Late referral to paediatric renal failure service impairs access to pre-emptive kidney transplantation in children.

BACKGROUND: Timing of referral to subspecialists may be a major determinant for access to adequate treatment. Kidney transplantation is the preferred modality of renal replacement therapy (RRT) in children. In adults, delayed referral from general physicians to nephrologists reduced access to kidney transplantation. This study investigated the association between timing of referral and the likelihood of pre-emptive kidney transplantation in children. METHODS: In this retrospective study, all patients in a tertiary paediatric nephrology centre were grouped according to first paediatric nephrologist visit (< or = 3 months prior to RRT was defined as 'late referral (LR)') and modality of first RRT. Descriptive, correlation and contingency statistics, Pearson's chi(2) test and logistic regression techniques were used for analysis. RESULTS: The median duration of nephrologists pre-RRT care of 111 children (50 girls and 61 boys; aged 8.0 years at first referral) was 1.5 (range 0-17.5) years. Thirty-two of 84 children who had their first visit >3 months prior to RRT were pre-emptively transplanted (38%), but only three of the 27 children with LR (11%; OR 4.9; 95% CI 1.37 to 17.7). Using a threshold of 12 months, the likelihood of pre-emptive kidney transplantation was still significantly influenced by timing of referral (OR 2.5; 95% CI 1.06 to 5.91). CONCLUSIONS: LR of children with chronic kidney disease to paediatric nephrology centre impairs the likelihood of receiving a pre-emptive kidney transplant. Specialised care of at least 12 months before the need for RRT arises is needed to allow for identification of and completion of the medical investigation of the living donor. Further studies using larger multicentre registries are needed to validate these single centre data.

[Suitability of sonographic evaluation of ovarian dynamics and uterine involution for prediction of postpartum fertility in the cow]. / Eignung der sonographischen Beurteilung von Ovardynamik und Uterusinvolution zur Fertilitätsprognose im Puerperium des Rindes.

To investigate the suitability of sonography for prediction of puerperal fertility, we used 34 cows with normal puerperium. For this purpose, the animals were examined gynecologically and by transrectal sonography at 10-day intervals between day 15 and day 45 p.p. as well as at oestrus, when they were inseminated. We judged uterine involution by diameter and sonographic structure of the uterine cross-section and ovarian activity by the presence of follicles and corpora lutea. Cows, which became pregnant after first insemination p.p., were assigned to group G1 (n = 16) and animals, which failed to conceive, to group G2 (n = 18). The cows of G1 obtained significantly better results concerning both uterine involution and ovarian activity than cows of G2. Thus, diameter of the uterine horn decreased faster and sonographic structure of the uterine cross section returned markedly earlier to the nonpregnant appearance in G1 than in G2. Group G1 also showed a significantly higher percentage of dominant follicles at all examinations. The results of the study show a distinct relationship between uterine involution and ovarian activity and puerperal fertility. But it has also to be resumed that the prediction of fertility for individuals will always be restricted by other reasons causing failure of conception.

Peritoneal dialysate fluid composition determines heat shock protein expression patterns in human mesothelial cells.

BACKGROUND: Low biocompatibility of peritoneal dialysis fluids (PDF) contributes to mesothelial injury. We investigated whether the heat shock proteins (HSP)-27, HSP-72, and HSP-90 are differentially induced upon exposure of mesothelial cells to PDF and whether this was affected by selective modulation of the physicochemical properties of PDF. METHODS: Human mesothelial cells (Met5A and primary human mesothelial cells) were exposed to acidic lactate and glucose-monomer based PDF (CAPD2 and CAPD3), to control culture media, or to a neutral lactate and glucose-monomer-based PDF with reduced levels of glucose degradation products (BALANCE). Expression of HSP-27, HSP-72, and HSP-90 and cellular distribution of HSP-72 were assessed by Western blotting and immunocytochemistry. RESULTS: Mesothelial cells exhibited strong constitutive expression of HSP-27 and to a lesser extent HSP-72 and HSP-90. Exposure of the cells to CAPD2 and CAPD3 resulted in strong up-regulation of HSP-72. HSP-27 levels were slightly increased, but HSP-90 levels were unchanged upon exposure to CAPD2 or CAPD3. In contrast, exposure of the cells to BALANCE did not affect HSP-27 or HSP-72 expression. The acidic pH and glucose degradation products were found to be principal in mediating increased HSP-72 expression upon exposure to PDF. CONCLUSIONS: Analysis of HSP expression represents a novel tool to assess biocompatibility of PDF. Among the HSP investigated, HSP-72 is the most predictive and accurate parameter to assess mesothelial cell injury in the early phase of exposure to PDF.

