Systemic diseases affecting the kidneys

Question 1

How to diagnose systemic diseases affecting the kidneys

Answer 1

U&Es – often first indication there is a renal problem – high creatinine.

Urine output
History and examination

Review previous results

Dipstick urinalysis – blood? Protein?

Quantitative proteinuria (uPCR)

Other blood tests: Non-specific: albumin, Diagnostic: special antibodies and other proteins, eosinophils

Imaging – help/rule out diagnosis. Possibly biopsy them

Question 2

Definition of renal artery stenosis

Answer 2

narrowing of the renal artery, caused by atherosclerosis or fibromuscular dysplasia

Question 3

Causes of renal artery stenosis

Answer 3

90% - Atherosclerosis -think elderly patients

10%- think fibromuscular dysplasia - young and women

Question 4

Diagnosis of renal artery stenosis

Answer 4

Doppler ultrasound - few risks

CT/Angiography- sensitive. However it causes contrast nephropathy and risk of embolic disease

Magnetic Resonance Imaging- also very sensitive but associated with nephrogenic fibrosing dermopathy - associated with the use of Gadolinium.

Co2 angriography- used but does have a risk of renal embolism

The stenosis in this case had completely obscured the blood supply to one kidney (shrunken) and had was putting increased pressure on the remaining kidney

Question 5

Pathogenesis of renovascular disease

Answer 5

Progressive narrowing of renal arteries with atheroma

Perfusion falls by 20%: GFR falls but tissue oxygenation of cortex & medulla maintained&raquo_space;

RA stenosis progresses to 70%: Cortical hypoxia causes microvascular damage and activation of inflammatory and oxidative pathways &raquo_space;

Parenchymal inflammation and fibrosis progress and become irreversible:

Restoration of blood flow provides no benefit.

Question 6

Management of RAS

Answer 6

• There is no benefit in surgical revascularisation over medical therapy, as it is a specific consequence of systemic diseaseno improvement on life and BP
• Medical: Blood pressure control- drugs (Stop ACEi, Avoid ACEi and ARBs in future) and salt restriction. Statin. If diabetic, good glycaemic control.
• Lifestyle: Smoking cessation, Exercise, low sodium diet.
• Radiologically- limited indications, only in: Rapidly deteriorating renal failure, uncontrolled hypertension on multiple treatments or Flash pulmonary oedema.

Question 7

Myeloma in the kidneys outcome

Answer 7

Outcome- based on the renal serum creatinine, the higher the worse the prognosis:
o 80% if sCr 500

Question 8

Presentation of myeloma in the kidney

Answer 8

• Acute Renal Failure: Dehydration, Hypercalaemia, Hyperuricaemia, Cast nephropathy and Acute tubular necrosis (ATN)
• Proteinuria/nephrotic syndrome: AL amyloid and LC deposition disease
• CKD: AL amyloid, Cast nephropathy and Ig deposition disease
• Tubular dysfunction: Fanconi syndrome- disease of the PCT and reduced reabsorption of glucose, bicarbonate etc.

Question 9

Pathogenesis of ARF in myeloma - cast nephroapthy

Answer 9

• Light chains are normally freely filtered through the glomerulus and be resorbed easily but when there is overproduction it can overload this system and cause toxic injury to the PCT
• Then in the thick ascending limb of the LoH, the LC combined with Tamm-Horsfall protein to produce Cast – plug in the tube.
• These casts lead to cast injury
• Process is aggravated/accelerated by: hypercalcaemia, diuretics, dehydration

Question 10

Management of myeloma ARF

Answer 10

• Correct reversible causes:
o ECF volume depletion using IV fluids
o Hypercalcaemia by IV fluids, IV bisphosphonates (pamidronate)
o Hyperuricaemiaallopurinol

Dialysis

Treatment of myeloma-remitting disease

Transplantation-BM, Kidney

Question 11

Amyloidosis definition

Answer 11

Deposition of insoluble proteineous material in Exctracellular spaces E.g. kidney, heart, liver, gut

Specific ultrastructural features: 7.5-10nm linear aggregated fibrils of variable length forming a felt like structure made of beta-pleated sheets.
• Affinity for the constituents of the capillary wall
a

Question 12

Two causes of amyloidosis

Answer 12

Two common classes:

AA=systemic amyloidosis
-inflammation (prev from chronic pyogenic or granulomatous infections – TB and familial Mediteranean fever)

AL=Ig LC (lambda>kappa), 12:1 if renal impairment-Myeloma

Question 13

Treatment of amyloid

Answer 13

• AL amyloid- mephalan, steroids, thalidomide, cyclophosphamide, lenalidomide, bortezomib
• AA amyloid- control underlying infection/inflammation, surgery, anbxs, cytotoxics, biological for RA, colchicine

Question 14

Diagnosis of amyloid

Answer 14

• Congo-red stain: shows apple green birefringence

* Amyloid fibrils: cause mesangial expansion

Question 15

SLE patho in kidneys

Answer 15

Auto-immune disease- immune complex mediated glomerular disease

Multiple antibodies directed against DNA, histones, snRNPs, transcriptional/translational machinery

Autoantibodies are filtered through the kidneys and causes a glomerular disease

Question 16

Clinical features of SLE in kidneys

Answer 16

proteinuria, nephrotic syndrome, macroscopic/microscopic haematuria and reduced renal function

Question 17

Treatment of SLE induced GN

Answer 17

• Non-specific
• BP control
• Immunpsuppression Induction (streiods/cyclophosphamide)
• Maintenance axathioprine, MMF

Question 18

Scleroderma and the kidneys

Answer 18

Scleroderma kidney disease usually presents as new systemic hypertension that may be asymptomatic. Evidence suggests that renal blood vessels suddenly constrict (Raynaud’s phenomenon of the kidney), dropping blood flow to the body or cortex of the kidney. Left untreated, the low blood flow leads to tissue damage and kidney failure. This reversible problem was the leading cause of death in scleroderma before new treatment was discovered

Question 19

Treat scleroderma kidneys disease with

Answer 19

Patients with hypertension should be treated as a medical emergency with rapid assessment of renal function (urinalysis and blood testing) and control of any blood pressure elevation with an angiotensin converting enzyme (ACE) inhibitor. Patients with evidence of renal crisis often need to be hospitalized to order to monitor blood pressure and renal function closely and to titrate medications