Non-nephrotic Proteinuria Research Articles

ANASARCA AND MALIGNANT PLEURAL EFFUSION

TOPIC: Lung Cancer TYPE: Medical Student/Resident Case Reports INTRODUCTION: Anasarca is commonly caused by proteinuria, gastroenteral protein loss, low-synthesis states, or low intake. Etiologies of anasarca include nephrotic syndrome, cirrhosis, protein-losing enteropathy, and malnutrition [1]. Our case describes diffuse edema secondary to protein loss from recurrent malignant pleural effusion, an etiology not previously reported in the literature. CASE PRESENTATION: A 59-year-old male with stage IV non-small cell lung cancer presented with complaint of increased bilateral lower extremity edema. In the preceding month he had experienced recurrent right-sided pleural effusions requiring multiple thoracenteses and placement of a right indwelling pleural catheter. He reported draining up to 800 cc daily, with volumes of 500 cc every other day at the time of admission. The patient's lower extremity edema evolved over a span of one month and had significantly increased just prior to admission, precluding his ability to don footwear. The patient's exam was significant for diffuse edema most prominent at the feet and ankles and diminished breath sounds with dullness to percussion at the right lung base. Workup showed non-nephrotic range proteinuria, no evidence of cirrhosis, and normal ejection fraction on transthoracic echocardiogram. His total serum protein was 5.3 g/dL and serum albumin was 2.6 g/dL. He continued to drain pleural fluid from his pleural catheter at an average of 150-250cc/day. Pleural fluid protein was as high as 2.2 g/dL. Average daily pleural drainage was 200 cc, resulting in a daily protein loss of approximately 4g/day. This degree of protein loss was surmised to be the likely cause of the patient's anasarca. Over the course of his admission, the patient underwent multiple dialysis sessions resulting in a total net weight loss of 15kg. He demonstrated improvement in edema about his abdomen and legs but his ankles and feet continued to have pitting edema to a depth of 4-5 mm. DISCUSSION: This is an unusual case of protein loss via recurrent pleural effusion leading to anasarca. Diffuse edema resulting from recurrent/persistent malignant has not been previously described and thus, there is no clear guidance regarding potential complications nor management options. Other more common causes of anasarca may give some insight regarding potential problems and possible therapies. In low-protein states, diuresis has been a standard of care. Data from the treatment of nephrotic syndrome has demonstrated the loss of clotting factors resulting in coagulopathy. Additionally, patients are at increased cardiac risk due to increased lipid levels from upregulated liver synthesis [2]. Furthermore, loss of antibodies and other proteins theoretically increases the risk for infection [3]. CONCLUSIONS: The prevalence of malignant effusions leading to anasarca is unclear. This case highlights a cause of anasarca that should be considered in similar patient populations. REFERENCE #1: Blankfield RP, Finkelhor RS, Alexander JJ, Flocke SA, Maiocco J, Goodwin M, Zyzanski SJ. Etiology and diagnosis of bilateral leg edema in primary care. Am J Med. 1998;105(3):192. REFERENCE #2: Crew RJ, Radhakrishnan J, Appel G. Complications of the nephrotic syndrome and their treatment. Clin Nephrol. 2004;62(4):245. REFERENCE #3: Umar SB, DiBaise JK. Protein-losing enteropathy: case illustrations and clinical review. Am J Gastroenterol. 2010;105(1):43. Epub 2009 Sep 29. DISCLOSURES: No relevant relationships by Jaime Stull, source=Web Response

Anti-glomerular basement membrane disease with intense nephrotic syndrome: a new case report.

Anti-glomerular basement membrane (anti-GBM) disease was usually described as a small vessel vasculitis presenting with acute kidney injury, haematuria and non-nephrotic proteinuria. We report a case of anti-GBM disease revealed by an intense nephrotic syndrome. The urinary protein level was 12g/day. Renal biopsy only showed crescent glomerulonephritis with linear staining of IgG in direct immunofluorescence without other glomerulonephritis. Immunoglobulin G (IgG) anti-GBM antibody titer was elevated.

