Renal Ultrasound Research Articles

A comprehensive study to find the association between biochemical markers and renal resistive index in patients with diabetes mellitus.

Context: Renal Doppler sonography provides an easily applicable and non-invasive method for investigating renal morphologic characteristics and measuring vascular resistance in the renal parenchyma which is defined by the renal resistive index (RI). RI is elevated in tubule interstitial and vascular pathologies. Estimation of RI and its role in the diagnosis of diabetic nephropathy in diabetes mellitus is not well defined.Aim of the study: To evaluate the association between renal resistive index, microalbuminuria and serum biochemical markers in patients with diabetes mellitus. Material and Methods: A cross sectional study was done in Department of Radiodiagnosis in Government medical college Baroda from December 2018 to September 2020. 100 diabetic patients without other comorbidities were enrolled in the study. Renal Doppler was done using a 3.5 MHz convex array probe. SPSS 16 software was used for statistical analysis. Results: Majority of patients belonged to the age group of 41- 50 years. Majority of patients were males (63%). The mean duration of diabetes in our study was 6.17 ± 5.16 years. 71% of our patients had uncontrolled diabetes mellitus (HbA1c >= 6.5) and 29% had controlled diabetes mellitus (HbA1c < 6.5). Statistically significant association was found between microalbuminuria and RI (P value of < 0.0001). Statistically significant correlation was found between RI and HbA1C (P=0.008), serum creatinine (P

A Novel Homozygous CLCNKB Mutation of Classic Bartter Syndrome Presenting with Renal Cysts in 6-year-Old Identical Twin Boys : A Case Report

Bartter syndrome is an autosomal recessive hypokalemic salt-losing tubulopathy, and classic Bartter syndrome is associated with mutations in the CLCNKB gene. While chronic hypokalemia is known to induce renal cyst formation in different renal diseases, renal cyst formation in Bartter syndrome is rarely reported. Russian six-year-old identical male twins were referred to our hospital for the evaluation of renal cysts, which were incidentally detected on abdominal sonography due to diarrhea. Both twins had shown symptoms of polydipsia, polyuria, and nocturia since they were one year olds. Vital signs including blood pressure were normal in both twins. Renal sonography revealed nephromegaly, increased echogenicity of renal cortex, and various sized multiple cysts in both kidneys for both twins. Laboratory findings included hyponatremia, hypokalemia, hypochloremia, and metabolic alkalosis. Bartter syndrome with renal cysts were suspected. Genetic analysis for both twins confirmed a homozygous c.1614delC deletion on exon 15 of the CLCNKB gene, which was confirmed as a previously unreported variant to the best of our knowledge. They were managed with potassium chloride, nonsteroidal anti-inflammatory drugs, and angiotensin-converting-enzyme inhibitors. Metabolic alkalosis, hypokalemia, hypochloremia, and polyuria partially improved during the short course of treatment. This is the first report of a homozygous mutation in the CLCNKB gene in an identical twin, presenting with renal cysts. Key words: Bartter syndrome, Type 3, Chloride channels, Cysts, Hypokalemia, Twins, Monozygotic, Case report

Chronic kidney disease stage identification using texture analysis of ultrasound images

Early detection of chronic kidney disease (CKD) stages is an important aspect of human healthcare. Clinical approach for identification of CKD stage is expensive, time consuming and mostly not accessible to common people living in remote locations. An automatic method based on ultrasound (US) imaging is more appropriate to receive the first-hand information of kidney health in quick time. Extraction of local features from US image and selection of classifier plays a major role to improve the CKD stage detection accuracy. In this paper, gray level co-occurrence matrix (GLCM) used to extract local features of US kidney images in terms of a fourteen-point feature-vectors. The classifier processes the extracted feature-vectors to identify CKD stage. Extensive simulation performed in MATLAB using different multiclass classifier on 300 sample US images collected by the radiologist to select the multiclass classifier suitable to identify CKD stages with higher accuracy. Simulation result shows that linear discriminant analysis (LDA) classifier performs better than other available multiclass classifiers to classify CKD stages with higher accuracy. Proposed scheme identifies, CKD stage-1, stage-2 and stage-3 with accuracies nearly 96.82%, 100% and 98.38%, respectively. The proposed scheme using the fourteen-point feature vector identify CKD stages with 16% higher accuracy over the exisitng schemes. However, the proposed scheme able to identify CKD stages with 24% higher accuracy than the existing scheme when both the fourteen-point feature-vector and the LDA classifier are used. Therefore, the proposed scheme could be an alternative to the existing scheme for automatic CKD stage identification.

