Restoration Of Renal Function Research Articles

5-Hydroxytryptamine 1F Receptor Agonist Lasmiditan Differentially Regulates Successful Repair and Failed Repair Genes in a Mouse Model of Acute Kidney Injury.

Increasing evidence substantiates the role of mitochondrial dysfunction, inflammation, fibrosis, and cell senescence in the onset and progression of acute kidney injury (AKI) to chronic kidney disease . The underlying governing cellular and transcriptional events, however, are not fully understood. Recently, the key factors that regulate successful and failed repair states in the proximal tubule have been identified at a single-cell resolution following bilateral ischemia-reperfusion (I/R) in a mouse model of AKI. Previously, our group showed that treatment with the FDA-approved selective 5-hydroxytryptamine receptor 1F agonist lasmiditan following AKI induces mitochondrial biogenesis , restores renal mitochondrial function, and increases renal and vascular recovery in vivo. Here, we assessed the effect of lasmiditan on transcriptional and translational changes that are responsible for successful repair, injury, and failed repair states in the renal cortex following I/R-induced AKI. Increased levels of successful repair genes such as acyl-coA synthase medium-chain family member 2a, low-density lipoprotein receptor-related protein 2, solute carrier family 5 member 12, and hepatocyte nuclear factor 4 alpha were observed with 6 and 12 days of lasmiditan treatment following AKI compared to vehicle control. While 6 days of lasmiditan treatment had no effect on failed repair genes, the administration of lasmiditan for 12 days decreased the levels of vascular cell adhesion protein 1, tumor necrosis factor α, and interleukin-1β, which drive maladaptive repair. These data reveal that lasmiditan treatment post-AKI differentially regulates successful and failed repair gene expression in the renal cortex, likely contributing to the restoration of renal function and providing a potential targeted therapeutic pathway for the treatment of AKI.

Management of severe ANCA-associated glomerulonephritis: comparison of international recommendations and narrative review

Severe kidney injury in ANCA-associated vasculitis remains a major challenge for healthcare practitioners due to the difficulty in defining the term and the limitations in the evidence base associated with the exclusion of the most severely ill patients from majority of clinical trial protocols. The ACR/VF, EULAR, and KDIGO recommendations intended to answer the questions regarding the management of this patient’s population, but some recommendations on both initial and supportive therapy, provided be the expert panels, differ, which increase the number of treatment options, but also leads to the uncertainty of the expected effect of the treatment. Kidney biopsy plays an important role in identifying patients with a favorable and unfavorable kidney prognosis. Timely histological assessment is necessary not only to confirm the diagnosis, but also to decide whether to intensify therapy if active changes are detected, or, conversely, to discontinue immunosuppressive treatment and switch to renal replacement therapy if chromic changes dominate and the extrarenal manifestations are quiescent. Several scoring systems for assessing kidney damage and risks in the in ANCA-associated vasculitis were proposed during the last decade. Glucocorticoid’s dosing and the choice between cyclophosphamide and rituximab for the initial therapy remains controversial, and the most controversial issue to date remain the indications for the plasma exchange usage. New treatment options for ANCA-associated nephritis, such as the usage of complementblocking therapy are likely to improve the prognosis for the patients with severe renal damage, taking into account the maximum effect on renal function restoration in this particular category.

Management of Acute Pancreatitis and Kidney Injury in a Dog

Concurrent acute pancreatitis and acute kidney injury represent significant pathological conditions in dogs, presenting challenges in diagnosis and management. In human medicine this is interconnected and complex co morbid condition. Renal impairment consequently leads to fluid and electrolyte imbalance, in turn causes metabolic disturbances that may predispose to pancreatitis in dogs. Identification of underlying etiology and predisposing factors prevents further recurrence in affected individuals. The critical interplay between AP and AKI needs comprehensive management procedure. This article poses a case study of an eight-year-old Dalmatian cross dog presenting with severe respiratory distress, jaundice and gastrointestinal symptoms. Laboratory findings revealed elevated markers of pancreas, liver and kidney injury. Prompt intervention with fluid therapy, antibiotics and supportive care led to significant clinical improvement. Subsequent re-evaluation demonstrated resolution of pancreatic inflammation and restoration of renal function. This case underscores the importance of early recognition, aggressive intervention and comprehensive management in achieving successful outcomes in dogs with concurrent pancreatitis and acute kidney injury in dogs.

