Efficacy of oral citrate administration in primary hyperoxaluria

Abstract

Abstract. Urinary citrate is a potent inhibitor of calcium oxalate (CaOx) crystallization, but oral citrate has rarely been used in patients with primary hyperoxaluria (PH). We studied the effect of sodium citrate administration (0.1-0.15 g/kg/day) on urinary citrate excretion and CaOx saturation in seven paediatric patients and the clinical response to long-term treatment (average 4 years) in five patients. Urinary citrate increased from 0.73 to 2.54 mmol/24h/l .73 m 2 and urinary saturation for CaOx (calculated by equil 2) decreased from 11.41 to 6.79 (for both, p<0.02). Long-term administration of alkali citrate [0.15 g (0.5mmol)/kg/day] resulted in stable or improved renal function in three and slow deterioration in two partially non-compliant patients. Alkali citrate is effective in patients with PH.

A 20-Year Experience of Combined Liver/Kidney Transplantation for Primary Hyperoxaluria (PH1): The European PH1 Transplant Registry Experience 1984–2004

“…Good results can be achieved with renal transplantation from a living donor and strict adherence to a high fluid protocol combined with the use of stone inhibitors and dietary manipulation [14, 15, 24] and probably does have a role in selected partially responsive cases. By contrast cadaveric renal transplantation alone has no role to play in the management of patients with PH1 with generally poor outcomes and it is probably only appropriate to carry out cadaveric renal transplantation in conjunction with liver grafting to reverse the underlying metabolic defect.…”

“…If a diagnosis is established early in life before renal impairment has occurred careful dietary management, high fluid intake (with the goal of maintaining a constant high urine output with dilute urine and thus reduced risk of crystallisation and stone formation) [14 ]and pharmacological manipulation [15,16,17] may delay or avoid the development of stone disease. These measures together with optimal management of calculi are the essential features of early patient management but can only be instituted after the diagnosis is established and as will be seen in this report and is evident from many previous publications diagnosis is often delayed and renal failure is often the presenting problem leading to the diagnosis being made [4, 5, 18].…”

A United States survey on diagnosis, treatment, and outcome of primary hyperoxaluria

“…PH type II (PH II, MIM 260000) is due to diminished activity of glyoxylate reductase (GR), an enzyme that also posseses both D-glycerate dehydrogenase and hydroxypyruvate reductase (HPR) activities, leading to elevated urinary excretion of both oxalate and L-glyceric acid (GR/HPR gene on chromosome 9p11, [1,2]). Both primary forms of hyperoxaluria have a highly elevated urinary excretion of oxalate (>0.5 mmol/1.73 m 2 per day [6,7,8]) and concomitantly, a urine supersaturated with respect to calcium oxalate (ß UCaOx >10 relative units [9]). These urinary abnormalities produce urolithiasis, medullary nephrocalcinosis, or both [6,8].…”

Primary Hyperoxaluria

“…It would, how ever, be logical to give calcium supplements to reduce the concentration of free oxalate while observing the effect of this on both the urinary oxalate and calcium excretions, aiming to minimise oxalate excretion without enhancing the urinary calcium excretion above the lowest level achievable when both dietary oxalate and calcium were restricted. [27]. Orally administered citrate increases the uri nary citrate, bicarbonate and pH, and decreases urine cal cium and ammonium concentrations.…”