1.
UTI ,AKI & CKD
Dr. Melaku Asfawesen
DBU
Feb/7/2017GC.
2/4/2023
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2.
Urinary Tract Infection

3.
Learning Objectives
• Definition.
• Terminology.
• Risk factors for UTI.
• Investigation.
• Treatment.
• Prevention.
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4.
Introduction
• UTI is infection of the urinary tract causing inflammatory
response.
• When normal flora of the periurethral area are replaced by
uropathogenic bacteria.
• Then ascend to cause cystitis,pyelonephritis.
• Third comment infection experianced by human.
• Respiratory tract infection > Gastro-intestinal infection > urinary
tract infection.
• Women are more afected than men.
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5.
Terminology.
• Asymptomatic bacteruria.
• Upper UTI and Lower UTI.
• Complicated and Uncomplicated UTI.
• Recurrent UTI
• Relapse
• Reinfection.
• Treatment Failure
• Catheter associated UTI.
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6.
Risk factors for UTI
Patients with voiding abnormalities related to:
Diabetes
Neurogenic bladder
Spinal cord injury
Pregnancy
Prostatic hypertrophy(BPH)

7.
Cont….
Urinary tract instrumentation Premenopausal women: sexual
intercourse, spermicides; previous UTI; history maternal UTI & age at
1st UTI (genetic component)
 Perimenopausal women: changes in vaginal microbial flora
 Postmenopausal women: mechanical & physiologic factors affecting
bladder emptying

8.
What organisms are generally
found in UTI?
Uncomplicated cystitis and pyelonephritis
 E. coli: >90%; S. saprophyticus: 5%-10%
 Other coliforms (Klebsiella, Proteus)
 Short-term catheters
 E. coli and typical hospital-acquired pathogens
 Klebsiella, Citrobacter, Enterobacter, Pseudomonas, coagulase-
negative staphylococci, enterococci, Candida
 Long-term catheters
 Typically polymicrobial
 Proteus, Morganella, and Providenciacommon, as well as
pathogens above

9.
Clinical Manifestation.
In noncatheterized individuals
Dysuria, urinary frequency, urgency
History provided by patient has high predictive value
 In catheterized patients
 Fever, rigors, altered mental status, malaise or lethargy with no
other identified cause
 Flank pain, CVA tenderness, acute hematuria, or pelvic discomfort
 If ≤48h since catheter removed: dysuria, urgency, frequent
urination, suprapubic pain or tenderness

10.
Differential Diagnosis.
Vaginitis
Candida, Trichomonasvaginalis, Bacteroidesspecies, Gardnerellavaginalis
Vaginal discharge, odor, or itching; “external” dysuria
 Urethritis
 Chlamydia trachomatis, Neisseriagonorrhoeae, or HSV
 Gradual onset of symptoms ± vaginal discharge; ± urinary frequency or
urgency

11.
Diagnosis.
 Urine Microscopy.
 Urine Culture.
 Indications
1. Patient with sign symptom of UTI.
2. Follow up of recntly treated UTI.
3. Removal of Induelling catheter.
4. Screening for asymptomatic bacteruria.
5. Patient with obstructive uropathy before procedure.
 Imaging study
1. Plain x-ray.
2. Ultrasound.
3. Intravenous urography.
4. Computed tomography.

12.
Is there a role for screening for UTI
or asymptomatic bacteriuria?
Early in pregnancy
High rate progression to symptomatic UTI
Associated with low birthweight and preterm labor
 Men undergoing transurethral resection of prostate
 Risk for bacteremia, with associated sepsis syndrome
 Urinary tract instrumentation causing mucosal bleeding
 Simple catheter placement does not warrant screening
 Renal transplant and neutropenic patients

13.
Indication For Hospital
Admission.
 Sepsis
 Unable to take oral therapy
 Vomiting
 Intolerance for available oral agents
 Upper urinary tract condition requires drainage or surgery
 Abscesses, emphysematous pyelonephritis, papillary necrosis,
xanthogranulomatouspyelonephritis
 Multidrug-resistantorganism susceptible only to parenterally
administered antimicrobials
 Serious comorbid condition, including pregnancy

14.
Treatment.
Recommended agents
Nitrofurantoin monohydrate
Penicilline
Trimethoprim-sulfamethoxazole
Avoid in pregnancy
Fluoroquinolones
 Avoid in pregnancy

15.
What are the usual reasons for
failure of UTI therapy?
 Antibiotic resistance
 Urologic complications
 Urinary tract stones
 Voiding disorder
 Indwelling catheter
 Stent
 Urinary obstruction,
 Anatomical abnormalities
 Vesicoureteral reflux

16.
How can UTI be prevented?