Rare Case of Acute Renal Artery Thrombosis in Nephrotic Syndrome: The Unusual Presentations and Outcomes of Endovascular Manual Aspiration Thrombectomy

Renal artery thrombosis is a rare condition that requires early diagnosis and urgent intervention to prevent renal infarction and permanent renal damage. Possibility of renal artery thrombosis should be considered in patients with underlying hypercoagulable state presented with acute unremitting flank pain, nausea and vomiting. We report a case of a 35-year-old man with underlying nephrotic syndrome who presented with three days history of acute non-localized and non-resolving abdominal pain and vomiting. He was initially referred to general surgery for acute intestinal obstruction. Contrast-enhanced computed tomography (CECT) abdomen revealed acute left renal infarction secondary to total thrombotic occlusion of the left renal artery. The patient was treated with endovascular manual aspiration thrombectomy resulting in partial revascularization of left renal artery with restoration of renal function, complete resolution of symptom and good clinical outcomes. This case report serves as a reminder for physicians to include renal infarction in the differential diagnosis when evaluating a patient with acute abdomen, particularly in patient with hypercoagulable state. This case also aligns with other experiences demonstrating positive outcomes after endovascular thrombectomy, even in the presence of prolonged renal ischemia time of more than 72 hours.

Urinary Insulin-Like Growth Factor-Binding Protein 7 (IGFBp7), Urinary Tissue Inhibitor of Matrix Metalloproteinase 2 (TIMP2), and Serum Transgelin as Novel Biomarkers of Kidney Injury in Multiple Myeloma.

Renal dysfunction is a common complication of MM and is associated with poor prognosis, particularly when progressive. Early identification of renal dysfunction is essential for prompt treatment for disease control and restoration of renal function. Urinary insulin-like growth factor-binding protein 7 (IGFBP-7), urinary tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), and serum transgelin levels were measured using enzyme-linked immunosorbent assays and evaluated as biomarkers for the prediction of renal impairment in patients with multiple myeloma. U IGFBP-7/creatinine ratio, U TIMP2/creatinine ratio, and serum transgelin levels were higher in patients with MM than healthy controls, and predicted renal insufficiency in MM. Serum transgelin, urinary IGFBp7, and TIMP2 levels may have utility as biomarkers of renal tubular injury and predict future renal impairment in patients with MM.

Current and Advance Treatment Approaches of Autosomal Dominant Polycystic Kidney Disease

Polycystic kidney disease is a genetic or acquired disorder in which balloon-like structures called cysts which are filled with fluid are formed inside the kidneys. The most common type of PKD is autosomal dominant polycystic kidney disease (ADPKD). The major cause of ADPKD are found to be abnormalities in the genes, and these abnormalities are inherited within generations. Genetic mutations such as spontaneous mutations are observed in some cases of ADPKD. Other causes of ADPKD can be hypertension and proteinuria. ADPKD develops due to mutations in the genes PKD1 or PKD2. It is found that 85% of the ADPKD patients have mutated PKD1 and 15% of the ADPKD patients have mutated PKD2. It is the 4th common cause which results in End-Stage Renal Disease (ESRD). Different researches and studies are undergoing to find novel treatments for the diseases. There is a need to have a clear understanding of molecular and genetic pathogenesis of ADPKD to help build novel therapies. After the approval of Tolvaptan, an V2R antagonist, slow growth of cyst and less chances of kidney failure were observed in ADPKD patients. Some other therapies like mTOR pathways inhibitors, somatostatin therapies also help in halting the progression of disease. Complementary therapies such as ayurveda and homeopathy, yoga, acupuncture which can help prevent the progression and symptoms of ADPKD. More and more advancement of technologies, stem cell and nanoscience have emerged in finding solutions for renal replacement therapies and restoration of renal function. Keywords: Autosomal dominant polycystic kidney disease (ADPKD), complementary therapies, stem cell and nanoscience.

