Syndromology in nephrology

1
Syndromology in nephrology

• Martina Peiskerová
• 1.LF UK Praha
• Klinika nefrologie
• 9/2007

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Syndromology in nephrology - outline

• Chronic glomerulonephritis ??
• Acute renal failure
• Chronic kidney disease
• (Chronic renal failure)
• Uraemia
• Tubular syndromes
• Hypertension
• Pain
• Obstruction

• Haematuria
• Proteinuria
• Leucocyturia
• Polyuria, oliguria, anuria
• Nephrotic syndrome
• Nephritic syndrome
• Acute glomerulonephritis
• Rapidly progressive glomerulonephritis
• Pulmonary-renal syndromes

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Haematuria

• Definition gt 2 red cells / hpf ,
• Hamburgers sediment (3 hours) gt 2000/min.
• microscopic x macroscopic
• persitent x transient (exercise, menstruation,
  trauma, infection)
• glomerular x non-glomerular x uncertain origin
  (exercise, over-anticoagulation, factitious)
• Source kidney x urinary tract
• Renal glomerular haematuria (IgA GN, thin
  basement memrane disease, Alport, other GN)
• Renal non-glomerular haematuria (tumours, cysts,
  calculs, pyelonephritis, papillary necrosis,
  renal vein thrombosis)
• Urinary tract bleeding (cystitis, prostate,
  tumours, stricture, Schistosoma haematobium)

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Clinical importance of haematuria

• Cause dependent
• The most frequent causes
• - inflammation or infection of the
  prostate or urinary bladder
• urinary calculi
• malignant neoplasms
• glomerular disorders
• Risk of malignity age gt40, smoking, NSA, pelvic
  irradiation, CFA treatment)
• Glomerular disorder more likely if
• proteinuria gt 0.5 g/24h
• dysmorphic erythrocytes present and red blood
  cells casts on phase-contrast microscopy
• ?BP

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Diagnosis of haematuria - history and physical
examination

• Pyuria or dysuria ? urinary tract infection
• Respiratory tract infection ? postinfectious GN,
  IgA nephropathy
• Family history ? polycystic kidney disease,
  hereditary nephritides
• Low back pain ? ureteral obstruction
• Physical exercise, injury ? post-exercise/post-tra
  umatic hematuria
• Micturition disorders in older men ? prostatic
  obstruction
• History of bleeding from multiple sources ?
  coagulation disorder

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Phase-contrast microscopy

• A-dysmorphic erythrocytes
• B-isomorphic erythrocytes
• C-acanthocytes
• (spur / spiny / star cells)
• D- neutrophils
• E-lymphocytes
• F-eosinophils (arrow),

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Diagnosis Treatment of haematuria

• Urinalysis
• Urine microscopy (sediment, phase-contrast)
• PSA
• Imaging (US, IVU,CT, angiography)
• Cystoscopy
• Urine cytology
• Renal biopsy (in glomerular hematuria)
• Early diagnosis is essential
• Treatment of the causing disorder

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Proteinuria

• benign (lt1g/day, age lt 30, fever, cold, exercise,
  CCF, seizures, postural), vs. pathological
• importance of abnormal proteinuria
• marker of intrinsic renal disease, prognostic
  factor for progression of renal insufficiency,
  risk factor for CV mortality, treatment target in
  CKD
• normally lt 150 mg/day (albumine lt 30 mg/ day)
• microalbuminuria 30-300 mg/day

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Proteinuria 2

• Pathophysiology
• glomerular (mostly albumin),
• tubular (beta2microglobulin),
• overflow (light chains in myeloma),
• secretory (tumour, inflammation)
• Quantity
• Mild lt 1,0 g/day
• Significant 1,0 3,5 g/day (probably glomerular)
• Nephrotic range gt 3,5 g/day (probably glomerular)

