Renal System

Question 1

when do you make a diagnosis of Acute Kidney Injury?

Answer 1

• If within 48 hours a patient has over 26.5micromol/L increase in serum creatinine
• The patients urine volume is <0.5mL/kg/hour for 6 hours;
• The patients serum creatinine has increased by over 1.5x the baseline which is known/presumed to occur within the prior 7 days​​

:<0.5 and 2.0x = injury; :<0.3 and 3.0x = failure

Persistent AKI>4 weeks = complete loss of kidney function; loss over 3 months = end stage renal disease

Question 2

What causes Acute Kidney Injury?

Answer 2

Physiologically AKI will be seen as failure of the Kidneys due to:

• Pre-renal: impaired renal perfusion, with an appropriate renal response.
• Intrinsic: direct injury to renal parenchyma.
• Post-renal: obstruction of urinary outflow.

Question 3

What are Pre-Renal causes of AKI?

Answer 3

Pre-Renal is any cause of decreased perfusion of the kidney. ⇒ Pre-renal azotaemia (organo-toxic nitrogenous waste build up)

• Hypovolaemia
  
  • Haemorrhage
  • D & V, heat, burns, dehydration
• Decreased perfusion by heart
  
  • Septic shock
  • cardiac failure
• Drugs
  
  • ACE inhibitors [post stenotic kidneys and HF]
    
    • cause intrarenal efferent vasodilation which decreases filtration pressure
  • NSAIDs
    
    • [Inhibit PG’s which normally dilate afferent artery = ^BP]

Question 4

What are renal causes of AKI?

Answer 4

Affects different kidney compartments via ic or dc GFR (filtering extras or not enough):

• Interstitum
  
  • Acute interstitial nephritis
    
    • kidney tubule swelling
      
      • can be due to allergic Drug rxn
• Tubule
  
  • Acute tubular necrosis (renovascular disease)
    
    • from Hypertension
    • Sepsis- causes ichaemia/haemodynamic changes and introduces inflamm cells to the renal parenchyma
    • Also: ACE inhibitor use w/underlying renal artery stenosis (atheroma etc) –> Ang II can no longer compensate the efferent arteriole GFR so it drops
• Glomerula
  
  • glomerulonephritis
• Vasculitis (BV damage inc SLE and Rheum Arth), scleroderma (affects connective tissue), multiple myeloma

Question 5

What are Post-renal causes of AKI?

Answer 5

Obstruction of passage of urine out of the body ⇒ AKI

• Pyelonephritis ~ascending UTIs
• Renal calculi
• Strictures
• Lymphoma
• Tumour
• Prostate hyperplasia

Question 6

What history/signs/symptoms may someone with AKI present with?

Answer 6

• Predispositions
  
  • CKD
  • Diabetes
  • peripheral vascular disease
• Trauma - pigment (heme) induced crush nepritis (is nephrotoxic)
• Radiological exams (contrast nephropathy)
• Current medications
  
  • allergic reaction (interstitial nephritis) - Beta lactam Ab
  • ACE inibitors
  • NSAIDs
• Hallucinations/Altered mental atate [uraemic sign]
• Asterixis [uraemic sign]
• Vomiting, Nausea
• Hypotension
  
  • (circulatory collapse e.g. pancreatitis, sepsis, fluid loss)
• Hypertension
• Pulmonary/peripharal oedema
  
  • protein loss

Question 7

What history/signs/symptoms may a patient with pre-renal AKI have?

Answer 7

• Increased fluid loss
  
  • haemorrhage
  • GI tract fluid loss
  • sweating
  • no replament therapy e.g. restriction of enteral input
• Hepatorenal syndrome in severe liver disease (a form of pre-renal azotaemia)

Question 8

What history/signs/symptoms may be seen in a paitent with intrinsic renal AKI?

Answer 8

• Rash
• Haematuria (nephritic syndrome - blood loss)
• Oedema (nephrotic syndrome - protein loss)
• Hypertension
• Vascular intervention –> cholesterol emboli [atheroembolic injury] or contrast induced injury
• Multiple myeloma
• Acute glomerulonephritis
• Renal vasculitis

Question 9

What history/signs/symptoms may be seen in a patient with post-renal AKI?

