Complete Loss Of Renal Function Research Articles

#2339 All-trans retinoic acid enhances the efficacy of mesenchymal stem cells in acute kidney injury

Abstract Background and Aims Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic strategy for acute kidney injury (AKI), but still suffer from the drawbacks of low survival rate, low homing rate, and uncertain differentiation. In search of better therapeutic strategies, we explored all-trans retinoic acid (ATRA) pretreatment of MSCs to observe whether it could improve the therapeutic efficacy on AKI. Method We established a renal ischemia/reperfusion (I/R) injury model induced by clamping of left renal artery for 30 minutes and contralateral nephrectomy. C57BL/6 mice were randomly divided into 4 groups: sham group, IRI group, MSCs group, and ATRA-MSCs group. MSCs or ATRA-pretreated MSCs were injected via tail vein. GFR was measured by transcutaneous monitoring the clearance of FITC-sinistrin. These mice were sacrificed 3 days after surgery, and the serum creatinine (SCr) and blood urea nitrogen (BUN) levels were measured. The renal pathological changes were examined by Periodic Acid-Schiff staining (PAS). The in vitro hypoxia/reoxygenation (H/R) model was established using human proximal tubular epithelial cells (HK-2 cells). Co-culturing HK-2 cells with MSCs or ATRA-pretreated MSCs. Western blot, quantitative real time-PCR (qRT-PCR), and immunohistochemistry were used to detect mRNA or protein expression. We performed RNA sequencing (RNA-seq) analysis in ATRA-pretreated MSCs. The content of hyaluronic acid (HA) in the supernatant of ATRA-pretreated MSCs culture was detected by ELISA. Hyaluronan synthase mRNA expression level in ATRA-pretreated MSCs assessed by qRT-PCR analysis. The HAS2 promoter-binding transcription factors were forecasted by the JASPAR Transcription Factor Binding Site database. Western blot was used to detect whether P13K/AKT pathway was activated by ATRA-pretreated MSCs. Whether this nephroprotective effect could be reversed were explored by silencing HAS2 or CD44 antibodies. Results The AKI mice showed a significant decrease in GFR and even complete loss of renal function. Administration of MSCs significantly increased GFR, and MSCs pretreated with ATRA further increased GFR. Mice injected with ATRA-pretreated MSCs had significantly lower levels of SCr, BUN and ATN scores compared with untreated MSCs. Western blot, quantitative real-time PCR (qRT-PCR), and immunohistochemistry showed that ATRA pretreated MSCs were more effective in reducing AKI inflammation and apoptosis and promoting proliferative repair than untreated MSCs. GO enrichment analysis demonstrated that the hyaluronan biosynthetic process may be a significantly expressed. HAS2 expression and HA content of MSCS were significantly increased after the addition of ATRA. Analysis for potential transcription factor binding sites revealed that the HAS2 promoter region has multiple potential binding sites for the retinoic acid receptor. Based on the predictions from the JASPAR database, the RXR-RAR heterodimer had the highest prediction score. We then performed ChIP analysis to experimentally verify the binding of RXR-RAR heterodimer transcription factor to HAS2 promoters. We further found that ATRA-pretreated MSCs activated the PI3K/AKT signaling pathway in AKI. As expected, we found that ATRA-pretreated MSCs anti-inflammatory, anti-apoptosis, and pro-proliferation effects were substantially reversed by silencing HAS2 or blocking CD44. Conclusion ATRA promotes HA secretion from MSCs and activates the PI3K/AKT pathway, which in turn enhances the therapeutic efficacy of MSCs on AKI.

BIOMARKERS OF ACUTE POST-CONTRAST KIDNEY INJURY IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTIONS

The high prevalence of coronary heart disease requires an increase in interventional interventions using X-ray contrast agents. One of the possible consequences is the development of acute kidney injury (AKI). Previously, the formation of AKI after the procedure with the introduction of contrast was always regarded as contrast-induced. Given the complexity of the pathogenesis of AKI, it is currently recommended to use a more comprehensive term "post-contrast AKI" (). The manifestations of PCAKI include an absolute (greater than or equal to 0.3 or more or equal to 0.5 mg / dL) or relative (greater than or equal to 25 %) increases in serum creatinine (sCr) compared with baseline values, occurring 48–72 hours after intravascular administration of RKV. PC-AKI is a common complication following intravascular administration of iodine-containing contrast media and is associated with prolonged hospital stay and poor long-term prognosis, including unwanted cardiovascular events, and complete loss of renal function. PC-AKI occurs in 5-20% of hospitalized patients undergoing percutaneous coronary interventions. Unfortunately, there are currently no analogues of iodine-containing RKV, and therefore the question of finding optimal PC-AKI biomarkers for the purpose of early diagnosis and prevention of this formidable complication remains relevant. The diagnosis of PC-AKI is based on an increase in serum creatinine, which is a late biomarker of kidney damage. New and earlier serum and urinary biomarkers for the diagnosis of kidney damage have now been identified that can be detected before serum creatinine levels rise. This article provides information on the most relevant and modern biomarkers of PC-AKI.

