The relationship of platelet distribution width with all-cause and cardiovascular mortality in peritoneal dialysis patients.

BACKGROUND: Cardiovascular disease (CVD) is a major complication in peritoneal dialysis (PD) patients. Previous studies have demonstrated that platelet distribution width (PDW) is associated with cardiovascular events in hemodialysis (HD) patients. In this study, we hypothesized that elevated PDW can predict all-cause and cardiovascular mortality in PD patients. METHODS: We recruited PD patients for a single-center retrospective cohort study from 1 January 2007, to 30 June 2020. Receiver-operating characteristic (ROC) curves were made to determine the PDW cutoff value for predicting all-cause mortality. The propensity score matching (PSM) method was used to improve the equilibrium between groups. The relation of PDW with all-cause and cardiovascular mortality was analyzed by Cox proportional hazards models. Restricted cubic spline (RCS) models were used to determine whether there was a linear relationship between PDW and all-cause and cardiovascular mortality. RESULTS: A total of 720 PD patients were screened, and 426 PD patients were enrolled after PSM. After adjusting for confounders, Cox proportional hazards models showed that the PDW value was positively correlated with the risk of all-cause and cardiovascular mortality (HR = 1.162, 95% CI 1.057-1.278, p = 0.002 and HR = 1.200, 95% CI 1.041-1.382, p = 0.012). The adjusted RCS analysis further showed that the relationship of PDW with all-cause and cardiovascular mortality was linear (p for nonlinearly = 0.143 and 0.062). CONCLUSION: Elevated PDW is independently associated with all-cause and cardiovascular mortality in PD patients.

Prognosis of severe drug-induced acute interstitial nephritis requiring renal replacement therapy.

OBJECTIVE: Drug-induced acute interstitial nephritis (DAIN) is often associated with improved outcomes, whereas some patients may still progress to chronic kidney disease (CKD). The aim of this study was to evaluate the prognosis of patients with severe DAIN requiring renal replacement therapy (RRT) at baseline, and to explore the risk factors of progression to CKD. METHODS: We performed a retrospective study of patients with severe DAIN confirmed by renal biopsies in our center over a 10 years period, all the patients received RRT at presentation. The clinical and pathological characteristics at baseline were recorded, and the outcomes (renal function recovered or progressed to CKD) during follow-ups were also evaluated. Univariate and multivariate logistic regression analysis were performed to identify the independent risk factors of progression to CKD. RESULTS: Seventy-two patients who met the inclusion criteria were enrolled, 13 patients (18.0%) progressed to CKD (GFR < 60 ml/min/1.73 m2) after at least 6 months of follow-up, the remaining 59 patients achieved a favorable renal function recovery. Compared with patients who achieved renal function recovery (recovery group), the patients progressed to CKD (progression group) were older and had longer interval from symptom onset to treatment with steroids. The peak serum cystatin C concentration was higher in progression group than recovery group. Higher score of interstitial fibrosis/tubular atrophy (IFTA) and more interstitial inflammatory cells infiltration were detected in renal tissue in progression group. According to multivariable analysis, higher peak cystatin C concentration (OR = 2.443, 95% CI 1.257, 4.746, p = 0.008), longer interval to treatment with corticosteroids (OR = 1.183, 95% CI 1.035, 1.352, p = 0.014) were independent risk factors of progression to CKD. The cutoff value of cystatin C concentration was 4.34 mg/L, at which the sensitivity and specificity were 76.9% and 89.3%, respectively; the cutoff value of interval to treatment with corticosteroids was 22.5 days, at which the sensitivity and specificity were 81.8% and 79.5%, respectively. CONCLUSION: Renal function was reversible in majority of patients with severe DAIN requiring RRT when early identification and treatment. Higher peak cystatin C concentration and longer interval to treatment with corticosteroids associated with worse renal prognosis.

