Remnant Kidney Research Articles

Proteinuria observed post-uninephrectomy stems from partial suppression of protein endocytosis along the proximal tubule

Living kidney donors are at higher risk of developing proteinuria, yet few studies have addressed the etiology. To investigate whether post-uninephrectomy (UNX) proteinuria was due to increased filtration and/or reduced endocytosis/reabsorption along the proximal tubule (PT), we compared renal function, morphology, and PT endocytic machinery in male Sprague Dawley rats before and after UNX.At 12 wk post-UNX, the weight of the remnant kidney rose by 50%, PT diameters by 30%, and single nephron GFR by 50% (based on 26% fall in creatinine clearance and 50% decrease in the number of nephrons). Urinary albumin excretion increased 10-fold post-UNX. Since the filtered load of proteins decreases in parallel with GFR post-UNX, increased albumin excretion likely reflects decreased endocytosis along the PT, a notion supported by a 50% reduction in abundance of albumin and plasminogen in renal cortex homogenates from remnant versus explant kidneys. We tested the hypothesis that the protein endocytic machinery was reduced following UNX. Immunoblot assays of renal cortex revealed decreased abundance of megalin and Dab2, two key mediators of protein endocytosis along the PT, and no change in cubilin abundance. Immunohistochemistry confirmed a 50% fall in megalin along the PT apical membrane.Mathematical modeling predicted that albumin uptake per nephron increases post-UNX, owing to higher single nephron GFR and PT hypertrophy, but is attenuated by the decrease in megalin abundance; moreover, modeling predicts that if the endocytic machinery were not partly suppressed, overall albumin excretion would remain at pre-UNX levels.In addition to albumin, urinary plasminogen and angiotensinogen were similarly increased post-UNX, while uromodulin (synthesized and secreted distally) was decreased post-UNX. Urinary biomarkers of renal injury, RBP4 and KIM-1, were increased post-UNX likely reflecting the impact of the increased endocytosis of albumin which can carry bound toxic lipids into the PT.Taken together, our findings suggest that the blunting of albumin endocytosis post-UNX, apparent as increased albuminuria, may serve to protect PT cells from albumin-induced cytotoxicity. DK083785; Keck School of Medicine Dean’s Pilot Funding This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Low dose Taxol ameliorated renal fibrosis in mice with diabetic kidney disease by downregulation of HIPK2.

Our previous studies reported that low-dose paclitaxel (Taxol) ameliorated renal fibrosis in the unilateral ureteral obstruction and remnant kidney models. However, the regulatory role of Taxol in diabetic kidney disease (DKD) is still unclear. Herein, we observed that low-dose Taxol attenuated high glucose-increased expression of fibronectin, collagen I and collagen IV in Boston University mouse proximal tubule cells. Mechanistically, Taxol suppressed the expression of homeodomain-interacting protein kinase 2 (HIPK2) via disrupting the binding of Smad3 to HIPK2 promoter region, and consequently inhibited the activation of p53. Besides, Taxol ameliorated RF in Streptozotocin mice and db/db-induced DKD via suppression of Smad3/HIPK2 axis as well as inactivation of p53. Altogether, these results suggest that Taxol can block Smad3-HIPK2/p53 axis, thereby attenuating the progression of DKD. Hence, Taxol is a promising therapeutic drug for DKD.

Effects of a High-Protein Diet on Kidney Injury under Conditions of Non-CKD or CKD in Mice.

Considering the prevalence of obesity and global aging, the consumption of a high-protein diet (HPD) may be advantageous. However, an HPD aggravates kidney dysfunction in patients with chronic kidney disease (CKD). Moreover, the effects of an HPD on kidney function in healthy individuals are controversial. In this study, we employed a remnant kidney mouse model as a CKD model and aimed to evaluate the effects of an HPD on kidney injury under conditions of non-CKD and CKD. Mice were divided into four groups: a sham surgery (sham) + normal diet (ND) group, a sham + HPD group, a 5/6 nephrectomy (Nx) + ND group and a 5/6 Nx + HPD group. Blood pressure, kidney function and kidney tissue injury were compared after 12 weeks of diet loading among the four groups. The 5/6 Nx groups displayed blood pressure elevation, kidney function decline, glomerular injury and tubular injury compared with the sham groups. Furthermore, an HPD exacerbated glomerular injury only in the 5/6 Nx group; however, an HPD did not cause kidney injury in the sham group. Clinical application of these results suggests that patients with CKD should follow a protein-restricted diet to prevent the exacerbation of kidney injury, while healthy individuals can maintain an HPD without worrying about the adverse effects.

