acid poisoning: salicylates, methanol
Metabolic alkalosis
Metabolic alkalosis may be caused by a loss of hydrogen ions or a gain of bicarbonate. It is due mainly to problems of the kidney or gastrointestinal tract
Causes
· vomiting / aspiration (e.g. peptic ulcer leading to pyloric stenos, nasogastric suction)
· diuretics
· liquorice, carbenoxolone
· hypokalaemia
· primary hyperaldosteronism
· Cushing's syndrome
· Bartter's syndrome
· congenital adrenal hyperplasia
Respiratory acidosis
Respiratory acidosis may be caused by a number of conditions
· COPD
· decompensation in other respiratory conditions e.g. life-threatening asthma / pulmonary oedema
· sedative drugs: benzodiazepines, opiate overdose
Respiratory alkalosis
Common causes
· anxiety leading to hyperventilation
· pulmonary embolism
· salicylate poisoning
· CNS disorders: stroke, subarachnoid haemorrhage, encephalitis
· altitude
· pregnancy
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:26
Acute vs. chronic renal failure
Best way to differentiate is renal ultrasound - most patients with CRF have bilateral small kidneys
Exceptions
· autosomal dominant polycystic kidney disease
· diabetic nephropathy
· amyloidosis
· HIV-associated nephropathy
Other features suggesting CRF rather than ARF
· hypocalcaemia (due to lack of vitamin D)
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:26
Chronic kidney disease: proteinuria
Proteinuria is an important marker of chronic kidney disease, especially for diabetic nephropathy. NICE recommend using the albumin:creatinine ratio (ACR) in preference to the protein:creatinine ratio (PCR) when identifying patients with proteinuria as it has greater sensitivity. For quantification and monitoring of proteinuria, PCR can be used as an alternative, although ACR is recommended in diabetics. Urine reagent strips are not recommended unless they express the result as an ACR
Approximate equivalent values
| ACR (mg/mmol) | PCR (mg/mmol) | Urinary protein excretion (g/24 h) |
| 30 | 50 | 0.5 |
| 70 | 100 | 1 |
Collecting an ACR sample
· by collecting a 'spot' sample it avoids the need to collect urine over a 24 hour period in order to detect or quantify proteinuria
· should be a first-pass morning urine specimen
· if the initial ACR is between 3 mg/mmol and 70 mg/mmol, this should be confirmed by a subsequent early morning sample. If the initial ACR is 70 mg/mmol or more, a repeat sample need not be tested.
Interpreting the ACR results
· the NICE guidelines state 'regard a confirmed ACR of 3 mg/mmol or more as clinically important proteinuria'
NICE recommendations for referral to a nephrologist:
· a urinary albumin:creatinine ratio (ACR) of 70 mg/mmol or more, unless known to be caused by diabetes and already appropriately treated
· a urinary ACR of 30 mg/mmol or more, together with persistent haematuria (two out of three dipstick tests show 1+ or more of blood) after exclusion of a urinary tract infection
· consider referral to a nephrologist for people with an ACR between 3-29 mg/mmol who have persistent haematuria and other risk factors such as a declining eGFR, or cardiovascular disease
Frequency of monitoring eGFR (number of times per year by eGFR and ACR categories) for people with or at risk of CKD
| eGFR categories (mL/min/1.73 m2) | ACR categories (mg/mmol) | ||
| A1 (< 3) Normal to mildly increased | A2 (3-30) Moderately increased | A3 (> 30) Severely increased | |
| G1 >=90 Normal and high | =< 1 | 1 | >= 1 |
| G2 60-89 Mild reduction related to normal range for a young adult | =< 1 | 1 | >= 1 |
| G3a 45-59 Mild to moderate reduction | 1 | 1 | 2 |
| G3b 30-44 Moderate to severe reduction | =< 2 | 2 | >= 2 |
| G4 15-29 Severe reduction | 2 | 2 | 3 |
| G5 <15 Kidney failure | 4 | >=4 | >=4 |
Management
· ACE inhibitors (or angiotensin II receptor blockers) are key in the management of proteinuria
o they should be used first-line in patients with coexistent hypertension and CKD
o if the ACR > 70 mg/mmol they are indicated regardless of the patient's blood pressure
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:26
Membranous glomerulonephritis
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 with nephrotic syndrome or proteinuria.
Renal biopsy demonstrates:
· electron microscopy: the basement membrane is thickened with subepithelial electron dense deposits. This creates a 'spike and dome' appearance
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
Management
· all patients should receive an ACE inhibitor or an angiotensin II receptor blocker (ARB):
o these have been shown to reduce proteinuria and improve prognosis
· immunosuppression
o as many patients spontaneously improve only patient with severe or progressive disease require immunosuppression
o 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
Prognosis - rule of thirds
· one-third: spontaneous remission
· one-third: remain proteinuric
· one-third: develop ESRF
Good prognostic features include female sex, young age at presentation and asymptomatic proteinuria of a modest degree at the time of presentation.
| | |
| © Image used on license from PathoPic | |
Silver-stained section showing thickened basement membrane, subepithelial spikes
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:26
Nephrotic syndrome
Triad of:
· 1. Proteinuria (> 3g/24hr) causing
· 2. Hypoalbuminaemia (< 30g/L) and
· 3. Oedema
Loss of antithrombin-III, proteins C and S and an associated rise in fibrinogen levels predispose to thrombosis. Loss of thyroxine-binding globulin lowers the total, but not free, thyroxine levels.
| | |
| |
Diagram showing the glomerulonephritides and how they typically present
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:26
Peritoneal dialysis
Peritoneal dialysis (PD) is a form of renal replacement therapy. It is sometimes used as a stop-gap to haemodialysis or for younger patients who do not want to have to visit hospital three times a week.
The majority of patients do Continuous Ambulatory Peritoneal Dialysis (CAPD), which involves four 2-litre exchanges/day.
Complications
· peritonitis: coagulase-negative staphylococci such as Staphylococcus epidermidis is the most common cause. Staphylococcus aureus is another common cause
· sclerosing peritonitis
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:26
Acute kidney injury: pathophysiology
Basic steps
· Final pathway is tubular cell death.
· renal medulla is a relatively hypoxic environment making it susceptible to renal tubular hypoxia.
· Renovascular autoregulation maintains renal blood flow across a range of arterial pressures.
· Estimates of GFR are the best indices of renal function. Useful clinical estimates can be obtained by considering serum creatinine, age, race, gender and body size. eGFR calculations such as the Cockcroft and Gault equation are less reliable in populations with high GFRs.
· Nephrotoxic stimuli such as aminoglycosides and radiological contrast media induce apoptosis. Myoglobinuria and haemolysis result in necrosis. Overlap exists and proinflammatory cytokines play and important role in potentiating ongoing damage.
· Post-operative renal failure is more likely to occur in patients who are elderly, have peripheral vascular disease, high BMI, have COPD, receive vasopressors, are on nephrotoxic medication or undergo emergency surgery.
· Avoiding hypotension will reduce the risk of renal tubular damage.
· There is no evidence that administration of ACE inhibitors or dopamine reduces the incidence of post-operative renal failure.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:26
Alport's syndrome
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 males with females rarely developing renal failure.
