Persistent Renal Insufficiency Research Articles

Prolonged renal function impairment in infants born during the peri-viable period: A retrospective longitudinal cohort study

BackgroundThe number of infants born during the peri-viable period who survive has been increasing. AimTo clarify renal function in infants from the time of birth during the peri-viable period until their due date. Study designThis retrospective cohort study was conducted at a single center. SubjectsWe reviewed the data of infants born at ≤28 weeks of gestation between 2018 and 2022 at our hospital. The infants were divided into the following groups: born at 22–24 weeks vs. 25–28 weeks (appropriate-for-gestational age [AGA] infants), and AGA infants vs. small-for-gestational age (SGA) infants (born at 22–28 weeks). Outcome measuresWe compared the perinatal data and renal function of the infants from birth until their due date. ResultsEighty-one infants were included. Their serum creatinine, fractional excretion of sodium, and urine glucose levels were high or positive soon after birth but gradually improved. The urine albumin level was significantly higher among AGA infants born at 22–24 weeks, even at term equivalent age, than among those born at 25–28 weeks. ConclusionsPersistent renal insufficiency was observed even around the term equivalent age in peri-viable infants. Follow-up data collected after the neonatal period should be investigated in these infants.

Colistin treatment in older adults: why should we know more?

Objectives We aimed to investigate the risk factors of colistin-associated nephrotoxicity in patients older than 65 years treated in the palliative care unit. Methods 119 palliative care patients who received intravenous colistimethate for at least 7 days were included in the study. The estimated glomerular filtration rate (GFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation. Data were obtained from the hospital information system. Results The mean age of the participants was 76.7 ± 9.9 years and 49.4% were female. Of the 119 patients, 57 had colistin-induced nephropathy (CIN) according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The rate of CIN was higher in women than in men. The baseline phosphate level was higher in the CIN (+) group than in the CIN (–) group. The lower GFR values in patients with pneumonia persisted at days 14 and 30, whereas the lower GFR in patients without pneumonia did not. According to multivariate logistic regression, female gender and baseline phosphate level ≥ 4.5 mg/dl were found as independent variables for the development of nephropathy. Conclusions The creatinine levels of the patients with pneumonia and CIN did not improve after nephrotoxicity, whereas the creatinine levels of the other patients without pneumonia and CIN did. Female gender and baseline phosphate were independent risk factors for CIN. Prolonged kidney failure may lead to a more difficult clinical follow-up process for clinicians. Therefore, clinicians should be aware of persistent renal insufficiency in older patients with pneumonia receiving colistimethate.

Kidney Transplantation and Clinical Outcomes in Patients With Multiple Myeloma: Evidence From the United States Nationwide Inpatient Sample.

Patients with multiple myeloma (MM) are prone to developing persistent renal insufficiency. Novel therapeutic medications have improved long-term survival, making kidney transplantation (KT) a viable treatment option for MM survivors with end-stage renal disease. This study aimed to investigate the clinical outcomes in patients with MM who have received KT. Data from hospitalized patients ≥ 40 years of age with MM in the Nationwide Inpatient Sample 2016-2018 of the United States were queried. Patients were classified as having or not having undergone KT, as well as the stage of chronic kidney disease (CKD) for those who had not received KT. Propensity-score matching (PSM) was applied to balance the characteristics between the groups. Binary logistic regression was utilized to determine the associations between study variables and inhospital mortality, unfavorable discharges, prolonged length of stay (LOS), and major complications. In total, 50,654 hospitalized patients with MM were identified, of whom 165 (0.3%) had received KT and 50,489 had not (5,905 at stage 5 CKD [CKD5D], 11,559 at stage 1-4 CKD [CKD1-4D], and 33,025 who were CKD-free). After PSM, between-group demographic and hospital-related characteristics were balanced. Binary regression analysis revealed that, compared to patients who were CKD-free, patients at CKD5D were significantly more likely to experience a prolonged LOS (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.01-1.70) after adjusting for relevant confounders. Furthermore, compared to CKD-free patients, those who underwent KT were significantly more likely to have sepsis (OR, 1.48; 95% CI, 1.02-2.14). However, KT showed no association with the other adverse inpatient outcomes. Although KT is not common in MM patients, those who had undergone KT had comparable hospital outcomes to CKD-free patients. These data will help clinicians deliver better consultations to MM patients attempting to receive KT.

