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Nephrology

Urine analysis;
physical exam
Appearance; colour, odour.
Sp Gravity; n= 1003 1030
Chemical exam; pH, protein, glucose, ketones, bl,
urobilinogen.
Microscopic exam; crystals, casts, cells, organisms.
NB; nitrite test detect G ve Bact.
leukocyte esterase detect WBC (5-15/HPF)
RBC casts acute GN ( nephritic)
wbc cast interstitial N, pyelon.
tubular cell cast ATN.
Granular cell cast chronic GN, pyelo.
hyaline proteinuria
fatty Nephrotic
hematuria = rbcs > 3.
pyuria = wbcs > 4.

Red urine

Hematuria.
Hemoglobinuria.
Myoglobinuria.
Porphyrins.
Drugs; MD, L-dopa, desferoxamine,
metronidazol. Cyclophosphamidehgic
cystitis, Beetroot,.
Orange brown; direct bil, drugs;
phenazopyridine, nitrofurantoin, Fe, B1,
rifampicin, phenytoin.

Approach for hematuria


If heavy proteinuria >1 gm/24h , RBCs casts ,
dysmorphic RBCs >70% glomerular
serology, KFTs, U/S, renal biopsy.
If proteinuria <1 gm/24h, no RBCs casts,
dysmorphic RBCs <30% Non glomerular
urine cytology, spiral CT or IVP, cystoscopy,
or MRA.
In between manage according to clinical &
lab clues e.g.; PT, PTT, TB test, PCR for TB,
urine Ca.

Approach for proteinuria


If proteinuria >2 gm/24h, hypoalbuminemia,
dysmorphic RBCs glomerular serology, renal
biopsy.
if K, P, uricemia, glucosuria, aminoaciduria
tubular urine B2 microglobulin, heavy metal screen.
If proteinuria >2 gm/24h,disparity bet dipstick &
prot/creat, anemia , Ca , globulins overflow
(= plasma LMWP as MM, Hb, myogl urine
electrophoresis, BM biopsy, radiological survey.

Functional proteinuria
Causes
fever.
Exercise.
Congestive heart failure (renal ischemiaAgII).
Orthostatic proteinuria;
- young male
- Regress in 5-10 yrs.
- Diagnosed by early morning sample & by 12
hrs ambulatory & 12 hrs overnight.

Choice of imaging procedure


RAS.
- for screening duppler, MRA, CTA.
- to assess function ACEI renogram (renal
scan)
Chronic pyelonephritis & reflux nephropathy
IVP, DMSA scan.
Medullary sponge IVP.
Neoplasm US , CT, MRI for staging.

Dynamic renal scans are used to;


1) Measure GFR DTPA. A split GFR can be
obtained for each kidney, which is not
possible with the creatinine clearance
method.
2) Assess renal blood flow (RBF) in patients
with suspected renal artery stenosis
hippuran/ MAG3 + ACEI renogram.

3) differentiate between obstructive


versus non obstructive causes of
hydronephrosis MAG3 + Lasix renogram.

Lasix renogram
Non obstructive
dilatation
Outflow
delay

+++

Parenchymal Normal
transit time
(PTT) after
IVI of 40 mg = immediate fall in time
activity curve
frusemide

Obstructive
dilatation
+++
delayed
= .fall less
.does not fall

2) Static renal scan

It consists of imaging of a radiotracer


(dimercaptosuccinic acid =DMSA) that is
taken up & retained by the renal proximal
tubular cells, providing a static image of
functioning nephrons.
Value,.
1. renal size, position, and axis.
2. focal renal parenchymal abnormalities,
e.g. scars appear as bites.

Renal biopsy

1.
2.
3.
4.

Indications;
Nephrotic S
Unexplained RF with normal Kid size.
Failure of recovery from ARF.
Asymptomatic prot., hematuria.

1.
2.
3.
4.
5.

1.

Contra indications;
Obese, oedema.
Uncontrolled HTN.
Bleeding tendency.
Shrunken kid.
Single kid except transplanted.
Complications;
Pain, hematoma, hematuria(in 20%, severe in 1-3%, need intervension
in 1;400)
AV aneurysm in in 20% but insignificant.
Infection
Mortality 0.1%.

2.
3.
4.

Glomerulopathies

Normal Glomerulus (PAS)

Granular mesangial

Granular

Linear Capillary

Clinical Presentations
* Asymptomatic proteinuria
* Nephrotic syndrome
* Nephritic syndrome
* Hypertension
* Hematuria which may be microscopic or macroscopic
* rapidly progressive renal failure
* chronic kidney disease.

Rapidly Progressive GN (or Crescentic)


- Pauci-immune ( ANCA associated Gn) =
- idiopathic cresentic.
- Microscopic Polyangiitis
- Wegener's Granulomatosis
- Churg-Strauss Syndrome.
- Immune complex e.g Post Streptococcal, IEC, lupus nephr.
- Goodpastures.

Hematuric Syndromes
(Isolated Hematuria,
nephritic, or RPGN)

Proteinuric Syndromes
(Isolated Proteinuria,
Nephrotic)

Nephritic and Nephrotic


Features

-Mesangioproliferative GN
(eg, IgA nephropathy)

-Minimal change disease

-Membranoproliferative GN

-Focal and segmental


glomerulosclerosis(FSGS)

-Mesangial proliferative GN

-Focal proliferative GN (eg,


lupus nephritis WHO III,
infective endocarditis)

-Fibrillary glomerulopathies
-Membranous nephropathy

-Diffuse proliferative GN
-Diabetic glomerulosclerosi
(eg, post- streptococcal GN,
lupus nephritis WHO IV)
-Amyloidosis.
-Crescentic GN ( severe IC,
pauci-immune nephritis,
anti-GBM nephritis)

-Light-chain deposition
disease

-Hereditary nephritis (Alport


syndrome)

What is this lesion encroaching the glomerular tuft.


What serious clinical condition is it associated with
Slide no 14

normal

Crescentic GN - (Trichrome Stain)

IgA Nephropathy

(Berger dis)

one of the most common forms of GN worldwide.


male /female 2/1.
2nd and 3rd decades of life.
Causes, -1ry
-2 ry;, celiac, dermatitis herpetiformis, IBD, psoriasis,
alcoholic C
ankylosing spondylitis, mycosis fungoides, HIV.
- familial.
Pathogenesis; IgA deposited in the mesangium(polymeric , IgA)
C/P; children synpharyngetic macroscopic hematuria during
adults asymptomatic microscopic hematuria.
Prognosis; benign disease , progression to renal failure in 25
30% over 2025 years;
Recur in 50% posttransplant but good Graft survival.

IF: mesangial IgA and C3 IgG or IgM

IgA Nephropathy

40 to 50 %
hematuria

No Treatment
Monitoring
/6 -12 m.

<10 %

30 to 40 %
CKD + proteinuria,

0.5 - 1g/day

ACEI & ARBS


+ fish oil + statins.

Acute
or RPGN.

progressive or severe disease.


1.0 -3.5 g/day

( s creat. >1.5 mg/dL,or rising ,


a GFR decline>15% /y,
nephrotic proteinuria,
marked proliferation without crescents

6-months course
of steroids

Combined immunosuppressives ;
prednisone + cyclophosphamide for 2 yrs.

As RPGN

What is this disease in a patient with abdominal


pain, hematuria, and renal impairment and a
palpable rash on thighs

Slide no 11

What is the
most common
glomerular
lesion on light
microscopy of
this patient
when a biopsy
is taken

Henoch-Schnlein purpura
distinguished clinically from IgA
nephropathy by;
- prominent systemic symptoms,
- a younger age (<20 years old),
- preceding infection, and
- abdominal complaints.
C/P; skin, arthritis, abd pain, Renal.
Ttt; arthralgias NSAIDs, severe abd pain,
renal steroids.

Poststreptococcal Glomerulonephritis
acute endocapillary proliferative glomerulonephritis
ages of 2 -14 years,
throat infections with particular strains of streptococci
(nephritogenic strains); After impetigo by 26 weeks
and 13 weeks after pharyngitis.
subepithelial "humps.
C/P; acute nephritic picture
C3 with normal levels of C4.
TTT; eradication of infection.
Postinfectious glomerulonephritis can occur in
patients with Subacute Bacterial Endocarditis ,
ventriculoatrial and ventriculoperitoneal shunts;
pulmonary, intra-abdominal, pelvic, or cutaneous
infections; and infected vascular prostheses.

