Congenital Kidney Research Articles

Correlation between aquaporins mRNA expression and renal parenchyma thickness in congenital hydronephrotic kidney in children

Objective To investigate the relationship between aquaporin-1, -2, -3, -4 mRNA (AQP1-4) and renal parenchyma thickness in congenital hydronephrotic kidney in children. Methods The expressions of aquaporin 1, -2, -3, and -4 mRNA in hydronephrotic kidney of 37 children (aged 60.3±48.8 months) were evaluated with congenital hydronephrosis and control kidney of 6 children (aged 62.7±17.1 months) by using semi-quantitative reverse transcriptase polymerase chain reaction technique. Hydronephrotic kidney parenchyma thickness was measured by B-Ultrasound preoperative-ly and verified at operation. The relations of aquaporin 1, -2, -3, and -4 mRNA to the hydronephrotic kidney parenchyma thickness were analyzed by correlation analysis. Results The aquaporin 1 ,-2,-3, and -4/beta-actin ratio in the hydronephrotic kidney and normal kidney were 0.39±0.22 vs 0.90± 0.10, 0.42±0.20 vs 0.92±0.09, 0.525±0.22 vs 0.98±0.12, 0.30±0.18 vs 0.74±0.21 respec-tively, and the differences were significant (P<0.01). Hydronephrotic kidney parenchyma thickness measured by D-Ultrasound was 5.01±2.38 mm, which was identical with those measured at opera-tion. Significant correlation was found between the levels of aquaporin 1,-2,-3, and -4 mRNA and hydronephrotic kidney parenchyma thickness (r=0.773, 0.772, 0.557, 0.625, respectively; P< 0.01). Conclusions Significant correlation exists between decreased expressions of aquaporin 1 ,-2, -3, and -4 mRNA and atrophic change of renal parenchyma. This result may provide evidence to ex-plain the mechanism why the thinner renal parenchyma thickness, the weaker renal concentration and dilution function. Key words: Aquaporins; Congenital hydronephrosis

Urinary transforming growth factor beta1 in children and adolescents with congenital solitary kidney

The aim of the study was to assess urinary transforming growth factor beta1 (TGF beta1) level in children and adolescents with congenital solitary kidney (CSK), depending on estimated glomerular filtration rate (eGFR) and compensatory overgrowth of the kidney. The study group (I) consisted of 65 children and young adults, 0.5-22 years of age (median 10.0 years) with CSK and no other urinary defects. The control group (C) contained 44 healthy children and adolescents, 0.25-21 years old (median 10.3 years). We used an enzyme-linked immunosorbent assay (ELISA) to determine the urinary level of TGF beta1, the Jaffe method to assess creatinine concentration, and the Schwartz formula to estimate GFR. Kidney length was measured while the patient was in a supine position, and overgrowth (O%) was calculated with reference to the charts. Urinary TGF beta1 level in CSK patients was more than twice as high as that in controls (P < 0.05). Also, eGFR in patients with CSK exceeded the values in the control group (P < 0.01). Compensatory overgrowth of the solitary kidney was found (median 19.44%). Urinary TGF beta1 concentration was positively correlated with eGFR (r = 0.247, P < 0.05), uric acid concentration (r = 0.333, P < 0.01), and percentage of overgrowth (r = 0.338, P < 0.01) and body mass index (BMI) centile (r = 0.274, P < 0.05). We concluded that, although proteinuria and progressive renal insufficiency is not observed in patients with CSK during childhood, the renal haemodynamic changes are present and may be a risk factor for impairment of renal function and hypertension in future life.

Neurodevelopmental follow-up of school-age children with congenital kidney disease and consecutive chronic renal failure

Neurodevelopmental follow-up of school-age children with congenital kidney disease and consecutive chronic renal failure

