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Primary hyperoxaluria type 1 (PH1) is a rare autosomal (2q37.3) recessive metabolic disease caused by a deficiency of the hepatic peroxisomal enzyme alanine:glyoxylate amino transferase. Molecular heterogeneity is important in PH1 as most of the patients (if the parents are unrelated) are compound heterozygotes for rare mutations. We describe the first large deletion in the AGXT gene, removing exons 1 to 7 (EX1_EX7del) that was responsible for one case of severe PH1. This 10 kb deletion was identified by Southern blotting of genomic DNA digested by Xba I and hybridized with different exonic probes. Both parents (from Turkey) are first cousin and carry the deletion. It is of note that the presently reported patient did not exhibit any AGT catalytic activity and even so, he progressed towards end-stage renal disease only at 19 years old.

Recombinant interleukin-2 (rIL-2) is a new promising treatment for cancer, but is associated with severe renal toxicity. This study is the first to analyse the renal effects of rIL-2 in children. Twenty-one cycles of continuous rIL-2 infusion were studied in 15 patients; mean age was 6.9 years and average weight 18.9 kg. Interstitial fluid retention and oliguria (baseline, 1.7 ml/kg per hour; nadir, 0.5 mg/kg per hour) were associated with hypotension (baseline, 101/56 mm Hg; nadir, 85/43 mm Hg) and decreased intravascular volume (plasma renin activity increased x 10). Weight gain (+7.9%) was observed in 13 cycles whereas weight loss (-6.3%) was shown in 8 cycles because of digestive and cutaneous losses, mainly in the youngest patients. This prerenal azotaemia was characterized by a decrease in creatinine clearance (from 101 to 36 ml/min per 1.73 m2) and a low fractional excretion of sodium (FENa) (from 0.70% to 0.09%). Hypotension and hypovolaemia needed vascular filling (n = 12), dopamine (n = 7) and interruption of rIL-2 (n = 2). Most abnormalities occurred as early as day 2 of therapy and were always reversible after a short period with sodium leakage (diuresis = 2.2 ml/kg per hour, FENa = 2.01%). Hypophosphataemia was associated with low urinary excretion of phosphorus, suggesting an increased uptake of inorganic phosphorus by rapidly proliferating lymphoid cells.

Two siblings born from consanguineous parents experienced infantile nephrotic syndrome with ocular and neurological abnormalities and a micropenis in the boy; both patients died before age 1. The opportunity to perform successively a renal biopsy and a two-step binephrectomy permitted a good histological follow-up. The lesions were characterized by mesangial involvement, followed by an extensive extracapillary proliferation and tubular dilatations with a high mitotic activity of the epithelium with anisocaryosis; the main features consisted in major ultrastructural changes of the glomerular basement membrane which were more significant and different from those previously described in the diffuse mesangial sclerosis. These 2 cases may either constitute a new entity or an extreme form of diffuse mesangial sclerosis, supported by recessive autosomal inheritance.

Introduction Nous decrivons le premier cas dans lequel une dysgenesie du segment anterieur a ete observee chez une fille presentant un deficit congenital en facteur VII (hypoproconvertinemie). Materiels et Methodes Une fille de 2 mois atteinte d’un deficit congenital en facteur VII nous a ete adressee pour des opacites corneennes bilaterales. L’enfant etait nee d’un mariage consanguin et le diagnostic de deficit congenital severe en facteur VII avait ete pose au 3e jour de vie apres un bilan etiologique de saignement intestinal. Observation L’examen sous anesthesie generale a montre des opacites corneennes bilaterales avec de multiples adherences irido-corneennes et des synechies anterieures peripheriques. La pression intraoculaire etait normale aux 2 yeux et le reste de l’examen ne retrouvait ni cataracte associee ni anomalies du fond d’œil. Discussion Le deficit congenital en facteur VII est une rare maladie hemorragique autosomique recessive dont les consequences cliniques sont variables d’un enfant a l’autre. Les formes les plus severes peuvent entrainer de graves symptomes hemorragiques tels que des hemorragies intracrâniennes massives avec haut risque de deces. A notre connaissance, il s’agit de la premiere description d’une dysgenesie malformative du segment anterieur chez un enfant atteint d’une telle maladie. Nous discutons dans cette observation les diagnostics differentiels possibles de cette atteinte oculaire et expliquons pourquoi ces diagnostics n’expliquent pas les anomalies observees. Conclusion A notre connaissance, il s’agit de la premiere description d’une dysgenesie du segment anterieur chez un enfant atteint d’une hypoproconvertinemie. Le but de cette observation est triple : 1) apporter de nouvelles informations concernant les possibles atteintes oculaires associees a l’hypoproconvertinemie, 2) suggerer la realisation d’un bilan complet de la coagulation devant un enfant atteint d’une dysgenesie du segment anterieur dite « idiopathique », 3) suggerer un examen ophtalmologique precoce chez tout patient atteint de deficit en facteur VII pour rechercher d’eventuelles anomalies du segment anterieur et effectuer dans ce cas un suivi ophtalmologique regulier.