Postcoital antibiotic prophylaxis
For women with 3 to 4 UTIs/yr, particularly if associated with coitus
 Continuous prophylaxis
 For more frequent recurrences
 Patient-initiated prophylaxis
 For recurrent, uncomplicated UTI unrelated to coitus
 Taken at symptom onset
 Intravaginal estriol cream
 Daily topical application for postmenopausal women
 Supports vaginal flora, acid vaginal pH, and reduced vaginal
colonization with E. coli

17.
Follow up
 Uncomplicated cystitis
No specific follow-up as long as symptoms resolve
 Pregnant women
 Urine culture to confirm bacteriuria eradicated
 Repeat urinalyses or urine cultures at intervals to confirm sterility
of urine through delivery
 Complicated UTI
 Monitor for symptomatic resolution
 Reevaluate if symptoms don’t improve ≤48h, worsen, or recur
quickly
 In CAUTI: monitor response by symptoms not by repeated urine
cultures

18.
Acute Kidney Injury
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19.
Learning Objectives
• Definitions and classification of AKI
• Epidemiology and clinical outcome
• Diagnosis and etiology
• Approach and management of AKI
• Risk factors and preventive strategies
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20.
Definitions of Terminology
• Azotemia - the accumulation of nitrogenous
wastes (high BUN)
• Uremia – clinical manifestation (symptomatic renal
failure)
• Oliguria – UOP < 400-500 mL/24 hours
• Anuria – UOP < 100 mL/24 hours
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21.
To function properly
kidneys require:
• Normal renal blood flow
• Functioning glomeruli and tubules
• Clear urinary outflow tract for drainage and
elimination of formed urine
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22.
Definition of AKI
• a sudden, sustained, and usually
reversible decrease in the glomerular
filtration rate (GFR) occurring over a
period of hours to days.
> 35 definitions used in published
studies
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23.
RIFLE Criteria for AKI (2005)
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24.
DefinitionofAKIbasedonAKIN
“AcuteKidneyInjuryNetwork”(2007 )
Stage Increase in Serum
Creatinine
Urine Output
1 1.5-2 times baseline
OR
0.3 mg/dl increase
from baseline
<0.5 ml/kg/h for >6 h
2 2-3 times baseline <0.5 ml/kg/h for >12 h
3 3 times baseline
OR
0.5 mg/dl increase if
baseline>4mg/dl
OR
Any RRT given
<0.3 ml/kg/h for >24 h
OR
Anuria for >12 h
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25.
KDIGO Definition of AKI
(2012 )
Defined by any of the following:
• Increase in SCr by ≥0.3 mg/dL within 48 hours
• Increase in Scr by ≥1.5 times baseline, which is known or
presumed to have occurred within the prior seven days
• Urine volume <0.5 mL/kg/h for six hours
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26.
KDIGO Classificationof AKI(2012 )
Stage Serum creatinine Urine output
1 1.5-1.9× baseline
OR
>0.3 mg/dL 
<0.5 ml/kg/hr for 6-12 hrs
2 2-2.9× baseline
<0.5 ml/kg/hr > 12 hrs
3 3 times baseline
OR
increase in Cr to ≥4.0 mg/dL
OR
Initiation of RRT
<0.3 ml/kg/hr > 24 hrs
OR
Anuria > 12 hrs
KDIGO Clinical Practice Guideline for AKI. Kidney Int 2012
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27.
Epidemiology
• ≈ 5-10% in hospitalized patients.
• ≈ 70% in critically ill patients.
• 5-6% ICU pts require RRT
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Acute
Tubular
Necrosis
Acute
Interstitial
Nephritis
Acute
GN
Acute
Vascular
Syndromes
Intratubular
Obstruction
Etiologies of AKI
Prerenal
AKI
Postrenal
AKI
Intrinsic
AKI
Acute
Renal
Injury
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29.
Cont….
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30.
Prerenal AKI
• Intravascular volume depletion:
-bleeding, GI loss, Renal loss, Skin loss (burn), Third space loss, poor oral
intake (NPO, AMS, anorexia)
• Decreased effective circulating volume:
-congestive heart failure, cirrhosis, nephrotic syndrome, sepsis
• Decreased flow through renal artery:
-pharmacologic impairment (RAAS blocker, NSAIDs, CNI)
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31.
Pre renal Azotemia treatment.
• In early stages can be rapidly corrected by aggressive
normalization of effective arterial volume.
• Correction of volume deficits
• Optimization of cardiac function
• Discontinuation of antagonizing medications
• NSAIDs/COX-2 inhibitors
• Diuretics
• RAAS blockers
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32.
Renal / Intrinsic AKI
• Tubule: ATN (sepsis, ischemic, toxins)
• Interstitium: AIN (Drug, infection, neoplasm)
• Glomerulus: AGN (primary, post-infectious,
rheumatologic, vasculitis, HUS/TTP)
• Vasculature:
• Atheroembolic disease, renal artery thromboembolism, renal artery
dissection, renal vein thrombosis.
