This document provides information on evaluating and managing patients with low-risk kidney stones. It discusses evaluating a patient's risk factors, performing metabolic testing including blood and urine tests, identifying any anatomical abnormalities, and analyzing stone composition. For treatment, it recommends increased fluid intake, dietary modifications like reducing protein and sodium, and medical therapy tailored to the underlying metabolic abnormality causing stone formation. The goal is to reduce stone recurrence through lifestyle and medical interventions.

1. Dr. Pankaj Tejasvi
M.S. MCh Urology

3. What is Low-Risk ??
 First-Time Stone Formers, with no h/o
 Intestinal disease (particularly chronic diarrhea)
 Pathologic skeletal fractures
 Osteoporosis
 UTI with calculi
 Gout
 Bowel resection / bypass bariatric surgery
 Should not be of infirm health (unable to tolerate repeat stone
episodes)
 No strong family h/o stones
 B/l kidney functioning well with no renal insufficiency
 No anatomic abnormalities
 Stones not composed of cystine, uric acid, struvite

4. 1) History
• Rule out any underlying pathological predisposing
conditions
eg. Intestinal disease (chronic diarrhea)
pathological fractures
osteoporosis
gout
DM
• Medications (calcium, vit-C, vit-D, acetazolamide,
steroids)
• Dietary excesses, inadequate fluid intake, excessive fluid
loss

5. 2) Blood screen
• Serum sodium, potassium, chloride, carbon dioxide
• BUN, serum creatinine
• Calcium, Phosphorus
• Intact parathyroid hormone (iPTH)
• Uric acid
helpful in identifying :
primary hyperparathyroidism (high serum Ca and low serum
phosphorus)
renal phosphate leak (hypophosphatemia)
uric acid lithiasis (hyperuricemia)
distal RTA (hypokalemia, decreased serum CO2)

6. 3) Urine
• Urinalysis
pH > 7.5: infection lithiasis / RTA
pH < 5.5: uric acid lithiasis
Sediment for crystalluria to know stone composition
• Urine culture
Urea-splitting organisms: suggestive of infection lithiasis
• Qualitative cystine
4) Radiography
• Xray KUB
• NCCT KUB –
may be obtained for radiolucent stones and also identify any
anatomic abnormalities predisposing to stone formation.
must be done in case of acute episode
In patients who are seen for metabolic evaluation, an NCCT may
not be justified because of concerns regarding cost and radiation
exposure.

7. 5) Stone analysis
Assessment of stone composition, not just urinary crystal
supersaturation, is helpful because most stones are a mixture of
more than one component, the relative ratios or predominance of
any particular molecule may have predictive value.
• uric acid stone is s/o gouty diathesis
• cystine stone is s/o cystinuria
• struvite, carbonate apatite suggests infection lithiasis
• Predominant hydroxyapatite (Ca-apatite) suggests RTA or 1
HPT
• Brushite stone is a/w RTA
Digital tomosynthesis –
performed with a plain abdominal radiograph and a single
tomographic sweep of the x-ray emitter. Multiple coronal slice
reconstruction by digital software
• Improved sensitivity and less radiation than NCCT in
detecting renal stone

8. NCCT-KUB
• Can identify radioluscent stones and renal anatomy
• Can predict stone composition based on HU, but difficult
to differentiate pure struvite from cystine, calcium oxalate
from brushite, and stones of mixed composition.
Dual-energy CT (DECT)
• Better characterize stone type
• Not able to differentiate Ca- ox frpm Ca-phosphate stone
* DECT is promising but must be confirmed in vivo before
incorporation into clinical decision

9. Simplified Metabolic evaluation (Followed currently)
Two 24-hour urine analysis on random diet is done
 Before and throughout the period of evaluation, discontinue any
medication that interfere with metabolism of calcium, uric acid, or
oxalate eg. vit-D, calcium supplements, antacids, diuretics,
acetazolamide, vit-C.
 Stop any current medication for stone treatment(thiazides,
phosphate, allopurinol, or magnesium)
How to collect the 24hr urine ?
Cornerstone of simplified protocol is development of a urine preservation
method that allows collection of urine without refrigeration.
• The first morning void is discarded
• From that point on, all urine must be collected in the appropriate,
laboratory provided container
• When the patient awakens the next morning, the first morning void is
collected with the rest of the specimen
Submit an aliquot to a central laboratory for the analysis of various stone-
forming substances.

