The Outcome of Childhood Immunoglobulin A Nephropathy with Acute Kidney Injury at the Onset of the Disease-National Study.

Introduction: IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. Decreased glomerular filtration rate is a known risk factor for disease progression. Aim: We aimed to examine factors that may contribute to disease progression in children that present with impaired eGFR at the onset of IgAN. Materials and methods: Of the 175 patients with IgAN from the Polish Registry of Children with IgAN and IgAVN, 54 (31%) patients with IgAN who had an onset of renal function impairment (GFR < 90 mL/min) were eligible for the study. All of them were analyzed for initial symptoms (GFR according to Schwartz formula, creatinine, proteinuria, IgA, C3), renal biopsy result with assessment by Oxford classification, treatment used (R-renoprotection, P-prednisone+R, Aza-azathioprine+P+R, Cyc-cyclophosphamide+P+R, CsA-cyclosporine+P+R, MMF-mycophenolate mofetil+P+R), and distant follow-up. Based on the GFR score obtained at the end, patients were divided into two groups: A-GFR > 90 mL/min and B-GFR < 90 mL/min. Results: In the study group, the mean age of onset was 12.87 ± 3.57 years, GFR was 66.1 ± 17.3 mL/min, and proteinuria was 18.1 (0-967) mg/kg/d. Renal biopsy was performed 0.2 (0-7) years after the onset of the disease, and MESTC score averaged 2.57 ± 1.6. Treatment was R only in 39% of children, P+R in 20%, Aza+P+R in 28%, Cyc+P+R in 9%, CsA+P+R in 7%, and MMF+P+R in 3%. The length of the observation period was 2.16 (0.05-11) years. At the follow-up, Group A had 30 patients (56%) and Group B had 24 patients (44%). There were no significant differences in any of the other biochemical parameters (except creatinine) or proteinuria values between the groups and the frequency of the MESTC score ≥ 2 and <2 was not significantly different between Groups A and B. Patients with normal GFR at the follow-up (Group A) were significantly more likely to have received prednisone and/or immunosuppressive treatment than those in Group B (p < 0.05) Conclusions: In a population of Polish children with IgAN and decreased renal function at the onset of the disease, 56% had normal GFR in remote observation. The use of immunosuppressive/corticosteroids treatment in children with IgAN and impaired glomerular filtration rate at the beginning of the disease may contribute to the normalization of GFR in the outcome, although this requires confirmation in a larger group of pediatric patients.

[13C2]oxalate absorption in children with idiopathic calcium oxalate urolithiasis or primary hyperoxaluria.

Intestinal oxalate absorption is an important part of oxalate metabolism influencing its urinary excretion and its measurement can be a valuable diagnostic tool in hyperoxaluric disorders. In this study, we use [(13)C(2)]oxalate absorption under standardized dietary conditions to assess intestinal oxalate absorption and its impact on urinary oxalate excretion. Tests were conducted in age-matched pediatric patients that included 60 with idiopathic calcium oxalate urolithiasis, 13 with primary hyperoxaluria, and 35 healthy children. In the idiopathic stone formers, median oxalate absorption was significantly higher than that in the controls or in patients with primary disease. From standardized values obtained in control patients, oxalate hyperabsorption was detected in 23 patients with idiopathic disease but not in any patients with primary hyperoxaluria; therefore, a significant correlation between intestinal absorption and urinary excretion was found only in those with the idiopathic disease. We have shown that increased intestinal oxalate absorption is an important risk factor of idiopathic calcium oxalate urolithiasis. In contrast, low intestinal oxalate absorption in patients with primary hyperoxaluria indicates that only foods with excessive oxalate content be restricted from their diet.

Recurrence of renal disease after kidney transplantation in children: 24 years of experience in a single center.

The aim of this study was to assess the frequency and clinical implications of a recurrence of the original renal disease in children after kidney transplantation. Thus, the records of patients with immunological and metabolic diseases transplanted between 1970 and 1994 were retrospectively analyzed. There were 113 renal transplantations in 99 patients, who had the following original diseases: focal segmental glomerulosclerosis (FSGS), membrano-proliferative glomerulonephritis type I and type II (MPGN I, II), Henoch-Schoenlein nephritis, IgA-nephropathy, hemolytic uremic syndrome (HUS) and hyperoxaluria type I (PH I) and other rare diseases. Recurrences were observed in FSGS, MPGN II, HUS and PH I but not in the other diseases. In FSGS, the recurrence rate was 20% with graft failure in 5 of 6 grafts. No specific risk factors for recurrent FSGS could be determined. In MPGN II, the recurrence was 60% but the loss of grafts occurred at the same rate as in the non-recurrence group. In HUS, recurrence was seen in 4 out of 24 renal grafts (16.6%) with subsequent graft loss in all cases. All cases had suffered from an atypical HUS. PH I recurred in 4 of 5 allografts with graft loss in all patients. The remaining graft was transplanted after a liver transplantation and graft function was well preserved for 4 years. We confirm that the risk of recurrence with loss of the graft is high in a certain group of renal diseases. In these the indication for transplantation, particularly with living related donor kidneys, needs special evaluation. A better understanding of the pathomechanism of the diseases should lead to prevention of recurrence, as in PH I in which a liver transplant is now the primary option.

