Observations of a large Dent disease cohort Blanchard, Anne; Curis, Emmanuel; Guyon-Roger, Tiphaine ...
Kidney international,
August 2016, 2016-08-00, 20160801, Letnik:
90, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Dent disease classically combines low-molecular-weight proteinuria, hypercalciuria with nephrocalcinosis, and renal failure. Nephrotic range proteinuria, normal calciuria, and hypokalemia have been ...rarely reported. It is unknown whether the changes in phenotype observed over time are explained by a decrease in glomerular filtration rate (GFR) or whether there is any phenotype-genotype relationship. To answer this we retrospectively analyzed data from 109 male patients with CLCN5 mutations (Dent-1) and 9 patients with mutation of the OCRL gene (Dent-2). In Dent-1 disease, the estimated GFR decreased with age, by 1.0 to 1.6 ml/min per 1.73 m2/yr in the absence and presence of nephrocalcinosis, respectively, with no significant difference. Median values of low-molecular-weight proteinuria were in the nephrotic range and remained at the same level even in late renal disease. End-stage renal disease occurred in 12 patients, at a median age of 40 years. Hypercalciuria decreased with glomerular filtration and was absent in 40% of the patients under 30 and 85% of those over the age of 30. Hypophosphatemia did not resolve with age and calcitriol concentrations were in the upper normal range. Kalemia decreased with age, with half of the patients over the age of 18 presenting with hypokalemia. Thus, no phenotype/genotype correlation was observed in this cohort of patients with Dent disease.
Neurologic involvement is the most threatening complication of diarrhea-associated hemolytic uremic syndrome (D+HUS).
We report a retrospective multicenter series of 52 patients with severe initial ...neurologic involvement that occurred in the course of D+HUS.
Verotoxigenic Escherichia coli infection was documented in 24. All except two patients had acute renal failure that required peritoneal dialysis, hemodialysis, or both techniques. A first group of eight patients remained with normal consciousness; five of them had protracted seizures. A second group of 23 patients had stuporous coma; five of these had protracted severe seizures, and 18 had a neurologic defect including pyramidal syndrome, hemiplegia or hemiparesia, and extrapyramidal syndrome. A third group of 21 patients had severe coma. Plasma exchanges were undertaken in 25 patients, 11 of whom were treated within 24 hours after the first neurologic sign; four died, two survived with severe sequelae, and five were alive without neurologic defect. Magnetic resonance imaging (MRI) for 29 patients showed that (1) every structure of the central nervous system was susceptible to involvement; (2) no correlation seemed to exist between special profile of localization on early MRI and the final prognosis; and (3) MRI did not exhibit any focal lesions in three patients. The overall prognosis of the series was marked by the death of nine patients and severe sequelae in 13.
Neurologic involvement is associated with a severe renal disease but does not lead systematically to death or severe disability.
Cerebello-oculo-renal syndrome (CORS), also called Joubert syndrome type B, and Meckel (MKS) syndrome belong to the group of developmental autosomal recessive disorders that are associated with ...primary cilium dysfunction. Using SNP mapping, we identified missense and truncating mutations in RPGRIP1L (KIAA1005) in both CORS and MKS, and we show that inactivation of the mouse ortholog Rpgrip1l (Ftm) recapitulates the cerebral, renal and hepatic defects of CORS and MKS. In addition, we show that RPGRIP1L colocalizes at the basal body and centrosomes with the protein products of both NPHP6 and NPHP4, known genes associated with MKS, CORS and nephronophthisis (a related renal disorder and ciliopathy). In addition, the RPGRIP1L missense mutations found in CORS individuals diminishes the interaction between RPGRIP1L and nephrocystin-4. Our findings show that mutations in RPGRIP1L can cause the multiorgan phenotypic abnormalities found in CORS or MKS, which therefore represent a continuum of the same underlying disorder.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Current therapy for congenital nephrogenic diabetes insipidus consists of appropriate water intake coupled with decreased urine output obtained by means of a low-sodium diet and a combination of ...thiazide diuretics with renal prostaglandins inhibitors or amiloride. We report a case of congenital nephrogenic diabetes insipidus that was complicated by paradoxical water intoxication secondary to liberal water intake and the initiation of hydrochlorothiazide and indomethacin combination therapy. This report emphasizes the importance of evaluating the water balance and of a quick response with strict protocols following the initiation of indomethacin and thiazide diuretics in nephrogenic diabetes insipidus.