11. 1) Extensive Metabolic evaluation (Historical importance)
2) Simplified Metabolic evaluation (Followed currently)
Pak and colleagues described extensive outpatient
(ambulatory) evaluation in 1980
• involves two outpatient visits
Visit 1
i. History and examination
ii. radiologic evaluation
iii. two 24-hour urine analysis on random diet
Visit 2
i. 24-hour urine on restricted diet (400 mg calcium and 100
mEq sodium/day)
ii. fast and calcium load test

12. • Extensive Metabolic evaluation is not done now due to
:
i. Cumbersome nature of the evaluation
ii. fast and calcium load test was done to differentiate b/w
absorptive hypercalciuria and renal leak, but they have
similar treatment.

13. Urinalysis done under Simplified Metabolic evaluation :
i. Urine volume (must be ≥ 2 Lt)
ii. pH
iii. Calcium
iv. Oxalate
v. Citrate
vi. Sodium
vii. Magnesium
viii. Potassium
ix. uric acid
x. Sulfate
xi. Relative supersaturation of CaOx, CaP, UA, Brushite
* All the investigations that are done for low risk stones are
also done.

14. Calcium-Based calculi
1) Absorptive hypercalciuria
Type I
Type II
2) Renal hypercalciuria / Renal Calcium leak
3) Primary hyperparathyroidism / Resorptive hypercalciurea
4) Idiopathic hypercalciuria
5) Hyperoxaluric calcium Nephrolithiasis
Enteric hyperoxaluria
Primary hyperoxaluria
Dietary hyperoxaluria
6) Hypocitraturic calcium Nephrolithiasis
Distal RTA
Chronic diarrheal syndrome
Thiazide-induced
Idiopathic
Hypercalciuria
>200mg/day

15. 7) Hypomagnesuric calcium nephrolithiasis
8) Hyperuricosuric calcium nephrolithiasis
Non Calcium-Based calculi
9) Gouty diathesis
10) Cystinuria
11) Infection calculi / Struvite
12) Low urine volume
13) No disturbance and miscellaneous

16. 1) Absorptive hypercalciuria -
• Have normal serum Ca and a normal iPTH.
In fact, often have low iPTH because of suppression from a constant
abundance of available serum calcium.
2) Renal hypercalciuria / Renal Calcium leak
• Normal serum Ca, but may have mildly elevated iPTH as the
regulatory systems attempt to keep up with the constant loss of
calcium i.e. normocalcemic secondary hyperparathyroidism.
3) Primary hyperparathyroidism / Resorptive hypercalciurea
• Hypercalcemia and increase iPTH
• Some have normocalcemic hyperparathyroidism. These patients are
hard to distinguish from renal leak hypercalciuria. In these cases,
give thiazide (eg. chlorthalidone 25mg od) for 2-weeks. If the patient
actually has renal leak, the calcium loss should be suppressed and
the iPTH should return to normal. Those with primary
hyperparathyroidism will continue to circulate elevated iPTH

17. 4) Idiopathic hypercalciuria
• unevaluated or unknown cause
5) Hyperoxaluric calcium Nephrolithiasis (>40 mg/day)
• prone to the formation of calcium oxalate calculi
Enteric Hyperoxaluria caused as a result of chronic diarrhea
with its attendant dehydration and bicarbonate losses.
• low urine volumes
• Bicarbonate loss from gut l/t low urine pH and the
consumption of citrate as an acid/base buffer thus,
hypocitraturia
Primary Hyperoxaluria extremely rare disorder caused by an
inborn error of metabolism
• Type 1- defect of enzyme alanine glyoxylate aminotransferase
(AGT)
manifests during childhood with early stone formation,
tissue deposition of oxalate (oxalosis), and
renal failure resulting from nephrocalcinosis.
Death often occurs before age 20 in untreated patients
• Type 1- Very rare

18. • Type 1- Very rare
Mild Metabolic Hyperoxaluria (Dietary) deficiency of a
bacterium Oxalobacter formigenes within intestinal flora is
a factor in the formation of calcium oxalate calculi
• Food rich in oxalates - Tea (black), Pepper, Chocolate,
Nuts, Spinach

