Primary Kidney Disease Research Articles

Basic nephropathology for pathologists-part1 : Kidney biopsy-inflammation and immune complexes

The assessment of kidney biopsies is mainly confined to specialized centres. However, sometimes akidney biopsy is submitted to ageneral pathologist, and in addition peritumorous renal parenchyma in tumour nephrectomies can have concomitant non-neoplastic renal disease. Here we present asurvey of inflammatory and immunologic changes in all renal compartments, which may in part indicate the need of prompt therapeutic intervention such as in vasculitis, glomerulonephritis and interstitial nephritis. It is important to take into account that renal involvement of vasculitis is mainly centred in glomeruli and only to amuch lesser extent in arteries, and that the frequently observed interstitial inflammation very often is an epiphenomenon of another primary kidney disease and not an independent disease process. Typical renal patterns of injury are emphasised.

Long-term follow-up of patients after acute kidney injury in the neonatal period: abnormal ambulatory blood pressure findings

BackgroundData on the long-term effects of neonatal acute kidney injury (AKI) are limited.MethodsWe invited 302 children who had neonatal AKI and survived to hospital discharge; out of 95 patients who agreed to participate in the study, 23 cases were excluded due to primary kidney, cardiac, or metabolic diseases. KDIGO definition was used to define AKI. When a newborn had no previous serum creatinine, AKI was defined as serum creatinine above the mean plus two standard deviations (SD) (or above 97.5th percentile) according to gestational age, weight, and postnatal age. Clinical and laboratory features in the neonatal AKI period were recorded for 72 cases; at long-term evaluation (2–12 years), kidney function tests with glomerular filtration rate (eGFR) by the Schwartz formula, microalbuminuria, office and 24-h ambulatory blood pressure monitoring (ABPM), and kidney ultrasonography were performed.ResultsForty-two patients (58%) had stage I AKI during the neonatal period. Mean age at long-term evaluation was 6.8 ± 2.9 years (range: 2.3–12.0); mean eGFR was 152.3 ± 26.5 ml/min/1.73 m2. Office hypertension (systolic and/or diastolic BP ≥ 95th percentile), microalbuminuria (> 30 mg/g creatinine), and hyperfiltration (> 187 ml/min/1.73 m2) were present in 13.0%, 12.7%, and 9.7% of patients, respectively. ABPM was performed on 27 patients, 18.5% had hypertension, and 40.7% were non-dippers; 48.1% had abnormal findings. Female sex was associated with microalbuminuria; low birth weight (< 1,500 g) and low gestational age (< 32 weeks) were associated with hypertension by ABPM. Twenty-three patients (33.8%) had at least one sign of microalbuminuria, office hypertension, or hyperfiltration. Among 27 patients who had ABPM, 16 (59.3%) had at least one sign of microalbuminuria, abnormal ABPM (hypertension and/or non-dipping), or hyperfiltration.ConclusionEven children who experienced stage 1 and 2 neonatal AKI are at risk for subclinical kidney dysfunction. Non-dipping is seen in four out of 10 children. Long-term follow-up of these patients is necessary.

Study protocol and baseline characteristics of newly induced dialysis patients: a prospective multi-center cohort study with a biological sample bank, the Ibaraki Dialysis Initiation Cohort (iDIC) study

