NEPHROTIC SYNDROME

There is massively increased filtration of macromolecules across the glomer-ular capillary wall due to structural and functional abnormalities of the glomerular podocytes.

■ Hypoalbuminaemia (serum albumin <30 g/L) develops as a consequence of heavy proteinuria (>3.5 g/24 h in adults) and increased renal catab-olism of filtered protein.

■ Oedema is primarily due to sodium retention in the renal collecting tubules together with an increase in capillary permeability. A reduction in effective circulating volume also leads to oedema through similar mechanisms that occur in cardiac failure and cirrhosis (p. 166).

■ Hypercholesterolaemia and hypertriglyceridaemia are common in neph-rotic syndrome due to increased synthesis and impaired catabolism.

Aetiology

Nephrotic syndrome with ‘bland’ urine sediments

Membranous nephropathy and focal segmental glomerulosclerosis are the most common causes in adults and minimal-change nephropathy in children (Table 9.2). Membranous nephropathy is usually idiopathic but may occur in association with drugs (e.g. penicillamine, gold, NSAIDs), autoimmune disease (e.g. systemic lupus erythematosus [SLE], thyroiditis), neoplasia (car-cinoma of lung, colon, stomach, breast and lymphoma), infections (e.g. hepa-titis B and C, schistosomiasis and Plasmodium malariae) and other causes (sarcoidosis, sickle cell disease). There is deposition of IgG and complement C3 along the outer aspect of the glomerular basement membrane. Expansion of the basement membrane appears with time as the deposits are surrounded

Table 9.2 Glomerulopathies associated with the nephrotic syndrome
Nephrotic syndrome with ‘bland’ urine sediments
Primary glomerular disease
Minimal-change glomerular disease
Membranous nephropathy
Focal segmental glomerulosclerosis
Congenital nephrotic syndrome
Secondary glomerular disease
Amyloidosis
Diabetic nephropathy
Nephrotic syndrome with ‘active’ urine sediments (mixed nephrotic/nephritic)
Primary glomerular disease
Mesangiocapillary glomerulonephritis
Mesangial proliferative glomerulonephritis
Secondary glomerular disease
Systemic lupus erythematosus
Cryoglobulinaemic disease
Henoch–Schönlein syndrome
Idiopathic fibrillary glomerulopathy
Immunotactoid glomerulopathy
Fibronectin glomerulopathy

by basement membrane and eventually undergo resorption. Focal segmental glomerulosclerosis is of unknown aetiology and is a particular common cause of nephrotic syndrome in black adults. A similar histological type occurs in human immunodeficiency virus (HIV) infection.

Minimal-change nephropathy occurs most commonly in boys under 5 years of age. It accounts for 90% of cases of nephrotic syndrome in children and 20-25% in adults. The pathogenesis is unknown; immune complexes are absent on immunofluorescence but the increase in glomerular permeabil-ity is thought to be immunologically mediated in some way. The glomeruli appear normal on light microscopy. On electron microscopy there is fusion of the foot processes of epithelial cells (podocytes) - a non-specific finding.

Nephrotic syndrome associated with renal amyloid (p. 697) and diabetes mellitus (p. 684) is not immune mediated. Other renal diseases, e.g. poly-cystic kidneys, reflux nephropathy may cause proteinuria, but are rarely severe enough to cause the nephrotic syndrome.

Nephrotic syndrome with ‘active’ urine sediments (mixed nephrotic/nephritic)

Mesangiocapillary (membranoproliferative glomerulonephritis) occurs with chronic infection (abscesses, infective endocarditis, infected ventriculo-peritoneal shunt), cryoglobulinaemia secondary to hepatitis C infection or may be idiopathic. A different type occurs with partial lipodystrophy (loss of subcu-taneous fat on the face and upper trunk). Most patients develop renal failure over several years. Mesangial proliferative glomerulonephritis presents with heavy proteinuria with minimal changes on light microscopy. There are deposits in the glomerular mesangium of IgM and complement (IgM neph-ropathy) or C1q (C1q nephropathy). Some patients respond to steroids and some will progress to renal failure.

Clinical features

Oedema of the ankles, genitals and abdominal wall is the principal finding. The face (periorbital oedema) and arms may also be involved in severe cases.

Differential diagnoses

Nephrotic syndrome must be differentiated from other causes of oedema and hypoalbuminaemia. In congestive cardiac failure (p. 435) there is oedema and raised JVP. In nephrotic syndrome the JVP is normal or low unless there is concomitant renal failure and oliguria. Hypoalbuminaemia and oedema occur in cirrhosis, but there are usually signs of chronic liver disease on examination (p. 144).