19. 6) Hypocitraturic calcium Nephrolithiasis
(<550 mg/d, Female; <450 mg/d, Male)
Distal RTA (Type 1)
F:M = 4:1
 Infants present with vomiting or diarrhea, failure to thrive, and
growth retardation;
 children present with metabolic bone disease and renal
stones;
 adults frequently present with nephrolithiasis and
nephrocalcinosis, Up to 70% of adults with distal RTA have
kidney stones. Those patients with onset at an early age or
with severe forms of the disorder may develop
nephrocalcinosis and eventual renal insufficiency.
• Severe hypocitraturia (<100 mg/d) with an inappropriately high
urine pH (>5.5)
• Often Hypokalemia, hyperchloremia & non−anion gap acidosis

20. • secondary RTA can be induced by many common
urologic disorders that also may be sought after a
diagnosis of acquired RTA.

21. • Some patients will have an incomplete variant of the
disease with less marked hypocitraturia and a more
normal urine pH level
Incomplete variants can be diagnosed by ammonium
chloride loading challenge :-
Fasting patient is given 0.1g ammonium chloride/kg body
weight. Subsequently, hourly measurements of urinary pH
and bi-hourly measurements of serum pH or bicarbonate
are taken over 4 to 6 hours. If serum pH falls <7.32, or
bicarbonate falls <16 mmol/L but urinary pH remains ≥5.5,
the diagnosis of incomplete distal RTA is confirmed.
If at any time the urinary pH falls below 5.5, the diagnosis
of incomplete distal RTA is excluded

22. • 6) Hypocitraturic calcium Nephrolithiasis….. cont..
Thiazide-Induced Hypocitraturia
One of the S/E of thiazide therapy is the development of
hypocitraturia
• Because thiazides are still widely used for management of
hypertension, some patients may present with a stone episode
after prolonged therapy
• Stone patients who are treated with thiazides for the control of
hypercalciuria should be screened for hypocitraturia
Chronic Diarrheal States
• Lab findings are similar to those in enteric hyperoxaluria.
However, these patients do not tend to suffer from the bowel
inflammation and subsequent heightened permeability to
oxalate. Therefore urinary oxalate may be mildly elevated, but
usually not to the extent as found in patients with bowel
resection or inflammatory disorders.
• These patients have moderate hypocitraturia with associated
low urine volumes

23. 7) Hypomagnesuric calcium nephrolithiasis
• Has low urinary magnesium, hypocitraturia, and low urine
volume
• a/w chronic thiazide therapy,
excessive dependence on laxatives,
inflammatory bowel disorders, particularly those that
cause malabsorption

24. 8) Hyperuricosuric calcium nephrolithiasis
d/t excessive intake of purines or increase in endogenous
uric acid production
• Elevated urinary uric acid (>600mg/d in F; >750mg/d in
M)
• Urinary pH>5.5
9) Gouty diathesis
• Because there are no known inhibitors of uric acid
crystallization, undissociated uric acid will precipitate
when the urine becomes supersaturated
• At a pH of 6.5 more than 90% of all uric acid is ionized
and therefore soluble. Fifty percent of uric acid will be
soluble at a pH 5.5. By definition, patients with gouty
diathesis have a urine pH <5.5

25. • possibility of a neoplastic or myeloproliferative disorder.
Patients with diabetes mellitus also may form uric acid calculi
as a result of disorders in ammonium handling with
subsequent low urine pH.
10) Cystinuria (>250 mg/L of urine)
autosomal recessive inborn error of metabolism
• May have affected first-degree relatives
• Staghorn calculi or multiple, filled calyces are common
• relatively faint on plain radiography
*hypercalciuria, hyperuricosuria, and hypocitraturia frequently
accompany cystinuria
Hyperuricosuria with:
i. pH>5.5 --- l/t – Ca oxalate stones (Hyperuricosuric calcium
nephrolithiasis)
ii. pH<5.5 --- l/t – Uric acid stone (Gout)
A dietary history should be obtained from all patients with uric acid calculi,
because they may have a tendency to purine gluttony (high intake of animal
protein)

26. 11) Infection calculi / Struvite
present with the symptoms of acute pyelonephritis,
including fevers, chills, flank pain, dysuria, frequency,
urgency, and malodorous, cloudy urine.
Some patients may exhibit more chronic symptoms of
malaise, fatigue, loss of appetite, and generalized
weakness
• F > M because of an increased susceptibility to UTI
• Urine pH >6.5 to 7.0
• h/o foreign body (e.g., forgotten stent, suture material,
staple) or neurogenic bladder may be noted
• Urine cultures often will reveal a urea-splitting bacteria
eg. Proteus mirabilis, although, presence of a sterile
urine culture does not preclude the sequestration of
bacteria within the calculus itself

27. • Although Escherichia coli is not able to spilt urea, it may
be a/w struvite calculi in up to 13% of infections (perhaps
through a metachronous infection)
* 60% of pure struvite–stone formers and 77% of mixed
struvite–stone formers had metabolic abnormalities on 24-
hour urine collections. The most common abnormalities
were hypercalcuria and hypocitraturia.

