Kidney Function and Disease PDF

Kidney function and disease Functions of the kidney 1. excretion of waste 2. maintenance of extracellular fluid balance 3. synthesis of hormones 4. produce glucose through gluconeogenesis Kidney Physiology blood delivered to kidneys via renal artery and returned via renal vein contains s...

Kidney function and disease Functions of the kidney 1. excretion of waste 2. maintenance of extracellular fluid balance 3. synthesis of hormones 4. produce glucose through gluconeogenesis Kidney Physiology blood delivered to kidneys via renal artery and returned via renal vein contains specialised function units called nephrons The Nephron each consists of tuft of capillaries → glomerulus and tubule blood capillaries pass alongside to allow functioning 1. glomerular function 2. tubular function 1 million nephrons in a fully functional kidney  the movement is under high pressure Ultrafiltration first process to remove metabolic waste from the blood occurs in the glomerulus and transfers waste from capillaries into Bowman’s capsule non-specific filtration occurs under high pressure forcing blood into capillary into capsule (increases efficiency) → everything needed to be filtered is filtered pressure generated by a wider entrance and thinner exit to glomerulus tuft of capillaries = lots of branches = increase SFA Bowman's capsule inner surface of cells = podocytes surround blood capillaries and have pores allowing blood content to pass into capsule space cellular layer known as basement layer between capillaries and podocytes allows blood content to pass through but blocks larger structures (blood cells) Produces the ultrafiltrate → similar to composition of plasma w/o plasma proteins Glomerular Filtration rate as which plasma is filtered at the glomeruli = glomerular filtration rate (GFR) approximately 120-140 mL/min in healthy adult (170-20 L/day) urine production → 1-2 L/day and most of filtrate is reabsorbed filtrate passes along tubule where absorption occurs via series of passive and active mechanisms large discrepancy between filtered and excreted: lots is reabsorbed Tubular Function when filtrate has passed to tubules to undergo selective reabsorption occurs in the proximal convoluted tubule water passively moves across barrier back into blood 75% of sodium is reabsorbed all glucose, amino acids, vitamins, hormones, potassium and bicarbonate reabsorbed Water Balance - Loop of Henle  Need to absorb MORE water 3rd process further filters blood and produce urine through osmoregulation begins by creating a salt gradient in the loop of henle → descends from nephron into medulla of kidney filtrate enters LoH in a hypotonic state (low Na) high Na level surrounding loop causes water to move out of loop and into ISF and water taken way by capillary network back into body loop is impermeable to Na → filtrate become hypertonic and increase in osmolality of ISF as loop descends causes more water to be removed hypertonic solution enters ascending loop where Na actively pumped back into ISF to maintain osmotic gradient (lots of solutes) Water Balance followed by further Na reabsorption (aldosterone) in the distal convoluted tubule water reabsorption in collecting ducts (vasopressin aids) Renal Osmoregulation  Measurement of kidney function kidney disorders effect glomerular or tubular function tubular function-specific disorders = uncommon generally loss of function across whole nephron we can therefore test glomerular function to help understand if kidney dysfunction is present usually tested by measuring clearance of low molecular weight components Creatinine Clearance estimating GFR done by measuring something completely filtered from blood into urine most common way → clinic through plasma and urine measurement of creatinine creatinine produced during turnover of creatine in muscles with relatively constant daily turnover rate U = urine creatinine concentration (µmol/L) V = urine flow rate (mL/min or L/24h/1.44) P = plasma creatinine concentration (µmol/L) Estimating GFR calculate GFR comparing urinary to plasma creatinine it is not practical for patients to collect urine over long period (24hrs) measuring plasma/serum creatinine is less complex however, not very reliable GFR decline of 50% can still show creatinine within the reference range Calculating Estimate GFR (eGFR) GFR has a number of confounding variable including age, sex, ethnicity, and body mass order to better estimate GFR in clinical populations, equations derived to do so all eGFR use serum creatinine measurement serum creatinine is heavily effected by total muscle mass → values normalised to body area of 1.73 m^2 most recent calculation → Chronic kidney disease epidemiology collaboration (CKD-EPI) formula (uses age, sex and serum creatinine) Investigating kidney function tests performed to try and understand why kidney function has declined important for this to be done so appropriate treatment strategies can be devised assessments