Tubulointerstitial Nephritis

 

• Can be acute of chronic
• Acute tubulointerstitial nephritis has a rapid clinical onset and is characterised histologically by interstitial oedema, often WBC infiltration (neutrophils and eosinophils) of the interstitium and tubules and focal tubular necrosis
• In chronic tubulointerstitial nephritis, there is infiltration with mononuclear cells, interstitial fibrosis and wide spread tubular atrophy
• They are distinguished clinically from glomerular disease by the absence of nephritic and nephrotic syndrome and by the presence of defects in tubular function e.g. polyuria and nocturia

 

Causes

• Infections
  • Acute bacterial pyelonephritis
  • Chronic pyelonephritis
  • Other infections – viruses, parasites
• Toxins
  • Drugs
  • Acute hypersensitivity interstitial nephritis
  • Analgesic nephropathy
  • Heavy metals
  • Lead, cadmium
• Metabolic disease
  • Urate nephropathy
  • Nephrocalcinosis (hypercalcaemic nephropathy)
  • Hypokalaemic nephropathy
  • Oxalate nephropathy
• Physical factors
  • Chronic urinary tract obstruction
  • Radiation nephropathy
• Neoplasms
  • Multiple myeloma (cast nephropathy)
• Immunological reactions
  • Transplant rejection
  • Sjogren syndrome
  • Sarcoidosis
• Vascular diseases

 

Pyelonephritis and urinary tract infection

 

• Affects the tubules, interstitium and renal pelvis
• Can be acute which is caused by a bacterial infection and is associated with a urinary tract infection
• Chronic disease is more complex and can be bacterial in origin but other factors such as vesicoureterical reflux and obstruction may play a role

 

 

 

Aetiology and pathogenesis

• Mostly due to urinary tract infections 85% are due to gram negative organisms that come from the gut
• Most common is E.col, Proteus, Klebsiella, Enterobacter, Streptococci faecalis and Staphlococci
• In immunosuppressed patients particularly transplant patients, viruses such as polyoma virus, CMV and adenovirus can cause a renal infection
• Latent polyoma virus is widespread in the population and immune suppression can lead to reactivation of infection and chronic nephropathy
• There are two ways infection can reach the kidneys; haematologically and via the urinary tract (ascending infection)
• Haematological infection is more common when there is septicaemia or infective endocarditis and in the presence of urinary tract obstruction. It is more common in immunosuppressed patients
• Ascending infection is the most common. Steps that are required for kidney infection to occur;
  • Colonisation of the distal urethra and in the female the introitus. This requires adhesins and pili to be expressed by the bacteria
  • From the urethra to the bladder. Long term catheterisation is a risk, otherwise females are more at risk due to our short urethra, our lack of the antibacterial effect of prostatic fluid, the hormonak changes that can effect the adherence of bacteria to the muscosa and urethral trauma that occurs during sex
  • Multiplication in the bladder. Increased if there is urine stasis in the bladder and therefore bacteria are not washed out. This occurs in lower urinary tract obstruction and in neurogenic bladder dysfunction caused by diabetes or spinal cord injury
  • Vesicoureteral reflux
    • Normally the vesicoureterical valve is a one way valve which closes, especially during micturition, to prevent retrograde flow of urine. Incompetence results in reflux of bladder urine into the ureters. Reflux can be due to;
      • Congenital absence of shortening of the intravesical portion of the ureter
      • Bladder infection itself – the effects of inflammation or bacterial products on bladder contractility
      • Acquired vesicoureteral reflux occurs in adults with persistant bladder atony resulting from spinal cord injury
  • Intrarenal reflux
    • Allows infected urine to be propelled to be propelled up to the renal pelvis and deep into the renal parenchyma through open ducts at the tips of the papillae
    • Uppers mostly at the upper and lower poles of the kidney where the papillae tend to have flattened or concave tips rather then the convex tips that are present in the midzone of the kidney

 

• Vesicoureterical reflux can occur in about 30% of people with a urinary tract infection
• In the absence of vesicouterical relux the infection remains in the bladder so most people suffer from cystitis and urethritis than pyelonephritis

 

Acute Pyelonephritis

 

• Acute suppurative inflammation of the kidney caused by bacteria and sometimes viruses

 

