Hot Topics in Diabetic Kidney Disease a primary care perspective DR SARAH DAVIES GP PARTNER WITH SPECIAL INTEREST IN DIABETES, CARDIFF DUK CLINICAL CHAMPION NB MEDICAL HOT TOPICS PRESENTER AND DIABETES LEAD
Woodlands Medical Centre, Cardiff
DKD is the leading cause of kidney disease in patients requiring renal replacement therapy Independent risk factor for cardiovascular disease Patients with DKD more susceptible to hypoglycaemia
Microalbuminuria is good predictor for overt nephropathy Some patients with microalbuminuria regress Data has improved In 1980s 80% of patients with microalbuminuria progressed to proteinuria, now around 30-45%
Screening is essential At diagnosis of T2DM Around 7% already have microalbuminuria Then annually Beware sending samples during a UTI, acute febrile illness after vigorous exercise, in uncontrolled hypertension Send ACR and egfr Some patients with normoalbuminuria develop low GFRs Likely different renal process but still diabetes related READCODING and the influence of QoF
Guidelines NICE CKD guidelines Chronic kidney disease in adults: assessment and management July 2014 What do I need to know?
Classification
Chronic kidney disease in adults: assessment and management Clinical guideline [CG182]
Frequency of monitoring
Chronic kidney disease in adults: assessment and management Clinical guideline [CG182]
Differential diagnosis DKD likely in T1 diabetes after 10 year duration especially if retinopathy present DKD very likely In T2 diabetes if proteinuric with retinopathy However can occur without retinopathy in 20%
Think of alternatives If urinary symptoms Infection, obstruction, stones If skin rash / arthritis SLE Risk factors for transmitted disease HIV, Hep B/C Family history PKD No retinopathy, good glycaemic control, rapid onset Other cause of glomerulonephritis?
Further investigation? USS If symptoms of obstruction, infection or stones Or if FH of PKD Criteria for renal biopsy In type 1 may be done if short duration of diabetes, rapid decline in kidney function especially if no retinopathy In type 2, less clear.
Treatment of DKD - primary care perspective
CV risk management in DKD Independent risk factor for CV disease CV risk directly related to declining renal function People with CKD have a 10-20 fold increased risk of CV death Most patients with CKD with have a CV death rather than renal, before even reaching ESRD
BP targets All guidelines advise lower targets in higher risk patients such as those with CKD NICE Type 2 Diabetes Guidelines 2015 Add medications if lifestyle advice does not reduce blood pressure to below 140/80 mmhg (below 130/80 mmhg if there is kidney, eye or cerebrovascular damage) US guidelines 2017 / European 2018 target 130/80 in higher risk patients SPRINT study intensive vs normal control in patients at higher risk incl CKD, 25% RRR in CV events / death, NNT 61 over 3 years (NEJM2015;373:2103)
Lipid targets Few RCTS SHARP trial in Oxford (Lancet. 2011 Jun 9; 377(9784): 2181 2192) 9000 pts with CKD, treated with statin and ezetimibe, reduce LDL by approx. 1mmol, 5 year follow up 17% reduction in major atherosclerotic events Qrisk 3
ACE/ARB treatment Slow renal disease and improve survival 50% reduction in doubling of creatinine and progression to ESRD (N Engl J Med 1993; 329:1456-1462) HOPE study Included 3500 patients with diabetes, randomised to receive ramipril or placebo Dramatic reduction in CV outcome for ACEi use in diabetes, above and beyond the effect on BP J Renin Angiotensin Aldosterone Syst. 2000 Mar;1(1):18-20. Anti platelets Well proven in secondary prevention Risk vs benefit in primary prevention ASCEND trial
Diabetes treatment in DKD
Risk of hypoglycaemia in DKD Many diabetes treatments including insulin are renally excreted Longer half lives in DKD At egfr less than 60 insulin requirements go down Many treatments need dose reduction Severe hypos 5 times more likely
Frequency of Hypoglycemia and Its Significance in Chronic Kidney Disease Clin J Am Soc Nephrol. 2009 Jun; 4(6): 1121 1127.
What HBA1c target in DKD? Grey area No RCTs, observational studies only and these are limited Need to be individualised and pragmatic approach Beware risk of hypoglycaemia Quality rather than quantity of life?
Findings from the Dialysis Outcomes and Practice Patterns Study (DOPPS) Diabetes Care 2012 Dec; 35(12): 2527-2532.
Diabetes medication choices in DKD Metformin Reduce dose at egfr < 45, Stop at egfr < 30 Sulphonylurea No need for dose adjustment but beware hypolgyameia Quality improvement idea? Pioglitazone No need for dose adjustment Beware fluid retention / bone issues DPP4 inhibitors Safe but dose adjustment needed except for linagliptin Recent CARMELINA study showed slowing in progression to albuminuria with linagliptin
GLP agonists and SGLT2 inhibitors in DKD Hot topic! Potential benefit in context of diabetic renal disease? Most GLP1s can now be used down to low egfr or ESRD Use of SGLT2 inhibitors currently restricted due to efficacy
Evidence from CV outcome trials EMPA-REG empaglifozin CANVAS canaglifozin LEADER liraglutide 22% reduction in macroalbuminuria SUSTAIN - 6 semaglutide 36% RRR in new or worsening nephropathy AWARD7 dulaglutide vs glargine in CKD 3 AND 4
egfr decline in CKD 3 & 4 with Dulaglutide vs Insulin **p<0.05 or p<0.001 versus baseline; *p<0.05 versus insulin glargine Tuttle KR et al 2017
Watch this space! Need for renal outcome trials CREDENCE First renal outcomes trial 4400 patients, on max tolerated ACE/ARB therapy, canaglifozin vs placebo Primary composite endpoints - end-stage kidney disease (time to dialysis or kidney transplantation), doubling of serum creatinine, and renal or cardiovascular (CV) death Halted early at interim analysis as met efficacy end points. SGLT2i already included on new ADA/EASD guidelines 2018 in context of DKD
Lifestyle, BP, lipid and HBA1c targets Sending ACRs Readcoding microalbuminuria and CKD staging DKD reducing Monitoring Polypharmacy management Optimise ACE/ARB risk Renal protective agents Referral at the right time
www.thinkkidneys.nhs.uk/
Learning Outcomes It is important to individualise the approach to HBA1c target setting in the context of DKD. DKD is associated with an increased risk of cardiovascular disease and cardiovascular risk management is vital. Patients with DKD are at increased risk of hypoglycaemia and thus we need to tailor our treatment approach. There are many options available to treat diabetes in the setting of DKD with dose modifications where needed. There is exciting emerging evidence that some of the newer agents for treating diabetes may be renal protective and potentially have a very important role to play in DKD management in future.