Major difficulties and pitfalls for the application of clinical trial results in an 85-year old patient:CHRONIC KIDNEY DISEASE

NICOLAS MARTINEZ VELILLACOMPLEJO HOSPITALARIO DE NAVARRA

PAMPLONA. SPAIN

OUTLINE1. Definition and staging2. Diagnosis and overdiagnosis3. Some special features in the elderly

Frailty, function, cognition

4. Treatment and clinical trials 5. THM

1. Definition• CKD is defined as abnormalities of the kidney

structure or function, present for >3 months, with implications for health

• It largely relies on 2 laboratory measures:– An estimate of Glomerular Filtration Rate (eGFR),

based on creatinine or cystatin levels– An assessment of kidney damage, derived from a

range of tests, most commonly, increased albumin in the urine (albuminuria)

2002 Staging and definition of CKD

NEW KDIGO GUIDELINES (2012)

From: Glomerular Filtration Rate and Albuminuria for Detection and Staging of Acute and Chronic Kidney Disease in Adults:  A Systematic Review

JAMA. 2015;313(8):837-846. doi:10.1001/jama.2015.0602

3. CKD and Frailty• Associated with all stages of CKD and particularly

from the moderate to severe stage Am J Med 2009

• Prevalence of frailty in CKD: 75% of age >60 years (largest study for prevalence of frailty in dialysis population) Am Soc Nephrol 2007

• Patients are 2.5 times more likely to die or to have to start dialysis during follow-up Am J Kid Dis 2012

• Potential to improve the identification of patients at risk for adverse frailty-associated outcomes and these patients might benefit from interventions Am Soc Nephrol 2007

• Frailty Index (score based on 70 components of health) excludes renal disease!!

3. CKD, function and cognition• Impaired cognitive function and ph

ysical perfomance are important factors impacting the lives of people with CKD Curr opin nephrol hypertens2014;23:291-7 J Gerontol A Biol Sci Med Sci 2014;69:315-22

• CKD is a significant independent somatic risk factor in the development of cognitive decline. Am J Nephr 2012;35:474-82

• In individuals with CKD, higher serum cystatin C levels were associated with worse cognition JAGS 2014

Interactions among eGFR, anemia, and mobility limitation define different profiles of risk in older patients discharged from acute care hospitals

4. Treatment and clinical trials

• Older patients are under-represented in clinical trials • Current clinical practice guidelines focus on specific

diseases and often fail to overtly take into consideration the presence of comorbid conditions

• Overall, there are no specific evidence-based guidelines available for the treatment of CKD in the elderly, particularly adults over 70 years of age, and guidelines are based on evidence obtained from younger populations

4. Treatment and clinical trials • The Ramipril Efficacy In Nephropathy study,63 which assessed

ramipril in patients with CKD 18–70 years• The Program for Irbesartan Mortality and Morbidity Evaluation

study assessed irbesartan in diabetic nephropathy: 30–70 years. • Hypertension (KDIGO): ungraded (based on expert opinion rather

than evidence)• Salt restriction RCT <79 years• Anemia: erythropoiesis-stimulating agents have not included the

elderly, particularly those over 75 years • Bicarbonate therapy: mean age 51 years

MANAGEMENT OF ESRD

• >65 years are the most rapidly increasing group of the ESRD population: substantial increase in the number of elderly patients accepted onto dialysis

• 1-year survival for patients >80 years starting hemodialysis was 48% (25% for nursing home residents). Careful assessment, determination of prognosis (CGA), considering adapted frailty criteria Arch Intern Med 2012 Nat Rev Nephrol 2011

• Burden of dialysis may be high for geriatric patients (QOL, functional status, life expectancy). Uncertanties between benefits & harms

THM: More research is needed!

– Risk of overdiagnosis (staging, GFR)– The concepts of frailty, cognitive and functional

impairment should be included in CKD– Older participants representative of those seen in

clinical practice must be included in clinical trials to better understand the benefits and potential adverse effects of new drugs in the elderly population