Kidney360

Patient-specific urine-derived cells are valuable tools for biomedical research and personalised medicine since collection is non-invasive and easily repeated, unlike biopsies. The full potential of urine-derived cells remains untapped, however, due to the short shelf life of samples and necessity for prompt centrifugation. This study aims to address this limitation by evaluating a novel filtration-based Cell Catcher device and comparing its efficiency to centrifugation. We obtained urine from 18 tubulopathy patients and using paired analysis demonstrated that the Cell Catcher device significantly improves the success rate of isolating viable renal cells, and the cell yield. The findings were confirmed in a second independent study, using 44 samples obtained from healthy controls or patients with Bardet-Biedl syndrome or tubulopathies, where colonies were established in 90% of the Cell Catcher-processed samples. Cultured cells displayed a variety of morphologies and expressed markers of podocyte and proximal tubule cells. Collectively, we describe an improved, point-of-care methodology to obtain live patient cells from urine using a filtration technique, with potential personalised medicine applications in nephrology, regenerative medicine, and urological cancers.

BackgroundSeveral biomarkers of acute kidney injury (AKI) have been examined for their ability to predict AKI earlier than serum creatinine. Few studies have focused on using kidney biomarkers to better predict major adverse kidney events (MAKE), an increasingly used composite outcome in critical care nephrology research. MethodsSingle-center prospective study collecting blood and urine samples from critically ill patients with AKI KDIGO stage 2 or above, and matched controls from a single, tertiary care intensive care unit. Samples were collected at 24-48 hours after AKI diagnosis (cases) or ICU admission (controls), 5-7 days later, and 4-6 weeks following discharge for AKI patients. The primary outcome of interest was MAKE at hospital discharge. ResultsSerum/urinary neutrophil gelatinase-associated lipocalin, serum/urinary cystatin C, and urinary kidney injury molecule-1 early in the AKI or ICU course were all significantly higher in patients with MAKE compared to those not experiencing MAKE at hospital discharge. Serum cystatin C, and to a lesser extent serum NGAL, significantly improved upon a clinical prediction model of MAKE as assessed by the area under the receiver operating characteristic curve. Patients without MAKE experienced a greater decline in serum NGAL from initial measurement to second measurement than those patients experiencing MAKE. ConclusionEarly measures of kidney biomarkers in critically ill patients are associated with MAKE. This relationship appears to be greatest with serum NGAL and cystatin C, which display additive utility to a clinical prediction model. Trending serum NGAL may also have utility in predicting MAKE.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are recommended for use in adults with chronic kidney disease (CKD) and are widely prescribed. SGLT2 inhibition markedly increases urine glucose excretion, which could interfere with laboratory assays. We assessed whether assays for several key urine tubular biomarkers (alpha-1 microglobulin [1M], dickkopf-3 [DKK-3], epidermal growth factor [EGF], interleukin-18 [IL-18], kidney injury molecule-1 [KIM-1], monocyte chemoattractant protein-1 [MCP-1], neutrophil gelatinase-associated lipocalin [NGAL], uromodulin [UMOD], and human cartilage glycoprotein-40 [YKL-40]) are affected by glycosuria using urine samples from participants with CKD. Each urine sample was divided into three aliquots, with one serving as control and the other two being spiked with glucose to reach effective concentrations of 28 mmol/l and 111 mmol/l. There was large positive mean bias [95% CI] observed at 28 mmol/l glucose concentration for IL-18 (0.10 [0.01, 0.23]) and YKL-40 (0.40 [0.32, 0.49]). The limits of agreement (LOA) for both biomarkers were wide, spanning >1 unit difference in log-transformed biomarker values. The rest of the biomarkers had narrow LOA. Modest negative mean bias at 28 mmol/l glucose concentration was observed for DKK-3 (-0.02 [-0.04, 0]), KIM-1 (-0.04 [-0.06, -0.02]), and UMOD (-0.08 [-0.11, -0.06]), with similar values observed at 111 mmol/l glucose concentration. There was no evidence of any bias in measurements of 1M, EGF, MCP-1, and NGAL. Glycosuria substantially interferes with IL-18 and YKL-40 measurements, without importantly affecting 1M, DKK-3, EGF, KIM-1, MCP-1, NGAL or UMOD.