Experimental renal transplantation in rats improves cardiac dysfunction caused by chronic kidney disease while LVH persists.

Chronic kidney disease (CKD) causes congestive heart failure (CHF) with systolic dysfunction and left ventricular hypertrophy (LVH), which is a major contributor to increased mortality in CKD patients. It remains unclear whether cardiovascular changes that occur during the course of CKD can be reversed when renal function is restored by transplantation. To investigate this, chronic kidney disease was established in F344 rats by subtotal nephrectomy (SNx) for 8 weeks, followed by transplantation of a functional kidney from an isogenic F344 donor. SNx rats without transplantation and sham-operated animals served as controls. Renal function was assessed before and throughout the experiment. In addition, cardiac ultrasound was performed at weeks 0, 8, 12 and 16. At the end of the experiment, intra-arterial blood pressure was measured and kidneys and hearts were histologically and molecularly examined. Eight weeks after SNx, rats developed marked renal dysfunction associated with significant glomerulosclerosis and tubulointerstitial fibrosis, but also an increase in left ventricular mass. After transplantation, renal function normalized but relative heart weight and ventricular mass as assessed by ultrasound scans showed no reduction compared with SNx controls. However, left ventricular wall thickness, fractional shortening and ejection fraction was normalized by renal transplantation. At 8 weeks after kidney transplantation, cardiac expression of BNP and FGF23 was also at levels comparable to healthy controls, whereas these factors were significantly increased in SNx rats. Cardiac fibrosis, as measured by fibronectin mRNA expression, was completely normalized, whereas cardiac fibronectin protein was still slightly but not significantly increased in transplanted animals compared to controls. In addition, the myofibroblast marker collagen 1, as assessed by immunohistochemistry, was significantly increased in SNx rats and also normalized by renal transplantation. Interestingly, CD68+ macrophages were significantly reduced in the hearts of SNx rats and in transplanted animals at slightly higher levels compared to controls. Restoration of renal function by kidney transplantation normalized early cardiac changes at most functional and molecular levels, but did not completely reverse LVH. However, further studies are needed to determine whether restoration of renal function can also reverse LVH at a later time point.

Cucumis callosus (Rottl.) Cogn. fruit extract ameliorates calcium oxalate urolithiasis in ethylene glycol induced hyperoxaluric Rat model

Cucumis callosus dry fruits are traditionally used as folk remedy to treat conditions like urethral irritations, urine stoppage or dribbling and other urinary ailments of man in north-west India. But no study is reported to validate this ethnic practice of using Cucumis fruit in urolithiasis. To evaluate anti-urolithiatic potential of Cucumis, hyperoxaluria was induced in rats by supplying 0.75% ethylene glycol (EG) + 1% ammonium chloride (AC) in drinking water for 14 days. Anti-urolithiatic activity of Cucumis callosus hydro-ethanolic extract (CCHEE) was assessed by measuring blood and urine biochemical parameters, oxidative stress indices, histopathology and osteopontin (OPN) expression. Administration of EG-AC to rats caused hyperoxaluria, crystalluria, azotaemia, oxidant/antioxidant imbalance (increase in lipid peroxidation (LPO), and decrease in glutathione (GSH) and catalase (CAT)), up-regulation of OPN and calcium oxalate (CaOx) crystal deposition in kidney. Treatment of afflicted rats with Cucumis fruits extract restored renal function to a great extent (CCHEE group), testified by improvement of stated parameters. Findings demonstrate curative efficacy of Cucumis fruit extract in EG induced urolithiasis of rats. The restoration of renal function was possibly by regulating renal stone formation via reducing urinary oxalate excretion, correcting oxidant/antioxidant imbalances, and reduced expression of OPN. Hence, results of this study validate the ethnic practice of using Cucumis fruit and conclude that fruit extracts have beneficial effects on CaOx urolithiasis and renal function.

