Nephritic Syndrome Research Articles

#1603 A potent protein inhibitor of HB-EGF protects kidneys from glomerular lesions in a pig model of crescentic glomerulonephritis

Abstract Background and Aims Crescentic glomerulonephritis (CGN) is a severe disease that rapidly destroys the glomerular architecture. CGN is due to immuno-inflammatory aggressions triggered by anti-neutrophil cytoplasmic autoantibody-associated vasculitides, anti-glomerular basement membrane (GBM) autoantibodies, or immune complexes deposition as occurs in systemic lupus erythematosus, IgA nephropathy or infections. Treatments are based on aggressive immunosuppression. Although required, immunosuppression doesn't directly target the deleterious glomerular response to inflammation and leads to significant morbidity. Moreover, most patients still develop chronic or end-stage kidney failure, indicating that complementary strategies are needed. We showed previously that local over-expression of the growth factor HB-EGF (Heparin-binding EGF-like growth factor) and subsequent activation of EGFR lead to dedifferentiation and proliferation of parietal epithelial cells and podocytes, leading to crescentic lesions that irreversibly obliterate the glomeruli. We aimed to evaluate the therapeutic potential of a protein inhibitor of HB-EGF in a pig model of CGN. Method We engineered a protein inhibitor of HB-EGF, DTR8, from the receptor-binding domain of diphtheria toxin, a highly selective natural ligand of HB-EGF. Twelve mutations improved solubility, led to pM affinity, and reduced immunogenicity and antigenicity. Pigs received decomplemented nephrotoxic serum (NTS) from sheep immunized against pig GBM to mimic anti-GBM antibodies disease responsible for one form of CGN. Ten pigs were treated with 0.3 mg/kg of DTR8 twice a day by intramuscular route for 20 days, and 12 pigs received vehicle only starting 6 hours after NTS. Animals were sacrificed on day 21, and blood, urine and kidneys were analyzed. Five animals that had received pre-immune sheep serum served as controls. Results Pigs developed a nephritic syndrome with high proteinuria, hypoalbuminemia, kidney failure with increased BUN and blood creatinine levels, anasarca and crescentic lesions typical of CGN along with de novo HB-EGF glomerular overexpression. The vehicle-treated group had only 24.8% of histologically normal glomeruli, while the DTR8-treated group had 57.3% of healthy glomeruli. DTR8 treatment significantly reduced the percentage of crescentic lesions (P = .0365) and preserved podocyte differentiation as assessed by the expression of nephrin that was markedly reduced in vehicle-treated animals but maintained close to normal in DTR8-treated animals (P = .0028). DTR8 administration reduced EGFR phosphorylation in glomerular cells (P = .0161), suggesting local inhibition of the HB-EGF/EGFR cascade. Lymphocyte infiltration was reduced (P = .2543). Notably, the treatment group also displayed a global reduction in interstitial fibrosis (P = .0313). Conclusion The therapeutic protein candidate DTR8 protects kidney glomeruli in a CGN model in pigs.

Clinicopathological Characteristics and Disease Chronicity in Glomerular Diseases: A Decade-Long Study at Romania's Largest Kidney Biopsy Reference Center.

Glomerular diseases (GDs), significant causes of end-stage kidney disease, are better understood through epidemiological studies based on kidney biopsies (KBs), which provide important insights into their prevalence and characteristics. This study aims to analyze the clinicopathological features of GDs diagnosed from 2008 to 2017 at Romania's largest reference center. In this decade-long study, 1254 adult patients diagnosed with GDs were included. The local previously validated renal histopathological prognostic score was calculated for each KB using four histopathologic lesions: global glomerulosclerosis, tubular atrophy, interstitial fibrosis and fibrocellular/fibrous crescents. The mean patient age was 50 years, with a male predominance (57%). The primary referral reasons were nephrotic syndrome (46%), nephritic syndrome (37%), chronic kidney disease (12%), asymptomatic urinary abnormalities (4%), and acute kidney injury (1%). Immunoglobulin A nephropathy (IgAN) was the most frequently diagnosed GD (20%), aligning with frequencies reported in European registries. Diabetic glomerular nephropathy was the most common secondary GD (10%). It also presented the highest median renal histopathological prognostic score (2), indicating a poorer prognosis. Lower eGFR and higher proteinuria were independently associated with higher scores. This decade-long study highlights IgAN as the most frequent GD diagnosed by KB. Diabetic glomerular nephropathy was identified as the most common secondary GD. The renal histopathological prognostic score, notably high in diabetic glomerular nephropathy patients, was correlated with lower eGFR and higher proteinuria, underlining its clinical relevance.