ANCA associated GN

pauci-immune glomerulonephritis
C-ANCA= anti-proteinase 3 (PR3) in Wegener's
P-ANCA= anti-myeloperoxidase (MPO) more common
in microscopic polyangiitis, and Churg-Strauss
syndrome.
TTT;
Induction therapy usually includes some combination
of methylprednisolone, and cycloph.
plasmapheresis in case of pulm hge.
Maintenance, steroid tapering & give
cyclophosphamide for up to 2 years after remission.

1)

Idiopathic Crescentic GN
Renal-limited glomerular capillaritis Pauci-immune
crescentic GN.
Both pANCA and cANCA +ve.
2) Microscopic Polyangiitis
Renal + systemic vasculitis.
3) Wegener's Granulomatosis
Renal + vasculitis + granulomas
nasal ulcers, sinus granuloma, hemoptysis
CXR...... nodules , cavities.
Biopsy of involved tissue small-vessel vasculitis and
noncaseating granulomas.
4) Churg-Strauss Syndrome
Renal + vasculitis + granulomas + eosinophilia.
Asthma, fleeting pulmonary infiltrates
May be associated with leukotriene receptor antagonists.

Antiglomerular Basement Membrane Disease

Autoantibodies directed against GBM


collagen IV.
focal or segmental necrosis with crescent.
IF; linear immunofluorescent staining for
IgG
TTT; 810 treatments of plasmapheresis
accompanied by oral prednisone and
cyclophosphamide in the first 2 weeks.

Goodpasture Syndrome:

Causes of pulmonary-renal S;
1.
2.
3.
4.
5.
6.

Microscopic Polyangiitis.
Wegener's Granulomatosis.
Good pasture $.
SLE.
Churg-Strauss Syndrome.
HSP, cryo.

Membranoproliferative GN=mesangiocapillary GN
Types;
Type I Disease (Most Common)
1ry.
2ry; SBE, SLE, HCV, cryo, HBV, solid malignancy.
Type II Disease (Dense Deposit Disease)
C3 nephritic factor-associated
Partial lipodystrophy
Type III Disease
Idiopathic
Complement receptor deficiency

Pathology;
1.
2.
3.
4.

Subendothelial deposits
mesangioproliferative changes
mesangial interposition between the capillary BM and endothelial
cellsThickening of the GBM with a double contour .
lobular segmentation

Lab: low serum levels of C3 are typical.

TTT;
Long term alternate day steroids (prednisone 2
mg/kg) for one year, followed by slow tapering to
a maintenance dose of 20 mg every other day
for 3 to 10 years.
The role of aspirin and dipyridamole is unclear.
DD of MPGN;
cryoglobulinemia
Lupus nephritis class IV.

Nephrotic Syndrome

1.
2.
3.
4.

Heavy proteinuria> 3.5 gm/d/1.73 m2, minimal


hematuria, hypoalbuminemia,
hypercholesterolemia, edema, and no
hypertension.
TTT;
lipid-lowering agents
diuretics
inhibitors of the renin-angiotensin system can
lower urinary protein excretion.
+/- anticoagulants.

Minimal Change Disease

7090% of nephrotic syndrome in childhood but only 1015% of nephrotic


syndrome in adults.
Causes; 1 ry or 2ry to Hodgkin's disease, NSAIDs, IFN, IMN, lead.
Lab; selective proteinuria= LMWP.
Pathology;
LM, IF=nil
EM=effacement of the foot process.
TTT:
1. Prednisone 60 mg/m2/d for 4 wks then 40 mg/m2/d for 4 wks then gradual
tapering over 4 wks.

2. and other immunosuppressive drugs, such as cyclophosphamide,


chlorambucil, and mycophenolate mofetil, are saved for frequent
relapsers, steroid-dependent, or steroid-resistant patients.
Prognosis;
complete remission (<0.2 mg/24 h of proteinuria)
Relapses occur in 7075% of children after the first remission
steroid-dependent=relapse as their steroid dose is tapered.
steroid-resistant patients fail to respond to steroid therapy.

Membranous
Causes;
1 ry =70-80%.
2 ry;
- Malignancy; solid, NHL.
- Infection; HBV, HCV, P malari, S, leprosy.
- syst; SLE, MCTD, sickle.
-drugs; gold, penicillamine, captopril.
Patho;
LM& EM Thick BM, supepithelial deposits. IF; granular Ig G, C3
Prognosis;
40% spont remission
30% persistant proteinuria
30% progress to RF. need cytotoxic therapy
TTT
Alternate monthly for 6-12 months;
- pulse steroid then 0.5 mg/kg/d
- chlorambucil or oral cyclophosphamide.

Membranous GN :

Focal Segmental Glomerulosclerosis


segmental glomerular scars in some glomeruli.
1/3 of cases of nephrotic syndrome in adults and 1/2 of cases
of nephrotic syndrome in African Americans.
poor outcome in;
- Nephrotic range proteinuria,
- African-American race,
- renal insufficiency.
Causes;
1. 1ry
2. 2ry
- genetic (cong nephrotic S, steroid resistant, familial FSGS,
Alport, Nail & patella)
- infection; HIV ,Parvo B19 , Bilh.
- drugs; Heroin, lithium, pamidronate.
- Glom. HTN dt long standing nephron loss; sickle, single,
obesity, HTN, rejection, reflux.

PAS

perihilar

Path;
LM; FSGS.
EM; 1rydiffuse efface of foot process.
2 ry patchy efface of foot process.
IF; -ve except for Ig M & C3 trapped in sclerotic lesions
TTT
2ry as any nephrotic, TTT of the cause.
1ry steroid 1mg/kg/d for 3-4 months then
- if complete responsetaper after 1-2 wks over 3 months.
- if partial response (>50%)taper over 6-9 months.
- if little response add cyclosporin & switch to alternate day
then taper over 3 wks.

Hereditary nephropathies
ALPORT'S SYNDROME & Thin GBM
Transmisson;
1) 80%XL -------------------------- Alport, Thin GBM
= mutation in type IV collagen fibrils fragile GBM.
2) 15%AR, --------------------------- homozygous Alport , heterozygous Thin GBM
mutation in type IV collagen fibrils
3) 5% AD.
Clinical picture;
Alport:
Microscopic hematuria; begins at about 5 to 7 years of age.
Nephrotic proteinuria, HTN, ESRD late adolescence.
Extrarenal manifestations;
1- sensorineural deafness, start gradually in childhood, handicap
by 20 years of age.
2- Ocular abnormalities;lenticonus, Dot-and-fleck retinopathy;
not interfere with vision.
3- esophageal leimyomas .
Thin GBM= Benign familial hematuria
represent 25% of patients with microscopic hematuria.

Nail-Patella Syndrome
AD.
Clinical picture; appear at any age.
1) proteinuria to nephrotic syndrome.
2) nail dysplasia. (absent thumb nails)
3) Skeletal manifestations; absent patella, elbow dysplasia.
4) Eye manifestations; Heterochromia of the iris, cataracts.

FABRY'S DISEASE

XLR inborn error of glycosphingolipid metabolism.


defective activity of the lysosomal enzyme a-galactosidase A accumulation of
neutral glycosphingolipid in cellular lysosomes.
endothelial damage contributes to much of the pathology in Fabry's disease.
TTT= Enzyme replacement therapy.
C/P;
1) Renal Manifestations; progressive proteinuria & decline of renal function.
2) Skin symptoms; Anhidrosis, Angiokeratoma.
3) Visual symptoms; cornea verticillata,
4) Neurological symptoms; PN, Hearing deficit .
6) Other symptoms: coarse facial features.

diabetic nephropathy
Incidence

The risk for ESRD is 12 times as high in type 1 diabetes


compared to type 2 diabetes.

About 80% type 1 will progress to proteinuria and ESRD


compared to only 20% of type 2.
Stages;
1. Renal hypertrophy & hyperfiltration.
2. Normoalbuminuria, but detectable glom lesions.
3. Microalbuminuria (30-300 mg/24h= 20-200Ug/min= U
alb/creat 0.03-0.3).
4. Overt proteinuria & azotemia.
5. ESRD.

Microalbuminuria

30-300 mg/24h
= 20-200 Ug/min
= U alb/creat 0.03-0.3.

Affects 25-30% of diabetics.

Progress in
- 80% of type 1 & 20% of type 2 without ttt.

Develop after 5-10 yrs of DM.

Screening for Microalbuminuria is recommended in


All type 2 diabetes at diagnosis.
Type 1 diabetes 5 years after diagnosis, at puberty.
Annually for all patient after.

Histopathology

LM;
Thick BM.
Mesangial expansion (diffuse, nodular=Kimmelstiel-Wilson lesion).
Aff & eff arteriolar hyalinosis.
EM;
-fibrin cap (esinophilic focal thickening of a peripheral cap loop)&
- capsular drop (esinophilic focal thickening of bowmans capsule).
IF; psuedolinear deposition of alb & Ig G along BM.