Ureteric Injuries During Gynecological Procedures and Repair

Introduction: Injury to the ureter is a risk of any pelvic or abdominal surgery. The anatomic proximity of the lower urinary tract and the female reproductive system renders the ureter vulnerable to injury during obstetric and Gynecologic procedures. Ureterovaginal fistula is an uncommon but serious sequela of unrecognized distal ureteral injury during pelvic surgeries because of their common embryologic origin. Method: This study involved a series of 25 patients, who developed ureterovaginal fistula after Obstetric and Gynecologic procedures managed in urology department Muhammad Islam teaching hospital Gujranwala. These patients were managed with open Ureteroneocystostomy, within 2 weeks of primary procedure. In this study we present our postoperative result of 6 months of follow up. Results: All patients were cured (100%) with complete cessation of urinary fistula with complete restoration of renal function and complete restoration of urinary anatomy. Conclusion: The results of our study showed that the patient with Ureteric injury should be evaluated and intervened at the earliest. Early identification and repair of ureterovaginal fistulas results in a high quality of life, less postoperative complications, and a high success rate and preservation of renal function. keywords: Ureteric injury, ureterovaginal fistula.

Contact ureterolithotripsy of a giant ureteral stone in a 3-year-old child

Giant ureteral stones in young children are extremely rare and their surgical treatment tactics are variable. The present case describes a case of effective and safe endoscopic treatment of giant ureteral stones in a young child. The patient is a 3-year-old male child. Examination findings of abdominal pain and fever verified a left distal ureteric stone up to 30 mm complicated by ureterohydronephrosis. The first treatment stage was ureteral stenting, in which the stone migrated to the middle ureteral third. The second treatment stage was contact ureterolithotripsy with a 9 Ch semi-rigid ureteroscope («Richard Wolf» GmbH, Knittlingen, Germany) and Swiss LithoClast® 2 pneumatic lithotripter («E.M.S. Electro Medical Systems» S.A., Nyon, Suisse), ureteral stenting (2-way PigTail, 4.5 Ch). The third treatment stage in the delayed period was extracorporeal shockwave lithotripsy of the steinstrasse using the Dornier Compact Sigma («Dornier MedTech» GmbH, Weßling, Germany) and stent removal. Residual stones were not revealed according to the follow-up examination. No treatment complications were registered. The multimodal staged treatment of a giant ureteral stone resulted in its complete elimination. Next-step ureteral endoscopy made it possible to identify concomitant pathology of the proximal ureter, which required its evaluation in the delayed period. Ureteral stenting contributed to the restoration of renal function. The result achieved reflects the maximum efficiency and high safety of the surgical technique applied.

CARDIORENAL SYNDROME AS EXTRA-ARTICULAR MANIFESTATION OF RHEUMATOID ARTHRITIS

The article provides a description of a complex clinical case of cardiorenal syndrome type II in a patient having rheumatoid arthritis and a high degree of activity. The aim of this work is to highlight the problem of multiple organ damage in severe autoimmune diseases, as well as to share the experience of diagnostic and therapeutic approaches in such situations. Under a long-term articular syndrome, the patient subacutely develops new threatening symptoms: signs of inflammatory cardiomyopathy, heart failure, nephropathy, acute renal failure. But thanks to intensive anti-inflammatory therapy, we managed to significantly mitigate the activity of myocarditis, restore myocardial, and as a result, renal function. The success of active anti-inflammatory treatment confirmed our diagnostic hypothesis of cardiorenal syndrome. Several clinical landmarks have become key points for us. First, we detected that myocarditis with myocardial dysfunction and nephropathy with renal failure occurred almost simultaneously. Since the patient was under observation for a long time, until recently, we knew for sure that there were no pathological changes in the function of the heart and kidneys. Then, we detected the subacute onset of cardiac and renal symptoms. Finally, NSAID-induced amyloidosis or nephropathy cannot clearly explain the active course of inflammatory cardiomyopathy. Therefore, based on the characteristics of this clinical situation, we made an assumption of cardiorenal syndrome, most likely type II. All subtypes have similar clinical signs, but their origin largely depends on the underlying disease, history, and features of specific kidney and myocardial damage. Kidney hypoperfusion in our case did not lead to severe irreversible changes in nephrons, which ensured the restoration of renal function. But a prolonged and deep episode of hypoperfusion may be partially or completely irreversible, due to ischemic necrosis of the epithelium of the nephron tubules. Thus, we have shown a complex clinical case of an extra-articular lesion in the form of a cardiorenal syndrome, as well as an algorithm of our actions regarding diagnosis and treatment. Relatively early diagnosis of cardiorenal syndrome obviously enables to achieve good treatment results in a relatively short period of time.

