Atypical histological abnormalities in an adult patient with nephronophthisis harboring NPHP1 deletion: a case report

Background Nephronophthisis (NPHP) is a chronic tubular interstitial disorder that exhibits an autosomal recessive genetic form and causes progressive renal failure in children. Patients with NPHP rarely show urinary abnormalities, edema, or hypertension. Thus, NPHP is often detected only when renal failure becomes advanced. NPHP can be divided into three types based on the age of end-stage renal failure, i.e., infant type (approximately 5 years old), juvenile type (approximately 13–14 years old), and adolescent type (approximately 19 years old). Here, we report a case of NPHP diagnosed by genetic analysis at 26 years of age with atypical histological abnormalities. Case presentation A 26-year-old woman showed no growth disorders or urinary abnormalities in annual school physical examinations. However, at a check-up at 26 years old, she exhibited renal dysfunction (eGFR 26 mL/min/1.73 m2). Urine tests indicated low specific gravity of urine, but not proteinuria or microscopic hematuria. Urinary β2-microglobulin was high (805 μg/L), and renal biopsy was performed for definitive diagnosis. Histological findings showed no significant findings in glomeruli. However, moderate fibrosis was observed in the interstitial area, and moderate atrophy was observed in the tubules. There were no significant findings in immunofluorescence analysis, and no electron dense deposits were detected by electron microscopy. Although cyst-like expansion of the tubules was unclear, tubular atrophy was dominantly found in the distal tubule by cytokeratin 7 staining. Genetic analysis of the NPHP1 gene showed complete deletion of this gene, leading to a definitive diagnosis of NPHP. Conclusions NPHP is not merely a pediatric disease and is relatively high incidence in patients with adult onset end-stage of renal disease. In this case, typical histological abnormalities, such as cyst-like expansion of the tubular lesion, were not observed, and diagnosis was achieved by genetic analysis of the NPHP1 gene, which is responsible for the onset of NPHP. In patients with renal failure with tubular interstitial disease dominantly in the distal tubules, it is necessary to discriminate NPHP, even in adult cases.

MO425RENAL SURGERY APPROACHES AND POST-OPERATIVE AKI DEVELOPMENT IN NORMAL RENAL FUNCTION PATIENTS; AN HIDDEN TREATH

Background and Aims Acute kidney injury (AKI) is a major postoperative complication in renal surgery for cancer, both in radical than in partial nephrectomy. One of the most intriguing arguments is to understand if normal renal function patients without renal urinary abnormalities can develop post-operative AKI after renal surgery. Aim of our study was to compare the AKI incidence in the two major renal surgeries approaches (radical and partial nephrectomies) in a selected cohort of patients with normal renal function. Method We performed a retrospective study of 216 patients who underwent radical (RN) or partial nephrectomy (PN) due to the presence of a kidney mass from 2000-2020 in a tertiary care Institution. Inclusion criteria: 1) Age> 18; 2) eGFR >;80 ml/min/1,73 using CKD-EPI formula 2012 3) absence of urinary abnormalities 4) presence of two kidneys at time operation. The following data were considered: age, gender, body mass index (BMI), TNM staging, hypertension, diabetes. Serum creatinine values were collected before surgery (t 0), at 48 hours after surgery and at dismissal. GFR was estimated at each time point using creatinine-based estimated glomerular filtration rate (eGFR) formula: CKD-EPI. We evaluated eGFR variation from the pre-surgical value to 48 h post and at dismissal. eGFR categories were created according to the KDIGO guidelines for G categories. Comparisons between groups were performed using Kruskal-Wallis ranks sum test for numerical variables and Pearson’s Chi square test for categorical variables. Logistic regression was used to identify variables ODDS Ratio for AKI onset after surgery. Results Clinical and pathological characteristics are reported in table 1. The cohort was composed by 216 patients with median Age 55 (IQR: 47, 64), M/F ratio 2.4, median BMI 25.8 (IQR: 23.3, 28.4), median eGFR 94.3 (IQR: 89.1, 101.6). According to CKD G classes, 79% were stage 1 and 2 1 were stage 2. The cohort was divided in two groups according to the type of surgery: 51% as RN and 49% as PN. Differences between the two groups were detected for Gender (Radical M/F ratio: 3.3; Partial M/F ratio: 1.8; p=0.4), basal eGFR (Radical Median:92.9 (88.1, 101.0); Partial Median:95.3 (90.7, 102.4); p=0.03) and CKD G class (Radical I:64%, II:36%; Partial I:78%, II:22%; p=0.02). Logistic regression for AKI onset showed as significant parameter (p<0.001) only the type of surgery observing for Radical Nephrectomy and ODDS Ratio of 4.6 (Confidence Interval: 2.6,8.5). The proportions of patients who developed AKI were 21% for PN and 55% for RN (Figure 1). Conclusion Our study highlights that both radical (55%) than partial (21%) nephrectomies harbor a non-negligible risk of post-operative AKI even in normal renal function patients without renal abnormalities. In addition, the impact of RN in normal renal function patients shows a dramatic incidence of AKI in the 50% of cases, suggesting that nephron sparing surgeries techniques should be always indicated to preserve renal function also in patients with an eGFR> 80 ml/min/1,73. A prospective comparison multicentric study with kidney living donor is on going.

