Longitudinal evaluation of transport kinetics in children receiving peritoneal dialysis

Functional stability of the peritoneal membrane is necessary for maintenance of peritoneal dialysis (PD) as a therapeutic option. Few studies have investigated this issue in children. We evaluated the peritoneal membrane solute transport capacity longitudinally in 26 children (mean age 11.0±5.5 years) receiving long-term PD. Each patient underwent a standardized peritoneal equilibration test on two occasions (mean interval between studies 19.8±5.9 months) to determine solute dialysate to plasma (D/P) ratios, dialysate glucose to initial dialysate glucose (D/D₀) ratios, and mass transfer area coefficients (MTAC). The correlation of transport capacity with peritonitis history was also assessed. No significant change in MTAC, D/P, or D/D₀ values were found when comparing original and follow-up data of the group overall. However, transport of creatinine and glucose was significantly (P<0.05) greater in the peritonitis group compared with the group without peritonitis, and differences in the change over time between the peritonitis groups was significant for MTAC creatinine (P=0.035) and D/D₀ glucose (P=0.020). In summary, this experience demonstrates functional stability of the peritoneal membrane in pediatric patients receiving PD. However, follow-up assessments of peritoneal solute kinetics may be necessary in patients with a history of peritonitis in order to permit early identification of those who may be at risk for ultrafiltration failure and sclerosing peritonitis. Received: 12 June 1998 / Revised: 8 December 1998 / Accepted: 13 December 1998     

Prophylactic calcium and vitamin D treatments in steroid-treated children with nephrotic syndrome

Steroid treatment has several side effects, including the deterioration of the bone and mineral metabolism in children with nephrotic syndrome. This randomized prospective study was conducted to determine the effects and prophylactic role of calcium plus vitamin D treatment on bone and mineral metabolism in children receiving prednisolone treatment. 40 children (27 boys and 13 girls) with NS (18 new onset and 22 relapsing) were included in the study. Their mean age was 4.6±1.8 years. All patients received prednisolone treatment (2 mg/kg/day for 4 weeks followed by alternate days at the same dose for 4 weeks). The patients were randomized into treatment (vitamin D 400 IU plus calcium 1 g daily) and non-treatment groups. Bone mineral density, serum Ca, P, alkaline phosphatase and urinary Ca and P excretions were analyzed at the beginning and 2 months after the treatment. The XR36 Norland device was used for bone mineral density analysis. Bone mineral density was significantly decreased in both the treatment (0.54±0.15 to 0.51±0.1 g/cm², P =0.001) and non-treatment (0.52±0.18 to 0.45±0.16 g/cm², P <0.001) group. But the percentage of bone mineral density decrease was found to be significantly lower in the treatment group than in the non-treatment group (4.6±2.1% vs. 13.0±4.0%, respectively; P <0.001). Serum calcium and urinary calcium excretion increased in the treatment group (8.0±1.0 to 10.0±0.5 mg/dl and 1.1±0.5 to 3.2±1.0 mg/kg/day) and non-treatment group (8.1±0.8 to 10.0±0.6 mg/dl and 1.4±0.9 to 3.8±3.3 mg/kg/day) after prednisolone treatment (P <0.001). Steroid treatment decreases bone mineral density in children with nephrotic syndrome. Vitamin D plus calcium therapy at the current doses reduces but does not completely prevent bone loss, with no additional adverse effects.     

Racial differences in the incidence and renal outcome of idiopathic focal segmental glomerulosclerosis in children