• Intratubular Obstruction
• myoglobin, hemoglobin, myeloma light chains,
uric acid, tumor lysis, drugs (bactrim, indinavir,
acyclovir, foscarnet)
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33.
Acute Tubular Necrosis (ATN)
• Sepsis (48%)
• Ischemia (32%)
• prolonged prerenal azotemia
• Hypotension
• hypovolemic shock
• Direct toxic Injury (20%)
• Exogenous
• Radiocontrast
• Aminoglycosides
• Vancomycin
• Amphotericin B
• Cisplatin
• Acyclovir
• Calcineurin inhibitors
• HIV meds (tenofovir)
• Endogenous (pigment
nephropathy)
• Rhabdomyolysis
• Hemolysis
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34.
Laboratory Findings in Acute Kidney Injury
Index Prerenal
Azotemia
Oliguric AKI
(ATN)
BUN/PCr Ratio >20:1 10-15:1
Urine sodium (UNa),
meq/L
<20 >40
Urine osmolality,
mosmol/L H2O
>500 <400
-Fractional excretion
of sodium
-FEUrea
<1%
<35%
>2%
>35%
Response to volume Cr improves with IVF Cr won’t improve much
Urinary Sediment Bland, Hyaline Muddy brown granular
casts, cellular debris,
tubular epithelial cells
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35.
Pitfalls: Fractional Excretion of Na
• Pre-existing CKD: FeNa 2-3 even without tubular injury
• Poor sensitivity with diuretics use
• Picture might be muddied by fluid therapy
• Etiologies of FeNa < 1%
• hepatorenal syndrome
• contrast nephropathy
• rhabdomyolysis
• acute glomerulonephritis
• early obstructive uropathy
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36.
Postrenal AKI: Classification
• Level of obstruction
• Upper tract (ureters)
• Lower tract (bladder outlet or urethra)
• Degree of obstruction
• Partial vs. Complete
• Type
• Anatomic lesion (unilateral vs. bilateral)
• Functional
• Duration (Acute vs Chronic)
• Cause (Congenital vs Acquired)
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Etiologies: Upper tract obstruction
• Intrinsic:
• Nephrolithiasis
• Blood clot
• Papillary necrosis
• Cancer
• Extrinsic:
• Retroperitoneal or pelvic
malignancy
• Endometriosis/Prolapsed
uterus
• Abdominal aortic aneurysm
or Iliac artery aneurysm
• Retroperitoneal fibrosis
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38.
Etiologies: Lower tract obstruction
• BPH or prostate cancer
• Bladder cancer
• Urethral strictures
• Bladder stones
• Blood clots
• Functional obstruction as a result of
neurogenic bladder
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Postrenal AKI treatment.
• Prompt recognition and relief of obstruction can prevent the
development of permanent structural damage.
• Lower tract obstruction (bladder catheter)
• Upper tract obstruction
• ureteral stents
• percutaneous nephrostomies
• Recovery of renal function dependent upon duration of
obstruction.
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40.
• U/A, Urine protein/Cr, Urine Eosinophilla
•Urine microscopy:
• Muddy brown casts in ATN
• WBC casts in AIN
• RBC casts in AGN
• CPK, uric acid
• Post-void residual (>100-150 ml c/w voiding dysfunction)
• bladder catheterization
• renal ultrasound
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41.
ManagementofAKI:generalprinciple
• Identify the etiology and treat the underlying cause
• Optimization of hemodynamics to increase renal
perfusion
• Lack of benefit – low dose dopamine, loop diuretics
only if markedly fluid overload
• Identify and aggressively treat infection (early removal
of Foley catheters, and minimize indwelling lines)
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42.
Cont….
• Correct fluid imbalances: strict I/O’s, daily wts. determine fluid
balance goals daily, fluid selection or diuresis, readjust for UOP
recovery, post diuresis or dialysis
• Electrolyte imbalances
• Metabolic acidosis (Bicarb deficit, mode and rate of replacement)
• Nutritional support
• Medication dose adjustment:
• Holding of offending drugs.
• Procedural considerations (prefer non-contrast CT, appropriate to
delay contrast exposure)
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43.
Be aware of pts who are at risk for AKI
Volume depletion or Hypotension
Sepsis
Pre-existing renal, hepatic, or cardiac disease.
Diabetes mellitus
Elderly
Exposure to nephrotoxins
Aminoglycosides, amphotericin,
immunosuppressive agents, chemo., NSAIDs,,
RAAS blockers, intravenous contrast media
Post cardiac or vascular Surgery pts or ICU pts with
multiorgan failure
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44.
Chronic Kidney Disease.
• Outline
• CKD Definition.
• Epidemiology.
