Diffusion tensor imaging for the study of early renal dysfunction in patients affected by bardet-biedl syndrome

Kidney structural abnormalities are common features of Bardet-Biedl syndrome (BBS) patients that lead to a progressive decline in renal function. Magnetic resonance diffusion tensor imaging (DTI) provides useful information on renal microstructures but it has not been applied to these patients. This study investigated using DTI to detect renal abnormalities in BBS patients with no overt renal dysfunction. Ten BBS subjects with estimated glomerular filtration rates over 60 ml/min/1.73m2 and 14 individuals matched for age, gender, body mass index and renal function were subjected to high-field DTI. Fractional anisotropy (FA), and mean, radial and axial diffusivity were evaluated from renal cortex and medulla. Moreover, the corticomedullary differentiation of each DTI parameter was compared between groups. Only cortical FA statistically differed between BBS patients and controls (p = 0.033), but all the medullary DTI parameters discriminated between the two groups with lower FA (p < 0.001) and axial diffusivity (p = 0.021) and higher mean diffusivity (p = 0.043) and radial diffusivity (p < 0.001) in BBS patients compared with controls. Corticomedullary differentiation values were significantly reduced in BBS patients. Thus, DTI is a valuable tool for investigating microstructural alterations in renal disorders when kidney functionality is preserved.

FREQUENCY OF CONGENITAL ANOMALIES OF THE KIDNEY AND URINARY TRACT BY MEANS OF ULTRASONOGRAPHY IN NEONATES AT A TERTIARY-CARE HOSPITAL

Objective: To determine the frequency of congenital anomalies of the kidney and urinary tract by means of ultrasound in neonates. Study Design: Cross-sectional study. Place and Duration of Study: Department of Radiology and Diagnostic Imaging, Rehman Medical Institute, Peshawar, from May 2015 to Jan 2016. Methodology: A total of 150 neonates reporting for routine abdominal ultrasonography were included. Honda Convex Scanner model HS-2000 with probe of frequency of 5-7 MHz was used for the ultrasonography. Results: Mean age of the neonates was 13.8 ± 7.5 days. Seventy-six (50.7%) were male and 74 (49.3%) were female. Congenital anomalies of the kidney and urinary tract were observed in 10 (6.7%) neonates. Most neonates had more than one anomaly. The left side was involved in 6 (4%) neonates while right side was involved in 4 (2.7%). Hydronephrosis was the most common abnormality found in 8 (5.3%) cases. The location of kidneys was abnormal (ectopic) in 2 (1.3%) neonates. Abnormal dimension was seen in seven cases and abnormal corticomedullary differentiation was found in 5 (3.3%) cases. Non-symmetrical cases were 5 (3.3%). Hydroureter was observed in 3 (2%) neonates and urinary bladder was abnormal in 2 (1.3%) neonates. Conclusion: The frequency of congenital anomalies of the kidney and urinary tract in neonates by means of postnatal ultrasonographic scan in our study population was 6.7%. Hydronephrosis was the most common anomaly.

Alternative pathways for the development of lymphoid structures in humans

Lymphoid tissue inducer (LTi) cells are critical for inducing the differentiation of most secondary lymphoid organs (SLOs) in mice. In humans, JAK3 and γc deficiencies result in severe combined immunodeficiency (SCIDs) characterized by an absence of T cells, natural killer cells, innate lymphoid cells (ILCs), and presumably LTi cells. Some of these patients have undergone allogeneic stem cell transplantation (HSCT) in the absence of myeloablation, which leads to donor T cell engraftment, while other leukocyte subsets are of host origin. By using MRI to look for SLOs in nine of these patients 16 to 44 y after HSCT, we discovered that SLOs were exclusively found in the three areas of the abdomen that drain the intestinal tract. A postmortem examination of a child with γc-SCID who had died 3.5 mo after HSCT showed corticomedullary differentiation in the thymus, T cell zones in the spleen, and the appendix, but in neither lymph nodes nor Peyer patches. Tertiary lymphoid organs were observed in the lung. No RAR-related orphan receptor-positive LTi cells could be detected in the existing lymphoid structures. These results suggest that while LTi cells are required for the genesis of most SLOs in humans, SLO in the appendix and in gut-draining areas, as well as tertiary lymphoid organs, can be generated likely by LTi cell-independent mechanisms.

A Hospital Based Study of Pulmonary Arterial Hypertension in Various Stages of Chronic Kidney Disease and Associated Risk Factors among Patients Attending a Tertiary Care Hospital in Ujjain, Madhya Pradesh

BACKGROUND Multiple mechanisms have been identified contributing to pulmonary arterial hypertension (PAH) in chronic kidney disease (CKD) patients and it is one of the important sequelae of CKD and needs early detection. We wanted to study PAH in various stages of CKD and its association with renal and cardiovascular parameters. METHODS This was an observational study. PAH was diagnosed if mean pulmonary artery pressure (MPAP) was ≥ 25 mmHg using 2D - Doppler echocardiography in 96 CKD patients. Staging of CKD was done as per Kidney Disease Improving Global Outcomes (KDIGO) stages 1 - 5. Age, gender, diabetes, hypertension, stages of CKD, corticomedullary differentiation (CMD), estimated glomerular filtration rate (EGFR), urinary albumin creatinine ratio (UACR), left ventricular ejection fraction (LVEF) and left ventricular hypertrophy (LVH) were included as risk factors. Data was analysed by calculating percentage, mean, standard deviation, chi square and t test. P value < 0.05 was taken as statistically significant. RESULTS PAH was detected in 37 (38.5 %) of CKD patients. Prevalence of PAH increased with stages of CKD being highest (59 %) in stage 5 and this was found to be statistically significant (P = 0.04). PAH was detected earliest in stage 2 (23.5 %). Lower mean eGFR ml / min / 1.733m2 (24.43 ± 17.8 vs 40.98 ± 25.7, P = 0.001) altered corticomedullary differentiation (50.9 % vs 20.5 % p = 0.003), reduced LVEF (81 % vs 26.7 % P = 0.000) and LVH (65 % vs 19.6 %, P = 0.000) were significantly associated with PAH in CKD patients. CONCLUSIONS PAH in CKD patients increases with CKD stages. Onset of PAH in CKD patients may be earlier and significantly associated with left ventricular dysfunction. KEYWORDS Pulmonary Arterial Hypertension, Chronic Kidney Disease, Left Ventricular Ejection Fraction, Left Ventricular Hypertrophy

