Presenting Problem in Renal & Urinary Disease:

❖ Dysuria: Painful Urination with supra-pubic Pain

o Urinary Tract Infection
o STD
o Bladder Stone
❖ Loin Pain: Renal colic: Acute loin pain radiating anteriorly to Groin.
o Obstruction: Renal stone, ureteric stones, Renal tumors, Pyelonephritis, UT obstruction
❖ Oliguria (<300ml)/ Anuria (<50ml)
o Bilateral renal infraction
o Rapidly Progressive Glomerulonephritis
o Complete Obstruction (Stone/Tumor): Both ureter/or distal to bladder neck.
o Partial Obstruction: Normal Volume/High volume (due to loss of tubular concentrating
ability)
❖ Polyuria: >3000ml/day
o Increase intake
o DM (Glycosuria)
o Diabetes Insipidus (Cranial & Nephrogenic: Lithium, Diuretics, Interstitial nephritis, hypo-
kalemia, hyper-calcemia)
❖ Nocturia: CKD & BEP (Poor stream, hesitancy, incomplete bladder emptying, terminal dribbling,
frequency)
❖ Urinary incontinence: OSTU***
o Stress incontinence: Bladder pressure> urethral pressure: poor pelvic floor (following child
birth)/weak urethral sphincter. (increased abdominal pressure, During daytime)
o Urge incontinence: Detrusor overactivity (mostly idiopathic/neurogenic: spina bifida,
Multiple sclerosis) (Hints: Mostly at night, involuntary)
o Overflow incontinence:
▪ Atonic bladder (failure of detrusor muscle/nerve damage during surgery)
▪ Chronic Overdistended bladder (BEP/Bladder neck obstruction)
o True incontinence/Continual incontinence: Fistula
❖ Erectile Dysfunction:
o Decreased libido: Hypogonadism & Depression
o Intact libido: Vascular insufficiency, Neurological (DM, MS, Alcohol) & Drug (beta-blocker,
Thiazide diuretics)
❖ Dark Urine:
o Dipstick positive: Hematuria (infection, tumor, Glomerular bleeding), Hemoglobinuria
(Intravascular haemolysis), Myoglobinuria (Rbadomyolysis)
o Dipstick Negative: Acanthocyanins (Red), Rifampicin (Orange), Bilirubinuria, Alkaptonuria,
Porphyria
❖ Hematuria & Proteinuria
❖ Oedema
o Increased total extracellular fluid (3 organ failure Heart, liver, Kidney)
o Infection/inflammation > increased capillary permeability
o Obstruction: Venous (DVT), Lymphatic (filariasis)
❖ HTN
 Hematuria:
❖ Visible/Macroscopic: Dipstick positive
o Painless: Cancer (Bladder)
❖ Non-Visible/ Microscopic: Dipstick Positive if RBC count is
15000-20000 cells/mL or more.
o Symptomatic (LUST-dysuria, hesitancy, urgency):
o Non-symptomatic: Think of systemic disease

Causes: GIST

❖ Glomerulonephritis & Nephropathy: Infection, Toxin (Drug-

CCCN: Captopril, Cephalosporin, Ciprofloxacin, NSAID), DM, HTN,
Autoantibody (SLE, Vasculitis)
❖ Infraction & Infection: UTI (Cystitis, Urethritis, Pyelonephritis)
❖ Stones: Renal, ureteric (Pelvi-ureteric, pelvic brim, vesico-
ureteric), Bladder
❖ Trauma & Tumor
❖ Others: Sex, Menstruation, Vigorous activity, Endometriosis,
PCKD

PROTEINURIA:

❖ Healthy individual excretes <150 mg of protein in urine per day.

❖ Transient proteinuria: Vigorous exercise, Fever, HF, UTI
❖ Orthostatic Proteinuria: During day in upright posture. Morning sample negative.
 ❖ Microalbuminuria: ID-DM
o Normally 3.3g Albumin is filtered by kidney per day, most of which is absorbed by PCT
(71%), LoH & DCT (23%), CT (3%) > Converted to AA.
o In early Diabetic Nephropathy PCT reabsorption hampered (decreased Megalin receptor)

Consequence of Proteinuria (Nephrotic Syndrome): Protein in urine…

❖ Albumin loss> Hypoalbuminemia> reduced oncotic pressure>Oedema

o Albumin responsible for 60-80% of blood oncotic pressure
o Liver synthesis 12g of Albumin per day,
o >12g albumin is filtered by kidney
o In which >3.5 g loss in urine, rest reabsorbed and converted to AA in kidney)
❖ Gamma-Globulin loss> Hypogammaglobulinemia>infection (Tx. Vaccine)
❖ Anticoagulant loss (Antithrombin III, Protein C,S) & procoagulant synthesis by liver>
Hypercoagulability> Venous Thromboembolism (Tx. Anticoagulant Prophylaxis)
❖ Compensatory Lipoprotein synthesis: Hypercholesterolemia (May be due to loss of inhibitory
protein loss in urine)> atherosclerosis (Tx. Statins, ezetimibe)
❖ Secondary Aldosteronism> Sodium Retention> Edema (Tx. Diuretics, low Na+ diet)

Dipstick vs ACR vs PCR

Dipstick ACR PCR ACR: Albumin Creatinine Ration: Expensive immunoassay.