• Staging
• Pathophysiology.
• C/M
• Treatment.
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45.
CKD
Definition:
final stage of numerous renal diseases resulting from
progressive loss of glomerular, tubular and endocrine
function in both kidneys. This leads to
 accumulation of toxins that normally undergo renal
excretion, including products of protein metabolism;
 those consequent to the loss of other kidney functions,
such as fluid and electrolyte homeostasis and
hormone regulation; and
progressive systemic inflammation and its vascular and
nutritional consequences
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46.
Epidemiology
Regional and racial incidence of CRF
• Britain 70-80/per million
• China 100/per million
• USA 60-70/per million
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Etiology
• Diabetic nephropathy,
• Hypertensive glomerular sclerosis,
• Chronic GN
• Cystic disease of the kidney(ADPKD)
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Pathogenesis
Unknown
Two theories
1. Intact nephron hypothesis
2. Trade-off hypothesis
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Intact nephron hypothesis
finalcommonpathway
(hemodynamicallymediatedglomerularinjury)
glomerular injury
adaptive single nephron hyperfiltration
glomerular capillary plasma flow,  hydraulic pressure
Intact nephron hypertrophy and sclerosis
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50.
Trade-off hypothesis
• CKD  Calcium phostate PTH  SHPT 
bone,heart,blood,nerves injury
• Hypertension and compensatory hypertrophy of glomeruli
• Hypermetabolism of renal tubuli
• cytokines and lipid disturbances
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51.
CKD Stages.
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52.
Clinical Manifestation.
General
Gastrointestinal tract
CNS
Musculoskeletal
System.
Hematologic.
Electrolyte disorders
 Heart
 Skin
 Infection
 Pulmonary.
 Endocrine and
metabolic
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53.
Cont….
Cardiovascular disorders
• Hypertension 90%
• Water and sodium retention
• IHD
•
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54.
Cont….
Pericarditis
Uremia
Dialysis associated
Signs and symptoms
Chest pain
Friction rub
Pericardial effusion and tamponade
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55.
Cont….
Hematologic disorders
• Anemia, bleeding disorder, platelet dysfunction
Causes:
• Relative deficiency of erythropoietin
• Decreased erythropoietin production
• Reduced red cell survival
• Increased blood loss
• Folate and Iron deficiency
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56.
Cont….
Neurologic Manifestation.
• Central nervous system
 Tiredness, insomnia, agitation, irritability,
depression,
• Peripheral nervous system
 Restless leg syndrome - the patient’s legs are
jumpy during the night, painful paresthesis of extremities,
twitching, loss of deep tendon reflexes , musclar weakness,
sensory deficits.
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57.
Cont….
Renal osteodystrophy
Type I: high turn-over bone disease
 Ostitis fibrosa cystica.
 Brown tumor
Type II: low turn-over bone disease
Adynamic bone disease
 Osteomalacia
 Calcyphylaxis
Tuberous calcinosis.
Type III: mixture
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58.
Cont….
Causes of renal osteodystrophy
• 1, 25(OH)2D3
• calcium phosphate 
• malnutrition
• iron and aluminum overload
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59.
Cont….
Water, electrolyte and acid-base disturbances
• Potassium  sodium  ,----- or 
• Calcium phosphate 
• Metabolic acidosis
• Magnesium 
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60.
Cont….
Causes of hyperkalemia.
Increased intake:
Impaired excretion
 chronic renal failure(GFR<15ml/min)
Shift of K out of cells.
metabolic acidosis
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61.
Diagnosis:
• History
• Physical examination
• Laboratory studies including
urinalysis , renal function tests ,
biochemical analysis of blood
• X-ray, ultrasound and Imaging Study.
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62.
Treatment of CRF
Non-dialysis
Dialysis (RRT)
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63.
Cont….
Non-dialysis
1. Diet therapy
2. Treatment of reversible factors
3. Treatment of the underlying disease
4. Treatment of complications of uremia
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64.
Cont….
Diet therapy
• Protein restriction (0.5-0.8mg/kg/d)
• Adequate intake of calories(30-35kcal/kg/d)
• Low phosphate diet(600-1000mg/d)
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65.
Cont….
Reversible factors in CRF
• Hypertension
• Reduced renal perfusion (renal artery stenosis,
hypotension , sodium and water depletion, poor cardiac
function)
• Urinary tract obstruction
• Infection
• Nephrotoxic medications
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66.
Cont….
Management of complications of uremia
1. Hyperkalemia .
2. Cardiac complication.
3. Hypertension management.
4. Anemia.
5. Osteodysterophy.
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67.
Cont….
Hyperkalemia
Identify treatable causes
Inject 10-20ml 10% calcium gluconate
50% glucose 50-100ml i.v.+insulin 6-12u
Infusion 250ml 5% sodium bicarbonate
Use exchange resin
Hemodialysis or peritoneal dialysis
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68.