Supplying rats with halfa-bar and liquorice extracts ameliorate doxorubicin-induced nephrotic syndrome

In the current work, we aimed to evaluate the protective effects of liquorice and halfa-bar extract against doxorubicin (DOX)-induced nephritic syndrome (NS) in rats. Twenty albino male rats were intraperitoneally injected with 50 mg/kg of DOX. The injected rats were supplied daily with 400 mg/kg of liquorice, halfa-bar extract, or their combination for 2 weeks. Our findings confirmed the induction of NS in rats indicated by alteration in Bowman’s space, damaged in glomerular capsules, and tubules. Moreover, the levels of produced tumour necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) were increased, accompanied by decreasing levels of IL-4 and IL-10. Supplement NS-rats with liquorice and halfa-bar extracts restored the glomerular and tubules damage and adjusted the level of produced TNF-α and IL-8. Interestingly, both extracts can stimulate the expression profile of small proline-rich protein 2 F (sprr2f) and metalloproteinase-10 (MMP-10), which are responsible for repairing and regeneration mechanisms of renal syndromes.

Genotype-Phenotype Correlations in Alport Syndrome-A Single-Center Experience.

Alport syndrome (AS) is a common and heterogeneous genetic kidney disease, that often leads to end-stage kidney disease (ESKD). This is a single-center, retrospective study that included 36 adults with type IV collagen (COL4) mutations. Our main scope was to describe how genetic features influence renal survival. A total of 24 different mutations were identified, of which eight had not been previously described. Mutations affecting each of the type IV collagen α chains were equally prevalent (33.3%). Most of the patients had pathogenic variants (61.1%). Most patients had a family history of kidney disease (71%). The most prevalent clinical picture was nephritic syndrome (64%). One-third of the subjects had extrarenal manifestations, 41.6% of patients had ESKD at referral, and another 8.3% developed ESKD during follow-up. The median renal survival was 42 years (95% CI, 29.98-54.01). The COL4A4 group displayed better renal survival than the COL4A3 group (p = 0.027). Patients with missense variants had higher renal survival (p = 0.023). Hearing loss was associated with lower renal survival (p < 0.001). Patients with COL4A4 variants and those with missense mutations had significantly better renal survival, whereas those with COL4A3 variants and those with hearing loss had worse prognoses.

Unravelling the Link between the Gut Microbiome and Autoimmune Kidney Diseases: A Potential New Therapeutic Approach.

The gut microbiota and short chain fatty acids (SCFA) have been associated with immune regulation and autoimmune diseases. Autoimmune kidney diseases arise from a loss of tolerance to antigens, often with unclear triggers. In this review, we explore the role of the gut microbiome and how disease, diet, and therapy can alter the gut microbiota consortium. Perturbations in the gut microbiota may systemically induce the translocation of microbiota-derived inflammatory molecules such as liposaccharide (LPS) and other toxins by penetrating the gut epithelial barrier. Once in the blood stream, these pro-inflammatory mediators activate immune cells, which release pro-inflammatory molecules, many of which are antigens in autoimmune diseases. The ratio of gut bacteria Bacteroidetes/Firmicutes is associated with worse outcomes in multiple autoimmune kidney diseases including lupus nephritis, MPO-ANCA vasculitis, and Goodpasture's syndrome. Therapies that enhance SCFA-producing bacteria in the gut have powerful therapeutic potential. Dietary fiber is fermented by gut bacteria which in turn release SCFAs that protect the gut barrier, as well as modulating immune responses towards a tolerogenic anti-inflammatory state. Herein, we describe where the current field of research is and the strategies to harness the gut microbiome as potential therapy.

