1 curs nefrologie-de prezentat-ii- 23 februariei-2016

Universitatea Titu

Maiorescu

Characteristics of Renal Structure and

Function

I. Physiological Anatomy of the Kidney

Renal cortex

Cortical lobules - which form caps over the bases of the pyramids

Renal columns - which dip in between the pyramids

Renal medulla

has 10 conical masses called renal pyramids, their apices form renal papillae

Renal sinus

Space that extends into kidney from hilus

Contains branches of renal artery and renal vein

Renal pelvis divides into 2-3 major calices and these in turn divide into 7-13 minor calices, each minor calyx (cup of flower) ends in an expansion which is indented by 1-3 renal papillae

Major Functions of the Kidneys

1. Regulation of:

-body fluid osmolarity and volume

-electrolyte balance

-acid-base balance

-blood pressure

2. Excretion of

. metabolic products,drugs

.foreign substances (pesticides, chemicals etc.)

.excess substance (water, etc)

3. Secretion of

-erythropoitin

-1,25-dihydroxy vitamin D3 (vitamin D activation)

- renin

-prostaglandin

-Nephron struc

Functions

Glomerulus

Proximal Tubule (PCT)

Loop of Henle

Distal tubule

Collecting tubule

Functions of the Nephron

Filtration

Reabsorption Secretion

Excretion

Glomerular Filtration

Figure 26.10a, b

Proximal Tubule (PCT)

Reabsorption

Bicarbonate

Glucose

Proteins

Aminoacids

K+, Mg, PO4+, uric acid,

Secretion

Organic anions

Organic cations

Ammonia products

Reabsorption of solutes in PCT

Loop of Henle 25-30% ultrafiltrate reaches loop of Henle 15-20% filtered Na+ load

Reabsorbed water reabsorption is passive and follows

concentration and osmotic gradients (except thick ascending loop)

Sodium reabsorption is coupled to both K+ and Cl- reabsorption

Cl- in tubular fluid is rate limiting factor Calcium and magnesium reabsorption Parathyroid hormone calcium reabsorption at this

site Loop diuretics inhibit Na and Cl reabsorption in TAL

compete with Cl- for its binding site on carrier protein

Distal tubule

Very tight junctions between tubular cells

relatively impermeable to water and Na+

5% of filtered Na+ load reabsorbed

Parathyroid hormone and vit D mediated

calcium reabsorption

The late distal segment (collecting segment) Hormone mediated Ca+ reabsorption

Aldosterone mediated Na+ reabsorption

Collecting tubule

5-7% of filtered Na+ load is reabsorbed

Cortical collecting tubule – two types of

cells: Principal cells secrete K+ aldosterone

mediated Na+ reabsorption

Intercalated cells acid base regulation

Nephron symphony

. Renal Pathology

Diseases of the kidney

1-Glomeruli

Glomerulonephritis

Primary

Secondary

Chronic

2-Tubulointerstitium

Acute tubular necrosis

Pyelonephritis

chronic

3-Vessels

Nephrosclerosis

4-Urinary obstruction

– Stones

– Hydronephrosis

5- Cystic diseases of the

kidney

6-Tumors

Benign

Malignan

7-Litiazis

. Glomerular diseases

GLOMERULONEPHRITIS

Acute Glomerulonephritis:

Rapidly Progressive

Glomerulonephritis

Chronic Glomerulonephritis

Nephrotic Syndrome

Asymptomatic urinary

abnormalities

Glomerular disease – Primary Glomerulonephritis

Minimal change GN

Membranous GN

Focal segmental GS

Membranoproliferative GN

Diffuse proliferative GN

Crescentic GN

Secondary Glomerulonephritis

Diabetes most common cause

– most common cause of renal failure

– glycoproteins deposit in basement membrane

Vascular disease

– atherosclerosis

– HTN

Vascultitis

SLE, DM, Amyloidosis, Goodpasture

– Hereditary Albort syndrome

Glomerular diseases:

Primary Glomerulonephritis

. Acute Glomerulonephritis

Acute glomerulonephritis is the inflammation of the glomeruli which causes the kidneys to malfunction

It is also called Acute Nephritis, Glomerulonephritis and Post-Streptococcal Glomerulonephritis

Predominantly affects children from ages 2 to 12

Incubation period is 2 to 3 weeks

Acute Glomerulonephritis

Definition

Headache

Malaise

Anorexia

Nausea and vomiting

High blood pressure

Pallor due to edema and/or anemia

Confusion

Lethargy

Loss of muscle tissue

Enlargement of the liver

General Symptoms

Hematuria: dark brown or smoky urine

Oliguria: urine output is < 400 ml/day

Edema: starts in the eye lids and face

then the lower and upper limbs then

becomes generalized; may be migratory

Hypertension: usually mild to moderate

Hypoproteinemia,

hypercholesterolemia),

Signs and Symptoms

Etiology

Infectious

– Streptococcal

– Nonstreptococcal postinfectious

glomerulonephritis

Bacterial

Parasitic

Noninfectious

– Multisystem systemic diseases

– Primary glomerular diseases

INVESTIGATIONS Base line measurements:

- ↑ Urea - ↑ Creatinine - Urinalysis (MSU): a) Urine microscopy (red cell cast) b) proteinuria

Hypertensive encephalopathy,

Heart failure and acute

Pulmonary edema may occur in severe

Acute renal necrosis due to injury of

capillary or capillary thrombosis

Complications

proper hygiene

prompt medical assessment for necessary antibiotic therapy should be sought when infection is suspected

prophylactic immunizations

Prevention

Treatment

Treat the underlying infections when acute GN is associated with chronic infections.

Antimicrobial therapy – Antibiotics (eg, penicillin) are used to control local symptoms and to prevent

spread of infection to close contacts.

– Antimicrobial therapy does not appear to prevent the development of GN, except if given within the first 36 hours.

Loop diuretic therapy – Loop diuretics may be required in patients who are edematous and

hypertensive in order to remove excess fluid and to correct hypertension.

– Relieves edema and controls volume, thereby helping to control volume-related elevation in BP.

Vasodilator drugs (eg, nitroprusside, nifedipine, hydralazine, diazoxide) may be used if severe hypertension or encephalopathy is present

Diet: – Sodium and fluid restriction

– Protein restriction for azotemic patients

Activity: Recommend bed rest until signs of glomerular inflammation and circulatory congestion subside.

. Chronic glomerulonephritis

Chronic glomerulonephritis

The condition is characterized

1 - irreversible and progressive glomerular and tubulointerstitial fibrosis

2-ultimately leading to a reduction in the glomerular filtration rate (GFR) and

3- retention of uremic toxins

. The diagnosis of CKD can be made without knowledge of the specific cause.

Etiology

Nearly all forms of acute glomerulonephritis have a tendency to progress to chronic glomerulonephritis.

The progression from acute glomerulonephritis to chronic glomerulonephritis is variable.

Whereas complete recovery of renal function is the rule for patients with poststreptococcal

glomerulonephritis, several other glomerulonephritides, such as

immunoglobulin A (IgA) nephropathy, often have a relatively benign course and many do not progress to ESRD.

Pathogenesis

Reduction in nephron mass from the initial injury reduces the GFR.

This reduction leads to hypertrophy and hyperfiltration of the remaining nephrons and to the initiation of intraglomerular hypertension.

These changes occur in order to increase the GFR of the remaining nephrons, thus minimizing the functional consequences of nephron loss.

The changes, however, are ultimately detrimental because they lead to glomerulosclerosis and further nephron loss.

Histologic Findings

In early stages, the glomeruli may still

show some evidence of the primary

disease.

In advanced stages, the glomeruli are

hyalinized and obsolescent.

