Keyword: Nephropathy

ABSTRACT: Background: Fabry disease is an X-linked lysosomal storage disorder caused by variants in the GLA gene, leading to progressive multisystem involvement of the kidneys, heart, and central nervous system. Marked phenotypic variability among female carriers is attributed to random X-chromosome inactivation, but pronounced discordance in organ predominance across multiple branches of a single family sharing an identical genotype is rarely documented. We describe such a family carrying the GLA variant c.137A>G (p.His46Arg).
Case presentation: The proband, a 47-year-old woman, presented with recurrent ischemic strokes (four episodes since 2004) and a spinal cord infarction, initially misdiagnosed as multiple sclerosis for over a decade until molecular testing in 2018 confirmed Fabry disease (α-galactosidase A activity 3.4; lyso-Gb3 5.4). She developed a fixed pyramidal tetrasyndrome with neuropathic pain, started enzyme replacement therapy, and recently experienced a sixth cerebrovascular event accompanied by new-onset oliguria suggestive of emerging renal involvement. Her mother had died of renal failure at age 31 (not genetically confirmed). Her 26-year-old daughter, despite abnormal biochemistry (enzyme 0.3; lyso-Gb3 46.2), remains largely asymptomatic, while her 16-year-old son does not carry the variant. The proband's maternal aunt (73 years), a confirmed carrier, required pacemaker implantation for cardiac conduction impairment; her three sons displayed a strikingly different, predominantly renal phenotype: one died young of acute kidney injury, one has required hemodialysis since 2013 and shows lacunar cerebral infarcts on MRI with left ventricular hypertrophy on ECG, and one has nephrotic syndrome but declined further evaluation. A second maternal aunt, also genetically confirmed, remains asymptomatic; her two mutation-positive sons have refused testing and treatment. All affected relatives share the identical GLA variant.
Conclusion: This three-generation family illustrates striking intrafamilial phenotypic heterogeneity - cerebrovascular, cardiac, and renal - despite a shared GLA genotype, underscoring the limited predictive value of genotype-phenotype correlation in Fabry disease. The decade-long misdiagnosis as multiple sclerosis highlights the need to consider Fabry disease in unexplained recurrent stroke. Cascade family screening should be offered to all at-risk relatives regardless of sex, age, or symptom status, since disease severity and target-organ involvement in one member do not predict outcomes in others.

ABSTRACT: Background: IgA nephropathy (IgAN) is an immune complex–mediated glomerular disease characterized by marked clinical and histopathological heterogeneity and a variable risk of progression. The coexistence of IgAN with features of TMA poses a particular diagnostic challenge, as a microangiopathic phenotype may emerge in the setting of severe glomerular injury, endothelial dysfunction, complement activation, and additional external triggers. The clinical consequences of such an interaction may be particularly significant in patients with a solitary functioning kidney.
Objective: To characterize the clinicopathological features of severe IgAN presenting with a clinical–hematological TMA phenotype in a young woman with a solitary functioning kidney and to explore the potential contribution of local complement activation and recurrent drug exposures as a putative “second hit” to endothelial injury and rapid deterioration of kidney function.
Case presentation: A 22-year-old woman had a solitary functioning right kidney following neonatal left nephrectomy. Kidney function remained preserved for years; however, persistent microscopic hematuria had been documented since 2022, retrospectively suggesting clinically silent glomerular disease. Between 2022 and 2026, she had substantial cumulative exposure to medications and supplements, including recurrent antiviral, antibacterial, and anti-inflammatory therapies, acne-directed treatments, vitamin/mineral preparations, and dietary supplements. These exposures preceded clinical deterioration and were considered potential external triggers in a susceptible renal background rather than evidence of definite drug-induced TMA. In June–July 2026, she developed recurrent massive edema followed by rapidly progressive kidney dysfunction with azotemia, hyperkalemia, active urinary sediment, and proteinuria, ultimately requiring hemodialysis. During hospitalization, microangiopathic hemolytic anemia, severe thrombocytopenia, schistocytosis, reticulocytosis, and elevated lactate dehydrogenase established a clinical–hematological TMA phenotype (Table 1). Preserved ADAMTS13 activity argued against immune-mediated thrombotic thrombocytopenic purpura (TTP), while autoimmune, anti-GBM, antiphospholipid, and infectious investigations were unrevealing. Given rapidly progressive dysfunction of the solitary kidney and an active nephritic syndrome, methylprednisolone and cyclophosphamide were administered before histopathological confirmation. Two sessions of therapeutic plasma exchange were subsequently performed in the setting of the pronounced TMA phenotype. Hematological parameters improved, whereas kidney function did not recover and dialysis dependence persisted. Kidney biopsy demonstrated advanced IgAN with severe chronic kidney damage (Oxford Classification M0E1S1T2C1) and intense mesangial IgA/C3 codeposition despite normal circulating C3. No definitive histopathological evidence of active TMA was identified.
Conclusion: This case demonstrates previously oligosymptomatic IgAN presenting with rapidly progressive kidney dysfunction, dialysis-dependent kidney failure, and a compelling clinical–hematological TMA phenotype. Preserved ADAMTS13 activity and an unrevealing investigation for major secondary causes supported a microangiopathic process distinct from immune-mediated TTP. Marked mesangial IgA/C3 codeposition despite normal circulating C3 raises the possibility that local complement activation may have amplified glomerular inflammation and endothelial injury. However, these findings are insufficient to establish complement-mediated TMA. The absence of active TMA lesions in a biopsy obtained later in the disease course likewise does not establish renal TMA, but cannot exclude a preceding transient or partially resolved microangiopathic process.  A distinctive feature was the substantial cumulative medication and supplement exposure preceding clinical deterioration. In the setting of pre-existing IgAN and a solitary functioning kidney, recurrent drug exposures may have constituted an external “second hit,” potentially promoting immune activation, endothelial stress, and clinical decompensation. The absence of a clear temporal relationship with a single agent, however, precludes attribution to definite drug-induced TMA. Collectively, this case supports a multifactorial, hypothesis-generating model: pre-existing IgAN in a solitary kidney → recurrent external/drug exposures as a potential “second hit” → possible local complement activation and endothelial injury → clinical–hematological TMA phenotype → rapid kidney function deterioration. This proposed sequence should not be interpreted as evidence of direct causality.
Clinical lesson: in patients with IgAN and rapidly deteriorating kidney function, particularly when anemia and thrombocytopenia develop, targeted evaluation for TMA and potential secondary triggers should be considered even when circulating C3 levels are normal.