Cardiovascular Morbidity in Systemic Lupus Erythematosus: A Single-Center Retrospective Study.

Systemic Lupus Erythematosus (SLE) is an autoimmune inflammatory condition affecting multiple systems. Cardiovascular morbidity is a significant concern, with around 25% of SLE patients experiencing cardiac complications. This study aims to determine the prevalence of cardiovascular morbidity in SLE patients in King Fahad Medical City (KFMC) in Riyadh, Saudi Arabia. This retrospective record-based research was conducted at KFMC from January 2015 to October 2023. A review of the medical files of all SLE patients was accomplished. The vast majority of the patients (90.9%) were females. The mean age for the patients was 36.5 years. The most common comorbidities were lupus nephritis (34.6%), hypothyroidism (18.4%), and anti-phospholipid syndrome (9.2%). The most commonly used medications were hydroxychloroquine (81.8%), corticosteroids (prednisolone) (43.0%), and mycophenolate mofetil (27.9%). Around 45.2% (n= 176) of the patients with SLE developed cardiovascular complications. The most commonly reported cardiovascular diseases that developed after diagnosing patients with SLE were hypertension (22.4%), valvular heart diseases (13.2%), and dyslipidemia (9.2%). The study also found that anti-dsDNA antibodies can reduce the likelihood of developing hypertension by 40%. This research contributes to the medical literature on SLE and sets the stage for future research on personalized healthcare strategies for managing SLE and its complications. This study highlights that a considerable proportion of SLE patients(~50%) develop cardiovascular complications, with hypertension, valvular heart diseases, and dyslipidemia being the most common. We also discovered that anti-double-stranded deoxyribonucleic acid antibodies (Anti-dsDNA) reduce the likelihood of developing hypertension.

Expression of Concern: Actinomyces urinae sp. nov., isolated from 13-year-old girl affected by nephritic syndrome

Expression of Concern: Actinomyces urinae sp. nov., isolated from 13-year-old girl affected by nephritic syndrome

Risk factors affecting the sleep quality of patients on dialysis: A single-center cross-sectional study.

Sleep quality is among the common complication in patients on dialysis and serious affect their health and quality of life; however, other associated risk factors are unclear. This study aimed to investigate the risk factors affecting sleep quality in patients on dialysis. Data were collected from 260 patients who met the inclusion criteria at out hospital from May 2023 to October 2023. Questionnaires were completed by patients, and biochemical indicators were obtained from past medical records. Univariate and multifactor analyses were used to find factors influencing sleep quality in patients on dialysis. Simple linear regression results showed that female, type of kidney primary disease, high systolic blood pressure (SBP), pruritus, pruritus frequency, restless legs syndrome (RLS), anxiety, and depression were associated with poor sleep quality. Blood biochemical parameters showed that low sodium and calcium levels and high ferritin levels were associated with poor sleep quality. Multiple linear regression statistics showed that female, pruritus, RLS, high SBP, depression, and high ferritin levels were associated with poor sleep quality. This study showed that female, chronic nephritis syndrome, high SBP, pruritus, RLS, low mood. and high ferritin levels were associated with poor sleep quality. Future development of individual nursing and targeted therapies is key to improving sleep quality in patients on dialysis.

