Tread Carefully Because you Tread on my Nephrons. Prescribing Hints in Renal Disease

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Vincent Wood
5 years ago
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Lecturer in Medicine and Consultant Nephrologist and General

1 Tread Carefully Because you Tread on my Nephrons Prescribing Hints in Renal Disease David WP Lappin,, MB PhD FRCPI Clinical Lecturer in Medicine and Consultant Nephrologist and General Physician, Merlin Park, UHG and Mayo General Hospitals

2 The most popular speaker is the one who sits down before he stands up John Pentland Mahaffy (1971)

3 Cured yesterday of my disease, I died last night of my physician Matthew Prior: The Remedy Worse Than the Disease (1772)

4 Classification of Chronic Kidney Disease GFR (ml/min/1.73m 2 ) Stage I > 90 with other evidence of kidney damage* Stage II with other evidence of kidney damage* Stage III Stage IV Stage V <15 or dialysis Mild Moderate Severe BNF *Other evidence of chronic kidney damage Persistent microalbuminuria Persistent proteinuria Persistent haematuria (after exclusion of urological disease) Structural abnormalities on U/S or radiological exam Biopsy proven glomerulonephritis

5 The Renal Failure Cocktail

6 ACEI + Diuretic +NSAID

7 ACEs, ARBs and DRIs

8 When Not to Use ACEI or ARB in a patient with Renal Disease? Hyperkalemia (K > 5.0 meq/l) Adverse Event or Allergy e.g. Angioedema Known or suspected critical bilateral renal artery stenosis or critical stenosis in a solitary kidney The level of serum creatinine alone is not a criterion! (caution egfr <30) Brenner et al. New Engl J. Med Sept

9 ACE Inhibitor is More Renal Protective than Conventional Therapy in Type 1 Diabetes (N = 409) % with Doubling of Baseline Creatinine Captopril Conventional therapy 100 Baseline creatinine > 1.5 mg/dl Decrease in Mean Blood Pressure (mm Hg) NS % Reduction in Proteinuria P <.001 Lewis et al. N Engl J Med. 1993;329:

10 Are ACEI and ARBs Equivalent?

11 Probably!

12 ACE = ARB? Barnett, NEJM Type II 80% microalb / 20 % macroalb 5 year follow-up Telmisartan v Enalapril Forced titration 93% on max dose therapy

13 ACE=ARB? Cr<140, micro or early overt nephropathy, 5 year follow up Barnett AH NEJM, Nov 2004

14 ACEs and ARBS Titrate UP! Parving H et al. N Engl J Med 2001;345:

15 Dual Blockade of the RAS

16 Dual Blockade, AVOID Trial Patients with type 2 diabetes and nephropathy Received either aliskiren, or placebo, in addition to maximal recommended dose of losartan and optimal antihypertensive therapy 599 patients enrolled Outcome reduction in ACR at 6 months

17 Changes from Baseline in the Urinary Albumin-to-Creatinine Ratio, Urinary Albumin Excretion Rate, and Blood Pressure According to Study Group Parving HH et al. N Engl J Med 2008;358:

18 Dual Blockade ONTARGET, NEJM ,000 patients with vascular disease or diabetes and end-organ damage Median follow up 56 months Ramipril, Telmisartan or Both Secondary end-point nephropathy 13% microalbuminuria at baseline

19 DUAL BLOCKADE, ONTARGET In the combination-therapy therapy group, the primary outcome occurred in 1386 patients (16.3%; relative risk, 0.99) As compared with the ramipril group, there was an increased risk of hypotensive symptoms (4.8% vs. 1.7%, P<0.001), syncope (0.3% vs. 0.2%, P=0.03), and renal dysfunction (13.5% vs. 10.2%, P<0.001). Conclusions: Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes The combination of the two drugs was associated with more adverse events without an increase in benefit

20 Hypertension

21 Controlling Hypertension Can Be Difficult

22 Multi-Drug Therapy is Required to Achieve BP Goal Bars indicate average number of medications per patient UKPDS (< 85 mmhg Diastolic) ABCD (< 75mmHg Diastolic) HOT (< 80 mmhg Diastolic) *MDRD (< 92 mmhg - MAP) *AASK (< 92 mmhg MAP) * Renal Failure Trials Number of BP Meds

23 Hypertension When prescribing for difficult disease a diuretic is essential When serum creatinine is above 130 micromoles, thiazides may be ineffective but loop diuretics may work

24 Lipids We all accept that lipid lowering is beneficial in both primary and secondary prevention of CVD in the general population But what about in CKD?

25 Primary/Secondary prevention

26 Risk of rhabdomyolysis < 0.1%

27 Statins, AURORA RCT of 2776 HD patients randomly assigned to 10mg rosuvastatin Death from CV cause, non fatal mi or stroke Median follow up 3.8 years NEJM, Apr 2009

28 Kaplan-Meier Curves for the Primary End Point in the Two Study Groups Statins, AURORA Fellstrom B et al. N Engl J Med 2009;360:

29 Summary Avoid NSAIDS RAS blockade appropriate first line therapy in renal disease ACE = ARB (= DRI?) Dual Blockade of the RAS still experimental When treating difficult hypertension diuretics have a central role Statins beneficial and safe in CKD

30 Questions?

Treating Hypertension in Individuals with Diabetes

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