Nephrolithiasis Flashcards
dietary factors that lead to nephrolithiasis
low fluid intake, calcium, K
high oxalate, protein, Na, sugar drinks
hipercalciuria= droga =tiazidicos-diminuir proteina, sodio, acucar e ingesta de calcio adequada
hiperoxaluira-diminuir a ingestao de oxalato, aumentar a ingesta de calcio,evitar vitamina c- piridoxina
hiperuricosuria= evitar purinas= inibidor da xantila oxilase
hipocitraturia= citrato de k, diminuir a ingesta de proteina, aumentar ingesta de frutas e vegetais
Inhibitors of stone formation
magnesium
, citrate
, pyrophosphate→retards the crystal growth of CaP and CaOx crystals by binding to the surface of basic CaP crystals
THprotein
acts as both promoter and inhibitor of stone formation THProtein
THProtein
Tamm-Horsfall protein and uromodulin are two names for the same gene.
Casts only form in the distal tubule & collecting duct, not in the proximal tubule. What is its function?
- Tamm-Horsfall protein acts as a constitutive inhibitor of calcium-based stone formation. Mice deficient for Tamm-Horsfall protein show an increased tendency towards nephrolithiasis.
- Tamm-Horsfall protein acts to prevent urinary tract infection. There is some data that certain strains of E. coli may be bound by Tamm-Horsfall protein; once cleaved this could represent a means of eliminating the organism from the urinary tract.
- Mutations in Tamm-Horsfall protein cause the autosomal dominant disorder medullary cystic kidney disease type 2 (MCDK2) as well as the disorder familial juvenile hyperuricemic nephropathy (FJHN) . This is a pediatric-onset disease characterized by hyperuricemia, gout, and progressive renal failure. Interestingly it appears that the pathophysiologic mechanism here is that mutations in this gene lead to defects in protein folding and intracellular deposition of mutant Tamm-Horsfall protein.
metabolic processes that induce ca stone formation
Increase urine ca >250-300 mg/day;
Urine Uric acid > 800 mg/day
, urine oxalate > 45 mg/d
, hipocitraturia < 320 mg/day;
alterations in urine ph
most common metabolic abnormality in ca stone formation
absorptive hypercalciuria
most common cause of resoprtive hypercalciuria primary hyperparathyroidism
uso de tiazidicos se hipercalciuria >200
clinical conditions with hypocitraturia
overproduction acidosis,
underexcretion acidosis
K deficiency
excess dietary protein
inflammatory bowel disease, jejunoileal bypass, bariatric surgery for morbid obesity
enteric hyperoxaluria
predispose to caphos lithiasis
alkaline urine (pH > 6.7)
most impt in uric acid stones
low urine pH
Uric Acid crystals
Precipitate in acid urine • Pleomorphic,rhombic plates or rosettes. • Seen under polarised light • Hyperuricemia • Diabetes mellitus • Metabolic syndrome • Acute uric acid nephropathy • Chronic uratenephropathy • Familial Juvenile Hyperuricemic Nephropathy (Medullary Cystic Kidney disease
Alkalinization of urine—urine pH is most important risk factor for uric acid stones – Potassium citrate or bicarbonate – Patient follow urine pH (aim for ~6.5 or higher
patients with gouty arthritis and kidney stones, UA > 10 md/d, urine ua > 1000 mg/day
hyperuricosuria
Increases saturation of all stone forming elements
low urine volume
Pathophysio of uric acid stones
Low urine pH, volume
Hyperuricosuria
genetic disease caused by inactivating mutations of the subunits of a dibasic aminoacid transporter in then proximal tubule
cystinuria
family hx of cystinuria (> 400 mg/day vs 30 mg), staghorn calculi, hexagonal crystals on urinalysis
most prevalent component of kidney stones
calcium oxalate
most likely cause of nephrolithiasis in a patient with distal RTA
hypocitraturia
depressions near the papillary tips, yellow crystalline deposits in the ducts of bellini, some randall plaques
Calcium phosphate
1st kidney stone work up
medical hx, stone analysis, urine analysis
Recurrent kidney stone
full metabolic evaluation - serum panel, PTH, VitD if hyperCa, 24ag urine >= 2 samples Na Ca Oxalate Uric acid citrate
calcio, citrato, oxalato, sodio, creatinina,acido urico
Complete Metabolic Evaluation for Nephrolithiasis
Blood
Serum calcium (if elevated, suggests primary hyperparathyroidism or other cause of hypercalcemia)Serum electrolytes (low total CO
2
raises the possibility of distal RTA)
Urine
Urinalysis—urine pH >7 with phosphate crystals in the urine sediment suggests calcium phosphate or struvite stones (struvite stones have a typical coffin-lid appearance); hexagonal cystine crystals arediagnostic of cystinuria; other crystals (calcium, uric acid, indinavir, etc.) may suggest etiology of stones24-hour urine collection(s) for urine stone risk diagnostic profile. This test is now standardized in mostclinical laboratories, with most using a reference laboratory that provides a graphical display of results(seeFig. 20
indicative of minimal fluid intake
urine volume less than 2.5L
pH with increase risk of uric acid precipitation, idiopathic uric acid stone, intestinal disease and diarrhea and intestinal bypass surgery
less than 5.5
Increase risk of caphos precipitation, dRTa, primary hyperparathyroidism, alkali, ca tx
pH > 6.7
pH that indicates urinary tract infection fom urease producing bacteria
> 7-7.5
Normal UCrea
F: 15-20 mk
M: 20-25 mk
reflects dietary Na and K intake
24H urine Na and K
O valor obtido em mEq/24h deve ser dividido por por 17 (Já que 1 g de NaCl corresponde a 17 mEq de sódio, dividimos o resultado por 17 para obter a quantidade em gramas de NaCl consumido no dia).
