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EVERYTHING YOU NEED TO KNOW ABOUT CKD Akul Karoshiand Diya Shah Reviewedby Dr Dhivya Ilangovan Here’s what we do: ■ Weekly tutorialsopen to all! ■ Focussed on core presentationsand teachingdiagnostictechnique If you’re new here… ■ By medicalstudents,for medical students Welcome to ■ Reviewed by doctors to ensure accuracy Teaching ■ We’ll keep you updated about our Things! upcomingevents via email and groupchats!High Yield CKD AkulWhat is Chronic kidney disease (CKD) and why is it important? Whatis CKD? - ChronicKidney Disease (CKD) is a long-standingconditionthat leads to a gradualloss of kidney functionover time. Whyis it important? - CKD is an extremelyprevalent condition,affectingan estimated9% of the g-obWith50% of people over 75 havingsome form of CKDWhat is glomerular filtration rate (GFR)? - Volume of liquid filtered by kidneys’nephronsper minute - Thiscanbe estimated (eGFR) from serum creatinine - however this has some limitations - Creatinineis a waste product of muscle breakdownCKD staging CKD GFR range stage 1 Greater than 90 ml/min, with some sign of kidney damage on other tests (if all the kidney tests* are normal, there is no CKD) 2 60-90 ml/min with some sign of kidney damage (if kidney tests* are normal, there is no CKD) 3a 45-59 ml/min, a moderate reduction in kidney function 3b 30-44 ml/min, a moderate reduction in kidney function 4 15-29 ml/min, a severe reduction in kidney function 5 Less than 15 ml/min, established kidney failure - dialysis or a kidney transplant may be needed Stage 1 and 2 can only be diagnosed if eGFR is as shown in table + there are abnormal kidney tests (deranged U+Es/proteinuria/haematuria/structural abnormality detected)CKD staging questions / defining features of CKDSymptoms of CKD - Oedema: e.g. ankle swelling, weight gain - Lethargy - Polyuria - Pruritus (secondary to uraemia) - Anorexia, which may result in weight loss - Insomnia - Nausea and vomitingLater stages of CKD - Decreased urine output - Fluid overload symptoms - Uraemic symptoms - Nausea and vomiting - Main symptom - Metallic taste in mouth - Pruritus - Encephalitis - Pericarditis - Anaemia - Bone and mineral disease - Metabolic acidosis symptoms - Cardiovascular diseaseLater stages of CKD - Decreased urine output - Fluid overload symptoms - Uraemic symptoms - Nausea and vomiting - Main symptom - Metallic taste in mouth - Pruritus - Encephalitis - Pericarditis - Anaemia - Bone and mineral disease - Metabolic acidosis symptoms - Cardiovascular disease Signs of CKD Pallor Frothy urine Uraemic frost Peripheral Arteriovenous fistula oedemaWhat is the most common cause of CKD? 2. Adult polycystickidney disease 3. Chronicglomerulonephritis 4. Diabetes 5. Longterm NSAID useWhat is the most common cause of CKD? 2. Adult polycystickidney disease 3. Chronicglomerulonephritis 4. Diabetes 5. Longterm NSAID usePathophysiology of diabetic nephropathy 1. Excess glucose in blood sticks to proteins 2. Affects efferent arteriole - causing it to become stiff and narrow 3. Makes it difficult for blood to leave glomerulus 4. Increased pressure -> hyperfiltration 5. High pressure cause supportive mesangial cells to secrete more ECM -> larger glomerulus 6. Glomerulosclerosisdiminishes nephrons ability to filter the blood These changes lead to the development of CKDPathophysiology of hypertensive nephropathy 1. Chronic Hypertension: Increased systemic pressure damages renal arterioles and glomeruli. 2. Renal Vasculature Changes: • Arteriosclerosis: Thickening of renal arterioles reduces blood flow. • Ischaemia: Decreased perfusion leads to glomerular injury. 3. Glomerular Hypertension: • Compensatory hyperfiltration in surviving nephrons increases intraglomerular pressure, causing further damage. 4. Progressive Damage: • Mesangial expansion. • Glomerulosclerosis. 