BackgroundRenal intratubular casts are frequently observed in the distal nephron segments of the kidney and have long been regarded as a sign of renal disease. However, the composition and pathological significance of intratubular casts have remained understudied. MethodsWe leveraged Hematoxylin and Eosin (H&E) staining to identify intratubular casts along with concurrent Co-detection by indexing (CODEX) multiplexed spatial protein imaging on human kidney biopsy sections from the Kidney Precision Medicine Project (KPMP). We also conducted immunoblotting of Prominin-1 (PROM1) in urine and assessed its levels from publicly available urinary proteomics datasets of the KPMP consortium. ResultsWe analyzed 424 intratubular casts across 33 individuals with kidney disease or healthy controls. We identified PROM1 and IGFBP7 as major constituents of casts (positive staining in 90.1% and 35.6%, respectively). Staining for UMOD, an established cast component, was present in 86.1%. These components exhibited distinct alterations depending on the disease state. Intratubular casts were predominantly detected in the distal nephron segments, and their presence was associated with a marked loss of NCC and AQP2 expression in the cast-containing tubular epithelium, suggesting underlying injury. The loss of these membrane transporters correlated with protein components within casts, and the presence of intra-cast PROM1 showed the strongest association, with an odds ratio of 30.8 (95% confidence interval: 13.4-71.0). Urinary PROM1 secretion was confirmed by immunoblotting and was increased in patients with acute kidney injury (AKI) compared to healthy controls (p = 0.01). ConclusionsWe identified PROM1, a dedifferentiation and injury marker expressed in epithelial cells, as a novel major constituent of intratubular casts. Our studies suggest that protein composition signature within casts varies with disease state and is associated with tubular injury in distal nephron segments. Our study also suggests that urinary PROM1 may serve as a biomarker for AKI. Key Points{checkmark} Utilized CODEX multiplex protein imaging to elucidate the intratubular cast components and the associated tubular alterations. {checkmark}Identified PROM1, a dedifferentiation marker, as a major constituent of intratubular casts. {checkmark}Protein components within casts were altered by disease state and were associated with the injury of the surrounding tubular epithelium.

The COVID-19 pandemic created an unprecedented strain on hospitals in New York City. Although practitioners focused on the pulmonary devastation, resources for the provision of dialysis proved to be more constrained. To deal with these shortfalls, NYC Health and Hospitals/Bellevue, NYU Brooklyn, NYU Medical Center and the New York Harbor VA Healthcare System, put together a plan to offset the anticipated increased needs for kidney replacement therapy. Prior to the pandemic, peritoneal dialysis was not used for acute kidney injury at Bellevue Hospital. We were able to rapidly establish an acute peritoneal dialysis program at Bellevue Hospital for acute kidney injury patients in the intensive care unit. A dedicated surgery team was assembled to work with the nephrologists for bedside placement of the peritoneal dialysis catheters. A multi-disciplinary team was trained by the lead nephrologist to deliver peritoneal dialysis in the intensive care unit. Between April 8, 2020 and May 8, 2020, 39 peritoneal dialysis catheters were placed at Bellevue Hospital. 38 patients were successfully started on peritoneal dialysis. As of June 10, 2020, 16 patients recovered renal function. One end stage kidney disease patient was converted to peritoneal dialysis and was discharged. One catheter was poorly functioning, and the patient was changed to hemodialysis before recovering renal function. There were no episodes of peritonitis and nine incidents of minor leaking, which resolved. Some patients received successful peritoneal dialysis while being ventilated in the prone position. In summary, despite severe shortages of staff, supplies and dialysis machines during the COVID-19 pandemic, we were able to rapidly implement a de novo peritoneal dialysis program which enabled provision of adequate kidney replacement therapy to all admitted patients who needed it. Our experience is a model for the use of acute peritoneal dialysis in crisis situations.