UK experience of ofatumumab in recurrence of focal segmental glomerulosclerosis post-kidney transplant

BackgroundSteroid-resistant nephrotic syndrome (SRNS), commonly caused by focal segmental glomerulosclerosis (FSGS), is associated with progression to stage 5 chronic kidney disease, requirement for kidney replacement therapy and a risk of disease recurrence post-kidney transplantation. Ofatumumab (OFA) is a fully humanised monoclonal antibody to CD20, with similar mechanisms of action to rituximab (RTX).MethodsWe report a case series of seven UK patients (five paediatric, two adult), all of whom developed FSGS recurrence after kidney transplantation and received OFA as part of their therapeutic intervention. All also received concomitant plasmapheresis. The 2-year outcome of these seven patients is reported, describing clinical course, kidney function and proteinuria.ResultsFour patients (all paediatric) achieved complete urinary remission with minimal proteinuria 12 months post-treatment. Three of those four also had normal graft function. Two patients showed partial remission—brief improvement to non-nephrotic proteinuria (197 mg/mmol) in one patient, maintained improvement in kidney function (estimated glomerular filtration rate 76 ml/min/1.73 m2) in the other. One patient did not demonstrate any response.ConclusionsOFA may represent a useful addition to therapeutic options in the management of FSGS recurrence post-transplantation, including where RTX has shown no benefit. Concomitant plasmapheresis in all patients prevents any definitive conclusion that OFA was the beneficial intervention.

The Effect of Add-on Acetazolamide to Conventional Diuretics for Diuretic-resistant Edema Complicated with Hypercapnia: A Report of Two Cases

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.

SLE strikes the heart! A rare presentation of SLE myocarditis presenting as cardiogenic shock

BackgroundAlthough systemic lupus erythematosus (SLE) can affect the cardiovascular system in many ways with diverse presentations, a severe cardiogenic shock secondary to SLE myocarditis is infrequently described in the medical literature. Variable presenting features of SLE myocarditis can also make the diagnosis challenging. This case report will allow learners to consider SLE myocarditis in the differential and appreciate the diagnostic uncertainty.Case presentationA 20-year-old Filipino male presented with acute dyspnea, pleuritic chest pain, fevers, and diffuse rash after being diagnosed with SLE six months ago and treated with hydroxychloroquine. Labs were notable for leukopenia, non-nephrotic range proteinuria, elevated cardiac biomarkers, inflammatory markers, low complements, and serologies suggestive of active SLE. Broad-spectrum IV antibiotics and corticosteroids were initiated for sepsis and SLE activity. Blood cultures were positive for MSSA with likely skin source. An electrocardiogram showed diffuse ST-segment elevations without ischemic changes. CT chest demonstrated bilateral pleural and pericardial effusions with dense consolidations. Transthoracic and transesophageal echocardiogram demonstrated reduced left ventricular ejection fraction (LVEF) 45% with no valvular pathology suggestive of endocarditis. Although MSSA bacteremia resolved, the patient rapidly developed cardiopulmonary decline with a repeat echocardiogram demonstrating LVEF < 10%. A Cardiac MRI was a nondiagnostic study to elucidate an etiology of decompensation given inability to perform late gadolinium enhancement. Later, cardiac catheterization revealed normal cardiac output with non-obstructive coronary artery disease. As there was no clear etiology explaining his dramatic heart failure, endomyocardial biopsy was obtained demonstrating diffuse myofiber degeneration and inflammation. These pathological findings, in addition to skin biopsy demonstrating lichenoid dermatitis with a granular “full house” pattern was most consistent with SLE myocarditis. Furthermore, aggressive SLE-directed therapy demonstrated near full recovery of his heart failure.ConclusionAlthough myocarditis during SLE flare is a well-described cardiac manifestation, progression to cardiogenic shock is infrequent and fatal. As such, SLE myocarditis should be promptly considered. Given the heterogenous presentation of SLE, combination of serologic evaluation, advanced imaging, and myocardial biopsies can be helpful when diagnostic uncertainty exists. Our case highlights diagnostic methods and clinical course of a de novo presentation of cardiogenic shock from SLE myocarditis, then rapid improvement.

The Role of Vascular Lesions in Diabetes Across a Spectrum of Clinical Kidney Disease

