Kidney360最新文献

Background: The presence of lymphoid tissues and their impact on long-term kidney graft outcome remains unclear. This study investigates the occurrence, molecular and phenotypic characteristics of lymphoid aggregates (LA) in protocol biopsies of clinically stable kidney transplant recipients, and their correlation with long-term clinical outcome.

Methods: We retrospectively analyzed 414 protocol biopsies from a multicenter cohort of 278 stable kidney transplant recipients taken at either 6-, 12- or 24-months post-transplant. On a subset of 16 biopsies at 6 months post-transplant, mRNA gene expression analysis was performed using Nanostring B-HOT panel alongside phenotypic analysis with immunostaining for developmental staging of LA. Finally, the presence of LA was correlated to various clinical kidney allograft outcomes.

Results: Stage I LA were characterized by upregulation of genes linked to immune regulation (LAG3, CTLA4, FOXP3), T-cell signaling, and chemotaxis pathways, with enrichment of regulatory T cells (Tregs), memory T cells, T follicular helper cells (Tfh), and dendritic cells. Immunohistochemistry confirmed higher numbers of FOXP3+ Tregs and dendritic cells in stage I LA, while high endothelial venules were absent. Over follow-up, participants with stage I LA showed slightly higher eGFR values and a trend toward better graft survival compared with those without LA or with stage II LA, although most differences did not reach statistical significance.

Conclusions: In stable kidney transplant recipients, stage I LA displayed molecular and phenotypic features consistent with a regulated immune environment. The molecular and immunohistochemical analysis of stage I LA suggests a more regulatory molecular phenotype and composition, which may contribute to better long-term graft survival observed in this cohort of functionally stable transplant recipients. Observed trends toward more favorable outcomes suggest that early LA may not be deleterious and could represent local immune regulation, though larger prospective studies are needed to confirm these findings.

Cisplatin remains a key chemotherapy for many solid tumors, but its dose-limiting nephrotoxicity affects up to one-third of patients and has no effective pharmacologic prevention beyond hydration and magnesium supplementation. Preclinical studies highlight sodium-glucose cotransporter 2 (SGLT2) inhibitors as promising nephroprotective agents during cisplatin therapy, independent of glucose lowering. We conducted a PubMed search using predefined terms related to cisplatin nephrotoxicity and SGLT2 inhibitors, identifying seven non-diabetic rodent studies. Across these models, SGLT2 inhibitors consistently attenuated kidney injury through complementary mechanisms: suppression of inflammatory, oxidative, and apoptotic pathways, activation of AMP-activated protein kinase-dependent autophagy, reduction of kidney platinum accumulation, and, uniquely, correction of cisplatin-induced hypomagnesemia, a clinically significant complication. Protective effects occurred without compromising cisplatin's antitumor efficacy in vitro. Overall, these findings support SGLT2 inhibitors as a mechanistically versatile strategy that targets key injury pathways in platinum nephrotoxicity. Although prospective clinical application remains untested, the strong biologic rationale, reproducibility across models, and established safety of SGLT2 inhibitors in other populations underscore the urgency of translation. Future clinical trials should incorporate rigorous assessments of kidney function, tubular injury biomarkers, and urinary extracellular vesicle profiling to define the safety, efficacy, and mechanistic insights of SGLT2 inhibitors in cisplatin nephrotoxicity.

Background: Over the past decade, machine learning (ML) has transformed histopathology, yet its application in lupus nephritis (LN) remains underexplored. Earlier reviews have centered on pathologist concordance in LN classification, biomarkers, and AI-enabled diagnosis and treatment-response prediction. Here, we conducted the first comprehensive scoping review of ML in LN, spanning across diagnosis, risk of renal flare, remission, treatment response prediction, and LN disease classification tasks.

Methods: PubMed and Scopus databases were searched for peer-reviewed studies published between January, 2000 and April, 2025 that applied ML to histopathological or clinical data in LN. Inclusion criteria encompassed any supervised or unsupervised ML approach addressing diagnosis, renal flare, treatment response, remission prediction, or LN disease classification. Two reviewers independently screened titles, abstracts, and full texts.

