International Journal of Nephrology最新文献

Aim: This retrospective cohort study aims to evaluate the prognostic factors for progression of immunoglobulin A nephropathy (IgAN) to kidney failure (defined as the initiation of kidney replacement therapy or death) and all-cause mortality in an Australian population. Methods: We conducted a retrospective analysis of 363 individual patients with biopsy-proven IgAN over a 21-year period (2000-2020) in the Hunter Region of New South Wales. Demographic data, comorbidities, biopsy features and biochemical markers were collected for a minimum of 12 months following biopsy diagnosis. A multivariable analysis using Cox regression was performed to examine their association with renal progression. Results: A total of 104 patients met the inclusion criteria and were followed for a median of 72 months. The cohort had a mean age at presentation of 45 years, with a predominantly male population. Most patients presented with haematuria and non-nephrotic range proteinuria. We stratified patients into three risk categories: low risk, intermediate risk, and high risk. Twenty-eight patients (26.92%) developed kidney failure and 15 patients (14.4%) experienced a > 20 mL/min eGFR decline within the first 12 months. The multivariable analysis revealed the following key factors associated with kidney failure: additional renal pathology on biopsy (HR 3.90, 95% CI 1.63-9.29), proteinuria (HR 1.15, 95% CI 1.02-1.29) and moderate-severe interstitial fibrosis/tubular atrophy (T2) (HR 7.00, 95% CI 2.32-21.05). There were 17 deaths (16.3%) in the cohort, with a mean survival time of 167.8 months (95% CI 152.6-183.1). Conclusion: In contrast to earlier reports from Australia, our findings emphasise that the progression to kidney failure is not uncommon in IgAN. We identified several predictors of the renal progression that are consistent with the previous studies. This highlights the need for a change in clinical management, as IgAN should no longer be considered a benign condition.

Introduction: The experiences with preterm and low birth weight babies indicate a special vulnerability of their kidneys, since different kinds of noxae can evoke the termination of nephron formation. This leads to oligonephropathy, which is associated with serious consequences for health in the later stages of life. While the clinical aspects have been intensely investigated, only few pathological data point to the initial traces left by the noxae. Up to this date, only the reduction in the width of the nephrogenic zone (NZ) and the lack of here occurring basophilic S-shaped bodies were reported. Methods and Materials: The relationship between the arising nephron and its structural neighbors changes throughout the developmental progress. Locally, this determines the vertical width of the NZ reflected by the radial expansion of both the parenchyma and the interstitium. Since information about the origin, the site, and the involved structures is not available, the related microanatomical features were recorded. Results: The data reveal that the renal vesicles, comma-shaped bodies, and S-shaped bodies are unequally distributed in the NZ. Due to their progressive sizes, it has an influence on the local vertical width of the NZ. This parameter is registered as the distance between the inner side of the renal capsule and the proximal pole of the respective stage of the nephron anlage. The vertical width can be further subdivided: the constant height of the district of progenitor cell recruitment and the variable height of the area of nephron shaping. Exclusively here, the radial expansion of the shaping nephron stages can be noticed. It starts at the section border between the head and the conus of the related collecting duct ampulla by positioning the primitive renal vesicle. While the respective proximal pole stays mounted next to the connecting tubule of a previously developed nephron, the distal pole sticks between the head and the conus at the CD ampulla for linking the future connecting tubule. This causes that henceforth the medial aspect of the extending renal vesicle, comma-shaped body, or S-shaped body stages radially expands in close proximity to the elongating conus of the CD ampulla. Conclusion: Between the arising nephron stages and the elongating conus of the CD ampulla, a linked radial expansion occurs. This new finding is essential to identify the extent of targeting of noxae that subsequently leads to a reduction in the width of the NZ.

