How to manage bilateral genu valgum in a patient with Chronic Kidney Disease (CKD) and short stature?

Management of Bilateral Genu Valgum in CKD with Short Stature

In a patient with CKD and short stature presenting with bilateral genu valgum, you must first aggressively optimize CKD-mineral and bone disorder (CKD-MBD) parameters—particularly correcting hyperparathyroidism, hyperphosphatemia, and vitamin D deficiency—before considering growth hormone therapy or orthopedic intervention. 1

Initial Metabolic Assessment and Correction

The genu valgum deformity in this context is most likely secondary to renal osteodystrophy, which develops from the complex interplay of hyperphosphatemia, secondary hyperparathyroidism, and vitamin D deficiency. 1, 2, 3

Immediately measure and optimize the following parameters:

• Serum calcium, phosphate, and intact PTH levels should be checked urgently, as these drive the bone disease underlying the deformity. 1
• 25-hydroxyvitamin D levels must be assessed and corrected to normal range using treatment strategies for the general population. 1
• Alkaline phosphatase should be measured as an indicator of bone turnover. 1
• Parathyroid hormone management is critical: In CKD G3a-G5 not on dialysis, reserve calcitriol and vitamin D analogs for severe and progressive hyperparathyroidism (PTH persistently elevated). 1

Phosphate Control Strategy

Target serum phosphate in the normal range through dietary restriction and phosphate binders if needed, as hyperphosphatemia directly promotes vascular calcification and worsens bone disease. 1, 4 The calcium load from binders must be carefully monitored, as excessive calcium in the setting of adynamic bone disease (low bone turnover) can paradoxically worsen vascular calcification since bone cannot buffer the absorbed calcium. 2

PTH Target Ranges

• For CKD G3a-G5 not on dialysis: Avoid over-suppression of PTH, as skeletal resistance to PTH develops early in CKD. 1, 3
• For CKD G5D (dialysis patients): Maintain intact PTH levels at approximately 2 to 9 times the upper normal limit for the assay. 1
• If PTH remains >500 pg/mL despite medical therapy: This is a contraindication to growth hormone therapy and may require parathyroidectomy. 1

Growth Hormone Therapy Considerations

Once CKD-MBD parameters are optimized, recombinant human growth hormone should be initiated at 0.045-0.05 mg/kg/day subcutaneously in the evening to address the short stature. 1

Prerequisites Before Starting GH

• Malnutrition must be addressed first, as nutritional deficits will blunt GH response. 1
• Biochemical abnormalities of CKD-MBD must be corrected before initiating therapy. 1
• PTH must be <500 pg/mL, as persistent severe secondary hyperparathyroidism is an absolute contraindication to GH therapy due to risk of unmasking or worsening renal osteodystrophy. 1

Critical Monitoring During GH Therapy

Clinic visits every 3-6 months (or more frequently for advanced CKD) to monitor:

• Height velocity, pubertal development, and skeletal maturation via wrist radiography. 1
• Renal function (eGFR) at 3-month intervals for CKD stage 3-4, as unexplained eGFR decline mandates stopping GH. 1
• Calcium, phosphate, bicarbonate, and PTH levels, as GH can aggravate secondary hyperparathyroidism through direct parathyroid stimulation or effects on calcium-phosphate homeostasis. 1
• Thyroid function (TSH, free T3) and serum glucose, as GH increases insulin secretion and can unmask glucose intolerance. 1

Absolute Contraindications to Continue GH

Stop GH immediately if:

• Slipped capital femoral epiphysis (SCFE) develops, as rapid growth in the setting of renal osteodystrophy significantly increases this risk—obtain bone radiographs if hip/knee pain occurs. 1
• PTH rises above 500 pg/mL persistently, indicating inadequate control of bone disease. 1
• Unexplained decrease in eGFR occurs. 1
• Intracranial hypertension develops. 1

Orthopedic Management Timing

Surgical correction of genu valgum should be deferred until metabolic parameters are optimized and growth potential is maximized with GH therapy. 5, 6

The case report of hereditary hypophosphatemic rickets with genu valgum demonstrates that surgical correction can successfully resolve pain and deformity, but bone histomorphometry does not improve without addressing the underlying metabolic defect. 5 Similarly, primary hyperparathyroidism causing genu valgum in adolescents resolves metabolically after parathyroidectomy. 6

Orthopedic referral is appropriate when:

• CKD-MBD parameters are stable and optimized
• Growth velocity on GH therapy has plateaued or epiphyseal closure is approaching
• Functional impairment or pain from the deformity warrants intervention despite ongoing medical management

Common Pitfall to Avoid

Do not proceed with orthopedic surgery before correcting the underlying metabolic bone disease, as the deformity will recur or worsen postoperatively if hyperparathyroidism and hyperphosphatemia persist. 5, 2, 3 The bone quality in untreated renal osteodystrophy is poor, with either high turnover (osteitis fibrosa) or low turnover (adynamic bone disease), both of which compromise surgical outcomes. 3

Special Consideration for Bone Biopsy

If biochemical trends are inconsistent or if you are considering antiresorptive therapy for low bone mineral density, a bone biopsy may be reasonable to distinguish between high-turnover and low-turnover bone disease, as this fundamentally changes management. 1 However, the 2017 KDIGO update no longer requires bone biopsy before antiresorptive therapy in CKD G3a-G4 patients, as there is growing evidence these medications are effective without inducing adynamic bone disease. 1