A favourite question is an Alport's patient with a failing renal transplant. This may be caused by the presence of anti-GBM antibodies leading to a Goodpasture's syndrome like picture.
Alport's syndrome usually presents in childhood. The following features may be seen:
· microscopic haematuria
· progressive renal failure
· bilateral sensorineural deafness
· lenticonus: protrusion of the lens surface into the anterior chamber
· retinitis pigmentosa
· renal biopsy: splitting of lamina densa seen on electron microscopy
Diagnosis
· molecular genetic testing
· renal biopsy
o electron microscopy: characteristic finding is of the longitudinal splitting of the lamina densa of the glomerular basement membrane, resulting in a 'basket-weave' appearance
*in around 85% of cases - 10-15% of cases are inherited in an autosomal recessive fashion with rare autosomal dominant variants existing
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:27
Anti-glomerular basement membrane (GBM) disease (Goodpasture's syndrome)
Anti-glomerular basement membrane (GBM) disease (previously known as Goodpasture's syndrome) is a rare type of small-vessel vasculitis associated with both pulmonary haemorrhage and rapidly progressive glomerulonephritis. It is caused by anti-glomerular basement membrane (anti-GBM) antibodies against type IV collagen. Goodpasture's syndrome is more common in men (sex ratio 2:1) and has a bimodal age distribution (peaks in 20-30 and 60-70 age bracket). It is associated with HLA DR2.
Features
· pulmonary haemorrhage
· rapidly progressive glomerulonephritis
o this typically results in a rapid onset acute kidney injury
o nephritis → proteinuria + haematuria
Investigations
· renal biopsy: linear IgG deposits along the basement membrane
· raised transfer factor secondary to pulmonary haemorrhages
Management
· plasma exchange (plasmapheresis)
· steroids
· cyclophosphamide
One of the main complications is pulmonary haemorrhage. Factors which increase the likelihood of this include:
· smoking
· lower respiratory tract infection
· pulmonary oedema
· inhalation of hydrocarbons
· young males
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:27
Arteriovenous fistulas
Arteriovenous fistulas are direct connections between arteries and veins. They may occur pathologically but are generally formed surgically to allow access for haemodialysis.
They are now regarded as the preferred method of access for haemodialysis due to the lower rates of complications.
The time taken for an arteriovenous fistula to develop is 6 to 8 weeks.
Potential complications include:
· infection
· thrombosis
o may be detected by the absence of a bruit
· stenosis
o may present with acute limb pain
· steal syndrome
| | |
| Image sourced from Wikipedia | |
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:27
Chronic kidney disease: bone disease
Basic problems in chronic kidney disease
· low vitamin D (1-alpha hydroxylation normally occurs in the kidneys)
· high phosphate
· low calcium: due to lack of vitamin D, high phosphate
· secondary hyperparathyroidism: due to low calcium, high phosphate and low vitamin D
Several clinical manifestations may result:
Osteitis fibrosa cystica
· aka hyperparathyroid bone disease
Adynamic
· reduction in cellular activity (both osteoblasts and osteoclasts) in bone
· may be due to over treatment with vitamin D
Osteomalacia
· due to low vitamin D
Osteosclerosis
Osteoporosis
| | |
| © Image used on license from Radiopaedia | |
X-ray of a Brown tumour caused by secondary hyperparathyroidism in a young female with chronic kidney disease
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:27
Diabetic nephropathy: management
Screening
· all patients should be screened annually using urinary albumin:creatinine ratio (ACR)
· should be an early morning specimen
· ACR > 2.5 = microalbuminuria
Management
· dietary protein restriction
· tight glycaemic control
· BP control: aim for < 130/80 mmHg
· benefits independent of blood pressure control have been demonstrated for ACE inhibitors (ACE-i) and angiotensin II receptor blockers (A2RB). Combinations of ACE-i and A2RB are not commonly used anymore following the ON-TARGET trial which showed worse outcomes for patients on dual blockade
· control dyslipidaemia e.g. Statins
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:27
IgA nephropathy
IgA nephropathy (also known as Berger's disease) is the commonest cause of glomerulonephritis worldwide. It classically presents as macroscopic haematuria in young people following an upper respiratory tract infection.
Associated conditions
· alcoholic cirrhosis
· coeliac disease/dermatitis herpetiformis
· Henoch-Schonlein purpura
Pathophysiology
· thought to be caused by mesangial deposition of IgA immune complexes
· there is considerable pathological overlap with Henoch-Schonlein purpura (HSP)
· histology: mesangial hypercellularity, positive immunofluorescence for IgA & C3
Presentations
· young male, recurrent episodes of macroscopic haematuria
· typically associated with a recent respiratory tract infection
· nephrotic range proteinuria is rare
· renal failure is unusual and seen in a minority of patients
Differentiating between IgA nephropathy and post-streptococcal glomerulonephritis
· post-streptococcal glomerulonephritis is associated with low complement levels
· main symptom in post-streptococcal glomerulonephritis is proteinuria (although haematuria can occur)
· there is typically an interval between URTI and the onset of renal problems in post-streptococcal glomerulonephritis
| | |
| |
Management
· steroids/immunosuppressants not be shown to be useful
Prognosis
· 25% of patients develop ESRF
· markers of good prognosis: frank haematuria
· markers of poor prognosis: male gender, proteinuria (especially > 2 g/day), hypertension, smoking, hyperlipidaemia, ACE genotype DD
| | |
| © Image used on license from PathoPic | |
Proliferation and hypercellularity of the mesangium is seen in the glomerulus
| | |
| © Image used on license from PathoPic | |
Immunostaining for IgA in a patient with HSP
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:27
Nephrotic syndrome: complications
Complications
· increased risk of thromboembolism related to loss of antithrombin III and plasminogen in the urine
o deep vein thrombosis, pulmonary embolism
o renal vein thrombosis, resulting in a sudden deterioration in renal function
· hyperlipidaemia
o increasing risk of acute coronary syndrome, stroke etc
· chronic kidney disease
· increased risk of infection due to urinary immunoglobulin loss
· hypocalcaemia (vitamin D and binding protein lost in urine)
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:27
Nephrotoxicity due to contrast media
Contrast media nephrotoxicity may be defined as a 25% increase in creatinine occurring within 3 days of the intravascular administration of contrast media.
Risk factors include
· known renal impairment (especially diabetic nephropathy)
· age > 70 years
· dehydration
· cardiac failure
· the use of nephrotoxic drugs such as NSAIDs
Contrast-induced nephropathy occurs 2 -5 days after administration.
Prevention
· the evidence base currently supports the use of intravenous 0.9% sodium chloride at a rate of 1 mL/kg/hour for 12 hours pre- and post- procedure. There is also evidence to support the use of isotonic sodium bicarbonate
· N-acetylcysteine has been given in the past but recent evidence suggests it is not effective*
* Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine. N Engl J Med. 2018;378(7):603
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:27
Post-streptococcal glomerulonephritis
Post-streptococcal glomerulonephritis typically occurs 7-14 days following a group A beta-haemolytic Streptococcus infection (usually Streptococcus pyogenes). It is caused by immune complex (IgG, IgM and C3) deposition in the glomeruli. Young children are most commonly affected.
