Hyperlipidemic profiles during remission in childhood idiopathic nephrotic syndrome.

Hyperlipidemia, an important characteristic of idiopathic nephrotic syndrome in children (NS), is usually observed during the active phase of the disease and disappears with the resolution of the proteinuria. However, persisting lipid anomalies during remission have been reported in a few studies and raise the question of the later development of atherosclerosis. Plasma lipid profiles in 25 children with NS at remission, with or without active prednisone treatment, were compared with those of an age-matched population. The results indicate that plasma total and LDL-cholesterol levels were above the 95(th) percentile for age and sex in 12 of the 25 patients (48%) with 7 of them having apolipoprotein B and triglyceride concentrations above the 95(th) percentile. Moreover, frequently relapsing children were more likely to have abnormal lipid profile during the remission. We conclude that close monitoring of lipid levels during the remission of the NS especially in those with frequent relapses, is necessary to select the high-risk patients.

Diabetes mellitus in transplantation: 2002 consensus guidelines.

Diabetes mellitus is a serious complication following organ transplantation that is underdiagnosed, possibly due to the inadequate definitions used in published literature and the lack of standardized screening. Diabetes in transplantation amplifies the already increased risk of cardiovascular disease among transplant patients, and increases the risk of graft loss and death. Patients at risk of developing diabetes in transplantation should therefore be prospectively identified and given individualized immunosuppressive therapy to minimize the risk of developing this disease. These guidelines are intended to: (1) help identify patients at risk for diabetes after transplantation; (2) set down a standard definition of posttransplant diabetes mellitus (PTDM); (3) create a standard monitoring protocol for the diagnosis of PTDM; and (4) optimize the management of patients at risk of developing or who develop diabetes after transplantation. With improved diagnosis, individualization of therapy, and proper early management, the incidence of diabetes in transplantation, and the accompanying additional burden of illness the disease carries, may be diminished. In turn, this will help achieve the therapeutic goals of reducing the risk of graft complications, improving quality of life, and reducing postoperative morbidity and mortality in transplant patients.

Study of psychosocial parameters related to the survival rate of renal transplantation in children.

The purpose of the present study was to assess the effect of intelligence, schooling, psychomotor, emotional, and social status on renal graft survival in children. Sixty-two cadaver renal transplant recipients were evaluated retrospectively and the influence of sex, age, weight, and the use of cyclosporin A (CyA) on the success rate of the graft from 1 to 5 years later was analyzed. Psychological and social scores were devised and included as factors predictive of survival of the graft. Univariate analysis showed that the following variables predicted renal graft survival: the use of CyA (P = 0.0002), pre-transplant dialysis (P = 0.04), weight at the time of transplantation (P = 0.072), and psychological scores (P = 0.064). Association analysis demonstrated that pre-transplantation dialysis was only a chance association and therefore the parameter was discarded. Multivariate analysis showed that the predictive parameters were the use of CyA, sex, weight in kilograms, and the psychological score. An equation was then derived from variables that predict the probability that a specific patient's graft will survive more than t months. This equation is the estimated survival distribution function and is as follow: S (t) = Exp {-Exp[-(0.8882x1 - 1.827x2 + 0.037x3 - 0.1746x4) + ln t - 4.7862]} where S (t) = the survival at t months post transplantation, x1 = sex (male 1, female 2), x2 = CyA (yes 1, no 2), x3 = weight in kilograms, and x4 = psychological score. The major impact of psychological factors on renal graft survival was surprising.

Smooth muscle tumors associated with X-linked Alport syndrome: carrier detection in females.

X-linked Alport syndrome (AS) associated with diffuse esophageal leiomyomatosis (DL) has been reported to be due to deletions removing the 5' ends of both the COL4A5 and COL4A6 genes, encoding the alpha 5 and alpha 6 chains of type IV collagen, respectively, whereas a variety of mutations in COL4A5 has been identified in patients with AS alone. Here we report three additional DL-AS patients who also display deletions removing the 5' ends of both COL4A5 and COL4A6 genes. Furthermore, we tracked the mutation in 15 females belonging to six DL-AS families by gene copy number determination. We found that, like AS, DL is transmitted as an X-linked dominant trait but, contrary to AS, DL is fully penetrant and completely expressed in females. These results are in agreement with our previous work suggesting that DL could be due to a dominant effect of an abnormal alpha 6 (IV) collagen chain. Finally, we have detected a similar deletion of the COL4A5 and COl4A6 genes in a DL affected female who showed no sign of nephropathy, demonstrating the AS carrier status of this DL patient. These results emphasize the importance of molecular analysis of female DL patients for genetic counseling.

A tiny renal renin-secreting tumor.

A small 5 mm renal renin-secreting tumor is described in a child. Suggestions are made to circumvent the difficulties in investigating such cases. It is stressed that the diagnosis is probably often missed especially in the case of very small tumors.