IntroductionAcute kidney injury (AKI) is associated with significant morbidity and mortality. The diagnosis is currently based on urine output and serum creatinine and there is a lack of biomarkers that directly reflect tubular damage. Here, we establish flow cytometric quantification of renal epithelial cells as a potential biomarker for quantifying the severity of tubular kidney damage and for predicting AKI outcome. MethodsA total of 84 patients with AKI were included in this study, divided into an exploratory cohort (n=21) and confirmatory cohort (n=63), as well as 25 controls. Urine of patients was collected and processed within 72 hours after AKI onset. Different urinary tubular epithelial cell (TEC) populations were identified and quantified by flow cytometry (FACS). Urinary cell counts were analyzed regarding AKI severity defined by KDIGO stage as well as renal recovery, length of hospital stay and occurrence of MAKE-30 events. ResultsUrinary TEC counts correlated with stages of AKI based on KDIGO classification and were significantly enriched in patients with AKI compared to healthy donors and inpatient controls in both cohorts. Furthermore, both proximal and distal TEC (pTEC, dTEC) counts performed well in identification of patients with AKI regardless of stage. Urinary amounts of pTEC and dTEC showed a strong correlation, with predominance of dTEC. Higher numbers of TEC were associated with extended length of hospital stay, while elevated pTEC counts were associated with the occurrence of MAKE-30 events. Follow-up measurements showed decreasing amounts of urinary TEC after AKI recovery over several days. ConclusionThe amount of urinary TEC directly reflects severity of tissue damage in human AKI. Our protocol furthermore provides a basis for a deeper phenotypic analysis of urinary TEC populations.

BACKGROUNDThe prevalence of urolithiasis in the general population has increased worldwide in the past decades. The aim of this study is to investigate the bacteriological profile of urine samples from patients with kidney stones. By analyzing the bacteria present in the urine, we can gain insights into potential associations between specific types of stones and the microbial flora. This information can be crucial for tailoring treatment strategies, including antibiotic therapy and preventive measures. METHODOLOGYIt is a retrospective cross-sectional study comprised of all patients who were diagnosed with urolithiasis at Ramaiah Memorial Hospital, Bengaluru, Karnataka. In this study we assessed a total of 235 patients who were admitted to our hospital due to kidney stones. The socio-demographic and epidemiological profile. Type of calculus, urinalysis and treatment method was considered. RESULTSOut of 235 patients, 189 (80.4%) were males, and 46 (19.6%) were females. 80 patients (34% of the total patients) were found to have clinical or laboratory evidence of urinary tract infection (UTI). Most common organism isolated was Escherichia coli in 19 patients (48.7%) followed by Klebsiella in 15 patients (38.46%). In biochemical analysis most common type of stone found was calcium oxalate monohydrate (97.43%) and calcium oxalate dihydrate (66.66%). CONCLUSIONPositive urine culture in stone formers should not be assumed to indicate purely infection-related stones; metabolic evaluation remains essential. In patients with recurrent CaOx stones and persistent bacteriuria, targeted antibiotic therapy and biofilm-disrupting strategies could be considered to reduce recurrence.

ObjectiveTo explore the frequency of occurrence of extra-renal manifestations associated with monogenic kidney stone diseases. MethodsA literature review was conducted to identify genes that are well-established monogenic causes of nephrolithiasis. The Online Mendelian Inheritance in Man (OMIM) and Human Protein Atlas (HPA) databases were used to identify associated diseases and their properties. Disease phenotypes were ascertained using OMIM clinical synopses and sorted into 24 different phenotype categories as classified in OMIM. Disease phenotypes caused by the same gene were merged into a single gene-associated phenotype (GAP) unit such that one GAP encompasses all related disease phenotypes for a specific gene. We measured the total number of GAPs involving each phenotype category and determined the median phenotype category. Phenotype categories were classified as overrepresented or underrepresented if the number of GAPs involving them was higher or lower than the median, respectively. A chi-square test was conducted to determine whether the number of GAPs affecting a given category significantly deviated from the median. ResultsFifty-five genes were identified as monogenic causes of nephrolithiasis. All GAPs comprised at least one extra-renal phenotype category. The median phenotype category was part of 10 (18%) unique GAPs. A total of 6 significantly overrepresented (growth, skeletal, neurologic, abdomen/gastrointestinal, muscle, metabolic features) and 5 significantly underrepresented (mouth, voice, neck, immunology, neoplasia) phenotype categories were identified among our group of monogenic kidney stone diseases (p<0.05) with impaired growth being the most common manifestation. ConclusionMonogenic nephrolithiasis is a multi-system disorder. Recognizing the extra-renal manifestations associated with monogenic causes of kidney stones is critical for earlier diagnosis and optimal prognosis in patients.