Clinical profile of children with primary vesicoureteric reflux and its association with renal parenchymal scarring

Context: Vesicoureteric reflux (VUR) has been implicated in renal injury before birth as well as in postnatal occurrence of urinary tract infection (UTI) and further renal damage. About 30–49% of children with primary VUR may develop renal scarring called reflux nephropathy. About 5–10% of children with reflux nephropathy may progress to chronic kidney disease in late childhood. Objectives: The objectives of the study were to study the clinical profile of children with primary VUR and to assess the relationship with grades of primary VUR and renal parenchymal scarring. Materials and Methods: Fifty children of age 1 month–5 years, diagnosed to have Primary VUR, were included in this prospective observational study. Detailed history was taken; examination was carried out as per the study protocol. Investigations included urine analysis, renal function tests, urine culture, renal ultrasonography, micturating cystourethrogram, and 99mTc dimercaptosuccinic acid (DMSA) scintigraphy. For those who had UTI, DMSA was carried out after a minimum period of 6 months after UTI episode. Results: Among the 50 children, 21 (42%) were male and 29 (58%) were female with male-to-female ratio of 0.72:1. Mean age at diagnosis was 9 months, ranging from 1 to 40 months. The number of children presented with UTI was 43 (86%), and 7 children (14%) were asymptomatic and were evaluated in view of abnormality in prenatal ultrasound scan. Unilateral VUR was found in 21 patients (42%), and 29 patients (58%) had bilateral VUR. Of all 79 refluxing units (21 unilateral plus 58 bilateral), 4% had VUR of Grade I severity, 30% of Grade II, 34% of Grade III, 28% of Grade IV, and 4% of Grade V severity. Renal parenchymal scarring on DMSA scan was detected in 42 (54%) of 79 refluxing units including 33% of Grade II, 55% of Grade III, 71% of Grade IV, and 100% of Grade V refluxing units. Prevalence of scarring in complicated, recurrent, and simple UTI was 100%, 93%, and 22%, respectively. Conclusion: Risk of renal scarring increased progressively with increasing severity of primary VUR. Complicated and recurrent UTI were found to be statistically significant risk factors for renal scarring. Renal scarring was also seen in absence of UTI in a small percentage of children with primary VUR.

Pro-Platelet Formation Is Impaired in Megakaryocytes of MYH9 -Related Disease Patients

IntroductionThe MYH9 gene encodes myosin-IIA, a nonmuscle myosin heavy chain that facilitates shape changes in diverse cell types. The mutation of MYH9 may lead to the MYH9 -related disease (MYH9 -RD), an autosomal dominant disorder with macrothrombocytopenia and leukocyte inclusion bodies at birth and the risk of developing nephropathy, deafness and cataracts during infancy or adult life. Currently, at least 44 different MYH9 mutations in all 40 exons have been reported. Mutated MYH9 protein expression is reduced in megakaryocytes and is clumped in a few aggregates together with the wild-type protein in neutrophils, where they form the inclusion bodies. In a mouse model, myosin-IIA protein inhibits pro-platelet formation and is regulated by Rho-associated kinase (ROCK). However, how the mutated myosin-IIA influences the pro-platelet formation (PPF) of megakaryocytes in patients has not been explored. The aim of this study is to determine the function and regulation of mutated myosin-IIA in MYH9 -RD patients' megakaryocytes.MethodsOne kindred with inherited macrothrombocytopenia was identified and 5 healthy donors were enrolled as controls. Peripheral blood smear review, slit lamp examination, pure-tone audiometry, renal ultrasonography and examination of blood (urea, creatinine, electrolytes) and urine were performed for each family member to diagnose and evaluate the disease. Bidirectional polymerase chain reaction (PCR) amplification and DNA sequence analysis were performed on all 40 MYH9 exons for each patient. Platelets from peripheral blood and megakaryocytes from bone marrow were fractionated for electron microscopy. Bone marrow tissues from patients were stained with fluorescein-labeled antibodies against CD41 and CD144 to observe the distribution of mature megakaryocytes in the vascular niche by confocal fluorescence microscopy. CD34+ cells were isolated from bone marrow samples by cell sorting for in vitro culture with TPO. On day 8, megakaryocytes were enriched using an albumin density gradient and seeded onto 96-well plates in serum-free medium with or without Y27632, the ROCK inhibitor. At the same time every day for 5 days, the percentage of proplatelet-displaying megakaryocytes was quantified by inverted microscopy.ResultsFive patients in the kindred were diagnosed with MYH9 -RD based upon peripheral blood smear review, one of whom had severe renal failure. None of the patients suffered from deafness or cataracts. A pathogenic heterozygous sequence variant in exon 39 (c.5521G>A, p.E1841K) was detected, which substitutes glutamate at codon 1841 to lysine. This mutation is one of the 44 reported pathogenic mutations. Electron microscopic results showed that platelets from patients had increased diameters and irregular shapes while megakaryocytes from patients had smaller diameters and a disorganized demarcation membrane system (DMS). Immunofluorescence results of bone marrow tissues showed that proplatelet-displaying mature megakaryocytes in MYH9 -RD patients located distally to the vascular niche, compared with the control group. CD34+ cells from bone marrow differentiated into megakaryocytes after in vitro culture with TPO. However, the PPF of megakaryocytes from MYH9 -RD patients appeared much earlier than that from controls. At the same time point, PPF megakaryocytes in MYH9 -RD patients were significantly increased compared to those of the control group. When cultured with Y27632, the PPF appearance time and proplatelet-displaying megakaryocyte percentage in the control group were advanced, while the MYH9 -RD group was not influenced.ConclusionThe mutation in exon 39 of the MYH9 gene may lead to morphological abnormalities of megakaryocytes and platelets. The regulation of myosin-IIA function by ROCK in patients may be decreased when the MYH9 gene is mutated. As a result, the timing of PPF of megakaryocytes with mutated myosin-IIA in the bone marrow niche of MYH9 -RD patients may be advanced, and their mis-location away from the vascular niche may lead to reduced platelet production and increased platelet destruction. DisclosuresNo relevant conflicts of interest to declare.

