4. A 34-year-old CKD5 female patient on HD due to unknown kidney disease. She received a kidney offer from her cousin. 111 mismatch with DSA (A2 with MFI 1000). Her blood pressure is well controlled. She is on the waiting list for the last 5 years. You noticed her recent parathyroid hormone is 1350 pg/ml (reference range 9 – 65 pg/ml) with normal serum calcium and phosphorus.
- Provided that all other investigations are satisfactory, would you proceed with transplantation or parathyroidectomy first?
- What is the relevance of DSA against HLA-A2
- How would you classify the risk of MFI of 1000 (low, intermediate or high)?
As this is a living donor transplant, the recommendation is that in severe cases of hyperparathyroidism (> 9x normal), the patient undergoes a parathyroidectomy prior to the transplant.
HLA-A2 is the most common HLA class I specificity and is found at high frequency in most populations, because this is less imunogenic.
This is low risk. The cutoff point for concern and measurement for the DSA antibody is 2000.
REFERENCE:
– Genetic diversity of HLA-A2: evolutionary and functional significance. Browning, Michael; Krausa, Peter. Immunology Today. Volume 17, Issue 4, April 1996, Pages 165-170
– Parathyroidectomy prior to kidney transplant decreases graft failure. Callender GG, Malinowski J, Javid M, Zhang Y, Huang H, Quinn CE, Carling T, Tomlin R, Smith JD, Kulkarni S. Surgery. 2017 Jan;161(1):44-50. doi: 10.1016/j.surg.2016.10.003. Epub 2016 Nov 15.
CKD patients with severe hyperparathyroidism should be treated first with a medication or surgical parathyroidectomy before receiving a transplant
As there is may be association with deterioration of allograft function with hyperparathyroidism with unkown pathogenesis .
First treatment with Calcimimetics and vitamin D if no response I will go for Parthyroidectomy
What is the relevance of DSA against HLA-A2?
HLA A2 is the most common antigen , it represent (30-50% ) with possibility with presence of antibodies upto 50-70 % .
However it less immunogenic but may lead to graft failure .
How would you classify the risk of MFI of 1000 (low, intermediate or high)?
Low
MFI is significant if more than 2000 against HLA class I
More than 5000 against HLA Class II
Ref :
Lawrence C, Willicombe M, Brookes PA, Santos-Nunez E, Bajaj R, Cook T, Roufosse C, Taube D, Warrens AN: Preformed complement-activating low-level donor-specific antibody predicts early antibody-mediated rejection in renal allografts. Transplantation 95: 341–346, 2013
Mizutani K, Terasaki P, Hamdani E, et al. The importance of anti- HLA-specific antibody strength in monitoring kidney transplant patients. Am J Transplant. 2007;7:1027–1031
Provided that all other investigations are satisfactory, would you proceed with transplantation or parathyroidectomy first?
This patient with severe hyperparathyroidism with normal calcium and phosphorous levels requires intervention before Tx whether medical treatment with vitamin D analogues or calcimimetics and if failed to reduce PTH below 800 pg/ml despite max treatment we shall proceed to parathyroidectomy after consultation of expert surgeon
What is the relevance of DSA against HLA-A2?
HLA-A2 is less immunogenic class I antigen as compared to HLA-B and HLA-A1.
How would you classify the risk of MFI of 1000 (low, intermediate or high)?
Significant cut-off levels are MFI > 2000 for class I and MFI > 5000 for class II antigens.
So It is considered low risk
But , this patient would require DSA monitoring post-transplant as even low levels of DSA have been shown to be associated with antibody mediated rejections
Female patient,34 years is on regular haemodialysis presented with hyperparathyrodism with PTH level 1350, normal calcium and phosphorus,
Trial of medical therapy to reduce PTH with calcimimetics,calcitriol or synthetic vitamin D analogs.
Patients who are responsive to therapy show significant reduction in PTH within first three to six months of therapy.
Refractory hyperparathyrodism defined as persistent and progressive elevations of serum PTH and cannot be lowered to less than 600.
Parathyroidectomy is indicated for symptomatic patients with refractory PTH more than 800 or asymptomatic patient with refractory PTH more than 1000
It is preferred to parathyrodictomy before kidney transplantation as severe hyperparathyrodism may persist after transplantation which is associated with declined graft function, the operation is also safer to be before transplantation.
Relevance of DSA against HLA-A2
Relevance of DSA against HLA-A2
HLA-A antigens are less immunological than HLA-B and HLA-DR ,HLA-A2 less than HLA-A1
MFI less than 1000 is low risk
cutoff for class I is 2000
Provided that all other investigations are satisfactory, would you proceed with transplantation or parathyroidectomy first?
Young lady:
· on dialysis
· Very high PTH level and no history of medical treatment
· Hypertensive * well controlled.
Regarding hyperparathyroidism:
Most renal transplant recipients have elevated parathyroid hormone (PTH) levels at the time of transplantation, and more than 30% of these patients continue to have elevated levels up to 3 years after transplantation. The duration of time on dialysis and the intensity of hyperparathyroidism before transplantation correlate with the severity of post-transplantation hyperparathyroidism
Guideline recommendations suggest medical therapy first but do not clarify optimal parathyroid hormone targets or indications and timing of parathyroidectomy. Ideally parathyroidectomy should be performed before kidney transplantation to prevent persistent hyperparathyroidism and improve graft outcomes.
So plan:
· Thyroid scan
· Trial of medical therapy Cinacalcet + vitamin D analogue * as KDIGO state surgery only after failure of medical.
· parathyroidectomy before kidney transplantation if persistent hyperparathyroidism
Close collaboration with endocrinologists and nephrologists is needed.
What is the relevance of DSA against HLA-A2? How would you classify the risk of MFI of 1000 (low, intermediate or high)?
The most common HLA antigen is A2, which is found in roughly 50% of individuals from populations around the world. Bot its less antigenic associated with low risk of rejection.
Cut-off/threshold MFI values for HLA antibodies and antigens can vary between transplant centers. Nevertheless, consensus guidelines developed by an international group of experts in the field, MFI levels are likely to correlate with positive crossmatches, with most laboratories reporting HLA antibodies >2000 MFI as being unacceptable, 1000 is consider low risk.
Cianciolo G, Tondolo F, Barbuto S, Angelini A, Ferrara F, Iacovella F, Raimondi C, La Manna G, Serra C, De Molo C, Cavicchi O, Piccin O, D’Alessio P, De Pasquale L, Felisati G, Ciceri P, Galassi A, Cozzolino M. A roadmap to parathyroidectomy for kidney transplant candidates. Clin Kidney J. 2022 Feb 23;15(8):1459-1474. doi: 10.1093/ckj/sfac050. Erratum in: Clin Kidney J. 2022 May 13;15(7):1437.
Chronic kidney disease is associated with a disorder in the regulation of calcium caused by disturbed activation of Vit D which used to be done by the kidney which leads to activation of the parathyroid gland trying to keep s.calcium within target on the expense of bones which also leads to increase risk of fracture. Secondary hyperparathyroidism is treated by kidney transplant by reversing the pathogenesis but tertiary hyperparathyroidism does not respond to kidney transplant and is associated with poor graft, patient survival, and increased risk of bone fracture. There is no clear cutoff of iPTH to decide that this is tertiary hyperparathyroidism but some investigation like neck ultrasound, and sestamibi scan, respond to medical treatment especially correction of hypocalcemia and treatment with cinacalcet as shown in the diagram.
Tartary hyperparathyroidism is usually associated with
– Hypercalcemia and hyperphosphatemia.
– Bone-related symptoms like bone pain and/or fractures.
– vascular calciphylaxis.
Most transplant experts suggest parathyroidectomy for symptomatic patients with persistent hyperparathyroidism with failed medical treatment.