Objective To describe the safety and efficacy of rituximab in the treatment of childhood-onset systemic lupus erythematosus (SLE). Study design We conducted a French multicenter retrospective study of childhood-onset SLE treated with rituximab. Results Eleven girls with severe SLE, including 8 girls with class IV or V lupus nephritis, 2 girls with severe autoimmune cytopenia, and 1 girl with antiprothrombin antibody with severe hemorrhage, were treated with rituximab. The mean age at onset of rituximab treatment was 13.9 years. Patients received 2 to 12 intravenous infusions of rituximab (350-450 mg/m2/infusion), with corticosteroids. Six patients also received different standard immunosuppressive agents, including Cyclophosphamide (2 patients). Remission was achieved in 6 of 8 patients with lupus nephritis and in the 2 patients with autoimmune cytopenia. Steroid therapy was tapered in 5 patients who responded to treatment, and low-dose prednisone treatment was maintained in 1 patient. The mean follow-up period was 13.2 months (range, 6-26 months), and remission lasted in all who patients who responded to treatment, except 1 patient who was successfully retreated with a second course of rituximab. Anti-double-stranded DNA antibody levels decreased in 6 of 11 patients, and anticardiolipin antibody levels decreased in 3 of 4 patients. Severe adverse events developed in 5 patients. Effective depletion of peripheral blood B cells was observed in 7 of 8 patients who were examined, and this paralleled the remission. Conclusion Rituximab may be an effective co-therapy; however, further investigations are required because severe adverse events occurred in 45% of the patients in this study.

Two children with toxic shock-like syndrome due to streptococcal infection are reported. In both cases (one fatal) the site of infection was in the soft tissues. Both strains of group A hemolytic streptococci isolated from blood culture produced large amounts of erythrogenic toxin B (ET B) small amounts of ET C but no ET A. This report confirms the implication of Streptococcus pyogenes in toxic shock like syndromes. When ET A seems to be responsible for most cases observed in the USA, our cases and others observed in Europe could be related to strains producing large amounts of ET B.

Background: Comparison between inulin clearance (glomerular filtration rate, ml/min/1.73m2) with (GFRu) and without (GFRp) urinary collection measured by constant infusion technique.

Longitudinal bone mineral changes after renal transplantation were studied in 14 children aged 8 +/- 4 years. Combination immunosuppressive therapy was given to all patients (prednisone, azathioprine, cyclosporine). Bone mineral density (BMD) measurements of the first through fourth lumbar vertebrae by dual-energy X-ray absorptiometry were performed within 1 year preceding renal transplantation and 6, 12, and 24 months afterward (M0, M6, M12, and M24, respectively). The results of BMD obtained in grams of hydroxyapatite per square centimeter of spine projected area were subsequently transformed to standard deviation scores for a normal pediatric population. In addition, we used a mathematical spine volume correction to give the results in grams per cubic centimeter. All patients had a well-functioning renal graft at M6, M12, and M24 and a normal serum creatinine level. Significant decreases in BMD, standard deviation score, and spine volume-corrected BMD were observed 6 months after renal transplantation (p0.05, p0.01, and p0.01 respectively); the median loss of BMD and spine volume-corrected BMD was 9.2% and 15.6% at M6, respectively, and the median serum parathyroid hormone level dropped from 125 to 34 pg/ml. Between M6 and M12, BMD increased significantly up to 95% (median) of pretransplantation values and reached 97.2% (median) at M24. Similar but less marked improvement was observed in spine volume-corrected BMD results, reaching 87.7% and 87.4% at M12 and M24, respectively. A negative correlation was found between the cumulative prednisone dose and BMD in grams per square centimeter at M6 (r2 = 0.603; p = 0.006), M12 (r2 = 0.532; p = 0.015), and M24 (r2 = 0.40; p = 0.014). There was no correlation between cumulative prednisone dose and spine volume-corrected BMD or standard deviation score. Mean 6-month cyclosporine levels did not correlate with any measure of BMD. We conclude that after renal transplantation children have a significant decrease of BMD during the first 6 months after the operation, despite normal graft function and growth improvement.