IntroductionThe clinical-histologic correlation in diabetic nephropathy is not completely known.MethodsWe analyzed nephrectomy specimens from 90 patients with diabetes and diverse degrees of proteinuria and glomerular filtration rate (GFR).ResultsThirty-six (40%) subjects had normoalbuminuria, 33 (37%) microalbuminuria, and 21 (23%) non-nephrotic proteinuria. Mean estimated GFR (eGFR) was 65±23 (40% <60 ml/min per 1.73 m2). About 170 glomeruli per patient were analyzed, and all samples included vascular tissue. Six subjects (7%) were classified in diabetic nephropathy class I, 61 (68%) in class II-a, 13 (14%) in class II-b, 9 (10%) class III, and 1 (1%) in class IV. Eighty percent to 90% of those with normoalbuminuria or microalbuminuria were classified in class II-a or II-b and <10% in class III; 52% of those with proteinuria were in class II-a, 15% in class II-b, and 19% in class III. Nodular sclerosis (57%) and mesangial expansion (15%) were more frequent in cases with proteinuria than in normoalbuminuria (28% and 8%; P = 0.028 and 0.017). About 20% to 30% of all cases, regardless the level of albuminuria or proteinuria or the histologic class had tubular atrophy, interstitial fibrosis, or inflammation in >10% to 20% of the sample. Moderate hyalinosis and arteriolar sclerosis were observed in 80% to 100% of cases with normoalbuminuria, microalbuminuria, proteinuria, as well as in class I, II, or III.ConclusionsWeak correspondence between analytical parameters and kidney histology was found. Thus, disease may progress undetected from the early clinical stages of the disease. Finally, vascular damage was a very common finding, which highlights the role of ischemic intrarenal disease in diabetes.

A patient with a homozygous diacylglycerol kinase epsilon (DGKE) gene mutation with atypical haemolytic uraemic syndrome and low C3 responded well to eculizumab: a case report

BackgroundAtypical haemolytic uraemic syndrome (aHUS) is a rare systemic syndrome characterized by non-immune haemolytic anaemia, thrombocytopenia, and kidney injury. In most cases, alternative complement pathway dysregulation is the identifying cause. Recently, other genetic causes have been identified, including a mutation in the diacylglycerol kinase epsilon (DGKE) gene, which theoretically affect the coagulation pathway and does not affect the complement pathway. Data about the management of these patients are limited. Ideal management and definitive treatment protocols have not yet been established.Case presentationA three-year-old boy presented with features of atypical haemolytic uraemic syndrome (aHUS) and low complement C3. He was presumed to have complement-mediated aHUS and was managed empirically with eculizumab. Two weeks after starting eculizumab, his haemoglobin levels, platelet count, and complement C3 level normalized but he continued to have non-nephrotic range proteinuria. His genetic testing revealed a homozygous DGKE mutation, with no other mutation detected. Six months after presentation, the patient was still in remission with no features of aHUS, a trial of weaning eculizumab by increasing dose interval was followed by nephrotic range proteinuria and severe oedema. His proteinuria improved and his oedema resolved after resuming his recommended eculizumab dose.ConclusionsDGKE gene mutation can lead to aHUS with theoretically no complement dysregulation. However, some patients with this mutation show alternative complement pathway activation. This case report describes a patient with aHUS due to a DGKE gene mutation and low C3 levels who responded to eculizumab, adding to the previously reported cases of patients with DGKE gene mutations who had complete remission with no relapse with C5 blockers and/or plasma exchange. A randomized controlled study on patients with DGKE mutations might be beneficial in understanding the disease and generating a management protocol.

Risk factors for renal involvement in Henoch–Schönlein purpura

ObjectiveHenoch–Schönlein purpura is a systemic vasculitis that mainly occurs in children. Renal impairment is a major complication of Henoch–Schönlein purpura, but there is no established predictive marker for renal involvement. Thus, in this study, we investigated the risk factors for renal involvement in children with Henoch–Schönlein purpura. MethodThe medical records of children newly diagnosed as having Henoch–Schönlein purpura between 2005 and 2020 were reviewed retrospectively. Selected laboratory data were recorded before treatment initiation. The date and the age at diagnosis; sex; and the presence of arthralgia, gastrointestinal and renal involvement were obtained retrospectively. ResultsThis study included a total of 186 patients with Henoch–Schönlein purpura. Among them, 36.0% had renal involvement; 28.4% had only microscopic hematuria, 53.7% had non-nephrotic range proteinuria, and 17.9% had nephrotic-range proteinuria during follow-up. The mean age was higher (p = 0.016) and female sex was predominant (p = 0.001) in patients with renal involvement than in those without renal involvement. Blood neutrophil/lymphocyte ratio (p = 0.002) and platelet/lymphocyte ratio (p = 0.002) were significantly higher than that of the patients without renal involvement. No statistically significant differences were observed in the hemoglobin concentration, platelet count, presence of arthralgia, and gastrointestinal involvement between patients with and without renal involvement. Logistic regression analysis revealed female sex (odd ratio = 3.213) and neutrophil/lymphocyte ratio (odd ratio = 1.329) as risk factors for renal involvement. ConclusionsFemale sex and high neutrophil/lymphocyte ratio were risk factors for renal involvement in Henoch–Schönlein purpura.