Differences in response to treatment in children with severe IgA nephropathy according to patient age.

To clarify whether the response to treatment of IgA nephropathy (IgAN) differs depending on patient age, we examined the response to treatment according to age of onset in children with IgAN. We collected data for 44 children with severe IgAN. The children were retrospectively divided into three groups based on their age at disease onset. Group 1 consisted of 24 children under 11 years old, group 2 consisted of 9 children aged 12 to 13 years, and group 3 consisted of 11 children aged over 14 years old. The clinical features and prognosis were analyzed for each group. The urinary protein excretion and serum IgA values in group 3 were higher than those in groups 1 and 2 at the most recent follow up, and histological findings showed that the MESTCG scores in group 3 were higher than those in group 1. Furthermore, the incidence of patients with persistent nephropathy or renal insufficiency in group 3 was higher than those in groups 1 and 2. Patients aged 14 years and older with IgAN may respond poorly to treatment compared with those younger than 14 years old. Therefore, care must be taken regarding response to treatment and relapse when treating older children.

Analysis of risk factors of major adverse kidney events within 30 days in patients with acute pancreatitis

To analyze the risk factors of major adverse kidney events within 30 days (MAKE30) in patients with acute pancreatitis (AP). A retrospective cohort study was conducted. A total of 162 patients who were first diagnosed with AP in the First Affiliated Hospital of Soochow University from June 2019 to June 2021 and the onset time was less than 72 hours were enrolled. Patients were divided into MAKE30 group and non-MAKE30 group according to the occurrence of MAKE30 after hospitalization. MAKE30 was defined as death from any cause, new renal replacement therapy (RRT), and persistent renal insufficiency (PRD). The clinical data of the two groups at admission were compared. The independent risk factors of MAKE30 were analyzed by multivariate Logistic regression method, and a regression equation was established as a quantitative prediction model of MAKE30. Receiver operator characteristic curve (ROC curve) was drawn to analyze the prediction of the quantitative prediction model value. All 162 patients were included in the final analysis, including 32 in the MAKE30 group and 130 in the non-MAKE30 group. Univariate analysis showed that compared with the non-MAKE30 group, the body mass index (BMI), the proportion of severe AP, and the acute physiology and chronic health evaluation II (APACHE II) score, the sequential organ failure assessment (SOFA) score, blood urea nitrogen (BUN), serum creatinine (SCr), C-reactive protein (CRP), HCO3-, Cl- levels and the proportion of hyperchloremia at admission in the MAKE30 group were significantly increased. Multivariate Logistic regression analysis showed that APACHE II score at admission [odds ratio (OR) = 1.659, 95% confidence interval (95%CI) was 1.426-1.956, P = 0.009], SOFA score (OR = 1.501, 95%CI was 1.236-1.840, P = 0.014) and hyperchloremia (OR = 1.858, 95%CI was 1.564-2.231, P = 0.004) were independent risk factors for MAKE30 in AP patients. The MAKE30 regression equation was established by the above risk factors [Logit(P) = 0.063+0.525×APACHE II score+0.328×SOFA score+0.895×hyperchloremia], which was used as the MAKE30 quantitative prediction model. ROC curve analysis showed that the area under the ROC curve (AUC) of the model for predicting MAKE30 was 0.846 (95%CI was 0.774-0.923, P = 0.001). The patients were divided into two subgroups with hyperchloremia (Cl- ≥ 110 mmol/L, n = 19) and non-hyperchloremia (Cl- < 110 mmol/L, n = 143) according to the blood Cl- level at admission. The incidence of MAKE30 and acute kidney injury (AKI) in the hyperchloremia group was significantly increased (MAKE30: 68.4% vs. 13.3%, AKI: 89.5% vs. 43.4%), and the levels of BUN and SCr at admission were significantly increased [BUN (mmol/L): 9.3±2.5 vs. 5.9±1.1, SCr (μmol/L): 162.3±26.4 vs. 78.6±9.2], the total length of hospital stay and length of intensive care unit (ICU) stay were significantly longer [total length of hospital stay (days): 10.2±1.6 vs. 5.6±1.2, length of ICU stay (days): 6.2±1.0 vs. 3.1±0.6], the cumulative intravenous infusion volume increased significantly at 48 hours and 72 hours (mL: 7 235.9±1 025.3 vs. 5 659.6±956.7 at 48 hours, 11 052.6±1 659.8 vs. 7 156.9±1 052.4 at 72 hours), differences were statistically significant (all P < 0.01). MAKE30 can be used as an important indicator to evaluate the short-term clinical prognosis of AP patients. APACHE II score, SOFA score and hyperchloremia at admission are the main risk factors. The risk model of MAKE30 based on these three indicators has good predictive performance. AP patients with hyperchloremia are at high risk of developing MAKE30, which should be highly regarded in clinical practice.

