KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention and Prevention of Chronic Kidney Disease–Mineral and Bone Disorder (CKDMBD): Indian Commentary

Introduction

Chronic kidney disease–mineral and bone disorder (CKDMBD) guidelines were initially framed in 2009.[1] Indian commentary was published in 2011.[2] The work group analyzed the studies done after 2009 and a Controversies conference held in 2013. Subsequently updated guidelines came in 2017[3] followed by KDIGO commentary.[45] There are 21 updated recommendations/suggestions reviewed in KDIGO 2017, 8 of them (38%) remain “ungraded” and all of the others were graded Level 2 which, according to the KDIGO nomenclature and description for rating guideline recommendations, means that “Different choices will be appropriate for different patients.” As a result, management of CKDMBD in patients should be individualized, multi-professional and often pragmatic in its approach. The most significant change in the update is a move away from treating to specific targets towards a more personalized approach. UK renal association published the UK commentary in 2018.[6] In view of recent updates by KDIGO 2017 and recent new evidences there is a need to update the Indian commentary as well.

Commentary

Earlier Indian commentary stated that routine BMD testing by Dual-energy X-ray absorptiometry (DEXA-BMD) should not be performed as DEXA-BMD does not help in determining type of renal bone disease and was earlier not thought of be predictive of fracture risk. Quantitative CT was suggested as a better tool for BMD assessment.[23] QCT can differentiate cancellous and cortical bone. However, QCT is expensive, has radiation exposure and has limited availability and is not useful for screening for BMD. Four prospective cohort studies subsequently demonstrated that measurement of BMD by DXA predicted fractures in adults with CKD stages G3a to G5D.[78910] Studies also demonstrated that the World Health Organization (WHO) T-score thresholds are predictive of fracture risk in CKD. BMD by DXA showed a low bone mass in 41.05% of patients and was more prevalent in CKD stage 5 in an Indian study.[11] Fracture is painful and incapacitates the individual and is associated with increased mortality; therefore, patients with or at risk for fractures require treatment. Fractures are 2100× as common in CKD and occur 1015 years earlier and mortality is 3 times higher.[12] Hence BMD is recommended to assess risk of fractures so that treatment can be initiated. BMD should be assessed by DEXA. Frequency of testing may be once in a year or once in 2 years.[12] If T score is <-2.5 and/or fracture, treatment is recommended. However, before initiating therapy adynamic bone disease or osteomalacia should be ruled out.

Fracture Risk Assessment Tool (FRAX) can be considered in stratifying patient for risk of fracture. If BMD testing cannot be done due to cost, Indian FRAX score which is independent of BMD can be used.[8] FRAX score has been studied both in non-dialysis[13] and dialysis CKD.[14] Data in Indian CKD is limited and there is need for studies in this area.

(KDIGO 2009)

3. 2.1. In patients with CKD G3a–G5D, it is reasonable to perform a bone biopsy in various settings, including, but not limited to: unexplained fractures, persistent bone pain, unexplained hypercalcemia, unexplained hypophosphatemia, possible aluminum toxicity, and prior to therapy with bisphosphonates in patients with CKDMBD (Not Graded).

(2017 UPDATE)

3. 2.2: In patients with CKD G3a to G5D, it is reasonable to perform a bone biopsy if knowledge of the type of renal bone disease will impact treatment decisions. (Not graded)

Order of guidelines changed as BMD may impact biopsy decision.

Commentary

Update suggests that circulating levels of parathyroid hormone (PTH) and bone specific alkaline phosphatase can be used in the clinic to evaluate patients for bone disease, because significantly high or low values reflect underlying bone turnover; bone biopsy may be used when diagnosis of turnover is not clear.

Although bone biopsy is the gold standard for the diagnosis of renal bone disease type and can inform treatment decisions, it is subject to important limitations, including cost, availability at only a few centers worldwide, time-consuming measurements, its ability to determine bone disease type at only a single time point, its degree of invasiveness and discomfort to the patient, and the fact that it has never been shown to predict fracture risk.[12] The update acknowledges these limitations. Although bone biopsy is the best test to confirm bone disorders in CKDMBD, it is currently not feasible in India, Indian clinicians and researchers need to work toward development of few referral centers for the same.