BackgroundPatients with end-stage kidney disease (ESKD) face higher risks of life-threatening events including cardiovascular disease. Various risk factors are identified as agents influencing the life prognosis of ESKD patients. Herein, we evaluated the risk factors related to the outcomes of Japanese patients with dialysis induction. We present the study protocol, the patients’ baseline characteristics, and their outcomes.MethodsThe Ibaraki Dialysis Initiation Cohort (iDIC) Study is a prospective multi-center cohort study in collaboration with 60 tertiary-care facilities in Ibaraki Prefecture, Japan. We collected baseline data from clinical records and analyzed blood and urine samples of these facilities’ patients with diabetic nephropathy, hypertensive nephrosclerosis, and chronic glomerulonephritis (CGN). The study’s primary outcome was the survival rate at 24 months after dialysis induction. We performed a Kaplan-Meier analysis for cumulative survival and a Cox proportional hazards analysis for all-cause mortality and hospitalization.ResultsWe analyzed 636 patients’ cases (424 males, 212 females, age 67.4 ± 13.1 yrs. [mean ± SD]). We compared the patients’ baseline data with those of similar cohort studies. As the primary kidney disease, 327 cases (51.4%) were diagnosed as diabetic nephropathy, 101 (15.9%) as hypertensive nephrosclerosis, and 114 (17.9%) as CGN. The mean serum creatinine value was 9.1 ± 2.9 mg/dL. The mean estimated glomerular filtration rate was 5.6 ± 1.8 mL/min/1.73m2. The cumulative survival rates at 6 months and 24 months after dialysis induction were 95.2 and 87.7%, respectively. The cumulative survival rate was significantly lower with increasing age. A Cox proportional hazards regression analysis demonstrated that high age was significantly associated with all-cause mortality.ConclusionsRegarding the clinical characteristics of these newly induced dialysis patients, the same trend as in other cohort studies was observed. Another study is underway to explore prognostic factors based on the iDIC Study’s findings.

Organization of Post-Transplant Care and the 5-Year Outcomes of Kidney Transplantation.

The outcomes of kidney transplantation depend on numerous factors and vary between transplant centers. The aim of this study is to assess the relationship between selected organizational factors, comorbidities, and patient and graft survival. This is a retrospective analysis of 438 renal transplant recipients (RTR) followed for 5 years. Patient and graft survival were evaluated in relation to hospitalization length, distance from the patient’s residence to the transplant center, the frequency of outpatient transplant visits, and the number and type of comorbidities. Five-year patient and graft survival rates were 93% and 90%, respectively. We found significant associations of patient survival with the prevalence of pre-transplant diabetes, cardiovascular diseases, malignancies, the number of comorbidities, and the first post-transplant hospitalization length. The incidence of infections, cardiovascular diseases, and transplanted kidney diseases was 60%, 40%, and 33%, respectively. As many as 41% of RTR had unknown etiology of primary kidney disease. In conclusion, the organization of post-transplant care needs to be adapted to the multi-morbidity of contemporary RTR and include multi-specialist care, especially in the context of current problems related to the COVID-19pandemic. The high proportion of patients with undetermined etiology of their primary renal disease carry the risk for additional complications during their long-term follow-up.

Shear Wave Elastography in the Evaluation of Renal Parenchymal Stiffness in Patients With Chronic Kidney Disease: A Meta-Analysis.

BackgroundChronic kidney disease (CKD) is a progressive loss of renal function, mainly due to hypertension, diabetes, and primary kidney disease. The histopathological findings are that of glomerulosclerosis, tubulointerstitial fibrosis and loss of renal parenchyma characterized. Therefrom, CKD can lead to higher morbidity and mortality. Patients with CKD have multiple risk factors, and the prevention work is complicated and arduous. Therefore, it is important to quantify the severity of CKD. The aim of this study is to investigate the value of shear wave elastography (SWE) in the evaluating renal parenchymal stiffness in patients with CKD.MethodsWe carried out the systematic search of databases for publications in PubMed, Embase and Cochrane Library on SWE evaluating renal fibrosis in patients with CKD. The Endnote X9, STATA 16, Review Manager 5.3 and other software were used to sort out documents, extract, integrate and analyze data.ResultsThe outcomes were utilized to appraise the diagnostic accuracy of SWE and diagnose the CKD with renal fibrosis. A total of 405 patients were enrolled and their data analysis results were as follows: summary of sensitivity (S-SEN) 84% (95% confidence interval (CI): 80-87%); specificity (S-SPE) 80% (95% CI: 76-84%); summary of DLR (digital light radiography) positive (DLR-P) 4.29 (95% CI: 3.43 - 5.37); and DLR negative (DLR-N) 0.20 (95% CI: 0.16 - 0.25). The corresponding areas under the curves of diagnostic odds ratio (DOR) and summary receiver operating characteristic curve (SROC) were 21.50 (95% CI: 14.69 - 31.46) and 89% (95% CI: 86-92%), respectively.ConclusionsSWE is highly accurate and has clinical significance for evaluating renal fibrosis, especially when the shear modulus value is used as the threshold.