Mild Idiopathic Infantile Hypercalcemia-Part 1: Biochemical and Genetic Findings.

Idiopathic infantile hypercalcemia (IIH), an uncommon disorder characterized by elevated serum concentrations of 1,25 dihydroxyvitamin D (1,25(OH)2D) and low parathyroid hormone (PTH) levels, may present with mild to severe hypercalcemia during the first months of life. Biallelic variants in the CYP24A1 or SLC34A1 genes are associated with severe IIH. Little is known about milder forms. This work aims to characterize the genetic associations and biochemical profile of mild IIH. This is a cross-sectional study including children between age 6 months and 17 years with IIH who were followed in the Calcium Clinic at the Hospital for Sick Children (SickKids), Toronto, Canada. Twenty children with mild IIH on calcium-restricted diets were evaluated. We performed a dietary assessment and analyzed biochemical measures including vitamin D metabolites and performed a stepwise molecular genetic analysis. Complementary biochemical assessments and renal ultrasounds were offered to first-degree family members of positive probands. The median age was 16 months. Median serum levels of calcium (2.69 mmol/L), urinary calcium:creatinine ratio (0.72 mmol/mmol), and 1,25(OH)2D (209 pmol/L) were elevated, whereas intact PTH was low normal (22.5 ng/L). Mean 1,25(OH)2D/PTH and 1,25(OH)2D/25(OH)D ratios were increased by comparison to healthy controls. Eleven individuals (55%) had renal calcification. Genetic variants were common (65%), with the majority being heterozygous variants in SLC34A1 and SLC34A3, while a minority showed variants of CYP24A1 and other genes related to hypercalciuria. The milder form of IIH has a distinctive vitamin D metabolite profile and is primarily associated with heterozygous SLC34A1 and SLC34A3 variants.

Estimated glomerular filtration rate and cardiometabolic risk factors in a longitudinal cohort of children

Associations between glomerular filtration rate (GFR) and cardiometabolic risk factors have been reported in adult and pediatric patients with renal disease. We aimed to assess the relationship between the estimated GFR (eGFR) and cardiometabolic risk factors in apparently healthy children. A longitudinal study in 401 asymptomatic Caucasian children (mean age 8 years) followed up after 4 years (mean age 12 years). GFR was estimated using the pediatric form of the FAS-equation. Children were classified at baseline according to their obesity status (normal weight and overweight) and according to eGFR levels (lower, average, and higher). The association of eGFR with anthropometric data [body mass index (BMI) and waist], blood pressure [systolic (SBP) and diastolic (DBP)], metabolic parameters [glucose, insulin resistance (HOMA-IR) and serum lipids], and renal ultrasonography measurements were assessed at baseline and follow-up. Baseline eGFR associated with several cardiometabolic risk factors at follow-up including higher waist, SBP, HOMA-IR, and kidney size (all p < 0.0001) in both normal weight and overweight children. In multivariate analysis, baseline eGFR was independently associated with follow-up HOMA-IR and SBP in both normal weight and overweight subjects (model R2: 0.188–0.444), and with follow-up BMI and waist in overweight subjects (model R2: 0.367–0.477). Moreover, children with higher filtration rates at baseline showed higher waist, SBP, DBP, HOMA-IR and renal size both at baseline and follow-up. eGFR is related to insulin resistance, blood pressure and adiposity measures in school-age children. eGFR may help to profile the cardiometabolic risk of children.

Doppler ultrasound in standing position is superior to demonstrate nutcracker phenomenon in children with varicocele

Background/Aim: The nutcracker phenomenon refers to the entrapment of the left renal vein between the superior mesenteric artery and the aorta. It is named nutcracker syndrome if accompanied by symptoms such as flank pain, hematuria, proteinuria, and varicocele. This study aimed to determine the rate of nutcracker phenomenon in children with varicocele by left renal vein Doppler US measurements in standing and supine positions. Methods: The hospital records of patients admitted to our clinic with grades 2 and 3 left varicocele between 2017 and 2019 were reviewed retrospectively. Demographic data, BMI values, blood pressure values, and urinalysis results of the patients were recorded. The diameter and the peak velocity (PV) of the left renal vein were measured at the level of the hilus and in the aortomesenteric part, both in supine and standing positions by Doppler ultrasonography (US). Results: Twenty-six cases were included in the study. No additional pathology was found other than varicocele. The diameter of the aortomesenteric part of the renal vein decreased, the hilar part of the renal vein increased, and the rate and the diameter ratio increased at the standing position. The incidence of the nutcracker phenomenon was 42.3-57.7% with different thresholds in the supine position, and 88-96.2% in the standing position. Conclusion: Doppler ultrasonography in the standing position is superior to that performed in the supine position in detecting the nutcracker phenomenon in patients with varicocele.