The North American Pediatric Registry reports that from 1987 to 1989 blacks and Hispanic children accounted for 23% of all renal transplants performed but 38% of those performed for focal segmental glomerulosclerosis (FSGS). From these data, we infer that blacks and Hispanics form a disproportionate number of FSGS patients who progress to end-stage renal disease (ESRD) compared with white children. To explore this hypothesis we assessed our single-center experience of FSGS comparing black and Hispanic with white children. Of 177 black and Hispanic children followed in our clinic for idiopathic nephrotic syndrome (NS) between 1974 and 1989, 57 were diagnosed as having FSGS (group I). The mean age at onset of NS of these group I patients was 7.3±4.6 years and the mean duration of follow-up was 8.25±4.3 years. During the same period, 13 of 65 white patients (group II) with idiopathic NS were found to have FSGS. Their mean age (7.8±4.8 years) and duration of follow-up (8.8±4.8 years) were similar. Therapeutic modalities in the two groups were also similar. Of group I patients, 78% (42/54) reached ESRD compared with 33% (4/12) of group II patients (P<0.01). Life table analysis showed that 50% of black and Hispanic children will reach ESRD within 3 years of FSGS. In a subset of patients, multiple regression analysis revealed that the higher the serum creatinine at the onset of NS (P<0.01,r=0.519), and the higher the serum cholesterol at the onset of NS (P<0.02,r=0.511), the more rapid the progression to ESRD. Based on our findings, a national survey to determine if FSGS is more virulent in black and Hispanic children is warranted.Presented in part at the 22nd Annual Meeting of the American Society of Nephrology, Washington, D. C., December 1989     

Intraperitoneal hypercoagulation and hypofibrinolysis is present in childhood peritonitis

 An increased rate of obstruction of peritoneal dialysis catheters is observed during peritonitis. Hypercoagulation and hypofibrinolysis may explain this increased occurrence. We studied plasminogen activator inhibitor type 1 antigen (PAI-1), tissue-type plasminogen activator antigen (t-PA), D-dimer (DD), plasmin-α₂-antiplasmin complexes (PAP), and thrombin-antithrombin III complexes (TAT) in 7 children with peritonitis (group A) and 12 children during stable peritoneal dialysis (group B). Albumin, β₂-microglobulin, IgG, and α₂-macroglobulin were measured for baseline transperitoneal protein transport. After a dwell of 6 h with 1.36% Dianeal, dialysate and serum samples were collected. Dialysate to plasma ratios of all proteins were calculated. During peritonitis (group A) TAT was higher: 34.7 versus 22.0 (P=0.01). PAI-1 was increased in group A: 76.5 versus 22.9 (P=0.004). PAP was decreased during peritonitis (group A): 24.9 versus 39.3 (P=0.01). In group A, DD were decreased. 10.8 versus 26.7 (P=0.002). t-PA was similar in both groups (23.7 in group A vs. 27.7 in group B; P=0.26). In both groups TAT, PAI-1, t-PA, PAP, and DD were significantly higher than in baseline transperitoneal transport, suggesting intraperitoneal production. Hypercoagulability and hypofibrinolysis were present during peritonitis compared with the control situation. Received: 9 April 1998 / Revised: 11 August 1998 / Accepted: 12 August 1998     

Automated peritoneal dialysis: a Spanish multicentre study

Background: A prospective sequential study on continuous ambulatory peritoneal dialysis (CAPD) and three techniques of automated peritoneal dialysis (APD) was conducted to assess peritoneal clearances, the influence of peritoneal permeability on nocturnal APD clearances and the suitability of the peritoneal equilibration test (PET) for predicting clearances on APD. Methods: After performing a PET, a series of clinical, biochemical and dialysis adequacy markers were evaluated after 2 months on CAPD, continuous cycling peritoneal dialysis (CCPD) and tidal volume peritoneal dialysis (TPD) with 50% and 25% tidal volumes. Forty five patients participated and 33 completed the study. Results: Serum urea and creatinine decreased significantly whereas haemoglobin and glucose increased. Mean peritoneal urea clearance (1/week) was 55.40±8.76 on CAPD, 74.82±12.62 on CCPD, 69.20±14.63 on TPD (tidal 50%) and 66.89±13.23 on TPD (tidal 25%); mean creatinine clearance (1/week/1.73 m²) was 42.80±9.95, 52.19±11.11, 51.31±13.3 and 49.17±11.83 respectively. Both clearances were significantly lower on CAPD than on APD (<0.001). CCPD was the automated technique that provided the best nocturnal urea clearance (P<0.01). Nocturnal creatinine clearance did not show significant differences between CCPD and TPD (tidal 50%), being better with both techniques than with TPD (tidal 25%). There were statistically significant differences between nocturnal dialysate to plasma (D/P) ratios and those corresponding to the nearest times in the PET. The urea D/P ratio at 180 min and the creatinine D/P ratio at 240 min of the PET were the parameters that better estimated nocturnal clearances on APD. Conclusions: This study confirms that TPD does not improve the results of CCPD. Significant differences between D/P ratios during actual nocturnal cycles and PETs were observed. Key words: automated peritoneal dialysis; CAPD; clearances; PET      

