1. Medical Aspects of Renal Stones Dr. Mohammed Hannon Al Sodani C.A.B.M., F.I.C.M.S. For 5 th year medical students 2015-2016 College of Medicine, University of Baghdad March,31 st,2016

2. Urinary tract calculi nephrolithiasis and nephrocalcinosis Very common, a lifetime risk of 10%. higher in the Middle East. - Most stones - occur in the upper urinary tract. - composed of calcium oxalate and phosphate; - Frequently a recurrent problem. - 50% a recurrence within 10 years. - recurrence increases if a metabolic or other predisposing to stone formation is present and is not modified by treatment. - Nephrolithiasis refers to stone formation within the renal tubules or collecting system, although calculi are often found within the ureters or in the bladder - Nephrocalcinosis augmented calcium content within the Kidney

3. Type and frequency of renal stones in the UK Type of renal stone Percentage Calcium oxalate usually with calcium phosphate 65 Calcium phosphate alone 15 Magnesium ammonium phosphate (struvite) 10–15 Uric acid 3–5 Cystine 1–2 Rarely drugs

4. Aetiology Normal urine :- - has crystals (at times) - extremely effective in maintaining a stable supersaturated state by certain components,Inhibitors of crystal formation, preventing the formation of stones. Postulated inhibitors include;- -- Inorganic :- magnesium, pyrophosphate and citrate. -- Organic ;- glycosaminoglycans and nephrocalcin (an acidic protein of tubular origin). Tamm–Horsfall protein may have a dual role in both inhibiting and promoting stone formation

5. Aetiology - Many stone-formers have no detectable metabolic defect, ‘idiopathic stone-formers’. - Factors predisposing to stone formation in those are:- - Chemical composition of urine - Concentrated urine as a consequence of ;- dehydration, hot climate or work in a hot environment. Impairment of inhibitors of crystallization in urine

6. Causes of urinary tract stone formation Predisposing factors for kidney stones Environmental and dietary Low urine volumes: Dehydration,high temp., low fluid intake Diet: high protein, Hyperuricaemia, hyperuricosuria high sodium, low calcium High sodium, oxalate & urate excretion Low citrate excretion Acquired causes Hypercalcaemia Ileal disease or resection (increases oxalate absorption and urinary excretion) RTA type I,.Infection

7. Causes of urinary tract stone formation Predisposing factors for kidney stones Congenital and inherited causes. Familial hypercalciuria APKD, Medullary sponge kidney Cystinuria Renal tubular acidosis type I (distal) Primary hyperoxaluria - Drugs

8. If the GFR is normal, hypercalcaemia almost leads to hypercalciuria. The common causes of hypercalcaemia leading to stone formation are: - primary hyperparathyroidism most common - vitamin D ingestion -sarcoidosis Hypercalciuria the most common metabolic abnormality detected in calcium stone-formers. Defined as 24-hour calcium excretion of >7.5 mmol in male more than 6.25 mmol in female stone-formers. Causes of hypercalciuria are: - Hypercalcaemia - Excessive dietary intake of calcium, - Excessive resorption of calcium from the skeleton, prolonged immobilization or weightlessness Idiopathic hypercalciuria.. Hypercalcaemia

9. Hyperoxaluria Autosomal recessive inborn errors of glyoxalate metabolism, increased endogenous oxalate biosynthesis associated with calcium oxalate stone formation - poor prognosis is owing to widespread calcium oxalate crystal deposition in the kidneys. CRF, in the late teens or early twenties. -Successful liver transplantation - cure the metabolic defect. Much more common causes of mild hyperoxaluria are:- - excess ingestion of foodstuffs high in oxalate, spinach, & tea - dietary calcium restriction, with compensatory increased absorption of oxalate - GIT disease (e.g. Crohn’s), usually with an intestinal resection, associated with increased absorption of oxalate from the colon

10. Hyperuricaemia and hyperuricosuria - Uric acid stones / 3–5% in the UK, 40%. ME - primary or secondary ( increased cell turnover MPD ) - Some, have hyperuricosuria (> 4 mmol per 24 hours on a low-purine diet) without hyperuricaemia. Dehydration alone may also cause uric acid stones to form. - Patients with ileostomies (dehydration and loss of bicarbonate from GIT secretions results in the production of an acid urine (uric acid is more soluble in an alkaline than in an acid medium).

