Nephrotic syndrome - definition
A triad of proteinuria (>3g in 24 hours or urine protein : creatinine ratio of >300 mg/mmol), hypoalbuminaemia (<25 g/dL) and oedema.
Severe hyperlipidaemia (>10 mmol/L) is also often present. (Oedema is thought to be caused by sodium retention in the extracellular compartment).
Nephrotic syndrome - clinical features
Ask about acute or chronic infections, drugs, allergies or systemic symptoms e.g. of vasculitis or malignancy.
- Signs – oedema is typically pitting, gravity dependant and occurs peri-orbitally (where tissue resistance is low) and peripherally. Genital oedema, ascites and anasarca (increase of fluid in organs and cavities) develop later. The blood pressure can be normal or raised.
Nephrotic syndrome - complications
Increased susceptibility to infection – (e.g. cellulitis, Strep infections and SBP) occurs in 20% due to decreased serum IgG, complement activity and T cell function (due to loss in urine and immunosuppression).
Thromboembolism – e.g. DVT, PE or renal vein thrombosis occurs in up to 40% due to increased clotting factors and platelet abnormalities.
Hyperlipidaemia – raised cholesterol and triglycerides thought to be due to hepatic lipo-protein synthesis in response to low oncotic pressure.
Nephrotic syndrome - investigations
As for glomerulonephritis and check serum lipids. Perform a renal biopsy in all adults but most children have minimal change GN so give a trial of corticosteroids first.
If proteinuria does not reduce after 1 month of steroids or if features suggest another cause e.g. age <1 year, family history, extra-renal disease (e.g. arthritis, rash or anaemia), renal failure or haematuria biopsy straight away.
Nephrotic syndrome - minimal change GN
The most common cause of nephrotic syndrome in children (76% and 20% of nephrotic adults). It is thought to be T cell mediated and may rarely present with haematuria or hypertension. It is associated with Hodgkin’s lymphoma and drugs e.g. NSAIDs.
- Renal biopsy – normal (minimal change) on light microscopy but fusion of podocytes on electron microscopy.
- Management – 95% of children and 70% of adults achieve remission with steroids but are prone to relapse. Cyclophosphamide can be used during relapses or if side effects to steroids.
Nephrotic syndrome - membranous nephropathy
Accounts for 20-30% of nephrotic syndrome in adults and 2-5% in children but the cause is unknown. It is associated with malignancy, drugs (gold, penicillamine or captopril), autoimmune (RA, SLE or thyroid disease) or infections (HBV, syphilis or leprosy).
- Diagnosis – biopsy shows diffuse thickened GBM - immunofluorescence will show IgG and C3.
- Management – steroids and cyclophosphamide can be given if renal function deteriorates.
Nephrotic syndrome - mesangiocapillary GN
A rare GN that often presents with nephrotic syndrome but in 30% presents with nephritic syndrome. It is diagnosed with a biopsy that shows large glomeruli due to mesangial proliferation and thickened capillary walls = tramline appearance of double BM walls.
- Type 1 – subendothelial immune deposits – idiopathic or seen with hepatitis B or C viruses, endocarditis, visceral abscesses or infected arteriovenous shunts – decreased C4 levels.
- Type 2 – intramembranous immune deposits – with partial lipodystrophy – decreased C3 levels.
- Management – none of proven benefit but steroids and rituximab (anti-CD20) have been used.
- Prognosis – 50% will develop end stage renal failure but MCGN can reoccur in transplants.
Nephrotic syndrome - focal segmental glomerulosclerosis
May be primary (idiopathic) or secondary (to vesicoureteric reflux, IgA nephropathy, Alport’s syndrome, vasculitis, sickle cell disease or heroin use).
- Presentation – usually with nephrotic syndrome and around 50% have impaired renal function.
- Renal biopsy – some glomeruli have scarring in certain segments (= focal sclerosis). There will be IgM and C3 deposits in affected areas on immunofluorescence.
- Management – 30% respond to corticosteroids but others may require cyclophosphamide.
- Prognosis – 30-50% progress to end stage renal failure and this can reoccur in a renal transplant.
Nephrotic syndrome - thin basement membrane nephropathy
An autosomal dominant condition that causes persistant microscopic haematuria and rarely minor proteinuria. Renal biopsy shows a thin basement membrane on electron microscopy. Prognosis – usually benign but there’s a small risk of progressing to CRF.
Nephrotic syndrome - management
Treat the underlying cause where possible.
- Monitor – U+Es, blood pressure, daily fluid balance and weigh the patient regularly.
- Treat oedema – create a negative sodium balance – Na+ intake <3g/day and fluid ̴1.5L/day.