ABSTRACT: Introduction: The development of amyloidosis in primary membranous nephropathy (PML) is extremely rare and is reported in medicine as isolated clinical cases. These two diseases have completely different development mechanisms. Primary membranous nephropathy is an autoimmune kidney disease caused by antibodies (most often to PLA2R receptors). Amyloidosis is a protein metabolism disorder in which abnormal fibrillar protein is deposited in tissues.
Case presentation: Patient M, woman, 69 years old.
Complaints: swelling throughout the body, decreased urine output, and increased blood pressure. History: In January 2026, the patient suddenly began to experience swelling throughout the body and decreased urine output. Due to the development of CHD, the patient received treatment in cardiology departments. Since the patient's condition did not improve for two months, the patient applied to nephrology center in May. Objective examination: Overall condition is moderately severe. Swelling is observed throughout the body. BP 110/70mmHg, HR-82bpm. BR-20bpm. Laboratory tests: CBC: Hemoglobin-125g/l, RBC-4.2, platelet-345.0, WBC-14.7, neutrophil-82, lymphocyte-9, ESR-14. Urine: color-yellow, protein-2.31g/l, epithelium-4, WBC-16, RBC-6, hyaline cylinder-8, granular-4. BA: 12.02.2026. Total protein-40.0, urea-5.4, albumin-23.0, creatinine-72.0. 17.02.2026. Total protein-37.0, albumin-22.0. 24.02.2026. Total protein-34.0, urea-5.0, albumin-16.0, creatinine-69.0. 10.03.2026. Total protein-32.0, albumin-17.0, creatinine-89.0. ANTI PLA2R-33.6 RU/ml (positive). Immunogram: CD3-44.38, CD4-61.69, CD8-35.06, CD19-21.61, CD16+-78.96, CD56+ -17.29. Compliment C3-1,19. C4-0.348.
The patient was diagnosed with primary membranous nephropathy because of the positive AntiPLA2R. Monoclonal antibody (rituximab) was chosen for pathogenetic treatment. The patient received 500 mg once a week for 4 weeks, a total of 2000 mg of the drug. However, the biochemical blood test showed no increase in total protein and albumin, the proteinuria hasn't decreased and the patient remained edematous. To clarify the diagnosis, the patient was recommended a kidney biopsy, and after the patient agreed, the procedure was performed (04.2026). Biopsy result: Kidney biopsy shows features of a deposit glomerulopathy with lambda immunoglobulin light chain restriction in glomeruli suggestive of an AL amyloidosis.
The patient was referred to a hematologist to confirm the diagnosis. The patient was diagnosed with Multiple myeloma from, System amyloidosis by hematologists. Then CyBorD (cyclophosphamide 400mg, bortezomid 2.5mg, dexamethasone 20mg) treatment was performed. The patient received 4 courses of chemotherapy. The patient's general condition improved clinically. Swelling throughout the body decreased. Laboratory tests showed hypoproteinemia and hypoalbuminemia. The patient's general condition improved over time. However, biochemical tests did not show an increase in total protein and albumin levels.