11. Etiology Some patients with calcium stones also have hyperuricaemia and/or hyperuricosuria; - it is believed the calcium salts precipitate upon an initial nidus of uric acid in such patients. Cystinuria is a rare condition in which reabsorption of filtered cystine, ornithine, arginine and lysine is defective. It is caused by mutations in the SLC3A1 amino acid transporter gene. The highconcentration of cystine in urine leads to cystine stone formation

12. Medications associated with nephrolithiasis and nephrocalcinosis. Calcium Stone Formation - Loop diuretics, Vitamin D, Corticosteroids - Calcium supplements - Antacids (calcium and non calcium antacids) - Theophylline Acetazolamide* Amphotericin B* Uric Acid Stone Formation Salicylates Probenecid Allopurinol ( xanthine stones) Melamine (in contaminated infant formula and milk products) Medications That May Precipitate into Stones Acyclovir (if infused rapidly intravenously) Triamterene Indinavir Nelfinavir

13. Urinary tract calculi and nephrocalcinosis - In developed countries, most calculi occur in healthy young men in whom investigations reveal no clear predisposing cause. Urinary concretions vary greatly in size - particles like sand anywhere in the urinary tract, - large round stones in the bladder. Staghorn calculi fill the whole renal pelvis and branch into the calyces ( they are usually associated with infection and composed largely of struvite.

14. 14 Radio-opaque bilateral staghorn calculi visible during IVU. The intravenous pyelogram demonstrates that, while some dye is being excreted by the right kidney, there is little function on the left.

15. Clinical assessment;- -The most common presentation is with renal colic, Acute loin pain radiating anteriorly and often to the groin,together with haematuria, is typical of ureteric obstruction ( stone becomes impacted in the ureter) most commonly due to calculi ( D.Dx sloughed renal papilla, tumour or blood clot ) - radiates round the flank to the groin and often into the testis or labium (sensory distribution of the L1) - The pain steadily increases in intensity /peak in a few minutes. - The patient is restless and generally tries unsuccessfully to obtain relief by changing position or pacing the room. - pallor, sweating and often vomiting. - Frequency, dysuria and haematuria may occur. -The intense pain usually subsides within 2 hours, but may continue unabated for hours or days.

16. Clinical assessment;- - It is usually constant during attacks, although slight fluctuations in severity may occur -Contrary to general belief, attacks rarely consist of intermittent severe pains coming and going every few minutes. - Subsequent to colic there may be intermittent dull pain in the loin or back. Asymptomatic Stone Disease - Even large staghorn calculi may be asymptomatic - - Obstructive uropathy may also be painless; - therefore, nephrolithiasis should always be considered in the D.Dx of unexplained renal failure. - In the recent outbreak of melamine-associated nephrolithiasis in Chinese infants, the majority presenting to a screening clinic had no symptoms or signs of stones. The diagnosis of nephrolithiasis was made by ultrasound in at-risk infants and toddlers.

17. Investigations and management Investigations Dx of renal colic is usually made easily from the history and by finding red cells in the urine. Investigations are required to confirm - the presence, number & site of the stone, - is stone overlying bone, - degree of obstruction & - the condition” of involved kidney - 90% of stones contain calcium / seen on a plain abdominal X-ray. -

18. Investigations and management Investigations When the stone is in the ureter an IVU shows delayed excretion of contrast from the kidney and a dilated ureter down to the stone - IVU the most commonly used, but spiral CT gives the most accurate assessment and will identify non- opaque stones (e.g. uric acid). Ultrasound may - show dilatation of the ureter if the stone is obstructing urine flow. - The stone may also cast an acoustic shadow.

19. Urine crystals. A, calcium oxalate B, Uric acid crystals: C, A typical hexagonal cystine crystal. D, Coffin lid crystals of magnesium ammonium phosphate (struvite).

20. Investigations and management - Patients with a first renal stone should have a minimum set of investigations - the yield of more detailed investigation is low, and hence usually reserved for those with;- - recurrent or multiple stones, - complicated - unexpected presentations (e.g. in the very young). - Chemical analysis of stones is helpful. - Since most stones pass spontaneously through the urinary tract, urine should be sieved for a few days after an episode of colic in order to collect the calculus for analysis

21. Radiopaque renal calculi. A, X-ray ;- multiple stones in the Rt kidney, ureter& bladder. B, X-ray left staghorn calculus & a single bladder stone.

22. Stone in the right renal pelvis. Helical (spiral) CT scanshowing a single stone in the right renal pelvis. There is no hydronephrosis.

23. Obstructive uropathy resulting from nephrolithiasis in AKI A, X-ray a stone in Rt upper ureter& small stone in Lt lower ureter B, IVU bilateral hydronephrosis caused by ureteral obstruction.

24. Unilateral obstruction. IVU of a patient with a stone (not visible) at the lower end of the right ureter. This film, taken 2 hours post-contrast injection, demonstrates persistence of contrast medium in the right kidney, pelvicalyceal system and ureter, whereas only a small amount remains visible in the normal left pelvicalyceal system.

25. Radiolucent urate calculi. Antegrade pyelogram showing multiple radiolucent urate stones obstructing the lower ureter.

