Table 3.

Patients with primary hyperoxaluria reported with RNAi medications outside clinical trials

Patient no. and sex	Age of Dx Genetic Dx	Clinical situation before RNAi	Age of starting RNAi medication and dose	Serum creatinine (Scr)/eGFR	Oxalate and Glycolate	Duration and dose of RNAi	Outcome/ Side effects	Other relevant information
1 [88]	7 years old (post KTx) c.33dupC Phe152Ile	KTx + HD + B6 + hyperhydration + citrate Oxalosis in eyes	7 years old (day 34 post-KTx) Lumasiran	38 ml/min/1.73m2 at 4 months after Tx	65.9% decrease Uox after 5 months. No raw value provided. Glycolate not measured	>5 months Fourth dose injected 3 months after third dose + B6 + citrate + hyperhydration	Slight elevation of GGT and alkaline phosphatase. Developed non-anion gap metabolic acidosis (HCO3- 14 mmol/L and anion gap 8mmol/L) after HD discontinuation due to elevated glycolate	Sodium bicarbonate resolved the metabolic acidosis
2 [87] Male Twin A	11 months old (p.Gly161Cys p.Gly170Arg)	Passed stones at 6 weeks old. Kidney stone (100% CaOx) at 9 months old, bilateral UL and bilateral double-J stent. UTI. Bilateral ureteroscopic stone extraction with laser lithotripsy and a complicated bilateral ureteral stent removal + B6 + citrate	12 months old Lumasiran	Prior: Scr 0.47 mg/dl Follow up: Scr 0,18 mg/dl	Prior: Uox/cr 0,19 mg/mg (normal <0.103) After: n/a Glycolate not measured	8 months 6 mg/kg monthly for 3 months, 3 mg/kg monthly thereafter	Improved psychologically, and emotionally expressive. Well tolerated	Preeclampsia at week 31. B6 and citrate discontinued when lumasiran started
3 [87] Male Twin B	11 months old p.Gly161Cys p.Gly170Arg (assumed from dizygotic twin A)	At 10 months old, bilateral renal (non-obstructive) and bladder calculi + B6 + citrate	12 months old Lumasiran	Prior: Scr 0.31 mg/dl Follow up: Scr 0,12 mg/dl	Prior: Uox/cr 0,125 mg/mg After: n/a Glycolate not measured	8 months 6 mg/kg monthly for 3 months, 3 mg/kg monthly thereafter	Stopped crying episodes. No new stone formation. No metabolic acidosis. Well tolerated	Preeclampsia at week 31. B6 and citrate discontinued when lumasiran started
4 [86] Female	9 years old Homozygous for duplication of entire exon 9	Recurrent kidney stones treated with ESWL and PNL since 3 years old. At 9 years old, bilateral coralliform stones. + hyperhydration + citrate + low-salt diet + B6 only for 3 months (Uox did not decrease) 5 urological interventions/year during 5 years (doubleJ in and out, ureteroscopy, laser therapy, and ESWL)	13 years old 3 mg/kg monthly, then quarterly, starting one month after last loading dose Lumasiran	Prior: Scr 0.75 mg/dl. eGFR 67-60 ml/min/1.73m2 After: eGFR 62 ml/min/1.73m2 at month 18 post 1st dose	Prior: Uox/cr 0.21–0.28 mol/mol (normal <0.06 mol/mol) Pox: 20 µmol/L, and 32 µmol/L 4 years later (normal <27) After: Uox/cr 0.08 mol/mol (after first dose) 70% mean reduction of ox/cr ratio Pox: 13 µmol/L (after first dose). 16 µmol/L at month 18 60% mean reduction Glycolate not measured	18 months	No substantial changes in kidney US at month 18. No new stones. No increase of old stones. No requirement of urological interventions. Temporary and asymptomatic episodes of macroscopic hematuria after the first four injections	No CaOx deposited in other tissue was observed prior to lumasiran No information provided about continuation of hyperhydration and/or citrate
5 [85] Male	Antenatal Dx (his sister was the index case) c.33dupC c.321_344del		9 days old 6 mg/kg/month Lumasiran At month 2: + hyperhydration + citrate At month 4: 3 mg/kg + stiripentol At month 5: 6 mg/kg + stiripentol At month 6: stiripentol withdrawal At month 8: 3 mg/kg/month	At birth: “normal” At month 10 of lumasiran: “normal”	At birth: Uox/cr 1263 µmol/mmol Pox 36 µmol/L and marked elevated glycolate (no value) After first injection: Uox/cr 2853–1500 to 1060–1000 µmol/mmol at month 0.5, 1, 2, and 3. Pox 12 µmol/L at 3 months After seventh injection: 226 µmol/mmol No glycolate measured after lumasiran started	10 months	Grade III NC after 2 months At month 10, hyperechogenicity started to decrease Well tolerated	Hyperhydration and citrate given from month 2 after starting lumasiran
