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Tyrosine kinase inhibitors (TKI) are anticancer agents widely used for a variety of malignancies including gastrointestinal stromal tumours (GIST). Although generally well-tolerated, TKIs have been associated with a number of adverse events including hypertension, proteinuria and nephrotic syndrome. We present the case of a 70-year-old patient with metastatic GIST on long-standing sunitinib who developed hypertension, oedema and hypoalbuminemia with a rising serum creatinine and was found to have nephrotic syndrome. Workup revealed elevated antiphospholipase A2 receptor (PLA2R) antibody IgG titres and a kidney biopsy confirmed PLA2R-positive membranous nephropathy without findings of thrombotic microangiopathy. Cessation of sunitinib led to reduction in anti-PLA2R antibody IgG titres while resumption, due to concern for cancer progression, led to worsening symptoms. Treatment with rituximab led to undetectable anti-PLA2R IgG titres. We highlight the importance of maintaining a systematic approach for evaluating nephrotic syndrome and provide a case showing that TKIs can exacerbate underlying nephrotic syndrome.

Objective Scleroderma renal crisis (SRC) is a rare and severe manifestation of systemic sclerosis (SSc). Although it is well documented that Blacks with SSc have worse morbidity and mortality than non-Blacks, racial predilection for SRC is underreported. We examine the association of race and future development of SRC in an SSc cohort. Methods Using the electronic health record of the United States Military Health System, we conducted a comprehensive chart review of each patient with SSc from 2005 to 2016. The final study cohort was comprised of 31 SRC cases and 322 SSc without SRC controls. We conducted logistic regression of SRC as the outcome variable and race (Black vs. non-Black) as the primary predictor variable, adjusted for age, estimated glomerular filtration rate, hypertension and proteinuria at SSc diagnosis. Results Out of 353 patients, 294 had identifiable race (79 Black, 215 non-Black). Thirteen out of 79 Blacks (16.5%) vs. 16/215 (7.4%) non-Blacks developed SRC (p=0.02). On adjusted analysis, Blacks had a significantly higher risk of developing SRC than non-Blacks (odds ratio 6.4, 95% CI 1.3-31.2, p=0.02). Anti-Ro antibody was present in a higher proportion of Black SRC patients vs. Blacks without SRC [45% vs. 14%, p=0.01]. Conversely, older age, thrombocytopenia, and anti-RNA polymerase III antibody at SSc diagnosis were significantly associated with future SRC in the non-Black cohort. Conclusion Black race was independently associated with a higher risk of future SRC. Further studies are needed to elucidate the mechanisms that underlie this important association. This article is protected by copyright. All rights reserved.

Nephrotic syndrome in patients with cancer may be related to the primary malignancy or chemotherapeutic therapy. Solid organ cancers may cause membranous glomerulonephritis manifesting with nephrotic syndrome; other less common histologic presentations include focal and segmental glomerulosclerosis and minimal change disease. In addition, chemotherapy agents can cause renal toxicity by affecting the small blood vessels, glomeruli, tubules, and interstitium. Tyrosine kinase inhibitors such as sunitinib may cause endothelial and podocyte damage leading to renal limited thrombotic microangiopathy, manifested by proteinuria and hypertension. We report a case of an elderly man with gastrointestinal stromal tumor (GIST) on treatment with sunitinib who had as a complication of a thrombotic microangiopathy manifested with nephrotic syndrome and difficult-to-control hypertension, which was controlled by stopping this drug but with a fatal outcome due to its malignant neoplasm.

Objective To evaluate the correlation of quantitative anti-dsDNA level with proteinuria levels in patients with lupus nephritis in a tertiary care hospital. Study design In this prospective cross-sectional study, 76 patients of newly diagnosed SLE coming to Fatima Memorial Hospital were included in the study period between January 2020 to June 2020. Demographic data such as age, gender, lupus manifestations such as serositis, arthritis, mucocutaneous disease, and neuropsychiatric manifestations were recorded. Quantitative anti-dsDNA was measured by enzyme-linked immunosorbent assay and proteinuria was estimated by 24 h urinary protein collection. Data was analyzed by SPSS 23. Association between categorical variables was assessed using chi-square test. For comparison of categorical independent and continuous dependent variable t-test or Mann–Whitney U test was applied. Results The median age of the cohort was 29 (with inter quartile range – IQR – of 13) years. The female gender comprised of 68 (89.4%) of the cohort population. The median anti-dsDNA level was 54.9 (183.6 IQR) IU, and baseline proteinuria of the cohort was 520 mg/dL (1.49 IQR). There was a significant association of anti-dsDNA level with systemic features such as arthritis (p = Conclusion Quantitative anti-dsDNA is directly correlated with nephritis measured as proteinuria, and can be detected even before organ involvement. Hence, it can determine disease course and guide early treatment.

Several novel antigens have recently been characterized in membranous nephropathy (MN), but those involved in the rare cases of MN associated with inflammatory neuropathies (IN) remain elusive. Although several antibody specificities were identified in the serum, there is no evidence so far for their deposition in glomeruli. We report the case of a 73 y/o woman who was referred because of subacute onset of proximal asymmetric lower limb weakness together with ataxic gait. She was diagnosed with IN. Blood tests showed an eGFR of 73 ml/min/1.73m2, hypoalbuminemia (2.89 g/dl) and proteinuria (3.6 g/24h). Autoantibodies (ANA, ENA, DNA, LAC, anti-cardiolipin, ANCA) were undetectable. Serum Ig and complement levels were normal. A kidney biopsy with electron microscopy examination showed a classical picture of MN. Anti-PLA2R antibody was negative in the serum and PLA2R and THSD7A antigens were not detected in kidney tissue. Anti-contactin1 (CNTN1) antibody was found by ELISA at 1:100 serum dilution and shown to be mostly of IgG4 subclass by Western blot. CNTN1 antigen was co-localized with IgG4 within immune deposits by confocal microscopy. This observation suggests a pathophysiological link between IN and MN. CNTN1 should be considered as a potential candidate antigen involved in MN and tested in PLA2R negative forms associated with IN.

PurposeWhile renal impairment is one of the first clinical manifestations of multiple myeloma (MM), declined renal function may conversely be a risk factor for cancers including MM. In this study, we investigated the relationship between chronic kidney disease and MM at a population level. Materials and MethodsA total of 9,809,376 adults who participated in a nationwide health screening program and had no MM, cancer or end-stage renal disease at baseline were investigated for incidence of MM. The impact of estimated glomerular filtration rate (eGFR) and random urine dipstick proteinuria, and interactive associations of the two factors on the MM incidence were evaluated. ResultsThe general incidence of MM was 4.8 per 100,000 person-years (mean follow-up of 8.3 years). Participants with eGFR < 60 mL/min/1.73 m2 (5.8% of participants) had higher MM incidence than those with eGFR ≥ 60 mL/min/1.73 m2 (adjusted hazard ratio, 1.29; 95% confidence interval, 1.17 to 1.43). When eGFR was graded into five levels, there was a significant inverse dose-response relationship between eGFR level and MM incidence at the lower eGFR levels (reference: eGFR 60-89 mL/min/1.73 m2). A dose-response relationship was also found with degree of dipstick proteinuria and incidence of MM.ConclusionAdults with decreased renal function indicated either by decreased eGFR or presence of proteinuria are at a higher risk of developing MM compared to those without, and there is a dose-response relationship between the severity of renal impairment and MM incidence.

A 70-year-old man received pembrolizumab as a second-line treatment for squamous cell lung cancer of the lower right lobe. After three courses, proteinuria and hematuria were observed, which worsened after seven courses. He was diagnosed with a combination of IgA nephropathy and active interstitial nephritis. Steroid pulse therapy was started, and the dose of prednisolone was gradually reduced from 60 mg/day. Renal dysfunction as an immune-related adverse event of pembrolizumab monotherapy for non-small cell lung cancer has been reported previously. Therefore, establishing a system for the early detection and treatment that distinguishes immune-related glomerular diseases is essential.

Metastatic disease in the kidney is relatively uncommon compared to other body sites. In most cases it presents as an unilateral and unifocal mass in the tubulointerstitial region. Intraglomerular metastases are even rarer, and their diagnosis is hampered by the limitation of imaging techniques to detect them. We describe the finding of intraglomerular metastases in a patient affected by a malignant melanoma considered to be in partial remission, with no evidence of melanoma progression on the previously performed computed tomography (CT) scan. This patient developed rapidly progressive kidney, failure, proteinuria and hematuria with dysmorphic red blood cells in the urine sediment. Kidney biopsy showed a marked crescentic proliferation caused by tumor cells, which even invaded the proximal convoluted tubule. Melanoma cells were also found in the lumina of the glomerular capillaries, distending their basement membranes. Our case describes the histologic and electron microscopic findings of this form of intraglomerular metastasis and reminds us of its inclusion in the differential diagnosis of rapidly progressive kidney failure.

