Nephrolithiasis N20.0

The first description of a cystine stone excreted in the urine was made in 1810 by Wollaston (Hoffmann 2014). In 1817, Marcet was the first to chemically examine a kidney stone. This consisted of pure xanthine (Opitz 1965). Extracorporeal shock wave lithotripsy of the urinary tract was developed by Chaussy in Munich in 1980 (Kramme 2007).

Nephrolithiasis refers to both the formation and occurrence of stones in the hollow system of the kidney and the draining urinary tract. The term "urolithiasis" is used synonymously (depending on the specialty) (Kuhlmann 2015).

Depending on the location of the stones, one differentiates between:

• Nephrolithiasis (in the kidney)
• Ureterolithiasis (in the ureter)
• Urethralithiasis (in the urethra)
• cystolithiasis (in the bladder)

Among the types of stones, a distinction is made:

• Calcium oxalate (70 % - 80 %, shadowing)
• urate stones (10 % - 15 %, not shadowing)
• Infectious stones (5 % - 10 %, weakly shadowing):
  • z. e.g. struvite
• calcium phosphate, carbonate apatite < 5 % (both shadowing)
• rare stones < 1 % (not shadowing) (Seitz 2018)
• cystine stones (weakly shadowing (Sigel 1993)

The prevalence of nephrolithiasis ranges from 5% (e.g. in Germany) to 15% in countries with hot, dry climates (the so-called"urinary stone belt of the world"). It has increased significantly in recent decades. The male sex is affected slightly more often than the female sex (1.3: 1).

The incidence decreases again with age (Kasper 2015). The risk of recurrence is 50% overall if untreated, but is highly dependent on the particular type of stone (Kuhlmann 2015).

Predisposing conditions:

• gastrointestinal malabsorption disorder such as Crohn's disease, gastric bypass surgery, etc.).
• primary hyperparathyroidism
• obesity
• diabetes mellitus type 2
• gout
• arterial hypertension
• chronic kidney disease (Kasper 2015)
• metabolic syndrome
• nephrocalcinosis
• polycystic kidney disease
• sarcoidosis
• neurogenic bladder (in spinal cord injuries) (Seitz 2018).

The presence of kidney stones doubles the risk of developing chronic kidney disease (Kuhlmann 2015).

With regard to the etiology of stone formation, lithiasis is divided into the following groups:

• non-infection-related stones (e.g. calcium oxalate stones, calcium phosphate stones, uric acid stones)
• infection-related stones (e.g. struvite, urate stones)
• genetic stones (e.g. cystine stones, xanthine stones, etc.)
• Stone formation triggered by medications (e.g., sulfonamides)(Kuhlmann 2015)
• Metabolic factors:
  • Increased excretion of lithogenic substances in:
  • Hypercalciuria in hypercalcemia (e.g., primary hyperthyroidism, vitamin D overdose, immobilization, etc.).
  • idiopathic hypercalciuria (occurrence of hypercalciuria with normal serum calcium)
  • Hyperoxaluria (e.g. genetically determined or due to a low-calcium or high-oxalate diet, inflammatory bowel diseases, etc.). [Schmelz 2006])
  • Hyperphosphaturia
  • Hyperuricosuria in hyperuricemia
  • Cystinuria (this is an autosomal recessive metabolic disease [Hoffmann 2014] in which there is impaired reabsorption in the proximal tubule)
  • Decreased excretion of lithogenic substances in:
  • Hypomagnesiuria
  • Hypocitraturia (e.g. in distal renal tubular acidosis, high sodium and protein intake, etc. [Wehling 2011])
  • critical urine pH of < 6.0 and > 7.0
  • Very high urine concentration (specific gravity ≥ 1,010 g / l (Herold 2020).
• Factors supporting lithiasis such as:
  • Obesity
  • Urinary outflow obstruction due to anatomical or functional changes
  • Urinary tract infections
  • High-protein diet
  • Thirst
  • weight reduction (Herold 2020)

Urinary tract infections play an important role in the development of kidney stones. Gram-negative bacteria (except E. coli) break down urea into NH3 and CO2, thereby increasing the pH of the urine, which leads to a change in ion solubility. Nephrolithiasis and urinary tract infection favor each other.