Features
· general
o headache
o malaise
· visible haematuria
· proteinuria
o this may result in oedema
· hypertension
· oliguria
· bloods:
o low C3
o raised ASO titre
| vi | |
| |
IgA nephropathy and post-streptococcal glomerulonephritis are often confused as they both can cause renal disease following an URTI
Renal biopsy features
· post-streptococcal glomerulonephritis causes acute, diffuse proliferative glomerulonephritis
· endothelial proliferation with neutrophils
· electron microscopy: subepithelial 'humps' caused by lumpy immune complex deposits
· immunofluorescence: granular or 'starry sky' appearance
Carries a good prognosis
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:27
Renal replacement therapy
Chronic kidney disease (CKD) is a relatively common condition, affecting 1 in 8 people in the UK. Around 10% of those with CKD will go on to develop renal failure, which is defined as a glomerular filtration rate of less than 15ml/min. For patients with renal failure, the management options are renal replacement therapy (RRT), to take over the physiology of the kidneys, or conservative management, which will be palliative.
There are several types of renal replacement therapy available to patients:
· haemodialysis
· peritoneal dialysis
· renal transplant
The decision about which RRT option to pick should be made jointly by the patient and their healthcare team, taking into account the following:
· predicted quality of life
· predicted life expectancy
· patient preference
· co-existing medical conditions
Haemodialysis is the most common form of renal replacement therapy. This involves regular filtration of the blood through a dialysis machine in hospital. Most patients need dialysis 3 times per week, with each session lasting 3-5 hours. At least 8 weeks before the commencement of treatment, the patient must undergo surgery to create an arteriovenous fistula, which provides the site for haemodialysis. Most commonly this is created in the lower arm. Some patients may be trained to perform home haemodialysis so that they do not have to regularly attend hospital.
Peritoneal dialysis is another form of renal replacement therapy where the filtration occurs within the patient's abdomen. Dialysis solution is injected into the abdominal cavity through a permanent catheter. The high dextrose concentration of the solution draws waste products from the blood into the abdominal cavity across the peritoneum. After several hours of dwell time, the dialysis solution is then drained, removing the waste products from the body, and exchanged for new dialysis solution. There are two types of peritoneal dialysis:
· Continuous ambulatory peritoneal dialysis (CAPD) - as described above, with each exchange lasting 30-40 minutes and each dwell time lasting 4-8 hours. The patient may go about their normal activities with the dialysis solution inside their abdomen
· Automated peritoneal dialysis (APD) - a dialysis machine fills and drains the abdomen while the patient is sleeping, performing 3-5 exchanges over 8-10 hours each night
Renal transplantation involves the receipt of a kidney from either a live or deceased donor. The average wait for a kidney in the UK is 3 years, though patients may also receive kidneys donated by cross-matched friends or family. The donor kidney is transplanted into the groin, with the renal vessels connected to the external iliac vessels. The failing kidneys are not removed. Following transplantation, the patient must take life-long immunosuppressants to prevent rejection of the new kidney. The average lifespan of a donor kidney is 10-12 years from deceased donors and 12-15 years from living donors.
Complications of renal replacement therapy
| Haemodialysis | Peritoneal dialysis | Renal transplantation |
| Site infection | Peritonitis | DVT / PE |
| Endocarditis | Sclerosing peritonitis | Opportunistic infection |
| Stenosis at site | Catheter infection | Malignancies (particularly lymphoma and skin cancer) |
| Hypotension | Catheter blockage | Bone marrow suppression |
| Cardiac arrhythmia | Constipation | Recurrence of original disease |
| Air embolus | Fluid retention | Urinary tract obstruction |
| Anaphylactic reaction to sterilising agents | Hyperglycaemia | Cardiovascular disease |
| Disequilibration syndrome | Hernias | Graft rejection |
| Back pain | ||
| Malnutrition |
The average life expectancy of a patient with renal failure that does not receive renal replacement therapy is 6 months. The symptoms of renal failure that is not being adequately managed with RRT are:
· breathlessness
· fatigue
· insomnia
· pruritus
· poor appetite
· swelling
· weakness
· weight gain/loss
· abdominal cramps
· nausea
· muscle cramps
· headaches
· cognitive impairment
· anxiety
· depression
· sexual dysfunction
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:28
Renal transplant: immunosuppression
Example regime
· initial: ciclosporin/tacrolimus with a monoclonal antibody
· maintenance: ciclosporin/tacrolimus with MMF or sirolimus
· add steroids if more than one steroid responsive acute rejection episode
Ciclosporin
· inhibits calcineurin, a phosphotase involved in T cell activation
Tacrolimus
· lower incidence of acute rejection compared to ciclosporin
· also less hypertension and hyperlipidaemia
· however, high incidence of impaired glucose tolerance and diabetes
Mycophenolate mofetil (MMF)
· blocks purine synthesis by inhibition of IMPDH
· therefore inhibits proliferation of B and T cells
· side-effects: GI and marrow suppression
Sirolimus (rapamycin)
· blocks T cell proliferation by blocking the IL-2 receptor
· can cause hyperlipidaemia
Monoclonal antibodies
· selective inhibitors of IL-2 receptor
· daclizumab
· basilximab
Monitoring
Patients on long-term immunosuppression for organ transplantation require regular monitoring for complications such as:
Cardiovascular disease - tacrolimus and ciclosporin can cause hypertension and hyperglycaemia. Tacrolimus can also cause hyperlipidaemia. Patients must be monitored for accelerated cardiovascular disease.
Renal failure - due to nephrotoxic effects of tacrolimus and ciclosporin/graft rejection/recurrence of original disease in transplanted kidney
Malignancy - patients should be educated about minimising sun exposure to reduce the risk of squamous cell carcinomas and basal cell carcinomas
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:28
Spironolactone
Spironolactone is an aldosterone antagonist which acts in the cortical collecting duct.
Indications
· ascites: patients with cirrhosis develop a secondary hyperaldosteronism. Relatively large doses such as 100 or 200mg are often used
· hypertension: used in some patients as a NICE 'step 4' treatment
· heart failure (see RALES study below)
· nephrotic syndrome
· Conn's syndrome
Adverse effects
· hyperkalaemia
· gynaecomastia: less common with eplerenone
RALES
· NYHA III + IV, patients already taking ACE inhibitor
· low dose spironolactone reduces all cause mortality
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:28
Urine
Hyaline casts
· consist of Tamm-Horsfall protein (secreted by distal convoluted tubule)
· seen in normal urine, after exercise, during fever or with loop diuretics
Acute tubular necrosis
· brown granular casts in urine
Prerenal uraemia
· 'bland' urinary sediment
Red cell casts
· nephritic syndrome
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:28
Acute kidney injury: NICE guidelines
This guideline tells what increases the risk of AKI:
· 1. Emergency surgery, ie, risk of sepsis or hypovolaemia
· 2. Intraperitoneal surgery
· 3. CKD, ie if eGFR < 60
· 4. Diabetes
· 5. Heart failure
· 6. Age >65 years
· 7. Liver disease
· 8. Use of nephrotoxic drugs
It also defines the criteria for diagnosing AKI
· 1. Rise in creatinine of 26 micromol/L or more in 48 hours OR
· 2. >= 50% rise in creatinine over 7 days OR
· 3. Fall in urine output to less than 0.5ml/kg/hour for more than 6 hours in adults (8 hours in children) OR
· 4. >= 25% fall in eGFR in children / young adults in 7 days.