ABSTRACT: Background: Diabetic chronic kidney disease (DKD) is a leading cause of kidney failure and cardiovascular morbidity worldwide. Although albuminuria and estimated glomerular filtration rate (eGFR) remain central markers of risk stratification, early progression is frequently driven by a broader cluster of metabolic, hemodynamic, inflammatory, and cardiometabolic factors. Identification of simple clinical predictors may support earlier intensification of nephroprotective therapy. This study aimed to evaluate clinical, biochemical, and renal predictors associated with early DKD progression.
Methods: This prospective observational study included 112 patients with type 2 diabetes mellitus and established chronic kidney disease. Baseline assessment included age, sex, diabetes duration, body mass index, systolic and diastolic blood pressure, glycated hemoglobin (HbA1c), fasting plasma glucose, lipid profile, serum creatinine, eGFR, urinary albumin-to-creatinine ratio (UACR), hemoglobin, uric acid, C-reactive protein, smoking status, hypertension, obesity, dyslipidemia, and cardiovascular disease history. Early CKD progression was defined as clinically significant eGFR decline during follow-up. Patients were divided into early progression and stable/slow progression groups. Between-group comparisons and multivariable logistic regression were performed.
Results: Early DKD progression was observed in 34 of 112 patients (30.4%), while 78 patients (69.6%) had stable or slowly progressive disease. Patients with early progression had longer diabetes duration (12.8±4.1 vs 8.9±3.6 years; p<0.05), higher systolic blood pressure (148±16 vs 134±14 mmHg; p<0.05), higher HbA1c (8.7±1.1 vs 7.6±0.9%; p<0.01), greater UACR (286 [164–420] vs 118 [62–210] mg/g; p<0.01), and lower baseline eGFR (52.4±13.8 vs 64.7±15.2 mL/min/1.73 m²; p<0.05). Progressors also had higher body mass index (31.2±4.6 vs 28.7±4.2 kg/m²; p=0.006), triglycerides (2.3±0.7 vs 1.8±0.6 mmol/L; p<0.01 ), uric acid (421±76 vs 368±69 µmol/L; p=0.05), and C-reactive protein (5.8 [3.4–8.6] vs 3.1 [1.8–5.2] mg/L; p=0.002), with lower hemoglobin (118±14 vs 126±13 g/L; p=0.004). In multivariable analysis, independent predictors of early progression were UACR above 300 mg/g (odds ratio [OR] 3.42, 95% confidence interval [CI] 1.48-7.91; p=0.004), HbA1c at least 8.0% (OR 2.76, 95% CI 1.27-6.01; p=0.011), uncontrolled hypertension (OR 2.58, 95% CI 1.17-5.68; p=0.018), and hyperuricemia (OR 2.21, 95% CI 1.02-4.79; p=0.044).
Conclusion: Early DKD progression affected nearly one-third of patients. Albuminuria, poor glycemic control, uncontrolled hypertension, hyperuricemia, reduced baseline eGFR, obesity, dyslipidemia, inflammation, and anemia were associated with accelerated renal decline. These clinically accessible variables may improve early risk stratification and guide individualized nephroprotective management.

