Kidney Recovery Research Articles

Outcomes Following Acute Kidney Injury Requiring Dialysis: A Cohort Study

ObjectiveRetrospective study to examine the outcomes of acute kidney injury requiring dialysis (AKI-D) patients that received outpatient hemodialysis as part of continued AKI-D care and explore factors associated with recovery of kidney function and discontinuation of dialysis. MethodsRecords of all admissions to Emory Dialysis centers between January 2010 to December 2021 were reviewed to include patients with confirmed diagnosis of AKI-D. Basic demographics, comorbidities, duration of hospitalization and cause of AKI were extracted from hospital records and cross-referenced with the dialysis center electronic health record. Patients were followed starting from the day of the first outpatient hemodialysis up to 180 days. All hemodialysis sessions and laboratory data were analyzed. Logistic regression models were used to examine factors associated with recovery of kidney function, defined as survival free of dialysis. Results132 patients were analyzed, corresponding to 12,662 patient-day of outpatient AKI-D care. Among those, 19 (14%) patients died during the observation period. 54% of patients were male and 70% were Black. Median Age was 64 years (IQR 49-79). 42 patients (32%) recovered enough kidney function to discontinue dialysis. Median time to kidney recovery was 31 days (IQR: 19-75), and the cumulative probability of kidney recovery at 6 months was 39%. Patients who discontinued dialysis were younger (58 vs 66 years), had higher estimated glomerular filtration rate (eGFR) at time of admission (69 vs 46 ml/min/1.73m2) to the hospital, and were less likely to have a history of hypertension (61% vs 82%). Intra-dialytic hypotension was more common in patients who did not recover kidney function. Conclusions39% of patients with AKI-D recovered kidney function within 180 days of outpatient HD start. The median time to recovery was 31 days. Younger age, higher e-GFR at time of hospital admission, and absence of hypertension were predictors of kidney recovery. Patients who recover kidney function experienced episodes of intradialytic hypotension less frequently.

Neuropilin-1 as a Key Molecule for Renal Recovery in Lupus Nephritis: Insights from an NZB/W F1 Mouse Model.

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organs, with lupus nephritis (LN) occurring in 40-50% of SLE patients. Despite advances in diagnosis and treatment, LN remains a major cause of morbidity and mortality, with 10-20% of patients progressing to end-stage renal disease (ESRD). While knowledge of LN's pathogenesis has improved, mechanisms of renal recovery are still largely unexplored. Neuropilin-1 (NRP-1), a transmembrane receptor expressed in renal tissue, has emerged as a promising biomarker for assessing renal recovery in LN. This study evaluates and correlates longitudinal levels of NRP-1 with kidney histology using an NZB/W F1 mouse model of LN. A total of 30 mice were used, with 15 receiving intravenous cyclophosphamide (CYC) and 15 being untreated. NRP-1 levels were measured in urine and serum, and kidney samples were taken from a subgroup of mice for histological evaluation. The results demonstrated a progressive increase in renal and urinary NRP-1 expression, particularly notable at weeks 26 and 32. Urinary NRP-1 levels above 34.40 ng/mL were strong predictors of favorable renal response, showing 100% sensitivity and 88% specificity. These findings indicate a robust correlation between urinary NRP-1 levels and renal histological recovery, underscoring the potential of NRP-1 as a valuable biomarker for assessing renal response in LN. This study demonstrates that renal production of NRP-1 is linked to histological recovery and establishes a foundation for future research into the role of NRP-1 in lupus kidney recovery.

Sex-specific proximal tubular cell differentiation pathways identified by single-nucleus RNA sequencing