The pathogenesis has not yet been fully clarified. Stone formation occurs intrarenally in the tubules. The stones consist of 95 % crystalline substance and 5 % organic matrix ( Schmelz 2006).

Recent studies have shown that in patients with lithiasis calcium phosphate is present in the renal interstitium. It is assumed that this calcium phosphate extends to the papilla, thus providing the calcium oxalate or calcium phosphate crystals with an opportunity for deposition (Kasper 2015).

For the formation of stones are of importance:

• Supersaturation of urine with lithogenic substances (these lead to crystallization)
• Lack of inhibitory substances
• Interaction of the crystals with the tubule epithelium (in the damaged urothelium this interaction is easier to achieve) (Kuhlmann 2015)

With calcium stones the pH value plays a major role. At a low pH value calcium oxalate stones are formed, at a high pH calcium phosphate stones (Kuhlmann 2015).

Pathophysiology of colic:

Colic occurs when a stone formed in the kidney becomes mobilized and causes an obstruction. The pain is caused by the increase in wall tension and pressure proximal to the blockage and not, as previously thought, by hyperperistalsis of the smooth muscles of the ureter (Ellinger 2011).

The frequency peak lies between the 30 - 40 years of age.

Nephrolithiasis becomes clinically symptomatic only when the stone passes through a physiological constriction (such as the outlet of the renal pelvis, the vascular junction of the ureter, or the ureterostium) or becomes obstructively lodged at a site of the urinary tract.

The symptoms are then:

• Colic
• Hematuria (Kuhlmann 2015).

The first colic usually occurs in adulthood. The course is uncomplicated in 75% of those affected.

Renal pelvic effusion stones: They are initially asymptomatic and do not cause urinary retention. They usually become symptomatic only after pyelonephritis (Kuhlmann 2015).

Parenchymal stones, renal pelvic and caliceal stones: In these, there are usually no symptoms. Lithiasis is often detected as an incidental finding during diagnostic imaging (Kuhlmann 2015).

In the context of renal colic, the following symptoms may occur:

• sudden onset of strongest swelling up and down pain in the area of the flank with radiation:
  • into the upper abdomen or back in case of obstruction in the proximal part of the ureter
  • into the middle and lower abdomen in case of obstruction at the pelvic junction of the ureter
  • into the groin, ipsilateral testis or ipsilateral labia in case of obstruction in the lower part of the ureter
• Hematuria: in 90 % there is microhematuria, macrohematuria is found in 1 / 3 of the cases
• Dysuria
• bladder amenorrhea
• motor restlessness of the patient (typical symptom)
• nausea
• vomiting
• reflex subileus with retention of stool and wind (Kasper 2015 / Herold 2020)

Stone score can be used to calculate the probability of renal colic:

• Sex: male (2 points)
• Timing: short duration of pain (> 24 h: 0 points, 6 - 24 h: 1 point, < 6 h: 3 points)
• Origin: no colored (colored: 0 points, no colored: 3 points)
• Nausea: there isnauseaor vomiting (only nausea: 1, only vomiting: 2)
• Erythrocyturia: (microhematuria: 3 points)

Evaluation:

• low probability at 0 - 5 points
• moderate probability at 6 - 9 points
• high probability at 10 - 13 points (Moore 2014).

Inspection and palpation

• unilateral palpitation of the kidneys
• abdomen distended
• no signs of peritonitis
• arterial hypotension (in urosepsis) (Ellinger 2011)

Abdominal radi ograph: In the abdominal radiograph, only shadowing concretions can be visualized. It can be useful in the context of therapy control or follow-up. The sensitivity is 44 % - 77 %, the specificity is 80 % - 87 %. (Seitz 2018)

Sonography: Ultrasound represents the first choice both in the acute situation and in routine examinations (Seitz 2018).

• Detection of a calculus (small stones are sometimes not depictable on ultrasound).
• Renal congestion
• Ectasia of the renal pelvis (Herold 2020).

Computed tomography: CT can be used as a low-dose CT without contrast agent if no calculus is detectable on sonography and also if complications occur. CT also provides information on stone composition and any inflammatory reactions (Kuhlmann 2015). The sensitivity and specificity are close to 99% (Herold 2020).