Faecalibacterium prausnitzii Attenuates CKD via Butyrate-Renal GPR43 Axis.

Despite available clinical management strategies, chronic kidney disease (CKD) is associated with severe morbidity and mortality worldwide, which beckons new solutions. Host-microbial interactions with a depletion of Faecalibacterium prausnitzii in CKD are reported. However, the mechanisms about if and how F prausnitzii can be used as a probiotic to treat CKD remains unknown. We evaluated the microbial compositions in 2 independent CKD populations for any potential probiotic. Next, we investigated if supplementation of such probiotic in a mouse CKD model can restore gut-renal homeostasis as monitored by its effects on suppression on renal inflammation, improvement in gut permeability and renal function. Last, we investigated the molecular mechanisms underlying the probiotic-induced beneficial outcomes. We observed significant depletion of Faecalibacterium in the patients with CKD in both Western (n=283) and Eastern populations (n=75). Supplementation of F prausnitzii to CKD mice reduced renal dysfunction, renal inflammation, and lowered the serum levels of various uremic toxins. These are coupled with improved gut microbial ecology and intestinal integrity. Moreover, we demonstrated that the beneficial effects in kidney induced by F prausnitzii-derived butyrate were through the GPR (G protein-coupled receptor)-43. Using a mouse CKD model, we uncovered a novel beneficial role of F prausnitzii in the restoration of renal function in CKD, which is, at least in part, attributed to the butyrate-mediated GPR-43 signaling in the kidney. Our study provides the necessary foundation to harness the therapeutic potential of F prausnitzii for ameliorating CKD.

Hypoxic mesenchymal stem cell-derived extracellular vesicles ameliorate renal fibrosis after ischemia–reperfusion injure by restoring CPT1A mediated fatty acid oxidation

BackgroundRenal fibrosis is a common pathological process of chronic kidney diseases induced by multiple factors. Hypoxic pretreatment of mesenchymal stem cells can enhance the efficacy of secreted extracellular vesicles (MSC-EVs) on various diseases, but it is not clear whether they can better improve renal fibrosis. The latest research showed that recovery of fatty acid oxidation (FAO) can reduce renal fibrosis. In this study, we aimed to examine whether hypoxic pretreatment with MSC extracellular vesicles (Hypo-EVs) can improve FAO to restore renal fibrosis and to investigate the underlying mechanism.MethodsHypo-EVs were isolated from hypoxia-pretreated human placenta-derived MSC (hP-MSC), and Norm-EVs were isolated from hP-MSC cultured under normal conditions. We used ischemia–reperfusion (I/R)-induced renal fibrosis model in vivo. The mice were injected with PBS, Hypo-EVs, or Norm-EVs immediately after the surgery and day 1 postsurgery. Renal function, kidney pathology, and renal fibrosis were assessed for kidney damage evaluation. For mechanistic exploration, fatty acid oxidation (FAO), mitochondrial morphological alterations, ATP production and mitochondrial mass proteins were detected in vivo. Mitochondrial membrane potential and reactive oxygen species (ROS) production were investigated in vitro.ResultsWe found that Hypo-EVs confer a superior therapeutic effect on recovery of renal structure damage, restoration of renal function and reduction in renal fibrosis. Meanwhile, Hypo-EVs enhanced mitochondrial FAO in kidney by restoring the expression of a FAO key rate-limiting enzyme carnitine palmitoyl-transferase 1A (CPT1A). Mechanistically, the improvement of mitochondrial homeostasis, characterized by repaired mitochondrial structure, restoration of mitochondrial mass and ATP production, inhibition of oxidative stress, and increased mitochondrial membrane potential, partially explains the effect of Hypo-EVs on improving mitochondrial FAO and thus attenuating I/R damage.ConclusionsHypo-EVs suppress the renal fibrosis by restoring CPT1A-mediated mitochondrial FAO, which effects may be achieved through regulation of mitochondrial homeostasis. Our findings provide further mechanism support for development cell-free therapy of renal fibrosis.