Acute kidney injury and its outcomes in melioidosis

Background Melioidosis is a potentially fatal tropical infection caused by Burkholderia pseudomallei. Kidney involvement is possible, but has not been well described. Aim This study aimed to assess the risk of acute kidney injury (AKI) and its outcomes in melioidosis. Methods A retrospective observational cohort study was performed. Case records of consecutive patients with culture-confirmed melioidosis, observed from January 1st, 2012 through December 31st, 2019 were analysed for demographics, presence of comorbidities, including chronic kidney disease (CKD), diabetes mellitus (DM), and presence of bacteraemia, sepsis, shock, AKI, and urinary abnormalities. The outcomes we studied were: mortality, need for hospitalisation in an intensive care unit (ICU), duration of hospitalization. We then compared the outcomes between patients with and without AKI. Results Of 164 patients, AKI was observed in 59 (35.98%), and haemodialysis was required in eight (13.56%). In the univariate analysis, AKI was associated with CKD (OR 5.83; CI 1.140–29.90, P = 0.03), bacteraemia (OR 8.82; CI 3.67–21.22, P < 0.001) and shock (OR 3.75; CI 1.63–8.65, P = 0.04). In the multivariate analysis, CKD (adjusted OR 10.68; 95% CI 1.66–68.77; P = 0.013) and bacteraemia (adjusted OR 8.22; 95% CI 3.15–21.47, P < 0.001) predicted AKI. AKI was associated with a greater need for ICU care (37.3% vs. 13.3%, P = 0.001), and mortality (32.2% vs. 5.7%, P < 0.001). Mortality increased with increasing AKI stage, i.e. stage 1 (OR 3.52, CI 0.9–13.7, P = 0.07), stage 2 (OR 6.79, CI 1.92–24, P = 0.002) and stage 3 (OR 17.8, CI 5.05–62.8, P < 0.001), however kidney function recovered in survivors. Hyponatremia was observed in 138 patients (84.15%) and isolated urinary abnormalities were seen in 31(18.9%). Conclusions AKI is frequent in melioidosis and occurred in 35.9% of our cases. Hyponatremia is likewise common. AKI was predicted by bacteraemia and CKD, and was associated with higher mortality and need for ICU care; however kidney function recovery was observed in survivors. Graphic abstract

Urinary screening for detection of renal abnormalities in asymptomatic pre-school children referred to Ardabil city health centers from 2016 to 2017

Background: Urinary screening for detection of proteinuria, hematuria, and pyuria for early diagnosis curable or preventable renal disease in three decade has been considered. The aim of this study was urinary screening for Detection of renal abnormalities in asymptomatic pre-school children referred to health center in Ardabil city from 2016 to 2017.Methods: This was a cross-sectional descriptive study that has been done on urine specimens of 350 children who referred to Ardabil city health center to injection DTP vaccine from April 2016 to Sep 2017. In these infants, proteinuria, hematuria, pyuria and urinary casts were examined and abnormal finding were referred to future investigation to nephrologist. Information was collected and analyzed by statistical methods in SPSS version 21.Results: A total of 350 children were enrolled in the study. There were 196 (56%) boys and 154 (44%) girls. The prevalence of urinary abnormalities in all children was 8.3%. Of all urinary abnormalities, proteinuria and hematuria were detected in 12 children (3.44 %). Of all infants, 9 children (2.57%) had pyuria. Also, 6 children (1.8%) had urinary casts that of them two cases had acid ureic cast and four cases had calcium oxalate cast.Conclusions: This study showed that the prevalence of urinary abnormalities in Ardabil city children was similar to other studies in other country or cities. The reasons of this may be different in race and ethnic. We suggest that routine urinalysis should be part of screening of children at the school entry in Ardabil.

