1. RENAL DISEASE – A GENERAL PRACTICE PERSPECTIVE Dr Shareen Hallas

2. REMEMBER THE KIDNEYS?

3. …..AND THE NEPHRON?

4. …AND WHAT GOES ON THERE?

5. WHAT’S IN THE NEWS? “Apple Shape” linked to higher risk of kidney disease. (BBC News 12 th April 2013)

6. RECENT RESEARCH BMJ 2013;346:f324 Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis Over 2 million participants Cohort study Conclusions Both sexes face increased risk of all-cause mortality, cardiovascular mortality, and end stage renal disease with lower estimated glomerular filtration rates ( 30). These findings were robust across a large global consortium

7. WHAT DO WE SEE IN PRIMARY CARE?

8. SCENARIO 1 A 60 year old man presents with urinary frequency and urgency. He is a smoker. He has hypertension and takes amlodipine 5mg. Urinalysis shows blood++. No nitrites or leucocytes What will you do next?

9. HAEMATURIA Visible haematuria REFER at any age to Urology 2 week rule if painless at any age Remember with renal stones up to 20% are negative for haematuria

10. NON VISIBLE HAEMATURIA Is it blood? (beetroot, rifampacin etc) Exclude UTI, menstruation, exercise) Refer symptomatic non visible haematuria at any age

11. SYMPTOMATIC NON VISIBLE HAEMATURIA Check U&E, creat, eGFR, bp, ACR. Refer if over 40 to UROLOGY 2 weeks Likely needs referral to urology if symptomatic at any age

12. ASYMPTOMATIC NON VISIBLE HAEMATURIA Check 3 urinalysis over a 2/52 period. If 2/3 positive this is a positive result If over 40 refer to UROLGY If under 40 refer NEPHROLOGY if: ACR>30 eGFR<60ml/min (2 readings, no reversible cause) BP>140/90 If these referral criteria are not met, annual follow up as likelihood of serious pathology is 8% and malignancy in 1.5%

13. REMEMBER Proteinuria is the best indicator of glomerular disease Approximately 10% people with non visible haematuria have a urological malignancy. The most common is bladder cancer Check a urinalysis when looking for causes of iron deficiency anaemia

15. SCENARIO 2 A 46 year old woman presents for follow up urinalysis after a recent UTI. No urinary symptoms. NoHx hypertension, diabetes. Not pregnant. No FH renal disease. Meds nil reg, intermittent NSAID for dysmennorhoea. O/E bp 140/80 no oedema. Urinalysis protein++. Nil else. What will you do next?

16. NSAIDS Most common cause of drug induced renal damage in general practice If on long term nsaids monitor renal function 2-3 times per year.

17. PROTEINURIA Positive urinalysis in 2 or more urine samples over a 1-2 week period. UTI can cause false positive Remember ACR has a greater sensitivity than PCR If ACR >70mg/mmol (PCR >100mg/mmol) REFER NEPHROLOGY If ACR >30mg/mmol (PCR > 50mg/mmol) WITH NON VISIBLE HAEMATURIA. REFER NEPHROLOGY

18. OTHER INVESTIGATIONS U&E, eGFR, BP, Hba1c Then select ix depending on potential cause May include; C3, C4, Igs, electrophoresis, RF, ASOT, ANCA, ANA, dsDNA, cholesterol (raised in nephrotic synd)…….. What about renal ultrasound?

19. LOTS OF CAUSES OF PROTEINURIA! Transient proteinuria Emotional stressEmotional stress. Exercise. Fever. Urinary tract infectionUrinary tract infection. Orthostatic (postural) proteinuria*. SeizuresSeizures. Persistent proteinuria. Primary glomerular causes Focal segmental glomerulonephritis.glomerulonephritis IgA nephropathyIgA nephropathy (ie Berger's disease). IgM nephropathy. Membranoproliferative glomerulonephritisMembranoproliferative glomerulonephritis. Membranous nephropathy. Minimal change diseaseMinimal change disease. Secondary glomerular causes Alport's syndromeAlport's syndrome. AmyloidosisAmyloidosis. SarcoidosisSarcoidosis. Drugs (eg non-steroidal anti-inflammatory drugs (NSAIDs), penicillamine, gold, angiotensin-converting enzyme (ACE) inhibitors).non-steroidal anti-inflammatory drugspenicillamine goldangiotensin-converting enzyme (ACE) inhibitors Anderson-Fabry diseaseAnderson-Fabry disease. Sickle cell diseaseSickle cell disease. Malignancies (eg lymphoma, solid tumours).lymphoma Infections (eg HIV, syphilis, hepatitis, post-streptococcal infection).HIVsyphilishepatitis Tubular causes AminoaciduriaAminoaciduria. Drugs (eg NSAIDs, antibiotics). Fanconi's syndromeFanconi's syndrome. Heavy metal ingestion. Overflow causes HaemoglobinuriaHaemoglobinuria. Multiple myelomaMultiple myeloma. MyoglobinuriaMyoglobinuria. Other important causes (likely to have multiple pathologies) Pre-eclampsiaPre-eclampsia/eclampsia.