Refer to a nephrologist if any of the following apply:
· 1. Renal tranplant
· 2. ITU patient with unknown cause of AKI
· 3. Vasculitis/ glomerulonephritis/ tubulointerstitial nephritis/ myeloma
· 4. AKI with no known cause
· 5. Inadequate response to treatment
· 6. Complications of AKI
· 7. Stage 3 AKI (see guideline for details)
· 8. CKD stage 4 or 5
· 9. Qualify for renal replacement hyperkalaemia / metabolic acidosis/ complications of uraemia/ fluid overload (pulmonary oedema)
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:28
Chronic kidney disease: hypertension
The majority of patients with chronic kidney disease (CKD) will require more than two drugs to treat hypertension. ACE inhibitors are first line and are particularly helpful in proteinuric renal disease (e.g. diabetic nephropathy). As these drugs tend to reduce filtration pressure a small fall in glomerular filtration pressure (GFR) and rise in creatinine can be expected. NICE suggest that a decrease in eGFR of up to 25% or a rise in creatinine of up to 30% is acceptable, although any rise should prompt careful monitoring and exclusion of other causes (e.g. NSAIDs). A rise greater than this may indicate underlying renovascular disease.
Furosemide is useful as a anti-hypertensive in patients with CKD, particularly when the GFR falls to below 45 ml/min*. It has the added benefit of lowering serum potassium. High doses are usually required. If the patient becomes at risk of dehydration (e.g. Gastroenteritis) then consideration should be given to temporarily stopping the drug
*the NKF K/DOQI guidelines suggest a lower cut-off of less than 30 ml/min
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:28
Fibromuscular dysplasia
Renal artery stenosis secondary to atherosclerosis accounts for around 90% of renal vascular disease, with fibromuscular dysplasia being the most common cause of the remaining 10%.
Epidemiology
· 90% of patients are female
Features
· hypertension
· chronic kidney disease or more acute renal failure e.g. secondary to ACE-inhibitor initiation
· 'flash' pulmonary oedema
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:28
Fluid compartment physiology
Body fluid compartments comprise intracellular and extracellular compartments. The latter includes interstitial fluid, plasma and transcellular fluid.
Typical figures are based on the 70 Kg male.
Body fluid volumes
| Compartment | Volume in litres | Percentage of total volume |
| Intracellular | 28 L | 60-65% |
| Extracellular | 14 L | 35-40% |
| Plasma | 3 L | 5% |
| Interstitial | 10 L | 24% |
| Transcellular | 1 L | 3% |
Figures are approximate
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:28
Focal segmental glomerulosclerosis
Focal segmental glomerulosclerosis (FSGS) is a cause of nephrotic syndrome and chronic kidney disease. It generally presents in young adults.
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.
Investigations
· renal biopsy
o focal and segmental sclerosis and hyalinosis on light microscopy
o effacement of foot processes on electron microscopy
Management
· steroids +/- immunosuppressants
Prognosis
· untreated FSGS has a < 10% chance of spontaneous remission
| | |
| © Image used on license from PathoPic | |
Sclerosis of the glomerulus is seen next to Bowman's capsule
| | |
| © Image used on license from PathoPic | |
Sclerosis is seen in the perihilar region of the glomerulus
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:28
Hypokalaemia: features
Features
· muscle weakness, hypotonia
· hypokalaemia predisposes patients to digoxin toxicity - care should be taken if patients are also on diuretics
ECG features
· U waves
· small or absent T waves
· prolonged PR interval
· ST depression
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:28
Polyuria
A recent review in the BMJ categorised the causes of polyuria by how common they were. This does not of course tally with how common they are in exams!
Common (>1 in 10)
· diuretics, caffeine & alcohol
· diabetes mellitus
· lithium
· heart failure
Infrequent (1 in 100)
· hypercalcaemia
· hyperthyroidism
Rare (1 in 1000)
· chronic renal failure
· primary polydipsia
· hypokalaemia
Very rare (<1 in 10 000)
· diabetes insipidus
Jakes A, Bhandari S. Investigating polyuria. BMJ 2013;347:f6772.
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:28
Reflux nephropathy
Overview
· term used to chronic pyelonephritis secondary to vesico-uretic reflux
· commonest cause of chronic pyelonephritis
· scarring usually occurs in first 5 years
· strong genetic disposition
· renal scar may produce increased quantities of renin causing hypertension
Diagnosis
· micturating cystography
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:28
Renal artery stenosis (secondary to atherosclerosis)
Renal artery stenosis secondary to atherosclerosis accounts for around 90% of renal vascular disease, with fibromuscular dysplasia being the most common cause of the remaining 10%.
Features
· hypertension
· chronic kidney disease
· 'flash pulmonary oedema'
From <https://www.passmedicine.com/review/textbook.php?s=#>
Primary and secondary aldosteronism can be differentiated by looking at the renin levels. If renin is high then a secondary cause is more likely, i.e renal artery stenosis.
Renal artery stenosis - the patient has a high renin level and therefore a secondary aldosteronism is more likely. The reduced perfusion results in decreased stimulation of the baroreceptors (or stretch receptors) in the wall of the afferent arteriole. The renin–angiotensin–aldosterone system is activated and with the increased aldosterone the potassium may be low, and the sodium high.
From <https://www.passmedicine.com/question/questions.php?q=0>
24 December 2020
14:28
Sterile pyuria
Causes
· partially treated UTI
· urethritis e.g. Chlamydia
· renal tuberculosis
· renal stones
· appendicitis
· bladder/renal cell cancer
· adult polycystic kidney disease
· analgesic nephropathy
From <https://www.passmedicine.com/review/textbook.php?s=#>
24 December 2020
14:29
Systemic lupus erythematosus: renal complications
Lupus nephritis is a severe manifestation of systemic lupus erythematosus (SLE) that can result in end-stage renal disease. SLE patients should be monitored by performing urinalysis at regular check-up appointments to rule out proteinuria.
WHO classification
· class I: normal kidney
· class II: mesangial glomerulonephritis
· class III: focal (and segmental) proliferative glomerulonephritis
· class IV: diffuse proliferative glomerulonephritis
· class V: diffuse membranous glomerulonephritis
· class VI: sclerosing glomerulonephritis
Class IV (diffuse proliferative glomerulonephritis) is the most common and severe form. Renal biopsy characteristically shows the following findings:
· glomeruli shows endothelial and mesangial proliferation, 'wire-loop' appearance
· if severe, the capillary wall may be thickened secondary to immune complex deposition
· electron microscopy shows subendothelial immune complex deposits
· granular appearance on immunofluorescence
| | |
| © Image used on license from PathoPic | |
Diffuse proliferative SLE. Proliferation of endothelial and mesangial cells. The thickening of the capillary wall results in a 'wire-loop' appearance. Some crescents are present.
