Fundamentals of

Geriatrics: Renal Disease

Douglas Shemin, MD

Renal Division, RIH

This is a big topic!!

Fundamentals of

Geriatrics: Renal Disease

1. Aging and Renal Function

2. Renal Disease in the Elderly

a. Acute Renal Failure

b. Chronic Renal Failure

c. Renal Transplantation

Anatomic renal changes

with aging

Renal weight/volume decreases by 20 - 30 % (0.4 g to 0.3 g) by age 80. Most of this weight loss is cortical, not medullary.

Number of glomeruli decreases by 30 - 50 % by age 80, and size of remaining glomeruli increase (hyperfiltration)

Increased percentage of sclerotic glomeruli,

atrophic tubules, mesangial sclerosis

Physiologic renal changes

with aging

Decreased glomerular filtration rate with aging: 1 ml/min/year after age 40

In most patients, this occurs without an increase in the serum creatinine, because endogenous creatinine production declines.

PCr = (Ucr) (urine flow rate)/GFR

Decreased urinary creatinine

excretion with advancing age:

Kampman et al., JASN 1996

Men Ucr SCr Cr Cl

30-39 1520(130) 1.1(0.2) 98(39)

40-49 1544(421) 1.1(0.2) 98(22)

50-59 1445(252) 1.2(0.2) 88(21)

60-69 1252(364) 1.2(0.1) 76(22)

70-79 919(132) 1.0(0.2) 64(15)

80-89 651(238) 1.1(0.3) 45(15)

> 90 612(188) 1.2(0.2) 35(9)

GFR and aging

Cockroft-Gault formula based upon 234 patients:

creatinine clearance analogous to GFR.

Cr Cl = (140-age)(wt in kg)

——————————

(SCr)(72)

ex: 40 year old and an 80 year old man, both 72 kg, with SCr of 1.2:

Cr Cl of the 40 year old: 83 ml/minute

Cr Cl of the 80 year old: 50 ml/minute

MDRD (modification of diet

in renal disease) formula

GFR = (186) (SCr –1.154)(age – 0.203)(0.742 if female)

(1.21 if African American)

Ex: 80 year old with SCr 1.4

MDRD GFR: White female: 38 ml/min

White male: 52 ml/min

Black female: 47 ml/min

Black male: 63 ml/min

New Classification for Chronic

Kidney Disease: NKF 2002

Stage Description GFR, in ml/min

1 early kidney disease 90 - 120

2 mild GFR 60 - 89

3 moderate GFR 30 - 59

4 severe GFR 15 - 29

5 kidney failure < 15

ARF is common in

hospitalized patients

0.02 % in the general population

Llano, Kidney Int 1996

1 % of patients admitted to the hospital

Kaufman, AJKD 1991

7 % of patients during hospitalization on med-surg services

Nash, AJKD 2002

15 % after cardiopulmonary bypass surgery

Zanardo, J Thor Cardiovasc Surg 1994

Predisposing factors for ARF are

common in the elderly

Reduced GFR

Medications: NSAIDs, ACEIs, ARBs, diuretics

Renal vascular disease

Obstruction, especially in men

Impaired thirst, impaired access to fluids

ARF in the elderly:

incidence

“Young” > 80 years old

Groeneveld 17 pmp/yr 949 pmp/yr

Nephron 1991

Llano 109 pmp/yr 1129 pmp/yr

Kidney Int 1996

RIH: 87 pts 55 % > 65 years

started on HD for 14 % > 80 years

ARF in 2006

ARF:

Causes/General Population

Study prerenal ATN

Hou/AJM 1983 48 % 41 %

Llano/ KI 1996 21 % 45 %

Nash/ AJKD 2002 44 % 39 %

ARF:

Causes: Geriatrics

Study prerenal ATN other

Druml 12 % 75 % AIN 7 %

CN 1994

Pascual 29 % 43 % obstruction 15 %

JAGS 1998

Kohli 37 % 57 %

NDT 2000

Sesso 53 % 32 % obstruction 13 %

AJKD 2004

Therapy in ARF

Non-dialytic therapies: supportive care, dopamine, diuretics

RRT: peritoneal dialysis

RRT: intermittent hemodialysis

RRT: continuous therapies: SCUF, CAVH, CVVH, CAVHD, CVVHD, CVVHDF

Rates of RRT in ARF

Study % RRT mortality rate in RRT

General population:

Kaufman 1991 27 % 56 %

Llano 1996 36 % 27 %

Mehta 2002 28 % 52 %

Nash 2002 14 % 38 %

Geriatric population:

Druml 1994 60 % 71 %

Kohli 2000 15 % 56 %

Sesso 2004 44 % 55 %

Age and risk of Mortality in

ARF

relative risk

Brivet 1996 1.45*

Douma 1997 NS

Pascual 1998 NS (65-74), 1.09* (>75)

Obialo 2000 NS

Nash 2002 NS

Mehta 2002 1.02*

Sesso 2004 NS

Which RRT type for

geriatric ARF patients?

