Tubulo-interstitial Disease Flashcards
What is tubulo-interstitial disease?
-Primarily affect the renal tubules and interstitial components of the renal parenchyma.
-Characterised by tubular dysfunction with electrolyte abnormalities, moderate levels of proteinuria and varying degrees of renal impairment.
-Often the urinary output may be relatively preserved for any given GFR, and indeed there may be polyuria and nocturia due to loss of concentrating ability in damaged tubules.
What is acute interstitial nephritis?
-Immune-mediated disorder, characterised by acute inflammation affecting the tubulo-interstitium of the kidney.
-It is commonly drug-induced, typically due to antibiotics and proton pump inhibitors (PPIs), but can be caused by other toxins, and can complicate a variety of systemic diseases and infections
=25% drug-induced AKI
-Often clinically silent
-Reduction in renal function over weeks to months
-Urine output often preserved, paradoxically may have polyuria/nocturia
-Usually euvolaemia, normotensive
-Urinalysis bland, but may see leukocytes
-May have eosinophilia
-Unlike ATN, which is caused by ischaemic or toxic injury, interstitial nephritis is an idiosyncratic allergic response, typically to drugs such as antibiotics (penicillins, cephalosporins), NSAIDS or proton pump inhibitors.
Causes of acute interstitial nephritis (mnemonic AIN)
-ALLERGIC
=commonly a reaction to a drug. If it does not improve quickly after stopping the drug, this often responds to treatment with steroids. Acute rejection of transplant looks same
-IMMUNE
=Autoimmune nephritis +/- uveitis (with inflammation of eyes= TINU syndrome meaning tubulointerstitial nephritis and uveitis)
==Sjogren’s syndrome (eyes and mouth dry), sarcoidosis (inflammation in the lungs, and with a high level of calcium in the blood)
==SLE
==Sarcoidosis
=Transplant rejection
-INFECTIONS!!
=Acute bacterial pyelonephritis
=Leptospirosis (bacteria)
=Tuberculosis
=Hantavirus
-NOXIOUS/ TOXINS
=Myeloma light chains (cast nephropathy)- autotoxins
=Mushrooms (Cortinarius)
-Drugs
=Penicillins
=Rifampicin
=NSAIDs
=Allopurinol
=Furosemide
=PPI
=Mesalazine (delayed)
Clinical features of acute interstitial nephritis
-AKI
-Rapid deterioration in renal function.
=AIN should always be considered in patients with non-oliguric AKI.
-Drug-induced AIN: signs of a generalised drug hypersensitivity reaction. Eosinophilia occurs in 20%–30% of cases, so its absence does not rule out AIN, but its presence should prompt a drug history.
-Proteinuria is generally modest (PCR <100 mg/mmol
-The urine may contain white blood cells and white cell casts but is sterile on culture!
=Leucocytes are commonly present on urinalysis.
-Fever, rash, arthralgia, mild renal impairment, hypertension, normal or polyuria
Investigations in AIN
-Renal biopsy is usually required to confirm the diagnosis
= intense inflammation, with infiltration of the tubules and interstitium by lymphocytes (connective tissue between renal tubules)
=Marked interstitial oedema
=The presence of eosinophils may suggest drug-induced AIN and a predominant neutrophil infiltration suggests infection.
=Often granulomas may be evident, especially in drug-induced AIN.
=The degree of chronic inflammation in a biopsy is a useful predictor of long-term renal function.
=Eosinophiluria may be present but is not a good discriminator for AIN.
-Eosinophilia, urine cultures, Ca (sarcoid)
- Here the urinalysis typically shows no or minimal blood and protein, but may be positive for leucocytes.
Management of AIN
-Some patients with drug-induced AIN recover following withdrawal of the drug alone, but high-dose glucocorticoids (prednisolone 1 mg/kg/day) may accelerate recovery and prevent long-term scarring.
-Other specific causes should be treated, if possible
-Drugs – stop offending drug- consider steroids to accelerate resolution
-Infections – antibiotics
-Immune – immunosuppress
-Sarcoidosis - steroids
What is chronic interstitial nephritis?
-Characterised by renal dysfunction.
-It may follow on from AIN that does not resolve, or may be associated with ingestion of various toxins and drugs, particularly those taken chronically, such as lithium or non-steroidal anti-inflammatory drugs (NSAIDs).
-Associated with metabolic and chronic inflammatory diseases
-In many patients, CIN presents at a late stage and no underlying cause can be identified.
Causes of CIN
-Acute interstitial nephritis
=Any of the causes of acute interstitial nephritis, if persistent (including allergic with continuing exposure to cause)
-Glomerulonephritis
=Varying degrees of interstitial inflammation occur in association with most types of inflammatory glomerulonephritis
-Immune/inflammatory
=Sarcoidosis (granulomatous, often with high calcium)
=Sjögren syndrome
=Chronic transplant rejection
=TubloInterstitial Nephritis with Uveitis.