A 39-year-old woman was hospitalized for nephrotic syndrome. Laboratory test results showed increased serum creatinine levels and urinary excretions of beta-2-microglobulin, and N-acetyl-beta-D-glucosaminidase. A renal biopsy revealed collapsing focal segmental glomerulosclerosis (FSGS) and acute interstitial nephritis. Despite treatment with pulse steroid followed by oral high-dose glucocorticoids and cyclosporines, heavy proteinuria persisted. After low-density lipoprotein apheresis (LDL-A) therapy was initiated, her proteinuria gradually decreased, leading to complete remission. A repeat renal biopsy after treatment revealed no collapsing glomeruli. Immediate LDL-A should be performed to treat cases of collapsing FSGS poorly responding to other treatments.

Background There is no a unified opinion in the treatment of IgA nephropathy. This prospective cohort study was to explore the effectiveness and safety of tacrolimus for treatment of IgA (Immunoglobulin A) nephropathy patients. Methods In this study, we assigned 50 patients with biopsy-proven IgA nephropathy in a 1:1.5 ratio to receive oral tacrolimus or full-dose glucocorticoid for 6 months. All the patients had 24-h urine protein excretion ≥ 2.0 g/24 h and estimated glomerular filtration rate ≥ 50 mL/min/1.73 m2. Primary endpoint was rate of complete remission. Results After 6 months of treatment, seven participants achieved complete remission in the tacrolimus group and twelve participants in the glucocorticoid group, the complete remission rate was 35% and 40%, respectively. There were not significantly differences between two groups (P = 0.7). However, the serum creatinine level from baseline was an increase of 13 ± 13.5 μmol/L in the tacrolimus group and a decrease of 8.2 ± 20 μmol/L in the glucocorticoid group. When patients stopped taking tacrolimus for 3 months, creatinine level can almost fall to normal level. Thus, patients with renal insufficiency have a high incidence in the tacrolimus group. Conclusions Tacrolimus was noninferior to full-dose glucocorticoid in inducing proteinuria remission at 6 months. This suggested that those IgA nephropathy patients who are unwilling to full-dose glucocorticoid could consider tacrolimus, but need to pay attention to the impact on renal function.

Membranoproliferative glomerulonephritis (MPGN) is the most typical Hepatitis C virus (HCV)-associated glomerulopathy, and the available data about the utilization of direct-acting antivirals (DAA) in HCV-associated glomerulonephritis is inadequate. We evaluated the renal and viral response in two cases of HCV-related MPGN; the first caused by cryoglobulinemia while the second was cryoglobulin-negative. Both patients received immunosuppression besides DAA in different regimens. They achieved partial remission but remained immunosuppression-dependent for more than 6 months after DAA despite sustained virological response, which enabled safer but incomplete immunosuppression withdrawal. Both patients were tested for occult HCV in peripheral blood mononuclear cells and found to be negative. Hence, the treatment of HCV-related MPGN ought to be according to the clinical condition and the effects of drug therapy. It is important to consider that renal response can lag behind the virological response. Resumo A glomerulonefrite membranoproliferativa (GNMP) é a glomerulopatia associada ao vírus mais típico da hepatite C (HCV), e os dados disponíveis sobre a utilização de antivirais de ação direta (AAD) na glomerulonefrite associada ao HCV são inadequados. Avaliamos a resposta renal e viral em dois casos de GNMP relacionados ao HCV; o primeiro causado por crioglobulinemia, enquanto o segundo era negativo para crioglobulina. Ambos os pacientes receberam imunossupressão além de AAD em diferentes esquemas terapêuticos. Eles alcançaram remissão parcial, mas permaneceram dependentes da imunossupressão por mais de 6 meses após os AAD, apesar da resposta virológica sustentada, que permitiu a retirada da imunossupressão mais segura, mas incompleta. Ambos os pacientes foram testados para HCV oculto em células mononucleares do sangue periférico e deram resultados negativos. Portanto, o tratamento do GNMP relacionado ao VHC deve ser de acordo com a condição clínica e os efeitos da terapia medicamentosa. É importante considerar que a resposta renal pode ficar aquém da resposta virológica.

BACKGROUND The existing guidelines for lupus nephritis (LN) recommend initial prednisone doses of 0.3-1mg/kg/day. However, recent studies reported non-inferior outcomes with lower doses. The aim of this study was to compare the complete renal response rates in LN patients treated with prednisone ≤30mg/day or ≥40mg/day. PATIENTS-METHODS Patients with new-onset LN and standard immunosuppressive treatment were followed for at least 12 months, divided into medium (≤30mg/day) and high prednisone groups (≥40mg/day) and matched (propensity score) based on the baseline differences. Complete renal response was defined as proteinuria

Este artículo de investigación se encuentra disponible en la siguiente URL: https://www.revistanefrologia.com/es-pdf-S0211699521001612 En este artículo de investigación también participan: Lorenzo Fácila Rubio, Javier Gamarra Ortiz, Jose A. García-Donaire, Lisardo García-Matarín, Sílvia Gràcia Garcia, María Isabel Gutiérrez Pérez, Julio Hernández Moreno, Pilar Mazón Ramos, Rosario Montañés Bermudez, Manuel Muñoz Torres, Pedro de Pablos-Velasco, Manuel Pérez-Maraver, Carmen Suárez Fernández, Salvador Tranche Iparraguirre y José Luis Górriz. La enfermedad renal crónica (ERC) es un importante problema de salud pública a nivel mun-dial afectando a más del 10% de la población espa˜nola. Se asocia a elevada comorbilidad,mal pronóstico, así como a un gran consumo de recursos en el sistema sanitario. Desde lapublicación del último documento de consenso sobre ERC publicado hace siete a˜nos, hansido escasas las evidencias y los ensayos clínicos que hayan mostrado nuevas estrategiasen el diagnóstico y tratamiento de la ERC, con excepción de los nuevos ensayos en la enfer-medad renal diabética. Esta situación ha condicionado que no se hayan actualizado lasguías internacionales específicas de ERC. Esta rigidez y actitud conservadora de las guíasno debe impedir la publicación de actualizaciones en el conocimiento en algunos aspectos, que pueden ser clave en la detección y manejo del paciente con ERC. En este documento, elaborado en conjunto por diez sociedades científicas, se muestra una actualización sobre conceptos, aclaraciones, criterios diagnósticos, estrategias de remisión y nuevas opciones terapéuticas. Se han revisado las evidencias y los principales estudios publicados en estos aspectos de la ERC, considerándose más bien un documento de información sobre esta patología. El documento incluye una actualización sobre la detección de la ERC, factores de riesgo, cribado, definición de progresión renal, actualización en los criterios de remisión con nuevas sugerencias en la población anciana, monitorización y estrategias de prevención de la ERC, manejo de comorbilidades asociadas, especialmente en diabetes mellitus, funciones del médico de Atención Primaria en el manejo de la ERC y qué no hacer en Nefrología. El objetivo del documento es que sirva de ayuda en el manejo multidisciplinar del paciente con ERC basado en las recomendaciones y conocimientos actuales. Chronic kidney disease (CKD) is a major public health problem worldwide that affects more than 10% of the Spanish population. CKD is associated with high comorbidity rates, poor prognosis and major consumption of health system resources. Since the publication of the last consensus document on CKD seven years ago, little evidence has emerged and few clinical trials on new diagnostic and treatment strategies in CKD have been conducted, apart from new trials in diabetic kidney disease. Therefore, CKD international guidelines have not been recently updated. The rigidity and conservative attitude of the guidelines should not prevent the publication of updates in knowledge about certain matters that may be key in detecting CKD and managing patients with this disease. This document, also prepared by 10 scientific societies, provides an update on concepts, clarifications, diagnostic criteria, remission strategies and new treatment options. The evidence and the main studies published on these aspects of CKD have been revie- wed. This should be considered more as an information document on CKD. It includes an update on CKD detection, risk factors and screening; a definition of renal progression; an update of remission criteria with new suggestions in the older population; CKD monitoring and prevention strategies; management of associated comorbidities, particularly in diabe- tes mellitus; roles of the Primary Care physician in CKD management; and what not to do in Nephrology. The aim of the document is to serve as an aid in the multidisciplinary management of the patient with CKD based on current recommendations and knowledge.