Management
· treat hypertension
· corticosteroids if clinical evidence of disease
· immunosuppressants e.g. azathioprine/cyclophosphamide
From <https://www.passmedicine.com/review/textbook.php?s=#>
22 December 2020
17:16
Acute kidney injury: a very basic introduction
Acute kidney injury (AKI), previously termed acute renal failure, describes a reduction in renal function following an insult to the kidneys. In years gone by the kidneys were very much a neglected organ in acute medicine - the recognition of decreasing renal function was often slow and action limited. Around 15% of patients admitted to hospital develop AKI.
Whilst most patients with AKI recover their renal function there are many patients who will have long term impaired kidney function due to AKI. As well as long-term morbidity, AKI may also result in acute complications including death. Whilst exact figures are difficult to calculate NICE estimate that inpatient mortality of AKI in the UK might typically be 25-30% or more.
Pre-renal:
· Caused by inadequate renal perfusion e.g. dehydration, haemorrhage, heart failure, sepsis
· Kidneys act to concentrate urine and retain sodium - urine osmolality high, urine sodium low
Renal:
· Most common = acute tubular necrosis
· Damage to tubular cells due to prolonged ischaemia or toxins
· Kidneys can no longer concentrate urine or retain sodium - urine osmolality low, urine sodium high
· Rarer causes = acute glomerulonephritis, acute interstitial nephritis
Post-renal:
· Obstruction of urinary tract
· Usually identified with hydronephrosis on renal ultrasound
| | |
| © Image used on license from PathoPic | |
Specimen from a patient who had an acute kidney injury. Note the marked pallor of the cortex in certain areas, contrasting to the darker areas of surviving medullary tissue.
What causes AKI?
Causes of AKI are traditionally divided into prerenal, intrinsic and postrenal causes
Prerenal
Think of what causes big problems in other major organs. In the heart, a lack of blood flow (ischaemia) to the myocardium causes a myocardial infarction. In a similar fashion, 85% of strokes are caused by ischaemia to the brain. The same goes for the kidneys. One of the major causes of AKI is ischaemia, or lack of blood flowing to the kidneys.
Examples
· hypovolaemia secondary to diarrhoea/vomiting
· renal artery stenosis
Intrinsic
The second group of causes relate to intrinsic damage to the glomeruli, renal tubules or interstitium of the kidneys themselves. This may be due to toxins (drugs, contrast etc) or immune-mediated glomuleronephritis.
Examples
· glomerulonephritis
· acute tubular necrosis (ATN)
· acute interstitial nephritis (AIN), respectively
· rhabdomyolysis
· tumour lysis syndrome
Postrenal
The third group relates to problems after the kidneys. This is where there is an obstruction to the urine coming from the kidneys resulting in things 'backing-up' and affecting the normal renal function. An example could be a unilateral ureteric stone or bilateral hydroneprosis secondary to acute urinary retention caused by benign prostatic hyperplasia.
Examples
· kidney stone in ureter or bladder
· benign prostatic hyperplasia
· external compression of the ureter
| | |
| © Image used on license from PathoPic | |
This patient had an invasive papillary tumour of the distal left ureter, indicated by the arrow. This resulted in the ureter becoming blocked, resulting in a left hydroureter and hydronephrosis. Note the thinning of the renal cortex of the left kidney compared to the right.
Who is at an increased risk of AKI?
One of the keys to reducing the incidence of AKI is identifying patient who are at increased risk. NICE support this approach and have published guidelines suggesting which patients are at greater risk.
Risk factors for AKI include:
· chronic kidney disease
· other organ failure/chronic disease e.g. heart failure, liver disease, diabetes mellitus
· history of acute kidney injury
· use of drugs with nephrotoxic potential (e.g. NSAIDs, aminoglycosides, ACE inhibitors, angiotensin II receptor antagonists [ARBs] and diuretics) within the past week
· use of iodinated contrast agents within the past week
· age 65 years or over
oliguria (urine output less than 0.5 ml/kg/hour)
· neurological or cognitive impairment or disability, which may mean limited access to fluids because of reliance on a carer
Preventing AKI
By identifying patients at increased risk of AKI (see above) it may be possible to take steps to reduce the risk. For example, patients who are at risk of AKI and who are undergoing an investigation requiring contrast are usually given IV fluids to reduce the risk. Certain drugs such as ACE inhibitors and ARBs may also be temporarily stopped.
What happens when kidneys stop working?
It's best to work backwards and think about what kidneys actually do. The kidneys are primarily responsible for fluid balance and maintaining homeostasis. Therefore two of the key ways AKI may be detected are:
· a reduced urine output. This is termed oliguria and is defined as a urine output of less than 0.5 ml/kg/hour
· fluid overload
· a rise in molecules that the kidney normal excretes/maintains a careful balance of. Examples include potassium, urea and creatinine
Symptoms and signs
Many patients with early AKI may experience no symptoms. However, as renal failure progresses the following may be seen:
· reduced urine output
· pulmonary and peripheral oedema
· arrhythmias (secondary to changes in potassium and acid-base balance)
· features of uraemia (for example, pericarditis or encephalopathy)
Detection
One of the most common blood tests performed on the wards is 'urea and electrolytes' or 'U&Es'. This returns a number of markers, including
· sodium
· potassium
· urea
· creatinine
NICE recommend that we can use a variety of different criteria to make an official diagnosis of AKI. They state:
Detect acute kidney injury, in line with the (p)RIFLE, AKIN or KDIGO definitions, by using any of the following criteria:
· a rise in serum creatinine of 26 micromol/litre or greater within 48 hours
· a 50% or greater rise in serum creatinine known or presumed to have occurred within the past 7 days
· a fall in urine output to less than 0.5 ml/kg/hour for more than 6 hours in adults and more than
Urinalysis
· all patients with suspected AKI should have urinalysis
Imaging
· if patients have no identifiable cause for the deterioration or are at risk of urinary tract obstruction they should have a renal ultrasound within 24 hours of assessment.
Management
The management of AKI is largely supportive. This means patients require careful fluid balance to ensure that the kidneys are properly perfused but not excessively to avoid fluid overload. It is also important to review a patient's medication list to see what treatments may either be exacerbating their renal dysfunction or may be dangerous as a consequence of renal dysfunction. The table below gives some examples of common drugs:
| Usually safe to continue in AKI | Should be stopped in AKI as may worsen renal function | May have to be stopped in AKI as increased risk of toxicity (but doesn't usually worsen AKI itself) |
| • Paracetamol • Warfarin • Statins • Aspirin (at a cardioprotective dose of 75mg od) • Clopidogrel • Beta-blockers | • NSAIDs (except if aspirin at cardiac dose e.g. 75mg od) • Aminoglycosides • ACE inhibitors • Angiotensin II receptor antagonists • Diuretics | • Metformin • Lithium • Digoxin |
Treatments which are not recommend include the routine use of loop diuretics (to artificially boost urine output) and low-dose dopamine (in an attempt to increase renal perfusion). There is however a role for loop diuretics in patients who experience significant fluid overload.
