Renal Flashcards

Question

RTA

Answer 1

Type 1 (distal), defect in H+ secretion in DT Urine pH >5.5 Hypokalaemia Urine: calcium is high Causes: Hereditary Collagen vascular dx Cirrhosis Nephrocalcinosis MM Type 2: Proximal, defect in HCO3 reabsorption in PCT urine pH <5.5 Hypokalaemia Causes: Sulfanomides Acetazolamide (Carbonic anhydrase inhibitors) Fanconi sx MM Type IV, Inadequate aldosterone --> reduced sodium reabsorption and K secretion Urine ph<5.5 Hyperkalaemia, hyperchloraemia Causes: - hyporeninemic hypoaldosteronism - HTN - DM - Chronic interstitial nephritis - Aldosterone resistance

Answer 2

- non atheromatous, non-inflammatory vascular condition - Women, 30-50 - Renal arteries in 60%, bilateral in 35% - **mid to distal artery**, string of beads appearance - RF: smoking, pregnancy

Answer 3

MPGN, aHUS FSGS and IgA least likely: anti-GBM

Answer 4

Histologically is similar to graft rejection Serum PCR is a specific and sensitive test for diagnosis Clinical outcome is good if detected earlier Presents as **patchy interstitial (plasma cells and Lt) nephritis presence of viral inclusions +SV40 ** BK lives in the medulla Decoy cells in urine (characteristic, but not patho) RF: - degree of immunosuppression, donor age, ureteral stent, viral co-infection Tx: is reduction of immunosuppression

Answer 5

§ Most common cause of primary GN § Peak 20s/30s **Male**:F 2:1 § Presentation: □ 40-50% Macroscopic haematuria +/- flank pain, low grade fever □ 30-40%: microscopic haematuria + mild proteinuria □ 10%: NS or RPGN ® Nephrotic sx is suggestive of advanced dx RARE: malignant HTN or AKI

Answer 6

HIV Cirrhosis/CLD - etoh, HBV, HCV Coeliac (1/3 of pts) GPA in remission

Answer 7

Proteinuria >1g/day *The need for dialysis and death increased in those presenting with protein excretion >1g/day * New onset HTN Elevated serum creatinine ## Footnote Degree of renal injury and HTN at presentation correlates with progression of dx to ESRD

Answer 8

Goal: reduce rate of decline BP control RAAS blockade SGLT2i >1g/day --> consider immunosuppression ## Footnote IS or dialysis: □ IS should NOT be considered in those with severe irreversible kidney damage eGFR <30 for >3mo , small echogenic kidneys, any evidence of severe interstitial fibrosis, tubular atrophy or glonerularsclerosis

Answer 9

HTN Proteinuria (rather than microalbuminuria) Poor prognostic factors: - MALE - Proteinuria >1-2g/day - HTN - Smoking - Hyperlipidemia - ACE genotype DD ## Footnote 25% will develop ESRF

Answer 10

neurologic symptoms related to cerebral edema. New patients who are just being started on intermittent hemodialysis are at greatest risk for DDS, particularly if the BUN is markedly elevated (>175 mg/dL or 60 mmol/L).

Answer 11

80% association with primary membranous nephropathy - specificity 99%, sensitivity 78% - good response to **rituximab** No correlation to secondary MN

Answer 12

IgG4 ab for THSD7A Smaller number of primary MN

Answer 13

**Nephrotic sx** Antibody and complement induced cytotoxicity on podocytes --> non exudative, non-proliferative capillary wall lesion (**granular deposits of IgG and C3 at the basement mb** Thickened basement mb **Spike and dome** - Subepithelial immune complex: > IgG ab binding tp foot processes on podocytes ( PLA2R, THSDA antigens) >** correlates with disease activity ** in primary MN - Complement activation via lectin pathway > syblytic effect > stimulates GEC-GBM degrading protease and TGF-beta > matrix production > **no inflammatory cells ** Associated with: Solid tumour malignancies: prostate, lung, lymphoma, leukaemia HBV, malaria, syphilis SLE (Class V), thyroiditis, RA NSAIDs/gold

Answer 14

PLA2R or TSHD7A positive in serum and proteinuria >3.5g/day

Answer 15

ACEi/ARB - improve proteinuria and improve prognosis Severe cases need IST: - - Rituximab - Cyclophosphamide + steroid - CNI +/- pred ## Footnote 1/3 will develop ESRF Steroids alone won't be effective consider anticoagulation for high-risk patients