Renal complications in patients with predominantly antibody deficiency in the United States Immune Deficiency Network (USIDNET)

BackgroundPrior studies have reported that renal insufficiency occurs in a small percentage of patients with predominantly antibody deficiency (PAD) and in about 2% of patients with common variable immunodeficiency (CVID). ObjectiveThe goal of our study was to understand and evaluate the prevalence and type of renal complications in PAD patients in the United States Immunodeficiency Network (USIDNET) cohort. We hypothesized there is an association between certain renal complications and severity of immunophenotype in patients with PAD. MethodsWe performed a query of patients with PAD from the USIDNET cohort with renal complications. Patients with documented renal disease such as chronic kidney disease (CKD), nephrolithiasis, nephritis, and renal failure syndrome were included. We compared immunophenotype, flow cytometry and immunoglobulin (Ig) levels of PAD patients with renal complications to the total PAD USIDNET cohort. ResultsWe identified that 140/2071 (6.8%) of PAD patients had renal complications. Of these 50 (35.7%) had CKD, 46 (32.9%) had nephrolithiasis, 18 (12.9 %) had nephritis, and 50 (35.7%) had other renal complications. Compared to the total USIDNET cohort of patients with PAD, patients with CKD had lower ALCs, CD3+ T-cells, CD4+ T-cells, CD19+ B-cells, CD20+ B-cells and CD27+IgD- B-cells (p<0.05 for all). Patients with nephritis had lower ALCs, CD19+ B-cells, CD27+ B-cells and IgE levels (p<0.05 for all) compared to PAD patients without renal disease. ConclusionsWe identified that 6.8% of PAD patients in the USIDNET cohort had a documented renal complication. The patients with nephritis and CKD had a more severe immunophenotype compared to the overall PAD cohort.

IgA Nephropathy and Lupus Nephritis in a 17-Year-Old Female: A Case Report

Background: Acute nephritic syndrome is classically presented with proteinuria, haematuria, azotemia, red blood casts, oliguria, and hypertension (PHARAOH) occurring acutely. Extensive inflammation of the glomeruli causes a decrease in the glomerular filtration rate so that it will produce uremic symptoms such as water and salt retention which will give a clinical picture of edema and hypertension, positive protein in the urine, the presence of erythrocytes or the appearance of dysmorphic erythrocytes in the urine.&#x0D; Case presentation: A 17 year old female with nephritic syndrome is reported to have nephritic lupus and IgA nephropathy. He has been treated with corticosteroids, immunosuppressants, antihypertensives, and also diuretics followed by progress of clinical and laboratory conditions. Biopsy has been performed to provide a definitive diagnosis in the patient and determine the type of nephritic syndrome experienced. The biopsy showed features of IgA nephropathy (IgAN) and lupus nephritis.&#x0D; Conclusion: Nephritic syndrome has been suspected due to the presence of haematuria, proteinuria, eyelid swelling, and hypertension. The management given to patients is supportive and symptomatic. Long-term administration of corticosteroids is needed in the treatment of nephritic syndrome as a maintenance therapy. Observation during treatment is needed to assess improvement or worsening of the disease experienced.

A Study Assessing the Role of Renal Grayscale Ultrasonography and Flowmetry in Correlation With Renal Function Tests Across Various Renal Diseases.

