Nephrology - Seminar 2
Seminars from internal medicine for the 5th year
Prof. Jiří Horák
NEPHROLOGY (2)
Specific causes of chronic tubulointerstitial disease
Urinary tract obstruction
is the single most important cause of chronic tubulointerstitial nephropathy
Chronic pyelonephritis
The term was formerly used to describe chronic tubulointerstitial nephropathy. It
is now reserved for the radiologic findings that demonstrate deformity of the
pelvis and calyces. Bacteriuria alone is unlikely to result in chronic renal injury.
The lesion of chronic pyelonephritis results from vesicoureteral reflux or urinary
tract infection in association with obstruction. The development of heavy
proteinuria us usually due to focal segmental sclerosis seen in association with
reflux and is a poor prognostic sign.
Analgesic nephropathy
Excessive consumption of certain analgesic agents (such as phenacetin or
acetaminophen, usually in combination with aspirin), may result in chronic
interstitial nephritis. AN occurs more frequently in women who have ingested 
3 kg of antipyretic/analgesic mixtures. Patients frequently do not report taking
analgesics. Anemia is present in most patients. Sloughing of a necrotic papilla
may be associated with ureteral colic and an abrupt decline in renal function.
Patients with AN are at increased risk for development of transitional cell
carcinoma of the urinary tract.
Th: cessation of analgesic use.
Hypertensive (benign) nephrosclerosis
The hallmark is an arteriolopathy that is most pronounced in the interlobular and
afferent arterioles. Interstitial and glomerular changes appear to result from the
subsequent ischemia.
Radiation nephritis
Histol: Tubular necrosis, thickening of the wall of the small renal arteries, gglomerulosclerosis, and interstitial fibrosis.
Presentation: proteinuria, urinary concentrating defects, and benign hypertension
with a reduced GFR, or malignant hypertention with ESRF.
Metabolic abnormalities
Hyperuricemia is associated with renal dysfunction; it may be due to lead
intoxication or hypertension that often accompanies hyperuricemia.
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Nephrology - Seminar 2
Seminars from internal medicine for the 5th year
Prof. Jiří Horák
Hyperoxaluria and cystinosis may result in ESRF from chronic interstitial
nephritis.
Chronic hypercalcemia  nephrocalcinosis and chronic interstitial nephritis with
reduced GFR
Multiple myeloma
Progressive renal insufficiency is senn in the majority of patients.
Lab: laminated tubular casts
Histol: tubular atrophy and interstitial fibrosis
Nephrotic syndrome due to amyloidosis in seen in  10% of patients
Cystic diseases of the kidney
Histol: epithelium-lined cavities filled with fluid
Simple cysts
increase in frequency with age, being present in  50% people over 50 years of
age
Clin: asymptomatic finding
Polycystic kidney disease
 Autosomal recessive polycystic kidney disease (= childhood PKD) – occurs in
association withcongenital hepatic fibrosis  death from renal failure in the
first year of life.
 Autosomal dominant polycystic kidney disease (= adult PKD) is the most
common hereditary disease in the US, affecting 500,000 people. At least 2
different genes; complete penetrance of the gene occurs by 90 years of age.
Clin: usually after 20 years of age. Pain and hematuria are the most common
clinical manifestations. Hypertension occurs in 60% of patients before the
onset of renal insufficiency. Nycturia due to a urinary concentrating defect is
often present at the time of diagnosis. Urinary tract infection is common. Up to
1/3 of patients with PKD have multiple asymptomatic hepatic cysts; about
10% have cerebral aneurysms and  25% have mitral valve prolaps. The
disease progresses to ESRF in  25% of individuals by age 50 and in almost
50% by age 70.
Dg: renal ultrasonography - multiple cysts distributed throughout the renal
parenchyma, renal enlargement, increased cortical thickness, and elongation of
renal calyces. Presymptomatic carriers can be identified through gene linkage
analysis.
Th: aimed at preventing complications and preserving renal function – control
of hypertension, treatment of urinary tract infection.
2/13
Nephrology - Seminar 2
Seminars from internal medicine for the 5th year
Prof. Jiří Horák
A. Radiographic appearance of medullary sponge kidney. Abdominal flat plate
reveals multiple bilateral calcifications.
B. Radiographic contrast material accumulates in the dilated and cystic
terminal collecting ducts and obscures the calcifications.
Urinary tract obstruction
Urinary tract obstruction as a cause of renal failure must be sought in any
patient who presents with renal failure of unknown etiology, esp. in the
absence of proteinuria.