Commentary

The KDIGO statement of lowering high phosphorus and maintaining serum calcium level to normal level was widely in agreement to all. However, phosphorus value may depend on nutritional status, dietary intake and dietary pattern whether patient is vegetarian or nonvegetarian. Study form India had observed a very high prevalence to malnutrition at beginning of dialysis from our CKD cohort, 68% of patients had mild to moderate malnutrition and 7% had severe malnutrition.[15] The study also observed that the average protein intake was also lower than recommended. In view of high prevalence of malnutrition and low protein intake in Indian subjects, the interpretation of low-normal phosphorus value become complex. Moreover, enforcing excessive dietary restrictions for control of hyperphosphatemia in those with protein energy malnutrition may ensue deterioration in nutritional status. Low phosphate levels should be managed by first judging the protein intake and nutritional status of the patients.

There is general consensus that phosphorus level should be brought towards the normal value. The recent KDIGO guidelines and the recent commentary by KDOQI (unlike older KDOQI) on KDIGO guideline agree for that part statement.[3] Although, they have not set forth any target phosphate values, but we feel that the older KDOQI targets, though less evidence-based, might still be useful to guide therapy in different stages of CKD in Indian scenario, where general physicians treat large number of early CKD patients and a general guidance will be required for them. It was suggested that the recommended targets for CKD stage 34 could be 34.6 mg/dl, whereas it is appropriate to try and bring the phosphate towards 3.5–5.5 mg/dl in Stage 5.

KDIGO also emphasized that calcium, phosphorus and PTH should be interpreted together, however the single values may be misleading and serial trending values should be encouraged particularly in stage-5D as these values may be dynamic on follow-up and substantial biological variability in PTH may complex it further. We agree that hypercalcemia should be avoided. However, we should also keep in mind that there is low dietary intake of calcium in the diet in both adult and children in general population in India and Asia during dietary prescription.[1617]

Serum calcium and corrected value for serum albumin level particularly in patients with malnutrition should also be considered in Indian scenario. Age appropriate serum calcium level is important for children of growing age.

The awareness about dialysate calcium content in India is low and not prevalent in practice in dialysis unit. However, it is important to emphasize that calcium dialysate should be used at a concentration of 5–6 mg/dL in patients on dialysis. Its value also lies in the fact that this allows increased use of the cheaper calcium-containing phosphate binders. There is not very strong evidence supporting the use of one phosphate binder over others. Strong evidences for lesser use of calcium-based phosphate binders are lacking. Emphasis should be on calcium level. In adults Calcium can be maintained between 8.5 and 10.2 mg/dl and must be adjusted for age in children. Average ost of calcium containing phosphate binders in India is 2.70 INR for 500 mg calcium carbonate (dose 1500 mg per day) while that of sevalamer 400 mg is 15 INR (dose 2400 mg per day) and lanthanum 500 mg is 20 INR per tablet (dose 30004500 mg per day). The choice of binders depends on the overall clinical and biochemical evaluation and economic factors such as cost of therapy and the reimbursement status.

It might be prudent to restrict the use of calcium-based phosphorus binders in high-risk subjects, such as those CVD risk including vulnerability to vascular calcification, risk of hypercalcemia and adynamic bone disease. In those without and risk factors, Calcium carbonate can be used as phosphate binder with maximum dose of 1500 mg elemental calcium per day. A combination of calcium containing and non- calcium containing binders may also be used.

To achieve desired serum phosphorus level, aluminum-based phosphate binder should be avoided in general and should only be advocated for a brief period, preferably 812 weeks when phosphorus level is very high and not well controlled with nonaluminum-based binders. The suggested limited period has been set arbitrarily in absence of any evidence. Studies regarding measurement of the daily phosphate consumption in various Indian meals are lacking. Bioavailability of phosphorus in phytate-based diet is inferior compared to animal protein-based phosphorus and phosphorus containing in processed food. An assessment of protein and phosphorus intake should be made before restricting phosphorus. In patients where a high protein intake is mandatory because of severe protein energy malnutrition, phosphate binders are preferred over dietary restrictions. It is also important that managing the various dietary issues requires the skills of an experienced dietician, even better if he/she is expert in taking care of patients with kidney disease. However, trained dietician for all calculation and providing dietary prescription is lacking in majority of Indian dialysis center and we feel that there is a need to develop this capability. We feel that in difficult scenario where serum phosphorus is difficult to control with measures like dietary intervention, and phosphate binders, the change in dialytic modality should be considered.