Neg <2.5 (Male) <25 Necessary to detect early Diabetic Nephropathy.
<3.5 (Female) Microalbuminuria ACR 3.5-15 mg/mmol.
+ to ++ 30-70 50-100
++ to +++ 70-300 100-350 PCR: done to detect non-albumin protein (β2 Microglobulin, Ig
+++ to ++++ >300 >350 light chain)

Proteinuria Investigation:

❖ >1 g/day: Consider renal biopsy

❖ <1g/day: Look for significant renal disease (HTN, Abnormal Renal function, Family history of Renal
disease)
o Present: Consider renal biopsy
o Absent: Observe (6-12 monthly – Urinalysis, Creatinine)

INVESTIGATIONS:

GFR:

❖ Normal 120±25 mL/min/1.73 m2 .

❖ Measured by Inulin clearance (more accurate, Injected), Creatinine clearance (Produced by muscle,
often used)
❖ GFR and CKD
 GFR Stage & Description Clinical Presentation
<15 5 Renal failure Needs Dialysis
15-29 4 Severe CKD Electrolyte problem
30-44 3B Anemia
45-59 3A Moderate CKD Asymptomatic
60-89 with kidney damage 2 Asymptomatic
>90 with kidney damage 1 Mild CKD Asymptomatic

Urinalysis:

Normal Increased Decreased

Gross Inspection
Colour Straw Red: Hematuria, hemoglobinuria, myoglobinuria, Rifampicin,
Phenytoin
Orange: Hyperbilirubinemia, Rifampicin
Black/Brown: Highly concentrated, Metronidazole, Nitrofurantoin
Appearance Clear Turbid: UTI, Proteinuria
Dipstick Test
Acidity (pH) 4.5-8 Acidemia Alkalemia, UTI due to Protease
Glucose Absent Hyperglycemia, Proximal tubular dysfunction (Fanconi syndrome)
Protein <300mg/day Nephrotic syndrome (Only detect albumin)
Microscopy Increased
Epithelial cell 1-2/HPF Carcinoma, UTI
RBC & RBC cast 1-3/HPF Glomerulonephritis, Hematuria
WBC & WBC cast 1-4/HPF UTI
Hyalin cast Present Non-specific
Blood Tests:

❖ CBC with PBF: Normochromic normocytic anemia in CKD: Decreased Erythropoietin & increased
toxin suppress bone marrow
❖ S. Creatinine: Raised in CKD < not excreted
❖ Phosphate & Ca: decreased 1,25 (OH)2D > increased PTH> Phosphate increase, Ca decrease

Imaging: USG, CT, MRI, IVU

Renal Biopsy:

Indication:

❖ AKI that not adequately explained

❖ CKD with normal size kidney
❖ Nephrotic Syndrome in Adult or in children with atypical features/not responding to treatment

Contraindication:

❖ General: Coagulopathy, Infection

❖ Specific: Uncontrolled HTN, solitary kidney, kidney <60% predicted size
GOMERULAR DISEASE
Glomerular Basement Membrane

From inside out the layers are

❖ Endothelial cells of the blood vessels

(fenestrated, 70-100nm in diameter)
❖ Glomerular basement membrane (Type
IV collagen)
❖ Podocytes (visceral epithelial cell)
❖ Bowman’s space
❖ Parietal cells
❖ In the center of the glomerulus are the
mesangial cells which help in regulating
blood flow the glomeruli.

NEPHROTIC SYNDROME
Classic Triad of Nephrotic Syndrome (Protein loss)

❖ Hypoalbuminemia (Weakness, leukonychia, peripheral

oedema) – Pitting, Rapid onset, severe.
❖ Hypogammaglobulinemia (Infection),
❖ Hypo-anticoagulant (Hypercoagulability, Thrombosis)
❖ Hyperlipidemia: Xanthelasma, Eruptive xanthomata
❖ Renal Hypoperfusion > increase Renin secretion >
Renin-angiotensin-Aldosterone mechanism activation >
Na+ and H2O retention > increase fluid volume > more
oedema & Hypertension
❖ Hypotension (Due to volume depletion)

Pathophysiology Differential Diagnosis (Primary & Secondary)

❖ Injury to podocyte
❖ Changed architecture
o Scarring
o Deposition of matrix/Other
elements
❖ Minimal Change Nephropathy
❖ Membranous Nephropathy
❖ Focal segmental glomerulosclerosis (FSGS)
❖ Diabetic Nephropathy
❖ SLE
❖ Hepatitis B/C
NEPHRITIC SYNDROME
Damage to GBM cause…