Effect of the response to preoperative treatment for hepatorenal syndrome on the outcome of recipients of living-donor liver transplantation.

The effect of pretransplant hepatorenal syndrome (HRS) on the outcomes of living-donor liver transplantation (LDLT) recipients with special reference to the recovery of HRS before LDLT was investigated. The rate of HRS was 43.9% (125/285) among the cohort, and the subjects were divided into three groups: those without HRS (No-HRS group, n=160), those with HRS but recovered following pretransplant renal function restoration treatment (Responders group, n=55), and those with persistent HRS (Non-responders group, n=70). While the 1-, 3-, and 5-year patient survival rates were comparable between those with and without HRS (89.6%, 84.7%, and 84.7% vs 95.6%, 92.2%, and 87.5%), the cumulative incidence of the development of posttransplant chronic kidney disease (CKD) was significantly higher in those with HRS (P < .001). In addition, there was a significant difference between Responders and Non-responders in the development of CKD (P=.01). In the Cox regression model, Non-responders (P=.032, HR 1.79 [95% C.I. 1.05-3.03]) and recipient age (P=.014, HR 1.62 [95% C.I. 1.10-2.37]) were independent predictors for the development of CKD after LDLT. Living-donor liver transplantation is safe and effective for patients with HRS, and CKD progression could be reduced among those with HRS who responded to renal restoration treatment.

The role of the NGAL biomarker in the assessment of early and prediction of late graft function in kidney transplantation from a living related donor

The aim. To study the role of NGAL in assessing the recovery of early graft function (GF) and in predicting GF in the first year after kidney transplantation (KT) from a living-related donor (LRD). Materials and methods. For this aim, a total of 60 kidney recipients who underwent KT from LRDs were examined. To study the early GF, NGAL concentrations in urine samples were measured on days 1, 2, 3, 7 after KT. To study the late GF, the glomerular filtration rate (GFR) was calculated at 3, 6, 12 months after KT. To study the prognosis of GF during the first year after KT, the relationship between u-NGAL and GFR levels at 3, 6, 12 months after KT was analyzed. The incidence of acute kidney transplant rejection (AKTR), delay of graft function (DGF), primary non-function was recorded. Results. DGF was observed in 5 (8.33 %) recipients with statistically significantly increased mean NGAL levels (P &lt; 0.05) on days 1, 2, 3, 7 as compared to those in normal GF. AKTR was detected in 10 (16.67 %) recipients with statistically significantly increased mean NGAL levels (P &lt; 0.05) on days 1, 2, 3, 7 compared to those in normal GF. Primary allograft non-function was diagnosed in 8 (13.33 %) recipients with statistically significantly increased mean NGAL levels (P &lt; 0.05) on days 1, 2, 3, 7 compared to those in normal GF. Assessing the relationship between NGAL levels on days 1, 2, 3, 7 and GFR at 3, 6, 12 months after transplantation, it was found that GFR was higher in recipients with NGAL levels on days 1, 2, 3, 7 after transplantation within the reference values (&lt;131.7 ng/ml) than that in recipients with NGAL levels on days 1, 2, 3, 7 after transplantation above 131.7 ng/ml. Conclusions. Evaluation of NGAL after KT informs about the restoration of renal function (rapid decrease in NGAL) or the development of complications (DGF, primary allograft non-function, AKTR) with slow decrease or increase in NGAL levels. Thus, u-NGAL is an early, non-invasive and accurate predictor of the need for dialysis in the first week after KT and the restoration of GF within 12 months.

Cell Cycle Dysregulation and Renal Fibrosis.