MO052COL4A3/COL4A4 AS A CAUSE OF MULTICYSTIC KIDNEY DISEASE

Abstract Background and Aims Thin basement membrane nephropathy (TBMN), the most common cause of persistent microhaematuria (mH), is due to mutations in genes codifying alfa-3 and alfa-4 collagen IV chains (COL4A4/COL4A3). Initially considered as a benign condition, subsequent studies have shown that an important number of patients develop proteinuria and CKD. We reported in a previous small study the presence of multicystic kidney disease (MCD) in some TBMD patients. In this study we aimed to evaluate the presence of MCD in a larger cohort of TBMD patients and analyze its association with renal outcomes. Method We collected 50 patients with a diagnosis of TBMD based on the presence of persistent mH (&amp;gt;5 erythocytes per high power field in more than 90% of urinary sediments and radiological examinations to exclude other causes of mH) and at least one first-degree relative with persistent mH. TBMD diagnosis was confirmed by renal biopsy (glomerular basement membrane thickness less than 150nm) in 18 patients and by genetic test (pathogenic mutations in COL4A3/COL4A4) in 6 patients. MCD was diagnosed by the presence of uncountable cysts on renal ultrasonography. Results Mean age at diagnosis was 43.7 years, 34% were males and 18% had hypertension. At baseline, serum creatinine (SCr) was 0.9 mg/dL, proteinuria 0.48 gr/24h and 9 patients (18%) had CKD (estimated glomerular filtration rate -eGFR- lower than &amp;lt;60 mL/min/1.73m2). 7 patients (14%) had CKD G3 and 2 (4%) CKD G4. Kidney cysts were found in 34 patients (68%) and 19 (38%) met MCD criteria. After a mean follow-up of 14.7±11.5 years, 23 patients (46%) had CKD. Among them, 17 patients (34%) had CKD G3, 2 (4%) CKD G4, and 4 (8%) CKD G5. Hypertension was more frequent among CKD patients as compared with no-CKD patients (39 vs 0%, p 0.00), proteinuria was higher (0.58±0.68 vs 0.39±0.58 g/24h, p 0.05) and MCD more frequent (65.2% vs 14.8%, p 0.00). Patients with MCD had higher SCr (2.1 vs 1.1 mg/dL, p 0.004) and lower eGFR (41.7 vs 77.2 mL/min/1.73m2, p 0.00) at the end of follow-up, and MCD was the only risk factor for the occurrence of CKD (OR 6.49, 95% CI 1.3-31.6) by multivariable analysis that included age, hypertension and proteinuria. Conclusion MCD is frequently observed in TBMD patients and is a risk factor for the progression of CKD.

Long-term follow-up of premature infants with urinary tract infection

Urinary tract infection (UTI) is common in preterm infants and may have long-term sequela, such as recurrent infections and renal scarring in older children. We assessed long-term outcomes of preterm infants with UTI, born during 1996-2008 in Schneider Children's Medical Center's neonatal intensive care unit (NICU), and incidence of UTI recurrence. Of 89 preterm infants, seven were excluded due to prenatal diagnosis of congenital anomalies of the kidney and urinary tract (CAKUT), 41 interviewed by phone, 18 presented for follow-up evaluation in the nephrology clinic, and 23 lost to follow-up. No patient who completed follow-up reported additional UTI episodes or issues related to kidney and urinary tract. Clinically evaluated participants were 17.1 ± 3.6 years, born prematurely at 29.4 ± 4 weeks. All had a normal estimated glomerular filtration rate of >90 ml/min/1.73m2; four (22%) had systolic blood pressure >90th percentile; none had proteinuria (mean protein/creatinine ratio 0.09 ± 0.04 mg/mg) or albuminuria (mean albumin/creatinine ratio 10.2 ± 6.3 mcg/mg). Renal ultrasonography done in the first years of life in 12 (66%) patients demonstrated normal kidney size and structure.Conclusion: In this pilot study, a single episode of UTI in premature infants without CAKUT did not constitute a risk factor for recurrence of infections or kidney injury in their first two decades of life. Thus, normal ultrasound in NICU excluding CAKUT may be sufficient for premature patients with UTI, with no need of further imaging or long-term nephrology follow-up. What is Known: • Urinary tract infection (UTI) is one of the most common bacterial infections in neonates and premature infants. Risk factors for UTI recurrence in children are congenital anomalies of the kidney and urinary tract (CAKUT) and bladder and bowel dysfunction. • The recurrence rate and long-term renal sequela of UTI in preterm infants have not been studied. Guidelines regarding management and long-term follow-up for infants less than 2 months old are lacking. What is New: • A single episode of UTI in premature infants without CAKUT probably does not constitute a risk factor for UTI recurrence, and it is unlikely to cause renal injury in the first two decades of life. • For premature infants with UTI without sonographic diagnosis of CAKUT in NICU, prophylactic antibiotic treatment, further imaging, or long-term nephrology follow-up may be unnecessary.