Bilateral Vesicoureteral Reflux in Congenital Nephrotic Syndrome

: Congenital nephrotic syndrome (CNS) is a rare genetic kidney disorder. Different associations between CNS and other organ anomalies have been reported previously. However, urologic abnormalities are not common. This case report can show the association of CNS as a genetic disorder with other abnormalities with a genetic basis. However, the association with urinary abnormalities is rare. We have reported a 25-day-old male newborn, who was referred to our hospital with generalized edema. During the initial evaluation, CNS was diagnosed. The baby, then four months old, was admitted to the hospital with high fever and poor feeding, and a diagnosis of febrile urinary tract infection was made. A voiding cystouretrography was performed that revealed bilateral high-grade vesicoureteral reflux. According to our findings in this case and the genetic basis of CNS and urinary tract anomalies, we recommend the investigation of the urinary tract in CNS patients if indicated.

Heterozygous Urinary Abnormality–Causing Variants of COL4A3 and COL4A4 Affect Severity of Autosomal Recessive Alport Syndrome

BackgroundAutosomal recessive Alport syndrome (ARAS) is an inherited renal disorder caused by homozygous and compound heterozygous mutations in COL4A3 or COL4A4, but the prognostic predictors for this disorder are not yet fully understood. Recently, the magnitude of the clinical spectrum of the COL4A3 and COL4A4 heterozygous state has attracted attention. This spectrum includes asymptomatic carriers of ARAS, benign familial hematuria, thin basement membrane disease, and autosomal dominant Alport syndrome.MethodsWe retrospectively analyzed 49 patients with ARAS from 41 families with a median age of 19 years to examine the clinical features and prognostic factors of ARAS, including the associated genotypes.ResultsThe median age of patients with ARAS at ESKD onset was 27 years. There was no significant association between the presence or absence of hearing loss or truncating mutations and renal prognosis. However, there was a statistically significant correlation between renal prognosis and heterozygous variants that cause urinary abnormalities. Where the urinary abnormality–causing variant was absent or present in only one allele, the median age of ESKD onset was 45 years, whereas the same variant present on both alleles was associated with an age of onset of 15 years (P<0.001).ConclusionsThis study was the first to demonstrate the clinical importance in ARAS of focusing on variants in COL4A3 or COL4A4 that cause urinary abnormalities in both the homozygous or heterozygous state. Although heterozygous mutation carriers of COL4A3 and COL4A4 comprise a broad clinical spectrum, clinical information regarding each variant is important for predicting ARAS prognosis.

Dipstick urine analysis for detection of renal abnormalities among school children

Background: Urine analysis by dipstick is a useful tool to identify children with asymptomatic renal diseases. Dipstick urinalysis screening was conducted in asymptomatic school children to detect prevalence of renal disease.Methods: A cross sectional study was carried out in 862 children of age 6 to 15 years studying in different schools of Birgunj, Nepal between January 2019 to June 2019. First morning mid-stream urine samples were obtained from students and tested by dipstick method. Children with abnormal findings were re-tested after fifteen days.Results: Ninety-six (11.13%) children had urinary abnormalities at the first screening; 8 children had specific urinary abnormalities after second screening. 4 children had urinary tract infection, followed by glomerulonephritis, type 1 diabetes, hydronephrosis and nephrotic syndrome. Urinary abnormalities were more common in females than in males.Conclusions: Asymptomatic urinary abnormalities are detected by urine screening program at school age. Further work-up reveals the specific diagnosis and effective interventions help reduce the renal disease in future.

Clinicopathological Implications of Proteinuria after Long-Term Isolated Hematuria due to Thin Basement Membrane Nephropathy and Focal Segmental Glomerulosclerosis

A 45-year-old obese man presented with persistent hematuria for 21 years. At the age of 37, he developed hypertension and proteinuria which later increased up to 1.6 g/g creatinine. Kidney biopsy revealed thin basement membrane nephropathy (TBMN) and focal segmental glomerulosclerosis (FSGS), which explained his urinary abnormalities. Although a subgroup of TBMN can be complicated by FSGS, his FSGS was associated with obesity because of its histological features. Reduction of body weight and increasing a dose of angiotensin-receptor blocker could transiently reduce the amount of proteinuria. Clinicopathological implications of proteinuria after long-term hematuria by TBMN and FSGS were further discussed.

Bilateral Pyelonephritis in a Cat with Multiple Urinary Malformations Including Ureteral Pseudodiverticulosis

ABSTRACT Ureteral pseudodiverticulosis is an unusual acquired abnormality in humans and dogs. This report describes the first feline case of ureteral pseudodiverticulosis, associated with right retrocaval ureter and malposition of the uretero-vesical junctions, in the context of pyelonephritis. The coexistence of pseudodiverticulosis with other urinary abnormalities suggested that this lesion should be considered in other patients with urinary pathology.