Risk Factors For Renal Survival Research Articles

Thrombotic microangiopathy mediates poor prognosis among lupus nephritis via complement lectin and alternative pathway activation.

The pathogenesis of thrombotic microangiopathy (TMA) in lupus nephritis (LN) remains complicated. This study aimed to detect the deposition of complement lectin pathway (LP) and alternative pathway (AP) components in renal tissues, then evaluate the clinicopathological characteristics and risk factors for renal survival between patients with or without TMA in LN cohorts. We included 79 patients with biopsy-proven LN-associated TMA and matched the same number of LN patients without TMA as the control group. The deposition of mannose binding lectin (MBL), MBL-associated serine proteases 1/3 (MASP1/3), complement factor B (CFB), complement factor D (CFD), C4d, and von Willebrand factor (VWF) in renal tissue was assessed by immunohistochemistry and immunofluorescence. Besides, co-localization of C5b-9 and CD34 was detected by confocal microscopy. In our retrospective cohort, the incidence of acute kidney injury (30% vs. 14%, p = 0.013), acute hemodialysis (35% vs. 5%, p < 0.001), and interstitial fibrosis (43% vs. 13%, p < 0.001) is higher in the TMA, compared with the control group. Despite aggressive steroids pulse, plasma exchange, and immunosuppressive therapy among TMA group, they still had significantly inferior 3-year renal survival rates (68% vs. 89%, p = 0.002) than those in the non-TMA group. COX regression analysis identified that TMA (HR 4.807, 95% CI [2.052, 11.263], p < 0.001) is a risk factor in LN. MBL, MASP1/3, CFB, CFD, C4d, and VWF deposited along the glomerulus among LN, while TMA had stronger staining intensity and deposition. The co-localized expression of CD34 and C5b-9 in the endothelial cells was also observed in the renal tissues. TMA is an independent risk factor for renal survival in LN patients. Moreover, LP and AP activation are involved in the pathogenesis of LN-associated TMA.

Prognostic evaluation model of diabetic nephropathy patients.

Diabetic nephropathy (DN) affects about 40% of diabetes mellitus (DM) patients and is the leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) globally, especially in advanced countries. We aimed to explore the risk factors affecting the prognosis of DN, and to establish a prognostic evaluation line map. We analyzed 471 cases of DN from December 2011 to April 2020, and extracted the basic clinical factors, including gender, age, and history of diabetes. Analysis included that of associations between DN and hypertension, creatinine (CR), body mass index (BMI), and fundus lesions. Statistical analysis was performed using R software and the related R package. The above clinical factors were analyzed by both single- and multiple-factor Cox regression. The participants were divided into two groups, including a high risk and a low risk group. A Kaplan-Meier curve was drawn for survival analysis of the high and low risk groups, and the log-rank method was used for statistical testing. A receiver operating characteristic (ROC) curve was drawn with the area under the curve (AUC) calculated to evaluate the predictive effectiveness of the line map. This study initially included 471 patients; however, 33 patients (7.0%) were lost to follow-up due to inaccessibility. A total of 93 cases (21.2%) died during the follow-up. The 3-year and 5-year renal survival rates were 74.5% and 22.6%, respectively. Single factor Cox analysis showed that the course of diabetes, fundus lesions, BMI, and grade of hypertension were risk factors for renal survival, and had adverse effects on prognosis (P<0.05). Multivariate Cox regression analysis showed that BMI and grade of hypertension were independent risk factors for survival of DKD, and had adverse effects on prognosis (P<0.05). Survival analysis showed that low risk group participants had significantly better survival rates than high risk group participants (P<0.05). The AUC was 0.742, which meant that the line map could accurately predict the survival rate of DN patients. The influence of risk factors on prognosis can be accurately evaluated by line diagram which can provide a basis for clinical decision making.

Clinicopathological characteristics and outcomes of anti-neutrophil cytoplasmic autoantibody-related renal vasculitis with hyperuricemia: a retrospective case-control study

The objective of the study was to evaluate the clinicopathological characteristics and investigate the clinical determinants of patient and renal survival in the first 12 months after diagnosis in anti-neutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis (AAV) patients with hyperuricemia. This was a retrospective case-control study in patients with AAV-related renal injury in the First Affiliated Hospital of Zhengzhou University from January 2014 to April 2019. Patients who met the study criteria were divided into two groups: patients without hyperuricemia (n = 92) and patients with hyperuricemia (n = 55). Participants were followed-up for 12 months, and progressing to end-stage renal disease (ESRD) and death was treated as the endpoint event. We found that the level of serum creatinine was an independent risk factor for hyperuricemia, and the level of serum uric acid was an independent risk factors for renal survival and patient survival in ANCA-associated renal vasculitis patients. The crescents formation and the proportion of fibrous crescent likely contributed to severe clinical characteristics and renal pathological changes in ANCA-associated renal vasculitis patients with hyperuricemia. Hyperuricemia has an important influence on the progression of ANCA-associated renal vasculitis. A good control of serum uric acid may improve the prognosis.