Longitudinal changes in peritoneal equilibration test with or without peritonitis in children

This study was conducted to evaluate longitudinal changes in the peritoneal equilibration test (PET) in children treated with continuous peritoneal dialysis (CPD). The effects of prolonged CPD and episodes of peritonitis on the PET were examined. PET was repeated up to five times in 12 paediatric patients who were subdivided into groups with and without peritonitis. In the peritonitis group (n=6), the dialysate/plasma (D/P) creatinine ratio at a 4-h dwell time decreased progressively with time on CPD in five of six patients. In a comparison of the initial and final PETs performed at a mean interval of 22.8±11.6 months, the D/P creatinine ratio in the final PET was significantly lower than in the initial PET (P<0.01). In contrast, in the non-peritonitis group (n=6), the D/P creatinine ratio in the final PET was unchanged for 28.2±12.3 months from the initial PET. The D/Do glucose ratio at a 4-h dwell time was unchanged over time in each group. Thus, repeated PET measurements revealed that membrane permeability for creatinine was not affected by prolonged CPD itself, but decreased with time after episodes of peritonitis. Although the protocol for PET is not standardised in children, PET was useful for determining the sequential changes in peritoneal function in such patients on CPD.     

Leptin in peritoneal dialysate from continuous ambulatory peritoneal dialysis patients.

The adipocyte-derived hormone leptin is the 16-kd product of the ob gene that regulates food intake and body weight. Plasma leptin level is elevated in patients with chronic renal failure, partly because of impaired clearance through the kidney. In this study, we examined whether leptin is cleared into peritoneal dialysate in patients with end-stage renal disease treated by continuous ambulatory peritoneal dialysis (CAPD). The subjects were 46 CAPD patients and 67 age- and gender-matched healthy subjects. Leptin concentration in peritoneal dialysate from CAPD patients was measurable by a sensitive enzyme-linked immunosorbent assay (ELISA), and the daily loss of leptin by the peritoneal route was estimated to correspond to the amount contained in approximately 2 L plasma. Dialysate leptin concentration correlated positively with plasma leptin level and with percent body fat measured by dual-energy X-ray absorptiometry. The dialysate-to-plasma (D/P) ratio of leptin concentration was twice higher than expected from its molecular weight. D/P ratios of beta2-microglobulin, albumin, and transferrin showed strong correlations with each other (r = 0.768 to 0.801), whereas the correlation between D/P ratios of leptin and beta2-microglobulin was less impressive (r = 0.378). This was also the case with the relationship between apparent peritoneal clearances of these macromolecules, suggesting that dialysate leptin had some origins other than passive transport of plasma leptin. To test the hypothesis that abdominal visceral fat may contribute to the unexpectedly raised peritoneal dialysate leptin concentration, multiple regression analysis was performed. Leptin concentration in peritoneal dialysate showed significant association with plasma leptin level and D/P ratio of beta2-microglobulin, and it also showed an independent association with abdominal visceral fat but not with subcutaneous fat assessed by ultrasonography. These results showed that peritoneal dialysate from CAPD patients contained a significant amount of leptin, which derived presumably from both plasma and local visceral fat tissue.     