Rationale & ObjectiveCompetency-based medical education emphasizes observable skills rather than time-based training. Entrustable Professional Activities (EPA) transform competencies into distinct, assessable clinical tasks but have not yet been systematically developed for U.S nephrology fellowships. We aimed to create and achieve consensus on a set of nephrology-specific EPAs and align them with Accreditation Council for Graduate Medical Education (ACGME) competency standards. Study DesignA consensus framework was developed using an online 3-round modified Delphi method. Settings & ParticipantsStudy was conducted within the University of New Mexico nephrology fellowship program. Participants included eight faculty nephrologists and one nephrology fellow. Analytical ApproachAn initial EPA list was generated by the study team using program objectives, literature review, and clinician insight. Participants rated each EPA using a 5-point Likert scale with consensus requiring strict criteria. Final EPAs were independently mapped to ACGME nephrology program requirements to ensure alignment with national competency. ResultsNine study participants (100% response rate) completed all survey rounds. Through iterative consensus, utilizing strict criteria, a final list of 22 distinct EPAs were achieved covering core domains of practice including dialysis management, acute kidney injury, chronic kidney disease, electrolyte abnormalities, hypertension, kidney stones, glomerular disease, pregnancy, transplant care, and education. Mapping demonstrated that the EPAs sufficiently corresponded to the breadth of ACGME-required sub competencies, offering a practical framework for translating broad milestones into observable clinical tasks. LimitationsThe study was conducted at a single fellowship program with a small number of participants which may limit generalizability. Implementation feasibility, resource implications, and potential unintended consequences such as checklist mentality and documentation burden were evaluated during a subsequent phase of the study. ConclusionsWe developed the first consensus-consensus based set of EPAs geared for U.S based nephrology fellowship programs while being systematically aligned with ACGME program requirements. This framework provides a foundation for standardized assessment and curriculum development in nephrology and may inform broader efforts to implement EPA-based evaluation across fellowship programs nationally.

BackgroundDistinguishing patients with the inherited salt-losing tubulopathies (SLT), Gitelman or Bartter syndrome (GS or BS) from wildtype (WT) patients who purge is difficult. We decided to identify clinical/biochemical characteristics which correctly classify SLT. Methods66 patients with possible SLT were recruited to a prospective observational cohort study at the UCL Renal Tubular Clinic (London). 31 datapoints were recorded on each patient. All patients were genotyped for pathogenic mutations in genes which cause SLT; 39 patients had pathogenic variants in genes causing SLT. We obtained similar datasets from cohorts in Taipei and Kobe; the combined dataset comprised 419 patients, 291 had genetically confirmed SLT. London and Taipei datasets were combined to train machine learning (ML) algorithms. These were then tested on the Kobe dataset to determine the best biochemical predictors of genetic confirmation of SLT. ResultsSingle biochemical variables (e.g. plasma renin) were significantly, but inconsistently different between SLT and WT, in the London and combined cohorts. A decision table algorithm using serum bicarbonate and urinary sodium excretion (FENa) achieved a classification accuracy of 74%. A simpler algorithm based on the FECl achieved a classification accuracy of 61%. This was superior to all of the single biochemical variables identified previously.

BackgroundCurrent definitions of neonatal acute kidney injury (nAKI) are not sensitive enough to identify all newborns with impaired kidney function (IKF) during the first week of life. Previous studies in term newborns with hypoxic ischemic encephalopathy showed that the rate of serum creatinine (SCr) decline during the first week of life could be used to assess their renal status. MethodsWe reviewed the medical records of 329 critically ill newborns [&ge;] 27 weeks of gestational age (GA), to determine whether the rate of SCr decline combined with SCr thresholds provides a sensitive approach to identify newborns with IKF during the first week of life. ResultsExcluding neonates with nAKI, identified based on standard definitions, a SCr decline < 31 % by the 7th day of life, combined with a SCr threshold [&ge;] 0.7 mg/dl, recognized newborns of 40-31 weeks of GA with IKF. A SCr decline < 21% combined with a SCr threshold [&ge;] 0.8 mg/dl identified newborns of 30-27 weeks of GA with IKF. These neonates (~ 17%) showed a more prolonged hospital stay and required more days of mechanical ventilation, vasoactive drugs, and diuretics, when compared to critically ill controls. Changes in urine output did not distinguish newborns with IKF. ConclusionThe rate of SCr decline combined with SCr thresholds identifies newborns with IKF during the first week of life. This distinctive group of newborns that is missed by standard definitions of nAKI, warrants close monitoring in the NICU to prevent acute and chronic renal complications.