Answer 9

• Flank pain
• Haematuria
• Urgency, frequency and hesitancy (prostatism)
• Renal calculi
• Papillary necrosis (blood supply loss)
• Hx of
  
  • Malignancy
  • Prostatism
  • Nephrolithiasis (kidney stone disease)

Question 10

What tests should be ordered if you suspect a patient has AKI?

Answer 10

1. Basic metabolic profile
   
   • Blood Urea Nitrates, Calcium, Chloride, Potassium, Sodium, Glucose, CO2, Creatinine
     
     • Elevated serum creatinine maybe the only/initial sign of dc renal function as only reduced glomerular function can cause increased creatinine (>3months is chronic)[though there is acute on chronic]
       
       • ?​increased K+ and ?metabolic acidosis
2. Serum Urea to creatinine (20:1 supports pre-renal azo)
3. Urinalysis
   
   • RBCs, WBCs, cellular casts, proteinuria, bacteria, positive nitrite (e.g. nitrates + bacteria) and leukocyte esterase (in cases of infection)
     
     • ?subsq urine culture
   • Microhaematuria and proteinurea; HTN and oedema - Glomerular disease
4. FBC
   
   • Anaemia
     
     • possible CKD, blood loss
   • Leukocytosis
     
     • infection
   • Thrombocytopenia
     
     • rare disorders such as;
     • cryoglobulinaemia (abnormal Ig proteins that can precipitate out and cause inflammation and damage);
     • haemolytic uraemic syndrome (low RBC, AKFailure & low platelets),
     • or thrombotic thrombocytopenic purpura (forms small blood clots in small vessels over the body, Low RBC and ptlts)
5. Functional excretion of sodium/urine sodium concentration (may explain hypovolaemia etc; will be increased in dieuretics)
6. Functional excretion of urea (if exposed to diuretics)
7. urinary eosinophil count (atheroembolic or interstitial nepritis)
8. fluid challenge - both diagnostic and therapeutic in pre-renal azotaemia
9. venous blood gas
   
   • Acidosis - high H+ and low bicarb from meta screen
10. Catherterisation
    
    • Diag and therap for bladder neck obstruction cause (significant urine release)
      
      • & assess residual urine
        
        • minimal residue - higher obstruction or impaired urine production
      • & sample for analysis
11. Urine osmolality - normal tubular function and respose to ADH in hypovolaemia; close to serum in acute tubular necrosis
12. renal USS (obstruction/dilated calyces; CKD/small/sclerotic kidneys)
13. CXR (heart failure)
14. ECG (hyperkalaemia)

• tests to consider:
• SLE check - ANA, anti-DNA, Complement (C3,4,CH50)
• HIV serology (assoicated nephropathy and the meds)
• Normal ESR =/= inflammatory or embolic renal disease
• Renal Biopsy
  • Biopsy is frequently required to further investigate positive serological studies.
  • Biopsies also done when the cause of kidney injury is unclear.
  • May confirm acute tubular necrosis, but not often performed for this diagnosis.

Question 11

What is the general therapy for AKI?

Answer 11

• Intervention in electrolyte and acid/base abnormalities; monitored and optomised
• optimisation of volume status,
  
  • replacing volume in the volume-contracted patient;
  • or removal of fluid in patients with volume overload
    
    • diuresis
    • renal replacement therapy
• Sodium and volume restriction are generally required & with limiting potassium and phosphorus intake.
• Dose adjustment of medications
  
  • do not potentially nephrotoxic drugs unless there is no alternative.

Patients who have had an episode of AKI should be seen by a nephrologist before undergoing any diagnostic or therapeutic intervention that carries an increased risk of acute renal injury.

NSAIDs should be avoided.

Question 12

What is the approach to treating pre-renal failure?

Answer 12

Improve the haemodynamic status of the patient.

P-RA predisposes the kidney to injury from other means, such as contrast or nephrotoxins, minimise nephrotoxins and dose adjust drugs!

1)Volume expansion and/or RBC transfusion

These increase oncotic pressure in the intravascular space

• Crystalloid
  
  • normal saline or lactated Ringer’s
    
    • Freely cross capillary walls
    • Shorter half life (30-60mins) than Colloids
    • give 3x amout fluid lost as 1/3 in Intvasc and 2/3 to tissues
    • Normal saline good for risk reduction of contrast nephropathy (1 mL/kg/hour)
• Colloid
  
  • considered in cases of significant hypoalbuminaemia
  • semi-synthetic hydroxyethyl starch not recommended (appears to increasemortality)
• Significant anaemia =fluids are infused along with packed RBCs
• Haemorrhage requires blood product replacement.
  