Preventive Strategies in Diabetic Nephropathy.


1. Tight glycemic control (A1C<7%)
.
(
2. Aggressive control of hypertension.
Goal; DM <130/80
Diabetic nephropathy (>1g proteinuria/day)
<125/75
3. Protein restriction.
4. Control of dyslipedemia.
5. Encourage smoking cessation.
6. Prevent sudden deterioration of kidney function.
function
7. Recent strategies in future.

Antihypertensives
1) ACEI;
Acute rise of serum creatinine of up to 30-35%, stabilize after 2
months, may occur in proteinuric patients with serum creatinine
>1.4mg/dl.
greater increase of serum creatinine should raise the possibility of
RAS.
Albuminuria, serum creatinine and K should be checked monthly till 23 months.
2) DHP CCBs (nefedipine- amlodipine):
may increase proteinuria and accerelate the progression of diabetic
nephropathy.
3) NDHP CCBs (deltiazem, verapamil) may reduce proteinuria.

Lupus Nephritis
(WHO) classification & clinical presentation
INormal;-------------------Mild proteinuria
II Mesangial proliferation;---------------------asymptomatic hematuria or proteinuria
III Focal proliferative (FPGN); <50% of all glomeruli----active generalized SLE
------------------------mild-to-moderate renal disease
IV Diffuse proliferative (DPGN);-------Nephritic nephrotic + active generalized SLE
VMembranous;-----------nephrotic syndrome, usually without manifestations of
active SLE.
VI Advanced sclerosis , >90% of glomeruli------------significant renal insufficiency
Lab of lupus nephritis activity; +ve anti DNA,C3, C4 , +ve anti C1q(most
specific), antinucleosome Ab , urine (hematuria, RBCs casts).
Value of renal biopsy; poor correlation between C/P & histopath., associated
pathology e.g. drug induced AIN, TMA.

Characteristic lesions
LM;
Wire-loop lesion = massive subendothelial immune deposits
Hyaline thrombi = large intracapillary immune deposits
Fibrinoid necrosis = intimal immune and fibrin deposits
IF: full-house with IgG, IgA, IgM, C1q, C3, fibrin, and light chains.
EM:
All level dense deposits IImesangial;
III and IV mesangial,subendothelial,
Vsubepithelial
Fingerprint subtructure immune deposits ,
Tubuloreticular inclusions, present also in HIV, most diagnostic.

Therapy
Class I: no specific therapy.
Class II: if proteinuria > 1 g/dprednisone (20-40 mg/d)
for 1-3 months.
Classes III and IV;
Induction; pulse steroid +IV cyclophosphamide or MMF
Maintenance; prednisone 1 mg/kg/d gradual tapering to 5-10
mg/d for 2 years + azathioprine or MMF.
Class V: as 1ry membranous.
Renal affection in rheumatoid arthritis;
- Drug toxicity; NSAIDs AIN+nephrotic.
- 2ry amyloidosis.

Gammopathies
= diseases of globulins
=immunoglobulin overproduction

Alb.= 3.3- 4.7 g/dl.


1 glob.=0.1-0.4 g/dl.
2 glob.=0.3-0.9 g/dl.
2 glob.=0.7-1.5 g/dl.
glob.=0.5-1.4 g/dl.

Monoclonal Gammopathy
Polyclonal Gammopathy
Due to proliferation of many
B cell clones
e.g. CLD, Chr. Inflammation,
infection.

= Plasma cell dyscrasias


=immunoproliferative diseases
Due to proliferation of a single
Clone of Ig-forming cells that
produce homogenous excess of
light, heavy chains or complete IG
molecule. (M-protein, where the
"M" stands for monoclonal).

MECHANISMS OF RENAL INJURY


I. Tubular precipitation; cast nephropathy (in MM)
II. Deposition; Amyloidosis, LCDD
III. Hyperviscosity; Waldenstrm macroglobulinemia
& Myeloma dt Igs.
IV. Glomerular reactions; MPGN, Pamidronate
induced FSGS
V. Tubular toxicity; ATN (NSAIDs, Iodinated
contrast), Fanconi syndrome.

DIAGNOSTIC APPROACH TO RENAL DYSFUNCTION IN


PLASMA CELL DYSCRASIA
I. Serum protein electrophoresis
- Monoclonal proteins will appear as a spike in the pattern
- Sensitivity (500-2000 mg/L)
- May not pick up small bands or bands outside of the gamma region
II. Urine protein electrophoresis
- Both serum and urine should be tested to increase detection to 95%
III. Immunofixation
- using Anti-serums to light chains.
- More sensitive than electrophoresis (detection limits 150-500 mg/L)
IV. Serum free light chains (FLC) assay
Most sensitive (detection limit of 0.5 mg/L)
Sensitivity is 99% when FLC is combined with serum and urine
immunofixation
V. Bone survey
VI. Bone marrow biopsy
VII. Abdominal pad of fat aspirate; 80% sensitive for AL amyloidosis
VIII. Renal biopsy
A. Should be performed on all cases if risk permits
B. Only way to distinguish between various kidney diseases

Multiple Myeloma
= CAST NEPHROPATHY
Precipitating factors
1. Volume depletion
2. Hypercalcemia
3. NSAIDs
4. Intravenous contrast
5. Infections
Pathogenesis
A. Increased tubular concentration of light chains enhanced by
decreased urine flow and furosemide.
B. Binding and co-aggregation with Tamm- Horsfall proteintubular
cast in the distal tubule then the proximal tubule
C/P;
Acute renal failure
10% to 15% present with ESRD
> 75% have subnephrotic range proteinuria
1. Mainly Bence-Jones proteinuria
2. Often dipstick negative

V. Treatment
A. Restore intravascular volume
B. Remove offending agents and nephrotoxic drugs
1. Hypercalcemia
i. Volume repletion
ii. Bisphosphonates in refractory cases.
C. Reduce light chain levels
1. Chemotherapy
i. Thalidomide plus dexamethasone,
or
ii. Bortezomib plus dexamethasone
D. Stem cell transplantation +/- kidney transplant is an option in
selected patients.
VI. Management of ESRD
A. Survival on dialysis is significantly decreased in patients with
dysproteinemia who reached ESRD.
1. Median survival was 2 -4 years for LCDD, & AL amyloidosis and 1
year for multiple myeloma.

What are these homogenous deposits with light microscopy


in this renal biopsy of a patient with long standing
rheumatoid arthritis who has recently developed nephrotic
syndrome

Slide no 12

AMYLOIDOSIS
TYPES OF AMYLOIDOSIS
1. AL amyloidosis
2. AA amyloidosis
3. Dialysis-related amyloidosis
4. Heritable amyloidoses e.g. heritable neuropathic
and/or cardiomyopathic amyloidosis due to deposition
of fibrils derived from transthyretin (also referred to as
prealbumin).
5. Organ-specific amyloid Amyloid deposition can be
isolated to a single organ, such as the skin, eye, heart,
pancreas, or genitourinary tract, resulting in specific
syndromes.

Renal Amyloidosis
1.
1.
2.
3.
2.
-

Congo red +ve.


Biopsy of involved liver or kidney is diagnostic 90% , abdominal fat pad
aspirates are positive about 70%.
SAP (serum amyloid P) scanning can identify the distribution of
amyloidSensitivity = 90 % & ; the specificity is 93 %.
AL amyloidosis, also called primary amyloidosis;
75% are of the lambda LC.
10% of these patients have overt myeloma.
nephrotic syndrome is common, and about 20% of patients progress to
dialysis.
treatment ;
melphalan+ dexamethazone, 4d courses/28 d for up to 9 courses.
autologous hematopoietic stem cell transplantation .
Thalidomide/dexamethazone.
AA amyloidosis is sometimes called secondary amyloidosis
nephrotic syndrome, 4060% of patients progress to dialysis.
It is due to deposition of -pleated sheets of serum amyloid A protein, an
acute phase reactant.
40% 2ry to rheumatoid arthritis, 10% have ankylosing spondylitis or psoriatic
arthritis, FMF
treatment of the primary disease, Colchicine in FMF, Eprodisate.

Light Chain Deposition Disease


kappa light chains that do not form amyloid fibrils. Instead, they
self-aggregate and form granular deposits along the glomerular
capillary and mesangium, tubular basement membrane,
nephrotic syndrome , 70% of patients progress to dialysis.
not fibrillar and do not stain with Congo red,
IF + anti-lightchain antibody.
EM granular deposits.
Treatment = Melphalan/prednisone for 2 years as MM.
DD of nodular sclerosis;
Diabetic glomerulosclerosis
LCDD.
Amyloidosis.
Idiopathic.

