Clinical Chronic Kidney Disease

Question 1

Epidemiology of CKD

Answer 1

-7% (10-20%)
-Increasing prevalence with age (>65)
-Patients above 70= 80% chance of some form of CKD
-The prevalence of CKD in patients with hypertension, diabetes and vascular disease is substantially higher

Question 2

Definition of CKD and MDRD equation

Answer 2

-Irreversible damage to the structure +/- function of the kidneys
-Typically develops and progresses slowly over years
-Often manifests as an incidental biochemical finding (asymptomatic until advanced)

-Modification of Diet in Renal Disease (MDRD) equation measures eGFR, which uses the following variables:
=serum creatinine (differences in muscle)
=age
=gender
=ethnicity
=Pregnancy, muscle mass (Amputee/ body-builders), eating red meat 12 hours prior to sample affects result

Question 3

Classification of CKD

Answer 3

1= Greater than 90 ml/min, with some sign of kidney damage on other tests (if all the kidney tests (normal U&Es, no proteinuria) 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

Question 4

Diagnosis and investigations of CKD

Answer 4

-Elevation in serum creatinine persistent for > 3 months
-Other markers of renal injury
=Albuminuria (ACR of 3 mg/mmol or more clinically important)
=Electrolyte abnormalities due to tubular dysfunction
=Structural abnormalities, e.g. cysts

-Exclude AKI: unexpectedly high urea and creatinine (when there is an increase from previous results or no prior results are available), renal function should be retested within 2 weeks to avoid missing AKI
-Screen for complications of CKD, such as anaemia and renal osteodystrophy

Question 5

Criteria for renal USS

Answer 5

have accelerated progression of CKD (see recommendation 1.3.5)

have visible or persistent invisible haematuria

have symptoms of urinary tract obstruction

have a family history of polycystic kidney disease and are older than 20

have a GFR of less than 30 ml/min/1.73 m2 (GFR category G4 or G5)

are considered by a nephrologist to need a renal biopsy

Question 6

General symptoms of CKD

Answer 6

-Usually asymptomatic until late stage 4 (incidental findings)
-Non-specific symptoms:
=Weakness and fatigue/ lethargy
=Oedema (ankle swelling, weight gain)
=Polyuria, nocturia (early symptom, loss of concentrating ability)
=Breathlessness (fluid retention/ metabolic acidosis/renal anaemia)
=Nausea / anorexia / altered taste/ loss of appetite
=Itching skin (advanced, secondary to uraemia)
=Muscle cramp (advanced)
=Restless legs
=Insomnia
=Confusion/ collapse/ coma death

-Can be hypertension and proteinuria (not always)

Question 7

AKI vs CKD

Answer 7

-One of the best ways to differentiate between acute kidney injury (AKI) and chronic kidney disease (CKD) is renal ultrasound - most patients with CKD have bilateral small kidneys. Exceptions to this rule include:
=autosomal dominant =polycystic kidney disease
=diabetic nephropathy (early stages)
=amyloidosis
=HIV-associated nephropathy

-Other features suggesting CKD rather than AKI
=hypocalcaemia (due to lack of vitamin D)

Question 8

Describe stage 1 CKD

Answer 8

-GFR 90+
-Normal kidney function but urine or other abnormalities point to kidney disease
-Stages 1-3 (5-10% of the population?)
Need assessment, long term monitoring, control of blood pressure and CV risk factors

Question 9

Describe stage 2 CKD

Answer 9

-GFR 60-89
-Mildly reduced kidney function; but must also have urine or other abnormalities (e.g. anatomical, genetic) to be classified as CKD
-Need assessment, long term monitoring, control of blood pressure and CV risk factors

Question 10

Describe stage 3 CKD

Answer 10

-GFR 30-59
-Moderately reduced kidney function; may be subdivided into 3a, 3b according to GFR over or under 45; and proteinuric or not.
-Few or no symptoms still
-Common: estimates of incidence vary, but it may be round about 5% of the population, mostly elderly (incidence rises over 70)- most never develop ESRF
-Need assessment, long term monitoring, control of blood pressure and CV risk factors

Question 11

Describe stage 4 CKD

Answer 11

-GFR 15-29
-Severely reduced kidney function
-0.2% of the population. Planning for end stage renal failure if progressive. Symptoms at lower GFRs.