Precise regulation of cell cycle is essential for tissue homeostasis and development, while cell cycle dysregulation is associated with many human diseases including renal fibrosis, a common process of various chronic kidney diseases progressing to end-stage renal disease. Under normal physiological conditions, most of the renal cells are post-mitotic quiescent cells arrested in the G0 phase of cell cycle and renal cells turnover is very low. Injuries induced by toxins, hypoxia, and metabolic disorders can stimulate renal cells to enter the cell cycle, which is essential for kidney regeneration and renal function restoration. However, more severe or repeated injuries will lead to maladaptive repair, manifesting as cell cycle arrest or overproliferation of renal cells, both of which are closely related to renal fibrosis. Thus, cell cycle dysregulation of renal cells is a potential therapeutic target for the treatment of renal fibrosis. In this review, we focus on cell cycle regulation of renal cells in healthy and diseased kidney, discussing the role of cell cycle dysregulation of renal cells in renal fibrosis. Better understanding of the function of cell cycle dysregulation in renal fibrosis is essential for the development of therapeutics to halt renal fibrosis progression or promote regression.

Features of nephropathy in various types of thrombotic microagniopathies in obstetric practice

Introduction. We assessed the features of kidney injury in patients with different types of TMA during pregnancy, taking into consideration the fact that the acute kidney injury (AKI) that occurs during pregnancy or in the early postpartum period is main- ly caused by various types of thrombotic microangiopathies (TMA), and AKI itself is a serious obstetric complication with the risk of serious complications and mortality for both mother and fetus.Objective of the study. To study the features of nephropathy in different types of pregnancy-associated TMA.Materials and methods. The study included 313 pregnant women, women in childbirth and puerperas, of which 71 women had atypical hemolytic uremic syndrome (aHUS), 124 – HELLP syndrome, 70 – varying degrees of severity of PE, a group of patients with more rare causes of TMA was also identified: TTP, CAPS and sepsis (13 patients) and 45 patients for the control group. We assessed and compared the main clinical, laboratory and instrumental data, and assessed the outcome of labour. Also, histological examination of the kidneys was performed in five patients with aHUS.Results and discussion. The results of the study have shown that the most severe manifestations of TMA in the form of target organ injury and nephropathy are usually occur in patients with aHUS, where all women developed AKI, in some cases with the formation of chronic kidney disease. In the HELLP syndrome group, AKI was recorded in 39%, but renal function quickly restored. It was found that the very fact of the presence of AKI points to a more unfavourable prognosis not only for the patients themselves, but also for the child, being the main risk factor for perinatal death. The findings of urinary sediment tests and morphological evaluation indicate that the resulting ischemia of the renal tissue in cases of aHUS, HELLP syndrome and other types of TMA can lead to tubular necrosis as compared with PE. Our results suggest that it is AKI in HELLP syndrome that is the main risk factor for perinatal death. Alas, this relationship is difficult to trace in patients with aHUS, as all of them had AKI.Conclusions. Timely recognition of the AKI phenomenon in all cases of obstetric TMA can reduce the risks for both mother and fetus. Both the prognosis for mother and the prognosis for child depend on AKI, and timely therapy can lead to a regression of AKI phenomena and the complete restoration of renal function.

Advanced glycation end products and oxidative stress as a basis for metabolic abnormalities in patients with type 1 diabetes after successful simultaneous pancreas-kidney transplantation

To compare advanced glycation end-products (AGE, RAGE) and 3-nitrotyrosine (3-HT) in patients with DM 1 after successful simultaneous pancreas-kidney transplantation (SPK) and kidney transplantation alone (KTA). To assess relationship between levels of AGE, RAGE, 3-HT and renal transplant (RT) function, carbohydrate and mineral metabolism. The study included 58 patients who received kidney transplantation in end-stage renal disease (ESRD). 36 patients received SPK. There were performed routine laboratory, examination of AGE, RAGE, 3-NT, parathyroid hormone (PTH), 25(OH)vitamin D, calcium, phosphorus, FGF23, osteoprotegerin (OPG), and fetuin-A levels. All patients after SPK reached normoglycemia (HbA1c 5.7 [5.3; 6.1] %; C-peptide 3.24 [2.29; 4.40] ng/ml) with the achievement of significant difference vs patients after KTA. Arterial hypertension (AH) was more frequent in recipients of SPK before transplantation than after (p=0.008). AH also persisted in greater number of cases in patients after KTA than after SPK. Patients after SPK had higher AGE (р=0.0003) and lower RAGE (р=0.000003) levels. OPG in patients after SPK was significantly higher (р=0.04). The correlation analysis revealed significant positive correlation between 3-HT and OPG (p0.05; r=0.30), RAGE and eGFR (r=-0.52), HbA1c (r=0.48), duration of AH (r=0.34), AGE with HbA1c (r=0.51). The results of the "metabolic memory" markers analysis may indicate their contribution to the persistence of the metabolic consequences of CKD and DM 1 after achievement of normoglycemia and renal function restoration and their possible participation in development of recurrent nephropathy, vascular calcification, and bone disorders.