OBJECTIVESPrimary care for chronic kidney disease (CKD) stage 1-2 has recently been shown to slow CKD progression. We describe an approach to detect early decline in glomerular filtration rate (GFR) above 60 milliliters per minute (mL/min), before CKD stage 3. METHODSWe re-examined a standard reference that found low tubular secretion of creatinine (TScr) at GFRs above 80 mL/min and suggested "...observation of subtle changes in serum creatinine levels". We explain why that method extends down to 60 mL/min and summarize why estimated GFR (eGFR) is unreliable above 60 mL/min. RESULTSFour patient cases show how serum creatinine (sCr) referenced to an individuals historical maximum suggests increased risk, triggering investigation to separate benign processes that alter sCr from decline in GFR of prechronic kidney disease (preCKD). CONCLUSIONSAt GFRs above 60 mL/min, serial creatinine is more reliable than GFR estimating equations and appears practical for race-free clinical monitoring and early intervention. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/24313678v9_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@1d7e4d6org.highwire.dtl.DTLVardef@f0b51dorg.highwire.dtl.DTLVardef@102a01forg.highwire.dtl.DTLVardef@15e7597_HPS_FORMAT_FIGEXP M_FIG C_FIG STRENGTHS OF THIS STUDYO_LIIncludes serial creatinine proof-of-concept cases that show preCKD C_LIO_LIReviews race-free properties that favor serial creatinine for early kidney disease C_LIO_LIAddresses mathematical limitations of GFR estimating equations C_LIO_LIRe-analyzes a 40-year-old standard reference that still influences research, showing its overlooked importance for CKD stage 1-2 C_LI

IntroductionEnd stage kidney disease (ESKD) affects an estimated 5500 persons living in the United States without legal residency documentation. One likely, but underappreciated cause of ESKD in the Hispanic migrant population, is chronic kidney disease of unknown etiology (CKDu). CKDu is an interstitial nephritis that disproportionately affects young adult agricultural workers in Central America who lack traditional risk factors for kidney disease. In underserved populations, such as those at risk for CKDu, substantial barriers to optimal kidney care translate to poorer health outcomes and widening health disparities. Without funding for non-emergent healthcare, this underserved population, often only have access to hemodialysis (HD) once a life-threatening condition occurs. Despite the presence of a migrant population from CKDu endemic countries and anecdotes of its presence, CKDu has very rarely been directly investigated or documented in the US. We undertook this study to establish the existence of CKDu in the United States and to characterize CKDu as a cause of ESKD in patients accessing emergent HD. MethodsIn a retrospective cross-sectional study among patients receiving emergent HD in Texas, we analyzed medical record data from a large, county hospital. We ascertained cause of ESKD and underlying hypertension and diabetes and compared these proportions to data on patients on maintenance HD from the US Renal Data System (USRDS). Undocumented immigrants are largely excluded from the USRDS, as with many health statistics databases in the US. We identified patients whose clinicians had indicated CKDu as a diagnosis and classified others as having suspected CKDu or possible CKDu based on clinically informed criteria. ResultsWe identified 346 patients with ESKD requiring emergent HD (2012-2015), who were younger than patients in the USRDS (median age 52 yrs vs. 61 yrs, p <0.001), had more comorbid diabetes (60% vs. 47%, p <0.001), and more often had an unknown cause of ESKD (16% vs. 4%, p<0.001). Patients requiring emergent HD also had less frequent arteriovenous access (12% vs. 82%, p<0.001). ESKD attributed to diabetes and/or hypertension accounted for only 67% of emergent HD patients, compared to 81% of USRDS patients (p<0.001). 14% of the patients on emergent HD died during the study period. Four patients had been clinically diagnosed with CKDu, while we classified 14 with suspected CKDu and 40 with possible CKDu, for a total of 58 patients (17%) with potentially CKDu-related ESKD. ConclusionOur analysis suggests that up to 17% of patients in this population utilizing emergent HD had CKDu-related ESKD, suggesting that CKDu is likely underdiagnosed in the US. Further, patients receiving emergent HD were younger but were at higher risk of infection or complication than patients receiving scheduled, maintenance HD. Understanding CKDu and improving access to scheduled dialysis for migrants without legal residency documentation should be prioritized to reduce stress on the healthcare system and improve health among vulnerable populations in the US.