Successful renal transplantation is supposed to correct the majority of bone mineral metabolism disturbances induced by chronic renal failure. We examined bone mineral density (BMD) in 14 children (8 girls, 6 boys) aged 8 ± 4 years at the time of renal transplantation (Tx). Dual energy X-ray densitometry of lumbar vertebrae (L1-L4) was performed within one year preceding Tx (T0), 6, 12 and 24 months after Tx (T6, T12 and T24 respectively). The results of BMD obtained in g of hydroxyapatite per cm2 of spine projected area were subsequently transformed to Z scores (Z) for normal pediatric population. All patients had a well functioning renal graft at T6, T12 and T24, median serum creatinine levels were 54, 63 and 84 μmol/l, respectively. BMD ± SD decreased from initial level of 0.65 ± 0.18 at T0 to 0.59 ± 0.16 at T6 (p < 0.05). BMD ± SD measured at T12 (0.61 ± 0.15) and T24 (0.67 ± 0.16) was not significantly different from T0. Similar significant (p < 0.01) decrease of BMD expressed in median Z was observed between T0 (0.19) and T6 (−1.04), remained significantly (p < 0.01) lower at T12 (−0.93) and increased to −0.52 at T24 (p < 0.05 vs T0). In conclusion, children after kidney transplantation experienced a significant decrease of bone mineral density during the first 6 months after operation despite normal graft function. Progressive improvement of BMD was noted 12 and 24 months after Tx.

Epidermal nevus syndrome is a rare congenital sporadic neuro-ectodermic disorder, characterized by the presence of epidermal nevi in association with various developmental abnormalities of the skin, eyes, nervous, skeletal, cardiovascular and urogenital systems. We describe a 5-year-old boy with conjunctival lipodermoid, cervical and facial sebaceous nevi who presented at 3 years of age with hypertension due to bilateral renal artery stenosis together with multiple vascular anomalies (aorta, celiac trunk, superior mesenteric artery) as shown by magnetic resonance angiography. Systemic arterial hypertension was difficult to control despite combined anti-hypertensive drugs and the surgical repair of the aortic coarctation.

Better long-term functional adaptation to the child's size with pediatric compared to adult kidney donors.BackgroundPros and cons for pediatric kidney donors have been debated, especially with respect to survival rates. However, the effect of donor age on kidney function remains conflicting. The aim of this study was to compare short and long-term renal function according to the age of the donor, in grafts from adult living related (LRD), adult cadaveric and pediatric cadaveric donors (PedCD) following pediatric transplantation (Tx).MethodsOne hundred and thirty-four children were repeatedly followed for four years, and 44 were followed for eight years. Absolute and relative glomerular filtration rate (GFR; inulin clearance,mL/min andmL/min/1.73m2, respectively) were determined within 6 months, and yearly thereafter.ResultsAbsolute GFR increased along with body growth in the PedCD group (P < 0.001) during the 4 years following Tx, leading to stable relative GFR, whereas absolute GFR of the LRD group did not change, with a progressive decrease of relative GFR (P < 0.001). Relative GFR did not differ between PedCD and LRD recipients by the sixth month but became higher in PedCD 4 years post-Tx (70 ± 25 vs 52 ± 19mL/min/1.73m2, P < 0.001). Among those followed for 8 years, relative GFR showed a slow decrease in both recipient groups from 6 years post-Tx. At 8 years post-Tx, relative GFR was still significantly higher in PedCD than in LRD (57 ± 19 vs. 45 ± 19; P < 0.05).ConclusionsAdult-sized grafts may adapt to pediatric recipients during the first months post-Tx, but graft function cannot improve thereafter along with the increase in body size of the recipient. Interestingly, the absolute GFR of children receiving pediatric grafts increased along with body growth, leading to a stable relative GFR up to 6 years post-Tx.

