Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of DebrecenIdentification number: TÁMOP-4.1.2-08/1/A-2009-0011

CHANGES OF RENAL FUNCTIONSIN THE ELDERLY

Miklós Székely and Erika PéterváriMolecular and Clinical Basics of Gerontology – Lecture 11

Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of DebrecenIdentification number: TÁMOP-4.1.2-08/1/A-2009-0011

TÁMOP-4.1.2-08/1/A-2009-0011

With aging:• Renal mass decreases• Renal blood flow (RBF) decreases• Number of functioning nephrons decreases• GFR decreases, glomerular dysfunctions• Tubular dysfunctions• Excretory capacity decreases• Role in salt/water regulation decreases• Role in pH regulation decreases• Non-excretory renal functions decrease

AGING vs. RENAL FUNCTIONS

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Macula densa

Red blood cells

Podocyte (visceral layer)

Mesangial cell

Basement membrane

Parietal layer ofBowman’s capsule

Afferent arterioleEfferent arteriole

Distal renal tubule

Glomerular structures

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Glomerular structures

Red bloodcell

Podocytes(visceral layer)

Mesangial cell

Basement membrane

Capillary

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Glomerular structures:filter surface

Podocyte(epithelial cell

with foot processes)

Mesangialcell

Red blood cell

Endothelialcell

Capillary lumen

Foot processes

Basement membrane

Red blood cell

Capillary lumen

Bowman’s space

Fenestrations

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filtration of polyanions accumulation of circulating

aggregates in mesangiumfusion of podocyte

foot processes

proteinuria mesangial matrixproduction and

proliferation

focal sclerosis

Anionic charge of glomerular capillaries

Development ofglomerulosclerosis 1

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Glomerular sclerosis

Glomerular sclerosis

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Chronic loss ofrenal tissueProtein intake Diabetes mellitus

hyperglycemia

Hypertrophy and vasodila-tion in remaining nephrons

Glomerular pressure

Altered permselectivity

Arterial pressure

Glomerular hyperfiltration

Direct cellular injury

Cell proliferation and platelet aggregation

Mesangial matrix overproduction

Glomerular sclerosis

Increased protein filtration

Compensatory polyuria

Albuminuria Mesangial cell damage

Development ofglomerulosclerosis 2

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rcen

t of t

otal

nep

hron

s

SNGFR (nl/min)

0

10

20

30

0 0 10 20 30 40 50 60 70 80

(37.5)

GFR100%

0

10

20

30

0 0 10 20 30 40 50 60 70 80

(20)

GFR~50%

0

10

20

30

0 0 10 20 30 40 50 60 70 80

(37.5)

40

GFR100%

Aging influences single-nephron-GFR (SNGFR)

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GFR

(ml/m

in)

Years

40

20

60

80

100

120

140

30 40 50 60 70 80

Age vs. GFR

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• In th elderly GFR, tendency for azotemia due to a fall of kidney perfusion (thirst, heat, CO redistribution e.g. heart failure), but no proportional rise in se-creatinine (less muscle lost)

• Tubular reabsorption changes: glucose reabsorbing tubular cells still function, minerals: tendency for K-loss, salt wasting (Na-reabsorption), phosphaturia, poor ADH action (water loss).

• Proteinuria more frequent.• Excretory capacity (drugs!) decreases.• Severe shifts in the osmotic pressure.

Age vs. nephron dysfunctions

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ADH effect decreases with age U/

P in

ulin

(urin

e/pl

asm

a co

nc.

ratio

)

Urine Collection Period0

0

102030405060708090

100110120

1 2 3 4 5 6 7 8 9 10

YoungMiddleOld

ADH

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80

300

400

600

1,000

1,500

Osmoticpressure

Proximal tubuleDistal tubule

Corticomedullary osmotic concentration gradient

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No ADH16 ml

1500

1200

900

600

300

0

Osm

olal

ity (m

Osm

/kg)

100 ml

20 ml

20 ml

2.0 ml

0.3 ml

Lot of ADH

Prox. tub. Loop of Henle Dist. tub +Cort.

collecting duct

Medullary collecting

duct

Concentrating and diluting the urine

NormalHyposthenuria

20 ml

Fluid volume along the nephron

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Spec

ific

grav

ity o

f urin

e

Number of nephrons

1,0002,000,000 1,500,000 1,000,000 500,000 0

1,010

1,020

1,030

1,040

Hyposthenuria

Development of hyposthenuria

Isosthenuria

Specific gravity of plasma

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• Impaired excretion of substances that are excreted through the kidneys the dose of drugs that are eliminated through the kidney has to be decreased!