The tubules are disrupted and atrophic,

and marked interstitial fibrosis and

arterial and arteriolar sclerosis occur.

Histologic Findings

1-Minimal-Change Disease

2-Focal segmental

glomerulosclerosis

3-Mesangiocapillary GN

4-Membranous nephropathy

Mesangial proliferative –MPGN

1-Hypercellularity,

2-Mesangial proliferation,

3-Inflammatory cell infiltrate,

4-Positive IF for IgG and C3 and

5-Subepithelial deposits on EM.

Clinical Manifestations

Uremia-specific findings

Edemas

Hypertension

Jugular venous distension (if severe volume overload is present)

Pulmonary rales (if pulmonary edema is present)

Pericardial friction rub in pericarditis

Tenderness in the epigastric region or blood in the stool (possible indicators for uremic gastritis or enteropathy)

Lab Studies

Urinalysis

Urinary protein excretion

Serum chemistry

– Serum creatinine and urea nitrogen levels are elevated.

– Impaired excretion of potassium, free water, and acid results in hyperkalemia, hyponatremia, and low serum bicarbonate levels, respectively.

– Impaired vitamin D-3 production results in hypocalcemia, hyperphosphatemia, and high levels of parathyroid hormone.

– Low serum albumin levels may be present if uremia interferes with nutrition or if the patient is nephrotic.

Renal ultrasonogram

– Obtain a renal ultrasonogram to determine renal size, to assess for the presence of both kidneys, and to exclude structural lesions that may be responsible for azotemia.

– Small kidneys often indicate an irreversible process.

Kidney biopsy

Imaging Studies

Treatment

The target pressure for patients with proteinuria greater than 1 g/d is less than 125/75 mm Hg; for patients with proteinuria less than 1 g/d, the target pressure is less than 130/80 mm Hg.

– Angiotensin-converting enzyme inhibitors (ACEIs)

– angiotensin II receptor blockers (ARBs)

– Diuretics are often required because of decreased free-water clearance, and high doses may be required to control edema and hypertension when the GFR falls to less than 25 mL/min.

– Beta-blockers, calcium channel blockers, central alpha-2 agonists (eg, clonidine), alpha-1 antagonists, and

– direct vasodilators (eg, minoxidil, nitrates) may be used to achieve the target pressure.

Treatment

Minimal change glomerulonephritis

1-Corticosteroids induce remission in >90% of

children and 80% of adults (slower response).

2-immunosuppression: (cyclophosphamide,

ciclosporin (=cylosporin)): early/ frequent

relapses; steroid SEs/dependence.

Prognosis: 1% progress to ESRF.

Treatment

Focal segmental glomerulosclerosis

Poor response to corticosteroids (10–

30%). Cyclophosphamide or ciclosporin

(=cylosporin) may be used in steroid-resistant

cases.

Prognosis: 30–50% progress to ESRF.

Treatment

Mesangial proliferative GN

1-Antibiotics,

2-Diuretics, and

3-Antihypertensives as necessary.

4-Dialysis is rarely required.

Prognosis: Good.

Treatment

Membranous nephropathy

If renal function deteriorates, consider

corticosteroids and chlorambucil.

Prognosis: Untreated, 15% complete

remission, 9% ESRF at 2–5yrs and 41% at

15yrs.

. Rapidly Progressive Glomerulonephritis

Rapidly Progressive Glomerulonephritis

Rapidly progressive

glomerulonephritis (RPGN) is a

disease of the kidney that results in

a rapid decrease in the glomerular

filtration rate of at least 50% over

a short period, from a few days to 3

months.

The cause of RPGN is unknown. A genetic predisposition may exist for the development of this disease.

Multiple studies have demonstrated that ANCA- (antineutrophil cytoplasmic antibodies) activated neutrophils attack vascular endothelial cells.

ANCA-associated vasculitis.

A viral etiology is possible.

Etiology

Pathology

Renal biopsshow

A diffuse, proliferative, necrotizing glomerulonephritis with crescent formation.

The main pathologic finding is fibrinoid necrosis (>90% of biopsy specimens); extensive crescent formation is present in at least 50% of glomeruli.

Clinical Manifestations

Symptoms and signs of renal

failure,

haematuria,

systemic symptoms (fever, malaise,

myalgia, weight loss).

Lab Studies The most important requirement in the diagnosis of

antineutrophil cytoplasmic antibodies (ANCA) ANCA-associated disease is a high index of suspicion. Rapid diagnosis is essential for organ preservation. Laboratory studies include the following:

– Routine chemistry: The most common abnormality is an increased serum creatinine level.

– Urinalysis with microscopy:

– Antinuclear antibody (ANA) titer:

– ANCA

Urine and serum protein electrophoresis: Perform this in any middle-aged or elderly person presenting with RPGN to exclude the presence of light-chain disease or overt multiple myeloma as a cause of the clinical findings.

Treatment

1-High-dose corticosteroids;

cyclophosphamide ± plasma

exchange/ renal

2-Transplantation.

Prognosis:

Poor if initial serum creatinine

>600µmol/L.

Proteinurea

≥3.5 g/day

(protein: creatinine ratio >3-3.5)

Generalized

Oedema

Hypoalbuminaeia

The Nephrotic Syndrome

Is not a disease but a group of signs and

symptoms seen in patients with heavy

proteinuria

presents with oedema

proteinuria usually > 3.5g / 24hrs (>0.05g

/ kg / 24hrs in children)

serum albumin < 30g/l

other features: hyperlipidaemia, and

hypercoaguable state

The Nephrotic Syndrome

Pathophysiology

proteinuria: due to an increase in glomerular

permeability

hypoalbuminuria: occurs when liver synthesis cannot

keep up with urine losses

oedema mechanism is complex and still in dispute:

primary salt and water retention associated with

reduced renal function as well as reduced plasma

oncotic pressure are primary factors (overfill and

underfill)

minimal change disease fits the underfill theory best

hyperlipidaemia: increased liver synthesis

hypercoagulation: increased fibrinogen and loss of

antithrombin III

DAMAGED Proteinuria

Primary (idiopathic):

Minimal change disease

Most common cause in children

Membranous Nephropathy

Most common cause in Adults

Focal Segmental Glomerulosclerosis

MembranoProliferative

Glomerulonephritis

Secondary to:

•DM (the leading cause of secondary nephrotic syndrome)

•SLE

•Amyloidosis

•Infections: Hepatitis B and C, HIV,syphilis, post-streptococcal

•Malignancy: multiple myloma , Hodgkin lymphoma, solid tumor

•Drugs (NSAIDs, gold, penicillamine ,heavy metals etc).

•Generalized Odema -The predominant feature -The face, particularly the periorbital area, is swollen in the morning& lower extremities and genital area later in the day -In advanced disease: the whole body (anasarca) shortness of breath •Frothy urine and urine dipstick proteinuria value of 3+ •Symptoms & signs for secondary cause if present

•24-hour urine collection >3,5 g/day (nephrotic-range proteinuria)

•Alternative : calculating the total protein-to-creatinine ratio (mg/mg)

on a random urine specimen.

•The history and physical examination Systemic disease

•Serologic studies (ANA), complement, hepatitis B and hepatitis C

serologies and the measurement of cryoglobulins ,serum or urine protein

electrophoresis.

•Renal biopsy required to establish the diagnosis in most of times.

BUN, creatinine, creatinin clearnce.Na,

K,bicarbonates,chloride

CBC , serum albumin, serum proteins, calcium,

Lipid profile, Coagulation tests

Renal biopsy

Disease-

spesific

Complication

symptoms

Oedema •Low salt diet •Diuretics •serial measurement of body weight Proteinuria •ACE inhibitors or ARBs

• Hypoalbuminaemia •High protein diet not indicated •0.8–1 g/kg/day

Ref: Up to date online 17.3.