Asymptomatic patients with parathyroid hormone (PTH) >1000 pg/mL have no clear guidelines. parathyroidectomy may be safer if performed prior to transplantation but also hyperparathyroidism resolves in most patients after transplantation
Parathyroidectomy for tertiary hyperparathyroidism is associated with a better outcome related to graft survival compared with cinacalcet management (9% vs 33 %).
• What is the relevance of DSA against HLA-A2?
The most common HLA antigen is A2, which is found in roughly 50% of individuals and also is one of the CREGs which cause positive reactions also against HLA-B57 and B58.
• How would you classify the risk of MFI of 1000 (low, intermediate, or high)?
MFI of 1000 depending on labs (still unfortunately not a standardized test but still considered as low/weak positive.
References:
– Cianciolo G, A roadmap to parathyroidectomy for kidney transplant candidates. Clin Kidney J. 2022 Feb 23.
– Finnerty BM, Chan TW, Jones G, et al. Parathyroidectomy versus Cinacalcet in the Management of Tertiary Hyperparathyroidism: Surgery Improves Renal Transplant Allograft Survival. Surgery 2019; 165:129.
– Pihlstrøm H, Dahle DO, Mjøen G, Pilz S, März W, Abedini S, Holme I, Fellström B, Jardine AG, Holdaas H. Increased risk of all-cause mortality and renal graft loss in stable renal transplant recipients with hyperparathyroidism. Transplantation. 2015 Feb;99(2):351-9. doi: 10.1097/TP.0000000000000583. PMID: 25594550.
-Rubin Zhang, Donor-Specific Antibodies in KidneyTransplant Recipients Clin J Am Soc Nephrol 13: 182–192, January, 2018
-Uptodate.
-Handbook of Kidney transplantation, 6th edition.
-Giuseppe Cianciolo, Francesco Tondolo, Simona Barbuto, Andrea Angelini, Francesca Ferrara, Francesca Iacovella, Concettina Raimondi, Gaetano La Manna, Carla Serra, Chiara De Molo, Ottavio Cavicchi, Ottavio Piccin, Pasquale D’Alessio, Loredana De Pasquale, Giovanni Felisati, Paola Ciceri, Andrea Galassi, Mario Cozzolino, A roadmap to parathyroidectomy for kidney transplant candidates, Clinical Kidney Journal, Volume 15, Issue 8, August 2022, Pages 1459–1474,
-McCaughan J, Xu Q, Tinckam K. Detecting donor-specific antibodies: the importance of sorting the wheat from the chaff. Hepatobiliary Surg Nutr. 2019 Feb;8(1):37-52. doi: 10.21037/hbsn.2019.01.01. PMID: 30881964; PMCID: PMC6383008.
This is young patient on hemodialysis for the last 5 years with unknown etiology of ESRD. Initial evaluation should include the possible causes of ESRD. Severe hyperparathyroidism associated with higher risk of developing cardiovascular complications and osteoporosis in postoperative period and reduce graft survival.
Calcium and phosphorus are normal, so we need to reduce PTH level using cinacalcet. Vitamin D supplementation is essential for high risk of fractures. Vitamin D analogues can be used for the treatment of 2ry hyperparathyroidism. If no response to medical treatment and PTH levels are consistently above 800 mg/dl ,the patient should undergo parathyroidectomy before transplantation.
– DSA against HLA-A2:
HLA- A2 is a common antigen with prevalence of 48% in white population. it is less immunogenic than HLA A1.
– Risk of MFI of 1000 :
Having MFI of 1000 is associated wit-h low risk for transplantation.
Cutoff of MFI that define high risk is >2000 for class I DSAs and>5000 for class II DSAs
· Q1: sever hyperparathyroidism could be troublesome after TX. Therefore, a parathyroid scan should be done and if there is adenoma, parathyroidectomy is preferred. However, if not possible, medical treatment with calcimimetics in addition to vitamin D analogues and phosphate binders is preferred.
· Q2: HLA-A2 is a prevalent Ag, SO, Anti-HLA Abs against A2 could be very troublesome in looking for a donor. Additionally, there is CREGs with this Ag.
1- Persistent HPT contributes to posttransplant complications such as hypercalcemia, hypophosphatemia, high FGF-23 and nephrocalcinosis and is associated with unfavourable graft and patient outcomes. Moreover, Persistent HPT in KTRs is associated with decreased bone density and an increased fracture rate. Medical treatment versus parathyroidectomy before or after KT: Persistent HPT post-KT often requires parathyroidectomy with a prevalence range from 0.6 to 5.6%. However, there are no clear guidelines on how to treat waitlisted dialysis patients to reduce the risk of persistent HPT post-KT. Moreover, the ap[1]propriate strategy in KTRs is debated, with particular focus on the risk of worsening of graft function related to medical and surgical therapy. SHPT before KT can be treated by medical (VDRAs, phosphate binders and calcimimetics) or surgical (parathyroidectomy) approaches. Both reduce PTH values, although parathyroidectomy provides better long-term control of calcium and PTH values. Medical treatment is generally the first step. Parathyroidectomy is suggested for patients with SHPT refractory to medical therapy. See the graph.
2- Individuals sensitized to HLA-A2 can develop an antibody which also reacted with HLA-B57 and B58. These groups of antigens which were cross reactive with a single antibody became known as the cross-reactive groups (CREGs).
3- MFI of 1000 depending on labs, however is considered as low/weak positive.
file:///C:/Users/FAKHRI~1/AppData/Local/Temp/msohtmlclip1/01/clip_image001.jpg
References:
1- Giuseppe Cianciolo, Francesco Tondolo, Simona Barbuto, Andrea Angelini, Francesca Ferrara, Francesca Iacovella, Concettina Raimondi, Gaetano La Manna, Carla Serra, Chiara De Molo, Ottavio Cavicchi, Ottavio Piccin, Pasquale D’Alessio, Loredana De Pasquale, Giovanni Felisati, Paola Ciceri, Andrea Galassi, Mario Cozzolino, A roadmap to parathyroidectomy for kidney transplant candidates, Clinical Kidney Journal, Volume 15, Issue 8, August 2022, Pages 1459–1474,
2- McCaughan J, Xu Q, Tinckam K. Detecting donor-specific antibodies: the importance of sorting the wheat from the chaff. Hepatobiliary Surg Nutr. 2019 Feb;8(1):37-52. doi: 10.21037/hbsn.2019.01.01. PMID: 30881964; PMCID: PMC6383008.
According to KDIGO guide lines, CKD patients with severe hyperparathyroidism should be treated first with a medical or a surgical parathyroidectomy prior to transplantation to avoid the risk of worsening graft function, fractures and cardiovascular risks.
It is expected that kidney transplantation would improve the bone mineral disorder. However, up to 80% of the transplanted patients have persistently high PTH levels.
In our index case with normal calcium and phosphorus, parathyroid imaging with ultrasound and MIBI scan is required first to exclude the presence of an adenoma that would necessitate surgery from the start. If no adenoma is present, medical treatment is started first with vitamin D analogues and clacimimetics and follow intact PTH levels, if it remained >800 pg/ml despite maximal medical therapy , proceed for surgical parathyroidectomy.
· What is the relevance of DSA against HLA-A2
HLA-A2 is MHC class I antigen. It is a commonly present in around 30- 50% of the population, but it is less immunogenic than A1 antigen. The presence of DSAs against A2 makes it difficult to find a suitable donor.