3- O KDIGO (Kidney Disease Improving Global Outcomes) de Hipertensão e Doença renal crônica, recomenda a ingestão < 2g de Sódio ou 5 gramas de NaCl por dia.
Major cause of hypercalciuria
High Na intake
Normal Urine Na K Ca
Na 100 K 40-60 Ca < 250-300 mg
Low Mg increases risk of
calcium stones
(UMg <30-120 mg)
Higher Uphos > 1100 mg
calcium phosphate formation
hyperuricosuria, Uuric acid > 600-800
CaOx stones Uph > 5.5
Uric acid stones UpH <5.5
marker of dietary acid intake
sulfate
high ammonium/sulfate ratio
GI alkali loss
Normal Urine NH4
30-40 meq
Petsistent high Uca on a restricted diet
intestinal hyperabsorption of Ca
Elevated fasting Ca/Crea (0.11 mg/100 ml or <2.7 umil/100 mg), high serum calcium, elevated pth
primary hyperparathyroidism
Elevated Ca/Crea, normal serum Ca, normal or suppressed PTH
resoprtive hypercalciuria
elevated Ca/Cr, normal Ca, elevated pth
Renal hypercalciuria
Elevated Ca/Cr (0.2 mg/mg or 0.56 mmol/mmol) 4h Ca/Crea after 1 g oral load
absorptive hypercalciuria
dumbless shaped crystals
calcium oxalate monohydrate
Envelope shaped crystals
calcium oxalate dihydrate
Flat shaped or wedge shaped prisms, often in rosettes
Calcium phosphate
Gold standard for kidney stone diagnosis
noncontrast ct
un enhanced ct scan
ct stonogram
time when surgical intervention is indicated
4 weeks
average days of stone passage
40 days
medical expulsive therapy
tansulosina, doxasozina
indicacoes-> calculo maior que 0,5 e menor q 1,0 em ureter distal
sem infeccao, sem insuf renal, sem dor
calculo menor q 1cm
expulsoiu? nova imagem 1 mes apos
target fluid intake
Urine volume > 2.5L
cystinuria > 4L water intake
Dietary mgt
Na < 100 meq/day
animal protein 50-60 g/day
Ca 1000-1200 mg
avoid > 1g Vit C
Fruits/vegetables
Drug of choice hypercalciuria in caOx and Caphos stone formers
Thiazides 25 bid
Tx hypocitraturia in caox and caphos, uric acid stones, cystine stones
20-80 meqs 3-4 doses
uric acid: pH goal > 6, cysteine pH > 7,
inhibits caox crystal formation and growth binding with oxalate
Magnesium
Treatment Ca stone formers with hyperuricosuria
Allopurinol 100-300 mg/d
Struvite stones when other interventions have failed
acetohydroxamic acid 15 mkd
first line therapy for uric acid stone formers
Urine alkalinization
tx of choice struvite stones, impacted stone; largest stone free rate and less recurrenfe rate
percutaneous nephrolithotomy
hexagonal stones- tx
Cystine, tiopronin
penicillamine
thiola captopril
treatment • Reduce [cystine] < 250mg/L • Increase fluid intake? – Urine output > 5 L/d • Tiopronin (“Thiola”) – Typically need at least 900 mg/d (300 mg TID) •
Continue alkalinization= bic ou citrato de k= alvo ph 7,7 7,5
RESTRICAO DE SODIO E PROTEINA ANIMAL
coffin lid like
struvite
uric acid stones are
pleomorphic
nao da pra ver na radiografia
calculo de estruvita
são chamados de “cálculos de infecção” e são compostos por uma mistura de magnésio, amônia, fosfato e carbonato de cálcio. Alguns tipos de bactérias formam amônia, elevam o pH, deixando a urina mais alcalina e promovendo a formação de estruvita.