POS-748 HYPOPHOSPHATEMIA AFTER KIDNEY TRANSPLANTATION IN CHILDREN: A RETROSPECTIVE SINGLE CENTER EXPERIENCE

Hypophosphatemia is among the common complications that are seen after kidney Transplantation (KTX). It’s noticed in the first few days in most of the KTX, particularly a well-functioning graft, and its tretment may continued many months after KTX in certain conditions. Our aim is to identify hypophosphatemia after KTX, as well its potential association with Parathyroid hormone and Vitamin D. A retrospective study of children underwent KTX between 2009-2021. We collected their Baseline demographics, type of KTX, their primary kidney diseases, time after KTX of first presentation of hypophosphatemia, initial serum phosphate level, initial levels of Parathyroid hormone, 25 OH vitamin D, Calcium, and Magnesium, time of its resolution after KTX. A 38 children underwent KTX between 2009 and 2021, their baseline demographics are shown in Table 1. A 26 (68%) of children developed hypophosphatemia with a mean of occurrence at 5 days after KTX, and range of 1 to 12 days. Early (within three days) drops in serum phosphate have been found more in living KTX, which have related to immediate functioning of the allograft, and tend to be more severe, while delayed ( more than 6 days) drops are seen more with deceased KTX, as its more likely to be associated with relative delay in graft function. The average serum phosphate level in hypophosphatemia group was 0.6 mmol/l with a range of 0.28 to 0.8 mmol/l. The mean duration of requirement of phosphate supplement after KTX was 6 months days with a range of 0.5 to 39 months. All the patients were managed with oral phosphate with a mean of dose of 650 mg/day and range of 250 mg/ day to 1500 mg/day, without the requirement of intravenous supplement except in four patients from living KTX group. The associated levels of serum Phosphate, serum Calcium, serum Magnesium, 25 OH vitamin D, and PTH for both hypophosphatemic group and normal phosphate group are shown in table 2 and 3 respectively. Children with hypophosphatemia tend to have a higher mean PTH and 25(OH)2 Vitamin D level, but the difference is not statistically significant. Table 1: Baseline Demographics Tabled 1VariableValueAge at TransplantationMean 8 yearsGenderMale 22 (58 %)Weight (Kg)22Deceased donor26 (68%)Live Related donor9 (24%)Live unrelated donor3 (8%)HLA mismatches4/6Causes of Chronic kidney diseaseCAKUT16(42%)FSGS10 (26%)CNS4 (10 %)Nephronophthesis2 (6%)Nephropathic cystinosis1 (3%)ARPKD1 (3%)Unknown4 (8%) Open table in a new tab Table 2: Hypophosphatemia group Tabled 1VariableMean (range)Phosphate (mmol/l)0.6 (0.28-0.8)Calcium (mmol/l)2.22 (1.91- 2.63)Magnesium (mmol/l)0.73 (0.52- 1.17)Alkaline Phosphatase (U/l)194 ( 51- 713)Parathyroid Hormone (Pg/ml)587 (34 - 1565)25 (OH)2 Vitamin D (nmol/l)53 ( 7- 110) Open table in a new tab Table 3: Normophosphatemia group Tabled 1VariableMean (range)Phosphate (mmol/l)1.22 (0.9-1.64)Calcium (mmol/l)2.30 (2.15- 2.78)Magnesium (mmol/l)0.75 (0.55- 1.03)Alkaline Phosphatase (U/l)176 ( 55- 297)Parathyroid Hormone (Pg/ml)520 (113 - 1354)25 (OH)2 Vitamin D (nmol/l)43 ( 7- 82) Open table in a new tab Hypophosphatemia is a commonly seen after kidney transplantation particularly those with immediately functioning graft, higher PTH is a known potential contributory factor but that was observed partly in our cohort. our result should be interpreted with caution because of small sample size and retrospective design, so prospective large sample study can delineate this area more clearly.