performed on urine output as it can be reflective of where kidney is dysfunctional focus trying to understand tubular dysfunction is often the goal Plasma and urine osmolality urine osmolality → general indicator of renal tubule function  tubular kidney disease often impairs water reabsorption in renal tubules compare urine and plasma osmolality → indication whether renal tubules are reabsorbing water healthy kidney produces urine osmolality higher than plasma (1.0-3.0 urine:plasma) ratio ~1.0, likely tubules not reabsorbing water Water deprivation test single urine osmolality test might not provide conclusive result tubule function be actively assessed causing body to retain water rise in urine osmolality (>600 mOsmol/kg) indicates no disruption in vasopressin secretion and water retention changes not seen → lack of vasopressin secretion/function desmopressin can be administered to understand issue is due to lack of vasopressin or blunted recognition stop drinking water for a period of time Issues with water deprivation test can be unpleasant (not drinking for prolonged period) there is very low or no reabsorption → dangerous >3L of urine are passed or >3% of body weight lost, test stopped alternative approach uses overnight fluid restriction (8pm - 10am) followed by single morning urine test Investigating urine output  used for other markers of renal disease overall term used for tests is urinalysis majority of urinalysis tests performed as point-of-care (POC) tests Point-of-care: medical testing performed outside of the laboratory and at the sit of patient, providing a rapid return of results disposable strip of colour indicators for certain tests of interest Proteinuria Abnormal excretion of protein in the urine (high levels) indicator of abnormal glomerular function high level of protein (dipstick analysis) indicates proteinuria spot urine sample can be measured for protein and creatinine concentration to give protein : creatinine ratio (PCR) 24-hour urine collections can be analyses for protein excretion → PCR x 10 main protein in blood = albumin Forms of proteinuria Glomerular Proteinuria damaged basement layer → proteins to pass into ultrafiltrate reduces blood protein concentration → lead to oedema >3g/day excretion known as nephrotic syndrome Tubular Proteinuria  small proteins which can pass through basement layer not correctly retained by the tubules Overflow Proteinuria too much blood protein 'overloads' the glomeruli and too high for reuptake Secreted/Secretory Proteinuria disease/damage to kidneys or urinary tract → proteins from cell linings to be secreted (distal nephron or urinary tract disease) Kidney Disease broad term to cover any disorders associated with the kidneys most common form → chronic kidney disease (CKD) NHS estimate: 15% of >35 yr olds have some kidney dysfunction estimated annual NHS cost of ~£1.4bn Chronic Kidney Disease (CKD) Abnormalities of kidney structure or function, present for >3 months, with implications for health KDIGO (Kidney Disease Improving Global Outcomes) “an independent, volunteer-lead, self-managed foundation using evidence-based clinical practice developing an implementing evidence-based clinical practice guidelines in kidney disease” CKD symptoms might be unnoticeable by the patient until kidney function drops very low earlier CKD is diagnosed, earlier a management plan can be initiated to slow the progression DIAGNOSIS principal feature of diagnosis = eGFR (glomerular filtration rate) values above >60 mL/min/1.73m2 → NORMAL KDIGO provide diagnostic guidelines which include the assessment of eGFR alongside assessment of albuminuria Albuminuria is a form of glomerular proteinuria where albumin from the blood is present in the urine clinicians can use imaging or kidney biopsies to investigate structural damage CLASSIFICATION AND CKD SEVERITY Severity can be segmented into 5 stages based on eGFR and 3 stages based on albuminuria CAUSES OF CKD  caused by many different conditions directly or indirectly related to the architecture of the kidney reduction in function is irreversible and continues to deteriorate over time 1. diabetes mellitus I & II 2. hypertension 3. polycystic kidney disease → Kidney failure in 30-40s 4. pyelonephritis (kidney infection) 5. glomerulonephritis (g-inflammation) 6. interstitial nephritis (t-inflammation) RISK FACTORS FOR CKD patients with identified risk factors may be more regularly monitored for kidney function 1. genetics 2. family history 3. sex 4. ethnicity (↑ non-Caucasian) 5. age 6. obesity or ↑ abdominal adipose tissue 7. socioeconomic status 8. smoking 9. diabetes 10. hypertension 11. CVD METABOLIC CONSEQUENCES OF CKD mild → moderate level to CKD can be managed carefully so that there isn't severe consequences as severity increases, metabolic side effects increase, contributing to a patient’s deteriorating state  CKD progression to stage 5, onset of End Stage Kidney Disease (EKSD) occurs EKSD or established kidney failure = eGFR