Nephrolithiasis
Eva Jančová
Nephrolithiasis Renal and ureteral stones are a common
problem in primary care practice Primary care physicians need to be alert to
the possibility of nephrolithiasis and its consequences to decide upon a diagnostic approach, therapy, and refferal to a urologist or stone specialist
Diagnosis and acute managment of suspected nephrolithiasis Epidemiology Etiology Clinical manifestation Differential diagnosis Diagnosis Acute therapy Evaluation and subsequent treatment
Diagnosis and acute managment of suspected nephrolithiasis Epidemiology Etiology Clinical manifestation Differential diagnosis Diagnosis Acute therapy Evaluation and subsequent treatment
Epidemiology The prevalence of renal calculi varies with the population
studied The rate of nephrolihiasis increases with
age (is higher in men compared to woman) whites compared to blacks
Patients discharged from hospital with diagnosis of stones 1.8 per 10 000
Incidence of stones in general practice 7 per 10 000
General practice incidence of stones in males aged 45–60 years
21 per 10 000
Diagnosis and acute managment of suspected nephrolithiasis Epidemiology
Etiology Clinical manifestation Differential diagnosis Diagnosis Acute therapy Evaluation and subsequent treatment
Etiology 85% of pts with n. form calcium stones
most of which are composed primary of calcium oxalate
less often calcium phosphate The other main types include
Uric acid Struvite (magnesium ammonium phosphate) Cystine stone
The same pts may have more than one type of stone currently Calcium and uric acid
Major Risk Factors for Calcium Stones
Low urine volume Hypercalciuria Hypocitraturia Hyperuricosuria Dietary factors
Low fluid intake Type of fluid intake-soft drinks, apple or grapefruite juice High protein intake Low calcium intake
History of prior calcium stones Hyperoxaluria (eg, enteric hyperoxaluria) Meddulary sponge disease Unexplained association with disorders-hypertension,
vasectomy
Other factors affect the risk of stone formation
History of prior calcium nephrolithiasis Family history of nephrolithiasis Inhanced of entetric oxalate absorption Urinary tract infection Medivations /indinavir, sulfadiazine,…)
Diagnosis and acute managment of suspected nephrolithiasis Epidemiology Etiology
Clinical manifestation Differential diagnosis Diagnosis Acute therapy Evaluation and subsequent treatment
Clinical presentations of urinary stones
Pain Ureteric colic Lumbar ache On micturition
Haematuria Sterile pyuria Asymptomatic
proteinuria Dysuria and increased
urinary frequency
Urinary tract infections Acute (single or
recurrent attack) Chronic Pyonephrosis
Calculus anuria Strangury and
interruption of urine stream
Clinical manifestions
Patients may occasionally be diagnosed with asymtomatic nephrolithiasis
The asymptomatic phase is more likely persist in those who have never had a clinical episode of renal colic
Clinical manifestions-Symptoms
Patients occasionally present after already having passed gravel or a stone
Uric acid stones are more likely present with gravel but they cal also produce acute obstruction
Clinical manifestions
Symptoms are usually produced when stones pass from the renal pelvis into the ureter
Pain is the most common symtom and varies from a mild and barely noticeable ache, to discomfort which is so intense
that it requires hospitalization and parenteral medications
Clinical manifestions-Pain
The pain typically waxes and wanes in severity, and develops in waves or paroxysms that are related to movement of the stone in the ureter and associated ureteral spasm
Pain is thought to occur due to muscular contraction of the ureter in response to the stone
Clinical manifestions-PainThe site of obstruction determines the
locaton of pain Upper ureteral or renal pelvic obstruction
lead to flak pain or tenderness Lower ureteral obstruction causes pain
that may radiate to the ipsilateral testicle or labia
The location of the pain may change as the stone migrates
Clinical manifestions-Pain
Variable location of pain can be misleading and occasionally mimics an acute abdomen or dissecting
Clinical manifestions-Hematuria Gross or microscopic hematuria occur in
the majority of patients presenting with symptomatic nephrolithiasis Unilateral flank pain, hematuria, and a
positivity plain of the abdomen are present in 90 percent of emergency room patients with a stone
Absence of hematuria in the setting of acute flank pain does not exclude the presence of nephrolithiasis
Clinical manifestionsOther symptoms Nausea Vommiting Dysuria Urgency
Complicantions Persistent renal obstruction Sepsis
Diagnosis and acute managment of suspected nephrolithiasis Epidemiology Etiology Clinical manifestation Differential diagnosis Diagnosis Acute therapy Evaluation and subsequent treatment
Differential diagnosis
Ectopic pregnancy Aortic aneurysm Acute intestinal obstruction Renal carcinoma (bleeding within the kidney)