Background Although the synthetic vitamin D analogue, Paricalcitol, and omega-3 Fatty acids (ω-3) alleviated diabetic nephropathy (DN), their combination was not previously explored. Objectives This study measured the potential ameliorative effects of single and dual therapies of Paricalcitol and/or ω-3 against DN. Methods Forty rats were assigned as follow: negative (NC) and positive (PC) controls, Paricalcitol, ω-3 and Paricalcitol + ω-3 groups. Diabetes was generated by high-fat/high-fructose diet and a single streptozotocin injection (40 mg/kg). DN was confirmed by raised fasting blood glucose (FBG), polyuria, proteinuria, and decreased urine creatinine levels. Paricalcitol intraperitoneal injections (0.25 µg/Kg/day; 5 times/week) and oral ω-3 (415 mg/kg/day; 5 times/week) started at week-9 and for eight weeks. Results The PC group showed hyperglycaemia, dyslipidaemia, abnormal renal biochemical parameters, elevated caspase-3 expression, and increased apoptosis by TUNEL technique. The mRNAs and proteins of the pathogenic molecules (TGF-β1/iNOS) and markers of tissue damage (NGAL/KIM-1) augmented substantially in the PC renal tissues relative to the NC group. The oxidative stress (MDA/H2O2/protein carbonyl groups) and pro-inflammatory (IL1β/IL6/TNF-α) markers increased, whereas the anti-inflammatory (IL10) and anti-oxidative (GSH/GPx1/GR/SOD1/CAT) declined, in the PC renal tissues. The monotherapy groups were associated with ameliorated FBG, lipid profile and renal functions, and diminished TGF-β1/iNOS/NGAL/KIM-1/Caspase-3 alongside the apoptotic index than the PC group. The oxidative stress and pro-inflammatory markers decreased, whilst the anti-oxidative and anti-inflammatory molecules escalated, in the monotherapy groups than the PC group. Although the Paricalcitol renoprotective actions were better than ω-3, all the biomarkers were abnormal than the NC group. Alternatively, the Paricalcitol + ω-3 protocol exhibited the best improvements in metabolic control, renal functions, oxidative stress, inflammation, and apoptosis. However, FBG and tissue damage were persistently higher in the co-therapy group than controls. Conclusions Both monotherapies showed modest efficacy against DN, whereas their combination displayed boosted renoprotection, possibly by enhancing renal anti-oxidant and anti-inflammatory pathways.

No scholar has explored whether immunosuppressive treatments at different histopathological stages are different for idiopathic membranous nephropathy (IMN).From January 1, 2012, to January 1, 2018, all biopsy confirmed IMN cases treated with glucocorticoid (GC) plus cyclophosphamide (CTX) or GC were retrieved from the patients' medical records.The present study included 67 patients who received GC alone (31 with stage I, 30 with stage II and 6 with stage III) and 157 patients who received GC + CTX (77 with stage I, 66 with stage II and 14 with stage III). Primary efficacy assessments included achieving complete remission and remission. Secondary efficacy assessments included proteinuria, serum albumin and adverse events. GC + CTX group showed higher complete remission rates than the GC group after 6 and 12 months in patients with stage II IMN (22% vs 10%, P = 0.04 and 59% vs 17%, P 0.001, respectively). However, the two groups showed no difference in stages I and III (29% vs 26%, P = 0.61, 71% vs 52%, P = 0.09 and 14% vs 17%, P = 0.81, 21% vs 17%, P = 0.88, respectively). The GC + CTX group suffered a higher rate of gastrointestinal symptoms than the GC group in stage I and a higher rate of abnormal liver function in stage II.Treatment with GC + CTX was more effective than GC in treating patients with stage II IMN; however, the advantage of GC + CTX was not significant for patients with stage I and III IMN.

Calciphylaxis is commonly associated with end-stage renal disease (ESRD) and renal transplant. We present a rare case of early onset calciphylaxis in a patient presenting with acute kidney injury (AKI) secondary to anti-glomerular basement membrane (anti-GBM) antibody disease. A 65-year-old obese Caucasian woman with type 2 diabetes mellitus and hypertension presented with a 1-month history of painless gross haematuria and worsening lower extremity oedema. Laboratory results indicated AKI and nephrotic-range proteinuria. Anti-glomerular antibodies were elevated. Renal biopsy revealed focal crescentic glomerulonephritis with linear capillary immunoglobulin G staining consistent with anti-GBM antibody disease. She was treated with haemodialysis, plasmapheresis, steroids, bumetanide and cyclophosphamide. Two months later, she developed necrotic lesions on bilateral thighs. Wound biopsy was consistent with calciphylaxis. This case highlights that calciphylaxis, usually seen in patients with chronic kidney disease or ESRD, can manifest in patients with AKI as well.

A 23-year-old primigravida presented to the emergency department with reports of headache. On examination, her blood pressure was found to be 190/140 mm Hg. Her laboratory results were notable for proteinuria, deranged liver function and low platelets. She was diagnosed with HELLP syndrome and was delivered via caesarean section. She noticed diminution of vision 2 days after delivery. Fundus examination revealed bilateral serous retinal detachment involving the maculae. She was managed conservatively and had complete recovery of her vision by 3 weeks postpartum.

We herein report a 43-year-old woman with Buerger's disease who presented with nephrotic syndrome, renal dysfunction, and mild hypertension. A kidney biopsy revealed focal segmental glomerulosclerosis (FSGS), but there were no findings associated with frequent secondary FSGS or a history of long-term hypertension. A small focal renal infarction was seen on 99mTc-dimercaptosuccinic acid renal scintigraphy, suggesting that FSGS was due to renal microinfarction associated with Buerger's disease. After the commencement of angiotensin-converting enzyme inhibitor therapy, the hypertension immediately improved, along with significant attenuation of proteinuria. Renal ischemia by vasoconstriction of the glomerular efferent arterioles in association with Buerger's disease may result in glomerular hyperfiltration followed by FSGS.

Aim To develop and validate a new risk prediction model for predicting the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) in Japanese adults. Methods A total of 2,454 participants aged 40-84 years without a history of cardiovascular disease (CVD) were prospectively followed up for 24 years. An incident ASCVD event was defined as the first occurrence of coronary heart disease or atherothrombotic brain infarction. A Cox proportional hazards regression model was used to construct the prediction model. In addition, a simplified scoring system was translated from the developed prediction model. The model performance was evaluated using Harrell's C statistics, a calibration plot with the Greenwood-Nam-D'Agostino test, and a bootstrap validation procedure. Results During a median of a 24-year follow-up, 270 participants experienced the first ASCVD event. The predictors of the ASCVD events in the multivariable Cox model included age, sex, systolic blood pressure, diabetes, serum high-density lipoprotein cholesterol, serum low-density lipoprotein cholesterol, proteinuria, smoking habits, and regular exercise. The developed models exhibited good discrimination with negligible evidence of overfitting (Harrell's C statistics: 0.786 for the multivariable model and 0.789 for the simplified score) and good calibrations (the Greenwood-Nam-D'Agostino test: P=0.29 for the multivariable model, 0.52 for the simplified score). Conclusion We constructed a risk prediction model for the development of ASCVD in Japanese adults. This prediction model exhibits great potential as a tool for predicting the risk of ASCVD in clinical practice by enabling the identification of specific risk factors for ASCVD in individual patients.

All units managing hypertensive pregnant women should maintain and review uniform departmental management protocols and conduct regular audits of maternal & fetal outcomes. The cause(s) of pre-eclampsia and the optimal clinical management of the hypertensive disorders of pregnancy remain uncertain; therefore, we recommend that every hypertensive pregnant woman be offered an opportunity to participate in research, clinical trials and follow-up studies.

Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminaemia, edema and hyperlipidaemia. Genetic studies of nephrotic syndrome have led to the identification of proteins playing a crucial role in slit diaphragm signaling, regulation of actin cytoskeleton dynamics and cell-matrix interactions. The laminin α5 chain is essential for embryonic development and, in association with laminin β2 and laminin γ1, is a major component of the glomerular basement membrane, a critical component of the glomerular filtration barrier. Mutations in LAMA5 were recently identified in children with nephrotic syndrome. Here, we have identified a novel missense mutation (E884G) in the uncharacterized L4a domain of LAMA5 where homozygous mice develop nephrotic syndrome with severe proteinuria with histological and ultrastructural changes in the glomerulus mimicking the progression seen in most patients. The levels of LAMA5 are reduced in vivo and the assembly of the laminin 521 heterotrimer significantly reduced in vitro. Proteomic analysis of the glomerular extracellular fraction revealed changes in the matrix composition. Importantly, the genetic background of the mice had a significant effect on aspects of disease progression from proteinuria to changes in podocyte morphology. Thus, our novel model will provide insights into pathologic mechanisms of nephrotic syndrome and pathways that influence the response to a dysfunctional glomerular basement membrane that may be important in a range of kidney diseases.