  • Blood transfusion is generally not given if only 1 unit is anticipated.

2. Vasopressors: Dopamine OR adrenaline OR noradrenaline OR phenylephrine

[vasopressin sometimes used as an adjunct to these other vasopressors]

• Used In severe hypotension e.g. sepsis to augment BP whilst optimising the patient’s volume status
• Keep the mean arterial pressure (MAP) >60 mmHg. (MAP = DP + 1/3 PP
  
  • [pulse pressure = systolic pressure - diastolic pressure.])

3. Diuretics: Impaired urine production and volume expansion are commonly seen in cases of AKI.

• Loop diuretics (e.g., furosemide) and metolazone may be effective in promoting diuresis, although diuretic resistance is often seen.
• hough diuretics can help manage fluid volime in pre-renal AKI. Diuretic-unresponsive volume overload is an reason to proceed to RRT - dialysis or filtration
• Patients also require sodium restriction.

If renal hypoperfusion results from impaired cardiac function e.g. poor left ventricular systolic function optomiise cardiac output and volume status. Inotropes, diuretics, or renal replacement therapy may be required with close following of renal function and urine production.

Renal replacement therapy

• severe acid/base (e.g. metabolic acidosis),
• Increased potassium electrolyte,
• uraemic symptoms/complications are present
• while the underlying cardiac or volume issues are treated.

Nephrologist consultation; for haemodynamically stable patients = Conventional haemodialysis for 4 to 6 hours.

Question 13

How do you manage intrinsic renal failure?

Answer 13

Impaired urine production and volume expansion are commonly seen in cases of AKI.

Intrinsic renal failure management varies according to aetiology.

• Co-existing pre-renal azotaemia - Volume expansion
  
  • Crystalloid (normal saline or lactated Ringer’s) is sufficient in most cases for volume expansion.
  • Colloid might be used if there is significant hypoalbuminaemia. (albumin is a colloid)
• volume overload require sodium restriction. and also may be managed with diuretics when effective. –> furosemide (primary drug)
  
  • REMEMBER: diuretic-unresponsive volume overload is an indication to proceed to RRT.
• Removal of offending drugs, when possible, (interstitial nephritis or drug-induced AKI)
• corticosteroids, cytotoxic agents, or other immune-modifying drugs for Acute glomerulonephritis and vasculitis management
  
  • depending on the specific diagnosis, often determined by renal biopsy and serology studies.
  • consult a nephrologist for acute glomerulonephritis particularly regarding the use of cytotoxic and immune-modifying agents.
• There is no specific therapy for acute tubular necrosis aside from supportive care in maintaining volume status and controlling electrolyte and acid/base abnormalities.
• Renal replacement therapy is generally required if there is severe acidosis, volume expansion refractory to diuretics, hyperkalaemia, or uraemia (avku). These interventions remain a main treatment modality for AKI of all causes.

Question 14

How do you manage someone with obstructive renal failure?

Answer 14

Obstructive renal failure requires relief of the obstruction e.g. mechanical decompression @obstruction level

Bladder catheter –> done in all AKI cases where bladder outlet obstruction cannot be quickly ruled out by ultrasound.

• Above bladder neck obstruction relief:
  
  • ureteral stenting,
  • lithotripsy,
  • Exploratory laparotomy (compressing tumours may require surgical removal); may be done following ureteral stenting.
• Percutaneous nephrostomy: placement of a catheter into the renal pelvis percutaneously for drainage of urine from a distal obstruction
  
  • (urologist, surgeon or interventional radiologist)
• Urological or surgical assistance for ureteral stenting, urinary diversion, debulking procedures, or other case-specific requirements may become necessary.

Renal replacement therapy may be needed if there is severe acidosis, volume overload unresponsive to diuretics (furosemide is 1º, 2º = torazemide or bumetanide or metolazone) or electrolyte or uraemic complications while the underlying obstructive issue is being addressed

Question 15

What is chronic kidney disease?