20. NEPHROTIC SYNDROME Heavy proteinuria. PCR > 200mg/mmol Hypoalbuminaemia <30g/l Oedema, particulalry periorbital

21. MODERATE PROTEINURIA (100- 200MG/MMOL) May be tubular disease eg drug induced interstitial nephritis.

22. PROTEINURIA WITH NVH MORE LIKELY TO BE: IgA nephropathy (most common cause of acute glomerulonephritis, 80% in age 16-35), polycystic kidneys, vasculitis, collagen multisystem disease, post infectious glomerulonephritis

23. WHAT ABOUT PRESCRIBING IN RENAL IMPAIRMENT? BNF - For many drugs with only minor or no dose-related side-effects very precise modification of the dose regimen is unnecessary and a simple scheme for dose reduction is sufficient. For more toxic drugs with a small safety margin, dose regimens based on GFR should be used Take care with many antibiotics, histamine H 2 - receptor antagonists, digoxin, anticonvulsants and NSAIDs, potassium sparing drugs, vit D, antacids (high Na content), ACE (watch out for renal artery stenosis), diuretics. Care after iodine contrast If patient on dialysis ask a specialist.

25. SCENARIO 3 A 55 year old woman presents after receiving a letter from the practice to come in to discuss he blood tests which show chronic kidney disease stage 3. She has hypertension controlled with amlodipine 5mg. Bp 140/90. eGFR 50ml/min/1.73m2 What will you do?

26. WHAT IS CKD DEFINED AS? eGFR < 60ml/min/1.73m2 for 3 months

27. CKD Stage 1 eGFR >90 with other evidence of kidney damage Stage 2 eGFR 60-90 with other evidence of kidney damage Stage 3A eGFR 45-59 Stage 3B eGFR 30-44 Stage 4 eGFR 15-29 Stage5 EGFR <15 Use suffix p to denote proteinuria Chronic kidney disease affects 10–16% of the general adult population in Asia, Europe, Australia, and the United States

28. HOW OFTEN SHALL I MONITOR CKD? CKD 1 and 2, yearly 3A and 3B, 6 monthly 4, 3 monthly 5, 6 weekly According to NICE CG 73 NB CKD is a part of the QRISK 2 score

29. REMEMBER Correct eGFR for ethnicity (African or Caribbean) X 1.21 New low eGFR repeat within 2 weeks Measure minimum 3 eGFRs over 90 day period - need at least 2 to diagnose CKD DO NOT EAT MEAT for 12 hour pre-test for eGFR Measure ACR ACE inhibitors can reduce creatinine by up to 20%. If creat inc by >20% or eGFR dec by >15% can be due to renal artery stenosis. Serum creatinine has limitations - can remain within the normal range despite the loss of over 50% of renal function

30. CKD 3 All cause mortality (and CVD mortality) is increased in stage 3 CKD, increase is much greater in stage 3B Progression of renal disease is rare (4% with esrf in 10 years) Cholesterol lowering in this group can reduce CV events (SHARP study) Over 10 years a patient with CKD 3 has a 25% chance of dying from CVD Need pneumococcal and annual flu immunisations

31. REMEMBER Will kidneys fail in your patient’s lifetime, or will they die of something else first?

32. TIP CSA CKD explained mattandhazelsmith video youtube

33. ACR IN DIABETES Normal is <2.5 in men and <3.5 in women In diabetes can get an initial increase in eGFR as glycosuria damages the basement membrane. Protein can therefore leak when the eGFR is still normal. EPO produced round prox tubules – damaged in Dm, hence can get EPO deficiency earlier in diabetic kidney disease.

