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Biomedical subjects

P Cochat

Publications and source records attributed to P Cochat.

At least 55 records · Page 3Linked to original sources
PubMed2000

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis maps to chromosome 3q27 and is associated with mutations in the PCLN-1 gene.

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC, MIM 248250) is a complex renal tubular disorder characterised by hypomagnesaemia, hypercalciuria, advanced nephrocalcinosis, hyposthenuria and progressive renal failure. The mode of inheritance is autosomal recessive. A primary defect in the reabsorption of magnesium in the medullary thick ascending limb of the loop of Henle (mTAL) has been proposed to be essential in FHHNC pathophysiology. To identify the underlying genetic defect we performed linkage analysis in eight families, including three with consanguineous marriages. We found linkage to microsatellite markers on chromosome 3q27 with a maximum two-point lod score (Zmax) of 5.208 for D3S3530 without evidence for genetic heterogeneity. Haplotype analysis revealed crucial recombination events reducing the critical interval to 6.6cM. Recently, mutations in the gene PCLN-1, mapping to 3q27 and coding for paracellin-1, were identified by Simon et al (1999) as the underlying genetic defect in FHHNC. Paracellin-1 represents a renal tight junction protein predominantly expressed in the TAL. Mutational analysis in our patient cohort revealed eight different mutations in the PCLN-1 gene, within six novel mutations. In seven of 13 mutant alleles we detected a Leu151 substitution without evidence for a founder effect. Leu151 is a residue of the first extracellular loop of paracellin-1, the part of the protein expected to bridge the intercellular space and to be important for paracellular conductance. This study confirms the implication of paracellin-1 defects in FHHNC and points to a predominant role of this protein in the paracellular reabsorption of divalent cations in the TAL.

Amino Acid Substitution↗
PubMed2000

Renal function of children exposed to cyclosporin in utero.

BACKGROUND: The use of cyclosporin (CsA) has improved graft survival in transplant (Tx) patients despite its potential nephrotoxicity. Children born to transplanted women may present with intrauterine growth retardation (IUGR). On the basis of potential reduced nephron mass both in IUGR and in newborn experimental animals exposed to CsA in utero, we investigated the renal function of children >1 year of age born to women under maintenance immunosuppression, including CsA. METHODS: Fourteen children born to 12 Tx women (nine kidney, one pancreas-kidney, one heart, one liver) were investigated using inulin clearance (C(in)), para-aminohippuric acid clearance (C(PAH)), microalbuminuria, and electrolyte reabsorption rate. RESULTS: Gestational age of the 14 infants was 34+/-3 weeks and birth weight 2018+/-620 g. During pregnancy, CsA trough blood level was 234+/-115 microg/l and plasma creatinine range was 96-136 micromol/l. Two children were excluded from the study because renal investigation led to a diagnosis of hereditary nephritis (one Alport syndrome, one familial dominant focal segmental glomerulosclerosis) that was retrospectively completed in the mother. Renal function tests were finally performed in 12 children at 2.6+/-1.8 years of age: BP 94+/-7/55+/-5 mmHg, C(in) 117+/-28 ml/min/1.73 m(2), C(PAH) 545+/-124 ml/min/1.73 m(2), filtration fraction 0.23+/-0.03, microalbuminuria 4.2+/-3.5 mg/mmol. Electrolyte tubular reabsorption rates and urine concentrating capacity were normal. CONCLUSION: These results suggest that in children born to transplanted women taking CsA, renal function develops normally despite prolonged exposure in utero.

Child↗
PubMed2000

Vesicoureteral reflux after kidney transplantation in children.

BACKGROUND: The prevalence and significance of vesicoureteral reflux (VUR) after kidney transplantation in adults varies between authors and there have been few reports in children. METHODS: We conducted a retrospective study in a single-centre paediatric cohort. Fifty-five of the 84 children who underwent kidney transplantation over a 5-year period were checked with routine cystography after a median of 8 months post-transplantation. Graft function and urinary-tract infections were assessed during the first 6 years after transplantation. RESULTS: VUR into the graft was present in 58% of the patients. Graft function and incidence of urinary-tract infections were similar in the two groups, independent of VUR. After having excluded infections attributed to the presence of a catheter, actuarial survival rates without pyelonephritis and without pyelonephritis following a first lower urinary-tract infection were worse in patients with VUR (P:=0.017 and P:=0.0039 respectively). None of the eight patients with VUR treated with antibiotic prophylaxis after a first acute pyelonephritis (APN) episode presented subsequent APN after 4.4+/-3.3 years on therapy. CONCLUSIONS: VUR to the graft occurred in more than half paediatric renal transplant recipients. This condition was associated with an increased risk of APN. Long-term antibiotic prophylaxis seems to be able to prevent APN in transplanted children with VUR.

