Atypical anti-glomerular basement membrane disease with membranous hyperplasia: diagnostic challenges and treatment variability.

This case report presents a detailed analysis of a 31-year-old male patient who presented with a complex array of clinical symptoms, including proteinuria, hematuria, edema, and kidney insufficiency. Despite undergoing multiple tests, the results for anti-glomerular basement membrane antibodies yielded negative findings. Subsequently, kidney biopsy pathology revealed a distinct diagnosis of atypical anti-glomerular basement membrane (anti-GBM) disease with membrane hyperplasia. Treatment was initiated with a comprehensive approach involving high doses of corticosteroids therapy and cyclophosphamide (CTX). However, contrary to expectations, the patient's kidney function exhibited rapid deterioration following this therapeutic regimen. The culmination of these complications necessitated a pivotal transition to maintenance hemodialysis. This case underscores the intricate challenges associated with diagnosing and managing rare and atypical presentations of kidney disorders. The negative anti-GBM antibody results and subsequent identification of atypical anti-GBM nephropathy highlight the need for tailored diagnostic strategies to discern subtle nuances within complex clinical scenarios. Additionally, the unexpected response to the treatment regimen emphasizes the potential variability in individual patient responses, underlining the necessity for vigilant monitoring and adaptable treatment strategies. This case report contributes to the evolving understanding of atypical kidney pathologies and the complexities involved in their management.

The Efficacy and Mechanism of Chinese Herbal Medicines in Lowering Serum Uric Acid Levels: A Systematic Review.

Background. Chinese herbal medicines are widely used to lower serum uric acid levels. However, no systemic review summarizes and evaluates their efficacies and the underlying mechanisms of action. Objectives. To evaluate the clinical and experimental evidences for the effectiveness and the potential mechanism of Chinese herbal medicines in lowering serum uric acid levels. Methods. Four electronic databases PubMed, Wed of Science, the Cochrane Library and Embase were used to search for Chinese herbal medicines for their effects in lowering serum uric acid levels, dated from 1 January 2009 to 19 August 2020. For clinical trials, randomized controlled trials (RCTs) were included; and for experimental studies, original articles were included. The methodological quality of RCTs was assessed according to the Cochrane criteria. For clinical trials, a meta-analysis of continuous variables was used to obtain pooled effects. For experimental studies, lists were used to summarize and integrate the mechanisms involved. Results. A total of 10 clinical trials and 184 experimental studies were included. Current data showed that Chinese herbal medicines have promising clinical efficacies in patients with elevated serum uric acid levels (SMD: -1.65, 95% CI: -3.09 to -0.22; p = 0.024). There was no significant difference in serum uric acid levels between Chinese herbal medicine treatments and Western medicine treatments (SMD: -0.13, 95% CI: -0.99 to 0.74; p = 0.772). Experimental studies revealed that the mechanistic signaling pathways involved in the serum uric acid lowering effects include uric acid synthesis, uric acid transport, inflammation, renal fibrosis and oxidative stress. Conclusions. The clinical studies indicate that Chinese herbal medicines lower serum uric acid levels. Further studies with sophisticated research design can further demonstrate the efficacy and safety of these Chinese herbal medicines in lowering serum uric acid levels and reveal a comprehensive picture of the underlying mechanisms of action.

Mortality and Associated Risk Factors in Dialysis Patients with Cardiovascular Disease.

BACKGROUND/AIMS: Although dialysis patients have a higher risk of morbidity and mortality related to cardiovascular disease (CVD) than the general population, the mortality and associated risk factors in Asian dialysis patients with CVD have not been well examined. METHODS: In this prospective cohort study, mortality and risk factors were investigated in 591 dialysis patients who were recruited from two dialysis centers from May 1, 2009 to May 1, 2014. The Cox proportional hazards regression assessed adjusted differences in mortality risk. A multivariate analysis was also performed, comparing the CVD and non-CVD groups. RESULTS: A total of 591 patients were enrolled in this study (mean age, 52.05 ± 16.46 years [SD]; 61.8% men; 20.8% with CVD), with a median follow-up of 21.9 (maximum, 72) months. The cumulative hazard of mortality was significantly higher in CVD patients (hazard ratio [HR], 1.835; 95% confidence interval [CI], 1.023-3.293; P=0.042) than in their non-CVD counterparts after adjusting for various confounders. On multivariate Cox analysis, stroke (HR, 4.574; 95% CI, 2.149-9.736; P<0.001) was an independent predictor of all-cause mortality in the CVD group. In the non-CVD group, diabetes mellitus (HR, 2.974; 95% CI, 1.560-5.668; P=0.001) and elevated high-sensitivity C-reactive lipoprotein (hs-CRP) (HR, 1.017; 95% CI, 1.005-1.030; P=0.005) were independent predictors of all-cause mortality. CONCLUSION: All-cause mortality was significantly higher in the CVD group than in the non-CVD group. Stroke is an independent risk factor for all-cause mortality in dialysis patients with CVD. These findings warrant further studies into preventive and interventional strategies.

