Electrolyte Imbalance post Renal Transplant

1. Electrolyte Imbalance Post Renal
Transplant
Dr. Qazi
1

2. Major Electrolytes

3. Major Electrolytes

4. Hypomagnesemia
Normal Range : Magnesium 1.4-1.8 mEq/L

5. Hypomagnesemia
Normal Range : Magnesium 1.4-1.8 mEq/L
4th most abundant cation in the body and 2nd most abundant
intracellular cation

6. Magnesium Homeostasis

7. Post transplant Hypomagnesemia

10. • Poorly understood
• Increased risk of IFTA
Holzmacher R. NDT 2005 Jul; 20(7):1456-62.
Hypomagnesemia & Graft Function

11. Hypomagnesemia & NODAT
Hypomagnesemia & NODAT

12. Hypomagnesemia
&
Insulin resistance
Huang et al. from University of Toranto :
• 948 non diabetic kidney transplant
recipients
• Objective: Relationship between serum
Magnesium level and post transplant
diabetes
• Duration : Median follow up of 3.4 years
• Results : Lower plasma Magnesium level
,defined as plasma magnesium less than
1.8mg/dL was associated with a
quantitatively increased risk of PTDM
Gupta et al. :
• 14 hypomagnesemic non diabetic
renal transplant recipients
• Objective: Effect on Lipid & Glucose
metabolism
• Duration : 6 months
• Results : Correction of
Hypomagnesemia was associated
with reduced serum total
cholesterol, LDL & total
cholesterol/HDL ratio.

13. Mg & Cardiovascular risk after Kidney Transplant

14. Clinical Manifestations
Hypomagnesemia
Clinical Manifestations of Hypomagnesemia:
Hypokalemia , Hypocalcemia, Metabolic acidosis
• Neuromuscular Disturbances
• Ventricular Arrhythmias
• Others: Tremors, Tetany & Convulsions.
ECG Changes Hypomagnesemia / Hypermagnesemia

15. Hypomagnesemia
Treatment

16. • GI intolerance
Oral Magnesium Supplements

17. Hyperkalemia
Normal Range : Potassium 3.5 - 5.0 mEq/L
Potassium (K+) is the most abundant intracellular cation
Concentration : 150 mEq/L intracellular , 4 mEq/L in the extracellular
compartment.
Hyperkalemia:
• Commonly encountered in Kidney transplant recipients
• Particularly in the early post transplant period when higher dose of CNI is used .
Major causes of hyperkalemia :
1. Increased potassium release from the cells and,
2. Reduced urinary potassium excretion
Hyperkalemia & CNIs
A. Episodic hyperkalemia develops in 44 to 73%
B. Reported incidence ranging from 25 to 44%
Mechanism(s) of CNI induced hyperkalemia include :
• Hyporeninism,
• Hypoaldosteronism,
• Aldosterone resistance &
• Inhibition of cortical collecting duct potassium secretory channels

18. Hyperkalemia in Kidney transplant recipient
Following Renal Transplant Hyperkalemia can result from:
1. Impaired allograft function
2. Concomitant use of medications :
• CNIs,
• ACE inhibitors or ARBs,
• Beta blockers and
• Trimethoprim-sulfamethoxazole

19. Medications causing Hyperkalemia
Medications cause for post-transplant hyperkalemia in
recipients with a well-functioning graft:
1. Trimethoprim imethoprim/Sulfamethoxazole
2. Pentamidine
3. ARBs
4. CNIs
• Tacrolimus activates the thiazide-sensitive sodium-chloride cotransporter (NCC)
in the DCT leading to hyperkalemia and hypertension
• Tacrolimus causes this effect predominantly by directly inhibiting calcineurin in
DCT cells .

20. The most common mechanisms of hyperkalemia in
the renal transplant recipient.

21. Clinical Manifestations of Hyperkalemia
1. Muscle weakness or paralysis
2. Cardiac conduction
abnormalities
3. Cardiac arrhythmias
Clinical Manifestation:
At serum potassium concentration is ≥7.0 mEq/L

22. Hyperkalemia Management
Initial approach : Dietary modification and addition of thiazide/ loop
diuretic
• Fludrocortisone
• Patriomer:
• Renal replacement therapy is reserved for severe hyperkalemia
and to patients with delayed graft function or allograft failure.
• Sodium polystyrene sulfonate : is a cation exchange resin that has
been commonly used to treat chronic hyperkalemia