Dg: renal sonography – hydronephrosis
Th: identification of the site and cause of obstruction
relief of obstruction
Elimination of obstruction is at times associated with a postobstructive
diuresis, due partly to a solute diuresis from salt and urea retained during
obstruction and partially to the renal concentrating defect.
Control of urinary tract infection is of paramount concern.
Pathophysiology of bilateral ureteral obstruction
Hemodynamic effects Tubule effects
ACUTE
Renal blood flow
Ureteral and tubule
pressures
GFR
Medullary blood flow Reabsorption of Na+,
Vasodilator
urea, water
prostaglandins
3/13
Clinical features
Pain (capsule distention)
Azotemia
Oliguria
Nephrology - Seminar 2
Seminars from internal medicine for the 5th year
Prof. Jiří Horák
CHRONIC
Renal blood flow
GFR
Vasoconstrictor
prostaglandins
Renin-angio- tensin
production
Medullary osmolarity
Concentrating ability
Structural damage;
parenchymal atrophy
Transport functions for
Na+, K+, H+
RELEASE OF OBSTRUCTION
Slow  in GFR
Tubule pressure
(variable)
Solute load per nephron
(urea, NaCl)
Natriuretic factors present
Azotemia
Hypertension
ADH-insensitive polyuria
Natriuresis
Hyperkalemic,
hyperchloremic acidosis
Postobstructive diuresis
Potential for volume
depletion and electrolyte
imbalance (Na+, K+,
PO42-, Mg2+ excretion)
Common mechanical causes of urinary tract obstruction
Ureter
Bladder outlet
Urethra
CONGENITAL
Ureteropelvic junction
Bladder neck
Posterior urethral
narrowing or obstruction
obstruction
valves
Ureterovesical junction
Ureterocele
Anterior urethral valves
narrowing or obstruction
Stricture
Ureterocele
Meatal stenosis
Retrocaval ureter
Phimosis
ACQUIRED INTRINSIC DEFECTS
Calculi
Benign prostatic
Inflammation
hyperplasia
Trauma
Cancer of prostate
Sloughed papillae
Cancer of bladder
Tumor
Calculi
Blood clots
Diabetic neuropathy
Uric acid crystals
Spinal cord disease
Anticholinergic drugs
and alpha-adrenergic
antagonists
4/13
Stricture
Tumor
Calculi
Trauma
Phimosis
Nephrology - Seminar 2
Seminars from internal medicine for the 5th year
Prof. Jiří Horák
ACQUIRED EXTRINSIC DEFECTS
Pregnant uterus
Carcinoma of cervix,
Retroperitoneal fibrosis
colon
Aortic aneurysm
Trauma
Uterine leiomyomata
Carcinoma of uterus, prostate,
bladder, colon, rectum
Retroperitoneal lymphoma
Accidental surgical ligation
5/13
Trauma
Nephrology - Seminar 2
Seminars from internal medicine for the 5th year
Prof. Jiří Horák
6/13
Nephrology - Seminar 2
Seminars from internal medicine for the 5th year
Prof. Jiří Horák
Nephrolithiasis
Major causes of renal stones
Stone type
% of all
and causes
stonesa
Calcium stones
Idiopathic hypercalciuria
75-85
% occurrence Ratio of Etiology
of specific
men to
a
women
causes
2:1 to 3:1
50-55
2:1
Hereditary (?)
Hyperuricosuria
20
4:1
Diet
Primary
hyperparathyroidism
Distal renal tubular acidosis
5
3:10
Neoplasia
Rare
1:1
Hereditary
Intestinal hyperoxaluria
~1-2
1:1
Bowel surgery
Hereditary hyperoxaluria
Rare
1:1
Hereditary
Idiopathic stone disease
20
2:1
Unknown
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Diagnosis
Treatment
Normocalcemia,
unexplained
hypercalciuriab
Urine uric acid >750
mg per 24 h (women),
>800 mg per 24 h (men)
Unexplained
hypercalcemia
Hyperchloremic
acidosis, minimum
urine pH >5.5
Urine oxalate >50 mg
per 24 h
Urine oxalate and
glycolic or
L-glyceric acid
increased
None of the above
present
Thiazide diuretic agents
Allopurinol or diet
Surgery
Alkali replacement
Cholestyramine or oral
calcium loading
Fluids and pyridoxine
Oral phosphate, fluids
Stone type
and causes
Ratio of
men to
women
Etiology
Nephrology - Seminar 2
Seminars from internal medicine for the 5th year
Prof. Jiří Horák
Diagnosis
Treatment
Hereditary
Clinical diagnosis
Alkali to raise urine pH
Hereditary (?)