Co-administration of cyclosporine and ketoconazole in idiopathic childhood nephrosis

The concomitant use of cyclosporine (CsA) and ketoconazole (keto) in children with nephrotic syndrome (NS) has never been reported in the literature. This retrospective cohort study was conducted to investigate cost saving, safety, and efficacy of co-administration of keto and CsA in children with NS. The study included 186 nephrotic children receiving CsA therapy. Most were steroid dependent or resistant, and the most common pathology was focal segmental glomerulosclerosis (62%). Among our patients, 137 received daily keto therapy (keto group) 50 mg/day in addition to CsA, while 49 received CsA alone (non-keto group). The characteristics of both groups were comparable and the mean (±SD) duration of treatment was 22.9 ± 8.1 months. Co-administration of keto significantly reduced the mean dose of CsA with an overall net cost saving of 37%. It also resulted in a significant improvement of CsA response, more successful steroid withdrawal, and decreased the frequency of renal impairment. Keto was generally well tolerated and safe. We conclude that co-administration of low-dose keto with CsA in children with idiopathic NS is safe, significantly reduces the cost of CsA therapy, and may improve the patient outcome.     

Neutral-pH peritoneal dialysis solution improves peritoneal function and decreases matrix metalloproteinase-2 (MMP-2) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD)

Background Conventional lactate-buffered peritoneal dialysis (PD) solutions have several bioincompatible characteristics, including acidic pH, lactate buffer, and the presence of glucose degradation products (GDPs), and these characteristics contribute to membrane dysfunction in PD patients. The formation of GDPs can be reduced by separating the glucose component of the solution from the lactate component during sterilization. This study was carried out to evaluate the clinical effect of dual-chambered neutral-pH PD solution in patients on continuous ambulatory peritoneal dialysis (CAPD).Methods Thirteen CAPD patients using conventional PD solution were enrolled in this study. The fast peritoneal equilibration test (fast PET) was performed periodically before and after treatment with neutral PD solution. The concentration of matrix metalloproteinase-2 (MMP-2) in dialysate effluent was measured using 4-h dwelling 2.5% glucose dialysis solution. The patients were categorized into two groups, according to the value of the initial dialysate/plasma (D/P) creatinine ratio: i.e., lower transporters (group L, D/PCr < 0.65) and higher transporters (group H, D/PCr 0.65).Results The mean D/P creatinine ratio measured by fast PET, was significantly decreased (0.72 ± 0.09 to 0.60 ± 0.06; P < 0.03) after treatment with neutral PD solution in group H. The mean glucose level in 4-h dwelling dialysate effluent was elevated (824.6 ± 195.9mg/dl to 942.6 ± 147.8mg/dl; P < 0.022) in all subjects. In group H, a significant decrease of MMP-2 in the dialysate effluent was recognized from 15 months after the beginning of treatment with the neutral PD solution (141.4 ± 52.5ng/ml to 91.3 ± 15.1ng/ml; P < 0.05), with the lowest value being shown at 21 months (80.0 ± 31.8ng/ml; P < 0.03).Conclusions Neutral-pH peritoneal dialysis solution decreased the MMP-2 level in dialysate and improved peritoneal function in high-transporter patients with CAPD treatment.     

ACE gene insertion/deletion polymorphism in childhood idiopathic nephrotic syndrome

The aim of this study was to determine the distribution of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, and its effects on clinical, laboratory, histological findings, treatment responses and progression to end-stage renal disease in childhood idiopathic nephrotic syndrome (NS). 227 children diagnosed with idiopathic NS were included in the study. Eighty-three of patients were steroid resistant and 77 of patients were focal segmental glomerulosclerosis. The control group was consisted of 287 unrelated healthy adult volunteers. ACE gene I/D polymorphism were analyzed by using PCR based method. In the entire group of children with NS, the frequencies of the II, ID, and DD genotypes of ACE gene were 13.7%, 38.3% and 48%, respectively. D allele frequency was higher in NS group than control group (0.67 vs. 0.56, p=0.001). Percentage of frequent relapser patients was found more frequently in ID or DD genotype (38.7%) than II genotype (15%) when only steroid sensitive patients were evaluated (p=0.045). The D-allele frequency was 0.65, 0.69 and 0.68 respectively in focal segmental glomerulosclerosis, biopsy proven minimal change and entire minimal change group (p>0.05) and 0.69 and 0.64 respectively in steroid sensitive and resistant groups (p>0.05). D allele frequency was not significantly different in patients with or without end-stage renal disease (0.64 vs. 0.67 respectively, p>0.005) when 115 patients who were at least five year follow-up were evaluated. The D allele frequency was higher in NS patients than healthy controls and DD or ID genotype was related with frequent relapses. ACE gene I/D polymorphism was not important in laboratory and histological findings and progression of the disease in children with NS.     