Efficacy of Laparoscopic Uretherolithotomy in the Treatment of Large and Fixed Ureteral Stones

Urolithiasis has been and remains one of the most pressing problems in modern urology. In urological clinics, the number of such patients reaches 20–40 % of the total number of patients. Half of them are patients with ureteral stones. Obstruction of the ureter with stones leads to impaired outflow of urine from the kidney, the accession of obstructive pyelonephritis, the development of ureterohydronephrosis until complete loss of renal function. Removal of large stones, especially those that are in the ureter for a long time, is a serious problem in urology. There are several methods of surgical treatment of ureterolithiasis: extracorporeal shock wave ureterolithotripsy (ESWL), contact ureterolithotripsy (CL), ureterolithoextraction, percutaneous nephrolithotripsy (when moving a stone from the ureter to the kidney). An alternative to these methods is laparoscopic ureterolithotomy.The objective: to evaluate the effectiveness of laparoscopic ureterolithotomy in the treatment of large and fixed ureteral stones.Materials and methods. We performed 43 laparoscopic ureterolithotomies in the clinic of theInstitute ofUrology of the National Academy of Medical Sciences ofUkraine for the period from 2014 to 2019. The size of the stones ranged from 15 to25 mm. In 32 (74.4 %) patients the stones were localized in the upper third of the ureter, in 11 (25.6 %) – in the middle third. The stones were in the ureter from two months to two years. In 11 patients the stones were recurrent. In 41 (95 %) on the side of the calculus developed ureterohydronephrosis. 8 patients underwent ESWL before admission to the clinic, three – CL, which were ineffective. In 32 (74.4 %) patients laparoscopic ureterolithotomy was performed as a primary treatment.Results. As the results of the operation showed, the stones in all patients were completely removed. There were no conversions or intraoperative complications. Postoperative bed-day was from 3 to 5 days. 1.5 months after surgery, renal function was completely restored in all patients, ureterohydronephrosis and recurrence of stone formation were not detected.Conclusion. Mild traumatisation of laparoscopic ureterolithotomy, the possibility of one-time complete removal of stones, smooth postoperative course, make this method first choice for the presence of large stones and stones that are long in the ureter, as well as ineffective ESWL, CL and others.

Pattern of presentation and management of benign upper urinary tract obstruction in Sokoto Northwest Nigeria

Background: Upper urinary tract obstruction is a common cause of severe symptoms, recurrent urinary tract infection and deterioration or complete loss of renal function when intervention is not timely.Objective: To document the pattern of presentation and the management options for the benign upper urinary tract obstruction in our practice.Materials and Methods: The study retrospectively reviewed patients managed for benign upper urinary tract obstruction in our facility from February 2011 to February 2016. A total of 52 patients were treated during the study period. All the patients with benign upper urinary tract obstruction were included in the study. While Patients with lower urinary tract obstruction without secondary vesico-ureteric reflux (VUR), upper urinary tract obstruction from malignancy and those with incomplete records were excluded.Data was collected via a proforma and analysis was done using SPSS 20.0 versionResults: The mean age of patients in the study was 32.9±12.8 years and Male: female ratio was 3.3:1. The mode of presentations were flank pain in 47 patients (90.2%), haematuria in 36 patients (69.2%), childhood haematuria in 23 patients (44.2%) and urinary tract infection (UTI) in19 patients (36.5 %). The causes of upper tract obstruction were urolithiasis in 32 patients (61.6%), ureteric obstruction in 15 patients (28.8 %) and pelvi-ureteric junction obstruction in 5 patients (9.6 %). The definitive treatments were open in 27 patients (51.9 %), endoscopic in 14 patients (26.9%), and non-operative in 11 patients (21.2%).Conclusion: Urolithiasis, ureteric obstruction and pelvi-ureteric junction obstruction are the commonest cause of benign upper tract obstruction in our environment. Treatment can be open, endoscopic or medical.Keywords: Ureteric obstruction, urolithiasis, pelvi-ureteric junction obstruction

Danno Renale Acuto da Mezzi Iodati di Contrasto. Fisiopatologia e Suggerimenti di Prevenzione

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Acute kidney injury.