23. Hyperkalemia Management
What’s New :
Zirconium cyclosilicate for hyperkalemia

24. 3. Hypercalcemia & contributing factors
Normal Range : Calcium 4.3 - 5.3 mEq/L
• Hypercalcemia common after transplantation & is generally a result of persistent
secondary hyperparathyroidism.
• Very high variability in occurrence from around 10 to 59% . Highest within 3 months after
transplant. In about two thirds of patients, resolves spontaneously within 6-12 months.
• Resolves spontaneously in less than half of those whose hypercalcemia existed before
transplantation.
• Severe and persistent hypercalcemia (> to 11.5 -12 mg/dL , 2.87 - 3.0 mmol/l) for longer
than 6 months in the first post transplant year required further evaluation.
• Imaging studies including neck ultrasound or parathyroid technetium - 99 meter (99 mTc)
- sestamibi scan,
• May be masked by high dose corticosteroid therapy but manifest during tapering
Potential Contributing factors : post transplant Hypercalcemia
• Improvement in production of Calcitriol post transplant
• Resorption of soft tissue calcium phosphate deposition
• Lack of parathyroid involution

25. • KDIGO guidelines recommend same principles for managing the mineral bone
disorders in patients with chronic kidney disease stages 3–5 to managing bone mineral
disorders after renal transplant.
• The first treatment option is a calcimimetic : Cinacalcet
• If there are no symptoms and patient does not have significant hypercalcemia, i.e.,
serum calcium greater than 11 mg/dL, wait for at least a year for spontaneous
resolution before opting for parathyroidectomy.
• Gastrointestinal side effects and cost of cinacalcet can limit the use of cinacalcet in
some patients.
• Parathyroidectomy is more cost effective when cinacalcet duration reaches 14–16
months.
Hypercalcemia Treatment

26. Hypocalcemia
• A decline in serum calcium levels may be seen in the immediate
posttransplant period.
• A study by Nobata et al. shows an average drop in serum calcium of 7%,
mainly due to a temporary increase in urinary calcium excretion.
Other possible reasons for this immediate drop in serum calcium levels
are:
• The abrupt discontinuation of calcium-containing phosphate binders
• Active vitamin D supplements,
• Glucocorticoid- induced calcium loss.
CNIs also induce osteopenia and bone loss by accelerating bone remodeling.
A few studies show that tacrolimus has a more favorable bone protective profile than
cyclosporine, most probably indirectly related to their steroid- sparing effect.
Finally, the presence of metabolic acidosis can also result in hypercalciuria.

28. 4. Hypophosphatemia
Normal range Phosphorous: 2.5-4.5 mg/dL
Hypophosphatemia in kidney transplant recipients :
1. Frequently encountered in the 1st month after transplantation
2. Concomitant hypercalcemia suggests post transplantation hyperparathyroidism
3. In the absence of hypercalcemia, renal phosphate wasting syndrome or malnutrition should
be considered
Early after transplantation hypophosphatemia is attributed to :
• Massive initial diuresis, particularly after a living donor kidney transplant
• Defective renal phosphate reabsorption caused by Ischemic injury, Glucosuria
& Corticosteroid use
• FGF -23 suggested to play a major contributory role independent of PTH level
• In contrast to hypophsophatemia in the early post transplant period, persistent
hypophosphatemia beyond 1 year post transplant is mainly due to persistent
hyperparathyroidism rather than increased FGF-23 levels
• Regulation is by renal phosphate reabsorption in the proximal tubule.

29. Phosphorous distribution in the body

31. Hypophosphatemia
Normal range Phosphorous: 2.5-4.5 mg/dL
Major Regulators of Phosphate Homeostasis :
1. Dietary phosphate,
2. Parathyroid hormone
3. Vitamin D,
4. Insulin and
5. Fibroblast growth factor 23 (FGF23)
Vitamin D increases phosphate absorption in gut and kidney while PTH
increases renal excretion of phosphate.