Adverse effect of peritonitis on peritoneal membrane function in children on dialysis

 The effect of peritonitis on peritoneal membrane solute transport characteristics was determined as part of a multicenter study in children on continuous ambulatory/cycling peritoneal dialysis. Ninety-three children each underwent a 4-h peritoneal equilibration test (PET) with 1,100 ml/m² 2.5% Dianeal for determination of mass transfer area coefficients (MTAC), dialysate to plasma ratios (D/P) for creatinine and urea at 0, 30, 60, 120, 180, and 240 min and dialysate glucose levels at 0, 30, 60, 120, 180, and 240 min for calculation of D/Do. The mean age of the study cohort was 10.1±5.6 years (range 0.1–19 years). There were 162 historical episodes of peritonitis; at the time of the PET tests, 36 children had never had an episode of peritonitis (group I) while 57 children had a history of one or more episodes of peritonitis (group II). In group II children, the 4-h glucose D/Do was significantly lower and the 4-h D/P creatinine ratio, the creatinine MTAC, and the glucose MTAC were significantly higher (each P<0.05) than in group I. In children with a history of peritonitis caused by Gram-negative organisms, the 4-h glucose D/Do (P<0.05) and the creatinine MTAC (P<0.05) were significantly lower and the glucose MTAC (P=0.07) nearly significantly lower than in children without a history of peritonitis. Linear regression analysis did not demonstrate a correlation between any of the variables and duration of peritoneal dialysis, while the rate of peritonitis was weakly correlated with glucose MTAC (r=0.34, P<0.05) and with 4-h glucose D/Do (r=–0.222, P<0.01). We conclude that children with a history of peritonitis have peritoneal membranes that are more permeable to glucose and creatinine than children without a history of peritonitis, and that the peritoneal membranes of children who have had peritonitis caused by Gram-negative organisms are also more permeable to creatinine and glucose. Such changes are likely to have an adverse effect on membrane function and could eventually contribute to ultrafiltration failure. Received: 29 December 1997 / Revised: 13 April 1998 / Accepted: 14 April 1998     

Pefloxacin in adriamycin induced nephrotic syndrome in the rat

Background. Pefloxacin, a fluorinated 4-quinolone, has recently been advocated as a first-line treatment for minimal-change nephropathy (MCN) or focal segmental glomerulosclerosis (FSGS). To further evaluate this issue we have utilized an animal model resembling human MCN, namely adriamycin-induced nephrotic syndrome in Wistar male rats. Methods. Adriamycin at a dose of 7 mg/kg was injected intravenously to all rats at day zero. Rats were divided into two groups: group A (n=20) given only water served as the control group while group B (n=19) was administered pefloxacin at 150 mg/kg. At days 7, 14, 21 and 28, the rats were placed in metabolic cages and daily proteinuria determined. Results. The nephrotic syndrome developed in all rats within 7 days of adriamycin administration. At day 7, proteinuria in group B was 173±78 vs 423±626 mg/day in group A, P <0.02, but thereafter at days 14, 21 and 28, no significant difference in urinary protein excretion was noted. Conclusion. These results suggest that in this animal model of NS mimicking human MCN, pefloxacin's antiprotienuric effect is only of a mild and transitory nature. In view of the above data and the overall results in human patients (detailed herein), the use of pefloxacin as definitive treatment of the NS cannot be recommended.     