Development and Validation of a Deep Learning Model to Quantify Interstitial Fibrosis and Tubular Atrophy From Kidney Ultrasonography Images

Interstitial fibrosis and tubular atrophy (IFTA) is a strong indicator of decline in kidney function and is measured using histopathological assessment of kidney biopsy core. At present, a noninvasive test to assess IFTA is not available. To develop and validate a deep learning (DL) algorithm to quantify IFTA from kidney ultrasonography images. This was a single-center diagnostic study of consecutive patients who underwent native kidney biopsy at John H. Stroger Jr. Hospital of Cook County, Chicago, Illinois, between January 1, 2014, and December 31, 2018. A DL algorithm was trained, validated, and tested to classify IFTA from kidney ultrasonography images. Of 6135 Crimmins-filtered ultrasonography images, 5523 were used for training (5122 images) and validation (401 images), and 612 were used to test the accuracy of the DL system. Kidney segmentation was performed using the UNet architecture, and classification was performed using a convolution neural network-based feature extractor and extreme gradient boosting. IFTA scored by a nephropathologist on trichrome stained kidney biopsy slide was used as the reference standard. IFTA was divided into 4 grades (grade 1, 0%-24%; grade 2, 25%-49%; grade 3, 50%-74%; and grade 4, 75%-100%). Data analysis was performed from December 2019 to May 2020. Prediction of IFTA grade was measured using the metrics precision, recall, accuracy, and F1 score. This study included 352 patients (mean [SD] age 47.43 [14.37] years), of whom 193 (54.82%) were women. There were 159 patients with IFTA grade 1 (2701 ultrasonography images), 74 patients with IFTA grade 2 (1239 ultrasonography images), 41 patients with IFTA grade 3 (701 ultrasonography images), and 78 patients with IFTA grade 4 (1494 ultrasonography images). Kidney ultrasonography images were segmented with 91% accuracy. In the independent test set, the point estimates for performance matrices showed precision of 0.8927 (95% CI, 0.8682-0.9172), recall of 0.8037 (95% CI, 0.7722-0.8352), accuracy of 0.8675 (95% CI, 0.8406-0.8944), and an F1 score of 0.8389 (95% CI, 0.8098-0.8680) at the image level. Corresponding estimates at the patient level were precision of 0.9003 (95% CI, 0.8644-0.9362), recall of 0.8421 (95% CI, 0.7984-0.8858), accuracy of 0.8955 (95% CI, 0.8589-0.9321), and an F1 score of 0.8639 (95% CI, 0.8228-0.9049). Accuracy at the patient level was highest for IFTA grade 1 and IFTA grade 4. The accuracy (approximately 90%) remained high irrespective of the timing of ultrasonography studies and the biopsy diagnosis. The predictive performance of the DL system did not show significant improvement when combined with baseline clinical characteristics. These findings suggest that a DL algorithm can accurately and independently predict IFTA from kidney ultrasonography images.

Recurrent FAN1 p.W707X Pathogenic Variant Originating Before ad 1800 Underlies High Frequency of Karyomegalic Interstitial Nephritis in South Pacific Islands

Recurrent FAN1 p.W707X Pathogenic Variant Originating Before ad 1800 Underlies High Frequency of Karyomegalic Interstitial Nephritis in South Pacific Islands

Role of renal Duplex ultrasonography in evaluation of hepatorenal syndrome

BackgroundHepatorenal syndrome is a potentially fatal complication of advanced liver disease. Markers for early diagnosis and identification of high-risk patients are lacking. Our aim was to evaluate the role of renal Duplex ultrasonography in the diagnosis and early prediction of hepatorenal syndrome. This study included 50 patients. Clinical assessment, liver function tests, hepatitis C virus antibody, kidney function tests, and abdominal and renal color Duplex ultrasound were done to all subjects.ResultsUnivariate regression analysis for hepatorenal syndrome showed a statistically significant positive correlation with the Model For End-Stage Liver Disease score (p-value <0.0001) and renal artery hilum resistivity index (p-value = 0.0017). Logistic multivariable regression analysis proved that the renal artery hilum resistivity index was an independent predictor of hepatorenal syndrome. Renal artery hilum resistivity index can be used as a predictor of hepatorenal syndrome with 100% sensitivity and 66.7% specificity with a cut-off value > 0.77.ConclusionThe renal resistive index could be a good predictor of hepatorenal syndrome.