MRI in the diagnosis of a peritoneal leak in continuous ambulatory peritoneal dialysis.

Mechanical problems in continuous ambulatory peritoneal dialysis (CAPD) can result in ultrafiltration failure and disruption of CAPD therapy. The recently described tool of CT peritoneography with water-soluble contrast medium has the disadvantage of radiation and instillation of nephrotoxic substances. We report a child with a peritoneal leak diagnosed by MRI after instillation of a gadodiamide-dialysate mixture. This method provided good anatomical detail without radiation or nephrotoxic agents.

Plasmapheresis-induced remission in otherwise therapy-resistant FSGS.

We report an 8-year-old Caucasian boy who presented with steroid-resistant nephrotic syndrome. Renal biopsy showed the cellular variant of focal segmental glomerulosclerosis (FSGS). Within 1 year he received a series of therapies that have induced remission in other patients with this disease, all to no avail (conventional-dose cyclosporin A, methylprednisolone pulse therapy, high-dose cyclosporin A, and therapy with mycophenolate mofetil). He achieved remission after five sessions of plasma exchange. This case argues for aggressive therapy of resistant nephrotic syndrome in the native kidney. Plasma exchange should be considered as a possible rescue therapy arm in future study protocols.

Reduction of delayed renal allograft function using sequential immunosuppression.

Previous data suggested that outcome in small children with cadaveric renal transplantation might be improved with sequential therapy. This protocol combines augmented immunosuppression [by including antibody induction (ATG)] with avoidance of nephrotoxic medication in the immediate postoperative phase (by delayed start of cyclosporin therapy). In this report, we describe effects of this approach in 12 consecutively transplanted small children of less than 5 years of age (mean 3.2 years) who received a cadaveric renal graft at our institution between 1991 and 1998. Up to 1996 triple therapy (prednisolone, azathioprine, cyclosporin) and since 1997 sequential therapy (prednisolone, azathioprine, ATG until serum creatinine <2 mg/dl, then cyclosporin) was used for immunosuppression. Five children had delayed graft function (45.4%), all of whom were treated with triple therapy including cyclosporin from the very beginning, whereas children treated by the sequential protocol gained immediate graft function (P<0.05). There was no statistical difference between the two protocols concerning frequency or severity of rejections (67% vs. 60%, all steroid responsive), difference in the incidence of either bacterial or viral infections, or between the incidence of hypertension. Although not reaching statistical significance, 1-year graft survival rates also increased from 60% for triple therapy to 80% for sequential therapy. In conclusion, our findings confirm previous studies showing that outcome in small children undergoing renal transplantation may be improved by specially tailored treatment protocols such as sequential therapy.

Low serial serum neopterin does not predict low risk for chronic renal graft rejection.

Research has provided new and potent immunosuppressants which can potentially stop ongoing rejection. Subclinical rejection is a particular problem in the pediatric age group and early identification of children at risk is of the utmost importance. Neopterin has been previously shown to be a non-specific but sensitive marker for immunologic activity. In this study we hypothesized that low serum neopterin in the 1st year after transplantation predicts a low risk of chronic rejection. We retrospectively analyzed serial neopterin data obtained beyond the early postoperative period in 21 children and correlated the peak and average with glomerular filtration rate (GFR) loss during the subsequent years (P = 0.63, NS, r = 0.10). Our results show that serum neopterin did not differ between the majority of children who developed chronic transplant dysfunction and children with stable transplant function beyond the early post-transplant period. Thus serum neopterin failed to delineate a low-risk population who might be spared more invasive diagnostic procedures such as protocol biopsy.

Timing of peritoneal dialysis catheter removal after pediatric renal transplantation.