Antiphospholipid antibody
Syndrome

Def & pathogenesis; auto Ab to phospholipids on endothelial cells


& LDL endothelial injury thrombotic microangiopathy.
Diagnostic criteria;
1 clinical (thrombosis arterial or recurrent venous/ recurrent
miscarriage before 34 wks of normal fetus)
+ 1 lab (anticardiolipin/ lupus anticoagulant)
C/P;
1. livedo reticularis, thrombosis; CNS, CVS, adrenal insufficiency, lung,
GIT, Kidney, ARF, TMA, HTN.
2. Catastrophic form => 3 organs simultaneously (Kid, lung, CVS).
Lab; PTT, +ve anticardiolipin/ lupus anticoagulant, false +ve
VDRL.
Ttt; APA +ve without previous thrombosis no ttt or aspirin.

APA +ve & previous clinical event long term warfarin, INR=2-3.
APA +ve & pregnancy heparin.

scleroderma
Renal failure in scleroderma;
- renal crises.
- TMA
- Membranous.
Path; as TMA but affect arcuate & interlobular arteries,
onion skin appearance, hypertrophy of JGA.
Marker of Scl renal crises; anti-RNA polymerase III
C/P; diffuse systemic scl + new onset severe HTN or
RPRF.
TTT; ACEI
Prognosis; continue ACEI after dialysis as 50% may
recover over 3-18 months.

Sickle cell;
Glomerular; hematuria , FSGS.
Tubular; DI , RTA , papillary necrosis.
Renal cell carcinoma.
Sarcoidosis; Ca stones, granulomas, TIN.
Sjogren $; Membranous, RTA.

Cryglobulinemia

Cryglobulins are proteins ((Ig & Ag) that precipitate on cooling to 4o


Precipitate in small cool Bvs in the peripheries complement activation
Raynaulds, vasculitis.
33% is called essential cryo (uknown cause, discovered to be mostly related to HCV)
Type I

Type II

Type III

Monoclonal

Mixed
Mono Ig M against poly Ig
G (RF activity)

Mixed
polyclonal

causes

Waldenstrom
MM

HCV
Plasma cell dyscrasia

- Autoimmune; SLE,
hepatobiliary, GN.
- Lymphoproliferative
- Chronic infection

C/P

Hyperviscosity, Raynaulds, cutaneous ulcers, Purpura, arthralgia, LN,


HSM, peripheral neuropathy,
GN; HTN, acute nephritic, nephrotic less common.

Gn;
LM: Marked leukocytic infiltration, intraluminal deposits,
vasculitis with fibrinoid necrosis, TI infiltration.
IF; Ig M&G, C3.
Lab; C4, C1q,+ve cryo, RF, HCV Ab.
Poor prognostic factors;
1. Old age.
2. Recurrent purpura.
3. High s creat.
4. High cryo titre; Clinical and histologic activity does not always
correlate directly with detection of circulating cryoglobulins.
5. Low C3
TTT;
- steroids (pulse then 0.5 mg/kg for 6 months) + TTT of HCV.
- If severe; add cyclophosphamide,
- plasmapharesis& Rituximab.

Hypocomplementemic GN;
- Lupus nephritis
- Post infectious.
- MPGN
- Cryoglobulinemia.
HCV associated nephropathy;
1. MPGN +/- cryoglobulin
2. Membranous GN
3. FSGS
4. Prolif, TMA, fibrillary.

Thrombotic microangiopathies (TMA)


Def; group of disorders ccc by fibrin deposition in the
lumen & wall of arterioles & glomerular cap.
Path;
LM; - intraluminal fibrin & plat.
- double contour of cap wall.
- fibrinoid necrosis of arterioles.
EM; tactoids of fibrin(subendothelial), swollen endo.
IF; no IC.
Lab; platelets, hemolytic anemia, shistocytes.
TTP more platelet.
HUS: more RBCs & cortical necrosis.

Thrombotic thrombocytopenic
purpura (TTP)
Pathogenesis;activity of VWF cleaving protein to < 5%
large VWF platelet adhesion dt;
- Familial ADAMTS13 mutation.
- Acquired Ig e.g. with ticlopedine,peripartum,sepsis,malig.
C/P; pentade;
fever, hemolytic anemia, thrombocytopenia, CNS, mild renal .
TTT; FFP, plasmapharesis,.
NB: platelet transfusion & antiplatelet e.g. aspirin are
contraindicated.
FU by LDH level.
Prognosis; mortality 90% if untreated, 90% survival if ttt.

Hemolytic Uremic Syndrome


(HUS)

1.
2.
3.

Pathogenesis; endothelial injury;


By shiga toxins of Eoli O157 H7 (Diarreal form
D+HUS).
Complement mediated in familial form dt factor H.
Complement mediated in the acquired form by a
triggering factor e.g.pregnancy, malignancy, drugs.
C/P; triad of hemolytic anenia, thrombocytopenia,
severe renal failure.
Ttt; supportive, recombinant factor H.
Poor prognostic factors; old, pregnant, D-HUS,
shigella, pneumococcal, HTN, cortical necrosis,
marked leuckocytosis, anuria, persistent proteinuria.


1.
2.
3.
4.
5.
6.

Uses of plasmapharesis in renal dis;


Good pasture.
ANCA +ve dis.
Idiopathic cresentic Gn.
Cryo.
MM with hyperviscosity.
TTP & HUS.

Tubulointerstitial diseases

Acute interstitial nephritis

1.
2.
3.
4.

Causes;
Drugs; antibiotics, diuretics, NSAIDs.PPI.
Infections e.g.bact, viral as CMV, Hanta V, fungal.
Immune dis; SLE, Sjogren, sarcoid, cryo, acute transplant
rejection.
Idiopathic.
C/P; Fever, rash, arthralgias +/- flank pain, hematuria.
Lab; Serum.., KFTs, & electrolytes.
Urine.....RBCs , WBCs, White cell casts, eosinophiluria,
Eosinophilia, tubular defects, proteinuria<1g.
TTT; stoppage of offending agent high dose steroid for 2-3
wks for drug induced & systemic dis. not for infection.

Chronic interstitial nephritis

1.
2.
3.
4.

Causes;
Drugs; analgesics, lithium, heavy metals as lead, calcinurin inhibitors.
Infections e.g. EBV.
Immune dis; SLE, Sjogren, sarcoid, cryo, chronic transplant rejection.
Obstructive uropathy.

CP.....> CKD,HTN, PCT defects, marked acidosis, hypo or hyperkalemia.


Lead; renal, blue line in gum, gout, wrist & foot drop.
diagnosis; lead mobilization test.
TTT; chelation with EDTA or oral succimer.
Lithium; DI; ttt; stop it , give amiloride , thiazide ,
endomethacin,carbamazepine
RTA, CIN, FSGS, ARF in acute intoxication, hypothyroidism, goiter,
hypercalcemia.

Effect of NSAIDS

Vasomotor ARF.
Acute interstitial nephritis + nephrotic S.
Acute papillary necrosis.
Nacl retension.
K in low RAA as DM, ACEI.
CKD; either NSAIDS- induced CKD.

NSAIDS- induced CKD

analgesic nephropathy
Mixture; aspirin,
paracetamol, caffeine ( 2-3)
Kg).

age> 60

40-50

less

Anemia out of proportion

Does not occur with low


dose aspirin

Diagnosed by non-contrast
CT papillary necrosis &
medullary calcification, small
kidneys, irregular contour.

RENAL FANCONI SYNDROME


generalized dysfunction of the PCT.
phosphate, glucose, amino acid, and bicarbonate
wasting by the proximal tubule.
C/P;
in children is usually rickets and impaired growth.
In adults, osteomalacia and osteoporosis.
+ polyuria, renal salt wasting, hypokalemia, acidosis,
hypercalciuria, and LMW proteinuria.

Papillary necrosis

Age > 60yrs except sickle.


Due to medullary blood flow.
Causes;
DM
UT obstruction.
Analgesic nephropathy.
Sickle cell anemia.
Graft rejection
Pyelonephritis, TB.
Hyperviscosity syndromes.
C/P; hematuria , necroturia , loin pain, UTI, sepsis, renal failure.
Diagnosis; IVP (best). signs;calyceal irregularities, sinus tract,
ring sign, clubbing, filling defects.
prevention; ACEI are protective.
TTT; control B sugar, avoid analgesics & drugs that Bl flow as
thiazides, BB, fluids,

Vesicoureteric reflux
Not inherited.
Most common cause of ESRD in children.
Child with UTI 30% VUR.
NB;
Most common inherited cause of ESRD ADPKD.
Most common inherited cause of ESRD in
childrennephronophthisis (as medullary cystic dis).
Reflux nephropathy=VUR + CIN.
Grades; I ureter
II ureter & pelvis ( without dilatation).
III pelvic dilatation, preserved forniceal angles.
IV blunting of forniceal angles.
V clubbing of forniceal angles.