Background: Vascular calcification (VC) is a common complication of chronic kidney disease, ultimately leading to high morbidity and cardiovascular mortality. In this study, we investigated the effects of the calcimimetic R568 in an in vitro model of human vascular smooth muscle cell (VSMC) calcification. Methods: Human VSMCs were cultured under elevated calcium (2.4 mmol/L) and phosphate (2.7 mmol/L) concentrations. Calcification was analyzed using von Kossa staining and colorimetric calcium measurement. Intracellular signaling was examined via Western blot, and apoptosis was assessed by the TUNEL assay. Results: Treatment with R568 significantly reduced VC over the 9-day treatment period. R568 treatment led to increased phosphorylation of extracellular signal-regulated kinase (ERK 1/2) compared to the control group. Calcimimetic treatment was also associated with a reduction in apoptosis. Blocking ERK 1/2 phosphorylation completely abolished the inhibitory effects of R568 on VC. Conclusion: Our study provides new insights into the mechanism of action of calcimimetics during VC and highlights the importance of ERK 1/2 signaling in this process.

Background and Objectives: Chronic kidney disease (CKD) remains a public health threat and a major cause of morbidity and mortality worldwide. A bidirectional relationship is found between sleep disorders and CKD worldwide. However, to our knowledge, this study is the first to assess the prevalence of obstructive sleep apnea (OSA) and to evaluate its impact on the progression of other comorbidities among Lebanese patients with CKD. Materials and Methods: The study is an observational cross-sectional study, carried out between September and November 2021. Lebanese patients with any stage of CKD were included. Patients' characteristics were collected via electronic health record and baseline questionnaires. We screened for obstructive sleep apnea using the STOP-Bang questionnaire. Results: We included 168 patients. The prevalence of OSA among our patients was 47.6%. The prevalence of OSA is higher in males compared with females (81.2% vs. 18.8%, p=0.002). Obesity was more prevalent in patients with OSA compared with patients without OSA (42.5% vs. 19.3%, p=0.002). Among the 168 patients, 69.6% had hypertension, with a significantly higher prevalence among those with OSA compared with those without OSA (81.2% vs. 59.1%, p=0.003). Patients with OSA reported significantly lower scores compared with those without OSA in several domains of physical and emotional health, including physical functioning (54.06 vs. 66.88, p=0.002), role limitations due to physical health (42.19 vs. 63.07, p=0.001), role limitations due to emotional problems (49.17 vs. 69.32, p=0.004), pain (61.31 vs. 70.45, p=0.019), and physical component score (52.53 vs. 69.53, p=0.002). All the abovementioned parameters were also examined in two subpopulations: patients with CKD and ESRD. Similarly, some comorbidities and a lower physical QOL score were observed more in patients with OSA in these two subpopulations. Conclusion: Patients with OSA in our study have higher probability of being male, obese, and hypertensive as well as poorer QOL compared with their counterparts without OSA. Implementing more effective screening and treatment of OSA in CKD patients is necessary.

Introduction: Medical research shapes public health actions, emphasising the need for greater investments in health. Despite a surge in scientific publications, disparities exist in authorship from low-income countries and among female researchers. Addressing these gaps is vital for studying real-world health outcomes and promoting universal healthcare delivery. Methods: A descriptive quantitative study using an online questionnaire to gather data from Indian nephrologists and nephrology fellows was conducted by members of Women in Nephrology, India, from September 2023 to December 2023. The survey collected data on demographics, publication experience and challenges in scientific paper writing. Statistical analyses were performed using SPSS Version 25.0, with significance at p < 0.05. Results: The survey included 156 participants, with a mean age of 35.55 ± 8.91 years. The majority were males (55.8%) and practicing nephrologists (69.9%). Most respondents practiced in medical institutions (45.5%) and metropolitan cities (60.3%), with an average practice duration of 12.29 ± 9.12 years. Only 44.9% published their thesis work, and 52.6% preferred writing case reports. Key challenges included time constraints (82.1%), funding (67.9%), limited access to research articles (65.4%), lack of statistical analysis knowledge (64.7%) and limited access to research software (60.2%). Younger nephrologists faced more funding (68.9%) and knowledge-related barriers (74.4%). Discussion: Multiple challenges exist in scientific paper writing among Indian nephrologists, emphasising the need for targeted interventions. Funding for research, burnout and article processing charges are significant barriers. Addressing these challenges is crucial for enhancing research output and improving healthcare outcomes in resource-limited countries.

