Three patterns of kidney involvement
1. Granulomatous Interstitial Nephritis (Gin)
- Sub-acute or chronic AKI
- Bland urine — no haematuria, minimal proteinuria
- Often associated with extra-renal sarcoid (lung, eye, skin, lymph node)
- Some patients present with kidney-isolated disease
- Biopsy required for diagnosis
2. Calcium Metabolism Abnormalities
- Granuloma macrophages express 1-alpha-hydroxylase → unregulated 1,25-(OH)₂D production
- Increased intestinal calcium absorption + bone resorption
- Hypercalciuria > hypercalcaemia (urinary calcium rises before serum calcium)
- Mechanism is INDEPENDENT of PTH (PTH usually suppressed)
- Vitamin D supplementation, sun exposure and dietary calcium amplify the problem
3. Stone & Nephrocalcinosis Disease
- Chronic hypercalciuria → calcium phosphate / oxalate stones
- Medullary nephrocalcinosis on imaging
- Can present as recurrent renal colic or incidental finding
- Long-term CKD risk
Other Rare Patterns
- Membranous nephropathy, IgA nephropathy, focal sclerosis (associations described but causation uncertain)
- Obstructive uropathy from retroperitoneal granulomas (rare)
Diagnosis
Bloods
- Creatinine ↑, eGFR ↓
- Calcium often ↑ (or normal); ionised Ca more sensitive
- PTH suppressed (key — distinguishes from primary hyperparathyroidism)
- 1,25-(OH)₂D ↑ with 25-OH-D typically low–normal
- ACE often raised (sensitivity ~60%, specificity poor — not diagnostic)
- ALP ↑ (granuloma activity, liver involvement)
- Soluble IL-2 receptor sometimes used
Urine
- Bland (in GIN), mild proteinuria
- 24-h urine calcium > 7.5 mmol/24h (hypercalciuria)
- Stone-formers — full stone metabolic work-up
Imaging
- Chest X-ray or CT — bilateral hilar lymphadenopathy, parenchymal disease
- Renal USS — usually normal; may show stones or nephrocalcinosis
- Cardiac MRI/PET if cardiac sarcoid suspected
- Eye review (uveitis screening)
Kidney Biopsy
- Non-caseating epithelioid granulomas (key finding)
- Negative ZN stain and TB PCR / culture
- Negative special stains for fungi
- Rule out drug-induced GIN (PPIs, NSAIDs, allopurinol)
Other Tissue Biopsy
- Skin lesions, peripheral lymph node, transbronchial lung biopsy can also confirm
- Endobronchial USS-guided node biopsy increasingly used
Treatment
Induction
- Prednisolone 0.5–1 mg/kg/day (typical 30–60 mg)
- 4–6 weeks at full dose
- Then slow taper over 6–12 months (typical taper: 5 mg every 2 weeks)
- Bone protection (calcium-aware) — bisphosphonate, vitamin D ONLY if 25-OH-D very low and under careful monitoring
- Pneumocystis prophylaxis (co-trimoxazole) for prednisolone ≥ 20 mg/day for > 4 weeks
- PPI for gastric protection
- Glucose monitoring (steroid-induced hyperglycaemia)
Hypercalcaemia Acute Treatment
- IV 0.9% sodium chloride
- Stop vitamin D supplements
- Avoid bright sun, calcium-rich diet, antacids
- Hydroxychloroquine 200–400 mg/day (reduces 1,25-D production)
- Steroids (as above)
- Pamidronate or zoledronate if severe (≥ 3.5 mmol/L) — caution with low eGFR
Steroid-sparing
- Methotrexate 7.5–25 mg/week
- Mycophenolate 1–3 g/day
- Azathioprine 1.5–2.5 mg/kg/day (check TPMT)
- Infliximab for refractory multi-system disease
- JAK inhibitors emerging
Stone Prevention
- 24-h urine calcium monitoring
- Thiazide diuretics reduce urinary calcium
- Adequate (NOT high) dietary calcium
- Avoid vitamin D supplements
- Citrate supplementation if low urinary citrate
Follow-up
- Joint nephrology + respiratory + ophthalmology + cardiology
- Annual eGFR, calcium, 24-h urine calcium, vitamin D
- Relapses common during steroid taper — counsel patient; re-induce if needed
- Long-term BP, lipid, bone health monitoring
Prognosis
- 60–80% partial renal recovery with steroids if treated early
- Late diagnosis with established interstitial fibrosis → CKD/ESKD risk
- Transplant outcomes are good; rare recurrence in graft
