Oral Coenzyme Q10 supplementation leads to better preservation of kidney function in steroid-resistant nephrotic syndrome due to primary Coenzyme Q10 deficiency.

Primary Coenzyme Q10 (CoQ10) deficiency is an ultra-rare disorder caused by defects in genes involved in CoQ10 biosynthesis leading to multidrug-resistant nephrotic syndrome as the hallmark kidney manifestation. Promising early results have been reported anecdotally with oral CoQ10 supplementation. However, the long-term efficacy and optimal prescription remain to be established. In a global effort, we collected and analyzed information from 116 patients who received CoQ10 supplements for primary CoQ10 deficiency due to biallelic pathogenic variants in either the COQ2, COQ6 or COQ8B genes. Median duration of follow up on treatment was two years. The effect of treatment on proteinuria was assessed, and kidney survival was analyzed in 41 patients younger than 18 years with chronic kidney disease stage 1-4 at the start of treatment compared with that of an untreated cohort matched by genotype, age, kidney function, and proteinuria. CoQ10 supplementation was associated with a substantial and significant sustained reduction of proteinuria by 88% at 12 months. Complete remission of proteinuria was more frequently observed in COQ6 disease. CoQ10 supplementation led to significantly better preservation of kidney function (5-year kidney failure-free survival 62% vs. 19%) with an improvement in general condition and neurological manifestations. Side effects of treatment were uncommon and mild. Thus, our findings indicate that all patients diagnosed with primary CoQ10 deficiency should receive early and life-long CoQ10 supplementation to decelerate the progression of kidney disease and prevent further damage to other organs.

The use of darbepoetin in infants with chronic renal impairment.

Darbepoetin is a newer analogue of epoetin, with a longer half-life, that allows less frequent administration. There are currently no published data available for its use in infants. We report our experience with this drug in infants with chronic renal impairment, weighing less than 8 kg. Infants had baseline haemoglobin (Hb), iron, ferritin and transferrin levels measured. They were started on approximately 0.5 microg/kg per week of darbepoetin. Hb levels were checked every 2-4 weeks, and iron studies were performed every 4 weeks. Iron supplementation was prescribed to maintain ferritin levels>100 microg/l and transferrin saturation levels>20%. Follow up was for 20 weeks. Six infants with a mean weight of 4.08 kg and a mean creatinine of 259 micromol/l were included. Three infants were medically stable throughout the study, and the mean darbepoetin dose was decreased to 0.25 microg/kg per week. Their dosing interval was increased to every 3-4 weeks. The other three infants were less stable and had multiple medical problems, including periods of haemodialysis and surgery. These infants failed to reach target Hb level, despite an increase in the mean dose of darbepoetin to 1.2 microg/kg per week. In conclusion, darbepoetin can be successfully administered to infants with chronic renal insufficiency, but the dose needs to be tailored to each individual. Administration would be facilitated by smaller unidose syringes.