- Diuretics – 80-250mg furosemide per 24 hours ± metolazone or spironolactone (monitor U+Es).
- Give an ACE inhibitor or angiotensin receptor blocker as these can decrease proteinuria.
- Treat infections promptly and vaccinations e.g. pneumococcal are recommended.
- Avoid prolonged bed rest – provide anticoagulation if patients are immobile and also when serum albumin is <20 g/L and proteinuria is within the nephrotic range (>3g in 24 hours).
Renal vein thrombosis
Can occur in nephrotic syndrome due to a hypercoaguable state (especially in membranous nephropathy). Other causes include invasion by renal cell carcinoma or thrombophilia.
- Signs – patients are often asymptomatic but may present with loin pain, haematuria, palpable kidney, sudden decline in renal function or with a pulmonary embolism.
- Diagnosis – doppler ultrasound, CT, MRI or renal angiography.
- Management – anticoagulate with warfarin for 3-6 months or until albumin >25 g/L (INR – 2-3).
ARF - definition
A significant deterioration in renal function occurring over hours to days. It manifests clinically as an abrupt and sustained rise in serum urea and creatinine. It can occur in isolation but more commonly occurs in the context of a circulatory disturbance (e.g. severe illness, sepsis, trauma or surgery) or nephrotoxic drugs. ARF is common in patients with diabetes, hypertension and the elderly.
ARF - presentation
Can be asymptomatic but often presents with oliguria (<400mL per 24 hours). Life threatening consequences of ARF include volume overload, hyperkalaemia and metabolic acidosis.
ARF - causes
Pre-renal failure and acute tubular necrosis account for >80% of cases of acute renal failure.
- Pre-renal – 40-70% of cases – due to renal hypoperfusion e.g. in hypovolaemia, sepsis (causes systemic vasodilation), chronic heart failure, cirrhosis, renal artery stenosis, NSAIDs or ACEi.
- Intrinsic – 10-50% of cases – acute tubular necrosis is damage to the renal tubular cells caused by ischaemia (due to hypoperfusion), nephrotoxins (drugs, radiological contrast agents, uric acid crystals, haemoglobinuria) or myeloma. Recovery of renal function usually occurs within weeks although mortality remains 50%. Other causes vasculitis, malignant hypertension, cholesterol emboli, HUS, TTP, GN, interstitial nephritis or hepatorenal syndrome.
- Post-renal – 10% of cases – due to urinary tract obstruction.
ARF - assessment
Make sure you know about the renal effects of all drugs taken.
- Acute or chronic? – suspect chronic renal failure when there’s a history of co-morbidities e.g. diabetes or hypertension, a long duration of symptoms, previously abnormal blood tests from GP records or lab results, small kidneys on ultrasound (<9cm) with increased echogenicity.
- Urinary tract obstruction? – should be suspected in patients with a single functioning kidney or in those with a history of caliculi, BPH or previous pelvic or retroperitoneal surgery. Examine the patient for a palpable bladder, pelvic or abdominal masses or an enlarged prostate. Renal ultrasound is the preferred method to detect dilatation of the renal pelvis and calyces.
- Is there a rare cause? – e.g. glomerulonephritis – this is usually associated with haematuria and proteinuria and warrant urgent renal referral for consideration of renal biopsy and treatment.
ARF - investigations
Bloods – Us+Es (look for hyperkalaemia), FBC, LFT, clotting, creatinine kinase, ESR and CRP. Consider ABG, blood cultures and hepatitis serology if dialysis is to be considered. If the cause is unclear then consider serum immunoglobulins, electrophoresis, complement levels, autoantibodies (ANA, ANCA, anti-dsDNA, anti-GBM) and ASOT (anti-streptolysin O titre).
Urine – dipstick (for leucocytes, nitrate, blood, protein, glucose), microscopy (for RBC, WBC, crystals and casts), culture, sensitivity or chemistry (Us+Es, creatinine, osmolality, BJ proteins).
Further tests – CXR for pulmonary oedema, ECG for hyperkalaemia and renal ultrasound.
ARF - management
Enlist specialist help and ensure recent U+Es and urine microscopy results available.
- Treat the treatable – identify and correct pre and post renal causes, check for a palpable bladder and get an urgent ultrasound, find and treat exacerbating factors – hypovolaemia, sepsis or hypertension, stop nephrotoxic drugs (e.g. NSAIDs, ACEi, gentamicin, vancomycin or amphoceracin) and metformin if creatinine >150 mmol/L and look for signs of vasculitis.
- Monitoring – monitor pulse, blood pressure, central venous pressure and urine output hourly. Complete a daily fluid and weight chart and match input to loss + 500mL for insensible losses.