Objectives The present study was designed to determine the effect of dietary phosphorus restriction, independent of protein intake, on the urinary protein excretion in patients with proteinuria. Methods Seventy-one patients with proteinuria were enrolled in a parallel randomized controlled trial study. The patients were randomly allocated to receive either a recommended phosphorus-restricted diet (n = 36) or a recommended control diet (n = 35), for 8 weeks. A diet was designed and recommended to participants in a way that both trial groups would receive the same amount of energy and protein and the only significant difference between them was the amount of phosphorus intake. The study outcomes included the changes in spot urine protein-to-creatinine ratio, the changes in serum and urine levels of phosphorus, as well as the changes in estimated glomerular filtration rate (eGFR). Results The mean ± standard deviation of age, body mass index, and eGFR of the participants were 59 ± 14 years, 29 ± 5.5 kg/m2, and 56.1 ± 21.7 mL/min/1.73 m2, respectively. The amount of phosphorus intake decreased significantly in the phosphorus-restricted group compared to the control one (−709 vs. −369 mg/day; P Conclusions Although adherence to a phosphorus-restricted diet by patients with proteinuria led to a significant decrease in urinary protein excretion, this change was not significantly different from that of the control diet. Further studies with larger sample sizes and different designs will reveal more evidence for a link between phosphorus intake and proteinuria.

Some cases of patients with IgA nephropathy diagnosed via kidney biopsy and antineutrophil cytoplasmic antibody (ANCA) positivity have been reported. This article describes a case series comprising patients with IgA nephropathy and ANCA positivity seen at a medical center in the city of São Paulo, Brazil, from 1996 to 2016. A total of 111 patients underwent diagnostic kidney biopsies for IgA nephropathy. Five were ANCA-positive at the time of diagnosis; their mean age was 45 ± 15.3 years and they were predominantly females with a mean proteinuria of 2.2 ± 0.9 g/day and a median serum creatinine level of 2.5 (2.0 - 8,6) mg/dL; all had hematuria. Four of the five were cANCA-positive (80%); all had normal serum C3 and C4 levels; and 80% were positive for ANA. One case presented an association with infection, but no associations were found with medication. One patient had granuloma and another had a collapsing lesion. This article describes the cases of five ANCA-positive patients (with predominantly cANCA positivity) submitted to diagnostic kidney biopsies for IgA nephropathy; one patient had a collapsing lesion, but progressed well. Resumo Alguns casos clínicos de biópsia renal diagnóstica de nefropatia por IgA em pacientes com títulos séricos positivos de anticorpo anticitoplasma de neutrófilos (ANCA) vêm sendo publicados. Descreve-se uma série de casos de nefropatia por IgA com ANCA positivo de centro único da cidade de São Paulo, Brasil, no período de 1996 a 2016. No período estudado, houve 111 pacientes com biópsia renal com diagnóstico de nefropatia por IgA; destes, 5 tinham ANCA positivo ao diagnóstico com média de idade de 45 ± 15,3 anos, predominando o sexo feminino, com média de proteinúria de 2,2 ± 0,9 g/dia, hematúria presente em 100% dos casos e mediana de creatinina sérica de 2,5 (2,0 - 8,6) mg/dL. O cANCA foi o padrão mais encontrado, em 4 dos 5 casos (80%), com os níveis séricos das frações de complemento C3 e C4 normais em todos e FAN positivo em 80% dos casos. Houve associação com infecções em um caso, mas sem associação com medicações. À microscopia óptica, um dos pacientes tinha granuloma e outro, lesão colapsante. Em resumo, descreve-se cinco casos de pacientes com biopsia renal diagnóstica de nefropatia por IgA com ANCA sérico positivo predominando cANCA, destacando um paciente desse grupo com microscopia óptica com lesão colapsante que, apesar disso, teve boa evolução.

Amyloidosis is a rare group of diseases characterized by abnormal folding of proteins and extracellular deposition of insoluble fibrils. It can be localized to one organ system or can have systemic involvement. The kidney is the most common organ to be involved in systemic amyloidosis often leading to renal failure and the nephrotic syndrome. The two most common types of renal amyloidosis are immunoglobulin light chain-derived amyloidosis (AL) and reactive amyloidosis (AA). A novel form of amyloidosis (ALECT2) derived from leukocyte chemotactic factor 2 (LECT-2) and primarily involving the kidneys was first described by Benson et al in 2008. The liver was subsequently identified as the second most common organ involved in ALECT2 amyloidosis. LECT-2 is a unique protein that can form amyloid deposits even in its unmutated form. Patients with ALECT2 present with minimal proteinuria in contrast to other forms of amyloidosis especially AL and AA. They may present with slightly elevated serum creatinine. Nephrotic syndrome and hematuria are rare. ALECT2 can be found in association with other types of amyloidosis as well as malignancies or autoimmune diseases. ALECT2 may be confused with amyloidosis associated with light and heavy chain monoclonal gammopathy if the immunofluorescence is positive with anti-light chain and anti-AA sera. The other organs involved are the duodenum, adrenal gland, spleen, prostate, gall bladder, pancreas, small bowel, parathyroid gland, heart, and pulmonary alveolar septa, but consistently uninvolved organs included brain and fibroadipose tissue. A renal biopsy along with characteristic features found on immunohistochemistry and mass spectrometry is diagnostic of ALECT2. ALECT2 should be suspected when all markers for AL and AA are negative. Proper diagnosis of ALECT2 can determine need for supportive care versus more aggressive interventions.

Preeclampsia is a devastating medical complication of pregnancy that can lead to significant maternal and fetal morbidity and mortality. It is currently believed that there is abnormal placentation in as early as the first trimester in women destined to develop preeclampsia. Although the etiology of the abnormal placentation is being debated, numerous epidemiologic and experimental studies suggest that imbalances in circulating angiogenic factors released from the placenta are responsible for the maternal signs and symptoms of preeclampsia. In particular, circulating levels of soluble fms-like tyrosine kinase 1, an antiangiogenic factor, are markedly increased in women with preeclampsia, whereas free levels of its ligand, placental, growth factor are markedly diminished. Alterations in these angiogenic factors precede the onset of clinical signs of preeclampsia and correlate with disease severity. Recently, the availability of automated assays for the measurement of angiogenic biomarkers in the plasma, serum, and urine has helped investigators worldwide to demonstrate a key role for these factors in the clinical diagnosis and prediction of preeclampsia. Numerous studies have reported that circulating angiogenic biomarkers have a very high negative predictive value to rule out clinical disease among women with suspected preeclampsia. These blood-based biomarkers have provided a valuable tool to clinicians to accelerate the time to clinical diagnosis and minimize maternal adverse outcomes in women with preeclampsia. Angiogenic biomarkers have also been useful to elucidate the pathogenesis of related disorders of abnormal placentation such as intrauterine growth restriction, intrauterine fetal death, twin-to-twin transfusion syndrome, and fetal hydrops. In summary, the discovery and characterization of angiogenic proteins of placental origin have provided clinicians a noninvasive blood-based tool to monitor placental function and health and for early detection of disorders of placentation. Uncovering the mechanisms of altered angiogenic factors in preeclampsia and related disorders of placentation may provide insights into novel preventive and therapeutic options.

Qualitative and quantitative measurement of urine protein excretion is one of the most common tests performed during pregnancy. For more than 100 years, proteinuria was necessary for the diagnosis of preeclampsia, but recent guidelines recommend that proteinuria is sufficient but not necessary for the diagnosis. Still, in clinical practice, most patients with gestational hypertension will be diagnosed as having preeclampsia based on the presence of proteinuria. Although the reference standard for measuring urinary protein excretion is a 24-hour urine collection, spot urine protein-to-creatinine ratio is a reasonable "rule-out" test for proteinuria. Urine dipstick screening for proteinuria does not provide any clinical benefit and should not be used to diagnose proteinuria. The classic cutoff cited to define proteinuria during pregnancy is a value of >300 mg/24 hours or a urine protein-to-creatinine ratio of at least 0.3. Using this cutoff, the rate of isolated proteinuria in pregnancy may reach 8%, whereas preeclampsia occurs among 3% to 8% of pregnancies. Although this threshold is widely accepted, its origin is not based on evidence on adverse pregnancy outcomes but rather on expert opinion and results of small studies. After reviewing the available data, the most important factor that influences maternal and neonatal outcome is the severity of blood pressures and presence of end organ damage, rather than the excess protein excretion. Because the management of gestational hypertension and preeclampsia without severe features is almost identical in frequency of surveillance and timing of delivery, the separation into 2 disorders is unnecessary. If the management of women with gestational hypertension with a positive assessment of proteinuria will not change, we believe that urine assessment for proteinuria is unnecessary in women who develop new-onset blood pressure at or after 20 weeks' gestation. Furthermore, we do not recommend repeated measurement of proteinuria for women with preeclampsia, the amount of proteinuria does not seem to be related to poor maternal and neonatal outcomes, and monitoring proteinuria may lead to unindicated preterm deliveries and related neonatal complications. Our current diagnosis of preeclampsia in women with chronic kidney disease may be based on a change in protein excretion, a baseline protein excretion evaluation is critical in certain conditions such as chronic hypertension, diabetes, and autoimmune or other renal disorders. The current definition of superimposed preeclampsia possesses a diagnostic dilemma, and it is unclear whether a change in the baseline proteinuria reflects another systemic disease such as preeclampsia or whether women with chronic disease such as chronic hypertension or diabetes will experience a different "normal" pattern of protein excretion during pregnancy. Finally, limited data are available regarding angiogenic and other biomarkers in women with chronic kidney disease as a potential aid in distinguishing the worsening of baseline chronic kidney disease and chronic hypertension from superimposed preeclampsia.