Question 12

Describe stage 5 CKD

Answer 12

-GFR 14 or less
-Very severe kidney failure. Sometimes used to imply end stage, ESRF or ESRD, but average GFR for starting dialysis is below 10
-0.2%

Question 13

Risk factors for developing ESRF

Answer 13

-Deteriorating function – unsurprisingly, if GFR falls with time, ESRF is more likely
-Severe of CKD – worse kidney function is more likely to deteriorate further
-Proteinuria is a strong risk factor, risk increasing with the severity of proteinuria.
-Haematuria can be an indicator of kidney inflammation
-High blood pressure – and blood pressure reduction reduces risk
-Young age – younger patients with CKD are more likely to reach ESRD
-Increased cardiovascular risk

Question 14

Complications of CKD

Answer 14

-Increased risk of heart attacks and all kinds of cardiovascular disease, and if a patient with CKD has a cardiovascular event, or an operation, the risk of doing badly is substantially increased.
=Hypertension is often an early feature.

-Fluid retention commonly becomes a major problem in late renal failure, requiring large doses of diuretics.

-Anaemia can be treated by recombinant erythropoietin injections after other causes have been excluded and adequate iron stores demonstrated. This often requires intravenous iron therapy. This is not usually a serious problem until GFR falls below 20

-Renal osteodystrophy

-Itching, neuropathy, pericarditis (late manifestations prevented or controlled by dialysis)

-Gastrointestinal symptoms – anorexia, progressing to nausea and ultimately vomiting =Usually late symptoms, GFR usually well below 20, and sometimes not becoming prominent until GFR <10. They may be helped by dietary modification but are often an indication that dialysis is required.

Question 15

Common causes of CKD/ CRF

Answer 15

Any disease process which interrupts structure or function of kidneys (systemic vs intrinsic)
-In many cases the underlying diagnosis is unclear, especially among the large number of older patients with stage 3 CKD. Many patients diagnosed at a late stage have bilateral small kidneys. Renal biopsy is rarely undertaken in this group since it is more risky, less likely to provide a histological diagnosis because of the severity of damage, and unlikely to alter management.

-Systemic
=Diabetes (20-45%): large racial and geographical differences
=Hypertension (5-20%, causality controversial, may be secondary to another primary renal disease)
=Vascular disease (5%, mostly atheromatous)
=Inflammatory disorders (5-10% SLE, vasculitis)
=Unknown (5-10%)
=Chronic pyelonephritis
=Hypertension
=Adult PKD

-Intrinsic
=Congenital/ inherited: PKD, Alport’s syndrome, Reflux nephropathy, renal dysplasia (5-10%)
=Glomerular disease 10-20% (IgA nephropathy)
=Interstitial disease (20-30%): drug-induced, reflex nephropathy
=Inflammatory (vasculitis)

-Circulatory problems such as renal artery stenosis
-Inflammation within the kidneys – interstitial nephritis or glomerulonephritis
-Diabetes is very important cause – diabetic kidney disease also affects glomeruli
-Urinary tract obstruction – in ureters, bladder, or below – more on obstruction
-Inherited diseases – more info on inherited/congenital diseases

Question 16

Risk factors for deterioration of renal function

Answer 16

-Worse renal function – higher serum creatinine (lower eGFR)
-Proteinuria – the higher, the greater the risk of progression
-Hypertension – the higher, the greater the risk
-Renal biopsy shows fibrosis, or continuing inflammation
-Young age – they have longer for trouble to develop

Question 17

Management strategies to prevent progression of CKD

Answer 17

-Blood pressure control to stringent targets. More on BP control
-ACE inhibitors if there is proteinuria.
=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.
-Prevention of acidosis by treatment with bicarbonate may play a role
-Furosemide
-Dietary restriction: intermediate course, recommending moderate protein restriction (0.6-0.8g/kg/day) but ensuring adequate calorie intake.

Question 18

CKD bone disease

Answer 18

-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

Question 19

How is renal osteodystrophy prevented?

Answer 19

REDUCE PHOSPHATE AND PTH

-Prescription of alfacalcidol or calcitriol, vitamin D metabolites; controls hypocalcaemia (but may cause hypercalcaemia).
-Parathyroidectomy if needed

-Phosphate
=dietary restriction
=phosphate binders such as calcium carbonate (hypercalcaemia vascular calcification) or acetate preparations, or aluminium hydroxide (risk of aluminium toxicity, now generally reserved for short-term use), or sevelamer (Renagel©), or lanthanum carbonate.
=Phosphate retention is not usually a severe problem until GFR is less than 20-25.

