Renal function impairment with growth failure

Branchio-oto-renal syndrome combines branchial arch defects, hearing impairment and renal malformations or hypoplasia. Due to the high phenotypic variability, prenatal diagnosis has a limited prognostic value in mutation-positive cases. We report the first branchio-oto-renal syndrome molecular prenatal diagnosis and ultrasonographic follow-up, showing a normal renal growth until the 24th week of pregnancy, a growth deceleration during the third trimester and a renal volume recovery during the first months of life.

Despite worldwide availability of prenatal ultrasound, many patients are diagnosed in adult life with congenital anomalies such as ureteropelvic junction obstruction (UPJO), undescended testicle (UDT), ureterocele, hypospadias, vesicoureteral reflux (VUR) and primary obstructing megaureter (POM). The aim of this review was to describe these clinical conditions and their suggested management based on the available medical literature.

Adult UPJO is not a rare condition; symptomatic patients should be treated rather than observed. Treatment options are nephrectomy for non-functioning kidneys and reconstructive surgery for functioning renal units. The adult UDT has low fertility potential and increased cancer risk; hence most of the data in the literature indicate performing an orchiectomy. Adult ureteroceles are usually related to single systems and they are intravesical and less obstructive. For symptomatic patients endoscopic incision showed high efficacy for symptom elimination with minimal side effects. Primary hypospadias correction in the adult patient is feasible, but success rates are low compared to the pediatric age group. Secondary correction, whether primary correction was performed in childhood or adulthood, is a challenging task with a high complication rate. Treatment decisions regarding adult patients with VUR are difficult to make as the available data are inconsistent; there is no strict evidence that reflux in an adult is directly related to renal growth impairment, ascending pyelonephritis, and/or embryo loss in a pregnant woman. In contrast to the pediatric age group, adult POM is usually a symptomatic condition and related to a high complication rate including infections, stone formation and renal failure. Spontaneous resolution is rare and hence active surgical management is advocated.

Congenital urological anomalies identified in adulthood are not rare and pose a management challenge to the urologist. For most of the reviewed diseases, evidence-based management direction is difficult due to a lack of randomized trials and long-term follow up.

Among the mitogen-activated protein kinase (MAPK) family members, extracellular signal-regulated kinase (ERK) promotes cell proliferation or differentiation, whereas c-jun N terminal kinase (JNK) and p38 MAPK are thought to inhibit cell growth and induce apoptosis. The MAPK family may plays some role during kidney development, when large-scale proliferation and apoptosis have been observed to occur. Also, in this period, the renin-angiotensin system is markedly activated. We have demonstrated that angiotensin-converting enzyme inhibition in the developing rat kidney increases apoptosis and decreases cell proliferation, which may account for renal growth impairment. The aim of this study, therefore, was to examine the relationship between the MAPK family and renin-angiotensin system during neonatal renal development. Newborn rat pups were treated with enalapril (30 mg . kg(-1) . d(-1)) or normal saline for 7 d. Right kidneys of both groups were selected for immunohistochemical stains of MAPKs and activating transcription factor-2 (ATF-2), and left kidneys were selected for reverse transcriptase-PCR and immunoblot analysis of MAPKs, phospho-MAPKs, and ATF-2. To determine whether apoptosis is involved in the same tubules that highly expressed JNK and p38, we performed terminal deoxynucleotide transferase-mediated nick-end labeling stain for apoptotic cells and immunohistochemical stains for JNK-2, p38, and ATF-2 expression in the serial sections from the same kidney of the enalapril-treated group. In the enalapril-treated group, JNK-2, p38, phospho-JNK-2, phospho-p38, and ATF-2 protein expressions were significantly increased, and their immunoactivities were strongly detected in the proximal tubular epithelial cells in the cortex, compared with the control group. Especially JNK-2 and p38 expressions were highly activated and were spatially in accordance with the occurrence of apoptosis. ERK1/2 and phospho-ERK expressions were not changed by enalapril. These results suggest that the expressions of the MAPK family are modulated by angiotensin-converting enzyme inhibition in the developing kidney. JNK and p38 may be implicated to participate in angiotensin II-related intracellular signaling pathways of renal apoptosis in the developing kidney.