bacterias produtoras de urease= proteus, klebsiella,
cirurgia
hiperoxaluria primaria
autosomal recessive condition in childhood with CaOx stones and nephrocalcinosis, frequent stone recurrence
disturbio do metabolismo hepatico do oxalato
demais funcoes hepatocelulares=normais
achados= osseos, coracao, tecidos e sangue
nefrolitiase, nefropatia por oxalato de calcio (nefrocalcinose) e drc
o q agrava= hipovolemia, inibidor do sraa, uso de diuretico, aumento da ingesta de OXALATO, use de antiinflamatorios alguns antibioticos
tipo1 = tx de figado e rim
tipo2 =tx renal
tipo3 =nao requer tto
autosomal recessive condition in childhood with CaOx stones and nephrocalcinosis, frequent stone recurrence
UOxalate > 100 mg/day
primary hyperoxaluria
hiperoxaluria secundaria
aumento da abs intestinal de oxalato= nao absorve a gorduta , normal o oxalato se liga ao calcio e sai pelas fezes, quando tem muita gordura = se liga ao calcio e deixa o oxalato livre para ser absorvido
cirurgia bariatrica
y de roux
by pass jejunoileal
doença inflamtoria intestinal
aumento da ingestao de oxalato
excesso de vitamina c
fibrose cistica /insuf pancreatica/
hiperoxaluria
>0,5 enterica= calcio 1 a 2g , depende da excrecao de oxalato + agnesio 200-400mg/dia
>1,0mmol /dia = primaria= piridoxima 5-20mg/kg/dia
novas drogas oxalobacter
lumasiram /nedosiram
individuals likely to form oxalate stones due to hyperoxaluria have a relative deficiency of the gut bacterium Oxalobacter formigenes, part of the normal GI flora which naturally digest oxalate.
hiperoxaluria
aumentar ingesta hidrica= >2-3L/dia
dieta com pouco oxalato
dieta pobre em gorduras
calcio normal , suplemento decalcio
colestiramina= absorve sair biliares e o oxalato
oxalobacter formigens
calculos de indinavir
nao da pra ver no exame de imagem
composicao dos calculos frequencia
Calcium oxalate 60
Calcium oxalate and phosphate 10
Calcium phosphate 10
Magnessium, ammonium phosphate(struvite)5-10
Uric acid5-10
Cystine1Others1
Crystalline composition of renal calculi & their frequency
análise fisica do calculo
difracao do rx
espectrocopia de infravermelho
microscopia eletronica
Urease producing bacteria are associated with the formation of?
Magnesium ammonium phosphate stone (Struvite).
.Struvite (magnesium ammonium phosphate) stones are typically largestones associated with urease producing bacteria and an alkaline urine4
. Ureabreakdown produces excess ammonium and hydroxyl ions, a rise in urinary pH,and a decrease in phosphate solubility thus encouraging the precipitation of insoluble magnesium ammonium phosphate
Common bacteria producing urease
Proteus
Haemophilus
Pseudomonas
Klebsiella
Yersinia
Staphylococcus epidermidis
Citrobacter, Serratia and UreaplasmaurealyciumNote: E.coli does not produce urease
oxalato de calcio
Calcium oxalate dihydrate – enveloped shaped crystals
Calcium oxalate monohydrate – dumbbell, spindle shaped crystals
The mainstain of treatment of calcium oxalate stones is to increase fluid intake to reach the goal of at least 2 L of urine output per day.
A reduction in calcium excretion by a low sodium diet (80-100 meg/day) may also be suggested.
Low sodium excretion will enhance proximal sodium and calcium absorption, thereby decreasing urinary calcium excretion and stone formation.
Drug therapy can also be added depending on the cause. If there is hypercalciuria, thiazide diuretics may be helpful.
Potassium citrate can be used in cases of hypocitraturia and type 1 renal tubular acidosis.
For hyperuricosuria, treatment of choice would be allopurinol or potassium citrate.
