Predictors of treatment outcomes in lupus nephritis with severe acute kidney injury and requirement of dialytic support.

INTRODUCTION/OBJECTIVES: Acute kidney injury (AKI) with the requirement of kidney replacement therapy (KRT) portends a poor prognosis for kidney function in lupus nephritis (LN). This study evaluated the kidney function recovery rates, the rates of reinitiation of KRT, and factors associated with these outcomes in LN. METHOD: All consecutive patients hospitalized for LN with KRT requirement between 2000 and 2020 were included. Their clinical and histopathologic characteristics were retrospectively registered. The outcomes and associated factors were evaluated by multivariable Cox regression analysis. RESULTS: Among 140 patients, 75 (54%) recovered kidney function, with recovery rates of 50.9% and 54.2% by 6 and 12 months of therapy. The factors associated with a lower probability of recovery included a previous history of LN flares, worse eGFR and higher proteinuria at presentation, immunosuppression with azathioprine, and hospitalizations within 6 months of therapy initiation. There was no difference in the kidney function recovery rates between mycophenolate and cyclophosphamide treatment schemes. Out of 75 patients who recovered kidney function, 37 (49%) reinitiated KRT, with KRT reinitiation rates of 27.2% and 46.5% by 3 and 5 years. Seventy-three (52%) patients had at least one hospitalization within 6 months of initial therapy, 52 (72%) of them secondary to infectious events. CONCLUSIONS: Approximately 50% of patients with LN and KRT requirement recover kidney function within 6 months. The risk-to-benefit ratio decisions may be aided by clinical and histological factors. These patients require close follow-up as ≈50% of those who recover kidney function will reinitiate dialysis in the long term. Key Points • Approximately 50% of patients with severe acute lupus nephritis with the need for kidney replacement therapy requirement recover their kidney function. • The factors associated with a lower probability of recovery of kidney function include a previous history of LN flares, worse eGFR and higher proteinuria at presentation, immunosuppression with azathioprine, and hospitalizations within 6 months of therapy initiation. • Patients who recover kidney function will require close follow-up as around 50% of them will eventually reinitiate kidney replacement therapy.

Causa rara de dolor abdominal recurrente; coexistencia del síndrome de Wilkie y el síndrome del cascanueces / A rare cause of recurrent abdominal pain; the coexistence of Wilkie's syndrome and nutcracker syndrome

El síndrome del cascanueces es un síndrome que presenta síntomas clínicos como hematuria, proteinuria ortostática, congestión pélvica, varicocele del lado izquierdo, hipertensión y dolor en fosa renal. Estos síntomas se producen por la compresión de la vena renal izquierda entre la aorta y la arteria mesentérica superior. En el síndrome de Wilkie, la tercera porción del duodeno está comprimida entre la arteria mesentérica superior y la aorta abdominal, lo que provoca diversos síntomas gastrointestinales. La coexistencia de estos dos síndromes constituye una afección rara y se incluye como casos clínicos en la bibliografía. En este artículo, se presentan los resultados clínicos y radiológicos de un paciente de 17 años que presentaba dolor abdominal recurrente debido al síndrome de Wilkie, acompañado del síndrome del cascanueces que le provocaba proteinuria, por lo que el paciente fue derivado a los consultorios externos de reumatología pediátrica con un diagnóstico preliminar de fiebre mediterránea familiar.

Nutcracker syndrome is a syndrome that has clinical symptoms such as hematuria, orthostatic proteinuria, pelvic congestion, left-sided varicocele, hypertension, and flank pain. These symptoms occur because of the compression of the left renal vein between the aorta and the superior mesenteric artery. In Wilkie's syndrome, the third part of the duodenum is compressed between the superior mesenteric artery and the abdominal aorta, causing various gastrointestinal symptoms. The coexistence of these two syndromes is a rare condition and is included as case reports in the literature. This article presents the clinical and radiological results of a 17-year-old male patient who had recurrent abdominal pain due to Wilkie's syndrome, which was accompanied by nutcracker syndrome that caused proteinuria, and for this reason, the patient was referred to the Pediatric Rheumatology outpatient clinic with a preliminary diagnosis of familial Mediterranean fever.

Acute kidney injury in coronavirus infectious disease: a study of incidence, risk factors, and prognosis during the first wave of the disease in Brazil.

