Chronic Renal Failure

Chronic Renal Failure

·        = Reduction in renal function for > 6 months

·        Causes in NZ in 1997:

§  Miscellaneous causes include: stone disease, interstitial nephritis, amyloidosis, myeloma, lithium toxicity, obstructive uropathy, renal cell carcinoma, post-partum failure

·        Symptoms:

o  Earlier: nausea, anorexia, lethargy, itch, nocturia, impotence

o  Later: oedema, SOB, chest pain (from pericarditis), vomiting, confusion, fits

·        See also:

o  Adult Polycystic Kidney

o  Wegner‟s granulomatosis, Microscopic Polyarteritis, and Henoch-Schonlein Purpura, Vasculitis

Diabetic Nephropathy

·        Epidemiology:  Nephropathy in

o  30 – 50% of type 1 diabetic patients (after ~ 10 – 15 years of disease)

o  20 – 30% of type 2 diabetic patients – many with overt disease at the time of presentation 

o  In both cases is associated with poor glycaemic control, hypertension and ­ proteinuria

·        Definitions:

o  Overt diabetic nephropathy = proteinuria > 500 mg/day in the absence of other renal disease

o  Microalbuminuria:

§  Albumin excretion 30 – 300 mg/day (= 20 – 200 mg/minute). Concentration is not relevant – it is the amount excreted per unit time. Albumin is more specific for nephropathy than total urine protein (normal protein < 150 mg/day – mainly from tubular cells). Normal dipsticks not sensitive enough at this level. Random early morning urine is dependent on concentration. Urinary albumin:creatinine ratio is a useful screening test 

§  Marker for endothelial damage elsewhere.  Strong association with retinopathy, IHD, etc

§  Prognosis for a diabetic with microalbuminaemia is worse than for HIV!

·        Natural History:

o  Type 1 Diabetes:

§  Not usually evident until after 10 – 15 years of disease. If none by 25 years then nephropathy unlikely

§  Once overt nephropathy starts, progresses to ESRF over 5 – 7 years 

§  Initial hyperfiltration in about 50% of diabetics (­GFR by about 25 – 50%). Overtime this reduces and hypertension ensues

o  Type 2 Diabetes: Similar progression to ESRF once overt nephropathy

·        Pathology:

o   ­Intra-glomerular pressure, glomerular hypertrophy, ?deposition of advanced glycosylation end products 

o   Glomeruli:

§  Glomerulosclerosis: nodular (Kimmelstiel-Wilson) or diffuse

§  Mesangial broadening with deposition of eosinophilic material

§  GBM irregularly thickened

o   Arterioles show evidence of subintimal arteriosclerosis and hyalinisation

o   Interstitial changes: tubular atrophy and fibrosis

·        Look for other renal pathology if:

o   No retinopathy

o   Active urinary sediment

o   Rapid onset nephrotic syndrome

o   Type 2 diabetes

·        Management:

o   Glycaemic control.  HBA1c < 8.5% delays progression in early phases – not later 

o   Anti-hypertensive treatment: All effective. ACE inhibitors are best at ¯ protein and ¯intra-glomerular pressure. May delay progression even in normotensive patients. Aim to lower blood pressure by as much as possible without creating hypotensive symptoms. Also calcium antagonists (diltiazem and Verapamil ® ¯proteinuria) 

o   Protein Restriction: Limiting intake may reduce progression. High intake ® ­intraglomerular pressure and hyperfiltration 

o   Dialysis: worse prognosis than non-diabetics due to concurrent IHD. Peritoneal dialysis better if CVS instability 

o   Transplant: best prognosis in the absence of CV disease. Disease can recur in the graft 5 – 10 years later

·        Other renal complications:

o   Urinary tract sepsis.  Should be treated even if asymptomatic 

o   ­Risk of pyelonephritis

o   Papillary necrosis.  May ® macroscopic haematuria or ureteric obstruction

o   Autonomic neuropathy ® neurogenic bladder ® infection/obstruction

o   Contrast nephropathy: always hydrate aggressively

Systemic Lupus Erythematosus

·        Renal involvement common:

o   Clinically apparent in around 50%

o   Histologic lupus nephritis in 100%

o   5% present with a renal syndrome

·        Presentation:

o   Usually heavy proteinuria, nephritic syndrome or RPGN

o   Test for SLE antibodies(see Blood tests in Inflammatory Arthritis)

o   Most patients have ¯complement

·        Histology:

o   Mimics anything!

o   Most severe: Diffuse proliferative glomerulonephritis with crescents

o   Common: membranous pattern, tubulo-interstitial damage

o   Immunoflouresence (IF): extensive deposition of IgG and C3, also C1q, IgA, IgM and fibrin

Reflux Nephropathy 

·        Most common cause of end-stage renal failure in children, secondary to vesico-ureteric reflux + infection in infancy 

·        May not appear till adulthood (ie slowly progressive)

·        Investigations:

o   Renal cortical scarring on ultrasound or DMSA scan

o   IVU may show clubbing of calyces

o   Biopsy: chronic interstitial disease with secondary focal glomerulosclerosis

·        Treatment: aggressive blood pressure control

Thrombotic Microangiopathy

·        Includes Haemolytic Uraemic Syndrome (HUS), Thrombotic Thrombocytopaenic Purpura (TTP) and HELLP Syndrome of Pregnancy (Haemolysis, elevated liver enzymes and low platelets)

·        Presentation:

o  Microangiopathic haemolytic anaemia, low platelets and renal and neurological manifestations

o  Renal involvement: haematuria and proteinuria, renal failure in 40 – 80% 

·        Investigations: Blood film ® marked fragmentation of red cells, Comb‟s test –ive

·        Treatment: 90% response to plasmapheresis with or without corticosteroids

 Amyloidosis

·        A dysproteinaemia that usually presents renally with nephrotic syndrome

·        Types: 

o  Primary amyloidosis: idiopathic or associated with myeloma. Amyloid protein is part of the Ig light chain. Poor prognosis 

o  Secondary amyloidosis: deposition of a different form of protein. Associated with chronic inflammatory or infective conditions (eg Rheumatoid arthritis, Tb, etc)

·        Particularly affects glomerular capillary walls, seen with Congo Red Stain