The Association of Postprandial Triglyceride Variability with Renal Dysfunction and Microalbuminuria in Patients with Type 2 Diabetic Mellitus: A Retrospective and Observational Study

Objective. We examined whether or not day-to-day variations in lipid profiles, especially triglyceride (TG) variability, were associated with the exacerbation of diabetic kidney disease. Methods. We conducted a retrospective and observational study. First, 527 patients with type 2 diabetes mellitus (DM) who had had their estimated glomerular filtration rate (eGFR) checked every 6 months since 2012 for over 5 years were registered. Variability in postprandial TG was determined using the standard deviation (SD), SD adjusted (Adj-SD) for the number of measurements, and maximum minus minimum difference (MMD) during the first three years of follow-up. The endpoint was a ≥40% decline from baseline in the eGFR, initiation of dialysis or death. Next, 181 patients who had no micro- or macroalbuminuria in February 2013 were selected from among the 527 patients for an analysis. The endpoint was the incidence of microalbuminuria, initiation of dialysis, or death. Results. Among the 527 participants, 110 reached a ≥40% decline from baseline in the eGFR or death. The renal survival was lower in the higher-SD, higher-Adj-SD, and higher-MMD groups than in the lower-SD, lower-Adj-SD, and lower-MMD groups, respectively (log-rank test p = 0.0073 , 0.0059, and 0.0195, respectively). A lower SD, lower Adj-SD, and lower MMD were significantly associated with the renal survival in the adjusted model (hazard ratio, 1.62, 1.66, 1.59; 95% confidence intervals, 1.05-2.53, 1.08-2.58, 1.04-2.47, respectively). Next, among 181 participants, 108 developed microalbuminuria or death. The nonincidence of microalbuminuria was lower in the higher-SD, higher-Adj-SD, and higher-MMD groups than in the lower-SD, lower-Adj-SD, and lower-MMD groups, respectively (log-rank test p = 0.0241 , 0.0352, and 0.0474, respectively). Conclusions. Postprandial TG variability is a novel risk factor for eGFR decline and the incidence of microalbuminuria in patients with type 2 DM.

Clinical and Histological Predictors of Renal Survival in Patients with Biopsy-Proven Diabetic Nephropathy

<b><i>Introduction:</i></b> Clinical indicators or pathological features alone cannot reliably predict renal survival in patients with biopsy-confirmed diabetic nephropathy (DN). Therefore, this analysis sought to develop and validate a predictive model incorporating both clinical and pathological markers to predict renal outcomes in patients with biopsy-confirmed DN. <b><i>Methods:</i></b> A predictive nomogram was developed based upon data pertaining to 194 patients with biopsy-confirmed DN. The prognostic relevance of individual clinicopathological variables was assessed through univariate and multivariate Cox regression analyses. A prognostic nomogram was then developed and validated based upon concordance (C)-index values and calibration curves. Internal validation was conducted through bootstrap resampling, while the clinical utility of this model was assessed via a decision curve analysis (DCA) approach. <b><i>Results:</i></b> Nephrotic-range 24-h proteinuria, late-stage CKD, glomerular classification III–IV, and IFTA score 2–3 were all identified as independent predictors of poor renal outcomes in DN patients and were incorporated into our final nomogram. Calibration curves revealed good agreement between predicted and actual 3- and 5-year renal survival in DN patients with the C-index value for this nomogram at 0.845 (95% CI: 0.826–0.864). DCA revealed that our nomogram was superior to models based solely upon clinical indicators. <b><i>Conclusion:</i></b> A predictive nomogram incorporating clinical and pathological indicators was developed and validated for the prediction of renal survival outcomes in patients with biopsy-confirmed DN. This model will be of value to clinicians, as it can serve as an easy-to-use and reliable tool for physicians to guide patient management based on individualized risk.

Discontinuation of Eculizumab treatment after hematological remission in patients with atypical and drug-induced hemolytic uremic syndrome

Introduction: To evaluate the effect of therapeutic plasma exchange(TPE) and eculizumab on hematological and renal survival in atypical hemolytic uremic syndrome(aHUS). Additionally, to examine the reliability of discontinuation of eculizumab treatment. Methods: This was an observational and retrospective study of 18 patients diagnosed with aHUS. Results: The median age of the study population was 30(22-66) years. Four of 18 patients achieved hematological remission with the TPE alone. However, one patient in the died after three sessions of TPE. Eculizumab was used in 13 patients and no death was observed. One year after treatment, improved kidney function was observed in 2 of 3(66%) patients for TPE and 5 of 9(56%) patients for Eculizumab. We discontinued eculizumab treatment in 9 patients. One of the patients who had a C3 gene mutation experienced disease relapse after Eculizumab discontinuation. None of the patients who had drug associated aHUS, developed disease relapse after Eculizumab discontinuation. Conclusion: Eculizumab treatment is a life-saving therapy in aHUS. Treatment discontinuation may be considered at least six months after hematologic remission in patients who had stable renal function or no expectancy for renal survival. Moreover, drug-associated cases seem to tend not to develop disease relapse in the long term.