The cutoff point varies between different labs, but in general, levels below 2000 for class I and 5000 for class II are not clinically significant. So, I would consider it of low risk. However, a post-transplant follow-up is required as the MFI titer is not only the factor that increases the risks for rejection ,but also the IgG subclass and ability to bind and activate the complement cascade
References:
1-Chadban SJ et al. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation. 2020 Apr;104(4S1 Suppl 1):S11-S103
2. Callender GG, Malinowski J, Javid M, Zhang Y, Huang H, Quinn CE, Carling T, Tomlin R, Smith JD, Kulkarni S. Parathyroidectomy prior to kidney transplant decreases graft failure. Surgery. 2017 Jan;161(1):44-50.
3. Browning M, Krausa P. Genetic diversity of HLA-A2: evolutionary and functional significance. Immunol Today. 1996 Apr;17(4):165-70.
Provided that all other investigations are satisfactory, would you proceed with transplantation or parathyroidectomy first?
The patient is 34-year-old young female with controlled hypertension
Her parathyroid hormone is quite raised
But the calcium and phosphorus are normal.
What is the relevance of DSA against HLA-A2
HLA-A2 is most common antigen
it is less immunogenic, but DSA against A2 has resulted in graft loss
How would you classify the risk of MFI of 1000 (low, intermediate or high)?
MFI cut-off is quite different at different institutions.
But, MFI of 1000 would be low risk as most common cut-off of MFI is 2000
Goulmy EA, Van der Poel JJ, Giphart MJ, Pool J, Persijn GG, Van Rood JJ, D’Amaro J. The influence of the HLA-A2 subtype mismatch on renal allograft survival. Transplantation. 1992;53:1381-2.
Chadban SJ, Ahn C, Axelrod DA, Foster BJ, Kasiske BL, Kher V, Kumar D, Oberbauer R, Pascual J, Pilmore HL, Rodrigue JR, Segev DL, Sheerin NS, Tinckam KJ, Wong G, Knoll GA. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation. 2020 Apr;104(4S1 Suppl 1):S11-S103. doi: 10.1097/TP.0000000000003136. PMID: 32301874.
I would allow patient to proceed with transplantation as patient is asymptomatic for CKD MBD with normal serum ca/ po4. Emphasize on low phosphate diet and ensure adequate treatment KT/V achieved.
DSA against HLA-A2 Low antigenicty.
MFI 1000. Low risk.
Provided that all other investigations are satisfactory, would you proceed with transplantation or parathyroidectomy first?
I would go for parathyroidectomy first as it reduces the chance of worsening graft function and hyperparathyroidism continues in 50% of renal transplant recipient.
This patient has got a living donor offer, so better to proceed for parathyroidectomy before transplantation.
She si on the waiting list for 5 years, I imagine that medical treatment for hyperparathyroidism was going on and was tried during this duration.
PTH> 800 pg/ml is an indication for parathyroidectomy.
What is the relevance of DSA against HLA-A2?
HLA-A2 is the commonest antigen MCH I where it reaches up to 30-50% of certain population.
This means that the chance of this patient (recipient) to be not sensitized to potential donor is 50-70%.
How would you classify the risk of MFI of 1000 (low, intermediate or high)?
It depends on the lab, kits used and intra-lab method variation/
Generally, MFI <1000 is low,
MFI>2000 FOR Class I, MFI>5000 for class II are highly significant.
As patients serum calcium level is normal, we will proceed for transplant without parathyroidectomy.
Indication for parathyroidectomy are-
Tertiary hyperparathyroidism
persistent severe hypercalcemia for 6 to 12 months or
Symptomatic or progressive hypercalcemia (associated with Nephrolithiasis, persistent MBD, calcium related allograft dysfunction and progressive vascular calcification and calciphylaxis )
What is the relevance of DSA against HLA-A2
The most common HLA antigen is A2 which is found in roughly 50 % of population around the world. Through it is less antigenic , presence of DSA against it is associated with allograft rejection
How would you classify the risk of MFI of 1000 (low, intermediate or high)?
Low
Hyperparathyroidism should be treated either medically or surgically prior to kidney transplantation so if adenoma or resistance to medical therapy we should proceed for surgery prior to kidney transplantation as per KDIGO guidelines
DSA To A2 and <1000 is low immunological risk ,but if from 1000-10000>>> we should see crossmatch result ,if negative we can proceed without desensitization but will need repeat of PRA and cross match after 3 to 6 months ,
DSA to HLA A2 is low antigenicity and found in 40% of population
but if repeated :negative crossmatch and MFI <1500 we can proceed with ATG induction
Provided that all other investigations are satisfactory, would you proceed with transplantation or parathyroidectomy first?
this patient has very high PTH with normal Ca and Phos4. and he is for transplantation
in case of hyperparathyroidism should be controlled before renal transplantation
I will do parathyroid U/S , and possibly sestamibi scan if there is adenoma then surgery is better
otherwise start with medical treatment
aalfacalcidol or cinacalcet
What is the relevance of DSA against HLA-A2
DSA against HLA-A2 has low antigenicity. so can proceed with transplant
HLA2 is commonest HLA alleles class I MHC
How would you classify the risk of MFI of 1000 (low, intermediate or high)?
Low
PTH more than 800 so parathyroid gland scanning to role gland hyperplasia or nodular hyperparathyroidism
medical therapy should be offered in form of cinacalcet or paricalcitol .
if there is resistance or still PTH above 500 surgical should be considered before transplantation to avoid impact on graft function
there is risk of rejection in spite of low level.
low
please see the attachment
will do her parathyroid scintigraphy and confirm the presence of adenoma and rule out parathyroid malignancy , if the scan suggest hyperplasia then will proceed with medical treatment including alfacalcidol if caxp product < 55
cinacalcet if caxp product > 55
might give Etelcalcitide to ensure compliance to treatment
Coyne and Delos Santos [2] suggest that calcimimetics should be stopped for 2–4 weeks before measuring PTH in KT candidates as part of the assessment for transplantation. If the PTH is >800 pg/mL, the patient’s risk of persistent HPT appears to be high. Hence parathyroidectomy is indicated. A cut-off for PTH of 1000 pg/mL without calcimimetic use or 500 pg/mL with calcimimetic use has also been proposed.
Ideally parathyroidectomy should be performed before kidney transplantation to prevent persistent hyperparathyroidism and improve graft outcomes
Persistent HPT contributes to posttransplant complications such as hypercalcemia, hypophosphatemia, high FGF-23 and nephrocalcinosis and is associated with unfavorable graft and patient outcomes (1)
REFERENCES:
1-A roadmap to parathyroidectomy for kidney transplant candidates .Giuseppe Cianciolo, Francesco Tondolo, Simona Barbuto, Andrea Angelini, Francesca Ferrara, Francesca Iacovella, Concettina Raimondi, Gaetano La Manna, Carla Serra, Chiara De Molo .Clinical Kidney Journal, Volume 15, Issue 8, August 2022, Pages 1459–1474,
2-Coyne DW, Delos Santos R. Evaluating the safety and rationale for cinacalcet posttransplant hyperparathyroidism and hypercalcemia. Am J Transplant 2014; 14: 2446–2447
HLA A2 though it is the commonest human MHC Class I molecule but it has low immunogecity , this makes the transplant possible inspite of its presence if there is DNS against it.
· How would you classify the risk of MFI of 1000 (low, intermediate or high)?
Low risk however as low as 100 can be associated with rejection as well, it the correlation between DSA strength and clinical outcome is far from perfect. DSAs with similar mean fluorescence intensity do not always activate the complement cascade.(3)
References
3-Donor-Specific Antibodies in Kidney Transplant Recipients. Rubin Zhang. CJASN January 2018, 13 (1) 182-192;
Provided that all other investigations are satisfactory, would you proceed with transplantation or Para thyroidectomy first?
Indication of Para thyroidectomy:
1.In case of secondary hyperparathyroidism is refractory (PTH were >800 pg./Ml) despite medical treatment.