Frequency of Ectopic Calcifications Among Patients With Hypophosphatasia in the Global HPP Registry

Abstract Ectopic calcifications have been observed in patients with hypophosphatasia (HPP)—a rare, inherited, metabolic disorder characterized by reduced enzymatic activity of tissue nonspecific alkaline phosphatase. The natural history of these calcifications is poorly understood. Using data from the Global HPP Registry, a cross-sectional, observational analysis was conducted to better understand the prevalence of nephrocalcinosis and eye calcifications in patients with HPP in the absence of treatment with the enzyme replacement therapy, asfotase alfa. The association between hypercalcemia (serum calcium ≤10.3 mg/dL [normal]; 10.4–11.9 mg/dL [mild hypercalcemia]; ≥12.0 mg/dL [moderate to severe hypercalcemia]) and ectopic calcification was also evaluated. Of the patients in the study population with renal ultrasound data (n=327), 11.0% had nephrocalcinosis; no patients had severe nephrocalcinosis. In children (aged &amp;lt;18 years; n=174), 13.2% had nephrocalcinosis, and the median age at the first diagnosis of nephrocalcinosis was 4 years (range: 0–17 years). In adults (aged ≥18 years; n=153), 8.5% had nephrocalcinosis, and the median age at the first diagnosis of nephrocalcinosis was 52 years (range: 27–72 years). Data on serum calcium levels were available for 318 patients with renal ultrasounds. Of these patients, 73 patients (23.0%) had a history of hypercalcemia, of whom 10 (13.7%; children: n=9; adults: n=1) also had nephrocalcinosis. In patients with moderate to severe hypercalcemia (n=7), 6 patients (85.7%) were diagnosed with nephrocalcinosis; the majority (68.8%) of patients with nephrocalcinosis did not have a documented history of hypercalcemia. Of the patients who had ophthalmological assessments (n=137), 6 patients (4.4%) had eye calcifications; no patients had moderate or severe eye calcifications. The median age at the first diagnosis of eye calcifications was 16 years (range: 15–16 years) in children and 51 years (range: 30–57 years) in adults. Data on serum calcium levels were available for 80 patients with ophthalmological assessments. Coexistence of eye calcifications and reported hypercalcemia was observed in only 3 of these patients, all of whom had mild hypercalcemia; the remaining 3 patients with eye calcifications exhibited no hypercalcemia. No patients in this analysis presented with both nephrocalcinosis and eye calcifications. These results indicate that the prevalence of ectopic calcifications in patients with HPP is low during the natural course of the disease, with nephrocalcinosis being more common than eye calcifications. In addition, the higher prevalence of nephrocalcinosis in patients with moderate to severe hypercalcemia suggests that very high serum calcium may be a risk factor in some patients. Future studies are needed to assess the impact of treatment with asfotase alfa on ectopic calcifications in patients with HPP.

A Rare Case of Perinatal Hypophosphatasia Treated With Asfotase Alfa

Background: Perinatal Hypophosphatasia (HPP) is a rare and lethal disorder associated with a 50–100% mortality rate, usually due to respiratory complications. HPP occurs due to a loss-of-function mutation in the ALPL gene, responsible for the function of tissue-nonspecific alkaline phosphatase (TNSALP). Clinically, HPP presents as a severe lack of bone mineralization leading to a rickets-like presentation. Clinical Case: A 4-month-old female presented from an outside hospital for the ongoing care of perinatal HPP. Prenatal scans with long-bone fractures raised concern for Osteogenesis imperfecta. However, alkaline phosphatase (ALP) at birth was <11 U/L, and vitamin B6 was elevated >250 ng/mL. Calcium, 25-OH vitamin D, and urine phosphoethanolamine were normal. A genetics panel for HPP confirmed two pathogenic autosomal recessive mutations on the ALPL gene.Treatment with asfotase alfa 3 mg/kg three times weekly was started on day two of life. The clinical course has been complicated by the need for mechanical ventilator support, seizure-event shortly after birth, recent EEG demonstrating epileptogenic potential in the bitemporal cortical regions now on treatment with Keppra, possible craniosynostosis with mild-to-moderate ventriculomegaly, and minimal grade 1 medullary nephrocalcinosis. Bone mineralization is monitored via skeletal surveys, and changes are measured using the Radiographic Global Impression of Change (RGI-C) and the Rickets Scoring Scale (RSS). After four months of asfotase alfa treatment, substantial progress in bone mineralization per RGI-C scoring has been noted, but RSS scoring still indicates severely low bone mineralization. ALP remains >3,000 U/L. Calcium, 25-OH vitamin D, and vitamin B6 are normal. Careful monitoring with weekly biochemical and urine profiles and monthly skeletal surveys, neuro assessments, and renal ultrasounds are ongoing. Conclusions: This clinical case demonstrates the improvement in bone mineralization with asfotase alfa, but the clinical course is slow and arduous. Despite the early initiation of asfotase alfa the patient’s bone mineralization remains severely low and is not in a safe range to proceed with G-tube, broviac, or tracheostomy placement. The current management goal is to maximize bone mineralization in preparation for the life-sustaining procedures mentioned above. With only a handful of surviving cases in the world, current long-term survival and outcomes for patients with perinatal HPP are unclear.