Investigations

Investigations are indicated to make the diagnosis, monitor progress and determine the underlying aetiology (Table 9.3).

Management

General oedema is treated with dietary salt restriction and a thiazide diu-retic, e.g. bendroflumethiazide 5 mg daily (p. 348) followed by furosemide (frusemide) and amiloride for unresponsive patients. Intravenous diuretics and occasionally intravenous salt-poor albumin are required to initiate a diuresis which, once established, can usually be maintained with oral diuret-ics alone. Proteinuria is reduced by administration of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists; patients should be advised to eat a normal rather than high protein diet, which increases proteinuria. Prolonged bed rest should be avoided and long-term prophylactic anticoagulation given in view of the thrombotic tendency (see complications). Infections are treated aggressively and patients should be offered influenza and pneumococcal vaccination (p. 534).

Specitic treatment Treatment of the underlying disease, e.g. SLE, or cessation of the offending drug, e.g. penicillamine, is usually associated with improvement in secondary glomerulopathy. Only selected patients with moderate or severe progressive idiopathic membranous nephropathy should receive specific treatment as there is a high rate of spontaneous

Table 9.3 Investigations indicated in glomerular disease
Investigations Significance
Baseline measurements To determine current status, monitor
progress and response to treatment
Estimated glomerular filtration rate
Urinary protein
Serum urea and electrolytes
Serum albumin
Diagnostically useful tests
Urine microscopy Red cell casts indicate glomerulonephritis
Culture (swab from throat or
infected skin)
Diagnosis of recent streptococcal infection
Serum antistreptolysin-O titre
Blood glucose Diagnosis of diabetes mellitus

Serum tests:
Antinuclear and anti-DNA antibodies
ANCA
Anti-GBM antibody
Hepatitis B surface antigen
Hepatitis C antibody
HIV antibody
Cryoglobulins

 
Present in significant titre in SLE
Positive in vasculitis
Present in anti-GBM glomerulonephritis
Hepatitis B infection
Hepatitis C infection
HIV infection
Increased in cryoglobulinaemia
Chest X-ray Cavities in Wegener’s granulomatosis,
malignancy
Ultrasound of kidneys Renal size, to look for renal vein
thrombosis
SLE, systemic lupus erythematosus; ANCA, anti-neutrophil cytoplasmic antibody; GBM,
glomerular basement membrane; HIV, human immunodeficiency virus.

improvement. Treatment is with cyclophosphamide or chlorambucil with prednisolone. Rituximab (p. 254) is used in resistant disease. Minimal-change nephropathy is almost always steroid responsive in children, although less commonly in adults. High-dose prednisolone therapy (60 mg/m2/day) is given for 4-6 weeks and then tapered down slowly. Further courses are given if the patient has a relapse. In patients with frequent relapses and in steroid-unresponsive patients, immunosuppressive therapy with cyclophosphamide or ciclosporin is used.

Complications

■ Venous thrombosis. Loss of clotting factors in the urine predispose to thrombus formation in both peripheral and renal veins. The latter presents with renal pain, haematuria and deterioration in renal function and is diagnosed by ultrasonography.

■ Sepsis. Loss of immunoglobulin in the urine increases susceptibility to infection, which is a cause of death in these patients.

■ AKI is rarely the result of progression of the underlying renal disease and more often a consequence of hypovolaemia (particularly after diuretic therapy) or renal vein thrombosis.

Acute glomerulonephritis (acute nephritic syndrome)

Acute nephritic syndrome is often caused by an immune response triggered by an infection or other disease (Table 9.4). The typical case of post-streptococcal glomerulonephritis develops in a child 1-3 weeks after a strep-tococcal infection (pharyngitis or cellulitis) with a Lancefield group A p-haemolytic streptococcus. The bacterial antigen becomes trapped in the glomerulus, leading to an acute diffuse proliferative glomerulonephritis.

