Nephrology in General Practice Dr. M. Imran MBBS, MRCP(UK), MRCP (renal medicine), Post grad cert in clin Ed. Consultant Nephrologist MRCP Examiner ( Royal College of Physicians UK) Senior clinical Tutor ( Hull York Medical School)

Brain storming You should all know these.

52 Male Diabetes 4 years Hypertension 4 years High blood pressure, poorly controlled diabetes Urine dipstick protein 2+, Blood 2+ ( repeated twice 2 weeks apart) latest creat 164, GFR 44 ml/min GFR last year 49 ml/min GFR 4 years before > 60 ml/min

Questions eGFR What ? Why? How? Reliable? When it is not reliable What is expected decline?

Has he got CKD? Define CKD Can I use GFR in children? Can I use it in AKI? What to do if GFR is low? ( Management)

Low GFR what to do? Exclude AKI, compare with old results Review Drugs (Metformin, NSAIDS,ACE) Treat underlying cause BP- targets Proteinuria CV Risk (smoking, cholesterol, anaemia) Has our patient got progressive CKD ?

ACR PCR BP /<90 ≥ 70 ≥ /<80 use ACE/ARB Diabetics ≥ 30 ≥ /<80 use ACE/ARB ACR >2.5 (male) >3.5 (female) – Use ACE irrespective of BP

Your patient GFR stabilized ACR 120 Which drug to add/increase? 2 weeks bloods K + =6.5 mmol/L

Proteinuria testing Ckd annual Diabetics annual Risk of ckd once If clinical need Should I send my patient’s urine for culture? How to convert PCR/ACR in 24 urinary protein excretion?

Do I need renal ultrasound in all CKD patients? Renal anaemia What about Calcium, phosphate, Pth test

Will you refer? 52 Male Diabetes 4 years Hypertension 4 years High blood pressure, poorly controlled diabetes Urine dipstick protein 2+ ( repeated twice 2 weeks apart) latest creat 164, GFR 44 ml/min GFR last year 49 ml/min GFR 4 years before > 60 ml/min

Will you refer? 52 Male Diabetes 4 years Hypertension 4 years High blood pressure, poorly controlled diabetes Urine dipstick protein 2+ Blood 2+ ( repeated twice 2 weeks apart) latest GFR 54 ml/min GFR last year 55 ml/min GFR 4 years before 57 ml/min

Will you refer? 28 Male Diabetes 10 years dvt on warfarin INR 3.6 Painless visible haematuria latest GFR 54 ml/min GFR last year 55 ml/min GFR 4 years before 56 ml/min

Will you refer? 18 Male Insurance check BP 110/58 Urine dipstick blood 2+ ( repeated 3 times) latest GFR >60 ml/min How to manage?

Will you refer? 72 Male Diabetes 14 years Hypertension 12 years UTI-dipstick prot 1+, blood 1+, Leuc 1+ Dipstick after treatment prot 1+ latest GFR 44 ml/min GFR last year 45 ml/min GFR 5 years before 48 ml/min Ultrasound- normal kidneys, left kidney 2 cm cyst with smooth outline

Will you refer? 72 Male Diabetes 14 years Hypertension 12 years UTI-dipstick prot 1+, blood 1+, Leuc 1+ Dipstick after treatment prot 1+ latest GFR 44 ml/min GFR last year 45 ml/min GFR 5 years before 48 ml/min Ultrasound- normal kidneys, left kidney 2 cm cyst with irregular outline and areas of concern in the cyst.

Will you refer? 19 Male Sports injury, leg and abdominal pain BP 138/98 Urine dipstick blood 1+ latest GFR >60 ml/min Family history- adopted Ultrasound abdomen- two cysts in each kidneys both size 4cm.

Will you refer? 28 Male IVDU, hep C BP 138/98 Rash and coughed up blood ( CXR normal) Urine dipstick blood 2+, prot 2+ latest GFR 40 ml/min No previous tests Will you refer? What not to miss?

