Medical Biotechnology Master’s Programmes
at the University of Pécs and at the University of Debrecen
Identification number: TÁMOP-4.1.2-08/1/A-2009-0011
CHANGES OF RENAL FUNCTIONS
IN THE ELDERLY
Miklós Székely and Erika Pétervári
Molecular and Clinical Basics of Gerontology – Lecture 11
Medical Biotechnology Master’s Programmes
at the University of Pécs and at the University of Debrecen
Identification number: 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
Macula densa
Red blood cells Podocyte
(visceral layer)
Mesangial cell
Basement membrane
Parietal layer of Bowman’s capsule
Afferent arteriole Efferent arteriole
Distal renal tubule
Glomerular structures
Glomerular structures
Red blood cell
Podocytes (visceral layer)
Mesangial cell
Basement membrane Capillary
Glomerular structures:
filter surface
Podocyte (epithelial cell with foot processes)
Mesangial cell
Red blood cell
Endothelial cell
Capillary lumen
Foot processes
Basement membrane
Red blood cell Capillary lumen
Bowman’s space
Fenestrations
filtration of polyanions accumulation of circulating aggregates in mesangium fusion of podocyte
foot processes
proteinuria mesangial matrix
production and proliferation focal sclerosis
Anionic charge of glomerular capillaries
Development of
glomerulosclerosis 1
Glomerular sclerosis
Glomerular sclerosis
Chronic loss of renal tissue
Protein 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 of
glomerulosclerosis 2
Percent of total nephrons
SNGFR (nl/min)
0 10 20 30
0 0 10 20 30 40 50 60 70 80 (37.5
) GFR
100%
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 )
GFR 100%
Aging influences single-nephron-GFR
(SNGFR)
GFR (ml/min)
Years
40
20 60
80 10
0 12
0 14
0
30 40 50 60 70 80
Age vs. GFR
• 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
ADH effect decreases with age
U/P inulin (urine/plasma conc. ratio)
Urine Collection Period
0 0 10 20 30 40 50 60 70 80 90 100 110 120
1 2 3 4 5 6 7 8 9 10
Young Middle Old
ADH
80
300
400
600
1,000 1,500 Osmotic pressure Proximal tubule
Distal tubule
Corticomedullary osmotic
concentration gradient
No ADH
16 ml
1500
1200
900
600
300
0
Osmolality (mOsm/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
Normal
Hyposthenuria
20 ml
Fluid volume along the nephron
Specific gravity of urine
Number of nephrons
1,000
2,000,000 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
• 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
• 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
Most 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
Renal failure in the elderly:
causes
The 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,
• drugs
Chronic ischemic renal disease and
progressive damage of the renal parenchyma lead to chronic renal failure.
Risk factors:
• diabetes mellitus
• hypertension
• hyperlipidemia
• obesity
Renal failure in the elderly:
dialysis and kidney transplantation
The 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).
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.
Incontinence
Definition:
Involuntary loss of urine through the urethra.
Types:
• functional,
• stress,
• urge, reflex,
• overflow.
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.
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.
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).
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).