Cont….
Cardiac complications
• Diuretics
• Digitalis
• Treat hypertension
• Dialysis
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69.
cont….
Hypertension Management.
Antihypertensive therapy
Target blood pressure 130/80mmHg
ACE inhibitors
Angiotensin II receptor antagonists
Calcium antagonists
-blockers
vasodilators
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70.
Cont….
Treatment of anemia
• Recombinant human erythropoietin(rhEPO)
• Target hemoglobin 10-11.5g/L
• Restore iron store.
• Folate supplementation.
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71.
cont….
Side effects of rhEPO
• Hypertension
• Hyper coagulation
• Thrombosis of the AVF
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72.
Cont….
rhEPO resistant
• Iron deficiency
• Active inflamation
• Malignancy
• Secondary hyperparathyroid
• Aluminum overload
• Pure red cell aplasia
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73.
Cont….
Treatment of renal osteodystrophy
Low phosphate diet
Calcium carbonate (1-6g/d)
Vitamin D (0.25ug/d for prophylactic, 0.5ug/d for symptomatic, pulse
therapy 2-4ug/d for severe cases)
Parathyroidectomy
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74.
Cont….
Renal replacement therapy
1. Hemodialysis
2. Peritoneal dialysis
3. Renal transplantation
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75.
Cont….
Indications of HD
• GFR<10ml/min.
• Uremic syndrome.
• Hyperkalemia.
• Acidosis.
• Fluid overload.
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76.
Contraindications of HD
• Shock
• Severe cardiac complications
• Malignancy etc
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77.
Cont….
Indications of RT
1. Maitenance dialysis patients without contraindications of RT
2. Age<60 years
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78.
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79.
Approach to patient with
glomerular diseases
t
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80.
Glomerulus
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81.
• Most glomerular diseases are immune-mediated, and
described as glomerulonephritis (GN).
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82.
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83.
Mechanism for the development of GN is
 glomerular ınflammatıon and injury
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84.
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85.
GN classification cont….
Primary&Secondary.
Primary GN
• Minimal Change Disease
• FSGS
• Membranous GN
• Idiopatic MPGN
• IgA nephropathy
• Proliferatifive GN
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86.
Secondary GN
İnfective
 Fungi (Candida albicans,Coccidioides immitis)
 Rickettsiae
Connective tissue diseases
 Henoch-Schönlein purpura
 Polyarteritis nodosa
 SLE
 Wegener’s granulomatosis
Glomerular basement membrane diseases
 Goodpasture’s syndrome
Hematologic dyscrasias
 cryoglobulinemia
 TTP/HUS
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87.
Viral
 Cytomegalovirus
 Epstein-Barr virus
 Hepatitis B virus
 Hepatitis C virus
 Herpes zoster virus
 Measles
 Mumps
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88.
GN classification cont….
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89.
Cont….
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90.
GLOMERULARDISEASESWITH
NEPHROTICSYNDROME
Nephrotic synd:
1. Edema,
2. Nephrotic-range proteinuria) greater than 50 mg/kg per
day or 40 mg/h/m2 in children and 3.5 g/24 h in adults ,
3. Hyperlipidemia
4. Hypoalbuminemia.
Causes are
 Minimal change disease (MCD)
 Focal Segmental Glomerulosclerosis (FSGS)
 Membranous nephropathy (MN)
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91.
MINIMALCHANGEDISEASE(MCD)
• characterized initially by dramatic increases in glomerular
permeability in association with little or no structural abnormalities
by light microscopy.
• lipoid nephrosis Munk (1913) nill disease.
• MCD is most common in children, In adults, especially in elderlies
associated with secondary causes
• 70% to 90% of cases of nephrotic syndrome in children younger
than age 10 years and 50% of cases in older children.
• Minimal change glomerulopathy also causes 10%-15% of cases of
primary nephrotic syndrome in adults.
• 15-20% nephritic features may occur
• MCD in children mostly (%80-90) idiopatic
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92.
HISTOPATHOLOGY
• The principal target of injury is the podocyte, ***podocytopathies
• Light microscopy: lack of definitive alteration in glomerular structure.
Lipid droplets in the tubuler cells
• Immunofluorescence: also shows no change
• Electron mic: fusion of epithelial foot processes
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93.
Laboratory findings of MCD
• Heavy proteinuria.
• Microscopic hematuria is seen in fewer than 15% of patients.
• Volume contraction may lead to a rise in both the hematocrit and hemoglobin.
• Hypoalbuminemia & dyslipedemia
• The serum albumin <2 g/dL and, in more severe cases, <1 g/dL.
• Total cholesterol, LDL, and triglyceride levels are increased.
• Pseudohyponatremia has been observed in the setting of marked
hyperlipidemia.