Urography with abdominal voiding: If sonography or CT are not available, urography can be performed . The sensitivity is 51 % - 87 %, the specificity 92 % - 100 % (Seitz 2018).

i. v. pyelogram: Nowadays, an i. v. pyelogram is considered obsolete in the acute situation (risk of fornix rupture, nephrotoxicity, allergy, etc.) (Kuhlmann 2015).

Renal scintigraphy: Renal scintigraphy can provide additional information in the case of chronic congestion and is sometimes useful before planning surgery. The examination also offers the possibility of a side-separated assessment of renal function (Schmelz 2006). However, renal scintigraphy hardly plays a role in the primary diagnosis of lithiasis. (Seitz 2018)

Urinalysis:

• Urine test strips
• Micro- or macrohematuria
• Leukocyturia
• Nitrite
• Protein
• Glucose
• Sediment (bacteria, crystals)
• Preparation of a culture for germ differentiation and preparation of an antibiogram
• 24h- collection urine:
  • Uric acid (elevated in urate stones)
  • Calcium (elevated in primary hyperparathyroidism)
  • Oxalate
  • Cystine
  • Phosphate
  • Dihydroxyadenine (DHA) in children (Schmelz 2006)
• Blood gas analysis
• small blood count
• Electrolytes
• CRP
• Creatinine
• Urea
• Uric acid
• PTT and INR for probable intervention (Seitz 2018).
• Analysis of departed calculi

The differential diagnoses are manifold.

• renal diseases:
  • tumours in the area of the draining urinary tract and the kidneys (sonography)
  • ureteral obstruction by e.g. blood clots, structures (sonography)
  • Renal infarction (occurs most frequently in patients with atrial fibrillation; there is hematuria, proteinuria, very high LDL with at most slight changes in GOT and AP; diagnosis by color Doppler sonography)
  • papillary necrosis due to e.g. analgesic nephropathy (the papillary defect can be visualized in the urogram )
  • renal vein thrombosis (proteinuria, in case of left-sided thrombosis venous congestion of the left-sided testis in men; diagnosis by color Doppler sonography)
  • renal abscess (diagnosis by CT [Ellinger 2011])
  • Pyelonephritis (high fever, diagnosis by ultrasound, CT / MRI [Ellinger 2011 / Schmelz 2007])
• extrarenal diseases:
  • Appendicitis (usually insidious onset, pressure pain McBurney point, temperature difference between rectal, axillary)
  • pedunculated ovarian cyst (sonography, gynecological examination)
  • extrauterine pregnancy (increased beta HCG in urine, sonography, gynaecological examination)
  • Adnexitis (sonography, gynecological examination)
  • Testicular torsion (diagnosis must be made within 6 hours, otherwise there is a risk of testicular loss; diagnosis by colour Doppler)
  • Biliary colic (pain radiating to the right shoulder, sonography)
  • Pancreatitis (amylase and lipase elevated, abdomen soft)
  • Rupture of abdominal aortic aneurysm (ultrasound, CT- angio [Debus 2018]).
  • Ileus (in mechanical: auscultatory no bowel sounds, exclude possible hernial orifices, abdominal sonography or abdominal radiography).
  • chronic inflammatory bowel disease (history)
  • Mesenteric infarction [Kuhlmann 2015] (age, serum lactate elevated, blood on finger stick rectal examination, diagnosis by biphasic contrast CT).
  • Diverticulitis (history, abdominal palpation)
  • lumbar spine syndrome
  • lumbar herpes zoster

• Urinary tract infection (UTI), as this can lead to urosepsis. UTI is the most important and also the most frequent complication (Herold 2020). Early symptoms of urosepsisare:
  • Tachypnea (> 20 breaths / min)
  • Tachycardia (> 90 beats / min)
  • Hyperthermia (> 38 ° C)
  • hypothermia (< 36 ° C, alternating with fevers)

Urinary tract infection with ureteral stenosis

• Fornix rupture due to pressure increase in the renal pelvic calices (Schmelz 2006)

Up to 90 % of ureteral stones < 5 mm pass spontaneously (Herold 2020) and do not require therapy. However, should colic occur, various therapeutic measures are possible:

1. pain therapy: in acute colic, analgesic treatment is the main treatment. Suitable analgesics are:

• Metamizol: 1 g - 2 g i.v. is the drug of first choice, as it also has a spasmolytic and antinociceptive effect on the ureter.
• Paracetamol: 1 g i. v.
• Diclofenac: 75 mg / kg bw i. v.
• Morphine: 0.1 mg / kg bw i. v. (Seitz 2018).

