1. NEPHROCALCINOSIS DM SEMINAR Dr. Vishal Golay 23/02/2011

2. TOPIC OVERVIEW Types of Nephrocalcinosis Causes Pathogenesis Diagnostic work up Treatment Vishal Golay's

3. INTRODUCTION The true incidence of nephrocalcinosis is difficult to establish due to the wide range of etiologies. Data available from case collections Mortensen and Emmett-91 cases (1954) J Urol 71:398–406 Monserrat et al -77 cases (1979) Wrong and Feest-375 cases (1976) Advanced medicine no 12. Pitman Medical, London, pp 394–206 Vishal Golay's

4. INTRODUCTION The term means an increase in the calcium content (generalized) of the kidney parenchyma. Three forms: Chemical Nephrocalcinosis Microscopic Nephrocalcinosis Macroscopic Nephrocalcinosis Vishal Golay's

5. Hypercalcemic Nephropathy Vishal Golay's

6. Hypercalcemic Nephropathy Renal vasocontriction Loss of concentrating capacity and resistance to vasopressin Alkalosis/acidosis K and Mg loss Hypertension Vishal Golay's

7. Microscopic Nephrocalcinosis Precipitation of Ca as phosphate or oxalate Midway in spectrum b/w Hypercalcemia and macroscopic nephrocalcinosis. Healthy kidneys contain Ca on autopsy. Many times diagnosis is made biochemically Vishal Golay's

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9. Macroscopic Nephrocalcinosis The calcium deposits are visualized by imaging techniques. Conventional X-ray, USG, CT and MRI can be used. Can affect the cortex as well as the medulla depending on the etiology Vishal Golay's

10. Etiology Cortical Nephrocalcinosis (2.4% of all cases) Chronic Glomerulonephritis Acute Cortical Necrosis Chronic Pyelonephritis Benign Nodular subcapsular type Post transplant Post traumatic Oxalosis Vishal Golay's

11. Etiology MedullaryNephrocalcinosis (97.6% of all cases) Conditions causing hypercalcemia Idiopathic Hypercalciuria Oxalosis dRTA MSK Renal papillary necrosis Dent’s disease Other rare causes Vishal Golay's

12. Pathogenesis There are two types of microscopic crystal deposition- One taking place within the tubular lumen (intratubularnephrocalcinosis), and the other in the interstitium(interstitial nephrocalcinosis). Vishal Golay's Nephrol Dial Transplant (2009) 24: 2030–2035

13. Intratubular nephrocalcinosis Two main pathogenetic processes are involved supersaturation Crystal formation failure of anti-crystal forming controls. epithelial crystal adhesion Crystal retention tubular crystal obstruction Vishal Golay's

14. Intratubular nephrocalcinosis Consequences: Crystal obstruction cause damage due to the decrease in no. of functioning nephronsacutely and secondarily due to the chronic changes caused by it. It can also lead to nephrolithiasis Crystal adhesion cause slow damage, hampers redifferentiation/regeneration of functioning tubules and also can form nidus for growth of other crystals Vishal Golay's

15. Interstitial Nephrocalcinosis Mechanisms of formation: Transcytosis Exocytosis Exotubulosis De novo formation Randall’s plaque Vishal Golay's

16. Vishal Golay's Mechanisms involved in renal crystal handling and the development of nephrocalcinosis

17. Some important causes of nephrocalcinosis Vishal Golay's

18. Hypercalcemia Primary hyperparathyroidism is the most important cause (in adults) according to all the series. Medullary location. More closely related to the duration of hypercalcemia rather than the severity. Degree of renal failure does not correlate with nephrocalcinosis. Vishal Golay's

19. Distal RTA Nephrocalinosis is an important manifestation of dRTA although any condition causing NC can lead to dRTA. Factors leading to stone formation in dRTA: Hypercalciuria Hypocitraturia Alkaline urinary pH Predominant crystal deposited is Calcium PO4 Vishal Golay's