5. Cycle of Damage: Reduced nephron number → worsened hypertension → further nephron loss. These changes result in a gradual decline in GFR and progression to CKD.Which feature would you see on renal biopsy of diabetic CKD? 1. Kimmelstiel wilson nodules 2. Amyloid deposits 3. Subepithelial humps 4. Glomerular crescents 5. Linear IgG depositsWhich feature would you see on renal biopsy of diabetic CKD 1. Kimmelstiel wilson nodules 2. Amyloid deposits 3. Subepithelial humps 4. Glomerular crescents 5. Linear IgG deposits ■ High pressure cause supportive mesangial cells to secrete more ECM -> larger glomerulus – Kimmelstiel wilson noduleInvestigations ■ Proteinuria – Albumin:creatinine ratio (ACR) is preferred to the protein:creatinine ratio (PCR) ■ ACR indicates how much albumin is in the urine (so higher is worse) ■ ACR of 3mg/mmol or more is ‘clinically important’ ■ How is ACR sample collected – First pass early morning urine specimen - If initial ACR is between 3 mg/mmol and 70 mg/mmol - Confirm by subsequent early morning sample - If initial ACR is >70 mg/mmol - Repeat sample not necessaryInvestigations ■ When to refer to nephrologist? – If ACR is >70 ■ Unless already treated or caused by diabetes – If ACR is >30 and ■ Persistent haematuria (⅔ dipstick tests show 1+ or more blood) after UTI excluded – Consider referral if ACR is between 3-29 and ■ Persistent haematuria and ■ Other risk factors – Cardiovascular disease – Declining eGFRDiagnosis ■ We use clinicalhistoryand examination,as well as the CKD stages1-5 to diagnose ■ Serum creatinineis used to calculatethe estimatedglomerularfiltrationrate (eGFR) – Themost commonly used equation used to do thisis the modificationof diet in renaldisease (MDRD) ■ This equation uses the following variables – Serum creatinine – Gender – EthnicityDiagnosis Serum creatinine may not always providean accurate estimationof renal function due to differencesin muscle Thereis an inverse relationshipbetween serum creatinineand eGFR - Pregnancy – IncreasedeGFR ■ In pregnancyheart pumpsharder so more bloodflow through kidneys so more excretion - Amputees ■ IncreasedeGFR (overestimation ofkidney function) – Low serum creatinine due to reducedmuscle mass - Bodybuilders ■ Lower eGFR – High creatinine due to increasedmuscle mass - Eatingred meat before test ■ Low eGFR due to creatinine in meatWhat is the gold standard test for glomerular filtration rate? 1. Inulin clearance test 2. Serum creatinine 4. Urea clearance testratio 5. Creatinine clearance testWhat is the gold standard test for glomerular filtration rate? 1. Inulin clearance test 2. Serum creatinine 3. Albumin creatinine ratio 4. Urea clearance test 5. Creatinine clearance test Most accurate test because inulin is 100% excreted by kidneys and is therefore the ideal substrate for measuring glomerular filtrationCKD management ■ Generalmanagement – Statin ■ For all CKD patients - for primary or secondary prevention of CVD – ACE inhibitors if ■ Diabetes + ACR >3 mg/mmol ■ Hypertension + ACR >30 mg/mmol ■ for all with ACR >70 mg/mmol - Dietary advice - Low protein, Low phosphate, Low sodium, Low potassium - Renal replacement therapy - Haemodialysis - Peritoneal dialysis - Renal transplant Hypertension in CKD management 1. ACEinhibitorsare first line a. Patients with CKDshould be on ACEinhibitorif ACR >30 mg/mmol i. Decrease in eGFR up to 25% or rise in creatinine of up to 30% acceptable if they have risen but within limits should recheck renal function in 2 weeks i. Also stop if k+ >6 from the ace-i/ARB Reduce filtration pressure Switch to another antihypertensive (not ARB) by vasodilation of efferent arteriole so small fall in GFR and rise in creatinine 1. Furosemide expected a. Useful as antihypertensive in CKD, particularly when GFR falls below 45Mineral bone disease and CKD ■ CKD disrupts calciumand phosphate balance – Kidney releases 1-alpha-hydroxylasewhich activates Vitamin D -> increase Ca2+ absorption from diet – In CKD -> reduced activated Vitamin D due to less 1-alpha-hydroxylase -> hypocalcaemia – Parathyroid hormone released due to low Ca2+ levels – PTH causes bones to lose calcium (resorption) -> weak and brittle bones Resultsin - Bone pain - Fractures - Feature of renal osteodystrophyMineral bone disease imaging Ruggerjersey Pepperpot Brownstumour - spine skull lytic area Mineral bone disease management Aim: to reduce phosphateand parathyroidhormonelevels 1. Reduce dietaryintakeof phosphate 1. Phosphatebinders a. Calciumbased binders i. Hypercalcaemiaside effects b. Sevelamer i. Non-calciumbased binder ii. Binds dietaryphosphateand prevents absorption 1. VitaminD a. Alfacalcidolused as doesn’trequire activationin kidneys 1. Parathyroidectomymay be needed in some casesAnaemia and CKD ■ Kidneysare responsiblefor producingerythropoietin(EPO) ■ EPOis responsiblefor red blood cell synthesis ■ In CKD the kidneysdon’t produce sufficientEPO -> low RBC levels – Additionally,uraemiahas toxic effects on bone marrow -> reduced erythropoiesis - Normochromicnormocyticanaemia - Becomes apparent when GFR is <35 ml/min (other causesof anaemia shouldbe consideredif the GFR is >60 ml/min) - How doesthisresult inthreefoldincreaseinmortality inrenal patients? - Anaemiain CKD predisposesto the development of left ventricular hypertrophyManagement of anaemia in CKD ■ Targethaemoglobinof 10-12g/dl 1. Determineand optimise ironstatus a. Should be carried out prior to administrationof erythropoiesis- stimulatingagents(ESA) b. Correct iron levels as required i. Ferrous sulphate/ferrous gluconate ii. Many patients(especiallyhaemodialysispatients)will requireIV iron infusion 1. Erythropoiesisstimulatingagents a. Erythropoietinand darbepoetin are examples i. Give ESAs if iron levels are normalWhat feature of end-stage renal disease is shown below Burr cell (echinocyte)Differentiating AKI and CKD On renal ultrasound, CKD will have bilateral small kidneys except in - autosomal dominant polycystic kidney disease - diabetic nephropathy (early stages) - Amyloidosis - HIV-associated nephropathy Other features suggesting CKD rather than AKI ● Hypocalcaemia (due to lack of vitamin D) ● Anaemia ● HyperphosphataemiaNephrotic and Nephritic Syndromes DiyaGlomerulus and Bowman's capsule Subepithelial- betweenthe podocytes(epithelium)and theglomerular basement membrane Subendothelial - betweenthe glomerularbasement membraneand endlotheliumof capillaries Mesangial- withinthemesangialcellsNephrotic syndrome ■ Tetrad:PALE Massive proteinuriaclassifiedas >3.5g/ 24 hr ■ Podocytes are negativelychargedand stop proteinsfrom gettingthrough - nephroticsyndromes affect the podocytes ■ Complications? – VTE - loss of proteins involved in clotting(antithrombin,Protein C, plasminogen…) – Hyperlipidaemia- liver compensatesloss of proteinby increasinglipid productionto maintainosmotic pressure – Infectionrisk - loss of antibodies – CKD ■ Generalmanagement- low salt diet, VTE prophylaxis,furosemide for oedemaSBA A 48-year-old male presents with worsening peripheral oedema and frothy urine over the past few weeks. His medical history includes treated hypertension. Laboratory findings reveal: ● Serum albumin: 25 g/L (normal: 35–50 g/L) ● Serum creatinine: 90 µmol/L (normal: 60–120 µmol/L) ● 24-hour urine protein: 9 g/day ● Serum cholesterol: 10.5 mmol/L (elevated) Here is his kidney biopsy. Describe the characteristic histological finding associated with this condition. A) Mesangial proliferation B) Subepithelial deposits with a spike and dome appearance and thickened basement membrane C) Podocyte effacement without immune complex deposition D) Crescent formation in glomeruli E) Fibrillary deposits in the mesangiumSBA A 48-year-old male presents with worsening peripheral oedema and frothy urine over the past few weeks. His medical history includes treated hypertension. Laboratory findings reveal: ● Serum albumin: 25 g/L (normal: 