Answer 16

GI losses/dehydration

Answer 17

- HTN - VTE - Seizures - Pure red cell aplasia Side-effects of erythropoietin - accelerated hypertension potentially leading to - encephalopathy and seizures (blood pressure increases in 25% of patients) -bone aches -flu-like symptoms -skin rashes, urticaria -pure red cell aplasia* (due to antibodies against erythropoietin) raised PCV increases risk of thrombosis (e.g. Fistula)* - iron deficiency 2nd to increased erythropoiesis

Answer 18

Can be** nephritic or nephrotic** Poor prognosis 3 types: - type 1 (90%): > **Hep C, cryoglobulinemia ** > > other: SLE, Hep B, Subacute endocarditis > Renal biopsy: EM: "**tram tracks**" due to subendothelial and mesangial immune deposits > Low C3 and C4 Type 2: dense deposit disease (DDD) - causes: **partial lipodystrophy **(patients classically have a loss of subcutaneous tissue from their face), factor H deficiency - caused by persistent activation of the **alternative complement pathway** - LOW serum C3 - C3b nephritic factor is found in 70% > an antibody to alternative-pathway C3 convertase (C3bBb) > stabilizes C3 convertase > renal biopsy electron microscopy: **intramembranous immune complex deposits with 'dense deposit** ## Footnote LM: - thickening of BM due to C3 deposition - mesangial cytoplasm between GBM and endothelial cells - Hypercellularity (mesangial cells and monocytes)

Answer 19

Female Young Asymp. proteinuria (modest)

Answer 20

Smoking - most important risk factor in western countries - hazard ratio is around 4 Exposure to aniline dyes - for example working in the printing and textile industry -examples are 2-naphthylamine and benzidine Rubber manufacture Cyclophosphamide

Answer 21

Schistosomiasis Smoking

Answer 22

- rare type of small-vessel vasculitis associated with both pulmonary haemorrhage and rapidly progressive glomerulonephritis - Ab againt **Type 4 collagen** - **M** 2x >F - Bimodal distribution (20s, 60s) - **HLA DR2** renal biopsy: **linear IgG deposits along the basement membrane** raised transfer factor secondary to pulmonary haemorrhages ( rasied DLCO) Tx: - PLEX - Steroids - Cyclophosphamide

Answer 23

IgA is days and PSGN is weeks

Answer 24

Nephritic syndrome Associated with GA beta haemolytic strep Usually infection 2-6 weeks prior Oliguria, oedema, HTN, tea/cola coloured urine Lab: low C3 (norm 6-8 wks after presentation), increased ASO and Anti DNase titre EM: **Hump-shaped subepithelial** deposits Endocapillary **diffuse proliferation** and exudative glomerulonephritis on light microscopy **immunofluorescence: **granular or 'starry sky' appearanc

Answer 25

Acute kidney injury (AKI) due to intratubular crystal precipitation is observed in association with many medications. Patients are generally asymptomatic, although occasionally present with flank pain. Urinalysis may show hematuria, pyuria, and crystals with a characteristic morphology —** Acyclovir is rapidly excreted in the urine (being both filtered and secreted) and has a relatively low solubility**. Thus, bolus intravenous (IV) therapy, especially if the patient is volume depleted, may lead to the deposition of acyclovir crystals in the tubules, resulting in intratubular obstruction and foci of interstitial inflammation

Answer 26

This patient has membranous nephropathy - depending on certain risk factors, patients with this disease are stratified to either low, moderate or high risk **Low risk of progression **– Protein excretion remains l**ess than 4 g/day** and creatinine clearance remains normal for a six-month follow-up period. ●Moderate risk of progression – Protein excretion is between 4 and 8 g/day and persists for more than six months, and creatinine clearance is normal or near normal and remains stable over 6 to 12 months of observation. ●High risk of progression – Protein excretion is greater** than 8 g/day** and persists for three months and/or creatinine clearance is reduced (and considered due to MN) or declines over three months of observation All patients with proteinuria are commenced on an ACE/ARB. For patients that are low risk, observation is recommended. For patients that are moderate and high risk - immunosupression is recommended, of which cyclophosphamide + corticosteroid combination is recommended

Answer 27

GI cause: negative Renal cause: positive (i.e. in RTA)

Answer 28

- RCC accounts for 85% of primary renal neoplasm - arises from proximal renal tubular epithelium - most common: clear cell - Men - middle age - vHL sx - TS - slight increase with ADPKD fx: - haematuria, loin pain, abdominal mass - PUO - Endocrine: EPO, PTHrp, renin, ACTH - 25% will have mets at presentation - paraneoplastic hepatic dysfunction sx - Veriocele **Stauffer syndrome** a paraneoplastic disorder associated with renal cell cancer typically presents as cholestasis/hepatosplenomegaly it is thought to be secondary to increased levels of IL-6 **Management**: - for confined disease a partial or total nephrectomy depending on the tumour size patients with a T1 tumour (i.e. < 7cm in size) are typically offered a partial nephrectomy - **alpha-interferon and interleukin-2** have been used to reduce tumour size and also treat patients with metatases - receptor tyrosine kinase inhibitors **(e.g. sorafenib, sunitinib) have been shown to have superior efficacy compared to interferon-alpha**

