NEPHROCALCINOSIS

DM SEMINARDr. Vishal Golay

23/02/2011

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TOPIC OVERVIEW

Types of Nephrocalcinosis Causes Pathogenesis Diagnostic work up Treatment

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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

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INTRODUCTION

The term means an increase in the calcium content (generalized) of the kidney parenchyma.

Three forms:› Chemical Nephrocalcinosis› Microscopic Nephrocalcinosis› Macroscopic Nephrocalcinosis

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Hypercalcemic Nephropathy

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Hypercalcemic Nephropathy

Renal vasocontriction Loss of concentrating capacity and

resistance to vasopressin Alkalosis/acidosis K and Mg loss Hypertension

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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

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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

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Etiology

Cortical Nephrocalcinosis (2.4% of all cases)› Chronic Glomerulonephritis› Acute Cortical Necrosis› Chronic Pyelonephritis› Benign Nodular subcapsular type› Post transplant› Post traumatic› Oxalosis

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Etiology

Medullary Nephrocalcinosis (97.6% of all cases)› Conditions causing hypercalcemia› Idiopathic Hypercalciuria› Oxalosis› dRTA› MSK› Renal papillary necrosis› Dent’s disease› Other rare causes

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Pathogenesis

There are two types of microscopic crystal deposition-

› One taking place within the tubular lumen (intratubular nephrocalcinosis), and

› the other in the interstitium (interstitial nephrocalcinosis).

Nephrol Dial Transplant (2009) 24: 2030–2035

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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

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Intratubular nephrocalcinosis

Consequences: Crystal obstruction cause damage due to the

decrease in no. of functioning nephrons acutely 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

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Interstitial Nephrocalcinosis

Mechanisms of formation: Transcytosis

Exocytosis Exotubulosis

De novo formation Randall’s plaque

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Mechanisms involved in renal crystal handling and the development of nephrocalcinosis

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Some important causes of nephrocalcinosis

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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.

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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

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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

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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.

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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).

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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.

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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

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Evaluation

Proper history and examination

Laboratory investigations:› RFT, Ca profile› Urinalysis› Urine c/s› 24 hour timed urine examination› iPTH, TSH› Urinary Magnesium Levels

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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

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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

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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)

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X-Ray KUB

Medullary Nephrocalcinosis

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

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Pyramidal calcification in right upper pole

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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)

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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.

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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

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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

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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

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