Renal

Dr Alan Shortt

45 Renal Physiology

Excretory Organs

Skin
Kidneys
Intestines
Liver
Lung

Functions of the Kidney
Glomerular	excretion of metabolic waste toxins and foreign substances
Tubular	acid-base water and electrolyte function
Endocrine	Vit D (calcium) Erythropoietin (Hb)
Carbohydrate Metabolism	Gluconeogenesis

Renin Angiotensin System

Renin – Angiotensin – Aldosterone

Activated by reduced intravascular volume – sodium depletion, haemorrhage, oedematous states

Causes renal sodium retention

Measure plasma and urine Na – if urine sodium < 10 mmol/l suggests R/A/A active

Haematuria (renal)

Non visible haematuria (renal)

Proteinuria

Proteinuria Haematuria in CKD

http://hacking-medschool.com/urinalysis

Proteinuria
Exclude UTI
Confirm with early morning urine sample sent to laboratory (to exclude postural proteinuria)
Persistent proteinuria at least 2 tests, 1-2 weeks apart.
Refer to nephrology if:
urine protein:creatinine ratio >100 mg/mmol
reduced GFR

Haematuria
Exclude infection, tumoour, trauma, menstruation
No need for laboratory confirmation
Check U&Es and for proteinuria.

Refer to urology if: macroscopic or microscopic and >50 years.
Refer to nephrology if: microscopic with proteinuria or <50 years.

Refer for investigation for renal artery stenosis
BP >150/90 despite three anti-hypertensive agents.
Recurrent pulmonary oedema despite normal echo.
Rising serum creatinine with raised CVD risk.
Unexplained hypokalaemia with hypertension. eGFR
UACR PCR proteinuria=<30 mmol/l (PCR>45..>100)

MCA M < 3 mmol/ml
F < 2.5 mmol/ml CKD Stage 3

CKD explained

egfr explained

Normal GFR is 120mls/min/1.73sqmetre

eGFR is a more accurate way of assessing renal function than serum creatinine assay in isolation but not as accurate as a 24 hour creatinine clearance assay.

CKD diagnosis

CKD Diagnosis / Definition		Renal function
CKD Grade 1	> 90 ml/min + other evidence kidney disease	normal/good
CKD Grade 2	60-89 ml/min + other evidence kidney disease	mildly impaired
CKD Grade 3a	45-59 ml/min	moderately impaired
CKD Grade 3b	30-44 ml/min	moderately impaired
CKD Grade 4	15-29 ml/min	severely impaired – pre-ESRF
CKD Grade 5	<15 ml/min	Established ESRF or dialysis

eGFR >60ml/min without other evidence of kidney disease is not CKD
other evidence includes:
persistant (2 or more occasions) proteinuria / haematuria /microalbuminuria
known structural abnormality
biopsy-proven glomerulonephritis

CKD Investigations	Thresholds	Action
BP	140/90 (130/80 in diabetics) +/- PCR > 100 mg/mol	meticulous control ACE/ARB if proteinuria, DM or CHF
eGFR	fall >5 ml/min per year or fall > 15% after ACE/ARB	refer
Potassium	>6 mmol/l >6.5 mmmol/l	exclude haemolysis/ drugs refer
Urine dipstick +/- PCR	haematuria proteinuria if > 100mg/mmol	investigate cause check PCR refer
Haemoglobin	<11 g/dl	exclude usual auses refer
Calcium	<2.1 mmol/l on 2 occassions	refer
Phosphate	> 1.6 mmol/l on 2 occasions	refer

@@@ CKD Guidelines

Defined as kidney damage or a glomerular filtration rate (GFR) of <60 ml/min/1.73m2 on at least two occasions in a period of over 3 months.

The US National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) classification of CKD was adopted by the National service framework for renal services, and has been modified by the NICE guideline

In addition to GFR measurement, stage 1 and 2 CKD also require other evidence of kidney disease such as haematuria, proteinuria, albuminuria, or structural abnormalities. Stages 3–5 can be defined by GFR alone but other features, such as those listed above, may also be present and should be looked for.

The prevalence of complications as a result of CKD begins to rise as the GFR falls below 45 ml/min/1.73m2. Therefore, stage 3 has been divided into two groups based on GFR values:
CKD 3A: 45–59 ml/min/1.73m 2
CKD 3B: 30–44 ml/min/1.73m 2.

Significant proteinuria (>0.5 g/24 h) (see below) is also associated with adverse CKD outcomes, and the suffix ‘p’ should be added to the staging of CKD to indicate proteinuria.

Here proteinuria = urinary ACR>30 mg/mmol, or PCR >50 mg/mmol (approx excretion 0.5 g/24 h or more).