Impact on clinical practice and recommendations to Indian nephrologists:

1. Recommendation 4.1. by KDIGO (2017) is valid in Indian Scenario as well

2. Serum phosphate level should be maintained within the normal range in patients with G3a–G5 and try lowering elevated phosphate levels toward the normal range in dialysis patients

3. Maintaining serum calcium within normal range and attempt should be made to avoid not only hypercalcemia, but hypocalcemia as well

4. In patients with poor nutritional status, suppressed appetite and inadequate dialysis, a prevalent situation in Indian scenario, we should look for calcium intake and corrected calcium for serum albumin level as well. Hypocalcemia may worsen secondary hyperparathyroidism and hypercalcemia vascular calcification. Low dialysate calcium should be used in patients with hypercalcemia

5. Consider analysing calcium, phosphorus, hypovitaminosis D and PTH level altogether to optimize the CKDMBD management

6. Instead of single value, serial changes in the values of biochemical parameters should be taken in account to decide the treatment.

Commentary

A major departure from the 2009 guidelines is that clinicians are advised to react to the trend of iPTH values rather than a single elevated value. The basis for this recommendation is that iPTH elevation is a compensatory phenomenon to promote phosphaturia, which aids in maintaining serum phosphate within the normal range, besides implying skeletal resistance to iPTH. In addition, intra and inter-assay coefficient of variation, diurnal[18] and dietary[19] variations, and individual patients’ adherence to prescribed medications,[20] all of which impact iPTH, serum phosphate and serum calcium levels, add to the inherent variability of iPTH levels. In light of these factors, aggressive lowering of iPTH-based on a single value that is above the upper normal limit is no longer justifiable. Whereas, this approach may seem conservative, the recommendation to act on “progressively rising” iPTH levels and not just values that are “persistently above the upper normal limit”, suggests that a rising trend, even in patients whose iPTH values lie within the normal range for the assay, should prompt clinicians to intervene. This is a pro-active rather than reactive approach, and of special relevance to CKD Stage G3-4 patients on follow up, in whom the management of CKDMBD is often accorded low priority. The scope for intervention is huge, given that, 5270% of incident Indian CKD Stage G3, and 7389% of incident Indian CKD Stage G4 and 5 patients have iPTH values more than 2 times the upper limit of normal.[1121222324] However, it is important to note that the response to persistently elevated or rising iPTH levels should take the form of an active search for modifiable factors, rather than the blanket administration of activated vitamin D to reduce iPTH levels, which is commonly practiced in India. The wisdom in this approach is amply brought out by the fact that hyperphosphatemia, hypocalcemia and vitamin D deficiency are present in 3283%, 2571% and 5095% of Indian CKD Stage G3-5 patients.[1121222324] Targeting these risk factors has been shown to lower iPTH levels.[2526] The 2017 guidelines have included high dietary phosphate intake as a modifiable risk factor, acknowledging that high phosphate intake can elevate PTH without a corresponding rise in serum phosphate levels. Upto 20% of incident Indian CKD Stage G4-5 patients are vegan,[23] and the remaining are lacto-ovovegetarians or nominal non-vegetarians. Barring regional, religious and cultural variations, dietary phosphate intake is unlikely to be a major driver of hyperparathyroidism in India, though with rising incomes, changing food habits and greater consumption of dairy products, processed food and carbonated beverages, this is likely to change. While we agree with these updates to the KDIGO recommendation, we believe it is important to recognize that in the Indian context, where CKD patient follow up is poor, many clinicians may not have access to more than one iPTH value, and the failure to act on modifiable risk factors at the first instance may be deleterious to the patient.

Points that need further clarification:

Despite the 2017 KDIGO guidelines laying emphasis on sequential monitoring of iPTH to determine the trend of iPTH values, the magnitude of increase in iPTH and the time period that must elapse before such increase becomes actionable, have not been defined. This assumes importance because KDIGO has not suggested any alteration in the frequency of iPTH measurement in Chapter 3.1. The frequency of iPTH monitoring remains at the discretion of the clinician in Stage G3, 612 monthly in Stage G4, and 36 monthly in Stage G5.