The Dietary Approach to Stop Hypertension (DASH) diet is a proven intervention to treat hypertension, yet its mechanism is not clearly known. We investigated the change in protein abundance patterns in urine extracellular vesicles (uEVs) following DASH diet implementation. A pilot study was carried out to compare uEVs isolated using three different methods: a low centrifugation (P20), high centrifugation (P100), and a combination of both (P20 and P100). Uromodulin was removed by size exclusion chromatography and low ionic strength washing. Mass spectrometry analysis identified 1,593 proteins in the combined fraction (P20+P100), 1434 in the P20 fraction and 1229 in the P100 fraction. The combined fraction was chosen for further analysis. Statistical analysis was carried out using R and Limma to identify all proteins that changed before and during 11 days of DASH intervention (p < 0.05) as well as between individual timepoints. Nine hypertensive volunteers were admitted for a 14-day supervised transition from American style diet to DASH diet. First-void urine was collected on days 0, 5, 11 for uEV processing. In total, 1800 proteins were identified across all 27 DASH samples with 22 proteins upregulated and 25 down regulated between day 0 and both days 5 and 11. These included increased abundance of SLC12A3 (NCC) and reduced abundance of Aquaporine 2. These changes could explain the increased urine volume and reduced sodium reabsorption that lead to blood pressure reduction following consumption of the high potassium and low sodium DASH diet. uEVs may serve as a surrogate to a more invasive procedure. Translational StatementMyriad studies have characterized blood pressure reduction following DASH diet implementation, yet its precise mechanism is unclear. Here, we demonstrate for the first time the effect of DASH nutritional changes, on kidney ion channel composition using proteomic analysis of urinary EVs. Using this innovative tool as a substitute for an invasive procedure, we show that the expression of Aquaporine2 increases and NCC decreases in response to DASH which may account for its antihypertensive effect. Our results indicate that urinary EV are a potential biomarker for DASH compliance, and targeting aquaporine2 may be an effective innovative therapeutic strategy for blood pressure reduction.

BackgroundThe International Immunoglobulin A nephropathy (IgAN) risk prediction assesses the risk of kidney failure in patients with IgAN. The performance of this risk prediction tool has not been studied in American Indians and Hispanics. We conducted a single-center study to assess the equation performance in this population. MethodsWe calculated the 5-year risk of developing kidney failure with the IgAN risk prediction equation without race and assessed the equation performance using the metrics of calibration, discrimination, and overall prediction error. ResultsThirty-four patients were included, most of whom identified as of Hispanic race/ethnicity (44.1%), or as American Indians (26.5%). At biopsy, the median (IQR) age, serum creatinine, and spot urine protein to creatinine ratio were 38 years (27-45), 2.15 mg/dl (1.51-3.04), and 2.7 g/g (1.5-5.8), respectively. The equation identified patients at high risk of developing kidney failure early with a concordance statistic of 0.79 (95% CI 0.68 - 0.89). The agreement between observed and predicted outcomes at 5 years was marginal, with over-estimation of risk for patients with low observed risk and vice versa. Overall prediction error was suboptimal in this cohort [index of prediction accuracy 0.34 (0.03 - 0.51)]. ConclusionsThe International IgAN risk prediction equation without race accurately identified patients at elevated risk of developing kidney failure. At 5 years, the agreement between the observed and predicted outcomes was sub-optimal, possibly due to advanced kidney disease in this cohort. A diverse development population may improve the risk prediction.

The development of acute kidney injury in patients with COVID-19 is estimated to about 0.5% from earlier studies from China. The incidence of AKI in patients with COIVID-19 in the largest inpatient series in the United States is 22.2%3. Development of AKI requiring kidney replacement therapy in hospitalized patients is a bad prognostic sign. Out of Fifty patients admitted to our hospital with COVID-19 13/50(26%) developed AKI. All patients required hospitalization in intensive care unit care and 12/13 required initiation of kidney replacement therapy. The median age was 41 years (31-85 years) and 50% were men. Common comorbidities were obesity (83%), diabetes (42%), and hypertension (25%). 10/12 (83%) patients were hypoxemic and required oxygen therapy. 11/12 (92%) patients required invasive ventilation. Majority of patients had elevated neutrophils counts (81.8%) and low lymphocyte counts (81.8%). All patients had chest x-ray findings suggestive of pneumonia. 11/12(91.6%) developed septic shock requiring vasopressors. Review of UA showed all patient (9/9) had active urine sediments with blood but 7/9 of them have sterile pyuria. At the end of study period, 1 patient remained hospitalized. 10/11(90%) patients died and one patient was discharged home with resolution of AKI. Median length of stay was 13 days. The exact mechanism of AKI is not well understood in COVID-19 but can be due to acute tubular necrosis due to septic shock because of cytokine storm in severe COVID-19 or direct invasion by SARS-CoV-2 on podocytes and proximal renal tubular cells. Our findings suggest poor prognosis despite continuous kidney replacement therapies in patients who develop AKI with COVID-19.