Lack of Renal Recovery Predicts Poor Survival in Patients of Multiple Myeloma With Renal Impairment

BackgroundRenal impairment (RI) confers a poor prognosis in multiple myeloma. Reversibility of renal function is associated with improved survival in such patients. Patients in developing countries often present at an advanced stage and renal impairment is present in up to 40% of patients at diagnosis. We studied the renal outcome and survival of these patients with bortezomib-based induction therapy. Materials and MethodsIt was a single-center prospective study in a tertiary care multi-specialty institute in patients of newly diagnosed multiple myeloma (NDMM) who presented with RI from July 2018 to December 2019. The diagnosis of multiple myeloma was made based on IMWG14 criteria. All patients received bortezomib and or immunomodulatory drug-based triplet or quadruplet induction therapy. Hematological and renal outcomes were assessed as per IMWG 2016 criteria. ResultsAmong 216 consecutive patients of NDMM, RI was seen in 91 (42.2%) patients. The median age of 91 patients was 60 years. (range- 32-80 years). Light chain myeloma was seen in 26% (n = 24) of patients. The median estimated glomerular filtration rate (eGFR) was 15.36 mL/min (3.1-38 mL/min) and a majority of patients were in the advanced ISS stage. (ISS III = 85.7%). Thirty-six (39.5%) patients received hemodialysis at presentation. Renal response was seen in 67 (73%) patients and 20 (out of 36; 55%) became dialysis independent over a median time of 38 days (Range 15-160 days). At a median follow-up of 14.7 months, 30 (33%) patients had died, of which, 14 (15.4%) patients had early mortality (within 2 months of diagnosis). Presence of light chain myeloma and cast nephropathy (definite or probable) were identified as independent predictors of poor renal recovery on multivariate analysis. (HR = 2.841; 95% CI [1.471-5.486], P = .002 for light chain myeloma; HR = 1.859; 95% CI (1.087-3.180); P = .024 for cast nephropathy) Patients with low eGFR at presentation (<12.5 mL/min) were more likely to have persistent renal insufficiency. (HR-3.521; 95% CI (1.856-6.679), P = .000). Patients who attained sustained renal recovery had improved survival as compared to patients in whom renal function failed to improve. (median OS- not reached vs. 8.3 months, P = .000) Achievement of hematological response and independence from hemodialysis was associated with improved survival on multivariate analysis. ConclusionRenal impairment was reversible in almost three-fourths of NDMM patients. achievement of hematological response and hemodialysis independence were independent predictors of improved overall survival in NDMM patients with RI.

Dermatologic Manifestations of Systemic Diseases in Childhood

Dermatologic Manifestations of Systemic Diseases in Childhood

Risk factors for chronic kidney disease following acute kidney injury in pediatric allogeneic hematopoietic cell transplantation.