Hyperlipidaemia •Regular Lipid profile •Statin if severe long lasting nephrotic syndrome •Control other CVD risk factors…target blood pressure 125/75

Thromboembolic risk •Routin Prophylactic anticoagulation not recommend •High index of suspicion for thromboemboli

Infections •High index of suspicion •Antipneumococcal and influenza vaccinations

Ref: Up to date online 17.3.

Management of the nephrotic

syndrome Na+< 60 mmol/24 hrs

water restriction

diuretics (if not volume depleted)

reduced protein diet (controversial)

treat infections

prophylaxis for thrombosis

specific therapy

corticosteroids

Immunosuppression

Diabetic Nephropathy

aggressive glucose control and aggressive BP control

with ACE

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Universitatea Titu

Maiorescu

. Other Renal Diseases

Other Renal Diseases

1. 1-Interstitial Nephritis

2. 2-Diabetic Nephropathy

3. 3-Microscopic Vasculitis and SLE

4. 4-Gout and the Kidney

5. 5-Myeloma Kidney

. 1-Interstitial Nephritis

ACUTE AND CHRONIC

INTERSTITIAL NEPHRITIS

Causes of interstitial nephritis

Infection

Autoimmune

Metabolic

Radiation

Neoplastic infiltration

Mechanical

Morphology of the interstitium

Fibrosis develops after infiltration by

mononuclear cells (lymphocytes) which is

accompanied by deposition of fibronectin,

collagen type I, III, VI and IV.

There is a physiological balance between

ongoing matrix formation and - degradation.

Composed of a loosely organized matrix

consisting of the collagen types I and III,

proteoglycans containing the “interstitial

cells”:

– matrix producing fibroblasts

– macrophages

– dendritic reticulum cells

– endothelial cells

Interferences with the

interstitium: broad

spectrum Infection:

– direct (BK virus, TBC, acute pyelonephritis),

– indirect( βStreptococci)

Immunologic

– Allergic: drug – induced

– Auto-immune: Sjögren syndrome

– Alloimmune: acute cellular allograft rejection

– Unknown: IgG4- associated acute interstitial nephritis

Toxic: Pb poisoning, cadmium poisoning, Balkan endemic nephropathy

Metabolic: oxalosis secondary to malabsorbtion , gout

Obstruction: ureteral- pelvic junction stenosis:

Radiation: radiation interstitial nephritis

Idiopathic: sarcoidosis

Different entities of interstitial disease

Acute interstitial nephritis

Chronic interstitial nephritis

Acute pyelonephritis

Chronic pyelonephritis (reflux related)

Xanthogranulomatous pyelonephritis

Malakoplakie

Myeloma kidney

IgG4 interstitial nephritis

Lead induced interstitial nephritis

Urate nephropathy

TX related Polyoma induced interstitial nephritis

Balkan interstitial nephritis

Most common etiologies are:

– a) those related to the use of medications: 85%

– b) those related to infectious agents: 10%

– c) those associated to systemic disease or

glomerular diseases: 1%

– d) idiopathic disease: 4%

Acute interstitial nephritis:

drugs Etiology: AB (penicillins and cephalosporins, methicillin),

diuretics, NSAID‟s, chinese herbs, lithium

Pathogenesis:

T cell mediated allergic - immune reaction on drug or drug-self protein conjugate (hapten) later followed by accumulation of lymphocytes, plasmocytes and histiocytes

Histology: – Early signs: oedema, lymphocytes focally

– Later: eosinophils, lymphocytes, plasmocytes and histiocytes with granuloma formation(with giant cells) in 30 %, especially after AB

– Tubulitis (distal tubules): with breaks of TBM, necrosis of tubular

cells and atrophy and loss of tubules.

– Tamm Horsfall may find its way to the interstitium (DD obstruction of nephron).

Acute drug induced interstitial

nephritis

Granuloma

Oedema and focal inflammation

Granuloma

nephritis

Normally are the glomeruli not afflicted.

One exception: use of NSAID‟s: can

combine ARF with Nephrotic Syndrome

(effect of cell- mediated lymphokine

directed reaction) inducing Minimal

Lesions (effacement of foot processes of

podocytes)

clinics Acute Renal Failure and

reduced glomerular filtration rate:

- depends on the severity of inflammation

- interstitial oedema causes elevated intratubular pressure

- intratubular obstruction through intra luminal cells

- tubular backleak

- vasoconstriction

- tubuloglomerular feedback

Outcome of drug- induced

interstitial nephritis Recovery?

– Drug withdrawal: 60-

90% in 1 to 12 mths

– Irreversible with

analgesics, NSAIDs,

longterm use

Adverse prognostic

features

– Marked interstitial

inflammation

– Granuloma (50%

irreversible)

– Tubular atrophy

– Fibrosis

Acute interstitial infectious

nephritis Infectious:direct invasion or remote infections

bacteria (ß hemolytic streptococci), parasites (Leishmania) and viruses (EBV, measles)

Pathogenesis: immunological hypersensitivity reaction to the infectious agent, effect of chemokines produced by the kidney in response

Histology: – Early signs: invasion by lymphocytes, eosinophils around the veins

– In casu there is tubular destruction: histiocytes accumulate

– Tubulitis with disappearance of the brush border in proximal tubules

ACUTE INTERSTITIAL INFECTIOUS NEPHRITIS

systemic

Association with: Goodpasture syndrome,

lupus nephritis, mixed cryoglobulinemia,

membranoproliferative glomerulonephritis

Etiology: chronic drug intake (analgesics, lithium), urinary obstruction, chronic reflux,

Pathogenesis: persistence of damageing factor: ischemia, chronic immune reaction

Histology: fibrosis + diffuse infiltration by lympho’s, plasmo’s, histiocytes (with granuloma). Tubular changes (atrophy, compensatory hypertrophy with microcystic changes)

Beware of: – Papillary necrosis, - sclerosis and- calcification: due to sclerosis

of the capillaries under the urothelial epithelium

– Tumor development: papillary tumors, multifocal

Papillary sclerosis

Chronic pyelonephritis

Etiology: reflux

Histology:

- wedge shaped interstitial fibrosis(follows the traject of the papillae and ascending tubules) accompanied by tubular atrophy, vascular atheromatosis, glomerular sclerosis, inflammation

- outside the wedges: normal parenchyma but with secondary changes in the glomeruli: glomerular hypertrophy, FSGS

Tamm Horsfall protein

Tubular disease

Acute tubular damage:

– Ischemia: vasoconstriction with endothelial activation

will determinate the extent of the tubular cell loss:

cellular, geographic, focal

– Toxins:

Myoglobinuria

Heavy metal exposure (Pb, Cd)

Oxalate crystal deposits: ethylene glycol toxicity

Calcineurin inhibitors: megamitochondria, isometric

vacuolisation

Tubular damage

Drugs and interstitial nephritis

methicillin 17%other penicillins <1%cephalosporins <1%rifampicin 1%ciprofloxacin 1%cotrimoxazole

fenoprofen <1%frusemide <1%bumetanide <1%cimetidine <1%allopurinol <1%5 aminosalicylates

omeprazole ? ranitidine (rare)

Bacterial infection

bacterial infection of the renal parenchyma

causes interstitial nephritis

infection without anatomical abnormality

seldom produces permanent damage

obstruction (stones, prostate etc) in

combination with infection can cause

progressive disease

tuberculosis causes extensive destruction from

granulomata, fibrosis and caseation

Autoimmune

systemic lupus

erythematosus

transplant

rejection

deposition of :

