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Acute nephritis and nephroses

Nephritis means inflammation of the kidneys whilst nephroses are non-inflammatory diseases of the kidney. When nephritis involves the glomeruli it is called glomerulonephritis and when it affects the tubules and other structures it is called tubulointerstitial nephritis or more commonly interstitial nephritis.

Acute interstitial nephritis (AIN) accounts for between 6.5 and 15% of patients presenting with acute renal failure. The diagnosis is suggested when renal failure develops in association with systemic illness. Uveitis may suggest one of several underlying diseases.

Aetiology:

• Infection as a cause is mainly confined to children. It follows septicaemia and presents as acute pyelonephritis with renal micro-abscesses that are apparent on biopsy. Viral infections that are implicated include Epstein-Barr virus⁴ and haemorrhagic fevers due to Hanta viruses found in Europe. HIV disease may also be involved.
• Autoimmune or multisystem disorders include SLE, Sjogren's syndrome and sarcoidosis.
• Idiopathic cases are found in associated with anterior uveitis or iritis (TINU - tubulo-interstitial nephritis with uveitis) syndrome affecting mainly young women and girls. Fever, weight loss and renal failure result.⁵
• Genetic disease, especially Alport's syndrome
• Drug hypersensitivity reactions

Proteinuria is usually mild and less than 2g a day. Nephrotic syndrome occurs in acute interstitial nephritis only if due to NSAIDs. Haematuria occurs only with beta-lactam hypersensitivity. Eosinophilia and eosinophiluria suggest adverse drug reactions. The kidneys are a normal size or enlarged.

Ultrasound shows increased cortical echogenicity.

A firm diagnosis is possible only by renal biopsy. It shows numerous mononuclear cells in the interstitium with interstitial oedema.

Treatment requires the immediate withdrawal of any implicated drug. This usually, but by no means invariably, leads to rapid resolution. High dose prednisolone may help with a faster and more complete reduction in serum creatinine.

Acute tubular necrosis: This is by far the commonest cause of intrinsic acute renal failure. Two main causes are:

1. Renal ischaemia as occurs in dehydration, surgery, sepsis and hypovolaemic shock. Obstetric haemorrhage is a high risk as a young woman with a responsive circulation may lose very large amounts of blood quite rapidly.
2. Exposure to nephrotoxins that include:
   • Exogenous - drugs (e.g. aminoglycosides, radio-contrast agents, ciclosporin, anti-cancer), organic solvents, heavy metals.
   • Endogenous - myoglobin (as in rhabdomyolysis or with crush syndrome), haemoglobin (as in haemolysis), hyperuricaemia (causes deposition of uric acid crystals), paraproteinaemia, usually with myeloma and amyloidosis.

It presents with acute renal failure. Urinalysis including microscopy will show signs of casts and epithelial cells.

Treatment: Swiftly correct hypovolaemia. Large doses of IV frusemide plus IV thiazide are required unless they are implicated in the cause. Careful management of plasma electrolytes is essential. Dietary protein restriction may be required. Haemodialysis may be necessary in severe cases. Dopamine may be valuable if renal perfusion is a problem. Recovery of renal function can occur over weeks to months but usually it takes 1 to 3 weeks. The mortality rate is about 37% in hospital and 79% in ICU.⁶

Haemolytic Uraemic Syndrome: The haemolytic uraemic syndrome is a triad of haemolytic anaemia (Coombs’ test –ve), thrombocytopenia and acute renal failure. It is most often associated with E coli O157 infection.

Acute glomerulonephritis causes of only 5% of acute renal failure. It is associated with inflammatory changes to the glomeruli. Immune complexes are found with:

• Berger's disease
• Goodpasture's syndrome
• Peri- or post-infection
• Lupus nephritis
• Cryoglobulinaemia is frequently with hepatitis C infection
• Membranoproliferative disease.

It can also occur in malignant hypertension, HUS and thrombotic thrombocytopenia purpura. Symptoms include hypertension and oedema.

Urinalysis with microscopy will show proteinuria, haematuria and red and white cell casts. The red cell casts are diagnostic.