Novel Heterozygous Calcium Sensing Receptor (CASR) Genetic Variant in Child with Unique Phenotype: Hypocalcemia, Mandibular Hypoplasia, Renal Cysts and Type E Brachydactyly

Background: There are over 230 disease-causing variants in the calcium-sensing receptor gene (CaSR). Gain-of-function missense mutations in CaSR cause Autosomal Dominant Hypocalcemia (ADH) characterized by hypocalcemia (hCa), hypoparathyroidism (hPTH), and hypercalciuria. Patients with ADH are sensitive to fluctuations in serum calcium (Ca); and supplementation with Ca and vitamin D can cause inappropriate renal calcium retention leading to hypercalcemic events and long-term renal complications. Clinical Case: A 15-year-old adopted (at age 18 months) Korean female was initially diagnosed with hPTH and chronic hCa after presenting with hCa seizures. Laboratory values showed hCa (7.7 mg/dL), hyperphosphatemia (7.6 mg/dL) and hPTH (< 3 pg/mL.) Initially, she was treated with Ca supplementation (20 mg/kg/day elemental Ca), and calcitriol (0.01 mcg/kg/day). She presented at age 4 with hematuria and was found to have obstructive nephrolithiasis requiring operative intervention. Renal ultrasound (US) showed bilateral medullary nephrocalcinosis. She continued treatment with Ca and calcitriol. At age 6, a thiazide diuretic and potassium citrate supplement were added due to hypercalciuria. She had recurrent nephrolithiasis and persistent nephrocalcinosis. Follow-up renal US also showed bilateral renal cysts. Biweekly laboratory evaluation demonstrated an exuberant response to calcium supplementation. Serum Ca levels oscillated between 7.0 -10 mg/dL, but she showed minimal symptoms of hCa. At age 14, she was also recognized to have submandibular hypoplasia and brachydactyly of the 4th and 5th metacarpals and metatarsals bilaterally and genetic testing for CaSR gene mutation was requested. Sshe developed acute kidney injury and hypercalcemia, possibly precipitated by viral illness. However, 3 weeks before, calcitriol dose was increased to 1.25 mcg twice a day (0.07 mcg/kg/day). At admission, serum Ca was 12.7 mg/dL, iPTH 5.2 mg/dL, phosphorus 4.5 mg/dL, BUN 36 mg/dL, creatinine 1.85 mg/dL. Symptoms included headache, muscle spasm and throat spasm. She received intravenous fluids and recovered, but had an extended hospital stay. Targeted genetic analysis of the CaSR gene was completed, and identified a heterozygous variant (c.2506G>T, p.V836L) which is predicted to be likely pathogenic and cause ADH. After CaSR gene mutation identification, the calcitriol and also elemental Ca dosing were decreased to achieve a low Ca level (~7 mg/dL) with normal urine Ca/creatinine ratio. Patient remains asymptomatic. Conclusion: This is the first case of a novel mutation in the CaSR (c.2506G>T, p.V836L) associated with ADH, brachydactyly, renal cysts, and mandibular hypoplasia. Timely genetic testing for ADH in patients with newly diagnosed hPTH can lead to changes in therapy and improved prognosis.

Deep Learning in Kidney Ultrasound: Overview, Frontiers, and Challenges.

Ultrasonography is a practical imaging technique used in numerous health care settings. It is relatively inexpensive, portable, and safe, and it has dynamic capabilities that make it an invaluable tool for a wide variety of diagnostic and interventional studies. Recently, there has been a revolution in medical imaging using artificial intelligence (AI). A particularly potent form of AI is deep learning, in which the computer learns to recognize pixel or written data on its own without the selection of predetermined features, usually through a specific neural network architecture. Neural networks vary in architecture depending on their task, and key design considerations include the number of layers and complexity, data available, technical requirements, and domain knowledge. Deep learning models offer the potential for promising innovations to workflow, image quality, and vision tasks in sonography. However, there are key limitations and challenges in creating reliable and safe AI models for patients and clinicians.

Preoperative clinical and renal ultrasonography variables associated with improved systolic and diastolic blood pressure reduction after renal artery stenting

IntroductionResponse to stent-assisted angioplasty (PTA) in hypertensive patients with atherosclerotic renal artery stenosis (ARAS) is unpredictable. Therefore, the present study aimed to search for preoperative clinical and renal ultrasonography variables associated with systolic (SBP) and diastolic blood pressure (DBP) reduction.Material and methodsPreoperative clinical assessment and renal ultrasonography were performed in 202 patients who underwent PTA for ARAS (2003–2018). Patients were categorized as responders if decrease of SBP of at least 20mmHg or DBP of 5mmHg was achieved. Logistic regression models, with percentage shares, were evaluated by basic decision characteristics for ultrasonographic and clinical variables.ResultsLogistic regression analysis showed that preoperative SBP ≥145mmHg (OR,20.0 [95%CI 8.67–46.2], p&lt;0.001), (2) baseline DBP &gt;82 mmHg (OR,3.46 [95%CI 1.61–7.42], p=0.001), (3) prior myocardial infarction (OR,3.14 [95%CI 1.09–9.0], p=0.033), and (4) Renal-Aortic-Ratio &gt;5.1 (OR,2.67 [95%CI 1.20-6.0], p=0.016) predicted the SBP response, with respective influence shares of 69.8%; 12.1%; 10.9%; and 7.2%. The DBP response was associated with (1) baseline SBP &gt;145mmHg (OR,3.79 [95%CI 1.87–7.70], p&lt;0.001), (2) baseline DBP &gt;82mmHg (OR,6.09 [95%CI 2.88–12.9], p&lt;0.001), (3) ARAS progression (OR,0.32 [95%CI 0.09–1.07], p=0.062), (4) contralateral kidney length&gt;106mm (OR,0.43 [95%CI 0.22–0.86], p=0.017), and (5) bilateral PTA (OR,2.39 [95%CI 1.08–5.27], p=0.03), with respective shares of 21.8%; 35.0%; 18.2%; 13.3% and 11.8%.ConclusionsCurrent study identified clinical and ultrasonographic characteristics of patients who are likely to respond to PTA for ARAS. The RAR and contralateral kidney size may enhance prediction of response likelihood.