Acute kidney injury.

Acute Renal Failure due to Obstructive Uropathy Secondary to Ureteral Endometriosis.

Ureteral involvement by endometriosis is a rare and often silent disease but capable of producing significant morbidity and leading to hydronephrosis and to renal failure. Surgery is the treatment of choice to remove endometriotic lesions and relieve ureteral obstruction if the kidney is still functional or a nephrectomy is performed if there is a complete loss of renal function. We report a case of acute renal failure induced ureteral endometriosis managed with laparoscopic unilateral nephrectomy and endometrioma cystectomy. Differential diagnosis is important to confirm diagnosis for patients with ureteral obstruction presenting nonspecific symptoms.

Complete loss of unilateral renal function secondary to endometriosis: a report of three cases

ObjectivesTo report the impact that urinary tract endometriosis may have on renal function. Ureteral endometriosis is an uncommon and silent cause of renal injury. It is therefore very important to be highly suspicious in order to be able to make an early diagnosis and thus prevent renal failure. Study designCase reports of the management and outcome of three cases of premenopausal women with deep endometriosis affecting the ureter, associated with secondary unilateral complete loss of renal function. Results and conclusionsUreteral involvement by endometriosis is a rare and often silent disease which is capable of producing significant morbidity, as it can lead to hydronephrosis and ultimately to renal failure. Because of the lack of specific symptoms and the limitations of imaging methods, a high index of suspicion is necessary to obtain an early diagnosis. On diagnosis of deep infiltrating endometriosis, urinary tract ultrasound is a screening tool to detect ureterohydronephrosis due to ureteral obstruction. MRI is of value to map the extent of disease. Surgery is the treatment of choice to remove endometriotic lesions and relieve ureteral obstruction if the kidney is still functional, or to perform a nephrectomy if there is a complete loss of renal function.

Urolithiasis: The Most Risk for Nephrectomy in Nonrenal Tumor Patients

The existence of upper urinary tract calculus may cause complete loss of renal function, which eventually results in nephrectomy. Our purpose was to describe the prevalence and clinical characteristics of upper urinary tract calculus cases among a series of patients undergoing nephrectomy during a 10-year period. The data of 1059 patients undergoing nephrectomy between January 2001 and December 2010 in our center were reviewed. The prevalence and clinical characteristics of upper urinary tract calculi-derived nonfunctioning kidney were analyzed. Among 1059 patients, 177 (16.7%) had nonfunctioning kidneys, which were second in number to renal tumor cases (801, 75.6%). Upper urinary tract calculi accounted for the greatest cause (101, 57.1%) in these nonfunctioning kidney cases. These patients were mainly screened by ultrasonography and the diagnosis confirmed by CT, intravenous urography, and nuclear renography. There were 44 (43.6%) patients with a single renal stone in the ureteropelvic junction, 36 (35.6%) with a single ureteral stone, and 21 (20.8%) with multiple unilateral renal and ureteral stones. The average size of the renal stones and ureteral stones were 15.6±8.8 mm (4-50 mm) and 13.4±4.0 mm (4-21mm) in diameter, respectively. Prevalence of urolithiasis derived nonfunctioning kidney had not changed significantly over 10 years and even showed a slight increase. Most of the stones were more than 10 mm in diameter. A nonfunctioning kidney was more likely to develop in females or patients with a low living standard. Upper urinary tract calculus (>10 mm) and loss to follow-up are the greatest risk factors for a nonfunctioning kidney. A nonfunctioning kidney develops more easily in females or patients with a low living standard. A regular urinary system health examination is recommended. Routine follow-up of urolithiasis is also recommended for patients with a stone history to prevent renal dysfunction.

A Case of Pyonephrosis Secondary to Ureteral Stent Calculus

Ureteric stents, a good solution to many urologic problems, can lead to significant morbidity if left in situ longer than required. Our case is that of an elderly male with a history of intractable hypertension presenting with urosepsis, anemia, diabetes and chronic renal failure. His work-up revealed a stent in the right kidney with secondary staghorn calcification in the renal pelvis and a large vesical calculus. He had apparently undergone stent placement 12 years previously, but was lost to follow-up due to relocation. A nuclear scan revealed a complete loss of renal function. Cystoscopic stent removal was futile, so he underwent an elective right subcapsular nephrectomy. The specimen revealed pyonephrosis with loculations of pus. Postoperatively his course was uneventful, with the hypertension resolving in 4 weeks.

Remission of renal disease: recounting the challenge, acquiring the goal.