Partial Nephrectomy Due to Renal Cell Carcinoma in a Patient Who Was a Prior Kidney Donor: Pitfalls About Living Kidney Donation, Case Report, and Review of the Literature

Cancer development in the remnant kidney in living kidney donors represents a challenging process in terms of patient management. Total nephrectomy is the preferred method for tumors exceeding 7 cm in size. In the case presented here, partial nephrectomy was preferred because the patient was a prior living kidney donor. On the other hand, being an organ donor always creates concerns for long-term safety and survival. The guidelines on the evaluation and care of living kidney donors have generally focused on assessment of the risk for chronic kidney disease in donors and donor-to-recipient infection or cancer transmission. In this case report, we also evaluated whether being a donor is a facilitating factor for cancer development in the remnant kidney.

Adipolin protects against renal injury via PPARα-dependent reduction of inflammasome activation

Although chronic kidney disease (CKD) is a major health problem worldwide, its underlining mechanism is incompletely understood. We previously identified adipolin as an adipokine which provides benefits for cardiometabolic diseases. Here, we investigated the role of adipolin in the development of CKD. Adipolin-deficiency exacerbated urinary albumin excretion, tubulointerstitial fibrosis and oxidative stress of remnant kidneys in mice after subtotal nephrectomy through inflammasome activation. Adipolin positively regulated the production of ketone body, β-hydroxybutyrate (BHB) and expression of a catalytic enzyme producing BHB, HMGCS2 in the remnant kidney. Treatment of proximal tubular cells with adipolin attenuated inflammasome activation through the PPARα/HMGCS2-dependent pathway. Furthermore, systemic administration of adipolin to wild-type mice with subtotal nephrectomy ameliorated renal injury, and these protective effects of adipolin were diminished in PPARα-deficient mice. Thus, adipolin protects against renal injury by reducing renal inflammasome activation through its ability to induce HMGCS2-dependent ketone body production via PPARα activation.

Klotho Supplementation Reverses Renal Dysfunction and Interstitial Fibrosis in Remnant Kidney

Introduction: While recent investigations show that klotho exerts renoprotective actions, it has not been fully addressed whether klotho protein supplementation reverses renal damage. Methods: The impacts of subcutaneous klotho supplementation on rats with subtotal nephrectomy were examined. Animals were divided into 3 groups: group 1 (short remnant [SR]): remnant kidney for 4 weeks, group 2 (long remnant [LR]): remnant kidney for 12 weeks, and group 3 (klotho supplementation [KL]): klotho protein (20 μg/kg/day) supplementation on the remnant kidney. Blood pressure, blood and urine compositions with conventional methods such as enzyme-linked immunosorbent assay and radioimmunoassay, kidney histology, and renal expressions of various genes were analyzed. In vitro studies were also performed to support in vivo findings. Results: Klotho protein supplementation decreased albuminuria (−43%), systolic blood pressure (−16%), fibroblast growth factor (FGF) 23 (−51%) and serum phosphate levels (−19%), renal angiotensin II concentration (−43%), fibrosis index (−70%), renal expressions of collagen I (−55%), and transforming growth factor β (−59%) (p < 0.05 for all). Klotho supplementation enhanced fractional excretion of phosphate (+45%), glomerular filtration rate (+76%), renal expressions of klotho (+148%), superoxide dismutase (+124%), and bone morphogenetic protein (BMP) 7 (+174%) (p < 0.05 for all). Conclusion: Our data indicated that klotho protein supplementation inactivated renal renin-angiotensin system, reducing blood pressure and albuminuria in remnant kidney. Furthermore, exogenous klotho protein supplementation elevated endogenous klotho expression to increase phosphate excretion with resultant reductions in FGF23 and serum phosphate. Finally, klotho supplementation reversed renal dysfunction and fibrosis in association with improved BMP7 in remnant kidney.