Membranous nephropathy and thrombotic microangiopathy secondary to metastatic prostate cancer after Iodine-125 prostate brachytherapy: A case report
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BACKGROUND: Prostate cancer is the second most common solid tumor leading to membranous nephropathy (MN). Thrombotic microangiopathy (TMA) has been reported to be related to prostate cancer. Nonetheless, the association between prostate cancer and MN and TMA has not been well established. CASE REPORT: A 73-year-old man presented with nephritic syndrome 40 days after implantation of iodine-125 seed for stage II T2N0M0 prostatic carcinoma. The prostatic-specific antigen (PSA) was normalized, and the tumor disappeared after the initial brachytherapy. The circulating autoantibody to phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain containing 7A (THSD7A) was undetectable. Kidney biopsy revealed MN and TMA in glomerulus. Staining of PLA2R, THSD7A, prostate-specific membrane antigen, and prostate acid phosphatase in glomeruli were all negative. The diagnosis of MN and TMA was made, and a combination of steroid therapy and tacrolimus was prescribed. Two weeks after immunosuppressive treatment with prednisone 30 mg/d and tacrolimus 2 mg/d, the patient achieved partial remission in terms of proteinuria. CONCLUSION: This case study was the first report of MN with TMA as manifestations in patients with prostate cancer after I-125 seeds implantation. We hypothesize that prostate cancer may cause MN and TMA, and the mechanism behind this relationship merits further study.
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Risk Factors of Central Venous Catheter-Related Bloodstream Infection for Continuous Renal Replacement Therapy in Kidney Intensive Care Unit Patients.

BACKGROUND: The incidence of central venous catheter-related bloodstream infection (CRBSI) for continuous renal replacement therapy (CRRT) in kidney intensive care unit (ICU) patients is worthy of particular attention and recently, we analyzed clinical characteristics and risk factors of CRBSI for CRRT in our kidney ICU patients. METHODS: To be part of this retrospective study, 1,523 patients who had a central venous catheter (CVC) for CRRT during the period April 2010 to May 2015 in our centre were enrolled. The clinical features and pathogens of CRBSI patients were investigated. Patients who also had CRRT of kidney ICU hospitalization without CRBSI were enrolled in a 1: 2 ratio as control. Risk factors of the CRBSI were analyzed. RESULTS: A total of 57 patients had central venous CRBSI. The incidence of the infection was 3.7%. The mean rate of CRBSI was 3.9 per 1,000 catheter days, and the catheter median indwelling time was 14 (7-30) days. The most common pathogens were Gram-positive bacteria, which were noted in 29 cases (50.9%), followed by Gram-negative bacteria (36.8%). The most common pathogens causing CRBSI were Staphylococcus aureus (10 cases) and sewer enterobacteriaceae (10 cases) followed by Staphylococcus epidermidis (9 cases). CVC insertion sites included internal jugular vein (33 cases) and femoral vein (24 cases), accounting for 2.9% of internal jugular vein catheterization (1,140 cases) and 6.3% of femoral vein catheterization (383 cases) respectively. In total, 16, 20, 7 and 14 cases of CRBSI were noted in Spring, Summer, Autumn and Winter, accounting for 28.1, 35.1, 12.3 and 24.6% respectively. The most common infectious manifestations were chills (68.4%), fever (100%), and septic shock (49.1%). Multivariate analysis showed that catheterization of the femoral vein, long catheter indwelling time, low CD4+ lymphocytes and high acute physiology and chronic health evaluation (APACHE) II scores were independent factors associated with CRBSI. CONCLUSIONS: The incidence of CRBSI in our kidney ICU was 3.7%. Central venous CRBSI for CRRT was associated with catheterization of the femoral vein, long catheter indwelling time, compromised immune function and high APACHE II scores. Understanding pathogens and risk factors for central venous CRBSI in kidney ICU can help doctors prevent and treat CRBSI earlier.

Urinary miR-196a predicts disease progression in patients with chronic kidney disease.

