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Nephritic Sx & Nephrotic Sx Case report 1 18 yr old man Bilateral loin pain Macroscopic haematuria Sore throat started one day earlier BP 140/90; euvolaemic Creatinine 120 μmol/l Proteinuria and haematuria on dipstix Case Report 2 20 yr old lady Completely well Haematuria on dipstix No proteinuria Normotensive Case Report 3 12 year old boy Impetigo two weeks earlier Headache Oliguric Frothy dark coloured urine Hypertensive Case report 4 15yr old woman 3/12 ankle swelling; face and fingers swollen in the am BP 130/80; JVP normal; Leg oedema Creatinine 54 μmol/l Cr Cl 140 ml/min Albumin 18 g/l 24 hr u.protein 10 g Case Report 5 30 year old man,diabetic Known hypertensive Ankle oedema Dipstix: ++++ proteinuria Creatinine 124 μmol/l (80 – 120) Albumin 30 g/l (36 – 45) Case Report 6 50 year old obese man Hypertension 10 years NIDDM 3 years No retinopathy Creatinine 124 μmol/l 24 hr urine protein 2 g HbA1 9.6% Structure of the filtration barrier Podocyte Foot processes Fenestrated endothelium 10 Minimal change disease Glomerular changes in disease Proliferation Sclerosis Necrosis Increase in mesangial matrix Changes to basement membrane Immune deposits Diffuse vs focal Global vs segmental Common Syndromes Nephrotic Syndrome Nephritic Syndrome Rapidly Progressive GN Loin Pain Haematuria Syndrome Features of Glomerular Disease Proteinuria Haematuria Renal Failure Salt and Water Retention Loin Pain Salt and Water Retention Hypertension Oedema Oliguria Loin Pain Rare Proteinuria Marker of renal disease Risk factor for cardiovascular disease – Dyslipidaemia – Hypertension – Something more? 24 hr protein vs urine protein:creatinine ratio Nephrotic syndrome Proteinuria > 40 mg/m2*hr Hypoalbuminaemia (<2.5mg/dl) Oedema Hyperlipidemia Thromboses Infection Learning Points Clinical features Commonest types Prognosis Causes Treatments Nephrotic Syndrome Causes of primary idiopathic NS – Minimal change disease – Mesangial proliferation – Focal segmental glomerulosclerosis Minimal Change Disease Usually children Nephrotic syndrome with highly selective proteinuria and generalised oedema Rarely hypertension or ARF T cell mediated – VPF Steroid sensitive usually Spectrum of disease to FSGS Focal Segmental Glomerulosclerosis Juxtamedullary glomeruli – may be missed due to sampling error Older patients Less sensitive to immunosuppression Hypertension, haematuria, progressive CRF FSGS: Familial VUR Drug abuse Obesity Common types of GN Primary Thin membrane disease IgA disease Minimal Change / FSGS spectrum Membanous Nephropathy Secondary PSGN & Diabetic Glomerulosclerosis Rarer Types Diffuse endocapillary proliferative GN (post infectious GN) Crescentic GN Membanoproliferative / mesangiocapillary GN Nephritic Syndrome Haematuria Hypertension Oliguria Edema Rapidly progressive GN Nephritic or nephrotic onset ESRF in six months General Treatment of GN Control BP Angiotensin blockade Statin Lose weight Stop smoking (pneumococcal prophylaxis) (anticoagulation) Help! I need a volunteer! 30 Case report 1 18 yr old man Bilateral loin pain Macroscopic haematuria Sore throat started one day earlier BP 140/90; euvolaemic Creatinine 120 μmol/l Proteinuria and haematuria on dipstix Case 1: indicative answers IgA Disease Renal failure, proteinuria, haematuria, oedema, hypertension, oliguria, loin pain All except oedema and oliguria Mesangial IgA disease Classical Berger’s Disease Microscopic haematuria Proteinuria (rarely nephrotic) Hypertension Chronic renal failure ? Failure of hepatic clearance of IgA Association with GI disease No specific treatment Ig A Nephropathy Ig A nephropathy is the most common primary GN worldwide Usually present with hematuria Episodes of gross hematuria are precipitated by flu like illness, exercise Urinary protein excretion usually non-nephrotic Associated with chronic liver ds, psoriasis, IBD and HIV disease. Ig A Nephropathy Only 30% of patients with IgA nephropathy has progressive disease. In progressive disease, use of fish oil may be beneficial. Immunosuppressive therapy in patients with Ig A nephropathy has not consistently shown to be of benefit Case Report 2 20 yr old lady Completely well Haematuria on dipstix No proteinuria Normotensive Case 2: indicative answers Exclude menstruation! Thin membrane disease (possibly IgA disease) Commonest cause of isolated microscopic haematuria in this age group. At this age, urological cause unlikely; nil to suggest infection / urolithiasis Thin membrane disease Most common GN Microscopic haematuria Familial Benign No treatment needed Most young