RENAL STONES - Etiology, Investigation and Management

Renal stones are formed because of the supersaturation of the urine. This supersaturation of urine leads to following processes: Nucleation, Aggregation, Crystallisation.

RANDALL’S PLAQUE

• They are called precursor lesions for the stone formation (plaque-like material in the renal papillae). They are the subepithelial calcification of renal papillae. They act as a nidus for the Ca2+ Oxalate stone formation.

INHIBITORS OF STONE FORMATION

• Magnesium, Citrate (Most important inhibitor), Nephrocalcin, Tamm- Horsfall mucoprotein, Uropontin, Bikunin

IDIOPATHIC CALCIUM UROLITHIASIS (IDIOPATHIC HYPERCALCIURIA)

• Present in 70% of patients with urinary stones. superscript level Unexplained hypercalciuria with normal serum Ca2+(↑sed Ca2+ level in urine, but normal Ca2+ level in blood). 
• It can be because of two factors, either: RENAL: Defect in superscript reabsorption  of Ca2+ from the kidney.  ABSORPTIVE: Excessive absorption of Ca2+ from GIT.

PRIMARY HYPERPARATHYROIDISM

• Present in less than 5% of the patients. Two causes:  Parathyroid adenoma (most common cause) and  parathyroid hyperplasia Both of these causes lead to ↑se in PTH level. ↑sed PTH level causes: ↑sed bone resorption, ↑sed renal absorption, superscript absorption ↑sed Vitamin D3 leads to ↑sed Ca2+ absorption from intestine. Ultimately it causes hypercalciuria leading to the Ca2+ stone formation.

MILK ALKALI SYNDROME

• Triad of hypercalcemia, alkalosis, and renal impairment.  Increase in Ca2+ and Vit D3 in the presence of an alkaline environment leads to hypercalcemia and alkalosis, ultimately leading to renal impairment. Associated with the promotion of stone formation. 

SARCOIDOSIS

• Characteristic because of granuloma formation. Non-caseating granulomas which produce Vitamin D3 ( ectopic Vit D3 production) are present in patients with sarcoidosis. Ectopic Vit D3 production causes Ca2+ absorption, leading to ↑sed risk of stone formation.

CALCIUM OXALATE STONE

• Most common type of renal stone. It is radio-opaque. Occurs because of ↑sed Ca2+ and ↑sed oxalate in urine. Associated with ethylene glycol toxicity.

CYSTINURIA

• IT is an autosomal recessive disorder. Defect in absorption of COLA amino acids: C- Cystine, O- Ornithine, L- Lysine, A- Arginine. Deficiency in absorption of cystine leads to formation of cystine stone. Cystine stone is hard and radio-opaque (because of Sulphur double bond, S=S).

HOW DO YOU SCREEN FAMILY MEMBERS OF PATIENTS WITH CYSTINURIA?

• Sodium Cyanide Nitroprusside Test. Mechanism: In the presence of cyanide, cystine is converted into cysteine. Cysteine binds with Nitroprusside, which gives Purple Hue in 2 to 10 minutes.

URIC ACID STONE

• 5 to 10% of stones are uric acid stones. Prerequisite for uric acid stone formation is acidic pH- < 5.5 (acidic pH is very important). Hyperuricemia can be because of: High protein diet, Myeloproliferative disorder, Tumour Lysis Syndrome (occurs after chemotherapy), IBD, ileostomy  keeps the patient in the dehydrated stat and low urine volume increase uric acid. Increased uric acid in urine and blood along with acidic pH leads to formation of uric acid stone.  Allopurinol inhibits the enzyme xanthine oxidase (which converts, Hypoxanthine Xanthine to UricAcid). Hence, Allopurinol can be used for medical management for uric acid stones. Uric acid stones are: Hard, smooth, multiple and multifaceted. But, they’re radiolucent (do not have calcium).

ENZYME DISORDERS

PRIMARY HYPEROXALURIA

• Autosomal recessive disorder of glyoxylate metabolism. Two types: Type I: Deficiency of Alanine Glyoxylate Aminotransferase. Type II: Deficiency of D- Glycerate Dehydrogenase. Enzyme deficiency causes ↑sed production of Endogenous Oxalate, which leads to Nephrocalcinosis, Nephrolithiasis.

XANTHINURIA

• Rare inherited disorder of Xanthine Oxidase. Allopurinol precipitates the stone formation (it will block the enzyme even further and xanthine accumulation in the body will ↑se Xanthinuria. 

SECONDARY UROLITHIASIS

• Can be because of: Secondary Hyperoxaluria, dietary excess, Infection, obstruction and stasis, Medullary Sponge Kidney, urinary diversion, drugs.