Answer 29

- a rapid loss of renal function associated with the formation of epithelial crescents in the majority of glomeruli. Causes - Goodpasture's syndrome (linear glomerular IF staining) - Wegener's granulomatosis (pauci immune) - others: SLE, microscopic polyarteritis Features -nephritic syndrome: haematuria with red cell casts, proteinuria, hypertension, oliguria - features specific to underlying cause (e.g. haemoptysis with Goodpasture's, vasculitic rash or sinusitis with Wegener's) - Anti-GBM/ANCA GN: fibrinoid necrosis and little/no endocapillary hypercellularity in the non-necrotic area. **more disruption to Bowman's capsule** - Immune complex crescenteric GN: more glomerular endocapillary hypercellularity, thickening of capillary wall, more diffuse process, less crescents

Answer 30

Essential HTN (80-95%) RF: - salt - obesity - Alcohol - angiotensin excess - sympathetic excess - FHx

Answer 31

DBP >95mmHg, steep increase in cardiovascular mortality Increase IHD and stroke risk with both increasing systolic and diastolic BP Clinical evidence showes treating HTN --> reduces stroke (35-40%), MI (20-25%), HF (50%) There is evidence for intensive BP control to <120mmHg systolic **Half dose drug combination is better than full dose monotherapy ** **Night time dosing improves mortality**

Answer 32

Common: - intrinsic renal disease - renovascular disease - Mineralocorticoid excess - OSA - Meds: OCP, NSAIDS Uncommon: - Pheochromocytoma - Glucocorticoid excess/cushing's - Coarctation of Aorta - Hyper/Hypothyroidism

Answer 33

Morning PAC and PRA - PAC >416, PRA <1.0 - AND: PAC/PRA >555 per hour (increases) - then investigate for primary aldosteron excess Confirmatory tests: 1. oral salt loading 2. IV salt loading 3. Fludrocortisone suppression Tx: Adrenal CT - unilateral **hypo**dense nodule >1cm <2cm > under 40 - consider APA or PAH > over 40: Adrenal venous sampling - if lateralisation -> APA or PAH otherwise: bilateral idiopathic hyperplasia - medical tx

Answer 34

- Angiogram is gold standard - CT angio: most sensitive - resistive indices >0.8: predicts poor outcome with angioplasty - treatment with stent doesn't work Tx: Unilateral RAS: - ACEi/ARB +/- thiazide - Angioplasty for FMD Bilateral - Avoid ACEi/ARB - no evidence for stenting

Answer 35

- metabolism of creatine in muscle and meat - Variable based on age, body size, and sex - Freely filtered, not reabsorbed, but secreted by PT - GFR 125ml/min

Answer 36

2 x NA + gluc + urea

Answer 37

- osmoreceptors in the hypothalamus sense osmolality - ParaVN and SON express gen coding for VP - posterior pituitary - V2 receptors in thick ascending LoH, DCT, and CD - cAMP pathway --> increases AQP2 gene transcription and phosphorylates already made AQP2 vesicles --> fusion to mb --> increases **AQP2** - water entry into cell **Tolvaptan:** blocks V2 receptors in distal nephrons and CD. Reduces cyst formation in PCKD V2 is released if there is a fall in arterial blood **volume ** ## Footnote - V1 receptor increase vascular resistance

Answer 38

RAAS Carotid sinus and aortic arch: baroreceptors --> medulla oblongata --> increase sympathetic activity Cardiac receptors: regular release of ANP and BNP

Answer 39

1. sympathetic nerve activation (acting through **β1-adrenoceptors)** 2. reduced Na delivery to distal tubules 3. renal artery hypotension (caused by systemic hypotension or renal artery stenosis)

Answer 40

SIADH, psychogenic, renal failure (adv), Thiazide Low serum Na, low serum osmolality, high urine osmolality >100 High urine Na, normal serum K and pH

Answer 41

- ADH secreation from Small CLC - CNS disorder - Drugs: SSRI, carbamazepine, cipro, amiodarone, immunosuppression -** Recent surgery - mediated by pain afferents** - Pulm. disease - Hormone def: hypopituitarism and **low TSH** - Idopathic: occult tumour or **GCA**