=Systemic lupus erythematosus, primary autoimmune
=Myeloma is a type of cancer of white blood cells. It often develops very slowly, and it can be treated. Some of the white blood cells that make antibodies overproduce a particular antibody. Fragments of these antibodies (‘light chains’, also called Bence Jones protein) leak into the urine and are toxic to the tubules
-Toxic
=Aristolochia in herbal medicines/ Lead/ Chronic interstitial nephritis in agriculture communities (CKDu)
-Drugs
=All drugs causing acute interstitial nephritis
=Tenofovir
=Lithium toxicity
=Analgesic nephropathy
=Ciclosporin, tacrolimus
=some antibiotics (e.g. amphotericin, gentamicin) and some types of chemotherapy (e.g. cisplatin) can cause interstitial nephritis.
-Infection
=Consequence of severe pyelonephritis
=Especially TB, but BK virus is a particular problem after renal transplantation
-Congenital/developmental
=Vesico-ureteric reflux: associated but causation not clear
=Renal dysplasias: often associated with reflux (Reflux nephropathy and renal dysgenesis looks mostly fibrotic and chronic inflammatory, if you biopsy it)
=Inherited: now well recognised but mechanisms unclear
=Other: Wilson’s disease, sickle-cell nephropathy, medullary sponge kidney (nephrocalcinosis)
-Metabolic and systemic diseases
=Calcium phosphate crystallisation after excessive phosphate administration (e.g. phosphate enemas in patients with chronic kidney disease)
=Hypokalaemia
=nephrocalcinosis – includes hyperoxaluria of genetic, gastrointestinal, or dietary origin?
=Papillary necrosis/ ischaemic (analgesic nephropathy, bends ‘Caisson disease’, sickle, diabetes)
Pathophysiology of CIN
-Genetic causes may underlie many of these cases while autoimmune mechanisms are also common.
-Chronic interstitial nephritis in agricultural communities (also known as CKD of unknown cause, CKDu) is observed in central American countries and Sri Lanka. The cause is unknown, but is likely to reflect a toxin used in agriculture exacerbated by episodes of dehydration due to heat exposure.
Clinical features of CIN
-Most patients with CIN present in adult life with CKD.
-A minority have salt-losing nephropathy due to impairment of urine-concentrating ability and sodium conservation.
=This presents with polyuria, nocturia and hypotension and puts them at risk of AKI during an acute illness.
-Renal tubular acidosis may complicate CIN but is seen most often in myeloma, sarcoidosis, cystinosis, amyloidosis and Sjögren syndrome.
-Fever, rash
Investigation in CIN
-Typically, urinalysis is unremarkable and small kidneys are observed on ultrasound scan.
-Renal biopsy demonstrates infiltration of the renal parenchyma by lymphocytes, plasma cells and macrophages, in association with tubular atrophy and interstitial fibrosis.
-Leucocyturia, White cell casts, Minimal proteinuria
Management of CIN
-Management is to identify and withdraw or treat the primary cause.
-Otherwise, treatment is supportive in nature, with correction of acidosis and hyperkalaemia; replacement of fluid and electrolytes, as required; and renal replacement therapy if irreversible renal damage has occurred.
What is acute tubular necrosis?
-This is the name given to a temporary injury to the kidney, in which many cells in the tubules die, but the tubules recover after a period lasting days to weeks. Dialysis treatment is often required to maintain health until recovery occurs
-Many patients with acute tubular necrosis develop it in hospital as a complication of a severe illness or a major operation. Acute tubular necrosis is common in hospital due to ischaemic injury in patients who are critically unwell. The diagnosis of acute tubular necrosis may seem almost certain if it occurs after such a severe illness.
-No treatment has been found to speed recovery. It is a matter of waiting. In very severe cases the damage is sometimes not reversible
Causes of acute tubular necrosis
Ischaemic:
-Low blood pressure, eg caused by severe bleeding. Prolonged hypotension leads to AKI
-Severe infection – usually with low blood pressure; Sepsis (septicaemia)
Toxic:
-Toxicity from drugs, chemicals, or infection: drugs (aminoglycosides, cisplatin, tenofovir, methotrexate, gentamycin, iodinated contrast, lead)/ Other (rhabdomyolysis so myoglobin, snake bite, Amanita mushrooms)
Presentation of ATN
-Ischemic:
=Prior decrease in ECF
=Oliguric/ anuric
=No blood, some protein in urinalysis
-This is the most common cause of AKI in patients in ICU. In addition to being a consequence of prolonged ischaemic damage as described above, tubules may be damaged/blocked by toxins such as hypercalcaemia, myoglobin (rhabdomyolysis), light chains (myeloma), crystals (oxalate crystals in ethylene glycol poisoning) or drugs (aminoglycosides, cisplatin).
-Toxic
=Increased ECF
=Increased BP
=Oliguric, dark myoglobin urine
=Lots of blood if myoglobin, protein