Background Renal insufficiency, a critical concern in native and transplant kidneys, necessitates effective screening modalities for evaluation and management. Grayscale sonography has been a cornerstone in renal diagnostics, providing basic anatomical insights such as renal length, cortical thickness, and collecting system dilatation. Despite technological advancements, its impact on the differential diagnosis or management of renal disease remains limited, often showing normal findings in the presence of severe renal dysfunction. On the other hand, Doppler sonography, particularly the Doppler resistive index (RI), has shown potential in enhancing the assessment of renal dysfunction by quantifying alterations in renal blood flow and correlating with various renal pathologies and prognoses. Thus, this study aims to assess and compare the sensitivity of transabdominal and Doppler sonography as a diagnostic modality to evaluate medical renal diseases with altered renal function tests (RFTs). Methodology Participants included patients visiting the ultrasonography (USG)room at our hospital for USG of the kidneys, ureters, and bladder (USG KUB) and USG of the whole abdomen(USG W/A) with altered RFTs. Each underwent renal grayscale USG and RImeasurement, alongside standard RFTs, aiming to investigate the relationship between USG and RI findings and RFT outcomes to assess their predictive accuracy for renal function. Renal grayscale USG assessed parameters including renal dimensions, echogenicity, corticomedullary differentiation, and RI. Data management and charting were conducted with Microsoft Excel 2021 and Microsoft Word 2021. IBM SPSS Statistics for Windows, Version 24 (IBM Corp.,Armonk, NY) was utilized for data analysis. The analysis of variance (ANOVA) test examined relationships between renal parameters and RI across diagnostic groups. Furthermore, the chi-square test evaluated associations of renal ultrasound findings with RFTs and their significance. Results The study analyzed 93 patients with altered RFTs. Chronic kidney disease (CKD) affected 68 patients, primarily males in their fifth and sixth decades, showing reduced renal dimensions, increased cortical echogenicity, and elevated Doppler RI mean (RIm) with 83% sensitivity. Acute kidney injury (AKI) was found in 12 patients, mainly in their fourth decade, displaying increased renal parameters and elevated RIm with 75% sensitivity. Glomerular diseases, including nephrotic syndrome (NS) and nephritic syndrome (NeS), occurred in 9 patients, predominantly males in their fourth decade, with heightened renal cortical echogenicity and elevated RIm with 55.5% sensitivity. Lupus nephritis (LN) was detected in 4 female patients, despite normal renal parameters, showing elevated serum creatinine levels. Conclusions Doppler assessment of renal vascular waveforms effectively identifies chronic renal changes, aiding in the diagnosis of altered RFTs and guiding prognosis. While it detects typical changes like decreased size and parenchymal atrophy, it may not be as indicative of diabetic nephropathy. Key ultrasound indicators such as changes in echotexture and size, along with associated findings like ascites and effusions, help recognize altered renal function and minimize unnecessary interventions.

As Milky as It Can Get; Chyluria: A Case Report and Review of Literature

Abstract Filariasis is an important public health problem in India. Extralymphatic manifestation of filariasis includes chyluria or passage of intestinal lymph or chyle into urine imparting a milky-white color, is an important manifestation of renal involvement. A young woman residing in a filaria endemic region, presented with persistent chyluria of 3-month duration. She did not have any features of nephrotic or nephritic syndrome or features of connective tissue disease. After routine hematological, biochemical, serological, and urinalysis, nephrotic range proteinuria and lipiduria were confirmed, and kidney biopsy was performed. Kidney biopsy showed an elongated parasitic sheathed structure with multiple basophilic nuclei spread along the length of the tail, suggestive of microfilaria, in capillaries of a single glomerulus; immunofluorescence was negative for immunoglobulin (Ig) A, IgM, IgG, C3, C1q, kappa, and lambda. She was given antifilarial drug and chyluria promptly subsided. The complex evaluation and management of chyluria have been discussed.

A NEPHROPROTECTIVE EFFECT OF CARISSA SPINARUM AGAINST GENTAMICIN INDUCED OXIDATIVE NEPHROTOXICITY

One of the most prevalent issues with the kidneys is nephrotoxicity, which happens when the body is exposed to a toxin or medicine. With the growing availability of powerful therapeutic medications such as aminoglycoside antibiotics, chemotherapeutic agents, and nonsteroidal anti-inflammatory drugs (NSAIDs), a variety of pharmaceuticals can have a negative impact on the kidney, leading to acute renal failure, chronic interstitial nephritis, and nephritic syndrome. Ethiopian native Carissa spinarum (Apocynaceae) is traditionally used to treat skin conditions, rheumatism, diarrhoea, chicken pox, and stomachaches. The herbal plant Carissa spinarum possesses antioxidant qualities. The term "nephrotoxicity" describes the detrimental effects that different drugs can have on the kidneys, which can result in damage and dysfunction. This illness offers a serious risk to kidney health and can be brought on by exposure to specific medicines, chemicals, or poisons. Understanding the methods by which these substances affect the structure and function of the kidneys—such as oxidative stress, inflammation, and interference with essential cellular processes—is necessary to comprehend the abstract idea of nephrotoxicity. Nephrotoxicity management also involves establishing prevention and management strategies, identifying, and tracking possible nephrotoxic substances, and managing and preventing nephrotoxicity. All things considered, an abstract comprehension of nephrotoxicity entails investigating the complex pathways and circumstances that lead to renal injury and formulating strategies to lessen or offset these detrimental effects on kidney function.