Adolescent↗
PubMed1999

Combined liver-kidney transplantation in primary hyperoxaluria type 1.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder characterised by an increased urinary excretion of calcium oxalate, leading to recurrent urolithiasis, nephrocalcinosis and accumulation of insoluble oxalate throughout the body (oxalosis) when the glomerular filtration rate falls to below 40-20 mL/min per 1.73 m(2). The disease is due to a functional defect of the liver-specific peroxisomal enzyme alanine: glyoxylate aminotransferase (AGT), the gene of which is located on chromosome 2q37.3. The diagnosis is based on increased urinary oxalate and glycollate, increased plasma oxalate and AGT measurement in a liver biopsy. AGT mistargeting may be investigated by immuno-electron microscopy and DNA analysis. End-stage renal failure is reached by the age of 15 years in 50% of PH1 patients and the overall death rate approximates 30%. The conservative treatment includes high fluid intake, pyridoxine and crystallisation inhibitors. Since the kidney is the main target of the disease, isolated kidney transplantation (Tx) has been proposed in association with vigorous peri-operative haemodialysis in an attempt to clear plasma oxalate at the time of Tx. However, because of a 100% recurrence rate, the average 3-year graft survival is 15%-25% in Europe, with a 5-10-year patient survival rate ranging from 10% to 50%. Since the liver is the only organ responsible for the detoxification of glyoxylate by AGT, deficient host liver removal is the first rationale for enzyme replacement therapy. Subsequent orthotopic liver Tx aims to supply the missing enzyme in its normal cellular and subcellular location and thus can be regarded as a form of gene therapy. Because of the usual spectrum of the disease, isolated liver Tx is limited to selected patients prior to having reached an advanced stage of chronic renal failure. Combined liver-kidney Tx has therefore become a conventional treatment for most PH1 patients: according to the European experience, patient survival approximates 80% at 5 years and 70% at 10 years. In addition, the renal function of survivors remains stable over time, between 40 and 60 mL/min per 1.73 m(2) after 5 to 10 years. In addition, liver Tx may allow the reversal of systemic storage disease (i.e. bone, heart, vessels, nerves) and provide valuable quality of life. Whatever the transplant strategy, the outcome is improved when patients are transplanted early in order to limit systemic oxalosis. According to the European experience, it appears that combined liver-kidney Tx is performed in PH1 patients with encouraging results, renal Tx alone has little role in the treatment of this disease, and liver Tx reverses the underlying metabolic defect and its clinical consequences.

Adolescent↗
PubMed1999

Mycoplasma pneumoniae-associated nephritis in children.

Mycoplasma pneumoniae infection is a rare cause of acute nephritis. Six children (2 girls) aged 5-10 years, admitted for nephritis, had serological tests showing recent Mycoplasma pneumoniae infection. The diagnosis of Mycoplasma pneumoniae infection was based on the presence of serum IgM, detected either by immunofluorescence (IF) (n = 1) or enzyme-linked immunosorbent assay (n = 5). Four children had a renal biopsy, with analysis of parenchymal Mycoplasma pneumoniae components by indirect IF and polymerase chain reaction. Extrarenal symptoms were: respiratory (n = 3), ear, nose and throat (n = 2), gastrointestinal (n = 3), hepatic (n = 1), neurological (n = 1), articular (n = 1), and hematological (n = 3). The patients presented with acute nephritis (1 had a nephrotic syndrome) or with acute renal failure and proteinuria. Pathological findings included type 1 membranoproliferative glomerulonephritis (MPGN, n = 1), proliferative endocapillary glomerulonephritis (n = 2) and minimal change disease (n = 1). The patient with type 1 MPGN progressed rapidly towards end-stage renal failure because of a congenital solitary kidney. Among the patients with endocapillary glomerulonephritis, 1 relapsed 6 months later and remained proteinuric, while the other recovered, as did the child with minimal change disease. The search for Mycoplasma pneumoniae antigens and nucleic acids in renal tissue was negative. However, the absence of the microorganism in the kidney is a common feature of post-streptococcal glomerulonephritis. We conclude that Mycoplasma pneumoniae is a rare yet potential cause of acute glomerulonephritis.

Acute Kidney Injury↗
PubMed1999

Primary hyperoxaluria in infants: medical, ethical, and economic issues.