We sought to ascertain the long-term outcome and genotype-phenotype correlations available for primary hyperoxaluria type 1 in a large retrospective cohort study. We examined the clinical history of 155 patients (129 families primarily from Western Europe, North Africa, or the Middle East) as well as the enzymatic or genetic diagnosis. The median age at first symptom was 4 years, and at diagnosis 7.7 years, at which time 43% had reached end-stage renal disease. Presentations included: (1) early nephrocalcinosis and infantile renal failure, (2) recurrent urolithiasis and progressive renal failure diagnosed during childhood, (3) late onset with occasional stone passage diagnosed in adulthood, (4) diagnosis occurring on post-transplantation recurrence, and (5) family screening. The cumulative patient survival was 95, 86, and 74% at ages 10, 30, and 50 years, respectively, with the cumulative renal survival of 81, 59, 41, and 10% at ages 10, 20, 30, and 50 years, respectively; 72 patients had undergone a total of 97 transplantations. Among the 136 patients with DNA analysis, the most common mutation was p.Gly170Arg (allelic frequency 21.5%), with a median age at end-stage renal disease of 47 years for homozygotes, 35 years for heterozygotes, and 21 years for other mutations. Our results underscore the severe prognosis of primary hyperoxaluria type 1 and the necessity for early diagnosis and treatment, as well as confirm a better prognosis of the p.Gly170Arg mutation.

Alport syndrome inevitably leads to end-stage renal disease and there are no therapies known to improve outcome. Here we determined whether angiotensin-converting enzyme inhibitors can delay time to dialysis and improve life expectancy in three generations of Alport families. Patients were categorized by renal function at the initiation of therapy and included 33 with hematuria or microalbuminuria, 115 with proteinuria, 26 with impaired renal function, and 109 untreated relatives. Patients were followed for a period whose mean duration exceeded two decades. Untreated relatives started dialysis at a median age of 22 years. Treatment of those with impaired renal function significantly delayed dialysis to a median age of 25, while treatment of those with proteinuria delayed dialysis to a median age of 40. Significantly, no patient with hematuria or microalbuminuria advanced to renal failure so far. Sibling pairs confirmed these results, showing that earlier therapy in younger patients significantly delayed dialysis by 13 years compared to later or no therapy in older siblings. Therapy significantly improved life expectancy beyond the median age of 55 years of the no-treatment cohort. Thus, Alport syndrome is treatable with angiotensin-converting enzyme inhibition to delay renal failure and therapy improves life expectancy in a time-dependent manner. This supports the need for early diagnosis and early nephroprotective therapy in oligosymptomatic patients.

Renal transplantation (Tx) is the treatment of choice for end-stage renal disease. The incidence of acute rejection after renal Tx has decreased because of improving early immunosuppression, but the risk of disease recurrence (DR) is becoming relatively high, with a greater prevalence in children than in adults, thereby increasing patient morbidity, graft loss (GL) and, sometimes, mortality rate. The current overall graft loss to DR is 7–8%, mainly due to primary glomerulonephritis (70–80%) and inherited metabolic diseases. The more typical presentation is a recurrence of the full disease, either with a high risk of GL (focal and segmental glomerulosclerosis 14–50% DR, 40–60% GL; atypical haemolytic uraemic syndrome 20–80% DR, 10–83% GL; membranoproliferative glomerulonephritis 30–100% DR, 17–61% GL; membranous nephropathy ∼30% DR, ∼50% GL; lipoprotein glomerulopathy ∼100% DR and GL; primary hyperoxaluria type 1 80–100% DR and GL) or with a low risk of GL [immunoglobulin (Ig)A nephropathy 36–60% DR, 7–10% GL; systemic lupus erythematosus 0–30% DR, 0–5% GL; anti-neutrophilic cytoplasmic antibody (ANCA)-associated glomerulonephritis]. Recurrence may also occur with a delayed risk of GL, such as insulin-dependent diabetes mellitus, sickle cell disease, endemic nephropathy, and sarcoidosis. In other primary diseases, the post-Tx course may be complicated by specific events that are different from overt recurrence: proteinuria or cancer in some genetic forms of nephrotic syndrome, anti-glomerular basement membrane antibodies-associated glomerulonephritis (Alport syndrome, Goodpasture syndrome), and graft involvement as a consequence of lower urinary tract abnormality or human immunodeficiency virus (HIV) nephropathy. Some other post-Tx conditions may mimic recurrence, such as de novo membranous glomerulonephritis, IgA nephropathy, microangiopathy, or isolated specific deposits (cystinosis, Fabry disease). Adequate strategies should therefore be added to kidney Tx, such as donor selection, associated liver Tx, plasmatherapy, specific immunosuppression protocols. In such conditions, very few patients may be excluded from kidney Tx only because of a major risk of DR and repeated GL. In the near future the issue of DR after kidney Tx may benefit from alternatives to organ Tx, such as recombinant proteins, specific monoclonal antibodies, cell/gene therapy, and chaperone molecules.

