nephrology for dentist students 1., 2. lecture. how to evaluate renal diseases? in a case suspicious...

NEPHROLOGYfor dentist students

1., 2. lecture

How to evaluate renal diseases?

In a case suspicious for renal disease the usual steps are:1) to evaluate diagnosis

– clinical– pathological– etiological

2) what is the renal function?– glomerular– tubulointerstitial

3) what kind of therapy may be useful– specific– non specific

4) follow- up of the patients

MAIN TYPE OF RENAL DISEASES

Renal parenchymal diseases:

I. GLOMERULAR DISEASES

II. TUBULOINTERSTITIAL DISEASES

III. VASCULAR DISEASES

The glomerular structure

I. GLOMERULAR DISEASES

difficulties in classification of glomerular nephropathies (NP)

A) Clinical picture:

1) acute nephritic syndrome

2) rapidly progressive glomerulonephritis (GN)

3) nephrotic syndrome

4) asymptomatic urinary abnormalities

(isolated PU and/or HU)

5) macrohaematuria with/without acute renal

insufficiency

6) chronic glomerulonephritis with chronic renal

insufficiency

B) Pathological picture and

pathophysiological approach:

glomerulus is a target that can

be attacked by different

pathogenic mechanisms

1.) immunologic mechanisms

immune complexes

antibodies against renal structures

Immune complexes in the glomerulus

B) Pathological picture and

pathophysiological approach:

glomerulus is a target that can

be attacked by different

pathogenic mechanisms

1.) immunologic mechanisms

immune complexes

antibodies against renal structures

Glomerular basement membrane antibodies

2.) non-immunologic mechanisms

systemic alteration of capillary basement

membranes

(diabetic nephropathy)

glomerular hyperfiltration (hypertension)

chr. intravascular coagulation (nephropathy of

pregnancy)

deposition of immunoglobulin light chains

secreted

inappropriately by plasma cells (amyloidosis,

light chain disease etc.)

C) C) Etiological picture:Etiological picture: "Primary" - unknown etiology

"Secondary" - a likely cause is known

1. Systemic disease: SLE, diabetes etc

2. Infections: bacteria (streptococcus ...) parasites: malaria ... viruses: hepatitis B ...

3. Toxins

gold, penicillamine, heroin ...

4. Neoplasms: carcinoma, lymphoproliferative

disorders ...

5. Familiar and hereditary diseases

Alport syndrome

6. Pregnancy

toxemia of pregnancy with NP

MAIN TYPE OF RENAL DISEASES

Renal parenchymal diseases:

I. GLOMERULAR DISEASES

II. TUBULOINTERSTITIAL DISEASES

III. VASCULAR DISEASES

Tubulointerstitial nephritis (TIN)

Inflammatory disease of the renal interstitium with tubular damage.

Acute - chronic

IncidenceAcute TIN: in 11-14 % of acute renal failure

Chronic TIN: in approximately 15 % of chronic renal failure

Acut TINEtiology1) Drug – induced acut TIN

2) Infections

- bacteria: Brucella

Leptospira etc.

- viruses: Hanta virus etc.

- parazites: Toxoplasma etc.

- others: Chlamydia etc.

3) Systemic diseases

- Sjögren’s syndome

- SLE etc.

4) Idiopathic

Acut drug – induced TIN

Etiology 1. Antibiotics

β-Lactam antibiotics (ampicilline, methicilline etc.)

Sulfonamides Trimethoprim-sulfamethoxazole Ciprofloxacin etc

2. Diuretics 3. Non-steroid antiinflammatory drugs (NSAID) 4. Others

Phenytoin, Cimetidin, Omeprazol Allopurinol etc

Clinical features of acute drug-induced TIN

Sign and Symptoms Laboratory Findings

Urine:fever (85-100 %) haematuria (95 %)maculopapular rash (25-50 %) sterile pyuriaarthralgias low grade

proteinuria

acute renal failure

Serum: eosinophilia (80 %)

decreased GFR

Therapy

- elimination of the drug

- steroid? (useful, but only uncontrolled studies proved it)

- acute dialysis treatment if necessary

Prognosis

complete recovery within 1 yr

rarely: irreversible renal damage

Chronic TINEtiology

1) Drugs

- analgesics

- NSAID etc.

2) Toxins

- heavy metals (lead etc.)

- Balkan nephropathy (ochratoxin A)

- Chinese herbal nephropathy

(aristolochialic acid) etc.

3) Metabolic

- se K+ ↓ se Ca++ ↑

- uric – acid nephropathy etc.

4) Immune – mediated

- SLE, Sjögren’s disease etc.

5) Haematological diseases

- myeloma kidney etc.

Analgesic nephropaty

Characteristic features:

• a chronic TIN with slow progression to end-stage renal failure• one of the few preventable renal diseases!

Etiology• prolonged daily use of 1. phenacetin alone 2. analgesic mixtures containing: phenacetin (or paracetamol?) + phenazone or salicylic acid (aspirin) + caffeine and/or codeine• caffeine and codeine are addicitive subtances (mood-altering effect)

Causes of chronic drug abuse:Causes of chronic drug abuse:• chronic headache• chronic joint pain etc.• every other chronic pain

Pathological alterations

1) Papillary necrosis

2) Chronic TIN

3) Uroepithelial tumours 6 %

4) Renovascular atherosclerosis 4 %

Clinicopathological picture

1. Papillary necrosis

rupture steril pyuria UTI of the papilla

renal colic HU (micro/macro)

2. Chronic TIN• hypertension• „early” anaemia (EPO)• slow progression to ESRD

3. Uroepithelial tumours ▪ micro/macro HU ▪ abnormality with imaging techniques

4. Renovascular atherosclerosis ▪ atheromatous renal artery stenosis/trombosis

Clinicopathological picture (cont.)