Optic nerve axon number in mouse is regulated by PAX2

Papillorenal syndrome is an autosomal-dominant disease caused by mutations in the PAX2 transcription factor gene. Patients often exhibit congenital excavation of the optic nerve and a spectrum of congenital kidney abnormalities. Using a novel mouse model of this syndrome (C57BL/6J PAX2(A220G/+)), we investigated the effect of PAX2 haploinsufficiency on optic nerve axon number. Because PAX2 expression and retinal pigment epithelium pigmentation have a mutually exclusive relationship during development and because tyrosinase (Tyr) has been shown to modify the penetrance of other ocular development genes, we also investigated whether tyrosinase modified the mutant PAX2 phenotype. C57BL/6J PAX2(A220G/+)Tyr(+/+) mice were crossed with mice of the same genetic background (C57BL/6J) that are homozygous for an effective null allele of tyrosinase (Tyr(c-2J/c-2J)) over two generations to create mice with four distinct genotypes: PAX2(A220G/+) Tyr(+/c-2J), PAX2(A220G/+) Tyr(c-2J/c-2J), PAX2(+/+) Tyr(c-2J/+), and PAX2(+/+)Tyr(c-2J/c-2J). Mouse optic nerves were examined clinically and histologically. Axon number was assessed in a masked fashion in optic nerves from mice of all four genotypes and compared with parental strains. Mice heterozygous for a PAX2 mutation show reduced optic nerve axon number compared with age-matched controls. Tyrosinase does not appear to modify this phenotype. Our results show that PAX2 is important in determining axon number in mouse optic nerve. The developmental effects of tyrosinase and PAX2 mutation appear to act via different pathways.

Distinct Roles and Regulations for Hoxd Genes in Metanephric Kidney Development

Hox genes encode homeodomain-containing proteins that control embryonic development in multiple contexts. Up to 30 Hox genes, distributed among all four clusters, are expressed during mammalian kidney morphogenesis, but functional redundancy between them has made a detailed functional account difficult to achieve. We have investigated the role of the HoxD cluster through comparative molecular embryological analysis of a set of mouse strains carrying targeted genomic rearrangements such as deletions, duplications, and inversions. This analysis allowed us to uncover and genetically dissect the complex role of the HoxD cluster. Regulation of metanephric mesenchyme-ureteric bud interactions and maintenance of structural integrity of tubular epithelia are differentially controlled by some Hoxd genes during renal development, consistent with their specific expression profiles. We also provide evidence for a kidney-specific form of colinearity that underlies the differential expression of two distinct sets of genes located on both sides and overlapping at the Hoxd9 locus. These insights further our knowledge of the genetic control of kidney morphogenesis and may contribute to understanding certain congenital kidney malformations, including polycystic kidney disease and renal hypoplasia.

Renal Function after Elective Infrarenal Aortic Aneurysm Repair in Patients with Pelvic Kidneys

Pelvic kidneys complicate aortic reconstructions because of increased risk of renal ischemia. Strategies for protection include shunting, cooling, and reliance on collaterals. A review identified two congenital pelvic kidney (not solitary) and five transplanted kidney patients who underwent elective abdominal aortic aneurysm repair. For congenital pelvic kidneys, topical cooling was used in one patient while no preservation was performed for the other patient. Three transplanted kidney patients were shunted, and one had endovascular repair. Postoperative creatinine values were compared to preoperative values. The two congenital pelvic kidney patients had no significant elevation of creatinine postoperatively. The transplanted kidney patient who underwent endovascular repair had no increase in creatinine postoperatively. All transplanted kidney patients who had open repair had significant but transient increase in creatinine postoperatively. Three patients who were shunted intraoperatively had normalization of creatinine. The patient who had persistent elevation of creatinine at discharge was not shunted. Aortorenal shunting or endovascular repair in transplanted pelvic kidney patients maintains renal function. For patients with congenital pelvic kidneys and adequate collaterals, cooling and collateral perfusion is usually sufficient. Though experience is limited, endovascular repair is likely to be superior to open repair in minimizing renal ischemia.

Dietary soya protein during pregnancy and lactation in rats with hereditary kidney disease attenuates disease progression in offspring

Dietary soya protein substitution for casein initiated at weaning slows disease progression in animal models of chronic renal disease. As there is increasing evidence that fetal programming can have a significant impact on kidney physiology and function in offspring, the objective of the current study was to determine whether exposure to soya protein in the diet earlier than weaning would have further benefits. Han:SPRD-cy (cy/+) breeder rats were fed a casein-based or soya protein-based diet 2 weeks prior to mating, throughout pregnancy and during lactation. Following this maternal period, 3-week-old pups were given either the same or the alternate diet for a 7-week weaning period. Dietary soya protein compared with casein in the maternal or weaning period both independently resulted in less renal inflammation (macrophage infiltration lower by 24% (P=0.0003) and 32% (P<0.001), respectively). When soya protein was given in both feeding periods, the effect was additive. Soya protein substitution for casein resulted in less oxidative damages as indicated by 28% lower oxidized-LDL staining (P=0.013) when present in the maternal period, or in the weaning period (by 56%, P<0.0001). Renal cell proliferation was reduced by 29-33% (P<0.05) in rats given soya protein whether the exposure was during the maternal or weaning period. Soya protein compared with casein in the maternal period also resulted in 33% (P=0.0013) less proteinuria, indicating superior renal function. Dietary soya protein during pregnancy and lactation represents a potential preventative approach in treating for those with congenital kidney diseases.