Background Smith-Magenis syndrome is a complex neurodevelopmental disorder that includes intellectual deficiency, speech delay, behavioral disturbance and typical sleep disorders. Ninety percent of the cases are due to a 17p11.2 deletion encompassing the RAI1 gene; other cases are linked to mutations of the same gene. Behavioral disorders often include outbursts, attention deficit/hyperactivity disorders, self-injury with onychotillomania and polyembolokoilamania (insertion of objects into body orifices), etc. Interestingly, the stronger the speech delay and sleep disorders, the more severe the behavioral issues. Sleep disturbances associate excessive daytime sleepiness with nighttime agitation. They are underpinned by an inversion of the melatonin secretion cycle. However, the combined intake of beta-blockers in the morning and melatonin in the evening may radically alleviate the circadian rhythm problems. Discussion Once sleep disorders are treated, the next challenge is finding an effective treatment for the remaining behavioral problems. Unfortunately, there is a lack of objective guidelines. A comprehensive evaluation of such disorders should include sleep disorders, potential causes of pain, neurocognitive level and environment (i.e. family and school). In any case, efforts should focus on improving communication skills, identifying and treating attention deficit/hyperactivity, aggressiveness and anxiety. Summary Treatment of Smith-Magenis syndrome is complex and requires a multidisciplinary team including, among others, geneticists, psychiatrists, neuropediatricians/neurologists, somnologists, developmental and behavioral pediatricians, and speech and language therapists.

Alport syndrome and diffuse leiomyomatosis: Deletions in the 5′ end of the COL4A5 collagen gene. Alport syndrome (AS) is an hereditary glomerulonephritis that is mainly inherited as a dominant X-linked trait. Structural abnormalities in the type IV collagen α5 chain gene (COL4A5), which maps to Xq22, have recently been detected in several patients with AS. The association of AS with diffuse esophageal leiomyomatosis (DL) has been reported in 24 patients, most of them also suffering from congenital cataract. The mode of transmission and the location of the gene(s) involved in this association have not been elucidated. Southern blotting using cDNA probes spanning the whole COL4A5 and a 5′ end COL4A5 genomic probe showed that three out of three patients with the DL-AS association had a deletion in the 5′ part of the COL4A5 gene extending beyond its 5′ end. This indicates that the same gene, COL4A5, is involved in classical AS and in DL-AS and that the transmission of DL-AS is X-linked dominant. These results also suggest that leiomyomatosis might be due to the alteration of a second gene involved in smooth muscle cell proliferation, which is located upstream of the COL4A5 gene, and that there might be a contiguous gene deletion syndrome, involving at least the genes coding for congenital cataract, DL and AS.