OBJECTIVES: Survey on the current medical approach to and the economic issues affecting infants with primary hyperoxaluria type 1. METHODS: Questionnaire to specialized centers worldwide. RESULTS: Seventy-eight infants were identified: 44% were of Muslim origin and 56% were not. The consanguinity rate was 76% and 0%, respectively. Thirty-three percent were treated in developing countries (group 1) and 67% in developed countries (group 2). Initial presentation (4.9 +/- 2.8 months) consisted of failure to thrive (22%), urinary tract infection (21%), and uremia (14%). Radiologic findings included nephrocalcinosis (91%), urolithiasis (44%), or both (22%). The diagnosis was based on family history, tissue biopsy, and urine oxalate level in most patients from group 1 and on urine oxalate and glycolate levels, alanine:glyoxalate aminotransferase activity, and DNA analysis in patients from group 2. Therapeutic withdrawal was the final option for 40% of children; financial reasons were given for 10 of 17 patients from group 1 and 0 of 9 from group 2. End-stage renal disease started at 3.2 +/- 6.4 years of age and was present in half of the patients at the time of diagnosis. Fifty-two percent of the patients died: 82% in group 1 versus 33% in group 2; 33% of patients who underwent transplantation died versus 71% of those who did not. CONCLUSION: The management of primary hyperoxaluria type 1 in infants is a major example of the ethical, epidemiologic, technical, and financial challenges that are raised by recessive inherited diseases with early life-threatening onset. In certain circumstances, oxalosis can be regarded as a condition for which therapeutic withdrawal may be an acceptable option.

Developed Countries↗
PubMed1999

[Treatment of isolated nocturnal enuresis: alarm or desmopressin?].

BACKGROUND: Monosymptomatic nocturnal enuresis is common in healthy school children. Treatment is often required because of social and psychological convenience. We therefore conducted a randomized prospective trial using either desmopressin (D) or alarm (A). PATIENTS AND METHODS: Patients (n = 135) aged 6 to 16 years were enrolled between January 1992 and December 1994. Desmopressin (Minirin spray, Ferring SA) was given intranasally at a dose of 20 micrograms at bedtime and increased to 40 micrograms after 2 weeks if partial result was obtained. The alarm was a pad-bell device (Wet-stop, Sega) and the sound source was attached to the upper part of the pajamas. Inclusion criteria were: primary monosymptomatic nocturnal enuresis in healthy children, age > or = 6 years, absence of previous treatment using either desmopressin or alarm. The aim of the treatment was to achieve 100% dry nights. Patients were evaluated after 15 days on therapy by phone call and thereafter by attending the outpatient clinic at 2-3 and 4-6 months. At the time of the second evaluation, a switch from alarm to desmopressin (or vice-versa) was proposed to those who did not respond to the initial treatment. RESULTS: In group D (n = 62), only 27 children were included since 12 (19%) were switched to alarm and 23 (37%) were excluded because they were either non-compliant or lost to follow-up. In group A (n = 73), only 31 were included since six (8%) were switched to desmopressin and 36 (49%) were excluded for the same reasons as in group D. Prior to inclusion, the percentage of dry nights was 21% in group D and 14% in group A. After 15 days on therapy, patients from group D achieved 80% dry nights compared to 50% in group A (P = 0.001). After 3 months, patients from group D attained 85% dry nights vs 90% in group A. After 6 months, children from group A achieved 94% dry nights vs 78% in group D (P = 0.01). CONCLUSION: Desmopressin offers better short-term results than enuresis alarm but the latter is significantly more efficient in the long term. In France, the alarm device is not reimbursed by the national health service and therefore is poorly accepted, as suggested from the high rate of patients lost to follow-up.

Adolescent↗
PubMed1999

[Early hypomagnesemia, hypercalciuria and nephrocalcinosis: two cases in a family].

BACKGROUND: Hypomagnesemia-hypercalciuria and nephrocalcinosis is a rare inherited syndrome which is characterized by persistent hypomagnesemia despite supplementation, hypercalciuria, nephrocalcinosis and progressive renal failure. OBSERVATIONS: Case 1. A girl was referred at the age of 18 months because of polyuria, polydipsia and vitamin-resistant rickets. There was hypomagnesemia, hypercalciuria and mild renal insufficiency; ultrasonography showed nephrocalcinosis. For two years, she received hydrochlorothiazide and the course of the disease was marked by a significant reduction of urine output and hypercalciuria, recurrent urinary tract infections and a progression toward chronic renal failure. Case 2. The brother of this child was investigated at the age of nine months because of polyuria and polydipsia. He also had hypomagnesemia, hypercalciuria and nephrocalcinosis. Renal function was initially normal. After two years on continuous treatment with hydrochlorothiazide, hypercalciuria decreased without deterioration of renal function. No signs of rickets were noted and nephrocalcinosis remained stable. CONCLUSION: To our knowledge, these two patients are the youngest reported in the literature. The long-term deterioration of renal function is hazardous but rickets may be avoided by early administration of hydrochlorothiazide.

Calcinosis↗
PubMed1998

Successful renal transplantation in Jeune syndrome type 2.