Results: Of 20 qualifying studies, 12 met the inclusion criteria. Additionally, through manual citation and reference screening we added eight more. A large set of studies (n = 11) are focused on tackling mainly histologic subtyping diagnosis and LN classification. Following this, two studies focused on developing renal flare prediction models leveraging traditional ML models and deep learning (DL) models. Moreover, three studies focused on developing remission prediction models (n = 3) using both clinical and histological data. Finally, four studies addressed treatment response prediction employing ML and DL using laboratory results, urinary biomarkers, and histology data.

Conclusions: ML has shown promise across multiple LN related tasks, from diagnosis to prognosis. To accelerate clinical translation, future efforts should prioritize larger multicenter, multimodal datasets, standardized annotation protocols, rigorous external validation, integration of explainable AI techniques, usage of whole slide image data, multi-omics data, development of webtools, use of advanced agentic AI, and digital twins to develop personalized actionable items in patients.

Background: Desmopressin has a theoretical rationale to reduce procedural bleeding risk but results from randomized controlled trials are mixed.

Methods: PubMed, EMBASE, and Google Scholar were searched on October 27, 2025 to identify studies evaluating Desmopressin administered prior to kidney biopsy. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. Statistical analysis was performed using RevMan software to calculate Odd's Ratios and assess heterogeneity with the I2 statistic. Publication bias was assessed with Egger's test. A sensitivity analysis was performed due to heterogeneity via the leave-one-out method with revised estimated odds presented thereafter.

Results: 17 studies including 5394 participants were analyzed. The pooled estimated odds ratio (OR) for total bleeding was 0.89 [0.59 - 1.36], p = 0.60, I2 = 85%. In subgroup analysis the pooled estimated OR for subcutaneous administration was 0.37 [0.21 - 0.65], p < 0.001, I2 = 0%); intravenous administration was 1.47 [1.05 - 2.05], p =0.03, I2 = 61%; intranasal administration was 0.68 [0.30 - 1.56], p = 0.37, I2 = 87%; and estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2 was 0.74 [0.40 - 1.37 p =0.34, I2 = 81%. After sensitivity analysis the revised OR for intranasal administration was 0.42 [0.31 - 0.59], p <0.001 and for eGFR < 60 was 0.55 [0.38 - 0.81], p = 0.002. The pooled estimated OR for severe hyponatremia was 3.85 (95% CI [2.12 - 7.00], p <0.001, I2 = 33%.

Conclusions: Overall there was no reduction in odds of bleeding but with high between-group heterogeneity. There were lower odds of bleeding in the intranasal and subcutaneous administration subgroups. Desmopressin resulted in higher odds of hyponatremia.

Background: Sodium zirconium cyclosilicate (SZC) and patiromer have recently been approved for the treatment of hyperkalemia. However, their efficacy in lowering serum potassium according to the phase of intervention, safety profile, and impact clinical outcomes remains to be fully defined. This study aims to assess their efficacy and tolerability in the management of hyperkalemia.

Methods: A comprehensive search of PubMed, Scopus, and CENTRAL was conducted up to June 6, 2025. Eligible studies included randomized controlled trials (RCTs) reporting the effects of SZC and patiromer on laboratory parameters, clinical outcomes, and safety profiles. Meta-analyses were synthesized using a random-effects model, with results presented as weighted mean differences (WMD) or relative risks (RR), along with 95% confidence intervals (CI).

Results: Nineteen RCTs involving 3,627 patients (1,911 on SZC; 1,716 on patiromer) were analyzed. During the initial 48-72 hours, only SZC significantly reduced serum potassium levels (WMD: -0.45 mEq/L; 95% CI, -0.61 to -0.29). At the end of treatment, both agents effectively lowered serum potassium (SZC: WMD -0.50 mEq/L; 95% CI, -0.63 to -0.38; patiromer: WMD -0.36 mEq/L; 95% CI, -0.51 to -0.21). SZC significantly normalized serum potassium and reduced hyperkalemia incidence, while patiromer enabled renin-angiotensin-aldosterone system (RAAS) inhibitor optimization by supporting target dosing and reducing discontinuation due to hyperkalemia. However, SZC was associated with a higher incidence of edema (RR: 2.92; 95% CI, 1.08-7.90), and patiromer with increased rates of constipation (RR: 2.96; 95% CI, 1.21-7.22) and hypokalemia (RR: 1.46; 95% CI, 1.05-2.03).