PS-B04-1: ANTI-HYPERTENSIVE AND ANTI-PROTEIURIC EFFECTS OF MELINJO SEED EXTRACT IN THE RAT REMNANT KIDNEY MODEL

Melinjo (Gnetum gnemon L.) is a fruit native to Indonesia and is considered as a healthy food. Melinjo resveratrol (MjR) is a resveratrol derivative extracted from the melinjo seed. Interestingly, recent literatures have documented that MjR exhibits the angiotensin converting enzyme inhibitory activity. Hence, we hypothesized that MjR exhibits beneficial effects in the chronic kidney disease. In order to test our hypothesis, MjR was administered in the rat remnant kidney (RK) model. Rats were divided into three groups: sham operated rats (SHAM, n = 4), untreated remnant kidney rats (RK, n = 5), RK rats treated with MjR 300 mg/kg/day (RK + MjR, n = 5). The rats were sacrificed at twelve weeks. Blood pressure and urinary protein levels significantly increased whereas creatinine clearance (CCr) significantly descread in the RK group compared to the SHAM group at twelve weeks. MjR significantly reduced systolic blood pressure (108 ± 2 vs. 147 ± 2 mmHg, p &lt; 0.05) as measured by tail-cuff methods. Urine protein excretion was significantly ameliorated by MjR compared with that in RK (79.8 ± 54.8 vs. 269 ± 87.5 mg/day, p &lt; 0.0015). Although Ccr was not altered in RK + MjR compared with RK rats, histological evaluation revealed that the glomerular sclerosis was attenuated in RK + MjR group. Podocytes in the RK rats showed increase in desmin, a marker of podocyte injury, which was alleviated with the administration of MjR. In conclusion, MjR reduced blood pressure, proteinuria and glomerular damage in the RK rats. These data suggest that MjR may mitigate the progression of chronic kidney disease, which needs further confirmation.

PS-R07-6: RENOVASCULAR HYPERTENSION SECONDARY TO MASSIVE ILIOPSOAS HEMATOMA

An 81-year-old female with stage G3 chronic kidney disease and post left nephrectomy for upper tract urothelial carcinoma 20 years ago, was admitted to our hospital for heart failure. She acutely developed right thigh pain, and contrast-enhanced computed tomography (CT) revealed an idiopathic iliopsoas hematoma for which transcatheter arterial embolization (TAE) was performed. Subsequently, her hypertension worsened despite multiple antihypertensive medications (Nifedipine, Carvedilol, Doxazosin, Spironolactone), remained uncontrolled over one month. At this point, plasma renin activity and plasma aldosterone concentration were both elevated on taking carvedilol and spironolactone. An angiotensin II receptor blocker (ARB, Olmesartan) was additionally started for refractory hypertension. Oliguric acute kidney injury (AKI) developed on the day following ARB administration, and her serum creatinine increased from 0.98 to 2.0 mg/dL. After stopping the ARB, the kidney function immediately recovered to the previous level. On review of the previously performed contrast CT, the remnant (right) kidney was ventrally displaced, and the right renal artery was kinked by the massive iliopsoas hematoma (Figure 1a and 1b). Three months after TAE, the hematoma completely disappeared, and the right kidney and renal artery returned to their original positions. Renal Doppler ultrasonography before the appearance, and after the disappearance of hematoma, demonstrated no abnormalities indicative of renal artery stenosis. Furthermore, hypertension also improved over the three months after TAE. Renal artery stenosis is primarily caused by atherosclerosis, fibromuscular dysplasia, and rarely external compression. We report a rare case of renovascular hypertension which would be induced by renal artery kinking due to massive iliopsoas hematoma. JOURNAL/jhype/04.03/00004872-202301001-01329/figure1/v/2023-10-24T163949Z/r/image-jpeg

Moderate hyperuricaemia ameliorated kidney damage in a low-renin model of experimental renal insufficiency.

