Interstitial Nephritis

Objectives Definition Classification. Causes. Clinical presentation. Management

A group of inflammatory, inherited and other diseases affect renal tubules and the surrounding interstitium. The clinical presentation is often simply with renal impairment. Proteinuria is generally low. Interstitial Nephritis classified into Acute and Chronic

Acute Interstitial Nephritis

In acute interstitial nephritis, the tubular damage leads to renal tubular dysfunction, with or without renal failure. Regardless of the severity of the damage to the tubular epithelium, the renal dysfunction is generally reversible, possibly reflecting the regenerative capacity of tubules with preserved basement membrane.

Urine may contain red and white blood cells. Acute inflammation within the tubulo-interstitium is most commonly allergic, particularly to drugs, but other causes include toxins and a variety of systemic diseases and. Deterioration of renal function in drug-induced AIN may be dramatic and resemble rapidly progressive glomerulonephritis.

Prognosis Tubulointerstitial disease may progress to end-stage renal disease. Analgesic nephropathy is 5-6 times more common in women. This is generally attributed to women taking more analgesics than men.

CAUSES OF ACUTE INTERSTITIAL NEPHRITIS Penicillins, Rifampin NSAIDs, Diuretics Allopurinol Many other drugs Allergic Autoimmune nephritis ± uveitis Immune Acute bacterial pyelonephritis Leptospirosis Tuberculosis Hantavirus Infections Myeloma light chains Mushrooms (Cortinarius) Toxic

Only a minority (perhaps 30%) of patients with drug-induced AIN have a generalised drug hypersensitivity reaction (e.g. fever, rash, eosinophilia) and dipstick testing of the urine is usually unimpressive. However, leucocyturia is common, and eosinophils are found in the urine in up to 70% of patients. Proteinuria is usually absent or modest. Urinalysis may show microscopic hematuria and/or sterile pyuria (with or without eosinophils).

Renal biopsy is usually required to confirm the diagnosis. Many patients are not oliguric despite moderately severe ARF, and AIN should always be considered in patients with non-oliguric ARF.

Management Some patients with drug-induced AIN recover following withdrawal of the drug alone, but corticosteroids (e.g. prednisolone 1 mg/kg/day) accelerate recovery and may prevent long-term scarring. Dialysis is sometimes necessary, but is usually only short-term. Other specific causes should be treated where possible.

Chronic Interstitial Nephritis

The chronic form is an insidious disease. It is quite common for the condition to be diagnosed late and for no aetiology to be apparent.

CAUSES OF CHRONIC INTERSTITIAL NEPHRITIS Any of the causes of AIN if persistent Varying degrees of interstitial inflammation occur in association with most types of inflammatory glomerulonephritis Glomerulonephritis Sarcoidosis Sjögren's syndrome SLE, primary autoimmune Chronic transplant rejection Immune/inflammatory Mushrooms Lead Chinese herbs Balkan nephropathy Toxic

Analgesic nephropathy Ciclosporin, tacrolimus All drugs causing AIN Lithium toxicity Analgesic nephropathy Ciclosporin, tacrolimus Drugs Consequence of severe pyelonephritis Infection VUR associated; causation not clear Renal dysplasias-often associated with reflux Inherited-now well recognised but mechanisms unclear Other-Wilson's disease, medullary sponge kidney, sickle-cell nephropathy Congenital/developmental Hypokalaemia, hypercalciuria, hyperoxaluria Amyloidosis Metabolic and systemic diseases

Long-term ingestion (years to decades) of analgesic drugs can cause renal papillary necrosis and CIN. Other causes of papillary necrosis are sickle-cell disease and occasionally in diabetes and other conditions.

Clinical and biochemical features Most patients present in adult life with CRF, hypertension and small kidneys. CRF is often moderate (urea < 150 mg/dl) but, because of tubular dysfunction, electrolyte abnormalities are typically more severe (e.g. hyperkalaemia, acidosis). Urinalysis abnormalities are non-specific.

A minority of patients present with hypotension, polyuria and features of sodium and water depletion (e.g. low blood pressure and jugular venous pressure)-salt-losing nephropathy. Proteinuria is usually mild, often less than 1 g/d.

Papillary necrosis is difficult to identify other than on IVU or retrograde pyelography. during an acute illness there is failure of sodium conservation places patients at risk of superimposed ARF.