people with isolated microscopic haematuria have thin membrane disease Case Report 3 12 year old boy Impetigo two weeks earlier Headache Oliguric Frothy dark coloured urine Hypertensive Case 3: indicative answers Acute nephritic syndrome Post-streptococcal glomerulonephritis Diffuse proliferative endocapillary glomerulonephritis Due to salt and water retention, so salt restriction or loop diuretic Acute Post-Infectious GN Usually occur in children Post-streptococcal GN is the most common cause of post infectious GN Occurs after a streptococcal sore throat or impetigo Caused by Group A, beta-hemolytic streptococci, particularly nephritogenic strains – Type 1,4,12 (throat) and 2,49(skin) Acute Post-Infectious GN Acute onset of gross hematuria (COLA COLORED) or microscopic hematuria after latent period of 10-14 days. Edema/hypertension RBC casts on U/A Elevated creatinine, increased ASO titer Decreased complement level Acute Post-Infectious GN LM – Diffuse proliferative and exudative GN IF – IgG and C3 “lumpy, bumpy” EM – Sub epithelial “Hump” or “Flame” like deposits Diffuse Endocapillary Proliferative GN (Post Streptococcal GN) Diffuse endocapillary proliferative GN Post infectious; usually Gp A Strep Acute nephritic syndrome Uraemia rare Self-limited; rarely death from BP Abnormal RUA for up to 2 yrs Circulating immune complex mediated Acute Post-Infectious GN Renal biopsy is generally not required. Treatment is supportive and consist of sodium restriction, control of BP and dialysis if this become necessary. Complications of the Nephritic Syndrome Hypertensive encephalopathy (seizures, coma) Heart Failure (pulmonary oedema) Uraemia requiring dialysis Prognosis in the Nephritic Syndrome More than 95% of children make a complete recovery Chronic renal impairment in the longer term is uncommon in children Bad prognostic features include severe renal impairment at presentation and continuing heavy proteinuria and hypertension Adults more likely to have long term sequellae than children Case report 4 15 yr old girl 3/12 ankle swelling; face and fingers swollen in the am BP 130/80; JVP normal; Leg oedema Creatinine 54 μmol/l Cr Cl 140 ml/min Albumin 18 g/l 24 hr u.protein 10 g Case 4: indicative answers Minimal change – focal segmental glomerulosclerosis spectrum Very nephrotic Age and borderline BP make FSGS more likely than MCN Effect of loss of colloid osmotic pressure gradient across glomerulus causing hyperfiltration Case Report 5 30year old man,diabetic Known hypertensive Ankle oedema Dipstix: ++++ proteinuria Creatinine 124 μmol/l (80 – 120) Albumin 30 g/l (36 – 45) Case 5: indicative answers Nephrotic syndrome secondary to diabetes / membranous disease Refer urgently to nephrology Diabetic glomerulosclerosis Retinopathy Hypertension Microalbuminuria Nephrotic syndrome Renal failure – usually progressive Poor prognosis on RRT What we’d like! Demography including tel no and occupation Reason for referral: presenting complaint, expectations Co-morbidities, incl other diagnoses, smoking, alcohol and BMI, social care needs Examination Medications (incl recently stopped), allergies etc Treatment and investigations to date Special requirements (eg interpreter) Case Report 6 50 year old obese man Hypertension 10 years NIDDM 3 years No retinopathy Creatinine 124 μmol/l 24 hr urine protein 2 g HbA1 9.6% Case 6: indicative answers Obesity-related FSGS more likely than diabetic nephropathy (duration diabetes, absence of retinopathy) Worsening nephrotic syndrome and progressive renal failure; Death from cardiovascular cause before reaches ESRF Stop smoking, lose weight, improve glycaemic control, regular exercise, healthy diet, moderate alcohol in that order Case 6: indicative answers contd Lack of ownership of responsibility for own health Withdrawal symptoms (smoking) Denial of calorie intake Difficulty exercising due to immobility No! – Problems with MDRD equation – No evidence of benefit of ACE inhibitors in absence proteinuria – Dangers of ACE inhibitors in patients with angioneurotic oedema, hypotension or bilateral renal artery stenosis Lessons Not all abnormal urinalysis is a UTI Acute pyelonephritis is very rarely bilateral Haematuria Urologist or Nephrologist? Age Other features – proteinuria etc Urine microscopy for casts Phase contrast microscopy Non-dysmorphic vs dysmorphic RBC Cast AntiGBM disease RPGN + Lung haemorrhage Destructive process – medical emergency! Antibody-mediated One hit High dose immunosuppression Plasma exchange Any Questions? Whoopee! It’s ......... ….Coffee Time
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