28. For all patients regardless of the underlying cause of their stone
disease
Fluid Recommendations
Volume
• forced increase in fluid intake to achieve a daily urine
output of at least 2 liters
• mechanical diuresis that ensues may prevent urinary
stagnation and the formation of symptomatic calculi.
• Creation of dilute urine alters the supersaturation of stone
components
Water Hardness
• although water hardness can alter urinary parameters,
this factor ultimately appears to have neglegible clinical
outcome.

29. Carbonated Beverages
carbonated water, which increases urinary citrate levels
offers increased protection against recurrent stone
formation as compared to still water
• increased intake of soda can confer an increased risk for
s
• Soda flavored with phosphoric acid may increase stone
risk, whereas those with citric acid may decrease risk.
*most evidence suggests that it is not the type of fluid
ingested that is important for stone prevention but rather
the absolute amount of fluid volume taken in per day.

30. Dietary Recommendations
Protein Restriction
• incidence of renal stones is higher in populations in which
there is an increased animal protein intake
• Protein intake increases urinary calcium, oxalate, and uric acid
excretion and the mathematically calculated probability of
stone formation even in normal subjects
Sodium Restriction
• high-sodium diet increases propensity for the crystallization of
calcium salts in urine
• RCTs have demonstrated a benefit of dietary sodium
restriction in both normal volunteers and stone formers

31. Obesity
• Obesity is an independent risk factor for nephrolithiasis,
particularly for women
• Obese patients have a higher propensity for uric acid calculi
Impact of Bariatric Surgery
• Roux-en-Y-gastric bypass surgery may significantly increase
overall risk for stone formation
Role of Dietary Calcium
• Maintenance a moderate calcium intake in the face of
calcareous nephrolithiasis
• Older recommendations to restrict calcium intake l/t an
increase in available intestinal oxalate, thus increase oxalate
absorption and thereby raising the supersaturation of calcium
oxalate
• Calcium citrate appears to be a more stone-friendly calcium
supplement because of the additional inhibitory action of
citrate

32. Oxalate Avoidance
• general advice on a restricted-oxalate intake might be
given to patients with recurrent nephrolithiasis, a low-
oxalate diet would be most useful in patients with enteric
hyperoxaluria, those with underlying bowel abnormalities,
or patients who have undergone gastric bypass surgery
• Repeated concerns have been raised regarding the risk
of vit-C (ascorbic acid) ingestion and the possibility of its
conversion to Oxalate
• Avoid heavy dosing of vitamin C. Limiting one’s intake to
a maximum daily dose <2 g

33. 1) Absorptive Hypercalciuria
Currently no treatment program is capable of correcting the
basic abnormality of absorptive hypercalciuria I
Thiazides
stimulate calcium resorption in the distal nephron
while promoting excretion of sodium
• Thiazides do not treat the underlying cause of absorptive
hypercalciuria, but do reduce urinary calcium and
manage its symptoms
• have a limited long-term effectiveness in absorptive
hypercalciuria type I

34. • dietary moderation of calcium and restriction in dietary
sodium and oxalate, combined with thiazide and
potassium citrate, satisfactorily controlled hypercalciuria,
while preventing the complication of osteopenia
commonly associated with absorptive hypercalciuria
• If thiazides lose their hypocalciuric action (after long-term
treatment), a drug holiday may be instituted and then
thiazide therapy may be resumed
Chlorthalidone (25 to 50 mg/day)
Indapamide (2.5 mg/day)
• Both these agents are equally efficacious, yet may
improve patient compliance with more convenient once-
daily dosing