POS-452 SAFETY AND EFFICACY OF ANG-3070 IN PATIENTS WITH PRIMARY PROTEINURIC KIDNEY DISEASE: A PHASE 2 STUDY DESIGN

Primary proteinuric kidney diseases (PPKDs) are among the leading causes of end-stage kidney disease (ESKD). Receptor tyrosine kinases, including platelet-derived growth factor receptor and discoidin domain receptors 1 and 2, are thought to play a role in the progression of PPKDs to ESKD. ANG-3070, a selective oral tyrosine kinase inhibitor, has demonstrated beneficial effects in chronic kidney disease animal models. Here we describe the design of a proof-of-concept study of ANG-3070 in the treatment of patients with PPKD who have persistent proteinuria while on standard of care (SOC). Planned enrollment is 100 patients for this 12-week, randomized, double-blind, placebo-controlled study. Eligible patients have biopsy-proven PPKD and persistent proteinuria (≥1 g/day) while on SOC, which may include maximum tolerated RAAS inhibitors. Patients will be randomized 1:1:1:1 to ANG-3070 200 mg or 400 mg once daily, or 300 mg twice daily, or placebo (Figure). The primary endpoint is the percentage change in 24-hr urinary protein at Week 12 compared to baseline. Key secondary endpoints evaluated at Week 12 include percentage change in 24-hr urinary albumin, number of patients with complete remission in proteinuria (24-hr urinary protein <300 mg), number of patients with partial remissions in proteinuria (24-hr urinary protein reduction of ≥50% from baseline and a 24-hr urinary protein <3.5 g if baseline 24-hr urinary protein >3.5 g), number of patients with ≥50% reduction in 24-hr urinary protein from baseline, and number of patients with ≥50% reduction in 24-hr urinary albumin from baseline. An independent data monitoring committee will review safety throughout the study. Enrollment will begin in 2021. This phase 2 study will provide data about the safety and efficacy of different dosing regimens of ANG-3070 in PPKD patients that will inform the design of a phase 3 study.

POS-384 EFFECT OF ANG-3070 IN THE PASSIVE HEYMANN NEPHRITIS RAT MODEL OF PRIMARY PROTEINURIC KIDNEY DISEASE

Primary proteinuric kidney diseases (PPKD) as a group are an important cause of end-stage kidney disease (ESKD). Many receptor tyrosine kinases, including platelet-derived growth factor receptor (PDGFR), contribute to the progression of PPKDs to ESKD. ANG-3070 is a novel and proprietary inhibitor of multiple tyrosine kinases including PDGFR. This study evaluated the effects of ANG-3070 in a passive Heymann nephritis (PHN) rat model of membranous glomerulopathy.

Increasing trends in hemodialysis and living donor kidney transplantation for children and young people in the United Kingdom.

The UK Renal Registry is responsible for the national collection and reporting of data on all children receiving long-term kidney replacement therapy [KRT], including kidney transplantation. All 13 UK pediatric nephrology centers contributed to providing individual patient data from the pediatric population incident to and prevalent to KRT as per the date 31 December 2018. Data for children aged 16-<18years were presented separately as some were managed under adult care settings with different methods of data collection. Demographics and biochemical data, including kidney function and prevalence of cardiovascular risk factors [hypertension, hypercholesterolemia, BMI] were reported. Eight hundred and twenty-six children (65.4 per million age-related population [pmarp]) and 199 young people (139.4pmarp) in the United Kingdom were prevalent to KRT on 31 December 2018. Overall, the incidence of KRT during 2018 was 9.1pmarp and 12.6pmarp in children and young people, respectively. Congenital anomalies of the kidney and urinary tract (CAKUT) were the most prevalent primary diagnoses (52%). Living and deceased donor transplantation was the most common treatment modality (78%). Patients on dialysis had lower age standardized mean height and weight ranges recorded in comparison to transplant patients [median height z score -1.8 vs. -1.1]. 73.1% patients had one or more cardiovascular disease risk factors. This study highlights increasing prevalence of hemodialysis and living donor transplantation as modalities for KRT. Of those incident to KRT, the highest patient survival was seen among 8-12years and lowest <2years. Moreover, there was a demographic shift from Caucasian toward Asian/other ethnicity and from CAKUT to other primary kidney diseases.