BACKGROUND: Urinary miRNAs may potentially serve as noninvasive biomarkers in various kidney diseases to reflect disease activity, severity and progression, especially those correlated with the pathogenesis of kidney diseases. This study demonstrates that urinary miR-196a, a kidney-enriched miRNA, can predict progression of chronic kidney disease (CKD). METHODS: Focal segmental glomerulosclerosis (FSGS) cohorts were used as the representative example of CKD. First, correlation of miR-196a with disease activity was analyzed using paired urine and plasma samples from FSGS patients with nephrotic-range proteinuria (FSGS-A), complete remission (FSGS-CR) and normal controls (NCs). Then, the value of urinary miR-196a in predicting disease progression was validated using another cohort of 231 FSGS patients who were followed-up until over 36 months or reaching end-stage renal disease (ESRD). MiR-196a levels were analyzed by quantitative reverse transcription-polymerase chain reaction. RESULTS: The results showed that urinary miR-196a significantly increased in FSGS-A compared with FSGS-CR and NCs, clearly distinguishing FSGS-A from FSGS-CR and NCs, whereas plasma miR-196a showed no difference among these groups. Moreover, urinary miR-196a, which was associated with proteinuria, estimated glomerular filtration rate (eGFR), interstitial fibrosis and tubular atrophy, significantly increased in patients progressed to ESRD compared to those not. Furthermore, patients with higher urinary miR-196a displayed poorer renal survival than those with lower urinary miR-196a. Multivariate Cox analysis confirmed urinary miR-196a as an independent risk factor for FSGS progression after adjusting for age, sex, proteinuria and eGFR. Prediction accuracy of ESRD was significantly improved by combining urinary miR-196a with other indicators including eGFR and proteinuria. CONCLUSION: Urinary miR-196a may serve as a biomarker for predicting CKD progression.

Clinical and morphologic spectrum of renal involvement in patients with HBV-associated cryoglobulinaemia.

AIM: Cryoglobulinaemic glomerulonephritis related to hepatitis B virus (HBV) infection has been rarely reported. The aim of this study was to investigate the clinical features, renal biopsy findings in patients with HBV-associated cryoglobulinaemia. METHODS: Twelve patients with HBV-associated cryoglobulinaemia were identified in this study. The demographic, clinical, pathological characteristics, treatment and follow-up data were analyzed. RESULTS: Renal involvement was characterized by nephrotic range proteinuria with microscopic haematuria in all patients, and impaired renal function in nine patients (75%). Purpuric rash was the main extrarenal manifestation (58.3%). Type II cryoglobulinaemia was presented in three patients and type III in nine patients. Hypocomplementaemia and positive of rheumatoid factors were present in all patients. Membranoproliferative glomerulonephritis (MPGN) was observed in all kidney specimens. Seven patients also had evidence of prominent cryoglobulins thrombi on renal biopsy, but only three patients had HBV antigen deposits in renal tissues. Antiviral and steroids or immunosuppressive agents have been used in most of patients. During follow-up, two patients died, and four reaching end-stage renal disease; three patients had complete remission, and three patients had renal function improved after therapy. CONCLUSIONS: Nephrotic syndrome with haematuria and renal insufficiency are the main clinical manifestation; cryoglobulinaemic glomerulonephritis are the main renal lesion in patients with HBV-Associated cryoglobulinaemia; half of patients have poor outcome even with antiviral and immunosuppressive therapy. The results of this study indicate that cryoglobulins should be detected in hepatitis B virus-Associated nephropathy in endemic area.

Comparison between patients with IgA nephropathy with minimal change disease and patients with minimal change disease.

OBJECTIVE: To compare the clinicopathological characteristics, treatment response, and prognosis between patients with IgAN nephropathy with minimal change disease (MCD-IgAN) and patients with minimal change disease (MCD). METHODS: 77 patients with biopsy-proven MCD-IgAN from the Jinling Hospital IgAN Registry and 77 patients with MCD followed up for ≥ 3 years were retrospectively reviewed. RESULTS: MCD-IgAN and MCD patients had similar clinical presentations, both were predominantly young males, the disease mainly manifested as nephrotic syndrome, and the patients rarely presented with microscopic hematuria. Compared with the MCD group, patients with MCD-IgAN had lower levels of baseline serum albumin (p < 0.01) and eGFR (p < 0.05), a higher level of urine n-acetylglucosaminidase (p < 0.01), higher proportion of mesangial hypercellularity (M1), and more severe acute tubulointerstitial lesions in renal pathology (p < 0.01, p < 0.01, respectively). After 8 weeks of corticosteroid therapy, no significant differences were observed in the rate of complete remission, partial remission, and no remission between MCDIgAN and MCD patients (88.3% vs. 90.9%, 10.4% vs. 5.2%, 1.3% vs. 3.9%, p > 0.05). The median time to achieve remission was 4 weeks (range 1 - 24 weeks) and 4 weeks (range 1 - 28 weeks), respectively. No significant difference existed in the efficacy of corticosteroid between the two groups. During 3.96 years (range 3.0 - 8.5 years) of follow-up, no patients in the two groups entered end-stage renal disease (ESRD), only 2 patients (2.6%) with MCD-IgAN had > 50% reduction of eGFR. CONCLUSIONS: MCD-IgAN may be controlled well achieving a comparable clinical outcome as MCD but more frequently necessitates additional immunosuppressive medication.