Postnatal kidney growth is substantial and involves expansion in kidney tubules without growth of new nephrons, which are the functional units of the kidney. Proliferation and differentiation pathways underpinning nephron elongation are not well defined. To address this, we performed sequential characterization of mouse kidney transcriptomics at the single cell level. Single nuclear RNA sequencing (snRNA-seq) was performed on kidney tissue from male and female mice at 1, 2, 4 and 12 weeks of age using the 10x Chromium platform. Unbiased clustering was performed on 68,775 nuclei from 16 animals. 31 discrete cellular clusters were seen, which were identified through comparison of their gene expression profiles to canonical markers of kidney cell populations. High levels of proliferation were evident at early time points in some cell types, especially tubular cells, but not in other cell types, for example podocytes. Proliferation was especially evident in Proximal Tubular Cells (PTCs) which are the most abundant cell type in the adult kidney. Uniquely when compared to other kidney cell types, PTCs demonstrated sex-specific expression profiles at late, but not early, time points. Mapping of PTC differentiation pathways using techniques including trajectory and RNA Velocity analyses delineated increasing PTC specialization and sex-specific phenotype specification. Our single-cell transcriptomics data characterise cellular states observed during kidney growth. We have identified PTC differentiation pathways that lead to sex-specific tubular cell phenotypes. Tubular proliferative responses are of central importance in postnatal kidney growth and have also been linked to kidney recovery versus fibrosis following injury. Our unbiased and comprehensive dataset of tubular cell development can be used to identify candidate pathways for therapeutic targeting.

Kidney function in newly diagnosed myeloma patients: factors associated with kidney impairment and recovery

Kidney disease is a common complication of multiple myeloma (MM) and a risk factor for increased morbimortality. In this retrospective cohort study based on medical records, we analyzed the kidney function of patients with renal disease related to MM during the first year of treatment. All patients included were consecutively admitted to the outpatient services of two hospitals between January 2009 and January 2019 and met the diagnostic criteria for MM regardless of the reason for seeking medical help. We excluded patients who had kidney disease or who were on dialysis before MM diagnosis. We investigated the factors associated with renal function recovery using multivariate analysis. We evaluated 167 patients (median age of 66 ± 11.49 years). Almost half of the patients had arterial hypertension (76; 45.5%). The majority had International Staging System (ISS) grades 3 (73; 43.7%) or 2 (60; 35.9%). Seventy-four (44%) patients had an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m² at the time of MM diagnosis. Fifty-two patients (31%) underwent hematopoietic stem cell transplantation (HSCT). After 12 months, 4 (2.3%) patients needed dialysis, and 18 (10.7%) died. The factors associated with an eGFR < 60 ml/min/1.73 m² were anemia, hyperuricemia, 24-hour proteinuria > 1.0 g, and extramedullary plasmacytoma. However, only baseline renal function (eGFR > 60 ml/min/1.73 m2) and HSCT were associated with greater recovery of renal function at 12 months of follow-up.

Surgical Experience and Functional Outcomes after Laparoscopic and Robot-Assisted Partial Nephrectomy: Results from a Multi-Institutional Collaboration

Background: In patients treated with partial nephrectomy, prior evidence showed that peri-operative outcomes, such as complications and ischemia time, improved as a function of the surgical experience of the surgeon, but data on functional outcomes after surgery are still scarce. Methods: We retrospectively analyzed data of 4011 patients with a single, unilateral cT1a-b renal mass treated with laparoscopic or robot-assisted partial nephrectomy. The operations were performed by 119 surgeons at 22 participating institutions between 1997 and 2022. Multivariable models investigated the association between surgical experience (number of prior operations) and acute kidney injury (AKI) and recovery of at least 90% of baseline estimated glomerular filtration rate (eGFR) 1 yr after partial nephrectomy. The adjustment for case mix included age, Body Mass Index, preoperative serum creatinine, clinical T stage, PADUA score, warm ischemia time, pathologic tumor size, and year of surgery. Results: A total of 753 (19%) and 3258 (81%) patients underwent laparoscopic and robot-assisted partial nephrectomy, respectively. Overall, 37 (31%) and 55 (46%) surgeons contributed only to laparoscopic and robotic learning curves, respectively, whereas 27 (23%) contributed to the learning curves of both approaches. In the laparoscopic group, 8% and 55% of patients developed AKI and recovered at least 90% of their baseline eGFR, respectively. After adjusting for confounders, we did not find evidence of an association between surgical experience and AKI after laparoscopic partial nephrectomy (odds ratio [OR]: 0.9992; 95% confidence interval [CI]: 0.9963, 1.0022; p = 0.6). Similar results were found when 1-year renal function was the outcome of interest (OR: 0.9996; 95% CI: 0.9988, 1.0005; p = 0.5). Among patients who underwent robot-assisted partial nephrectomy, AKI occurred in 11% of patients, whereas 54% recovered at least 90% of their baseline eGFR. On multivariable analyses, the relationship between surgical experience and AKI after surgery was not statistically significant (OR: 1.0015; 95% CI: 0.9992, 1.0037; p = 0.2), with similar results when the outcome of interest was renal function one year after surgery (OR: 1.0001; 95% CI: 0.9980, 1.0022; p = 0.9). Virtually the same findings were found on sensitivity analyses. Conclusions: In patients treated with laparoscopic or robot-assisted partial nephrectomy, our data suggest that the surgical experience of the operating surgeon might not be a key determinant of functional recovery after surgery. This raises questions about the use of serum markers to assess functional recovery in patients with two kidneys and opens the discussion on what are the key steps of the procedure that allowed surgeons to achieve optimal outcomes since their initial cases.

