Decreased Podocyte Vesicle Transcytosis and Albuminuria in APC C-Terminal Deficiency Mice with Puromycin-Induced Nephrotic Syndrome

In minimal change nephrotic syndrome, podocyte vesicle transport is enhanced. Adenomatous polyposis coli (APC) anchors microtubules to cell membranes and plays an important role in vesicle transport. To clarify the role of APC in vesicle transport in podocytes, nephrotic syndrome was induced by puromycin amino nucleoside (PAN) injection in mice expressing APC1638T lacking the C-terminal of microtubule-binding site (APC1638T mouse); this was examined in renal tissue changes. The kidney size and glomerular area of APC1638T mice were reduced (p = 0.014); however, the number of podocytes was same between wild-type (WT) mice and APC1638T mice. The ultrastructure of podocyte foot process was normal by electron microscopy. When nephrotic syndrome was induced, the kidneys of WT+PAN mice became swollen with many hyaline casts, whereas these changes were inhibited in the kidneys of APC1638T+PAN mice. Electron microscopy showed foot process effacement in both groups; however, APC1638T+PAN mice had fewer vesicles in the basal area of podocytes than WT+PAN mice. Cytoplasmic dynein-1, a motor protein for vesicle transport, and α-tubulin were significantly reduced in APC1638T+PAN mice associated with suppressed urinary albumin excretion compared to WT+PAN mice. In conclusion, APC1638T mice showed reduced albuminuria associated with suppressed podocyte vesicle transport when minimal change nephrotic syndrome was induced.

Role of the Renal Androgen Receptor in Ammonia Metabolism

Background: There are sex differences in renal ammonia metabolism and structure, many of which are mediated by testosterone. This study's goal was to determine the role of renal expression of testosterone's canonical receptor, androgen receptor (AR), in these sexual dimorphisms. Methods: We studied mice with kidney-specific AR deletion (KS-AR-KO) generated using Cre/loxP techniques; control mice were Cre-negative littermates (WT). Results: In male, but not female, mice, KS-AR-KO increased ammonia excretion, which eliminated sex differences. Although renal structural size typically parallel ammonia excretion, KS-AR-KO decreased kidney size, cortical proximal tubule volume density and cortical proximal tubule cell height in males; neither were altered in females and collecting duct volume density was unaltered in both sexes. Analysis of key protein involved in ammonia handling showed in male mice that KS-AR-KO increased both PEPCK and NKCC2 expression, and decreased NHE3 and NBCe1-A expression. In female mice, KS-AR-KO did not alter these parameters. These effects occurred even though KS-AR-KO did not alter plasma testosterone, food intake or serum Na+, K+, or HCO3- significantly in either sex. Conclusions: AR-dependent signaling pathways in male, but not female, kidney regulate PEPCK and NKCC2 expression and lead to the sexual differences in ammonia excretion. Opposing effects on NHE-3 and NBCe1-A expression likely limit the magnitude of ammonia excretion changes. Since AR is not present in the TAL, the effect of KS-AR-KO on NKCC2 expression is indirect. Finally, AR mediates the greater kidney size and PT volume density in male than in female mice.

CYSTATIN–C AS AN EARLY INDICATOR FOR INCIPIENT RENAL DISEASE IN RHEUMATOID ARTHRITIS-A HOSPITAL BASED CROSS SECTIONAL STUDY

Background: The aim of the present study was to examine the diagnostic capacity of this new parameter towards early signs of renal disease in patients suffering from prolonged RA requiring potential nephrotoxic therapy. Methods: The present study was a cross sectional observational type of study conducted in the department of medicine Mathura Das Mathur Hospital, Dr. S.N. Medical College, Jodhpur. A total of 50 subjects that fulfilled the inclusion and exclusion criteria were enrolled in the study after informed and written consent. As per methodology complete blood count, ESR, liver function test, kidney function test, cystatin-c, urine complete, 24 hours urine creatinine, USG abdomen for kidney size were performed. Results: cystatin–C level below 0.95 mg/dl was considered normal. 19 patients have normal and 31 patients have abnormal more than 0.95 mg/dl. Conclusion: In conclusion, as compared to serum creatinine, the determination of serum cystatin C is comparably simple, but by far more sensitive for the diagnosis of incipient renal damage in RA, and therefore valuable for clinical screening particularly in cases with prolonged antirheumatic treatment. Keywords: Cystatin C, RA, KFT

Effects of prematurity on long-term renal health: a systematic review

ObjectiveTo investigate the literature and determine if prematurity has an impact on long-term adverse kidney outcomes.DesignSystematic review.Data sourcesOVID Medline, PubMed, SCOPUS, CINAHL and EMBASE databases were searched for studies relating to the adverse outcomes of prematurity from 1990 to April 2021.Eligibility criteria for selecting studiesAll articles published between January 1990 and April 2021 that investigated whether premature infants developed long-term adverse renal outcomes were included in this review. Articles must have been human studies and written in English. Case series with less than 20 participants and case studies were excluded.Data extraction and synthesisOne reviewer completed the database searches. Article selection was performed independently and in a non-blinded manner by both reviewers. Initial screening was by title and abstract. Full texts of remaining articles were reviewed. Articles for which inclusion was unclear were re-reviewed by both reviewers, and a unanimous decision was taken as to whether they should be included. The Newcastle–Ottawa Scale was used for quality assessment of the included articles.ResultsThe literature search yielded 31 human studies, which investigated the short-term and long-term kidney outcomes of prematurity. These studies were conducted in 17 different countries. The most common outcomes measured were blood pressure (BP) and glomerular filtration rate. Other common outcomes measured included kidney size and mass, proteinuria, albuminuria, chronic kidney disease (CKD) and physical parameters such as height, weight and body mass index.ConclusionPrematurity is likely linked to increased risk of kidney dysfunction and high BP in childhood and into early adulthood. Premature birth conferred a twofold increased risk of CKD and extremely premature birth conferred a threefold increased risk of CKD. However, further larger multicentre studies are needed to draw definitive conclusions on the long-term kidney outcomes of prematurity.