INTRODUCTION: Acute kidney injury (AKI) is one of the main complications of COVID-19 caused by SARS-CoV-2. This study aimed to evaluate the incidence of AKI in Brazilian hospitalized patients diagnosed with COVID-19 and identify the risk factors associated with its onset and those associated with its prognosis. METHODS: A prospective cohort study of hospitalized patients diagnosed with COVID-19 at a public and tertiary university hospital in São Paulo from March to December 2020. RESULTS: There were 347 patients hospitalized with COVID-19, 52.4% were admitted to the intensive care unit (ICU) and 47.6% were admitted to the wards. The overall incidence of AKI was 46.4%, more frequent in the ICU (68.1% vs 22.4, p < 0.01) and the overall mortality was 36.1%. Acute kidney replacement therapy was indicated in 46.6% of patients with AKI. In the general population, the factors associated with AKI were older age (OR 1.03, CI 1-1.05, p < 0.05), mechanical ventilation (OR 1.23, CI 1.06-1.83, p < 0.05), presence of proteinuria (OR 1.46, CI 1.22-1.93, p < 0.05), and use of vasoactive drugs (OR 1.26, CI 1.07-1.92, p < 0.05). Mortality was higher in the elderly (OR 1.08, CI 1.04-1.11, p < 0.05), in those with AKI (OR 1.12, CI 1.02-2.05, p < 0.05), particularly KDIGO stage 3 AKI (OR 1.10, CI 1.22-2.05, p < 0.05) and in need of mechanical ventilation (OR 1.13, CI 1.03-1.60, p < 0.05). CONCLUSION: AKI was frequent in hospitalized patients with COVID-19 and the factors associated with its development were older age, mechanical ventilation, use of vasoactive drugs, and presence of proteinuria, being a risk factor for death.

A rare cause of recurrent abdominal pain; the coexistence of Wilkie's syndrome and nutcracker syndrome. / Causa rara de dolor abdominal recurrente; coexistencia del síndrome de Wilkie y el síndrome del cascanueces.

Nutcracker syndrome is a syndrome that has clinical symptoms such as hematuria, orthostatic proteinuria, pelvic congestion, left-sided varicocele, hypertension, and flank pain. These symptoms occur because of the compression of the left renal vein between the aorta and the superior mesenteric artery. In Wilkie's syndrome, the third part of the duodenum is compressed between the superior mesenteric artery and the abdominal aorta, causing various gastrointestinal symptoms. The coexistence of these two syndromes is a rare condition and is included as case reports in the literature. This article presents the clinical and radiological results of a 17-year-old male patient who had recurrent abdominal pain due to Wilkie's syndrome, which was accompanied by nutcracker syndrome that caused proteinuria, and for this reason, the patient was referred to the Pediatric Rheumatology outpatient clinic with a preliminary diagnosis of familial Mediterranean fever.

El síndrome del cascanueces es un síndrome que presenta síntomas clínicos como hematuria, proteinuria ortostática, congestión pélvica, varicocele del lado izquierdo, hipertensión y dolor en fosa renal. Estos síntomas se producen por la compresión de la vena renal izquierda entre la aorta y la arteria mesentérica superior. En el síndrome de Wilkie, la tercera porción del duodeno está comprimida entre la arteria mesentérica superior y la aorta abdominal, lo que provoca diversos síntomas gastrointestinales. La coexistencia de estos dos síndromes constituye una afección rara y se incluye como casos clínicos en la bibliografía. En este artículo, se presentan los resultados clínicos y radiológicos de un paciente de 17 años que presentaba dolor abdominal recurrente debido al síndrome de Wilkie, acompañado del síndrome del cascanueces que le provocaba proteinuria, por lo que el paciente fue derivado a los consultorios externos de reumatología pediátrica con un diagnóstico preliminar de fiebre mediterránea familiar.

Diagnosis and Course of Membranous Nephropathy in Adults: Comparison by Age Group.