Mechanism of Radix Astragali and Radix Salviae Miltiorrhizae Ameliorates Hypertensive Renal Damage.

Hypertensive-induced renal damage (HRD) is an important public health and socioeconomic problem worldwide. The herb pair Radix Astragali- (RA-) Radix Salviae Miltiorrhizae (RS) is a common prescribed herbal formula for the treatment of HRD. However, the underlying mechanisms are unclear. The purpose of our study is to explore the mechanism of combination of Radix Astragali (RA) and Radix Salviae Miltiorrhizae (RS) ameliorating HRD by regulation of the renal sympathetic nerve. Thirty 24-week-old spontaneously hypertensive rats (SHRs) as the experimental group were randomly divided into the RA group, the RS group, the RA+RS group, the valsartan group, and the SHR group and six age-matched Wistar Kyoto rats (WKY) as the control group. After 4 weeks of corresponding drug administration, venipuncture was done to collect blood and prepare serum for analysis. A color Doppler ultrasound diagnostic instrument was used to observe renal hemodynamics. Enzyme-linked immunosorbent assay was used to detect norepinephrine (NE), epinephrine (E), angiotensin II (Ang II), and B-type brain natriuretic peptide (BNP). Simultaneously, the kidneys were removed immediately and observed under a transmission electron microscope to observe the ultrastructural changes. And the concentration of transforming growth factor-β1 (TGF-β1), angiotensin type 1 receptor (AT1), and nitric oxide (NO) was detected by immunohistochemistry. Our results showed that renal ultrasonography of rats showed no significant difference in renal size among groups. The RA+RS group had obviously decreased vascular resistance index. The levels of NE, E, BNP, Ang II, AT1, and TGF-β1 were decreased (P < 0.05), and the density of NO was increased. Pathological damage of the kidney was alleviated. In conclusion, the results of the present study suggested sympathetic overexpression in the pathogenesis of HRD. The combination of RA and RS may inhibit the hyperexcitability of sympathetic nerves and maintain the normal physiological structure and function of kidney tissue and has a protective effect on the cardiovascular system.

Virus-related neurological lower urinary tract dysfunction: Lessons learned during 4-year follow-up of patients with Congenital Zika Syndrome

We have previously reported on neurogenic bladder dysfunction among Congenital Zika Vírus Syndrome (CZS) patients, but it is unknown how they will respond to treatment. To assess whether children with neurological lower urinary tract dysfunction and CZS will respond to Standard therapies. A prospective observational cohort study of children with CZS referred for urological assessment between 2016 and 2020 to our quaternary center in Brazil. Urological protocol included clinical history, urinalysis and culture, renal and bladder ultrasonography and urodynamic study. Patients were treated based on findings from the first evaluation, with oxybutynin chloride for overactive bladder and low bladder compliance, clean intermittent catheterization for ineffective bladder emptying, or dual therapy when both were observed. Urological outcomes were evaluated between the first and second visits considering patient's adherence. Outcomes measured included clinical, imaging, and urodynamic variables. Data was analyzed using the IBM SPSS 22 software. From the cohort of 90 patients, 56 completed the second urodynamic assessment and were included. One presented underactive bladder and 55 overactive bladder. Among these 55, 39 were adherent and 16 non-adherents to the prescribed treatment. Among the 39 adherents, 8 adhered regularly to oxybutynin and clean intermittent catheterization (CIC), 29 to oxybutynin alone, and two to catheterization alone. During follow-up, the number of patients with urinary tract infection and postvoid residual increased, but all other parameters had improved. Renal and bladder ultrasonography improved in 10, maximum bladder pressure decreased in 22 and maximum cystometric capacity and compliance increased in 14 patients. Sixteen patients did not adhere regularly to the prescribed treatment and although the number of patients with urinary tract infection reduced with antibiotic therapy, their bladder capacity and compliance did not improve during follow-up. Ultrasonographic and urodynamic improvements were observed after 10.8±7.5 months of treatment, including one patient with ureterohydronephrosis that resolved. Adherence to CIC remains a challenge and reflected in the number of patients presenting urinary tract infection and postvoid residual. The immediate clinical relevance is the major study strength, given the previously uncharacterized therapy options for this patient population. The number of patients remains one of the study limitations, reducing our ability to perform more advanced statistical analyses. Patients with Zika-related neurological lower urinary tract dysfunction may benefit from conventional therapies. Results confirmed ultrasonographic and urodynamic improvements after treatment, although not statically significant. Adherence to treatment, specifically to CIC, remains a challenge.