Risk factors associated with the progression of acute kidney injury to chronic kidney disease in pediatric allogeneic hematopoietic cell transplantation (AlloHCT) recipients are not well described. We retrospectively investigated the risk factors for the progression to CKD in 275 AlloHCT recipients. AKI and CKD grading was defined according to the Kidney Disease Improving Global Outcomes classification. PRI90 was defined as persistent renal insufficiency (estimated GFR < 90 ml/min/1.73 m2) 90 days after the first episode of AKI. The median age was 9.1 years. Incidence of stages 1, 2, and 3 AKI were 43%, 41%, and 15%, respectively. 86.1% met our study criteria for PRI90. Of the 236 PRI90 patients, 213 and 152 patients were evaluable for CKD at 1 and 3 years, respectively. The incidence of CKD at 1 and 3 years was 63.1% and 62.9%, respectively. On multivariable analysis, estimated GFR at initial episode of AKI (<80 ml/min/1.73 m2) and estimated GFR (<70 ml/min/1.73 m2) at PRI90 was a risk factor associated with CKD development and both risk factors were associated with significantly lower overall survival. To conclude, eGFR at the time of AKI and PRI90 may be considered for screening pediatric AlloHCT recipients at risk for the progression to CKD.

Mitochondrial dysfunction and the AKI-to-CKD transition

Acute kidney injury (AKI) has been widely recognized as an important risk factor for the occurrence and development of chronic kidney disease (CKD). Even milder AKI has adverse consequences and could progress to renal fibrosis, which is the ultimate common pathway for various terminal kidney diseases. Thus, it is urgent to develop a strategy to hinder the transition from AKI to CKD. Some mechanisms of the AKI-to-CKD transition have been revealed, such as nephron loss, cell cycle arrest, persistent inflammation, endothelial injury with vascular rarefaction, and epigenetic changes. Previous studies have elucidated the pivotal role of mitochondria in acute injuries and demonstrated that the fitness of this organelle is a major determinant in both the pathogenesis and recovery of organ function. Recent research has suggested that damage to mitochondrial function in early AKI is a crucial factor leading to tubular injury and persistent renal insufficiency. Dysregulation of mitochondrial homeostasis, alterations in bioenergetics, and organelle stress cross talk contribute to the AKI-to-CKD transition. In this review, we focus on the pathophysiology of mitochondria in renal recovery after AKI and progression to CKD, confirming that targeting mitochondria represents a potentially effective therapeutic strategy for the progression of AKI to CKD.

Renal arteriography with endovascular ultrasound for the management of renal infarction patients

BackgroundRenal infarction (RI) is a rare disease with poor prognosis. Appropriate secondary prevention treatment is essential and requires an exhaustive etiological assessment. We aimed to determine whether invasive endovascular explorations may improve the diagnostic process and change the secondary prevention treatment strategy in RI patients.MethodsWe report a retrospective observational study of 25 RI patients referred to Tours University Hospital between 2011 and 2018 for etiological investigation including renal arteriography and intravascular ultrasonography (IVUS). We sought for antithrombotic treatment regimen, vital status, bleeding and ischemic outcomes during the median follow-up of 59 months.ResultsInvasive explorations showed local arterial disease in 14 patients (56%). This led to a diagnosis or change in diagnosis in 9 patients (36%) and to a change in antithrombotic strategy in 56% of cases, with an increased prescription of antiplatelet therapy. No patient died, only two patients (8%) had persistent mild renal insufficiency. One IVUS complication was reported and treated without any significant long-term consequences.ConclusionInvasive endovascular investigations of RI may modify the secondary prevention treatment through a better assessment of the aetiology of RI. Multicentric randomized studies are necessary to advocate the hypothesis that invasive exploration of renal artery can improve long-term prognosis.

Treatment and disease-related complications in multiple myeloma: Implications for survivorship.

