The evidence base for interventions to slow the progression of chronic kidney disease: Medical interventions Jonathan Evans Paediatric Nephrologist
CKD in adults Often unrecognised Preventable Major cardiovascular risk
Evidence, broadly construed, is anything presented in support of an assertion. This support may be strong or weak.
Preventative measures for CKD 3 0 Mx / prevent Complications 2 0 Modify Disease - BP/Proteinuria/ACEI, Rx Chronic GN 1 0 Prevent Disease lifestyle, AUTA screening, UTI Mx
Are we reducing the number of children with ERF through our preventative care? 350 300 250 200 150 100 New cases of ERF in UK aged <16yr (Renal Registry Report 2013) Dysplasia +/- VUR Obstructive Uropathy All other causes 50 0 1998-02 2003-07 2008-12
Prophylactic Antibiotics?
CG54 UTI in Children (2007) 1.2.3.1 Antibiotic prophylaxis should not be routinely recommended in infants and children following first UTI. 1.2.3.2 Antibiotic prophylaxis may be considered in infants and children with recurrent UTI. Long-term antibiotics for preventing recurrent urinary tract infection in children (Review) 2011 Williams G, Craig JC Long term antibiotics reduce the risk of UTI in susceptible children (+/- VUR) but the benefit is small and there is increased risk of antimicrobial resistance Nitrofurantoin most effective but high incidence of AE
Interventions for primary vesicoureteric reflux(review) 2011 Nagler V, Williams G, Hodson E Craig JC Author Conclusions : 1. long-term, low-dose antibiotics did not reduce the number of repeat symptomatic or febrile UTIs in children with VUR. 2. Antibiotic prophylaxis associated with 3X incidence of resistance 3. Considerable heterogeneity in the analyses and inclusion of only one adequately blinded study, made drawing firm conclusions challenging. 4. Antibiotic prophylaxis significantly reduced the risk of developing new or progressive renal damage, but assuming an 8% baseline risk, 33 children would need long-term antibiotic prophylaxis to prevent one more child developing kidney damage over the course of two to three years. So if you believe the results the question is... Is the damage (progressive or new renal scar) avoided sufficient to justify long term Rx
Prompt Treatment of UTI as recommended by NICE & AAP Guidelines? Does prompt treatment of urinary tract infection in preschool children prevent renal scarring: mixed retrospective and prospective audits. Coulthard 2013 Treating UTI in 3 days, halves the risk of acquiring kidney scars. Incidence of focal scars on DMSA reduced from ~ 0.4% to 0.2% Risk of scars increased with VUR This reduction in scarring rates could not have been detected if the NICE CG had been implemented locally.
Early Treatment of Acute Pyelonephritis in Children Fails to Reduce Renal Scarring: Data From the Italian Renal Infection Study Trials. Hewitt (2008) Pooled results from 2 prospective RCTs analysing ~300 children with first UTI & acute pyelonephritis with rpt DMSA at 12 months No change in % scarring with delay in treatment (1-5d) No difference in % scarring at different ages Fever normalised within average of 1.6 days we recommend prompt treatment of febrile UTIs to facilitate rapid recovery from the acute illness,
Antibiotics to prevent CKD Variable evidence they work! But no proof they don t in my patient! So. Treat UTIs Consider prophylaxis Consider stopping prophylaxis sooner
Mechanisms of CKD progression
1. Recognise child at risk of progressive CKD 2. Know what to do 3. Do it well Risk Factors for Progression of CKD Chronic Glomerulonephritis Progressive disorders (e.g ARPKD, Cystinosis, Alports) Uropathies (obstruction, infection, bad bladder) Bilateral renal disease/poor renal growth Obesity Advanced CKD (stage 3+) Hypertension Proteinuria Anaemia Hyperlipidaemia Hyperphosphataemia
Creatinine Inaccurate assay Tubular secretion Reciprocal relationship to GFR Insensitive at detecting low GFR
egfr is Egfr Lab & age specific value for K?
BP & Proteinuria Proteinuria PCR or ACR EMU or random PCR <15 Normal 15-50 Mild >50 Clinical >250 Nephrotic
KDIGO categories
1. Recognise child at risk of progressive CKD 2. Know what to do 3. Do it well
Delaying CKD progression - adults Hypertension & glomerular hyperfiltration cause progressive nephron loss Proteinuria indicates accelerated decline Treatment Good BP control delays CKD progression Reducing proteinuria also delays CKD ACEI or ARBs are best antiproteinuric, antiinflammatory, antifibrotic ACEI reduce rate of decline by ~ 50% What about children?
Strict BP control & Progression of Renal Failure in Children All hypertensive, CKD 2-4 & treated with ACEI Additional antihypertensives to achieve Conventionnal BP control (< 90%ile) Intensified BP control (< 50%ile) End point = 50% reduction in egfr
KDIGO - includes children Recommend If BP >90%ile treat BP and restrict sodium intake (1C) All CKD pts considered as at risk of AKI (1C) Suggest Target BP of <50%ile (if tolerated) especially if proteinuric (2D) Use ACEI/ARB irrespective of proteinuria (2D)
1. Recognise child at risk of progressive CKD 2. Know what to do 3. Do it well child... with a disease not disease in a child
Kidney function (% of normal) change in kidney function (egfr) over time expressed as a percentage of normal 60 50 40 30 20 10 0 7 9 11 13 15 Age (years)
says The evidence base for interventions to slow the progression of chronic kidney disease: Medical interventions... Is Identify who is at risk & look after them! Treat BP well Especially if there is clinical proteinuria Use ACEI and Consider prophylactic antibiotics in children with VUR/RN Prevent AKI treat UTIs promptly, avoid dehydration and nephrotoxic drugs
There s nothing really wrong with you but I think a little surgery would make us both feel better