Paediatric bilateral femoral neck fractures in osteopetrosis treated conservatively

The treatment of pathological femoral neck fracture in children due to osteopetrosis is not clear as only a few cases have been reported to date. We encountered a 7-year-old osteopetrotic girl with asynchronous bilateral femoral neck fractures. Radiographical assessment showed markedly dense bones with loss of corticomedullary differentiation, sandwich vertebrae and increased density of the ribs. Her mother had a similar radiological picture. Genetic testing showed CLCN-7 mutation which confirmed the diagnosis of autosomal dominant osteopetrosis. As the parents opted against operative treatment, the femoral neck fractures were managed conservatively with skin traction. At the 2-year follow-up, both fractures had united, although with coxa vara, and the patient had excellent functional outcome as she could walk without difficulty, had unrestricted motion at both hips, and there was no pain. Lifestyle modifications were suggested to prevent recurrent fractures and genetic counselling was done.

Application of T1-weighted BLADE sequence to abdominal magnetic resonance imaging of young children: a comparison with turbo spin echo sequence

Background The image quality of abdominal magnetic resonance imaging (MRI) in children who cannot hold their breath has been severely impaired by motion artifacts. Purpose To evaluate the usefulness of T1-weighted (T1W) BLADE MRI for axial abdominal imaging in children who cannot hold their breath. Material and Methods Two different BLADE sequences, with and without an inversion recovery (IR-BLADE), were compared to conventional turbo-spin echo (TSE) with a high number of excitations in 18 consecutive patients who cannot hold their breath. Overall image quality, motion artifact, radial artifact, hepatic vessel sharpness, renal corticomedullary differentiation, and lesion conspicuity were retrospectively assessed by two radiologists, using 4- or 5-point scoring systems. Signal variations of each sequence were measured for a quantitative comparison. The acquisition times of the three sequences were compared. Results IR-BLADE and BLADE showed significantly improved overall image quality and reduced motion artifact compared with TSE. IR-BLADE showed significantly better hepatic vessel sharpness and corticomedullary differentiation compared to both BLADE and TSE. Radial artifacts were only observed on IR-BLADE and BLADE. In nine patients with lesions, there were no significant differences in lesion conspicuity among three sequences. Compared to TSE, both IR-BLADE and BLADE showed decreased signal variations in the liver and muscle, and an increased signal variation through air. The mean acquisition times for IR-BLADE, BLADE, and TSE were comparable. Conclusion Compared to the TSE sequence, T1W IR-BLADE for pediatric abdominal MRI resulted in improved image quality, tissue contrast with a diminished respiratory motion artifact, and a comparable acquisition time.

Nephron-specific knockout of TMEM16A leads to reduced number of glomeruli and albuminuria

TMEM16A is a transmembrane protein from a conserved family of calcium-activated proteins that is highly expressed in the kidney. TMEM16A confers calcium-activated chloride channel activity, which is of importance for various cellular functions in secretory epithelia and involved in secretion-dependent renal cyst growth. However, its specific function in renal physiology has remained elusive so far. Therefore, we generated conditional nephron-specific TMEM16A-knockout mice and found that these animals suffered from albuminuria. Kidney histology demonstrated an intact corticomedullary differentiation and absence of cysts. Electron microscopy showed a normal slit diaphragm. However, the total number of glomeruli and total nephron count was decreased in TMEM16A-knockout animals. At the same time, glomerular diameter was increased, presumably as a result of the hyperfiltration in the remaining glomeruli. TUNEL and PCNA stainings showed increased cell death and increased proliferation. Proximal tubular cilia were intact in young animals, but the number of properly ciliated cells was decreased in older, albuminuric animals. Taken together, our data suggest that TMEM16A may be involved in ureteric bud branching and proper nephron endowment. Loss of TMEM16A resulted in reduced nephron number and, subsequently, albuminuria and tubular damage.

Primary renal diffuse large B-Cell lymphoma causing haemodialysis-dependent nephromegaly in a child

A 4-year-old boy presented with fatigue and was found to have severe kidney injury requiring haemodialysis. A renal ultrasound demonstrated bilateral nephromegaly with mild loss of corticomedullary differentiation but preserved echogenicity. He had a persistent isolated monocytosis. Renal biopsy revealed extensive infiltration by primary renal diffuse large B-cell lymphoma. He required haemodialysis for 18 days and received chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab and intrathecal methotrexate. He achieved remission with an estimated glomerular filtration rate of 50 mL/min/1.73 m2, and his kidneys returned to normal size. Nephromegaly due to renal-limited haematolymphoid disease is extremely rare, especially in children.