New treatments have transformed multiple myeloma into a chronic disease. Hence, optimal management of treatment and disease-related complications remains a critical component of survivorship care. Survivorship care model in cancers requiring a fixed-duration therapy may not be applicable to myeloma, since patients are exposed to multiple lines of continuous therapy along the disease trajectory. The two most common therapy-related causes of death, which require special consideration, are infection and second cancers. Identifying patients at a high risk of toxicities will facilitate individualized treatment selection and designing clinical trials for protective strategies targeting those patients. For example, prophylactic antibiotic or immunoglobulin replacement can be tested for primary prevention of infections in high-risk patients. Long-term follow up of ongoing trials and epidemiologic data will help identify the nature and trajectory of rare toxicities with a long latency, such as secondary cancers. Patients who are frail, have persistent renal insufficiency, and refractory to multiple lines of therapy need special attention regarding treatment toxicity and quality of life. In this review, we discuss the incidence, risk-factors, and management of treatment and disease-related complications in myeloma, discuss knowledge gaps and research priorities in this area, and propose a survivorship care model to improve health-care delivery to a growing pool of myeloma survivors.

Does Dent disease remain an underrecognized cause for young boys with focal glomerulosclerosis?

Focal glomerulosclerosis (FGS) is a histologic entity that causes significant proteinuria in children. Although its etiology varies, recent reports indicated that some young male patients with FGS had underlying Dent disease. We describe the case of a 14-year-old Japanese boy who presented with persistent non-nephrotic range proteinuria, hematuria, and renal insufficiency. The patient was initially diagnosed as having FGS associated with scattered tubulointerstitial fibrosis. Although he had neither nephrocalcinosis nor family history of renal disease including urolithiasis, increased excretion of urinary β2 microglobulin was noted. Genetic analysis for Dent disease indicated a mutation (c.726 + 1G > A) in Chloride Channel, Voltage-Sensitive 5 (CLCN5). Given a recent hypothesis that Dent disease may be underrecognized in children with FGS, a careful diagnostic evaluation for possible underlying Dent disease should be considered in young boys who present with persistent albuminuria associated with high-grade low-molecular-weight proteinuria.

Impact of renal involvement on survival in ANCA-associated vasculitis.

Renal involvement is a serious complication of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). We describe the pattern of renal involvement and its correlation with outcomes. Medical records of 92 patients seen in rheumatology clinic and diagnosed as AAV between January 2007 and June 2014 were analysed. Patients were classified as granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA) and undifferentiated AAV. Overall and renal outcomes were analysed. Patients were classified as advanced renal failure (creatinine >5.7mg/dl or requiring dialysis), deranged RFT not qualifying the above parameters, and normal renal function. Sixty-seven (72.8%) patients had GPA, 14 (15.2%) had MPA, 8 (8.7%) had EGPA, and 3 (3.3%) had undifferentiated AAV. Renal involvement was seen in 51 (55.4%) patients (46.3% of GPA patients, 78.6% of MPA, 37.5% of EGPA and 33.3% of unclassifiable AAV patients). Renal involvement was more common in males (p=0.008). Patients with renal involvement had higher mean BVAS scores as compared to patients without renal involvement (p<0.01). Thirteen patients (25.5%) presented with advanced renal failure (creatinine >5.7mg/dl or requiring dialysis), 21 (41.2%) had deranged renal functions but did not require dialysis, and the rest had proteinuria and active sediments with normal serum creatinine. Twenty-four patients (47.1%) had good renal outcome with normal creatinine, 12 (23.5%) had persistent renal insufficiency, 12 (23.5%) died, and one (2%) remained dialysis dependent. Mean survival and mortality did not differ in patients with and without renal involvement (p=0.454, p=0.388). Renal involvement was more common in males. BVAS was higher in patients with renal involvement. The mean survival and mortality were similar in patients with or without renal involvement.

Clinical and histological changes associated with corticosteroid therapy in IgG4-related tubulointerstitial nephritis