Impact on clinical practice and recommendations to Indian nephrologists:

1. We suggest that in CKD Stage G3-5, iPTH be monitored as follows:

   • CKD Stage G3: Once at baseline and yearly thereafter

   • CKD Stage G4: Once every 6 months

   • CKD Stage G5 and G5D: Once every 3 months

   We agree with the KDIGO recommendation that modifiable factors must be identified if there is either a persistent rise in iPTH levels or persistently high iPTH levels above the normal range of the assay

2. We further suggest, that in CKD Stage G3–5 patients presenting with iPTH above the normal range of the assay, who are likely to be irregular on follow up, modifiable risk factors be addressed at the first instance.

KDIGO 2009

4. 2.2. In patients with CKD G3a–G5 not on dialysis, in whom serum PTH is progressively rising and remains persistently above the upper limit of normal for the assay despite correction of modifiable factors, we suggest treatment with calcitriol or vitamin D analogs (2C).

UPDATE 2017

4. 2.2. In adult patients with CKD G3a–G5 not on dialysis, we suggest that calcitriol and vitamin D analogs not be routinely used (2C). It is reasonable to reserve the use of calcitriol and vitamin D analogs for patients with CKD G4– G5 with severe and progressive hyperparathyroidism (Not Graded).

In children, calcitriol and vitamin D analogs may be considered to maintain serum calcium levels in the age-appropriate normal range (Not Graded).

Commentary

The PRIMO (Paracalcitol Capsule Benefits in Renal Failure Induced Cardiac Morbidity)[27] and OPERA (Oral Paracalcitol in Stage 35 Chronic Kidney Disease)[28] randomized control trials failed to demonstrate improvement in cardiac structure or function with paricalcitol supplementation (2 μg and 1 μg PO once daily over 48 and 52 weeks, respectively), despite a decrease in iPTH levels. On the contrary, an increased risk of hypercalcemia was seen (22.6% in PRIMO had 2 consecutive serum calcium readings >10.5 mg/dL, 43.3% in OPERA had a single reading >10.2 mg/dL). These studies formed the basis for the KDIGO update suggesting that calcitriol and vitamin D analogs be reserved for patients with severe and progressive hyperparathyroidism. However, several important observations regarding these RCTs need to be made. At baseline, the median iPTH level was 1.5-2 times to the upper limit of the assay (100 pg/ml in PRIMO and 156 pg/ml in OPERA) and neither study included patients with iPTH levels >300 pg/ml. Mean serum calcium concentration at baseline was 9.29.6 mg/dL and there was high concomitant use of calcium-based phosphate binders (70% of those who developed hypercalcemia in the OPERA study; the PRIMO study did not report calcium supplement usage). By study end, median iPTH level in the treatment arms was 51 pg/ml. OPERA, which was carried out in Chinese patients, used a lower paricalcitol dose than PRIMO (which was a multicenter study but enrolled only 12% Asian patients) and was still able to demonstrate significant iPTH (over) suppression, indicating that racial differences in response to vitamin D analogs need to be taken into consideration. Although not a primary endpoint, the intervention arm in both studies had fewer cardiovascular related hospitalizations.

In India, dietary intake of calcium is poor and influenced by socioeconomic status.[16] Vitamin D deficiency is widespread due to low dietary intake, lack of a vitamin D food fortification programme, darker skin pigmentation and lower sunlight exposure owing to sedentary habits and atmospheric pollution.[29] As a result, nutritional bone disease is ubiquitous even in healthy adults.[30] In incident CKD Stage G4-5 patients, upto 60% have biochemical features consistent with high turnover bone disease with osteopenia and osteoporosis present in 37% and 12%.[22] Osteoporosis was also linked to elevated iPTH. A small RCT in 30 Indian adult CKD patients (20 in the intervention arm, 10 in the control arm) with iPTH >180 pg/ml (mean iPTH was 549 pg/ml) and eGFR <30 ml/min studied the effect of calcitriol 0.5 μg PO administered daily for 12 weeks on left ventricular systolic and diastolic function. While systolic function was not different between the two arms, diastolic function, in the form of A velocity and E/A ratio, improved significantly in the intervention arm.[31] Notably, the mean serum calcium at baseline in this study was 8.8 mg/dL and rose to 9.3 mg/dL by study end. Although the study duration was short and the sample size small, we believe this provides preliminary evidence that vitamin D analogs may still have a role in the Indian CKD population. The 2009 KDIGO guidelines recommended that calcitriol and vitamin D analogs should only be considered if hyperparathyroidism persists despite correction of modifiable risk factors. This suggests that vitamin D analog therapy should be initiated when serum calcium levels are in the normal range, the unintended consequence being a higher incidence of hypercalcemia.