– calcium salts

– uric acid

Infiltration in neoplastic and other

diseases

lymphoma and leukaemias

myeloma

– Bence-Jones protein (light chains from

malignant plasma cell clone) causes interstitial

nephritis, tubular obstruction(cast nephropathy)

and amyloid deposition

– called myeloma kidney

sarcoidosis

mechanical causes of interstitial

nephritis

reflux nephropathy

calculi

ureteric fibrosis

prostatic hypertrophy

urethral stenosis

tumours

pathophysiolgical changes in

interstitial nephritis

hypertension (50%)

proteinuria (~1-2 g/24hrs)

reduced urinary concentrating ability

salt wasting

renal tubular acidosis

Diagnosis and Treatment

renal impairment

“inactive” urine sediment common (cf nephritis)

eosinophils in urine and interstitium in acute

hypersensitivity reactions

renal biopsy

improvement after withdrawal of drugs and toxins

use of corticosteroids (prednisone)

water and and electrolyte

treatment of hypertension

. 2-Diabetic nephropathy

Diabetic Nephropathy

Pathological lesions:

– diffuse glomerular sclerosis

– nodular sclerosis (Kimmelstiel -Wilson lesion)

– arteriolar hyalinisation

Associated lesions:

– Papillary necrosis

– Pyelonephritis

– Bladder dysfunction

– Radio contrast renal failure

– hyporeninaemic hypoaldosteronism with

hyperkalaemia

Pathophysiology of Diabetic Nephropathy

renal hypertrophy and hyperfiltration

microalbuminuria (< 100mg/24hrs and negative to

protein test strip-albustix)

hypertension

hyperfiltration and microalbuminuria can be improved

by good diabetic control

microalbuminuria is a predictor of diabetic

nephropathy and mortality in diabetics - it probably

has no predictive value for other renal diseases

. 3- Lupus Nephritis Vasculitis

WHO classification

Lupus Nephritis Type I no pathology

Type II : mesangial

Lupus nephritis

Hematuria and proteinuria

HTN common

Active urine sediment: rbc casts

Decreased C3 and C4

anti-double stranded DNA antibody specific for active nephritis

Prognosis varies greatly based on initial pathology, usually guarded

Type IV greatest risk of progressing to CKD stage 5

Treatment with steroids, cytoxan

Systemic Lupus Erythematosus

Diagnosis:

– clinical presentation - rash, arthralgia, fever,

tiredness, anaemia etc

– hypocomplementaemia - (low C3 and C4)

– antinuclear antibodies and anti DNA antibodies

Treatment:

– depends on histological severity (WHO class I - V)

– nearly all get corticosteroids

– WHO Class IV usually get corticosteroids and

cyclophosphamide

. Gout, Uric Acid and Renal

Disease

Gout, Uric Acid and Renal Disease

uric acid calculi, parenchymal deposits of

uric acid and tubular obstruction with

urate can cause renal damage

an elevated plasma uric acid does not in

itself seem to cause renal damage

1/4 of patients with gout get uric acid

stones

1/4 of patients with uric acid stones will

have gout

Acute and Chronic urate nephropathy

acute nephropathy with overproduction of uric acid

and kidney obstruction with uric acid crystals

can occur with treatment of malignant disease with

cytotoxics, heat stroke and status epilepticus

treat with fluids and prophylaxis with allopurinol

role of uric acid in chronic renal failure disputed but

does occur with some familial disorders

association between hyperuricaemia, hypertension

vascular disease, hyperlipidaemia and diabetes

. Amyloidosis and Myeloma Kidney

Amyloidosis and Myeloma Kidney

amyloid represents a family of proteins which

polymerize to produce the beta pleated sheet of

amyloid and deposit in tissues

AL amyloid (primary amyloid) made from

light chains associated with plasma cell

disorders, mostly overt myeloma

AA amyloid (secondary amyloid) is made from

A protein and is an acute phase reactant

associated with chronic inflammatory diseases

like rheumatoid arthritis and bronchiectasis

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. Acute and chronic

Renal Failure

. Acute Renal Failure

Acute renal failure -ARF

Deterioration of renal function over a period of hours to days, resulting in

• the failure of the kidney to excrete nitrogenous waste products and

• to maintain fluid and electrolyte homeostasis

ARF Rapid deterioration of renal function

– (increase of creatinine of >0.5 mg/dl in <72hrs.)

– “azotemia” (accumulation of nitrogenous wastes)

– elevated BUN and Creatinine levels

– decreased urine output (usually but not always)

Oliguria: <400 ml urine output in 24 hours

Anuria: <100 ml urine output in 24 hours

Hilton, R. BMJ 2006;333:786-790

Causes of acute renal failure

Pre-renal

– Volume depletion Renal losses (diuretics, polyuria)

GI losses (vomiting, diarrhea)

Cutaneous losses (burns, Stevens-Johnson syndrome)

Hemorrhage

Pancreatitis

– Decreased cardiac output Heart failure

Pulmonary embolus

Acute myocardial infarction

Severe valvular heart disease

Abdominal compartment syndrome (tense ascites)

– Glomerular

Anti–glomerular basement membrane (GBM) disease (Goodpasture syndrome)

Anti–neutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-associated GN) (Wegener granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis)

Immune complex GN (lupus, postinfectious, cryoglobulinemia, primary membranoproliferative glomerulonephritis)

– Tubular Ischemi

Totoxic

– Heme pigment (rhabdomyolysis, intravascular hemolysis)

– Crystals (tumor lysis syndrome, seizures, ethylene glycol poisoning, megadose vitamin C, acyclovir, indinavir, methotrexate)

– Drugs (aminoglycosides, lithium, amphotericin B, pentamidine, cisplatin, ifosfamide, radiocontrast agents)

Post-renal

– Ureteric obstruction

Stone disease,

Tumor,

Fibrosis,

Ligation during pelvic surgery

– Bladder neck obstruction

Benign prostatic hypertrophy [BPH]

Cancer of the prostate

Neurogenic bladder

Drugs(Tricyclic antidepressants, ganglion blockers,

Bladder tumor,

Stone disease, hemorrhage/clot)

– Urethral obstruction (strictures, tumor)

Clinical feature-1

Signs and symptoms resulting from loss of

kidney function:

– decreased or no urine output, flank pain,

edema, hypertension, or discolored urine

Asymptomatic

– elevations in the plasma creatinine

– abnormalities on urinalysis

Clinical feature-2

Symptoms and/or signs of renal failure: – weakness and

– easy fatiguability (from anemia),

– anorexia,

– vomiting, mental status changes or

– Seizures

– edema

Systemic symptoms and findings: – fever

– arthralgias,

– pulmonary lesions

Acute Renal Failure

Diagnosis

Blood urea nitrogen and serum creatinine

CBC, peripheral smear, and serology

Urinalysis

Urine electrolytes

U/S kidneys

Serology: ANA,ANCA, Anti DNA, HBV, HCV, Anti

GBM, cryoglobulin, CK, urinary Myoglobulin

Acute Renal Failure

Diagnosis

Urinalysis

– Unremarkable in pre and post renal causes

– Differentiates ATN vs. AIN. vs. AGN

Muddy brown casts in ATN

WBC casts in AIN

RBC casts in AGN

– Hansel stain for Eosinophils

Acute Renal Failure

Diagnosis

Laboratory Evaluation:

– Scr, More reliable marker of GFR

Falsely elevated with Septra, Cimetidine

small change reflects large change in GFR

– BUN, generally follows Scr increase

Elevation may be independent of GFR

– Steroids, GIB, Catabolic state, hypovolemia

– BUN/Cr helpful in classifying cause of ARF

ratio> 20:1 suggests prerenal cause

Treatment of

acute renal failure

Optimization of hemodynamic and

volume status

Avoidance of further renal insults

Optimization of nutrition

If necessary, institution of renal

replacement therapy

The function has to be temporarily replaced by dialysis

Indication for dialysis

Symptoms of uremia (

encephalopathy,…)