35. 2) Renal hypercalciuria / Renal Calcium leak
Thiazides are first-line therapy
• This diuretic has been shown to correct the renal leak
of calcium by augmenting calcium reabsorption in the distal
tubule and by causing extracellular volume depletion and
stimulating proximal tubular reabsorption of calcium
3) Primary hyperparathyroidism / Resorptive
hypercalciurea
• Hyperparathyroidism complicated by stone disease is
best treated with surgical excision of the adenoma(s)
• There is no established medical treatment for the
nephrolithiasis of primary hyperparathyroidism
• Orthophosphates (safety or efficacy has not yet been
proved) can be given if patient not fit for surgery

36. 5) Hyperoxaluric calcium Nephrolithiasis
Enteric Hyperoxaluria
Cholestyramine binds bile salts in the bowel lumen,
thereby decreasing the irritation of the colonic mucosa and
the subsequent hyperabsorption of oxalate
Potassium citrate (60 to 120 mEq/day) may correct the
hypokalemia and metabolic acidosis in patients with enteric
hyperoxaluria
High fluid intake should be strongly encouraged to correct
the relative state of dehydration
Calcium citrate lower urinary oxalate by binding oxalate in
the intestinal tract
Probiotics use of lactic acid bacteria and O. formigenes
has preliminarily demonstrated reduction in urinary
excretion of oxalate
Low-oxalate diet and pyridoxine

37. Primary Hyperoxaluria
Low-oxalate diet and pyridoxine
• It is converted to pyridoxal phosphate, which is a cofactor for
AGT, and thus increase the expression, catalytic activity, and
peroxisomal import of AGT
6) Hypocitraturic calcium Nephrolithiasis
• Citrates are first-line therapy for the management of RTA,
thiazide-induced hypocitraturia, and idiopathic hypocitraturia
7) Hypomagnesuric calcium nephrolithiasis
• restoration of urinary magnesium levels with either
magnesium oxide or magnesium hydroxide, as well as
correction of the hypocitraturia with potassium citrate
• Use of magnesium has been limited by the risk for diarrhea.
• Potassium-magnesium citrate may restore urinary
magnesium and citrate levels with minimal GI side effects

38. 8) Hyperuricosuric calcium nephrolithiasis
• Allopurinol (300 mg/day) block the ability of xanthine
oxidase to convert xanthine to uric acid
spontaneous nucleation of calcium oxalate is slowed by
allopurinol treatment, probably via inhibition of monosodium
urate–induced stimulation of calcium oxalate crystallization
• Dietary purine restriction
• Potassium citrate may be particularly useful in patients
with mild-to-moderate hyperuricosuria (<800 mg/day),
especially in whom hypocitraturia is also present

39. 10) Cystinuria (>250 mg/L of urine)
The object of treatment for cystinuria is to reduce the urinary
concentration of cystine to below its solubility limit (200 to 300
mg/L)
• Aggressive fluid intake, urinary alkalinization, salt avoidance,
and the use of a cystine-binding agent
• α-Mercaptopropionylglycine (Thiola) is the most frequently
used cystine-binding agent
11) Infection calculi / Struvite
• Struvite calculi are best managed with surgical removal
rather than chemical dissolution
• Recurrent infections (and therefore recurrent calculi) may be
avoided with the use of antibiotic prophylaxis
• Acetohydroxamic acid (Lithostat) can effectively inhibit
urease, but its widespread use is precluded by significant side
effects (thromboembolic phenomena, tremor, headache,
palpitations, edema, GI distress, loss of taste, rash, alopecia,
anemia, and abdominal pain

40. Pregnancy create a unique urinary environment that is
prone to stone formation
Although the amount of urinary calcium rises quite notably,
this effect is offset by an accompanying increase in urinary
citrate. As a result, it is widely assumed that there is no net
increase or decrease in the risk for calculi formation during
pregnancy.
As a result of these temporary physiologic changes, a
metabolic evaluation is not generally undertaken to
determine the cause of the stone disease until after the
woman has delivered and returned to her baseline state of
health.

41. USG is the first-line imaging
Drawbacks of USG :
• difficult to fully discern the ureters and their contents
• Hydronephrosis of pregnancy may be confused for
hydronephrosis from an obstructing calculus
• A limited intravenous pyelogram (IVP) may be
obtained that consists of one scout image followed by
one plate taken approximately 30 minutes after the
injection of contrast. Each plain film exposes the fetus to
0.1 to 0.2 rads, well below the threshold of 1.2 rads, at
which the risk begins to increase.