2.Elevated calcium phosphate product (> 55 to 70)
3.The development of calciphylaxis or severe renal osteodystrophy.
So in this case I will start with medical therapy (cinacalcet), if there is no response or inadequate response, Para thyroidectomy should be done before surgery. is the relevance of DSA against HLA-A2
It can be found in 48% white population. It has low antigenicity . It is Class 1 MHC Allele at HLA -A Locus. HLA- A1 is more antigenic. HLA- A2 can cause graft loss but still one can proceed with transplantation. However induction and close follow up will be required.
How would you classify the risk of MFI of 1000 (low, intermediate or high)?
A MFI of 1000 is considered as low risk but still a follow up and close monitoring is required. There is high immunological risk if MFI is >2000.
Secondary even tertiary hyperparathyroidism is common in ESRD patients. As her calcium and phosphorus are in the normal range, medical management with cinacalcet can be given. Parathyroid scintigraphy can be done to evaluate parathyroid adenoma.
If there is adenoma then parathyroidectomy should be done before transplant. Extensive cardiovascular evaluation should be carried out focusing vascular calcification.
HLA A2 is more common than A1.
MFI up to 1000- low risk
Secondary hyperparathyroidism is very common in CKD5d patients, since her calcium and phosphorus are in the normal range, medical management with calcimimetics can be given. We need to monitor calcium levels as there is a risk of hypocalcemia.
nevertheless we should evaluate by doing dug neck, sestamibi scan to look for parathyroid adenoma. If that is suggestive of adenoma than parathyroidectomy should be done before transplant.
even if there is no parathyroid Adenoma, post transplant monitoring of phosphorus should be done as it raised PTH will cause phosphaturia and hypophosphatemia can cause use rhadomyolysis and ATN
also cardiac and vascular evaluation as it can cause calcification
HLA A2 is more common than A1, however any DSA against class 1 there is a risk for ABMR. MFI up to 1000 against A2 is less immunogenic. Induction agent ATG should be used and after that Triple immunosuppression
2ry hyperparathyroidism is a common complication in CKD that deserves attention and follow up , post transplant persistence of high PTH accord in 20-50% of recipients .
Calcium total and ionized, phosphorus , 25 hydroxy vitD3, neck US , parathyroid scan and bone scan should be done to assess the risk and the MBD if any .
Adenoma is an indication for surgical removal , other wise medical ttt should be implemented using vitamin D , and calcimimetics .
MFI of 1000 is considered a low risk but DSA’s , if -ve cross match we will go for the transplant but with ATG induction .
HLA-A2 is present in up to 40% of population more common than A1
Provided that all other investigations are satisfactory, would you proceed with transplantation or parathyroidectomy first?
if sestamibi done and provide no parathyroid adenoma , i believe can pass for transplantation specially normal ca and po4 main not tertiary hyperparathyroidisim
and no clear cause for surgery and hope improve PTH level with medical treatment like cinacalcet and vit d and transplantation it self .
I,m not study immunological chapter of kidney transplantation before so i’m sorry i can’t answer immunological related question
What is the relevance of DSA against HLA-A2
I donot know the answer exactly
How would you classify the risk of MFI of 1000 (low, intermediate or high)?
for me I donot know the answer exactly as I have very little immunological information
Provided that all other investigations are satisfactory, would you proceed with transplantation or Para thyroidectomy first?
Indication of Para thyroidectomy:
1.In case of secondary hyperparathyroidism is refractory (PTH were >800 pg./Ml) despite medical treatment.
2.Elevated calcium phosphate product (> 55 to 70)
3.The development of calciphylaxis or severe renal osteodystrophy.
So in this case I will start with medical therapy (cinacalcet), if there is no response or inadequate response, Para thyroidectomy should be done before surgery.
What is the relevance of DSA against HLA-A2?
HLA A2 is the most common human MHC Class I molecule, up to as high as 30-50% in certain populations (6).
If the recipient has DSA against HLA-A2, the prospective donor pool for the patient gets limited as donors with HLA-A2 will not be acceptable for the recipient. However, its low immunogenicity makes it acceptable to proceed for transplantation.
How would you classify the risk of MFI of 1000 (low, intermediate or high)?
▪︎We can classify it as low risk.
▪︎The anti-HLA antibodies specificity is classified into 1000, 3000, and 10,000 based on the MFI value.
MFI < 1000 is very weak, < 3000 is weak, 3000 ≤ MFI < 10,000 is moderate, and above 10,000 is strong.
Ref:
[1] Sarah C. Oltmann, etal. KDIGO guidelines and Para thyroidectomy for renal hyperparathyroidism
I agree with my colleague, but I want to add: It will be helpful If we investigate tertiary causes of hyperthyroidism. this patient will respond to cinacalcet. normally we expect low Ca in secondary hyperparathyroidism, but in practice, we face such a case with no adenoma. If only hyperplasia without autonomous foci, medical treatment, and postponing thyroidectomy after transplantation may be reasonable. Ca/P/PTH follow-up is needed and will guide us.
according to (2018 Feb;163(2):373-380. doi: 10.1016/j.surg.2017.10.016. Epub 2017 Dec 25.) data support operation before transplantation or after 1st year if not possible
I will perform partial thyroşidectomy after investigating for adenoma/hyperplasia.
*Provided that all other investigations were satisfactory , I would go for management of hyperparathyroidism first before renal transplantation:
According to KDIGO: I will give chance to medical treatment by cinacalcet starting dose 30mg per day then increase 60 ,90, 120mg reaching to 180mg as necessary, check serum calcium 2 weeks after treatment , if hypocalcemia happened , decrease dose, if no satisfactory response to medical treatment , then proceed for para-thyroidectomy to avoid low turn over disease and wait at least six months for completion of bone healing and, stable bone mineral density . Specially if PTH is still above 1000 pg/mL, it prefers to do pre-transplant para-thyroidectomy , to increase bone healing and bone mineral density.
*In Post renal-transplantation, patient with high parathyroid hormone levels more than 2 folds normal, will continue to rise with persistent hyperparathyroidism post transplantation .
* Although ; Several studies documented that PTH post-kidney transplantation showing initial decrease in first year post-transplant .
* The relevance of DSA against HLA-A2:
HLA-A2 is very common more than HLA-A1 up to 48% and also ; less immunogenic, although any DSA carries risk of AMR.
*MFI of 1000 : is considered to be low risk in most centers and there will be no need for desensitization regimen but follow-up DSA after 3-6 months post-transplantation.
•Provided that all other investigations are satisfactory, would you proceed with transplantation or parathyroidectomy first?
This patient was on dialysis for long time she has hyperparathyroidism which may be secondary or tertiary no data about her ca ,Phosphorus, vitamin D level, parathyroid scanning.
I will start medical treatment first although satisfactory response is uncommon in PTH level above 1000 if failed medical treatment i will go for surgery before transplantation
One of the accompanying conditions from CKD that can remain problematic post-transplantation is secondary hyperparathyroidism (SHPT), which occurs in virtually all patients who have CKD and requires ongoing management during dialysis.
Even after kidney transplantation, recipients can continue to have elevated parathyroid hormone (PTH) levels .
Several studies have evaluated the levels of PTH post-kidney transplantation showing an initial decrease in the PTH levels within the first 12 months post-transplant .
However, in up to 50% of patients there is evidence of a persistent elevation in the PTH years after a successful transplantation
PTH level greater than two times normal (> 130 pg/mL) is consistent with persistent post-transplant hyperparathyroidism
Proper management of SHPT prior to transplantation can minimize PT-HPT and its complications of hypercalcemia and hypophosphatemia.
In general, hypercalcemia post-transplantation is unusual if PTH is maintained in the advanced CKD and ESRD population at less than 600 pg/mL through use of active vitamin D and control of serum phosphate to < 6.0 mg/dL.