Background The global pediatric nephrology workforce is poorly characterized. The objectives of our study were to assess pediatric nephrologists’ perceptions of the adequacy of the pediatric nephrology workforce, and understand regional challenges to fellow recruitment and job acquisition. Perceptions regarding optimal length of training and research requirements were also queried. Methods A 17-question web-based survey comprised of 14 close-ended and 3 open-ended questions was e-mailed to members of the International Pediatric Nephrology Association. Quantitative and qualitative analyses were performed. Results We received 341 responses from members of the International Pediatric Nephrology Association from 71 countries. There was a high degree of overall perceived workforce inadequacy with 67 % of all respondents reporting some degree of shortage. Perceived workforce shortage ranged from 20 % in Australia/New Zealand to 100 % in Africa. Respondents from Africa (25 %) and North America (22.4 %) reported the greatest difficulty recruiting fellows. Respondents from Australia/New Zealand (53.3 %) and Latin America (31.3 %) reported the greatest perceived difficulty finding jobs as pediatric nephrologists after training. Low trainee interest, low salary, lack of government or institutional support, and few available jobs in pediatric nephrology were the most frequently reported obstacles to fellow recruitment and job availability. Conclusions Globally, there is a high level of perceived inadequacy in the pediatric nephrology workforce. Regional variability exists in perceived workforce adequacy, ease of recruitment, and job acquisition. Interventions to improve recruitment targeted to specific regional barriers are suggested. Electronic supplementary material The online version of this article (doi:10.1186/s12882-016-0299-2) contains supplementary material, which is available to authorized users.