Answer 15

Chronic kidney disease or chronic renal failure, is defined by either:

• a pathological abnormality of the kidney, such as haematuria and/or proteinuria,
• OR/AND a reduction in the glomerular filtration rate to <60 mL/minute/1.73 m²
• for ≥3 months’ duration
  
  • Abnormal kidney structure or function present for over 3 months with implications for health

AKI =

• serum creatinine of ≥23 micromol/L (≥0.3 mg/dL) from baseline, a
• 50% increase in serum creatinine from baseline,
• or a reduction in urine output of <0.5 mL/kg/hour for more than 6 hours that occurs over a period of days to weeks.

CKD is defined by

• evidence of kidney damage based on
  
  • pathological diagnosis,
  • abnormalities of radiographic imaging/biopsy,
  • tubule disorder,
  • transplant
• or laboratory evidence of kidney damage such as haematuria and/or proteinuria
• or a reduction in the glomerular filtration rate (GFR) to <60 mL/minute/1.73m² for ≥3 months.

CKD is divided into 6 distinct stages based on GFR, as follows:

• Stage 1: kidney damage with normal or increased GFR, ≥90 mL/minute/1.73m²
• Stage 2: kidney damage with mild decrease in GFR, 60 to 89 mL/minute/1.73m²
  
  • these 2 stages are only CKD if other evidence of kidney damage e.g. Lab/Path (not GFR)
• Stage 3a: kidney damage with (mild-)moderate decrease in GFR, 45 to 59 mL/minute/1.73m²
• Stage 3b: kidney damage with moderate(-severe) decrease in GFR, 30 to 44 mL/minute/1.73m²
• Stage 4: kidney damage with severe decrease in GFR, 15 to 29 mL/minute/1.73m² [dialysis, ?transplant]
• Stage 5: kidney failure (end-stage kidney disease), with GFR <15 mL/minute/1.73m² [transplant]

The majority of people are asymptomatic with the diagnosis determined only by laboratory studies. –> dont present until later stage

Albumin exrection: <30 = A1; 30-300 = A2; >300 = A3

Albumin:creatinine ratio; <3 = A1; 3-30=A2; >30=A3

The most common causes are diabetes mellitus, hypertension and glomerulornephritis.

• Glycaemic control for diabetic nephropathy and optimisation of blood pressure are key in slowing the progression of disease.
• CKD gives Increased risk for cardiovascular disease.

Question 16

What are the risk factors and causes of CKD?

Answer 16

• Ageing population; include age >50 years,
• Male sex
• Smoking, obesity,
• long-term analgesic use
• autoimmune disorders
• Diabetes
  
  • This is the most common cause in the adult population
  • Est. 1/3 of diabetics will develop diabetic kidney disease within 5-10 years of diagnosis
    
    • macroalbuminurea (>300 mg albumin/24 hours)
    • and/or reduction in GFR (<90 mL/minute/1.73 m²)
• Hypertension
  
  • 2nd most common cause of CKD
  • diagnosis of hypertensive renal disease often given if no other identifiable aetiology is evident.
• increased incidence of glomerular disorders such as focal segmental glomerulosclerosis.
• Black, Hispanic ethnicity = higher risk than gen population
• Family member with diagnosis of kidney disease
• Previous Acute Kidney Injury = risk for CKD and ESRD in the future.

Less frequent causes of CKD include

• cystic disorders of the kidney (polycystic kidney disease),
• obstructive nephropathy,
• glomerular nephrotic (proteinurea due to podocyte damage) and nephritic (haematurea due to inflammatory damage) syndromes such as
  
  • focal segmental glomerulosclerosis,
    
    • Kidney scarring (of certain segments), has many different causes
  • membranous nephropathy,
    
    • Auto-Immune complexes (abs made by the immune system attached to ags) get caught in the kidney filters (glomeruli). In most cases of MN, antibodies are made to an antigen that is part of the kidney filter (glomerulus) itself.
  • lupus nephritis,
    
    • autoimmune against nuclear components e.g. dsDNA
  • amyloidosis,
    
    • pathological folding of proteins –> ECM accumulation
  • rapidly progressive glomerulonephritis
    
    • autoimmune, any agressive GN (renal failure/CKD over days/weeks)

Question 17

What is the disease progression of CKD?

Answer 17

Regardless of the method of renal injury (i.e., diabetes, hypertension, or glomerular disorders), once renal damage has occurred –> cascade of events ensues where structural alterations and accompanying biochemical, cellular, and molecular changes lead to progressive renal scarring and loss of kidney function.

