Nephrology JC078: Glomerular And Tubulo-interstitial Diseases And Acute Kidney Injury Flashcards

Question

Investigations of Chronic GN

Answer 1

Ascertain ***chronic nature of disease 1. CBC - ***Normochromic normocytic anaemia 2. Renal biochemistry - ↑ Urea, Creatinine, ***PO4 - ***↓ Ca - +/- ↑ K - Metabolic acidosis 3. Urine protein quantification 4. USG (↓ kidney size, ↑ echogenicity) 5. Renal biopsy (usually unnecessary, ∵ only show fibrosis, glomerulosclerosis —> cannot identify underlying cause anyway)

Answer 2

1. Supportive therapy 2. Minimise metabolic disturbance + complications 3. Renal replacement therapy (if approaching stage 5 CKD)

Answer 3

- Anatomically >95% of kidney - Acute TIN may cause important renal dysfunction (***~5-15% acute renal failure causes) - If left unchecked, Chronic TIN is major pathway leading to ***CKD Clinical manifestations (∵ Interstitial inflammation + Tubular dysfunction): 1. Loss of renal function 2. Abnormal urine sediment (e.g. WBC (but without infection), proteinuria) 3. ***Electrolyte disturbance 4. ***Acid-base disorders

Answer 4

1. ***Acute TIN - Drugs (e.g. Penicillins, NSAID, PPI, Mesalazine (delayed) (Davidson)) - Infections (e.g. pyelonephritis, leptospirosis, TB, Hantavirus (Davidson)) - Autoimmune disease 2. ***Chronic TIN - Etiology unknown Davidson: - ANY causes of Acute TIN if persistent - Drugs (e.g. Tenofovir, Lithium, Ciclosporin, Tacrolimus, Analgesic nephropathy) - Autoimmune disease (e.g. SLE, Sjogren's) - Metabolic (e.g. CaPO4 crystallisation, HypoK, Hyperoxaluria) 3. K-wasting tubular disorders 4. ***Renal tubular acidosis (∵ inability of tubules to excrete H / reabsorb HCO3)

Answer 5

Definition: - Abrupt decrease in kidney function - Even mild, reversible AKI can progress to CKD - AKI viewed as same to Acute lung injury / ACS Characterised by: 1. Abrupt ↓ in GFR over a period of hours / days 2. 50% ↑ SeCr (3. ↑ in some damage markers e.g. NGAL, KIM-1, IL18) Risk factors of AKI: 1. ***Pre-existing CKD 2. ***Diabetic nephropathy 3. Heart failure 4. Liver disease 5. ***Hypovolaemia 6. Age >50 7. Sepsis 8. Trauma 9. Post-operative (e.g. Post-CABG) 10. Cancer

Answer 6

Various etiologies - May have >=1 of below conditions 1. Pre-renal (>50%) - Prerenal azotaemia (Hypotension, Dehydration, Sepsis, Shock, Heart failure, Hepatorenal syndrome) - Renal artery (Occlusion, Vasculitis) - Small vessel disease (Thrombotic microangiopathy, Renal atheroembolism, Vasculitis) 2. Intrinsic (<50%) - Acute GN (All causes of RPGN) - Acute tubular necrosis (Drugs, Toxins, Ischaemia (from dehydration, hypotension, cardiogenic shock, hypovolaemic shock), Rhabdomyolysis, Radiocontrast) - Acute interstitial nephritis (Drugs, Infection, Autoimmune disease) - Intratubular obstruction (Cast nephropathy, Drugs, Crystalluria) 3. Post-renal (<10%) - Renal vein thrombosis - Obstructive causes (e.g. Ureteric stone, BPH, Neurogenic bladder)

Answer 7

General principles: 1. Rapid + Accurate diagnosis 2. Identify + Reverse underlying cause (e.g. nephrotoxins, sepsis, hypovolaemia, obstruction, cardiogenic) Treatment: 1. ***Diuretics (for fluid overload, acute pulmonary edema) 2. Electrolyte disturbance (***HyperK, ***acidosis): ***Polysulphonate (for binding K in gut), ***D/I drip (drive K into cells, dextrose is buffer for insulin to prevent hypoglycaemia), ***HCO3 3. HCO3 (for acidosis) 4. ***Acute dialysis support - usually ***HD - vascular access - ICU admission if indicated Indications for dialysis (Blue book + SpC Medicine): 1. Severe HyperK 2. Severe Metabolic acidosis 3. Fluid overload (e.g. APO) 4. Uraemia complications (Uraemic encephalopathy / pericarditis)

Answer 8

First changes - ***Microalbuminuria - ***Glomerular BM thickening —> Microangiopathy - Accumulation of matrix material in mesangium Subsequent changes - ***Heavy proteinuria - Nodular deposits - ***Glomerulosclerosis Pathogenesis: 1. Chronic hyperglycaemia —> ***↑ Mesangial Cell matrix production + apoptosis —> Mesangial cell expansion + injury 2. Glomerular hypertrophy (↑ Renal size) —> ↑ shear stress on glomerular capillary wall 3. Glomerular hyperfiltration (↑ GFR) —> dilatation of afferent arteriole by ***AGEs, Sorbitol, IGF-1 —> ↑ Renal blood flow —> ↑ Intra-glomerular pressure (Intra-glomerular hypertension) 4. Glomerulosclerosis —> ∵ Intra-glomerular hypertension —> ∵ Hyaline narrowing of vessels supplying the glomeruli (Hyaline deposition induced by ischaemic injury) Histology: 1. Diabetic ***Glomerulosclerosis —> ECM deposition in glomeruli 2. ***Mesangial expansion 3. ***GBM thickening 4. ***Arteriolar Hyalinosis / Arteriolosclerosis Consequence: Microalbuminuria Management: 1. Protein restriction 2. Antihypertensive 3. Glycaemic control