Conclusions: Both SZC and patiromer effectively lower serum potassium and provide clinical benefits, with distinct safety considerations. Therapy selection should be guided by treatment goals and the patient's individual risk profile.

Background: Polycystic kidney disease (PKD) encompasses a group of genetic disorders characterized by the proliferation of fluid-filled renal cysts, leading to progressive renal failure and death. A key feature of PKD is its variable expressivity across patients, even when caused by the same variant, highlighting the importance of genetic background in PKD expression.

Methods: We identified an ostensibly healthy Sprague Dawley rat line with a variant that modifies PKD expressivity in Han:SPRD-Cy rats (caused by a missense variant [p.Arg717Trp] in the ankyrin repeat and sterile alpha motif domain-containing 6 [Anks6] gene), which we named mcy (modifier of Cy). We used whole genome sequencing and segregation analysis to identify the mcyvariant, quantitative PCR and mRNA sequencing to evaluate its effects on gene expression, western blotting and immunohistochemistry to assess its protein consequences, and ultrasound and histology to examine its impact on rat embryonic development.

Results: We identified a nonsense variant in the Anks6 gene as the genetic basis of the mcy phenotype (c.1126G>T [p.Glu376X]). While mcy+/- rats are ostensibly healthy and do not develop PKD, mcy-/- rats exhibit laterality defects and die prenatally at E16.5 due to apparent perturbations in cardiovascular development. Notably, mcy+/-Cy+/- rats develop PKD much more rapidly than Cy+/- rats and in a timeframe consistent with Cy-/-rats. Transcripts with the mcy variant allele appear to undergo nonsense-mediated decay, and no ANKS6 protein is detected. However, gene expression patterns in the kidneys did not differ significantly between age-matched mcy+/+ and mcy+/- rats, indicating that ANKS6 insufficiency does not cause PKD.

Conclusions: We identified a novel nonsense variant in Anks6. The findings indicate that the absence of wild-type ANKS6 accelerates PKD development in the Han:SPRD-Cy rat, and that complete ANKS6 deficiency prevents normal embryonic development in rats.

Background: People with kidney failure have complex care needs and frequently access care using the emergency department (ED). Little is known about how continuity of care (CoC) relates to ED care seeking for people with kidney failure. To understand the experiences of CoC among adults with kidney failure in relation to their recent ED encounter.

Methods: Using a qualitative descriptive methodology, we purposively sampled adults with kidney failure (defined as eGFR <15 mL/min/1.73m2 and/or receipt of maintenance dialysis) from Alberta who accessed the ED for a non-life-threatening indication within the preceding six weeks between May 2024 and January 2025. We conducted individual semi-structured interviews and analyzed transcripts in duplicate using a framework analysis approach with reference to an established framework defining CoC according to 3 types (i.e., relational, management, and informational). Thematic development involved both inductive and deductive techniques.

Results: 29 patients were included (12 in-center hemodialysis, 1 in-center nocturnal hemodialysis, 7 peritoneal dialysis, 5 home hemodialysis, and 4 without kidney replacement therapy). Themes were identified within CoC types and across settings of before, during, and after the acute care encounter. Key relational continuity themes included: stability and trust in care teams, disrupted therapeutic relationships, and re-establishing engagement in circles of care. Management continuity themes included: safeguarding kidney supports and kidney care fragmentation in the ED. Informational continuity themes included: patients as continuity self-advocates, bridging care through information sharing, and extending continuity beyond the ED.

Conclusions: Patients with kidney failure expressed varied experiences of CoC and identified important gaps relevant to the emergency care context. Strategies that bridge these perceived gaps across outpatient and acute care settings may help to mitigate the burden of ED use in this population.