In a planned extracorporeal shock wave lithotripsy (ESWL), ASA is contraindicated because of the risk of renal hematoma (Herold 2020). In a randomized trial, the combination of paracetamol and diclofenac was shown to be superior to the administration of morphine for pain relief (Seitz 2018).

2. urinary diversion: The indication for urinary diversion is given in:

• high degree of obstruction with consecutive urinary stasis kidney
• increasing retention values (indication of postrenal failure)
• colic that cannot be controlled with medication

Patients presenting with urinary retention and signs of infection are a medical emergency requiring immediate relief by ureteral splinting or percutaneous nephrostomy plus antibiotic treatment (according to the antibiogram) (Kuhlmann 2015). Implementation:

• transurethral insertion of a DJ- ureteral splint
• percutaneous nephrostomy

Both procedures are considered equivalent in terms of urinary diversion. Any discomfort of the ureteral splint can be reduced with an alpha blocker (Seitz 2018). Dosage recommendation: e.g. tamsulosin 1 x 0.4 mg / d (Truß 2005).

3. endourological procedures for stone removal: Before an intervention must be clarified:

• Is there a urinary tract infection? If yes, antibiotic treatment must be started immediately according to the antibiogram.
• Discontinue any existing anticoagulation. If the low-dose treatment with ASA cannot be interrupted, it is possible to continue it after risk assessment for ureterorenoscopy (URS) (Seitz 2018).

Ureterorenoscopy (URS), extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL), laparoscopic or open procedures, and chemolitholysis are available for endourological intervention (Seitz 2018). Indications for interventional therapy include:

• Obstruction with anuria
• Obstruction with existing febrile urinary tract infection
• Obstruction of a single kidney
• obstruction after kidney transplantation
• Bilateral obstruction
• stone size ≥ 5 mm
• uncontrollable pain

3.1 Ureterorenoscopy (URS): Ultrasound, laser, pneumatic, and electrohydraulic lithotripsy as well as baskets and forceps are available for ureterorenoscopy (Herold 2020). Indications:

• in the proximal ureter:
  • Concrements > 10 mm (equivalent to ESWL).
  • Concrements ≤ 10 mm (2nd recommendation).
• in the middle and distal ureter:
  • Concrements (1st recommendation) (Seitz 2018).

Complications:

• Fever
• persistent haematuria
• Renal colic
• Ureteral perforation (2% - 4%)
• ureteral rupture (< 1%)
• injury of the ureteral mucosa
• Postinterventional ureteral strictures (1% - 3%) (Kuhlmann 2015).

Serious complications are rare, occurring in < 1% (Seitz 2018). The success rate depends on the location of the stones:

• proximal ureteral stones: 60 % - 90 %.
• distal ureteral stones: 90 % - 100 %
• renal pelvic stones: 60 % - 90 % (Schmelz 2006).

3.2 Extracorporeal shock wave lithotripsy (ESWL): A prerequisite for ESWL is sonographic or radiological localization of the calculus. Before starting the treatment, an internal urinary splint (splint) should be inserted, if necessary (Seitz 2018), so that the stone fragments can pass the ureter without pain (Herold 2020). Any existing urinary tract infection must be covered with antibiotics before starting therapy. Adequate analgesia should be provided throughout the duration of ESWL (Seitz 2018).

Indications are:

• Pyelon and caliceal calculi from 5 mm - 20 mm.
• in the proximal ureter
  • Concrements > 10 mm (equivalent to URS).
  • Concrements of ≤ 10 mm (1st recommendation).
• in the middle and distal ureter
  • Concrements (2nd recommendation) (Seitz 2018).

