Interstitial nephritides and nephrotoxins

Question 1

What is the pathology behind acute interstitial nephritis AIN?

Answer 1

Immune reaction to drugs, infections and autoimmune disorders.

Drugs - NSAIDs, antibiotics, diuretics, allopurinol, omeprazole, phenytoin,

Infections - Staphs, Streps, Brucella, Leptospira, some viruses

Immune disorders - SLE, Sarcoidosis

Question 2

What are the features of AIN?

Answer 2

• Mild renal impairment
• Raised BP / oliguria are uncommon
• Drug reactions - often with an allergic picture of fever, rash, peripheral eosinophilia
• Biopsy shows inflammatory cell infiltrate in the interstitium.

Question 3

How is AIN treated?

Answer 3

Stop / treat causative agent.

If renal function doesn’t improve within 1 week - Prednisolone 1mg/kg/24hr for 4 weeks (controversial)

Question 4

What is the picture with chronic interstitial nephritis CIN?

Answer 4

Common in disorders the display abnormal anatomy e.g. reflux nephropathy, cystic kidney disease.

Much less common in normal kidneys.

Analgesia nephropathy is the most common cause, along with other drugs and toxins. Autoimmune causes are rarer.

Often seen in haematological conditions such as myeloma, light chain disease and sickle cell disease.

Question 5

What is analgesic nephropathy?

Answer 5

• Used to be more common
• History or chronic, heavy analgesic use, usually NSAIDs.
• Patients may complain of loin pain (papillary necrosis)
• More often it is silent, until late CKD
• Urine can show sterile pyuria and mild proteinuria but ma be normal
• USS shows small irregular kidneys
• ‘cup and spill’ appearance on IVU Intravenous urography
• sudden flank pain may signify obstruction from a sloughed papilla
• increased risk of atherosclerosis

Question 6

What plant and alternative medicine chemical can lead to interstitial nephritis?

Answer 6

Aristolochic acid:

• Causes CIN in geneticall susceptible individuals.
• Effects are often delayed

Question 7

Which crystal commonly causes a nephropathy?

Answer 7

Urate:
Acute: AKI due to uric acid precipitation within tubules, most often due to tumour lysis syndrome, seen in haematological malignancies with chemotherapy.
- renal parenchyma appears bright on USS
- Plasma urate is often markedly raised. Urinary bifringent crystals on microscopy
- best treatment is prevention, allopurinol before chemo, keep hydrated
-
Chronic: Much reduced incidence with improved diet and earlier treatment of gout with allopurinol

Question 8

What is the role of calcium kidney disease?

Answer 8

Hypercalcaeima causes AKI no matter the cause.

Reduce the calcium acutely with hydration and bisphosphonates.

Ultimately treat the underlying cause (myeloma, sarcoid, malignancy, nephrocalcinosis etc.)

Question 9

What happens with radiation and the kidneys?

Answer 9

Radiation nephritis -

- Occurs acutely (

Question 10

List 13 nephrotoxins.

Answer 10

1) Analgesics - NSAIDs
2) Antimicrobials - gentamicin, sulphonamides, penicillins, rifampicin, amphotericin, aciclovir
3) Anticonvulsants - Lamotrigine, valproate, phenytoin
4) Other drugs - omeprazole, furosemide, thiazides, ACE-i, + ARBs, cimetidine, lithium, iron, calcineurin inhibitors, cisplatin
5) Anaesthetic agents - methoxyflurane, enflurane
6) Radiocontrasts material
7) Crystals - urate
8) Toxins - aristolochia, cadmium, lead, arsenic, ethylene glycol
9) Haemoglobin in haemolysis, myoglobin in rhabdomyolysis
10) Proteins - IgGs in myeloma, light chains
11) Bacteria - streptococci, legionella, brucella, mycoplasma, chlamydia, TB, salmonella, campylobacter
12) Viruses - EBV, CMV, HIV, polyoma virus, adenovirus, measles
13) Other pathogens - leptospirosis, syphilis, toxoplasma, leishmania

Question 11

What happens with aminoglycasides and the kidney?

Answer 11

Gentamicin, amikacin, streptomycin:

All give a mild non-oliguric AKI, typically 1-2 weeks into treatment.

Exacerbated by other renal risk factors.

Aminoglycasides can be as effective in a bolus administration as in multiple doses, and less reno-toxic

Question 12

What is the most important point to remember regarding radio contrast nephrotoxicity?

Answer 12

Prevention is the best form of treatment.

Stop other nephrotoxic drugs peri-procedure, hydrate.

Question 13

What is the main points to remember regarding rhabdomyolysis and nephrotoxicity?

Answer 13

• Muscle breakdown releases not only myoglobin but K, phosphate, urate and creatinine kinase.
• Myoglobin obstructs renal tubules.
• Causes are multiple but include trauma, ischaemia, seizures, toxins, infections, inherited muscle disorders.
• Remember red / brown urine. Muscle pain,
• Test plasma CK (>1000), and exclude MI with Trop T
• Note no red blood cells in urine.
• AKI arises 12-24 hrs later and DIC is a complication

Treat high K, hydrate until myoglobin has passed through, sodium braced is used to alkalise the urine.