A child with Imerslund-Gr\xe4sbeck syndrome concealed by co\u2010existing \u03b1-thalassaemia presenting with subacute combined degeneration of the spinal cord: a case report

BackgroundImerslund-Gräsbeck syndrome is a rare genetic disease characterised by vitamin B12 deficiency and proteinuria.Case presentationA 4-year old Sri Lankan boy presented with gradually worsening difficulty in walking for two weeks duration. He was previously diagnosed and managed as having non-transfusion-dependent α-thalassaemia based on the presence of hypochromic microcytic anaemia, haemoglobin H inclusion bodies in the blood film and compound heterozygous α-thalassaemia genotype with a gene deletion. However, his transfusion requirement increased over the past three months and he gradually lost his motor developmental milestones during two weeks before admission. The neurological examination revealed generalised hypotonia, exaggerated knee jerks and extensor plantar response. His complete blood count showed pancytopenia, and bone marrow biopsy revealed megaloblastic changes. Serum vitamin B12 and red blood cell folate levels were low. MRI revealed sub-acute combined degeneration of the spinal cord with characteristic ‘inverted V sign’. Urine analysis showed non-nephrotic range proteinuria. The diagnosis of Imerslund-Gräsbeck syndrome was made due to the presence of non-nutritional vitamin B12 deficiency and asymptomatic proteinuria. He showed a rapid haematological and neurological improvement to intramuscular hydroxocobalamin.ConclusionsThis case report presents a rare occurrence of severe vitamin B12 deficiency due to Imerslund-Gräsbeck syndrome masked by co-existent α-thalassaemia, resulting in serious consequences. It highlights the need for a high index of suspicion in evaluating children with severe anaemia, especially in the presence of mixed pathologies.

A case of dasatinib-induced focal segmental glomerulosclerosis in a patient with Philadelphia chromosome positive chronic myeloid leukemia

Focal segmental glomerulosclerosis is a common glomerular histological lesion, which is usually characterised by non-nephrotic range proteinuria or nephrotic syndrome. It may be idiopathic or occurs secondarily to drugs, diabetes, obesity or HIV nephropathy and other infections. Dasatinib, a tyrosine kinase inhibitor that has been used for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia, has a few renal adverse effects. Exceptional cases with non-nephrotic range proteinuria have been reported in relation with dasatinib. In this case, we report a patient with symptoms of nephrotic syndrome and nephrotic range proteinuria, who was diagnosed as focal segmental glomerulosclerosis by kidney biopsy after treated with dasatinib.

Usefulness of rebiopsy in the case of mesangial pathology.

Immunologically different types of glomerulopathies show varied symptoms and clinical courses. Unlike in lupus nephritis, repeated biopsy is rarely performed in cases of mesangial glomerulonephritis. We reviewed 200 cases wherein rebiopsy was performed in patients with diagnosed mesangial glomerular pathology over a 30-year period and analyzed the symptoms follow-up in these cases. Further, we evaluated the morphological changes between the first and final biopsies to identify cases of histological progression and histological remission and examined the correlation between such changes and clinical symptoms. The time between the first and last biopsies ranged from 7 months to 35 years. The most common for the initial biopsy was nephrotic syndrome, followed by non-nephrotic proteinuria; other symptoms occurred rarely. Histological progression occurred at various stages of observation, ranging from within a few months to after several years. Histological progression and remission were detected in 118 and 3 patients, respectively, whereas there was no difference in morphological findings between the first and last biopsies in 79 patients. Rebiopsy is useful in patients who do not respond adequately to treatment, and especially in those with increased clinical symptoms. Moreover, electron microscopic examination is necessary to discover early signs of histological progression.