34. ACE INHIBITORS Check u&e 1-2 weeks after starting ACE If creatanine rises by >20% or eGFR drops by >15% consider renal artery stenosis Repeat after dose increase Stop ACE in dehydrating illness Counsel women of childbearing age

35. WHEN DO I DO A RENAL ULTRASOUND? Obstructive symptoms FH polycystic kidneys Haematuria, progressive CKD Stage 4 or 5 CKD

36. WHEN DO I REFER A PATIENT WITH CKD? Stage 4 or 5 (check Hb and Ca/PO4) Proteinuria (ACR >70) ACR >30 AND haematuria Rapidly declining eGFR (>5ml/min in one year) Poorly controlled hypertension despite 4 drugs (aim bp <140/90) Suspected renal artery stenosis or rare cause CKD

37. REMEMBER LIFESTYLE Stop smoking Reduce salt Men have bigger kidneys than women After age 40 renal function decreases by 1ml/min/year

38. DIALYSIS Around 40,000 people in the UK are having dialysis or have functioning kidney transplants

39. DIALYSIS Usually starts when GFR 10 ml/min ( 15ml/min in diabetes) Indications: Presence of clinical features of uraemia (eg, pericarditis, gastritis, hypothermia, fits or encephalopathy).pericarditishypothermia Fluid retention leading to pulmonary oedema: inability to reduce excess volume with diuretics with urine volume under 200 mL in twelve hours.pulmonary oedema Severe hyperkalaemia (potassium above 6.5 mmol/L) unresponsive to medical management.hyperkalaemia Serum sodium above 155 mmol/L or below 120 mmol/L. Severe acid-base disturbance (pH under 7.0) that cannot be controlled by sodium bicarbonate. Severe renal failure (urea greater than 30 mmol/L, creatinine greater than 500 μmol/L. Toxicity with drugs that can be dialysed

40. HAEMODIALYSIS Arterio-venous fistula formed 3-6 months before starting dialysis Dialysis 3 times a week, 4 hours each time Complications: Access-related: local infection, endocarditis, osteomyelitis, creation of stenosis, thrombosis or aneurysm. Hypotension (common), cardiac arrhythmias, air embolism. Nausea and vomiting, headache, cramps. Fever: infected central lines. Dialyser reactions: anaphylactic reaction to sterilising agents. Heparin-induced thrombocytopenia, haemolysis. Disequilibration syndrome: restlessness, headache, tremors, fits and coma. DepressionDepression.

41. PERITONEAL DIALYSIS CAPD involves 4 exchanges of 20 minutes through the day Can do peritoneal dialysis at night too Greater flexibility Contra-indications to peritoneal dialysis Intra-abdominal adhesions and abdominal wall stoma. Obesity, intestinal disease, respiratory disease and hernias are relative contra-indications. Complications of peritoneal dialysis Peritonitis, sclerosing peritonitis. Catheter problems: infection, blockage, kinking, leaks or slow drainage. Constipation, fluid retention, hyperglycaemia, weight gain. Hernias (incisional, inguinal, umbilical). Back pain. Malnutrition. Depression

42. RENAL TRANSPLANT Good survival rates 1 year and 10 year graft survival rates are 89% and 67% for adult kidneys from 'brain death donors' and 96% and 78% for kidneys from live donors.

44. SCENARIO 4 A 20 year old woman presents to you in tears as her mother is going to start dialysis for ESRF due to Polycystic kidney disease. She wants to know if she has this too, What is her risk? What are you going to do?

45. ADULT POLYCYSTIC KIDNEY DISEASE Affects 1 in a 1000 (50% in ESRF by age 60) Accounts for 10% people on dialysis Autosomal dominant (but de novo mutation in 5% cases) Loin pain is the most common symptom (60%) Hypertension in 10-15% affected children and 50% affected adults Intracranial berry aneurysms in 6% with no fh and 16% with fh. If FH MRI scan 5 yearly. Mitral valve prolapse in 25% When to screen family members? (uss after age 20)

46. POST STREPTOCOCCAL GLOMERULONEPHRITIS Mainly in under 5s 7-14 days after group A B haemolytic strep infection, usually sore throat Accounts for 90% of acute glomerulophritis GFR usually returns to normal in 10-14 days 92%-98% recover fully Haematuria may persist asymptomatically for 2 years.

47. HELP FOR YOUR PATIENTS http://pkdcharity.org.uk/ http://www.kidneyresearchuk.org/home.php http://www.gosh.nhs.uk/medical-conditions/ http://www.britishkidney-pa.co.uk/