Adenine Phosphoribosyltransferase Deficiency Bollée, Guillaume; Harambat, Jérôme; Bensman, Albert ...
Clinical journal of the American Society of Nephrology,
09/2012, Letnik:
7, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Complete adenine phosphoribosyltransferase (APRT) deficiency is a rare inherited metabolic disorder that leads to the formation and hyperexcretion of 2,8-dihydroxyadenine (DHA) into urine. The low ...solubility of DHA results in precipitation of this compound and the formation of urinary crystals and stones. The disease can present as recurrent urolithiasis or nephropathy secondary to crystal precipitation into renal parenchyma (DHA nephropathy). The diagnostic tools available-including stone analysis, crystalluria, and APRT activity measurement-make the diagnosis easy to confirm when APRT deficiency is suspected. However, the disease can present at any age, and the variability of symptoms can present a diagnostic challenge to many physicians. The early recognition and treatment of APRT deficiency are of crucial importance for preventing irreversible loss of renal function, which still occurs in a non-negligible proportion of cases. This review summarizes the genetic and metabolic mechanisms underlying stone formation and renal disease, along with the diagnosis and management of APRT deficiency.
After stone removal, accurate analysis of urinary stone composition is the most crucial laboratory diagnostic procedure for the treatment and recurrence prevention in the stone-forming patient. The ...most common techniques for routine analysis of stones are infrared spectroscopy, X-ray diffraction and chemical analysis. The aim of the present study was to assess the quality of urinary stone analysis of laboratories in Europe. Nine laboratories from eight European countries participated in six quality control surveys for urinary calculi analyses of the Reference Institute for Bioanalytics, Bonn, Germany, between 2010 and 2014. Each participant received the same blinded test samples for stone analysis. A total of 24 samples, comprising pure substances and mixtures of two or three components, were analysed. The evaluation of the quality of the laboratory in the present study was based on the attainment of 75% of the maximum total points, i.e. 99 points. The methods of stone analysis used were infrared spectroscopy (n = 7), chemical analysis (n = 1) and X-ray diffraction (n = 1). In the present study only 56% of the laboratories, four using infrared spectroscopy and one using X-ray diffraction, fulfilled the quality requirements. According to the current standard, chemical analysis is considered to be insufficient for stone analysis, whereas infrared spectroscopy or X-ray diffraction is mandatory. However, the poor results of infrared spectroscopy highlight the importance of equipment, reference spectra and qualification of the staff for an accurate analysis of stone composition. Regular quality control is essential in carrying out routine stone analysis.
In most industrialized countries, different epidemiologic studies show that chronic renal failure is dramatically increasing. Such major public health problem is a consequence of acquired systemic ...diseases such as type II diabetes, which is now the first cause for end stage renal failure. Furthermore, lithogenic diseases may also induce intratubular crystallization, which may finally result in end-stage renal failure (ESRF). Up to now, such rare diseases are often misdiagnosed. In this study, based on twenty four biopsies, we show that SR µFTIR (Synchrotron Radiation-µFourier transform infrared) spectroscopy constitutes a significant opportunity to characterize such pathological µcalcifications giving not only their chemical composition but also their spatial distribution in the tissues. This experimental approach offers new opportunities to the clinicians to describe at the cell level the physico-chemical processes leading to the formation of the pathological calcifications which lead to ESRF.
Our aim was to investigate the validity of osmolality from 24-h urine collection in examining the risk for calcium-oxalate (CaOx) kidney stone formation in patients with recurrent urolithiasis. Three ...hundred and twelve subjects (males/females: 184/128) from France with a history of recurrent kidney stones from confirmed or putative CaOx origin were retrospectively included in the study (46 ± 14 years, BMI: 25.3 ± 5.0 kg·m
−2
). Tiselius’ crystallization risk index (CRI) was calculated based on urinary calcium, oxalate, citrate, magnesium, and volume from 24-h samples. The diagnostic ability of 24-h urine osmolality to classify patients as high risk for kidney stone crystallization was examined through the receivers operating characteristics analysis. High risk for CaOx crystallization was defined as CRI > 1.61 and > 1.18, for males and females, respectively. The accuracy of urine osmolality to diagnose risk of CaOx stone formation (AUC, area under the curve) for females was 84.6%, with cut-off point of 501 mmol·kg
−1
(sensitivity: 83.3%, specificity: 76.0%). Males had AUC of 85.8% with threshold of 577 mmo·kg
−1
(sensitivity: 85.5%, specificity: 77.6%). A negative association was found between 24-h urine volume and osmolality (
r
= − 0.63,
P
< 0.001). Also, a positive association was found between 24-h urine osmolality and CRI (
r
= 0.65,
P
< 0.001), as well as urea excretion with CRI (
r
= 0.37,
P
< 0.001). In conclusion, urine osmolality > 501 and > 577 mmol·kg
−1
, in female and in male, respectively, was associated with a risk for CaOx kidney stone formation in patients with a history of recurrent urolithiasis. Thus, when CaOx origin is confirmed or suspected, 24-h urine osmolality provides a simple way to define individualized target of urine dilution to prevent urine crystallization and stone formation.