Cilia Protein Defects Implicated in More Diseases

Until recently, cilia were thought to be simple external cellular organelles, but now they are thought to play important roles in cell signaling, in sensing chemical and physical activity, in intracellular communication, and as photoreceptors. Cilia dysfunction has been implicated in congenital kidney disease, Bardet-Biedl syndrome, obesity, diabetes, …

Normal Glomerular Filtration Rate in Long-Term Follow-up of Children after Orthotopic Liver Transplantation

Cyclosporine A (CyA) and tacrolimus are the principal immunosuppressive agents used for OLT in children. However, progressive deterioration of renal function from calcineurin inhibitor toxicity after OLT has been widely reported. The aim of this study was to assess long-term renal function in children after OLT. We reviewed all OLT patients surviving >1 year at Sainte Justine Hospital from 1987 to 2003. The GFR (ml/min/1.73 m) was measured yearly by the Tc-99m DTPA single injection technique In all, 101 OLT patients (27 tyrosinemia, 33 biliary atresia, 5 fulminant hepatic failure, 36 miscellaneous) were studied. Median age at OLT was 35 months (range 6-178 months) in tyrosinemia group and 58 months (range 1-226 months) in the "Others" (P = NS), median pediatric end-stage liver disease score was respectively 3 (range -9 to 21) and 15 (-9 to 35), (P=0.001), and median follow-up was 6 (range 1-14) and 6 (range 1-17) (P = NS) years, respectively. Median annual GFR values in tyrosinemia fluctuated between 61 and 104 ml/min/1.73 m, with an improving tendency, and 94-121 ml/min/1.73 m in the Others. GFR did not differ on CyA vs. tacrolimus treatment. The median duration of therapy with calcium-channel blocker in the tyrosinemia group was 5 (1-13) vs. 2 (1-13) years in the Others. Median GFR remained normal in most nontyrosinemia patients (Others). Tyrosinemia patients remained stable at a lower GFR. CyA administration in three daily doses and prolonged calcium-channel blocker therapy may have contributed to this stability. Impairment of kidney function was associated with congenital kidney disease, toxic kidney injury, and portal hypertension.

Calculus in a toddler with end‐stage renal disease due to prune‐belly syndrome

Prune-belly syndrome is a congenital kidney and urinary tract anomaly which may lead to end-stage renal failure (ESRF). The present case describes an infant suffering from end-stage kidney disease due to prune-belly syndrome, undergoing chronic hemodialysis, with excessive calculus deposits which disappeared following kidney transplantation. Possible explanations are discussed. The first mechanism is associated with lack of oral function which may have caused pooling of saliva around the teeth enhancing precipitations of minerals. The second possible mechanism is associated with the child's uremic state. The third mechanism could be a disturbance in calcium-phosphor metabolism. It is possible that in the present case, the gastrostomy and the electrolyte disturbances characterizing ESRF had an additive effect.

Traumatic rupture of the congenital solitary kidney

Traumatic rupture of the congenital solitary kidney

Rein thoracique : origine congénitale ou traumatique ?

The discovery of a thoracic kidney in adult patients can lead to three diagnoses, yielding different prognoses and treatment. It can either mean traumatic or congenital diaphragmatic hernia, or a congenital ectopic kidney. Intrathoracic herniation of the left kidney trough a left diaphragmatic rupture is an exceptional discovery. We report the case of a 44 year-old man who met with a car accident 20 years ago, and presented abdominal pain. CT-scan showed an intrathoracic herniation of the left kidney trough a left posterior diaphragmatic rupture. Laparoscopic approach in lateral position showed a traumatic hernia of the left costo-diaphragmatic hiatus only containing the left kidney and its pedicle. After reduction of herniated left kidney into the abdomen, the hiatus was closed by non-resorbable prosthetic mesh. Postoperative course was uneventful.