The pathogenesis of primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) remains unknown to date. Some circulating permeability factors are being discussed. This work assessed molecule candidates for permeability in serum samples of patients with nephrotic syndrome (NS). MATERIALS AND METHODS 41 patients with chronic glomerulonephritis (CGN) were included in our study. 17 patients had FSGS, 7 patients had MCD, 5 patients had membranoproliferative glomerulonephritis (MPGN), 6 patients had IgA nephropathy, and 6 patients had membranous nephropathy (MN). The laboratory data were compared with the clinical and histological features of nephritis. Serum levels of plasminogen activator urokinase receptor (uPAR) and cardiotrophin-like cytokine factor 1 (CLCF-1)were measured by ELISA. RESULTS The serum levels of uPAR were higher in FSGS patients before treatment than in patients with other morphological forms (MCD, IgA nephropathy, MN, and MPGN). The levels of uPAR in serum did not correlate with daily proteinuria, serum creatinine/eGFR, arterial hypertension, the number of sclerosed glomeruli, or tubulointerstitial fibrosis. No correlations were found between the levels of CLCF-1 in serum and creatinine levels/glomerular filtration rate, the percentage of sclerosed glomeruli, or the severity of tubulointerstitial fibrosis. There were no significant differences between the histological variants of nephritis. However, we found correlations between CLCF-1 levels and proteinuria and lipid levels. CONCLUSION The data indicate an increase in the serum uPAR levels of FSGS before treatment. CLCF-1 levels in serum do not depend on histological forms of CGN, kidney function, or immunosuppressive treatment, but they correlate with proteinuria and serum lipids in patients with NS.

Objective This study aimed to review pregnancy hypertension clinical practice guidelines to inform international clinical practice and research priorities. Study Eligibility Criteria Relevant national and international clinical practice guidelines, 2009-19, published in English, French, Dutch or German. Study Appraisal and Synthesis Methods Following published methods and prospective registration (CRD42019123787), a literature search was updated. CPGs were identified by 2 authors independently who scored quality and usefulness for practice (Appraisal of Guidelines for Research and Evaluation II instrument), abstracted data, and resolved any disagreement by consensus. Results Of note, 15 of 17 identified clinical practice guidelines (4 international) were deemed “clinically useful” and had recommendations abstracted. The highest Appraisal of Guidelines for Research and Evaluation II scores were from government organizations, and scores have improved over time. The following were consistently recommended: (1) automated blood pressure measurement with devices validated for pregnancy and preeclampsia, reflecting increasing recognition of the prevalence of white-coat hypertension and the potential usefulness of home blood pressure monitoring; (2) use of dipstick proteinuria testing for screening followed by quantitative testing by urinary protein-to-creatinine ratio or 24-hour urine collection; (3) key definitions and most aspects of classification, including a broad definition of preeclampsia (which includes proteinuria and maternal end-organ dysfunction, including headache and visual symptoms and laboratory abnormalities of platelets, creatinine, or liver enzymes) and a recognition that it can worsen after delivery; (4) preeclampsia prevention with aspirin; (5) treatment of severe hypertension, most commonly with intravenous labetalol, oral nifedipine, or intravenous hydralazine; (6) treatment for nonsevere hypertension when undertaken, with oral labetalol (in particular), methyldopa, or nifedipine, with recommendations against the use of renin-angiotensin-aldosterone inhibitors; (7) magnesium sulfate for eclampsia treatment and prevention among women with “severe” preeclampsia; (8) antenatal corticosteroids for preterm birth but not hemolysis, elevated liver enzymes, and low platelet count syndrome; (9) delivery at term for preeclampsia; (10) a focus on usual labor and delivery care but avoidance of ergometrine; and (11) an appreciation that long-term health complications are increased in incidence, mandating lifestyle change and risk factor modification. Lack of uniformity was seen in the following areas: (1) the components of a broad preeclampsia definition (specifically respiratory and gastrointestinal symptoms, fetal manifestations, and biomarkers), what constitutes severe preeclampsia, and whether the definition has utility because at present what constitutes severe preeclampsia by some guidelines that mandate proteinuria now defines any preeclampsia for most other clinical practice guidelines; (2) how preeclampsia risk should be identified early in pregnancy, and aspirin administered for preeclampsia prevention, because multivariable models (with biomarkers and ultrasonography added to clinical risk markers) used in this way to guide aspirin therapy can substantially reduce the incidence of preterm preeclampsia; (3) the value of calcium added to aspirin for preeclampsia prevention, particularly for women with low intake and at increased risk of preeclampsia; (4) emerging recommendations to normalize blood pressure with antihypertensive agents even in the absence of comorbidities; (5) fetal neuroprotection as an indication for magnesium sulfate in the absence of “severe” preeclampsia; and (6) timing of birth for chronic and gestational hypertension and preterm preeclampsia. Conclusion Consistent recommendations should be implemented and audited. Inconsistencies should be the focus of research.

We herein report two cases in which add-on acetazolamide to furosemide was effective for diuretic-resistant volume overload and hypercapnia. Case 1 was a woman in her 40s presenting with volume overload due to the nephrotic syndrome with diabetes mellitus. Case 2 was a man in his 60s with fluid overload and non-nephrotic proteinuria and sepsis. In both cases, although fluid overload was resistant to high-dose loop diuretics and complicated with hypercapnia due to pulmonary effusion, add-on acetazolamide administration resulted in symptom resolution. The additional effect of acetazolamide occurred regardless of the degree of proteinuria and kidney function.

Childhood IgA nephropathy (IgAN) includes a wide spectrum of clinical presentations, from isolated hematuria to acute nephritis with rapid loss of kidney function. In adults, IgAN is an autoimmune disease and its pathogenesis involves galactose deficient (Gd) IgA1, IgG anti-Gd-IgA1 autoantibodies and the soluble IgA Fc receptor (CD89). However, implication of such factors, notably soluble CD89, in childhood IgAN pathogenesis remains unclear. Here, we studied these biomarkers in a cohort of 67 patients with childhood IgAN and 42 pediatric controls. While Gd-IgA1 was only moderately increased in patient plasma, levels of circulating IgA complexes (soluble CD89-IgA and IgG-IgA) and free soluble CD89 were markedly increased in childhood IgAN. Soluble CD89-IgA1 complexes and free soluble CD89 correlated with proteinuria, as well as histological markers of disease activity: mesangial, endocapillary hypercellularity and cellular crescents. Soluble CD89 was found in patient's urine but not in urine from pediatric controls. Mesangial deposits of soluble CD89 were detected in biopsies from patients with childhood IgAN. Serum chromatographic fractions containing covalently linked soluble CD89-IgA1 complexes or free soluble CD89 from patients induced mesangial cell proliferation in vitro in a soluble CD89-dependent manner. Recombinant soluble CD89 induced mesangial cell proliferation in vitro which was inhibited by free soluble recombinant CD71 (also a mesangial IgA receptor) or mTOR blockers. Interestingly, injection of recombinant soluble CD89 induced marked glomerular proliferation and proteinuria in mice expressing human IgA1. Thus, free and IgA1-complexed soluble CD89 are key players in mesangial proliferation. Hence, our findings suggest that soluble CD89 plays an essential role in childhood IgAN pathogenesis making it a potential biomarker and therapeutic target.