ABR differences before and after dialyses.

The aim of the study was the objective evaluation of the hearing organ in children. Seven children aged 6-17 with end stage renal failure treated by haemodialysis were examined. Four- to five-hour dialyses were performed 2-3 times a week. Pure-tone audiometry was normal in five children. The reactions of brain stem responses (latency and interpeak latency) were analysed before and after haemodialyses. We conclude that the ABR differences were connected with biochemical parameters of uraemia. The present study is a preliminary one and will be continued in the future.

[Urinary N-acetyl-beta-D-glucosaminidase (NAG) activity in women with preeclampsia]. / Aktywnosc N-acetylo-beta-D-glukozaminidazy (NAG) w moczu u kobiet w ciazy powiklanej stanem przedrzucawkowym.

OBJECTIVES: Preeclampsia is the pregnancy specific disorder in which reduced organ perfusion and ischemia of the kidney, liver and brain can be detected. In the kidney, the most typical anatomopathological lesion is glomerular endotheliosis but renal tubular damage was also demonstrated. The NAG is an enzyme which is released into urine from the lysosomes of the proximal renal tubules epithelium and therefore increased urinary NAG activity is a marker of tubular damage or dysfunction. DESIGN: The aim of the study was to assess the renal tubular damage in women with preeclampsia by measuring of urinary NAG activity. MATERIALS AND METHODS: The study group consisted of 46 pregnant women in third trimester with preeclampsia. 36 normal pregnant women in third trimester and 26 healthy nonpregnant women served as two control groups. Urinary activity of NAG was measured in the second morning urine sample by colorimetric method and the results were expressed as NAG/creatinine ratio (U/mmol). RESULTS: Urinary NAG/creatinine ratio was increased in normal pregnant women in third trimester (0.77 +/- 0.44 U/mmol) exceeding that of nonpregnant women (0.23 +/- 0.16). In women with preeclampsia, the urinary NAG/creatinine ratio was significantly higher when compared to the normal pregnant women in third trimester (1.46 +/- 1.63 U/mmol). There were no correlation between urinary NAG excretion and blood pressure results in women with preeclampsia. CONCLUSIONS: The increased urinary NAG activity in women with preeclampsia seems to be a sign of proximal tubular damage. The renal function follow up study in such women is indicated.

[Use of mid-arm and head circumference to estimate gestational age and nutritional status of newborns]. / Zastosowanie wskaznika ramienno-glowowego dla oceny wieku ciazowego i stanu odzywienia noworodka.

1110 neonates, from 30 to 42 of estimated gestational age (EGA) were measured on the 1st day of life to estimate upper mid-arm circumference (MAC) and head circumference (HC). Individual MAC/HC ratio was calculated. MAC/HC ratio was used to estimate gestational age and nutritional status of the newborns. We proved that MAC/HC ratio increased linearly between 30 and 38 week of pregnancy and it stabilized between 38-42 week. We compared MAC/HC ratio with birth weight, skin fold score, and ponderal index. We concluded that this ratio may be very useful to estimate gestational age and to include the neonates to "the group of risk".

[Evaluation of oxalate/creatinine ratio in the second morning urine sample of health school children]. / Ocena wskaznika szczawianowo-kreatyninowego w II rannej porcji moczu u zdrowych dzieci w wieku szkolnym.

The evaluation of urinary oxalate excretion is one of the most important diagnostic methods in patients with urolithiasis and/or nephrocalcinosis. Since reliable 24-h urine collections are difficult to obtain in children, excretion ratios of oxalate over creatinine are increasingly being used from single urine specimens. The aim of the study was to determine the normal values of oxalate/creatinine ratios in the second morning urine sample in healthy school children. The study involved 109 children between 6 and 16 years of age. The results showed that the values of Ox/Cr ratios are decreased in older children and there was significant difference between children under and above 12 years of age (values of the 95th percentile--0.076 and 0.051 mmol/mmol respectively). The significant correlation between 24-hours urinary oxalic acid excretions and Ox/Cr ratios (r-0.756) was found. We conclude, that Ox/Cr ratio is valuable parameter for screening purposes in children.