Successful therapeutic response with sequential therapy of rituximab and belimumab in a hispanic patient with refractory lupus nephritis

Lupus nephritis (LN) is the most common severe organ manifestation of systemic lupus erythematosus (SLE). Life expectancy and renal survival is reduced in these patients. A partial remission in LN is associated with a significantly better patient and renal survival rate compared with no remission. We report the case of a 27-year-old Hispanic patient with diffuse proliferative lupus nephritis (grade IV with high activity index) managed with induction therapy with mycophenolate mophethyl (MMF, 1000 mg daily escalating to 3000 mg daily and prednisone (PDN) 1 mg/kg/day. Progression of proteinuria with preserved renal function and extra-renal activity were observed (alopecia). Re-induction with IV cyclophosphamide (CYC, 1 gr.) and pulse IV methylprednisolone (500 mg for three days) was administered, followed by a lower starting dose of PDN (0.5 mg/kg/day). Treatment failure was observed. A second renal biopsy evidenced renal damage (chronicity index 4/12 and activity index 4/24). The patient also developed non-renal clinical manifestations (malar rash, oral ulcers and arthritis). Treatment with IV rituximab (RTX) 1000 mg X2 associated with MMF 1000 mg per day and IV methylprednisolone 500 mg X3 was initiated, followed by PDN 0.5 mg/kg/day with a dose-tapering scheme similar to CYC re-induction. Treatment continued with IV Belimumab (BLM) 600 mg every month associated with MMF 1000 mg per day. Sequential therapy with RTX + BLM showed a partial renal and complete extra-renal response in a patient with severe lupus despite two 2 immunosuppressive treatment schemes.

Clinicopathological features and outcomes of coexistent light chain cast nephropathy and light chain deposition disease in patients with newly diagnosed multiple myeloma

AimsA varying proportion of patients with multiple myeloma suffer from more than one type of kidney disease simultaneously, of which the most common pattern is coexistent light chain cast nephropathy and light chain deposition disease (LCCN+LCDD). We investigated clinicopathological characteristics and outcomes of LCCN+LCDD in comparison with pure LCCN and pure LCDD.MethodsWe retrospectively analysed 45 newly diagnosed multiple myeloma patients with pure LCCN (n=26), LCCN +LCDD (n=9) and pure LCDD (n=10) between 2000 and 2019 at Peking University First Hospital.ResultsPathologically, patients with LCCN+LCDD were more likely to have λ light chain isotype and presented atypical features of LCDD including less nodular glomerulosclerosis and less deposit distribution than patients with pure LCDD. In clinical characteristics, patients with LCCN +LCDD and patients with pure LCCN shared similar features. The death-censored renal survival in patients with LCCN +LCDD was similar to patients with pure LCCN but worse than patients with pure LCDD, but the overall survival was much better than patients with LCCN alone and similar to patients with pure LCDD. For patients with pure LCCN, the independent predictor of death-censored renal survival was lactate dehydrogenase, and the independent predictors of overall survival were the mean number of casts and serum albumin.ConclusionsPatients with LCCN+LCDD had similar renal outcome compared with patients with pure LCCN but the overall survival is much better. Thus, for patients with LCCN, especially those with λ restriction, pathologists should carefully evaluate the kidney specimens to exclude the possibility of combined LCDD.

Association of Urinary Dickkopf-3 with Residual Renal Function Decline in Patients Undergoing Peritoneal Dialysis

Background and Objectives: Urinary levels of dickkopf-3 (DKK-3) are associated with poor renal survival in patients with non-dialytic chronic kidney disease. However, it remains unknown whether urinary DKK-3 levels can predict residual renal function (RRF) decline in patients undergoing peritoneal dialysis (PD). Therefore, we investigated the correlation between urinary levels of DKK-3 and the subsequent rate of RRF decline in PD patients. Materials and Methods: This study included 36 PD patients who underwent multiple peritoneal equivalent tests during 2011–2021. The relationship between baseline clinical characteristics and the subsequent annual rate of Kt/V decline was investigated. Results: The annual rate of renal Kt/V decline was 0.29 (range: 0.05–0.48), which correlated with renal Kt/V (r = 0.55, p = 0.0005) and 24 h urinary DKK-3 excretion (r = 0.61, p < 0.0001). Similarly, 24 h urinary DKK-3 excretion (β = 0.44, p = 0.0015) and renal Kt/V (β = 0.38, p = 0.0059) were independently associated with the annual rate of renal Kt/V decline in multivariate analyses. Conclusions: Urinary DKK-3 assessment may help identify PD patients at a high risk of RRF decline.