Transient renal artery stenosis in infants: myth or reality?

We describe two infants with bilateral renal artery stenoses and severe hypertension. Adequate control of blood pressure was achieved by medical management. Endoluminal balloon dilatation of the renal arteries had been deferred because of their small size. On follow-up it was noticed that blood pressure had become progressively easier to control, with lesser amounts of antihypertensive medication. In fact, medication could be completely discontinued and blood pressure remained normal. On repeat arteriogram, bilateral renal artery stenoses had almost resolved in both patients. The etiology of the stenoses was not established in these patients. However, regardless of etiology, the transient nature of hypertension and renal artery stenoses in these two cases demonstrates that patient medical management of hypertension in infants can be a valid therapeutic option and occasionally obviate the need for unnecessary risky procedures.

Focal segmental glomerulosclerosis (FSG) 20 years later. From toddler to grown up.

In 1981, we reported the outcome of 25 children with FSG after a follow-up of 10 years. In 1991, all the living patients were reevaluated. Ten patients are now in sustained remission. Four patients still present heavy proteinuria with a normal glomerular filtration rate, four required dialysis and seven patients have died. The renal survival curve has stabilized at 56%. These data show an overall outcome slightly more favourable than we had initially reported in 1981. The difference probably stems from our referral system which enables us to see the patients at an earlier stage of their disease. The percentage of deaths is important. Among the various clinical or histological factors of predictive prognostic value only the degree of interstitial damage has reached statistical significance (p < 0.02).

Pathogenesis of the essential hypertensions.

The pathogenesis of essential hypertension (EH) is reviewed with a special focus on the development phase or the pre-hypertensive period. Three animal models are presented: the spontaneously hypertensive rat, the Dahl's salt-sensitive rat, and the Milan hypertensive rat. Some of the findings in animal models have inspired new fields and technical approaches for studying EH in man. From the original idea of Page, a new mosaic of various etiological parameters serves as a basis for reviewing the multiple facets of EH in man. One must conclude that EH is heterogeneous disease and most likely every single hypertensive patient belongs to a subgroup of the whole population of hypertensives.

Longitudinal study of various transport abnormalities as an index of severity in children and adolescents suffering from essential hypertension.

Erythrocyte cation fluxes were measured in fresh cells, on two different occasions, in 90 children and adolescents suffering from essential hypertension who were followed for a prolonged period. The purpose of the present study was to track the stability of erythrocyte cation fluxes with time, and to determine whether a known sodium transport abnormality can predict the severity of essential hypertension. The patients with an increased Na-Li countertransport were the most severely hypertensive in three different ways. Clinically, they presented a stable rather than a labile form of hypertension. Hemodynamically, the mean arterial pressure was higher than that of the other subgroups. Finally, in those children followed for more than 2 years, this subgroup remained hypertensive with time. The patients with a decreased Na,K cotransport activity were second in severity; however, blood pressure was often labile, mean arterial pressure was slightly lower than that of the previous subgroup and all patients remained hypertensive with time but in four out of six patients the hypertension was labile. The patients with increased passive sodium permeability presented a mild form of hypertension. The patients with normal erythrocyte cation fluxes seemed to form a heterogeneous group. A few were severely hypertensive, but in most the hypertension was borderline and transient. We conclude that determination of erythrocyte cation fluxes may be reproducible, and may be a useful index of the severity of essential hypertension in children and adolescents.

[Continuous peritoneal dialysis in children]. / La dialyse péritonéale chronique chez l'enfant.

Thirty-two uremic children were treated by chronic peritoneal dialysis (CPD) since February 1982. Fifteen chose chronic ambulatory peritoneal dialysis (CCPD) while the 17 others were treated by continuous cycle peritoneal dialysis (CCPD). To this day, 10 patients (31%) are alive with a functioning kidney transplant, 16 (50%) are still treated by CPD awaiting a transplant, 5 have died (16%) and one went back to hemodialysis (3%). Complication in ranking order were peritonitis, mechanical drainage problems of the catheter and hernias. Linear growth was from good to excellent in the majority of patients. Globally, CPD was found to be attractive mainly because it allows a good quality of life.

Clinical efficacy of levamisole in the treatment of primary nephrosis in children.

The purpose of the study was to evaluate the efficacy and the toxicity of levamisole given for 1 year to 16 children suffering from minimal change primary nephrosis who were relapsing frequently. The overall results showed that under levamisole the relapse rate decreased by 55% and the steroid requirements by 50%. After cessation of levamisole administration, most children (11/16) relapsed again. A second course of levamisole treatment reduced the relapse rate significantly once again. At the dosage of 2.5 mg/kg given every other day for 1 year or more, no side effects of levamisole does not cure nephrosis but reduces the incidence of relapses for the period it is administered. It also reduces the steroid requirements without any important side effects.