For patients with diabetes, microalbuminuria is clinically significant if ACR >2.5 mg/mmol in men or >3.5 mg/mmol in women

At any given stage of CKD, management should not be influenced solely by age.

NKF KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification.

Diagnosis of CKD
As it is difficult to measure GFR directly, an estimated GFR (eGFR) should be used; this is based on serum creatinine and other factors, such as age and gender.

(NB if the patient is of African origin, e.g. AfricanCaribbean ethnicity, the eGFR should be multiplied by a correction factor of 1.21. 1,5 )

Serum creatinine can be increased artificially after eating meat, therefore patients should be advised not to eat it in the 12 hours before creatinine is measured.

If the eGFR result is ?60 ml/min/1.73m2 the measurement should be repeated at an interval that is appropriate to the clinical context, usually 2 weeks.
Providing this does not reveal a rapid decline, eGFR should be measured again after 3 months.

A decline of >5 ml/min/1.73m2 per year or >10 ml/min/1.73m2 in 5 years indicates progressive CKD, and should prompt referral to a specialist. An eGFR ?60 ml/min/1.73m2 is inaccurate; therefore, significant reduction in
renal function should be inferred from an increase in serum creatinine concentration of >20%.1,5

Testing for protein and blood in urine
The continual presence of protein, albumin, or red blood cells in urine is evidence of kidney damage. The degree of proteinuria can be assessed by collecting urine over a 24hour period, but this is not usually practical, and so spot testing of urine is performed. Ideally the sample should be a ‘first pass’ morning
specimen. Dipsticks are rarely accurate enough for this purpose.

In patients with CKD but without diabetes, significant proteinuria is regarded as >0.5 g/24 h.
This is equivalent to an albumin:creatinine ratio (ACR) of >30 mg/mmol or a protein:creatinine ratio (PCR) of >50 mg/mmol.

For patients with diabetes, microalbuminuria is considered to be clinically significant if the ACR is >2.5 mg/mmol in men or >3.5 mg/mmol in women.
The presence of haematuria should be assessed by reagent strips; if there is a result of 1+ or more, further evaluation is required. Urine microscopy should not be used to confirm a positive result.
Renal ultrasound
Ultrasound can be used to assess structural changes to the kidneys. Renal ultrasound should be offered if: 1,5
there is visible or persistent invisible haematuria symptoms of urinary tract obstruction are present
there is a family history of polycystic kidney disease and the patient is aged over 20 years patients have already been referred to secondary care.
Predisposing factors
Comorbid conditions are common in CKD: in a large scale primary care study of patients with stages 3–5 CKD, the adjusted age and gender odds ratio for diabetes=1.33 ; for hypertension=2.1; and for cardiovascular disease (CVD)=1.69.Patients with these conditions should be offered testing. General practitioners also need to be aware of atrisk groups and offer testing for CKD if patients have been prescribed nephrotoxic drugs (most commonly nonsteroidal antiinflammatory drugs) on a longterm basis or have any of the following risk factors:
structural renal tract disease, renal calculi (stones), prostatic hypertrophy multisystem diseases with possible kidney involvement a family history of stage 5 CKD or hereditary kidney disease incidental haematuria or proteinuria.
Management of CKD
It is important to establish the rate of decline of renal function as early as possible because this will indicate if referral is needed. At least two readings of eGFR are required for this purpose. Certain factors (e.g. CVD, smoking, black or Asian ethnicity) increase the risk of progression of CKD and these should be borne in mind.
People with CKD should be offered education and information that is tailored to their stage and cause of CKD.

As the disease progresses, patients may require referral for specialist predialysis education.

Healthcare professionals should also be aware of the psychological impact of CKD and offer appropriate support.

Lifestyle modification
Patients with CKD should be encouraged to exercise and maintain a healthy weight. Smoking increases the risk of progression for both CKD and CVD so advice and intervention in this area is a priority. Dietary interventions apply more to advanced stages of CKD.

Blood pressure
The NICE guideline recommends that blood pressure (BP) should be controlled within a systolic range of 120–139 mmHg and the diastolic BP should be below 90 mmHg.

If the patient has significant proteinuria, the target range for BP is within a systolic range of 120–129 mmHg and the diastolic blood pressure should be below 80 mmHg. The priority is to achieve the systolic range even if diastolic BP falls below its optimal range during treatment.
Angiotensinconverting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs) should be offered for the control of hypertension to all patients with significant proteinuria. Before initiating drug treatment, serum potassium, creatinine, and eGFR should be measured. These measurements should then be taken again (between 1 and 2 weeks after starting therapy) and after each dose increase, or at intervals indicated by clinical context.
Drug therapy should be stopped if serum potassium is ?6 mmol/l and other drugs known to promote hyperkalaemia have been discontinued. Initiation, and an increase in the dose of ACE inhibitor/ARB therapy may result in a decrease in GFR (or an increase in serum creatinine).