Contraindications are:

• Existing anticoagulation (ASA treatment may be continued under certain circumstances with careful indication assessment).
• Coagulation disorder
• untreated urinary tract infections
• pregnancy
• aneurysm in the focal zone
• severe nephrocalcinosis
• obstruction distal to the stone
• pancreatitis
• unadjusted arterial hypertension (Seitz 2018).

Complications may include:

• Skin suffusion
• subcapsular renal hematoma
• colic and congestion caused by residual fragments.

The complication rate (e.g. haematoma, sepsis, etc.) is low (Seitz 2018). The success rate is 90%.

3.3 Percutaneous nephrolithotomy (PCNL).

PCNL is the treatment of choice for kidney stones > 2 cm or for stones in the lower caliceal group of > 1.5 cm. Here, too, an existing UTI must be treated preoperatively according to the antibiogram and perioperative antibiosis must be performed in all patients (Seitz 2018). Contraindications:

• existing anticoagulation
• untreated UTI
• Pregnancy
• atypical colonic interposition (Seitz 2018)

Complications (e.g. fever, perforation of adjacent organs, bleeding, etc.) occur rarely (Seitz 2018). Success rate ranges from 71% -89%, depending on stone size and location. Nearly 90% of patients with renal pelvic stones and > 90% with lower caliceal stones are stone free after 3 months (Schmelz 2006).

3.4 Chemolitholysis: Chemolitholysis should only be used as a first-line therapy for uric acid stones. The pH of the urine is adjusted to a value between 7.0 - 7.2 using sodium bicarbonate or potassium citrate (Kuhlmann 2015). Parallel to this, treatment with allopurinol (e.g. 300 mg / d) is carried out. Long-term chemolitholysis should be avoided because of the risk of calcium phosphate stone formation (Seitz 2018).

3.5 Laparoscopic or open procedures: Nowadays, laparoscopic or open procedures are only used in exceptional cases, e.g. in the case of additional existing anatomical changes that require correction or in the case of very large renal or ureteral stones (Seitz 2018).

Procedure for ureteral stones: If the stone size is < 5 mm (Herold 2020), spontaneous discharge should be awaited - with regular monitoring of body temperature and urine. In approx. 90 % these stones pass spontaneously (Herold 2020). However, spontaneous clearance depends on the location of the stones:

• proximal ureter: 25 %
• middle ureter: 45 %
• distal ureter: > 70 % (Schmelz 2006)

Drug expulsive therapy (MET) with alpha blockers and calcium channel blockers can increase the excretion rate and accelerate the rate of stone passage. (Seitz 2018) Dosage recommendation: e.g. tamsulosin 1 x 0.4 mg / d (Truß 2005) or nifedipine 40 mg - 60 mg / d (Kuhlmann 2015). Supportive effects are also:

• drink plenty of fluids
• local application of heat
• exercise (Herold 2020)

If fever and / or anuria occur, the patient should be immediately transferred to inpatient treatment (Herold 2020).

Procedure for renal pelvic stones: In the case of smaller renal pelvic (caliceal) stones, depending on their location, the patient can initially be kept under constant observation. Concrements > 20 mm in diameter should be treated with EKWL, as this is superior to URS in this case.

Overall, the prognosis for nephrolithiasis is good. Up to 90 % of the concrements are spontaneously removed (Herold 2020).

The risk of recurrence can be reduced to < 15 % by appropriate metaphylaxis (Kuhlmann 2015).

Metaphylaxis comprises preventive measures designed to prevent the development of new kidney stones (Kuhlmann 2015). The basis for metaphylaxis is the analysis of the urinary stone composition, which should be performed for every kidney stone (Seitz 2018). One divides metaphylaxis into general measures for patients in the low-risk group and specific metaphylaxis for high-risk groups (Herold 2020)

For all urinary stone patterns:

• Increase the amount of drinking up to a urine volume of at least 2 l
• circadian drinking
• avoid apple and grapefruit juice
• urine density < 1.010 kg / l
• high-fiber, balanced (Mediterranean) diet
• potassium intake 1 - 1.2 g / d
• protein limitation to 0.8 - 1.0 g / kg bw / d
• salt intake < 6 g / d
• Regulation of body weight
• adequate physical activity
• Stress limitation (Herold 2020 / Kasper 2015 / Kuhlmann 2015 / Schmelz 2006).