35–50 g/L) ● Serum creatinine: 90 µmol/L (normal: 60–120 µmol/L) ● 24-hour urine protein: 9 g/day ● Serum cholesterol: 10.5 mmol/L (elevated) Here is his kidney biopsy. Describe the characteristic histological finding associated with this condition. A) Mesangial proliferation B) Subepithelial deposits with a spike and dome appearance and thickened basement membrane C) Podocyte effacement without immune complex deposition D) Crescent formation in glomeruli E) Fibrillary deposits in the mesangiumMembranous glomerulonephritis ■ Most common nephroticsyndromeinadults ■ 3rd most common cause of ESRF ■ Antibodiesdeposit in subepithelialspace ■ Causes: – Idiopathic – Malignancy- caninvestigatewithCT – Drugs - gold, pencillamine,NSAIDs – SLE ■ Management – ACEi,immunosuppression,treat secondarycauses ■ Prognosis- rule of thirdsSBA A 36-year-old woman presents with progressive generalised oedema and frothy urine over the past two months. She is a known IV drug user. Physical examination reveals pitting oedema in the lower limbs, and her blood pressure is 125/80 mmHg. Laboratory investigations reveal: A kidney biopsy is performed. Light microscopy shows focal and segmental sclerosis of some glomeruli. Immunofluorescence is negative for immune deposits, and electron microscopy demonstrates widespread podocyte foot process effacement. Which of the following is the most likely diagnosis? A) Minimal change disease B) Focal segmental glomerulosclerosis (FSGS) C) Membranous nephropathy D) IgA nephropathy E) Lupus nephritisSBA A 36-year-old woman presents with progressive generalised oedema and frothy urine over the past two months. She is a known IV drug user. Physical examination reveals pitting oedema in the lower limbs, and her blood pressure is 125/80 mmHg. Laboratory investigations reveal: A kidney biopsy is performed. Light microscopy shows focal and segmental sclerosis of some glomeruli. Immunofluorescence is negative for immune deposits, and electron microscopy demonstrates widespread podocyte foot process effacement. Which of the following is the most likely diagnosis? A) Minimal change disease B) Focal segmental glomerulosclerosis (FSGS) C) Membranous nephropathy D) IgA nephropathy E) Lupus nephritisFocal segmental glomerulosclersis (FSGS) ■ Specific area of damage to podocytes wherethereis depositionof collagen ■ Histologyshowsfocal area of sclerosis ■ ClassicSBA sign - patientwithHIV or heroinuser ■ Renalbiopsy findings: – Focal and segmentalsclerosison LM – Effacement of foot process on EM ■ Management – Steroids – Immunosuppression – Transplantin ESRD ■ High rate of recurrence in transplanted tissueSBA A previously healthy 6-year-old child presents with generalised oedema and weight gain. Laboratory investigations reveal the following: ● Serum albumin: 20 g/L (normal: 35–50 g/L) ● Serum creatinine: 30 µmol/L (normal for age) ● Urinalysis: 4+ protein, no haematuria ● Cholesterol: 8.5 mmol/L (elevated) Which of the following is the most likely diagnosis? A) Focal segmental glomerulosclerosis (FSGS) B) IgA nephropathy C) Membranous nephropathy D) Minimal change disease E) Alport syndromeMinimal change disease ■ Most common nephroticsyndromeinchildren ■ Why is it called minimalchangedisease? ■ Podocyte fusionand effacement of foot processes(key exam phrase) ■ Risks – Majority Idiopathicbut linkedto Hodgkin’slymphoma,infectious mononucleosis ■ Treatment – Majority of cases are steroid-responsive – Cyclophosphamideif resistant – Progressionto CKD very rareNephritic syndrome ■ Haematuria (microscopicor macroscopic) ■ Red cell casts in urine ■ Sterile pyuriainloss (less proteinuriathannephrotictypically) ■ Hypertention ■ Oliguria ■ Pathophysiology – Inflammationcausinginjury to glomerularcapillaries= RBC leak – Some injuryto BM - proteinuria – WBC are recruitedfor inflammation- sterilepyuria – RAAS activation- glomerulardamage = decreasedGFR = more renin release = hypertensionSBA A 25-year-old manpresents with recurrent episodesof visible haematuria, typically occurring 1–2 days after upper respiratory tract infections.He also reportsoccasional flank pain but deniesany significant weight loss, fever,or othersystemic symptoms.Urinalysis reveals proteinuria (1+) and microscopic haematuria. Bloodpressure is 135/85 mmHg, and renal function tests are within normal limits. A renal biopsyis performed. Histological findings show mesangial proliferation, and immunofluorescencereveals prominentmesangial deposits of IgA. What is the most likely diagnosis? A) Post-infectious glomerulonephritis B) Membranousnephropathy C) Focal segmental glomerulosclerosis (FSGS) D) IgA nephropathy E) Minimal change diseaseSBA A 25-year-old manpresents with recurrent episodesof visible haematuria, typically occurring 1–2 days after upper respiratory tract infections.He also reportsoccasional flank pain but deniesany significant weight loss, fever,or othersystemic symptoms.Urinalysis reveals proteinuria (1+) and microscopic haematuria. Bloodpressure is 135/85 mmHg, and renal function tests are within normal limits. A renal biopsyis performed. Histologicalfindingsshowmesangial proliferation,and immunofluorescence reveals prominent mesangial deposits ofIgA. What is the most likely diagnosis? A) Post-infectious glomerulonephritis B) Membranousnephropathy C) Focal segmental glomerulosclerosis (FSGS) D) IgA nephropathy E) Minimal change diseaseIgA nephropathy ■ Aka. Berger’s disease ■ Associated conditions? ■ Most common nephritic syndrome with 25% developing ESRF ■ Macroscopic haematuria 1-2 days following URTI ■ Pathophysiology - IgA complex deposition in mesangial cells ■ Oftens affects young male ■ Renal biopsy – Mesangial hypercellularity with positive immunofluorescence for IgA and C3 ■ Management – ACEi, and steroids if failure to responseSBA A 42-year-old womanpresents with a two-weekhistoryof fatigue, malaise, and rapidly worseningswelling in her legs. Shealso reports dark-coloured urine and reducedurine output. On examination,her bloodpressure is 160/95 mmHg, and she has bilateral pedal oedema. Investigationsreveal: ● Serum creatinine:380 µmol/L (elevated) ● Urinalysis: 3+ blood,2+ protein ● Microscopy:Dysmorphicred bloodcells and red bloodcell casts ● Serum anti-glomerular basementmembrane (anti-GBM) antibodies: Positive A kidney biopsy shows crescentformation in >50% of glomeruli. What is the most likely diagnosis? A) Post-infectious glomerulonephritis B) IgA nephropathy C) Rapidly progressiveglomerulonephritis (RPGN) D) Membranoproliferativeglomerulonephritis E) Minimal change diseaseSBA A 42-year-old womanpresents with a two-weekhistoryof fatigue, malaise, and rapidly worseningswelling in her legs. Shealso reports dark-coloured urine and reducedurine output. On examination,her bloodpressure is 160/95 mmHg, and she has bilateral pedal oedema. Investigationsreveal: ● Serum creatinine:380 µmol/L (elevated) ● Urinalysis: 3+ blood,2+ protein ● Microscopy:Dysmorphicred bloodcells and red bloodcell casts ● Serum anti-glomerular basementmembrane (anti-GBM) antibodies: Positive A kidney biopsy shows crescent formation in>50%of glomeruli. What is the most likely diagnosis? A) Post-infectious glomerulonephritis B) IgA nephropathy C) Rapidly progressive glomerulonephritis(RPGN) D) Membranoproliferativeglomerulonephritis E) Minimal change diseaseRapidly progressive glomerulonephritis ■ Rapid loss of renalfunctionwithover 50% within3 months ■ Causes – SLE – Goodpasture’ssyndrome – Wegener’sgranulomatosis ■ Nephriticsyndromefeatures withspecific features dependanton cause ■ Renalbiopsy – Glomerular cresentshaped scarringSummary of intrarenal conditionsOther intrarenal disease not covered Nephritic Post streptococcal GN Anti GBM Membranoproliferative HSP THANKS FOR WATCHING! Tutor 1: Akul Karoshi Tutor 2: Diya Shah on Medall and see you next week!m