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Kidney Diseases: What is New

Kidney Diseases: What is New. W. Khawandi MD, MBA, FACP, FASN. Disclosure No financial interests or relationships. Objectives.

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Kidney Diseases: What is New

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  1. Kidney Diseases: What is New W. Khawandi MD, MBA, FACP, FASN

  2. Disclosure No financial interests or relationships

  3. Objectives Review the evaluation and diagnosis of CKDImplement evidence-based cost-effective clinical strategies for the diagnosis and treatment of CKD in adultsDiscuss latest updates / clinical pearls in nephrology and hypertension.

  4. TRI-CITIES

  5. A GFR loss of > 1 mL/min/year beginning at age 25 can result in end-stage renal disease within a normal lifespan. Small changes make a big difference Lee A Hebert et al. Kidney International (2001) 59, 1211–1226

  6. CKD and Primary Care Physicians

  7. CKD Screening and Evaluation

  8. Estimate GFR and test for kidney damage markers • Serum creatinine to estimate GFR • Urinalysis for leukocytes and red blood cells • Qualitative test for urine albumin (or protein) with dipstick; if positive, measure amount to calculate an albumin-to-creatinine (or a protein-to-creatinine) ratio

  9. Screening Tools: eGFR • Considered the best overall index of kidney function. • Normal GFR varies according to age, sex, and declines with age. • The NKF recommends using the CKD-EPI Creatinine Equation (2009) to estimate GFR. • Other useful calculators related to kidney disease include MDRD and Cockroft Gault. • GFR calculators are available online at www.kidney.org/GFR. Summary of the MDRD Study and CKD-EPI Estimating Equations: https://www.kidney.org/sites/default/files/docs/mdrd-study-and-ckd-epi-gfr-estimating-equations-summary-ta.pdf

  10. Screening Tools: ACR • Urinary albumin-to-creatinine ratio (ACR) is calculated by dividing albumin concentration in milligrams by creatinine concentration in grams. • Spot urine albumin-to-creatinine ratio for quantification of proteinuria • First morning void preferable • 24hr urine test rarely necessary

  11. Protein estimation from random spot urine • Albumin-to-creatinine ratio • Normal to mildly increased <30 mg/g • Moderately increased 30-300 mg/g • Severely increased >300 mg/g • Protein-to-creatinine ratio • Normal to mildly increased <150 mg/g • Moderately increased 150-500 mg/g • Severely increased >500 mg/g • Type 2 diabetes: screen for albuminuria annually • Positive when >30 mg/g creatinine in a spot urine sample

  12. What is the definition of CKD? • Kidney damage or GFR <60 mL/min / 1.73 m2 for >3 mo • Kidney damage can be either functional or structural • Functional abnormalities • Proteinuria, albuminuria • Abnormalities of urinary sediment (dysmorphic red cells) • Structural abnormalities • On ultrasound scanning or other radiological tests • Polycystic kidney disease, reflux nephropathy, or other abnormalities

  13. Classification of CKD Note: GFR is given in mL/min/1.732m² KDIGO, Kidney Disease: Increasing Global Outcomes National Kidney Foundation. KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Am J Kidney Dis 2002;39(suppl 1):S1-S266

  14. What’s the relevance of the CKD classification?

  15. Classification of CKD Based on GFR and Albuminuria Categories Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. Kidney Int Suppls. 2013;3:1-150.

  16. Risk: interaction of eGFR and proteinuria

  17. Risk: Interaction of eGFR and proteinuria

  18. Who gets CKD?

  19. Diabetes and hypertension are leading causes of kidney failure Incident ESRD rates, by primary diagnosis, adjusted for age, gender, & race. ESRD, end stage renal disease USRDS ADR, 2007

  20. Risk for CKD • Diabetes • Hypertension • Obesity • Nephrotoxic drugs (Lithium, Calcineurin Inhibitors, NSAID) • Cardiovascular disease • Structural renal tract disease, stones, prostate etc • FH of renal disease • Multisystem disease likely to affect kidneys e.g. lupus • History of significant acute kidney injury • Age 60 or older (GFR declines normally with age) • Race/U.S. ethnic minority status

  21. Nephrotoxicity and CKD Environmental exposure leading to chronic interstitial disease: Agricultural workers Balkan nephropathy Lead nephropathy (roofers) Cadmium nephropathy (battery manufacturing) Medications, various modes of injury: Acyclovir: crystal formation and tubular obstruction NSAID: hemodynamic, papillary necrosis and interstitial disease ACE: Hemodynamic with immediate increase in creatinine (but <25%) Proton pump inhibitors: interstitial nephritis typically takes 10-13 weeks Statins: Rhabdomyolysis

  22. Only rarely presents with classical rash, fever, acute kidney injury. Time course First exposure: onset many weeks-months Repeat exposure: can be days AIN can emerge de-novo after years of exposure Risk of AIN especially high in the elderly Penicillins Fluroquinolones Cephalosporins Sulfonamides Macrolides Anti retrovirals NSAID Sulfasalazine PPI and H2 blockers (esp. Cimetidine) Thiazides Anticonvulsants (esp. Phenytoin) Allopurinol Interstitial Nephritis

  23. Proton pump inhibitors and CKD • Atherosclerosis risk in communities (ARIC) • 4 communities, SW USA • N=10,462, 1996-2011 • Geisinger Health System • Philadelphia • N=248,751, 1997-2014 Lazarus B, JAMA Intern Med 2016

  24. AKI and CKD • Multiple studies have demonstrated an increase in the risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) among patients who recover from AKI. • Acute kidney injury (AKI) appears to be associated with a higher risk of CKD by 3.3 years compared with matched control patients who did not develop AKI. 1.Kidney Int. 2009;76(8):893. Epub 2009 Jul 29 2. JAMA. 2009;302(11):1179. 3. J Am Soc Nephrol. 2009;20(1):223. Epub 2008 Nov 19.