If the change in GFR is less than 25% (increase in serum creatinine is <30%), measurements should be repeated in a further 1–2 weeks. A decrease in GFR of >25% (or change in serum creatinine>30%) should be investigated; this may be caused by volume depletion or concurrent drug treatment. If no other cause is found, the dose of ACE inhibitor/ARB therapy should either be stopped or reduced, and an alternative form of hypertensive pharmacotherapy added. If the fall is catastrophic, urgent referral should be considered to exclude renal artery stenosis.
Prevention of CVD
Primary and secondary prevention of CVD in patients with CKD should not differ from normal practice in those patients without CKD. However, it should be noted that in people with CKD, the Framingham risk tables significantly underestimate risk.
Hyperuricaemia
There was not enough evidence to recommend the use of drugs to lower uric acid in people with CKD who have asymptomatic hyperuricaemia.

Complications of CKD
Renal bone disease
There is no need to routinely measure calcium, phosphate, parathyroid hormone, or vitamin D levels at CKD stages 1, 2, or 3 (A or B) but they should be quantified in stages 4 and 5.

At stages 1, 2 and 3 (A or B), prevention of osteoporosis and vitamin D supplementation is no different to that recommended for people without CKD, and should be offered if indicated. 1,5

Anaemia
If haemoglobin (Hb) has not already been measured, it should be determined in people with CKD stage 3B or worse to identify anaemia (<11.0 g/dl).

Healthcare professionals should refer to the NICE guideline on Anaemia management in people with chronic kidney disease for further guidance. If a patient with CKD is found to have anaemia, other causes should be considered apart from anaemia of CKD. Iron deficiency is a common problem and should be diagnosed if the patient has stage 5 CKD and serum ferritin is <100 ?g/l; it can be considered a possible diagnosis if the patient has stage 3 or 4 CKD and if ferritin level is <100 g/l.

Functional iron deficiency may be present in patients with CKD7 even if serum ferritin is >100 ?g/l.

In practice, iron supplementation should be given to patients with anaemia at least until serum ferritin exceeds 200 ?g/l. If there is no response to iron supplementation, referral for erythropoietin treatment should
be considered. In patients with anaemia of CKD, Hb levels should be maintained between 10.5 and 12.5 g/dl for adults.
The age of the patient should not influence the use of any of these interventions, and the risks and benefits should be judged in a holistic assessment of each individual.
Referral of patients with CKD
Referral should be made when:
there is doubt about the diagnosis
the disease has reached an advanced stage
specialised treatments are indicated.

People with CKD in the following groups should be considered for referral:
Stage 4 and 5 CKD unless receiving palliative care
Proteinuria ?1 g/24 h (equivalent to ACR ?70 mg/mmol; PCR ?100 mg/mmol)
Proteinuria ?0.5 g/24 h (equivalent to ACR ?30 mg/mmol; PCR ?50mg/mmol) and haematuria
Rapidly declining GFR (>5 ml/min/1.73 m2 in 1 year or >10 ml/min/1.73 m2 in 5 years or less)
Hypertension that remains poorly controlled after use of four antihypertensive drugs
People with, or who are suspected to have, a rare genetic cause of CKD
Suspected renal artery stenosis based on renal ultrasound or fall in GFR after ACE inhibitor or ARB therapy
Patients with anaemia who do not respond to iron supplements

Conclusion
Chronic kidney disease is an important and prevalent condition that leads to increased morbidity and mortality in people at all ages, but especially in those aged over 50 years who have CVD, diabetes and/or hypertension. It results in a significant burden to both individuals and society. The guideline development group for the NICE guideline on early identification and management of CKD reviewed interventions that have been found to reduce the decline of renal function and mitigate complications. Many of the recommendations in the guideline can be implemented in general practice; the main interventions that can be conducted in primary care include management of the underlying condition and BP control. The reduction of cardiovascular risk should also be optimised in patients through lifestyle changes, BP control, and the use of statins. Furthermore, it should be taken into account that the Framingham risk score underestimates the likelihood of CVD events in people with CKD.
Key points
CKD is a common condition, which is asymptomatic in the majority of individuals
GPs should be aware of the risk factors for CKD and offer testing as appropriate
Classification of CKD is dependent on the GFR)
The prevalence of complications resulting from CKD rises as GFR
falls below 45 ml/min/1.73m2—significant proteinuria is also associated with adverse CKD outcomes
If the eGFR is <60 ml/min/1.73m2, a repeat measurement should be taken within 2 weeks—if there is no rapid decline, eGFR should be measured again after 3 months
A decline of >5 ml/min/1.73m2 per year or >10 ml/min/1.73m2 in 5 years indicates progressive CKD and the patient should be referred to a specialist
An eGFR value of ?60 ml/min/1.73m2 is inaccurate and deterioration in renal function should be inferred from an increase in serum creatinine concentration of >20%
Comorbid conditions, such as diabetes, hypertension, and CVD, are common in patients with CKD—individuals with these conditions should be offered testing
Patients with CKD should be offered education and information, and should be encouraged to exercise and maintain a healthy weight
Referral should be considered when there is suspicion of progressive renal disease, a rapid decline in function, resistance to treatment, or advanced kidney disease (stage >4 CKD)