If the PTH is > 1000 pg/mL, this is indicative of severe HPT-related bone disease and its prefered to do pre-transplant parathyroidectomy (PTX) with 3½ glands removed as this will lead to marked bone healing and increased bone mineral density (BMD) and obviates the need for cinacalcet post-transplant.
PTX during the pre-transplant period increases BMD much more than surgery after transplantation, it is recommended to wait about 6 months after PTX to allow maximal bone healing and stable serum calcium and phosphate Which can be done in this scenario as we have living donor .
HLA-A2 is very common and present in 40 % of population ,
It is less antigenic but still presence of
DSA is risk factor for ABMR
MFI of 1000 is considered low risk in many centrs and no desensitization is needed if CDC XM and FCXM are negative with follow-up of DSA After transplantation
Management of Post-transplant Hyperparathyroidism and Bone Disease.Rowena Delos Santos, Ana Rossi,Drugs. 2019; 79(5): 501–513.
Provided that all other investigations are satisfactory, would you proceed with transplantation or parathyroidectomy first?
The aim is to avoid complication of hypercalcemia. Hyperparathyroidism can be associated with poor graft outcome and loss. There can be risk of hypertension, peripheral vascular disease and cardiovascular disease , all affecting graft. Hyperparathyroidism after transplant can lead to bone disease including osteopenia and osteoporosis. This along with immune suppressive agents can worsen bone disease.
Her high Parathyroid hormones levels need to be controlled by medical treatment first. This can be done by using Cinacalcet, Vitamin D or Vitamin D analogue. After this response to treatment need to be assessed. If there is failure of medical treatment and PTH level is more than 800 pg/ml then patient will need further testing by ultrasound Neck and Sesmibi scan. She will need review by dedicated parathyroid surgeon and depending upon scan finding may require parathyroidectomy.
What is the relevance of DSA against HLA-A2
It can be found in 48% white population. It has low antigenicity . It is Class 1 MHC Allele at HLA -A Locus. HLA- A1 is more antigenic. HLA- A2 can cause graft loss but still one can proceed with transplantation. However induction and close follow up will be required.
How would you classify the risk of MFI of 1000 (low, intermediate or high)?
A MFI of 1000 is considered as low risk but still a follow up and close monitoring is required. There is high immunological risk if MFI is >2000.
# Provided that all other investigations are satisfactory, would you proceed with transplantation or parathyroidectomy first?
Study of (5094) KT recipients who were treated for SHPT while on dialysis, 228 (4.5%) underwent parathyroidectomy, and 4866 (95.5%) received cinacalcet. There was no association between treatment of SHPT and posttransplant delayed graft function, graft failure, or death. However, compared with patients treated with cinacalcet, those treated with parathyroidectomy had a lower risk of developing THPT (adjusted hazard ratio, 0.56; 95% confidence interval, 0.35-0.89) post-KT. Furthermore, this risk differed by dialysis vintage (Pinteraction = 0.039). Among patients on maintenance dialysis therapy for ≥3 y before KT (n = 3477, 68.3%), the risk of developing THPT was lower when treated with parathyroidectomy (adjusted hazard ratio, 0.43; 95% confidence interval, 0.24-0.79).(1)
** In this case with normal calcium phosphorus and high PTH medical treatment is advise, if no response(tertiary hyperaparathyroidism,
adenoma) then parathyroidectomy can be done.
# What is the relevance of DSA against HLA-A2
* HLA-A*02 is one particular class I HLA. The A*02 allele group can code for many proteins; as of December 2013 there are 456 different HLA-A*02 proteins.Serotyping can identify as far as HLA-A*02, which is typically enough to prevent transplant rejection (the original motivation for HLA identification). Genes can further be separated by genetic sequencing and analysis. HLAs can be identified with as many as nine numbers and a letter (ex. HLA-A*02:101:01:02N).
* HLA-A*02 is globally common Ag (2)
*It is also weakly antigenic.
# How would you classify the risk of MFI of 1000 (low, intermediate or high)?
MFI of 1000 class 1 HLA is low risk , but it need induction with ATG to prevent AMR and close follow up of the patient.
(1)Influence of Pre-Kidney Transplant Secondary Hyperparathyroidism on Later Evolution After Renal Transplantation
García, Victoria; Sánchez-Agesta, Marina; Luisa Agüera, M.; Calle, Oscar; Navarro, M Dolores; Rodríguez, Alberto; Aljama, Pedro
(2) Arce-Gomez B, Jones EA, Barnstable CJ, Solomon E, Bodmer WF (Feb 1978). “The genetic control of HLA-A and B antigens in somatic cell hybrids: requirement for beta2 microglobulin”. Tissue Antigens. 11 (2): 96–112. doi:10.1111/j.1399-0039.1978.tb01233.x. PMID 77067.
Provided that all other investigations are satisfactory, would you proceed with transplantation or parathyroidectomy first?
Progressive decrease in PTH levels is common in the first 3 to 6 months posttransplantation and involution of parathyroid hyperplasia occurs very slowly.
50% of recipients continue to have elevated PTH levels at 1-year
posttransplant; longer-term follow-up has shown that only approximately 25% of recipients have normal PTH levels and 25% continue to have elevated PTH levels > two times normal at 5 years after transplantation.
since it has been described that cinacalcet use prior to transplant is a risk factor for persistent posttransplantation hyperparathyroidism and the patient’s Ca and phosphorus levels are still within normal range. I would prefer no intervention and proceed with transplantation and then close monitoring of PTH and Ca levels.
if he developed hypercalcemia post-transplantation;
There is a lack of evidence supporting specific recommendations regarding the choice between medical and surgical parathyroidectomy but I would prefer cinacalcet (even if its use is still off-label and has not been approved for the treatment of hypercalcemia after transplant by the FDA)
in case of persistent (tertiary) hyperparathyroidism, I would prefer subtotal or total parathyroidectomy with autotransplantation rather than Limited glandular resection.
What is the relevance of DSA against HLA-A2
the presence of DSA against HLA-A2 carries some risk of graft rejection but we can still proceed with transplantation with induction and close monitoring of DSA titer post-transplantation.
How would you classify the risk of MFI of 1000 (low, intermediate or high)?
It is of low risk, yet it is centre-dependent.
◇Provided that all other investigations are satisfactory, would you proceed with transplant- ation or parathyroidectomy first?
▪︎In this case correction of hyperparathyroidism
prior to transplantation is advisable because hyperparathyroidism may compromise outcomes through post-transplant hypercalcemia and graft dysfunction. Transplant recipients may experience bone demineralization and are at increased risk of fracture; however, proven strategies to prevent post-transplant fracture are lacking [1].
▪︎We can start with medical treatment then referred for surgical parathyroidectomy after the patient is felt to be refractory to medical management which is considered when PTH level >800 pg/mL despite treatment [1].
◇What is the relevance of DSA against HLA-A2?
HLA-A*02 is one particular class I MHC allele group at the HLA- A locus. The A*02 allele group can code for many proteins.
▪︎ HLA-A*02 is globally common, but particular variants of the allele can be separated by geographic prominence. So, a significant anti HLA antibodies to this allele can delay transplantation due to decrease the chance of finding a compatible donor.
▪︎ Generally, donor specific antibodies increase the risk of AMR.
◇How would you classify the risk of MFI of 1000 (low, intermediate or high)?
▪︎We can classify it as low risk.
▪︎The anti-HLA antibodies specificity is classified into 1000, 3000, and 10,000 based on the MFI value. MFI < 1000 is very weak, 1000 ≤ MFI < 3000 is weak, 3000 ≤ MFI < 10,000 is moderate, and above 10,000 is strong.