Diagnosis;
- early micturating cystography, dynamic renal scan.
- late U/S, DMSA scan.
Screening for VUR in:
: 1st attack of UTI at any age.
: 2nd attack or- 1st with family history,
- abn. Voiding,
- HTN,
- poor growth,
TTT;
Grade I nothing.
Grade II, III till puberty antibiotics TMP-SMX or nitrofurantoin,
cephalexin.
Grade IV, V Long-term antibiotics or surgery.
NB: Surgical correction of VUR in children have failed to show significant
benefit in terms of renal function & progressive scarring. Surgical
correction is reserved for the child who, in a 2- to 4-year period, appears
to be not responding to medical therapy.

Cystic diseases of the kidneys


1.
2.
-

Hereditary;
ADPKD.
ARPKD.
Tuberous sclerosis
Von Hippel-Lindau disease (VHL)
Juvenile nephronophthisis and medullary cystic disease.
Acquired renal cysts;
Medullary Sponge Kidney.
acquired cystic disease.
Simple cysts.

cystic Kidney Disease


Inherited Cystic
Kidney Disease

Mode of
Inheritance

Renal
Abnormalities

Extra-Renal
Abnormalities

ADPKD

AD

Cortical and
medullary cysts

Cerebral aneurysms; liver


cysts, othera

Nephronophthisis

AR

Small fibrotic
kidneys; medullary
cysts

Retinitis pigmentosa

Medullary cystic
kidney disease

AD

Small fibrotic
kidneys; medullary
cysts

None

Tuberous sclerosis

AD

Renal cysts;
angiomyolipomas;

Adenoma sebaceum; CNS


hamartomas

Von Hippel-Lindau
disease

AD

Renal cysts; renal


cell carcinoma

Retinal angiomas; CNS


hemangioblastomas;
pheochromocytomas

Adult Polycystic disease

1.

Commonest inherited kidney disease.


Accounts for 5-10% of (ESRD).
Clinical Picture
Renal disease; Abdominal pain , hematuria, Palpable kidneys, Recurrent
UTI,stones, Hypertension, Renal Failure .
2. Extra renal disease; Cerebral Aneurysm (Berrys) (5-10%), Hepatic,
Pancreatic cysts, Mitral Valve Prolapse (26%),diverticulosis.

Diagnostic radiological criteria


If +ve Family history

< 30 years ----- 2 cysts in at least one kidneys.

30 - 59 years ----- 2 cysts in each kidney.

> 60 ---4 cysts in each kidney.


If -ve Family history 5 cysts in each kidney.

TTT;
1. ACEI, ARBs
2. If Hge; analgesics, rest, hydration.
3. If infected; bl culture not urine,sutrim, cipro, vanco not ceph nor aminogly.
4. Recently V2 receptor blockersprogression.
5. Sirolimus.

APKD

Tuberous sclerosis
AD, hamartin (tumor suppressor)multiple hamartomas.

Clinical Picture;
CNS epilepsy in 80%, Mental retardation.
SkinFacial adenoma sebaceum, Shagreen patches
(lower back), Ash leaf (Hypomelanotic macules).
Periungual fibromas.
Renal (60%) cysts, Angiomyolipomas.
Retinal hamartoma (50%), is almost always
asymptomatic.
Liver ( 40% ), angiomyolipomas and cysts.
Heart (rhabdomyoma).
Lung (lymphangiomyomatosis; affects females)

Acquired renal cysts


Medullary Sponge Kidney
- dilatation of collecting ducts,
Benign course.
Calcify nephrocalcinosis, Nephrolithiasis and UTI.
Defective concentrating ability & RTA.
Diagnosed by IVPradial, linear striations in the papillae
or cystic collections of contrast .
Dialysis Cysts= acquired cystic disease.
the size of the kidneys is usually not markedly increased,
Precancerous.
Simple cysts
- Fluid filled, may enlarge to 10 cm.
- Single or multiple.
- Common 2% of people< 50y, up to 20% > 70yrs.

Acquired cystic disease of the


kidney

Acquired cystic disease of the


kidney

Vascular renal diseases

Renovascular HTN
Clues;
- abrupt onset, accelerated HTN.
- recurrent flash pulmonary edema.
- Deterioration in renal function with BP reduction
and/or ACE inhibitor therapy.
- Generalized atherosclerosis obliterans.
- asymmetrical kidneys.

Causes;
- RAS (narrowing > 50%)
- vasculitis
- TMA.

Atherosclerotic renal artery disease


(ASO-RAD)

5th to 7th decades of life.


70-80% ostial stenosis.
Tend to progress, renal impairement.
TTT; anti HTN, lipid lowering,antiplat.
interfere if; > 60% stenosis.
progressiveKFTs
evidence of salvageability;
- normal Kid size
- good function in renal scan
- RI<80
TTT percutaneous angioplasty +stent .
if failed surgical revascularization

114

Classification of renal artery


stenosis:
1. Atherosclerotic renal artery disease (60 - 80%)
2. Fibrous dysplasias (20 - 40%).

FMD

Female, 30-50 yrs.


Slow progression.
Renal functions preserved.
1% of HTN.
Most frequent is medial dysplasia with multiple contiguous
stenosis string of beads.
TTT; ACEI, percutaneous angioplasty (curable, low
restenosis), if failed surgical revascularization

Hypertensive Nephrosclerosis
27% of ESRD patients.
risk factors for progression to ESRD include age,
sex, race, smoking, hypercholesterolemia,
duration of hypertension, and preexisting renal
injury.
Kidney biopsies (not needed); arteriolosclerosis,
chronic nephrosclerosis, and interstitial fibrosis
in the absence of immune deposits .
TTT; Treating hypertension <130/80 mmHg if
there is preexisting diabetes or kidney disease,
most patients begin therapy with two drugs,
classically a thiazide diuretic and an ACE
inhibitor.

Renal vein thrombosis


Etiology; History of nephrotic syndrome or
pulmonary embolism.
C/P; Flank pain.
Urine analysis; Mild proteinuria Occasional
hematuria.
Renal venogram or MR venogram are
diagnostic.

Atheroembolic disease
Def; separation of cholesterol crystals from atheromatous
plaques to small renal arteries.
Etiology; Vascular disease; classically occurs within days
weeks of manipulation of the aorta or other large vessels as
coronary angio, or in the setting of anticoagulation.

Clinical picture; Retinal plaques, palpable purpura, livedo


reticularis, slow deterioration of renal function.
Lab; Eosinophilia, Hypocomplementemia, Eosinophiluria
Diagnosis; Skin or renal biopsy ccc clefts, concentric
intimal fibrosis, FSGS.
TTT; stop anticoagulation, low dose steroids.

Urinary tracts

Urinary Tract Infection


The infecting organism
E coli =80-95%
Staph. Sapro. = 5-10%
Enterococci (Strept. fecalis) =5-14%
Others; proteus = 2-3%,Klebsiella = 2-3%, Pseudomonas, candida esp in
complicated cases.
Uncomplicated UTI= healthy young woman.
1. Uncomplicated cystitis;
- C/P; dysuria, frequency, suprapubic pain.
- diagnosis; history, urine analysis pus cells>4/HPF.
- TTT; 3 daysTMP/SMX or Quinolones or 5d Nitrofurantoin.
- if recurrent long term small dose postcoital or 3 times/wks at bed time.
2. Uncomplicated pyelonephritis;
- C/P; fever, loin pain.
- diagnosis; urine culture; bact count >104
- TTT; TMP/SMX or Quinolones (IV if vomiting) till culture sensitivity for a total of 14
days.

Complicated UTI;
- In structural or functional abn e.g. anatomic
abnormality, Instrumentation, Medical condition; as
Pregnant, Diabetic CKD,
transplant,Nosocomial,Childhood UTI, symp.> 7d, Drugs;
antibiotics, immunosup.
- Elderly, men & children.
diagnosis; bact count >105.
TTT; 7 days for lower & 14 days for upper UTI with broader
spectrum Ab covering pseudomonas e.g.
Piperazin/tazobactam, Cefepime, Imipenem, Meronem,.
if recurrentlong term suppressive therapy ie full dose
then dose when culture ve.

Catheter-Associated UTI
Asymptomatic patient
no therapy is indicated. (as relapse is very
common).
In symptomatic patient
antibiotics is based on the Gram's stain of urine
or the antimicrobial sensitivity patterns.
Prophylactic antimicrobial therapy
In case the time of catheterization is clearly
limited (e.g., in gynecologic , vascular surgery,
kidney transplantation).