Between 20 and 39% of Indian Stage G35 CKD patients are on calcitriol at the time of presentation to a tertiary care hospital,[1123] most commonly in a fixed dose combination with calcium. While the prevalence of hypercalcemia at baseline in incident patients is low (1.98.8%),[11212324] in prevalent CKD Stage 5D patients, this figure is 15%,[21] reflecting the impact of unmonitored calcium and vitamin D analog supplementation. The OPERA trial showed that hypercalcemia with paricalcitol therapy was easily managed by discontinuation of calcium containing phosphate binders. In the light of these observations, we believe that vitamin D analog therapy should not be withheld from patients with persistently rising or elevated iPTH after correction of modifiable factors, and that the dose of calcium containing phosphate binder should be reduced, or patients shifted to a non-calcium containing phosphate binder when doing so. We agree with the KDIGO recommendation to initiate calcitriol and vitamin D analog therapy to maintain serum calcium in the age appropriate range in children.

Commentary

The Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial, in which patients with moderate to severe hyperparathyroidism on dialysis were randomized to receive cinacalcet or placebo for upto 64 weeks, failed to meet its composite primary endpoint of reduction in all-cause mortality, nonfatal myocardial infarction, hospitalization for unstable angina, peripheral vascular events and congestive heart failure.[32] The guideline summary acknowledged that cinacalcet may still be of benefit in patients aged >65 years, in whom the primary end point was met[33] and a significant reduction in fragility fractures was seen.[34] In addition, cinacalcet use was associated with a reduction in incidence of severe unremitting hyperparathyroidism (>1000 pg/ml), with hypercalcemia and parathyroidectomy.[35] However, owing to the negative results with respect to the primary end point in the EVOLVE study, and the results of the PARADIGM trial[36] that compared cinacalcet and active vitamin D monotherapy in dialysis patients and found them to be equally effective in lowering PTH,[36] the KDIGO 2017 guidelines do not recommend the use of any one PTH lowering therapy over the other. To emphasize this, the authors have clarified that PTH lowering drugs have been mentioned in alphabetical order, and not in order of preference in the recommendation. In a departure from the 2009 guideline, the 2017 guideline no longer mentions the factors that need to be taken into consideration while choosing the appropriate PTH lowering therapy, nor does it specify when therapy must be discontinued.

We agree that there is currently no evidence to support the use of one PTH lowering therapy over the other, and emphasize that the clinician must choose the appropriate therapy keeping in mind the individual patient's calcium, phosphate and iPTH levels. Regular monitoring of these parameters, in keeping with KDIGO recommendations, is essential to avoid treatment related complications. In India, the cost of cinacalcet and higher propensity to develop hypocalcemia without concomitant vitamin D and/or calcium supplementation is a major consideration to be kept in mind.

Impact on clinical practice and recommendations for Indian nephrologists

1. We recommend that in CKD G5D patients, clinicians choose the appropriate PTH lowering therapy weighing biochemical parameters such as calcium, phosphate and iPTH levels as well as the cost of treatment

2. We recommend that once PTH lowering therapy is initiated, calcium, phosphorus and iPTH be monitored as recommended, to avoid iatrogenic complications of hypercalcemia, hypocalcemia and hyperphosphatemia.

(KDIGO 2009. UPDATE 2017 No change)

4. 2.5: In patients with CKD G3a–G5D with severe hyperparathyroidism (HPT) who fail to respond to medical or pharmacological therapy, we suggest parathyroidectomy (2B).

Commentary

The 2009 KDIGO CKDMBD guidelines suggested that patients with CKD Stage G1-3 with low BMD and/or fragility fractures and iPTH in the normal range be managed with anti-resorptive therapy along the same lines as the general population. In patients with CKD Stage G4-G5D with biochemical abnormalities of CKD-MBD, low BMD on DEXA and/or history of fragility fractures, bone biopsy is advised before anti-resorptive therapy. The 2017 KDIGO CKD-MBD recommendation has broadened the consideration for anti-resorptive therapy and anabolic therapy to include Stage G4-G5D, and bone biopsy is suggested, but no longer considered essential prior to initiating anti-resorptive therapy. This change in policy was mandated by the growing body of evidence supporting the safety and efficacy of anti-resorptive agents, such as bisphosphonates (alendronate, risedronate)[373839] raloxifene,[4041] denosumab,[42] and anabolic agents e.g., Teriparatide[4344] in CKD G3a-G4, the recognition that fracture risk progressively increases with declining GFR[32] and the lack of conclusive evidence that anti-resorptive therapy use in CKD causes low bone turnover over and above that seen in the general population. Moreover, facilities for performing and interpreting bone biopsies are not widely available even in the developed world, due to which patients with high fracture risk who might have benefited from anti-resorptive therapy were denied it. The guideline makes note of the fact that biochemical abnormalities contribute to low BMD and increased fracture risk, and it is therefore implied that wherever these are identified, appropriate measures for their correction be implemented.