32. Hypophosphatemia
Pathophysiology & Clinical Manifestations
Tacrolimus :
• Increases renal phosphate wasting by decreasing the abundance of NaPi-2a
Other contributors to that determine Phosphate wasting Factors :
• Dialysis vintage,
• Low calcitriol levels,
• Elevated parathyroid hormone level, and
• tubular damage

33. • No specific guidelines for the management of post-transplant
hypophosphatemia
• Oral phosphate supplements Well tolerated.
• Persistent post- transplant hyperparathyroidism with concurrent
hypercalcemia and hypophosphatemia Cinacalcet
Hypophosphatemia Treatment

34. Hyperphosphatemia
Normal range Phosphorous: 2.5-4.5 mg/dL
•The serum phosphorus level at 1 year after transplantation exhibits a U-shape
association with death- censored graft failure and patient mortality in the kidney transplant
cohort characterized by a relatively high rate of living donor kidney transplant and low
incidence of diabetes and prior CVD.
• In case of impaired graft function, hyperphosphatemia might recur, which needs dietary
and/or pharmacological interventions.
• KDIGO guidelines suggest to manage these abnormalities as for patients with CKD
G3a–G5 without kidney transplantation .
• It should be taken into account that the phosphate binder Sevelamer has been shown to
reduce the peak plasma concentration and area under the curve of mycophenolate
mofetil reflecting interference with its gastrointestinal uptake.
• Because of this, phosphate binders should be used with caution in patients taking
immunosuppressive drugs, including renal transplant recipients.

35. Hyperphosphatemia & Graft Survival
• Higher serum phosphorus levels in kidney transplant recipients (KTR) are associated
with increased risks for allograft failure and premature death, according to a new study.
• Serum phosphorus levels were measured at baseline in 3138 participants in the
FAVORIT (Folic Acid for Vascular Outcome Reduction in Transplantation;
NCT00064753) trial. Mean phosphorus levels were 3.07 mg/dL, and ranged from 0.79 to
8.32 mg/dL.
• During 4 years of follow-up, 436 cardiovascular disease (CVD) events, 238 transplant
failures, and 348 deaths occurred, according to results published in the American
Journal of Kidney Diseases (2017;70:377-385).
• Patients in the highest decile of serum phosphorus (3.93 mg/dL or higher) had double
the risk of transplant failure compared with those in the lowest quintile (2.51 mg/dL or
lower)
Am J Kidney Dis. 2017 Sep;70(3):377-385.

36. Hyponatremia
• Considered an important risk factor for high morbidity and
mortality because it can decrease brain function, compromise
cardiac contractility, increase insulin resist- ance and induce
neuromuscular dysfunction.
•Kidney transplant patients are predisposed to develop hyponatremia since
they are exposed to immunologic, infectious and pharmacologic changes, the
combination of which alters their salt and water homeostasis.

37. Hyponatremia Management

38. • Cyclosporine reduces proximal tubular sodium reabsorption by
decreasing sodium–hydrogen exchanger activity, responsible for
reabsorbing 30–60% of the filtered sodium.
• Tacrolimus alters distal tubular sodium handling by inducing aldosterone
resistance,
• Salt-losing nephropathy.
Hyponatremia

39. 5. Metabolic Acidosis
✦ Epidemiology
• Not an uncommon finding post renal transplant.
• Varying prevalence from 12 to 58%. 1 year post kidney transplantation, prevalence 13–
16%.
• In renal transplant recipients seen at higher GFR, even in patients with normal
renal function.
• Factors : Suboptimal allograft function, Donor age, Deceased donor
transplantation, Graft rejection, Hyperparathyroidism, and the use of CNI
✦Pathophysiology
• Mechanisms specific to the kidney transplant status
• Diarrhea
• Immunological injury from rejection
• Subclinical tubular dysfunction
• Reduced nephron mass
• Effect of various medications (CNIs, TMP/SMX, etc.).

40. Metabolic Acidosis

41. Metabolic Acidosis Treatment
Retrospective cohort study of 2318 adult kidney transplant recipients, a
strong detrimental association between low bicarbonate levels (less than
22 mEq/L) and graft function as well as death censored graft failure was
noted even after adjusting for estimated GFR.
Treatment:
• Alkali therapy : Inexpensive and relatively safe, Bicarbonate supplementation
is recommended at least to protect the bone.
• Dietary factors have an influence on the post- transplant acidosis.
• Modification of diet by higher intake of fruits and vegetables and lower animal
protein intake

42. THANK YOU!!!!
Source :
1. Frontiers in Medicine | www.frontiersin.org , October 2018 | Volume 5 | Article 261
2. Acta Clinica Belgica, International Journal of Clinical and Laboratory Medicine ,ISSN: 1784-3286 (Print) 2295-3337 (Online)
Journal homepage: http://www.tandfonline.com/loi/yacb20
3. J Am Soc Nephrol 27: 1793–1800, 2016. doi: 10.1681/ASN.2015040391
4. UpToDate
https://www.uptodate.com/contents/overview-of-care-of-the-adult-kidney-transplant-recipient.
5. Brenner