Heredity and blood pressure in humans: an overview.

This paper presents a review of the genetic transmission of normal blood pressure and of essential hypertension. Familial aggregation of normal blood pressure has been reported in adults, in children and even in newborns. Blood pressure aggregation phenomenon, however, is the result of both a genetic component and shared environmental factors. More specific for each etiological factor were the studies of blood pressure aggregation in twins and in adopted children. Attention was focused on the Montreal Adoption Study. In essential hypertension, a Japanese study is reviewed showing the occurrence of hypertension in the offspring of hypertensive parents. The heterogeneity of essential hypertension is underlined and two of the multiple etiological factors are particularly considered for their genetic component: the response to salt intake and erythrocyte cation fluxes. The conclusion from the literature reviewed is that essential hypertension is a polygenic disease transmitted by polygenic systems.

The influence of genetics and household environment upon the variability of normal blood pressure: the Montreal Adoption Survey.

The Montreal Adoption Survey was conducted as a cross-sectional epidemiologic study of cardiovascular risk factors in French Canadian families. Analysis included blood pressure readings of 756 adopted and 445 natural children as well as 1176 parents. A genetic model was applied to the analysis of our data. Interindividual variability of blood pressure was studied and observed correlatives of systolic and diastolic pressure of parental and non parental subjects were calculated. Based on the maximum likelihood estimates presented in the models the explanation of the parent offspring and the between sibs expected population correlatives for systolic blood pressure was the following: 61% was due to shared genes and 39% to environment shared by both parents and children. For diastolic blood pressure the explanation between parents and offspring was the following: 58% was due to shared genes and 42% due to shared environment across generation. The explanation between sibs was estimated to be the following: 33% due to generation, 24% to shared environment across generation and 43% to shared environment within generation.

Long-term follow-up of patients who underwent unilateral nephrectomy in childhood.

The long-term damaging potential of remnant nephron hyperperfusion was investigated in patients who had undergone unilateral nephrectomy in childhood. 27 such patients were examined after a mean of 23.3 years postnephrectomy. The average creatinine clearance was 83.9 +/- 16.5 ml/min/1.73 m2 or 74.3% of that in healthy controls with two kidneys; it was a value similar to that reported 3 to 6 months postnephrectomy in kidney donors. Age at the time of nephrectomy, duration of follow-up, or sex had no influence on the residual creatinine clearance. None of these patients had clinically important hypertension or proteinuria. Since so little evidence of kidney damage could be documented after such a long observation period, hyperperfusion would seem to be seldom of clinical importance in man unless other factors were present.

Local renal graft irradiation in children.

Between 1974-1979, 64 renal cadaveric transplants were performed in 54 pediatric recipients at our institution. Forty eight of these 64 transplants experienced at least one episode of acute rejection. These patients were divided in two equal groups including 24 transplants in 21 recipients, one group treated with chemical immunosuppression alone, the other group treated by chemical immunosuppression and radiotherapy. Kidney survival at 2 years was 54.1% (13/24) in the control group treated by chemical immunosuppression alone. In the group treated by radiotherapy and immunosuppression, kidney survival after 2 years gave a success rate of 45.8% (11/24). Thus, it would appear that addition of radiotherapy to standard immunosuppressive treatment exerted no beneficial long term effect in acutely rejected renal transplants. In view of the disappointing results obtained with radiotherapy, it is felt that this mode of treatment should be restricted to use in particular circumstances as a temporary means of immunosuppression where systemic immunosuppression is hazardous.

Erythrocyte cation fluxes in essential hypertension of children and adolescents.

The maximal rate of ouabain sensitive Na+ (pump), the maximal rate of Na+ and K+ furosemide (co-transport), the maximal rate of Na+ lithium countertransport and the rate constant of Na+ and K+ passive permeability were determined in the following population: 27 controls, 39 labile essential hypertensive, 10 stable hypertensive children, 6 normotensive offspring of hypertensive parent (s), and 19 hypertensive secondary to renal disease. The normal values for children were determined for all these various fluxes. When a rigid technique was applied and particularly when the post loading concentration of intracellular Na+ was determined and when the cells were not swollen by Na+ loading, the technique was reliable, reproducible and our results could be compared with the results found in adults by researchers using the same rigid technical criteria. In labile hypertension, 21% of adolescents had a decreased co-transport, 17% an increased countertransport and 6% an increased Na+ leak. In stable hypertension none had a decreased co-transport, 29% had an increased countertransport and 25% had an increased Na+ leak. Moreover, plasma norepinephrine was elevated in most of the patients presenting a decreased co-transport. Our results suggest that adolescents with labile essential hypertension and elevated plasma norepinephrine present with a decreased co-transport whereas adolescents with stable essential hypertension and normal or subnormal plasma norepinephrine present with an increased countertransport.