Kidney diseases are a major health concern worldwide. Currently there is a large unmet need for novel biomarkers to non-invasively diagnose and monitor kidney diseases. Urinary cells are promising biomarkers and their analysis by flow cytometry has demonstrated its utility in diverse clinical settings. However, up to date this methodology depends on fresh samples, as cellular event counts and the signal-to-noise-ratio deter over time. Here we developed an easy-to-use two-step preservation method for conservation of urine samples for subsequent flow cytometry. The protocol utilizes a combination of the formaldehyde releasing agent imidazolidinyl urea (IU) and MOPS buffer, leading to gentle fixation of urinary cells. The preservation method increases acceptable storing time of urine samples from several hours to up to 6 days. Cellular event counts and staining properties of cells remain comparable to fresh untreated samples. The hereby presented preservation method facilitates future investigations on flow cytometry of urinary cells as potential biomarkers and may enable broad implementation in clinical practice.

BackgroundEstimated glomerular filtration rate (eGFR) slope and proteinuria reduction have been proposed as surrogate endpoints for kidney outcomes in IgA nephropathy (IgAN), but their validity remains under debate. We aimed to evaluate the surrogate potential of these markers in the context of corticosteroid therapy within a large Japanese cohort. MethodsPatients with biopsy-proven IgAN from the Japan IgA Nephropathy Cohort Study (J-IGACS) were analyzed. Patients were categorized based on corticosteroid exposure within 12 months of diagnosis. To minimize confounding, overlap weighting was used to balance baseline characteristics. The primary outcome was a composite kidney endpoint defined as a [&ge;]40 decline in eGFR or the initiation of kidney replacement therapy. Secondary outcomes included 2-year eGFR slope and proteinuria ratio at 1-year. ResultsCorticosteroid therapy was associated with a lower incidence of the composite kidney outcome (15.5 vs. 28.2%, P = 0.007), slower decline in eGFR (-0.30 vs. -2.99 mL/min/1.73 m2/year, P = 0.001), and lower proteinuria ratio (0.521 vs. 0.235, P < 0.001). These associations were consistent with predictions from established meta-regression models that linked changes in surrogate markers to kidney outcomes across diverse kidney diseases including IgAN. ConclusionBoth the eGFR slope and proteinuria ratio demonstrated strong and consistent associations with kidney outcomes in the context of corticosteroid therapy. These findings support their validity as surrogate endpoints for clinical trials and suggest their usefulness for risk stratification and therapeutic monitoring in routine nephrology practice. Lay-SummaryIgA nephropathy (IgAN) is a common kidney disease that can lead to kidney failure over time. To monitor treatment effectiveness, researchers often use early indicators like how quickly kidney function declines (eGFR slope) and changes in protein levels in urine (proteinuria). However, whether these markers truly reflect long-term outcomes remains uncertain. In this study, we analyzed over 1,000 patients with biopsy-confirmed IgAN from a nationwide Japanese cohort. We compared those who received corticosteroid treatment within a year of diagnosis to those who did not. After adjusting for differences between groups, we found that corticosteroid use was linked to better kidney outcomes, slower decline in kidney function, and reduced proteinuria. These results matched predictions from large-scale international studies. Our findings support the use of eGFR slope and proteinuria as reliable surrogate endpoints in clinical trials and everyday care, helping doctors assess treatment response more quickly and accurately.