  25. Renal status one year following discharge from AKI hospitalization Medicare (aged 66+) Data Source: Special analyses, Medicare 5% sample. (a) Medicare patients aged 66 and older who had both Medicare Parts A & B, no Medicare Advantage plan, did not have ESRD, were discharged alive from a first AKI hospitalization in 2013 or 2014, and did not have any claims with a diagnosis of CKD in the 365 days prior to the AKI. (Abbreviations: AKI, acute kidney injury; CKD, chronic kidney disease; ESRD, end-stage renal disease.

  26. Analgesics and Kidney Disease

  27. NSAID and Kidney Disease Acute Kidney Injury • Clearly associated with NSAID • Acute interstitial nephritis +/- nephrotic syndrome • Hemodynamic • NSAID block protective vasodilatory prostaglandins (underperfused states) Chronic Kidney Disease • New onset (incidence): • Uncertain association, not found in two major studies (Physicians Health Study, Nurses Health Study) • Established CKD (progression) • Clearly worsens progression of CKD1 1Gooch K, Am J Med 2007

  28. Hypotension / Underperfused Glomerulus PgE2 Angiotensin II PgE2 Angiotensin II NSAID ACEI Glom Glom  GFR GFR maintained

  29. NSAID and Kidney Disease Acute Kidney Injury • Clearly associated with NSAID • Hemodynamic • NSAID block protective vasodilatory prostaglandins (underperfused states) • Acute interstitial nephritis +/- nephrotic syndrome Chronic Kidney Disease • New onset (incidence): • Uncertain association, not found in two major studies (Physicians Health Study, Nurses Health Study) • Established CKD (progression) • Clearly worsens progression of CKD1 1Gooch K, Am J Med 2007

  30. Management

  31. What is the role of blood pressure management? • Treat to <140/90 mm Hg • If proteinuria is significant or urine albumin-to-creatinine ratio >30mg/g: treat to <130/80 mm Hg • Use ACE inhibitors and ARBs (improve kidney outcomes) • Diuretics reduce extracellular fluid volume, lower BP, and reduce risk for CVD • Diuretics also potentiate effects of antihypertensives • Thiazide-type diuretic if GFR ≥30 mL/min per 1.73 m2 • Loop diuretic if GFR <30 mL/min per 1.73 m2

  32. When should clinicians prescribe ACE inhibitors / ARBs? • Prescribe either for reducing progression of diabetic nephropathy • Prescribe either in non-diabetic proteinuria • Do not combine an ACE inhibitor with an ARB

  33. Slowing CKD Progression: ACEi or ARB • Check labs after initiation • If less than 25% SCr increase, continue and monitor • If more than 25% SCr increase, stop ACEi and evaluate for RAS • Continue until contraindication arises, no absolute eGFR cutoff • Better proteinuria suppression with low Na diet • Avoid volume depletion • Kunz R, et al.Ann Intern Med. 2008;148:30-48. • Mann J, et al. ONTARGET study. Lancet. 2008;372:547-553.

  34. Does lowering blood pressure substantially below the usual target of 140/90 improve outcomes?

  35. 2009 Cochrane Review • Does lowering of BP to targets below 135/85 reduce morbidity or mortality as compared to the usual target of<140/90? • Seven randomized trials (n=22,089) identified • Despite clear BP differences, there was no effect on any major endpoint Cochrane DB Syst Rev 2009;3:CD004349

  36. AASK Trial - Results • Despite a significant difference in BP achieved (130/78 vs 141/86), there were no differences in the primary outcome measure N Engl J Med 2010;363:918-29

  37. Blood Pressure Treatment Trialists • Meta-analysis of intensive versus standard BP control in patients with CKD (26 trials, n=152,290) • No difference in CV outcomes BMJ 2013;347:F5680

  38. HOPE - 3 • Despite a 6 mmHg difference in blood pressures between the two groups, no differences were seen for any outcome N Eng J Med 2016;374:2032-2043

  39. ACCORD Trial • 4,733 diabetics were randomized to intensive blood pressure control (SBP < 120) vs. usual control (SBP <140) – followed for 4.7 years • 10 composite outcome was nonfatal MI, nonfatal stroke, or CV death • No difference in primary outcome • A small but significant decrease in stroke was noted in the intensive control group (NNT  450 over 5 years) N Engl J Med 2010;362:1575-85

  40. ACCORD - Adverse Events N Eng J Med 2010;362:1575-85

  41. Theme thus far – no benefits to going lower than SBP < 140

  42. JNC 8 Recommendations Initiate Therapy • Age ≥ 60 >150/90 • Ages 18 - 59 >140/90 • DM or CKD >140/90 JAMA 2014;311:507-520

  43. SPRINT • RCT of 9,361 non-diabetic pts over age 50 with high risk for ASCVD events (>20% 10-year risk) • Included many older pts (28% > 75 yrs) • Pts randomized to aggressive BP control (SBP < 120) vs standard control (SBP<140) N Eng J Med 2015;373:2103-2116

  44. SPRINT • Primary composite outcome of MI, ACS, stroke, decompensated CHF, or CV death • Average follow up of 3.2 years - stopped prematurely due to evidence of benefit N Eng J Med 2015;373:2103-2116

  45. N Eng J Med 2015;373:2103-2116

  46. N Eng J Med 2015;373:2103-2116

  47. How have the guidelines changed since the SPRINT trial? Data are conflicting – SPRINT vs most other studies

  48. ACC/AHA Categories of BP in Adults

  49. Blood Pressure (BP) Thresholds and Recommendations for Treatment and Follow-Up

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