Primary hyperoxaluria type 1 results from alanine:glyoxylate aminotransferase deficiency. Due to genotype/phenotype heterogeneity in this autosomal recessive disorder, the renal outcome is difficult ...to predict in these patients and the long-term impact of conservative management in children is unknown. We report here a multicenter retrospective study on the renal outcome in 27 affected children whose biological diagnosis was based on either decreased enzyme activity or identification of mutations in the patient or his siblings. The median age at first symptoms was 2.4 years while that at initiation of conservative treatment was 4.1 years; 6 children were diagnosed upon family screening. The median follow-up was 8.7 years. At diagnosis, 15 patients had an estimated glomerular filtration rate (eGFR) below 90, and 7 children already had stage 2–3 chronic kidney disease. The median baseline eGFR was 74, which rose to 114 with management in the 22 patients who did not require renal replacement therapy. Overall, 20 patients had a stable eGFR, however, 7 exhibited a decline in eGFR of over 20 during the study period. In a Cox regression model, the only variable significantly associated with deterioration of renal function was therapeutic delay with a relative risk of 1.7 per year. Our study strongly suggests that early and aggressive conservative management may preserve renal function of compliant children with this disorder, thereby avoiding dialysis and postponing transplantation.
GPB are often performed in PRT to detect subclinical acute rejection or IF/TA. Reducing immunosuppression side effects without increasing rejection is a major concern in PRT. We report the results of ...GPB in children transplanted with a steroid‐sparing protocol adapted to immunological risk. Children under 18 yr who received a renal transplantation between April 1, 2009 and May 31, 2012 were included. Immunosuppression consisted of an antibody induction therapy, tacrolimus, and MMF for all recipients. CSs were administered to children under five yr old, or receiving a second allograft. Twenty‐eight children were included, 50% were CSs free. GPB were performed between three and six months. IF/TA was documented in seven biopsies; four of these seven children were CS free. One child, with CSs, presented a borderline rejection, and another child, steroid free, with significant inflammatory interstitial infiltrate, considered as a subclinical rejection, was treated with CSs pulses. The median eGFR was stable (74, 67.5, and 82 mL/min/1.73 m² at, respectively, seven days, three months, and one yr). Patient and graft survival were 100%. These results have to be confirmed in a larger cohort, with long‐term follow‐up.
Background
Familial steroid-sensitive nephrotic syndrome (SSNS) is a rare condition. The disease pathophysiology remains elusive. However, bi-allelic mutations in the
EMP2
gene were identified, and ...specific variations in
HLA-DQA1
were linked to a high risk of developing the disease.
Methods
Clinical data were analyzed in 59 SSNS families.
EMP2
gene was sequenced in families with a potential autosomal recessive (AR) inheritance. Exome sequencing was performed in a subset of 13 families with potential AR inheritance. Two variations in
HLA-DQA1
were genotyped in the whole cohort.
Results
Transmission was compatible with an AR (
n
= 33) or autosomal dominant (AD,
n
= 26) inheritance, assuming that familial SSNS is a monogenic trait. Clinical features did not differ between AR and AD groups. All patients, including primary (
n
= 7) and secondary steroid resistant nephrotic syndrone (SRNS), (
n
= 13) were sensitive to additional immunosuppressive therapy. Both
HLA-DQA1
variations were found to be highly linked to the disease (OR = 4.34 and OR = 4.89;
p
< 0.001). Exome sequencing did not reveal any pathogenic mutation, neither did
EMP2
sequencing.
Conclusions
Taken together, these results highlight the clinical and genetic heterogeneity in familial SSNS. Clinical findings sustain an immune origin in all patients, whatever the initial steroid-sensitivity. The absence of a variant shared by two families and the
HLA-DQA1
variation enrichments suggest a complex mode of inheritance.
Des recommandations spécifiques à la néphrologie ont été rédigées sous l’égide de l’Association internationale de néphrologie pédiatrique en 2011. Ces recommandations préconisent une transition ...individualisée, débutant entre 12 et 14 ans, avec des informations sur la maladie et les traitements du patient adaptées à l’âge et au niveau intellectuel. Les recommandations insistent sur l’importance d’identifier un référent pédiatre et un référent en service adulte, ainsi qu’une équipe paramédicale et de travailleurs sociaux ; elles insistent également sur l’importance d’associer les aidants (les familles et l’entourage proche, etc.), la nécessité d’un dossier spécifique de transition et d’une visite préalable du service adulte avant le transfert. L’International Pediatric Nephrology Association recommande que le transfert soit réalisé au « bon moment » de la vie du jeune et non à ses 18 ans ; ce « bon moment » étant défini par le moment où le jeune se sent prêt, en période de stabilité aussi bien médicale que familiale, scolaire et sociale. Afin de fournir au jeune des compétences d’autogestion (empowerment) appropriées de sa maladie et de sa vie, dans le cadre de la filière maladies rénales rares (ORKiD), nous avons élaboré un programme avec questionnaire adapté à l’âge en nous inspirant de celui mis en place à Southampton au Royaume-Uni. Ce document présente les outils développés par le groupe de travail de la filière de soins ORKiD.
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