[A nineteen year observation of a boy with branchio-oto-renal syndrome and chronic renal failure]. / Dziewietnastoletnia obserwacja chlopca z zespolem skrzelowo-uszno-nerkowym i przewlekla niewydolnoscia nerek.

Branchio-oto-renal syndrome is a rare autosomal dominant disorder of the first and second embryonic branchial arches and the urinary tract. It is characterized in its full expression by branchial fistulas or cysts, preauricular pits, outer, middle and inner ear defects, hearing loss, lachrymal duct stenosis, facial paralysis and mental retardation. Renal anomalies may range from mild hypoplasia to complete absence. Our report demonstrates the patient with classical BOR syndrome and severe renal insufficiency since infancy up to end stage renal failure at 18 years of age caused by bilateral renal hypoplasia. Although no definitive histological diagnosis was made, the clinical findings in our patients, like mild proteinuria, normal blood pressure, polyuria, polydypsia, hyperchloremic acidosis and typical course of renal failure support the diagnosis of oligomeganephronia in this case.

[Urinary calcium/creatinine, phosphate/creatinine, magnesium/creatinine and Sulkowicz test in the second morning urine sample in neonates and infants]. / Wskaznik wapniowo-kreatyninowy, fosforanowo-kreatyninowy, magnezowo-kreatyninowy i próba sulkowicza w drugiej rannej porcji moczu noworodków i zdrowych niemowlat.

The aim of the paper was to determine the values of the 5th and 95th percentiles of Ca/Cr, P/Cr and Mg/Cr, ratios in the second-morning urine samples in healthy neonates and infants. The collected Ca/Cr ratios were correlated with the results of Sulkowicz test performed on the same urine sample. The tests were done on the group of 30 neonates and 43 infants. The comparison of the 95th percentiles in the individual ratios in tested groups showed low values in the early newborn, distinctive increase in the first half followed by the decrease in the second half of the first year of live. There was no correlation found between the Ca/Cr ratios and the results of Sulkowicz tests.

Biologically active analogues of arginine vasopressin containing conformationally restricted dipeptide fragments.

In this study we described the synthesis and pharmacological properties of five new analogues of arginine vasopressin (AVP). Four of these analogues contained ethylene-bridged dipeptide Phe-Phe in positions 2 and 3; one had two N-Me-Phe residues. All new peptides were tested for vasopressor and antidiuretic activities. We also estimated the uterotonic activities of these compounds in vitro. Three analogues were highly potent V1-antagonists. One of them, namely [Cpa1,(Phe-Phe)2,3,Val4]AVP, which seemed to not interact with either V2 and oxytocic receptors, was outstandingly selective. It is interesting that the high antipressor potency of our second peptide, [(N-Me-Phe)2,3]AVP, was achieved without modification of position 1. Our results open new possibilities for the design of very potent and selective V1-antagonists of AVP.

Influence of L-naphthylalanine in position 3 of AVP and its analogues on their pharmacological properties.

We describe the synthesis and pharmacological properties of two series of analogues: one which consists of three peptides having L-1-naphthylalanine in position 3 and the second composed of analogues substituted in position 3 with L-2-naphthylalanine. All peptides were tested in bioassays for pressor and antidiuretic activities. We also checked the uterotonic activity in vitro. We observed that the activity of counterparts in both series is, in two cases, strikingly different. One of the new analogues, [(L-2-Nal)3,(D-Arg)8]VP is among the most potent antagonists of the vasopressor response to AVP. Moreover, it is the first potent V1 antagonist devoid of antiuterotonic activity. This analogue was designed without modification of position 1, which was previously thought to be essential for substantial pressor antagonism. Two other peptides, [Mpa1;(L-2-Nal)3;(D-Arg)8]VP and [Mpa1,(L-1-Nal)3,D-Arg)8]VP, are highly potent V2 agonists. The second analogue is highly selective. With the exception of [(L-2-Nal)3]AVP, which showed weak antioxytocic activity, (L-Nal)3 modification resulted in the almost complete removal of interaction of our analogues with oxytocic receptors in vitro. Our results suggest that position 3 in AVP and its analogues is important not only for binding and recognition as previously though, but also for pressor, antidiuretic and uterotonic activities. We also assume that the hindering effect caused by bulky naphthyl moiety has a significant impact on the bioactive conformations of molecules which contain Nal residue, and can thus influence their interaction with V1, V2 and oxytocic receptors.