Cardinal Manifestations
of Renal Disease
JOSELITO A. MORA, MD, FPCP, FPSN, MHA
Adult Nephrology
Cardinal manifestations of renal disease
• Reduction in GFR (azotemia)
• Abnormalities of urine sediment
• RBC, WBC, casts, crystals
• Abnormal excretion of proteins (proteinuria)
• Disturbance in urine volume
• Oliguria, anuria, polyuria
• Presence of hypertension / expanded total body fluid volume
(edema)
• Electrolyte abnormalities
• Fever / pain
Critically important renal abnormalities
• Reduction in GFR leading to azotemia
• Alterations of the urinary sediment and/or
protein excretion
• Abnormalities of urinary volume
AZOTEMIA
• Assessment of GFR
• Primary metric for kidney function
• Direct measurement using inulin or iothalamate
• Filtered but not reabsorbed or secreted
• Indirect measurement - Serum Creatinine
• Surrogate marker to estimate GFR
• Affected by several factors
• Ingestion of cooked meat
• Secretion thru the organic cation pathway
AZOTEMIA
• Assessment of GFR
• Estimated GFR / Creatinine Clearance Formula:
• Cockcroft – Gault: CrCl (mL/min)
• MDRD: eGFR (mL/min/1.73m2)
• CKD – EPI: eGFR (mL/min/1.73m2)
MEMORIZE !!!
• Cockcroft-Gault equation
Creat Clearance (140-age) x lean BW (kg)
(mL/min)* Plasma Creat (mg/dL) x 72
* Multiply result by 0.85 if patient is female
AZOTEMIA
• Assessment of GFR
• Cystatin C
• Cysteine protease inhibitor
• Produced at a relatively constant rate from all
nucleated cells
• More sensitive marker of early GFR decline
• Affected by: smoking, diabetes, markers of
inflammation
Practical Tool:
eGFR Calculator for Handheld Devices
eGFR calculator downloadable for free at Play Store (Android) and App Store
(Apple)
Compute!!! Patients Have Different eGFR at the
Same Level of Creatinine
22-year-old male 47-year-old female 80-year-old female
Serum Creatinine
(mg/dL) 1.1 1.1 1.1
eGFR by CKD-EPI
(mL/min/1.73m2) 95 60 47
Kidney Function Normal Stage 2 Stage 3
Adapted from National Kidney Foundation
GFR estimates - limitations
• Assumes that px is in a steady state
• Loss of muscle from chronic illness,
glucocorticoid use or malnutrition
• Influenced by age, sex and race
Case #1
• A 52 y/o male consulted due to azotemia with a
creatinine of 256 mmol/L (normal: 60-110). He is
diabetic for 12 years with relatively poor control. He
developed hypertension 3 years ago. 3 days prior to
admission, he started to have loose watery stool after
eating vegetable salad. He is nauseated and in fact has
episodes of vomiting the previous day. The following
are his VS:
• BP 100/60 (UBP of 150/90) CR 116/min RR 21/min
APPROACH TO PATIENT WITH
AZOTEMIA
• The first task is to distinguish whether the
azotemia is due to acute or chronic renal
injury.
• Look at the clinical situation, history and
laboratory data.