Serum Bilirubin Is Correlated With the Progression of IgA Vasculitis With Nephritis

Background: Bilirubin has been identified as an endogenous antioxidant and cellular protectant. The present study was performed to clarify the potential influence of serum bilirubin on IgA vasculitis with nephritis (IgAV-N).Methods: One hundred and eighty-nine IgAV-N patients over 14 years old were enrolled. The patients were divided into two groups by the optimum cut-off value calculated by ROC curve. The composite endpoints were defined as a 60% decline in estimate glomerular filtration rate (e-GFR), end-stage renal disease (ESRD) and/or death. Kaplan-Meier (K-M) analysis and multivariate Cox analysis were carried out to determine the predictors for renal outcomes. In order to eliminate the influence of different baseline data, a 1:2 propensity score (PS) match was performed to make the results comparable and convictive.Results: The baseline data suggested that patients in low serum bilirubin group had significantly higher levels of systolic blood pressure, proteinuria, serum creatinine and crescent formation ratio and lower levels of serum albumin and hemoglobin. Renal survival analysis indicated that lower serum bilirubin levels were significantly correlated with a poorer prognosis. Multivariate Cox analysis demonstrated that the higher level of serum bilirubin was an independent protective factor for renal survival (HR, 0.172; 95% CI, 0.030–0.991; P = 0.049). After PS matching, the baseline characters of two groups had no statistical differences. Similar outcomes were demonstrated in K-M curve and the multivariate Cox analysis.Conclusion: Elevated bilirubin levels might be related to the favorable renal outcomes.

MO646PATHOLOGICAL PROGNOSTIC FACTORS IN DIABETIC NEPHROPATHY: A RETROSPECTIVE STUDY

Background and Aims Kidney Biopsies (KB) performed in patients with Type-2 diabetes (T2D) usually aim at differentiating diabetic nephropathy (DN) from other kidney diseases. However, KB could also help refining patients’ prognosis, both in terms of renal survival, and in terms of patient survival. In 2010, the Renal Pathology Society developed a pathological classification of DN, but the prognostic value of the described items , is still imperfectly documented. We aimed to assess the prognostic performances of these items to predict renal and patient survival. Method Native KBs with diabetic and/or hypertensive nephropathy (DN/HN) performed in patients with T2D in four French centers were analyzed and scored according to the classification developed by the Renal Pathology Society. Clinical and biological data was collected from the patients’ records. Survival analyses were performed for renal survival (time to first dialysis or preemptive transplantation) and death after dichotomization of continuous data). For each of the analyses, we first established a model comprising clinical data only. We then assessed the benefit of adding each of the pathological item to the clinical model. Finally, we performed a backward stepwise analysis to identify items predictive of renal and/or patient survival. Results We analyzed 165 biopsies with DN/HN from patients with T2D and with at least 12 months of follow-up (unless they reached an endpoint during the first year). Among them, 73 (44%) were male, 155 (94%) had hypertension, 53 (34%) hematuria, 22 (15%) had proliferative diabetic retinopathy (DR), 33 (23%) had non-proliferative DR, 90 (62%) had no DR (20 had missing data). Mean (SD) age was 63 (11), median [IQR] eGFRCKD-EPI was 29 [18;45] ml/min/1.73m², urinary protein-to-creatinine ratio was 0.38 [0.14;0.83] g/mmol, HbA1c was 7 [6.2;8.2] % and diabetes duration before KB was 10 [5;19] years. The median [IQR] follow-up was 33 months[18;57]. During the follow-up, 43 (26%) patients died and 69 (42%) required renal replacement therapy (RRT). The percentage of ischemic glomeruli, and presence of more than one area of arteriolar hyalinosis (ah=2), were predictive of renal survival and improved the predictive value of the model when added to clinical parameters. Presence of at least one convincing Kimmelstiel–Wilson lesion (nodular glomerulosclerosis or Class III DN) was predictive of death and similarly improved the predictive model (See figure). Conclusion Pathological findings on KB, as classified by the Renal Pathology Society, carry significant prognostic value in patients with T2D and DN/HN. Vascular lesions (presence of arteriolar hyalinosis and less than 7% of ischemic glomeruli) predicted the need for RRT, while nodular glomerulosclerosis was predictive of death.