ARF - complications
Hyperkalaemia – may cause arrhythmias or cardiac arrest. Treat with IV calcium gluconate (10mL of 10% over 2 mins and repeat as necessary), IV insulin and glucose (check capillary glucose), nebulised Salbutamol or haemodialysis or haemofiltration if the patient is anuric.
Pulmonary oedema – sit up and give high flow oxygen, give 2.5mg IV morphine (a venous vasodilator) with 10mg IV metoclopramide and 120-250mg IV furosemide over 1 hour. If there is no response the patients may require haemodialysis or haemofiltration and finally CPAP.
Bleeding – impaired haemostasis due to high levels of urea may be compounded by the precipitating cause. Give PPIs or H2 antagonists and when there is active bleeding give fresh frozen plasma and platelets if there are clotting abnormalities or a blood transfusion.
ARF - indications for dialysis
Refractory pulmonary oedema, persistent hyperkalaemia (>7 mmol/L), severe metabolic acidosis (pH <7.2 or base excess <10), uraemic encephalopathy or uraemic pericarditis.
CRF - definition
Kidney damage for >3 months based on findings of abnormal structure or function or a GFR <60 mL/min for >3 months with or without evidence of kidney damage. Classified into 5 stages:
- Stage 1 - >90 - normal GFR but there is evidence of kidney damage.
- Stage 2 - 60-89 - slightly impaired GFR with other evidence of kidney damage.
- Stage 3A - 45-59 and 3B - 30-44 - moderately impaired GFR with or without other evidence of damage (e.g. proteinuria, haematuria or evidence of renal disease).
- Stage 4 -15-29 - severely impaired GFR with or without evidence of kidney damage.
- Stage 5 - <15 - end stage renal failure
CRF - problems with MDRD
This is the formula used to grade renal disease by eGFR. It is only validated for patients with established renal disease – not for screening the general population. Most elderly patients are in stage 3 renal failure but this may not progress and labelling them may be damaging. In addition eGFR is affected by diet – a recent meal containing meat may artificially lower the result.
CRF - causes
The main causes are hypertension and diabetes mellitus.
- Common – glomerulonephritis, renovascular disease, pyelonephritis, polycystic kidney disease, benign prostatic hypertrophy, interstitial nephritis, analgesic nephropathy or renal caliculi.
- Rare – myeloma, amyloidosis, systemic lupus erythematous, scleroderma, vasculitis, HUS, nephrocalcinosis, gout, renal tumours, Alport’s syndrome or Fabry’s disease.
CRF - screening
High risk groups should be screened for chronic renal failure – diabetes, hypertension, age >60 years, recurrent UTIs, urinary obstruction, a systemic illness that affects the kidneys e.g. SLE, cardiovascular disease (IHD, CCF, peripheral vascular disease), cerebral vascular disease, structural renal tract disease, renal stones, BPH, family history of stage 5 or hereditary kidney disease.
CRF - clinical assessment
History – ask about previous UTIs, known hypertension or diabetes, family history of kidney disease, a detailed drug history, any signs of uraemia (fatigue, weakness, anorexia, vomiting, metallic taste, pruritus or restless legs) or pulmonary oedema (dyspnoea or leg swelling).
Signs – pallor, yellow skin pigmentation, brown nails, purpura, bruising, excoriation, hypertension, cardiomegaly, pericardial rub, pleural effusion, pulmonary or peripheral oedema or proximal myopathy plus the signs of the underlying causes e.g. diabetes and retinopathy.
CRF - investigations
Blood – anaemia (normochromic and normocytic), ESR, U+Es (raised urea and creatinine), glucose for diabetes, hypocalcaemia, hyperphosphataemia, raised alkaline phosphatase (renal osteodystrophy) and raised hyperparathyroid hormone.
Urine – microscopy, culture and sensitivity, dipstick and 24 hour urinary protein.
Imaging – renal ultrasound (size is usually small (<9cm) but may be normal or large with CRF in diabetes, polycystic kidney disease, amyloidosis or myeloma), DTPA scan (renogram), chest x-ray (for cardiomegaly, pleural or pericardial effusion or pulmonary oedema) or bone x-rays.
Renal biopsy – should be considered if the cause is unclear and the kidneys are normal size.
CRF - management - reversible causes
Look for and relieve any obstructions, stop nephrotoxic drugs and deal with hypercalcaemia and cardiovascular risk.
CRF - management - lifestyle advice
Patients should exercise, maintain a healthy weight and stop smoking. Dietary and fluid intake should be matched with excretion and Na+ restriction can help control blood pressure and prevent oedema. K+ restriction is only necessary if there is hyperkalaemia and HCO3- supplements can be given when acidosis requires correction.
CRF - management - associated features