UTI in Men
In men > 50 years with UTI,
- Intensive therapy for at least 4 to 6 weeks
up to 12 weeks is recommended due to deep
tissue invasion of the prostate & the kidneys
even in the absence of overt signs of
infection at these sites.
Treat Relapse
(1) long-term antimicrobial suppression
(2) surgical removal of the infected prostate.

Asymptomatic bacteriuria in Pregnancy


Screening for asymptomatic bacteriuria by
urine culture at the first prenatal visit (12-16
wks pregnancy) is mandatory (for fear of
pyelonephritis that develop by the end of the
second trimester & so may lead to premature
delivery).

If +ve repeat to confirm then


treat with 5- 7 days of nitrofurantoin (100 mg twice daily) ,
amoxacillin (500 mg PO three times daily )
cephalexin (500mg twice daily).
FU culture 1 week after and then monthly until the completion of the
pregnancy.

1.
2.

Fungal Infection of the Urinary Tract

Candida AlbicansFluconazole, itraconazole or 5 flurocytosine.


Treat if:
symptomatic,
Asymptomatic only if neutropenia, or urinary tract manipulation or
repeated culture counts > 10.000.
otherwise rapid recurrence is common, selection of resistant
Candida, and clinical outcomes do not appear to be improved .
Regimens:
1. Catheter-associated candidal UTI,
removal of the preceding catheter,
insertion of a three-way catheter, and
infusion of an amphotericin rinse for a period of 3 to 5
days .
2. Without catheter, fluconazole, 200 mg/day for 10 to 14
days, (insertion of a catheter for an amphotericin rinse carry risk
of bacteriuria).
Success is increased if such contributing factors as hyperglycemia,
corticosteroid use, and antibacterial therapy can be eliminated.

Etiology of Urolithiasis
Anatomical causes
- ureteropelvic junction (UPJ) obstruction,
- Horseshoe or ectopic kidney
- vesicoureteral reflux,
- calyceal diverticula
- medullary sponge kidney
Metabolic causes
- low urinary volume,
- hypercalcuria (25%40%),
- hyperoxaluria (10%50%),
- hyperuricosuria(8%30%) and
- hypocitraturia (5%30%)

Major Causes of Renal Stones


Stone Type and
Causes

Etiology

Diagnosis

Treatment

Alkali supplements +

Calcium stones 85% ,

Idiopathic hypercalciuria
50%

Hereditary (?)

Normocalcemia, unexplained
hypercalciuria ( > 300
mg / 24 hrs ).

diet; thiazide

1ry hyperPTH

Neoplasia

Unexplained hypercalcemia

Surgery

Distal RTA

Hereditary

Hyperchloremic acidosis,
minimum urine pH >5.5

Alkali replacement

hyperoxaluria

High oxalate or low


calcium diet
Bowel surgery
Hereditary

Urine oxalate >45 mg per 24 h

Low oxalate diet


Cholestyramine
pyridoxine

Hypocitraturia

Hereditary (?), diet

Urine citrate <320 mg per 24 h

Alkali supplements

%Occurrence

Etiology

Diagnosis

Treatment

Uric acid stones 5-10%


Hereditary
Intestinal, habit

Clinical diagnosis
Uric acid stones,
Urine uric acid
>750 mg /d (women),
>800 mg /d (men)

Alkali and allopurinol


if urine uric acid >1000
mg/d

Cystine stones 1%

Hereditary

Stone type; elevated


cystine excretion

Massive fluids, alkali,


D-penicillamine

Struvite stones
5-10%

Infection

Stone type

Antimicrobial agents

Hyperuricosuria

50% Gout
50% Idiopathic
Dehydration

Acetohydroxamic acid
judicious surgery

Dietary modification
Increase fluid intake to maintain urine output of 2-3 l/day:
Decrease intake of animal protein
Restrict salt intake
Normal calcium intake.
Decrease dietary oxalate;

RENAL STONES
Calcium oxalate stones are the commonest kind of stones.
Calcium phosphate stones are the second commonest and
associated with 1ry hyperpara, d RTA, CAI (alkaline urine(.
Uric acid stones (5% of all stones) are associated with high
purine metabolism, chronic diarrhoea, gout.
cystine stones associated with amino aciduria; a disorder of
proximal tubular cells. (COAL cystine, ornithine, arginine,
lysine) .
Proteus splits urea into ammonia, causing alkaline urine
struvite stones (magnesium ammonium phosphate).
Radiopaque stones are: Calcium oxalate, calcium phosphate,
triple phosphate, cystine stones.
Radiolucent stones are: Uric acid, xanthine stones.

comprehensive metabolic evaluation


serum calcium, bicarbonate, creatinine, chloride,
potassium, magnesium, phosphate, and uric acid.
24 hour urine collections for: volume, pH, calcium,
oxalate, citrate, uric acid, phosphate, sodium,
potassium, and creatinine.
Na nitroprusside test & 24 hour measurement of cystine
Intact PTH and 1,25 dihydroxycholecalcifirol in
hypercalcaemic patients.
Indicated for;
1. Patients with multiple stones at first presentation,
2. Patients with family history of urinary stones.
3. Patients with recurrent urinary stone.
Noncontrast helical Computed Tomography (CT)
91% sensitive and 98% specific in detecting urolithiasis

Beverage type

risk

Coffee and tea

Decreased

Alcohol

Decreased

Milk

Decreased

Lemon juice

Decreased

Grapefruit juice

Increased

Cranberry juice

Increased

Carbonated
beverages
Cola

Increased
Increased

Promotors & Inhibitors of stone formation


Dietary factor

Proposed mechanism(s)
Promotors

Oxalate

Increased urinary oxalate excretion

Sodium

Increased urinary calcium excretion

Animal protein

Increased urinary calcium and uric acid excretion; reduced

Vitamin C

urinary citrate excretion


Increased oxalate generation and excretion
Inhibitors

Dietary calcium

Binding of dietary oxalate in gut

Potassium

Increased urinary citrate excretion; reduced urinary

Phytate

calcium excretion
Inhibition of calcium oxalate crystal formation

Magnesium

Reduced dietary oxalate absorption; inhibition of calcium

Urinary citrate
Vitamin B6

oxalate crystal formation


oppose crystal formation by thermodynamic and kinetic
mechanisms
Vitamin B6 deficiency may increase oxalate production and
oxaluria

Hyperoxaluria

urinary excretion of oxalate in excess of 45 mg/day.


Primary (Inherited) Hyperoxaluria.
Rare AR , excessive oxalate production and systemic deposition of
calcium oxalate tissue damage e.g. heart, bone, retina, kidneys
Nephrocalcinosis.
Secondary (Enteric) Hyperoxaluria.
- Reduced availability of free calcium to bind intestinal oxalate in malabs.
- The colon absorbs unbound oxalate.
- increased colonic permeability in IBD.
- Contributing factors include a low urinary citrate concentration,
decreased urine volumes, and a low urinary pH, all due to diarrhea and
consequent loss of fluid and bicarbonate in the stool.
NB; Renal stones are primarily composed of calcium oxalate when the ileum is
involved (e.g., ileocolonic Crohns disease), and uric acid when patients
have copious diarrhea or small bowel ostomies.

Retroperitoneal fibrosis

1.
2.
3.
4.
5.

Definition; ureter embedded in dense


fibrous tissue
Causes;
Idiopathic (, 40th-50th)
Trauma, surgery, radiation.
Inflammation; infection, granuloma, autoimmune (sclerosing
cholangitis)
Neoplastic; lymphoma, Cx, bladder.
Drugs; methysergide, bromocriptine, ergotametrine ,MD,
hydralazine, BB.
C/P; insidious onset of dull aching pain.
IVP & U/Smedial indrawing of ureter at junction of middle
& lower part.
CT; periaortic mass.
ESR very high.
TTT; surgical releave of ureter, steroid for idiopathic type.

Acute Renal Failure

Def; Acute renal failure (ARF) is characterized by a rapid decline in glomerular

filtration rate (GFR) over hours to days.