The increasing prevalence of elderly patients with end-stage kidney disease (ESKD) poses unique challenges in nephrology. These patients often present with multiple comorbidities, cognitive impairments, and frailty, which significantly impact treatment options and outcomes. Conservative kidney management (CKM) offers a viable alternative to dialysis for many elderly patients by focusing on symptom management and enhancing quality of life rather than merely prolonging life. However, clinicians face difficulties in approaching patients and deciding between CKM and dialysis. In addition, advocating for dialysis involves challenges in selecting the appropriate modality and vascular access. Nutritional management, often overlooked, is critical due to the high prevalence of protein-energy wasting and sarcopenia among elderly dialysis patients. Similar to the initiation of dialysis, there are dilemmas in determining when to withdraw from dialysis. This practical review aims to guide clinicians through the complex and challenging process of managing dialysis in the elderly, emphasizing a holistic, patient-centered approach that prioritizes quality of life. A multidisciplinary strategy, integrating clinical expertise and patient autonomy, is essential to address the complex needs of this vulnerable population.

Aims: The outcome of acute kidney injury (AKI) depends on causes, patient factors and care received. We studied the causes, complications and 90-day outcomes of patients with AKI at a tertiary referral centre in Sri Lanka. Methods: Patients aged 18 years or older with AKI referred to nephrology services were analysed retrospectively. AKI severity was assessed using the KDIGO classification. Information was gathered from hospital and clinic records. Results: Of the 464 patients studied, 262 (56.5%) were males. The mean age of the study sample was 57.04 (SD 16.85) years. The majority (212-45.69%) were discharged with normal renal functions, 173 (37.28%) were discharged with impaired functions, and 79 (17.03%) died during hospital stay. There were 377 patients at 3 months follow-up; 331 (87.8%) had normalised renal function, 40 (10.6%) had not recovered fully and 6 (1.6%) had succumbed. Progression of AKI to chronic kidney disease or death was significantly high in patients aged > 60 years (p=0.017). More severe AKI was associated with type 2 diabetes (p=0.0042), hypertension (p < 0.0001) and multiple comorbidities (p=0.0014). Persons with no comorbidities had less severe AKI (p=0.0004). Even in the early stages of AKI, there was significantly high mortality (11% in AKI stages 1 and 2) which doubled in stage 3 (22%). Mortality was low in patients with prerenal causes of AKI (OR: 0.59, 95% CI: 0.35-0.99 and p=0.047). Conclusions: AKI in elderly and comorbid patients has high morbidity and mortality. Identification of individuals who are at high risk of developing AKI is important for its prevention, early diagnosis and proper treatment. Limitations in infrastructure, manpower, local research, reporting and recording of AKI are key challenges in providing optimal care for AKI in Sri Lanka.

Background: Thrombotic microangiopathy is a severe complication of renal transplantation. Little is known about risk factors, incidence of autoantibodies against complement components, and prognosis. Methods: Clinical and laboratory data were retrospectively collected for 13 patients diagnosed with post-transplant thrombotic microangiopathy (PT-TMA) in 2011-2018. Enzyme-linked immunosorbent assay (ELISA) results were compared to transplant recipients without PT-TMA and healthy controls. Results: Nine patients (69%) had potential PT-TMA risk factors other than exposure to calcineurin inhibitors (CNIs). Stratification by time to PT-TMA yielded two groups. Patients diagnosed within 6 months of transplantation (n = 6) were characterized by positive donor-specific antibody (DSA) test, complement-associated renal disease, and acute rejection. Two had IgG and IgA autoantibodies to complement Factors H and I, respectively. Patients diagnosed ≥ 3 years after transplantation (n = 7) had a high rate of infection. Renal biopsy yielded dense deposits in 6 patients, and only one with primary immune complex renal disease. Within 2 years, graft failure requiring dialysis occurred in 6 patients (46%). Three patients with early-onset PT-TMA showed improved renal function and remained stable under eculizumab treatment. Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorder (EPTLD) developed in 3 patients, 2 of whom had received eculizumab for more than 5 years. Five patients (39%) died during follow-up. Conclusion: In this study, PT-TMA was associated with other risk factors besides CNI exposure, with differences by time of onset from transplantation. Prognosis was generally poor but better for early-onset PT-TMA managed with eculizumab. The development of late EPTLD in 3 patients raises concerns.