Experience Summary of Laparoscopic Treatment for Pediatric Ureteral Polyps

Objective: To investigate surgical techniques and challenges of laparoscopic in treating pediatric ureteral polyps under laparoscopy.Methods: The clinical data of 7 of pediatric ureteral polyps patients who were admitted to the hospital from July 2015 to January 2020 were analyzed retrospectively. There were 6 males and 1 female from 7.7 to 13.9 years old at the mean age of 10.4. Before surgery, all children performed urinary B ultrasound, magnetic resonance urography (MRU), and renal radionuclide scanning. Six cases were observed on the left lateral and 1 on the right. The lesions of 5 cases were located at the ureteropelvic junction, 1 in the upper ureter and 1 in the middle ureter. The polyps were treated intraoperatively by the resecting of the lesion segment and simple polypectomy to retain the attached part of the original diseased segment of the ureter. All surgeries were performed under laparoscopy and B-ultrasound was performed during follow up after surgery.Results: All 7 surgeries were performed successfully under the laparoscope. The surgery time was 80–110 min, and the average surgery time was 97.5 min. The intraoperative bleeding was 10–25 ml and the average postoperative hospital stay was 6 d. Postoperative hematuria occurred in 1 case. Neither urinary leakage nor urinary tract infection was reported post surgery. Preoperative affected pyelectasis of all patients was 2.0–3.7 cm. Three months postoperatively, the affected pyelectasis was measured at 1.2–3.0 cm. No recurrence of polyps was reported after surgery. During the follow-up to April 2020, there was no significant change in the kidney size of all patients, and hydronephrosis was alleviated compared with that before surgery.Conclusions: Laparoscopy is a safe, effective and minimally invasive surgical technique for pediatric multiple ureteral polyps. The surgery plan was designed according to the location and size of polyps, including segmental ureterectomy of polyps + pyeloureterostomy, segmental ureterectomy of polyps + ureter - ureteral anastomosis.

Time dependant functional and morphological recovery of the kidney after relief of obstruction in patients with impacted ureteral stones

Objectives: To assess the course of functional and morphological recovery of the kidney following the relief of obstruction with ureteral JJ stent in cases with unilateral impacted stones. Materials and methods: A total of 42 adult patients who were admitted to our clinic with unilateral obstructing impacted ureteral stones requiring JJ stent placement were included in the study. The course of functional recovery was assessed by evaluating the serum creatinine levels, renal resistive index (RRI) values and urinary levels of kidney injury molecule-1, neutrophil gelatinaseassociated lipocalin as well as microalbumin before at 1 day, 1 week and 4 weeks after JJ stent placement. Course of morphologic recovery was evaluated by evaluating the degree of hydronephrosis, kidney size, perirenal straining and ureteral diameter. Results: Our results showed that all relevant parameters began to decrease after 24 hours and continue to normalize during 1 week evaluation; majority of these variables indicating the functional and morphological recovery were in normal range after 4 weeks. Decompression of the obstructed kidneys with JJ stent placement in patients with impacted ureteral stones was found to be effective enough with recovery of normal renal functional and morphological status after a minimum time period of 4 weeks. Morphological recovery of affected kidneys following JJ stenting was obtained with a significant difference between baseline and 1-month evaluation findings (p = 0.001, p < 001, p < 001, respectively). KIM-1 excretion began to decline to normal levels after 4 weeks (3.52 ± 0.99 ng/ml versus 2.84 ± 0.66 ng/ml, p < 0.001). The same findings were observed for the urinary excretion levels of NGAL, which normalized at the 1-month evaluation (604.55 ± 140.28 ng/ml versus 596.87 ± 80.17 ng/ml p = 0.895). Urinary microalbumin excretion levels however remained high even until 1-month follow-up with a statistically significant difference when compared with the normal excretion values (p < 0.001). There was a statistically significant difference in RRI values between baseline and 1-month follow-up findings in obstructed kidney (p < 0.001). Conclusions: Elective management of the obstructing impacted ureteral stone(s) will be safer with limited risk of infective complications after functional and morphological normalization in such kidneys following 4 weeks of JJ stent placement.

CLINICAL AND HISTOPATHOLOGICAL CHARACTERIZATION OF LUPUS NEPHRITIS IN A TERTIARY HEALTH CENTRE, NORTH-EASTERN NIGERIA: REPORT OF FIVE CASES.

Background: Lupus nephritis (LN) is an immune complex glomerulonephritis that complicates up to 40% of SLE patients. A kidney biopsy is required for diagnosis and staging of the disease. Case report: We report a cohort of five patients with LN from a tertiary health facility in northeastern Nigeria. The five patients were all women with age ranging from 26 to 55 years, and eGFR of between 6 to 154ml/minute. Four patients had normal kidney size and were biopsied whereas 1 patient had contracted kidney. Diffuse proliferative LN (Class IV) was seen in two patients while the other two patients had glomerular sclerosis (Class VI). Patients were given induction with methylprednisolone and mycophenolate mofetil (MMF). At one year follow up 2(40%) patients were in remission, 1(20%) was on maintenance hemodialysis and 2(40%) patients had died. Conclusion: Lupus nephritis is a common complication of SLE in northeastern Nigeria. Patients have features of advanced kidney disease at presentation.