Schistosomiasis Associated Glomerulopathy (Glomerulonephristis / Nephrotic Syndrome): A review and Update of the Literature

Schistosomiasis may affect a number of organs within the human body. Schistosomiasis may also be associated with glomerular disease of the kidney in the form of glomerulonephritis and nephrotic syndrome. The association between Schistosomiasis and glomerulopathy may not be well known by a number of practitioners and its pathophysiology may not be very well understood and this could be due to the underdiagnosis of the disease due to the possibility of lack of facilities within the Schistosomiasis endemic areas of the world especially within tropical Africa. Nevertheless, there are a number of patterns of renal involvement in Schistosomiasis which include (a) upper urinary tract sequelae of lower urinary tract Schistosomiasis pathology, (b) immune-related glomerulonephritis, (c) as well as oxidant-stress-mediated renal tubular glomerulonephritis. The renal involvement by Schistosomiasis does tend to be ensued by the development of Schistosomiasis-associated Glomerulopathy (Glomerulonephritis / Nephrotic Syndrome) of varying severity. Individuals affected by Schistosomiasis-associated kidney disease may develop (a) asymptomatic disease which tends to related to self-limited and asymptomatic glomerular disease (b) symptomatic disease which most commonly would tend to present with nephrotic syndrome most often in patients who develop hepato-splenic schistosomiasis with liver fibrosis associated with Schistosoma mansoni infection. Symptomatic patients tend to develop severe hypo-proteinemia, half of the patients tend to have elevated blood pressure. In the absence of nephrotic syndrome, patients who have Schistosomiasis-associated glomerulopathy may manifest with: (a) isolated non-nephrotic syndrome proteinuria (b) acute glomerulonephritis associated with haematuria and heavy proteinuria, (c) Nephrotic syndrome together with systemic manifestations of co-infection with salmonella (class II) or hepatitis C virus (Class I), (d) End stage renal disease (ESRD). Some of the patients who have Schistosomiasis of the kidney may present with Haematuria, Hypertension, Hepato-splenic Schistosomiasis. The diagnosis should be suspected with regard to the following scenarios: (a) clinical suspicion in a patient with kidney disease who is known or has been known to have Schistosoma mansoni; (b) exposure to an endemic area, (c) clinical evidence / demonstration of chronic hepatosplenic schistosomiasis, (d) if the patient has not been diagnosed as having been afflicted with schistosomiasis, then schistosomal infection should be documented, (e) majority of patients with schistosomiasis and kidney disease should have kidney biopsy. (f) The patients should be evaluated for co-infection with salmonella, hepatitis C virus, and hepatitis B virus in order to ensure adequate treatment of the disease. Schistosomiasis is the second most devastating tropical parasitic disease globally which tends to be responsible for many urological complications. Nevertheless, glomerular injury is an uncommon complication which has mainly or most often described with Schistosoma Mansoni. When patients who have Schistosomiasis-associated Kidney disease are managed and followed-up on long-term basis with renal end points, one third of the patients independent of the histopathology examination features of the kidney biopsies would tend to progress dialysis. Membranoproliferative glomerulonephritis (MPGN) is an uncommon complication associated with Schistosoma Haematobium infection which tends to be associated with potentially poor prognosis. MPGN could lead quickly to End Stage Renal Disease (ESRD). Anti-helminthic and immunosuppressive medicaments tend not to be effective at advanced stages of the disease and hence efforts need to be focused upon the prevention, early detection, as well as treatment of Schistosoma infections among at-risk groups of individuals. In order to reduce morbidity related to Schistosoma-associated nephropathy, public health policy, should be concentrated upon the prevention of the disease by the control of snail, improved sanitation, and health education, as well as by the implementation, and sustenance of chemotherapy-based control strategies. Considering that many individuals are found yearly to be inflicted by Schistosomiasis who tend to dwell in more rural parts of their countries where facilities for the undertaking of renal function tests and biopsies of the kidney tend not to be readily available, there is the likelihood that Schistosomiasis-associated nephropathies may be highly underdiagnosed globally.

Kidney Biopsy

The introduction of renal biopsies has transformed practice in nephrology, particularly with regard to glomerular disease and the care of kidney transplant recipients. A biopsy can provide information about the diagnosis and prognosis of kidney disease while most importantly often leading to changes in therapy that can be life saving. Four groups of patients benefit most from renal biopsy: those with nephrotic syndrome, those with acute nephritic syndromes with rapid deterioration of renal function, those with unexplained acute kidney injury and renal transplant recipients. Non-nephrotic range proteinuria and/or hematuria or unexplained chronic kidney disease represent indications in selected cases. The evaluation of patients prior to undergoing a kidney biopsy requires a careful assessment that includes a detailed history to confirm the relative benefit of a biopsy in making an accurate diagnosis compared with individual’s risk of bleeding. The use of real-time ultrasound or CT-guidance with gun-mounted biopsy needles is paramount for the successful performance of the biopsy and reduction of risks. renal biopsies are mostly done as an inpatient but can be performed on an outpatient basis in selected cases. A renal biopsy has a bleeding risk of up to 5% and is considered a “high bleeding risk procedure”. For patients receiving -antithrombotic therapy, the approach to periprocedural use of antithrombotic agents needs to be individualized. Because it is a high-risk procedure, all efforts must be undertaken to minimize the risk including a careful assessment of the patient's specific situation, and only experienced operators at institutions that can care for post-biopsy complications should perform the procedure. This review contains 7 tables, 7 figures and 83 references Key words: kidney biopsy, native kidney, transplant kidney, indications, preparation, performing biopsy, ultrasound guidance, transjugular, CT-guided, complications

