Renal disorder in systemic disease
A huge variety of systemic conditions can affect the function of the
kidneys, from acute illnesses to drugs and more insidious illnesses.
Diabetic nephropathy
Hypertensive nephropathy/nephrosclerosis
Vasculitides
Sickle cell disease
Diabetic nephropathy
Definition: A microvascular complication of diabetes marked by albuminuria and
a deteriorating course from normal renal function to ESRD.
Diabetic nephropathy is the commonest cause of end stage renal failure (ESRF)
in the developed world (about 30–40% of cases of ESRF).
Incidence rising in line with diabetes.
It is more common as a complication of type 1 diabetes mellitus but also affects a
significant proportion of type 2 patients
It usually affects patients who have had diabetes for >10 years, with peak
incidence of ~3% per year in those who have had diabetes for 10–20 years
The diabetic kidney
The kidney may be damaged by diabetes in three main ways:
glomerular damage
ischaemia resulting from hypertrophy of afferent and efferent arterioles
ascending infection.
Pathology
Expansion of mesangial matrix with diffuse and nodular
glomerulosclerosis (Kimmelstiel-Wilson nodules)
Thickening of glomerular and tubular BM
Arteriosclerosis and hyalinosis of afferent and efferent arterioles
Tubulointerstitial fibrosis
Signs and Symptoms
Approximately 25% to 40% of patients with DM 1
ultimately develop diabetic nephropathy (DN), which
progresses through five predictable stages.
Stage 1 (very early diabetes)
Increased demand upon the kidneys is indicated by an
above-normal glomerular filtration rate (GFR).
Hyperglycemia leads to increased kidney filtration
(see later)
This is due to osmotic load and to toxic effects of high
sugar levels on kidney cells
Increased Glomerular Filtration Rate (GFR) with
enlarged kidneys
Stage 2 (developing diabetes)
Clinically silent phase with continued hyper filtration
and hypertrophy
The GFR remains elevated or has returned to normal,
but glomerular damage has progressed to significant
microalbuminuria (small but above-normal level of the
protein albumin in the urine).
Significant microalbuminuria will progress to end-
stage renal disease (ESRD).
Therefore, all diabetes patients should be screened
for microalbuminuria on a routine basis.
Stage 3 (overt, or dipstick-positive diabetes)
Glomerular damage has progressed to clinical
albuminuria.
Basement membrane thickening due to AGEP
The urine is "dipstick positive," containing more than
300 mg of albumin in a 24-hour period.
Hypertension (high blood pressure) typically develops
during stage 3.
Stage 4 (late-stage diabetes)
Glomerular damage continues, with increasing amounts
of protein albumin in the urine.
The kidneys’ filtering ability has begun to decline
steadily, and blood urea nitrogen (BUN) and creatinine
(Cr) has begun to increase.
The glomerular filtration rate (GFR) decreases about
10% annually. Almost all patients have hypertension at
stage 4.
Stage 5 (end-stage renal disease, ESRD)
GFR has fallen to <10 ml/min and renal replacement
therapy (i.e., haemodialysis, peritoneal dialysis, kidney
transplantation) is needed.
Diagnosis
The urine of all diabetic patients should be checked regularly for the presence of protein.
detected by measuring the albumin/creatinine ratio on a spot urine sample
Clinical suspicion of a non-diabetic cause of nephropathy may be provoked by an atypical
history, the absence of diabetic retinopathy (usually but not invariably present with diabetic
nephropathy) and the presence of red –cell casts in the urine.
Renal biopsy should be considered in such cases, but in practice is rarely necessary or helpful.
The risk of intravenous urography is increased in diabetes, especially if patients are allowed to
become dehydrated pri or to the procedure, and a renal ultrasound is preferable but not so
informative.
A 24-hour urine collection is performed to quantify protein loss and to measure creatinine
clearance, and regular measurement is made of the plasma creatinine level.
Investigation
Urine microscopy
Culture
Serum protein electrophoresis
Serum calcium
Serum urate
ESR
Antinuclear factor.