___________________
Ref:
[1] Sarah C. Oltmann, etal. KDIGO guidelines and parathyroidectomy for renal hyperparathyroidism
Provided that all other investigations are satisfactory, would you proceed with transplantation or parathyroidectomy first?
In CKD5 Inspite of well controlled calcium and phosphorus levels, secondary hyperparathyroidsm is still persisting. I expect that patient was given trial of calcimimetic agent (Cinacalcet) to lower down PTH levels but that therapy also failed. this clinically indicates the possibility of developing parathyroid adenomas.
Hence, it will be necessary to do parathyroid nuclear scan (Sestamibi). If there is evidence of adenoma on scan, then she should be managed accordingly for adenona/s removal otherwise parathyroidectomy should be done before transplantation.
What is the relevance of DSA against HLA-A2
Malfait T, Emonds MP, Daniëls L, Nagler EV, Van Biesen W, Van Laecke S. HLA Class II Antibodies at the Time of Kidney Transplantation and Cardiovascular Outcome: A Retrospective Cohort Study. Transplantation. 2020 Apr;104(4):823-834. doi: 10.1097/TP.0000000000002889. PMID: 31369517.
How would you classify the risk of MFI of 1000 (low, intermediate or high)?
I would classify MFI of 1000 as low risk
PTH part is very good.
Please revise HLA- A2
Hi Dr Yashu Saini,
What is the evidence that pre-transplant parathyroidectomy better than post-transplant parathyroidectomy?
Ajay
this patient further evaluation for her high PTH level ( neck u/s , sestamibi scan , ) looking for advanced MBD , correct hper or hypocalcemia , hyperphosphatemia , vit D deficiency ,
If patient had adenoma , persistent hyperparathyroidism despite medical management ,and persistent or symptomatic hypercalcemia she needs parathyredectomy , otherwise she should treated with medical management first such as cinacalcet .
we should try to correct hyperparathyroidism before transplantation because the most important risk factor for post transplant complication is the pth status and degree of high pth before transplantation .
according to : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439149/
Persistent post-transplant hyperparathyroidism is common after kidney transplantation, affects metabolic parameters, and is accompanied by morbidity.Treatments for persistent post-transplant hyperparathyroidism include vitamin D, its analogues, and calcimimetics; regular monitoring is required to avoid adverse effects from treatment.If medical management fails, parathyroidectomy should be considered.
according to : https://journals.lww.com/transplantjournal/abstract/2018/07001/treatment_of_persistent_hyperparathyroidism_after.1028.aspx#:~:text=Hyperparathyroidism%20is%20a%20frequent%20complication,cardiovascular%20events%2C%20fracture%20and%20death.
Hyperparathyroidism is a frequent complication in chronic kidney disease and may persist after transplant in 20 to 50% of cases, manifest by hypercalcemia and hypophosphatemia. Persistent disease is associated with an increase in the incidence of cardiovascular events, fracture and death
HLA- A2 common in population up to 48% and less immunogenic compared to HLA A1
Exellent
Early diagnosis and treatment of nutritional vitamin D deficiency, metabolic acidosis, hyperparathyroidism, osteomalacia, and adynamic bone disease are important in the pretransplantation period. Doing neck u/s and Sestamibi parathyroid scan . Control of hyperparathyroidism with vitamin D analogues, calcimimetic agents for older children and adolescents or even parathyroidectomy, may be required.
For most cases of octeomalacia and dialysis related amyloid bone disease successfully renal transplantation is the best treatment . Persistence of hyperparathyroidism after renal transplantation is common. Most renal transplant recipients have elevated parathyroid hormone (PTH) levels at the time of transplantation, and more than 30% of these patients continue to have elevated levels up to 3 years after transplantation. The duration of time on dialysis and the intensity of hyperparathyroidism before transplantation correlate with the severity of post-transplantation hyperparathyroidism . Hypercalcemia is the most common marker of hyperparathyroidism after transplantation. Patients with persistent hyperparathyroidism that is unresponsive to medical therapy
and those with adenoma may need pretransplant parathyroidectomy
indications of parathyroidectomy tertiary hyperparathyroidism, persistent severe hypercalcemia (>11.5 to 12 mg/dL) for >6 to 12 months, or in those with symptomatic or progressive hypercalcemia (nephrolithiasis, persistent metabolic bone disease, calcium-related allograft dysfunction, progressive vascular calcification, or calciphylaxis) failure of medical treatment and adenoma .
specifically presence of DSA against both HLA class I and II and the strength, as quantified by DSA MFI-Sum, is useful to estimate AMR and graft failure risk in kidney graft recipients. Elevated risk of graft failure is attributable to increased risk of AMR.
Positive with low risk
Very good
Need more information for HLA A2
I would proceed with parathyroidectomy first. in fact, persistent hyperparathyroidism (likely tertiary in this given scenario) carries an adverse progrnosis of the transplant outcome in terms of morbidity and graft survivial.
about DSA against HLA-A2: HLA-A2 is class I HLA antigen, it is quite common in the general population (about 50% prevelance). it carries low immunogencity. i would procced to the transplant without prior desensitization, keeping an eye on antiHLA-A2 DSA levels posttransplantation, especially with an MFI of 1000
MFI of 1000 would classify as low risk. MFI more than 3000 are generally considered high risk, it would also depend on the type (antigenecity) of HLA against which the Abs are produced
Very good .
Try medical treatment first except if you have an adenoma.
· Provided that all other investigations are satisfactory, would you proceed with transplantation or parathyroidectomy first?
This is 34-year-old female patient with:
1. End-stage renal disease (ESRD), on regular haemodialysis
2. Suspect tertiary hyperparathyroidism (PTH > 800pg/ml), ESRD related
3. Hypertension
Successful kidney transplant should free the patient from hyperparathyroidism with renal osteodystrophy (ie chronic kidney disease related mineral bone disease, CKD-MBD). However, up to 80% of the post-KT patients are found to have persistently elevated PTH level. Persistent hyperparathyroidism can lead to several post-KT complications, such as hypercalcemia, hypophosphatemia and related bone disease, as well as nephron-calcinosis and hypertension, which put the patient at risk of recurrent kidney damage. Hence, any hyperparathyroidism in kidney transplant recipients ought to be managed appropriately. Medical therapy for hyperparathyroidism is always the first approach. Parathyroidectomy should be performed prior to transplantation if treatment trial with Cinacalcet has failed to normalize the patient’s serum PTH level.
· What is the relevance of DSA against HLA-A2? How would you classify the risk of MFI of 1000 (low, intermediate or high)?
HLA-A2 is one of the commonest antigens of HLA class I; it’s of low antigenicity and can be found in nearly 48% of the white population. A MFI of 1000 is classified as low risk. However, close monitoring of DSA after transplantation is still required.
References
1. Giuseppe Cianciolo, et al. A roadmap to parathyroidectomy for kidney transplant candidates, Clinical Kidney Journal, Volume 15, Issue 8, August 2022, Pages 1459–1474, https://doi.org/10.1093/ckj/sfac050
Very good.
most of renal transplant patients have high PTH at time of transplantation & more than 30 % of them continue to have elevated PTH up to 3 years after transplantation .
we have to our best for control of metabolic profile pre transplant with control of calcium , phosphorus & PTH ij pre transplant period .
so , the ideal here is to control hyperparathyroidism medically by cinacalcet & vit D analogues first & if failed medical treatment or presence of adenoma by sestamibi scan , this is an indications of parathyroidectomy before transplantation .
HLA-A2 is one particular class I MHC Allele group at the HLA-A locus.
it is very common (found in nearly 50 % of the population).
less antigenic compared to HLA-A1.
presence of DSA against HLA-A2 before transplant can cause early rejection and graft loss and graft loss but here , still we can proceed for transplantation with close monitoring of DSA .
it depend on each laboratory cut off value , but generally , MFI of 1000 is considered low risk
True he is low risk but induction will be needed+ close follow up.