Kidney Biopsy

The introduction of renal biopsies has transformed practice in nephrology, particularly with regard to glomerular disease and the care of kidney transplant recipients. A biopsy can provide information about the diagnosis and prognosis of kidney disease while most importantly often leading to changes in therapy that can be life saving. Four groups of patients benefit most from renal biopsy: those with nephrotic syndrome, those with acute nephritic syndromes with rapid deterioration of renal function, those with unexplained acute kidney injury and renal transplant recipients. Non-nephrotic range proteinuria and/or hematuria or unexplained chronic kidney disease represent indications in selected cases. The evaluation of patients prior to undergoing a kidney biopsy requires a careful assessment that includes a detailed history to confirm the relative benefit of a biopsy in making an accurate diagnosis compared with individual’s risk of bleeding. The use of real-time ultrasound or CT-guidance with gun-mounted biopsy needles is paramount for the successful performance of the biopsy and reduction of risks. renal biopsies are mostly done as an inpatient but can be performed on an outpatient basis in selected cases. A renal biopsy has a bleeding risk of up to 5% and is considered a “high bleeding risk procedure”. For patients receiving -antithrombotic therapy, the approach to periprocedural use of antithrombotic agents needs to be individualized. Because it is a high-risk procedure, all efforts must be undertaken to minimize the risk including a careful assessment of the patient's specific situation, and only experienced operators at institutions that can care for post-biopsy complications should perform the procedure. This review contains 7 tables, 7 figures and 83 references Key words: kidney biopsy, native kidney, transplant kidney, indications, preparation, performing biopsy, ultrasound guidance, transjugular, CT-guided, complications

Biopsy-proven Henoch-Sch\xf6nlein purpura nephritis: a single center experience

BackgroundKnowledge on normal progress and treatment of Henoch-Schönlein purpura nephritis (HSPN) is limited. This study reviews outcome, clinical, pathological, and therapeutic factors affecting the prognosis of HSPN patients.MethodsForty-nine children with biopsy-confirmed HSPN diagnosed between September 2008 and 2018 were included. Demographics, clinical and laboratory data, treatment, and outcome were recorded at the time of biopsy, 3, 6, 12, and 24 months and at last visit. Clinical outcome was graded according to Meadow’s criteria.ResultsThe median age at time of biopsy was 10.1 years (IQR:5.7) and female/male ratio 24/25. At presentation, 40.8% of patients had nonnephrotic proteinuria, 18.4% nephrotic syndrome (NS), 4.1% nephritic syndrome (NephrS), and 36.7% NephrS+NS. There were 11 patients with an estimated glomerular filtration rate below 90 ml/min/1.73 m2. Biopsy specimens were classified according to International Study of Kidney Diseases in Children (ISKDC) and Oxford Classification MEST-C scoring systems. Forty-one patients received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, 37 patients steroids, and 35 patients other immunosuppressive medications. At last visit, 24 patients had stage 1 chronic kidney disease (CKD), three stage 2 CKD, and two had stage 5 CKD. Neither clinical parameters nor ISKDC biopsy grade or treatment modalities effected the final outcome. The Oxford classification showed significantly increased segmental glomerulosclerosis in patients with unfavorable outcome. Favorable outcome was associated with shorter time from kidney involvement to biopsy and start of treatment.ConclusionA large proportion of patients continued to show signs of CKD at last follow-up while only a small proportion developed stage 5 CKD.