Tubulointerstitial Nephritis and Uveitis Syndrome During the COVID-19 Pandemic: A Case Series.

To report the ocular findings, laboratory results, and management of patients with tubulointerstitial nephritis and uveitis syndrome (TINU), whose numbers increased during the 2019 coronavirus disease (COVID-19) pandemic. Demographic characteristics, ophthalmic examination findings, laboratory results including polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), serum SARS-CoV-2 immunoglobulin G (IgG) antibody, and treatment of patients diagnosed with TINU between March 2020 and March 2022 were evaluated retrospectively. The study included 19 eyes of 10 patients (6 female/4 male). The mean age was 13.5±2.4 years (range: 8-16 years). The mean follow-up duration was 13.5±6.1 months (range: 6-24 months). All patients presented with anterior uveitis. Anterior uveitis was bilateral in 9 patients (90%) and unilateral in 1 patient (10%). Posterior segment findings were normal in 8 patients (80%), and bilateral optic disc edema was observed in only 2 patients (20%). None of the patients had a previous SARS-CoV-2 infection and/or vaccination history. The SARS-CoV-2 PCR test was negative in all patients at presentation. The SARS-CoV-2 IgG antibody test was reactive in 7 patients (70%). Recurrent uveitis developed in 8 patients (80%) during follow-up. Systemic immunomodulatory therapy was required for the control of ocular inflammation in 7 patients (70%) with severe uveitis flare-ups. TINU is a multisystemic autoimmune disease, especially in response to environmental triggering factors such as viral infections. Although TINU is a rare disease, the number of cases increased during the COVID-19 pandemic. SARS-CoV-2 antibodies were detected at a significant rate of 70% in these patients, who did not have a history of SARS-CoV-2 infection and vaccination. Previous asymptomatic SARS-CoV-2 infection in children may be a triggering factor in the development of TINU.

Activated phosphoinositide 3-kinase δ syndrome caused by PIK3CD mutations: expanding the phenotype

BackgroundGermline heterozygous gain-of-function (GOF) mutations in the PIK3CD gene lead to a rare primary immunodeficiency disease known as activated phosphoinositide 3-kinase (PI3K) δ syndrome type 1(APDS1). Affected patients present a spectrum of clinical manifestations, particularly recurrent respiratory infections and lymphoproliferation, increased levels of serum immunoglobulin (Ig) M, Epstein-Barr virus (EBV) and cytomegalovirus (CMV) viremia. Due to highly heterogeneous phenotypes of APDS1, it is very likely that suspected cases may be misdiagnosed.MethodsHerein we reported three patients with different clinical presentations but harboring pathogenic variants in PIK3CD gene detected by trio whole-exome sequencing (trio-WES) and confirmed by subsequent Sanger sequencing.ResultsTwo heterozygous mutations (c.3061G > A, p.E1021K and c.1574 A > G, p.E525G) in PIK3CD (NM_005026.3) were identified by whole exome sequencing (WES) in the three patients. One of two patients with the mutation (c.3061G > A) presented with abdominal pain and diarrhea as the first symptoms, which was due to intussusception caused by multiple polyps of colon. The patient with mutation (c.1574 A > G) had an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)-like clinical manifestations, including multisystemic inflammation, acute nephritic syndrome, and positive perinuclear ANCA (p-ANCA), thus the diagnosis of ANCA-AAV was considered.ConclusionsOur study expands the spectrums of clinical phenotype and genotype of APDS, and demonstrates that WES has a high molecular diagnostic yield for patients with immunodeficiency related symptoms, such as respiratory infections, multiple ecchymosis, ANCA-associated vasculitis, multiple ileocecal polyps, hepatosplenomegaly, and lymphoid hyperplasia.Trial registrationRetrospectively registered.

