NEPHROLOGY
for 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) 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
Incidence
Acute TIN: in 11-14 % of acute renal failure
Chronic TIN: in approximately 15 % of
chronic renal failure
Acut TIN
Etiology
1)
2)
3)
4)
Drug – induced acut TIN
Infections
- bacteria:
Brucella
Leptospira etc.
- viruses:
Hanta virus etc.
- parazites:
Toxoplasma etc.
- others:
Chlamydia etc.
Systemic diseases
- Sjögren’s syndome
- SLE etc.
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 pyuria
arthralgias
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 TIN
Etiology
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:
• 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
of the papilla
renal colic
steril pyuria
HU
(micro/macro)
2. Chronic TIN
•
•
•
hypertension
„early” anaemia (EPO)
slow progression to ESRD
UTI
Clinicopathological picture (cont.)
3. Uroepithelial tumours
▪ micro/macro HU
▪ abnormality with imaging techniques
4. Renovascular atherosclerosis
▪ atheromatous renal artery stenosis/trombosis
Diagnosis
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 !!
Urinary tract infections (UTI)
Classifications, definitions:
1. Localisation of UTI
a) - upper UTI
- acute bacterial
pyelonephritis
(PN)
- chronic bacterial
pyelonephritis
(PN)
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 pathogenesis
1. 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 factors
1.) age and sex
2.) diabetes mellitus
3.) 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 diagnosis
I. Detection of pyuria:
1. Donne probe
2. microscopic examination of centrifuged
urine sediment
from 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
FUNCTIONS OF THE KIDNEY
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
3) Production and secretion of enzymes and hormones
a) renin
catalyzes the formation of AT I
angiotensinogen renin
blood pressure regulation
AT I
ACE
AT II.
b) erythropoietin
stimulates the maturation of erythrocytes in the bone
marrow
c) 1,25 - dihydroxyvitamin D3, the biologically most
active form of vitamin D3
regulation of body Ca and P balance
4) Production of vasoactiv mediators
NO etc.
EXAMINATION OF RENAL FUNCTION

For screening: serum creatinine and CN

For correct glomerular filtration rate (GFR)
measurement:
creatinine clearance (ml/min)
GFR = UV
P
U = urine creatinine
P = plasma creatinine
V = urine volume/min
Urine collection!
GFR may estimate from se creatinine using the
following 2 formula:
1. Cockroft formula:
if se creatinine is in mg/dl:
GFR =
USA
(140 - age in yrs) x weight in kg
men
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
GFR =
se creatinine
”-”
”-”
”-”
x 0.85
men
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
women
125 ± 25 ml/min
95 ± 20 ml/min