Morphology

• Hallmarks;
  • Patchy interstitial suppurative inflammation – can be discrete focal abscesses that can develop into wedge shaped areas. In pyelonephritis associated with reflux, damage occurs most commonly at the upper and lower poles
  • Intratubular aggregates of neutrophils – start off in the interstitium
  • Tubular necrosis – glomerulus is mostly unaffected  by large areas of necrosis can eventually destroy the glomerulus also and fungal pyelonephritis particularly affects the glomerulus
• Particular complications of acute pyelonephritis;
  • Papillary necrosis
    • Seen mainly in diabetics and in those with urinary tract obstruction
    • Usually bilateral but can be unilateral
    • One or all of the pyramids can be affected
    • Macroscopically the tips or upper 1/3 of the pyramid exhibited yellow/grey necrosis
    • Microscopically the outline of the tubules are intact and the leukocytic response is limited to the junction between the preserved and destroyed tissue
  • Pyonephrosis
    • Seen in total or almost complete obstruction particularly when it is high in the urinary tract
    • The suppurative exudates is unable to drain and fills the renal pelvis, calyces and ureter
  • Perinephric abscess
    • Extension of suppurative inflammation through the renal capsule into the perinephric tissue
    • After the acute phase of the infection, healing occurs and the neutrophilic infiltrate is replaced by mononuclear cells. There is atrophy of the tubules, interstitial fibrosis and atophy of the tubules

 

Clinical course

·        Acute pyelonephritis is associated with the following conditions;

• • Urinary tract obstruction
  • Instrumentation of the urinary tract – catheterisation
  • Vesicoureteral reflux
  • Pregnancy
  • Age and sex – common in the first year of life. Up until the age of 40 more common in females, they the incidence in males rises due to prostatic hypertrophy
  • Pre-existing renal lesions – causing intrarenal scarring and obstruction
  • Diabetes – more frequent instrumentation, increased susceptibility to infection and neurogenic bladder dysfunction
  • Immunosuppression and immunodeficiency

 

·        Onset is generally sudden and present with pain. There may be indications of bladder or urethral irritation such as polyuria, dysuria and urgency

·        The urine will contain leukocytes but this doesn’t distinguish between a lower and upper urinary tract infection

·        The presence of leukocyte casts indicates renal involvement

Chronic Pyelonephritis and Reflux Nephropathy

 

• Chronic tubulointerstital renal disorder in which chronic tubulointerstitial inflammation and renal scarring are associated with pathological involvement of the calyces and pelvis
• Of the causes of tubulonephritis listed above only chronic pyelonephritis and analgesic nephropathy affect the calyces
• Can result in end-stage renal disease

 

Can be divided into two forms;

Reflux nephropathy

• Most common form
• Occurs mostly in childhood with superimposition of a urinary infection on congenital vesicoureteral reflux and intrarenal reflux
• Can be unilateral or bilateral
• Vesicoureteral reflux causes damage in the absence of infection (sterile reflux) but only in the presence of severe obstruction

 

Chronic obstructive pyelonephritis

• Recurrent infections superimposed on diffuse or localised obstructive lesions leads to bouts of renal inflammation and scarring resulting in chronic pyelonephritis
• The disease can be bilateral, due to obstructive anomalies of the urinary tract and resulting in renal insufficiency
• Or it may be unilateral such as occurs with caliculi or unilateral obstructive anomalies

 

Morphology

• Kidneys are irregularly scarred (in chronic glomerulonephritis the kidneys are diffusely and symmetrically scarred)
• The hallmark is a coarse, discrete corticomedullary scar overlying a dilated, blunted or deformed calyx
• Most scars occur in the upper and lower poles
• Microscopically changes involves predominantly the interstitium and the tubules. With the tubules showing atrophy in some areas and hypertrophy/dilation in others
• Dilated tubules may be filled with colloid casts
• During active infection there may be neutrophils in the interstitium and pus casts in the tubules

 

• Xanthogranulomatous pyelonephritis
  • Rare form of chronic pyelonephritis often associated with proteus infection and obstruction
  • Characterised by accumulation of foamy macrophages, plasma cells, lymphocytes, polymorphs and occasional giant cells
  • Lesions can contain large, yellow/orange nodules that can be confused with renal cell carcinoma

 

Clinical course

• May be insidious in onset or may present with acute features of back pain, fever, frequent pyuria and bacteruria
• Chronic pyelonephritis associated with reflux may have a silent onset and present late with hypertension and renal insufficiency
• Some patients may develop focal segmental glomerulosclerosis and proteinuria and nephrotic syndrome