• Renal function is usually normal, although a minority of patients have
substantial AKI.
• Complement levels are typically normal in patients with minimal change
glomerulopathy
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94.
Secondarycauses of MCD
• Drugs
-NSAID
-penicillin
-trimetoprim
• Toxins
-Mercury
-lead
• Infection
-Mononucleosis
- HIV
Tumors
 Hodgkins lymphoma
 Other lymhoproliferative dis.,
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95.
• Emprical steroid theraphy for children <10
• In children who have received empirical treatment, a renal
biopsy is indicated when there is failure to respond to a 4- to
6-week course of prednisone.
• oral prednisone be administered as a single daily dose
starting at 60 mg/m2 /day
• or 2 mg/kg/day to a maximum 60 mg/day
Specific treatment: corticosteroids
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96.
Clinical course of MCD as related to
steroid theraphy
• STEROID-SENSITIVE NEPHROTIC SYNDROME (SSNS)
Complete remission of proteinuria within 8-12 weeks with
infrequent relapses
• FREQUENTLY RELAPSING and STEROID DEPENDENT
(FR-SD)
Relapses occur during the taper of steroids
• STEROID-RESISTANT NEPHROTIC SYNDROME (SRNS)
Failure to obtain a remission within 12 weeks
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97.
PROGNOSIS
• 85-90 % survival rate
• Untreated idiopathic MCD was associated with a risk of
mortality due to infection and less commonly
thromboembolism
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98.
complications
• Related to persistent NS (peritonitis, ARF, CKD in steroid
resistant patients)
• Side effect of therapy( cataracts, acne, cushingoid face,
hyperglycemia, Hhypertension)
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99.
FOCALSEGMENTALGLOMERULOSCLEROSIS(FSGS)
• Common cause of nephrotic syndrome in adults and a frequent
lesion in children and adolescents
• Pathology: a focal process; not all glomeruli are involved, the
glomeruli are segmentally sclerotic, and portions of the
involved glomeruli may appear normal by light microscopy.
• The ultrastructural features of FSGS on electron microscopy
include focal foot process effacement.
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100.
Causes of FSGS
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101.
histologic variants
Classical
Collapsing
Tip lesions
NORMAL Glomerulus
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102.
Clinical manifestations
 Peripheral edema,
 Hypoalbuminemia, and
 Nephrotic range proteinuria.
 Patients with FSGS also commonly have
hypertension, and many have microscopic
hematuria.
 The level of kidney function may vary.
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103.
The relative frequencies of clinical
manifestations :
 Nephrotic range proteinuria - 60 to 75 %
 Microscopic hematuria - 30 to 50 %
 Hypertension - 45 to 65 %
 Renal insufficiency - 25 to 50 %
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104.
Laboratory findings
• Hypoproteinemia is common in patients with
FSGS and the serum albumin concentration may
fall to below 2 g/dL, especially in patients with
the collapsing variant.
• Hypogammaglobulinema and hyperlipidemia are
typical; serum complement components are
generally in the normal range.
• Serologic testing for HIV infection should be
obtained for all patients with FSGS, especially
those with the collapsing pattern.
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105.
Treatment of FSGS
• Prednisone theraphy: not to exceed 60 mg/day
• 50% responding 2-6 wk
• Cyclosporine therapy is the second choice for
FSGS
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106.
Cont….
• ACEI may provide a substantial reduction in
proteinuria and a long-term renoprotective
effect that may be equal to,or greater than, that
of immunosuppressive therapy.
• Response rates to immunosuppressive therapy in
primary FSGS
45% for complete remission,
10% for partial remission,
45% for no response.
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107.
Response to therapy
• The strongest prognostic indicator is the degrees of
reduction in proteinuria
• Complete response : <200 to 300 mg/day.
• Partial response reduction ≥ 50 %
• Relapse is return of proteinuria to ≥ 3.5 g/day after a
complete or partial remission.
• Steroid-dependence relapse while on therapy or
requirement for continuation of steroids
• Steroid-resistance little or no reduction in
proteinuria after 12 to 16 weeks of prednisone
therapy
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108.
PROGNOSIS OF FSGS
• Untreated primary FSGS often follows a
progressive course to end-stage renal disease
(ESRD).
• The rate of spontaneous complete remission
among patients with nephrotic syndrome is
unknown, but is probably less than 10 percent.
• Spontaneous remission is more likely to occur
among patients with normal kidney function and
non-nephrotic proteinuria.
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109.
Membranous GN
• Idiopathic membranous glomerulopathy is the most common cause of
nephrotic syndrome in adults (25% of adult cases) and can occur as an
idiopathic (primary) or secondary disease.