Renal excretory function begins at the glomerular capillaries with the formation of a nearly ideal ultrafiltrate of plasma. The volume and composition of the ultrafiltrate undergo sequential change along the nephron, ultimately regulated to preserve near-constancy of mineral, electrolyte, and fluid balance. Modest derangement of these processes often escapes clinical or laboratory detection, because the myriad of unimpaired nephrons compensate more or less completely. Beyond a certain level of injury, however, compensatory adaptations no longer keep pace with nephron loss. As a result, glomerular filtration rate declines and organic nitrogenous wastes (e.g., creatinine, urea) accumulate in plasma and other body fluids. In acute renal failure, injury is usually transient, so that deterioration of function is short-lived and reversible. Not so, however, with the many forms of irreversible nephron damage, which typically progress over time, often eventuating in complete loss of renal function, systemic toxicity (uremia), and death unless the lost function is replaced by chronic dialysis and/or successful renal transplantation. Much of the effort in nephrology since the 1970s has been concerned with improving the effectiveness of these renal-replacement therapies. In the late 1960s, we fortuitously gained access to a unique strain of rats with many glomeruli that are situated on the renal cortical surface. For the first time, mammalian glomeruli were therefore accessible to direct study by new microtechniques developed in our laboratory. We therefore addressed the following questions: (a) What are the precise hemodynamic forces and biophysical properties that govern glomerular capillary function in health? (b) How are these elements modified during renal injury? (c) Do these modifications contribute to the relentless progression of renal disease? (d) If so, can they be reversed, so as to retard further deterioration of renal function and prevent end-stage renal disease (ESRD)?

Long-term renal function preservation after renal artery stenting in patients with progressive ischemic nephropathy.

We assessed the long-term effect of successful renal artery stent revascularization on renal function, blood pressure control, and survival in patients with progressive renal dysfunction due to ischemic nephropathy. Ischemic nephropathy presents a potentially serious risk of complete loss of renal function. Surgical renal revascularization is associated with significant risk of mortality/morbidity in this patient population. The potential role and long-term effect of renal artery stent revascularization in this patient population is not well defined. A cohort of 51 patients (mean age, 72 years; 52.9% men) with progressive azotemia, defined as a preprocedure serum creatinine (Scr) value of >or= 1.5 mg/dl and a negative slope of the reciprocal 1/Scr curve during the 12 months preceding revascularization, underwent successful primary stent deployment in 93 atherosclerotic renal artery lesions (42 bilateral, 9 solitary kidneys). Estimated glomerular filtration rate (EGFR) and serum creatinine values, blood pressure, antihypertensive medication requirements, and survival rates were monitored over a mean of 30-month follow-up. Renal artery duplex Doppler or renal angiography were performed at a mean of 13 months (range, 7-15 months) to assess stent patency. Stent implantation was successful in 92/93 (98.9%) stenotic renal arteries (mean preprocedure serum creatinine 2.3 +/- 0.9 mg/dl; range, 1.5-8.2 mg/dl). Forty-seven patients were eligible for 30-month follow-up of the procedural effect on renal function, blood pressure control, number of antihypertensive medications, and survival. At 1-year follow-up, the slope of the 1/Scr curve increased and the EGFR values significantly improved compared to preprocedure values (19.9 +/- 6.2 to 26.8 +/- 10.1 ml/min; P < 0.0001), serum creatinine decreased from the mean preprocedure value to 1.75 +/- 0.69 mg/dl (P < 0.001), with renal function improvement or stabilization observed in 94% of patients; three patients (7.3%) required permanent hemodialysis during the 30-month follow-up period. Systolic and diastolic blood pressure significantly decreased (from 177 +/- 28 to 148 +/- 25 mm Hg and from 92 +/- 15 to 78 +/- 14 mm Hg, respectively; P < 0.001) with fewer antihypertensive medications required to control blood pressure (3.5 +/- 0.9 vs. 1.9 +/- 1.3; P < 0.001). The patient survival rate after 30-month follow-up was 87%, with three deaths related to end-stage renal failure. Renal artery stent revascularization reversed progressive renal dysfunction within the first 12 months and maintained the improved level of renal function at 30-month follow-up while improving blood pressure control and reducing the number of antihypertensive medication requirements. Renal stent revascularization should be considered a valid therapeutic option for the long-term treatment of ischemic nephropathy.

Nutritional implications of renal disease. I. Current overview and general principles

Treatment exclusively by nutritional means does not appear to provide a therapeutic answer for the patient with complete loss of renal function. Clearly, however, rational dietary treatment prior to ultimate loss of renal function is a valuable, ameliorating therapy in chronic progressive renal failure and--once the patient is on maintenance dialysis--it is a major deciding factor in the success of this life-maintaining regimen.