BACKGROUND: A peritoneal dialysis (PD) catheter is in place at the time of kidney transplantation in children receiving PD. Removal of the catheter eliminates the risk of catheter-related infections. However, the patient benefits from leaving the catheter in place if dialysis is necessary posttransplantation. There is currently no consensus on the proper timing of PD catheter removal after kidney transplantation in children. OBJECTIVE: To identify the risks and benefits of an in-dwelling PD catheter after renal transplantation in children. DESIGN: Retrospective single-center study of infectious complications and posttransplantation PD catheter use in 31 renal transplantations in 26 children. RESULTS: Peritoneal dialysis catheters were used postoperatively in 13 of the 31 transplantations. In 12 instances the catheter was needed during the first month after transplantation, and 2 of the patients involved did not have a catheter in place when needed. Six catheter-related infections occurred in 5 patients posttransplantation, with only 1 infection taking place within 1 month after transplantation. CONCLUSION: Our data suggest that the need for catheter use occurs predominantly during the first month, while infectious complications usually happen later. This strongly suggests that PD catheters should not be removed until approximately 1 month after kidney transplantation.

Heat shock protein-70 repairs proximal tubule structure after renal ischemia.

BACKGROUND: Recent studies have suggested a role of heat shock protein (HSP)-70 in cytoskeletal repair during cellular recovery from renal ischemia. The aim of this study was to test the hypothesis that HSP-70 interacts in vitro with cytoskeletal elements obtained from rat renal cortex during early reflow after renal ischemia. METHODS: Cellular proteins were fractionated into cytoskeletal pellets and noncytoskeletal supernatants by Triton X-100 extraction of rat renal cortex obtained after 15 minutes or 18 hours of reflow after 45 minutes of renal ischemia, or from controls. Aliquots of isolated pellets were coincubated with aliquots of isolated supernatants in different combinations. A repeat Triton extraction was performed, and differential distribution of Na, K-ATPase or HSP-70 was assessed by Western blots and densitometric analysis. RESULTS: Coincubation of cytoskeletal pellets obtained during early reflow after renal ischemia (exhibiting severe injury of the cytoskeletal anchorage of Na,K-ATPase) and noncytoskeletal supernatant obtained during later reflow (showing high HSP expression) resulted in specific translocation of HSP-70 from the supernatant into the pellet, functionally associated with dose-dependent stabilization of Na,K-ATPase within this cytoskeletal fraction. These effects could be reproduced by incubation with purified HSP-70 and were abolished by the addition of anti-HSP-70 antibodies. CONCLUSION: These data support the hypothesis that HSP-70 interacts with cytoskeletal elements during the restoration of proximal tubule cell structure and polarity after renal ischemia. This experimental approach represents a new in vitro assay to study further the role of HSP in cellular repair.

Reproducible erythroid aplasia caused by mycophenolate mofetil.

Anemia secondary to mycophenolate mofetil (MMF) was recently described in experimental animals. A clinical association between MMF and anemia has been observed, but there are no proven reports. We describe a girl with chronic graft failure who developed erythroid aplasia under immunosuppression with MMF. She showed prompt resolution when MMF was discontinued and a recurrence of this clinical course when MMF was restarted. As re-challenge with a medication is the most definitive approach for showing a direct relationship between the drug and the side effect, this case clearly demonstrates that MMF can cause erythroid aplasia.

Uterine androgen receptor mRNA expression in metestrous and anestrous bitches being healthy or suffering from Pyometra.