Kidney function after liver transplantation: the contrasting roles of inflammation and tubular repair.

Kidney injury is a significant complication in end-stage liver disease (ESLD), leading to increased morbidity and mortality. While liver transplant alone (LTA) can promote kidney recovery (KR), non-recovery associates with adverse outcomes, but the underlying pathophysiology is still unclear. We studied 10 LTA recipients with or without kidney failure (KF) and measured serum levels of OPN and TIMP-1 (previously identified predictors of KR), 92 proinflammatory proteins (Olink), and urinary cell populations. Our findings revealed elevated OPN and TIMP-1 levels in KF patients, strongly correlated with tubular epithelial cells in urine. Proteomic analysis showed distinct profiles in KF, non-KF, and healthy donors, indicating an ongoing proinflammatory signature in KF. Cytokines correlated with OPN and TIMP-1 levels. We propose that high pre-LTA OPN and TIMP-1 levels are crucial for tubular regeneration and normalize with kidney recovery. Insufficient pre-LTA OPN levels may lead to persistent kidney failure. Our present data also newly indicate that kidney failure post-LTA is an active condition, in which tubular cells are persistently shed in the urine. The strict association between systemic inflammation and tubular cell loss suggests a pathogenic link that could offer therapeutic opportunities to promote kidney recovery.

Clinicopathological Characteristics and Kidney Outcomes in Biopsy-Confirmed Acute Interstitial Nephritis

IntroductionAcute interstitial nephritis (AIN) is a significant cause of acute kidney injury, with varying etiologies and outcomes. This study aimed to examine the causes, clinical characteristics, management, and kidney outcomes in patients with biopsy-confirmed AIN. MethodsA retrospective review was conducted on 166 patients diagnosed with AIN via kidney biopsy at Mayo Clinic between 2012 and 2023. Demographic, clinical, laboratory, and pathological data were collected. The primary outcome was kidney function recovery within the first six months. Statistical analyses included univariable and multivariable logistic regression, Kaplan-Meier survival analysis, and Cox proportional hazards modeling. ResultsMedications were the primary cause of AIN (67%), followed by autoimmune diseases (20%) and infections (6%). Within six months, 76% of patients achieved kidney recovery. Multivariable analysis indicated that moderate to severe interstitial fibrosis and tubular atrophy (IFTA) and dialysis requirement were associated with non-recovery, whereas a prebiopsy diagnosis of AIN was positively associated with kidney recovery. Drug-related AIN had higher recovery rates compared to all other causes (81% versus 66%, P = 0.04), and moderate to severe IFTA and dialysis need remained significant predictors for decreased recovery. Steroid therapy, used in 81% of patients, did not significantly influence kidney recovery in the overall cohort or in drug-induced AIN. ConclusionThis study provides insights into the characteristics and outcomes of biopsy-confirmed AIN. IFTA and dialysis requirement were significant factors associated with worse kidney outcomes. These findings may help inform clinical management and prognostication in AIN patients.

