GRU-D-Weibull: A Novel Real-Time Individualized Endpoint Prediction

Accurate prediction models for individual-level endpoints and time-to-endpoints are crucial in clinical practice. In this study, we propose a novel approach, GRU-D-Weibull, which combines gated recurrent units with decay (GRU-D) to model the Weibull distribution. Our method enables real-time individualized endpoint prediction and population-level risk management. Using a cohort of 6,879 patients with stage 4 chronic kidney disease (CKD4), we evaluated the performance of GRU-D-Weibull in endpoint prediction. The C-index of GRU-D-Weibull was ~0.7 at the index date and increased to ~0.77 after 4.3 years of follow-up, similar to random survival forest. Our approach achieved an absolute L1-loss of ~1.1 years (SD 0.95) at the CKD4 index date and a minimum of ~0.45 years (SD0.3) at 4 years of follow-up, outperforming competing methods significantly. GRU-D-Weibull consistently constrained the predicted survival probability at the time of an event within a smaller and more fixed range compared to other models throughout the follow-up period. We observed significant correlations between the error in point estimates and missing proportions of input features at the index date (correlations from ~0.1 to ~0.3), which diminished within 1 year as more data became available. By post-training recalibration, we successfully aligned the predicted and observed survival probabilities across multiple prediction horizons at different time points during follow-up. Our findings demonstrate the considerable potential of GRU-D-Weibull as the next-generation architecture for endpoint risk management, capable of generating various endpoint estimates for real-time monitoring using clinical data.Comment: 30 pages, 7 figures, 4 supplementary figure

Henoch-Schönlein purpura in an older man presenting as rectal bleeding and IgA mesangioproliferative glomerulonephritis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Henoch-Schönlein purpura is the most common systemic vasculitis in children. Typical presentations are palpable purpura, abdominal pain, arthritis, and hematuria. This vasculitic syndrome can present as an uncommon cause of rectal bleeding in older patients. We report a case of an older man with Henoch-Schönlein purpura. He presented with rectal bleeding and acute kidney injury secondary to IgA mesangioproliferative glomerulonephritis.</p> <p>Case presentation</p> <p>A 75-year-old Polish man with a history of diverticulosis presented with a five-day history of rectal bleeding. He had first noticed colicky left lower abdominal pain two months previously. At that time he was treated with a 10-day course of ciprofloxacin and metronidazole for possible diverticulitis. He subsequently presented with rectal bleeding to our emergency department. Physical examination revealed generalized palpable purpuric rash and tenderness on his left lower abdomen. Laboratory testing showed a mildly elevated serum creatinine of 1.3. Computed tomography of his abdomen revealed a diffusely edematous and thickened sigmoid colon. Flexible sigmoidoscopy showed severe petechiae throughout the colon. Colonic biopsy showed small vessel acute inflammation. Skin biopsy resulted in a diagnosis of leukocytoclastic vasculitis. Due to worsening kidney function, microscopic hematuria and new onset proteinuria, he underwent a kidney biopsy which demonstrated IgA mesangioproliferative glomerulonephritis. A diagnosis of Henoch-Schönlein purpura was made. Intravenous methylprednisolone was initially started and transitioned to prednisone tapering orally to complete six months of therapy. There was marked improvement of abdominal pain. Skin lesions gradually faded and gastrointestinal bleeding stopped. Acute kidney injury also improved.</p> <p>Conclusion</p> <p>Henoch-Schönlein purpura, an uncommon vasculitic syndrome in older patients, can present with lower gastrointestinal bleeding, extensive skin lesions and renal involvement which responds well to systemic steroid therapy. A history of diverticulosis can mislead physicians to the diagnosis of diverticular bleeding which is more common in this age group. The clinical manifestations of the disease, including characteristic skin rash, abdominal pain, joint inflammation and renal involvement raised the suspicious of Henoch-Schönlein purpura.</p

Effects of Statins on Renal Outcome in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis

Background: HMG CoA reductase inhibitors (statins) are known to prevent cardiovascular disease and improve lipid profiles. However, the effects of statins on renal outcomes, including decline in estimated glomerular filtration rate (eGFR) and proteinuria in patients with chronic kidney disease (CKD), are controversial. This meta-analysis evaluated the impact of statins on renal outcomes in patients with CKD. Materials and Methods: We comprehensively searched the databases of MEDLINE, EMBASE, and Cochrane Databases. The inclusion criteria were published RCT and cohort studies comparing statin therapy to placebo or active controls in patients with CKD (eGFR <60 ml/min/1.73 m²) not requiring dialysis. The primary outcome was the differences in the change of eGFR. We also examined change of protein concentration in urine as a secondary outcome. A meta-analysis comparing statin and its control groups and a subgroup analysis examining intensity of statin were performed. Results: From 142 full-text articles, 10 studies were included in the meta-analysis. Overall, there was a significant difference in rate of eGFR change per year favoring statin group (mean difference (MD) = 0.10 ml/min/1.73 m², 95% CI: 0.09 to 0.12). In our subgroup analysis, those who received high-intensity statins had a significant difference in eGFR with a MD of 3.35 (95% CI: 0.91 to 5.79) ml/min/1.73 m² compared to control. No significant change in eGFR was found with moderate- and low-intensity statin therapy. Compared with the control group, the statin group did not have a difference in reduction of proteinuria with MD in change of proteinuria of 0.19 gm/day (95% CI: -0.02 to 0.40). Conclusion: Overall, there was a difference in change of eGFR between the statin and control group. High-intensity statins were found to improve a decline in eGFR in population with CKD not requiring dialysis compared with control, but moderate- and low-intensity statins were not. Statins were not found to decrease proteinuria in patients with CKD