Uremic pericarditis

Refractory volume over load

Refractory hyperkalemia

Refractory metabolic acidosis

. Chronic Renal Failure

Definitions

Chronic Renal Failure Results form gradual, progressive loss of renal

function

Occasionally results from rapid progression of acute renal failure

Symptoms occur when 75% of function is lost but considered cohrnic if 90-95% loss of function

Dialysis is necessary D/T accumulation or uremic toxins, which produce changes in major organs

Subjective symptoms Chronic Renal Failure

Subjective symptoms are relatively same as acute

Objective symptoms

– Renal

Hyponaturmia

Dry mouth

Poor skin turgor

Confusion, salt overload, accumulation of K with muscle weakness

Fluid overload and metabolic acidosis

Proteinuria, glycosuria

Urine = RBC’s, WBC’s, and casts

Chronic Renal Failure

Objective symptoms

– Cardiovascular Hypertension

Arrythmias

Pericardial effusion

Peripheral edema

– Neurological Burning, pain, and

itching, parestnesia

Motor nerve dysfunction

Muscle cramping

Shortened memory span

Apathy

Drowsy, confused,

seizures, coma, EEG

changes

Objective symptoms

– GI

Stomatitis

Ulcers

Pancreatitis

Uremic fetor

Vomiting

consitpation

– Respiratory

^ chance of

infection

Pulmonary edema

Pleural friction

rub and effusion

Dyspnea

Kussmaul’s

respirations from

acidosis

Objective symptoms

– Endocrine

Stunted growth in

children

Amenorrhea

Male impotence

^ aldosterone secretion

Impaired glucose levels

R/T impaired CHO

metabolism

Thyroid and parathyroid

abnormalities

– Hemopoietic

Anemia

Decrease in RBC

survival time

Blood loss from dialysis

and GI bleed

Platelet deficits

Bleeding and clotting

disorders – purpura and

hemorrhage from body

orifices , ecchymoses

Objective symptoms

– Skeletal

Muscle and bone pain

Bone demineralization

Pathological fractures

Blood vessel

calcifications in

myocardium, joints,

eyes, and brain

– Skin

Yellow-bronze skin

with pallor

Puritus

Purpura

Uremic frost

Thin, brittle nails

Dry, brittle hair, and

may have color

changes and alopecia

Chronic Renal Failure Lab findings

– BUN – indicator of glomerular filtration rate and is affected by the breakdown of protein. Normal is 10-20mg/dL. When reaches 70 = dialysis

– Serum creatinine – waste product of skeletal muscle breakdown and is a better indicator of kidney function. Normal is 0.5-1.5 mg/dL. When reaches 10 x normal, it is time for dialysis

– Creatinine clearance is best determent of kidney function. Must be a 12-24 hour urine collection. Normal is > 100 ml/min

– K+ -

– Hypocalcemia = tetany

Other abnormal findings

– Metabolic acidosis

– Fluid imbalance

– Insulin resistance

– Anemia

– Immunoligical problems

Chronic Renal Failure Medical treatment

IV glucose and insulin

Na bicarb, Ca, Vit D, phosphate binders

Fluid restriction, diuretics

Iron supplements, blood, erythropoietin

High carbs, low protein

Dialysis - After all other methods have failed

Hemodialysis

– Vascular access

Temporary – subclavian or femoral

Permanent – shunt, in arm

–Care post insertion

– Can be done rapidly

– Takes about 4 hours

– Done 3 x a week

Peritoneal dialysis – Semipermeable

membrane

– Catheter inserted through abdominal wall into peritoneal cavity

– Cost less

– Fewer restrictions

– Can be done at home

– Risk of peritonitis

– 3 phases – inflow, dwell and outflow

Automated peritoneal

dialysis

– Done at home at night

– Maybe 6-7 times /week

– Continous ambulatory

peritoneal dialysis

– Done as outpatient

– Usually 4 X/d

Transplant

– Must find donor

– Waiting period long

– Good survival rate – 1 year 95-97%

– Must take immunosuppressant’s for life

– Rejection

Watch for fever, elevated B/P, and pain over site

of new kidney

Transplant Meds

Patients have decreased resistance to infection

Corticosteroids – anti-inflammarory

– Deltosone

– Medrol

– Solu-Medrol

Cytotoxic – inhibit T and B lymphocytes

– Imuran

– Cytoxan

– Cellcept

T-cell depressors - Cyclosporin

Universitatea Titu

Maiorescu

. RENAL TUMOURS

. CYSTIC DISEASES OF

THE KIDNEY

CYSTIC DISEASES OF

THE KIDNEY

Fluid filled spaces within the kidney

May involve cortex or medulla or both

May be unilateral or bilateral

May be unilocular or multilocular

May be congenital or acquired

May be sporadic or genetically

determined

Clinical significance may be trivial or

CLASSIFICATIONS OF

RENAL CYSTIC DISEASES

Polycystic kidney diseases:

1. Autosomal recessive (ARPKD)

classic infantile polycystic disease

with congenital hepatic fibrosis

2. Autosomal dominant (ADPKD)

Simple renal cysts

Acquired renal cystic disease

RENAL CYSTIC DISEASES

Enlarged but normally shaped pelvi-calyceal

system

Normal reniform shape complete with fetal

lobation & normal sized (undilated) ureter

Normal glomeruli and tubules

Normal interstitium and no dysplasia

Congenital hepatic fibrosis is almost always

present

Normal numbers of nephrons, no interstitial

fibrosis and no dysplasia

RENAL CYSTIC DISEASES Pathological Features

Bilaterally enlarged kidneys (up to 4000 gms)

Diffuse cystic (1-2% cystic nephrons) change with uninvolved intervening parenchyma

Varying sized, numerous to innumerable generally spherical unilocular cysts, distributed in cortex and medulla obscuring normal reniform shape and corticomedullary junction, containing yellowish to turbid to brown to black colored fluid

Distorted pelvi-calyceal system

Cysts arising from any part of nephron or collecting duct

Simple Renal Cysts

Extremely common as age advances

Incompletely understood pathogenesis

Commonly associated with scarred

kidneys

Asymptomatic with normal renal function

May be

solitary/multiple/unilateral/bilateral

Generally unilocular, round to oval of

varying sizes

Adult polycystic kidney disease

Renal cancer

In infants and children :

–Nephroblastoma ( Wilms’

tumour )

In adults :

–Renal cell carcinoma

–Renal cell adenoma

–Renal oncocytoma

NEPHROBLASTOMA ( Wilms’

tumour )

Embryonal tumour arising from nephrogenic

blastemal cells

– can differentiate in to several cell lines - blastemal,

epithelial and stromal

– many replicate developing kidneys

Common in young children / uncommon in

neonates and infants

90% in < 6yrs. old ( mean: 3yrs. in boys and

3.5yrs. in girls )

NEPHROBLASTOMA Clinical Features

Most common genitourinary cancer

Age: 1-3yrs., 98% in <10yrs

Abdominal mass, pain, & hematuria

Usually unicentric, may be multicentric (7%)

or bilateral (5%)

Imaging technique to reveal smaller lesions

No specific tumor markers identified

NEPHROBLASTOMA prognosis and treatment

Depends upon :

– stage, age and histology

Surgery with chemotherapy for :

– stage I & II with favorable histology

– surgery with chemotherapy and

radiotherapy for higher stages and

unfavorable histology

RENAL CELL CARCINOMA

Hypernephroma / Grawitz’s tumour

seems to be arising from mature renal tubules

RENAL CELL CARCINOMA

Clinical Features & Diagnosis

classic triad :