• Secondary membranous glomerulopathy is caused by autoimmune
diseases (e.g., lupus erythematosus, autoimmune thyroiditis),infection
(e.g., hepatitis B, hepatitis C), drugs (e.g., penicillamine,gold), and
malignancies (e.g., colon cancer, lung cancer).
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110.
Membranous GN
• In patients over the age of 60, membranous glomerulopathy is associated
with a malignancy in 20% to 30% of patients.
• The peak incidence of membranous glomerulopathy is in the fourth or
fifth decade of life.
Pathology
• The characteristic histologic abnormality in MGN is diffuse global capillary
wall thickening and the presence of subepithelial immune complex
deposits.
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111.
Clinical manifectations
• Nephrotic syndrome 80%
• Asymtomatic non-nephrotic proteinuria 20%
• Proteinuria (5-15 g/day)
• Microscobic hematuria may be seen 50% of adults
• Renal vein thrombosis 40%
• Renal function usually well preserved at the on set of disease.
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112.
Laboratory findings in MGN
• Proteinuria is usually more than 3 g of protein per 24 hours and may
exceed 10 g/day in 30% of patients.
• Microscopic hematuria is present in 30% to 50% of patients
• Renal function is typically preserved at presentation.
• Hypoalbuminemia is observed if proteinuria is severe.
• Complement levels are normal; however, the complex of terminal
complement components known as C5b-9 is found in the urine in
some patients.
• Tests for hepatitis B, hepatitis C, syphilis, and immunologic disorders
such as lupus, mixed connective tissue disease, and cryoglobulinemia
should be obtained to exclude secondary causes.
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113.
Theraphy of MGN
• Supportive care including ACEI, lipid-lowering therapy
• Corticosteroids
• Cyclosporine
• The high prevalence of deep vein thrombosis in patients with
membranous glomerulopathy (up to 45%) has led to the use of
prophylactic anticoagulation for patients with proteinuria greater than
10 g/day
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114.
Management of MGN
• Adult patients with good prognostic features, with less than 4 g/day
proteinuria and normal renal function, should be managed
conservatively.
• Patients at moderate risk (persistent proteinuria between 4 and 6
g/day after 6 months of conservative therapy and normal renal
function) or high risk of progression (persistent proteinuria greater
than 8 g/day with or without renal insufficiency) should be considered
for immunosuppressive therapy
• Individuals who have advanced chronic kidney disease and in whom
serum creatinine exceeds 3 to 4 mg/dL are best treated by supportive
care awaiting dialysis and renal transplantation
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115.
Prognosis of MGN
• Spontaneous complete remission of proteinuria occurs in 5 to
30 %
• Spontaneous partial remission (≤ 2 g of proteinuria per day)
occurs in 25 to 40 %
• ESRD in untreated patients is
 14 % at 5 years,
 35 % at 10 years,
 41 % at 15 years
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116.
Nephritic syndrome.
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• Oliguria
• Hematuria
• Proteinuria <3gm/24hour
• Hypertension.
• Abrupt in onset.

117.
GLOMERULARDISEASESTHATCAUSE
NEPHRITICSYNDROME
IgA nephropathy (IgAN)
• Most common lesion found to cause primary glomerulonephritis
throughout most developed countries of the world.
• IgA nephropathy common among Asians and Caucasians,
• 2:1 male to female predominance.
• The etiology of IgA nephropathy is unknown, but infections and/or
genetic characteristics may predispose to the development of kidney
disease.
• IgA nephropathy is often suspected on the basis of the clinical
history, but can be confirmed only by kidney biopsy.
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118.
Clinical findings
Most patients with IgAN present with
• gross hematuria (single or recurrent), usually following an
upper respiratory infection (40–50%)
• microscopic hematuria with or without mild proteinuria
incidentally detected on a routine examination. (40%)
• Malignant hypertension (<5%)
• Rarely, patients may develop AKI with or without oliguria,
due either to crescentic IgAN, or to gross hematuria causing
tubular occlusion and/or damage by red cells.
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119.
Cont….
• Episodes of macroscopic hematuria tend to
occur with a close temporal relationship to
upper respiratory infection,including tonsillitis or
pharyngitis.
• The timing differs from that for PSGN, which has
an interval period of 7 to 14 days between the
onset of infection and overt hematuria.
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120.
Cont….
• Systemic symptoms are frequently found,
including nonspecific symptoms such as malaise,
fatigue, muscle aches and pains, and fever.
• Microscopic hematuria and proteinuria persist
between episodes of macroscopic hematuria.
• Associated hypertension is common
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121.
Cont….
• Although IgA nephropathy was previously thought to carry a
relatively benign prognosis, it is estimated that renal
insufficiency may occur in 20% to 30% of patients within 2
decades of the original presentation.
• Renal failure typically follows a slowly progressive course,
 a minority of patients with IgA nephropathy
manifests a fulminant course resulting in a rapid
progression to end-stage renal disease.