DiagnosisDiagnosis

1. Significant history of analgesic abuse

2. Non - sepecific clinical picture renal colic! macro HU! (tumour ?!) „early” anaemia! chronic renal failure (with unknown origin)

3. Imaging techniques US CT

1. Renal volume depletion

2. Bumpy contours

3. Papillary calcification

Therapy

Specific• total avoidance of phenacetin and combined analgesics (single analgesics?) (paracetamol?)• to find the etiology of chronic pain and to treat it

Non-specific non-specific renal protective therapy (treatment of hypertension, anaemia etc.)

Prevention !!

Classifications, definitions:

1. Localisation of UTI a) - upper UTI - acute bacterial pyelonephritis (PN) - chronic bacterial pyelonephritis (PN)

Urinary tract infections Urinary tract infections (UTI)(UTI)

b) - lower UTI - cystitis - urethritis - prostatitis

2. Symptoms of UTI a) symptomatic b) asymptomatic

3. a) complicated UTI - with obstruction, functional or

anatomic abnormalities of urinary tract

(e.g. nephrolithiasis, VUR etc), - with recent urological

instrumentation (catheterization etc.)

b) uncomplicated UTI

Etiology and pathogenesis1. ascending UTI - bacteria migrate from the patients own interstinal flora to the urethra pili of

bact. (e.g. Type I of E. Coli) adhere to the uroepithelial cells of urethra and

bladder colonisation of bacterium urethra bladder ureter kidney

parenchyma prostata

2. haematogen UTI originating from the blood

UTI are most common in females in age group of 15-40 yrs: ♂ : ♀ =

1:8 with increasing age the incidence

in males rises (prostata hypertrophy!)

Risk factors1.) age and sex2.) diabetes mellitus3.) immunosuppressive th. 4.) factors that alter urinary flow a) obstruction to urine flow

● Intraluminal - ureteral stones, blood clot,

necrotic papilla - ureteral or urethral

strictures

● Extraluminal - prostate hypertrophy - retroperitoneal fibrosis - pelvis tumours etc. b) vesicoureteral reflux (VUR) c) residual urine in bladder - neurogenic bladder etc. d) instrumentation of UT - catherization - cystoscopy etc.

Laboratory diagnosisI. Detection of pyuria: 1. Donne probe 2. microscopic examination of centrifuged urine sedimentfrom properly collected and processed

midstream specimens!(presence of squamous epithelial cells and

mixed bacterial flora = suspect for contamination!)II. Detection of bacteriuria: Urine culture Collection of urine specimens for culture

(into a steril container!)

MAIN TYPE OF RENAL DISEASES

Renal parenchymal diseases:

I. GLOMERULAR DISEASES

II. TUBULOINTERSTITIAL DISEASES

III. VASCULAR DISEASES

III. VASCULAR DISEASES renal artery stenosis with/without

thrombosis (chronic) or embolism (acute)

nephrosclerosis acute (malignant)

malignant HTN-caused chronic (benign)

benign HTN-caused systemic vasculitis (ANCA pos/neg)

PAN (polyarteritis nodosa) progressive systemic sclerosis Wegener's granulomatosis etc.

renal vein thrombosis

1) Excretion of metabolic end products and

foreign substances (e.g. urea, creatinin,

toxins, drugs etc.) with the urine

2) Regulation of body fluid volume

osmolality, electrolyte content, fluid content

(concentration – dilutions) and acidity

FUNCTIONS OF THE KIDNEY

3) Production and secretion of enzymes and hormonesa) renin

catalyzes the formation of AT I

angiotensinogen AT I AT II. blood pressure regulation

b) erythropoietinstimulates the maturation of erythrocytes in the bone

marrow

c) 1,25 - dihydroxyvitamin D3, the biologically mostactive form of vitamin D3regulation of body Ca and P balance

4) Production of vasoactiv mediators NO etc.

renin ACE

EXAMINATION OF RENAL FUNCTION

For screening: serum creatinine and CN For correct glomerular filtration rate (GFR)

measurement:

creatinine clearance (ml/min)

GFR = UV U = urine creatinine

P P = plasma creatinine

V = urine volume/min

GFR may estimate from se creatinine using the

following 2 formula:

Urine collection!

1. Cockroft formula:

if se creatinine is in mg/dl: USA

(140 - age in yrs) x weight in kg men GFR = 72 x serum creatinine (in mg/dl)

”-” ”-” ”-” x 0.85 women

if se creatinine is in μmol/l: Europe

1.23 x (140 - age in yrs) x weight in kg men

GFR = se creatinine

”-” ”-” ”-” x 0.85

women

2. MDRD-175 formula with 4 variable

GFR =

175 (serum creatinine/88,4) -1,154

X age (years) -0,203

(men)

175 (serum creatinine/88,4) -1,154

X age (years) -0,203

X 0,742

(women)

Normal range: men 125 ± 25 ml/min

women 95 ± 20 ml/min