Changes of renal functions IN the elderly

1. 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 Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011

2. 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 Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011 Miklós Székely and Erika Pétervári Molecular and Clinical Basics of Gerontology – Lecture 11 Changes of renalfunctionsIN theelderly

3. AGING vs. RENAL FUNCTIONS With aging: • Renal mass decreases • Renalblood 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

4. Glomerular structures Distal renal tubule Macula densa Efferent arteriole Afferent arteriole Mesangial cell Podocyte(visceral layer) Basement membrane Red blood cells Parietal layer of Bowman’s capsule

5. Glomerular structures Podocytes (visceral layer) Red blood cell Mesangialcell Capillary Basement membrane

6. Glomerular structures:filter surface Podocyte(epithelial cell with foot processes) Bowman’s space Endothelial cell Foot processes Fenestrations Capillary lumen Basement membrane Mesangial cell Capillary lumen Red blood cell Red blood cell

7. Development ofglomerulosclerosis1 Anionic charge of glomerular capillaries  filtration of polyanions accumulation of circulatingaggregates in mesangium fusion of podocytefoot processes proteinuria mesangial matrixproduction and proliferation focal sclerosis

8. Glomerular sclerosis Glomerular sclerosis

9. Development ofglomerulosclerosis2 Protein intake Chronic loss ofrenal tissue Diabetes mellitus hyperglycemia Hypertrophy and vasodila-tion in remaining nephrons Arterial pressure  Glomerular pressure  Altered permselectivity Glomerularhyperfiltration Direct cellular injury Increased protein filtration Cell proliferation and platelet aggregation Albuminuria Mesangial cell damage Glomerular sclerosis Compensatory polyuria Mesangial matrix overproduction

10. Aging influences single-nephron-GFR (SNGFR) (37.5) 40 30 30 30 GFR 100% GFR ~50% GFR 100% (37.5) 20 20 20 Percent of total nephrons (20) 10 10 10 0 0 0 0 0 10 20 30 40 50 60 70 80 0 0 10 20 30 40 50 60 70 80 0 0 10 20 30 40 50 60 70 80 SNGFR (nl/min)

11. Age vs. GFR 140 120 100 GFR (ml/min) 80 60 40 20 30 40 50 60 70 80 Years

12. Age vs. nephron dysfunctions • In th elderlyGFR, 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.

13. ADH effect decreases with age 120 Young Middle 110 Old 100 90 80 70 U/P inulin(urine/plasma conc. ratio) 60 50 40 30 ADH 20 10 0 0 1 2 3 4 5 6 7 8 9 10 Urine Collection Period

14. Corticomedullary osmotic concentration gradient Osmoticpressure Distaltubule Proximaltubule 80 300 400 600 1,000 1,500

15. Concentrating and diluting the urine 20 ml 0.3 ml 1500 1200 900 600 300 0 Normal Hyposthenuria Lot of ADH Osmolality (mOsm/kg) 2.0 ml 100 ml 20 ml No ADH 20 ml 16 ml Prox. tub. Loop of Henle Dist. tub +Cort. collecting duct Medullary collecting duct Fluid volumealongthenephron

16. Development of hyposthenuria 1,040 Hyposthenuria Isosthenuria 1,030 1,020 Specific gravity of urine Specific gravity of plasma 1,010 1,000 2,000,000 1,500,000 1,000,000 500,000 0 Number of nephrons

17. Kidney and drugs • 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.

18. Aging vs. non-excretory kidney functions • 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 gonadalhormon secretionanemia. • Active D-vitamin formation decreases  bone abnormalities (senile osteoporosis).

19. Most common renal diseases and genitourinary conditions intheelderly • Diabetic nephropathy • Glomerulonephritis • Pyelonephritis • Interstitial nephropathy • - analgesic nephropathy • - uricacidnephropathy • - 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, prostatecancer • Atrophicvaginitis

20. Renal failure in the elderly:causes • The incidence of acute renal failureincreases 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

21. Renalfailureintheelderly:dialysis and kidneytransplantation • 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 kidneytransplantation.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).

22. 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 extremelydifficult. • Pathogens:E. Coli, Enterococci, Streptococci, Proteus. • Treatment: oral rehydration, frequent urination, selectedantibiotics, roboration.

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

24. 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.

25. Stress incontinence • Involuntary lossof 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.

26. Urge/reflex incontinence • Sudden, unexpected urge to void after certainstimuli. • 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).

27. Overflow incontinence • Unexpectedurinelossfromtheoverfilledbladder. • Causes: • benign prostatic hyperplasia(BPH), • fibroticstenosis of theurethra, • muscles of the bladder and pelvic floor weak. • Management: • casual treatment, • avoiding coffee/tea/alcohol, • estrogen, medication (Ditropan), • behavioral training (biofeedback).