SECONDARY HYPEROXALURIA

• Small Bowel Resection (fat malabsorption), IBD (mucosa is more permeable), Chronic Pancreatitis, Jejuno-Ileal bypass all of them lead to ↑sed oxalate absorption. Fat malabsorption- Inside intestine superscript binds to oxalate and prevents oxalate absorption. But, if the fat binds to Ca2+, then oxalate is free and it gets absorbed easily leading to formation of oxalate stone. Since bile salt has a detergent property, exposure of colonic mucosa to bile salt will cause increased permeability to charged ions including oxalate.

DIETARY EXCESS

• Some people have the misconception that milk should not be taken because it contains Ca2+, but some amount of Ca2+ is necessary. Balanced diet is the answer.

INFECTION

• Infection by urease producing organisms such as Proteus (most common), Pseudomonas, Staphylococcus. Urease breaks down, Urea Ammonia + CO2. Ammonia can form a bond with Ca2+ and Mg2+, ultimately leading to the formation of Calcium Magnesium Ammonium Phosphate. It is called ‘Triple phosphate stone’ or ‘Struvite stone’ or ‘Staghorn Calculi'. E. coli can never be the cause of staghorn calculi (since it doesn’t produce urease). Staghorn calculi grow along the pelvicalyceal system and do not cause obstruction to urine flow. Hence, the presentation is delayed. Resembles the horns of Antler, that’s why it is called Staghorn Calculi. Don’t confuse the X- ray of Staghorn calculi given above with the IVP (Intravenous pyelogram). For reasoning, observe these things: It’s a plain X–ray, there’s no corticomedullary differentiation. Kidney, urinary bladder, and ureters are not appreciated.

OBSTRUCTION AND STASIS

• Delayed crystal washout leading to the aggregation and stone formation.

MEDULLARY SPONGE KIDNEY

• 20% patients with Ca2+ stone formation may have medullary sponge kidney.

URINARY DIVERSION

• Infection, acidosis, stasis predispose to urinary stone formation. Urinary diversion: Continent urinary diversion and incontinent diversion (ileal conduit). In ileal conduit, chances of stone formation is very less; because stasis is very less. In continent mechanisms of urinary diversion, stasis is present. Hence, there is ↑sed risk of urinary stone formation.

DRUGS

• Acetazolamide: causes RTA, increases risk of stone formation. Allopurinol: precipitate Xanthine stone . Thiazide: has a property of acidifying the urine leading to uric acid stone formation. (Promoter). Triamterene and Indinavir: directly precipitate as drugs. Other factors- Geography, climate and seasonal factors, water intake, diet and occupation.

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CLINICAL FEATURES OF PATIENTS WITH RENAL STONES

• Pain: Dull aching pain (constant feeling of discomfort in the flanks; stone inside kidney leads to this type of pain), colicky pain (when stone is obstructing the ureter). Increased frequency of urination. Burning micturition (dysuria). Hematuria

INVESTIGATIONS

1.URINE EXAMINATION 

• Routine microscopy: Examine for colour, pH, specific gravity, no. of RBCs and WBCs (↑sed), hematuria, and crystal formation. Important crystal shapes [Dumbbell shaped- Calcium oxalate monohydrate; Bipyramidal- Calcium oxalate dihydrate; Hexagonal- Cystine; Coffin lid- Staghorn calculi.]. Culture sensitivity: If there is an UTI, the corresponding organism will be isolated. And antibiotics to be given can be decided.

X- RAY KUB

•  90% of renal stones are radiopaque.

INTRAVENOUS PYELOGRAM (IVP) 

• Practically, nowadays it is not performed. Dye is put inside the blood, and the kidney filters the blood. Dye comes into the renal pelvis ureter urinary bladder excreted out. If stone is present in the pelvicalyceal system, it will show a filling defect. Can demonstrate 2 things: renal function (bad accuracy) and renal stones.

CT SCAN

• Non- Contrast CT Scan - Investigation of choice for diagnosing renal stones. Contrast Enhanced CT Scan - helps us to know the renal function. Better than IVP, but less better as compared to renal scan.

RENAL SCAN

• DMSA Static scan tells us about Cortical function (gives information about renal scarring). DTPA & MAK- 3 Dynamic scan tells us about Tubular function. Renal scan is better than CECT as renal scan gives you differential function. (Tells us the contribution of an individual kidney).

