Nephrology最新文献

Complement 3 glomerulonephritis (C3GN) is a rare glomerular disease involving dysregulation of the complement system. We describe our experience using pegcetacoplan, an inhibitor of C3 and its activation fragment, C3b, for treatment-resistant C3GN in a 9-year-old boy referred for evaluation of refractory membranoproliferative glomerulonephritis. Despite treatment with intense immunosuppression (high-dose steroids, mycophenolate mofetil and calcineurin inhibitor), he continued to have high disease activity with low C3 levels (35 mg/dL), hypertension, symptomatic oedema, anaemia, and nephrotic-range proteinuria (e.g., urine protein-to-creatinine ratio [uPCR], 10 g/g; serum creatinine, 0.4 mg/dL). Given the concern for refractory C3GN following a steroid taper and tacrolimus trial with modest response (reduced proteinuria), we initiated pegcetacoplan 540 mg twice weekly for 1 week, followed by 648 mg twice weekly. Laboratory values before pegcetacoplan initiation included uPCR, 1.1 g/g, serum creatinine, 0.87 mg/dL, serum albumin, 4.7 g/dL, and serum C3, 30 mg/dL. Clinically significant improvements in serum C3 (142 mg/dL) and uPCR (422 mg/g) were observed within 1 week of pegcetacoplan initiation; within 3 months (uPCR, 322 mg/g; serum creatinine, 0.69 mg/dL; serum C3, 297 mg/dL), all immunosuppressive and antihypertensive medications were discontinued. No adverse effects of pegcetacoplan were reported. A kidney biopsy after 6 months of pegcetacoplan treatment showed mesangial and focal endocapillary proliferative glomerulonephritis with isolated C3c deposition by immunofluorescence, consistent with previous C3GN diagnosis. In this paediatric patient, compassionate use of pegcetacoplan was associated with rapid clinical improvement without adverse effects, and clinical effectiveness was confirmed by laboratory and histologic results within 6 months of treatment initiation.

Aim: National data registries provide a valuable source of data for epidemiological research but may be subject to inaccuracies. Whilst studies have compared agreement between cause of death (COD) data from Australia and New Zealand's dialysis and transplant registry (ANZDATA) to other databases, no studies have manually compared agreement with electronic medical records (EMR). This study aimed to assess the agreement between COD for dialysis patients in the Western Sydney renal service according to ANZDATA and EMR.

Methods: We conducted a retrospective cohort study on dialysis patients from the Western Renal Service who died between January 1, 2016 and July 31, 2022, inclusive. We matched ANZDATA patient records to our service's EMR, extracted data on COD from EMR and coded COD according to ANZDATA's categorisation system. Agreement between COD from EMR and ANZDATA was assessed using kappa statistics.

Results: There were 709 deaths in the study period. 449 (63.3%) were male and 260 (36.7%) were female. Of the 539 patients with available records, the most common COD categories were cardiovascular (201, 37%) and infection (154, 29%). There was poor agreement between individual COD from EMR and ANZDATA (kappa of 0.39). However, this improved when comparing broader COD categories (kappa of 0.53). Subgroup analysis showed no difference in agreement between males and females or patients who died between 2016-2018 and 2019-2022.

Conclusion: There is poor agreement between ANZDATA and EMR for individual COD. However, agreement improved to moderate using broader categories of COD, suggesting higher accuracy when utilising registry COD data for epidemiological analysis.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

The case report presents a male patient in his mid-60s with a history of hypertension, benign prostatic hyperplasia and chronic kidney disease (CKD). He presented with gradually increasing serum creatinine levels and hyperglobulinemia, leading to suspicion of multiple myeloma. However, subsequent testing revealed features consistent with systemic lupus erythematosus (SLE) and IgG4-related kidney disease (IgG4-RKD). The patient's laboratory results included anaemia, positive ANA and anti-dsDNA and elevated serum IgG4 levels. A kidney biopsy showed extensive interstitial fibrosis, plasma cell infiltration and a high number of IgG4-positive plasma cells, suggesting the diagnosis of IgG4-RKD overlapping with SLE. Treatment involved prednisolone, mycophenolate mofetil for IgG4-RKD and hydroxychloroquine for SLE. The patient's case highlights the challenges in diagnosing overlapping IgG4-RKD and SLE. The current criteria for diagnosing these diseases may be complicated by atypical presentations, leading to potential diagnostic confusion. This report underscores the importance of histopathological confirmation and comprehensive diagnostic criteria to differentiate between overlapping autoimmune conditions. Immunosuppressive therapy remains the cornerstone for managing both IgG4-related disease and SLE, with treatment tailored based on disease severity and organ involvement. The patient's response to treatment and follow-up monitoring are crucial for assessing outcomes and adjusting management to minimise disease relapse and therapy-related complications.

