Paediatric Renal Disease

Transcription

1 Pharmacy Department Paediatric Renal Disease NUH Pharmacy

2 At the end of the session you should be able to: Determine the level/type of renal dysfunction in a child and what the implications might be for drug dosing. Identify common drug causes of Acute Kidney Injury and ways in which damage can be minimised or avoided. Describe the key features of Nephrotic Syndrome and outline the management of this condition.

3 Quiz NUH Pharmacy

4 What is normal?

5 Renal Dose Adjustments Calculate egfr using the Schwartz equation Child over 1 year: Estimated GFR (ml/min/1.73 m 2 )= 40 height (cm) serum creatinine (micromol/l) Neonate: Estimated GFR (ml/min/1.73 m 2 )= 30 height (cm) serum creatinine (micromol/l)

6 (Unless you are in Nottingham.)

7 Paediatric Renal Dosing BNFC Renal Drug Handbook Others.?

8 BNFC Cefuroxime Gentamicin

9 Others Drug Prescribing in Renal Failure, 5th Edition- Aronoff Micromedex Lexicomp / Up to Date

10 Renal Drug Handbook/Database Cefuroxime: Gentamicin:

11 Acute Kidney Injury

12 Case 1

13 Grading of AKI

14 Causes of AKI Pre-renal Sepsis Dehydration Shock Medication Post-renal Medication Obstruction Intra-renal Endotoxin Immune mediated Medication

15 Drug-Induced Pre-renal AKI Hypovolaemia: Excessive renal fluid loss: inappropriate use of diuretics. Systemic Hypotension: Usually due to cardiogenic shock/sepsis, but can arise due to pharmacological vasodilatation Renal Hypoperfusion: Afferent Arteriolar Constriction: NSAIDs, amphotericin, ciclosporin, adrenaline, noradrenaline Efferent Arteriolar Dilatation: ACE Inhibitors (ACEIs), Angiotensin II Inhibitors (ARBs)

16 ACEIs, ARBs and the Kidney Contraindicated in bilateral renal artery stenosis. Creatinine usually rises on starting/dose increase: NICE CCF Guideline: If egfr change is >25% or plasma creatinine >30% AND no other causes of deterioration is found stop ACEI/ARB or reduce dose to previously tolerated dose. Reno-protective in diabetic and non-diabetic microalbuminuria / proteinuria, irrespective of whether BP raised or not

17 Drug-induced Intra-renal AKI Drug Statins Contrast Media Aminoglycosides Effect on kidney Induce rhabdomyolysis Renal vasoconstriction & free radical production Direct toxic effect on tubular cells

18 Drug-Induced Post-Renal AKI Drug causes rare- due to obstruction of urine flow: Retroperitoneal haemorrhage due to overanticoagulation: bleeding creates external pressure on the ureters Retroperitoneal fibrosis: methotrexate, beta-blockers Crystallisation of urate and stone formation within the ureter: Tumour lysis syndrome Other drugs include: aciclovir, acetazolamide, cisplatin and naftidofuryl, topiramate, mirtazepine, risedronate

19 Medication Review in AKI Avoid and/or stop known nephrotoxins- where possible Avoid drugs which raise serum potassium. Stop/review antihypertensives (including diuretics). Adjust doses of drugs which are to continue in light of reduced renal clearance. Start with low doses and titrate slowly. Consider if alternative drug may be more suitable. Monitor levels whenever you can.

20 Not all cases are quite so obvious 9 year old girl Abdominal pain, joint pain and fever-? Cause Treated with cefuroxime No improvement Day 3: Trough level 5mg/L Dose increased by 20% Day 5: Trough level 8mg/L Serum creatinine 60 micromol/l Increased to 6-hourly Vancomycin added 15mg/kg 8-hourly Day 8: Trough level 25mg/L Serum creatinine 135 micromol/l

21 Not all cases are quite so obvious What are the possible learning points from this case? What information is missing? NUH Pharmacy

22 Not all cases are quite so obvious Learning points: Rapid increase in dose and frequency. Initial creatinine 25 micromol/l- increase not identified Concomitant use of NSAID not identified, Poor communication of plan to stop vanc

23 Prevention Avoid Nephrotoxic preparations / combinations. If unavoidable, monitor patients very closely. Remember that 25-50% of kidney function may have been lost before any rise in creatinine seen. Sick day rules for patients on ACE Inhibitors / ARBs. Be alert to the risk factors.

24 Sick Day Rules for ACE Inhibitors/ARBs NUH Pharmacy

25 Risk Factors for AKI Pre-renal: Limited access to fluids. Hypovolaemia and / or hypotension Sepsis Deteriorating PEWS Others: Heart Failure Liver Disease Haematological maligancy Nephrotoxic drugs Intra-renal: Chronic Kidney Disease History of AKI or oliguria Severe diarrhoea, particularly bloody diarrhoea. Signs or symptoms of nephritis Urinary obstruction. Renal Transplant

26 Nephrotic Sydrome

27 What is it?

28 What is it? Characterised by: Heavy proteinuria (protein:creatinine ratio > 250mg/mmol). Hypoalbuminaemia (serum albumin <25g/l). Oedema. Relapsing/Remitting Condition. Annual incidence in the UK of 2 per 100,000 children. More common in children from South Asia with an incidence up to 16 per children.