Circulating miRNAs and Vascular Injury Markers Associate with Cardiovascular Function in Older Patients Reaching End-Stage Kidney Disease.

The prevalence of end-stage kidney disease (ESKD) is rapidly increasing and mostly occurring in patients aged 65 years or older. The main cause of death in these patients is cardiovascular disease (CVD). Novel markers of vascular integrity may thus be of clinical value for identifying patients at high risk for CVD. Here we associated the levels of selected circulating angiogenic miRNAs, angiopoietin-2 (Ang-2) and asymmetric dimethylarginine (ADMA) with cardiovascular structure and function (as determined by cardiovascular MRI) in 67 older patients reaching ESKD that were included from ‘The Cognitive decline in Older Patients with End stage renal disease’ (COPE) prospective, multicentered cohort study. We first determined the association between the vascular injury markers and specific heart conditions and observed that ESKD patients with coronary heart disease have significantly higher levels of circulating ADMA and miR-27a. Moreover, circulating levels of miR-27a were higher in patients with atrial fibrillation. In addition, the circulating levels of the vascular injury markers were associated with measures of cardiovascular structure and function obtained from cardiovascular MRI: pulse wave velocity (PWV), ejection fraction (EF) and cardiac index (CI). We found Ang-2 and miR-27a to be strongly correlated to the PWV, while Ang-2 also associated with ejection fraction. Finally, we observed that in contrast to miR-27a, Ang-2 was not associated with a vascular cause of the primary kidney disease, suggesting Ang-2 may be an ESKD-specific marker of vascular injury. Taken together, among older patients with ESKD, aberrant levels of vascular injury markers (miR-27a, Ang-2 and ADMA) associated with impaired cardiovascular function. These markers may serve to identify individuals at higher risk of CVD, as well as give insight into the underlying (vascular) pathophysiology.

Nephrinuria and podocytopathies.

The discovery of nephrin in 1998 has launched a new era in glomerular diseases research, emphasizing its crucial role in the structure and function of the glomerular filtration barrier. In the past 20 years, substantial advances have been made in understanding podocyte structure and function as well as the discovery of several podocyte-related proteins including nephrin. The glomerular filtration barrier is comprised of podocytes, the glomerular basement membrane and endothelial cells. Podocytes, with their specialized slit diaphragm, form the essential backbone of the glomerular filtration barrier. Nephrin is a crucial structural and functional feature of the slit diaphragm that prevents plasma protein, blood cell and macromolecule leakage into the urine. Podocyte damage results in nephrin release. Podocytopathies are kidney diseases in which podocyte damage drives proteinuria, i.e., nephrotic syndrome. Many kidney diseases involve podocytopathy including congenital nephrotic syndrome of Finnish type, diffuse mesangial sclerosis, minimal change disease, focal segmental glomerulosclerosis, collapsing glomerulonephropathy, diabetic nephropathy, lupus nephropathy, hypertensive nephropathy and preeclampsia. Recently, urinary nephrin measurement has become important in the early detection of podocytopathies. In this chapter, we elaborate the main structural and functional features of nephrin as a podocyte-specific protein, pathomechanisms of podocytopathies which result in nephrinuria, highlight the most commonly used methods for detecting urinary nephrin and investigate the diagnostic, prognostic and potential therapeutic relevance of urinary nephrin in primary and secondary proteinuric kidney diseases.

