Systemic diseases and the kidney Flashcards
Diabetic Nephropathy 5 stages
Stages of diabetic nephropathy
1. Renal hypertrophy and glomerular hyperfiltration: GFR may be 20-50% above normal.
2. Normalisation of GFR with early histological changes: clinically silent disease.
3. Microalbuminuria (albumin level in urine is detectable by laboratory testing but not by urine dip
[<300mg/24h; albuminuria – albumin excretion >300mg/day] or urine albumin/creatinine ratio <30mg/mmol), commonly accompanied by hypertension.
Persistent microalbuminuria:
* Typically develops 5–15 years following diagnosis of Type 1 diabetes and is prevalent in 40% of
patients after 30 years of diagnosis.
* Is present in a quarter of patients with Type 2 diabetes 10 years after diagnosis.
4. Overt diabetic nephropathy: increasing proteinuria, falling GFR.
5. ESRF.
Pathologic hallmarks of diabetic kidney disease on renal biopsy
Pathological hallmarks of diabetic kidney disease on renal biopsy are:
* Nodular intercapillary sclerosis (Kimmelstiel-Wilson nodules) or diffuse glomerular sclerosis.
* Mesangial expansion and GBM thickening.
* Interstitial fibrosis and atherosclerosis and arterial/arteriolar hyalinosis.
Management of microalbuminuria in diabetes
- The threshold for microalbuminuria is >2.5mg/mmol in men and >3.5mg/mmol in women.
- If microalbuminuria is detected, tests should be repeated within 3-4 months; microalbuminuria is
confirmed if two of three specimens are positive in the absence of an alternative diagnosis e.g.
urinary tract infection. - Microalbuminuria requires further investigation if there is: hypertension which is resistant to
treatment, heavy proteinuria (albumin creatinine ratio > 100 mg/mmol), haematuria, rapid deterioration of GFR, or the patient is systemically unwell.
Alternative aetiology is likely if microalbuminuria occurs in absence of retinopathy.
Renoprotective strategies in diabetic nephropathy to slow down progression of disease
- Strict BP control: this is the key intervention, with a target of <130/80 mmHg; tighter target of < 120/75 in patients with proteinuria >1g/day).
Blockade of the renin-angiotensin system with either ACE inhibitors or ARBs has anti-proteinuric and renoprotective effects, independent of controlling the BP. - Strict glycaemic control, which also helps prevent development of proteinuria and clinically evident diabetic nephropathy in patients up to CKD Stage 31
- Reduction of cardiovascular risk: (as with other forms of CKD) through smoking cessation, weight management, increasing activity and managing dyslipidaemia.
SLE - lupus nephritis
Classification
Diagnosis requires kidney biopsy
◆ Class I: Mesangial deposits identifiable on electron microscopy (‘minimal mesangial lupus
nephritis’).
◆ Class II: Mesangial proliferative lupus nephritis.
◆ Class III: Less than 50% of glomeruli involved (‘focal lupus nephritis’).
◆ Class IV: Greater than 50% of glomeruli involved (‘diffuse lupus nephritis’).
◆ Class IV-S: Less than 50% of glomerular surface area involved (‘diffuse segmental lupus nephritis’).
◆ Class IV-G: Greater than 50% of glomerular surface area involved (‘diffuse global lupus nephritis’).
◆ Class V: Deposits in the subepithelium (‘membranous lupus nephritis’).
◆ Class VI: Greater than 90% glomerular damage (‘advanced sclerosing lupus nephritis’).
Management of severe lupus nephritis
High dose corticosteroids
Cyclophosphamide
MMF
Aza
Systemic vasculitis with renal involvement
Small vessel vasculitides
- Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis:
a. GPA (formerly called Wegener’s granulomatosis).
b. Microscopic polyangiitis (MPA).
c. Renal-limited vasculitis.
d. Eosinophilic granulomatosis with polyangiitis (formerly called Churg–Strauss syndrome). - Henoch-Schönlein purpura.
- Cryoglobulinaemic vasculitis.
Systemic vasculitis with renal involvement
Medium vessel vasculitides
Polyarteritis nodosa
Polyarteritis nodosa (PAN) is a vasculitis affecting medium-sized arteries with necrotizing inflammation leading to aneurysm formation. PAN is more common in middle-aged men and is associated with hepatitis B infection.
Features of PAN
Features
fever, malaise, arthralgia
weight loss
hypertension
mononeuritis multiplex, sensorimotor polyneuropathy
testicular pain
livedo reticularis
haematuria, renal failure
perinuclear-antineutrophil cytoplasmic antibodies (ANCA) are found in around 20% of patients with ‘classic’ PAN
hepatitis B serology positive in 30% of patients
ANCA associated vasculitis
Distinguish between c-anca and p-anca
ANCAs are directed against intracellular antigens, and are classically differentiated on immunofluorescence according to binding patterns, which are either cytoplasmic (C-ANCA) or perinuclear (P-ANCA)
- C-ANCA is usually directed against neutrophil and monocyte proteinase 3 (PR3).
- P-ANCA is usually directed against myeloperoxidase (MPO).
ANCAs are probably directly pathogenic, causing activation of neutrophils and monocytes, and endothelial injury.
Renal histopathology in all ANCA-associated kidney disease
typically shows a focal segmental necrotising crescentic glomerulonephritis. Granulomata may also be present. Immunofluorescence or immunohistochemistry is classically pauci-immune (lack of immune deposits), unlike conditions such as anti-GBM disease and lupus nephritis.
Management of ANCA kidney disease
Induction of remission is achieved with high-dose steroids and a cytotoxic agent (usually cyclophospha- mide).
Maintenance treatment is with azathioprine after a minimum of 3 months if remission has been achieved.
Anti-CD20 monoclonal antibody (rituximab) is an alternative to cyclophosphamide in select patients. Plasma exchange is also used at the outset if there is AKI with serum creatinine >500 μmol/L or requiring dialysis, or concomitant pulmonary haemorrhage. Without treatment, AAV has a high mortality.
In myeloma cast nephropathy what is the name of the protein causing pathology?
Tamm Horsfall protein - freely filtered immunoglobulin light chains complex with uromodulin
Primary vs secondary amyloidosis
The abnormal protein that binds serum amyloid P protein can be a monoclonal light chain, causing primary (AL) amyloidosis, or a serum amyloid A protein, causing secondary (AA) amyloidosis
Renal involvement in amyloidosis usually manifests as nephrotic syndrome.
Renal biopsy shows amorphous deposits in glomerular mesangial and capillary walls, with orange-red staining with Congo red, which shows apple-green birefringence with polarised light. Immunohistochemistry can distinguish between AL and AA amyloidosis.
Scleroderma and renal disease
Features of renal crisis
Up to 50% of patients with systemic sclerosis have renal disease in the form of reduced GFR, proteinuria or hypertension.
Usually benign course of kidney disease
Microangiopathic haemolytic anaemia, hypertensive encephalopathy or heart failure can also occur in association with the hypertension.