A pediatric case of tubulointerstitial nephritis and uveitis syndrome

Tubulointerstitial Nephritis and Uveitis Syndrome (TINU Syndrome) is a rare entity of unknown origin. Most cases described affect adolescents and women. It often implies a renal biopsy and is established upon the presence of uveitis and tubulointerstitial nephritis in the same patient, after all possible causes are excluded. The authors report the case of a 12-year-old teenage boy with nausea, vomiting, and weight loss lasting two weeks, taken to his local hospital with acute kidney injury, oliguria, and high blood pressure. After transfer to a specialized centre and exclusion of infectious, toxic, and autoimmune causes, intravenous and oral corticosteroid therapy was started. Renal biopsy confirmed interstitial nephritis of undetermined aetiology and the patient was discharged after favourable restauration of renal function, with a course of 4 weeks of steroids and progressive decrements over 10 weeks. Four months after the onset of the condition, the teenager was taken to the hospital with eye redness and tenderness. Bilateral anterior uveitis was described, which established the diagnosis of TINU Syndrome. After two years of joint follow-up by Paediatric Nephrology and Ophthalmology, the patient remains stable, without relapses, or ocular or renal sequelae.

Kidney Biopsy and Immuno-Rheumatological Diseases: A Retrospective and Observational Study.

Renal involvement is a common occurrence in patients with immuno-rheumatological diseases (IRDs). Several instances of glomerulonephritis (GN) occur in the setting of IRD and complicate the clinical course of an underlying condition. The aim of this study was to observe the spectrum of nephropathies according to age, kidney function, history of IRD at the time of biopsy, and histopathological kidney diagnosis. We evaluated data relating to 699 consecutive kidney native biopsies (female 52.1%) with a median age of 48 years (IQR 34-62) performed in adult patients collected over 15 years. The study population was divided into three groups: patients with kidney histological findings correlated to underlying IRD (Group 1), patients with kidney histological findings not correlated to underlying IRD (Group 2), and patients with kidney histological findings compatible with "de novo" IRD (absent in personal medical history) (Group 3). Kidney involvement related to IRD was found in 25.2% of patients. Group 1 was mostly represented by lupus nephritis (76.6%), with a younger age than Group 3 (p < 0.001) and by a higher percentage of females than other groups (p < 0.001). Group 3 was the most represented by microscopic polyangiitis (50.8%) when compared with the other two groups (p < 0.001). Acute nephritic syndrome (p < 0.001), acute kidney injury (AKI), and abnormal urinalysis (p < 0.001) were more represented in Group 3 than the other groups. In conclusion, IRDs are characterized by different clinical presentations and heterogeneous histological findings. Kidney biopsy remains fundamental to achieving the correct diagnosis and starting targeted therapy.