Uric acid stones, no
gout
Allopurinol if daily
urine uric acid above
1000 mg
Alkali, fluids, reversal
of cause
Uric acid stones
Gout
% of
% occurrence
all
of specific
stones causesa
a
5-8
~50
Idiopathic
~50
3:1 to
4:1
1:1
Dehydration
?
1:1
Intestinal, habit
History, intestinal fluid
loss
Lesch-Nyhan syndrome
Rare
Men
Hereditary
Reduced hypoxanthine- Allopurinol
guanine
phosphoribosyltransferase level
Malignant tumors
Rare
1:1
Neoplasia
Clinical diagnosis
Allopurinol
1:1
Hereditary
Stone type; elevated
cystine excretion
Massive fluids, alkali,
D-penicillamine if
needed
Cystine stones
1
102:10
Infection
Stone type
Antimicrobial agents
15
and judicious surgery
a Values are percent of patients who form a particular type of stone and who display each specific cause of stones.
b Urine calcium above 300 mg per 24 h (men), 250 mg per 24 h (women), or 4 mg/kg per 24 h either sex. Hyperthyroidism, Cushing syndrome,
sarcoidosis, malignant tumors, immobilization, vitamin D intoxication, rapidly progressive bone disease, and Paget's disease all cause
hypercalciuria and must be excluded in diagnosis of idiopathic hypercalciuria.
Struvite stones
8/13
Nephrology - Seminar 2
Seminars from internal medicine for the 5th year
Prof. Jiří Horák
Calcium stones can be either calcium oxalate or calcium phosphate. Only a
minority of patients with calcium stones have identifiable systemic disease
such as hyperparathyroidism, sarcoidosis, hypervitaminosis D, RTA, or GIT
disease responsible for hyperoxaluria.  50% of patients have hypercalciuria
in the absence of any of these conditions with normal serum calcium nad
PTH. 90% of patients with hypercalciurua are idiopathic.
Hyperuricosuria is a risk factor because urate crystals increase the
precitability of calcium oxalate and calcium phosphate.
Th: identify and treat the metabolic disorder; fluids; surgery in loss of renal
function or hydronephrosis
Renal tumors
Benign tumors: cortical adenomas and angiomyolipomas (hamartomas).
Renal cell carcinoma (hypernephroma) is thought to be of proximal tubular
origin. It is the most frequent malignant renal neoplasm in adults and
accounts for ~ 2% of cancer deaths in both sexes.
Clin: The triad of hematuria, flank pain, and palpable flank mass is seen in
only ~ 10% of patients.
Paraneoplastic features: erythrocytosis, leukemoid reaction, varicocele,
hepatopathy, hypercalcemia, Cushing syndrome, galactorrhea.
Extension of the tumor into the renal vein and even into the vena cava is
common.
Metastatic spread: lungs, bone liver.
Calcification within a renal mass, the result of internal necrosis, is a
significant radiographic indicator of malignancy.
Th: radical nephrectomy; a small, localized tumor may be removed by
heminephrectomy. The tumors respond poorly to radiation and
chemotherapy. 10-year-survival ranges from 10 to 50%.