Pauci immune rapidly progressive glomerulonephritis is often due to Wegener's granulomatosis and microscopic polyangiitis.

Chronic interstitial nephritis probably represents the response to a number of agents over a number of years. It is often insidious and asymptomatic and found on routine investigation of other causes. Hypertension is common but not invariable. There may be a modest elevation in creatinine with some renal tubular acidosis and Fanconi syndrome.

• Analgesic nephropathy was originally thought to be associated with just phenacetin but aspirin, NSAIDs and especially paracetamol have since been implicated. It is commonest in women in their 50s and 60s who have used analgesics for various disorders for many years. It is 7-8 times more common in women than men. It is unclear if this is just due to greater consumption of analgesics or an inherent susceptibility. CT may show microcalcifications at the papillary tips. Analgesic use should cease. Chronic renal failure may lead to end-stage renal failure and carcinoma of the urinary tract is more common.
• Ciclosporin and tacrolimus can both cause the disease in transplant recipients. In most kidney transplant patients it resembles chronic rejection but renal function often remains stable. In heart transplant patients, 10% eventually require dialysis. These drugs may also cause hypertension and hyperkalaemia.
• Up to half those on lithium have problems of concentrating urine but chronic interstitial nephritis occurs in a small minority, most of whom have had recurrent toxic levels.
• Heavy metal poisoning with mercury or cadmium but especially lead poisoning can cause the disease. It can accumulate in the body over many years. Hypertension is almost invariably present but the kidney disease is often misdiagnosed as being associated with the hypertension. There is often gout too.
• Urinary tract obstruction from whatever cause can cause nephropathy. Superimposed infection with pyelonephritis may complicate the picture.
• Atherosclerotic kidney disease may occur in association with the other risk factors for this condition, especially hypertension. All risk factors, including raised cholesterol should be treated.
• Hypercalcaemia, chronic potassium depletion, and cystinosis can lead to chronic tubulointerstitial nephritis. Of these, hypercalcaemia is the commonest cause and that is secondary to other causes such as hyperparathyroidism, sarcoidosis and myeloma.
• It has also been reported with use of Chinese herbal medicines, especially aristolochic acid for weight loss. There may be many other unrecognised causes of renal damage from complementary therapies and direct questioning is advised.⁷

The prognosis varies according to the cause of chronic interstitial nephritis but generally the course is a slow, even very slow, progression towards end-stage renal failure.

References:

1. Alexopoulos E; Drug-induced acute interstitial nephritis.;Ren Fail 1998 Nov;20(6):809-19.[abstract]
2. Ravnskov U; Glomerular, tubular and interstitial nephritis associated with non-steroidal antiinflammatory drugs. Evidence of a common mechanism.;Br J Clin Pharmacol 1999 Feb;47(2):203-10.[abstract]
3. Cheng HF, Harris RC; Renal effects of non-steroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors.;Curr Pharm Des 2005;11(14):1795-804.[abstract]
4. Verma N, Arunabh S, Brady TM, et al; Acute interstitial nephritis secondary to infectious mononucleosis.;Clin Nephrol 2002 Aug;58(2):151-4.[abstract]
5. Sessa A, Meroni M, Battini G, et al; Acute renal failure due to idiopathic tubulo-intestinal nephritis and uveitis: "TINU syndrome". Case report and review of the literature.;J Nephrol 2000 Sep-Oct;13(5):377-80.[abstract]
6. Gill N, Nally JV Jr, Fatica RA; Renal failure secondary to acute tubular necrosis: epidemiology, diagnosis, and management.;Chest 2005 Oct;128(4):2847-63.[abstract]
7. Colson CR, De Broe ME; Kidney injury from alternative medicines.;Adv Chronic Kidney Dis 2005 Jul;12(3):261-75.[abstract]

Internet:

• Batuman V interstitial nephritis, from emedicine
• www.kidney.org.uk IgA nephropathy, information for patients. National Kidney Federation.

Acknowledgements EMIS is grateful to the Mentor authoring team for updating this article from an original by doctoronline.nhs.uk. The final copy has passed peer review of the independent Mentor GP authoring team. ©EMIS 2006.

Last issued 08 May 2006