INTRODUCTION: There have been few studies comparing younger and older adults with membranous nephropathy. The objective of this study was to compare younger and older patients with membranous nephropathy, in terms of the clinical, etiological, remission, and survival data. METHOD: This was a retrospective study of patients with membranous nephropathy who underwent renal biopsy between 2009 and 2017. RESULTS: We included 214 patients with membranous nephropathy. At diagnosis, 169 (79%) of those patients were <60 years of age and 45 (21%) were ≥60 years of age. There was a predominance of males in both groups. The degree of proteinuria and the prevalence of hematuria did not differ significantly between the groups. However, the median serum creatinine level was higher in the ≥60-year group as was the prevalence of hypertension. Of the patients evaluated, 36 (16.8%) had secondary membranous nephropathy. Although the proportions of infectious and autoimmune causes were comparable between the two groups, neoplastic etiologies were more common in the ≥60-year group. A total of 86 in the <60-year group and 25 in the ≥60-year group were followed long term, and partial or complete remission was achieved in 68.5% and 68.0% of the younger and older patients, respectively. However, whom progressed to requiring dialysis eight (9.3%) were in the <60-year group patients and eight (32.0%) of the ≥60-year group patients (p = 0.0045). CONCLUSION: Despite having worse renal function at diagnosis, older patients with membranous nephropathy appear to have remission rates comparable to those of younger patients with the disease, which demonstrates the benefits of seeking diagnosis and treatment.

Reduction of proteinuria in patients with diabetes kidney disease and dysautonomia through measures aimed at controlling supine hypertension.

In diabetes kidney disease (DKD), orthostatic hypotension and supine hypertension often coexist, which, when uncontrolled, contributes to the progression of proteinuria and renal dysfunction. Chronotherapy and elevation of the head of the bed during sleep are feasible clinical measures and could contribute to the control of supine hypertension and proteinuria in this group of patients. This study consists of a series of cases, in which nine consecutive patients with DKD, dysautonomia and supine hypertension (intervention group) were instructed to use chronotherapy and inclination of the head of the bed in six degrees during sleep. These patients were compared with a historical control group. The primary outcome was proteinuria behavior. The intervention group had a significant drop in proteinuria levels, while there was an increase in proteinuria in the control group (variation in the proteinuria/creatininuria index in an isolated sample from the intervention group: -6.60 ± 3.90 g/g; variation in the group control: +1.70 ± 7.10 g/g, p = 0.008). Chronotherapy and six-degree inclination of the head of the bed during sleep were associated with a significant decrease in proteinuria in patients in the intervention group, with conversion of nephrotic into non-nephrotic proteinuria in most of these patients.

Quality or Quantity of Proteins in the Diet for CKD Patients: Does "Junk Food" Make a Difference? Lessons from a High-Risk Pregnancy.

BACKGROUND: How to manage patients with severe kidney disease in pregnancy is still a matter of discussion, and deciding if and when to start dialysis is based on the specialist's experience and dialysis availability. The effect of toxic substances usually cleared by the kidney may be more severe and readily evident. The review, and related case, underlines the importance of considering the presence of additives in food in delicate conditions, such as CKD pregnancy. The Case: A 39-year-old indigenous woman from a low-resourced area in Mexico was referred to the obstetric nephrology at 25 gestational weeks because of serum creatinine at 3.6 mg/dL, hypertension on low-dose alpha-methyl-dopa, and nephrotic-range proteinuria. Kidney ultrasounds showed small poorly differentiated kidneys; foetal ultrasounds detected a female foetus, normal for gestational age. The patient's baseline protein intake, which was estimated at 1.2-1.3 g/kg/day, was mostly of animal-origin (>70%) poor-quality food ("junk food"). In the proposed diet, protein intake was only slightly reduced (1.0-1.2 g/kg/day), but the source of proteins was changed (only 30% of animal origin) with attention to food quality. A remarkable decrease in BUN was observed, in concomitance with adequate dietary follow-up, with rapid rise of BUN when the patient switched temporarily back to previous habits. A healthy female baby weighing 2,460 g (11th centile for gestational age) was delivered at 37 gestational weeks. Discussion and Literature Review: While data on patients with chronic kidney disease are scant, the long list of contaminants present in food, especially if of low quality, should lead us to reflect on their potential negative effect on kidney function and make us realize that eating healthy, unprocessed "organic" food should be encouraged, in delicate conditions such as pregnancy and breastfeeding and for young children, in particular when kidney function is failing. The case herein described gave us the opportunity to reflect on the importance of diet quality and on the potential risks linked to food additives, many of which, including phosphates and potassium, are not declared on food labels, while others, including dyes, antioxidants, thickeners, emulsifiers, and preservatives, are qualitatively, but not quantitatively, reported.