CKD filter
BP > 140/90 mmHg	no further assesment
egfr > 60 ml/min/1.73m2	check ACR
egfr < 60 ml/min/1.73m2
ACR EMU in white bottle
abnormal ACR > 2.5 mg/mmol	men
abnormal ACR > 3.5 mg/mmol	women
Do not test during acute illness or menses If raised repeat after at least 2 weeks to confirm microalbuminuria

Management of CKD in primary care

CKD in GP RACGP

CKD Management	Actions	Repeat egfr
CKD Stage 1	attend to CVD risk factors	yearly
CKD Stage 2	attend to CVD risk factors	yearly
CKD Stage 3a	attend to CVD risk factors	if stable yearly if unstable 6 monthly
CKD Stage 3b	attend to CVD risk factors monitor Hb and treat if < 11 g/dl (exclude other causes)	if stable yearly if unstable 6 monthly
CKD Stage 4	refer to renal team	if stable 6 monthly unstable 3 monthly
CKD Stage 5	specialist supervision manage CVD risk factors and bone conditions Monitor and treat Hb	3 monthly – 6 weekly(BJPCN Craft Cards Sep 09)

DO NOT code a patient as having CKD 3 from a single abnormal eGFR result.
Only code after confirmed on two or more readings, (first repeat should be within two weeks if no prior abnormal readings and it should be a fasting blood test).

QOF payments relate to stages 3, 4 and 5. Do not code stages 1 or 2.
CKD and QOF

Any patient with two or more creatinines producing an eGFR of < 60 should have their CKD stage coded and the Sumary Page updated.

Any patient suspected of having CKD 3 or worse should have an abdominal and cardiovascular examination, BP check, diabetes screen (fasting BS), MSU and a urinary Albumin Creatinine Ratio (don’t forget nephrotoxic drugs).

If the patient is not hypertensive or diabetic then consider arranging a renal USS and once the result is available consider referral to a renal physician.

A FBC is only required in patients found to have eGFR < 45 i.e. CKD3b or worse.

hacking-medschool/dm-ckd

Referal Criteria CKD

K>6.5
egfr fall >5ml/min/yr or 15% with ACE
HB<11
Ca<2.1
P04>1.6

Current referral guidelines 2008
eGFR 60 to 89 – referral not required unless other problems present

eGFR 30-59 – routine referral if
Documented progressive eGFR > 5ml/min/1.73m2 over 12 months (needs 3 or more U&E/eGFR tests)
Microscopic haematuria
Elevated ACR (>70mg/mmol in non diabetics)
Unexplained anaemia, or abnormal K
Uncontrolled BP > 150/90 on three agents
Suspected systemic illness, such as SLE
Suspected renal artery stenosis

eGFR 15-29 urgent referral
eGFR <15 immediate referral (?admit)

CKD chart

Drug in renal impairment

Cautions

trimethoprim
nitrofurantoin
NSAIDS
thiazides
ACEIs
First line in younger patients DM CKD and proteinuria but caution during acute dehydrating illness

Statins in CKD

Chronic Renal Failure

Uraemia

Anaemia in CKD Erythropoeitin

Renal Osteodystrophy

Vitamin D in renal disease

End Stage Renal Disease

Dialysis

Renal transplantation

Kidney Transplant BMJ Nov 2011

Acute Renal Failure

Polycystic Kidney Disease

UTI (renal)

UTI adults NIDDK

Acute UTls should be treated according to the MSU sensitivities.
Generally, a 3-day course of antibiotics is sufficient for uncomplicated UTI in
women, but longer courses are usually needed if there is evidence of
pyelonephritis or if the patient is pregnant. Men and children may also need
longer courses.

Usual first-line options are trimethoprim or nitrofurantoin. Cefalexin should usually be reserved for resistant infection.

Pyelonephritis (Adults)
Fever/loin pain/rigors.
1st line Co-amoxiclav 625mg three times daily for 14 days.
Cotrimoxazole 960mg twice daily for 14 days.
Referral If no response to treatment within 24 hours.

Excretory Organs

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