oxalato de cálcio
aumentar ingesta hidrica
diminuir ingesta de sal
tiazidico
citrato se hipocitraturia
Crystals
Presence & type of crystals is determined by urine concentration, constituents, inhibitors, pH etc4
Important drugs/toxins:
– Acyclovir (needle shaped)
– Sulphonamide antibiotics (variable, needle shaped/rosettes) –
Ethylene glycol (calcium phosphate)
– High dose Vit C (calcium oxalate)
– Methotrexate (rarely seen, variable) –
Indinavir (needle shaped)
– Phosphate laxatives (calcium phosphate
estruvita
Triple phosphate crystals- estruvita
• Magnesium ammonium phosphate • Struvite • ‘Coffinlid’shapedcrystals • Seeninalkalineurine • Associatedwithinfectionwithurea-splitting organisms
types of Stones and Cause
Calcium oxalate—low urine volume, low citrate, high calcium, high oxalate
- Calcium phosphate—alkaline urine, high calcium, low urine volume, low citrate
- Uric acid—persistently acid urine
- Cystine—autosomal recessive disorder
- Struvite—urease producing bacteria
exames
- Hypercalciuria – Males: > 300 mg/d – Females: > 250 mg/d – Either: > 4 mg/kg/d
- Hyperoxaluria: > 45 mg/d • Hyperuricosuria – Males: > 800 mg/d – Females: > 750 mg/d
epidemiologia nefrolitiase
Kidney stones (nephrolithiasis) will occur in 12% of men and 5% of women during their lifetime. 1 em cada dez pessoas apresentara
The major types of stones are calcium (70%-80%, oxalate more common thanphosphate), uric acid (5%-10%), cystine (<1%), and magnesium ammonium phosphate (struvite) (10%).Combined calcium/urate stones are also often seen
A patient with a calcium-containing stone episode has anoverall 50% chance of recurrence within 10 years, which is higher for men than for women. Some patients willhave many recurrent stones, leading to substantial morbidity, medical costs, and even mortality
avaliacao do pac
historia clinica, ocupacao, antecedentes de litiase, antecedente familiar,
sindrome metabolica, uso de medicacoes, dieta, ingesta de sal e agua
infeccoes urinarias
exames na uergencia
hemograma= ureia, creat, na , k, calcio, acido urico, pcr, urina rotina , urocultura
analgesia
dipirona
paracetamol ,
aines
opioides
abordagem urologica
urgencia= sepse, crise algica, recorrencia da dor, questoes de trabalho, dificuldade de manejo pos alta,solicitacao do pac, calculos ureterai >1cm
eletiva= calculos ureterais>15mm
baixa evidencia clinica
escopolamina para manejo da dor
bloqueador alfa para calculo renal ou calculo menor 1 5 mm
bcc
corticoide
dent disease
is a rare, X-linked inherited disease of pediatric nephrology. It can be filed under the category of “renal tubular dysfunction” and is also known as “X-linked Recessive Nephrolithiasis.”
Clinical characteristics of Dent Disease include recurrent renal stones, nephrocalcinosis, hypercalciuria, low molecular weight proteinuria, and a gradual progression to ESRD, usually within childhood.
The disease is caused by mutations in the gene CLCN5, a chloride channel present in proximal tubular cells which appears to be necessary for the processing of endosomes. It is not clear why these individuals are so predisposed to nephrolithiasis and hypercalciuria. There is no good therapy for Dent Disease, though a logical case could be made for treating with oral citrate supplementation and thiazide diuretics in an attempt to mitigate hypercalciuria and delay the nephrocalcinosis-induced renal failure as much as possible.
dent disease
is a rare, X-linked inherited disease of pediatric nephrology. It can be filed under the category of “renal tubular dysfunction” and is also known as “X-linked Recessive Nephrolithiasis.”
Clinical characteristics of Dent Disease include recurrent renal stones, nephrocalcinosis, hypercalciuria, low molecular weight proteinuria, and a gradual progression to ESRD, usually within childhood.
The disease is caused by mutations in the gene CLCN5, a chloride channel present in proximal tubular cells which appears to be necessary for the processing of endosomes. It is not clear why these individuals are so predisposed to nephrolithiasis and hypercalciuria. There is no good therapy for Dent Disease, though a logical case could be made for treating with oral citrate supplementation and thiazide diuretics in an attempt to mitigate hypercalciuria and delay the nephrocalcinosis-induced renal failure as much as possible.
drpad
Patients with ADPKD are predisposed to nephrolithiasis. The postulated reasons for this increased prevalence of stone disease have ranged from metabolic abnormalities (previous reports have shown an increased tendency for hyperoxaluria, hypercalciuria, hypocitraturia, hyperuricosuria, and distal RTA) to anatomic abnormalities (large, obstructing cysts and dilated tubular lumens may create a situation of tubular stasis, which predisposes to stone formation).
rim em ferradura= fusao dos polos inferiores
litiase em 60%
risco de neop renal e infeccao
has renovascular
avaliacao ambulatorial por exames
solicitacao de exames
: hemograma, gaso,
funcao renal, sodio, k,
calcio, fosforo, PTH, glicemia, acido urico, lipidograma e magnesio.
solicitacao de exames de urina=
urina pH , densidade / urocultura com TSA
ca u > 250-300
oxalato>40
citrato<340
acido urico >750-800
pesquisa qualitativa de cistina na urina positiva