20. Medullary Sponge Kiney Ectatic dilatation of the distal collecting tubules confined to the renal pyramids Not exactly a true NC as the calcium deposition lies in the dilated tubules. 70% of the concretions is Calcium PO4 Relatively benign condition. Diagnosis by radiology Vishal Golay's

22. Clinical implications of NC Features of the underlying primary condition. Renal stone formation. UTI Polyuria and thirst (decreased concentrating capacity). Renal Failure. Hypertension is not a usual feature. Vishal Golay's

23. Clinical implications Sterile pyuria (uniform finding). Erythrocytosis. Proteinuria is also not marked(except in Dent’s disease and Fanconi syndrome). Impairment in urinary acidification (makes the diagnosis of dRTA difficult). Vishal Golay's

24. Natural History Nephrocalcinosis generally persists for life with a few exceptions. Barring a few exceptions the majority of the causes are incurable. Many of the conditions can lead to development of renal failure. Vishal Golay's

25. Natural History Probability of development of ESRD in various diseases causing NC: Best: 1. Idiopathic hypercalciuria 2. MSK 3. dRTA 4. Hypercalcemic conditions 5. Papillary Necrosis 6. Dent’s Disease 7. Hypomagnesemia-hypercalcemia syndrome Worst: Primary Hyperoxaluria type 1 Vishal Golay's

26. Evaluation Proper history and examination Laboratory investigations: RFT, Ca profile Urinalysis Urine c/s 24 hour timed urine examination iPTH, TSH Urinary Magnesium Levels Vishal Golay's

27. Evaluation (Radiological Investigations) Overview: Forms the basis of diagnosis. May detect asymptomatic cases. CT scan is the most sensitive and specific test but carries radiation risk. USG has inter-observer variation. Conventional radiography cannot detect NC until attenuation exceeds 100HU Vishal Golay's

28. X-Ray KUB Requires attenuation values above 100HU <2mm deposits are rarely picked up. the spatial resolution of the recording technique, and contrast factors also influence the detection rate. Useful as a screening tool Vishal Golay's

29. X-Ray KUB Cortical Nephrocalcinosis: Single cortical, calcified, thin peripheral band, often with calcified extensions into the necrotic septa of Bertin. Hyperattenuating tram lines (more commonly interrupted s/o patchiness of CAN) Punctate calcification (CGN) Vishal Golay's

31. X-Ray KUB MedullaryNephrocalcinosis Appears as clusters of stippled calcifications, mainly within the regions of the renal pyramids. Many of the disease causing medullary NC also causes nephrolithiasis which can be seen Vishal Golay's

32. Vishal Golay's Pyramidal calcification in right upper pole

33. Spiral CT Scan Most sensitive modality. Can pick up diseases at an earlier stage, and better information about the extent of disease. Also picks up other findings eg. Cysts Use of contrast to d/f between stones and true NC, and also for MSK Radiation is an issue (10 times more than KUB X-ray) Vishal Golay's

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35. USG Can pick up NC even at an earlier stage than by X-ray. In medullay ND the pryamids are visualized as rounded or echogenic structures. Shadowing can also be seen. In cortical NC, increased cortical echogenicity and shadowing in severe cases. Secondary pyramidal fibrosis with increased echotexture can be seen. Vishal Golay's

36. Treatment Hypercalcemic nephropathy: Supportive treatment of the hypercalcemia and treatment of the underlying etiology For the other causes treatment of the underlying cause forms the only possible care Vishal Golay's

37. Treatment (some examples) Thiazide diuretics and dietary salt restriction Potassium and Mg supplementation Citrate supplementation-increases urinary citrate and decreases Ca excretion (useful in dRTA and idiopathic hypercalciuria) Magnesium supplementation in Mg losing disorders Vishal Golay's

38. Treatment (some examples) Pyridoxine in Type1 hyperoxaluria. Oral calcium supplementation, low fat diet and cholestyramine in hyperoxaluria to decrease intestinal absorption Alkali supplementation in dRTA Surgical attempts at removing the nodules of NC can cause further destruction and should be avoided Vishal Golay's

39. THANK YOU Vishal Golay's