Objectives This study aimed to investigate the clinicopathological changes induced by corticosteroid therapy in immunoglobulin (Ig)G4-related tubulointerstitial nephritis (TIN).Methods We studied six IgG4-related TIN patients receiving renal biopsies before and after corticosteroid therapy. Their clinical data and histological findings were evaluated before and after therapy.Results Elevated serum creatinine levels rapidly improved after corticosteroid therapy except for two patients, in whom it persisted. Abnormal radiological findings improved in all patients, although focal cortical atrophy persisted in three. Histologically, TIN-like dense lymphoplasmacytic infiltration, interstitial fibrosis, IgG4-positive plasma cell, CD4+CD25+ T cell, and Foxp3+ cell infiltration were characteristic before therapy. After therapy, the area with cell infiltration decreased and regional fibrosis became evident in the renal interstitium. The number of IgG4-positive plasma cells and Foxp3+ cells significantly diminished even in the early stage of therapy, whereas low to moderate numbers of CD4+ and CD8+ T cells still infiltrated where inflammation persisted in the later stage.Conclusions Our study shows that persistent renal insufficiency associated with macroscopic atrophy and microscopic fibrosis is not so rare in IgG4-related TIN. Pathologically, the behavior of regulatory T cells during the clinical course is quite similar to that of IgG4-positive plasma cells, and the behavior pattern of those cells is distinctive.

Significant impact of transient deterioration of renal function on dosimetry in PRRT

Peptide receptor radionuclide therapy (PRRT), with (90)Y-DOTATOC and (177)Lu-DOTATATE as most clinically used radiopeptides, is widely used in the management of metastatic neuroendocrine tumors. With respect to radiation dosimetry, the kidneys are the critical organ for (90)Y-DOTATOC. Renal irradiation is significant because of reabsorption of the radiopeptide from the proximal tubuli and the resulting retention in the interstitium, mainly in the inner cortical zone. The high energy and consequently wide range in tissue of the yttrium-90 beta particle result in high absorbed doses to the kidney cortex and medulla. Accurate renal dosimetry can help minimizing radiation nephropathy. We report a case of a 69-year-old candidate for PRRT with an acceptable kidney function at the time of screening. When performing (111)In-octreotide pretreatment dosimetry 3 weeks later, we observed a drastic deterioration in kidney function, caused by undisclosed non-steroidal anti-inflammatory drug intake. The calculated kidney biological effective dose (BED) was 153 Gy after four projected cycles. PRRT was canceled as our full-course BED limit is 37 Gy and the patient was switched to morphine analgesics. Renal function normalized after 3 months and repeated dosimetry yielded an acceptable kidney BED of 28 Gy after four projected cycles (7 Gy/cycle). This case emphasizes that acute kidney insufficiency can yield toxic kidney doses in a single therapy cycle, with an inherent risk of persistent renal insufficiency. All clinical factors which might influence kidney function should be verified at screening and before PRRT administration.

Indicators of Acute and Persistent Renal Damage in Adult Thrombotic Microangiopathy

BackgroundThrombotic microangiopathies (TMA) in adults such as thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are life-threatening disorders if untreated. Clinical presentation is highly variable and prognostic factors for clinical course and outcome are not well established.MethodsWe performed a retrospective observational study of 62 patients with TMA, 22 males and 40 females aged 16 to 76 years, treated with plasma exchange at one center to identify clinical risk factors for the development of renal insufficiency.ResultsOn admission, 39 of 62 patients (63%) had acute renal failure (ARF) with 32 patients (52%) requiring dialysis treatment. High systolic arterial pressure (SAP, p = 0.009) or mean arterial pressure (MAP, p = 0.027) on admission was associated with acute renal failure. Patients with SAP>140 mmHg on admission had a sevenfold increased risk of severe kidney disease (OR 7.464, CI 2.097–26.565). MAP>100 mmHg indicated a fourfold increased risk for acute renal failure (OR 4.261, CI 1.400–12.972). High SAP, diastolic arterial pressure (DAP), and MAP on admission were also independent risk factors for persistent renal insufficiency with the strongest correlation for high MAP. Moreover, a high C-reactive protein (CRP) level on admission correlated with renal failure in the course of the disease (p = 0.003). At discharge, renal function in 11 of 39 patients (28%) had fully recovered, 14 patients (23%) remained on dialysis, and 14 patients (23%) had non-dialysis-dependent chronic kidney disease. Seven patients (11%) died. We identified an older age as risk factor for death.ConclusionsHigh blood pressure as well as high CRP serum levels on admission are associated with renal insufficiency in TMA. High blood pressure on admission is also a strong predictor of sustained renal insufficiency. Thus, adult TMA patients with high blood pressure may require special attention to prevent persistent renal failure.