– hematuria, flank pain and abdominal

may be clinically occult, 30% presents

with metastatic lesion

Polycythemia due to erythropoietin

constitutional symptoms

imaging techniques - useful

RENAL CELL

CARCINOMA

prognosis Influenced by multiple factors :

– tumour size

– infiltrative margins

– histological type

– tumour stage - most important

Can be expressed in terms of histological

Renal cell carcinoma

RENAL CELL

ADENOMA Incidental findings at autopsy (22%)

Well demarcated, unencapsulated

Pale yellow-gray, discrete cortical mass

Up to 2 cms. in maximum dimension

Bladder Carcinoma

Derived from transitional epithelium

Present with painless hematuria

Prognosis depends on grade and depth of invasion

Overall 5y survival = 50%

. DIALYSIS

Dialysis

Definition

Artificial process that partially replaces renal

function

Removes waste products from blood by

diffusion (toxin clearance)

Removes excess water by ultrafiltration

(maintenance of fluid balance)

Wastes and water pass into a special liquid –

dialysis fluid or dialysate

Haemodialysis (HD)

Peritoneal Dialysis (PD)

They work on similar principles: Movement

of solute or water across a semipermeable

membrane (dialysis membrane)

Diffusion

Movement of solute

Across semipermeable membrane

From region of high concentration to one of

low concentration

Ultrafiltration

Made possible by osmosis

Movement of water

Across semipermeable membrane

From low osmolality to high osmolality

Osmolality – number of osmotically active

particles in a unit (litre) of solvent

Haemodialysis

Dialysis process occurs outside the body in a machine

The dialysis membrane is an artificial one: Dialyser

The dialyser removes the excess fluid and wastes from the blood and returns the filtered blood to the body

Haemodialysis needs to be performed three times a week

Each session lasts 3-6 hrs

AV Fistula Access

Matures in about 6 weeks

Ensure good working order

– Avoid tight clothing or wrist watch on fistula arm

– Assess fistula daily; notify immediately if not working

– Avoid BP cuff on fistula arm

– Avoid blood sampling on fistula arm (except daily

HD Rx)

– Avoid sleeping on fistula arm

– Grafts (synthetic) may be used to create an AV fistula

AV Fistula

Vascular Access Catheter

Hemodialysis

3-4 times a week

Takes 2-4 hours

Machine filters

blood and

returns it to

Problems with HD Rapid changes in BP

– fainting, vomiting, cramps, chest pain, irritability, fatigue, temporary loss of vision

Fluid overload

– esp in between sessions

Fluid restrictions

– more stringent with HD than PD

Hyperkalaemia

– esp in between sessions

Problems with access – poor quality, blockage etc. Infection (vascular access catheters)

Bleeding

– from the fistula during or after dialysis

Infections

– during sessions; exit site infections; blood-borne viruses e.g. Hepatitis, HIV

Peritoneal Dialysis (PD)

Uses natural membrane (peritoneum) for

dialysis

Access is by PD catheter, a soft plastic tube

Catheter and dialysis fluid may be hidden

under clothing

Suitability

– Excludes patients with prior peritoneal scarring e.g.

peritonitis, laparotomy

– Excludes patients unable to care for self

Peritoneal Dialysis

Principles of Peritoneal Dialysis (PD)

Standard dialysis solution contains: Na+ – 132 mEq/l

Cl- – 96 -102 mEq/l

Ca2+ – 2.5 – 3.5 mEq/l

Mg2+ – 0.5 -1.5 mEq/l

Dialysis solution buffer:

– Sodium lactate

– Pure HCo3-

– HCo3- /Lactate combinations

Lactate is absorbed and converted to HCo3- by

the liver

Dextrose solution strengths: 1.5%, 2.5%, 4.25%

Continuous Ambulatory Peritoneal Dialysis

(CAPD)

Automated peritoneal Dialysis (APD)

– Continuous cyclical

– Intermittent

Continuous Ambulatory Peritoneal Dialysis

(CAPD)

CONTROLLING DIET Foods to control are those containing:

Protein

Potassium

Sodium

Phosphorous

FLUIDS

Healthy kidneys remove fluids as urine

Check for fluid and sodium retention

Need to restrict fluid intake

VITAMINS

Folic acid

Iron supplements

Do not take OTC‟s without consulting the

doctor.

MANAGING DIET

INDICATORS OF GOOD CONTROL:

Weight loss or gain

Blood pressure

Swelling of hands and feet

Blood samples

Plasmapheresis:

plasma exchange and immunoadsorption

An adult donor kidney transplanted to the left iliac

fossa of an adult recipient.

. Kidney Stones

ETIOLOGY HYPEREXCRETION OF RELATIVELY INSOLUBLE URINARY

CONSTITUENTS –

1. Oxalate – Though oxalate is the major component of 70%

of all renal stones, yet hyperoxaluria as a cause of formation of such

stone is relatively rare. Cabbage, rhubarb, spinach, tomatoes, black tea and cocoa

contain large amount of oxalate. Ingestion of excessive amounts of ascorbic acid

and orange juice also increase urinary oxalate excretion.

2. Calcium - On regular diets normal urinary excretion of calcium ranges

between 200 mg to 300 mg per day. The major calcium in foods are in milk and

cheese. Milk and dietary protein also cause increased absorption of calcium from

the gut.

3. Uric acid - Many patients with gout form uric acid calculi particularly when under treatment. If the urine is made alkaline and dilute while treating this disease chance of uric acid stone formation is less

4. Cystine –

Cystinuria is an herditary disease which is more common

in infants and children. Only a small percentage of patients with

Cystinuria form stones.

5. Drug induced stones –

In rare cases, the long term use of magnesium trisilicate in

the treatment of peptic ulcer has produced radio opaque silicon

stones.

LOCATION OF STONES IN KIDNEY

EFFECTS OF STONE The size and position of the stone usually govern the development

of secondary pathologic changes in the urinary trace.

A. SAME KIDNEY –

1. Obstruction 2. Infection B OPPOSITE KIDNEY 1. Compensatory hypertrophy

2. Stone formation may be bilateral

3. Infection

4. Calculus anuria

CLINICAL FEATURES Symptoms - Symptom wise cases can be divided into 4 groups :-

1. Quiescent calculus – A few stones, particularly the phosphate

stones, may lie dormant for quite a long period.

These stone are also discovered due to symptoms of Urinary

Infection

2. Pain - Plain is the leading symptom of renal calculus in majority of

cases (80%). Three types of pain .

a) Fixed renal pain

b) Ureteric colic

c) Referred pain

3. Hydronephrosis

4. Occasionally haematuria is the leading and only symptom.

(iii) Swelling - When there is Hydronephrosis or

pyonephrosis associated with renal calculus, a swelling may be felt

in the flank.

The characteristic of a renal swelling are :-

(a) Oval or reniform in shape

(b) Swelling is almost fixed and cannot be moved.

(c) A kidney lump is ballot able.

3.Radiography

A) STRAIGHT X-RAY - Before taking straight X-ray for KUB region (both

kidneys, ureters and bladder), the bowels must be made empty by giving laxative.

B) Excretory Urogram

4 Ultrasonography –

Helpful to distinguish between opaque and non-opaque stones. It is also of

value in locating the stones for treatment with extra corporeal shock wave therapy.

5 Computed topography –

Particularly helpful in the diagnosis of non-opaque stones.

6 Renal Scan

7 Instrumental examination :- Cystoscopy

8 Examination of the stone

MANAGEMENT OF NEPHROLITHIASIS

ASYMPTOMATIC CALCULI

TREATMENT

Solitary kidney

Occupation (pilot, business traveler

Simultaneous contralateral treatment

It‟s difficult to make an asymptomatic patient feel any better !