Background: Sepsis-associated acute kidney injury (AKI) is a condition that increases in-hospital mortality and the risk of progression to CKD. The current method of detecting AKI, which relies on increased serum creatinine levels or a decrease in urine output, has low sensitivity. Early diagnosis and appropriate intervention in AKI can lead to improved patient outcomes. Several low molecular weight proteins and microRNAs detected in AKI are considered early biomarkers of AKI, such as miR-10a-5p and miR-210-3p. Method: A cross-sectional study was conducted among 62 participants, consisting of 26 sepsis patients with AKI, 26 sepsis patients without AKI, and 10 healthy controls. AKI was determined according to KDIGO criteria. MicroRNA expression was analyzed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Statistical analysis was obtained using the Kruskal-Wallis test, Spearman's correlation coefficient, and ROC curve analysis. Result: The median miR-10a-5p expression of the healthy controls versus sepsis with AKI versus sepsis without AKI groups was 10.38 (5.50-33.82) versus 10.32 (3.32-31.53) versus 9.76 (0.32-97.36), while the median miR-210-3p expression was 0.20 (0.03-0.41) versus 0.38 (0.04-1.24) versus 0.29 (0.06-1.67), respectively, with p = 0.721 for miR-10a-5p and p = 0.013 for miR-210-3 p. A significant increase in miR-210-3p expression was found in the sepsis with AKI compared to the healthy controls (p = 0.013) and sepsis without AKI (p = 0.034). miR-210-3p significantly correlated with creatinine and urea serum level (p < 0.05); miR-10a-5p did not have a significant correlation. The sensitivity and specificity of miR-10a-5p were 61.5% and 47.2%, and miR-210-3p were 84.6% and 63.9% for determining AKI. Conclusion: The study's findings revealed a significant increase in miR-210-3p expression in sepsis patients with AKI, indicating its potential as a promising biomarker for determining AKI. This discovery demonstrates that the diagnostic performance of miR-210-3p surpasses that of miR-10a-5p, providing a more accurate biomarker for diagnosing AKI in sepsis patients.

Background and Objectives: Soluble alpha Klotho (s.Klotho) is an emerging marker for chronic kidney disease (CKD) prognosis. The objective was to study the association between s.Klotho and CKD-related decrease in glomerular filtration rate (GFR), bone and vascular damage. Method: A total of 118 patients with CKD stage 2-4 were enrolled and 107 patients continued in the study. Clinical and laboratory parameters were recorded at time of enrollment and 12 months. A double sandwich ELISA for s.Klotho was recorded in controls (n = 25) and patients' serum samples at 6 months (n = 107) and 12 months (n = 102). Primary endpoints like 40% or more fall in GFR, a requirement for renal replacement therapy (RRT), and death with different grades of s.Klotho deficiency were studied. Results: Of the 107 patients (80 male and 27 female), mean s.Klotho was 3.46 ng/mL (02.3-04.2). The GFR fall was significantly different (p value < 0.0001) in the different grades of s.Klotho deficiency with Grade 4 s.Klotho deficiency (0.1-2.99 ng/mL) having the maximum fall of GFR at 9.2 mL/min/1.73 m² (04.8-12.0) and minimum in Grade 2 (3-5.99 ng/mL) at 1.35 mL/min/1.73 m2 (03.0-02.75). The Ankle Brachial Pressure Index positively correlated with s.Klotho and the correlation coefficient was 0.536 (0.382-0.662) (p < 0.001). The carotid intimal medial thickness negatively correlated with s.Klotho and the correlation coefficient was -0.712 (95% CI: -0.797--0.601, p < 0.001). All five deaths had s.Klotho Grade 4 (severe) deficiency. The event-free survival rate was maximum (100%) in Grade 2 Klotho deficiency and lowest (55%) in Grade 4 s.Klotho deficiency. Conclusions: s.Klotho levels decreased significantly in patients with progressive kidney failure. s.Klotho levels significantly correlated with the presence of vascular disease. Death and need for RRT were significantly more in patients with severe s.Klotho deficiency.