Association of Glomerular Complement C4c Deposition With the Progression of Diabetic Kidney Disease in Patients With Type 2 Diabetes.

Objectives: As accumulating data supporting the potential role of the complement system in the pathogenesis of diabetic kidney disease (DKD), the present study aimed to explore the association of glomerular complement C4c deposition with the baseline clinicopathological characteristics and the prognosis of DKD in type 2 diabetes (T2DM) patients.Methods: A total of 79 T2DM patients with biopsy-proven DKD were enrolled. Clinicopathological features and renal outcomes were compared between groups divided by the glomerular C4c deposition patterns and median values of serum C4. Renal outcomes were defined by doubling of serum creatinine level or progression to end-stage renal disease (ESRD). A Cox proportional hazards model was employed to identify the risk factors associated with renal events.Results: Patients with glomerular C4c deposition had worse renal insufficiency than those without C4c deposits, along with higher 24-h urinary protein, triglyceride, but lower serum albumin and higher interstitial inflammation score. Besides, serum C4 levels positively correlated with urinary protein and serum C3 levels. During 21.85 ± 16.32 months of follow-up, Kaplan-Meier curve analysis showed significantly faster deterioration of renal function for patients with positive glomerular C4c deposition as well as higher levels of serum C4. More specifically, more than 50% of the patients with glomerular C4c had co-deposition of C3c or C1q, and patients with glomerular complement complex of C4c and one or two of C3/C1q deposition had more severe proteinuria and a higher rate of DKD progression than those with negative C4c deposits. The univariate Cox regression indicated that factors of combined serum and glomerular C4, urinary protein, serum creatinine, serum C3, combined glomerular C4c and IgM and interstitial inflammation were associated with an increased risk of DKD, but only glomerular C4c intensity (HR 1.584, 95% CI [1.001, 2.508], p = 0.0497), as well as baseline age and diabetic neuropathy, were independent risk factors for renal survival by the multivariate Cox analysis.Conclusions: Glomerular C4c deposition was associated with deteriorated renal function and outcomes in patients with T2DKD. Glomerular C4c deposition was an independent risk factor for DKD progression.

Risk factors affecting renal function and survival of patients with myeloperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis

To determine the prognostic values of clinical and laboratory features at the time of presentation on renal function and survival of patients with myeloperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis. (MPO-ANCA GN). A total of 119 patients (52 males and 67 females) with MPO-ANCA GN and hospitalized at the First Affiliated Hospital of Nanjing Medical University from January 2010 to April 2018 were enrolled. The baseline clinical characteristics, renal biopsy pathological data, and risk factors predictive of renal and patient survival were retrospectively analyzed. Among these 119 patients, the median serum creatinine at diagnosis was 354.30 (range, 216.10 - 637.30) mmol/L and the median estimated glomerular filtration rate (eGFR) was 14.78(range, 7.23-29.21) mL/min. In total, 58(48.7%) patients received initial renal replacement therapy (RRT). During a median follow-up duration of 32 (range, 3 - 113) months, 57(47.9%) patients progressed to end-stage renal disease (ESRD). Initial renal function status (i.e., initial RRT, serum creatinine, and eGFR) (p < 0.001) and hemoglobin level (p = 0.027) were significant risk factors for renal survival. During the follow-up, 69 (57.6%) of 119 patients survived. Age (p = 0.009) and urine red blood cell count (p = 0.012) were predictive of patient survival. Among patients with MPO-ANCA GN, poor renal function and lower hemoglobin level were predictive of ESRD, while older age and higher urinary red blood cell count were associated with a higher risk for all-cause mortality.