IntroductionGenomic testing is reshaping nephrology practice, yet the structure, outcomes, and implementation of kidney genetics services remain poorly characterized. MethodsWe conducted a two-part scoping study comprising (i) a literature review (JBI methodology, PRISMA-ScR compliant; OSF registration doi.org/10.17605/OSF.IO/N32VA) of English-language publications (2000-2025) describing kidney genetics services and outcomes, and (ii) an international stakeholder consultation of clinic leads to capture real-world service and implementation experiences. ResultsSixty studies were included, predominantly from North America (n=23), followed by United Kingdom/Ireland (n=5), Europe (n=17), Australia/New Zealand (n=10), and Asia (n=5). Among the 25 studies describing clinic models, four types were identified: multidisciplinary integrated (n=12), nephrologist-led (n=9), mainstreaming (n=2), and traditional genetics referral (n=2). Clinic structure varied by region. Outcome reporting focused on diagnostic yield (92%), with limited data on timeliness (16%), patient-reported outcomes (12%), or implementation outcomes (4%). Test penetration was high across regions and models, while diagnostic yield varied. Nephrologist-led clinics demonstrated comparable performance to multidisciplinary models when adequately supported. International stakeholder consultation data (n=48) revealed diversification of clinic models across regions. In Australia/New Zealand, multidisciplinary clinics predominated, supported by public funding and in-house or hybrid laboratory. United Kingdom/Ireland clinics used public funding and a national laboratory. North American clinics show greater heterogeneity, with higher prevalence of nephrologist-led models, reliance on commercial laboratories, and mixed or private funding. Asian clinics reported nephrologist-led models, with resource constraints, and hybrid testing and funding arrangements. Comprehensive sequencing with virtual panels predominated in Australia/New Zealand, United Kingdom, and Europe; phenotype-driven panels {+/-} reflex testing were more common in North America. ConclusionsKidney genetics care is expanding but remains unevenly implemented. Nephrologist-led and multidisciplinary models can be effective with appropriate support. Patient selection may influence diagnostic yield more than testing modality. Standardized outcome reporting and theory-driven implementation evaluation are essential for delivering equitable, sustainable genomic services. Lay SummaryThis study examined how kidney genetics services are delivered across the globe. We reviewed 60 studies (2000-2025) and consulted 48 clinic leaders globally. Four service models were identified--multidisciplinary integrated, nephrologist-led, mainstreaming, and traditional genetics referral--and mapped variation in care teams, test strategies, test laboratories, and funding. Most studies reported diagnostic yield, but few assessed patient experience or how well services were implemented. European programs showed the highest performance, attributed to clear referral criteria, deep phenotyping, detailed family histories, multidisciplinary review, and strong public funding. Clinics led by nephrologists performed comparably to multidisciplinary teams when adequately supported. Across all settings, patient selection was more important than the specific type of genetic test used in determining diagnostic success. Kidney genetics services are expanding but remain uneven. This study highlights the need for context-specific, theory-informed, and determinants-targeted strategies to support scalable, equitable, and sustainable genomic care worldwide.

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is a genetic kidney disease with high phenotypic variability. Insights into ADPKD progression could lead to earlier detection and management prior to end stage kidney disease (ESKD). We sought to identify patients with rapid decline (RD) in kidney function and to determine clinical factors associated with RD using a data-driven approach. MethodsA retrospective cohort study was performed among patients with incident ADPKD (1/1/2002-12/31/2018). Latent class mixed models were used to identify RD patients using rapidly declining eGFR trajectories over time. Predictors of RD were selected based on agreements among feature selection methods, including logistic, regularized, and random forest modeling. The final model was built on the selected predictors and clinically relevant covariates. ResultsAmong 1,744 patients with incident ADPKD, 125 (7%) were identified as RD. Feature selection included 42 clinical measurements for adaptation with multiple imputations; mean (SD) eGFR was 85.2 (47.3) and 72.9 (34.4) in the RD and non-RD groups, respectively. Multiple imputed datasets identified variables as important features to distinguish RD and non-RD groups with the final prediction model determined as a balance between area under the curve (AUC) and clinical relevance which included 6 predictors: age, sex, hypertension, cerebrovascular disease, hemoglobin, and proteinuria. Results showed 72%-sensitivity, 70%-specificity, 70%-accuracy, and 0.77-AUC in identifying RD. 5-year ESKD rates were 38% and 7% among RD and non-RD groups, respectively. ConclusionUsing real-world routine clinical data among patients with incident ADPKD, we observed that six variables highly predicted RD in kidney function.