Congenital polycystic kidney disease in lambs

AIM: To describe the pathology and inheritance of a congenital polycystic kidney disease (PKD) of sheep. METHODS: Mode of inheritance of PKD was investigated by evaluation of results of the disorder from planned matings in two consecutive years within subsets of a flock that had a high prevalence of PKD in lambs. Gross pathological and histopath- ological studies were based on tissues derived from this study. Haematoxylin and eosin (H&E)-stained paraffin sections of kidney, liver, extrahepatic biliary and pancreatic ducts, pancreas and epididymis were used to describe the lesions. RESULTS: Twenty-five lambs affected by PKD, of both sexes, were born, numbers in accord with those expected for an autosomal recessive disorder in the population studied. In all cases for which tissues were available, the renal, bile ductal (intrahepatic and extrahepatic), pancreatic and epididymal tissues had widespread dysplastic changes and associated cyst formation. CONCLUSIONS: The findings of renal cysts in conjunction with cysts in other organs are unifying features in many of the human and animal forms of PKD and suggest a related pathogenic and genetic base consistent with an autosomal recessive disorder.

Sprouty1 Is a Critical Regulator of GDNF/RET-Mediated Kidney Induction

Intercellular signaling molecules and their receptors, whose expression must be tightly regulated in time and space, coordinate organogenesis. Regulators of intracellular signaling pathways provide an additional level of control. Here we report that loss of the receptor tyrosine kinase (RTK) antagonist, Sprouty1 (Spry1), causes defects in kidney development in mice. Spry1(-/-) embryos have supernumerary ureteric buds, resulting in the development of multiple ureters and multiplex kidneys. These defects are due to increased sensitivity of the Wolffian duct to GDNF/RET signaling, and reducing Gdnf gene dosage correspondingly rescues the Spry1 null phenotype. We conclude that the function of Spry1 is to modulate GDNF/RET signaling in the Wolffian duct, ensuring that kidney induction is restricted to a single site. These results demonstrate the importance of negative feedback regulation of RTK signaling during kidney induction and suggest that failures in feedback control may underlie some human congenital kidney malformations.

Laparoscopic adrenalectomy for Conn?s syndrome complicated by ipsilateral congenital pelvic kidney

A patient presented with hypertension, hypokalemia, and a 1.2-cm left adrenal tumor. Conn's syndrome was diagnosed, for which laparoscopic adrenalectomy is now the therapy of choice. This case was complicated by an ipsilateral ectopic pelvic kidney. A laparoscopic left adrenalectomy was performed via a lateral transabdominal approach. Without the usual anatomic landmark of the ipsilateral kidney, the left adrenal gland was difficult to identify, so intraoperative ultrasound was used to locate the lesion. Postoperatively, the patient's blood pressure and potassium normalized. This is the first documented report of a laparoscopic adrenalectomy performed for adrenal adenoma with the anatomic disruption of an ipsilateral pelvic kidney.

Polycystic kidney disease in lambs in New Zealand

Extract A lethal congenital polycystic kidney disease (PCKD) has been known in lambs in New Zealand for more than 50 years and assumed to be genetic in origin. We have studied this in lambs from an experimental mating in a flock experiencing an outbreak the previous year. Two Perendale rams identified by DNA profiling (SignaGen) as sires of PCKD lambs were each mated to the other's daughters. From 71 such matings, 10 ewes gave birth to 15 PCKD lambs of both sexes. The results are in accord with those expected for a recessive autosomal trait. All lambs were dead or died shortly after birth. Their abdomens were distended by enlarged kidneys 40–140 mm in length. Their cut surface showed a multitude of cystic spaces 1–5 mm in diameter in both the cortex and medulla. Livers of affected lambs showed complex tubular and cystic patterns of bile ducts containing bile, and supported by an excess of fibrous tissue. Cystic changes also occurred in the pancreas and salivary glands.

Mass screening for early detection of congenital kidney and urinary tract abnormalities in infancy.

Recent widespread use of ultrasound has led to new efforts at screening for congenital kidney and urinary tract abnormalities. However, a standard screening methodology, criteria defining abnormalities, and follow-up procedures remain to be established. In order to establish screening criteria for these abnormalities, we performed a preliminary study in 800 1-month-old infants using provisional methods and criteria. Based on the results of preliminary study, we screened 2700 1-month-old infants in a prospective study using the criteria of renal size (longitudinal diameter <or=35 mm or >or=60 mm, or a difference between sides of >or=10 mm), and of pelvic dilatation (Society for Fetal Urology [SFU] grade 2 or higher) as positive at the first ultrasound screening. We used the SFU grading system instead of anteroposterior pelvic diameter measurements for pelvic dilatation. One hundred and twelve (4.1%) of the 2700 infants had abnormalities at the first ultrasound screening, while 18 (0.67%) had congenital kidney and urinary tract abnormalities on further examination. Use of the SFU grading system enabled us to reduce the false-positive rate at first screening, while maintaining a high diagnostic rate. The abnormalities consisted of ureteropelvic junction obstruction in seven infants, megaureter in two, hypoplastic kidney in four, vesicoureteral reflux in six (three were accompanied by hypoplastic kidneys or multicystic dysplastic kidney), multicystic dysplastic kidney in one, and horseshoe kidney in one. These results indicate that our screening methods and criteria are useful variables for detecting congenital kidney and urinary tract abnormalities.