In order to develop prediction models of one-year treatment response in lupus nephritis, an approach using machine learning to combine traditional clinical data and novel urine biomarkers was undertaken. Contemporary lupus nephritis biomarkers were identified through an unbiased PubMed search. Thirteen novel urine proteins contributed to the top 50% of ranked biomarkers and were selected for measurement at the time of lupus nephritis flare. These novel markers along with traditional clinical data were incorporated into a variety of machine learning algorithms to develop prediction models of one-year proteinuria and estimated glomerular filtration rate (eGFR). Models were trained on 246 individuals from four different sub-cohorts and validated on an independent cohort of 30 patients with lupus nephritis. Seven models were considered for each outcome. Three quarters of these models demonstrated good predictive value with areas under the receiver operating characteristic curve over 0.7. Overall, prediction performance was the best for models of eGFR response to treatment. Furthermore, the best performing models contained both traditional clinical data and novel urine biomarkers, including cytokines, chemokines, and markers of kidney damage. Thus, our study provides further evidence that a machine learning approach can predict lupus nephritis outcomes at one year using a set of traditional and novel biomarkers. However, further validation of the utility of machine learning as a clinical decision aid to improve outcomes will be necessary before it can be routinely used in clinical practice to guide therapy.

Background: There have been some cases where abnormal histopathologic findings could not be found in the kidney could even with proper specimen collection through percutaneous renal biopsy (PRB) in accordance with its indication. We analyzed the incidence and clinical outcomes of children who showed normal histopathological findings in their PRBs.Methods: The medical records of 552 pediatric subjects who underwent PRB between 2005 and 2016 were reviewed. Twenty-six subjects were excluded because allograft biopsy was performed in nine subjects, and the age at biopsy was greater than 18 years in 17 subjects. Finally, 526 subjects were enrolled in this study.Results: Of the 526 pediatric patients, 32 (6.1%) showed no histopathological abnormalities in their PRBs. The male-to-female ratio of the patients was 1.9:1, and the mean ages at the first visit and at biopsy were 10.6 ± 4.1 and 11.4 ± 3.8 years, respectively. In accordance with the biopsy indications, recurrent gross hematuria showed the highest incidence rate, but combined hematuria and proteinuria had the lowest incidence rate regarding normal renal histopathology among all the subjects. At a mean follow-up of 35.5 ± 23.6 months, urinary abnormalities had improved in more than 50% of the subjects with normal renal histopathology, and none of the patients showed progression to end-stage renal disease or required rebiopsy due to symptom worsening during the follow-up period.Conclusion: The clinical outcomes of children with normal PRB histopathologic findings are generally good. Further studies to evaluate their long-term outcomes are needed.

Background. Patients with inflammatory joint diseases, which include systemic scleroderma (SS), have increased cardiovascular disease risk compared with the general population. Arterial hypertension (AH) is a major modifiable risk factor contributing to increased cardiovascular disease risk in inflammatory joint diseases. The purpose of the study was to investigate the prognosis and predictors of AH development in patients with SS. Materials and methods. We have conducted a 5-year prospective observation of 73 patients, who were in the regional registry. The investigation of risk for AH development was performed using the Kaplan-Meier procedure. Calculations of predictors’ influence on the risk of AH were performed using Cox regression. Results. The 5-year risk of AH development in SS was 20.3 %. Estimated risk of AH on the first, third and fifth year of the disease is 18.2, 25.0 and 19.4 %, respectively. The resulting impact of the initial clinical and laboratory parameters on the risk of AH development (hazard ratio): age > 45 years — 2.04, diffuse scleroderma — 0.65, Raynaud phenomenon — 1,17, tightness of the skin of the hands — 1.74, arthritis — 0.99, pulmonary fibrosis — 1.84, anemia — 0.78, erythrocyte sedimentation rate (ESR) > 25 mm/h — 1.68, C-reactive protein (CRP) level > 5 mg/l — 1.52, rheumatoid factor (RF) > 14 IU/ml — 1,48, proteinuria — 1.09. Conclusions. The 5-year risk of AH in SS is 20.3 %. The strongest influence on the risk of AH development in SS showed: age > 43.7 years, the presence of the tightness of the skin of the hands, pulmonary fibrosis, ESR > 25 mm/h, CRP > 5 mg/l, RF > 14 IU/mL. AH in systemic scleroderma has a heterogeneous nature. In patients, who had AH at the onset of SS, in a five-year term, we can expect an increase in the occurrence of proteinuria and glomerular filtration rate decline.

Огляд присвячено питанням лікування артеріальної гіпертензії (АГ) у пацієнтів з гострими ураженнями нирок та хронічною хворобою нирок з протеїнурією та без неї. Підкреслено, що лікування АГ у пацієнтів із хворобами нирок призначається після уточнення типу ураження нирок, наявності протеїнурії, набрякового синдрому, швидкості клубочкової фільтрації. АГ при гострому захворюванні клубочків з набряками потребує видалення рідини сечогінними засобами або, при необхідності, діалізом. У хворих із хронічною хворобою нирок та протеїнурією як терапія першої лінії для лікування АГ використовуються інгібітори ангіотензинперетворюючого ферменту або блокатори рецепторів ангіотензину. Доведено, що олмесартану медоксоміл має найбільш виражені ренопротекторні властивості серед усіх препаратів — блокаторів рецепторів ангіотензину.

Focal segmental glomerulosclerosis (FSGS) is a major renal complication of human mitochondrial disease. However, its pathogenesis has not been fully explained. In this study, we focused on the glomerular injury of mito-miceΔ and investigated the pathogenesis of their renal involvement. We analyzed biochemical data and histology in mito-miceΔ. The proteinuria began to show in some mito-miceΔ with around 80% of mitochondrial DNA deletion, then proteinuria developed dependent with higher mitochondrial DNA deletion, more than 90% deletion. Mito-miceΔ with proteinuria histologically revealed FSGS. Immunohistochemistry demonstrated extensive distal tubular casts due to abundant glomerular proteinuria. Additionally, the loss of podocyte-related protein and podocyte's number were found. Therefore, the podocyte injuries and its depletion had a temporal relationship with the development of proteinuria. This study suggested mitochondrial DNA deletion-dependent podocyte injuries as the pathogenesis of renal involvement in mito-miceΔ. The podocytes are the main target of mitochondrial dysfunction originated from the accumulation of mitochondrial DNA abnormality in the kidney.

Introducción La amiloidosis secundaria (AA) es una complicación grave asociada a enfermedades inflamatorias. Se caracteriza por el depósito sistémico de proteína fibrilar AA, con especial repercusión renal. La participación de la interleucina 6 en su mecanismo patogénico ha supuesto que tocilizumab (TCZ) sea considerado una opción terapéutica en estos pacientes. Varias series publicadas muestran su eficacia en el tratamiento de la amiloidosis AA, permitiendo incluso la regresión de depósitos renales ya presentes. Material y método Revisión retrospectiva que incluyó pacientes con diagnóstico histológico de amiloidosis renal AA en tratamiento con TCZ durante los años 2018-2019 en nuestro centro. Registramos variables clínicas y demográficas; evaluamos la función renal mediante filtrado glomerular (FG) calculado por CKD-EPI e índice proteína/creatinina a los 3, 6 y 12 meses de seguimiento. Definimos «respuesta renal» como la disminución > 30% de la proteinuria y/o estabilización o mejoría del FG. Consideramos «respuesta antiinflamatoria» la disminución > 50% de las cifras de proteína sérica amiloide (PSA) y/o proteína C reactiva (PCR). Resultados Presentamos una serie de 3 pacientes (2 varones y una mujer; 55, 74 y 75 años, respectivamente), con un tiempo de seguimiento de 13, 14 y 75 meses, respectivamente. Con la terapia con TCZ, el FG se estabilizó en 2 pacientes; el tercero permaneció en hemodiálisis durante el seguimiento, aunque con excelente control de su enfermedad inflamatoria de base; a los 12 meses recibió un trasplante renal. En los 3 casos se objetivó reducción de proteína PSA y PCR. No se han producido eventos adversos. Conclusiones El TCZ es una opción terapéutica eficaz y segura para los pacientes con amiloidosis AA y afectación renal. Nuestros resultados lo posicionan como una opción terapéutica a considerar en estos casos, aunque sería necesario la realización de estudios prospectivos en los que se evalúe el papel global de TCZ en la amiloidosis AA. Introduction AA (secondary) amyloidosis is a severe complication of chronic inflammatory disorders. It is characterized by the systemic deposition of an abnormal protein called amyloid, affecting mainly renal function. IL-6 is a cytokine with a relevant role in this disease development. Interleukin-receptor antagonists, like Tocilizumab (TCZ), have become possible treatment choice for AA amyloidosis. In published reports, TCZ has shown good efficacy for AA amyloidosis, being associated with regression of renal amyloid deposits. Methods Retrospective review that included patients with histological diagnosis of AA renal amyloidosis under treatment with TCZ during the years 2018-2019 in our center. We have registered clinical and demographic variables. Renal function was measured by means of CKD-EPI equation to estimate the glomerular filtration rate (FG) and protein/creatinine ratio (IPC) at 3, 6 and 12 months. We define renal response as a decrease by at least 30% of proteinuria and/or stabilization or improvement of FG. We consider that an anti-inflammatory response is a decrease of more than 50% in serum amyloid protein (PSA) and/or C-reactive protein (CRP). Results We collected 3 cases of patients with histologically proven AA amyloidosis treated with TCZ (2 men; 1 woman; aged 55, 74 and 75 years). The follow-up was 13, 14 and 75 months. FG was stabilized in two patients. The third patient remained on hemodialysis during follow-up, although with excellent control of her underlying inflammatory disease. In all three cases, reduced PSA and CRP were observed. There have been no adverse events. Conclusions The TCZ may be an effective and safe option in treatment of AA amyloidosis with renal involvement. Our results position it as an interesting therapeutic option to consider in these cases, although prospective studies would be necessary to evaluate the global role of TCZ in AA amyloidosis.