Answer 42

- ADH secreation from Small CLC - CNS disorder - Drugs: SSRI, carbamazepine, cipro, amiodarone, immunosuppression -** Recent surgery - mediated by pain afferents** - Pulm. disease - Hormone def: hypopituitarism and **low TSH** - Idopathic: occult tumour or **GCA**

Answer 43

- Renal fluid loss: high urine Na and chloride - GI loss: > diarrhoea or sequ in 3rd space -> low urine Na > vomiting: high urine Na , due to metabolic alkalosis --> Na excretion with loss of urinary bicarb, and low urine chloride

Answer 44

HFrEF, reduced tissue perfusion, arterial vasodilatation

Answer 45

HYperglycaemia IVIG infusion Sorbitol or mannitol irrigation in uro or gynae procedures

Answer 46

Bartter = loop diuretic - high levels of prostaglandin production --> stimulates renin - **hypokalaemia and metabolic alkalosis** - will also have low Ca and Mg level in serum Gitelman: thiazide **- high serum Ca, and low serum Mg** cramps in limbs, polyuria and fatigue Tx: - electrolytes - NSAIDS to block PGE2

Answer 47

stimulated by decrease in chloride

Answer 48

Renin level increase

Answer 49

- angiotensinogen produced by the liver (others) - ACE: vascular endothelial cells in the lung (others) >Converts AT1 to AT2 > breaks down bradykinin - AT2: > arterial vasoconstriction --> increase BP (early) > Hypothalamys: increase thirst, increase ADH --> increase CO > Renal: low levels: vasoconstrict efferent (increase GFR). High levels: vasoconstrict afferent and efferent: dec. GFR > Adrenal (late) via AT1R: zona glomerulosa to increase aldosterone --> R. on CD *principal cells of CD*--> cGMP --> N/K atpase and increase ENaC --> Na retension AT2 receptor 1: vasoconstricts, inflammatory mediator, proliferation of vascular smooth muscle recep 2: opposite, but less in the kidneys **Intrarenal RAS:** - AT2 in renal interstitial fluid is 1000x more than systemic system - very sensitive to sodium intake ## Footnote ACE2: produced by endothelium of coronary and intrarenal vessels have opposing action to ACE1

Answer 50

- activation of inflammatory cascade and production of proinflammatory cytokines - insulin resistance - promates **cardiac fibrosis** -

Answer 51

Insulin Aldosterone Catecholamines, GH Alkalosis ## Footnote Increased potassium secretion during daylight hours

Answer 52

Hyperkalaemia --> increase K+ into cells, thus H+ out of cells --> acidosis in plasma

Answer 53

- No bicarb in the urine - 90% reabsorbed in PCT - 10% in distal nephrons

Answer 54

Loss of bicarb compensated by increase in Cl- - Severe diarrhoea - Renal failure - Proximal Type 2 RTA Impaired acid secretion: - mod renal impairment - RTA - Typw 1 and 4

Answer 55

Methanol Ureamia DKA Paraldehyde Isoniazid/iron Lactic acidosis Ethylene glycol, ethanol Salicylates CAT Carbon monoxide Aminoglycoside Theopyllines

Answer 56

Distal defect in H-ATPase Normal anion gap/metabolic acidosis urine pH increased >5.5 Causes: - **autoimmune disease** - Sjogrens, RA -* Hypercalciuria as a primary defect* Urine: - increased calcium - reduced citrates - high urine pH = increased risk of nephrolithiasis Hypokalaemia: - lack of H+ excretion for Na, means K+ has to exchange for Na+ - **Metabolic acidosis at PCT --> reduced Na reabsorption** --> aldosterone activation --> increased Na reabsorption in CD *exchange for K+* ## Footnote Hypokalaemia reversed with Nabicarb (alkali) therapy

Answer 57

Proximal Loss of bicarb reabsorption **secondary to Na/H+ pump in PCT** - increased bicarb distally, overwhelms pump - increased excretion of bicarb - **fall in serum bicarb** 12-20 - metabolic acidosiss Causes: Myeloma Fanconi - global PCT dysfunction (so you lose phosphate, glucose, AA, Na, bicarb). Genetic: associated with wilson's. Acquired: **cisplatin, heavy metals** Drugs Urine pH <5.5, rapid rise in pH when serum bicarb is corrected Urine calcium is low **Hypercalcaemia** Hypokalaemia *Treatment with bicarb requires higher dose cf type 1.* increased bicrb diuresis stimulates potassium secretion --> hypokalaemia