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Leucocyturia

• neutrophiles infection, GN, TIN
• sterile pyuria (treated UTI, Chlamydia, calculi,
  prostatitis, bladder tumor, papillary necrosis,
  TIN, TB)
• lymphocytes TIN
• Active urinary sediment
• red blood cells, proteinuria, white blood cells,
  and "casts" of cells

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Urinary sediment abnormalitiesMixed urinary
findings

• isolated haematuria or haematuria mild
  proteinuria (lt1g/day) good prognosis
• isolated proteinuria (lt3,5g/day) .. worse
  prognosis
• nephrotic proteinuria haematuria the worst
  prognosis

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Nephrotic syndrome clinical complex consisting
of

• Proteinuria of gt3.5g / 1.73m2 / 24 hours
• Hypoalbuminaemia
• Oedema
• Hyperlipidaemia
• Lipiduria
• Hypercoagulability

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Patophysiology of the nephrotic syndrome. Primary
insult- increased glomerular permeability,
causing plasma protein leakage into urine.
Hypoalbuminemia is the cause of the main clinical
features.
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Metabolic albumin turnover in healthy subjects
vs. subjects with nephrotic syndrome.
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??
The underfill mechanism of edema formation. In
this theory, hypovolemia (caused by
hypoalbuminemia and decreased oncotic plasma
pressure) is the main cause of renal Na a H20
retention.
16
??
The overfill mechanism of edema formation. In
this theory, abnormal renal Na and H20 retention
is the main cause of Starling forces alteration
at local tissue level.
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(Possible) consequences of proteinuria and lipid
spectrum abnormalities.
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Diagram showing pathogenetic factors leading to
hypercoagulability, tromboembolism and renal vein
thrombosis.
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Causes of nephrotic syndrome
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Treatment of nephrotic syndrome

• Symptomatic
• NaCl, H20 restriction
• diuretic therapy
• ultrafiltration
• nephrectomy

• Specific (depending on the causative disease)
• immunosuppressive therapy
• in amyloidosis, treatment of the causative process

• Treatment and prevention of complications
• thromboembolism
• lipid metabolism disturbances
• immunoglobulin deficiency
• Ineffective high protein diets, albumin
  supplementation.

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Nephritic syndrome

• Glomerular inflammatory changes leading to
• ? GFR
• moderate proteinuria
• oedema
• hypertension
• haematuria (red cell casts).
• Typical example Poststreptococcal
  glomerulonephritis in children

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Differences between nephrotic and nephritic
syndromes
Typical features Nephrotic syndrome Nephritic syndrome
onset slow acute
swelling
arterial blood pressure normal increased
central venous pressure normal/low increased
proteinuria
hematuria present/not present
red cell casts not present present
glomerular filtration normal normal/low
serum albumin low normal/slightly decreased
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Histology (light microscopy) of acute
poststreptococcal GN (marked invasion of
polymorphonuclear cells)
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• Histology of acute poststreptococcal GN
  (subepithelial hump-like deposits (strait
  arrows), subendothelial (arched arrows) and
  mesangial deposits). Endocapillary
  hypercellularity caused by neutrophil
  infiltration, endothelial and mesangial
  proliferation.

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Immunological findings in poststreptococcal GN

• 1. The serial estimation of complement -
• Early in the acute phase, the levels of hemolytic
  complement activity (CH50 and C3) reduced.
• Within 8 weeks return to normal
• 2. Serial ASO titer measurements - twofold or
  greater rise in titer are highly indicative of a
  recent infection.

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Continuous alterations of structural changes
caused by glomerular inflammation (upper part),
clinical syndromes (middle part) and specific
nosologic units (lower part).
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Rapidly progressive GN (RPGN)

• Severe glomerular disorder ? ? glomerular
  filtration in days or weeks.
• Clinical features acute uremic or nephritic
  syndrome with renal insufficiency rapidly ? renal
  failure
• Histology negative IF (pauci-immune), crescentic
  GN (crescent half-moon-shaped lesion in
  Bowmans space composed of proliferating parietal
  epithelial cells and infiltrating monocytes).
  Crescentic GN gt70 glomeruli are involved.
• Typical diseases WG, GP and SLE.
• Extrarenal symptoms pulmonary, skin, ORL,
  CNS..