Early-onset COQ8B (ADCK4) glomerulopathy in a child with isolated proteinuria: a case report and literature review

BackgroundHerein, a 3-year-old boy presented with hidden-onset isolated proteinuria was reported. The disease was induced by COQ8B (previously termed ADCK4) compound heterozygous variants, including c.[271C > T] and c.[737G > A], which were inherited from his father and mother, respectively.Case presentationThe patient visited our clinic due to non-nephrotic range proteinuria for 3 months, but no obvious abnormality was detected in the vital signs or laboratory test results. Renal histopathology revealed mitochondrial nephropathy, which manifested as mild glomerular abnormalities under light microscope, together with mitochondrial proliferation and hypertrophy and crowded arrangement under electron microscope. As suggested by whole exome sequencing, the patient inherited the COQ8B compound heterozygous variants from both of his parents who showed normal phenotype. After literature review, it was confirmed that one of the variant site (c.[271C > T]) had not been reported among the East Asian populations so far.ConclusionsSteroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis are the most common phenotypes and renal histopathological manifestations of COQ8B variant. Nonetheless, our case shows that such variant may have hidden and mild clinical manifestations at the early onset. Therefore, early diagnosis will help to identify children at the early disease stage who have opportunity to benefit from oral coenzyme Q10 supplementation.

Outcomes of Mycophenolate Mofetil vs. Intravenous Cyclophosphamide in Induction Therapy of Childhood-Onset Lupus Nephritis

Background: Intravenous cyclophosphamide (IVCY) concomitant with corticosteroids demonstrated better outcomes in therapy of proliferative lupus nephritis albeit adverse effects may occur. Mycophenolate mofetil (MMF) is a newer oral medication for treating lupus nephritis. Objective: To compare renal outcomes between IVCY and MMF in conjunction with corticosteroid for induction therapy of proliferative lupus nephritis. Materials and Methods: The authors reviewed the medical records from four university hospitals of children who received prednisolone with either MMF or IVCY for induction therapy of proliferative lupus nephritis between 2005 and 2014 in the present retrospective cohort study. Results: Twenty-eight and 85 patients were included in the MMF and IVCY group, respectively. The respective mean age at MMF and IVCY initiation was 12.36±2.87 and 11.84±3.04 years. Renal remission was not significantly different between the groups (p=0.690). Non-nephrotic range proteinuria (adjusted OR 2.93, 95% CI 1.23 to 6.94, p=0.015), and high initial GFR (adjusted OR 2.93, 95% CI 1.14 to 7.56, p=0.026) were significantly associated with achieving renal remission. Both infectious (82.1%) and non-infectious complications (96.9%) were more common in the IVCY group. Neither death nor end-stage renal disease (ESRD) occurred during the induction therapy. Conclusion: There was no significant difference in renal remission whether children received MMF or IVCY for induction therapy of lupus nephritis; however, adverse events occurred less frequently in the MMF group. Keywords: Children, Lupus nephritis, Systemic lupus erythematosus, Mycophenolate, Cyclophosphamide, Induction

Renal Effects of Sulodexide in Type 2 Diabetic Patients without Nephrotic Range Proteinuria.

Background Glycosaminoglycan plays an important role in the maintenance of glomerular charge selectivity of diabetic nephropathy. Sulodexide, a mixture of naturally occurring glycosaminoglycan polysaccharide components, has shown a nephroprotective effect in an experimental model of diabetic nephropathy. Although sulodexide reduced albuminuria in patients with type 1 and type 2 diabetes, long-term effects in patients with type 2 diabetes with significant proteinuria have not been established. Objectives The study was aimed at investigating the effects of sulodexide on proteinuria and renal function in patients with type 2 diabetes and nephropathy. Methods Fifty-two patients with proteinuria between 500 and 3000 mg/day received sulodexide 200 mg/day for 12 months, while 56 matched patients with type 2 diabetes constituted the control group. All patients received standard metabolic and blood pressure controls. Primary outcome was evaluated as percentage of reduced proteinuria compared with the control group. Renal function was assessed using estimated glomerular filtration rate (GFR). Results Proteinuria significantly increased in the control group [0.9 (IQR 0.3 to 1.78) to 1.16 (IQR 0.44 to 2.23) g/gCr, P = 0.001], whereas it remained stable in the sulodexide group [0.66 (IQR 0.23 to 0.67) to 0.67 (IQR 0.17 to 1.51) g/gCr, P = 0.108]. At 12 months, proteinuria was higher by 19.4% (IQR 10.3 to 37.6) in the control group while proteinuria was lower by -17.7% (IQR -53.1 to 3.2) in the sulodexide group with a significant difference between groups (P = 0.001). Renal function was noted as a change of estimated GFR, and serum creatinine decreased significantly during the study in both groups but did not significantly differ between groups. No significant changes in the blood pressure, fasting plasma glucose, and hemoglobin A1C were reported. Conclusion In addition to standard treatment, sulodexide is efficient in maintaining proteinuria in patients with type 2 diabetes with nonnephrotic range proteinuria, but it did not provide an additional benefit concerning renal disease progression.