• renal injury response
  
  1. increase in intra-glomerular pressure with glomerular hypertrophy,
     
     • because the kidney attempts to adapt to nephron loss to maintain constant glomerular filtration.
  2. Increase in glomerular permeability to macro-molecules
     
     • E.g. transforming growth factor-beta (TGF-beta), fatty acids, pro-inflammatory markers of oxidant stress, and protein
     • Results in toxicity to the mesangial matrix, (associated with the capillaries)
       
       • causes mesangial cell expansion, inflammation, fibrosis, and glomerular scarring.
  3. Renal injury results in an increase in angiotensin II production:
     
     • ​​ causing an upregulation of TGF-beta,
     • (TGF-beta) directly stimulating synthesis of many extracellular matrix components and reducing collagenase production, collagen synthesis
     • contributing to and renal scarring within the glomerulus
• All forms of CKD are also associated with tubulo-interstitial disease;
  
  • Not known but thought to be secondary to dc in blood supply + infiltration of lymphocytes + inflammatory mediators ==> interstitial fibrosis and tubular atrophy.

Question 18

What history/signs/sypmtoms maybe seen in a patient with CKD?

Answer 18

Signs and symptoms are often vague:

• Fatigue
  
  • From Anaemia assoc. w/CKD
    
    • lack of erythropoietin produced by the kidney (interstital fibroblasts of the PCT)
    • Occurs once GFR is <50 mL/minute/1.73 m²
    • So wont get symptoms until the GFR ~stage 3b or even <30 (severe, stage 4/5 stages)
• Nausea
  
  • with/without vomiting
  • from circulation toxic waste product accumulation in the blood e.g. urea that is not excreted by the kidney.
  • As kidney failure progresses to the more advanced stages of uraemia, patients may report vomiting.
• Development of oedema.
  
  • Salt and water retention due to dc GFR= Periorbital and peripheral oedema

As kidney failure progresses to the more advanced stages of uraemia = uraemic symptoms

• yellow skin tinge
• anorexia
  
  • especially to meat and high-protein foods,
• nausea,
• vomiting,
• pruritus,
• overall not feeling well
• Most advanced stages of uraemia: seizures or coma

Lack of urine production:

• will increase in peripheral oedema (?JVP) and resultant pulmonary oedema
  
  • dyspnoea (difficult breathing)
  • orthopnoea (lying flat SoB)

end-organ damage associated with disease states such as diabetes or hypertension, which cause CKD.

• A fundoscopic eye examination is critical for the diagnosis of diabetic or hypertensive retinopathy as
  
  • will evidence microvascular damage that has probably occurred in the kidney, resulting in CKD.

Diagnosis of obstructive uropathy:

• rectal examination for prostatic enlargement or diagnosis of prostate nodules can in men

In glomerular nephrotic (foamy urine = proteinurea) and nephritic syndromes, (tea or cola coloured in haematuria setting) the signs and symptoms of CKD may be more acute presentation.

Patients w/Autoimmune disorders: accelerated hypertension, peri-orbital and peripheral oedema, rashes, or arthritis on musculoskeletal examination

Rashes:

• Ecchymosis and purpura (bleed vs small BV blees respectively) are signs of haematological consequences of chronic kidney disease.
• Or of concomitant autoimmune disorder e.g. SLE & butterfly rash.

Question 19

What investigations are needed for chronic kidney disease?

Answer 19

Initial investigations

• Serum creatinine and GFR,
  
  • Screening test to determine abnormality of the GFR.
    
    • May be falsely low in conditions of low muscle mass, as in older or malnourished people, or patients with liver failure.
    • Elevated Men = >97 micromol/L (>1.1mg/dL)
    • Elevated Women >105 micromol/L (>1.2 mg/dL)
• Urine microalbumin
  
  • Check for the development of CKD and coronary artery disease assoc.w/diabetes and hypertension.
  • Do a microalbuminuria test in patients with diabetes and CKD if there was no evidence of proteinuria on urine dipstick.
• Urinalysis to assess for haematuria and proteinuria
  
  • Proteinuria is both a diagnostic and a prognostic variable in the evaluation of patients with CKD.
• Renal ultrasound to evaluate for
  
  • Kidney Size
    
    • Kidney atrophy = CKD,
    • hydronephrosis = obstruction
  • Obstruction
    
    • Kidney stones
    • Bladder retention
  • with a duplex examination can look at renal arterial blood flow.