basic calcium phosphate (BCP) crystals are commonly found in osteoarthritis (OA) and are associated with cartilage destruction. BCP crystals induce in vitro catabolic responses with the production of ...metalloproteases and inflammatory cytokines such as interleukin-1 (IL-1). In vivo, IL-1 production induced by BCP crystals is both dependant and independent of NLRP3 inflammasome. We aimed to clarify 1/ the role of BCP crystals in cartilage destruction and 2/ the role of IL-1 and NLRP3 inflammasome in cartilage degradation related to BCP crystals.
synovial membranes isolated from OA knees were analysed by alizarin Red and FTIR. Pyrogen free BCP crystals were injected into right knees of WT, NLRP3 -/-, ASC -/-, IL-1α -/- and IL-1β-/- mice and PBS was injected into left knees. To assess the role of IL-1, WT mice were treated by intra-peritoneal injections of anakinra, the IL-1Ra recombinant protein, or PBS. Articular destruction was studied at d4, d17 and d30 assessing synovial inflammation, proteoglycan loss and chondrocyte apoptosis. BCP crystals were frequently found in OA synovial membranes including low grade OA. BCP crystals injected into murine knee joints provoked synovial inflammation characterized by synovial macrophage infiltration that persisted at day 30, cartilage degradation as evidenced by loss of proteoglycan staining by Safranin-O and concomitant expression of VDIPEN epitopes, and increased chondrocyte apoptosis. BCP crystal-induced synovitis was totally independent of IL-1α and IL-1β signalling and no alterations of inflammation were observed in mice deficient for components of the NLRP3-inflammasome, IL-1α or IL-1β. Similarly, treatment with anakinra did not prevent BCP crystal effects. In vitro, BCP crystals elicited enhanced transcription of matrix degrading and pro-inflammatory genes in macrophages.
intra-articular BCP crystals can elicit synovial inflammation and cartilage degradation suggesting that BCP crystals have a direct pathogenic role in OA. The effects are independent of IL-1 and NLRP3 inflammasome.
Parathyroidectomy (PTX) is routinely performed in hypercalciuric renal stone patients with primary hyperparathyroidism (PHPT). However, some data indicate a persistent stone activity following PTX, ...raising the issue of the link between PHPT and stone disease. We performed an observational study on 30 renal stone patients diagnosed with PHPT. Patients were selected among 1448 hypercalciuric patients referred in our department for a diagnostic evaluation. Patients with no parathyroid surgery or any biological follow-up were excluded. Clinical and biological data (including 24-h urine collection and a calcium load test) were collected before and within 12 months following surgery. Stone recurrence was evaluated by direct phone contact (median 43 months). Comparison of biological data before and after surgery showed a significant decrease of ionized calcium and serum parathyroid hormone after PTX. All stones contained calcium-dependent species such as carbapatite, brushite or dihydrate calcium oxalate. Urine saturation indexes and calciuria significantly decreased after surgery (from 9.9 to 5.9 mmol/d,
p
< 0.0001), but a persistent hypercalciuria was detected in 47% of patients. The other stone risk factors including diuresis stayed similar. Stone activity that was increasing (from 0.20–0.30 to 0.50–0.75/year) the 2 years before PTX, significantly decreased after surgery 0.05–0.15/year (
p
< 0.001). PTX in calcium-dependent renal stone formers with PHPT significantly decreases both stone recurrence and urine saturation indexes. However, PTX unmasked an underlying renal stone disease related to idiopathic hypercalciuria in half of patients with a remaining stone activity, testifying the need for patient’s follow-up to prevent stone recurrence.