Evaluation of the significance of complement-related genes mutations in atypical postinfectious glomerulonephritis: a pilot study.

BACKGROUND: Postinfectious glomerulonephritis with C3-dominant glomerular deposition (C3-PIGN) involves C3-dominant glomerular deposition without immunoglobulin. Atypical C3-PIGN involves persistent hypocomplementemia. We investigated the clinical features and explored complement-related gene mutations in atypical PIGN patients. METHODS: We enrolled atypical C3-PIGN patients and collected data regarding the clinical presentation and pathological characteristics and follow-up data. We measured the levels of complement associated antibodies and performed whole-exome sequencing (WES) to detect mutations in complement-related genes. RESULTS: The analysis included six atypical C3-PIGN patients. All patients were antistreptolysin-O (ASO) positive. All patients had varying degrees of hematuria, and four patients had proteinuria. None of the patients were positive for complement-related antibodies. All patients possessed mutations of genes related to the complement pathway, including alternative complement pathway genes-CFI, CFH, CFHR3, CFHR5; the lectin pathway gene-MASP2; and the common complement pathway gene-C8A. The rare variant of CFHR3 has been reported in C3 glomerulonephritis. During 56-73 months of follow-up, the levels of urine markers in three patients recovered within 6 months, and the remaining patients had abnormal urine test results over 12 months. Patients who received glucocorticoid therapy recovered faster. CONCLUSIONS: Our study suggested that complement-related gene mutations may be an important cause of persistent hypocomplementemia in atypical C3-PIGN patients. In addition to variations in alternate pathway-related genes, we also found variations in lectin pathway-related genes, especially MASP2 genes. Although the overall prognosis was good, atypical C3-PIGN patients exhibited a longer period for recovery. Our results suggested that atypical C3-PIGN patients should receive more medical attention and need testing for mutations in complement-related genes.

Successful treatment of peritoneal dialysis for two patients with refractory nephrotic syndrome and acute kidney injury: a case report.

Two patients with refractory nephrotic syndrome were treated with peritoneal dialysis (PD) for diuretic resistance, anasarca and acute kidney injury. Following PD, their fluid overload was promptly alleviated, accompanied by an increase in urine volume and an improvement in renal function. PD as an adjuvant approach enabled them to resume corticosteroids and immunosuppressive agents. Eventually, both patients could be withdrawn from PD and achieved remission of proteinuria.

Comparison between the influence of roxadustat and recombinant human erythropoietin treatment on blood pressure and cardio-cerebrovascular complications in patients undergoing peritoneal dialysis.

Introduction: Roxadustat treatment in PD patients is equivalent to ESAs in increasing hemoglobin (Hb). But blood pressure, cardiovascular parameters, cardio-cerebrovascular complications and prognosis in the two groups before and after treatment has not been sufficiently discussed. Methods: Sixty PD patients who were treated with roxadustat for renal anemia in our PD center recruited from June 2019 to April 2020 as roxadustat group. PD patients treated with rHuEPO were enrolled at a 1:1 ratio as rHuEPO group using the method of propensity score matching. Hb, blood pressure, cardiovascular parameters, cardio-cerebrovascular complications and prognosis were compared between the two group. All patients were followed up for at least 24 months. Results: There were no significant differences in baseline clinical data or laboratory values between roxadustat group and rHuEPO group. After 24 months of follow-up, there was no significant difference in Hb levels (p > 0.05). There were no significant changes in blood pressure, or the incidence of nocturnal hypertension before and after treatment in roxadustat group (p > 0.05), while blood pressure significantly increased in rHuEPO group after treatment (p < 0.05). Compared with roxadustat group after follow-up, rHuEPO group had a higher incidence of hypertension, the levels of cardiovascular parameters were worse and cardio-cerebrovascular complications had a higher incidence (p < 0.05). Cox regression analysis showed age, systolic blood pressure, fasting blood glucose, and rHuEPO use before baseline were risk factors for cardio-cerebrovascular complications in PD patients, while treatment with roxadustat was a protective factor for cardiovascular and cerebrovascular complications. Conclusion: Compared with rHuEPO, roxadustat had less influence on blood pressure or cardiovascular parameters, and it was associated with a lower risk of cardio-cerebrovascular complications in patients undergoing PD. Roxadustat has a cardio-cerebrovascular protective advantage in PD patients with renal anemia.