Impacts of Skeletal Muscle Mass and Quality on Kidney Recovery after AKI Receiving Continuous Kidney Replacement Therapy

Impacts of Skeletal Muscle Mass and Quality on Kidney Recovery after AKI Receiving Continuous Kidney Replacement Therapy

Cumulative Detrimental Effect of Hypotension during Intermittent Hemodialysis on Kidney Recovery in Critically Ill Patients with AKI Requiring Dialysis

Cumulative Detrimental Effect of Hypotension during Intermittent Hemodialysis on Kidney Recovery in Critically Ill Patients with AKI Requiring Dialysis

Association between Hemoglobin Levels and Kidney Recovery after AKI Requiring Continuous Kidney Replacement Therapy

Association between Hemoglobin Levels and Kidney Recovery after AKI Requiring Continuous Kidney Replacement Therapy

Early Clinical Indicators of ESKD Transition or Kidney Recovery in Patients with AKI on Dialysis

Early Clinical Indicators of ESKD Transition or Kidney Recovery in Patients with AKI on Dialysis

Eculizumab Therapy and Kidney Recovery in SARS-CoV-2-Induced Complement-Mediated Thrombotic Microangiopathy (CM-TMA)

Eculizumab Therapy and Kidney Recovery in SARS-CoV-2-Induced Complement-Mediated Thrombotic Microangiopathy (CM-TMA)

Total Kidney Volume and Recovery of Kidney Function in AKI Patients with Kidney Replacement Therapy

Total Kidney Volume and Recovery of Kidney Function in AKI Patients with Kidney Replacement Therapy

Complete Kidney Recovery after Prolonged Hemodialysis Dependency in Multiple Myeloma-Associated Kidney Failure: A Case Report

Complete Kidney Recovery after Prolonged Hemodialysis Dependency in Multiple Myeloma-Associated Kidney Failure: A Case Report

Kidney Recovery Prognosis after Allogeneic Hematopoietic Stem-Cell Transplantation

Kidney Recovery Prognosis after Allogeneic Hematopoietic Stem-Cell Transplantation

Characterising the Natural History of Kidney Recovery after AKI in a Prospective Cohort: Does Timing Matter?

Characterising the Natural History of Kidney Recovery after AKI in a Prospective Cohort: Does Timing Matter?

A Novel Pharmacological Agent, MARY1, Induces Mitochondrial Biogenesis and Restores Kidney Recovery in a Mouse Model of AKI

A Novel Pharmacological Agent, MARY1, Induces Mitochondrial Biogenesis and Restores Kidney Recovery in a Mouse Model of AKI

Establishment and characterization of a mouse model for studying kidney repair in diabetes.

The prognosis of acute kidney injury (AKI) is markedly worse in diabetic patients. Diabetes not only exaggerates the severity of AKI but may also prevent kidney repair or recovery from AKI. Little is known about the cellular and molecular basis of defective kidney repair in diabetes. One obstacle in studying kidney repair in diabetes is the lack of suitable animal models. Specifically, diabetes increases AKI severity, making it difficult to induce the same level of AKI in diabetic and non-diabetic animals to compare their kidney repair. Here, we have identified a time-window of 4 days immediately after the completion of streptozotocin (STZ) treatment in mice when blood glucose has yet to rise. Within this time-window, renal ischemia-reperfusion injury (IRI) induced the same level of AKI in STZ-treated mice [127.2±12.82 mg/dL blood urea nitrogen (BUN), 2.275±0.4728 serum creatinine] and vehicle solution-treated mice (128.6±11.83 mg/dL BUN, 2.087±0.4748 mg/dL serum creatinine]. By day 5-6, the post-AKI kidney entered into the phase of kidney repair when diabetic hyperglycemia started in STZ-treated mice, providing the opportunity to study the effect of diabetes on kidney repair without affecting initial AKI. In this model, kidney repair was indeed impaired by diabetes (116.5±8.052 mg/dL BUN and 1.382±0.2732 mg/dL serum creatinine in IR+vehicle group; 136.6±8.740 mg/dL BUN and 1.916±0.3756 mg/dL serum creatinine in IR+STZ group). The impairment was associated with decreased tubular cell proliferation and increased tubular cell senescence, peritubular capillary (PTC) rarefaction, inflammation, and 40.90% more interstitial fibrosis.

Kidney Outcomes Following Angiotensin Receptor-Neprilysin Inhibitor vs Angiotensin-Converting Enzyme Inhibitor/Angiotensin Receptor Blocker Therapy for Thrombotic Microangiopathy.