Answer 58

Hyperkalaemia Mild normal anion gap metabolic acidosis Causes: - hyporeninemic hypoaldosteronism >**NSAIDs, CNI, chronic interstitial nephritis, DM, acute GN** >ARBs or K+ sparing diuretics >Heparin (toxin to zona glomerulosa cells) >Primary adrenal insufficiency (addison's)

Answer 59

ADPKD (*commonest inherited renal disease*) PKD1 on **Chr16**, PKD2 (Chr 4) OTher: GANB, DNAJB11 PKD1/PKD2: polycystin 1/2 --> ciliopathy **100% penetrance** mostly monoallelic, most mutations are point mutations. nontruncating mutations (33%) 15% don't have family history - de novo, mosaicism, mild disease **PKD1 is more severe thatn PKD2** Kidney function is usually intact till 4th decade 50% reach ESKD by 60 (ESKD is 55 for PKD1 and 75 for PKD2)

Answer 60

- PKD1, truncting mutation - MALE - Early onset of sx - FHx of early ESKD - **Kidney size** - HTN - Proteinuria *(usually absent in PCKD)*

Answer 61

PKD1 have more cysts than PKD2 Cysts can occur in other organs **not associated with RCC** HTN Haematuria Proteinuria (less common) Renal failure Flank pain: >cyst haemorrhage >Cyst infection *(quinolone are good for cyst penetration* >Calculi >UTI Chronic pain sx

Answer 62

Cerebral aneurysm *5% in young 20% in >60* - usually have **MCA** involved - Avoid smoking and BP control is important - Screen high risk pt: MRI without gad or CTA Hepatic cysts: - mod- sev PLD in 15% of ADPKD - More severe in post-menopausal females (**avoid estrogen replacement**) - **hepatomegaly** --> early satiety, reflux, abdo bloating/pain, dypnoea,backpain, ascites, oedema - IVC obstruction/ cholangitis Pancreatic cysts (a/w IPMN) Seminal vesicle cysts Cardiac: **-MVP and AR** - less frequent MR/TR - CM, LVH, diastolic dysfucntion, **AF, coronary aneurysm/dissection**, asymptomatic pericardial effusion - *consider beta blockers* Aortic aneurysm/dissection Colonic and duodenal diverticulae Abdominal wall/inguinal hernia

Answer 63

- enlarged kidneys and bilateral diffuse cysts - MRI is more sensitive - **if no FHx:** > more than **10 cysts** and bilateral enlargement **no Cyst on MRI by 18 excludes dx** If Fhx positive: - <40: >3 cysts total involving both kidneys -*if <5 cysts on MRI by 40 = exclude dx* - 40-59: 2 cyst in each kidney on USS - >60: >4 cysts in each kidneys

Answer 64

- multiple benign simple cysts - Acquired renal cystic dx: dialysis pt - ADTKD (dilation of Med. CD, prog fibrosis, not enlarged, **cortex spared**, bland urine sediment - ARPKD (**PKHD1 gene mutation**), more **severe disease** - TS: can coexist (PKD1 + TSC2 = early ESKD) > angiomyolipoma, skin angiofibromoas, cortical tubers, **astrocytoma**, seizrues, LAM (lymphangioleiomyomatosis), cardiac rhambo, sclerotic bone disease

Answer 65

1. HTN: contributes to GFR decline and CV morbidity. - *BP control **reduced TKV and GFR decline*** - *i**mproves CV mortality** cf non-PCKD CKD* - ACEi/ARB 2. Reduce salt intake (2.3-3 g/day) 3. Increase fluid intake >3L/day - *maintain urine osmolality <280* - *hypotonic urine: helps reduce cyst growth and GFR decline* 4. Lipid control Drugs: 1. Tolvaptan: V2-R antagonist - earlier tx is more beneficial - reduce rate of TKV growth, GFR decline, kidney pain - Effects of eGFR is sustained and cumulative *4 yrs of tx delays dialysis by 1 year* indication: eGFR <90, and deciline >5ml/min/year or 2.5 for 5 years or more Dose: 45mg mane, then 15mg 8hrs later Max: 90mg mane, 30mg afternoon if hypernatraemic: hydrate or reduce dose if hyponatraemia: reduce hydration or increase dose *low osmolar diet* **Often need to drink 5L/day** ADR: - 6-8% decline in eGFR (is ok) - polydipsia, polyuria, nocturia - abnormal LFTs - Hypernatraemia **Contraindication for Tolvaptan**: - baseline hypernatraemia - inability to sense or respond to thirst - Hypovolemia - Concomitant diuretic use - **interacts with CYP3A4**