Jeune syndrome (asphyxiating thoracic dystrophy) is a rare inherited disease which is fatal in early childhood in 70% of cases. Severe renal involvement may occur and lead to chronic renal insufficiency in patients who survive respiratory failure. Therefore the opportunity to perform kidney transplantation is quite rare. We report a successful cadaver renal transplantation in a 10-year-old boy with Jeune syndrome type 2.

Asphyxia Neonatorum↗
PubMed1998

Recombinant human growth hormone treatment of children on hemodialysis. French Society of Pediatric Nephrology.

Forty-two children, aged 2-21.5 years on hemodialysis with a height below -2.0 standard deviation score (SDS) for age, were selected to receive recombinant human growth hormone (rhGH) therapy at 17 French centers. Of the 42 children, 36 were prepubertal and 8 were in early puberty (testicular volume between 4 and 8 ml for boys, breast development B2 or B3 in girls). All received 1 IU/kg per week by daily subcutaneous injection for 1-5 years. The year before rhGH therapy served as a control period. During the 1st year of treatment, mean growth velocity increased from 3.5 to 7.0 cm/year (P < 0.0001) and was always over 2.5 cm/year. This velocity allowed a catch-up growth of +0.5 height SDS. Neither weight nor the body mass index varied compared with the pretreatment year. No change was observed in urea, creatinine, or glucose tolerance. The mean increment in bone age was 0.9 years. The mean growth velocity decreased over subsequent years (P < 0.0001), but remained higher than the prestudy velocity. A significant negative correlation was observed during the 1st year between the increase in growth velocity and the prestudy velocity (P < 0.0001), with the least gain in patients who had the best spontaneous velocity. Pubertal status had no influence on response to rhGH. No significant side effects were observed during the 103 treatment-years. Five patients developed secondary hyperparathyroidism and 1 suffered from acute pancreatitis, but the relationship with rhGH therapy remains uncertain. rhGH therapy appears indicated for children on hemodialysis, even though the potential benefits appear somewhat lower for those with a spontaneous growth velocity over 6 cm/year.

Adolescent↗
PubMed1998

Long-term nephrotoxicity of cisplatin, ifosfamide, and methotrexate in osteosarcoma.

The acute renal effects of chemotherapy are known, but long-term nephrotoxicity has rarely been investigated. The aim of the present study was to assess long-term renal function in children and adolescents who received at-risk chemotherapy, including cisplatin, ifosfamide, and methotrexate, to treat an osteosarcoma. Renal function tests [creatinine clearance, microalbuminuria, and renal excretion of sodium, potassium, chloride, calcium, magnesium (Mg), phosphorus (P), and uric acid] were prospectively performed 5.4+/-2.2 (+/-SD) years after chemotherapy (total cumulative dose: methotrexate 41+/-31 g/m2, ifosfamide 39+/-14 g/m2, cisplatin 674+/-188 mg/m2) in 18 children and adolescents. The results were compared with 13 normal volunteers matched for age and sex. Creatinine clearance, which was greater than 80 ml/min per 1.73 m2 in all patients, correlated with the total dose of ifosfamide (r=0.55, P<0.05) and cisplatin (r=0.48, P<0.05). Microalbuminuria was noted in 4 patients. Hypomagnesemia was present in 4 and hypercalciuria in 3 patients; renal excretion of P, Mg, and uric acid was higher in patients than in controls. Glomerular function was not significantly altered and only mild tubular dysfunction was present. Since renal excretion of P and Mg were increased in patients compared with normal volunteers and hypercalciuria was occasionally seen, divalent ion disorders are the most-likely potential complications.

Adolescent↗
PubMed1998

Kidney transplantation after a severe form of pseudotumor cerebri.

Pseudotumor cerebri is a syndrome characterized by intracranial hypertension (intracranial pressure >200 mmH2O) and a normal ventricular system. The diagnosis should be made as early as possible to prevent impairment of vision. Several diseases have been reported in association with pseudotumor cerebri in pediatric patients, and have been occasionally also noted with chronic renal failure, heart and renal transplantation. We report a 7-year-old boy who complained of severe headaches and visual impairment 2 years after hemodialysis for renal hypoplasia. Pseudotumor cerebri was suspected and, despite treatment with corticosteroids, acetazolamide, and lumboperitoneal diversion, visual impairment worsened. Bilateral optic nerve sheath decompression (ONSD) was performed without success and the child completely lost his vision within 2 weeks. He was successfully transplanted 2 months later. Two years post transplantation, the blind child has a normal renal function and school performance. Pseudotumor cerebri must be rapidly suspected in a child with renal failure suffering from headaches and papilledema. Visual loss may progress rapidly and ONSD seems to be the best surgical treatment when medical treatment fails. In this patient renal transplantation was well tolerated, with no deterioration in the neurological status over 2 years of follow-up.

Blindness↗