Hypercalcemia

1. Hypercalcemia
Dr Vilas Naik,Dr Vilas Naik, DM (Nephrology)DM (Nephrology)
Fellowship in Nephrology and KidneyFellowship in Nephrology and Kidney
transplant, Toronto, Canadatransplant, Toronto, Canada

2. Rare cause of ARF

3. Case
• 65/ male, Mr SH.
• PMHx
– CAD- anterior wall thrombolysed- aug 10, s/p CABG
October 2010
– Burning feet- 3 yrs, multivitamins and sym meds
• HOPI:
– very low appetite and weight loss, nausea & vomiting-
1m.
– Admitted for evaluation of the same: 3rd
may 2011

4. Case: 4th
May 11
• Investigations:
– Hb- 9.8 gms, TLC- 4200, plat- 1.13
– Creatinine- 3.1 mg%
(eGFR= 20.16 ml/min)
– Electrolytes:134/5.3/97
– LFT- normal
– Total Prot/ Sr Albu- 6.9 / 3.4

5. Case
• UGI scopy:- grade 2 GERD
• Sr Vitamin and folate- N
• NCS- demyelinating polyneuropathy
• Progressive confusion- CT brain- WNL,
– MRI brain- N,
– CSF- WNL.
• Chest X-Ray: WNL
• USG:
– RK- 9.6 x 4.8
– LK – 9.8 x 4.2

6. Case- 11th
may 2011
• Progressive worsening of LOC, stuporous
• Creatinin 2.1 3.1 5.1 7 mg%
• Urine output- 1.5 to 2 L
• Referred to nephrology for potential
dialysis

7. Case- 12th
may
• Hb- 9.4, TLC- 3900, plat- 100000.
• Electrolytes: Na-130, K- 3.5,Cl- 89,
• Cal- 9.5 meq/L (19 mg %)
• Albumin- 3.9
• Urine- proteins – 2+, blood- 2+, PCs- 50,
Heme granular casts- Acute tubular necrosis

8. Interpretation of results
• Hypercalcemia: almost always ⇑ in physiologically
important ionized (or free) Ca
• 40 to 45 % bound to protein, principally albumin
• Increased protein binding - elevation in the serum
tCa without rise in the iCa----
– Hyperalbuminemia: severe dehydration & rare patients
with multiple myeloma who have a calcium-binding
paraprotein.
– pseudohypercalcemia (or factitious hypercalcemia), as
iCa normal.

9. Case- 12th
may
• Clinically:
– BP- 130/80, no edema, volume depleted
– Chest clear- SpO2- 98 % on room air
– No lymphadynopathy
– CNS- stuporous, no focal neurodeficit.

10. Treatment
Aim:
• lowering the serum calcium concentration
– inhibiting bone resorption,
– increasing urinary calcium excretion,
– or decreasing intestinal calcium absorption
• if possible, treating the underlying disease
Start treatment urgently
Start evaluating for the cause

11. Treatment
• Normal saline
• Furosemide: bolus f/b drip to match UO
Both increase urinary Ca excretion
• Steroids- decrease 1-25 (OH)2 D3, intestinal absorption
inhibited.
• Calcitonin - Inhibits bone reabsorption
• Biphosphonates- inhibits bone reabsorption

12. Treatment
• Calcimimetics: Cinacalcit- PTH receptor
antagonist
• Dialysis: Low or no calcium dialysate
– Fastest method
– Needs vascular intervention

13. In our patient…..
• NS bolus 2 L, then 250 ml/hr
• Lasix- bolus, drip to match urine output
• Hydrocort 100mg 6 hrly
• Biphosphonate:
– 4 mg in 100 ml NS over 30 min

14. Case
• Creat 7.1 6.1 4.8 3 1.8 mg%
• Parallel decrease in Sr Ca
• Clinical and biochemical improvement
• CBC- still pancytopenia

15. Approach
Cause of
Hypercalcemia

16. Case
Hypercalcemia + renal failure (acute)
Approach
Suggestions

17. Our patient….
• Sr electrophoresis- no M band
• Skeletal survey- no lytic lesions
• Sr immunofixation- negative
• Sr 25 hydroxy and 1-25 dihydroxy vit D3
levels- normal
• Sr iPTH (appropriately collected and sent)

18. Our patient….
• Sr ACEI levels- normal.
• T3/ T4/ TSH- WNL
• PSA
• CT chest (HRCT and CECT)- WNL

19. Case..
• BMA- in v/o persistent pancytopenia-
WNL, only mild erythroid hyperplasia

20. CAUSES
• PTH dependent
– Primary hyper PTH
• Familial
• Sporadic
– Tertiary hyper PTH
(Acute Renal Failure)
• PTH independent
– Hypercalcemia of malig:
• PTHrp
• Activation of extrarenal 1
alpha-hydroxylase
(increased calcitriol)
• Osteolytic bone metastases
and local cytokines
– Vitamin D intoxication

21. PTH independent factors
• Chronic granulomatous
disease
– Extrarenal 1 alpha-
hydroxylase (⇑ calcitriol)
• Medications:
– Thiazides
– Lithium
– Excessive Vitamin A
• Miscellaneous:
• Hyperthyroidism
• Adrenal insufficiency
• Immobilization
• Parenteral nutrition

22. Causes
• Primary hyperparathyroidism & malignancy: -90%
• Malignancy often evident clinically by the time it
causes hypercalcemia
• hypercalcemia of malignancy-higher calciums &
more symptomatic from than primary hyper PTH.

23. Approach
Hypercalcemia affecting the kidney
Mechanisms
– Nephrogenic DI:
• downregulation of aquaporin-2 water channels
• calcium deposition in the medulla with secondary
tubulointerstitial injury
• Decreased medullary osmolality and hence
decreased concentrating ability

24. Hypercalcemia affecting the kidney
• Nephrolithiasis
• Renal tubular acidosis type 1
• Renal insufficiency
– Severe vasoconstriction
– CSR stimulation (loop on Henley)- volume depletion
– calcification, degeneration, and necrosis of the tubular
cells
– Tubular atrophy

25. Ca Sensing Receptor stimulation

26. CSR activation
Lasix
receptor
inhibited

27. Follow of the patient
• Creatinine- 1.2 mg%
• Pancytopenia persistent
• Otherwise healthy
• Decided to go to Mumbai for hematology
evaluation

28. Follow up of the patient
• Complete hematology work up was
negative
• Follow up till 2014 november – mild
thrombocytopenia, otherwise healthy