To provide transplant physicians with a summary of the pathogenesis and diagnosis of adenine phosphoribosyl transferase (APRT) deficiency and primary hyperoxaluria and, focussed on kidney transplantation, and to discuss interventions aimed at preventing and treating the recurrence of crystalline nephropathy in renal transplant recipients.Pubmed literature search.Primary hyperoxaluria and APRT deficiency are rare inborn errors of human metabolism. The hallmark of these diseases is the overproduction and urinary excretion of compounds (2,8 dihydroxyadenine in APRT deficiency, oxalate in primary hyperoxaluria) that form urinary crystals. Although recurrent urolithiasis represents the main clinical feature of these diseases, kidney injury can occur as a result of crystal precipitation within the tubules and interstitium, a condition referred to as crystalline nephropathy. Some patients develop end-stage renal disease (ESRD) and may become candidates for kidney transplantation. Since kidney transplantation does not correct the underlying metabolic defect, transplant recipients have a high risk of recurrence of crystalline nephropathy, which can lead to graft loss. In some instances, the disease remains undiagnosed until after the occurrence of ESRD or even after kidney transplantation.Patients with APRT deficiency or primary hyperoxaluria may develop ESRD as a result of crystalline nephropathy. In the absence of diagnosis and adequate management, the disease is likely to recur after kidney transplantation, which often leads to rapid loss of renal allograft function. Primary hyperoxaluria, but not APRT deficiency, becomes a systemic disease at low GFR with oxalate deposition leading to malfunction in non-renal organs (systemic oxalosis). We suggest that these diagnoses should be considered in patients with low glomerular filtration rate (GFR) and a history of kidney stones. In APRT deficiency, stones may be confused with uric acid stones, unless specialized techniques are used (infrared spectroscopy or X-ray crystallography for urinary crystals or stone analysis; Fourier transform infrared microscopy for crystals in kidney biopsy). Where these are unavailable, and for confirmation, the diagnosis can be made by measurement of enzyme activity in red blood cell lysates or by genetic testing. In patients with primary hyperoxaluria, levels of urinary and plasma oxalate; and the presence of nearly pure calcium oxalate monohydrate in stones, which often also have an unusually pale colour and unorganized structure, increase diagnostic suspicion. Molecular genetic testing is the criterion measure. Lifelong allopurinol therapy, with high fluid intake if appropriate, may stabilize kidney function in APRT deficiency; if ESRD has occurred or is near, results with kidney transplantation after initiation of allopurinol are excellent. In primary hyperoxaluria recognized before ESRD, pyridoxine treatment and high fluid intake may lead to a substantial decrease in urinary calcium oxalate supersaturation and prevent renal failure. In non-responsive patients or those recognized later in their disease, liver transplantation cures the underlying defect and should be considered when the GFR falls below 30 ml/min/1.73 m(2); in those which or near ESRD, liver transplantation and intensive dialysis before kidney transplantation may be considered to reduce the total body oxalate burden before kidney transplantation.The availability of diagnostic tests varies between countries and centres. Data on long term outcomes after kidney transplantation are limited, especially for APRT deficiency patients.Increasing transplant physicians knowledge of APRT deficiency and primary hyperoxaluria should enable them to implement adequate diagnostic and therapeutic interventions, thereby achieving good outcomes after kidney transplantation.Fournir aux médecins transplantologues un résumé de la pathogénie, de même que les diagnostics de déficit en adénine phosphoribosyl transférase (APRT) et d’hyperoxalurie primaire, dans le contexte de la greffe rénale, ainsi que discuter des interventions visant à prévenir et à traiter la récurrence d’une néphropathie cristalline chez les greffés du rein.Recherche de documentation dans Pubmed.L’hyperoxalurie primaire et déficit en APRT sont des maladies enzymatiques humaines. Ces maladies se caractérisent par la surproduction et l’excrétion urinaire d’éléments (2,8-dihydroxyadénine pour le déficit en APRT et oxalate pour l’hyperoxalurie primaire) qui forment des cristaux urinaires. Bien que l’urolithiase récurrente représente la caractéristique clinique principale de ces maladies, la précipitation des cristaux au niveau tubulo-interstitiel peut entraîner des lésions rénales, un état pathologique appelé néphropathie cristalline. Certains patients développent une insuffisance rénale terminale (IRT) et peuvent devenir candidats à la greffe rénale. Étant donné que la greffe du rein ne corrige pas le défaut métabolique sous-jacent, les greffés présentent un risque élevé de récurrence de néphropathie cristalline, qui peut mener à la perte du greffon. Dans certains cas, la maladie n’est diagnostiquée qu’après l’occurrence de l’IRT, voire à la suite de la greffe du rein.Les patients souffrant d'un déficit en APRT ou d’hyperoxalurie primaire risquent de développer une IRT engendrée par la néphropathie cristalline. En l’absence d’un diagnostic et d’une gestion adéquate, la maladie réapparaîtra probablement suite de la greffe du rein, ce qui entraînera souvent la perte précipitée de l’allogreffe. L’hyperoxalurie primaire, et non le déficit en APRT, devient une maladie systémique à faible débit de filtration glomérulaire (DFG) caractérisée par des dépôts d’oxalate, et menant à la défaillance d’organes autres que le rein (oxalose systémique). Nous suggérons que ces diagnostics soient priss en considération chez les patients comportant un faible DFG, de même que des antécédents de calculs rénaux. Dans le cas d'un déficit en APRT, les calculs rénaux pourraient être confondus avec des calculs d’acide urique, à moins que ne soient employées des techniques spécialisées (spectroscopie infrarouge ou radiocristallographie pour l’analyse des cristaux urinaires ou des calculs par rayon X; microscopie infrarouge à transformer de Fourier pour les cristaux au cours de la biopsie des calculs). Lorsque possible, et à des fins de confirmation, le diagnostic peut être effectué par la mesure de l’activité enzymatique de la lyse des cellules sanguines rouges ou par le dépistage génétique. Chez les patients atteints d’hyperoxalurie primaire, les taux d’oxalates urinaire et plasmique, de même que la présence d’oxalate calcique monohydrate à l’état presque pur dans les calculs, qui présentent aussi généralement une pâleur et une structure désorganisée, éveillent les soupçons quant au diagnostic. Le dépistage génétique moléculaire constitue le critère de mesure. Un traitement d’allopurinol à vie, ainsi qu’un apport élevé en liquides si nécessaire, peut stabiliser la fonction rénale en situation de déficit en APRT. Si l’IRT s’est produite ou approche, les résultats de la greffe du rein à la suite du début du traitement à l’allopurinol sont excellents. Dans le cas d’une hyperoxalurie détectée avant l’IRT, un traitement à la pyridoxine et un apport élevé en liquides peuvent mener à une baisse substantielle de la sursaturation en oxalate calcique urinaire et ainsi, prévenir l’insuffisance rénale. Chez les patients qui ne répondent pas au traitement ou ceux chez qui la maladie est détectée tardivement, la transplantation hépatique enraye le défaut sous-jacent, et devrait être envisagée si le DFG chute en dessous de 30 ml/min/1,73 mL’accessibilité à des tests de dépistage varie selon les pays et les unités. Les données sur les résultats à long terme de la greffe rénale sont limitées, particulièrement en ce qui concerne les patients présentant un déficit en APRT.Enrichir les connaissances des transplantologues au sujet du déficit en APRT et de l’hyperoxalurie primaire devrait leur permettre de mettre en œuvre des interventions diagnostiques et thérapeutiques adéquates, et ainsi d’obtenir de bons résultats à la suite des greffes rénales.