Provided that all other investigations are satisfactory,
would you proceed with transplantation or
parathyroidectomy first?
First of all control PTH before renal transplantation medical by vitamin D, Vit D analog and cinacalcet, If there’s refractory to medical therapy should be referred to surgical intervention for parathyriodectomy if PTH level more than 800 pg/ml before renal transplant. The aim is to avoid complications of hypercalcimea
untreated hyper parathyroid associated with decrease survival rate of allograft function. However secondary hyperparathrodism has risk of cardiovascular and peripheral vascular disease and resistant hypertension which effects function of graft.
persistent hyperparthyrodism after kidney transplantation can also be associated with bone disease, especially bone loss and osteopenia, osteoporosis.
With use of immunosuppressive therapy like steroid and tacrolimus also contribute to osteoporosis with presence of hyperparathyrodism.
What is the relevance of DSA against HLA-A2
HLA-A2 is more common with low immunological risk
How would you classify the risk of MFI of 1000 (low,
intermediate or high)?
It’s low immunological risk
High immunological risk if MFI more than 2000.
What is the relevance of DSA against HLA-A2
HLA-A2 is more common with low immunological risk
It is need desensitisation therapy prior to transplant and close DSA monitoring before and after transplant
With MFI 1000 you will need induction and close followup
Hyperparathyroidism adds many harms to ESRD as cardiovascular events, stone formation, calcifilaxis, refractory anemia to ESA, and pathological fractures.
This patient likely have secondary hyperparathyroidism, excluding the presence of pituitary adenoma or carcinoma is necessary pretransplantation by ultrasound and parathyroid scan.
Correction of hyperparathyroidism must be performed before transplantation to reach acceptable levels around 800 pg/ml. Trial should be started by cinacalcet by 30 mg then titration of the dose after three weeks gradually up to 180 mg provided that monitoring of calcium levels as cinacalcet may induce hypocalcemia.
Parathyroidectomy is indicated after failure of response to cinacalcet, refractory hypocalcemia, hypophosphatemia, parathyroid adenoma, parathyroid malignancy, resistant anemia.
Renal transplantation in this case is considered an elective procedure as it is from a living donor and no vascular access failure for haemodialysis. So treatment of hyperparathyroidism comes first in this lady before renal transplantation.
The relevance of DSA against HLA A2:
A2 is considered by far less antigenic than A1, but it is still weak immunogenic proposing risk of graft rejection as it is a common allele by about 50 % of population. It still requires regular monitoring against their titres and interference by immunoadsorption or plasmapheresis if their level exceeded the acceptable range.
Many centers classify MFI of 1000 of low value, titers are considered high when they exceed 3000 and require follow up as well as adopting desensitization plan according their protocol.
Thankyou very good
Most ckd patients have some degree of secondary hyperparathyroidism (15-50 may persist following transplantation)
The optimal treatment of hyperparathyroidism before transplant prevent post transplant recurrence.
All patient with refractory or moderate to sever disease or sever symptoms sould undergo parathyroidectomy.
Patient with mild or no symptoms with pth >800 also recommend to do parathyroidectomy
Cause it unlikley to response to treatment and increase risk for graft failure
Cinacalcet may be used before transplantation in refractory patient.
I will do parathyroidectomy for this patient then proceed to transplantationwith monitor of pth calcim phosphore after transplantation .
It is a common hla class 1 founded in 50 % of population
It is weak immunogenic, however could cause graft rejection.
It depends on the center that do the transplantation and the type of hla molecule class.
For class 1 hla molecule ,an mfi of 1000 consider low risk
However, it is not always reiable and correlation between dsa stregnth and clinicaly outcome is far from perfect
Reference
Uptodate
Very good
Provided that all other investigations are satisfactory, would you proceed with transplantation or Para thyroidectomy first?
Dialysis patients who have PTH levels >800pg/ml are more prone to develop fractures and have increased cardiovascular morbidity and mortality .KDIGO recommendation is to proceed for Para thyroidectomy if medical treatment fails before renal transplantation to control severe hyperparathyroidism. In the above vignette, as the patient has normal calcium and phosphorus but have elevated PTH levels, medical therapy should be tried followed by subtotal Parathyroidectomy or total Parathyroidectomy with fore-arm auto-transplantation
What is the relevance of DSA against HLA-A2?
Class I has two allele group HLA-A1 and HLA-A2 .A2 is more common, but less immunogenic. However, presence of DSA against A2 can still lead to graft rejection and ultimately graft failure.
How would you classify the risk of MFI of 1000 (low, intermediate or high)?
Different centers have different cutoff values for MFI. Generally,MFI>2000 for class I and MFI >5000 for class II are considered significant. In the above case, the patient has MFI of 1000, so considered low risk. But still the patient will need close monitoring post transplant due to the risk of rejection.
REFERENCES:
1-Chadban SJ, Ahn C, Axelrod DA,et al. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation. 2020 Apr;104(4S1 Suppl 1):S11-S103
Thankyou Batool very good.
This 34years old ESKD on hemodialysis on the waiting list for 5years, now she has an offer from her cousin. She is found to have PTH 1350pg/ml.
The question is can we go for transplantation first or do parathyroidectomy before that?
The current PTH level is far above KDIGO guidelines which is up to 9times the upper limit of normal, i.e. up to 585pg/ml. If she is on maximum medical management and not improving, she needs to go for parathyroidectomy before transplantation as this was shown to be better. Also, it is known that the success of medical treatment when PTH level above 1000 is very low. Before parathyroidectomy we need to do imaging of the gland to see if there is single adenoma, carcinoma or just hyperplasia. The modalities available are parathyroid ultrasound and sestamibi scan. Since the patient has living donor and no urgency for transplant it is better to optimize the parathyroid level to at least less than 800pg/ml at time of transplantation as per KDIGO guidelines.
What is the relevance of DSA against HLA-A2 and How would you classify the risk of MFI of 1000 (low, intermediate or high)?
HLA A2 is relatively common in up to half of transplant candidate, there for finding DSA against it will make it difficult to find suitable donor. However, it is less antigenic than HLA A1 and HLA B and level of 1000 is considered low by most laboratories.
References:
1-(Transplantation 2020;104: S1–S103).
2-Tissue Antigens 1995 Apr;45(4):223-31. doi: 10.1111/j.1399-0039.1995.tb02444.x
3-Am Surg . 2002 Sep;68(9):812-5. The sestamibi scan as a preoperative screening tool
4-Clinical Kidney Journal, 2022, vol. 15, no. 8, 1459–1474 A roadmap to parathyroidectomy for kidney transplant candidates
Provided that all other investigations are satisfactory, would you proceed with transplantation or parathyroidectomy first?
KDIGO guidelines suggest Treating hyperparathyroidism before transplant medically after scanning by USG and sestamibi parathyroid scan to rule out adenoma or surgically.
As this pt has normal calcium and phosphorus level , so we will give chance for medical treatment and if failed then for surgical removal with target i PTH less than 800 as per KDIGO guidelines
Hyperparathyroidism increases risk of fractures and cardiovascular complications also treating hyperparathyroidism before transplant reduce risk of graft function worsening.
Also this pt has live related donor ,so no hurry to go first for transplant and must treat her parathyroidism first.
What is the relevance of DSA against HLA-A2?
HLA A2 is MHC class I and is very common around 30- 50% of the population has A2 , so presence of DSA against A2 making difficulty in finding suitable donor
Although it is common , it is less antigenic but still preformed antibodies can cause rejection
How would you classify the risk of MFI of 1000 (low, intermediate or high)?