P0291MYELOMA CAST NEPHROPATHY, LIGHT CHAIN DEPOSITION DISEASE, AND BOTH IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA

Abstract Background and Aims The pathological patterns of myeloma-related kidney disease are various, in which myeloma cast nephropathy (MCN) and light chain deposition disease (LCDD) are two of the main patterns. Of note, in patients with multiple myeloma (MM), these two patterns of pathology can occur at the same time. However, there are limited data available showing the difference of clinical characteristics and outcomes among newly diagnosed MM patients with these three patterns of pathology. In this study, we retrospectively reviewed 42 newly diagnosed MM patients with renal biopsy-proven pure MCN, pure LCDD or MCN with coexistent LCDD in Peking University First Hospital, to describe the clinical characteristics, treatment, and outcomes, in order to help define the spectrum of prognostic profiles. Method All the native renal biopsies between September 1999 and October 2019 at Peking University First Hospital were retrospectively restudied. A total of 42 newly diagnosed MM patients with pure MCN (n=24), pure LCDD (n=8) and MCN with coexistent LCDD (n=10) were enrolled. The clinical features, as well as prognostic risk factors for renal survival and overall survival were retrospectively investigated. Results The 42 parents consisted of 26 men and 16 women with a mean age of 53.2±10.9 years. There was no significant difference in age and gender among the 3 groups. Patients with pure LCDD had significantly higher hemoglobin levels, a higher percentage of albumin in urine protein, a lower incidence of progressing to ESRD and more likely to present with AKD than patients with pure MCN or with MCN+LCDD. Patients with pure LCDD had significantly higher serum creatinine levels, a lower eGFR, a lower incidence of death and more likely to present with nephrotic syndrome than patients with pure MCN, but no different than patients with MCN+LCDD. No significant difference between pure MCN and MCN+LCDD. Median renal survival in LCDD group (not reached) was significantly higher compared to MCN (11 months, p = 0.002) group and MCN+LCDD group (1months, p = 0.012, Figure 1). Median overall survival in LCDD group (not reached) was significantly higher compared to MCN (39 months, p = 0.014) group, but had no difference with MCN+LCDD group (not reached, p = 0.199, Figure 2). According to the multivariate analysis, the independent predictors of renal survival were hemoglobin (HR: 0.957, 95% CI: 0.922-0.994; p = 0.022) and eGFR (HR: 0.940, 95% CI: 0.880-0.995; p = 0.034), the independent predictors of overall survival were hemoglobin (HR: 0.943, 95% CI: 0.895-0.993; p = 0.025) and pure MCN (HR: 7.597, 95% CI: 1.171-49.272; p = 0.034). Conclusion Patients with MCN+LCDD presented similar in clinical characteristics to patients with pure MCN and both suffer from more serious and more urgent renal damage than patients with pure LCDD. However, the overall survival in patients with MCN+LCDD was similar to patients with pure LCDD while the renal survival was worse. Hemoglobin and eGFR were independent predictors of renal survival and hemoglobin and pure MCN were independent predictors of overall survival.

Prognosis and its risk factors in ANCA-associated glomerulonephritis patients treated with initial renal replacement therapy

Objective: To explore the prognosis and its risk factors in anti-neutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (AAGN) patients who needed initial renal replacement therapy (RRT). Methods: One hundred patients [54 females, 46 males, with a median age of 54(41, 60) years] with biopsy-proven AAGN and requiring initial RRT between January 1996 and December 2016 in Nanjing Jinling Hospital were included. Intensive immunotherapy indicated that the patients received corticosteroids in combination with cyclophosphamide or mycophenolate mofetil, or immunoadsorption (IA) or double filtration plasmapheresis (DFPP). The clinical and histological risk factors for renal survival were analyzed. Results: Forty-one patients were free of RRT after a median time of 1 (0.5, 2) month treatment (dialysis-independent group), and the remaining 59 patients were on maintenance dialysis (dialysis-dependent group). The multivariate logistic analysis revealed that the proportion of normal glomeruli <8% (OR=5.95, P=0.002) and global sclerotic glomeruli ≥50% (OR=4.87, P=0.003), and not receiving intensive immunotherapy (OR=7.81, P=0.004) were the risk factors for the renal recovery in these patients. During a median follow-up time of 22 (10, 50) months, 15 patients(36.6%) in the dialysis-independent group progressed into maintenance dialysis, and the 1 and 3 year renal survival rate were 86% and 60%, respectively. During a median follow-up time of 6 (2, 24) months, 12 (12%) patients died, among whom four patients died of therapy. The multivariate Cox regression analysis revealed that IA/DFPP treatment (HR=10.85, P=0.034) and low albumin level (HR=1.26, P=0.009) significantly associated with a higher risk of therapy-related death. Conclusions: The renal recovery rate in AAGN patients with initial RRT was low. The proportion of normal and global sclerotic glomeruli, receiving intensive immunotherapy or not were associated with renal outcome, and IA/DFPP treatment as well as lower albumin level were independently associated with therapy-related death.