ABSTRACT: Background: Immunoglobulin A nephropathy is among the most commonly observed glomerular disorders. Its development is associated with immune dysfunction, which initiates a cascade of pathological changes within the glomeruli. The clinical course can range from minimal urinary abnormalities to progressive renal impairment, potentially culminating in end-stage kidney disease. Despite considerable advances in understanding its pathogenesis, optimal therapeutic strategies remain an active focus of scientific investigation.
Aim: To assess current and emerging therapeutic strategies for IgA nephropathy, with an emphasis on efficacy, safety, and the potential of targeted agents addressing key pathogenic pathways.
Methods: We conducted a narrative review of recent literature in PubMed, Scopus, Web of Science, and eLIBRARY databases, focusing on publications from the last decade. Studies published in English and Russian that reported results from clinical trials or meta-analyses on therapeutic interventions for IgA nephropathy were included. Search terms included «IgA nephropathy», «treatment», «targeted therapy», «new therapies», «immunosuppressants», and «clinical trials». Priority was given to randomized controlled trials and studies with high-quality evidence, though relevant observational data were also considered.
Results: Key studies identified included 52 publications, among which 20 were randomized clinical trials and a systematic review. Corticosteroid therapy remains a cornerstone of treatment but is limited by significant adverse effects. Recent therapeutic developments in IgA nephropathy have focused on interventions that selectively target inflammatory and immune pathways involved in disease progression. Certain novel agents aimed at modulating immune signaling or addressing pathogenic plasma cells have shown potential to reduce proteinuria and stabilize renal function. Early-phase clinical investigations indicate promising efficacy and manageable safety profiles, suggesting these approaches may represent important advances in disease management.
Conclusions: Recent progress in targeted and immunomodulatory therapies offers new perspectives for personalized treatment of IgA nephropathy. Comprehensive, large-scale randomized studies with extended follow-up are warranted to thoroughly assess the therapeutic potential, safety profile, and optimal positioning of these interventions within future clinical management strategies.

ABSTRACT: A 41-year old female patient who underwent kidney transplantation as an outcome of chronic glomerulonephritis came to the hospital with the signs of acute upper respiratory tract infection. As the patient further developed oliguria, peripheral edema, fever, and an increased BP, she was further relocated to the University Medical Center (UMC). Upon admission to UMC, signs of septic shock were detected, and acute transplant rejection was suspected, to exclude which kidney biopsy was performed and stage 3 chronic kidney disease (CKD) in allograft kidney was detected. Antibacterial treatment as well as pulse therapy were performed as patient had septic shock and tubulointerstitial nephritis (TIN).

ABSTRACT: The advent of targeted complement inhibitors represents a paradigm shift in managing complement-mediated nephropathies. Integrating these therapies into healthcare systems, particularly in resource-variable settings, requires strategic planning.
A national council of experts was convened in October 2024 with the purpose of obtaining a clinical expert opinion to develop practical recommendations for improving the organization and optimization of medical care for patients with C3 glomerulopathy (C3G) and IgA nephropathy (IgAN) in Kazakhstan.
The council identified critical systemic gaps, including inconsistent use of renal biopsy, lack of specialized nephropathology, absence of treatment algorithms, and fragmented patient care. A consensus was reached on key recommendations for a new national clinical protocol. These include mandating pathological confirmation, creating detailed treatment and monitoring algorithms, establishing a national registry and coordination center, and investing in specialized training for healthcare professionals.
The systematic framework proposed by the council provides an actionable roadmap to overcome barriers to care. This model ensures equitable patient access to novel therapies and may serve as a blueprint for other nations navigating the integration of advanced treatments into clinical practice.

ABSTRACT: A 46-year old male was admitted to the University Medical Center (UMC) hospital with the following symptoms of anuria, abdominal fullness, hypotension, exertional dyspnea, and peripheral edema. The purpose of his visit was the insertion of a peritoneal dialysis catheter. He had chronic kidney disease stage 5 as a consequence of diabetic nephropathy, liver cirrhosis due to hepatitis C infection, and HIV. His disease course was further complicated by the presence of a urinary tract infection. As a result of his multiple comorbidities, he underwent a complex treatment regimen which included renal replacement therapy with ultrafiltration, blood transfusions for his anemia, platelet transfusions for his thrombocytopenia, albumin infusion for his hypoalbuminemia, and antibiotic treatment for his concurrent infection. Additionally, he received diuretic treatment for his hypervolemia and anti-hypertensives to control his blood pressure. After peritoneal dialysis (PD) insertion, the patient successfully underwent PD and was discharged home.

ABSTRACT: Diabetic kidney disease (DKD) is a major complication of diabetes mellitus and the leading cause of end-stage renal disease (ESRD) worldwide. Despite considerable research efforts, the pathogenesis of DKD remains incompletely understood, largely due to its multifactorial etiology and pronounced phenotypic heterogeneity. Genome-wide association studies (GWAS) have identified over 40 loci associated with DKD; however, these common variants collectively explain only a small fraction of the disease’s heritability. Rare and low-frequency variants, often undetected by GWAS, are increasingly recognized as important contributors, and next-generation sequencing (NGS) technologies offer valuable tools for their identification. Kazakhstan, characterized by a unique genetic landscape and substantial ethnic admixture, remains underrepresented in DKD genomics research. Expanding integrative, high-resolution genomic studies in such settings is essential for identifying population-specific risk variants, improving diagnostic accuracy, and advancing precision medicine approaches to DKD prevention and management.