Management of diabetic nephropathy:
Tight glycaemic control, ideally achieved through combination of dietary modification,
pharmacotherapy (including insulin regimen) and regular physical activity.
Tight BP control of at least 130/80 through the use of ACE inhibitors/Angiotensin-2 receptor
antagonists ± diuretics/beta-blockers.
ACE inhibitors are of benefit in normotensive diabetics with microalbuminuria.
Optimisation of other vascular risk factors through use of aspirin and statins (vastly increased
cardiovascular risk caused by diabetic nephropathy).
Renal replacement therapy (including transplantation) in those with established kidney disease.
Hypertensive nephropathy/nephrosclerosis
Renal disease can cause hypertension, but sustained hypertension
damages the vasculature of the kidneys. This is particularly so in cases
of accelerated or malignant hypertension. Hypertensive nephropathy
accounts for about a quarter of all patients with ESRF. Hypertension
causes a pathology known as nephrosclerosis due to ischaemia
affecting the glomeruli, and hyperfiltration causing intraglomerular
hypertension.
Hypertension also increases the risk of renal failure through the effects of:
Cholesterol embolisation to the kidneys
The presence of renal artery stenosis (particularly if bilateral)
Most patients present with significant hypertension and/or its
complications (e.g. cardiac failure, MI, stroke) or biochemical/clinical
evidence of renal failure. There has usually been a history of
hypertension for about 10 years, but some patients will present without
having had any previous evidence of hypertension.
Management
Management is through use of a range of anti-hypertensive agents, particularly ACE
inhibitors/angiotensin-2 antagonists and diuretics, but other agents are also used.
The cohort of patients with hypertensive nephropathy are at risk of bilateral renal artery
stenosis which may preclude the use of ACE inhibitors due to worsening of renal function.
Renal parameters must be monitored very closely after introduction/dose-alteration of an anti-
hypertensive agent.
Close attention to modification of other cardiovascular risk factors and renal replacement
therapy are also useful in improving long-term outlook.
Revascularisation of the kidneys (via angioplasty/stenting) may be considered in cases of
bilateral renal artery stenosis where there is evidence from captopril renography that it is
significantly affecting renal function.
Vasculitides
Primary systemic vasculitides may cause renal dysfunction through their
ability to cause a focal necrotising glomerulonephritis.
They usually cause a pattern of renal disease known as rapidly progressive
glomerulonephritis (RPGN).
Vasculitides that affect the renal vasculature tend to be those that affect
medium-sized arteries.
Vasculitides that tend to cause renal impairment:
Wegener's granulomatosis
Microscopic polyangiitis
Churg-Strauss syndrome
Polyarteritis nodosa
Sickle cell disease
Many children with sickle cell disease develop hyposthenuria, an inability to form concentrated
urine, that may cause nocturnal enuresis and polyuria.
Acute severe haematuria may occur due to renal papillary necrosis or sickling within the
substance of the kidney and is usually treated with DDAVP/epsilon-aminocaproic acid.
A post-mortem series of adult patients with sickle cell disease found that renal failure was the
cause of death in about 20% of cases.
The disease causes a glomerulopathy with proteinuria and progressive renal insufficiency,
leading to ESRF; renal papillary necrosis is another possible mechanism of acute renal
syndromes.
Albuminuria is a sensitive marker of glomerular damage and precedes the onset of renal failure.
There are no effective therapies to prevent the onset of renal failure other than good
management of the condition in order to reduce the incidence of, and ameliorate, sickling
crises.
Multiple myeloma
Acute renal failure is relatively common in myeloma, occurring in 20-
30% of affected individuals at the time of diagnosis, and is mainly due
to the nephrotoxic effects of the abnormal immunoglobulins.
Acute renal failure due to cast nephropathy is usuallyirreversible.
Treatment of underlying myeloma is indicated
Cast nephropathy in a patient with multiple myeloma. Light microscopy picture
showing characteristic fractured cast and giant cell reaction (arrows).