STONE MANAGEMENT

OPTIONS

Open surgery

Percutaneous

nephrolithotomy

Ureteroscopy

Shock wave lithotripsy

Medical therapy

STONE MANAGEMENT

OPEN surgery NEPHROLITHOTOMY

SHOCK WAVE LITHOTRIPSY .

SHOCK WAVE LITHOTRIPSY STONE FRAGMENTATION

SHOCK WAVE LITHOTRIPSY

INDICATIONS

Surgical stone

No obstruction

Reasonable chance

of expeditious removal

RELATIVE CONTAINDICATIONS

Large stones Calcium oxalate > 20 mm Struvite > 30 mm

Cystine stones

Distal obstruction

Poorly informed patients

CLINICAL SIDE-EFFECTS

Hematuria

Obstruction

(Steinstrasse)

IDEAL CANDIDATES

Small stone (< 1.5 cm)

Mid or upper pole location

Normal renal anatomy

No distal obstruction

LIMITATIONS

Completeness of stone fragmentation

Completeness of fragment elimination

STONE MANAGEMENT PERCUTANEOUS NEPHROLITHOTOMY

SURGICAL STONE MANAGEMENT

CURRENT ROLE OF PNL

SURGICAL STONE MANAGEMENT STAY OUT OF TROUBLE

Pre-op KUB Pre-op IVP

URETERAL CALCULI

TREATMENT OPTIONS

Observation

Shock wave lithotripsy

Ureteroscopy

Blind basket extraction

Percutaneous approach

Open surgery

. FINAL

ACUTE AND CHRONIC

INTERSTITIAL NEPHRITIS

Fibrosis develops after infiltration by

mononuclear cells (lymphocytes) which is

accompanied by deposition of fibronectin,

collagen type I, III, VI and IV.

There is a physiological balance between

ongoing matrix formation and - degradation.

Composed of a loosely organized matrix

consisting of the collagen types I and III,

proteoglycans containing the “interstitial

cells”:

– matrix producing fibroblasts

– macrophages

– dendritic reticulum cells

– endothelial cells

Importance of interstitial cells

Interstitial fibroblasts:

– Fibrogenesis

– Production of erythropoietine (they lose this function during the process of fibrogenesis)

– Can transform into myofibroblasts (expression of SMA)

– Changes in the interstitial area play an important negative predictive value on the long term follow up of the primary kidney disease. Important and determining factors are interstitial volume (=fibrosis) and inflammation

Interferences with the

interstitium: broad

spectrum Infection:

– direct (BK virus, TBC, acute pyelonephritis),

– indirect( βStreptococci)

Immunologic

– Allergic: drug – induced

– Auto-immune: Sjögren syndrome

– Alloimmune: acute cellular allograft rejection

– Unknown: IgG4- associated acute interstitial nephritis

Toxic: Pb poisoning, cadmium poisoning, Balkan endemic nephropathy

Metabolic: oxalosis secondary to malabsorbtion , gout

Obstruction: ureteral- pelvic junction stenosis:

Radiation: radiation interstitial nephritis

Idiopathic: sarcoidosis

Different entities of interstitial disease

Chronic pyelonephritis (reflux related)

Xanthogranulomatous pyelonephritis

Malakoplakie

Myeloma kidney

IgG4 interstitial nephritis

Lead induced interstitial nephritis

Urate nephropathy

TX related Polyoma induced interstitial nephritis

Balkan interstitial nephritis

Most common etiologies are:

– a) those related to the use of medications: 85%

– b) those related to infectious agents: 10%

– c) those associated to systemic disease or

glomerular diseases: 1%

– d) idiopathic disease: 4%

drugs Etiology: AB (penicillins and cephalosporins, methicillin),

diuretics, NSAID‟s, chinese herbs, lithium

Pathogenesis:

T cell mediated allergic - immune reaction on drug or drug-self protein conjugate (hapten) later followed by accumulation of lymphocytes, plasmocytes and histiocytes

Histology: – Early signs: oedema, lymphocytes focally

– Later: eosinophils, lymphocytes, plasmocytes and histiocytes with granuloma formation(with giant cells) in 30 %, especially after AB

– Tubulitis (distal tubules): with breaks of TBM, necrosis of tubular

cells and atrophy and loss of tubules.

– Tamm Horsfall may find its way to the interstitium (DD obstruction of nephron).

nephritis

Granuloma

Oedema and focal inflammation

Granuloma

nephritis

Normally are the glomeruli not afflicted.

One exception: use of NSAID‟s: can

combine ARF with Nephrotic Syndrome

(effect of cell- mediated lymphokine

directed reaction) inducing Minimal

Lesions (effacement of foot processes of

podocytes)

clinics Acute Renal Failure and

reduced glomerular filtration rate:

- depends on the severity of inflammation

- interstitial oedema causes elevated intratubular pressure

- intratubular obstruction through intra luminal cells

- tubular backleak

- vasoconstriction

- tubuloglomerular feedback

Outcome of drug- induced

interstitial nephritis Recovery?

– Drug withdrawal: 60-

90% in 1 to 12 mths

– Irreversible with

analgesics, NSAIDs,

longterm use

Adverse prognostic

features

– Marked interstitial

inflammation

– Granuloma (50%

irreversible)

– Tubular atrophy

– Fibrosis

Acute interstitial infectious

nephritis Infectious:direct invasion or remote infections

bacteria (ß hemolytic streptococci), parasites (Leishmania) and viruses (EBV, measles)

Pathogenesis: immunological hypersensitivity reaction to the infectious agent, effect of chemokines produced by the kidney in response

Histology: – Early signs: invasion by lymphocytes, eosinophils around the veins

– In casu there is tubular destruction: histiocytes accumulate

– Tubulitis with disappearance of the brush border in proximal tubules

ACUTE INTERSTITIAL INFECTIOUS NEPHRITIS

systemic

Association with: Goodpasture syndrome,

lupus nephritis, mixed cryoglobulinemia,

membranoproliferative glomerulonephritis

Etiology: chronic drug intake (analgesics, lithium), urinary obstruction, chronic reflux,

Pathogenesis: persistence of damageing factor: ischemia, chronic immune reaction

Histology: fibrosis + diffuse infiltration by lympho’s, plasmo’s, histiocytes (with granuloma). Tubular changes (atrophy, compensatory hypertrophy with microcystic changes)

Beware of: – Papillary necrosis, - sclerosis and- calcification: due to sclerosis

of the capillaries under the urothelial epithelium

– Tumor development: papillary tumors, multifocal

Papillary sclerosis

Interstitium in transplants

Calcineurin inhibitors:

– Heart, liver, pancreas, kidney transplants in different doses

– Different levels of interstitial damage

– Most structural nephrotoxic effects in arterioles and glomeruli are manifestations of Thrombotic MicroAngiopathy(TMA) with different patterns of severity. The interstitial fibrosis has an uncertain pathogenesis but is probably vascular.

Toxicity of calcineurin

inhibitors

Cellular rejection in kidney Tx

Histology:

– Very early: eosinophils

– Followed by T lymphocytes

– Later: Plasmocytes IgG+ if IgM+ : be aware of

polyoma infection

– In peritubular capillaries (PTC):

lymphocytes++

Cellular rejection

Tubulitis

Etiology: ascending infection from the pyelon

Pathogenesis: microbial release of degradative

enzymes and toxic molecules, direct contact or

penetration of the host cell by the infectious agent

and the inflammatory response mediated by

antibodies, T cells

Histology:

– Tubules are damaged by neutrophils (Congored)

Etiology: reflux

Histology:

- wedge shaped interstitial fibrosis(follows the traject of the papillae and ascending tubules) accompanied by tubular atrophy, vascular atheromatosis, glomerular sclerosis, inflammation

- outside the wedges: normal parenchyma but with secondary changes in the glomeruli: glomerular hypertrophy, FSGS

Tamm Horsfall protein

Tubular disease

Acute tubular damage:

– Ischemia: vasoconstriction with endothelial activation

will determinate the extent of the tubular cell loss:

cellular, geographic, focal

– Toxins:

Myoglobinuria

Heavy metal exposure (Pb, Cd)

Oxalate crystal deposits: ethylene glycol toxicity

Calcineurin inhibitors: megamitochondria, isometric

vacuolisation

Tubular damage

URETERAL CALCULI

Stone-free is not everything !!