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Large cellular crescent filling the Bowmans
space and compressing the glomerular tuft in WG.
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Acute renal failure 1

• due to rapid ? GFR (hours, days)
• retention of urea, creatinine, disorders in
  electrolytes, acid-base, fluid homeostasis
• oliguric x non-oliguric
• anuria lt 100 ml/day, oliguria lt 400 ml/day,
  polyuria gt 3l/day
• RIFLE classification
• Risk.. InjuryFailure.. LossEnd-stage)
• Acute kidney injury classification
• 1. s-creat to 1,5-2x baseline / oliguria gt 6
  hours
• 2. s-creat to 2-3x baseline / oliguria gt 12
  hours
• 3. s-creat above 3x baseline / anuria
• the highest risk pulmonary edema,
  hyperkalemia

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Acute renal failure 2 - causes

• Prerenal (from ? BP ? ? GFR, or arterial
  stenosis or NSA, ACEI)
• Intrinsic
• - ATN (ischemic e.g.myoglobinuria, myeloma
• casts, nephrotoxic radiocontrast, drugs
  gentamicin,
• vancocin, cisplatin)
• - vascular
• - acute GN
• - acute TIN
• Postrenal (obstructive)
• Patients at risk of developping ARF ?age, DM,
  pre-existing renal disease, surgery, volume
  depletion, cardiac disease, cirrhosis, drugs
  NSA, ACEI, ARB), myeloma

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Chronic kidney disease ? Renal insufficiency ?
Renal failure

• exocrine dysfunction (ions K, Na, P, H..,
  fluid, and other catabolites uremic toxins
  retention)
• endocrine dysfunction (erythropoietin, 1,25
  vitamin D metabolism, renin-angiotensin system)
• ? laboratory GF lt 1,0 ml/s, hyperkalemia,
  hypocalcemia, hyperphosphatemia, metabolic
  acidosis, anemia

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Stages of kidney disease NKF/ KDOQI

• Asymptomatic urinary abnormalities
• GFR gt 90
  ml/min (gt 1,5 ml/s)
• Mild CRF GFR 60-89 ml/min (1-1,5
  ml/s)
• Moderate CRF GFR 30-59 ml/min (0,5-1 ml/s)
• Severe CRF GFR 15-29 (0,25-0,5
  ml/s)
• 5 Approaching ESRD GFR lt 15 ml/min (lt 0,25
  ml/s)

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Uremic syndrome - clinical features 1

• Gastrointestinal
• Anorexia, nausea, vomiting
• Neurological
• Central uremic encefalopathy (daytime
  drowsiness, disorientation, myoclonus, coma)
• Peripheral uremic polyneuropathy (restless legs
  syndrome)
• Respiratory
• pulmonary edema

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Uremic syndrome - clinical features 2

• Cardiac
• uremic pericarditis
• Dermatological
• pruritus
• Hematological
• fatigue due to anemia
• Endocrinological
• secondary hyperparathyreoidism (bone pain),
  dysmenorrhea

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• Uremia
• in 3 different clinical situations ?
  different clinical
• features
• acute renal failure exocrine dysfunction, no
  time for endocrine dysfunction development
• chronic renal failure endocrine and exocrine
  renal dysfunction (fluid excretion usually
  preserved until late stages)
• dialysis treated CRF caused by insufficient
  dialysis treatment and/or insufficient
  substitution of the decreased renal endocrine
  production (EPO, vitamin D, etc.).