Patología hipertensiva durante el embarazo y el producto de la concepción / Hypertensive pathology during pregnancy and the product of conception

El Hospital Nacional Dr. Mario Catarino Rivas (hospital de segundo nivel de atención), sirve como centro de atención para embarazos de alto riesgo de la zona noroccidental de Honduras; reportó 1,702 casos de trastor-nos hipertensivos del embarazo en 2017 y 2,070 casos en 2018. Se caracterizó pacientes con signos y síntomas de trastornos hipertensivos del embarazo agrupadas desde un punto de vista obstétrico, epidemiológico y clínico. Se realizó un estudio, descriptivo de corte transversal en gestantes que presentaron cefalea, cifras tensionales elevadas (≥ 140/90mmHg); registrando ausencia o presencia de proteinuria, atendidas en la emergencia de labor y parto de un hospital nacional de segundo nivel de atención en San Pedro Sula, Honduras, desde junio hasta octubre del 2019. Se incluyeron 110 pacientes de entre 18-43 años, mestizas y amas de casa, la edad gestacional promedio por fecha de ultima menstruación de 37.7 semanas; el 28.2% presentó preeclampsia severa. Las manifestaciones clínicas frecuentes fueron edema de miembros inferiores y cefalea. El 57.3% desarrolló trabajo de parto espontá-neo, la resolución del embarazo fue cesárea en el 57.3% de las gestantes. Respecto al producto de la concepción, 66.4% tenían peso normal y talla apropiada para la edad gestacional, un APGAR de 8 al primer minuto y de 9 a los 5 minutos. En este estudio, se reporta una prevalencia del 13.72% con respecto a los trastornos hipertensivos del embarazo. Particularmente en pacientes mayores de 35 años, multípara, con índice de masa corporal ≥ 32 kg/m2, presentando antecedentes de hipertensión arterial, diabetes mellitus y preeclampsia.

The National Hospital Dr. Mario Catarino Rivas (second-level care hospital), serves as a care center for high-risk pregnancies in the northwestern part of Honduras; it reported 1,702 cases of hypertensive disorders of pregnancy in 2017 and 2,070 cases in 2018. Patients with signs and symptoms of hypertensive disorders of preg-nancy were characterized grouped from an obstetric, epidemiological and clinical point of view. A descriptive cross-sectional study was carried out in pregnant women who presented headache, high blood pressure (≥ 140 / 90mmHg); registering the absence or presence of proteinuria in urine, attended in the labor and delivery emer-gency of a national hospital of second level of care in San Pedro Sula, Honduras; from June to October 2019. 110 patients between 18-43 years old, mixed race and housewives were included, the average gestational age by date of last menstruation of 37.7 weeks, 28.2% presented severe preeclampsia. The frequent clinical manifestations were lower limb edema and headache. 57.3% developed spontaneous labor, the pregnancy termination route was cesarean section in 57.3% of pregnant women. Regarding the product of conception, 69.1% had weight and height appropriate for gestational age, an APGAR of 8 at the first minute and of 9 at 5 minutes. In this study, a prevalence of 13.72% is reported with respect to hypertensive disorders of pregnancy. Particularly in patients older than 35 years, multiparous, with a body mass index ≥ 32 kg / m2, presenting a history of arterial hypertension, diabetes mellitus and pre-eclampsia.

In situ evaluation of podocytes in patients with focal segmental glomerulosclerosis and minimal change disease.

Podocyte injury in focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) results from the imbalance between adaptive responses that maintain homeostasis and cellular dysfunction that can culminate in cell death. Therefore, an in situ analysis was performed to detect morphological changes related to cell death and autophagy in renal biopsies from adult patients with podocytopathies. Forty-nine renal biopsies from patients with FSGS (n = 22) and MCD (n = 27) were selected. In situ expression of Wilms Tumor 1 protein (WT1), light chain microtubule 1-associated protein (LC3) and caspase-3 protein were evaluated by immunohistochemistry. The foot process effacement and morphological alterations related to podocyte cell death and autophagy were analyzed with transmission electronic microscopy. Reduction in the density of WT1-labeled podocytes was observed for FSGS and MCD cases as compared to controls. Foot process width (FPW) in control group was lower than in cases of podocytopathies. In FSGS group, FPW was significantly higher than in MCD group and correlated with proteinuria. A density of LC3-labeled podocytes and the number of autophagosomes in podocytes/ pedicels were higher in the MCD group than in the FSGS group. The number of autophagosomes correlated positively with the estimated glomerular filtration rate in cases of MCD. The density of caspase-3-labeled podocytes in FSGS and MCD was higher than control group, and a higher number of podocytes with an evidence of necrosis was detected in FSGS cases than in MCD and control cases. Podocytes from patients diagnosed with FSGS showed more morphological and functional alterations resulting from a larger number of lesions and reduced cell adaptation.