38 female- real patient Cleaner Coughed up blood, twice BP- 142/98 CXR- haziness right base- treated antibiotics Still coughs up blood in most of the mornings. Very well looking No rash Urine dipstick blood 2+, Prot 2+ GFR > 60 Urgent or routine?

When to refer GFR less than 30 ml/min/1.73 m2 (GFR category G4 or G5), with or without diabetes ACR 70 mg/mmol or more, unless known to be caused by diabetes and already appropriately treated ACR 30 mg/mmol or more (ACR category A3), together with haematuria sustained decrease in GFR of 25% or more, and a change in GFR category or sustained decrease in GFR of 15 ml/min/1.73 m2 or more within 12 months hypertension that remains poorly controlled despite the use of at least 4 antihypertensive drugs at therapeutic doses (see also Hypertension [NICE clinical guideline 127]) known or suspected rare or genetic causes of CKD suspected renal artery stenosis. amended 2014]

Urgent referral Acute Kidney Injury malignant hypertension hyperkalaemia (K+ > 7mmol/L) uraemia fluid overload nephrotic syndrome/suspected vasculitis

Quality and Outcomes Framework CKD 3-5 register6 CKD BP recorded6 CKD BP<140/8511 CKD+HT on ACEI/ARB4 DM BP recorded3 DM BP<145/8517 DM screen for albuminuria3 DM+albuminuria on ACEI/ARB3 DM eGFR/creatinine checked3 Total56 (1000)

Drugs any concerns Nitrofurantoin Gout treatment: Allupurinol Immune suppression NSAIDS Any other drug?

Now sit back and relax Remember if you can.

GFR categoryGFR (ml/min/1.73 m 2 )Terms G1>90Normal or high G260–89Mildly decreased* G3a45–59Mildly to moderately decreased G3b30–44Moderately to severely decreased G415–29Severely decreased G5<15Kidney failure Improving Global Outcomes (KDIGO) CKD Work Group (2013) Kidney Disease Improving Global Outcomes GFR categories Kidney Disease Improving Global Outcomes ACR categories What did NICE say in 2014? 59 pages

ACR categoryACR (mg/mmol)Terms A1<3Normal to mildly increased A23–30Moderately increased* A3>30Severely increased** Improving Global Outcomes (KDIGO) CKD Work Group (2013) KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney International (Suppl. 3): 1–150KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease Kidney Disease Improving Global Outcomes ACR categories Late presentation of people with kidney failure increases morbidity What did NICE say in 2014?

Consider using eGFR cystatinC at initial diagnosis to confirm or rule out CKD in people with: an eGFRcreatinine of 45–59 ml/min/1.73 m 2, sustained for at least 90 days and no proteinuria (albumin:creatinine ratio [ACR] less than 3 mg/mmol) or other marker of kidney disease. [new 2014] marker of kidney disease Do not diagnose CKD in people with: an eGFRcreatinine of 45–59 ml/min/1.73 m 2 and an eGFRcystatinC of more than 60 ml/min/1.73 m 2 and no other marker of kidney disease. [new 2014]marker of kidney disease Offer testing for CKD using eGFRcreatinine and ACR to people with any of the following risk factors:

Vitamin D supplements in the management of CKD–mineral and bone disorders Do not routinely offer vitamin D supplementation to manage or prevent CKD–mineral and bone disorders. [new 2014] Offer colecalciferol or ergocalciferol to treat vitamin D deficiency in people with CKD and vitamin D deficiency. [new 2014] If vitamin D deficiency has been corrected and symptoms of CKD–mineral and bone disorders persist, offer alfacalcidol (1-alpha-hydroxycholecalciferol) or calcitriol (1-25-dihydroxycholecalciferol) to people with a GFR of less than 30 ml/min/1.73 m2 (GFR category G4 or G5). [new 2014] Monitor serum calcium and phosphate concentrations in people receiving alfacalcidol or calcitriol supplements. [2014]