Clinical features

The syndrome comprises:

■ Haematuria (visible or non-visible) - red cell casts are typically seen in urine microscopy

■ Proteinuria (usually <2 g in 24 hours)

■ Hypertension and oedema (periorbital, leg or sacral) caused by salt and water retention

Table 9.4 Diseases commonly associated with the acute nephritic syndrome
Post-streptococcal glomerulonephritis
Non-streptococcal post-infectious glomerulonephritis, e.g. Staphylococcus,
mumps, Legionella, hepatitis B and C, schistosomiasis, malaria
Infective endocarditis
Shunt nephritis
Visceral abscess
Systemic lupus erythematosus
Henoch–Schönlein syndrome
Cryoglobulinaemia

■ Oliguria

■ Uraemia.

Investigations

The history and examination will help to assess the severity of the illness and to determine any associated underlying conditions. Investigations performed in the nephritic syndrome are listed in Table 9.3. If the clinical diagnosis of a nephritic illness is clear-cut, e.g. in poststreptococcal glomerulonephritis, renal ultrasonography and renal biopsy are usually unnecessary.

Management

Post-streptococcal glomerulonephritis usually has a good prognosis, and supportive measures are often all that is required until spontaneous recovery takes place. Hypertension is treated with salt restriction, loop diuretics and vasodilators. Fluid balance is monitored by daily weighing and daily recording of fluid input and output. In oliguric patients with evidence of fluid overload (e.g. oedema, pulmonary congestion and severe hypertension) fluid restric-tion is necessary. The management of life-threatening complications such as hypertensive encephalopathy (see p. 482), pulmonary oedema (p. 443) and severe uraemia (p. 389) are discussed in the appropriate chapters. In glom-erulonephritis complicating SLE or the systemic vasculitides (see below), immunosuppression with prednisolone, cyclophosphamide or azathioprine improves renal function.

Rapidly Progressive glomerulonephritis

There are three main causes: on a background of acute nephritic syndrome (see above), anti-glomerular basement membrane disease (which with lung involvement is called Goodpasture's syndrome, p. 552) and antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (p. 307). Investigations are listed in Table 9.3 and the management is based on general treatment of AKI (p. 383) and specific treatment directed against the causes.

Ebook Essentials of Kumar and Clark's Clinical Medicine, 5e

1. Ethics and communication

Ethics and communication

2. Infectious diseases

Infectious diseases

3. Gastroenterology and nutrition

Gastroenterology and nutrition

4. Liver, biliary tract and pancreatic disease

Liver, biliary tract and pancreatic disease
LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS
SYMPTOMS AND SIGNS OF LIVER DISEASE
JAUNDICE
HEPATITIS
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
CIRRHOSIS
COMPLICATIONS AND EFFECTS OF CIRRHOSIS
LIVER TRANSPLANTATION
TYPES OF CHRONIC LIVER DISEASE AND CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
BUDD - CHIARI SYNDROME
LIVER ABSCESS
LIVER DISEASE IN PREGNANCY
LIVER TUMOURS
GALLSTONES
THE PANCREAS
CARCINOMA OF THE PANCREAS
NEUROENDOCRINE TUMOURS OF THE PANCREAS

5. Haematological disease

Haematological disease
ANAEMIA
Assessment and treatment of suspected neutropenic sepsis
HAEMOLYTIC ANAEMIA
INHERITED HAEMOLYTIC ANAEMIAS
ACQUIRED HAEMOLYTIC ANAEMIA
MYELOPROLIFERATIVE DISORDERS
THE SPLEEN
BLOOD TRANSFUSION
THE WHITE CELL
HAEMOSTASIS AND THROMBOSIS
THROMBOSIS
THERAPEUTICS

6. Malignant disease

Malignant disease
MYELOABLATIVE THERAPY AND HAEMOPOIETIC STEM CELL TRANSPLANTATION
THE LYMPHOMAS
THE PARAPROTEINAEMIAS
PALLIATIVE MEDICINE AND SYMPTOM CONTROL

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Rheumatology
COMMON INVESTIGATIONS IN MUSCULOSKELETAL DISEASE
COMMON REGIONAL MUSCULOSKELETAL PROBLEMS
BACK PAIN
OSTEOARTHRITIS
INFLAMMATORY ARTHRITIS
THE SERONEGATIVE SPONDYLOARTHROPATHIES
Clinical features, Investigations
INFECTION OF JOINTS AND BONES
AUTOIMMUNE RHEUMATIC DISEASES
SYSTEMIC INFLAMMATORY VASCULITIS
DISEASES OF BONE
THERAPEUTICS