AZOTEMIA - ACUTE
• Prerenal failure
• Postrenal azotemia
• Intrinsic renal disease
Prerenal failure
• Decreased renal perfusion – 40-80% of AKI
• Causes:
• Decreased circulating blood volume
• Volume sequestration
• Decreased effective arterial volume
• Reduction in cardiac output
• Peripheral vasodilatation
• Profound renal vasoconstriction
True / “effective” hypovolemia
MAP
(+)arterial/cardiac (+)afferent arteriolar
baroreceptors stretch receptor
SNS(+)
RAAS(+)
AUTOREGULATION
ADH release (afferent: relax
efferent: constrict)
Maintain BP
Maintain GFR
Restore cardiac &
cerebral perfusion
GFR depends on diameters of afferent and efferent arterioles
Glomerulus
Afferent arteriole Efferent arteriole
GFR GFR
Glomerular filtrate
Eff. Art. constriction Aff. Art. constriction Eff. Art. dilatation
Aff. Art. dilatation
Prostaglandins, Angiotensin II (low Ang II (high dose), Angiotensin II
Kinins, Dopamine dose) Noradrenaline (Symp blockade
(low dose), ANP, NO nerves), Endothelin, ADH,
NSAIDs)
URINARY INDICES
INDEX PRERENAL OLIGURIC ACUTE
AZOTEMIA RENAL FAILURE
BUN / Crea ratio >20:1 10-15:1
Urine sodium, mEq/L <20 >40
Urine osmolality, mosmol/L H2O >500 <350
Fractional excretion of sodium
FENa = UNa x PCr x 100
PNa x UCr <1% >2%
Urine / plasma Creat (UCr/PCr) >40 <20
Postrenal Azotemia
• Urinary tract obstruction - <5% of ARF
• Usually reversible
• Early diagnosis
• Presence of ureteral and renal pelvic dilatation
on ultrasound
• May be negative in:
• Early obstruction
• Ureters unable to dilate (encasement)
Postrenal Azotemia
• Requisites:
• Obstruction at the urethra or bladder outlet
• Bilateral ureteral obstruction
• Unilateral obstruction in a patient with single functioning
kidney
• Unilateral obstruction in a patient with bilateral moderate
to severe renal dysfunction
Intrinsic renal disease
• Involves:
• Large renal vessels
• Intrarenal microvasculature and glomeruli
• Tubulointerstitium
• Ischemic and toxic - ~90% of ATN
• Prerenal and ATN – spectrum of renal
hypoperfusion
• ATN – evidence of structural tubule injury
10 Syndromes in Nephrology
• Acute or rapidly progressive • Urinary tract infection /
renal failure pyelonephritis
• Acute nephritis • Renal tubule defects
• Chronic renal failure • Hypertension
• Nephrotic syndrome • Nephrolithiasis
• Asymptomatic urinary • Urinary tract obstruction
abnormalities
Case #2
• A 34 y/o female consulted due to progressive
development of bipedal edema that started 5 weeks
ago. On initial evaluation 2 weeks PTC, she was noted
to have BP of 140/100 mmHg. She claims to have
foamy urine. No other signs and symptoms were noted.
She presented with a urinalysis report showing 4+
protein. There were no other significant findings of note.
The PMH was unremarkable.
EVALUATION OF PROTEINURIA
• Initiated after detection of proteinuria by
dipstick
• Detects only albumin
• False (+)
• pH >7.0
• Concentrated urine
• Blood contaminated sample
• Quantify – spot albumin-to-creatinine ratio
• Approximates 24-hour albumin excretion
• Glomerular proteinuria
• Charge and size selectivity
Glomerular Barrier:
• Glomerular endothelial cells
• Glomerular basement
membrane
• Podocytes with “slit
diaphragm”
• Tubular proteinuria
• Proteins <20 kDa – freely filtered but
reabsorbed by PCT
• Normal:
• <150 mg/d total protein
• <30 mg/d albumin
• Tubular proteins (Tamm-Horsfall, IgA, urokinase)
• Filtered b2-microglobulin, apoproteins, enzymes,
peptide hormones
• Overflow proteinuria
• Excessive production of abnormal proteins
• Capacity of tubular reabsorption overwhelmed
• Ex: plasma cell dyscrasia, lymphoma,
amyloidosis
Case #3
• A 19 y/o male presented to the OPD due to passage of
tea-colored urine 4 hours PTC. He developed cough,
colds and low-grade fever 2 days ago. There was no
rash noted but patient complained of knee joint
tenderness but without swelling. No associated dysuria
or frequency was reported and flank pain was absent.
Physical examination revealed BP of 140/90 mmHg.
There was no edema.
Evaluation of hematuria
• Normal RBC excretion
• 2 million per day
• Micro hematuria – 2-5 RBCs/HPF
• Isolated hematuria
• Bleeding from the urinary tract
• Stones, neoplasms, trauma, infection (TB, prostatitis)
• Menstruation, viral illness, allergy, exercise
• Hypercalciuria, hyperuricosuria
Evaluation of hematuria
• Isolated micro hematuria
• Glomerular disease
• Dysmorphic
• RBC cast
• Proteinuria >500mg/day
• 3 most common:
• IgA nephropathy
• Hereditary nephritis
• Thin basement membrane disease
• Renal biopsy
Thank you !