Oral bicarbonate supplements in the management of metabolic acidosis Consider oral sodium bicarbonate supplementation for people with both: a GFR less than 30 ml/min/1.73 m2 (GFR category G4 or G5) and a serum bicarbonate concentration of less than 20 mmol/litre. [new 2014]

Consequences of late presentation Higher mortality, morbidity, hospital stay, cost Due to poorer clinical state at presentation, lack of vascular access No possibility of pre-emptive transplantation Winkelmayer WC. J Am Soc Nephrol 2003; 14:

UKRR 13 th Annual Report

Stage 5 0.2% Stage 4: 0.2% Stage 3: 4.3% Stage 2: 3.0% Stage 1: 3.3%

100 patients with eGFR < 60

1 year later: 1 patient needs RRT, 10 patients have died (> 50% CV death)

10 years later: 8 patients need RRT, 65 patients have died, 27 have ongoing CKD

ACE REIN (n=352) CAPTOPRIL (n=409) RENAAL (n=1513) IDNT (n=1715)

BUT Combined Angiotensin Inhibition for the Treatment of Diabetic Nephropathy Combination therapy with an ACE inhibitor and an ARB was associated with an increased risk of adverse events among patients with diabetic nephropathy.

Event Rates by Grade of Proteinuria Framingham Heart Study: 16 Year Follow-up Event Rates per 1000 Person Years No ProteinuriaTrace Proteinuria> Trace Proteinuria Culleton BF. Am J Med 2000 Men n = 1045  = 68 yrs Women n = 1541  = 69 yrs

Diagnosis of patients starting RRT during 2011 DiagnosisPercentage of patients Diabetes24.8 Glomerulonephritis13.3 Pyelonephritis7.1 Hypertension7.0 Polycystic kidney disease7.2 Renal vascular disease6.9 Other16.3 Uncertain17.3 UKRR 15 th Annual Report

Background-UKRR data

Cardiovascular Mortality Annual mortality (%) 25–3445–5465–74  85 35–4455–6475–84 Male Female Black White Dialysis General population Age (years)

Nordio et al. American Journal of Kidney Diseases 2012; 59: (DOI: /j.ajkd )American Journal of Kidney Diseases 2012; 59: Relative Survival by Illness

Dialysis May Not Mean Greater Survival in Older Patients with Poor Prognosis Kaplan-Meier survival curves for those with high comorbidity (score=2), comparing 5 dialysis and conservative groups (log rank statistics <0.001, df 1, P=0.98. Murtagh. Nephrol Dial Transplant. 2007; 22(7):

Optimal Hb levels [new 2011] PopulationHb range Adults, young people and children > 2 years of age 10 and 12 g/dl Children < 2 years9.5 and 11.5 g/dl

Pathway: diagnosis Is anaemia due to CKD? Consider other causes if eGFR ≥60 ml/min/1.73m 2 Consider treating anaemia when: Hb falls to ≤ 11 g/dl (or ≤10.5 g/dl if younger than 2 years), or symptoms attributable to anaemia develop Determine iron status: Iron deficiency anaemia: diagnosed when serum ferritin < 100 μg/l in stage 5 CKD considered when serum ferritin < 100 μg/l in stage 3 and 4 CKD Functional iron deficiency defined by: serum ferritin > 100 μg/l and either % hypochromic red cells > 6% (if test available), or transferrin saturation < 20%

Pathway: treatment Iron Iron correction should maintain: serum ferritin > 200 μg/l transferrin saturation > 20% (unless ferritin > 800 μg/l) % hypochromic red cells 800 μg/l) Review iron dose: when serum ferritin reaches 500 μg/l (should not rise above 800 μg/l) Optimise iron status: before or when starting ESAs before deciding whether to use ESAs in non-dialysis patients