Nephrotic syndrome (proteinurea due to podocyte pathology) = 24-hour urine collection >3.5 g proteinuria.

• In non-nephrotic syndromes, proteinuria of >1000 mg/day is associated with a more rapid progression to end-stage renal disease.

Estimation of eGFR

Determines more accurately, by mathematical equations such as Cockcroft-Gault, the MDRDF, or the CKD EPI equation: the GFR and the severity and stage of CKD.

• More accurate than serum creatinine alone.
• But Formulas not proven to be reliable estimators in patients with a GFR >59 mL/minute/1.73 m².
  
  • results in CKD will be <60 mL/minute/1.73 m²

Additional investigations

A renal biopsy –> used to determine a pathological diagnosis if

• glomerular nephrotic or nephritic syndrome is suspected,
  
  • nephrit/rotic = suggested by severe presenting symptoms
    • accelerated hypertension, periorbital and peripheral oedema
  • or with symptoms of underlying autoimmune diseases
    • rashes or arthritis
• or in people with diabetes with atypical presentations such as rapidly progressive kidney failure.
• Certain infections, - hepatitis B and C, syphilis, and streptococcal pharyngitis - are associated with glomerular disorders.
• A renal biopsy is essential in these cases to determine the pathological lesion.
  
  • & will insight into treatment options based on severity or chronicity of scarring of glomeruli and interstitium.

Imaging of the genitourinary tract may be helpful in the evaluation of a patient with CKD.

• Plain abdominal x-ray (non-specific test)
  
  • aid in the detection of calcium-containing kidney stones.
  • as medicine and urate stones are not apparent on plain radiography
• abdominal (CT),
  
  • may reveal kidney stones, renal masses, or cysts and allow further evaluation/characterisation of these
  • AKI risk of Intravenous contrast is Use in CKD/high risk patients with a reduction in the estimated GFR <60 mL/minute
• Magnetic resonance imaging (MRI) is reserved for renal mass lesions such as renal cell carcinoma.
• No Gadolinium-based MRI examinations in pts w/eGFR<30 mL/minute/1.73m² (unclear in 30-60 gfr)
  
  • has been associated with nephrogenic systemic fibrosis in patients with kidney disease. If required, use haemodialysis to remove gadolinium.

Question 20

What is the management of CKD?

Answer 20

*tobacco cessation and weight loss are also recommended

Cardiovascular disease is a major cause of death in CKD so in stages 1-4:

• optimising glycaemic control
• BP is one of the greatest risk factors for CKD progression. Pts will need >2 anti-HTs. Aim: <140/90
  
  • angiotensin-converting enzyme (ACE) inhibitor
    
    • Lisonpril/ramipril/enalapril/peridopri
  • or an angiotensin-II receptor antagonist
    
    • losartan/irbesartan/telmasartan
  • (not used in the same regimien though only maybe if for neprotic syndromes to dc proteinurea)
  • thiazide diuretics - hydrochlorothiazide
  • beta-blockers - atenolol/metoprol
  • Non-dihydropyridine calcium-channel blockers (if intolerant to ace inhib/ang2 antag)
• introducing lipid-lowering agents
  
  • ≥50 years with CKD stage 3 or 4,
    
    • ezetimibe (reduces gut absorption of cholesterol) can be
    • combined with the statin simvastatin.
• reducing proteinuria

Stage 2 - Continue CVS risk factor modification, + est. the rate of loss of kidney function to determine the eventual need for RRT

S3- Identification and treatment of comorbidities

• anaemia (excule Fe, b12, folate and blood loss as cause)
  
  • EPO stimulating agents if Hb<100g/L + anaemic symptoms;
    
    • only want Hb to target of 100-110g/L though and ?stroke risk above
    • epoetin alfa/darbepoeitin alfa
  • CDK = iron deficiency, so assess Fe stores & transferrin and then replacement
    
    • Iron = ferrous sulphate/gluconate
• secondary hyperparathyroidism
• Ca ,PO4 and PTH measure every 6-12 months.
• Maintain Ca and PO4 in the normal range
  
  • with dietary restriction and/or phosphate-binding medications –> calcium acetate/sevelamer
  • Use of active vitamin D analogue therapy in patients with CKD (w/o dialysis) = only if hyperPTH is progressive or severe
    
    • Calcitriol
  • Vit D supplements = ergocalciferol (OH by lvier and kidney)

Stage 4 – patient education about RRT modality choice–> surgical referral

• haemodialysis, peritoneal dialysis,
  
  • education on vein preservation w/limiting venipuncture and IV access
• kidney transplantation –> eGFR is <20 mL/minute and the patient has been evaluated and undergone the required testing process by a transplant team.