Chronic renal failure in children in Yugoslavia

The aim of this study was to analyse the demographic variables of chronic non-terminal (CRF) and terminal (TRF) renal failure patients (pts) younger than 19 years treated in Serbia in June 2001. The prevalence of CRF pts was registered as 4.7 per million total population (pmtp) or 14.1 per million child population (pmcp) while corresponding values for TRF pts were 4.5 pmtp or 13.5 pmcp. The incidence of TRF pts during the period Jan. 2000-Jan. 2002 was 4.35 pmcp. Boys dominated only among CRF pts (34:14); 60.4% being between the ages of 6 and 19 yrs while at the time of diagnosis of HBI, 33.3% of boys were yanger than 2 yrs. The causes of CRF were: reflux nephropathy 58.3%, congenital kidney disease 16.7%, familial/hereditary 14.6%, glomerulonephritis 6.2% and Willms tu 4.1%. Reflux nephropathy was also the most common underlying disease of TRF accounted for 36.9% of total cases, while glomerulonephritis was responsible for 23.9%. Reflux nephropathy was associated with neural tube defect in 53.3% and with congenital lower urinary tract obstruction in 66.7%. The most of CRF (81.25%) and TRF pts (95.6%) were from Serbia, the others were from Monte Negro and Republic Srpska. The most of CRF (65%) and TRF (80%) pts were treated in University Children's Hospital in Belgrade. Of CRF pts 46% had serum creatinine 100-200 mumol/l, in 11% of pts it was 400-600 mumol/l and 2% of pts were in pre-terminal CRF. One third of CRF pts had proteinuria 150-500 mg/l, and second third had proteinuria greater of 1000 mg/l. Anemia was present in 54% of CRf pts, and arterial hypertension in 56%. Hemodialysis was dominant treatment modality for TRF pts and only 23.9% had functioning transplant. This is the first national study of demographic characteristics of pediatric CRF in Serbia. Since its prevalence is considerably lower than that in Western and North European countries the true prevalence is some what higher. The increasing incidence of pediatric TRF from 2.85 pmcp to 4.35 pmcp reflect better diagnosis and treatment of these patients in the recent years.

Repair of Bilateral Iliac Artery Aneurysms Associated with a Congenital Pelvic Kidney

The association of iliac artery aneurysms with a congenital pelvic kidney is extremely rare. Although multiple techniques are well described for renal preservation with renal ectopia in the setting of aortic reconstruction, few reports exist describing techniques for renal preservation in the setting of bilateral iliac artery aneurysms. A case is presented of a middle-aged man with a 6-cm right common iliac artery aneurysm and a 3-cm left common iliac artery aneurysm and a right pelvic kidney. A double-proximal-clamp technique and temporary shunting to the pelvic kidney were used during the aneurysm repair. The technical aspects of this procedure are presented as well as a brief discussion of the various options for renal preservation with renal ectopia when repairing complex aneurysmal disease.

Prune belly syndrome and congenital kidney tumors

High end sonography allows the prenatal localization of the kidneys and the corresponding urine drainage system as early as 10-13 weeks of gestation. In mid second trimester, the voiding and filling of the urinary bladder can be demonstrated by ultrasound. Obstructions are the most common abnormalities of the urogenital tract. Though less frequent in incidence, more complex sequences of anomalies such as Prune Belly Syndrome or Megacystis-Microcolon-Intestinal-Hypoperistalsis-Syndrome (MMIHS) can also be detected in early gestational age. Pathogenesis, prenatal diagnosis, pre- and postnatal treatment options and prognosis are discussed. The same risk-adapted procedures aimed to protect the fetal urinary excretory function known in the therapeutic regimen of obstructive uropathy are available as treatment options. These range from non-invasive ultrasound for diagnosis and surveillance to needle procedures or even endoscopic interventions. Another rare entity of renal abnormalities are congenital neoplasm's--megaloblastic nephroma, nephroblastoma and neuroblastoma. Prognosis and obstetrical management are to be determined individually for each patient.