Risk Factors for Renal Survival in Chinese Patients with Myeloperoxidase-ANCA-Associated GN.

Our study explored the association of histopathologic classification of ANCA-associated GN with renal survival in Chinese patients with myeloperoxidase-ANCA-associated GN. Two hundred fifteen patients with biopsy-proven myeloperoxidase-ANCA-associated GN were included from January of 1996 to December of 2014. The biopsies included focal (n=27), mixed (n=82), crescentic (n=47), and sclerotic (n=59) classes. The long-term renal outcome and risk factors of myeloperoxidase-ANCA-associated GN for different histopathologic classes were retrospectively analyzed. During a median follow-up time of 22 (9-51) months, 88 (40.9%) patients reached ESRD. The 5-year renal survival (overall 58.7%) was highest in the focal class (100.0%) and lowest in the sclerotic class (20.7%), with no difference between the mixed (58.9%) and crescentic (67.4%) classes. Patients in the mixed (hazard ratio, 0.34; 95% confidence interval, 0.20 to 0.57; P<0.001) and crescentic (hazard ratio, 0.31; 95% confidence interval, 0.16 to 0.59; P<0.001) classes were at lower risk for ESRD compared with patients in the sclerotic class, as were patients who received glucocorticoids plus mycophenolate mofetil (hazard ratio, 0.32; 95% confidence interval, 0.18 to 0.60; P<0.001) compared with those receiving glucocorticoids alone. In addition, patients with a serum creatinine level ≥4 mg/dl (hazard ratio, 2.93; 95% confidence interval, 1.77 to 4.85; P<0.001) or hypoalbuminemia (hazard ratio, 2.11; 95% confidence interval, 1.32 to 3.34; P=0.002) were at higher risk for ESRD. A serum creatinine level ≥4 mg/dl and a percentage of global sclerotic glomeruli ≥60% were the two independent risk factors for ESRD in the sclerotic class. The histopathologic classification of ANCA-associated GN in combination with serum creatinine and serum albumin levels and treatment regimen is associated with renal outcome in myeloperoxidase-ANCA-associated GN. The evaluation of serum creatinine level and percentage of global sclerotic glomeruli provides additional information on the risk of renal survival in the sclerotic class of myeloperoxidase-ANCA-associated GN.

Impact of Posttransplantation Glomerulonephritis on Long‐term Outcome of Kidney Transplants: Single‐Center 20‐Year Experience

Successful renal transplantation has been performed in patients with end-stage renal disease and has been routine in patients with end-stage renal failure for more than two decades. Despite advances in the use of immunosuppressants, there has been only modest improvement in long-term allograft survival. Accumulating data have demonstrated that chronic rejection and recurrent glomerulonephritis are major causes of long-term allograft loss. However, data regarding the long-term impact of posttransplantation glomerulonephritis (PTGN) on ethnic Chinese populations are still unavailable. From 1984 to 2010, a total of 268 patients who underwent renal allograft biopsies were reviewed retrospectively. Renal outcomes were compared by Kaplan-Meier analysis, and risk factors for renal survival and all-cause mortality were analyzed using the Cox proportional hazards model. In all, 85 patients (31.7%) had PTGN, and the mean time of disease onset was 5.32±5.18 years after transplantation. Among the 85 PTGN cases, 33 (39%) were immunoglobulin A (IgA) nephropathy, 24 (28%) were focal segmental glomerulosclerosis, and 8 (9.4%) were membranous GN. Significant risk was associated with posttransplant IgA GN in hepatitis B virus carriers (odds ratio 5.371, 95% confidence interval 1.68, 17.19; p=0.0064). A total of 45 PTGN patients had allograft loss, of whom 49% had IgA nephropathy. Patients with PTGN had inferior allograft survival rates compared to those with other pathologic findings (p<0.0003). Taken together, our results indicate that PTGN had a strong negative impact on long-term kidney graft survival. Posttransplant IgA nephropathy is a leading cause of allograft loss in Chinese kidney transplant patients with PTGN.