Differentials Acute Renal Failure. Acute GN. Urinary Tract Obstruction.

Treatment Treatment depends on the etiology and generally consists of supportive measures, such as adequate blood pressure control and management of anemia.

Cystic kidney diseases

Adult Polycystic kidney disease APKD is a common condition that is inherited as an autosomal dominant trait. Small cysts develop from infancy or childhood and enlarge slowly and irregularly. Renal failure is associated with grossly enlarged kidneys.

Mutations in the PKD1 gene account for 85% of cases and PKD2 for about 15%. ESRD occurs in approximately 50% of patients with PKD1 mutations with a mean age of onset of 52 years, but in a minority of patients with PKD2 mutations with a mean age of onset of 69 years.

Adult Polycystic kidney disease: Common Clinical Features Vague discomfort in loin or abdomen due to increasing mass of renal tissue Acute loin pain or renal colic due to haemorrhage into a cyst Hypertension (Is one of the most common early manifestations of ADPKD) Haematuria (with little or no proteinuria) usually is self-limited Urinary tract infection Renal failure usually in the fourth to sixth decade of life

Affected subjects are usually asymptomatic until later life. After the age of 20 there is often insidious onset of hypertension. One or both kidneys may be palpable and the surface may feel nodular. There is then a gradual reduction in renal function.

About 30% of patients with PKD have hepatic cysts, but disturbance of liver function is rare. Sometimes (almost always in women) this causes massive and symptomatic hepatomegaly, usually concurrent with renal enlargement, but occasionally with only minor renal involvement.

Berry aneurysms of cerebral vessels are an associated feature, and about 10% of patients have a subarachnoid haemorrhage. This feature appears to be largely restricted to certain families (and presumably specific mutations). Mitral and aortic regurgitation are frequent but rarely severe. Colonic diverticula and abdominal wall hernias may occur. PKD is not a pre-malignant condition. The rate of renal malignancy is no different from that of other patients with renal failure (but is higher than the general population).

Investigations and screening The diagnosis is usually based on family history, clinical findings and ultrasound. Ultrasound demonstrates cysts in ∼95% of affected patients over the age of 20, but may not detect small developing cysts in younger patients. Computed tomography (CT) scan more sensitive than ultrasonography.

Investigations and screening Specific genetic diagnosis. Screening for intracranial aneurysms is not generally indicated. Where non-invasive MR angiography is available, some centres screen patients in families with a history of subarachnoid haemorrhage.

Ultrasonographic diagnostic criteria for ADPKD1 are as follows: At least 2 cysts in 1 kidney or 1 cyst in each kidney in an at-risk patient younger than 30 years At least 2 cysts in each kidney in an at-risk patient aged 30-59 years At least 4 cysts in each kidney for an at-risk patient aged 60 years or older

Treatment No treatment has been proved to prevent cyst growth or the decline in kidney function. Hypertension control with a target blood pressure of 130/80 mmHg or less is recommended. Lipid-soluble antimicrobials such as trimethoprim-sulfamethoxazole and fluoroquinolones that have good cyst penetration are the preferred therapy for infected kidney. Those undergoing kidney transplantation may require bilateral nephrectomy if the kidneys are massively enlarged or have been the site of infected cysts

OTHER CYSTIC DISEASES Medullary cystic diseases: Medullary sponge kidney is characterised by cysts confined to papillary collecting ducts. The disease is not inherited and its cause is unknown. Patients usually present as adults with renal stones. These are often recurrent, and preventive measures need to be implemented if so, but the prognosis is generally good. The diagnosis is made by ultrasound or IVU. Contrast medium is seen to fill dilated or cystic tubules, which are sometimes calcified.

The childhood variants are characterised by thirst and polyuria due to nephrogenic diabetes insipidus, often with a family history of similar disease. Sometimes affected patients are 'salt-losing', which aggravates the degree of renal failure. Even when they are treated appropriately, serious renal failure is usual.

Acquired cystic disease Patients with a very long history of renal failure (usually on long-term dialysis) often develop multiple renal cysts in their shrunken kidneys. Kidneys are enlarged but not to the size of kidneys in PKD. Acquired cystic disease is associated with increased erythropoietin production, and sometimes with the development of renal cell carcinoma.

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