Preoperative proteinuria is associated with increased rates of acute kidney injury after partial nephrectomy

ABSTRACT Purpose We investigated the association between preoperative proteinuria and early postoperative renal function after robotic partial nephrectomy (RPN). Patients and Methods We retrospectively reviewed 1121 consecutive RPN cases at a single academic center from 2006 to 2016. Patients without pre-existing CKD (eGFR≥60 mL/min/1.73m2) who had a urinalysis within 1-month prior to RPN were included. The cohort was categorized by the presence or absence of preoperative proteinuria (trace or greater (≥1+) urine dipstick), and groups were compared in terms of clinical and functional outcomes. The incidence of acute kidney injury (AKI) was assessed using RIFLE criteria. Univariate and multivariable models were used to identify factors associated with postoperative AKI. Results Of 947 patients, 97 (10.5%) had preoperative proteinuria. Characteristics associated with preoperative proteinuria included non-white race (p<0.01), preoperative diabetes (p<0.01) and hypertension (HTN) (p<0.01), higher ASA (p<0.01), higher BMI (p<0.01), and higher Charlson score (p<0.01). The incidence of AKI was higher in patients with preoperative proteinuria (10.3% vs. 4.6%, p=0.01). The median eGFR preservation measured within one month after surgery was lower (83.6% vs. 91%, p=0.04) in those with proteinuria; however, there were no significant differences by 3 months after surgery or last follow-up visit. Independent predictors of AKI were high BMI (p<0.01), longer ischemia time (p<0.01), and preoperative proteinuria (p=0.04). Conclusion Preoperative proteinuria by urine dipstick is an independent predictor of postoperative AKI after RPN. This test may be used to identify patients, especially those without overt CKD, who are at increased risk for developing AKI after RPN.

Acute kidney injury in hospitalized patients who underwent percutaneous kidney biopsy for histological diagnosis of their renal disease.

BACKGROUND: Performing a kidney biopsy is necessary to accurately diagnose diseases such as glomerulonephritis and tubulointerstitial nephritis, among other such conditions. These conditions predispose patients to chronic kidney disease, as well as acute kidney injury (AKI). Notably, most epidemiological studies describing AKI have not investigated this patient population. METHODS: Included patients admitted to the nephrology ward of a tertiary hospital who underwent percutaneous kidney biopsy. AKI was diagnosed based on the Kidney Disease: Improving Global Outcomes criteria. RESULTS: Of the 223 patients investigated, 140 (62.8%) showed AKI. Of these, 91 (65%), 19 (13.6%), and 30 (21.4%) presented with AKI classified as stages 1, 2, and 3, respectively. The primary indication for performing biopsy was nephrotic syndrome or nephrotic proteinuria (73 [52.1%] in the AKI vs. 51 [61.4%] in the non-AKI group, p = 0.048). Focal segmental glomerulosclerosis was the most prevalent primary disease (24 [17.1%] in the AKI vs. 15 [18.0%] in the non-AKI group, p = 0.150). Multivariate analysis of risk factors associated with AKI showed hemoglobin levels (odds ratio [OR] 0.805, 95% confidence interval [CI] 0.681-0.951, p = 0.011), serum high-density lipoprotein cholesterol levels (HDL-c, OR 0.970, 95% CI 0.949-0.992, p = 0.008), and baseline serum creatinine levels (OR 2.703, 95% CI 1.471-4.968, p = 0.001) were significantly associated with AKI. CONCLUSIONS: We observed a high prevalence of AKI in hospitalized patients who underwent kidney biopsy to investigate their renal disease, particularly glomerulonephritis. Higher levels of hemoglobin and serum HDL-c were associated with a lower risk of AKI.

Preoperative proteinuria is associated with increased rates of acute kidney injury after partial nephrectomy.