Efficacy and Safety of Dapagliflozin in Children With Inherited Proteinuric Kidney Disease: A Pilot Study

Efficacy and Safety of Dapagliflozin in Children With Inherited Proteinuric Kidney Disease: A Pilot Study

Malignancies in renal transplant recipients: A retrospective single-center descriptive study

The risk of malignancy development in kidney transplant recipients (KTRs) is 2-3 times higher than in the general population. This picture, which emerged with chronic immunosuppressive use, has become more prominent in recent years as the ongoing cause of death in this population. This study aims to determine the common features of KTRs with malignancy in follow-up under a single-center experience. Thus, it is to save time by correctly determining our focus points in patient follow-up.&#x0D; Methods. The files of 403 patients who underwent kidney transplantation between 2005 and 2020 in our hospital were reviewed retrospectively. The clinical findings at admission were age, gender, primary disease, use of cyclophosphamide before transplant, duration of dialysis, number of human leukocyte antigen mismatch, transplantation time, previous rejection, the existence of associated viral infections, comorbid diseases, used induction therapy, maintenance immunosuppressive therapy, allograft survival, recipient survival, malignancy development time after transplantation, serum creatinine, glomerular filtration rate (GFR) and presence of proteinuria and hematuria. Using these data, we retrospectively analyzed the incidence and types of malignancies in KTRs.&#x0D; Results. During the follow-up period, 22cancer cases have been developed. The median age of the patient was 60 years (IQR 45-64.3) and patients were mostly male (77.3%) The median follow-up period was 111.5 months (IQR76.3–128.3). The median duration of dialysis was 54 months (IQR 11.5-78). The etiology of primary kidney disease in most KTRs recipients was unknown. The percentage of patients with mismatch 3 and above 3 was 86.3%. While the majority of patients received anti-thymocyte globulin (86.4 %) as induction therapy, maintenance therapy was mostly tacrolimus + mycophenolate mofetil + prednisolone (86.4 %). The median time from transplantation to the initial malignancy was 17.5 months (IQR 5-61.3). The most common initial malignancy was skin cancer (22.7%), followed by renal cell carcinoma originating from the native kidney (18.2%).&#x0D; Conclusion. Renal transplantation is the most favorable renal replacement therapy. Malignancies are now among the important causes of death in KTRs and these patients have a higher risk of developing cancer than the general population. Therefore, screening for cancer at certain intervals, especially in long-term and elderly recipients after transplantation, will positively affect the survival of the patient and functional renal graft.

The Role of Mutations on Gene WDR73 in Galloway-Mowat Syndrome

Galloway-Mowat syndrome is a very rare genetic disorder characterized by a variety of physical and developmental abnormalities, especially neurological abnormalities and progressive primary kidney disease. Physical characteristics may include microcephaly (a condition that indicates that the size of the head circumference is significantly smaller than expected for the child’s age and sex) and, in some cases, protrusion of part of the stomach through an abnormal opening in the diaphragm. Galloway-Mowat syndrome is caused by changes (mutations) in the WDR73 gene in a subset of cases.

SGLT2 Inhibition for Diabetic and Non-diabetic Kidney Disease

Chronic kidney disease (CKD) can be progressive, and its prognosis is worse because of increased mortality when it is associated with diabetes and cardiac disease. The outcomes of diabetic kidney disease (DKD) need to be improved, despite multifactorial interventions including glucose and blood pressure (BP) control, and the use of renin-angiotensin system (RAS) inhibitors, statins, and aspirin. Recent clinical trials suggest that sodium-glucose cotransporter-2 (SGLT2) inhibitors offer additional cardiorenal protection in DKD and non-diabetic CKD on top of RAS inhibition. The action of SGLT2 inhibitors is derived from the proximal tubule of the kidney, but their systemic effects beyond glucose-lowering involve hemodynamic and non-hemodynamic mechanisms. First, SGLT2 inhibitors restore tubuloglomerular feedback and relieve glomerular hypertension and albuminuria. Second, natriuresis and renal glycosuria lead to fluid and weight loss, resulting in BP lowering and prevention of heart failure. Third, SGLT2 inhibitors have anti-inflammatory and anti-oxidative actions that can reduce renal and cardiac inflammation and fibrosis, probably via adenosine monophosphate-activated protein kinase and sirtuin-1 activation. Finally, the proximal tubular workload is relieved, accompanied by increased erythropoiesis. Hypoxia-inducible factor 1 may be stimulated by renal outer medullary hypoxia when tubular sodium transport shifts from the proximal convoluted tubule to the proximal straight tubule and thick ascending limb, due to SGLT2 inhibition. These effects may also be beneficial in non-diabetic CKD, and we anticipate that SGLT2 inhibitors will prove effective for albuminuria reduction and preservation of kidney function in primary kidney diseases, including glomerulonephritis.