Clinical and histological changes associated with corticosteroid therapy in IgG4-related tubulointerstitial nephritis

ObjectivesThis study aimed to investigate the clinicopathological changes induced by corticosteroid therapy in immunoglobulin (Ig)G4-related tubulointerstitial nephritis (TIN).MethodsWe studied six IgG4-related TIN patients receiving renal biopsies before and after corticosteroid therapy. Their clinical data and histological findings were evaluated before and after therapy.ResultsElevated serum creatinine levels rapidly improved after corticosteroid therapy except for two patients, in whom it persisted. Abnormal radiological findings improved in all patients, although focal cortical atrophy persisted in three. Histologically, TIN-like dense lymphoplasmacytic infiltration, interstitial fibrosis, IgG4-positive plasma cell, CD4+CD25+ T cell, and Foxp3+ cell infiltration were characteristic before therapy. After therapy, the area with cell infiltration decreased and regional fibrosis became evident in the renal interstitium. The number of IgG4-positive plasma cells and Foxp3+ cells significantly diminished even in the early stage of therapy, whereas low to moderate numbers of CD4+ and CD8+ T cells still infiltrated where inflammation persisted in the later stage.ConclusionsOur study shows that persistent renal insufficiency associated with macroscopic atrophy and microscopic fibrosis is not so rare in IgG4-related TIN. Pathologically, the behavior of regulatory T cells during the clinical course is quite similar to that of IgG4-positive plasma cells, and the behavior pattern of those cells is distinctive.

Use of covered chimney stents for pararenal aortic pathologies is safe and feasible with excellent patency and low incidence of endoleaks

To present the clinical experience of consecutive series with use of balloon-expandable and self-expanding chimney endografts (balloon-expandable covered stent group [BECS] vs self-expanding covered stent group [SECS]) in the endovascular treatment of challenging aortic pathologies requiring renal and/or visceral revascularization. Between January 2009 and May 2011, data for 37 high-risk patients from one center and 35 patients from another institution, with pararenal aortic pathologies treated by the chimney endovascular technique, were prospectively collected. The chimney-graft technique is based on the deployment of a covered or bare-metal stent parallel to the aortic endograft, thereby creating a conduit that runs outside the aortic main endograft, and has been proposed to ensure secure proximal fixation extending the sealing zones. Forty-six consecutive target vessels (43 renal arteries and 3 superior mesenteric arteries) were revascularized by the Advanta (Atrium, Hudson, NH) BECS (1.2 chimneys/patient); in contrast, 81 consecutive target vessels (64 renal arteries, 11 superior mesenteric arteries, and 6 celiac trunks) were revascularized by the Viabahn (Gore, Flagstaff, Ariz) SECS (2.3 chimneys/patient). The success rate for target vessel preservation was 97.8% for the BECS group and 100% for the SECS group in the entire follow up. There was one symptomatic left renal artery occlusion of the BECS group treated by open thrombectomy of the left renal artery and placement of 8-mm Dacron (BBraun, Aesculap AG, Tuttlingen, Germany) iliorenal bypass. Additionally, one patient underwent repeat balloon angioplasty with a 5-mm balloon due to high-grade in-stent stenosis of a 6 × 59 Advanta stent graft 12 months postoperatively. Overall, one perioperative (and not present in the computed tomography angiography at discharge) type Ia endoleak was detected in the BECS group. In contrast, five perioperative type Ia endoleaks were present in the SECS group; however, only one of them was persistent in the radiological imaging and was treated by proximal extension of a 5-mm cuff, 1 year postoperatively, due to continuous aneurismal sac increase. No patient of any subgroup developed postoperative persistent renal insufficiency with need of hemodialysis. Thirty-day and during the follow-up procedure-related mortality was 0% for both BECS and SECS groups. In summary, midterm results of use of covered chimney stents for pararenal aortic pathologies show safety and feasibility with excellent patency and low incidence of endoleaks.