Answer 66

AL: Daratumumab (CD38), CyBorDex or BMD AA: TNF alpha blocker Hereditary ATTR: Liver transplant WT ATTR: tafamidis - prevents misfolding

Answer 67

Polyomavirus DNA Decoy cells in urine is characteristic Biopsy: - interstitial nephritis, and tubular injury - Viral inclusions in **epithelial cells** - DCT and CD mostly involved Occurs 2-60 month post transplant present with progressive graft dysfunction with no symptoms Graft failure in 45% of affected pts RISK Tac or MMF Recccurent episode of rejection HLA mismatch Men Tx: reduce IS

Answer 68

- tissue - Methylpred for 3 days - Failure to respond: > OKT3 or Antithymocyte depleting ab - +/- increase CNI - PLEX/IVIG/Ritux if antibody mediated - REfractory or recurrent: High dose Tac or MMF

Answer 69

cyclosporin or azathiopurine

Answer 70

Improves QoL Increases life expectancy Return to employment Ability to travel Improves fertility and pregnanct outcome ## Footnote Where as, dialysis has reduced life expectancy, reduced QoL

Answer 71

- For deceased donor transplant: high mortality in the first 100 days **- Live donor is better: graft survival and pt survival; attenuates early mortality risk in elderly pts** - younger pt, greater mortality cf. to gen popn - pre-empttive transplant is associated with best long term outcomes - HLA sensitised patients are difficult to match -CDC>flow>virtual XM (risk of rejection/graft loss) - Single kidney: probable increase in BP, increased risk of ESKD but absolute risk ~0.5% ABO incompatible donors: - higher AR and AMR - comparable outcomes to matched living donors in the long term. **Duration of dialysis pre-tx --> reduced survival post** - death with graft function is the most common cause of graft loss in older people -

Answer 72

- low perioperative risk - Acceptable lifetime risk of ESKD (rememeber that accumulative risk for young people are greater) - pre donation risk --> post donation risk > age, HTN, DM (**absolute contraindication**), BMI, GFR, albuminuria, smoking

Answer 73

Belatacept: Target CD80/86 ligand (preventing signal two) - *it's a CTLA4 attached to IgG Fc)* Induction with Basiliximab or ATG: Basiliximab - Anti CD 25 (IL-2R ab): inhibit T-cell proliferation Maintenance: Prednisone CNI: TAC/cyclosporin Mycophenolate (95%) vs Aza (anti metabolite)

Answer 74

Better survival, GFR at 3yrs, low rate of rejection

Answer 75

- B has less acute rejection and minimal SE - ATG: less acute rejection **high immunological risk group** - Increased risk of infection and malignancty > EBV D+/R- has high risk of PTLD > can use in steroid resistance rejection

Answer 76

- Steroids - CNI - Antimetabolite

Answer 77

- rate limiting enzyme in T-cell proliferation - Inhibit IL2 mediated T-cell proliferation - inherently **nephrotoxic** with long term use - Causes HTN, lipids, **Thrombotic microangiopathy** - (without CNI --> **high rate of rejection and poor graft survival** Remembers ther is **NO bone marrow suppression** - **can use in pregnancy**

Answer 78

TAC is stronger so less rejection and de novo DSA *(results is chronic rejection)* If they have risk of T2DM --> use cyclosporin If they have immunological risk --> tacrolimus ## Footnote Tac: More hypomg/phos, more neurotoxic and tremor Cyclo: more hum hypertrophy, more hirsutism, interaction with drugs ie statin

Answer 79

Inhibits T-cell proliferation in the cell cycle (G1-S) - MMF results in less early rejection MMF/MPA: - inhibits IMPDH involved in purine synthesis - levels lowered by cyclosporin (not Tac) - AE: **Bone marrow suppression** * worsened with the use of valgangciclovir +/- bactrim Myco vs Aza: - less rejection - more diarrhoea -** MMF CI in pregnancy **--> switch to AZA

Answer 80

Less viral infection Less renal toxicity Less malignancy Less neutropenia and diarrhoea More rejection and discontinuation rate

Answer 81

Early: CVD, Infection, Cancer Late: Cancer, CVD, infection

Answer 82

Early (<1yr): graft thrombosis, rejection, GN Late: Chronic allograft nephropathy > Chronic antibody mediated rejection - Early unresolved rejection - Non adherence - De novo DSA (esp class 2 DQ) GN

Answer 83

- delayed graft function - mostly due to ischaemic ATN >RF: deceased donor, donor AKI, Donor age, DCD, cold ischaemia time >24h, mode of dialysis Other causes other than ATN: - Thrombosis - not salvageable, USS /MAG-3 scan - Obstruction/urine leak - Rejection (biopsy 1 week after) - Early recurrence