PARAMETERS FOR COMPARISON

URETERAL CALCULI

Effectiveness

Morbidity

Convalescence

PARAMETERS FOR COMPARISON

SWL FOR URETERAL CALCULI

Upper Middle Lower N= 33 N=248 N=381

Success of 94.8% 85.9% 98.2% 1O procedure

Re-tx rate 6.8% 15.7% 1.8%

Complications 10% 15.3% 8.4%

DORNIER HM-3

Lingeman, et al, 1993

DISTAL URETERAL CALCULI

URS is 10 - 18% more effective than SWL (depending on type of SWL unit)

Morbidity / convalescence reduced with SWL

Need for stents 40-60% less with SWL

Cost issues not addressed in monotherapy studies

COMPARISON OF MONOTHERAPY STUDIES

SWL URS

Effectiveness Slightly better

Morbidity Less

Hospitalization Less

Cost Slightly less

OVERVIEW OF HISTORICAL CONTROL STUDIES

80 patients randomized to receive SWL or URS 40 patients had stones > 5 mm 40 patients had stones < 5 mm

SWL performed on Dornier MFL 5000

URS performed with 6.5F or 9.5F semi-rigid ureteroscopes (basket vs. pneumatic lithotripsy)

PROSPECTIVE, RANDOMIZED TRIAL

Peschel & Bartsch, 1999

URS SWL

OR time (min) 19 63

Fluoro time (min) 0.8 5.1

Stone-free (days) 0.2 10.8

Stent (days) 7.2 0

Re-treatment rate 0 15%

PROSPECTIVE, RANDOMIZED TRIAL STONES < 5 MM

Peschel & Bartsch, 1999

SWL OF DISTAL URETERAL CALCULI

Initial animal studies suggest ovarian trauma Impaired fertility Mutagenesis

Subsequent animal investigations demonstrate no impact on fertility or offspring

Mice Rats Rabbits

ADVERSE EFFECTS TO FEMALE REPRODUCTIVE TRACT?

SWL OF DISTAL URETERAL CALCULI

Analyzed Rx data and radiation exposure in 84 women of reproductive age

7 children born to 6 patients with no malformations or chromosomal anomalies

Miscarriages in 3 patients (but occurred at least 1 year after SWL)

ADVERSE EFFECTS TO FEMALE REPRODUCTIVE TRACT?

Viewig & Miller, 1992

URETEROSCOPY

URETERAL CALCULI

FLEXIBLE URETEROSCOPY

ANTEGRADE MANIPULATION OF URETERAL CALCULI

Large stone burden

Body habitus

Urinary diversion

Transplant kidney

INDICATIONS

URETERAL CALCULI

PERCUTANEOUS APPROACH

URETERAL STONE MANAGEMENT

Advantages Minimal anesthesia requirements Non-invasive procedure No stenting/less complications Similar approach for all ureteral calculi

Disadvantages Lower success rate than URS Higher re-treatment rate

IN SITU SWL

URETERAL STONE MANAGEMENT

URETEROSCOPY

Advantages Highest success rate Definitive Rx - No waiting for stone passage

Disadvantages More invasive than SWL Higher complication rate Requires greater technical expertise

URETERAL CALCULI: CURRENT OPTIONS

PROX AND MID URETERAL STONES

Approach Invasive Stent S-F Rate Re-

RxRate

URS +++ 100% 75-90% 10-15%

Push/Smash ++ Rarely 92% 9%

SWL + Stent + 100% 75-80% 20-25%

In situ SWL 0 No 75-80% 20-25%

Defined as complete stone removal with single procedure

URETERAL CALCULI: CURRENT OPTIONS

DISTAL URETERAL STONES

Approach Invasive Stent S-F Rate Re-

RxRate

URS +++ 100% 98-100% 0-2%

Push/Smash ++ Rarely 92% 9%

SWL + Stent + 100% 75-80% 20-25%

In situ SWL 0 No 75-80% 20-25%

Defined as complete stone removal with single procedure

SURGICAL STONE MANAGEMENT

CHANGING TREATMENT PHILOSOPHIES

1980‟s 1990‟s 2000‟s 20

10‟s

Shock wave lithotripsy 95% 85% 75% ???

Endoscopic procedures 5% 15% 25% ???

Open stone surgery < 1% < 1% < 1% 0

NEPHROLITHIASIS

Peak incidence age 30 - 60

Gender (Male : Female) 3 : 1

Family history 3 - fold risk

Body size risk with weight

Recurrence after first stone: Year 1 10 - 15% Year 5 50 - 60% Year 10 70 - 80%

NATURAL HISTORY & RISK FACTORS

RECURRENT STONE FORMATION One Year Two Years

Post SWL Post SWL

Stone Free New stones 8% 10%

Residual Stones Stone growth 22% 21%

Lingeman, et al, 1989

EFFECT ON STONE RISK FACTORS

Urine Values Pre- 3 Mo Post- (mg/day) Lithotripsy Lithotripsy

Calcium 254 261

Uric Acid 552 548

Citrate 249 257

Oxalate 42 41

Brown, et al, 1989

MEDICAL MANAGEMENT OF NEPHROLITHIASIS

PROGRESS Elucidation

Urinary environment conducive to stone formation

Diagnosis Detection of underlying physiologic abnormalities

Medical Therapy Development of new treatment strategies

STONE FORMATION

Concentration / solubility of stone-forming

Promoters of crystallization and aggregation

Inhibitors of crystallization and aggregation

MAJOR FORCES

DIETARY CALCIUM

Early recommendations suggest that low calcium diet will decrease urinary Ca++ excretion, thereby reducing risk of stone formation

Potential risk factors involving low calcium diet:

Reduced bone mass

Increased urinary oxalate

IMPACT OF LOW CALCIUM DIET

DIETARY CALCIUM

Moderate calcium restriction in patients with

Limit dietary intake of oxalate

Spinach, tea, chocolate, nuts

Limit dietary sodium intake

RECOMMENDATIONS

CALCIUM SUPPLEMENTS

Calciuric response to calcium supplementation

Depends on duration of treatment and patient

population

PHYSIOLOGICAL EVIDENCE

CALCIUM SUPPLEMENTS

Give HCTZ during initial three months to prevent hypercalciuria, then discontinue for one month

If urinary calcium up at 4 months, re-start HCTZ

Alternative: Significantly increase fluid intake for first three months and then check 24-hour urinary calcium

RECOMMENDATIONS: PREMENOPAUSAL WOMEN

Henoch Schönlein Purupura

Answer 1.

Renin – Angiotensin II- ACE- ADH – Aldosterone

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Peritoneal Dialysis

Is performed as an intracorporeal (inside the body) therapy making use of the peritoneal membrane.

Is the process of cleaning the blood by using the lining of the peritoneal cavity (peritoneum) as a filter – the peritoneum acts as a dialyzing membrane, permitting wastes from the body to cross it and empty into the instilled dialysate fluid .

Is a type of dialysis usually done by the patient at home.

Hemodialysis

3-4 times a week

Takes 2-4 hours

Machine filters

blood and

returns it to

Peritoneal Dialysis

Abdominal lining filters blood

3 types

– Continuous ambulatory

– Continuous cyclical

– Intermittent

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