IgA-Dominant Postinfectious Glomerulonephritis: Not Peculiar to Staphylococcal Infection and Diabetic Patients

Background: IgA-dominant postinfectious glomerulonephritis (PIGN) is a unique form of PIGN. It has been linked to staphylococcal infection and underlying diabetic glomerulosclerosis. However, the significance of glomerular IgA-dominant deposition in PIGN remains unclear. Methods: We reported 10 patients with IgA-dominant PIGN encountered at a single center, each characterized by subepithelial humps. Their demographic, clinical, and renal biopsy findings were summarized and compared with the data of 32 patients with non-IgA-dominant PIGN. Results: The mean age was 57 years. An immunocompromised background was present in 70% of patients; only one patient had diabetes mellitus. The causative infectious agents included Staphylococcus (30%), Streptococcus (20%), and gram-negative organisms (50%). Decreased serum complement was present in 60%. Increased serum IgA was noted in 75%. The mean peak serum creatinine was 5.1 mg/dL, and 20% required acute dialysis. Diffuse endocapillary-proliferative glomerulonephritis was found in all cases, and three patients also had crescentic glomerulonephritis. Electron microscopy revealed large subepithelial hump-shaped deposits in all cases. At the last follow-up, one patient had died, five had achieved complete recovery, three had persistent renal insufficiency, and one was on chronic dialysis. Compared to patients with non-IgA-dominant PIGN, increased serum IgA was more commonly present in IgA-dominant group (p = 0.007). There were no significant differences in other clinical parameters and outcome between the two groups. Conclusions: IgA-dominant PIGN resembles poststreptococcal glomerulonephritis in its histological spectrum and ultrastructural appearance. Increasing serum IgA may be involved in the pathogenesis of this form of PIGN. Our data suggested that IgA-dominant PIGN was not peculiar to staphylococcal infection and diabetic patients.

Reappraisal of treatment-induced renal dysfunction in patients receiving antiangiogenic agents in phase I trials

Several phase I trials are currently evaluating new antiangiogenic compounds. While hypertension and proteinuria have been largely reported as a class side effect of these agents, data on renal function [i.e. the glomerular filtration rate (GFR)] in patients (pts) treated with new antiangiogenic compounds in phase I trials are much scarcer. Between November 2005 and March 2008, we identified 72 pts with solid tumors who had been included in four Phase I trials testing antiangiogenic or related compounds. Thirty-two pts had received a pan-HER/VEGFR inhibitor (A), 29 had received a vascular-disrupting agent (B) and 11 had received a pan-VEGFR inhibitor in combination with CPT11 (C). For each patient, we retrospectively analyzed the serum creatinine level (SCr), Cr clearance (CrCl) calculated by both the Cockcroft and Gault and aMDRD equations at baseline, during treatment and at the end of treatment. Acute renal failure (ARF) was defined as a decrease of >25% in CrCl, and severe renal failure (SRF) as a decrease of >50% in CrCl. Chronic renal failure (CRF) was defined according to the KDOQI-KDIGO classification. Renal dysfunction was defined as Cl <60 ml/min with a normal Cr level (<125 μmol/l). Each pt had received an average of 4 cycles of treatment (1 to 12). During treatment, the incidence of ARF ranged from 40.2% to 44.4% (A = 11/32, B = 19/29, C = 2/11). Seven to 9.7% of these cases were severe (A = 1/32, B = 6/29, C = 0/11). Moreover, 26.4 to 27.7% of the pts had exhibited persistent renal insufficiency at the end of the study (A = 5/32, B = 15/29, C = 0/11). From the start till the end of treatment, ARF had been documented in 20.8% to 22.2% of the pts. The average reduction in clearance was 9.8 to 11.6 ml/min/1.73 m2 between baseline and the end of treatment. The incidence of renal toxicity in phase I pts treated with antiangiogenic compounds was much higher than expected. Simple screening of Cr levels appears to be insufficient and careful nephrologic monitoring at baseline and during treatment should be implemented in early clinical trials assessing the risk/benefit ratio of new antiangiogenic compounds.