Aim: Henoch-Schönlein purpura (HSP) nephritis leads to end-stage renal disease (ESRD) in upto 3% of cases, necessitating kidney transplantation (KT). This study compared graft and patient survival outcomes between HSP and non-HSP KT recipients and identified factors associated with HSP recurrence.

Methods: Data from the Scientific Registry of Transplant Recipients (SRTR) were analysed for adult and paediatric KT patients listed between January 2005 and April 2021. HSP recipients were extracted from the database and non-HSP recipients were selected and propensity-matched 3:1 based on demographic factors.

Results: A total of 371 KT recipients with HSP were matched to 1113 non-HSP recipients. When stratified by age, adult and paediatric HSP patients showed similar death-censored graft survival (DCGS) at 5 years compared to their non-HSP counterparts. Furthermore, paediatric patients with HSP had comparable DCGS to adult HSP patients at 5 years (86.5% vs. 88.3%, p = 0.221). Amongst HSP recipients, 27.2% experienced recurrence, with higher rates in adults (29.7%) compared to children (13.0%). Recurrent HSP was associated with increased graft failure and mortality. Regression analysis showed that older age (OR [95% CI]: 1.018 (1.001-1.035), p = 0.037) was associated with a higher risk of recurrence, while a higher BMI (0.95 [0.91-0.99], p = 0.020) was linked to a lower risk.

Conclusion: In a contemporary cohort of HSP KT patients, graft survival was comparable between HSP and matched non-HSP patients in both adult and paediatric groups. However, graft loss was more frequent in HSP patients who experienced disease recurrence.

Chronic kidney disease is characterised by the progressive loss of kidney function. However, predicting who will progress to kidney failure is difficult. Artificial Intelligence, including Machine Learning, shows promise in this area. This narrative review highlights the most common and important variables used in machine learning models to predict progressive chronic kidney disease. Ovid Medline and EMBASE were searched in August 2023 with keywords relating to 'chronic kidney disease', 'machine learning', and 'end-stage renal disease'. Studies were assessed against inclusion and exclusion criteria and excluded if variables inputted into machine learning models were not discussed. Data extraction focused on specific variables inputted into the machine learning models. After screening of 595 articles, 16 were included in the review. The most utilised machine learning models were random forest, support vector machines and XGBoost. The most commonly occurring variables were age, gender, measures of renal function, measures of proteinuria, and full blood examination. Only half of all studies included clinical variables in their models. The most important variables overall were measures of renal function, measures of proteinuria, age, full blood examination and serum albumin. Machine learning was consistently superior or non-inferior when compared to the Kidney Failure Risk Equation. This review identified key variables used in machine learning models to predict chronic kidney disease progression to kidney failure. These findings lay the foundations for the development of future machine learning models capable of rivalling the Kidney Failure Risk Equation in the provision of accurate kidney failure prediction.

Chronic kidney disease (CKD) prevalence varies widely across different regions of India. We aimed to identify the status of CKD in India, by systematically reviewing the published community-based studies between the period of January 2011 to December 2023. PubMed, Scopus, and EMBASE were searched for peer-reviewed evidence. Records identified for full-text screening were imported into the Litmaps literature review tool to identify more relevant studies. Two researchers independently examined and retrieved the data. Quality assessment was conducted using the JBI tool for prevalence studies. A random effects model pooled the estimates. Subgroup analysis, meta-regression and sensitivity analysis explored heterogeneity sources and estimated robustness. Publication bias was assessed with a DOI plot and LFK index. Among the 7062 records identified, 18 studies were included in this review. The pooled prevalence of CKD from community-based studies in India was 13.24% (confidence intervals (CI) 10.52 to 16.22, I² 99%, p < 0.001). CKD prevalence among men was 14.80%, while among women it was 13.51%. Southern administrative zone had a pooled CKD prevalence of 14.78%. Pooled CKD prevalence was higher in studies from rural areas (15.34%) compared to those from urban areas (10.65%). Significant heterogeneity was found. Subgroup analyses based on sampling strategy, quality score, publication year, and eGFR estimation equation showed no effect on the pooled prevalence. Prediction Intervals confirmed CKD prevalence in India in future studies will fall between 2.64% and 30.17%. This review indicates a rising trend of CKD (from 11.12% during the period 2011 to 2017, to 16.38% between 2018 to 2023) among Indians aged 15 years and above, over the past years. More future regional research is needed to tailor-make CKD interventions to detect early and manage well.