PURPOSE: We investigated the association between preoperative proteinuria and early postoperative renal function after robotic partial nephrectomy (RPN). PATIENTS AND METHODS: We retrospectively reviewed 1121 consecutive RPN cases at a single academic center from 2006 to 2016. Patients without pre-existing CKD (eGFR≥60 mL/min/1.73m2) who had a urinalysis within 1-month prior to RPN were included. The cohort was categorized by the presence or absence of preoperative proteinuria (trace or greater (≥1+) urine dipstick), and groups were compared in terms of clinical and functional outcomes. The incidence of acute kidney injury (AKI) was assessed using RIFLE criteria. Univariate and multivariable models were used to identify factors associated with postoperative AKI. RESULTS: Of 947 patients, 97 (10.5%) had preoperative proteinuria. Characteristics associated with preoperative proteinuria included non-white race (p<0.01), preoperative diabetes (p<0.01) and hypertension (HTN) (p<0.01), higher ASA (p<0.01), higher BMI (p<0.01), and higher Charlson score (p<0.01). The incidence of AKI was higher in patients with preoperative proteinuria (10.3% vs. 4.6%, p=0.01). The median eGFR preservation measured within one month after surgery was lower (83.6% vs. 91%, p=0.04) in those with proteinuria; however, there were no significant differences by 3 months after surgery or last follow-up visit. Independent predictors of AKI were high BMI (p<0.01), longer ischemia time (p<0.01), and preoperative proteinuria (p=0.04). CONCLUSION: Preoperative proteinuria by urine dipstick is an independent predictor of postoperative AKI after RPN. This test may be used to identify patients, especially those without overt CKD, who are at increased risk for developing AKI after RPN.

Acute Kidney Injury in Pediatric Cancer Patients.

OBJECTIVE: To analyze the incidence of acute kidney injury (AKI) in the first year after cancer diagnosis in children and to evaluate the short-term and long-term effects on renal function and proteinuria. STUDY DESIGN: Retrospective review of medical records was done on children who were diagnosed and treated for cancer at Seoul National University Hospital between 2004 and 2013. AKI was defined according to the Kidney Disease: Improving Global Outcomes criteria. Impaired renal function of estimated glomerular filtration rate less than 90 mL/minute/1.73 m2 and development of proteinuria of cancer survivors were also assessed. RESULTS: This study included 1868 patients who were diagnosed with cancer at a median age of 7.9 years. During the course of treatment, 983 patients (52.6%) developed 1864 episodes of AKI, and the cumulative incidence at 2 weeks, 3 months, and 1 year after diagnosis was 28.9%, 39.6%, and 53.6%, respectively. The 1-year cumulative incidence was the highest in patients with acute myeloid leukemias (88.4%). In all, 6.1% of patients had more than 4 episodes of AKI and 11.8% of patients had stage 3 AKI. Among the 1096 childhood cancer survivors, 22.6% were found to have impaired renal function. A greater number of AKI episodes (≥4 times) and nephrectomy were independent risk factors of impaired renal function. Also, 8.2% of the survivors developed proteinuria among 742 childhood cancer survivors. CONCLUSIONS: A large percentage of children with cancer experience AKI during the course of treatment, and AKI is associated with impaired long-term renal function.

Síndrome nefrótico del lactante: presentación de caso clínico / Nefrotic infant syndrome: clinical case report

El síndrome nefrótico se define por proteinuria de rango nefrótico (40 mg/m2/hora o relación proteína/creatinina de orina 200 mg/ml o 3+ proteína en tira reactiva de orina), hipoalbuminemia (25 g/L) y edema. El presente caso clínico se centra en la clasificación, epidemiología, fisiopatología, estrategia de manejo y pronóstico del síndrome nefrótico exclusivo del lactante, como etiología los más frecuentes asociados son mutaciones en genes que codifican las proteínas reguladoras y estructurales de la barrera de filtración glomerular. Estas mutaciones han sido identificadas en: NPHS1, NHPS2, WTI, LAMB2, mediante Biopsia Renal la lesión histológica más frecuente es la Glomerulonefritis mesangial difusa proliferativa con esclerosis, suele ser de mal pronóstico y con tendencia a fallo de tratamiento o cortico-resistencia terminando en falla renal y diálisis. Se presenta paciente femenina lactante mayor de 17 meses de edad, sin antecedentes durante el periodo perinatal, con síntomas característicos de síndrome nefrótico, a su corta edad, sin antecedentes infecciosos, presentando relación proteína/creatinina en orina positiva, llamando la atención los resultados de biopsia renal de la misma, ya que se sale de las lesiones histológicas más frecuentes a esta edad...(AU)

[Hepatocellular damage, proteinuria and autoimmunity: multisystemic disorder or coexistence of diseases?] / Daño hepatocelular, proteinuria y autoinmunidad: ¿enfermedad multisistémica o coincidencia de enfermedades? Caso clínico.