Hyperkalaemia also needs prompt treatment to avoid arrhythmias which may potentially be life-threatening. The table below categorises the different treatments for hyperkalaemia:
| Stabilisation of the cardiac membrane | • Short-term shift in potassium from extracellular to intracellular fluid compartment | • Removal of potassium from the body |
| • Intravenous calcium gluconate | • Combined insulin/dextrose infusion • Nebulised salbutamol | • Calcium resonium (orally or enema) • Loop diuretics • Dialysis |
Specialist input from a nephrologist is required for cases where the cause is not known or where the AKI is severe.
All patients with suspected AKI secondary to urinary obstruction require prompt review by a urologist.
Renal replacement therapy (e.g. haemodialysis) is used when a patient is not responding to medical treatment of complications, for example hyperkalaemia, pulmonary oedema, acidosis or uraemia.
From <https://www.passmedicine.com/question/questions.php?q=0>
21 December 2020
21:51
Metabolic acidosis
Metabolic acidosis is commonly classified according to the anion gap. This can be calculated by: (Na+ + K+) - (Cl- + HCO-3). If a question supplies the chloride level then this is often a clue that the anion gap should be calculated. The normal range = 10-18 mmol/L
Normal anion gap ( = hyperchloraemic metabolic acidosis)
· gastrointestinal bicarbonate loss: diarrhoea, ureterosigmoidostomy, fistula
· renal tubular acidosis
· drugs: e.g. acetazolamide
· ammonium chloride injection
· Addison's disease
Raised anion gap
· lactate: shock, sepsis, hypoxia
· ketones: diabetic ketoacidosis, alcohol
· urate: renal failure
· acid poisoning: salicylates, methanol
Metabolic acidosis secondary to high lactate levels may be subdivided into two types:
· lactic acidosis type A: sepsis, shock, hypoxia, burns
· lactic acidosis type B: metformin
From <https://www.passmedicine.com/review/textbook.php?s=#>
Tuesday, 22 December 2020
18:25
Chronic kidney disease: anaemia
Patients with chronic kidney disease (CKD) may develop anaemia due to a variety of factors, the most significant of which is reduced erythropoietin levels. This is usually a normochromic normocytic anaemia and becomes apparent when the GFR is less than 35 ml/min (other causes of anaemia should be considered if the GFR is > 60 ml/min). Anaemia in CKD predisposes to the development of left ventricular hypertrophy - associated with a three fold increase in mortality in renal patients
Causes of anaemia in renal failure
· reduced erythropoietin levels - the most significant factor
· reduced erythropoiesis due to toxic effects of uraemia on bone marrow
· reduced absorption of iron
· anorexia/nausea due to uraemia
· reduced red cell survival (especially in haemodialysis)
· blood loss due to capillary fragility and poor platelet function
· stress ulceration leading to chronic blood loss
Management
· the 2011 NICE guidelines suggest a target haemoglobin of 10 - 12 g/dl
· determination and optimisation of iron status should be carried out prior to the administration of erythropoiesis-stimulating agents (ESA). Many patients, especially those on haemodialysis, will require IV iron
· ESAs such as erythropoietin and darbepoetin should be used in those 'who are likely to benefit in terms of quality of life and physical function'
21 December 2020
21:51
Rhabdomyolysis
Rhabdomyolysis will typically feature in the exam as a patient who has had a fall or prolonged epileptic seizure and is found to have an acute kidney injury on admission.
Features
· acute kidney injury with disproportionately raised creatinine
· elevated creatine kinase (CK)
· myoglobinuria
· hypocalcaemia (myoglobin binds calcium)
· elevated phosphate (released from myocytes)
· hyperkalaemia (may develop before renal failure)
· metabolic acidosis
Causes
· seizure
· collapse/coma (e.g. elderly patients collapses at home, found 8 hours later)
· ecstasy
· crush injury
· McArdle's syndrome
· drugs: statins (especially if co-prescribed with clarithromycin)
Management
· IV fluids to maintain good urine output
· urinary alkalinization is sometimes used
From <https://www.passmedicine.com/review/textbook.php?s=#>
Tuesday, 22 December 2020
18:20
Chronic kidney disease: eGFR and classification
Serum creatinine may not provide an accurate estimate of renal function due to differences in muscle. For this reason, formulas were developed to help estimate the glomerular filtration rate (estimated GFR or eGFR). The most commonly used formula is the Modification of Diet in Renal Disease (MDRD) equation, which uses the following variables:
· serum creatinine
· age
· gender
· ethnicity
Factors which may affect the result
· pregnancy
· muscle mass (e.g. amputees, body-builders)
· eating red meat 12 hours prior to the sample being taken
CKD may be classified according to GFR:
| CKD stage | GFR range |
| 1 | Greater than 90 ml/min, with some sign of kidney damage on other tests (if all the kidney tests* are normal, there is no CKD) |
| 2 | 60-90 ml/min with some sign of kidney damage (if kidney tests* are normal, there is no CKD) |
| 3a | 45-59 ml/min, a moderate reduction in kidney function |
| 3b | 30-44 ml/min, a moderate reduction in kidney function |
| 4 | 15-29 ml/min, a severe reduction in kidney function |
| 5 | Less than 15 ml/min, established kidney failure - dialysis or a kidney transplant may be needed |
*i.e. normal U&Es and no proteinuria
eGFR variables - CAGE - Creatinine, Age, Gender, Ethnicity
A
| Albuminuria categories in CKD | ||
| Category | ACR (mg/g) | Terms |
| A1 | <30 or <3 mg/mmol | Normal to mildly increased |
| A2 | 30-300 or 3-29 mg/mmol | Moderately increased* |
| A3 | >300 >30mg mmol | Severely increased** |
| Abbreviations: ACR, albumin-to-creatinine ratio; CKD, chronic kidney disease. *Relative to young adult level. **Including nephrotic syndrome (albumin excretion ACR >2220 mg/g) |
**Collectively referred to as “CGA Staging”
From <https://www.kidney.org/professionals/explore-your-knowledge/how-to-classify-ckd>
21 December 2020
21:50
Henoch-Schonlein purpura
Henoch-Schonlein purpura (HSP) is an IgA mediated small vessel vasculitis. There is a degree of overlap with IgA nephropathy (Berger's disease). HSP is usually seen in children following an infection.