The Value of Protocol Biopsies to Identify Patients With De Novo Donorâ Specific Antibody at High Risk for Allograft Loss

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137430/1/ajt14161_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137430/2/ajt14161-sup-0001-TableS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137430/3/ajt14161.pd

Use of Machine Learning Consensus Clustering to Identify Distinct Subtypes of Black Kidney Transplant Recipients and Associated Outcomes

Importance: Among kidney transplant recipients, Black patients continue to have worse graft function and reduced patient and graft survival. Better understanding of different phenotypes and subgroups of Black kidney transplant recipients may help the transplant community to identify individualized strategies to improve outcomes among these vulnerable groups. Objective: To cluster Black kidney transplant recipients in the US using an unsupervised machine learning approach. Design, Setting, and Participants: This cohort study performed consensus cluster analysis based on recipient-, donor-, and transplant-related characteristics in Black kidney transplant recipients in the US from January 1, 2015, to December 31, 2019, in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Each cluster\u27s key characteristics were identified using the standardized mean difference, and subsequently the posttransplant outcomes were compared among the clusters. Data were analyzed from June 9 to July 17, 2021. Exposure: Machine learning consensus clustering approach. Main Outcomes and Measures: Death-censored graft failure, patient death within 3 years after kidney transplant, and allograft rejection within 1 year after kidney transplant. Results: Consensus cluster analysis was performed for 22 687 Black kidney transplant recipients (mean [SD] age, 51.4 [12.6] years; 13 635 men [60%]), and 4 distinct clusters that best represented their clinical characteristics were identified. Cluster 1 was characterized by highly sensitized recipients of deceased donor kidney retransplants; cluster 2, by recipients of living donor kidney transplants with no or short prior dialysis; cluster 3, by young recipients with hypertension and without diabetes who received young deceased donor transplants with low kidney donor profile index scores; and cluster 4, by older recipients with diabetes who received kidneys from older donors with high kidney donor profile index scores and extended criteria donors. Cluster 2 had the most favorable outcomes in terms of death-censored graft failure, patient death, and allograft rejection. Compared with cluster 2, all other clusters had a higher risk of death-censored graft failure and death. Higher risk for rejection was found in clusters 1 and 3, but not cluster 4. Conclusions and Relevance: In this cohort study using an unsupervised machine learning approach, the identification of clinically distinct clusters among Black kidney transplant recipients underscores the need for individualized care strategies to improve outcomes among vulnerable patient groups

Impact of functional status on outcomes of simultaneous pancreas-kidney transplantation: Risks and opportunities for patient benefit

Background. The impact of functional status on survival among simultaneous pancreas-kidney transplant (SPKT) candidates and recipients is not well described. Methods. We examined national Scientific Registry of Transplant Recipients (SRTR) data for patients listed for SPKT in the United States (2006-2019). Functional status was categorized by center-reported Karnofsky Performance Score (KPS). We used Cox regression to quantify associations of KPS at listing and transplant with subsequent patient survival, adjusted for baseline patient and transplant factors (adjusted hazard ratio,(95% LCL)aHR(95%UCL)). We also explored time-dependent associations of SPKT with survival risk after listing compared with continued waiting in each functional status group. Results. KPS distributions among candidates (N = 16 822) and recipients (N = 10 316), respectively, were normal (KPS 80-100), 62.0% and 57.8%; capable of self-care (KPS 70), 23.5% and 24.7%; requires assistance (KPS 50-60), 12.4% and 14.2%; and disabled (KPS 10-40), 2.1% and 3.3%. There was a graded increase in mortality after listing and after transplant with lower functional levels. Compared with normal functioning, mortality after SPKT rose progressively for patients capable of self-care (aHR,(1.00)1.18(1.41)), requiring assistance (aHR,(1.06)1.31(1.60)), and disabled (aHR,(1.10)1.55(2.19)). In time-dependent regression, compared with waiting, SPKT was associated with 2-fold mortality risk within 30 days of transplant. However, beyond 30 days, SPKT was associated with reduced mortality, from 52% for disabled patients (aHR,(0.26)0.48(0.88)) to 70% for patients with normal functioning (aHR,(0.26)0.30(0.34)). Conclusions. While lower functional status is associated with increased mortality risk among SPKT candidates and recipients, SPKT can provide long-term survival benefit across functional status levels in those selected for transplant

Habitual sleep and kidney function in chronic kidney disease: the Chronic Renal Insufficiency Cohort study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142952/1/jsr12573.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142952/2/jsr12573_am.pd