Efficacy of novel agents in patients with nephropathy associated with POEMS syndrome.

OBJECTIVE: To evaluate the clinical characteristics and outcomes of patients with nephropathy associated with POEMS syndrome who received novel agents in combination with dexamethasone therapy, and renal pathological changes based on repeat biopsy in some patients after these novel-agent-based therapies. METHODS: The records of patients with nephropathy associated with POEMS syndrome in a single hospital from May 2017 to February 2021 were retrieved and studied in detail. All the patients received four cycles of initial novel-agent-based regimens such as bortezomib and dexamethasone (BD) or thalidomide plus dexamethasone (TD) or lenalidomide plus dexamethasone (RD) treatment. We further evaluated the pathological efficacy of these novel agents by repeat renal biopsy. RESULTS: Twelve patients with an average age of 48.6 ± 8.3 years diagnosed with nephropathy associated with POEMS syndrome were enrolled in this study. The duration from disease onset to renal biopsy was 28(8.3 ~ 54.5) months. All patients achieved good clinical responses in different degree after four cycles of initial novel agents in combination with dexamethasone therapy. After the treatment with novel-agent-based regimens, the levels of proteinuria decreased in most patients and were negative in five patients. The levels of serum creatinine (SCr) decreased in ten patients. Serum M protein was negative in four patients and still positive in the other eight patients. The levels of serum vascular endothelial growth factor (VEGF) were detected in seven patients, which were all decreased. The levels of interleukin-6 (IL-6) were detected in eight patients, which were also decreased. Repeat biopsies were performed after four cycles of novel-agent-based therapies in four patients who were all treated with BD treatment. Mesangiolysis, mesangial cells proliferation, endothelial cells proliferation, subendothelial space widening and acute renal tubulointerstitial lesions improved, the chronic renal tubulointerstitial lesions were stable. CONCLUSIONS: Novel agents improved clinical manifestations in patients with nephropathy associated with POEMS syndrome. In addition, novel-agent-based regimens such as BD treatment improved renal pathological manifestations, which suggested that novel agents could improve renal prognosis of the patients from the perspective of renal pathology.

The Effect of Sacubitril/Valsartan Treatment on Cardiac and Renal Functions of a Patient With Cardiorenal Syndrome Type 4 and Stage 5 CKD After More Than Three Years of Follow-Up.

It is difficult to treat cardiorenal syndrome (CRS) in clinical practice, which is the common reason for the death of patients. This report aimed to describe the effects of sacubitril/valsartan treatment on cardiac and renal functions of a patient with cardiorenal syndrome type 4 (CRS4) after more than 3 years of follow-up. A 77-year-old Chinese woman was admitted to our hospital because of CRS4 and stage 5 chronic kidney disease (CKD), who had a history of long-term proteinuria and renal failure. The patient's cardiothoracic ratio (CTR) measured by chest X-ray was 0.6. Cardiac ultrasonography showed that the left ventricular ejection fraction (LVEF) was 0.40. The patient had been treated for heart failure (HF) for 5 months, but there was no improvement in clinical manifestations, and the renal function gradually deteriorated. In our hospital, she received sacubitril/valsartan treatment for at least 40 months. The symptoms of HF relieved, and the indices of cardiac function improved. In addition, the patient's renal function was stable. During the treatment, the dosage of sacubitril/valsartan needed to be adjusted to achieve the optimal therapeutic effect. Follow-up results showed that she achieved cardiac function of New York Heart Association (NYHA) class II with an ejection fraction of 0.60 and E/A > 1 indicated by echocardiogram, and did not develop hyperkalemia. In summary, the improvement of cardiac and renal functions of the CRS4 patient was associated with the long-term sacubitril/valsartan treatment.