Prevalence and Impact on Stroke in Patients Receiving Maintenance Hemodialysis versus Peritoneal Dialysis: A Prospective Observational Study.

BACKGROUND: Patients undergoing maintenance dialysis are at increased risk of stroke, however, less is known about the prevalence and impact on stroke in the patients. METHODS: In this prospective cohort study, 590 patients undergoing hemodialysis (HD; n = 285) or peritoneal dialysis (PD; n = 305) from January 1, 2008 to December 31, 2012 were recruited. Baseline demographic, clinical, and laboratory data were collected. Timeline incidence data were analyzed using a Poisson model. The Cox proportional hazards regression assessed adjusted differences in stroke risk, a multivariate analysis was also performed. RESULTS: 62 strokes occurred during 1258 total patient-years of follow-up. Stroke occurred at a rate of 49.2/1,000 patient-years with a predominance in HD patients compared with PD patients (74.0 vs. 31.8/1,000 patient-years). The cumulative hazard of developing stroke was significantly higher in HD patients (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.15-3.62; p = 0.046) after adjusting for potential confounders. HD patients had an increased risk of ischemic stroke (HR, 2.62; 95% CI, 1.56-4.58; p = 0.002). The risk of hemorrhagic stroke was not significantly different between PD and HD patients. On multivariate Cox analysis, risk factors of stroke in both HD and PD patients were older age, diabetes, and cardiovascular disease. Other independent risk factors of stroke were lower albumin-corrected calcium in HD patients and higher triglycerides in PD patients. CONCLUSIONS: Patients undergoing PD were less likely to develop ischemic stroke than those undergoing HD. Comprehensive control of diabetes, cardiovascular disease, calcium-phosphorus metabolism, and triglyceride levels may be useful preventive strategies for stroke in dialysis patients.

Neutrophil Gelatinase-associated Lipocalin in the Prediction of Contrast-induced Nephropathy: A Systemic Review and Meta-analysis.

OBJECTIVE: The aim of this study was to investigate the predictive value of neutrophil gelatinase-associated lipocalin (NGAL) in the early diagnosis of contrast-induced nephropathy (CIN). METHODS: We searched MEDLINE and Embase until December 2014 for articles evaluating the diagnostic accuracy of plasma/serum and urinary NGAL levels to predict CIN. The primary analysis was based on a hierarchical, bivariate, generalized, linear, mixed model. Diagnostic odds ratio (DOR) and sample size-weighted area under the curve for the receiver operating characteristic (AUROC) were calculated. RESULTS: Ten studies involving 1310 patients were analyzed. Overall, the DOR/AUROC for NGAL level to predict CIN was 20.56 [95% confidence interval (CI), 9.67-43.74]/0.87 (95% CI, 0.84-0.90), with sensitivity and specificity of 0.80 (95% CI, 0.74-0.85) and 0.83 (95% CI, 0.73-0.90), respectively. Subgroup analysis showed that the diagnostic performance of the DOR/AUROC of urinary NGAL [29.48 (95% CI, 12.19-71.27)/0.87 (95% CI, 0.84-0.90)] was better than that of plasma/serum NGAL [14.63 (95% CI, 4.51-47.38)/0.85 (95% CI, 0.82-0.88)] (DOR, P = 0.005, and AUROC, P = 0.04, respectively). CONCLUSIONS: Plasma/serum and urinary NGAL levels seem to be useful biomarkers in the early prediction of CIN. Moreover, urinary NGAL levels perform better than plasma/serum NGAL.

Correlation of Doppler parameters with renal pathology: A study of 992 patients.

Ultrasound examination is a non-invasive diagnostic technique that is used on patients with suspected or established renal disease. The purpose of this study was to determine the role of intrarenal Doppler ultrasonography in the assessment of the renal pathology of patients with chronic kidney disease (CKD), as shown by kidney biopsy. This retrospective analysis enrolled 992 consecutive patients with CKD who underwent intrarenal Doppler ultrasonography and a kidney biopsy at the Departments of Nephrology of three hospitals between January 2006 and December 2010. Doppler parameters, including the peak systolic velocity (PSV), end-diastolic velocity and resistive index (RI) of the interlobar arteries, were compared with the renal biopsy findings. The RI of the interlobar arteries was correlated with the estimated glomerular filtration rate and the histological damage scores, demonstrating the most evident correlation with the tubulointerstitial damage (TI) score among the three histological components. The PSV of the interlobar arteries increased as the CKD stage progressed and correlated with a number of the renal histological changes, including the glomerulosclerosis and TI scores. The RI and PSV of the interlobar artery are correlated with the histopathological pattern in CKD. Thus, the RI and PSV of the interlobar artery may be potential indicators for monitoring the progression of renal damage.