1.
Prerenal (60-70%)
- ESF volume; renal loss e.g,diuretics,
extrarenal e.g. diarrhea, burns
- effective bl volume; COP , VD , oedematous states.
- intrarenal VC; cyclosporin, NSAIDs, ACEI, HRS.
2.
Intrinsic renal (25-40%);
- ATN; ischemic, toxic e.g. G-ve sepsis/ Endogenous as rhabdomyolysis, hemolysis,
cast neph, tumour lysis / exogenous toxins; aminoglycosides, amphotericin,
cisplatinum,cyclosporin.
- tubular obstruction; Endogenous: myeloma proteins, uric acid (tumor lysis syndrome).
Exogenous: acyclovir, gancyclovir, methotrexate, indinavir, ethylene glycol.
- AIN.
- vascular; TMA e.g. DIC, malignant hypertension, preeclampsia.
- glomerular; acute nephritis.
3.
Postrenal ARF (Obstruction)
I. Ureteric (bilateral, or unilateral in the case of one kidney): calculi, blood clots,
sloughed papillae, cancer, external compression (e.g., retroperitoneal fibrosis(
II. Bladder neck: neurogenic bladder, prostatic hypertrophy, calculi, blood clots.
III. Urethra: stricture or congenital valves

Prerenal ARF;
- High BUN/CR ratio>20.
- FENa < 1 %
-UNa <10 mmol/L
- high urine osmolarity > 500 mosm/l.
- SG >1.018.

Renal (Acute tubular necrosis);


- Muddy brown granular or tubular epithelial cell casts
- FENa > 1 %
- UNa > 20 mmol/L
- low urine osmolarity < 500 mosm/l.
- SG <1.015

Diagnosis

cause

serum

urine

ttt

Rhabdomyolysis
(Myoglobinuria)

Physical
Metabolic &
elect.
Drugs.
infections

Increased
U/A positive for
myoglobin,
heme but no
CPK,creatinine, RBCs
P, K, uric acid,
high AG MA,
Ca.
BUN/creat<10

Hemolysis:
recent blood
transfusion,
G6PD, PNH,
cold Ab

Fever,
other evidence
of transfusion
reaction

Pink plasma,
Increased LDH

Pink, hemeAs Myoglob.


positive urine
without
hematuria,
hemosiderinuria

Tumor lysis

recent
chemotherapy

Hyperuricemia,
increased LDH

Urate crystals
urine uric
acid/u creat>1

Fluid therapy
forced alkaline
diuresis with
HCO3,
mannitol in
dextrose

alkalinization
of urine,
allopurinol,
uricase,
fuboxostat

Hepatorenal syndrome

1.
2.
3.
4.
5.

1.
2.
3.
4.

It is a functional impairement in kid functions 2ry to


intrarenal VC in LC with S. creat > 1.5 mg/dl or GFR < 40
ml/min in the absence of any other cause of kid
dysfunction.
Major criteria for diagnosis;
LCF with portal HTN.
S creat > 1.5 mg/dl or GFR < 40 ml/min
No improvement after stopping diuretics & fluid chalenge of
1.5 L.
Absence of shock, infection, nephrotoxins.
Proteinuria <0.5 gm/dl, US normal, no obst or parenchymal
change.
Minor criteria;
S Na < 130 meq/l
Urine Na< 10 meq/l
Urine/P osm>1
Urine volume<1 l.

Contrast nephropathy
Non oliguric ATN acute rise of serum creatinine 24-48 hrs
after administration of IV contrast, peak = 3-5 days, baseline =
7-10 days.
Risk factors; DM, CKD, MM, ACEI, NSAIDS, prerenal failure,
high dose.
Pathophysiology; VC & tubular toxicity.
Prevention;
1. Use of low osmolality, non ionic contrast agent e.g. gadopentate
dimeglumine (ultravest).
2. Least dose.
3. IV infusion of NS 1-2 hrs before to 24 hrs after at a rate of 1
ml/kg/hr.
4. Acetylcysteine 600 mg sachet/12 hr 2 days before.
5. +/- theo 2 ds before, nefidipine 10 mg subluigual before.
6. # mannitol, frusemide, dopamine, ANP.
TTT; fluid chart, electrolytes, HD.
NB; Gadolinium in MRInephrogenic systemic fibrosis.

Chronic Kidney Disease


Classification of Chronic Kidney Disease (CKD)
Stage

GFR, mL/min per 1.73 m2

> 90b

6089

3059

1529

< 15

bWith demonstrated kidney damage (e.g., persistent proteinuria, abnormal urine


sediment, abnormal blood and urine chemistry, abnormal imaging studies).
Cockcroft-Gault equation; GFR e= (140-age) x BW/s. creat x 72 X 0.85 for
women

Clinical and Laboratory Manifestations of CKD and Uremia


Fluid and electrolyte
disturbances
Volume expansion
Na, K,P
Endocrine-metabolic
disturbances
Secondary PTH
Adynamic bone dis.
Vitamin Ddeficient
osteomalacia
Carbohydrate resistance
Hyperuricemia
Hypertriglyceridemia.
Decreased HDL
Protein-energy malnutrition
Impaired growth
Infertility and sexual dysfunction
Amenorrhea

Neuromuscular disturbances
Fatigue, Sleep disorders
Headache, Impaired mentation
Lethargy, Asterixis
Muscular irritability PN,
Myoclonus, Myopathy
Restless legs syndrome
Seizures, Coma
Muscle cramps
Dialysis disequilibrium
Cardiovascular and
pulmonary disturbances
Arterial hypertension CHF
Pericarditis,Hypertrophic or
dilated cardiomyopathy ,
Accelerated atherosclerosis
Hypotension and arrhythmias
Vascular calcification)

Dermatologic disturbances
Pallor, Hyperpigmentation
Pruritus Ecchymoses
Nephrogenic fibrosing
dermopathy ,Uremic frost
Gastrointestinal
disturbances
Anorexia, Nausea and
vomiting, Peptic ulcer
Gastrointestinal bleeding
Idiopathic ascites.
Hematologic and
immunologic disturbances
Anemia
Bleeding diathesis
Increased susceptibility to
infection
Leukopenia
Thromboathenia

Treatment
* Slowing the Progression of CKD
1.
2.
3.
4.
5.
6.

Protein Restriction, between 0.60 and 0.75 g/kg per


day.
Reducing Intraglomerular Hypertension and
Proteinuria; ACE inhibitors and ARBs, target blood
pressure in proteinuric CKD patients=125/75 mmHg.
Slowing Progression of Diabetic Renal Disease;
hemoglobin A1C should be < 7%.
Managing Other Complications of Chronic Kidney
Disease.
Medication Dose Adjustment.
Preparation for Renal Replacement Therapy.

* Renal replacement therapy.

Dialysis in the Treatment of Renal Failure


Hemodialysis

Hemodialysis relies on the principles of solute


diffusion across a semipermeable membrane.
Movement of metabolic waste products takes
place down a concentration gradient from the
circulation into the dialysate.

Complications during Hemodialysis;

1.
2.
3.
4.

Hypotension.
Muscle cramps.
Anaphylactoid reactions to the dialyzer.
Disequilibrium S.

Peritoneal Dialysis
In peritoneal dialysis, 1.53 L of a dextrosecontaining solution is infused into the peritoneal
cavity and allowed to dwell for a set period of
time, usually 24 h.
As with hemodialysis, toxic materials are
removed through a combination of ultrafiltration
and down a concentration gradient.
The major complications of peritoneal dialysis
are peritonitis, catheter-associated infections,
weight gain and other metabolic disturbances,
and residual uremia.

Anemia of CKD

2.
3.
4.

Develops when the GFR < 60 mL/min, symptomatic


only when GFR<30 ml/min due to increase 2,3DPG &
LVH.
normocytic and normochromic.
due to;
reduced renal erythropoietin production (reduction in
functioning renal mass) and,
shortened red cell survival (60-90d vs. 120d).
Hemolysis, bl loss during HD.
Bleeding tendency & Fe deficiency.

Anemia may be a risk factor for progression of CKD.

1.

TTT
1.

1.
2.

1.
2.

Correct Fe deficiency
if ferritin <200 ng/ml & TSAT<20%.
Target ferritin 200-500 ng/ml & TSAT=20- 50%.
For predialysis oral 200mg elemental Fe/d or IV 200mg/1-3
months.
for HDIVI, 100mg for 10 sessions then /wk.
Side effects;
free Fe reaction; N,V,BP, back pain.
Anaphylaxis (Fe dextran due to anti-dextran Ab).
Contraindications;
Active inflammation.
Fe overload.

2) Erythropoietin

1.
2.
3.
4.

When Hb of < 11 g/dL .