• Kidney perfusion decreases frequently for a number of reasons, e.g. redistribution in heart failures, exsiccosis – impaired excretory functions – drug doses have to be adjusted.

Kidney and drugs

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• Atrophy of renal parenchyma + sclerotic a. renalis regulation of blood pressure defective, tendency for hypertension, but hypovolemia may cause hypotension.

• Erythropoietin deficiency due to reduced renal parenchyma and gonadal hormon secretion anemia.

• Active D-vitamin formation decreases bone abnormalities (senile osteoporosis).

Aging vs. non-excretory kidney functions

TÁMOP-4.1.2-08/1/A-2009-0011Most common renal diseases and genitourinary conditions in the elderly• Diabetic nephropathy• Glomerulonephritis• Pyelonephritis• Interstitial

nephropathy - analgesic nephropathy- uric acid nephropathy- myeloma kidney

• Urinary retention(The muscles of the bladder and pelvic floor weaken.)

• Urinary incontinence(The capacity of the urinary bladder reduces which leads to frequent urination.)

• Urinary infections • Benign prostatic

hyperplasia, prostate cancer

• Atrophic vaginitis

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Renal failure in the elderly:causesThe incidence of acute renal failure increases following acute tubular necrosis.Risk factors: • age-related decrease

of RBF, GFR, and of ability to concentrate or to dilute urine,

• diabetes mellitus, • hepatic cirrhosis,• congestive heart

failure,

• drugsChronic ischemic renal disease and progressive damage of the renal parenchyma lead to chronic renal failure.Risk factors:• diabetes mellitus• hypertension• hyperlipidemia• obesity

TÁMOP-4.1.2-08/1/A-2009-0011Renal failure in the elderly:dialysis and kidney transplantationThe most common indication of dialysis due to chronic renal failure is diabetic nephropathy (35-40%). There is an increase in the number of renovascular diseases. Among the dialyzed there are less candidates for transplantation due to co-morbidity. The overall survival increases due to the improved efficacy of dialysis. With higher capacity of dialysis, the age-related limits of dialysis have faded away.Age is not a contraindication of kidney transplantation. Both the cadaveric and the living donor can be an option in the elderly. The only limiting factor for kidney transplantation is the presence of multimorbidity (hypertension, DM, significant atherosclerosis).

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Urinary tract infection

Symptoms: fever, dysuria (pain upon urination), urgency, frequency, incontinence, impaired physical and/or mental status. Sepsis can develop quickly and atypically — treatment of urosepsis is extremely difficult. Pathogens: E. Coli, Enterococci, Streptococci, Proteus.Treatment: oral rehydration, frequent urination, selected antibiotics, roboration.

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Incontinence

Definition: Involuntary loss of urine through the urethra.Types: • functional, • stress, • urge, reflex, • overflow.

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Functional incontinence

The patient is not able to control his bladder due to altered circumstances. Causes: • disability, • impaired vision, • dementia, • bigger amount of urine (i.e. diuretics, diabetes

mellitus)Management: • changes in the environment, • timed voiding (scheduled bathroom visits), • urinary indwelling catheter as required,• diapers.

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Stress incontinence Involuntary loss of urine upon elevated intra-abdominal pressure.Causes:• urethral sphincter insufficiency due to weakness of

pelvic floor musculature,• obesity,• prolapsed uterus, atrophic vaginitis, bladder hernia.Management:• weight loss,• Kegel exercises, electro-stimulation,• estrogen, medication (Ditropan, Melipramin), • surgery,• panty liners.

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Urge/reflex incontinence Sudden, unexpected urge to void after certain

stimuli.Causes:• atrophic vaginitis, cystitis,• benign prostatic hyperplasia (BPH),• certain drugs or foods, cold.Management:• casual treatment,• avoiding coffee/tea/alcohol,• estrogen, medication (Ditropan),• electro-stimulation, behavioral training (biofeedback).

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Overflow incontinence Unexpected urine loss from the overfilled

bladder.Causes:• benign prostatic hyperplasia (BPH),• fibrotic stenosis of the urethra,• muscles of the bladder and pelvic floor weak.Management:• casual treatment,• avoiding coffee/tea/alcohol,• estrogen, medication (Ditropan),• behavioral training (biofeedback).