26. Investigations for renal stones

27. Management General Treatment ;- Intervention for stone removal may be required when pain, obstruction, and infection due to nephrolithiasis do not respond to conservative management. Surgical management of stones includes - extracorporeal shock wave lithotripsy - endoscopic or percutaneous surgical removal of stones The risk for development of renal impairment varies with types of stone, and this must be considered in planning management -The immediate treatment of renal pain or renal colic is ;- - bed rest and application of warmth to the site of pain. - Powerful analgesia, morphine (10–20 mg), pethidine (100 mg) IM - or diclofenac as a suppository (100 mg).

28. Management - Patients are advised to drink 2 L per day +/- IV fluids (no benefit from forced diuresis) - Size of stone dictates outcome Diameter (mm) % of stones passing spontaneously <490 4-650 >6 10 - may require endoscopic surgical intervention. - All stones are potentially infected and surgery should be covered with appropriate antibiotics

29. Management - Immediate action is required if there is anuria or pyonephrosis (severe Infection occurs in the stagnant urine proximal to the stone). -Attempts to develop drugs that dissolve stones ??? unsuccessful. ESWL EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY most stones can now be fragmented by shock waves generated outside the body are focused on the stone, breaking it into small pieces which can pass easily down the ureter. This requires free drainage of the distal urinary tract. - Large stones, or stones which do not pass spontaneously through the urinary tract, may require surgical removal and/or fragmentation by extracorporeal shock wave lithotripsy

30. Indications for intervention Obstructive anuria or severe infection(pyonephrosis) → Emergency percutaneous nephrostomy only Severe pain or solitary kidney → Urgent ESWL or surgery Pain and failure of the stone to move → Elective ESWL or surgery

31. management Urate stones can be prevented by allopurinol, Stones formed in cystinuria can be reduced by penicillamine therapy. attempt to alter urine pH with ammonium chloride (low pH discourages phosphate stone formation) sodium bicarbonate (high pH discourages urate and cystine stone formation).

32. Diet Fluid prevent supersaturation - Water! Water and more water enough to make at least 2 L UOP/day (intake 3–4 L / distributed throughout the day (especially before bed) Sodium Restrict intake Protein Moderate, not high Calcium Plenty in diet (because calcium forms an insoluble salt with dietary oxalate, lowering oxalate absorption and excretion) Avoid supplements away from meals (increase calcium excretion without reducing oxalate excretion) Oxalate Avoid rich in oxalate (spinach, rhubarb) N.B. Citrate supplementation is of unproven value Measures to prevent calcium stone formation

33. Drugs Thiazide diuretics Reduce calcium excretion Valuable in recurrent stone-formers and patients with hypercalciuria Allopurinol If urate excretion high (unproven except for uratestones) Avoid Vitamin D supplements as increase calcium absorption and excretion Vitamin C hypersupplementation as this increases oxalate excretion

34. Foods High in Oxalate and Purine High Purine Foods (avoid in setting of hyperuricosuria) -Organ meats: liver, kidney, brains, heart Shellfish - Meat: beef, pork, lamb, poultry - Fish sardines, tuna, carp -Certain vegetables: cauliflower, peas, spinach, mushrooms, lima and kidney beans, lentils High Oxalate Foods (avoid in setting of hyperoxaluria) Green beans Beets Green onions Leeks Leafy greens, spinach, Cocoa Chocolate Black tea Berries: blackberries, blueberries, strawberries, raspberries, Orange peel Lemon peel Dried figs Nuts, peanut

35. Nephrocalcinosis augmented calcium content within the Kidney Deposits of calcium may be present throughout the renal parenchyma, giving rise to fine calcification within the renal parenchyma (nephrocalcinosis), Medullary Nephrocalcinosis (the majority) - calcification tends to occur in the area of the renal pyramids, - Elevated urinary Ca++, phosphate, and oxalate, any of hypercalcemia or hypercalciuria. Instead of stone formation, smaller parenchymal calcifications are deposited in the medulla,usually bilateral and relatively symmetric

36. Urinary tract calculi and nephrocalcinosis Cortical Nephrocalcinosis - usually the result of dystrophic calcification, which follows parenchymal tissue destruction rather than the precipitation of excessive urinary constituents. - typically asymmetric & is usually localized to the renal cortex. - secondary to infarction, neoplasm, and infection. -cortical nephrocalcinosis Transplant rejection, cortical necrosis, tuberculosis, ethylene glycol toxicity, and chronic GN - RTA, - hyperparathyroidism, - vitamin D intoxication

37. Nephrocalcinosis. Dense cortical and medullary calcification in the shrunken kidneys (oxalosis and longstanding renal failure )

38. Medullary nephrocalcinosis. Plain radiograph;- bilateral metastatic medullary nephrocalcinosis Distal RTA

39. Cortical nephrocalcinosis. Non–contrast-enhanced CT scan ;- cortical nephrocalcinosis in the right kidney ( cortical necrosis).