Target Hb= 11 to 12 g/dL , NOT above 13 g/dL (adverse CVS effects,
increase risk for hypertension ) .
EPO , , Darbipoitin.
Dose= 80-120 U/Kg/wk SC, dose by 30-50% iv.
SC rather than IV ; stable level, more biologically active but PRCA
with EPO.
dose by 25% when target reached.
Benefit;
regression of left ventricular hypertrophy.
aerobic capacity,
cognitive and
sexual function.
Side effects
Hypertension
Headache
PRCA; due to neutralizing anti-erythropoietin antibodies

Causes of EPO resistance;


1. Iron deficiency (most common )
2. Bone disease due to 2ry hyperparathyroidism.
3. Occult malignancy
4. vitamin B12 and folic acid deficiency.
5. Multiple myeloma/myelofibrosis/myelodysplastic
syndrome.
6. Chronic inflammation.
7. Aluminum toxicity.
8. Hemoglobinopathies.
9. ACEI or ARBs.
10.pure red cell aplasia with neutralizing anti-erythropoietin
antibodies esp. with SC EPO .
11.HIV infection.

Renal Osteodystrophy
A systemic disorder of mineral and bone
metabolism due to CKD manifested by either
one or a combination of the following:
- Abnormalities of calcium, phosphorus, PTH,
or vitamin D metabolism
- Abnormalities in bone turnover,
mineralization, volume, linear growth, or
strength
-Vascular or other soft tissue calcification

Renal Osteodystrophy

A systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following:
- Abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism
- Abnormalities in bone turnover, mineralization, volume, linear growth, or strength
-Vascular or other soft tissue calcification
Pathogenesis;

1.
2.
3.
4.

Classification;
High turnover disease (2 ry PTH > 300 pg/ml or osteitis fibrosa).
low turnover (adynamic) bone disease ( PTH<150 pg/ml ) due to Ca load= overtreated.
Osteomalacia ( defective mineralization) due to Alm. Toxicity, Vit D, metabolic acidosis, P.
Mixed uremic osteodystrophy; 2 ry PTH + Osteomalacia

PO4
Vit D
Ca

Bone
PTH

Normal pulsatile action+ osteoblast


Continuous high
downregulate osteoblast receptors
unopposed osteoclastCa/P efflux


1.
2.

1.
2.
3.
4.
5.
6.

C/P;
Bony aches, reccurent pathological fractures.
Soft tissue calcifications; vascular, valvular, skin.
calcifications in atherosclerotic plaques, arteriosclerosis,
calciphylaxis.
Diagnosis;
Intact PTH= full length PTH (1-84)(active) + PTH
fragment (7-84)( inactive accumulate in RF).
Bone specific ALK P (osteoblastic act).
Bone biopsy.
X rays.
DEXA.
Desferoxamine test for Alm tox.

C
7

PTH

84

TTT

1.

2.

3.

Best= sevelamer + Vit D analogue.


P;
- dietary restriction
- Ca based P binders; Ca carbonate, acetate.
- if Ca AL OH, sevelamer, lanthanum carbonate.
PTH;
- Vit D (calcitriol).
- Vit D analogues (1 , paricalcitol)
- calcimimetics (cinacalcet= CaSR agonist)
- PTH dectomy if;
PTH > 800 + Ca or P despite medical TTT.
calciphylaxis
severe sympt.
Transplantation.

This is a patient with end stage renal disease, with


severe uncontrolled hyperparathyroidism. What is
the skin lesion

Slide no 9

Transplantation

1.
2.
3.
4.

Tissue Typing;
ABO(O) blood groups
human leukocyte antigen (HLA) class I
(A, B, C) or class II (DR) antigens
Punnel of reactive antibodies (PRA)
cross-match of recipient serum with
donor T lymphocytes

Hyperacute

Accelerated
acute

Acute

Chronic

immediate

5 days

5 d-4 m

> 4m

Mechanism Humoral

cellular &
humoral

cellular

cellular &
humoral

Effector

memory T
cells

T cytotoxic

T helper & B
lymphocytes

Interstitial
tissue
mononuclear
& neutrophyl
infiltration &
vasculitis

Interstitial
tissue
mononuclear
infiltration

Chronic
interstitial
nephritis &
fibrosis

onset

preformed Ab

Pathology Intravascular
thrombosis

Immunosuppressive Treatment
1. Induction therapy with Antibodies to Lymphocytes;
Depleting Ab e.g.
- ATGAM, OKT3
- Thymoglobulin is the most common
agent currently in use.
- Alemtuzumab
non- Depleting Ab e.g.
- anti CD25 (IL2 receptors); Basiliximab &
Daclizumab.
- Belatacept (costimulatory pathway blockade)
2. Maintenance Immunosuppressive Drugs

Agent

Mechanisms

Side Effects

Glucocorticoids

Binds heat shock proteins.


Blocks transcription of IL-1,-2,-3,6, TNF and IFN

Hypertension, glucose intolerance,


dyslipidemia, osteoporosis

Cyclosporine CsA

calcineurin --block IL-2


production; however, stimulates
TGF production

Nephrotoxicity, HTN, dyslipidemia,


glucose intolerance, hirsutism/
hyperplasia of gums

Tacrolimus (FK506)

Similar to CsA, but


hirsutism/hyperplasia of gums
unusual, and diabetes more likely

Azathioprine

inhibit purine synthesis

Marrow suppression (WBC > RBC


> platelets)

Mycophenolate
mofetil (MMF)

Inhibits purine synthesis

Diarrhea/cramps; dose-related
liver and marrow suppression is
uncommon

Sirolimus

blocks p70 S6 kinase in the IL-2


receptor pathway for proliferation

Hyperlipidemia, thrombocytopenia

The Most Common Opportunistic Infections in the Renal Transplant Recipient


Peritransplant (<1 month)
Wound infections
Herpes virus
Oral candidiasis
Urinary tract infection
Early (16 months)
Pneumocystis carinii
Cytomegalovirus
Legionella
Listeria
Hepatitis B
Hepatitis C

Late (>6 months)


Aspergillus
Nocardia
BK virus (polyoma)
Herpes zoster
Hepatitis B
Hepatitis C

BK virus
BK virus nephropathy & ureteral stenosis.
Urothelial carcinoma,vasculopathy.
Biopsy; patchy interstitial infiltration, IF; Ab to
simian v. 40.
Urine cytology +ve for decoy cells(tubular cells
appear malignant due to viral inclusions.
PCR.
TTT; reduce IS, leflunamide, cidofovir.

Malignancy
The incidence of tumors in patients on
immunosuppressive therapy is 56%, or approximately
100 times greater than that in the general population of
the same age range.
The most common lesions are cancer of the skin and lips
and carcinoma in situ of the cervix, as well as
lymphomas such as non-Hodgkin's lymphoma.
The risks are increased in proportion to the total
immunosuppressive load administered and time elapsed
since transplantation.
Surveillance for skin and cervical cancers is necessary.

Slide no 2
This skin lesion
appeared 2 months
after a successful
renal transplant
What is the most
likely diagnosis

Rate of relapse & graft loss


Glomerular disease
FSGS
Membranous
Ig A
MPGN
Alport

recurrence
15%
10%
50%
50%

graft loss
50%
50%
15%

anti-GBM

Pregnancy related kidney diseases


ARF in pregnancy;
1st trimester; hyperemesis, septic abortion.
2nd trimester; TTP (any time).
3rd trimester; acute fatty liver, HELLP, post renal dt
enlarged fibroid, stones, Gravid uterus,
Polyhydramnios.
Post partum; HUS, bil cortical necrosis.

TTP

HELLP

Acute fatty
liver

HUS

Cortical
necosis

timing

2nd, 3rd trimester

3rd trimester

3rd trimester
(more common)

postpartum

postpartum
Hge e.g.
abruptio
placentae

C/p

Fever
neuro

-Mild renal
failure
-Proteinuria
-HTN

-ANV abd pain


-Hepatic
encephalopathy
- hypoglycemia
-Jaundice
- DIC
-Severe renal
failure

-Severe
renal failure
- Poor renal
prognosis

Oliguria
Hematuria
Flank pain

Lab

-plat, Hb
-uncong. bilirubin
-shistocytes

-liver enz
-uric acid
-Hypocalcuria
-PT, PTT,
plat

-liver enz
-PT, PTT, plat
-fibrinogen
-congugated bil
- hypoglycemia

ttt

plasmapharesis

termination

termination

Hypo or
hyper echoic
areas in US

Supportive
dialysis

dialysis

Hypertensive disorders in pregnancy;


1.Pre-eclampsia (27%); de novo, after 20th week
gestation, resolve within 3 months + proteinuria.
2.Chronic HTN (23%); before pregnancy, before
20th week gestation, does not resolve post partum
(essential 19% or 2ry 4%)
3.Pre-eclampsia superimposed upon underlying
HTN(7%)
4.Gestational HTN (43%); mild, de novo, after 20th
week gestation, resolve within 3 months without
maternal organ dysfunction.

NB; preeclampsiaafter 20 wks, liver


enzymes, normal Complement.
Lupus activity complement.