WHAT CAUSES KIDNEY STONES Part II. NON-MODIFIABLE RISK FACTORS
WHAT CAUSES KIDNEY
STONES
Part II. NON-MODIFIABLE RISK
FACTORS
List of
abbreviations:
o
AB: Antibiotics.
o
ADH: antidiuretic
hormone
o
ALK: alkaline
phosphatase
o
Ca+:
Calcium
o
CAI: carbonic anhydrase
inhibitors
o
DASH: Dietary Approaches
to Stop HT.
o
FA: Fatty acids
o
FH: Family history
o
GIT: Gastrointestinal
tract
o
Hpara:
hyperparathyroidism
o
K+:
Potassium.
o
KCl: Potassium chloride
o
Mg+: Magnesium
o
Na+:
Sodium
o
NaPi-IIa: Sodium-dependent
phosphate transporter 2A
o
NaPi-IIa: Sodium-dependent
phosphate transporter 2A
o
NC: nephrocalcinosis
o
NHANES: The National Health
and Nutrition Examination Survey.
o
Nlith: Nephrolithiasis
o
Nlth: Nehrolithiasis = Kidney stone
disease
o
Ox : Oxalate
o
PO4:
Phosphate.
o
RTA: Renal tubular
acidosis
o
UTI: Urinary tract
infection
o
+ ve: Positive
o
-ve: Negative
[1] Family history (FH): The relation between FH & risk of kidney stone evolution was assessed in 38,000 males in the Health Professionals Follow-up Study in the US. Along an 8-y period, subjects with a +ve FH had a relative risk of 2.6 of expressing a stone as compared to those without such a history. An elevated familial risk has also been observed in Italy.
[2] Genetic factors: FH data do not distinguish genetic from
environmental circumstances. However, there’s enough evidence of genetic liability
to developing Ca+ stone formation.
Most clinicians consider that several genetic loci have been implicated, possibly
involving Ca+ absorption, resorption,
& excretion; Ox absorption; & Ctr
absorption
& excretion. Particular
genes have been included e.g. Ca+-sensors,
junction protein, renal and intestinal Ca+ channel,
vit D receptors, vit. D 24-hydroxylase, PO4
transporter(s), & Ox exchanger(s).
Particular genes for common types of stone formation have not been fully
recognized, however, a large genome-wide
relations study recognized an association with NaPi-IIa, ALK, claudin-14,
& possibly Ca+-sensors receptors. Another
report: showed that a genome-wide polygenic risk
score was related to UT stones
in absence of other risk factors. Additional support of the genetic impact on Nlth was given
by a twin study from the US. Concordant rates for PH of Nlth
have been compared in monozygotic & dizygotic
twins in 7500
male-male 2 pairs. According to differences in pro-band rate, possible heritability of
stone risk was estimated to be almost 50 %. A less commonly observed is the Dent disease, where
an X-linked recessive deficit
involving Cl channel >>
hypophosphatemia & hypercalciuria.
What medical diseases associated
with kidney stones?
[3] Medical conditions: medical conditions associated with an
increased risk of stone formation:
1)
Primary
hyperparathyroidism: involved ptns are more liable to have Ca+ PO4
stones, but Ca+ Ox stones can be also seen. Secondary Hpara does not elevate the risk of stone
disease.
2)
Hypertension: Primary (essential)
HT has been related to an increased
risk of Ca+ & UA stone disease. Suggested
mechanism (s):
1.
Low urine Ctr,
2.
Increased urine Ca+,
3.
Increased urine Ox,
4.
Increased supersaturated
Ca+ Ox,
&
5.
Increased supersaturated
urine UA.
URIC ACID STONE
3)
Gout: Presence of gout
has been related to a higher risk of kidney stone in males that ca be
explained by a persistent acidic urine (urine pH of 5-5.5)
that promote UA stones precipitation.
4)
Diabetes
mellitus: risk in DM may be partially related
to high urine Ca+, with low urine pH leading to UA
nephrolithiasis.
5)
Obesity: Obesity &
weight gain considered important risk factors for Nlth.
Mechanism of higher risk related to obesity is idiopathic but can be attributed
to high urinary UA & low urine pH.
6)
Medullary
sponge kidney: in Ca+ stone developer,
this disorder is presented in 12-20 % overall & 20-30 % of females or ptns < 20 ys. It’s not known whether anatomic alterations
can induce metabolic alterations (e.g., higher urine Ca+, lower urine Ctr) or if they predisposed to NC (& interstitial deposited Ca+PO4)
increasing the possibility of Nlth.
7)
Distal
(type 1) RTA: urine pH is persistently elevated leading to metabolic acidosis with liability to develop
medullary NC. Moreover, they also
tendency to show low urine Ctr.
8)
Inflammatory
bowel disease, short gut syndrome, bowel resection, or GIT bypass surgery: These disorders can
increase the risk of Ca+ Ox stones by elevating urine Ox (due to increased GIT absorption), decreased
urine Ctr (GIT lost alkali) & urine volume (higher GIT loss of
fluids). Rate of hyperoxaluric stone formation is increased in ptns undergone bariatric surgery.
Series: ptns with Nlth undergoing bariatric surgery, average duration for 1st stone
formation = 3.6 ys. Mean urinary
Ox = 83
mg/d in undergoing mal-absorptive bariatric
surgery (Roux-en-Y gastric bypass), that was evidently higher than
that in usual kidney stone ptns or normal individuals. In contrary, stone disease risk could
be lowered with restrictive
procedures of bariatric surgery.
9) UTI: Persistent upper UTI with urease-producing organism e.g., Proteus or Klebsiella could be at an increased risk for struvite stones.
10)
Cystinuria: cystinuria (autosomal recessive) are at risk for cystine
stone formation owing to the little solubility of extra amounts of cystine excreted
in urine.
[4] Other
factors: Certain environmental circumstances, e.g., warm climate
& geographical zones & occupation (e.g., steel
worker, physician practice in operating room) have been related to a
higher risk of kidney stones. Lack of adequate fluid intake in
these conditions could be the underlying factor for stone disease. Betel quid chewing, a common habit in Southeast Asia, has also been implicated on Ca+ Ox &
Ca+ PO4 kidney stones.
COMMENTS