Answer 84

DGF Rejection Vascular- thrombosis Obstruction

Answer 85

Rejection Drugs (CNI toxicity) Obstruction Infection Recurrence of underlying GN

Answer 86

Volume depletion Drugs Rejection Obstruction Recurrence - earluy: FSGS, aHUS, MPGN, ANCA - Late: IgAN, MbN, MPGN RAS De novo

Answer 87

- either cell mediated (T-cell) or Ab mediated or mixed - Rising creatinine - rejection until proven otherwise (BIOPSY) RF: Prev. HLA sensitisation Pre-tx ab against donor - ABO, HLA, non-HLA - Younger pt, older donor - Ischaemia time, DGF - HLA mismatch (More MM, the worse graft survival, DQ MM is important) Treatment: 1. TCMR: - methylpred - ATG if steroid resistant 2. AbMR - PLEX - IVIG - +/- Rituximab Prophylaxis: PJP CMV Rejection without return baseline --> affects survival

Answer 88

most common opportunistic infection - associated with increased mortality - **increased risk with D+, R- status and degree of IS** Proph vs pre-emptive: - D+/R-: prophylaxis for 6 months - D-/R+ or D+/R+: 3 months - D-/R-: no proph unless ATG used for induction Tx: - Valgang is good for both prophylaxis and tx (2x) - Gang for severe or poor GI absorption - if resistant: **UL97 mutation** - --> **Foscarnet or cidofovir** *foscarnet inhibits viral specific DNA polymerase*

Answer 89

**NHL, Kidney, Melanoma** Cancer death in tx pt: NHL, lung, colorectal

Answer 90

**Met. SCC** - common cancer related death in post tx Avoid AZA

Answer 91

HLA is coded on **chr 6** **DR>B>A**

Answer 92

- RR of kaposi sarcoma is very high (400-500) - post tx lymphoproliferative dx - Bcell monoclonal, EBV associated, relflects over IS. - **diabetes **: 10-15% at 1 year > increased graft failure and increased mortality > infrequently develops nephropathy > More potent pred. of graft failure than AR Smoking 2x risk of graft loss and 50% overall survival BP affects graft survival Obesity: surgical complication, DGF, increased mortality and poor graft survival common cause of early graft loss is non-adherence

Answer 93

it's angiotension mediated so tx with ACEi or ARBs

Answer 94

- hypomagnesemia: CNI renal wasting - hypophosphataemia: diuresis, increased PTH or FGF 23, which increases phosphate excretion

Answer 95

- ATN: normal perfusion, slow wash out and persistent isotope accumulation - Hyperacute rejection: no perfusion - Cyclosporin toxicity: prolonged clearance

Answer 96

Urinary factors: High urine calcium High urine oxalate Low urine citrate Low pH – e.g. chronic diarrhoea with HCO3 loss Dietary: Low calcium intake High oxalate intake High animal protein intake Low potassium intake High sodium intake Lower fluid intake Other: previous hx of stones, FHx, those with increased enteric oxalate absorption (malabsorption post-bariatric surgery), drugs (acyclovir), diabetes/obesity/gout/HTN

Answer 97

Renal involvement is common Proteinuria>haematuria Female and black people WHO classification class I: normal kidney class II: mesangial glomerulonephritis class III: focal (and segmental) proliferative glomerulonephritis class IV: diffuse proliferative glomerulonephritis class V: diffuse membranous glomerulonephritis class VI: sclerosing glomerulonephritis **Class IV (diffuse proliferative glomerulonephritis)** is the most common and severe form. Renal biopsy characteristically shows the following findings: - glomeruli shows **endothelial and mesangial proliferation, 'wire-loop' appearance** - if severe, the **capillary wall may be thickened** secondary to immune complex deposition - electron microscopy shows s**ubendothelial immune complex deposits** - **granular appearance on immunofluorescence**

Answer 98

Everyone should be on HCQ IS for active III/IV - Steroid + MMF or CYC - Maintenance: MMF or AZA V: - RAAS blockade, HCQ, BP optimise - IS if nephrotic range proteinuria

Answer 99

Everyone should be on HCQ IS for active III/IV - Steroid + MMF or CYC - Maintenance: MMF or AZA V: - RAAS blockade, HCQ, BP optimise - IS if nephrotic range proteinuria