Proteinuria is a transient physiological phenomenon that occurs with a range of physical activities and during ascent to altitude. Exercise intensity appears to dictate the magnitude of postexercise proteinuria; however, evidence also indicates the possible contributions from exercise-induced hypoxemia or reoxygenation. Using an environmental hypoxic chamber, this crossover-designed study aimed to evaluate urinary alpha-1 acid glycoprotein (α1-AGP) excretion pre/postexercise performed in hypoxia (HYP) and normoxia (NOR). Sixteen individuals underwent experimental sessions in normoxia (NOR, 20.9% O

Introduction The usefulness of the Oxford classification (MEST-C score) for deciding the management approach for IgA nephropathy (IgAN) remains unclear. Methods Effects of steroid therapy on the long-term prognosis for all 858 patients with IgAN and patients classified according to each MEST-C score were evaluated using Kaplan-Meier and Cox regression analyses. Steroid responder score (SRS) and steroid nonresponder score (SNRS) were determined using individual pathology scores when steroids were found to be independently associated, or not, with clinical benefits. In addition, the effects of steroid therapy according to the total SRS/SNRS were analyzed. Results Steroid therapy improved the 20-year renal survival rates of patients with IgAN after matching (steroids[+] vs. steroids[−]; estimated glomerular filtration rate [eGFR] [ml/min per 1.73 m2]: 79.4 vs. 77.0, not significant; proteinuria [g/d]: 0.80 vs. 0.62, not significant; renal survival rate: 75.5% vs. 61.7%; P = 0.025) and of patients with M1, E1, S1, C1+2, and T0 scores. Therefore, we considered the total of the M1, E1, S1, and C1+2 scores (point 0: low, 1–2: medium, and 3–4: high) as the SRS and the total of the T1+2 scores (0: low and 1: high) as the SNRS. Multivariate Cox regression analyses revealed that steroid therapy improved the renal prognosis of patients with IgAN with high SRS and any SNRS, unlike patients with IgAN with medium SRS and any SNRS. Conclusion Patients with M1, E1, S1, and C1+2 scores responded to steroid therapy; however, those with T1+2 scores did not. Although a high SRS was a useful indicator for steroid therapy, SNRS indicated resistance to steroid therapy., Graphical abstract

Hematuria or proteinuria may be just a normal transient finding in children, usually accompanying a non-specific viral infection, or it can be an indicator of a kidney or urinary tract disorder. In this chapter, the various causes and significance of discolored urine, hematuria and proteinuria in children are discussed. A pragmatic clinical approach to evaluate a child with isolated hematuria or isolated proteinuria is suggested to reduce unnecessary extensive workup in benign cases and yet not miss the cases with significant glomerular or urinary tract disease. Early detection and treatment of significant disorders would hopefully delay or prevent the onset of renal insufficiency in children.

Laboratory evaluation is a major component of the assessment for renal disease in children. Because clinical examination rarely provides sufficient information to establish a diagnosis, nephrologists rely heavily on laboratory evaluation. Knowing the indications for each test and the normal reference ranges is important for the clinician. This chapter reviews the tests for renal disease most commonly used in clinical practice.

Unlike patients with congestive heart failure (CHF) and cirrhosis, patients with nephrotic syndrome have some underlying renal disease. Also, effective circulating volume (ECV) is not decreased in all patients with nephrotic syndrome. This syndrome is characterized by proteinuria in excess of 3.5 g/day, hypoalbuminemia, hyperlipidemia, edema, and lipiduria. The mechanism for salt and water retention is not clear. The traditional (“underfill”) theory implies that loss of protein in the urine causes hypoalbuminemia and decreased plasma oncotic pressure. These factors favor fluid movement into the interstitium, resulting in intravascular hypovolemia and activation of salt-retaining mechanisms (Fig. 9.1). Two lines of evidence, however, argue against this traditional theory. First, not all patients with congenital deficiency of albumin (analbuminemia) develop edema. Second, some patients with nephrotic syndrome have either normal or increased intravascular volume despite hypoalbuminemia. This evidence suggests that mechanisms other than hypoalbuminemia and decreased intravascular volume play a role in renal retention of Na+ in nephrotic syndrome.

Progression of childhood chronic kidney disease towards end-stage renal failure is common and once a significant impairment of renal function has occurred renal failure tends to progress almost irrespectively of the type of underlying kidney disease. The phenomenon of renal failure progression following kidney injury or maldevelopment is a current focus of renal research in adults and children. There is clear evidence from clinical studies that hypertension and proteinuria are key players in the pathophysiology of CKD progression in humans. The renin-angiotensin system is intrinsically involved in the process; presumed modifiers of disease progression include the genetic background, altered mineral homeostasis, anemia, metabolic acidosis, dyslipidemia, inflammation and oxidative stress, on top of general cardiovascular risk factors such as diabetes, smoking and obesity. This chapter summarizes the current state of knowledge regarding the pathophysiology of renal disease progression and discusses the evidence base of renoprotective strategies in pediatric CKD.

OBJECTIVE To characterize the signalment, clinical signs, clinical pathological and histologic findings, and outcome in 8 related Bracchi Italiani with proteinuric kidney disease. ANIMALS 8 client-owned Bracchi Italiani. PROCEDURES Health records submitted to the Bracco Italiano Health Foundation and the Bracco Italiano Club of America between 2012 and 2019 were reviewed for dogs with evidence of nephropathy for which histologic diagnoses were obtained. Pedigree, signalment, clinical signs, diagnostic test results (including microscopic examination of kidney tissue samples collected ante- or postmortem), and outcome were acquired. Results were presented as descriptive statistics. RESULTS The most common clinical sign in affected dogs was inappetence. All dogs were proteinuric, and 4 dogs were azotemic. Seven dogs developed clinical signs of kidney disease and were euthanized a median of 75 days postdiagnosis. Six dogs had glomerular amyloidosis, and 1 dog each had nephrosclerosis and nonamyloidotic fibrillar glomerulopathy. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the clinical presentation may vary in affected dogs, and proteinuria in young or middle-aged Bracchi Italiani should raise the concern for hereditary nephropathy. Prognosis is likely poor once clinical signs are noted.

Many kidney donor candidates with impaired fasting glucose (IFG) and all candidates with diabetes are currently excluded from kidney donation, fearing the development of an accelerated course of diabetic kidney disease in the remaining kidney.We studied mortality, proteinuria, and end-stage kidney disease (ESKD) in 8280 donors who donated between 1963 and 2007 according to donation fasting plasma glucose (FPG):100 mg/dL (n = 6204), 100-125 mg/dL (n = 1826), and ≥126 mg/dL (n = 250).Donors with IFG and those with FPG ≥126 mg/dL were older, less likely to be non-Hispanic White, had a higher body mass index, and were more likely to be related to their recipient. After 15.7 ± 10.5 y from donation to study close, 4.4% died, 29.4% developed hypertension, 13.8% developed proteinuria, and 41 (0.5%) developed ESKD. In both the logistic and Cox models, IFG was associated with a higher diabetes risk (adjusted hazard ratio [aHR], 1.65; 95% confidence interval [CI], 1.18-2.30) and hypertension (aHR, 1.35; 95% CI, 1.10-1.65; P = 0.003 for both), but not higher risk of proteinuria or ESKD. The multivariable risk of mortality in donors with ≥126 mg/dL was higher than the 2 other groups, but risks of proteinuria, cardiovascular disease, and reduced estimated glomerular filtration rate were similar to those with FPG126 mg/dL. Three cases of ESKD developed in the 250 donors with FPG ≥126 mg/dL at 18.6 ± 10.3 y after donation (aHR, 5.36; 95% CI, 1.0-27.01; P = 0.04).Donors with IFG and the majority of donors with ≥126 mg/dL do well and perhaps should not be routinely excluded from donation.