Aim: Proteinuria commonly accompanies acute ischaemic stroke (AIS) patients undergoing reperfusion therapies such as intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT). Understanding its influence on outcomes is crucial for prognosis and optimising management strategies. This study aims to elucidate proteinuria's role in mediating outcomes among reperfusion-treated patients.

Methods: Through a random-effects meta-analysis, we analysed data to assess the association of proteinuria with functional outcomes, symptomatic intracerebral haemorrhage (sICH) and mortality. A total of 33 140 patients were included in the meta-analysis.

Results: Proteinuria demonstrated a pooled prognostic sensitivity of 58% (95% CI: [48%; 67%]; p < 0.001) for poor functional outcomes at 90 days. It was linked with increased odds of unfavourable functional outcome at 90 days in both IVT (OR 2.27; 95% CI: [1.95; 2.66]; p < 0.001) and EVT (OR 2.57; 95% CI: [2.16; 3.05]; p < 0.001) groups. Furthermore, it was associated with increased odds of 90-day mortality in IVT-treated patients (OR 2.31; 95% CI: [1.76; 3.02]; p < 0.001), while EVT-treated patients exhibited increased odds of in-hospital mortality (OR 2.71; 95% CI: [1.22; 6.04]; p < 0.05).

Conclusions: The clinical significance of proteinuria is underscored by its impact on outcomes for AIS patients receiving reperfusion treatments. This awareness may guide individualised treatment by considering the intricate interplay between kidney function and its correlation with stroke. Consequently, this has the potential to improve prognosis and overall outcomes in AIS therapy.

Aim: Autosomal recessive primary hyperoxalurias (PH) are genetic disorders characterised by elevated oxalate production. Mutations in genes involved in glycoxylate metabolism are the underlying cause of PH. Type 1 PH (PH1) results in malfunctioning of alanine-glyoxylate aminotransferase enzymes of liver due to a change in the genetic sequence of alanine-glyoxylate aminotransferase (AGXT) gene. We encountered a large family segregating genetic disease of high oxalate kidney stones. A genetic analysis was carried out with the aim to identify underlying genetic defect.

Methods: A large family with multiple affected individuals was recruited for this study. An extensive clinical evaluation, followed by genetic analysis, was carried out. Due to the heterogeneous nature of the disease, two members of the family having disease symptoms were subjected to whole exome sequencing (WES). Variants were annotated, filtered, and prioritised using various bioinformatic tools to detect disease associated genetic defects.

Results: Unbiased and hypothesis-free WES data analysis was performed. Raw reads (fastq files) were mapped to the reference genome and duplicates were removed. Variants were annotated, filtered, and prioritised. A low-frequency missense variant (c. 1049G>A) in the AGXT gene was considered the candidate variant. This variant replaces the highly conserved glycine amino acid with aspartate (p.Gly350Asp). The variant is destabilising for protein-protein interaction based on predicted change in binding free energy (ΔΔG). All members having disease phenotype were found homozygous to the mutation. Both parents and unaffected individuals in a family are heterozygous for the variant.

Conclusion: Identification of pathogenic variant in the AGXT gene, in this family, provides genotype-phenotype correlation and permits accurate clinical diagnosis as well as carrier detection. Moreover, this variant extends the AGXT mutation spectrum in a different population and highlights the clinical significance and diagnostic relevance of the variant.

Prevention of end-stage kidney disease (ESKD) is a major objective in the management of patients with lupus nephritis (LN). Chronic kidney disease (CKD) of variable severity is common in these patients, but recent literature has mostly focused on novel immunosuppressive treatments for acute LN, while the data on CKD is relatively limited. This scoping review aims to summarise available data on the prevalence and risk factors for CKD in patients with LN. PubMed and Web of Science databases were systematically searched on the 1st November 2024 for 'real world' SLE and LN cohorts with longitudinal follow-up which reported the outcome of CKD or CKD progression and its associated risk factors. Fifteen studies were included. The prevalence of CKD ranged from below 10% to almost 50% across diverse LN and SLE cohorts. Major risk factors for CKD or CKD progression included renal impairment at presentation, renal function at 1 year post-treatment, delayed diagnosis, established chronic pathological lesions on kidney biopsy, unsatisfactory treatment response, nephritic flares, hypertension, and persistent proteinuria during follow-up. Many of the identified risk factors are amenable to therapeutic intervention. CKD not only contributes to morbidity and mortality and inferior quality of life, but also influences the choice of therapy and optimal dosing of medications. Attention to immunomodulatory medications for disease control, and non-immune strategies for renoprotection and prevention of CKD complications, are both important in the management of patients with LN to reduce their life-time risk of ESKD.