9/13
Nephrology - Seminar 2
Seminars from internal medicine for the 5th year
Prof. Jiří Horák
Diagnostic evaluation of a renal mass
10/13
Nephrology - Seminar 2
Seminars from internal medicine for the 5th year
Prof. Jiří Horák
Renal tubule defects
Renal morphologic
Disease
abnormalities
Adult polycystic disease Cortical and medullary
cysts
Infantile polycystic
Distal tubule and
disease
collecting duct cysts
Childhood polycystic
Medullary ductal ectasia
disease
Medullary sponge
Ectatic ducts of Bellini
kidneys
Medullary cystic
Distal tubule and
disease, recessive
collecting duct cysts
Medullary cystic
Same
disease, dominant
Bartter's syndrome
Hyperplasia of
juxtaglomerular and
medullary interstitial
cells
Liddle's syndrome
None
Familial nephrogenic
diabetes insipidus
Renal tubular acidosis,
type 1
Renal tubular acidosis,
type 2
Renal tubular acidosis,
type 4
Functional
abnormalities
Chronic renal failure
Mode of
Inheritancea
AD
Associated
abnormalities
Hepatic cysts, intracranial aneurysms
Renal failure in the newborn AR
Intrahepatic bile duct abnormalities
Variable chronic renal
failure
Nephrocalcinosis
AR
Hepatic fibrosis and portal hypertension
AD+S
None
Chronic renal failure, <20 yr AR
salt wasting, polyuria
Chronic renal failure, >20 yr AD
salt wasting, polyuria
Hypokalemia, high renin and AR
aldosterone levels, polyuria
Hypokalemia, low
aldosterone levels
None
Vasopressin-resistant renal
concentrating defect
Papillary nephroInability to lower urine pH
calcinosis
normally, reduced acid
excretion
None
Reduced bicarbonate
reabsorption
Underlying renal disease Reduced proton and
potassium secretion
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Variable retinal degeneration (renal retinal
dysplasia)
None
None
AR
None
XL
None
AD
Periodic paralysis, hypokalemia, nonanion-gap metabolic acidosis, growth
retardation, rickets
Non-anion-gap metabolic acidosis, growth
retardation rickets, Fanconi syndrome
Azotemia
AR
AD, XL
ACQ
X-linked
hypophosphatemia
None
Vitamin D-dependent
None
rickets, type 1
Vitamin D-dependent
None
rickets, type 2
Oncogenic osteomalacia None
Renal glucosuria
None
Isolated hypouricemia
None
Cystinuria
Cystine stones
Hartnup disease
None
Iminoglycinuria
None
Adult Fanconi
syndrome
Swan neck deformity of
the proximal tubule
Reduced phosphate
reabsorption,
hypophosphatemia
Defective renal
1,25(OH)2D production
Defective cell,
1,25(OH)2D receptors
Reduced phosphate
reabsorptions,
hypophosphatemia
Reduced glucose
reabsorption
Reduced urate reabsorption
XL
Reduced reabsorption of
dibasic amino acids
Reduced reabsorption of
mono-amino and carboxylic
amino acids
Reduced reabsorption of
proline, hydroxyproline, and
glycine
Reduced proximal tubule
reabsorption of bicarbonate,
glucose, uric acid,
phosphate, and amino acids
Same
Nephrology - Seminar 2
Seminars from internal medicine for the 5th year
Prof. Jiří Horák
Rickets, osteomalacia, normal serum
1,25(OH)2D
AR
AR
ACQ
AD
None
AR
AR
Variable hypercalciuria, bone
demineralization
Short stature
AR
Pellagra-like rash, ataxia, delirium
AR
None
AR
Rickets, osteomalacia, acidosis, dwarfism,
low serum potassium
Lowe's syndrome
Same
XL
(oculocerebrorenal
syndrome)
a AR, autosomal recessive; AD, autosomal dominant; XL, X-linked; ACQ, acquired; S, sporadic.
12/13
Rickets, osteomalacia, low serum
1,25(OH)2D
Rickets, osteomalacia,
high serum 1,25(OH)2D, variable alopecia
Osteomalacia; mesenchymal tumors;
cancer of the prostate or lung
Ocular and cerebral malformations
Nephrology - Seminar 2
Seminars from internal medicine for the 5th year
Prof. Jiří Horák
Vascular disorders of the kidney
Renal arterial occlusion
Partial obstruction by atheromatous plaque or fibromuscular dysplasia →
renovascular hypertension.
Complete occlusion: thrombosis, embolism.
Dg: nuclear renography, renal arteriography
Th: surgical embolectomy, bypass grafting, thrombolytic agents, transluminal
angioplasty.
Clinical presentations of ischemic renal disease
1
Acute renal failure
2
Progressive azotemia in a patient with known renovascular hypertension
(usually on medical therapy)
3
Unexplained progressive azotemia in an elderly patient with or without
refractory hypertension
4
Hypertension and azotemia in a renal transplant patient
Renal vein occlusion
is a thrombotic event. The incidence in nephrotic glomerulopathies, esp.
membranous nephropathy, is up to 30%.
Clin: the venous occlusion is usually asymptomatic. The thrombus can
embolize.
Dg: renal ultrasonography; renal venography.
Th: anticoagulation is indicated in patients with pulmonary embolism.
Fibrinolytic therapy may be considered.
Conditions associated with renal vein thrombosis
1
Trauma
2
Extrinsic compression (lymph nodes, aortic aneurysm, tumor)
3
Invasion by renal cell carcinoma
4
Dehydration (infants)
5
Nephrotic syndrome
6
Pregnancy or oral contraceptives
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