We report a 19 years old male presenting with knee pain, elevated liver enzymes and proteinuria. Further investigation found positive antinuclear and anti-smooth muscle antibodies and a liver biopsy revealed the presence of an autoimmune hepatitis. Treatment with corticosteroids and azathioprine was started, resulting in normalization of liver enzymes but proteinuria persisted and a kidney biopsy disclosed a focal segmental glomerulosclerosis. The use of lisinopril resulted in a significative reduction of proteinuria and, after 30 months of follow up, he continues with azathioprine, lisinopril and a low prednisone dose without evidence of liver or kidney disease activity.

Daño hepatocelular, proteinuria y autoinmunidad: ¿enfermedad multisistémica o coincidencia de enfermedades? Caso clínico / Hepatocellular damage, proteinuria and autoimmunity: multisystemic disorder or coexistence of diseases?

We report a 19 years old male presenting with knee pain, elevated liver enzymes and proteinuria. Further investigation found positive antinuclear and anti-smooth muscle antibodies and a liver biopsy revealed the presence of an autoimmune hepatitis. Treatment with corticosteroids and azathioprine was started, resulting in normalization of liver enzymes but proteinuria persisted and a kidney biopsy disclosed a focal segmental glomerulosclerosis. The use of lisinopril resulted in a significative reduction of proteinuria and, after 30 months of follow up, he continues with azathioprine, lisinopril and a low prednisone dose without evidence of liver or kidney disease activity.

Hemoglobinuria paroxística nocturna / Paroxysmal nocturnal hemoglobinuria

ResumenLa hemoglobinuria paroxística nocturna es una anemia hemolítica crónica, adquirida, poco común, que afecta con igual frecuencia ambos sexos. Se manifiesta a cualquier edad y con mayor incidencia en países del sudeste asiático. Es el resultado de la expansión clonal no maligna de células progenitoras hematopoyéticas. Se caracteriza por anemia hemolítica intravascular, tendencia a la trombosis y un componente variable de insuficiencia medular.Se asocia a otras patologías hematológicas como anemia aplásica y síndrome mielodisplásico. La citometría de flujo es el método de elección para diagnóstico. El eculizumab y el trasplante de médula ósea alogénico son las únicas terapias efectivas.

Abstract:Paroxysmal nocturnal hemoglobinuria is a rare acquired chronic hemolytic anemia, which affects both sexes with equal frequency. It occurs at any age and more frequently in Southeast Asian countries. It is the result of non malignant clonal expansion of hematopoietic progenitor cells. It is characterized by intravascular hemolytic anemia, recurrent thrombosis and a variable component of bone marrow failure. It is associated with other hematologic disorders such as aplastic anemia and myelodysplastic syndrome. Flow cytometry is the method of choice for diagnosis. Eculizumab and allogeneic bone marrow transplantation is the only effective therapies.

Prevalence of Glomerulopathies in Canine Mammary Carcinoma.

The incidence and prevalence of paraneoplastic glomerulopathy, especially associated with carcinoma, are a matter of debate and the causal link between cancer and glomerular diseases remains unclear. The aim of this study was to evaluate renal biopsies of selected bitches with spontaneous mammary gland carcinoma. We hypothesized that dogs with mammary carcinomas would show histologic evidence of glomerular pathology. A prospective study was performed in dogs with naturally occurring mammary carcinoma that were undergoing tumor resection and ovariohysterectomy. We evaluated renal biopsies of 32 bitches with spontaneous mammary gland carcinoma and 11 control dogs without mammary gland neoplasia. Samples were obtained from the left kidney and the biopsy material was divided for light microscopy (LM), immunofluorescence (IF) and transmission electron microscopy (TEM). Light microscopy abnormalities were identified in 78.1% of dogs with mammary carcinoma (n = 25) and in none of the dogs in the control group. Focal glomerular mesangial matrix expansion was the most common alteration (n = 15, 60.0%), but mesangial cell proliferation (n = 9, 36.0%) and focal segmental glomerulosclerosis (n = 9, 36.0%), synechiae (n = 7, 28.0%), and globally sclerotic glomeruli (n = 6, 24.0%) were also frequent in dogs with malignancy. Immunofluorescence microscopy revealed strong IgM staining was demonstrated in 64.3% (n = 18) of carcinoma dogs. Transmission electron microscopy from dogs with carcinoma revealed slight changes, the most frequent of which was faint sub-endothelial and mesangial deposits of electron-dense material (78%). Mesangial cell interpositioning and segmental effacement of podocyte foot processes were identified in some specimens (45%). Changes in the glomerulus and proteinuria are common in dogs with naturally occurring mammary carcinoma and this condition appears to provide an excellent large animal model for cancer-associated glomerulopathy in humans.