Uric acid has promoted renal fibrosis and inflammation in experimental studies, but some studies have shown nephroprotective effects due to alleviated oxidative stress. We studied the influence of experimental hyperuricaemia in surgically 5/6 nephrectomized rats. Three weeks after subtotal nephrectomy or sham operation, the rats were allocated to control diet or 2.0% oxonic acid (uricase inhibitor) diet for 9 weeks. Then blood, urine and tissue samples were taken, and renal morphology and oxidative stress were examined. Inflammation and fibrosis were evaluated using immunohistochemistry and real-time PCR (RT-PCR). Remnant kidney rats ingesting normal or oxonic acid diet presented with ~60% reduction of creatinine clearance and suppressed plasma renin activity. Oxonic acid diet increased plasma uric acid levels by >80 μmol/L. In remnant kidney rats, moderate hyperuricaemia decreased glomerulosclerosis, tubulointerstitial damage and kidney mast cell count, without influencing the fibrosis marker collagen I messenger RNA (mRNA) content. In both sham-operated and 5/6 nephrectomized rats, the mast cell product 11-epi-prostaglandin-F2α excretion to the urine and kidney tissue cyclooxygenase-2 (COX-2) levels were decreased. To conclude, hyperuricaemic remnant kidney rats displayed improved kidney morphology and reduced markers of oxidative stress and inflammation. Thus, moderately elevated plasma uric acid had beneficial effects on the kidney in this low-renin model of experimental renal insufficiency.

P8.064: Development and Validation of a Nomogram for Remnant Kidney Function After Living-Donor Donation

P8.064: Development and Validation of a Nomogram for Remnant Kidney Function After Living-Donor Donation

Acute kidney injury and the compensation of kidney function after nephrectomy in living donation.

Acute kidney injury (AKI) incidence is growing rapidly, and AKI is one of the predictors of inpatient mortality. After nephrectomy, all the patients have decreased kidney function with AKI and recover from AKI. However, the characteristic and behavior of AKI is different from usual AKI and compensatory kidney function has been well known in the postoperative setting, especially in living donors. In this review, we have focused on the compensation of kidney function after nephrectomy in living donors. We discuss factors that have been identified as being associated with kidney recovery in donors including age, sex, body mass index, remnant kidney volume, estimated glomerular filtration rate, and various comorbidities.

Predictive factors of glomerular filtration rate loss associated with living kidney donation: a single-center retrospective study.

Living kidney donors (LKD) partially compensate the initial loss of glomerular filtration rate (GFR), a phenomenon known as renal functional reserve (RFR). RFR is reduced in the elderly, a population with increased prevalence of chronic kidney disease. We hypothesized that the selected, healthy population of LKD, would specifically inform about the physiological determinants of the RFR and studied it using measured GFR (mGFR). We retrospectively analyzed pre-donation and post-donation mGFR in 76 LKD from Tenon Hospital (Paris, France) between 2002 and 2018. In addition to GFR measurements, we collected pre-donation morphologic parameters, demographic data, and kidney volumes. Mean pre-donation mGFR was 90.11 ± 12.64mL/min/1.73m2 and decreased to 61.26 ± 9.57mL/min/1.73m2 1year after donation. Pre-donation mGFR correlated with age (p = 0.0003), total kidney volume (p = 0.0004) and pre-donation serum creatinine (p = 0.0453). Pre-donation mGFR strongly predicted 1-year post-donation mGFR. Mean RFR (increase in GFR of the remnant kidney between pre-donation and post-donation) was 36.67 ± 16.67% 1year after donation. In the multivariate linear model, RFR was negatively correlated to total kidney volume (p = 0.02) but not with age or pre-donation serum creatinine. We found that pre-donation mGFR decreases with age and identified low total kidney volume as a predictor of RFR in healthy individuals. This suggests an adaptative and reversible decrease in kidney function rather than age-related damage. Older subjects may have reduced metabolic requirements with subsequent reduction in glomerular filtration and kidney volume and preserved RFR. Therefore, low GFR in older subjects should not preclude kidney donation.

MO389: Klotho Supplementation Reverses Renal Dysfunction and Interstitial Fibrosis in Remnant Kidney

Abstract BACKGROUND AND AIMS Several studies demonstrate that klotho shows renoprotective actions. However, it has not been assessed whether klotho supplementation is able to reverse the renal injury. METHOD In the present study, the effects of klotho protein supplementation on remnant rat kidneys were assessed using three groups: renal ablation for 4 weeks, renal ablation for 12 weeks and klotho supplementation (20 μg/kg/day). RESULTS Klotho supplementation suppressed blood pressure, albuminuria, renal renin-angiotensin system (RAS), serum phosphate and fibroblast growth factor (FGF) 23 levels, fibrosis index, renal expression of transforming growth factor β and collagen I. Klotho protein supplementation increased glomerular filtration rate (GFR), fractional excretion of phosphate, renal expression of klotho, bone morphogenetic protein (BMP) 7 and superoxide dismutase. CONCLUSION Our data indicated that klotho supplementation reduced blood pressure and albuminuria with inactivation of renal RAS in the remnant kidney. In addition, exogenous klotho protein supplementation increased endogenous klotho expression, facilitating phosphate excretion with reductions in serum phosphate and FGF23. Finally, klotho protein supplementation upregulated BMP7, at least partly contributing to an increase in GFR and reversal of fibrosis in the remnant kidney.