The importance of androgens for the female reproductive system has been investigated for decades and a number of androgen sensitive processes has now been identified in female reproductive organs. For carnivore species no data were available so far about uterine androgen sensitivity and its regulation. The present study therefore aimed to investigate whether androgen receptors (AR) are present in the dog uterus, whether they are regulated throughout the ovarian cycle and whether pyometra affects their expression rate. Uterine tissue samples were collected from 28 bitches of different ages and various breeds. The samples were grouped according to the stage of estrous cycle (metestrus ME or anestrus AE) and the pathological status of the uterus (i.e. suffering from pyometra or not). Androgen receptor mRNA (AR mRNA) was quantified from 500 ng of total RNA isolated from the tissue samples using an internally standardized reverse transcription polymerase chain reaction (RT-PCR) described previously. The amount of total RNA extractable per g tissue was elevated during pyometra. The successful amplification of the expected 172 bp fragment from canine uterine RNA together with the confirmation of the identity of this fragment by sequence analysis, demonstrates that AR is expressed in this particular tissue. Comparing the expression rates in uteri from bitches during ME or AE being healthy (H) or suffering from pyometra (P), the only significant (p < 0.01) difference was found between H and P uteri during ME with 3.5-fold lower expression rates in P. Although the same seems true for AE bitches, a significant difference could not be demonstrated due to the low number (n = 2) of diseased animals in the AE group. There was no evident effect of the stage of ovarian cycle on uterine AR mRNA levels.

[Immunoglobulin transfer in the viable, newborn calf]. / Der Immunglobulintransfer beim vitalen, neugeborenen Kalb.

Parturitions of 26 dairy-cows were observed and the viability of the newborn calves assessed. Immediately after birth as well as after the first and forth colostrum intake a blood probe was taken from the neonates and investigated for the following parameters: blood gas, blood picture, total-IG, concentrations of IGG1, IGM and IGE, total proteins and albumin. Before each feeding a colostrum sample was assayed for the same parameters with the exception of blood gas, blood picture and albumin. A transferindex (KLOBASA et al., 1994) was calculated to investigate the absorption of TP, IG, IGG1, IGM and IGE. In some of the blood samples there was no IGE detectable, even after colostrum intake. High individual differences were striking and blood concentrations were not related to the milk contents or the time until first feeding. The total proteins were strongly correlated to the serum concentrations of IGG1, but only in samples taken after first colostrum feeding. Vital calves showed the following tendency: colostrum intake of less than 1 l within the first 15 hours after birth and/or colostrum intake with TP-concentrations of 80 I.U./l was partly compensated by increased absorption of TP. 24 hours after birth serum-immunoglobulinconcentrations were 6-12 mg/ml; weight gain was normal and no calf became ill. In 60% of cases the transferindex for IGM was higher than for IGG1 or IGE.

Clinical impact of peritoneal equilibration testing in treatment of congenital lactic acidosis by acute peritoneal dialysis.

Although peritoneal equilibration testing (PET) is increasingly used in chronic peritoneal dialysis, there is little knowledge about the clinical impact of PET in the acute setting. We report about more than threefold increases in lactate removal by adjusting the dialysis prescription according to the results of PET in an infant with severe congenital lactic acidosis.

[Effect of quality markers of ejaculates of beagle dogs after frequent semen collection]. / Beeinflussung der Qualitätsmerkmale des Ejakulates bei Beagle-Rüden durch häufige Samengewinnung.

Semen was collected from 4 adult beagle-dogs twice weekly during six months. The libido did not alter and frequent semen collection did not deteriorate the investigated parameters. Because of a bad constitution, the semen quality of one male was not sufficient. The mean volume of the second fraction of the remainder slightly decreased from January until June from 1.2 to 0.5 ml. On the contrary the mean volume of the first and third fraction increased, mainly from April until May from 0.3 to 1.0 (first fraction) and from 1.0 ml to 5.0 ml (third fraction), resp. The average of the sperm number/microliter augmented from month to month from 71.3 to 324.4 x 10(3)/microliter. The transmigration rate reached its maximum in April (52.2%). The monthly average number of the percentage of morphologically abnormal spermatozoa correlated with the corresponding transmigration rate. There were negative, linear relationships between specific morphological abnormalities of spermatozoa and both estimated motility and transmigration rate.

[Modification of the quality indicators of the ejaculate of beagle dogs due to frequent collections over time]. / Beeinflussung der Qualitätsmerkmale des Ejakulates bei Beagle-Rüden durch Dauerbelastung.