8. Water, electrolytes and acid–base balance

WATER AND ELECTROLYTE REQUIREMENTS
BODY FLUID COMPARTMENTS
REGULATION OF BODY FLUID HOMEOSTASIS
PLASMA OSMOLALITY AND DISORDERS OF SODIUM REGULATION
DISORDERS OF POTASSIUM REGULATION
DISORDERS OF MAGNESIUM REGULATION
DISORDERS OF ACID - BASE BALANCE
THERAPEUTICS

9. Renal disease

Renal disease
INVESTIGATION OF RENAL DISEASE
GLOMERULAR DISEASES
NEPHROTIC SYNDROME
URINARY TRACT INFECTION
TUBULOINTERSTITIAL NEPHRITIS
HYPERTENSION AND THE KIDNEY
RENAL CALCULI AND NEPHROCALCINOSIS
URINARY TRACT OBSTRUCTION
ACUTE RENAL FAILURE/ACUTE KIDNEY INJURY
CHRONIC KIDNEY DISEASE
RENAL REPLACEMENT THERAPY
CYSTIC RENAL DISEASE
TUMOURS OF THE KIDNEY AND GENITOURINARY TRACT
DISEASES OF THE PROSTATE GLAND
TESTICULAR TUMOUR
URINARY INCONTINENCE

10. Cardiovascular disease

COMMON PRESENTING SYMPTOMS OF HEART DISEASE
INVESTIGATIONS IN CARDIAC DISEASE
CARDIAC ARRHYTHMIAS
HEART FAILURE
ISCHAEMIC HEART DISEASE
RHEUMATIC FEVER
VALVULAR HEART DISEASE
PULMONARY HEART DISEASE
MYOCARDIAL DISEASE
CARDIOMYOPATHY
PERICARDIAL DISEASE
SYSTEMIC HYPERTENSION
ARTERIAL AND VENOUS DISEASE
ELECTRICAL CARDIOVERSION
DRUGS FOR ARRHYTHMIAS
DRUGS FOR HEART FAILURE
DRUGS AFFECTING THE RENIN - ANGIOTENSIN SYSTEM
NITRATES, CALCIUM - CHANNEL BLOCKERS AND POTASSIUM - CHANNEL ACTIVATORS

11. Respiratory disease


Respiratory disease
TUBERCULOSISnd
DIFFUSE DISEASES OF THE LUNG PARENCHYMA
OCCUPATIONAL LUNG DISEASE
CARCINOMA OF THE LUNG
DISEASES OF THE CHEST WALL AND PLEURA
DISORDERS OF THE DIAPHRAGM

12. Intensive care medicine

Intensive care medicine

13. Drug therapy, poisoning, and alcohol misuse

Drug therapy, poisoning, and alcohol misuse

14. Endocrine disease

Endocrine disease
PITUITARY HYPERSECRETION SYNDROMES
THE THYROID AXIS
MALE REPRODUCTION AND SEX
FEMALE REPRODUCTION AND SEX
THE GLUCOCORTICOID AXIS
THE THIRST AXIS
DISORDERS OF CALCIUM METABOLISM
DISORDERS OF PHOSPHATE CONCENTRATION
ENDOCRINOLOGY OF BLOOD PRESSURE CONTROL
DISORDERS OF TEMPERATURE REGULATION
THERAPEUTICS

15. Diabetes mellitus and other disorders of metabolism

DIABETES MELLITUS
DIABETIC METABOLIC EMERGENCIES
COMPLICATIONS OF DIABETES
SPECIAL SITUATIONS
HYPOGLYCAEMIA IN THE NON - DIABETIC
DISORDERS OF LIPID METABOLISM
THE PORPHYRIAS

16. The special senses

THE EAR
THE NOSE AND NASAL CAVITY
THE THROAT
THE EYE

17. Neurology

COMMON NEUROLOGICAL SYMPTOMS
COORDINATION OF MOVEMENT
THE CRANIAL NERVES
COMMON INVESTIGATIONS IN NEUROLOGICAL DISEASE
UNCONSCIOUSNESS AND COMA
STROKE AND CEREBROVASCULAR DISEASE
EPILEPSY AND LOSS OF CONSCIOUSNESS
NERVOUS SYSTEM INFECTION AND INFLAMMATION
HYDROCEPHALUS
HEADACHE, MIGRAINE AND FACIAL PAIN
SPINAL CORD DISEASE
DEGENERATIVE NEURONAL DISEASES
DISEASES OF THE PERIPHERAL NERVES
MUSCLE DISEASES
MYOTONIAS
DELIRIUM
THERAPEUTICS

18. Dermatology

Dermatology

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