Icariin improves renal interstitial fibrosis in a rat model of chronic renal failure by regulating mitochondrial dynamics

This study aims to explore the effect of icariin(ICA) on mitochondrial dynamics in a rat model of chronic renal failure(CRF) and to investigate the molecular mechanism of ICA against renal interstitial fibrosis(RIF). CRF was induced in male Sprague-Dawley(SD) rats with 5/6(ablation and infarction, A/I) surgery(right kidney ablation and 2/3 infarction of the left kidney). Four weeks after surgery, the model rats were randomized into the following groups: 5/6(A/I) group, 5/6(A/I)+low-dose ICA group, and 5/6(A/I)+high-dose ICA group. Another 12 rats that received sham operation were randomly classified into 2 groups: sham group and sham+ICAH group. Eight weeks after treatment, the expression of collagen-Ⅰ(Col-Ⅰ), collagen-Ⅲ(Col-Ⅲ), mitochondrial dynamics-related proteins(p-Drp1 S616, p-Drp1 S637, Mfn1, Mfn2), and mitochondrial function-related proteins(TFAM, ATP6) in the remnant kidney tissues was detected by Western blot. The expression of α-smooth muscle actin(α-SMA) was examined by immunohistochemical(IHC) staining. The NRK-52 E cells, a rat proximal renal tubular epithelial cell line, were cultured in vitro and treated with ICA of different concentration. Cell viability was detected by CCK-8 assay. In NRK-52 E cells stimulated with 20 ng·mL~(-1) TGF-β1 for 24 h, the effect of ICA on fibronectin(Fn), connective tissue growth factor(CTGF), p-Drp1 S616, p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 was detected by Western blot, and the ATP content and the mitochondrial morphology were determined. The 20 ng·mL~(-1) TGF-β1-stimulated NRK-52 E cells were treated with or without 5 μmol·L~(-1) ICA+10 μmol·L~(-1) mitochondrial fusion promoter M1(MFP-M1) for 24 h and the expression of fibrosis markers Fn and CTGF was detected by Western blot. Western blot result showed that the levels of Col-Ⅰ, Col-Ⅲ, and p-Drp1 S616 were increased and the levels of p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 were decreased in 5/6(A/I) group compared with those in the sham group. The levels of Col-Ⅰ, Col-Ⅲ, and p-Drp1 S616 were significantly lower and the levels of p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 were significantly higher in ICA groups than that in 5/6(A/I) group. IHC staining demonstrated that for the expression of α-SMA in the renal interstitium was higher in the 5/6(A/I) group than in the sham group and that the expression in the ICA groups was significantly lower than that in the 5/6(A/I) group. Furthermore, the improvement in the fibrosis, mitochondrial dynamics, and mitochondrial function were particularly prominent in rats receiving the high dose of ICA. The in vitro experiment revealed that ICA dose-dependently inhibited the increase of Fn, CTGF, and p-Drp1 S616, increased p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6, elevated ATP content, and improved mitochondrial morphology of NRK-52 E cells stimulated by TGF-β1. ICA combined with MFP-M1 further down-regulated the expression of Fn and CTGF in NRK-52 E cells stimulated by TGF-β1 compared with ICA alone. In conclusion, ICA attenuated RIF of CRF by improving mitochondrial dynamics.