Abstract 16932: Primary Hyperaldosteronism And Resistant Hypertension In Pregnancy

Case Presentation: A 42-year-old woman with history of primary hyperaldosteronism (PA), IDDM and chronic kidney disease stage 3b (baseline Cr 2.5 mg/dl) presented at 10 weeks gestation with uncontrolled hypertension during pregnancy. Given prior difficulties conceiving and lack of discussions surrounding pregnancy risks, preconception counseling had not been done. She was taking carvedilol, spironolactone, and furosemide at pregnancy diagnosis. Given unclear safety profile in pregnancy, her spironolactone was discontinued. Her regimen was uptitrated to nifedipine 90 mmHg, carvedilol 50mg BID, hydralazine 50mg TID and furosemide 80mg BID. At 18 weeks gestation, she was readmitted with severe range hypertension and fluid overload unresponsive to escalating diuretic dosing. Due to poor urine output and creatinine to 5.5 mg/dl, she was initiated on dialysis. Her fetus was diagnosed with severe intrauterine growth restriction (IUGR) and umbilical doppler noted reversal of umbilical artery end-diastolic flow indicating severely elevated arterial resistance (Figure). During admission, she developed resistant hypertension requiring nicardipine and esmolol drips and severe headache, concerning for superimposed preeclampsia (SIPE). At 25 weeks gestation, she was taken for urgent c-section. Given extreme prematurity and growth restriction, her newborn baby passed away shortly after delivery. Discussion: This case highlights complications which arise from PA and antepartum persistent hypertension including progression of kidney disease, heart failure, IUGR, SIPE, and preterm delivery. It further highlights unique challenges using targeted therapies of mineralocorticoid receptor antagonists in PA in pregnancy. This information is crucial as PA is an increasingly recognized cause of resistant hypertension in young adults. Both PA and preeclampsia involve pathophysiologic mechanisms in the RAAS pathway and deserve further attention and research.

Proteomic profile of mesothelial exosomes isolated from peritoneal dialysis effluent of children with focal segmental glomerulosclerosis

Peritoneal dialysis (PD) is the worldwide recognized preferred dialysis treatment for children affected by end-stage kidney disease (ESKD). However, due to the unphysiological composition of PD fluids, the peritoneal membrane (PM) of these patients may undergo structural and functional alterations, which may cause fibrosis. Several factors may accelerate this process and primary kidney disease may have a causative role. In particular, patients affected by steroid resistant primary focal segmental glomerulosclerosis, a rare glomerular disease leading to nephrotic syndrome and ESKD, seem more prone to develop peritoneal fibrosis. The mechanism causing this predisposition is still unrecognized. To better define this condition, we carried out, for the first time, a new comprehensive comparative proteomic mass spectrometry analysis of mesothelial exosomes from peritoneal dialysis effluent (PDE) of 6 pediatric patients with focal segmental glomerular sclerosis (FSGS) versus 6 patients affected by other primary renal diseases (No FSGS). Our omic study demonstrated that, despite the high overlap in the protein milieu between the two study groups, machine learning allowed to identify a core list of 40 proteins, with ANXA13 as most promising potential biomarker, to distinguish, in our patient population, peritoneal dialysis effluent exosomes of FSGS from No FSGS patients (with 100% accuracy). Additionally, the Weight Gene Co-expression Network Analysis algorithm identified 17 proteins, with PTP4A1 as the most statistically significant biomarker associated to PD vintage and decreased PM function. Altogether, our data suggest that mesothelial cells of FSGS patients are more prone to activate a pro-fibrotic machinery. The role of the proposed biomarkers in the PM pathology deserves further investigation. Our results need further investigations in a larger population to corroborate these findings and investigate a possible increased risk of PM loss of function or development of encapsulating peritoneal sclerosis in FSGS patients, thus to eventually carry out changes in PD treatment and management or implement new solutions.