Arterial calcification is a common feature of pseudoxanthoma elasticum (PXE), a disease characterized by
mutations, inducing a deficiency in pyrophosphate, a key inhibitor of calcium phosphate ...crystallization in arteries.
we analyzed whether long-term exposure of Abcc6
mice (a murine model of PXE) to a mild vitamin D supplementation, with or without calcium, would impact the development of vascular calcification. Eight groups of mice (including Abcc6
and wild-type) received vitamin D supplementation every 2 weeks, a calcium-enriched diet alone (calcium in drinking water), both vitamin D supplementation and calcium-enriched diet, or a standard diet (controls) for 6 months. Aorta and kidney artery calcification was assessed by 3D-micro-computed tomography, Optical PhotoThermal IR (OPTIR) spectroscopy, scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDS) and Yasue staining.
at 6 months, although vitamin D and/or calcium did not significantly increase serum calcium levels, vitamin D and calcium supplementation significantly worsened aorta and renal artery calcification in Abcc6
mice.
vitamin D and/or calcium supplementation accelerate vascular calcification in a murine model of PXE. These results sound a warning regarding the use of these supplementations in PXE patients and, to a larger extent, patients with low systemic pyrophosphate levels.
Nephrolithiasis affects around 10% of the population and is frequently associated with impaired dietary factors. The first one is insufficient fluid intake inducing reduced urine volume, urine ...supersaturation, and subsequently urinary lithiasis. Kidneys regulate 24 h urine volume, which, under physiological conditions, approximately reflects daily fluid intake. The aim of this study is to synthesize and highlight the role of hydration in the treatment of nephrolithiasis. Increasing fluid intake has a preventive effect on the risk of developing a first kidney stone (primary prevention) and also decreases the risk of stone recurrence (secondary prevention). Current guidelines recommend increasing fluid intake to at least at 2.5 L/day to prevent stone formation, and even to 3.5-4 L in some severe forms of nephrolithiasis (primary or enteric hyperoxaluria or cystinuria). Fluid intake must also be balanced between day and night, to avoid urinary supersaturation during the night. Patients should be informed and supported in this difficult process of increasing urine dilution, with practical ways and daily routines to increase their fluid intake. The liquid of choice is water, which should be chosen depending on its composition (such as calcium, bicarbonate, or magnesium content). Finally, some additional advice has to be given to avoid certain beverages such as those containing fructose or phosphoric acid, which are susceptible to increase the risk of nephrolithiasis.
Renal oxalosis is a rare cause of renal failure whose diagnosis can be challenging. Synchrotron deep ultraviolet (UV) fluorescence was assayed to improve oxalosis detection on kidney biopsies spatial ...resolution and sensitivity compared with the Fourier transform infrared microspectroscopy gold standard. The fluorescence spectrum of synthetic mono‐, di‐ and tri‐hydrated calcium oxalate was investigated using a microspectrometer coupled to the synchrotron UV beamline DISCO, Synchrotron SOLEIL, France. The obtained spectra were used to detect oxalocalcic crystals in a case control study of 42 human kidney biopsies including 19 renal oxalosis due to primary (PHO, n = 11) and secondary hyperoxaluria (SHO, n = 8), seven samples from PHO patients who received combined kidney and liver transplants, and 16 controls. For all oxalocalcic hydrates samples, a fluorescence signal is detected at 420 nm. These spectra were used to identify standard oxalocalcic crystals in patients with PHO or SHO. They also revealed micrometric crystallites as well as non‐aggregated oxalate accumulation in tubular cells. A nine‐points histological score was established for the diagnosis of renal oxalosis with 100% specificity (76–100) and a 73% sensitivity (43–90). Oxalate tubular accumulation and higher histological score were correlated to lower estimated glomerular filtration rate and higher urinary oxalate over creatinine ratio.
Synchrotron deep ultraviolet imaging highlighting pathological calcium oxalate detection in kidney is presented.
Introduction
The therapy to reduce urinary oxalate excretion in primary hyperoxaluria type 1 is still required.
Case presentation
A 37‐year‐old hemodialyzed man suffered from systemic oxalosis ...secondary to primary hyperoxaluria type 1 exhibited a drastic plasma oxalate decrease from 110 to 22 µmol/L two months after adjunction of lanthanum carbonate to classical treatment (intensive hemodialysis with pyridoxine). A 34‐year‐old woman with normal kidney function presented 10 years of bilateral kidney stones due to primary hyperoxaluria type 1 hyperoxaluria (109.2 mg/24 h), plasma oxalate (56.0 µmol/L). The oxalate level remained uncontrolled despite of low oxalate‐normal calcium diet, pyridoxine and increased water intake though the lanthanum carbonate adjunction resulted in significant decrease in plasma oxalate and oxaluria.
Conclusion
We report the lanthanum efficacy in reducing circulating and urinary oxalate levels in type 1 primary hyperoxaluria. Possible mechanism of observed falls in oxalate concentration would be a decrease in the intestinal absorption of oxalate.
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