4/26/2016. Chronic Kidney Disease for PCPs CLAIRE KASSAKIAN, MD NORTHWEST RENAL CLINIC ANNUAL PRACTICAL ADVANCES IN IM SYMPOSIUM

Transcription

1 Chronic Kidney Disease for PCPs CLAIRE KASSAKIAN, MD NORTHWEST RENAL CLINIC ANNUAL PRACTICAL ADVANCES IN IM SYMPOSIUM 1

2 Disclosures None Overview Epidemiology of CKD in 2016 Hope for HCV Treatment in the CKD Population PPIs and CKD: Cause for Concern? Hyperkalemia Who is Hyperkalemic New Horizons for Management Hypertension Management in the Elderly Questions 2

3 More CKD Patients Than Ever? What We Know Mortality falling in ESRD and Transplant patients since 1996 By 28% and 40%) 13.6% of adults in the US are affected by CKD Prevalence of ESRD is increasing 467K in 2013 An increase of 63% larger than in 2000 What We Don t Know Most attributable factors (HTN, DMII) do not appear to account for the rise Looking for other variables. Who Needs a Nephrologist 3

4 Hope For Hepatitis C Treatment Motivation to Treat HCV in Patients with CKD Prevent liver complications Prevent post-renal transplant complications Prevent progression of glomerulonephritis: Mixed cryoglobulinemia Membranoproliferative glomerulonephritis (MPGN) Membranous Nephropathy 4

5 The Interferon Era Standard or pegylated interferon with or without ribavirin Suboptimal efficacy High potential for therapy toxicity Interferon Free Era New direct-acting antiviral agents (DAA) In some cases Ribavirin-free treatment regimens Where Ribavirin is used, dose reductions made based on GFR. IDSA and AASLD guidelines recommend treatment for all patients with chronic HCV infection except for those with short life expectancies due to comorbidities. 5

6 HCV Treatment with Advanced CKD Safety in this population is based on limited but growing evidence. Reasonable to consider therapy for those with: advanced fibrosis or cirrhosis, renal transplant candidates, HCV related kidney disease from cryoglobulinemia, and those with HCV related GN. HCV Treatment in ESRD HCV is more common in the ESRD population (5-10% seropositivity for HCV Ab) KDIGO (Kidney Disease Improving Global Outcomes) guidelines recommend weighing benefits and risk of HCV therapy, life expectancy, comorbidities, and potential for kidney transplant candidacy. 6

7 Treating by Genotype Different thresholds for treatment 1 and 4. Elbasvir-Grazoprevir (phase III clinical trial evidence for safety and efficacy in renal impairment) 2,3,5, and 6. Uncertainties about safety with Sofosbuvircontaining regimens (may need to use Interferol) Specific DAA Agents Elbasvir plus Grazoprevir Most robust data for a DAA regimen in patients with severe renal impairment (egfr <30ml/min) Excellent efficacy C-SURFER trial: 122 genotype 1 infected patients with EGFR<30ml/min, 75% of them on dialysis, 94% achieved sustained viral response (SVR) for 12 weeks of therapy. 7

8 More Specific DAA Agents Less Robust Data though growing Sofosbuvir Major elimination pathway is renal though studies are underway. In a study of 11 patients on hemodialysis, half-dose sofosbuvir plus standard dose simeprevir resulted in an SVR rate of 91% and only minor adverse events. Currently FDA approved for patients with egfr of >30. More Specific DAA Agents Ombitasvir-paritaprevir-ritonavir plus dasaburvir Metabolized primarily in the liver Simeprevir Primarily metabolized by the liver. Safety has not been studied in patients with severe renal impairment or ESRD Ledipasvir Biliary elimination but only available in a fixed-dose combination with Sofosbuvir. Daclatasvir Metabolized primarily in the liver. Also only given in combination with Sofosbuvir. 8

9 Proton Pump Inhibitors and CKD: Cause for Concern? A history of overuse and some harm. JAMA Internal Medicine - Benjamin Lazarus [doi: /jamaintermed ] 2 databases Atherosclerosis Risk in Communities and Geisinger Health System with 10,482 pts followed for a median of 13.9 years and 248,751 for 6.2 years respectively Hazard ratio for CKD was 1.5 (absolute risk difference 3.3%) Hazard ratio for AKI was 1.64 A study with its limits Proton Pump Inhibitors and Hypomagnesemia American Journal of Kidney Diseases [2015;66(5): ] Highest Risk: PPI + Loop Diuretic Can be associated with secondary hypokalemia and hypocalcemia Close to 5% were hypomagnesemic Risk increased with prolonged use 9

10 Who Is Hyperkalemic? Stage 3 CKD or greater DMII Type IV RTA Heart Failure Treatment with RAAS Inhibitors, K-Sparing Diuretics, and Beta Blockers New Horizons for Safe Management of Hyperkalemia PATIROMER (Veltassa, Relypsa) Non-absorbent Potassium Binder Studied in patients with CKD and hyperkalemia ( mmol/L) on RAAS Inhibitors Associated with a decrease in serum K and recurrence of hyperkalemia vs Placebo 10

11 New Horizons for Safe Management of Hyperkalemia ZS-9 Insoluble Zirconium based silicate designed molecule Mechanism of action involves trapping K ions Similar promise but not yet approved Hypertension Management in the Elderly HYVET SHEP STOP Syst-Eur Syst-China JNC-8 11

12 Questions 12