Ferroptosis, a new target for treatment of renal injury and fibrosis in a 5/6 nephrectomy-induced CKD rat model

Ferroptosis is a non-traditional form of regulated cell death, characterized by iron overload and lipid peroxidation. Exploration of ferroptosis in chronic kidney disease (CKD) has been extremely limited to date. In this study, we established a rat model of CKD by 5/6 nephrectomy, treated CKD rats with the ferroptosis inducer, cisplatin (CDDP), and the ferroptosis inhibitor, deferoxamine mesylate (DFO), and observed the resulting pathologic changes (injury markers and fibrosis) and ferroptotic biochemical indices. Kidney iron deposition, lipid peroxidation, mitochondrial defects, ferroptosis marker induction, and TUNEL staining positivity were detected in CKD group rats. Further, treatment with CDDP or DFO influenced renal injury and fibrosis by affecting ferroptosis, rather than apoptosis, and ferroptosis occurs in the remnant kidney due to disordered iron metabolism. In conclusion, our study shows for the first time that 5/6 nephrectomy induces ferroptosis in the remnant kidney and clarifies the underlying pathogenesis. Moreover, we demonstrate that ferroptosis is involved in CKD progression and represents a therapeutic target in chronic kidney injury and renal fibrosis.

Factor Xa inhibitor, edoxaban ameliorates renal injury after subtotal nephrectomy by reducing epithelial-mesenchymal transition and inflammatory response.

Chronic kidney disease (CKD) is an increasing and life‐threatening disease worldwide. Recent evidence indicates that blood coagulation factors promote renal dysfunction in CKD patients. Activated factor X (FXa) inhibitors are safe and first‐line drugs for the prevention of thrombosis in patients with atrial fibrillation. Here, we investigated the therapeutic effects of edoxaban on CKD using the mouse 5/6 nephrectomy model. Eight‐week‐old wild‐type mice were subjected to 5/6 nephrectomy surgery and randomly assigned to two groups, edoxaban or vehicle admixture diet. Edoxaban treatment led to reduction of urinary albumin excretion and plasma UN levels compared with vehicle group, which was accompanied with reduced glomerular cross‐sectional area and cell number. Edoxaban treatment also attenuated fibrinogen positive area in the remnant kidneys after subtotal nephrectomy. Moreover, edoxaban treatment resulted in attenuated tubulointerstitial fibrosis after 5/6 nephrectomy, which was accompanied by reduced expression levels of epithelial‐mesenchymal transition (EMT) markers, inflammatory mediators, and oxidative stress markers in the remnant kidneys. Treatment of cultured proximal tubular cells, HK‐2 cells, with FXa protein led to increased expression levels of EMT markers, inflammatory mediators, and oxidative stress markers, which were abolished by pretreatment with edoxaban. Treatment of HK‐2 cells with edoxaban attenuated FXa‐stimulated phosphorylation levels of extracellular signal‐regulated kinase (ERK) and NF‐κB. Our findings indicate that edoxaban can improve renal injury after subtotal nephrectomy by reducing EMT and inflammatory response, suggesting that FXa inhibition could be a novel therapeutic target for CKD patients with atrial fibrillation.

Prevalence of reflux nephropathy in Iranian children with solitary kidney: results of a multi-center study

BackgroundGiven the importance of the function of the remnant kidney in children with unilateral renal agenesis and the significance of timely diagnosis and treatment of reflux nephropathy to prevent further damage to the remaining kidney, we aimed to determine the prevalence of reflux nephropathy in this subgroup of pediatric patients.MethodsIn general, 274 children referred to pediatric nephrologists in different parts of Iran were evaluated, of whom 199 had solitary kidney and were included in this cross-sectional study. The reasons for referral included urinary tract infection (UTI), abnormal renal ultrasonography, being symptomatic, and incidental screening. Demographic characteristics, including age and gender were recorded. History of UTI and presence of vesicoureteral reflux (VUR) were evaluated.ResultsOf the 274 children evaluated in this study with the mean age (SD) of 4.71 (4.24) years, 199 (72.6%) had solitary kidney. Among these, 118 (59.3%) were male and 81 (60.7%) were female, 21.1% had a history of UTI, and VUR was present in 23.1%. The most common cause of referral was abnormal renal ultrasonography (40.2%), followed by incidental screening (21.1%), being symptomatic (14.1%), and UTI (5.5%). In 116 children (58.3%), the right kidneys and in 83 (41.7%) the left kidneys were absent. Besides, 14.6% of the participants had consanguineous parents and 3% had a family history of solitary kidney. Upon DMSA scan, the single kidney was scarred in 13.1%, of which only 7.5% were associated with VUR. In addition, proteinuria and hematuria were observed in 6.5% and 1.5% of children, respectively.ConclusionsThe prevalence of reflux nephropathy was 7.5% in children with solitary kidney with a male predominance. Given the relatively high prevalence of reflux nephropathy in these children, screening for VUR in the remnant kidney appears to be essential in this population.