Diagnosis and acute managment of suspected nephrolithiasis Epidemiology Etiology Clinical manifestation Differential diagnosis Diagnosis Acute therapy Evaluation and subsequent treatment
Diagnosis
The diagnosis of nephrolithiasis is initially suspected by clinical presentation
Confirmatory radiologic tests include Abdominal plain film (KUB) Intravenous pyelography (IVP) Ultrasonography CT scan (including spiral CT) MRI
Abdominal plain film (KUB)Will identify radiopaque stones Calcium-containing stones Struvite stones Cystine stones
Abdominal plain film (KUB)Advantages Readily available Inxpensive Limited radiation Useful in acute setting
Disadvantages Requies skilled
radiologist to interpret Limited sensitivity and
specificity
Intravenous pyelography (IVP)
High sensitivity and specificity for detection of stones and provides data about the degree of obstruction
Intravenous pyelography (IVP)
Advantages Useful in planning
therapy and confirming diagnosis
Long established history as gold standard
Disadvantages Moderately expensive Intravenous contrast
required Moderate x-ray exposure
Ultrasonography
Advantages Readily available Roughly equivalent to
IVP as a diagnostic test Improved sensitivity with
use of color Doppler No radiation exposure Good for hydronephrosis
Disadvantages Moderately expensive Poor performance with
small stones Requires skilled
technician and radiologist
CT scan (including spiral CT)
Advantages Probably new gold
standard Can distinguish
radiolucent stones from blood and tumor
Disadvantages Expensive Moderate x-ray exposure Not uniform available
MRI
Advantages Great potential for
localizing sight of stone in ureter
Disadvantages Vera expensive Largely investigational
so far except in certain centres
Results of diagnostic imaging in patients presenting with renal colicSites of calcific lesions which may be confused with radio-
opaque urinary stones: gallstones, costal cartilages, mesenteric lymph nodes,
adrenals, pancreas, renal and splenic arteries, pelvic veins.
The radiotranslucent stones uric acid, xanthine, oxipurinol, 2,8-dihydroxyadenine,
orotic acid, and triamterine.Finely stippled nephrocalcinosis suggests long-standing hypercalcaemiaDense coarse nephrocalcinosis suggests primary hyperoxaluria or renal tubular acidosis.
Results of diagnostic imaging in patients presenting with renal colicObstructive uropathy due to: Radio-opaque stone Radiotranslucent obstructive lesion (stones, crystals,
sloughed papillae, clots, carcinoma) Generalized nephrocalcinosis Medullary sponge kidney Renal papillary necrosis (sloughed papilla) Cortical scars due to chronic pyelonephritis Renal carcinoma (cause of ‘clot colic’) Coincidental calcific lesion (e.g. tuberculosis,
Randall’s plaques)
Diagnosis and acute managment of suspected nephrolithiasis Epidemiology Etiology Clinical manifestation Differential diagnosis Diagnosis Acute therapy Evaluation and subsequent treatment
Acute Therapy Pain control
Nonsteroidal antiinflammatory drugs (NSAIDs)
Narcotics Hydration Urology consultation
Acute Therapy
Patients can be managed at home if they are able to take oral medications and fluids
Hospitalization is required for those who cannot tolerate oral intake have very severe pain
Acute Therapy
Hospitalization is required for those who cannot tolerate oral intake have very severe pain
Urology consultationUrgent urologic consultation is warranted in patients
with Urosepsis Acute renal failureOutpatient urology referral is indicated in patients Who fail to pass the stone after a trial of
conservative management (usually two to four weeks)
A stone more 5mm in diameter Uncontrolled pain
Diagnosis and acute managment of suspected nephrolithiasis Epidemiology Etiology Clinical manifestation Differential diagnosis Diagnosis Acute therapy
Evaluation and subsequent treatment
Evaluation and subsequent treatment The patient shoud be evaluated for possible
underlying causes of stone disease These include:
Hypercalcemia Hypercalciuria Hyperuricosuria Hypocitraturia Hyperoxaluria
Evaluation and subsequent treatment-Calcium stones
Composed purely or predominantly of calcium oxalate can occur in many differënt disordes
Calcium phosphate stones are associated with the same risk factors as calcum oxalate stones. One exception- calcium phosphate stones are more typical of complete or incomplete distal renal acidosis
Calcium stones Oxalate crystals
Urinary risk factors for idiopathic calcium stones
Low volume, which increased the concentrations of the lithogenic factors
Hypercalciuria, with or without hypercalcemia Hyperuricosuria, which in calcium oxalate-stone formers, is
usually due to increased protein intake and therefore uric acid production
Hypocitraturia, which can be marked in patients wih chronic metabolic acidosis
Hyperoxaluria, which may be present in up to 40 percent of male and 15 percent of female stone formers
Defects of macromolecular inhibitors
Urinary risk factors for idiopathic calcium stones
Calcium stone formation is most often idiopathic, but can occur a number of other disorders.