Treatment of anaemia and secondary hyperparathyroidism should be continued.

• serum calcium and phosphate check every 3-6 months,
• intact PTH every 6-12 months.

if metabolic acidosis develop =

• oral sodium bicarbonate
• to target serum bicarb >20 mEq/L (slows progression of CKD & ic nutrition)

Stage 5 & Uraemia

RRT initation @ stage 5 disease or signs of uraemia:

• Uraemia = weight loss, lack of appetite, nausea, vomiting, acidosis, hyperkalaemia, or fluid overload.
• Protein restriction should not be recommended until late stage 4 or 5 disease = to control uraemia to delay dialysis initiation.
• Severe protein restriction may result in malnourishment and poorer outcomes.

Those with stage 5 CKD on dialysis, calcium, phosphorus, and intact PTH:

• phosphate binding agents,
• calcimimetics,
  
  • (e.g., cinacalcet, etelcalcetide) negatively feedback on the parathyroid glands and do not have the consequences of calcium augmentation.
  • Cinacalcet lowers PTH levels in patients with CKD and secondary hyperparathyroidism both prior to and after the initiation of dialysis, but it is associated with hypocalcaemia, and long-term benefits are not known.
• active vitamin D analogues/calcitriol
• OR combination of these based on serial labs of calcium and phosphate every 1-3 months, and PTH every 3-6 months.

There is no other medical therapy to keep patients alive once they have reached the need for dialysis, other than kidney transplantation.

Of note, patients

• > 80 y/o
• with significant comorbidities, such as
  
  • e.g advanced congestive heart failure,
• may do poorly with dialysis and frequently are not considered transplant candidates.
• For these patients, and all others approaching ESRD, nephrologist –> discussion with the patient regarding palliative care

For transplant candidates:

transplant > dialysis due to a decrease in the risk of cardiovascular death.

All patients who are on dialysis therapy are potentially eligible for kidney transplantation. after complete med history and evaluation. Final eligibiltiy = A transplant centre w/nephrologist and transplant surgeon.

Question 21

What is respiratory acidosis and its causes?

Answer 21

• CO2 retention e.g. PCO₂ is above the 4.7-6.0 kPa range
  
  • due to inefficient CO2 clearance
  • H+ accumulation
  • arterial pH falls below the normal 7.35-7.45 range
• Respiratory Acidosis may be acute or chronic, and if not recognised/treated –> can lead to respiratory failure and death.
• Acute respiratory acidosis (often life-threatening) is commonly caused by:
  
  • drug use (e.g., narcotics, alcohol, sedatives, anaesthetics),
  • oxygen therapy in COPD,
  • head trauma,
  • status asthmaticus,
  • foreign body aspiration,
  • multilobar pneumonia,
  • cardiogenic pulmonary oedema,
  • pneumothorax, and
  • inadequate mechanical ventilation.
    
    • All cause inefficient CO2 clearance which = build up!
• Chronic respiratory acidosis
  
  • is commonly caused by:
    
    • obesity (both hypoventilation syndrome in obesity and impaired chest wall mobility)
    • COPD
  • Clinical features include
    
    • respiratory depression (hypoventilation),
    • obtundation (altered consciousness),
    • haemodynamic instability (perfusion failure),
    • respiratory muscle fatigue (accessory muscle use, dyspnoea, tachypnoea).
• The compensation mechanism for respiratory acidosis is metabolic alkalosis [kidneys get rid of more H+ & this also allows more bicarb to be free]

Question 22

What is respiratory alkalosis?