Utility of abdominal skin plus subcutaneous fat and rectal mucosal biopsy in the diagnosis of AL amyloidosis with renal involvement.

OBJECTIVES: Skin fat biopsy of the abdominal wall is a simple and safe method for detecting amyloidosis, and rectal mucosal biopsy is also frequently used for screening for the disease; however, the sensitivity of these approaches has not been fully studied. The aim of this study was to evaluate the efficacy of skin fat biopsy combined with rectal mucosal biopsy as a screening procedure for the diagnosis of systemic immunoglobulin light-chain (AL) amyloidosis. METHODS: We retrospectively analyzed 224 AL amyloidosis patients confirmed by renal biopsy, including a test group of 165 patients and validation group of 59 patients. Surgical skin fat biopsy from the abdominal wall and rectal mucosal biopsy under endoscopy was performed to obtain specimens. Congo red staining and immunofluorescence staining with antibodies against light chains were performed to type the disease. Pathology reports were reviewed to assess the diagnostic sensitivity of skin fat biopsy and rectal mucosal biopsy. Diagnostic specificity was not examined in the present study, because no healthy volunteers and only few patients with other diseases had performed immunofluorescence staining on skin fat and rectal specimens. RESULTS: Of the 165 patients in the test group, Congo red staining of skin fat and rectal mucosal specimens was associated with a sensitivity of 89.3% and 94.8%, respectively. The sensitivity increased to 98.9% by combining both biopsy methods. Immunofluorescence stains were positive in 81.1% of patients undergoing skin fat biopsy and 84.7% of patients undergoing rectal mucosal biopsy. Immunofluorescence stains yielded positive results in 86.7% of cases combining skin fat biopsy with rectal mucosal biopsy. The diagnostic results also performed well in the validation group. CONCLUSIONS: Surgical skin biopsy including the subcutaneous fat pad can be performed safely at the bedside and is useful for diagnosing AL amyloidosis. Combining skin fat biopsy with rectal mucosal biopsy may identify amyloid deposits in almost all patients, and a negative result of both biopsies makes the diagnosis very unlikely.

Long-term outcome of IgA nephropathy with minimal change disease: a comparison between patients with and without minimal change disease.

BACKGROUND: The clinicopathological characteristics, treatment response and long-term outcome of immunoglobulin (Ig)A nephropathy with minimal change disease (MCD-IgAN) are not well defined. METHODS: Patients with biopsy-proven MCD-IgAN from the Jinling Hospital IgA nephropathy Registry were systematically reviewed and compared with those with IgA nephropathy without minimal change disease (Non-MCD-IgAN). RESULTS: We compared data of 247 MCD-IgAN patients and 1,121 Non-MCD-IgAN patients. Compared to Non-MCD-IgAN, MCD-IgAN patients were younger,with male predominance, had higher levels of proteinuria, total cholesterol and estimated glomerular filtration rate (eGFR), lower incidence of hypertension and microhematuria, lower level of serum creatinine, and had less severe glomerular, tubulointerstitial and vascular lesions in renal pathology. In the Non-MCD-IgAN group, 157 patients (14.0 %) reached the renal endpoint and 103 patients (9.2 %) entered end-stage renal disease (ESRD). The 5-,10-, 15- and 20-year cumulative renal survival rates from ESRD, calculated by Kaplan-Meier method, were 95.0, 83.0, 72.9 and 65.4 %, respectively. In the MCD-IgAN group, no patients entered ESRD and only 4 (1.6 %) reached the renal endpoint. Patients with MCD-IgAN had a significantly better renal outcome than Non-MCD-IgAN (p < 0.01). At multivariate Cox analysis, proteinuria >1.0 g/day, hypertension, eGFR <60 ml/min/1.73 m(2), hypoproteinemia and hyperuricemia were independent risk factors of renal survival for Non-MCD-IgAN patients [hazard ratio (HR) 3.43, p < 0.001; HR 1.65, p < 0.05; HR 2.61, p < 0.001; HR 2.40, p < 0.001; HR 2.27, p < 0.001, respectively), but not for patients with MCD-IgAN. CONCLUSIONS: The long-term outcome of patients with MCD-IgAN is significantly better than that of patients with Non-MCD-IgAN.