End-Stage Renal Failure
End-stage renal failure (ESRF), as evidenced by a decline in glomerular filtration rate (GFR) such that function is inadequate for health, is relatively common and the prevalence increases with age. It can be classified in two ways, either, according to its temporal progression, or according to its cause.
Classification by temporal progression
The rapid onset of renal failure over a period of days or weeks is termed ‘acute renal failure’ or ‘acute kidney injury’ (AKI), whereas a decline in GFR occurring over months to years is termed ‘chronic renal failure’ or ‘chronic kidney disease’ (CKD).
Classification of renal failure by cause
The cause of renal failure can be classified using the terms:
These indicate the anatomical site at which the aetiological factor is acting. For example, systemic hypotension due to blood loss will compromise the renal blood flow and is a ‘pre-renal’ cause of renal failure. In contrast, inflammatory disease of the glomerulus (glomerulonephritis, GN) is a ‘renal’ cause of renal failure. Enlargement of the prostate causing obstruction to the outflow of urine is a ‘post-renal’ cause of renal failure.
Acute kidney injury
The most common cause of AKI is pre-renal failure, which if left untreated will progress to acute tubular necrosis (ATN). ATN occurs if there is persistent hypotension/hypovolaemia and/or exposure to nephrotoxins or sepsis. It is the cause of 60–80% of cases of AKI. ATN is quite common because the renal tubular blood supply is relatively precarious, so that any drop in blood pressure (secondary to hypovolaemia or reduced peripheral vascular resistance as seen in sepsis) can lead to tubular ischaemia. This is a direct result of the anatomical arrangement of the blood supply, which comes to the tubules only after it has passed through the glomerular capillary bed. Thus, there is always relative hypoxia in the renal medulla compared with the cortex. When the mean arterial pressure falls, there will be a reduced blood flow into the glomerulus via the afferent arteriole and a consequent fall in GFR. This prompts an increase in vasoconstriction in the efferent glomerular arteriole in an attempt to maintain GFR, which will further compromise the blood supply to the medulla, leading to increased hypoxia and tubular ischaemia. Tubular cells are also very metabolically active, with a number of energy-requiring electrolyte pumps. All of these factors contribute to susceptibility to ATN.
Histologically, ATN is manifest as ragged, dying tubular cells, which lose their nuclei and begin to slough off into the tubular lumen. Patients with pre-renal failure should be given fluid to restore intravascular volume and nephrotoxins (non-steroidal anti-inflammatory drugs [NSAIDs], gentamicin or ACEi) should be removed. ATN usually recovers spontaneously, although the patient may temporarily require renal replacement therapy (RRT). Some patients sustain irreversible tubular atrophy and a degree of chronic kidney damage.
Other causes of AKI include GNs (5–10%), obstruction (5– 10%), and acute tubulointerstitial nephritis (TIN) (<5%).
GNs are named according to the appearance of the renal biopsy. For example, in minimal change GN there is no abnormality in the biopsy when viewed with a light microscope; in membranous GN there is thickening of the glomerular basement membrane. IgA nephropathy is characterised by the deposition of IgA in the mesangium, etc. Some primary and secondary GNs commonly present with an acute decline in renal function, while others commonly result in CKD (see below). GNs presenting as AKI include:
• Primary – pauci immune crescentic GN, anti-glomerular basement membrane disease (Goodpasture’s disease).
• Secondary – lupus nephritis, antineutrophil cytoplasmic anti- body (ANCA)-associated vasculitis.
Patients with acute GN may require RRT as well as treatment for the underlying disease (e.g. immunosuppression +/– plasma exchange). The success of these treatments is variable; some patients partially regain renal function while others become permanently dialysis-dependent.
Acute TIN often occurs as the result of an ‘allergic reaction’ to medications, both prescription drugs such as proton pump inhibitors or antibiotics, and herbal remedies. Renal biopsy demonstrates an intense lymphocytic infiltrate in the interstitium, including numerous eosinophils. Management involves removal of the likely causative agent and the administration of oral corticosteroids to reduce renal inflammation. This usually results in the resolution of acute inflammation, but some patients are left with irreversible interstitial fibrosis and tubular atrophy, which may contribute to the subsequent development of CKD.
CKD can be completely asymptomatic until its very terminal stages. Eventually anaemia (manifest as tiredness or even congestive cardiac failure), uraemia (resulting in nausea, reduced appetite and confusion), phosphate build-up (leading to itchiness) and/or severe hypertension (causing headache or blurred vision) may prompt the patient to seek medical attention, where a routine blood test reveals high urea and creatinine due to a reduced GFR. In contrast to AKI, where pre-renal and post-renal causes predominate, the causes of CKD tend to be renal in origin. These include:
• diabetes mellitus with associated diabetic nephropathy
• hypertensive nephropathy
• obstructive uropathy (often secondary to prostatic hypertrophy)
• chronic primary GN, e.g. IgA nephropathy or focal segmental glomerulosclerosis (FSGS)
• chronic secondary GN, e.g. lupus nephritis
• adult polycystic kidney disease (APKD)
• chronic pyelonephritis
• renovascular disease.
CKD is classified into different stages according to the patient’s GFR and the presence of urine dipstick abnormalities. These have allowed the development of management guidelines for patients with stable CKD, and facilitate the provision of consistent care.
Diseases that recur in the transplant
A number of causes of renal failure may reoccur in the allograft. These include:
• structural problems – bladder outflow obstruction
• renal calculi
• urinary tract infections with associated chronic pyelonephritis
• primary GNs – IgA, FSGS, mesangiocapillary glomerulonephritis (MCGN)
• secondary GNs – ANCA-associated vasculitis, lupus nephritis, diabetic nephropathy.