Clinicopathological spectrum of two common conditions encountered in renal biopsies: acute diffuse proliferative glomerulonephritis and lupus nephritis

Background: Acute diffuse proliferative glomerulonephritis (ADPGN) and lupus nephritis (LN) are commonly encountered conditions in renal biopsies. ADPGN is usually a self-limiting childhood disease occurring commonly after streptococcal infection. LN is a common complication of systemic lupus erythematosus (SLE) with diverse clinical and histological features. Objectives: The objective of this study is to describe the clinico-pathological spectrum of ADPGN and LN in renal biopsies. Method: A retrospective-descriptive study was done by retrieving all renal biopsies (1225) received in the year 2018 at the Department of Pathology, Faculty of Medicine, University of Peradeniya. Biopsies diagnosed as ADPGN and LN were selected. Results: Out of all renal biopsies (1225), 63(5.1%) were diagnosed as ADPGN and 92(7.5%) as LN. ADPGN was seen in an age range of 3-78 years. 24(38.1%) were children and 39(61.9%) were adults. Nephritic syndrome (NS) was the commonest presentation in both children and adults (n=23,36.5%) while 13(20.6%) showed nephrotic-nephritic mixed picture (NNMP). Cellular crescents were seen in 11 patients (17.4%) and most were adults with NNMP. Tubular injury was seen in 19 (30.1%) and most were children with NNMP. 34 (53.9%) patients showed classic uncomplicated ADPGN. Immunofluorescence showed IgG-positivity in 9(14.2%). C3 was positive in 27(42.8%). In LN cases, 47(51.09%) patients were women with Class IV lesions, which was the commonest group. Of the class IV patients (n=56) most presented with non-nephrotic range proteinuria (NNRP), while 35 (62.5%) had microscopic haematuria (MH) and 26(46.4%) showed elevated serum creatinine. All class II patients(n=15) were women (100%). 9 (60%) patients showed NNRP, 9 (60%) MH and 4(26.7%) elevated SC. All class III patients(n=5) were also women who had NNRP and MH. SC was elevated in 1(20%) patient. Conclusions: Most children and adults who underwent renal biopsy for ADPGN had presented with NS while a lesser number had NNMP. A study done by Wijewickrama et al. in 2015 also revealed that NS was the commonest presentation of ADPGN in adults. Common complications detected in our study were cellular crescents and tubular injury which were found more in patients with NNMP than NS. C3-positivity was commoner than IgG possibly because biopsies were performed during the latter phase of the disease. Common classes of LN were class IV, II and III. Most of these patients had NNRP and MH while a lesser number showed elevated serum creatinine.

Obesity is associated with severe clinical course in children with Henoch-Schonlein purpura.

We aimed to evaluate the role of obesity on the clinical course and response to treatment in patients with Henoch-Schonlein purpura (HSP). Data charts of children with HSP followed in a tertiary hospital between 2000 and 2018 were reviewed retrospectively. Persistent purpura was defined as skin involvement persisting for ≥ 30days. Mild nephropathy was defined as the presence of microscopical hematuria and/or non-nephrotic proteinuria, while severe nephropathy as nephrotic proteinuria, nephritic syndrome, and/or kidney insufficiency. Obese and non-obese patients were compared for demographic, clinical, and laboratory parameters. There were 199 patients (M/F, 104/95; median (IQR) presenting age 7.1 (5.0-9.2) years; follow-up period 17.5 (6-50) months). Obese patients (n = 35 (17.6%)) had significantly higher rate of persistent purpura (46% vs 21%), severe renal involvement (58% vs 31%), high-grade renal histopathological lesions (83% vs 39%), hypertension (29% vs 9%), and increased erythrocyte sedimentation rate (79% vs 56%). Obese patients also showed delayed improvement of cutaneous (25 vs 14days), articular (12.5 vs 10.0days), and kidney (280 vs 57days) symptoms. Obese children used steroids for significantly longer period of time (236 vs 40days). Furthermore, need for immunosuppressive medications were higher in obese patients (40% vs 9%). Obese children with HSP had higher erythrocyte sedimentation rate, hypertension, and severe renal involvement; showed delayed improvement of skin, joint, and kidney findings; and need more immunosuppressive medications and a longer period of steroid treatment. These findings may be associated with the effect of adipose tissue on inflammation.