Theoretical advantages to CRRT over IHD: slower ultrafiltration and diffusion rates, causing less acute hemodynamic instability.

In the general population, no convincing evidence that either therapy is superior.

Geriatric patients not analyzed independently.

ESRD in the elderly:

demographic trends

2005 USRDS data:

prevalent patients with ESRD

total 324,826

> 65 143,213 (44 %)

> 80 34,819 (11 %)

incident patients with ESRD

total 100,499

> 65 50,705 (50 %)

> 80 13,837 (14 %)

Incident patients

beginning ESRD therapy

% of patients beginning ESRD therapy over 65 years old

USA 50 %

Italy 61 %

France 58 %

Spain 53 %

UK 47 %

Male predominance in

ESRD: Incident data 2005

Incidence rates per million population (Caucasians only)

Male Female

65-69 3738 2758

70-79 4429 2808

80 + 4280 1787

Cause of ESRD by Dx, age:

USRDS 2002

0

10

20

30

40

50

all pts < 20 20-64 > 65

GN

DM

BP

High degree of comorbidity

in geriatric ESRD patients

65-74 >75

Hypertension 77 % 75 %

Diabetes 49 % 34 %

CHF 40 % 44 %

CAD 33 % 35 %

MI 13 % 13 %

CVA/TIA 11 % 13 %

PVD 20 % 18 %

CA 7 % 8 %

Inability to walk 5 % 6 % USRDS 2002

Lab values on initiation of

dialysis in geriatric ESRD

From USRDS, 2003 Mean Lab value 70-79 80+

serum albumin 3.2 3.2

BUN 88 88

creatinine 6.6 6.1

Estimated GFR 9.6 10.1

hemoglobin 9.9 10.1

Most geriatric ESRD pts

treated with Center HD

0

10

20

30

40

50

60

70

80

90

all pts > 65 all pts,

> 2 yrs

>65, 2

yrs

center HD

home HD

PD

Morbidity in Geriatric

ESRD: Hospitalization Days

0

2

4

6

8

10

12

14

16

18

All p

ts

DM

All

ages

65-79

> 80

From USRDS 2003:

Slightly higher hospital days/patient year at risk in patients over 65.

ESRD Mortality Rates by Age Group,

per 1000 pt years at risk

0

100

200

300

400

500

6000

-1

4

20

-2

4

30

-3

4

40

-4

4

50

-5

4

60

-6

4

70

-7

4

80

-8

4

Life expectancy with ESRD

therapy (dialysis)

Life expectancy

Age Dialysis Rx General US Pop

40 – 44 7.8 37.5

50 – 54 5.9 28.6

60 – 64 4.3 20.4

70 – 74 3.1 13.4

80 – 84 2.2 7.8

USRDS, 2005

Mortality rate with ESRD

therapy (dialysis)

Rate (per 1000 yrs at risk)

Age

40 – 49 126.9

50 – 59 168.6

60 – 64 225.6

65 - 69 265.1

70 - 74 340.9

80 + 469.2

USRDS, 2005

Causes of Mortality in ESRD

per 1000 pt years at risk

> 65 all ages

cardiac arrest 103 61

withdrawal 73 41

sepsis 37 27

acute MI 31 21

CVA 20 13

Risk factors for mortality in ESRD

(Rakowski, JASN 2006)

adjusted hazard 95 % CI ratio for death at 2 y Dementia 1.91 1.77-1.98 Unable to ambulate 1.36 1.30 –1.43 PVD 1.16 1.13 - 1.18 Cancer 1.16 1.15 –1.17 Diabetes 1.10 1.08 - 1.12 Stroke 1.20 1.18 – 1.23 CAD 1.12 1.10 – 1.14 CHF 1.28 1.26 – 1.30 Lung disease 1.22 1.19 – 1.25

Withdrawal (WD)from dialysis:

USRDS 2005

all 70 - 79 80 +

WD (access) 1 % < 1 % 1 %

WD (FTT) 13 % 16 % 21 %

WD (med comp) 8 % 9 % 9 %

No WD 79 % 75 % 70 %

Withdrawal from dialysis

> 25 % of all ESRD deaths in patients over 65 years old (USRDS 2005)

Cohen, Arch Int Med 2000: 131 patients electively withdrawing from ESRD therapy followed by multidisciplinary team. “good deaths” in ESRD (pain-free, peaceful, brief) in 85 % of sample.