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122.
Poor prognostic features
• Sustained hypertension,
• Persistent proteinuria greater than 1
g/day,
• Impaired renal function,
• Nephrotic syndrome
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123.
Laboratory Findings of IgAN
• microscopic hematuria and dysmorphic erythrocytes
• Proteinuria majority of subjects have less than 1 g/day of
protein.
• There are no specific serologic or laboratory tests diagnostic of
IgA nephropathy.
• Although serum IgA levels are elevated in up to 50% of
patients, the presence of elevated IgA in the circulation is not
specific for IgA nephropathy.
• Complement levels such as C3 and C4 are typically normal
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124.
PATHOLOGY
Immunofluorescence microscopy
• globular deposits of IgA (often accompanied by C3 and IgG) in the
mesangium and, to a lesser degree, along the glomerular capillary
wall.
large, globular mesangial IgA deposits
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125.
Treatment of IgA N
• ACE-I or ARB treatment (1B) in IgAN, use blood pressure treatment
goals of 130/80mmHg in patients with proteinuria <1 g/day, and
125/75mmHg when initial proteinuria is >1 g/day
• Corticosteroids(2C)in IgAN patients with persistent proteinuria>1
g/day, despite 3–6 months of optimized supportive care (including
ACE-I or ARBs and blood pressure control), and GFR >50 ml/min per
1.73m2, receive a 6-month course of corticosteroid therapy.
• Fish oil in treatment(2D)of IgAN with persistent proteinuria >1 g/d,
despite 3–6months of optimized supportive care (including ACE-I or
ARBs and blood pressure control).
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126.
Poststreptococcal
glomerulonephritis (PSGN)
• affects primarily children, with peak incidence between the ages of
2 and 6 years.
• It may occur as part of an epidemic or sporadic disease, and only
rarely do PSGN and rheumatic fever occur concomitantly.
• A latent period is present (7–21 days) from the onset of pharyngitis
to that of nephritis.
• The hematuria is microscopic in more than two thirds of cases.
• Hypertension occurs in more than 75% of patients
• The clinical manifestations of acute PSGN typically resolve in 1 to 2
weeks as the edema and hypertension disappear after diuresis.
• Both the hematuria and proteinuria may persist for several months,
but are usually resolved within a year.
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127.
Laboratory findings
• presence of dysmorphic red blood cells or red
blood cell casts.
• Proteinuria is nearly always present, typically
in the subnephrotic range.
• Nephrotic-range proteinuria may occur in as many as 20% of
patients and is more frequent in adults than in children.
• Throat or skin cultures may reveal group A streptococci
• elevated ASO titer above 200 units may be found in 90% of
patients;
• CH50 and C3 are reduced
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128.
Treatment of acute PSGN
• Supportive
• Supportive therapy may require the use of loop diuretics such
as furosemide and
• Hypertension treatment
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129.
ANCA-associated syndromes
• Microscopic polyangiitis
• Wegener granulomatosis
• Churg-Strauss syndrome
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130.
Discriptions….
• The presence of arteritis in a biopsy specimen with pauci-
immune crescentic glomerulonephritis indicates that the
glomerulonephritis is a component of a more widespread
vasculitis, such as microscopic polyangiitis,
• Wegener granulomatosis,or the Churg-Strauss syndrome.
• The pathogenesis of pauci-immune crescentic
glomerulonephritis is currently not fully understood.
• Many patients have a circulating ANCA, it has not been
conclusively proved that ANCA are involved in the
pathogenesis of pauci-immune small vessel vasculitis or
glomerulonephritis.
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131.
Laboratory Findings
• Approximately 80% to 90% of patients with pauci-immune
necrotizing and crescentic glomerulonephritis will have a circulating
ANCA.
• By indirect fluorescence microscopy on alcohol fixed neutrophils,
ANCA yields two patterns of staining:
• Perinuclear (P-ANCA)
• Cytoplasmic (C-ANCA)
TREATMENT= Immunosuppresive Therapy.
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132.
Lupus nephritis
• Renal involvement is common in idiopathic systemic lupus
erythematosus (SLE).
• An abnormal urinalysis with or without an elevated plasma
creatinine is present in a large proportion of patients at the
time of diagnosis, and may eventually develop in more than
75 % of cases.
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133.
EPIDEMIOLOGY
• The prevalence of clinically evident renal disease in patients
with SLE ranges from 40 to 75 percent.
• Most renal abnormalities emerge soon after diagnosis
(commonly within the first 6 to 36 months)
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134.
PATHOGENESIS
• The pattern of glomerular injury seen in systemic lupus
erythematosus (and in other immune complex-mediated
glomerular diseases) is primarily related to the site of
formation of the immune deposits, which are primarily due
to anti-DNA.
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135.
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136.
Treatment of LN
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137.
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