Allogeneic Kidney Transplantation After COVID-19: A Case Report

BackgroundPatients undergoing organ transplantation are immunosuppressed and already at risk of various diseases. We report about a patient who underwent ABO-incompatible kidney transplantation after coronavirus disease 2019 (COVID-19) without a recurrence of infection.Case ReportA 68-year-old woman presented with end-stage renal failure owing to primary autosomal dominant polycystic kidney disease; accordingly, hemodialysis was initiated in September 2020. Her medical history included bilateral osteoarthritis, lumbar spinal stenosis, hypertension, and hyperuricemia. In mid-January 2021, she contracted severe acute respiratory syndrome coronavirus 2 infection from her husband. Both of them were hospitalized and received conservative treatment. Because their symptoms were mild, they were discharged after 10 days. The patient subsequently underwent ABO-incompatible kidney transplantation from her husband who recovered from COVID-19 in March 2021. Before kidney transplantation, her COVID-19 polymerase chain reaction test was negative, confirming the absence of pre-existing COVID-19 immediately before the procedure. Computed tomography revealed no pneumonia. Initial immunosuppression was induced by administering tacrolimus, mycophenolate mofetil, methylprednisolone, basiliximab, rituximab, and 30 g of intravenous immunoglobulin. Double-filtration plasmapheresis and plasma exchange were performed once before ABO-incompatible kidney transplantation. The renal allograft functioned immediately, and the postoperative course was normal without rejection. COVID-19 did not recur. In addition, her serum creatinine levels and renal function had otherwise remained stable.ConclusionLiving kidney transplantation was safely performed in a patient with COVID-19 without postoperative complications or rejection. During the COVID-19 pandemic, the possibility of severe acute respiratory syndrome coronavirus 2 infection during transplantation surgery must be considered.

Safety and Efficacy of ANG-3070 in Patients with Primary Proteinuric Kidney Disease: A Phase 2 Study Design

Safety and Efficacy of ANG-3070 in Patients with Primary Proteinuric Kidney Disease: A Phase 2 Study Design

Особенности поражения почек при системных заболеваниях соединительной ткани

Системные заболевания соединительной ткани (СЗСТ) — достаточно большая гетерогенная группа заболеваний, имеющих определенные характерные клинические проявления и нарушения иммунорегуляции, приводящие к образованию аутоантител. Субклинические или явные признаки вовлечения почек имеют значительное усугубляющее влияние на клиническое течение СЗСТ. Нарушение функции почек характерно для таких СЗСТ, как системная красная волчанка (СКВ), ревматоидный артрит (РА), системная склеродермия, синдром Шегрена, аутоиммунные миопатии (дерматомиозит и полимиозит). На современном этапе, учитывая доступность многих диагностических манипуляций и возможности этиопатогенетического лечения, терапевтам, ревматологам и нефрологам необходимо своевременно заподозрить наличие заболевания почек у пациентов с СЗСТ и принять необходимые меры по диагностике и лечению. Современные стратегии классификации и лечения СКВ скорректированы с учетом результатов биопсии почек, что значительно улучшило прогноз поражения почек при этом заболевании. Одно из наиболее тяжелых поражений почек у пациентов с СЗСТ — это почечный склеродермический криз (ПСК), характеризующийся тяжелой гипертонией, прогрессирующим снижением функции почек и тромботической микроангиопатией, своевременное назначение ингибиторов ангиотензинпревращающего фермента таким пациентам показывает значительный эффект в борьбе с ПСК. Контроль активности основного заболевания улучшает функцию почек у большинства пациентов с синдромом Шегрена, аутоиммунными миопатиями и РA. С другой стороны, хроническое использование иммунодепрессантов и нестероидных противовоспалительных препаратов, а также сопутствующие заболевания, такие как диабет, гипертония и сердечно-сосудистые осложнения, могут являться основными причинами поражения почек у пациентов с ревматическими заболеваниями. Кроме того, первичные заболевания почек с длительным анамнезом могут привести к проявлениям, имитирующим первичные ревматологические расстройства. В этом обзоре мы фокусируемся на диагностике нарушений функции почек вследствие основного заболевания, побочных эффектах препаратов и принятии решений о своевременном соответствующем лечении.