Prostaglandin-mediated loss of proteins during peritonitis in continuous ambulatory peritoneal dialysis

The loss of proteins into the dialysate and the peritoneal generation of the immunoreactive prostanoids PGE2, 6-keto-PGF1 alpha, PGF2 alpha, and TXB2 were studied in 12 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) during 16 episodes of peritonitis and in inflammation-free periods. Protein permeability, defined as the ratio of dialysate/plasma protein (D/P), decreased with increasing molecular weight, independent of the condition of the peritoneum. With peritonitis a general rise of permeability was noticed for total protein (TP) and the individual proteins beta 2-microglobulin (beta MG), albumin (Alb), immunoglobulin G (IgG), and alpha 2-macroglobulin (alpha MG) (P less than 0.001). Simultaneously, an increase of dialysate prostanoids occurred with predominance of the vasodilative acting prostaglandins PGI2, determined as its metabolite 6-keto-PGF1 alpha, and PGE2 by factors of 8.4 and 9.7, respectively (P less than 0.001), in comparison to peritonitis-free control. In the early phase of peritonitis (0 to 12 hr after the onset of therapy) the augumented peritoneal prostaglandin synthesis correlated positively with the increased permeability of TP (r greater than or equal to 0.7446, P less than 0.01) and the individual proteins beta MG, Alb, IgG, and alpha MG (r greater than or equal to 0.5970, P less than 0.05). Inhibition of cyclo-oxigenase activity by local administration of indomethacin inhibited both the generation of 6-keto-PGF1 alpha and PGE2 by 39 and 42%, respectively (P less than 0.05), and the peritoneal loss of TP by 34% (P less than 0.05). In the absence of peritonitis indomethacin only diminished the synthesis of PGE2 whereas the generation of the other prostanoids remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low serum apolipoprotein AI levels in amyloidosis related to familial Mediterranean fever

Amyloidosis (A) related to familial Mediterranean fever (FMF) causes serious morbidity and mortality in children. Our study evaluates serum levels of apolipoprotein (Apo) AI, AII, B, and E and Apo AII/AI ratios as a non-invasive diagnostic tool for amyloidosis in children with FMF and FMF-A. Results were compared with those of patients with childhood nephrotic syndrome (NS) and healthy children (controls). Significantly lower serum levels of Apo AI (90.20±28.30 mg/dl) were documented in patients with FMF-A than in all other groups (FMF 126.89±51.07 mg/dl, NS 140.38±33.73 mg/dl, and controls 134.67±12.73 mg/dl) (P<0.01). Diagnostic sensitivity, specificity, and predictive value for this test were 85%, 80%, and 85%, respectively. Apo AII/AI ratio results were essentially equal in all groups (P>0.05). It is concluded that a decreased Apo AI serum level, but not Apo AII/AI ratio, is a useful, non-invasive test for the early diagnosis of FMF-A in children.     

Peritoneal kinetics in children undergoing continuous ambulatory/cycling peritoneal dialysis

We present a report on peritoneal kinetics in children undergoing continuous ambulatory/cycling peritoneal dialysis (CAPD/CCPD). The effect of long-term treatment with CAPD/CCPD, peritonitis episodes, and dialysate inflow volume on peritoneal kinetics in children was evaluated. Peritoneal kinetic studies (PKSs) were performed in 47 pediatric patients at different times following initiation of CAPD/CCPD. In 18 of these patients, PKSs were repeated up to four times with an unchanged dialysate inflow volume after up to 55 months of CAPD/CCPD treatment. The PKS consisted of a 120-minute dwell with a 1.5% dextrose dialysate solution. Peritoneal clearance, dialysance, and dialysate to plasma (D/P) concentration ratios were calculated after 30, 60, and 120 minutes. The results of the serial PKSs demonstrate stable peritoneal creatinine and urea-N clearance, dialysance or D/P concentration ratios. Furthermore, there was no adverse effect of 32 peritonitis episodes. Finally, inflow volumes correlated directly with clearances of creatinine (P less than .01), urea-N (P less than .001), and potassium (P less than .001), and there was an inverse relationship to the D/P concentration ratios of creatinine (P less than .01), urea-N (P less than .01), potassium (P less than .01), and uric acid (P less than .01). Thus, CAPD/CCPD is a useful and effective long-term treatment modality for pediatric patients. Maximal dialysate inflow volumes should be provided to enhance peritoneal kinetics.     