Ejaculates from five adult beagle dogs were investigated for changes of spermatologic parameters. Semen was collected daily during 12 weeks. The parameters volume, sperm count, and transmigration rate (TMR) increased during the first three to five weeks and decreased in the middle of the experiment. The percentage of morphologically abnormal spermatozoa just exceeded 20% from the fifth to the seventh week and in the tenth week, respectively. Either the results remained on a low level (volume), or they returned to normal from the tenth week on (morphology, TMR, sperm count). Semen quality diminished after five weeks. It is concluded, that daily semen collections during more than five weeks can cause decreased libido, aspermia, and impairment of the conception rates.

Increased cyclin dependent kinase in aortic tissue of rats fed homocysteine.

BACKGROUND: Hyperhomocyst(e)inemia is strongly associated with occlusive arterial disease. Several mechanisms for the development of vascular lesions have been described. A direct effect of homocysteine on proliferation of smooth muscle cells and collagen expression was proposed recently. These observations led us to examine the effect of homocysteine on cyclin dependent kinase, the starter of mitosis and reflecting proliferation. METHODS AND RESULTS: Thirty Him: OFA rats were divided into three groups. Ten animals were fed for a period of six weeks 50 mg/kg body wt per day homocysteine, ten the same dose of homocysteic acid and ten remained untreated controls. At the end of the experiment we determined aortic cyclin dependent kinase, phosphokinases A and C, aortic homocyst(e)ine and aortic hydroxyproline. Aortic cyclin dependent kinase was significantly (p = 0.0001) elevated in the homocysteine treated group (mean 120 +/- 15) compared with the homocysteic acid treated group (mean 71 +/- 11) or the untreated group (mean 72 +/- 10 fmol/mg aortic tissue). Aortic homocyst(e)ine was significantly higher in homocysteine treated animals (p = 0.0002) strongly correlating with cyclin dependent kinase (r squared = 0.85, p = 0.0001) and with aortic hydroxyproline (r squared = 0.66, p = 0.0001), which in turn was significantly (p = 0.0001) increased in the homocysteine treated group. Phosphokinases A and C determined to rule out nonspecific effects on kinases were not increased by administered homocysteine. CONCLUSIONS: Our findings indicate that homocysteine stimulates aortic cyclin dependent kinase with the possible consequence of proliferation of aortic cells. Aortic collagen accumulation could be explained by either the homocysteine-effect on collagen synthesis described in literature, or secondarily, by increased proliferation of collagen produced aortic cells.

Hereditary osteo-onycho-renal dysplasia with excess urinary pyridinoline cross-links and abnormal kidney collagen cross-linking.

HOOD syndrome is a rare genetic disorder also known as nail patella syndrome. Biochemical and molecular biological data are rare and not conclusive. Preliminary data suggest the involvement of collagen type IV. This would, however, not be enough to explain nail or bone involvement. As kidney pathology would be consistent with a cross-linking disorder, we tested collagen IV and kidney collagen cross-linking on SDS-PAGE. This method showed a remarkable reduction in high-molecular-weight collagen polymers. The patient's and his mother's urinary pyridinoline cross-link excretion was manifold increased. Disturbed cross-linking of connective tissue proteins would help to explain the multiorgan involvement.

[Traumatically caused prolapse of the vaginal mucosa and retroflexion of the bladder in the bitch]. / Traumatisch bedingter Vorfall der Vaginalschleimhaut und Retroflexion der Harnblase bei der Hündin.

Four years after having been heavily injured in the perineal region by a firearm the presented bitch showed dysuria and signs of intense irritation. Clinical and radiological examinations revealed the fact of a partial loss of the vaginal channel and supporting tissues, consequently leading to a retroflexion of the bladder into the extroverted part of the vagina. The bitch recovered completely after a plastic operation.

Determination of the urinary D/L trans-3-hydroxyproline ratio: a noninvasive screening test for Alport syndrome.

Because disturbed conformation of connective tissue proteins can be accompanied by increased racemization (i.e., an increased ratio of dextrorotatory (D) to levorotatory (L) amino acid molecules), we studied by high-performance liquid chromatography the renal excretion of the D-form of the basement membrane-specific trans-3-hydroxyproline in patients with Alport syndrome. The D/L ratio was significantly higher in patients with Alport syndrome than in patients with other renal diseases or in healthy control subjects. We therefore suggest that this factor may be a simple noninvasive (screening) test for Alport syndrome.