Introduction Loss of kidney function is a common feature of COVID-19 infection, but serum creatinine (SCr) is not a sensitive or specific marker of kidney injury. We tested whether molecular biomarkers of tubular injury measured at hospital admission were associated with acute kidney injury (AKI) in those with COVID-19 infection. Methods This is a prospective cohort observational study consisting of 444 consecutive patients with SARS-CoV-2 enrolled in the Columbia University emergency department (ED) at the peak of the pandemic in New York (March 2020-April 2020). Urine and blood were collected simultaneously at hospital admission (median time: day 0, interquartile range: 0-2 days), and urine biomarkers were analyzed by enzyme-linked immunosorbent assay (ELISA) and a novel dipstick. Kidney biopsies were probed for biomarker RNA and for histopathologic acute tubular injury (ATI) scores. Results Admission urinary neutrophil gelatinase-associated lipocalin (uNGAL) level was associated with AKI diagnosis (267 ± 301 vs. 96 ± 139 ng/ml, P 150 ng/ml had 80% specificity and 75% sensitivity to diagnose AKI stages 2 to 3. Admission uNGAL level quantitatively associated with prolonged AKI, dialysis, shock, prolonged hospitalization, and in-hospital death, even when admission SCr level was not elevated. The risk of dialysis increased almost 4-fold per SD of uNGAL independently of baseline SCr, comorbidities, and proteinuria (odds ratio [OR] [95% CI]: 3.59 [1.83-7.45], P < 0.001). In the kidneys of those with COVID-19, NGAL mRNA expression broadened in parallel with severe histopathologic injury (ATI). Conversely, low uNGAL levels at admission ruled out stages 2 to 3 AKI (negative predictive value: 0.95, 95% CI: 0.92-0.97) and the need for dialysis (negative predictive value: 0.98, 95% CI: 0.96-0.99). Although proteinuria and urinary (u)KIM-1 were implicated in tubular injury, neither was diagnostic of AKI stages. Conclusion In the patients with COVID-19, uNGAL level was quantitatively associated with histopathologic injury (ATI), loss of kidney function (AKI), and severity of patient outcomes.

Objectives: Patients with Diabetic Kidney Disease (DKD) and foot ulcer have poor prognosis. However, no study have found association of diabetic foot ulcer (DFU) with diabetic kidney dysfunction and their co-existing risk factors. Materials and Methods: This cross sectional study collected the data for 10,680 patients for 15 years. All variables were analyzed biochemically and statistically by standardized methodology. Results: Levels of HbA1c, creatinine, systolic and diastolic blood pressures, microalbuminuria, spot urine protein, and spot urine protein to creatinine ratio were higher among the groups with foot ulcers (p-value < 0.0001 for all). Average ABI was observed to be lower among the groups demonstrating nephropathy and DKD (p=0.025 and 0.022 respectively. DFU was significantly associated with HTN (odds ratio 2.2; 95% CI 1.66 to 2.9; p < 0.0001), nephropathy (odds ratio 4.77; 95% CI 3.53 to 6.5; p < 0.0001) and DKD (odds ratio 4.77 and 6.83; 95% CI 4.6 to 10.2; p < 0.0001). HbA1c of 7.8% was 60% sensitive and 52% specific for the development of DFU. Creatinine of 1.2 mg/dl was 75% sensitive and 48% specific for DFU. Spot urine protein excretion from nephrons of 35 mg/dl was 88% sensitive and 90% specific for the development of DFU. Conclusion: Nephropathy/DKD are risk factors for the development of DFU. With optimal diabetes control, regular and routine assessment of the feet and early screening of diabetic patients for neuropathy, nephropathy, hypertension, dyslipidaemia and other diabetic complications are essential. Doi: 10.28991/SciMedJ-2021-0304-6 Full Text: PDF

BACKGROUND: Variation in dose and duration of corticosteroids for childhood-onset steroid-sensitive nephrotic syndrome occurs worldwide, likely reflecting the evolving evidence on optimal dosing and variable severity of the disease observed between patients. We conducted a study to determine the associations between site, physician, and patient factors, and average daily corticosteroid dose and duration of therapy. METHODS: Data were derived from the Canadian Childhood Nephrotic Syndrome (CHILDNEPH) Project, an observational longitudinal study from 2013 to 2019 of children with nephrotic syndrome involving pediatric nephrologists in 11 sites across Canada. The primary outcome was average daily corticosteroid dose prescribed per episode of proteinuria, reported as mg/m(2) prednisone equivalents. Secondary outcome was duration of treatment for each episode of proteinuria in days. Exposure variables were categorized into site-, physician-, and patient-level variables. RESULTS: In total, 328 children, median age at enrollment of 4.3 years old (interquartile range [IQR], 3.6), participated and were followed for a median time of 2.62 years (IQR, 2.6). The observed variability in average daily corticosteroid dose and in duration of therapy was mostly attributed to the site where the patient was treated. Accounting for between patient, physician, and site differences, average daily corticosteroid dose decreased with increasing age (beta coefficient, −0.07; 95% confidence interval [95% CI], −0.09 to −0.05], P

Acute kidney injury (AKI) in hospitalized patients with COVID-19 is associated with higher mortality and a worse prognosis. Nevertheless, most patients with COVID-19 have mild symptoms, and about 5% can develop more severe symptoms and involve hypovolemia and multiple organ dysfunction syndrome. In a pathophysiological perspective, severe SARS-CoV-2 infection is characterized by numerous dependent pathways triggered by hypercytokinemia, especially IL-6 and TNF-alpha, leading to systemic inflammation, hypercoagulability, and multiple organ dysfunction. Systemic endotheliitis and direct viral tropism to proximal renal tubular cells and podocytes are important pathophysiological mechanisms leading to kidney injury in patients with more critical infection, with a clinical presentation ranging from proteinuria and/or glomerular hematuria to fulminant AKI requiring renal replacement therapies. Glomerulonephritis, rhabdomyolysis, and nephrotoxic drugs are also associated with kidney damage in patients with COVID-19. Thus, AKI and proteinuria are independent risk factors for mortality in patients with SARS-CoV-2 infection. We provide a comprehensive review of the literature emphasizing the impact of acute kidney involvement in the evolutive prognosis and mortality of patients with COVID-19.

Background The development of vaccines to prevent COVID-19 breakouts came with highly positive results but some unexpected side effects. Rare side effects have been seen with the BNT162b2 SARS-CoV 2 vaccine. Case Presentation We present the case of a 45-year-old female patient who developed an acute kidney injury needing urgent hemodialysis one week after the second administration of the BNT162b2 SARS-CoV 2 vaccine. She developed a macular rash on her lower limbs and palms as well. A kidney biopsy was performed 10 days after vaccine inoculation, diagnosing acute interstitial nephritis and acute tubular necrosis with cellular casts. The patient was treated with three corticosteroid pulses followed by daily prednisolone. We witnessed clinical improvement 4 days after the initial corticosteroid treatment with progressive recovery of kidney function and hemodialysis withdrawal. After 2 weeks, the patient had recovered her kidney function. Immunophenotyping was performed, diagnosing a hypersensitivity to the vaccine and the polyethylene glycol excipient. Conclusion Patients may develop acute reactions to vaccines. In this case, symptoms seem to correlate significantly with its inoculation and, although this case had a favourable outcome, these side effects must be made aware for clinicians and patients.

International audience; Primary focal and segmental glomerulosclerosis (FSGS) frequently recurs after transplantation and is associated with a poor prognosis. We describe here the successful kidney graft reuse in an adult recipient, 8 months after early primary FSGS recurrence resistant to all available therapeutics. Patient 1, a 23-year-old man, followed for kidney failure secondary to primary FSGS, was first transplanted in 2018 with a deceased donor graft. Unfortunately, we observed an immediate recurrence of biopsy-proven primary FSGS. After 4 lines of treatment (intravenous cyclosporine + corticosteroids, plasma exchanges, immunoadsorption, and rituximab), the patient was still highly nephrotic and kidney function was slowly deteriorating. After approval from both the patient and the health authority (Biomedicine Agency), the graft was detransplanted 8 months after transplantation and reimplanted in patient 2, a 78-year-old nonimmunized and anephric recipient (bi-nephrectomy 2 years previously for bilateral renal carcinoma). We observed immediate kidney function and progressive resolution of proteinuria (serum creatinine of 1.2 mg/dL and proteinuria of 0.1 g/d 1 year later). Biopsies performed after surgery showed persistent FSGS lesions with a decrease in overall foot-process effacement. To our knowledge, this is the first reported case showing that kidney graft transfer may still be a viable option for refractory primary FSGS several months after transplantation.