We agree with the letter and spirit of this recommendation and make two additional comments. First, Indian nephrologists need to rule out locally prevalent metabolic bone disease syndromes prior to initiating anti-resorptive therapy. These include osteomalacia due to vitamin D deficiency, endemic fluorosis, and aluminum related bone disease due to antacid preparations and leaching from aluminum cooking vessels. Second, the decision to choose anti-resorptive or anabolic therapy, and which agent to choose, must be based on the estimated fracture risk of the patient (e.g., FRAX score,[8] and side effect profile, local availability and cost of anti-resorptive agents).

In those with high turnover bone disease (high PTH and high alkaline phosphatase) anti-resorptive therapies are useful.[12]

• Bisphosphonates-If GFR is >30 ml/min then bisphosphonates can be used. Alendronate can be used with a GFR >35 ml/min/1.73 m² though some studies show that it can be used in patients with lower GFR

• Denosumab can be used safely at a dose of 60mg once in 6 months at any level of GFR

• Raloxifene can also be used in a dose of 60 mg daily.

• Calcitonin is not used for prevention but can be used for treatment.

In patients with low turnover or adynamic bone disease (low PTH and low alkaline phosphatase), anti-resorptive therapies are contra-indicated. Anabolic agents can be used to increase bone turnover and result in increased BMD.[12]

• Teriparatide can be used as 20 mcg daily injection for 1 year if severe osteoporosis and bone turnover is low

• Abaloparatide is the new drug similar to Teriparatide.

Commentary

Kidney transplant recipients are at a heightened risk of developing fractures in the early part of the post-transplant period,[45] i.e., fracture rate of 3.3 per 1000-patient years, more than a third higher than in their pre-transplant period.[46] There is insufficient prospective evidence to show that Dual Energy X-ray Absorptiometry bone mineral density (DEXA BMD) scores predict the incidence of fractures. However, retrospective data suggests that fracture risks were higher in recipients who had osteopenia (HR: 2.7, 95% CI: 1.6–4.6) or osteoporosis of the hip (HR: 3.5, 95% CI: 1.8–6.4).[47] In the light of this data, the guideline recommends BMD testing of all transplant recipients.

The authors of the guideline freely admit insufficient data to contemplate treating transplant recipients beyond the first year, during which period, those with osteopenia or osteoporosis and estimated glomerular filtration rate (eGFR) more than 30 ml/min/1.73 m² are to receive treatment. A Cochrane systematic review showed that nutritional supplementation of vitamin D, calcitriol (or vitamin D3 analogues), and anti-resorptive agents (like bisphosphonates and denosumab) prevent bone loss in the early post-transplantation period.[48] However, there is as yet, no definite proof of this resulting in lower risk of fractures and remains an area of much needed research. As with other stages of chronic kidney disease, CKD-MBD markers, i.e., serum levels of calcium, phosphate, PTH, alkaline phosphatases, and 25(OH)D3 are to guide definitive therapy.[49] The optimum levels of PTH and vitamin D3 in transplant patients also need to be proven. When needed, the treating physician should consider a bone biopsy when it is vital to correctly classify the type of renal osteodystrophy to guide treatment. Its availability, though, is scarce worldwide and is likely to remain a research tool for the most part.

Impact on clinical practice and recommendations to Indian nephrologists

1. Bone mineral density estimation using Dual Energy X-ray Absorptiometry (DEXA) should be done at least once in the first year after transplantation

2. To prevent bone loss, supplementation of vitamin D, calcitriol (or vitamin D3 analogues), and anti-resorptive agents (like bisphosphonates and denosumab) must be prescribed to prevent bone loss in the early post-transplantation period although there is no evidence of reduced fracture risk.