6 [85] (no gender displayed)	2.5 months old p.Ile244Thr p.Ile244Thr	At age 2.5 months, grade III NC + hyperhydration + B6 + Mg citrate	3 months old 6 mg/kg/month Lumasiran	At Dx: Scr 243 µmol/L, eGFR 8 ml/min/1.73m2 After 9th: Scr 120 µmol/L, eGFR 20 ml/min/1.73m2	At Dx: Uox/cr 806 µmol/mmol and Pox 194 µmol/L Elevated glycolate (no value given) After 9th: Uox/cr 310 µmol/mmol (60% reduction)	10 months	Grade III NC persisted	B6 withdrawn after 3 months under lumasiran
7 [85]	3.5 months (clinically) 5.5 months: p.Ile244Thr p.Ile244Thr	At age 3.5 months, grade III NC + hyperhydration + B6 + citrate	4 months old 6 mg/kg/month first 3 months 3 mg/kg/month other 3 months Lumasiran	Prior: Scr 30 µmol/L (eGFR 77 ml/min/1.73m2) After: “remained stable”	Prior: Uox/cr1651–2167 µmol/mmol Pox 36 µmol/L After: Uox/cr 1640–662 µmol/mmol after first and second dose. Elevated plasma glycolate (no value given)	6 months	After fifth injection, nephrocalcinosis improved from grade III to grade II	Lumasiran started prior to genetic diagnosis, as allowed in France
8 [91] Female	Not mentioned	At age 36 years: ESKD and systemic oxalosis. Conventional HD At age 39 years: HD daily	39 years old (6 months after HD started) 3 mg/kg monthly loading dose and quarterly maintenance (started 1 month after last loading) Lumasiran	Post KTx: Scr 140 µmol/L Methylprednisolone and antithymocyte globulin treatment resulted in Scr of 200 µmol/L (day 25 post KTx). 10 weeks post KTx, Scr 169 µmol/L	Prior: Pox ~100 µmol/L (normal <33) After: Pox ~80 µmol/L after second dose, >100 µmol/L after third dose, and ~27 µmol/L after fifth dose (before KTx) After KTx (d25): Pox 24 µmol/L and Uox 1.15 mmol/day (normal < 0.45); 10 weeks after Pox 20.9 µmol/L Glycolate not measured	6 months, and continued on the seventh week after KTx	KTx after fifth dose. Inmunosuppression: basiliximab, steroids, tacrolimus, and everolimus + 1HD session + hyperhydration + citrate + B6 + indapamide + low-oxalate diet No adverse events or drug interactions	Oxalate nephropathy and rejection day 25 post-KT due to release of systemic oxalate stores
9 [90] Female	40 years old c.680+1G>A c.680+1G>A (after kidney biopsy positive for CaOx crystals)	NL at age 19 years and 33 years, requiring lithotripsy. At age 40 years: hypertension, acrocyanosis, ESKD, systemic oxalosis in skin, and subcutaneous vessels. HD + B6	41 years old (11 months after HD initiation) 1mg/kg/month for 3 months, then quarterly Lumasiran	Prior: Scr 103 µmol/L (19 months before) and at presentation: Scr 1644 µmol/L (eGFR 2 ml/min/1.73m2)	At presentation: Uox 319 µmol/day Pre-HD prior lumasiran: Pox 98.2 µmol/L Pre-HD post 3 months of lumasiran: 62.8 µmol/L Glycolate not measured	3 months	No signs of renal recovery, increased of extra-renal involvement: bilateral swan-neck deformities, reduced cardiac systolic function, and pulmonary hypertension	Stones of calcium, magnesium, oxalate, and phosphate Awaiting kidney-liver transplantation after lumasiran withdrawal
10 [89] Male	38 years old p.Arg122* p.Arg122*	Long-standing HD for ESKD Severe calcified kidneys, osteosclerosis, and focal calcification of the iliac-femoral axis. Cardiac oxalate deposits	38 years old (dose not reported) Lumasiran	On non-HD days, Scr 6 mg/ml	Prior: Pox 130 µmol/L No follow-up reported Glycolate not measured	1 month
11 [93] Female	5 years old c.973delG c.973delG	Symptomatic NL since 3 years old needing multiple ureteroscopy and ESWL. At age 20 years: ESKD and HD started	20 years old (5 months after starting HD) 1.5 mg/kg Nedosiran	Prior HD: Scr 6 mg/dL (eGFR 9 ml/min/1.73m2)	Prior HD: Pox >60 µmol/L On HD: max 83 µmol/L Pre-nedosiran: 55.5 µmol/L Post-fifth dose: 13.9 µmol/L	6 months	Decreased weekly HD sessions over nedosiran treatment (from 6 per week to 3 per week) No new NL events Only temporary injection site discomfort as a side effect	Patient elected to be removed from liver transplant waiting list during nedosiran treatment Awaiting renal transplantation

B6 vitamin B₆, CaOx calcium oxalate, Dx diagnosis, eGFR estimated glomerular filtration rate, ESKD end-stage kidney failure, ESWL extracorporeal shock wave lithotripsy, GGT gamma glutamyl transferase, HD hemodialysis, KT kidney transplantation, n/a not assessed, NC nephrocalcinosis, NL nephrolithiasis, Pox plasma oxalate, UL urolithiasis, Uox urinary oxalate, Uox/cr oxalate/creatinine ratio, US ultrasound, UTI urinary tract infection, PNL percutaneous lithotripsy, RNAi RNA interference