Features
· palpable purpuric rash (with localized oedema) over buttocks and extensor surfaces of arms and legs
· abdominal pain
· polyarthritis
· features of IgA nephropathy may occur e.g. haematuria, renal failure
| |
| © Image used on license from DermNet NZ |
Treatment
· analgesia for arthralgia
· treatment of nephropathy is generally supportive. There is inconsistent evidence for the use of steroids and immunosuppressants
Prognosis
· usually excellent, HSP is a self-limiting condition, especially in children without renal involvement
· around 1/3rd of patients have a relapse
| |
| © Image used on license from DermNet NZ |
| |
| © Image used on license from DermNet NZ |
From <https://www.passmedicine.com/review/textbook.php?s=#>
21 December 2020
23:00
Anion gap
The anion gap is calculated by:
(sodium + potassium) - (bicarbonate + chloride)
A normal anion gap is 8-14 mmol/L
It is useful to consider in patients with a metabolic acidosis:
Causes of a normal anion gap or hyperchloraemic metabolic acidosis
· gastrointestinal bicarbonate loss: diarrhoea, ureterosigmoidostomy, fistula
· renal tubular acidosis
· drugs: e.g. acetazolamide
· ammonium chloride injection
· Addison's disease
Causes of a raised anion gap metabolic acidosis
· lactate: shock, hypoxia
· ketones: diabetic ketoacidosis, alcohol
· urate: renal failure
· acid poisoning: salicylates, methanol
· 5-oxoproline: chronic paracetamol use
From <https://www.passmedicine.com/review/textbook.php?s=#>
22 December 2020
20:18
ADPKD
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
| ADPKD type 1 | ADPKD type 2 |
| 85% of cases | 15% of cases |
| Chromosome 16 | Chromosome 4 |
| Presents with renal failure earlier |
The screening investigation for relatives is abdominal ultrasound:
Ultrasound diagnostic criteria (in patients with positive family history)
· two cysts, unilateral or bilateral, if aged < 30 years
· two cysts in both kidneys if aged 30-59 years
· four cysts in both kidneys if aged > 60 years
Management
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.
| | |
| © Image used on license from PathoPic | |
Extensive cysts are seen in an enlarged kidney
From <https://www.passmedicine.com/question/questions.php?q=0#>
21 December 2020
23:10
Amyloidosis
Overview
· amyloidosis is a term which describes the extracellular deposition of an insoluble fibrillar protein termed amyloid
· amyloid is derived from many different precursor proteins
· in addition to the fibrillar component, amyloid also contains a non-fibrillary protein called amyloid-P component, derived from the acute phase protein serum amyloid P
· other non-fibrillary components include apolipoprotein E and heparan sulphate proteoglycans
· the accumulation of amyloid fibrils leads to tissue/organ dysfunction
Classification
· systemic or localized
· further characterised by precursor protein (e.g. AL in myeloma - A for Amyloid, L for immunoglobulin Light chain fragments)
Diagnosis
· Congo red staining: apple-green birefringence
· serum amyloid precursor (SAP) scan
· biopsy of rectal tissue
From <https://www.passmedicine.com/question/questions.php?q=0>
22 December 2020
18:10
Chronic kidney disease: causes
Common causes of chronic kidney disease
· diabetic nephropathy
· chronic glomerulonephritis
· chronic pyelonephritis
· hypertension
· adult polycystic kidney disease
From <https://www.passmedicine.com/question/questions.php?q=0>
21 December 2020
21:35
Rapidly progressive glomerulonephritis
Rapidly progressive glomerulonephritis is a term used to describe a rapid loss of renal function associated with the formation of epithelial crescents in the majority of glomeruli.
Causes
· Goodpasture's syndrome
· Wegener's granulomatosis (c ANCA)
· others: SLE, microscopic polyarteritis
Features
· nephritic syndrome: haematuria with red cell casts, proteinuria, hypertension, oliguria
· features specific to underlying cause (e.g. haemoptysis with Goodpasture's, vasculitic rash or sinusitis with Wegener's)
| | |
| © Image used on license from PathoPic | |
Glomeruli are full of crescents.
| | |
| © Image used on license from PathoPic | |
Another image showing the glomeruli full of crescents
cANCA - c = Crescenteric glomerulonephritis!
From <https://www.passmedicine.com/question/questions.php?q=0>
Next question
Save my notes
Search
Go
Google search on "Rapidly progressive glomerulonephritis"
Media
| | |
| Osmosis - YouTube | 50 |
From <https://www.passmedicine.com/question/questions.php?q=0>
21 December 2020
21:50
Fluid therapy
The prescription of intravenous fluids is one of the most common tasks that junior doctors need to do.
In the 2013 guidelines NICE recommend the following requirements for maintenance fluids:
· 25-30 ml/kg/day of water and
· approximately 1 mmol/kg/day of potassium, sodium and chloride and
· approximately 50-100 g/day of glucose to limit starvation ketosis
So, for a 80kg patient, for a 24 hour period, this would translate to:
· 2 litres of water
· 80mmol potassium
For the first 24 hours NICE recommend the following::
When prescribing for routine maintenance alone, consider using 25-30 ml/kg/day sodium chloride 0.18% in 4% glucose with 27 mmol/l potassium on day 1 (there are other regimens to achieve this).
The amount of fluid patients require obviously varies according to their recent and past medical history. For example a patient who is post-op and is having significant losses from drains will require more fluid whereas a patient with heart failure should be given less fluid to avoid precipitating pulmonary oedema.
The table below shows the electrolyte concentrations (in millimoles/litre) of plasma and the most commonly used fluids:
| Na+ | Cl- | K+ | HCO3- | Glucose | |
| Plasma | 135-145 | 98-105 | 3.5-5 | 22-28 | - |
| 0.9% saline | 154 | 154 | - | - | - |
| 5% glucose | - | - | - | - | 50g |
| 0.18% saline with 4% glucose | 30 | 30 | - | - | 40g |
| Hartmann's solution | 131 | 111 | 5 | 29 | - |
Specific points
0.9% saline
· if large volumes are used there is an increased risk of hyperchloraemic metabolic acidosis
Hartmann's
· contains potassium and therefore should not be used in patients with hyperkalaemia
From <https://www.passmedicine.com/review/textbook.php?s=#>
Wednesday, 23 December 2020
01:01
Haematuria
The management of patients with haematuria is often difficult due to the absence of widely followed guidelines. It is sometimes unclear whether patients are best managed in primary care, by urologists or by nephrologists.
The terminology surrounding haematuria is changing. Microscopic or dipstick positive haematuria is increasingly termed non-visible haematuria whilst macroscopic haematuria is termed visible haematuria. Non-visible haematuria is found in around 2.5% of the population.
Causes of transient or spurious non-visible haematuria
· urinary tract infection
· menstruation
· vigorous exercise (this normally settles after around 3 days)
· sexual intercourse
Causes of persistent non-visible haematuria
· cancer (bladder, renal, prostate)
· stones
· benign prostatic hyperplasia
· prostatitis
· urethritis e.g. Chlamydia
· renal causes: IgA nephropathy, thin basement membrane disease
Spurious causes - red/orange urine, where blood is not present on dipstick
· foods: beetroot, rhubarb
· drugs: rifampicin, doxorubicin
Management
Current evidence does not support screening for haematuria. The incidence of non-visible haematuria is similar in patients taking aspirin/warfarin to the general population hence these patients should also be investigated.
Testing
· urine dipstick is the test of choice for detecting haematuria
· persistent non-visible haematuria is often defined as blood being present in 2 out of 3 samples tested 2-3 weeks apart
· renal function, albumin:creatinine (ACR) or protein:creatinine ratio (PCR) and blood pressure should also be checked
· urine microscopy may be used but time to analysis significantly affects the number of red blood cells detected
NICE urgent cancer referral guidelines were updated in 2015.