Focal segmental glomerulosclerosis in children: comparison of nonedematous and edematous patients

Persistent proteinuria without edema, associated with focal segmental glomerulosclerosis (FSGS), has been increasingly observed in our pediatric population. The clinical and pathological features and long-term outcome of these patients are poorly understood and less frequently reported. Ten nonedematous children (10.3±1.4 years) with proteinuria and FSGS are compared with 16 children (9.0±0.4 years) with FSGS and nephrotic syndrome (NS). Urinary protein excretion and serum cholesterol were statistically higher and serum albumin statistically lower in the children with FSGS-NS. The percentage of glomeruli with sclerosis was similar in the two groups. Mesangial proliferation was observed more frequently in the nephrotic children and focal or diffuse tubular atrophy more often in the nonedematous children with FSGS. Followup serum creatinines are more than 1 SD above the mean for age in 3 of 10 nonedematous patients with FSGS and 9 of 16 patients with FSGS-NS. Of 10 nonedematous patients with FSGS, 1 progressed to renal failure 20 months after diagnosis, while 3 of 16 patients with FSGS-NS progressed to renal failure. We conclude from these data that NS is a poor prognostic sign in FSGS in children and that neither the percentage of glomeruli with sclerosis nor the presence of tubular atrophy is predictive of NS in our patients.     

Lymphocyte subpopulations,interleukin-2 and interleukin-2 receptor expression in childhood nephrotic syndrome

Abnormal T lymphocyte function and reduced interleukin-2 (IL-2) production have been implicated in the pathogenesis of the nephrotic syndrome (NS). We investigated: (1) lymphocyte subpopulations and expression of IL-2 receptor (IL-2R) on T cells using two-colour flow cytometry, (2) serum IL-2 and (3) the soluble component of IL-2R (sIL-2R) in serum, using enzyme-linked immunosorbent assay, in 38 children with NS. All children, except those in remission, had marked proteinuria. They were divided into groups according to renal pathology: (1) steroid-sensitive NS (SSNS) not receiving prednisolone therapy, (2) SSNS on prednisolone, (3) focal segmental glomerulosclerosis (FSGS), (4) SSNS in remission and not receiving prednisolone therapy, (5) congenital NS (CNS). Results were compared with 26 age-matched controls. Total T lymphocytes (CD3) were reduced in groups 1 and 2; CD4 count was reduced in groups 1–4; CD8 count increased in groups 2 and 3; CD8 and CD19 (B lymphocytes) were significantly reduced in group 5. Increased IL-2R expression (CD25) on CD4 lymphocytes was noted in groups 1, 2 and 3 implying activation of these cells. In patients with SSNS, increased serum sIL-2R was recorded during relapse (1,273±497 U/l vs. 913±401 U/l in remission,P<0.005) but free serum IL-2 was not detectable at any stage. The specific alterations in lymphocyte subpopulations in SSNS and FSGS would imply an involvement of the immune system distinct from that in CNS.     

Long-term linear growth of children with severe steroid-responsive nephrotic syndrome

The present study was designed to evaluate the risk of permanent linear growth impairment in a selected group of 42 children with steroid-dependent nephrotic syndrome (SDNS) and 14 children with frequently relapsing nephrotic syndrome (FRNS). Longitudinal height measurements were available in all patients from the onset of the disease for a mean follow-up of 11.7±3.5 years. During the prepubertal period, patients lost 0.49±0.6 height SD score (HtSDS) (P<0.001). Twenty-three patients have reached their final height with an average loss of 0.92±0.8 HtSDS from the onset of their disease (P<0.001) and 0.68±0.7 from their target HtSDS (P<0.001). The pubertal growth spurt was mildly delayed in male but not female patients. Steroid therapy, calculated as the mean duration of prednisone (PDN) treatment or as the average cumulative PDN dose, was the only predictor of poor growth evolution. Partial catch-up growth occurred after PDN withdrawal. Children with early onset NS and adolescent patients, who were still receiving PDN after the age of 9 years in girls and 11 years in boys, were at higher risk for HtSDS loss. In conclusion, children with severe steroid-responsive NS are at risk of permanent growth retardation secondary to prolonged courses of steroid treatment.     