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Potentially Toxic Compounds That Accumulate in
Renal Failure
Urea Pyridine
derivatives Phenols
Guanidino compounds Indoles
b2-Microglobulin Skatoles
Aliphatic amines Hormones
Hippurate esters Polyamines
Trace elements (Mg) Aromatic amines
Serum proteineases
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Toxic Sequelae of Metabolic Acidosis Organ
Mechanism ? Sequelae Muscle
Proteolysis ? Loss of lean body
mass Bone Inhibition of osteoblasts ?
Dissolution of bone matrix Stimulation of
osteoclasts ? Dissolution of bone mineral
Hormonal ? PTH level ? Osteopenia ?
Vitamin D3 ? Osteomalacia ? Cortisol ?
Activation of catabolism ? Thyroxine ?
Hypometabolism ? Growth hormone
? Stunted growth ? Insulin resistance ?
Activation of catabolism
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Treatment of uremia

• Conservative
• diet Na, K, PO3 and protein restriction
• control of hypertension
• NaHC03 treatment to reduce metabolic acidosis
• anemia management (erythropoietin)
• secondary hyperparathyroidism management (vitamin
  D, phosphate binders)
• Renal replacement therapy hemodialysis,
  peritoneal dialysis, renal transplantation

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Pulmonary-renal syndromes

• Acute kidney disease (ARF or RPGN) Pulmonary
  haemmorhage
• Features cough, anaemia, dyspnoea, haemoptysis,
  hypoxaemia, alveolar shadowing on CXR (df.dg.
  pulmonary oedema) features of systemic disease
  skin rush, sinusitis, artritis, fever, fatigue
• Main causes ANCA vasculitis, antiGBM nephritis,
  SLE, Henoch-Schonlein purpura
• Other causes pulmonary oedema, infection
  (pneumonia Pneumocystis, viruses..),
  hantavirus, pulmonary emboli, acute respiratory
  distress syndrome

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Hypertension

• Primary hypertension kidney is victim
• - vascular nephrosclerosis..
• Secondary hypertension kidney is vilain
• - glomerular and vascular diseases
• Control of hypertension is crucial in slowing
  progression of kidney disease ? aim BP 120/75 mm
  Hg

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Tubular syndromes

• Tubular dysfunction may occur in any renal injury
• Tubular syndromes in the context of normal GFR
• Generalised Fanconi syndrome multiple tubular
  defects caus in variable degree
• ? phosphaturia ? rickets, osteomalacia,
  osteoporosis
• ? aminoaciduria no clinical sequelae
• ? glycosuria rarely hypoglycemia
• ? defective bicarbonate reabsorption
  renal tubular acidosis
• ? Na loss ? rarely ?BP or metabolic
  alcalosis
• ? K loss ? hypokalaemia ? muscle weakness,
  constipation, arrhytmias
• ? proteinuria LMW, no clinical sequelae
• ? polyuria dehydration
• ? hypercalciuria ? rarely
  nephrolitihiasis/calcinosis
• Isolated genetic mechanisms involved
• - glycosuria - to distinguish from DM
• - aminoaciduria - e.g. cystinuria ? recurrent
  cystin stone formation (AR inheritance)
• - phosphaturia e.g. vitamin D resistant
  rickets (XR inheritance)

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Pain

• An agressive and destructive renal disease may be
  painless !!
• Loin pain - constant dull ache, may irradiate to
  abdomen, genitalia
• cause distension of the renal capsule
• differential nerve root irritation (T10-12)
• Ureteric colic - sudden onset, extremely sever,
  pale, distressed patient
• localisation loin, iliac fossa, genitalia, upper
  thigh
• cause passage of the stone, blood clot or
  necrotic papillae
• Suprapubic pain
• causes over-distension of the bladder, cystitis,
  bladder cancer
• Bladder irritability - dysuria, frequency,
  urgency
• causes over-distension of the bladder, cystitis

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Bladder outflow obstruction

• Symptoms
• Obstructive voiding hesitancy, impaired force
  of stream, incomplete emptying
• Storage filling frequency, dysuria, urgency
• Causes
• Structural prostatic hyperplasia, carcinoma,
  urethral stricture
• Functional bladder neck dyssynergia, DM,
  multiple sclerosis, spinal corde lesions, drugs -
  antidepressants