Answer 100

1. Mutation in factor H predom. C-terminal 2. autoantibody bind to C terminal epitope 3. C3 mutation prevents factor H binding >50% have an underlying mutation, then get an environmental second hit Tx: Eculizumab - high risk of meningococcal infection thus vax and abx for first 2 weeks of treatment PLEX **Avacopan** is a complement** 5a receptor (C5aR) antagonist** that blocks C5a-induced upregulation of C11b (integrin alpha M) on neutrophils and inhibits C5a-mediated neutrophil activation and migration. - used in ANCA +ve vasculitis

Answer 101

abnormality in Ca, PO4, PTH, FGF23, Klotho and Vit d metabolism Ab bone turnover, mineralisation and linear growth or strength Each biochemial abnormality is associated with high mortality rate due to CVS MBD develops as early as Stage 2 CKD Klotho is lost, FGF23 is raised (**associated with mortality)** bone formation is reduced and vascular calcification develops **Phosphate:** - doesn't rise til later on as FGF23 and PTH maintain PO4 excretion ** Pattern of Bone dx:** - Osteitis fibrosa cystica - high turnover mediated by PTH - Adynamic bone disease - low turnover - *higher # risk and ectopic calcification cf high turnover dx* - Osteomalacia: low turnover with abnormal mineralisation - Mixed **treatment**: - Control phosphate - Maintain calcium - lower PTH (once >2x ULN): > - Calcitriol usually given when PTH >50, aiming to turn off the PTH production. no effect on outcome > Calcimimetics (cinacalcit) - once started need to continue forever. *Cinacalcet directly lowers parathyroid hormone levels by increasing the sensitivity of the calcium sensing receptors to activation by extracellular calcium, resulting in the inhibition of PTH secretion. The reduction in PTH is associated with a concomitant decrease in serum calcium levels.* > Surgery: - complication post op: hungry bone: hypocalcemia, hypophosphataemia, hypomg, - K+ may go up

Answer 102

- increases all cause mortality - lower GFR and albuminuria are independent RF for **CVD and mortality ** - non-traditional RF for CVD in CKD: > Vascular calficification due to bone mineral metabolism abnormality > Uraemia > Inflammation ## Footnote RF: age, DM, HTN, ethinicity, F - CKD, M- ESKD, FHx, obesity, episodes of AKI

Answer 103

improvement in decline in RF, ESKD and renal or CV death Improvement in all cause mortality and CVD and hosp. from HF Independent of DM status

Answer 104

Excess mortality

Answer 105

Most potent predictor of ESKD *not in PCKD ACEi/ARB similar affect MRA added to RAS blockade improves proteinuria Reduction in proteinuria slow GFR decline Independent RF for CVD

Answer 106

Wouldn't start statin on pt on HD - no change in mortality - high PO4, low calcium, high PTH and high FGF23 are all independently associated with increased mortality

Answer 107

Salt intake <2.5g, 100mmol/day

Answer 108

- reduce renal reabsorption of PO4, increase bone turnover, increase FGF23, increase 1,25 Vit-D

Answer 109

increases renal reabsorption of PO4 and gut absorption, increase FGF23 production, and reduced PTH release

Answer 110

reduce renal reabsorption, reduce 1,25 VitD, reduce PTH

Answer 111

produced by osteoclast and osteoblasts in response to increase PO4, increase PTH, increase Vit D less in response to high calcium FGFR/Kloth *co-receptor*: in PCT and, DCT, PTH gland - In the PCT: inhibits Na/Phosphate --> phosphaturia - inhibit 1,25 Vit D by inibiting alpha 1 hydroxylase and stimulating 24 hydroxylase (catabolic) - directly inhibits PTH secretion Klotho is produced in the kidney, this in CKD, FGF23 is unable to inhibit PTH production due t lack of **klotho**

Answer 112

- DEXA not validated - difficult to diagnose - Treat CKD-MBD first - anti-resorptive therapy may increase risk of # (in animal model)

Answer 113

**Causes** * idiopathic * secondary to other renal pathology e.g. IgA nephropathy, reflux nephropathy * HIV * heroin * Alport's syndrome * sickle-cell **renal biopsy**: focal and segmental **sclerosis and hyalinosis** on light microscopy **effacement of foot processes on electron microscopy**

Answer 114

NPHS1 – nephrin

Answer 115

NPHS2 – podocin TRPC6 Do not respond to steroids

Answer 116

Primary shows **diffuse** foot process effacement, where as secondary shows focal/segmental

Answer 117

Up to two thirds patients with **FSGS **have elevated levels of Renal disease only occurs when sufficient circulating suPAR **activates podocyte β3 integrin** causing foot process effacement, proteinuria and FSGS like glomerulopathy ## Footnote Immature myeloid cells produce suPAR

Renal Flashcards

(144 cards)