Urgent referral (i.e. within 2 weeks)
Aged >= 45 years AND:
· unexplained visible haematuria without urinary tract infection, or
· visible haematuria that persists or recurs after successful treatment of urinary tract infection
Aged >= 60 years AND have unexplained nonvisible haematuria and either dysuria or a raised white cell count on a blood test
Non-urgent referral
Aged 60 >= 60 years with recurrent or persistent unexplained urinary tract infection
Since the investigation (or not) of non-visible haematuria is such as a common dilemma a number of guidelines have been published. They generally agree with NICE guidance, of note:
· patients under the age of 40 years with normal renal function, no proteinuria and who are normotensive do not need to be referred and may be managed in primary care
22 December 2020
19:48
Hypokalaemia: features
Features
· muscle weakness, hypotonia
· hypokalaemia predisposes patients to digoxin toxicity - care should be taken if patients are also on diuretics
ECG features
· U waves
· small or absent T waves
· prolonged PR interval
· ST depression
From <https://www.passmedicine.com/question/questions.php?q=0#>
This gentleman has severe hypokalaemia, defined as a serum potassium < 2.5mmol/l. Mild to moderate hypokalaemia can be asymptomatic but the more severe the electrolyte derangement the more likely that symptoms will develop. Symptoms include weakness, leg cramps, palpitations secondary to cardiac arrhythmias and ascending paralysis.
Causes can be secondary to:
1.) Increased potassium loss:
· Drugs: thiazides, loop diuretics, laxatives, glucocorticoids, antibiotics
· GI losses: diarrhoea, vomiting, ileostomy
· Renal causes: dialysis
· Endocrine disorders: hyperaldosteronism, Cushing's syndrome
2.) Trans-cellular shift
· Insulin/glucose therapy
· Salbutamol
· Theophylline
· Metabolic alkalosis
3.) Decreased potassium intake
4.) Magnesium depletion (associated with increased potassium loss)
ECG changes seen in hypokalaemia include:
· U waves
· T wave flattening
· ST segment changes
Treatment of hypokalaemia depends on severity. Any causative agents should be removed. Gradual replacement of potassium via the oral route is preferred if possible.
Mild to moderate hypokalaemia 2.5 - 3.4 mmol/l can be treated with oral potassium provided the patient is not symptomatic and there are no ECG changes.
Severe hypokalaemia (<2.5mmol/l) or symptomatic hypokalaemia should be managed with IV replacement. The patient should be managed in an area where cardiac monitoring can take place. If there are no contraindications to fluid therapy (e.g. volume overload, heart failure) potassium should be diluted to low concentrations as higher concentrations can be phlebitic. The infusion rate should not exceed 20mmol/hr. In this case, 3 bags of 0.9% Saline with 40mmol KCL is the correct answer.
From <https://www.passmedicine.com/question/questions.php?q=0#>
Intrinsic AKI differences
01 January 2021
16:24
Membranous glomerulonephritis histology:
basement membrane thickening on light microscopy
subepithelial spikes on sliver stain
positive immunohistochemistry for PLA2
classically causes nephrotic syndrome (protein +hypoalbuminaemia)
Membranous glomerulonephritis also causes a hypercoagulable state,
Minimal change disease would typically affect children, who would be normotensive, with no haematuria and no findings on light microscopy.
Goodpasture's disease would cause nephritic syndrome (never nephrotic), lung symptoms and more systemic upset. It also would not cause these histology findings.
Focal segmental glomerulosclerosis would cause similar symptoms, urine dip and blood test findings to membranous glomeulonephritis but would not cause these histology findings.
IgA nephropathy is the commonest cause of glomerulonephritis in adults worldwide, particularly affecting young males. It can cause nephrotic or nephritic syndrome or isolated haematuria. It would not cause these histology findings.
From <https://www.passmedicine.com/question/questions.php?q=0>
nephrotic syndrome and nephritic syndrome are on a continuous spectrum
Causes of bladder outlet obstruction
04 January 2021
22:11
potential causes of bladder outlet obstruction:
· Genitalia: Meatal stenosis, phimosis, paraphimosis, atrophic vaginitis
· Urethra: Stones, strictures, diverticulum, posterior urethral valves, carcinoma, surgery
· Prostate: Benign prostatic hyperplasia, calculi, abscess, prostate carcinoma
· Gynaecologic: Prolapse, cystocele, pregnancy, ovarian mass, uterine tumour, cervical tumour
· Bladder: Calculi, blood clot, tumour, bladder neck dysfunction
· Bowel: Faecal impaction
· Neurogenic: Multiple sclerosis, diabetes, spinal cord trauma, Parkinson disease, cerebrovascular accident
From <https://mle.ncl.ac.uk/cases/page/17216/>
Pulmonary renal syndrome
04 January 2021
22:21
Pulmonary-renal syndrome is almost always a manifestation of an underlying autoimmune disorder.
Goodpasture syndrome is the prototype cause, but PRS can also be caused by SLE, granulomatosis with polyangiitis, microscopic polyangiitis, and, less commonly, by other vasculitides, connective tissue disorders, and drug-induced vasculitides.
From <https://mle.ncl.ac.uk/cases/page/16998/>
Pulmonary-renal syndrome (PRS) is diffuse alveolar haemorrhage plus glomerulonephritis, often occurring simultaneously. Cause is almost always an autoimmune disorder. Diagnosis is by serologic tests and sometimes lung and renal biopsy. Treatment typically includes immunosuppression with corticosteroids and cytotoxic drugs.
Pulmonary-renal syndrome (PRS) is not a specific entity but is a syndrome that suggests a differential diagnosis and a specific sequence of testing.
Systemic Symptoms: night sweats, abdominal pain, bloody diarrhoea
Signs of Sepsis: Fever, lymphadenopathy
Signs of Autoimmune Conditions: Joint pains, myalgia, rash, sicca, epistaxis, deafness, ulcers
Other Significant PMH: DVT/ PE thrombotic disorders, SLE, Autoimmune conditions
There are many potential reasons for coughing up blood. Causes for haemoptysis include:
Bronchitis (acute or chronic), the most common cause of coughing up blood. Haemoptysis due to bronchitis is rarely life-threatening.
Bronchiectasis
Lung cancer or non-malignant lung tumours
Use of anticoagulation
Pneumonia
Pulmonary embolism
Congestive heart failure, especially due to mitral stenosis
Tuberculosis
Inflammatory or autoimmune conditions (lupus, Granulomatosis with polyangiitis (GPA previously called Wegener’s), Microscopic polyangiitis (MPA), or Eosinophilic granulomatosis with polyangiitis (EGPA, previously called Churg-Strauss) and many others)
Pulmonary arteriovenous malformations (AVMs)
Crack cocaine
Trauma, such as a gunshot wound or motor vehicle accident
Dialysis indications
04 January 2021
22:58
AKI and dialysis indications (AEIOU)
Acidosis
· intractable metabolic acidosis
· Bic 14, PH <7.2
Electrolytes
· severe persistent hyperkalemia
· >6 – esp if anuric
Intoxication
· methanol, ethylene glycol, lithium, aspirin
Overload :hypervolemia
· Diuretics not effective
· Pulmonary oedema
Uraemia
· uremic pericarditis
· encephalopathy