Question 20

Why is diet important in CKD?

Answer 20

-As well as excreting the processed metabolites of the body, the kidneys also get rid of all excess fluid, salt etc that we take in over our daily requirements.
-Diet becomes increasingly important as renal function deteriorates, because the body becomes less able to deal with excessive intake first, and later, with the normal output of the body.

Question 21

Describe the diet in different scenarios of CKD

Answer 21

-Deteriorating kidney function
=Restrict salt; moderate protein; in late stages, phosphate and potassium often become important issues.
=Where blood pressure control is possible, evidence no longer supports restricting protein below moderate levels. It does not seem to protect kidney function, and severe restriction of protein can be hazardous.

-Dialysis
=Salt, protein, fluid, potassium and phosphate are important to varying degrees depending on the type and frequency of dialysis, and on whether there is a little bit of residual renal function

-Transplantation
=With good kidney function, it is important to eat a healthy diet to minimise cardiovascular risk.

Question 22

What is ESRF?

Answer 22

-Implies a level of renal function at which death is likely within weeks or months.
-Symptoms are those of severe chronic renal failure
-It is not the same as CKD stage 5: the average GFR for commencing dialysis in the UK is below 10ml/min, but there is wide individual variation, and some may require renal replacement therapy (RRT) much earlier

Question 23

Management options in ESRF

Answer 23

-Haemodialysis
-Peritoneal dialysis
-Renal transplantation
-Conservative management

Question 24

Decisions about management in ESRF

Answer 24

-Younger and ‘low risk’ patients are favoured for transplantation. For some patients who are at a high risk of dying on dialysis, conservative management may provide a higher quality of life than renal replacement therapy, with little shortening of life.

-Risk is related to both age and co-existing diseases. Prognosis with renal replacement therapy tends to be very good in younger patients with no other serious diseases, especially after transplantation. However even in this group, mortality from cardiovascular disease is many times higher that of the general population. Infectious causes of death are the second major problem in patients on renal replacement therapy.

-High risk patients are the very elderly (over 80 years) or those of any age with two major comorbid conditions (clear evidence of coronary, cerebrovascular or peripheral vascular disease; diabetes; non-skin malignancy); or those aged 70-80y with one major comorbid disease. The median survival of the high risk group defined this way is generally under 18 months, although up to a quarter may survive >4y.

-Conservative management includes all usual measures to retard progression of renal disease and reduce symptoms, including particularly close attention to diet, and use of erythropoietin and other treatments to reduce symptoms.

Question 25

Screening for CKD in high-risk patients

Answer 25

-Hypertension
-Diabetes
-Family history of genetic renal disease (PKD)
-Renal disorders in childhood

-Biochemistry (urea, creatinine)
-Urinalysis (albuminuria)
=Annually or more often if advanced
=Trend in readings over time

Question 26

Principles of management of CKD and evaluation

Answer 26

1. Identify the cause of CKD
2. Identify reversible factors / prevent further damage
3. Mitigate the consequences of renal impairment
4. Preparing (if appropriate) for renal replacement therapy

-Clinical context (new diagnosis? Known and progressive?)
-Social factors (family members, genetic?, smoking obesity alcohol)
-Medications (diabetes, high BP, recurrent AKI)
-Physical examination (RA, inflammatory arthropathy, SLE, vasculitis, usually unremarkable, pulses, fluid balance)
Additional investigations
=Urinalysis
=Additional laboratory investigations
=Renal imaging (USS: 2 kidneys? Equal size, obstruction)
=Histopathology (unclear aetiology reversible pathology)

Question 27

Additional laboratory investigations

Answer 27

-Immunoglubilins (myeloma)
-Protein electrophoresis
-Serum free light chains
-Urinary Bence Jones Protein (myeloma)
-ANA +/- Anti-DS DNA (inflammatory disorder like lupus, connective tissue disorder)
-ENA (connective tissue disorder)
-ANCA and Anti-GMB antibodies
-Cryoglobulins
-Hep and HIV serology (if dialysis or transplant planned)