Answer 9

1. ***Uncorrectable bleeding diathesis - check Plt, Clotting profile - stop Antiplatelet, Anticoagulants 2. ***Small kidneys which are generally indicative of chronic irreversible disease - futile + risky due to puncturing a hard fibrotic structure —> bleeding 3. ***Severe hypertension, which cannot be controlled with antihypertensive - one dose of amlodipine —> wait several hours for BP to decrease 4. Multiple, bilateral cysts / renal ***tumour 5. Hydronephrosis 6. Active renal / perirenal ***infection 7. Uncooperative patient 8. Solitary kidney - ∵ in case of several bleeding may need embolisation / nephrectomy

Answer 10

“Nephrotic syndrome, normal-looking glomeruli + absence of hypertension, haematuria or azotaemia” Epidemiology: - ***Children: >90% of nephrotic syndrome - Adult: 10-15% of nephrotic syndrome - Elderly: suspect possible underlying malignancy, esp. lymphoid origin (e.g. Hodgkin’s disease) Clinical features: 1. Heavy proteinuria 2. Onset of edema may be insidious / acute, initially affecting periorbital area upon awakening and shifting to the ankles towards the end of day 3. Ascites / Pleural effusion in severe cases Pathology: - Light microscopy demonstrates essentially ***normal glomerular morphology - Immunofluorescence is usually ***negative for immunoglobulins - Only detectable abnormality is ***total effacement of foot processes (podocytes) of visceral epithelial cells shown on ultrastructural examination by ***EM - These morphological alterations are typical of nephrotic syndrome but not specific to MCNS - Some patients with clinical features of MCNS have ***positive mesangial IgM staining, along with mesangial ***proliferative changes - These patients, more likely to also have ***microscopic haematuria and less likely to respond to steroid, are said to have ***IgM nephropathy - Relationship between MCNS, IgM nephropathy, and FSGS is ***poorly defined, but responsiveness to steroid therapy is a shared feature —> ***Continuum of pathology Treatment: 1. Corticosteroid - Adult: Prednisolone started at 1 mg/kg/day (up to max 80 mg/day) —> slowly tailed off over a period of around 4 months - Children: Prednisone at 60 mg/m2/day (up to max 80 mg/day) for 4 to 6 weeks —> 40 mg/m2 every other day for 4 to 6 weeks 2nd line agents 2. Alkylating agents 3. Cyclosporine, Tacrolimus 4. Levamisole - antihelminthic agent with immunomodulatory effects, used alone / in combination with steroid in MCNS in children - well tolerated - SE: neutropenia, rash, liver toxicity

Answer 11

- Most common cause of nephrotic syndrome in adults - Defined by the presence of ***subepithelial immune deposits leading to a spectrum of glomerular capillary wall alterations, most typically the formation of intervening ***"GBM spikes" - Primary vs Secondary - Primary MN is regarded as ***prototypic glomerular disease mediated by ***in situ immune complex formation - Can also occur secondary to autoimmune disease, neoplasia, infection, exposure to certain therapeutic agents Epidemiology: - Most common in Caucasian individuals + Adults - Rare in infants and young children - M:F = 2:1 - Secondary MN most commonly encountered in young children and in individuals >60 yo Clinical features: 1. ***Proteinuria (defining clinical feature of MN) - majority of patients have full nephrotic syndrome 2. Normal RFT (most patients at time of presentation) 3. Microhaematuria (~50%) Secondary MN: - 25% of cases - 4 categories: 1. Autoimmune / Collagen vascular diseases, - SLE (most notably, i.e. membranous lupus nephritis) - RA - Sjogren's syndrome - mCTD - Sarcoidosis - Grave's disease - Hashimoto's thyroiditis 2. Malignancy - Carcinomas of the lung, prostate, breast, GI tract 3. Drugs - Gold - Penicillamine - NSAIDs, COX-2 inhibitors - Captopril 4. Infections - Hepatitis B / C - Syphilis - Malaria - Parasites

Answer 12

1. Membranous GN 2. Mesangiocapillary glomerulonephritis (MCGN) 3. IgA nephropathy Clinical features: 1. Proteinuria, usually in the nephrotic range 2. Mild to moderate renal impairment (may be present at presentation) Children: - Male preponderance - Nephrotic syndrome most frequent - Transaminase levels are usually normal Adults: - Proteinuria / Nephrotic syndrome - More likely than children to have HT, renal dysfunction, and clinical evidence of liver disease Prognosis: - Children: Favourable; high rates of spontaneous remission - Adults: Worse in patients with nephrotic range proteinuria and overt hepatitis at presentation Treatment: 1. General measures for CKD - Optimise BP control - Reduce proteinuria with ACEI / ARB - Control lipid levels - Sodium restriction - Quit smoking - Optimise body weight - Regular exercise 2. Specific measures - Eradication of the underlying HBV by nucleoside analog e.g. Lamivudine