ОПЫТ ПРОВЕДЕНИЯ И ДИАГНОСТИЧЕСКАЯ ЗНАЧИМОСТЬ ПУНКЦИОННОЙ НЕФРОБИОПСИИ В СТАЦИОНАРЕ РЕГИОНАЛЬНОГО УРОВНЯ

Modern diagnosing of kidney diseases is based on a complex of clinical, laboratory, and instrumental studies, among which kidney biopsy occupies an important place. The study aims to assess the diagnostic value of kidney biopsy in patients with nephrological pathology. The study included 70 patients (n = 70) who underwent percutaneous puncture kidney biopsy from 2019 to 2022 for the following causes: nephrotic syndrome (42 %), chronic nephritic syndrome (35 %), and acute kidney injury of unclear etiology (23 %). The morphological examination revealed that two-thirds of all patients with kidney diseases (60 %) (p = 0,05) had glomerulopathy. Among glomerular diseases, IgA-nephropathy prevails (26 %) (p &lt; 0,05), as well as membranous nephropathy (14 %). Amyloidosis (AA/Al) is registered in every seventh patient (14 %), while diabetic nephropathy – in every tenth (10 %). Complications of kidney biopsy develop in a quarter of cases (26 %). Anti-neutrophil cytoplasmic antibody-associated vasculitis, thrombotic microangiopathies and tubulointerstitial nephritis manifest more often in the form of acute kidney injury, IgA-nephropathy manifests itself in the onset of the disease with nephritic syndrome, while diabetic nephropathy, membranous nephropathy, focal segmental glomerulosclerosis, amyloidosis start with nephrotic syndrome in most cases. Kidney biopsy often has a significant impact on patient management tactics: according to the results of the morphological study, active pathogenetic therapy was initiated or corrected, and the vector of diagnostic search was also changed in 83 % of patients (p = 0,005). The data obtained confirm the need for the widespread introduction of kidney biopsy in order to optimize the quality of medical care provided to patients with a nephrological profile.

Determination of the relationship between the polymorphic genes of metaloproteinases MMP9 (A-8202G) RS11697325 and the level of cystatin c in children with chronic nephritic syndrome

An analysis of the scientific literature in recent years reliably indicates the importance of molecular diagnostics in the field of nephrology. Research contains information on the role of genetic factors in the chronicization of the process of nephritic syndrome, ongoing research in this area. The pathology of development is explained by the fact that the chronicity of the process occurs primarily due to genetic inferiority of parts of the nephron, which leads to changes in the structure of the protein. The results of the study show the relationship between changes in the genotype of MMP9 (Matrix metalloproteinase-9) (A-8202G) rs11697325 with the development of the chronicization process. Our results provide evidence that cystatin C is an accurate diagnostic and prognostic marker of chronic nephritic syndrome in the pediatric population. At the same time, chromosomal polymorphic MMP9 genes affect the glomerular filtration rate by increasing the amount of Cystatin C, which is a gold marker in the diagnosis of chronic nephritic syndrome in children, determining the prognosis of the disease, which makes it possible for timely treatment and further tactics of the doctor.

Тубулоинтерстициальный нефрит с увеитом: серия клинических наблюдений

Tubulointerstitial nephritis and uveitis syndrome (TINU) is a rare autoimmune disease that develops predominantly in young people and is characterized by variable clinical manifestations and an uncertain prognosis. A single-center retrospective observational study included 3 pediatric patients (a girl and two boys) with clinically and morphologically confirmed TINU. Age of onset, clinical symptoms, gender-age-height-standardized blood pressure (BP), proteinuria (g/l), excretion level of β2-microglobulin, glucose, phosphorus in urine, blood pH and bicarbonate levels, Bedside Schwartz equation estimated glomerular filtration rate (eGFR, ml/min/1.73 m2, norm≥90 ml/min/1.73 m2), ophthalmoscopy data and the therapy were analyzed at the time of disease manifestation and during the follow-up. The duration of follow-up ranged from 3 to 7 years. The disease debuted at the age of 10 to 14 y/o with severe symptoms of intoxication, inflammatory activity, acute kidney damage (eGFR=22 to 35 ml/min/1.73 m2) and the development of Fanconi syndrome. Anterior uveitis had manifested in 1 to 5 months after the kidney disease. The TINU diagnosis was established after 6 to 9 months from the onset of the disease. All children received systemic steroid therapy coupled with the local treatment for uveitis. A significant decrease in blood creatinine levels and urine β2-microglobulin excretion with partial restoration of renal filtration function was noted by the sixth month of the therapy. All children developed chronic kidney disease (CKD) stages 2 to 3 over time. Stable remission of uveitis was achieved in 2 children after 3 to 10 months of treatment without complications; and in one patient a subacute uveitis led to the secondary changes in the cornea and decreased visual acuity. Conclusion: children with TINU have a high risk of developing CKD as a result of acute kidney disease; uveitis is characterized by a chronic course and, in the absence of remission, can lead to the development of ophthalmological complications.