Special problems in

geriatric ESRD

As GFR decreases, planning for vascular access important: AV fistulae/graft associated with better outcomes than temporary catheters.

Anemia, malnutrition major cause of morbidity: erythropoietin, dietician therapy beneficial

“Trial of dialysis” with clear endpoint occasionally helpful in ambivalent patient

Lower mortality rate in ESRD patients

treated with transplantation

Wolfe, NEJM 1999

age dialysis waitlist cad Tx

all 16.1 6.3 3.8

>60 23.2 10.0 7.4

Renal Transplantation

Requires use of immunosuppression to decrease risk of rejection: steroids, mycophenolate mofetil, calcineurin antagonist or sirolimus

Greater immunosuppression with cadaveric donors

Wait list > 3 years for cadaveric donor

Renal Transplantation

Cadaveric transplants done most often: in 2003:

Deceased donor 8705 (70 %)

Living donor 3666 (30 %)

But…living donor transplants do better—

Living Deceased

1 yr survival 95 % 89 %

5 yr survival 74 % 68 %

10 year survival 55 % 39 %

USRDS 2004

Most renal transplants in geriatrics

are cadaveric (USRDS 2003)

Age Living Cadaveric

< 20 47 % 53 %

20-44 37 % 63 %

45-64 24 % 76 %

65-74 21 % 79 %

> 75 17 % 83 %

< 1 500 0.3 %

1 – 4 962 0.6 %

5 – 9 1,714 1.0 %

10 – 14 2,903 1.7 %

15 – 19 5,128 3.0 %

20 – 29 19,392 11.5 %

30 – 39 35,382 20.9 %

40 – 49 41,943 24.8 %

50 – 59 36,699 21.7 %

60 – 64 12,825 7.6 %

65 – 69 7,925 4.6 %

70 – 79 3,449 2.0 %

> 80 86 0.1 %

Renal transplants

By age of recipient

1991 – 2003

(USRDS 2004)

Renal Transplantation

Exclusion criteria:

Recipient Donor

malignancy (5 yrs) Hypertension

3 vessel CAD Diabetes

LV dysfunction GFR < 80 ml/minute

CVA/PVD

uncontrolled infection

Patient and graft survival

in patients > 65 years old

Pt survival Graft survival

> 65 1yr 5yr 1yr 5yr

Cadaver 86 56 80 43

Living 95 62 95 49

20-44

Cadaver 97 88 90 61

Living 99 93 96 74

Higher rate of graft loss in patients >

65 years

(USRDS 2003)

Cadaveric TX Living TX

Age Hazards ratio Hazards ratio

<18 1.28* 0.99

18 – 34 1.00 1.00

35 – 49 0.87 0.91

50 – 64 1.01 1.17*

>65 1.42* 1.68*

Renal Transplantation, RIH

64 recipients aged > 60

(From Yango et al, Clinical Nephrology, 2006)

Age range 60 -72

65 % male

Cause of renal disease: 29 % DM, 23 % TI disease, 14 % PCKD

64 % cadaveric Tx, 36 % living Tx

Renal Transplantation, RIH

1997-2004 (Yango, et al, 2004)

< 60 > 60

number of Tx 338 64

Patient survival:

1 year 95 % 78 %

3 years 93 % 71 %

Graft survival:

1 year 94 % 83 %

3 years 87 % 82 %

Renal Transplantation, RIH

1997-2004 (Yango, et al, 2004)

3 year pt survival rates: renal Tx recipients > 60

Diabetes 78 % nondiabetics 73 %

Living Tx 87 % Cadaveric Tx 63 %

CAD 66 % no CAD 74 %

Smokers 61 % nonsmokers 76 %

Active 86 % inactive 24 % p < 0.001

3 year graft survival rates: renal Tx recipients > 60

Active 94 % Inactive 0 % p < 0.001

Conclusions

1. The incidence of acute renal failure increases with age.

2. ESRD primarily affects the geriatric population. The number of elderly individuals with ESRD is increasing.

3. Renal transplantation, especially with living donors, is performed much less often in geriatric patients.

4. Morbidity and mortality in patients with ARF, with ESRD treated with dialysis, and in transplant recipients, are both clearly increased in geriatric patients. Patients in all groups have a high degree of comorbidity, and the poorer outcome is probably more related to comorbid conditions, rather than age.