-Creatinine, eGFR (assess stability/progression, compare to previous)
-Urinalysis (haematuria and proteinuria indicate glomerular disease and need for biopsy/ progressive CKD requiring preventative ACEi or ARB)
-Electrolytes (hyperkalaemia and acidosis)
-Calcium, phosphate, parathyroid hormone, vit D (assess renal osteodystrophy)
-Albumin (low in malnutrition, inflammation, nephrotic syndrome)
-FBC (anaemia)
-Lipids, glucose, HbA1c (cardiovascular risk)
-Renal USS (obstructive urinary symptoms, persistent haematuria, FHx PKD, progressive CKD has small kidneys, asymmetric in renovascular or congenital)

Question 28

Disease specific management of CKD

Answer 28

-Tolvaptan therapy in PKD
-Immunosuppression in immune/inflammatory diseases

Question 29

General management of CKD

Answer 29

-Treatment of hypertension (140/90 if diabetic, 130/80 if not)
-Suppression of proteinuria- ACE inhibitors / ARBs
-SGLT2 inhibitors (beneficial in HF, slows rate of progression CKD, reduce cardiovascular)- Proteinuric CKD
-Cardiovascular risk factors (statins, anti-platelet)
=Left ventricular hypertrophy and cardiac calcification may increase the risk of arrhythmias and sudden cardiac death, which is a much more common mode of death in patients with CKD than in the general population, particularly in those with more advanced disease and those on dialysis.
-Dietary salt restriction

Question 30

Follow up in CKD

Answer 30

-Frequency of follow up is decided on a case-by-case basis.
-Dependent upon:
=Stage of CKD
=Rate of decline in eGFR/ rate of progression
=Level of proteinuria
-Primary Care vs. Secondary Care
-Annually/ up to every 3-4 weeks

Question 31

Who is seen in renal clinic?

Answer 31

-New diagnosis of Stage 3b-5 CKD
-(Rapidly) progressive CKD
-Nephrotic syndrome (+/- reduced eGFR)
-Haemoproteinuria (+/- reduced eGFR)
-Possible genetic renal disease
-Hypertension poorly controlled on 4 antihypertensives
-eGFR <30 mL/min/1.73 m 2

Question 32

Management of advanced CKD with the function of kidneys

Answer 32

1. Regulate fluid status and electrolytes (so fluid overload, electrolyte disturbance)
   =Diuretics
   =Fluid restriction
   =Dietary modifications (salt restriction, potassium restriction, phosphate restriction, adequate calorific intake)
2. Regulation acid-base status (so metabolic acidosis)
   =Sodium bicarbonate (capsule/tablets, variable dose, caution re: Na+ load and fluid retention)
   =plasma bicarbonate concentrations should be maintained above 22 mmol/L by prescribing sodium bicarbonate supplements (starting dose of 1 g 3 times daily, increasing as required).
3. Blood pressure regulation (hypertension)
   =Salt restriction
   =Fluid restriction
   =Anti-hypertensives: target blood pressure of less than 140/90 mmHg is recommended for patients with CKD and no albuminuria (ACR <3 mg/mmol OR 130/80 mmHg is recommended for those with diabetes or an ACR of more than 70 mg/mmol.
4. Endocrine functions (anaemia, renal bone disease)
   =Erythropoietin-stimulating agents (ESAs)
   =Activated Vitamin D replacement
5. Drug metabolism/ toxin excretion (uraemia, increase risk ADRs)
   =Symptomatic
   =Medication review

Renal replacement therapy (RRT) vs. Conservative Care
-If dialysis, which modality?
-If transplantation, what are the options?

Question 33

Monitoring of renal function

Answer 33

-Monitored every 6 months in patients with stage 3 CKD, but more frequently in patients who are deteriorating rapidly or have stage 4 or 5 CKD

Question 34

Reduction of proteinuria

Answer 34

-ACE inhibitors and ARBs reduce proteinuria and retard the progression of CKD.
=may be accompanied by an immediate reduction in GFR; patients should therefore have their renal function checked within 7–10 days of initiating or increasing the dose of an ACE inhibitor or ARB.
=stop taking the medication if they become unwell, such as with fever, vomiting or diarrhoea, restarting once they are better.
=should not be commenced in patients with baseline potassium >5.5 mmol/L.