Thrombotic microangiopathy (TMA) on kidney biopsy is a pattern of endothelial injury commonly seen in malignant hypertension (mHTN), but treatment strategies are not well established. To evaluate the kidney outcomes of angiotensin receptor-neprilysin inhibitor (ARNI), specifically sacubitril/valsartan, vs angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy for patients with mHTN-associated TMA. This single-center cohort study enrolled consecutive patients in China diagnosed with mHTN-associated TMA through kidney biopsy from January 2008 to June 2023. Follow-up was conducted until the conclusion of the study period. Data were analyzed in September 2023. Treatment with sacubitril/valsartan or ACEI/ARBs during hospitalization and after discharge. The primary outcome was a composite of kidney recovery: a 50% decrease in serum creatinine level, decrease in serum creatinine levels to the reference range, or kidney survival free from dialysis for more than 1 month. The secondary and tertiary outcomes were a 15% increase in the estimated glomerular filtration rate (eGFR) relative to baseline and kidney survival free from dialysis, respectively. Propensity score matching (PSM) and Cox proportional hazards regression analysis were used to evaluate the association between sacubitril/valsartan and ACEI/ARB therapy with kidney recovery outcomes. Among the 217 patients (mean [SD] age, 35.9 [8.8] years; 188 men [86.6%]) included in the study, 66 (30.4%) received sacubitril/valsartan and 151 (69.6%) received ACEI/ARBs at baseline. Sacubitril/valsartan treatment was associated with shorter time to the primary outcome compared with ACEI/ARB treatment (20 of 63 [31.7%] vs 38 of 117 [32.5%]; adjusted hazard ratio [aHR], 1.85; 95% CI, 1.05-3.23). Sacubitril/valsartan treatment was independently associated with shorter time to a 15% increase in eGFR (15 of 46 [32.6%] vs 46 of 83 [55.4%]; aHR, 2.13; 95% CI, 1.09-4.17) and kidney survival free from dialysis (11 of 23 [47.8%] vs 16 of 57 [28.1%]; aHR, 2.63; 95% CI, 1.15-5.88) compared with ACEI/ARB treatment. These differences remained significant in the PSM comparison. In this cohort study, sacubitril/valsartan treatment was associated with a potential kidney function benefit in patients with mHTN-associated TMA compared with ACEI/ARB treatment. The findings suggested that sacubitril/valsartan could be a superior therapeutic approach for managing this serious condition in terms of kidney recovery.

MiRNA-133a-3p Attenuates Renal Tubular Epithelial Cell Injury via Targeting MALM1 and Suppressing the Notch Signaling Pathway in Diabetic Nephropathy.

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes characterized by structural and functional changes of kidneys. Human renal tubular epithelial (HK-2) cells are important for kidney recovery post injury and usually used for establishment of DN cell models. The study explored the role of microRNA (miR)-133a-3p in DN cell model and animal model. A cell model for DN was established via high glucose (HG) stimulation to HK-2 cells. Cell viability and apoptotic rate were measured by cell counting kit 8 and flow cytometry. Polymerase chain reaction was performed to quantify levels of miR-133a-3p and targets. Luciferase reporter assay was conducted to verify the binding of miR-133a-3p and MAML1. After establishment of a mouse model of DN, levels of renal function indicators were measured by biochemical analysis. Hematoxylin-eosin and periodic acid-schiff staining of kidney samples were performed to analyze histological changes. Western blotting was conducted to quantify levels of apoptotic markers, MAML1, and factors related to Notch signaling. Results showed that HG induced HK-2 cell apoptosis and the reduction of cell viability. MiR-133a-3p was lowly expressed in HG-stimulated HK-2 cells. Overexpressed miR-133a-3p improved HK-2 cell injury by increasing cell viability and hampering apoptosis under HG condition. In addition, miR-133a-3p directly targets MAML1 3'-untranslated region. MAML1 overexpression countervailed the repressive impact of miR-133a-3p on cell apoptosis in the context of HG. Moreover, miR-133a-3p inhibited the activity of Notch pathway by downregulating MAML1. MiR-133a-3p inhibits DN progression in mice, as evidenced by reduced fasting blood glucose level, improved levels of renal function parameters, and alleviation of kidney atrophy. In conclusion, miR-133a-3p improves HG-induced HK-2 cell injury and inhibits DN progression by targeting MAML1 and inactivating Notch signaling.