Kidney Disease Progression in Autosomal Recessive Polycystic Kidney Disease.

OBJECTIVE: To define glomerular filtration rate (GFR) decline, hypertension (HTN), and proteinuria in subjects with autosomal recessive polycystic kidney disease (ARPKD) and compare with 2 congenital kidney disease control groups in the Chronic Kidney Disease in Children cohort. STUDY DESIGN: GFR decline (iohexol clearance), rates of HTN (ambulatory/casual blood pressures), antihypertensive medication usage, left ventricular hypertrophy, and proteinuria were analyzed in subjects with ARPKD (n = 22) and 2 control groups: aplastic/hypoplastic/dysplastic disorders (n = 44) and obstructive uropathies (n = 44). Differences between study groups were examined with the Wilcoxon rank sum test. RESULTS: Annualized GFR change in subjects with ARPKD was -1.4 mL/min/1.73 m(2) (-6%), with greater decline in subjects age ≥ 10 years (-11.5%). However, overall rates of GFR decline did not differ significantly in subjects with ARPKD vs controls. There were no significant differences in rates of HTN or left ventricular hypertrophy, but subjects with ARPKD had a greater percent on ≥ 3 blood pressure medications (32% vs 0%, P < .0001), more angiotensin-converting enzyme inhibitor use (82% vs 27% vs 36%, P < .0005), and less proteinuria (urine protein: creatinine = 0.1 vs 0.6, P < .005). CONCLUSIONS: This study reports rates of GFR decline, HTN, and proteinuria in a small but well-phenotyped ARPKD cohort. The relatively slow rate of GFR decline in subjects with ARPKD and absence of significant proteinuria suggest that these standard clinical measures may have limited utility in assessing therapeutic interventions and highlight the need for other ARPKD kidney disease progression biomarkers.

Inhibition of cellular transdifferentiation by losartan minimizes but does not reverse type 2 diabetes-induced renal fibrosis.

HYPOTHESIS/INTRODUCTION: Transformer Growth Factor (TGF-ß1) and angiotensin II (AngII) induce epithelial mesenchymal transition (EMT) and myofibroblastic transdifferentiation (MFT) contributing to renal fibrosis. The present study evaluated the capacity of an AT1 receptor blocker (losartan) to induce the regression of pre-existing fibrosis via interference with MFT and EMT in a rat model of type 2 diabetes, and in cultured mesangial cells (MCs) stimulated with high glucose and AngII. MATERIALS AND METHODS: After 12 weeks of diabetes induction (D12 group), animals showing evidence of nephropathy, were divided in groups untreated for additional 8 weeks (D20 group) and treated for additional 8 weeks with losartan (D20+los group). RESULTS: D12 animals presented hyperglycemia, insulin resistance, hypertension, proteinuria, increased levels of TGF-ß1 and MFT/EMT markers. Losartan stabilized all of these parameters and hindered the progression of fibrosis, but it did not reverse the pre-existing fibrotic manifestations. Losartan reduced TGF-ß1 in the tubules, but not in the glomeruli. Stimulated MC exhibited myofibroblast phenotype and capacity for migration, which were completely reversed by losartan. CONCLUSIONS: Cellular transition may play a role in diabetes-inducing renal fibrogenesis in both AngII-TGF-ß1 axis-dependent and independent manners. Losartan was efficient in preventing cells from undergoing further transdifferentiation, but this strategy was not sufficient to induce regression of the pre-existing tissue fibrosis.