Answer 22

• Can be acute or chronic in nature
• Increased CO2 loss
  
  • PCO₂ < 4.7-6.0 kPa
    
    • (alveolar hyperventilation with excess CO₂ excretion compared to production)
  • leading to a pH > 7.45
  • subsequent low bicarbonate < 24 mmol/L
• The aetiologies of respiratory alkalosis are multiple and include:
  
  • hypoxia (causes hyperventilation response)
  • parenchymal lung disease,
  • asthma,
  • drug effects,
  • mechanical ventilation,
  • central nervous system disorders,
  • metabolic causes,
  • pregnancy (from increased intra-abdo pressure)
  • hyperventilation syndrome.
• Compensation is metabolic acidosis [increased H+ retention of kindey and H+ from cells]

Question 23

What is metabolic acidosis

Answer 23

Metabolic acidosis

• Caused by: Acid ingestion, Increased acid production, Reduced acid excretion
• indicated by an arterial pH < 7.35,
• a decrease in the plasma bicarbonate level (22-28),
• and/or a marked ^ in serum anion gap (SAG)
  
  • SAG = (sodium) - (Cl + HC03)
  • e.g. the major measured cation (sodium) takeaway, the sum of major measured anions (chloride and bicarbonate)
• Where SAG is normal (6-12 mmol/L)
  
  • gastrointestinal or renal causes are common.
  • = hyperchloraemic or non-anion gap metabolic acidosis.
• Where SAG is increased (e.g. lots of Na/less chloride and bicarb; if kindeys try to get rid of H+, Na is retained), causes include:
  
  • diabetic ketoacidosis,
  • alcoholic ketoacidosis,
  • lactic acidosis,
  • kidney disease, or
  • ingestion of methanol, ethanol, ethylene glycol, propylene glycol, 5-oxoproline (e.g., in patients with chronic ingestion of paracetamol), or salicylic acid
• Compensation: respiratory alkalosis
  
  • With simple metabolic acidosis, the normal adaptive respiratory response will decrease the arterial PCO₂ 1.0 to 1.5 times the decrease in serum hydrogen carbonate (bicarbonate)

Question 24

What is metabolic alkalosis?

Answer 24

Metabolic alkalosis is

• an elevated arterial pH of above 7.45,

Caused by:

• loss of hydrogen ions from the body
  
  • Causes include gastric secretion (contains H+) loss (e.g., vomiting, diarrhoea)
  • mineralocorticoid excess
    
    • aldosterone causes Na resorption in DCT but H+ (and K+) loss
• or an increase in plasma bicarbonate from a normal value of 24 mmol/L (24 mEq/L).
  
  • It is a very difficult primary disturbance to produce and maintaining proton producers! (Very specific factors required)

Patients may present with tingling, muscle cramps, weakness, cardiac arrhythmias, and/or seizures.

• Some symptoms = from decrease in circulating calcium, which happens when the pH is high.
  
  • It’s possible patients may die from v. high metabolic acidosis/circulating calcium then because of
    
    • serious/fatal arrhythmias and/or seizures without preceding symptoms.

Compensation – respiratory acidosis

• E.g. Retain CO2/hypoventilation

Compensatory metabolic alkalosis may be an incidental finding in patients with chronic respiratory acidosis e.g. COPD

Question 25

What is hyponatraemia?

Answer 25

Hyponatraemia = serum sodium <135 mmol/L (<135 mEq/L) with severe hyponatraemia being <120 mmol/L (<120 mEq/L).

it occurs in 15% of all hospital inpatients. Hyponatraemia is often iatrogenic and avoidable. Common causes are administration of hypotonic fluids to patients (dilutes the sodium that is in the body fluids) and use of thiazide diuretics (more likely to affect older people).

With few exceptions, when the serum sodium level is low, plasma osmolality is also low (hypotonic hyponatraemia). While defined by the level of sodium, hypotonic hyponatraemia is, in fact, a disorder of water balance.

Hyponatraemia may also be a clue to the presence of serious underlying medical disorders. Patients who develop hyponatraemia as a result of head injury, intracranial surgery, subarachnoid haemorrhage, stroke, or brain tumours may have cerebral salt-wasting syndrome or syndrome of inappropriate antidiuretic hormone (SIADH).

Question 26

What is hypernatraemia?

Answer 26

plasma sodium concentration of >145 mmol/L (>145 mEq/L).

Hypernatraemia is a state of hyperosmolality, and is primarily a result of water deficit or sodium gain.

Normally, persistently high sodium levels trigger antidiuretic hormone (ADH) release, stimulating thirst mechanisms so that hypernatraemia rarely develops.

Hospitalised patients often have impaired thirst mechanisms, restricted access to water, and an increased risk of water loss (e.g., due to vomiting or fever).

They are also at risk for iatrogenic inadequate fluid replacement.

Endocrine abnormalities such as diabetes insipidus and mineralocorticoid excess may also lead to hypernatraemia