29 Initial Treatment Aim is to induce remission with steroids and therefore promote diuresis. Most patients respond within 7-14 days. Prednisolone 60mg/m 2 (max 80mg) once daily for 28 days, then 40 mg/m 2 on alternate days for the next 28 days and then stop. Intensified Regimen: Weeks 1-4: 60 mg/m 2 /day Weeks 5 8: 40 mg/m 2 on alternate days Weeks 9 12: 25 mg/m 2 on alternate days Weeks mg/m 2 then stop. PREDNOS Study Children who do not respond to prednisolone within 28 days need a renal biopsy.

30 Preventing Complications Hypovolaemia Increases the risk of thrombosis. Tachycardia, hypertension, cool peripheries and delayed capillary refill time. If severe consider albumin and thromboprophylaxis. Give albumin if symptomatic hypovolaemia or severe diuretic resistant oedema. Shock: 4.5% albumin 20 ml/kg over mins repeated if necessary. Mild hypovolaemia + oedema = 20% albumin 5 ml/kg (1g/kg) over 4 hrs. Preventing Thrombosis: Avoid hypovolaemia Prevent sepsis Encourage mobilisation and avoid bedrest Consider TEDS and LMWH.

31 Preventing Complications Oedema and Ascites: Fluid restriction and low salt diet. Diuretics if severe/worsening oedema/ascites in the absence of hypovolaemia. Usually furosemide and spironolactone. Can add metolazone. Infection: Oral Penicillin V given to oedematous/ascitic patients to protect against pneumococcal infection. 125 mg twice daily if 0-5yrs 250 mg twice daily 5-12 yrs 500mg twice daily if > 12 years. Give Pneumovax II pneumococcal vaccine if not already given.

32 Classification Steroid Sensitive (SSNS). Steroid Resistant (SRNS). Frequently Replapsing (FRNS). Steroid Dependant (SDNS).

33 Steroid Sensitive NS Most cases will respond completely to steroids. Some will fail to come off steroids completely. 80% will have a relapse: May be frequent

34 Relapses Often triggered by viral infection. Treated with high dose steroids to induce remission. May be possible to prevent relapses by giving a low dose of daily steroids for 5 days at the time of an URTI without waiting for proteinuria to develop. Potential to have a large impact on long-term steroid burden. Subject of a national multicentre trial, PREDNOS2.

35 Steroid Dependant / Frequently Relapsing NS

36 Levamisole Increased likelihood of remission when given for 16 weeks May be best suited in frequent relapsers who are not steroid dependent. Takes several months to become effective. Usually started alongside slow steroid wean. Dose: 2.5 mg/kg (max 150 mg) on alternate days. Can crush tablets. Side-effects: leucopenia, gastro-intestinal effects and vasculitis. Monitor FBC and cunsel parents to seek medical attention if unusual or severe infection. Usually continued for at least 1-2 years.

37 Cyclophosphamide Significantly reduces risk of relapse in FRNS. Dose 2-3mg/kg orally once daily for 8 weeks. Alternate day dosing with tablets. Liquid special. Generally well tolerated: Weekly FBC during treatment. May lead to hair thinning Minimal effect on fertility. Preferred second-line agent in pre-pubertal children where there is steroid dependence. In peri- and post-pubertal children consider tacrolimus instead due to a theoretical increased risk of gonadal toxicity at this age. IV alternative to oral if concern about concordance 500 mg/m 2 monthly for 6 months.

38 Tacrolimus Effective at reducing frequency of relapses. Usually 3 rd line agent. Starting dose 0.15 mg (max 5mg) twice daily. Target trough level 4-8 nanograms/ml. Prescribe/dispense by brand: Prograf, Adoport, Modigraf, Adoport. If relapse free after 2 years on tacrolimus, it should be stopped. If early relapse, restart after induction of remission with prednisolone. If taking for >2 years, renal biopsy needed. If significant nephrotoxicity, switched to rituximab or mycophenolate. Dose related side-effects: headache, tremor, abdo pain, visual disturbance and hyperglycaemia.

39 Rituximab Indications: Frequent relapses on tacrolimus SRNS unresponsive to 3 months of tacrolimus FRNS/SDNS if poor concordance tacrolimus or levamisole Life-threatening nephrotic complications In FRNS/SDNS, usually consolidates remission for at least 6 months Dose: 375 mg/m 2 : Increasing rate, pre-med. Hepatitis B status must be determined before starting. Repeat dose on relapse / B-cell repopulation. Long-term effects not known. On current evidence, give maximum 4 prophyactic doses before waiting to see if in long-term remission.

40 Mycophenolate Effective as add-on agent when already on tacrolimus: Some evidence as a sole prophylactic agent less effective than ciclosporin or tacrolimus. If used with tacrolimus, dose is 300 mg/m 2 bd but due to GI side effects often started at lower dose initially. Dose if used without tacrolimus is 600 mg/m 2 bd, but again start at low dose. Prescribe by brand.

41 Steroid Resistant NS If unresponsive after 4 weeks of prednisolone give methylprednisolone (300 mg/m 2 ) for 3 days. If no response renal biopsy indicated. Tacrolimus then usually commenced. Followed if needed by rituximab. Focal and segmental sclerosis (FSGS) More steroid-resistant disease with a poorer prognosis Other drugs to consider for persistent nephrotic states: ACE inhibitors and ARBs; statins; and anticoagulants or antiplatelets.

42 Any questions?

43 NUH Pharmacy