Charge and size selectivity of proteinuria in children with idiopathic nephrotic syndrome

 Experimental studies have pointed to charge selectivity as an important determinant of glomerular permeability to macromolecules. Loss of glomerular basement membrane (GBM) polyanion has been proposed as a cause of the selective proteinuria in minimal change nephrotic syndrome (MCNS). However, the presence of less-anionic albumin in urine than plasma from MCNS and focal and segmental glomerulosclerosis (FSGS) patients has been interpreted both as evidence for partial maintenance of charge selectivity and for involvement of other pathogenic mechanisms. The exact role of charge selectivity in the pathogenesis of nephrotic proteinuria remains controversial. We have examined the clearance of endogenous proteins of differing size and charge in children with idiopathic nephrotic syndrome (NS). Chromatofocusing was used to determine the isoelectric points (pIs) of albumins in paired plasma and urine samples from patients with FSGS (n = 6) and MCNS (n = 6). Charge selectivity was assessed by comparing the pIs of the fractions with the highest albumin concentration (modal pI) in plasma and urine. The difference between the modal pIs was defined as the delta modal pI. Charge selectivity was also assessed from the albumin/transferrin and IgG4/IgG1 clearance ratios; size selectivity from the IgG1/albumin and IgG1/transferrin as well as the IgG4/albumin and IgG4/transferrin clearances. In children with FSGS, the mean (± SD) delta modal pI was  – 0.05 ± 0.16, and in MCNS  – 0.05 ± 0.11. Neither value differed significantly from zero. The albumin/transferrin clearance ratio showed no significant difference between FSGS and MCNS, but the IgG4/IgG1 clearance ratio was significantly higher in MCNS (P<0.05). Size selectivity was significantly reduced in FSGS compared with MCNS (for IgG1/transferrin P<0.01 and for IgG1/albumin P<0.05). For IgG4/transferrin and IgG4/albumin, P was <0.05. In conclusion, there was no evidence for residual charge selectivity in idiopathic NS associated with either MCNS or FSGS during nephrotic-range proteinuria. There was a significant loss of GBM size selectivity in children with FSGS with heavy proteinuria compared with children with MCNS with heavy proteinuria. Received August 7, 1996; received in revised form and accepted December 16, 1996     

Effect of fosinopril in children with steroid-resistant idiopathic nephrotic syndrome

We aimed to test if fosinopril reduces urinary protein excretion and alleviates renal tubular damage in normotensive children with steroid-resistant idiopathic nephrotic syndrome (SRINS). We also aimed to evaluate whether there are changes in steady-state blood pressure and serum concentrations of serum angiotensin-converting enzyme (ACE) and plasma renin activity or angiotensin II (AT-II) in children under this treatment. Forty-five normotensive patients with SRINS were randomly divided into two groups. Group I was treated with fosinopril and prednisone for 12 weeks, while group II was treated with prednisone alone for the same duration. The values of 24-h urinary protein excretion were 1.25±0.64 vs 2.52±0.56 g/24 h (P<0.05), 1.16±0.45 vs 2.42±0.24 g/24 h (P<0.05), and 1.10±0.41 vs 2.05±0.46 g/24 h (P<0.05) in group I and group II patients, respectively, at 4, 8, and 12 weeks. Patients in group I showed lower serum concentrations of urinary retinol-binding protein and β₂-microglobulin (P<0.01) at the end of the study, but the patients’ blood pressure and components of the renin-angiotensin system (RAS) had no change during treatment. The result suggested that fosinopril significantly reduced proteinuria and alleviated renal tubular damage, but did not influence blood pressure and components of systemic RAS in normotensive children with SRINS.