The high-risk group includes:

• early onset of lithiasis (already in childhood)
• familial stone information
• single kidney
• certain stones like:
  • brushite-containing
  • uric acid containing
  • infectious stones (Seitz 2018)

In addition to the above measures, depending on the type of stone, certain behavioral rules or medications can also prevent recurrence.

Calcium-containing stones: Calcium oxalate stones form in acidic urine, calcium phosphate stones in alkaline urine (Kuhlmann 2015).

Hypercalciuria is differentiated between:

- absorptive hypercalciuria (results from increased enteric reabsorption)

- resorptive hypercalciuria (is the result of an increased mobilization of calcium from the bones in e.g. ankylosing spondylitis, immobilization, osteoporosis, etc.).

The calcium content of the urine can be reduced by medication with a thiazide diuretic. The commonly used hydrochlorothiazide (HCT) can - according to recent data - increase the risk of white skin cancer with long-term use. Therefore, the guideline

- Chlortalidone (dosage recommendation e.g. Hygroton 12.5 mg - 25 mg / d [Lemmer 2007]) or

- Indapamide (dosage recommendation e.g. INDA- Puren 1.5 mg - 2.5 mg / d [Lemmer 2007]) are recommended (Kuhlmann 2015).

Patients should not reduce the calcium intake of 1 - 1.2 mg / d recommended by nutritionists. This is especially true for patients suffering from osteoporosis. It has been shown that with a reduced calcium diet, urinary stone incidence actually increases (Herold 2020).

Pure uric acid stones: The urinary pH is high (> 6.5) in pure uric acid stones. The urine can be neutralized by dietary measures such as avoidance of foods containing purine (e.g. offal, beans, peas, asparagus, spinach, etc.), protein restriction, etc.

The pH value of the urine can be lowered medicinally by potassium citrate (recommended dosage: 3 g - 5 g / d).

If hyperuricosuria and gout persist, allopurinol 300 mg / d should also be given (Kuhlmann 2015).

- Ammonium-urate stones: There are several starting points for ammonium-urate stones:

1. in case of recurrent infections, immediate antibiotic treatment according to the antibiogram.

2. acidification of the urine with L-methionine (recommended dosage: 500 mg 2 - 3 times / d) to pH values between 5.8 - 6.2.

3. drug reduction of uric acid levels in blood and / or urine by allopurinol. Dosage recommendation: 100 mg - 300 mg / d.

(Seitz 2018)

Oxalate stones: Avoiding oxalate-containing foods (such as spinach, cocoa, beet, rhubarb, nuts, parsley, dark chocolate) helps only to a limited extent, because oxalate is produced in the intermediate metabolism (Herold 2020).

The intake of magnesium should therefore be 200 mg - 400 mg / d (daily requirement approx. 300 mg - 400 mg [Herold 2020]) and of calcium > 500 mg / d (daily requirement approx. 1,000 mg [Herold 2020]). Medication can be used to treat

- for values between 0.5 - 1 mmol / d with alkali citrate: recommended dosage: 9 - 12 mg / d

- at levels of > 1 mmol / d with pyrodoxine initial 5 mg / kg bw / d (Seitz 2018).

Phosphate stones: In phosphate stones should always be digested:

- Hyperparathyroidism (Herold 2020).

- primary hyperoxaluria

- secondary or enteric hyperoxaluria

- renal tubular acidosis (RTA) (Seitz 2018)

Infectious stones: Infectious stones are primarily caused by urinary tract infections with urase-forming bacteria (Kuhlmann 2015). Therefore, when a urinary tract infection occurs, targeted antibiosis according to antibiogram should be performed immediately (Herold 2020).

However, alkaline urine can also lead to the appearance of infection stones (Kuhlmann 2015). To acidify the urine, one can urge the patient to drink more apple juice or cranberry juice (Herold 2020) or use methionine (dosage recommendation: 500 mg 2 - 3 x / d) medicinally (Kuhlmann 2015).

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