[Effects of urokinase on renal interstitial fibrosis and transforming growth factor-beta1 in the kidney of rats with chronic cyclosporine A nephropathy].

OBJECTIVE: To investigate the effects of urokinase on renal interstitial fibrosis and transforming growth factor-beta1 (TGF-beta1) in the kidney of rats with chronic cyclosporine A nephropathy. METHODS: Male Sprague-Dawley rats on low-salt diet were randomly divided into control (VH), CsA-treated (CsA), CsA+2000 U/kg.day uPA (CsA+U2) and CsA+6000 U.kg.3 days (CsA+U6) groups. The rats were given CsA intragastrically for 4 weeks to prepare CsA-induced chronic nephropathy model. Masson staining was used to examine fibrin deposition. Western blotting and reversal transcription polymerase chain reaction were employed to evaluate urokinase-type plasminogen activator (uPA) and TGF-beta1 protein and gene expressions, respectively. RESULTS: CsA can increase fibrin deposition and the expression of TGF-beta1 in the renal tissue, which were significantly reduced after uPA treatment (P<0.05). CONCLUSION: Continuous low-dose uPA treatment can reduce renal interstitial fibrosis in rats possibly in association with its inhibitory effect on TGF-beta1 expression.

[Role of integrin-linked kinase in renal tubular epithelial-mesenchymal transition and the regulatory effect of urokinase on its expression in mice with obstructive nephropathy].

OBJECTIVE: To investigate the role of integrin-linked kinase (ILK) on renal tubular epithelial-mesenchymal transition and the regulatory effect of urokinase on LIK expression in mice with obstructive nephropathy. METHODS: Normal male mice were randomly divided into sham-operated group (n=20), unilateral ureteral obstruction (UUO) group (n=28), and UUO with urokinase treatment group (uPA, n=28), and UUO was induced surgically in the latter two groups. The mice were sacrificed on days l, 3, 7 and 14 after the surgery, and renal interstitial fibrosis (RIF) was graded according to the result of Masson staining. The expression of ILK in the renal tissues of the rats was examined by immunofluorescence staining and Western blotting, and the expression of E-cadherin was detected by immunohistochemistry. RT-PCR was used to examine the mRNA expressions of ILK, E-cadherin and alpha-smooth muscle actin (alpha-SMA). RESULTS: The expressions of ILK mRNA and protein were significantly increased in UUO group, but significantly decreased by treatment with uPA (P<0.05). The expression of alpha-SMA mRNA level was significantly increased, while E-cadherin decreased in mice with UUO on day 3 after the surgery. Treatment with uPA significantly inhibited such effects (P<0.05). CONCLUSION: ILK plays an important role in renal interstitial fibrosis by mediating epithelial-mesenchymal transition. Urokinase attenuates renal tubulointerstitial fibrosis in mice with UUO possibly by inhibiting ILK expression and preventing tubular epithelial-mesenchymal transition.

[Effect of urokinase on renal interstitial inflammation in rats with chronic cyclosporine A nephropathy and its possible mechanism].

OBJECTIVE: To investigate the protective effect of urokinase on renal interstitial inflammation and fibrosis in rats with chronic cyclosporine A (CsA)-induced nephropathy. METHODS: Male SD rats were fed on low salt diet (0.05% sodium) for 7 days and randomized into 4 groups for treatment with CsA, CsA+continuous low-dose uPA (U2), intermittent CsA+ high-dose uPA (U6) or vehicle (control group). In the former 3 groups, the rats were subjected to daily intragastric administration of CsA (25 mg/kg) for 4 weeks to establish CsA-induced chronic nephropathy model, and those in U2 and U6 groups were given uPA at 2000 U/kg daily or at 6000 U/kg every 3 days, respectively. Four weeks after the treatment, the renal function and 24-h proteinuria were assessed, and Masson staining was used for examining fibrin deposition. Semi-quantitative immunohistochemical staining was employed for evaluation of ED-1-positive cells, urokinase-type plasminogen activator (uPA) and transforming growth factor-beta1 (TGF-beta 1). RESULTS: Four weeks after the treatment, the CsA-treated rats showed significantly elevated serum creatinine (Scr), blood urea nitrogen (BUN) and increased urine proteins. Continuous administration of low-dose uPA resulted in significantly reduced Scr, BUN and 24-h urine protein excretion, while intermittent high-dose uPA treatment did not produce such changes. CsA increased fibrin deposition, total number of macrophages in renal interstitium and TGF-beta1 expression in the renal tissue, which were significantly reduced in U2 group (P<0.05) but not in U6 group (P>0.05). CONCLUSION: Continuous administration of low-dose uPA may reduce interstitial fibrin deposition and alleviate renal interstitial inflammation in rats with chronic CsA nephropathy, possibly by reducing the number of macrophages and TGF-beta1 expression in the renal tissue.