Underlying systemic or renal disorders in calcium stone disease Primary hyperparathyroidism Medullary sponge kidney Distal renal tubular acidosis (complete or
incomplete) Sarcoidosis (and other granulomatous diseases) Hyperoxaluria
Enteric Primary
Evaluation and subsequent treatment-Uric acid stones
Pure uric acid stones primary occur in patients in whom a persistently acid urine promotes uric acid precipitation
In the absence of gout, uric acid stones may be seen other causes of chronic overproduction of uric acid or in chronic diarrheal states in which bicarbonate loss and volume depletion lead to a concentrated, acid urine
Caused of Secondary due to increased Purine Biosynthesis and/or Urate Production Inherited enzyme defects leading to purine overproduction Clinical disorders leading to purine and/or overproduction
Myeloproliferative disorders Lymfoproliferative disorders Malignancies Hemolytic disorders Psoriasis Obesity Tissue hypoxia Down Syndrome Glycogen storage diseases (type III,V,VII)
Caused of Secondary due to increased Purine Biosynthesis and/or Urate Production-continue
Drug-,diet, or toxin-induced purine and /or urate overproduction Ethanol Excessive dietary purine ingestion Pancreatic extract Fructose Vitamin B12 (pts with pernicious anemia) Nicotinic acid Cytotoxic drugs Warfarin
Evaluation and subsequent treatment-Struvite stones
Struvite stones only form in pts with a chronic urinary tract infection due to a urease production organism such as Proteus or Klebsiella
The stone may grow rapidly over a period of week to months and, if not, adequately treated, can develop into a staghorn or branched calculus involving the entire renal pelvis and calyces
Evaluation and subsequent treatment-Cystine stones
Cystine stones developt in pts with cystinuria due to the insolubility of cystine in the urine
The diagnosis of cystinuria is made from the family history, by identification of the pathognomonic hexagonal cystine crystal on urinalysis
Cystine stones
Typical hexagonal crystals of cystine under (a) non-polarized and (b) polarized light.
Focused HistoryAll pts with a first stone should undergo a focused history
to identify stone risk factors such as a family history of stone disease and certain dietary habits
Low fluid intake (high concetration of lithogenic factors)
High animal protein diet (which can lead to hypercalciuria, hyperuricosuria, hypocitraturia
High salt diet (which increases urinary calcium excretion)
Increased intake of oxalate-containing foods Vitamin D supplements
Investigations in a Calcium Stone-former
Blood tests Serum calcium 2-3x Serum uric acid Serum bicarbonate Serum creatinine (electrolytes) PTH
Investigations in a Calcium Stone-former
Urinalysis Urine microscopy and culture Urine pH
24-hour collections (2-3x) Volume pH creatinine calcium oxalate uric acid citrate (sodium) (urea)
Methods for stone analysis Wet chemical analysis (qualitative or
quantitative) Optical crystallography X-ray diffraction Thermogravimetric analysis Scanning electron microscopy IR spectroscopy
Evaluation and subsequent treatment Subsequent therapy is based upon the type of
stone and the biochemical abnormalities that are present
Therapy to prevent new stone formation is required: All pts shoud increase fluid intake to above 2L/day,
including drinking at night Pts with calcium stones can be treated with a
thiazide diuretic and low sodium diet for hypercalciuria, allopurinol for hyperuricosuria, and potassium citrate for hypocitraturia
Evaluation and subsequent treatment Therapy to prevent new stone formation is
required-continued: Pts wit uric acid stones can bez treated with
potassium citrate to alkalinize the urine ao allopurinol
Pts with cystine stones can be treated with high fluid intakem urinary alkalinizatin, and drugs such as penicillamine or captopril
Treatment of struvite stones is difficult
Causes of macroscopic nephrocalcinosis (cortical x medullary)Cortical Chronic glomerulonephritis Acute cortical necrosis Chronic pyelonephritis Benign nodular subcapsular
Nephrocalcinosis Cortical
nephrocalcinosis (necropsy specimen)
Causes of macroscopic nephrocalcinosis (cortical x medullary)Medullary Autonomous
hyperparathyroidis Milk alkali syndrome Hypervitaminosis D Sarcoidosis Idiopathic hypercalciuria MacGibbon–Lubinsky
syndrome
Oxalosis Distal renal tubular acidosis Acetazolamide Dent's disease Hypomagnesaemia-
hypercalciuria syndrome
Medullary sponge kidney Renal papillary necrosis Others (Williams' and
Bartter's
Nephrocalcinosis Medullary
nephrocalcinosis in a 25-year-old man with familial distal renal tubular acidosis.
Prognosis for overall renal function-continue
Best Idiopathic hypercalciuria Medullary sponge kidney Distal renal tubular acidosis Autonomous hyperparathyroidism and other rectifiable hypercalcaemias Papillary necrosis Dent’s disease/X-linked recessive nephrolithiasis Hypomagnesaemia–hypercalciuria (Michelis–Manz) syndrome
Worst Primary hyperoxaluria, type 1
Renal Neoplasms
Renal Cell Carcinoma Primary renal neoplasms
Renal cell carcinoma (80-85%) Transitionla cell carcinoma (6%) Oncocytomas Collecting duct tumors Rema sarcomas Nephroblastomas
Secundary renal neoplasms Rarelly
Clinical features Hematuria Abdominal or flan mann Scrotale varicocele Vena cava involvement (ascies, hepatic dysfunction, pulmonary emboli) Systemic or paraneoplastic syndroms
Fever Cachexia Amyloidosis Anemie Hepatic dysfunction Erythrocytosis and thromocytosis Hypercalcemia Polymyalgia-like syndrome