Question 35

Describe renal bone disease

Answer 35

-Secondary hyperparathyroidism
-osteitis fibrosa cystica
-Deposition of calcium phosphate in many tissues, most notably blood vessels and heart valves, which may contribute to the increased risk of cardiovascular disease in patients with CKD
-Tertiary hyperparathyroidism: hypercalcaemia.
-Low bone turnover (adynamic bone disease)

-Hyperphosphataemia should be treated by dietary restriction of foods with high phosphate content (milk, cheese, eggs and protein-rich foods) and by the use of phosphate-binding drugs that inhibit phosphate reabsorption in the gut. Various drugs are available, including calcium carbonate, aluminium hydroxide, lanthanum carbonate and polymer-based phosphate binders such as sevelamer.

-Active vitamin D metabolites (either 1-α-hydroxyvitamin D or 1,25-dihydroxyvitamin D) should be administered in patients who are hypocalcaemic or have serum PTH levels more than twice the upper limit of normal.

-In patients with persistent hypercalcaemia (tertiary hyperparathyroidism), parathyroidectomy may be required. If parathyroidectomy is unsuccessful or not possible, calcimimetic agents, such as cinacalcet, may be used.

Question 36

Causes of anaemia in CKD

Answer 36

-Deficiency of erythropoietin
=Toxic effects of uraemia on marrow precursor cells
=Reduced intake, absorption and utilisation of dietary iron
=Reduced red cell survival
=Blood loss due to capillary fragility and poor platelet function

-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

-Haemoglobin can be as low as 50–70 g/L in CKD stage 5, although it is often less severe or absent in patients with polycystic kidney disease.
-Iron deficiency is common in patients with CKD, and even more prevalent in those on haemodialysis as a result of haemolysis in the dialysis circuit. target haemoglobin of 10 - 12 g/dl
=iron supplements, which may be given intravenously for those with iron intolerance or in situations where adherence may be difficult 3 months no benefit
=recombinant human erythropoietin is very effective in correcting the anaemia of CKD and improving symptoms.
==higher risk of hypertension and thrombosis, therefore the target haemoglobin is usually between 100 and 120 g/L or avoidance of blood transfusions.
==Erythropoietin is less effective in the presence of iron deficiency, active inflammation or malignancy, in particular myeloma.

Question 37

Definition of diabetic nephropathy

Answer 37

-Any form of diabetes with:
=Albuminuria (micro to nephrotic syndrome)
=Evolving hypertension (near normal to severe)
=Declining renal function (normal creatinine to ESRD): 10 to 20 years from diagnosis

-Can have associated diabetic complications (microvascular)
=90% T1DM retinopathy
=70% T2DM

Question 38

Risk factors for diabetic nephropathy

Answer 38

-Hyperglycaemia
-Hypertension
-Hyperlipidaemia (Macrovascular)
-Smoking (macrovascular disease)
-Genetics (parental history)

Question 39

Natural history of diabetic nephropathy

Answer 39

-Stage 1: silent
-Stage 2: paradoxical increase eGFR (vasodilatation of afferent arteriole causing increase in glomerular pressure)
-Stage 3 (incipient): eGFR falls, clinically detectable microalbuminuria, subtle loss in nocturnal dipping in BP
-Stage 4 (overt): detectable by dipstick, BP rises, GFR falls (progressive accumulation of scarring , nodular/ Wilson’s nodule)
-Stage 5 (chronic): GFR approaches 10
=Poor survival (45-64 3 years)

Question 40

Investigations in diabetic nephropathy

Answer 40

-24 hr urinary albumin excretion
-Timed overnight collection
-Albumin/creatinine ratio
=Microalbuminuria (3-30mg/mmol): annually (T1DM from 5years, T1DM from diagnosis)
=Overt proteinuria (>30)

Question 41

Who do we need to biopsy in diabetic nephropathy?

Answer 41

-T1DM <10 years
-Rapid progression of proteinuria
-Rapid deterioration of kidney function (10ml/year)
-Absence of retinopathy
-Presence of haematuria
-Additional systemic symptoms

Question 42

Management of diabetic nephropathy

Answer 42

-Weight loss, increase exercise, stop smoking
-Tight glycaemic control (HbA1c <7%)
-Tight blood pressure control (140/80, 130/80 if microalbuminuria or proteinuria)
=ACEi, ARB in microalbuminuria even if BP normal
=SGLT-2 inhibitors
-Treat cardiovascular risk factors