Approach to the patient with renal disease

Dr. Silvia Spnu

Reminder
Syndrome = an association of signs and symptoms which form together a characteristic morbid frame, which can be observed in different diseases.

Disease = a morbid entity characterized usually by at least two of these criteria: - recognized etiologic agent(s) - identifiable group of signs and symptoms - consistent pathological alterations.

Identification of renal disease

Reno-urinary signs/symptoms Urinary or blood abnormalities identified occasionally or by screening Abnormal reno-urinary imaging studies (US, CT, etc.) First stage renal investigations (routine) Clinical examination: anamnesis, physical examination Urinalysis, quantitative determinations (eg. proteinuria/24 h) Serum creatinine and urea (creatinine clearance calculation); electrolytes; acid-base balance Imaging: US, intravenous urography

Recognizing the renal syndromes Targeted renal investigations Diagnosis of the renal disease

Renal syndromes
Renal failure (acute, rapidly progressive, chronic) Nephritic syndrome Nephrotic syndrome Macroscopic hematuria Asymptomatic urinary abnormalities Urinary tract infection Renal tubule defects Hypertension Nephrolithiasis Urinary tract obstruction

Acute renal failure

Definition= abrupt of GFR (hours or days) with consecutive azotemia Dx. criteria: - rapid increase of sU and sCr - oliguria (D<400 ml/24h) or anuria - signs and symptoms of uremia - hyper K+-emia, metabolic acidosis Etiology: prerenal, renal, postrenal

Rapidly progressive renal failure

Definition= progressive of GFR in the course of weeks with consecutive doubling of serum creatinine in less than 3 months. Etiology: - primary extracapillary (rapidly progressive) GN and secondary GN (vasculitis, Goodpasture syndrome). - other: thrombotic microangiopathies (HUS), tubulointerstitial nephritis.

Chronic renal failure

Definition= complex of clinical and biochemical abnormalities resulting from a progressive and ireversible damage of the nephrons. Dx. criteria: - GFR with consecutive azotemia documented for >3 months - US: decreased kidney size - anemia Etiology: the majority of chronic nephropathies

The structure of the glomerular capillary wall

The role /function of the glomerular capillary wall

Role = to assure the selective passage of substances into urine. Permselectivity - assured by all 3 components of the barrier: - size selectivity and/or - electrical charge selectivity Damage to any of the 3 components => proteinuria

The nephritic syndrome (Acute GN) Pathophysiology Definition= the result of acute inflamation in the renal glomeruli.
acute of GFR damage of the glomerular capillary wall (GCW)

Hydrosaline retention

Glomerular macro/microscopic hematuria (dysmorphic erythrocytes, erythrocyte casts) Glomerular proteinuria

Facial and peripheral edema

Oliguria, hypervolemia hypertension, acute pulmonary edema

The nephritic syndrome Dx. criteria: Hematuria (glomerular) Edema Hypertension Proteinuria (glomerular) Acute of GFR
Etiology: primary and secondary glomerular diseases

Types of hematuria
nonglomerular glomerular

Erythrocyte casts

Proteinuria
Physiological proteinuria - up to 150 mg/24h - globulins + albumin (~2-20 mg/24h) Microalbuminuria = urinary loss of albumin between 30-300 mg/24h - pathological! - marker of early glomerular injury (eg. diabetic nephropathy) - marker of vascular endothelial dysfunction assessment of cardiovascular risk

Types of proteinuria
Glomerular: - proteins with intermediate MW (mostly albumin) - Cause: defective glomerular barrier Tubular: - Proteins with low MW (2-microglobulin, retinol binding protein)-normally filtered in the glomerulus and reabsorbed in the proximal tubule. - Cause: tubulointerstitial nephritis (reabsorbtion) Prerenal (overflow proteinuria): - proteins with low MW (/ light chains) - production that overcomes tubular reabsorbtion capacity - Cause: plasma cell dyscrasias (eg. myeloma)

Types of proteinuria (urine protein electrophoresis): glomerular (G), prerenal (PR) and tubular (T)

The nephrotic syndrome

Definition= glomerular proteinuria >3,5 g/24 h edema, hypoproteinemia, hypoalbuminemia, hyperlipidemia. Pathogenesis: damage of the GCW as an electric/mechanic barrier. Etiology: primary and secondary glomerular diseases.

The nephrotic syndrome - Pathophysiology

Damage of the GCW as an electric/mechanic barrier glomerular proteinuria >3,5g/24h Consequences of nephrotic range proteinuria: - hypoproteinemia, hypoalbuminemia, malnutrition - hydrosaline retention (edema), hypotension, acute kidney failure - thromboembolic complications (urinary loss of anticoagulant proteins: ATIII, plasminogen) - hyperlipidemia, lipiduria (reactive hepatic lipoprotein synthesis) - increased risk for infections (urinary Ig losses) - deficient binding and transport of some drugs - ionic and hormonal disbalances (urinary losses of binding proteins) - increased tubular reabsorbtion of filtered proteinstubulointerstitial toxicity

The nephrotic syndrome - Treatment

Specific treatment = treatment of the underlying glomerular disease Non-specific treatment: - reduction of proteinuria: dietary protein restriction, ACEI/ARB, NSAID, nephrectomy - reduction of edema: dietary salt restriction, diuretics, albumin, hemofiltration

- in case of hypovolemia and acute kidney failure: albumin

- treatment /prophylaxis of thrombosis: fractioned heparin - reduction of hyperlipidemia: HMG-CoA reductase inhibitors (statins) - prophylaxis of infections: vaccines (eg. antipneumococcal vaccine)

Differentiation between nephrotic syndrome and nephritic syndrome

Typical Features Onset Edema Blood pressure Jugular venous pressure Proteinuria Nephrotic Insidious ++++ Normal Normal/low ++++ Nepritic Abrupt ++ Raised Raised ++

Hematuria
Red-cell casts Serum albumin

May/may not occur

Absent Low

+++
Present Normal/slightly reduced

Macroscopic hematuria
Recurrent / single episode Glomerular / non- glomerular

Etiology: - uropathies: stones, tumours, infections - nephropathies: IgA nephropathy, thin basement membrane nephropathy

Asymptomatic urinary abnormalities

Proteinuria <3,5g/ 24h: glomerular, tubular + normal GFR Microscopic hematuria: glomerular/ non-glomerular + normal GFR

Leukocyturia
Casts: erythrocyte, leukocyte

Urinary tract infection (UTI)

Def.= colonization of the urine and urinary tract tissues from the bladder to the renal parenchima, with pathogenic microorganisms. Etiology: nonspecific bacteria (E.coli, etc) M. tuberculosis, fungi (Candida), viruses Dx. criteria: - isolation of the pathogenic agent from urine - symptoms and clinical signs of UTI - radiological modifications

Renal tubule defects - anatomic: autosomal dominant polycystic kidney disease (ADPKD) - functional (deficient tubular transport) Hypertension: - renovascular (renal artery stenosis) - renal parenchymal (glomerular diseases) Nephrolithiasis: eliminated kidney stones, stones removed by urology procedures or identified by imaging (US, i.v urography) Urinary tract obstruction: obstacle + retrograde dilatation of the urinary tract.

Classification of the medical nephropathies Glomerular diseases

Tubulointerstitial diseases Vascular diseases