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MANAGEMENT OF STONES

CONSERVATIVE MANAGEMENT

• It is indicated when: Stone size < 5mm, no fever, no hematuria, creatinine level is normal, blood parameters are normal. Hydration therapy is given. Tamsulosin and CCB are given. (Act on 1A and 1B receptors present on the lower part of the ureter, and relaxes the ureter allowingthe stones to pass through)

MEDICAL MANAGEMENT OF STONE

• Ask the patient to drink at least 2.5L of water. So, at least 2.5L of urine in 24 hours. Idiopathic Calcium Lithiasis:  Increased fluid intake. Thiazides- Reduce urine Ca2+ excretion by increasing functional Ca2+ reabsorption in distal nephron. Cellulose Phosphate- Given enterally; useful in absorptive hypercalciuria. Citrate mixture- Inhibitor of urinary stone formation. Hypercalcemic Disorder: In sarcoidosis patients, corticosteroids reduces serum Ca2+. Renal Tubular Acidosis (RTA): Na+, citrate, and HCO3- increases the renal citrate excretion. (Citrate is an important inhibitor for stone formation). In Cystinuria:  K+citrate (more preferred) >>> Na+HCO3-. Target is to increase the pH. (Target pH = 7.5 to 8), hydration, D- Penicillamine:  D- Penicillamine + Cysteine = Soluble salt reduces formation of cystine. Toxic drug: has serious side effects such as rash, fever, agranulocytosis, arthralgia, lymphadenopathy. Instead, 6- Mercaptopropionyl Glycine (MPG) is used, having fewer side effects.  Captopriarrows the urinary cystine levels in homozygous cystinuria patients. Methionine restriction- Methionine is a precursor of cysteine. Uric Acid Lithiasis:  Since acidic pH is a prerequisite for uric acid stone formation, we increase the pH by giving Na+bicarbonate and K+citrate. (Target pH = 6.5). Allopurinol Xanthine oxidase inhibitor May reduce the uric acid excretion. Primary Hyperoxaluria: Large doses of Pyridoxine - Reduces oxalate excretion in 20 to 50% of patients. Neutral Orthophosphates - Used to halt the growth of existing calculi. Enteric Hyperoxaluria: Fat restriction- Necessary, Oral Ca2+ supplementations are indicated. Cholestyramine- Used to block acidic components of gut lumen including oxalate. Intestinal bypass- May need to be reversed. Stones associated with Infection:  After surgical removal, long-term antibiotic prophylaxis is maintained for 2 to 3 months. (Best antibiotic for prophylaxis- Nitrofurantoin). Urinary acidification + Ammonium chloride. Dissolution of stone by: Hemiacidrin; Suby G&M solution; Acetohydroxamic acid.

SURGICAL INTERVENTION

1.ESWL: Extracorporeal Shock Wave Lithotripsy. Machine gives shockwaves to the stones; to break the stones into small pieces which pass out through the ureter. Complications: Pain (most common) , bleeding, Infection, streim strause (street of stones)- larger/ lead stone obstructs the ureter and smaller stones make a line behind it. Treatment is URS (Ureteroscopic Retrieval of Stone). Cardiac arrhythmias. Contraindications: absolute pregnancy, bleeding disorder. Relative: Size > 2 cm, hard stone (higher Hounsfield unit), distal obstruction, obese patients, pacemaker.

2.PCNL

Percutaneous Nephrolithotomy- Indications: All the relative contraindications of ESWL will be the indication of PCNL. Stone size > 2 cm, hard stone, distal obstruction, obese patients, lower calyx stone, pacemaker. Contraindications: Pregnancy, coagulation disorder. Complications:  Organ injury: Spleen, Pleura, Colon. Haemorrhage: Acute and delayed. In case of delayed, pseudoaneurysm/ AV fistula can be present. Next line of investigation in this case will be CECT KUB. And if there is active bleeding, go ahead with angioembolization. Sepsis, Extravasation of urine due to rupture of calyx, Retained stone fragment.

3.URS

• Ureteroscopic Retrieval of Stone. Ureteroscopes can be  flexible or semi rigid. Semi rigid scope is usually used. Through the ureteroscope, we go inside the bladder and into the ureter. Basket (e.g. Dormia basket) is passed beyond the stone, and then opened. Stone trapped inside the basket is pulled out. Indications: Pregnancy, patients with bleeding disorder. Complications: Ureteric injury, ureteric avulsion (not common but very serious complication).

4. IMPORTANT CASE SCENARIO

• Patient is having a ureteric calculi due to which the patient has back pressure changes and creatinine level is raised. What should be the next step in the management of this patient?

In such a scenario, we do not do stone retrieval procedures like URS, etc. 

The primary aim in such a scenario will be to bypass the particular stone. So, we perform DJ Stenting. DJ Stent is put for 14 days, after that stone is removed.

5. RIRS

Retrograde Intrarenal Surgery, Flexible scope is used to reach till the kidney.

• Holmium Yag Laser: Preferred laser for management of Stone Disease. (Nowadays, Thulium lasers are used.)

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