Люпус-нефрит: сучасна парадигма лікування

Вовчаковий нефрит є найпоширенішим та життєзагрозливим проявом системного червоного вовчака і продовжує зумовлювати високий відсоток термінальної ниркової недостатності. У даному огляді описуються сучасне лікування вовчакового нефриту, а також нові терапевтичні стратегії. Діагностика ураження нирок при системному червоному вовчаку (люпус-нефрит), згідно з рекомендаціями ACR, базується на таких критеріях: клінічні та лабораторні прояви у вигляді протеїнурії &gt; 0,5 г на добу (або більше 3 «+» при визначенні тест-смужкою) і/або наявність клітинних скупчень, включаючи скупчення еритроцитів і циліндрів (гемоглобінових, зернистих, тубулярних або змішаних). Додатковим критерієм є результати гістологічного дослідження біоптату нирки з підтвердженням наявності характерного для люпус-нефриту імунокомплексного ураження нирок. Тактика ведення пацієнтів із вовчаковим нефритом складається з двох послідовних фаз: початкової (індукційної) і підтримуючої, коли використовуються поєднання глюкокортикоїдів і імуносупресорів. Під час індукційної фази проводиться інтенсивне лікування глюкокортикоїдами в комбінації з іншими імунодепресантами для швидкого пригнічення імунокомплексного запалення нирок і припинення розвитку їх пошкодження. Метою даного підходу і головним завданням індукційної терапії є відновлення ниркової функції і індукція ремісії шляхом контролю імунологічної активності процесу. Підтримуюча терапія застосовується для закріплення ремісії і запобігання загостренням шляхом використання препаратів або режимів лікування з меншим ризиком ускладнень. Незважаючи на невтішні результати декількох недавніх досліджень, нові методи лікування, спрямовані на різні імунологічні шляхи, активно вивчаються при вовчаковому нефриті. Найбільш перспективним напрямком є терапія, спрямована на В-клітини. Поглиблення розуміння патогенезу вовчакового нефриту, розробка нових методів лікування та оптимізація дизайну клінічних випробувань забезпечать успішний розвиток і впровадження нових ліків при вовчаку.

Experience of managing neonates and breastfed in-fants with grade IV bilateral hydronephrosis

To analyze the clinical cases of four patients with grade IV bilateral hydronephrosis. Ultrasound examination of the urinary system was used as the main examination method. During the first stage of surgical treatment, all children underwent preliminary urinary diversion; a month later, the results were assessed. The result of the preliminary urinary diversion was the implementation of the Heines-Andersen-Kucher reconstructive operation. According to the control ultrasound performed a month after the nephrostomy, pelvis on the nephrostomy was reduced in all cases, parenchyma thickness increased by an average of 4.5 times, improvement in intragranular blood flow was noted. Evaluation of the effectiveness of pyeloplasty was carried out according to three criteria: restoration of urodynamics, restoration of kidney function and the presence of infectious complications. The parenchyma of the operated kidney grew by an average of 3 times, the pelvis decreased by an average of 3.5 times. Restoration of intrarenal blood flow to the cortical layer, inclusive, was noted in 5 of 8 renal units. Before pyeloplasty, there were marked changes in the renal parenchyma and a decrease in its function by an average of 34 14 %; a year after reconstructive surgery, the changes became moderate, there was an improvement in renal function, a decrease in function by 25 10 %. In our opinion, the starting method for providing urgent surgical care to neonates and breastfed infants with grade IV GN is preliminary urinary diversion, which allows us to determine the functional reserve of the renal parenchyma, delay reconstructive surgery, thereby giving time for the restoration of renal function and avoiding organ-carrying surgery.