Volume preservation of a shattered kidney after blunt trauma by superselective renal artery embolization.

PURPOSE We examined whether superselective embolization of the renal artery could be effectively employed to preserve traumatic kidneys and assessed its clinical outcomes. METHODS Between December 2015 and November 2019, 26 patients who had American Association for the Surgery of Trauma grade V traumatic shattered kidneys were identified. Among them, a retrospective review was conducted of 16 patients who underwent superselective renal artery embolization for shattered kidney. The mean age was 41.2 ± 15.7 years, and the mean follow-up duration was 138.2 ± 140.1 days. Patient data including procedure details and clinical outcomes were reviewed, and the preserved volume of kidney parenchyma was calculated. RESULTS Bleeding control was achieved in 13 (81%) patients and kidney preservation was achieved in 11 (79%). There was no mortality, and the median intensive care unit stay was 1.5 days. The mean volume of remnant kidney was 122.3 ± 66.0 cm3 (70%) on the last follow-up computed tomography. The estimated glomerular filtration rate was not significantly changed after superselective renal artery embolization. CONCLUSION Superselective renal artery embolization using a microcatheter for the shattered kidney effectively controlled hemorrhage in acute stage trauma and enabled kidney preservation.

Role of miRNA-671-5p in Mediating Wnt/β-Catenin-Triggered Podocyte Injury.

Podocyte injury and proteinuria are the most common features of glomerular disease, which is the leading cause of end-stage renal failure. Hyperactivated Wnt/β-catenin signaling is closely associated with podocyte injury, but the underlying mechanisms are incompletely understood. Here we show that miRNA-671-5p (miR-671-5p) plays a crucial role in mediating β-catenin-triggered podocyte injury by targeting Wilms tumor 1 (WT1). Microarray-based expression profiling revealed that miR-671-5p was the most upregulated miRNA in podocytes after β-catenin activation. MiR-671-5p was colocalized with β-catenin in the glomeruli of proteinuric CKD in vivo. Bioinformatics analyses and luciferase reporter assays confirmed that miR-671-5p targeted WT1 mRNA. Overexpression of miR-671-5p mimics inhibited WT1 and impaired podocyte integrity, whereas miR-671-5p antagomir preserved the expression of WT1 and other podocyte-specific proteins under basal conditions or after β-catenin activation. In mouse remnant kidney model, overexpression of miR-671-5p aggravated podocyte injury, worsened kidney dysfunction and exacerbated renal fibrosis after 5/6 nephrectomy. In contrast, miR-671-5p antagomir alleviated podocyte injury and attenuated proteinuria and renal fibrotic lesions after glomerular injury in vivo. These studies underscore a pivotal role of miR-671-5p in mediating WT1 depletion and podocyte injury induced by β-catenin. Targeting miR-671-5p may serve as a new approach to prevent podocyte injury and proteinuria in proteinuric CKD.

Is Compensation Prediction Score Valid for Contralateral Kidney After Living-Donor Nephrectomy in the United States?

Compensation after living donor nephrectomy is well known, and a compensation prediction score (CPS) was made in Japan previously. The aim of this study was to perform external validation of CPS in the United States. We studied retrospectively 78 living donor nephrectomies in our institution. We defined a favorable compensation as a postdonation estimated glomerular filtration rate (eGFR) at 1 year of >60% of the predonation eGFR. We analyzed the living donors' clinical characteristics and outcomes and validated CPS score. The median (range) donor age was 43 (21-63) years, and median body mass index was 26.9 (18.3-35.9) kg/m2. Forty-four percent of donors were White. The donor predonation eGFR was 105 (61-134) mL/min/1.73 m2, and the postdonation eGFR at 1 year was 73.2 (0-115) mL/min/1.73 m2. Eighty-three percent of donors had a favorable compensation. The CPS was 9.6 (1.6-15.6) and showed strong diagnostic accuracy for predicting favorable compensation (area under the curve, 0.788; 95% confidence interval, 0.652-0.924; P=.001). The CPS showed a significant positive correlation with the postdonation eGFR at 1 year (R=0.54; P < .001). In the United States, the CPS would be a valid tool with which to predict a favorable compensation of remnant kidney function.