NephrologyTier 1Disease (DEADMAN)

Minimal change disease

Description

Nephrotic syndrome with a normal glomerulus on light microscopy
- The only abnormality is diffuse podocyte foot process effacement on EM
Abrupt onset, highly steroid-responsive, does not scar
*MCD and FSGS are probably a spectrum - a 'MCD' that is steroid-resistant is often unsampled FSGS*

The characteristic clinical signature

Children: 80-90% of nephrotic syndrome (peak 2-6 yrs, M:F 2:1)
- So steroids are given empirically without biopsy
Adults: ~10-15% of nephrotic syndrome; second peak >60 yrs
In adults over 60, look hard for a secondary cause - NSAIDs, haematological malignancy

A podocytopathy - the circulating factor and the T-cell hypothesis
- Historically attributed to a T-cell-derived permeability factor ('MCD is a disorder of T cells')
- Anti-nephrin autoantibodies are detectable in the majority of adults and children with active MCD and fall with remission - the strongest current candidate for the pathogenic mechanism
- This explains the striking rituximab response
Loss of the charge and size barrier -> selective albuminuria with normal-sized glomeruli
No immune deposits (IF negative), no complement activation, no scarring - hence preserved renal function

Secondary causes - exclude in every adult

Drugs - NSAIDs (with concurrent AIN), lithium, interferon, gold, penicillamine, checkpoint inhibitors, pamidronate
Malignancy - Hodgkin lymphoma (the classic association), other lymphoproliferative disease, thymoma
Infection - syphilis, HIV, TB, mycoplasma, schistosomiasis
Atopy and allergy - insect stings, food allergy, pollen; ~30% of paediatric cases have atopy
Post-vaccination, post-viral triggers

Clinical

Rapid onset of heavy oedema, frothy urine, weight gain over days-weeks
BP usually normal; microscopic haematuria in ~20%; eGFR normal
- AKI in ~20-25% of adults - from intravascular depletion, interstitial oedema, or concurrent NSAID-induced AIN

Bloods and urine

Biopsy

Children: NOT required before an empirical steroid trial
- Biopsy if: age <1 or >12 yrs, steroid resistance, macroscopic haematuria, hypertension, low complement, renal impairment
Adults: biopsy everyone
LM: normal glomeruli (may show tubular fat droplets - 'lipoid nephrosis')
IF: negative (mesangial IgM/C3 may be present - 'IgM nephropathy', more relapse-prone)
EM: diffuse (>80%) foot process effacement - the diagnostic finding
Sampling matters: a segmental sclerotic lesion in a deep juxtamedullary glomerulus reclassifies it as FSGS

Definitions that drive every subsequent decision

Term	Definition
Complete remission	Proteinuria <0.3 g/day, normal albumin
Relapse	Proteinuria >3.5 g/day (or dipstick 3+ x3 days) after remission
Frequently relapsing	>=2 relapses in 6 months, or >=4 in 12 months
Steroid-dependent	Relapse during taper, or within 2 weeks of stopping
Steroid-resistant	No remission after 16 weeks of adequate steroids (re-examine the biopsy - usually FSGS)

First episode

Prednisolone 1 mg/kg (max 80 mg) daily, or 2 mg/kg alternate-day (max 120 mg)
- Continue at full dose for at least 4 weeks after remission is achieved, then taper over 3-6 months
- Children remit in ~2 weeks; adults are slower - many take 8-16 weeks. Do not declare resistance before 16 weeks
>80-90% achieve complete remission

Relapse

Infrequent relapse -> repeat the steroid course
Frequently relapsing or steroid-dependent -> a steroid-sparing agent, because the cumulative steroid toxicity becomes the dominant problem

Steroid-sparing agents

Rituximab - increasingly first choice; especially valuable where further glucocorticoid exposure is unacceptable (after an osteoporotic fracture, diabetes, psychiatric effects, growth impairment in children)
- Highly effective at maintaining remission; consistent with the anti-nephrin mechanism
Cyclophosphamide 2 mg/kg PO for 8-12 weeks - highest chance of durable drug-free remission; one course only, gonadal toxicity and malignancy risk
Calcineurin inhibitor (tacrolimus or ciclosporin) - effective but high relapse rate on withdrawal; nephrotoxic long-term
Mycophenolate - less effective, better tolerated; useful in children
Levamisole in children where available

Supportive

Loop diuretic + salt restriction for oedema; cautious - intravascular volume may be low
ACEi/ARB - useful in resistant disease; less central than in FSGS/membranous because remission is usually rapid
Statin while nephrotic
Thromboprophylaxis if albumin <20-25 g/L - VTE risk lower than membranous but present
Vaccination (pneumococcal, influenza); no live vaccines on immunosuppression
Bone protection, PJP prophylaxis on prolonged high-dose steroid

Hodgkin lymphoma - the classic paraneoplastic association; also non-Hodgkin lymphoma, CLL, thymoma
NSAIDs - MCD with concurrent acute interstitial nephritis
Lithium, interferon, gold, penicillamine, pamidronate, immune checkpoint inhibitors
Atopy - eczema, asthma, allergic rhinitis, insect stings, food allergy
Infection - syphilis, HIV, TB, mycoplasma, schistosomiasis
HLA-DQA1/DQB1 associations; NPHS1 (nephrin) as the antigen
FSGS - the same disease spectrum; steroid resistance should prompt re-review

The best prognosis of any nephrotic glomerular disease - ESKD is rare
>80-90% remit with steroids; but 50-75% relapse, and 10-25% become frequently relapsing or steroid-dependent**
Relapse frequency falls with age; most children outgrow it by adolescence
Steroid responsiveness is the single best prognostic marker - responders essentially never reach ESKD
Steroid-resistant disease behaves like FSGS: progressive, ~50% ESKD at 10 years

Complications

Infection - spontaneous bacterial peritonitis and cellulitis with encapsulated organisms (urinary IgG and factor B loss); the historical cause of death
VTE and renal vein thrombosis
AKI - hypovolaemia, over-diuresis, interstitial oedema, NSAID-related AIN
Cumulative corticosteroid toxicity is the main long-term harm - growth suppression, osteoporosis and fracture, cataract, diabetes, obesity, avascular necrosis, psychiatric effects
- This, not the kidney, is what drives the move to steroid-sparing agents
Hyperlipidaemia and accelerated atherosclerosis while nephrotic

6 more sections, plus exam facts

Premium unlocks every note across every specialty, and the full exam fact library behind it.