There is difference in cutoff value for MFI from center to center
Generally, it is considered significant if class I MFI more than 2000 and class II more than 5000
So in this case considered low but need regular follow up post transplant .
Exellent
Exellent and to the point
In the first instance I would investigate her high PTH as this could be also be a primary hyperparathyroidism (as this may present with normal serum phosphate and borderline normal-high serum Calcium). I would request a radiological investigation (ultrasound, sestamibi scan) to elucidate the underlying diagnosis.
This patient will require a treatment before transplantation (medical or surgical treatment) as per KDIGO guidelines.
She is a haemodialysis patient therefore at high cardiovascular risk. We have to remember that hyperparathyroidism may persist after transplant in 20 to 50 % of cases, manifest by hypercalcemia and hypophosphatemia. Patient with hyperparathyroidism are associated with increased incidence of cardiovascular events as well as fracture and death.
Patients with severe Hyperparathyroidism need to be treated before Kidney Transplant (as per KDIGO guidelines), and if medical treatment fails, parathyroidectomy before kidney transplant should be done. Guidelines suggest measuring serum PTH at the time of transplant evaluation and that patients with severe hyperparathyroidism (PTH > 800 mg/dL) should not be transplanted until they are adequately treated.
HLA-A2 is one particular class I MHC Allele group at the HLA-A locus. HLA-A2 is globally common (found in nearly 50 % of the population), but particular variants of the allele can be separated by geographic prominence with low immunogenicity compared to HLA-A1.
DSA identified before kidney transplant can cause early rejection and graft loss and graft loss
It depend on the laboratory as the cut off varies with different lab. However, for most of the lab an MFI of 1000 is considered low risk
References:
1) Clin Kidney J. 2022 Aug; 15(8): 1459–1474. Published online 2022 Feb 23.
A roadmap to parathyroidectomy for kidney transplant candidates
Giuseppe Cianciolo, Francesco Tondolo, Simona Barbuto, Andrea Angelini, Francesca Ferrara, Francesca Iacovella, Concettina Raimondi, Gaetano La Manna, Carla Serra, Chiara De Molo, Ottavio Cavicchi, Ottavio Piccin, Pasquale D’Alessio, Loredana De Pasquale, Giovanni Felisati, Paola Ciceri, Andrea Galassi, and Mario Cozzolino
2) Donor-Specific Antibodies in Kidney Transplant Recipients. Rubin Zhang. Clinical Journal of the American Society of Nephrology
3) Transplantation 2013 Jan 15;95(1):19-47. doi: 10.1097/TP.0b013e31827a19cc.
Consensus guidelines on the testing and clinical management issues associated with HLA and non-HLA antibodies in transplantationBrian D Tait 1, Caner Süsal, Howard M Gebel, Peter W Nickerson, Andrea A Zachary, Frans H J Claas, Elaine F Reed, Robert A Bray, Patricia Campbell, Jeremy R Chapman, P Toby Coates, Robert B Colvin, Emanuele Cozzi, Ilias I N Doxiadis, Susan V Fuggle, John Gill, Denis Glotz, Nils Lachmann, Thalachallour Mohanakumar, Nicole Suciu-Foca, Suchitra Sumitran-Holgersson, Kazunari Tanabe, Craig J Taylor, Dolly B Tyan, Angela Webster, Adriana Zeevi, Gerhard Opelz
Exellent
First of all, this is young patient on hemodialysis for the last 5 years with unknown etiology of end stage renal disease. So initial evaluation should target the possible causes of ESRD. Severe hyperparatyhroidism in this lady put the patient at higher risk of developing cardiovascular complications along with osteoporosis in the postoperative period and also reduce graft survival.
In this clinical scenario calcium and phosphorus are normal, so we aim to reduce PTH level using cinacalcet or etelcalcetide. Vitamin d supplementation is essential in this patient with high risk of fractures. Vitamin d analogues van be also used as part of the treatment of 2ry hyperparathyroidism. If this patient does not respond to medical treatment and PTH levels are consistently above 800 mg/dl then the patient should undergo parathyroidectomy before transplantation.
HLA- A2 ia a common antigen iwith a prevalence of 48% in white population. it is less immunogenic when compared to HLA A1.
Having MFI of 1000, indicates low risk for transplantation by most labs.
Cutoff of MFI that define high risk is >2000 for class I DSAs and>5000 for class II DSAs
Hi Dr Shawky,
How useful is nuclear scan or MRI in localizing parathyroids in a patient with secondary hyperparathyroidism?
Hi dear professor,
We usually start with parathyroid gland ultrasonography which can only visulaize large ademoas. Then nuclear scan is the best modality to detect adenoma as MRI has poor delineation and high possibilty of artefact in addition of inability to use iodinated contrast especially in predialysis CKD
During surgery for secondary or tertiary hyperaparathyroidism one has to look at all the 4 parathyroids.
The most important step in surgical management of secondary or tertiary hyperparathyroidism is ‘localize a good endocrine surgeon’.
1. Optimization of CA, phosphorus and PTH levels prior to transplantation is essential as persistent hyperparathyroidism after transplantation can be associated with the risk of hypercalcemia, hypercaciuria and graft loss. In addition to hypophosphatemia with it’s deleterious effect on muscles and rhabdomyolysis
_ so, 1st we should revise medical treatment if this patient.
_ medical treatment include phosphate binders either calcium containing (used if Ca level is low) or non CA containing (selevamer) if Ca level is normal.
_ active vit D , as long as CA ,phosphorus product is less than 55, or in case of low ca level.
_ optimization of the dialysis parameters and ensuring adequate dialysis duration is essential to control hyperphosphatemia.
_ in such very high readings of PTH, and normal CA , calcimimetics (cinacalcet )can be used to imhibit PTH.
_ if all above lines of medical treatment were used and failed to reduce PTH. Level, this means that secondary hyperparathyroidism turned to be 3ry or parathyroid adenoma is present with autonomous PTH secretion (regardless CA and po4 levels).
_ parathyroid gland scan to detect adenoma is essential prior to transplantation and parathyroidectomy in order to reach accepted levels of PTH prior to transplantation.
_ persistent hyperparathyroidism post transplantation is associted with risk of graft loss, hypercalcemia and bone fractures.
2. HLA , A2 is most common antigen of HLA class I , which means that it can be unacceptable Ag if the recipient has DSA against it. However, its low immunogenicity makes it acceptable to proceed for transplantation. ( With rATG induction and tac based triple immunosupressives). With close follow up of DSA after transplantation.
_ although DSA MFI is low, it can be still associted with risk of ABMR.
3. MFI is considered significant if more than 2000 in class I and more than 5000 in class II, so level of 1000 is considered low Risk.
Exellent Mai
HLAa2 is also a very common antigen nearly 48% in white comunities
It is also weakly antigenic.
True you can proceed with a low MFI (weak + FCXM) but a memory T lymphocyte and B cells reaction can take place so DSA levels have to be closely monitored .
Medical treatment is generally the first step of SHPT but parathyroidectomy provides better long-term control of calcium and PTH values
* The 2020 KDIGO clinical practice guidelines on evaluation of candidates for KT contains a chapter dedicated to the preparation of the KT candidate with CKD-MBD. The rationale is that severe HPT needs to be treated before KT, and if medical therapy fails, pre-KT parathyroidectomy is indicated.
* As our patient has two risk factors of persistent SHPT ( long dialysis vintage, high pre-KT PTH levels ) So I’ll proceed with parathyroidectomy before kidney transplantation to prevent persistent hyperparathyroidism and improve graft outcomes
” HLA A2 is the most common class I molecule Therefore presence of HLA A2 antibodies will reduce the donor pool.
Most centers use a cut-off MFI of 1,000–1,500 so I consider MFI of 1000 is low risk