❖ Hematuria (Visible, Cola colour urin)

❖ Oliguria > Azotemia
❖ Variable Proteinuria
❖ Fluid retention > Hypertension

Pathophysiology DD:
❖ Inflammation ❖ IgA nephropathy & Henoch–Schönlein purpura
❖ Damage to GBM ❖ Post streptococcal GN (PS-GN)
❖ Reactive cell proliferation ❖ Mesangiocapillary GN/Membranoproliferative GN
❖ Crescent formation ❖ Anti GBM disease
❖ Small vessel Vasculitis

INVESTIGATION: (NS & GN)

❖ Blood: CBC with ESR, CRP, Immunoglobulin electrophoresis, Complement (C3, C4), Autoantibodies
(ANA, ANCA, anti-dsDNA, anti-GBM), ASOT, HBsAg, Anti-HCV
❖ Urine: R/E, ACR, Bence Jones Protein
❖ Imaging: CXR, Renal USG

Management:
Nephritic Syndrome:
❖ Diet: Protein, Fluid (500mL + Output) &
Fruits restriction (Prevent hyperkalemia)
❖ Antibiotic: Pen-V 250 QD in AGN
❖ Diuretics: to reduce edema
❖ Antihypertensive: ARB/ACE-I to reduce
proteinuria and HTN
❖ Steroid: in RPGN (Methylprednisolone)
Nephrotic Syndrome:
❖ Diet: Salt & Water restriction
❖ Diuretics: To reduce edema
❖ ACE-I/ARB: To reduce proteinuria
❖ Anticoagulant: To prevent
thromboembolism
❖ Statins: To reduce hyperlipidemia

DIFFERENCE BETWEEN NEPHROTIC AND NEPHRITIS SYNDROME

Nephrotic Syndrome Nephritic Syndrome

Onset Slow Acute

Swelling ++++ ++
 Blood Pressure Normal Increased

Proteinuria ++++ ++

Hematuria +/- +++

Red cell casts Not present Present

GFR Normal Normal/low

Serum albumin Low Normal/low

Serum lipids High Normal

Most common cause Diabetic Nephropathy IgA nephropathy

Immune complex Deposition mediated Glomerular injury:

Range of Proteinuria and Hematuria in Glomerular Disease:

Pathophysiology of Specific Glomerular disease:
Minimal Change disease: Minimal = not visible in light microscope, Seen in Electron Microscope
❖ Acute and severe form of NS
❖ Most common in Children (2-6 years)
❖ Etiology unknown
❖ T cell released cytokines cause damage and
effacement of foot processes of Podocyte which
allow the protein to pass through
❖ Occur after Respiratory infection/Prophylactic
immunization
❖ Dramatic response to Steroid (1mg/kg
prednisolone for 6 weeks)
❖ Increase incidence in Hodgkin lymphoma
patient.

MEMBRANOUS NEPHROPATHY

❖ Autoantibody to podocyte surface

antigen (M-type phospholipase A2)
❖ Deposition of Immune complex in Sub-
epithelial space > Complement activation >
MAC formation > damage to the podocyte
foot processes & mesangial cell >
Proteinuria
❖ Causes: Antigenic property…
o Drug: Penicillamine, captopril, NSAID
o SLE & Autoimmune disorder
o Infection: Chronic Hepatitic B, C, syphilis
o Malignant Tumor: Lung and colon ca

Treatment:

❖ 1/3 spontaneous remission, 1/3 develops

Nephrotic syndrome, 1/3 develops CKD
❖ High dose corticosteroid &
Cyclophosphamide is used in case of severe
nephrotic syndrome or deteriorating renal
function
FOCAL SEGMENTAL GLOMERULOSCLEROSIS
❖ Etiology mostly unknown
❖ HIV infection/ podocyte toxin/ Obesity may
cause FSGS
❖ Focal (only some nephron are involved),
segmental (part of glomeruli is involved), sclerosis
(affected part becomes sclerosed)
❖ Immunofluorescence: deposition of C3 & IgM
❖ Treated with high dose corticosteroid (0.5-
2mg/kg) and immunosuppressive drug
(cyclophosphamide, ciclosporin)

POST-STEPTOCOCCAL GLOMERULONEPHRITIS (PSGN)

❖ 1-2 weeks after Throat infection (pharyngitis)/ 6 weeks

after skin infection (impetigo)
❖ Treatment usually supportive. Spontaneous resolve
within months
❖ ¼ may progress to Rapidly progressive GN > Renal
Failure

IgA NEPHTOPATHY & HENOCH SCHONLEIN PURPURA (HSP)

Rapidly Progressive Glomerulonephritis:
ALPORT SYNDROME
AKI & CKD

Renal Function:

➢ Urine Production
o Glomerular filtration
o Tubular Reabsorption
o Tubular secretion
➢ Secretion:
o Erythropoietin
o