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